掲載種別：研究論文（学術雑誌）  

Background/Aim: Pancreatic cancer has a very poor prognosis with a 5-year survival rate of less than 5% among patients with distant metastasis, a figure that has not improved over many decades. Only 10 to 20% patients are candidates for curative surgery at presentation due to the aggressive nature and asymptomatic progression of pancreatic cancer. Although first-line chemotherapy, such as FOLFIRINOX and gemcitabine + nab paclitaxel, improved the median survival from 8.5 to 11.1 months, more effective treatments are immediately needed. The aim of the present study was to evaluate the efficacy of methionine restriction with oral rMETase (o-rMETase) and a low-methionine diet combined with first-line chemotherapy on a patient with stage Ⅳ metastatic pancreatic cancer. Case Report: A 63-year-old female was diagnosed with metastatic pancreatic cancer in October 2023. The patient started FOLFIRINOX as first-line chemotherapy in combination with methionine restriction, which comprised o-rMETase 250 units twice a day and a low-methionine diet. The patient was monitored using computed tomography and CA19-9 blood tests. After five months from the start of combination therapy, the size of the primary tumor decreased by 40% along with liver-metastasis regression. The CA19-9 blood marker decreased by 86%. The patient sustains a high performance status and continues the combination therapy without severe side effects. Conclusion: Methionine restriction consisting of o-rMETase and a low-methionine diet, in combination with first-line chemotherapy, was highly effective in a patient with inoperable stage IV pancreatic cancer.

DOI： 10.21873/anticanres.17215

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND/AIM: Pancreatic cancer has a very poor prognosis with a 5-year survival rate of less than 5% among patients with distant metastasis, a figure that has not improved over many decades. Only 10 to 20% patients are candidates for curative surgery at presentation due to the aggressive nature and asymptomatic progression of pancreatic cancer. Although first-line chemotherapy, such as FOLFIRINOX and gemcitabine + nab paclitaxel, improved the median survival from 8.5 to 11.1 months, more effective treatments are immediately needed. The aim of the present study was to evaluate the efficacy of methionine restriction with oral rMETase (o-rMETase) and a low-methionine diet combined with first-line chemotherapy on a patient with stage IV metastatic pancreatic cancer. CASE REPORT: A 63-year-old female was diagnosed with metastatic pancreatic cancer in October 2023. The patient started FOLFIRINOX as first-line chemotherapy in combination with methionine restriction, which comprised o-rMETase 250 units twice a day and a low-methionine diet. The patient was monitored using computed tomography and CA19-9 blood tests. After five months from the start of combination therapy, the size of the primary tumor decreased by 40% along with liver-metastasis regression. The CA19-9 blood marker decreased by 86%. The patient sustains a high performance status and continues the combination therapy without severe side effects. CONCLUSION: Methionine restriction consisting of o-rMETase and a low-methionine diet, in combination with first-line chemotherapy, was highly effective in a patient with inoperable stage IV pancreatic cancer.

DOI： 10.21873/anticanres.17215

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The real-world efficacy, prognostic factors, and adverse events of second-line nivolumab monotherapy and subsequent third-line therapy for unresectable or metastatic esophageal cancer have not been fully evaluated. METHODS: This multi-institutional retrospective cohort study evaluated 184 consecutive patients treated with second-line nivolumab monotherapy for esophageal cancer between March 2021 and December 2022. We assessed tumor response, adverse events, long-term survival, and prognostic factors. RESULTS: Among 128 patients with measurable lesions, the response rate was 23% and the disease control rate for all enrolled patients was 45%. The incidence of grade 3 or higher adverse events was 14%, but no treatment-related deaths presented. Median progression-free survival was 5.1 months and overall survival was 14 months, respectively. C-reactive protein level and performance status were identified as significant prognostic factors of overall survival through Cox proportional hazards analysis. The group with two favorable prognostic factors showed better overall survival than the groups with either one or zero prognostic factors (median overall survival: 22, 15, and 4.4 months, respectively). Among 69 patients who received third-line taxane anticancer agents, the progression-free survival was 6.7 months. CONCLUSIONS: Our study demonstrated that the real-world outcomes of second-line nivolumab monotherapy were comparable to those of previous randomized clinical trials in terms of tumor response, safety, and long-term survival. Furthermore, a good performance status and low C-reactive protein levels may identify patients who are likely to benefit from therapy. Third-line chemotherapy after nivolumab treatment may have an enhanced effect; however, further prospective studies are required to confirm this finding.

DOI： 10.1007/s00535-024-02141-8

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掲載種別：研究論文（学術雑誌）  

Introduction: Primary small bowel carcinoma in pregnant women is extremely rare. Small bowel cancer is difficult to diagnose because of its rarity, lack of specific clinical symptoms, and particular anatomical features. We experienced a case of primary small bowel adenocarcinoma with ovarian metastasis during pregnancy. This is the first reported case of a patient with small bowel adenocarcinoma whose pregnancy continued to term and ended in delivery. Case Presentation: A 32-year-old pregnant woman developed abdominal pain, and imaging examination revealed an ovarian tumor at 29 weeks of gestation.We performed laparotomy and resected the ovarian tumor, which was initially suspected to be primary ovarian cancer. The patient continued the pregnancy to term. A detailed examination of the abdominal cavity during cesarean delivery at 37 weeks revealed that the primary lesion was located in the small bowel. Conclusion: It is important to recognize that the small bowel may be the primary site of metastatic ovarian cancer. Detailed and careful examination is necessary to diagnose small bowel cancer during pregnancy.

DOI： 10.1159/000540524

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Although handheld ultrasound devices (HUDs) are commonplace, their ability to diagnose fecal retention (FR) remains unclear. This prospective observational study examined HUDs' usefulness in diagnosing FR in patients with constipation in a palliative care setting. Between 10 December 2020 and 30 June 2022, we compared rectal ultrasonographic findings obtained using HUDs with clinical manifestations in 64 males and 70 females (48%, 52%, 68 ± 11 years old) with constipation who had undergone computed tomography (CT). FR was diagnosed using a HUD and compared with CT and digital rectal examination (DRE) results. In total, 42 (31%), 42 (31%), and 41 (31%) patients were diagnosed using HUDs, CT, and DRE, respectively. Thirty-nine (93%) patients in the CT group were also diagnosed with FR using HUDs. A total of 89 of 92 patients with a negative CT diagnosis also had a negative HUD diagnosis. Among the 41 patients in the DRE group, 37 were also diagnosed with FR using HUDs. Among 93 patients with a negative DRE diagnosis, 86 had a negative HUD diagnosis. The sensitivity, specificity, positive predictive value, and negative predictive value of HUDs for CT were 93%, 97%, 93%, and 97%, respectively. Those of HUDs for DRE were 88%, 94%, 86%, and 95%, respectively. The concordance rates for FR diagnosis were 128/134 for CT and HUDs and 123/134 for DRE and HUDs. HUD was useful for diagnosing FR in this setting. HUDs could provide valuable support for appropriate treatment selection. Developing a constipation treatment algorithm based on rectal ultrasonographic findings is warranted in the future.

DOI： 10.3390/diagnostics14151626

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掲載種別：研究論文（学術雑誌）  

Background/Aim: Gliomas are the most common and recalcitrant malignant primary brain tumors. All cancer types are addicted to methionine, which is a fundamental and general hallmark of cancer known as the Hoffman effect. Particularly glioma cells exhibit methionine addiction. Because of methionine addiction, [11C]-methionine positron emission tomography (MET-PET) is widely used for glioma imaging in clinical practice, which can monitor the extent of methionine addiction. Methionine restriction including recombinant methioninase (rMETase) and a low-methionine diet, has shown high efficacy in preclinical models of gliomas, especially in combination with chemotherapy. The aim of the present study was to determine the efficacy of methionine restriction with oral rMETase (o-rMETase) and a low-methionine diet, combined with radiation and temozolomide (TMZ), on a teenage female patient with high-grade glioma. Case Report: A 16-year-old girl was diagnosed with high-grade glioma. Magnetic resonance imaging (MRI) showed a left temporal-lobe tumor with compression to the left lateral ventricle and narrowing of sulci in the left temporal lobe. After the start of methionine restriction with o-rMETase and a low-methionine diet, along with TMZ combined with radiotherapy, the tumor size shrunk at least 60%, with improvement in the left lateral ventricle and sulci. The patient’s condition remains stable for 19 months without severe adverse effects. Conclusion: Methionine restriction consisting of o-rMETase and a low-methionine diet, in combination with radiation and TMZ as first-line chemotherapy, were highly effective in a patient with high-grade glioma.

DOI： 10.21873/invivo.13591

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掲載種別：研究論文（学術雑誌）  

Background/Aim: Colorectal cancer (CRC) is the third-leading cause of death in the world. Although the prognosis has improved due to improvement of chemotherapy, metastatic CRC is still a recalcitrant disease, with a 5-year survival of only 13%. Irinotecan (IRN) is used as first-line chemotherapy for patients with unresectable CRC. However, there are severe side effects, such as neutropenia and diarrhea, which are dose-limiting. We have previously shown that methionine restriction (MR), effected by recombinant methioninase (rMETase), lowered the effective dose of IRN of colon-cancer cells in vitro. The aim of the present study was to evaluate the efficacy of the combination of low-dose IRN and MR on colon-cancer in nude mice. Materials and Methods: HCT-116 colon-cancer cells were cultured and subcutaneously injected into the flank of nude mice. After the tumor size reached approximately 100 mm3, 18 mice were randomized into three groups; Group 1: untreated control on a normal diet; Group 2: high-dose IRN on a normal diet (2 mg/kg, i.p.); Group 3: low-dose IRN (1 mg/kg i.p.) on MR effected by a methionine-depleted diet. Results: There was no significant difference between the control mice and the mice treated with high-dose IRN, without MR. However, low-dose IRN combined with MR was significantly more effective than the control and arrested colon-cancer growth (p=0.03). Body weight loss was reversible in the mice treated by low-dose IRN combined with MR. Conclusion: The combination of low-dose IRN and MR acted synergistically in arresting HCT-116 colon-cancer grown in nude mice. The present study indicates the MR has the potential to reduce the effective dose of IRN in the clinic.

DOI： 10.21873/invivo.13539

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The real-world efficacy, feasibility, and prognostic factors of immune-checkpoint inhibitor combination therapy for unresectable or metastatic esophageal cancer are not fully established. METHODS: This multi-institutional retrospective cohort study evaluated 71 consecutive patients treated with immune-checkpoint inhibitor combination therapy for esophageal cancer between March 2021 and December 2022. We assessed tumor response, safety, and long-term survival. RESULTS: In patients with measurable lesions, the response rate was 58%, and the disease control rate for all enrolled patients was 80%. Five patients (7.0%) underwent successful conversion surgery. Grade 3 or higher immune-related adverse events occurred in 13% of patients, and one patient (1.4%) died due to cholangitis. Median progression-free survival was 9.7 (95% confidence interval: 6.5-not reached). C-reactive protein levels and performance status were identified as significant predictors of progression-free survival through Cox proportional hazards analysis. CONCLUSIONS: Immune-checkpoint inhibitor combination therapy for esophageal cancer demonstrated comparable tumor response, safety, and long-term survival to previous randomized clinical trials. Patients with good performance status and low C-reactive protein levels may be suitable candidates for this treatment.

DOI： 10.1007/s10147-024-02532-0

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND/AIM: Breast cancer is the most common and the deadliest cancer among women in the world. Treatment options for HER2-positive metastatic breast cancer patients are limited. Trastuzumab deruxtecan (T-DXd), an antibody-drug conjugate (ADC), has recently been introduced as second-line chemotherapy for HER2-positive metastatic breast cancer. The aim of the present study was to evaluate the efficacy of methionine restriction with oral recombinant methioninase (o-rMETase) and a low-methionine diet combined with T-DXd, on a patient with HER2-positive recurrent stage IV breast cancer. CASE REPORT: A 66-year-old female was diagnosed with HER2-positive metastatic breast cancer. Computed tomography (CT) indicated peritoneal dissemination, thickening of the sigmoid colon and splenic flexure and widespread bone metastases. The patient was previously treated with fulvestrant, trastuzumab, pertuzumab, paclitaxel and capecitabine which were ineffective. T-DXd was administered as a second-line chemotherapy. Since the patient experienced strong side effects, the dose of T-Dxd was decreased. The patient began methionine restriction using o-rMETase and a low-methionine diet along with T-DXd. After the start of the combined treatment, CA15-3 and CA27.29, tumor markers for breast cancer, decreased rapidly from a very high level. The levels of both tumor markers are currently normal. Additionally, peritoneal-dissemination nodules, ascites and the thickness of the sigmoid colon and splenic flexure are no longer detected on CT. The patient maintains a high performance status, without severe side effects of the combination treatment. CONCLUSION: Methionine restriction consisting of o-rMETase and a low-methionine diet, in combination with T-DXd as second-line chemotherapy, was highly effective in a patient with HER2-positive stage IV breast cancer.

DOI： 10.21873/anticanres.16946

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掲載種別：研究論文（学術雑誌）  

Background/Aim: Breast cancer is the most common and the deadliest cancer among women in the world. Treatment options for HER2-positive metastatic breast cancer patients are limited. Trastuzumab deruxtecan (T-DXd), an antibody-drug conjugate (ADC), has recently been introduced as second-line chemotherapy for HER2-positive metastatic breast cancer. The aim of the present study was to evaluate the efficacy of methionine restriction with oral recombinant methioninase (o-rMETase) and a low-methionine diet combined with T-DXd, on a patient with HER2-positive recurrent stage IV breast cancer. Case Report: A 66-year-old female was diagnosed with HER2-positive metastatic breast cancer. Computed tomography (CT) indicated peritoneal dissemination, thickening of the sigmoid colon and splenic flexure and widespread bone metastases. The patient was previously treated with fulvestrant, trastuzumab, pertuzumab, paclitaxel and capecitabine which were ineffective. T-DXd was administered as a second-line chemotherapy. Since the patient experienced strong side effects, the dose of T-Dxd was decreased. The patient began methionine restriction using orMETase and a low-methionine diet along with T-DXd. After the start of the combined treatment, CA15-3 and CA27.29, tumor markers for breast cancer, decreased rapidly from a very high level. The levels of both tumor markers are currently normal. Additionally, peritoneal-dissemination nodules, ascites and the thickness of the sigmoid colon and splenic flexure are no longer detected on CT. The patient maintains a high performance status, without severe side effects of the combination treatment. Conclusion: Methionine restriction consisting of o-rMETase and a low-methionine diet, in combination with T-DXd as second-line chemotherapy, was highly effective in a patient with HER2- positive stage IV breast cancer.

DOI： 10.21873/anticanres.16946

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND/AIM: Irinotecan (IRN), a topoisomerase I inhibitor and pro-drug of SN-38, is first-line treatment of colon cancer as part of FOLFIRI and FOLFOXIRI combination chemotherapy. However, IRN causes dose-limiting adverse events such as neutropenia and diarrhea. Dose reductions are sometimes required, which reduce efficacy. Recombinant methioninase (rMETase) targets the fundamental basis of cancer, methionine addiction, known as the Hoffman effect, and enhances the efficacy of numerous chemotherapy drugs. The present study determined the efficacy of rMETase when administered in combination with IRN. MATERIALS AND METHODS: Cell viability was assessed by cultivating the HCT-116 human colorectal cancer cell line in 96-well plates at 1×103 cells per well in Dulbecco's modified Eagle's medium (DMEM). Subsequently, HCT-116 cells were treated with increasing concentrations of SN-38, the active form of IRN, ranging from 0.5 nM to 32 nM, and/or rMETase ranging from 0.125 to 8 U/ml. After treatment for 72 h, the half-maximal inhibitory concentration (IC50) of SN-38 alone and rMETase alone for HCT-116 cells were determined. Using the IC50 concentration of rMETase, we determined the IC50 of SN-38 in combination with rMETase. Cell viability was determined with the cell-counting Kit-8 with the WST-8 reagent.. RESULTS: The IC50 of rMETase alone for the HCT-116 cells was 0.55 U/ml, and the IC50 of IRN (SN-38) alone was 3.50 nM. rMETase at 0.55 U/ml lowered the IC50 of SN-38 to 0.232 nM (p<0.0001), a 15-fold reduction. CONCLUSION: rMETase and IRN are strongly synergistic, giving rise to the possibility of lowering the effective dose of IRN for the treatment of patients with colon cancer, thereby reducing its severe toxicity. This new strategy will allow more patients with cancer to be effectively treated with IRN.

DOI： 10.21873/anticanres.16785

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND/AIM: Gliomas are the most common and recalcitrant malignant primary brain tumors. All cancer types are addicted to methionine, which is a fundamental and general hallmark of cancer known as the Hoffman effect. Particularly glioma cells exhibit methionine addiction. Because of methionine addiction, [11C]-methionine positron emission tomography (MET-PET) is widely used for glioma imaging in clinical practice, which can monitor the extent of methionine addiction. Methionine restriction including recombinant methioninase (rMETase) and a low-methionine diet, has shown high efficacy in preclinical models of gliomas, especially in combination with chemotherapy. The aim of the present study was to determine the efficacy of methionine restriction with oral rMETase (o-rMETase) and a low-methionine diet, combined with radiation and temozolomide (TMZ), on a teenage female patient with high-grade glioma. CASE REPORT: A 16-year-old girl was diagnosed with high-grade glioma. Magnetic resonance imaging (MRI) showed a left temporal-lobe tumor with compression to the left lateral ventricle and narrowing of sulci in the left temporal lobe. After the start of methionine restriction with o-rMETase and a low-methionine diet, along with TMZ combined with radiotherapy, the tumor size shrunk at least 60%, with improvement in the left lateral ventricle and sulci. The patient's condition remains stable for 19 months without severe adverse effects. CONCLUSION: Methionine restriction consisting of o-rMETase and a low-methionine diet, in combination with radiation and TMZ as first-line chemotherapy, were highly effective in a patient with high-grade glioma.

DOI： 10.21873/invivo.13591

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND/AIM: Colorectal cancer (CRC) is the third-leading cause of death in the world. Although the prognosis has improved due to improvement of chemotherapy, metastatic CRC is still a recalcitrant disease, with a 5-year survival of only 13%. Irinotecan (IRN) is used as first-line chemotherapy for patients with unresectable CRC. However, there are severe side effects, such as neutropenia and diarrhea, which are dose-limiting. We have previously shown that methionine restriction (MR), effected by recombinant methioninase (rMETase), lowered the effective dose of IRN of colon-cancer cells in vitro. The aim of the present study was to evaluate the efficacy of the combination of low-dose IRN and MR on colon-cancer in nude mice. MATERIALS AND METHODS: HCT-116 colon-cancer cells were cultured and subcutaneously injected into the flank of nude mice. After the tumor size reached approximately 100 mm3, 18 mice were randomized into three groups; Group 1: untreated control on a normal diet; Group 2: high-dose IRN on a normal diet (2 mg/kg, i.p.); Group 3: low-dose IRN (1 mg/kg i.p.) on MR effected by a methionine-depleted diet. RESULTS: There was no significant difference between the control mice and the mice treated with high-dose IRN, without MR. However, low-dose IRN combined with MR was significantly more effective than the control and arrested colon-cancer growth (p=0.03). Body weight loss was reversible in the mice treated by low-dose IRN combined with MR. CONCLUSION: The combination of low-dose IRN and MR acted synergistically in arresting HCT-116 colon-cancer grown in nude mice. The present study indicates the MR has the potential to reduce the effective dose of IRN in the clinic.

DOI： 10.21873/invivo.13539

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

INTRODUCTION: Primary small bowel carcinoma in pregnant women is extremely rare. Small bowel cancer is difficult to diagnose because of its rarity, lack of specific clinical symptoms, and particular anatomical features. We experienced a case of primary small bowel adenocarcinoma with ovarian metastasis during pregnancy. This is the first reported case of a patient with small bowel adenocarcinoma whose pregnancy continued to term and ended in delivery. CASE PRESENTATION: A 32-year-old pregnant woman developed abdominal pain, and imaging examination revealed an ovarian tumor at 29 weeks of gestation. We performed laparotomy and resected the ovarian tumor, which was initially suspected to be primary ovarian cancer. The patient continued the pregnancy to term. A detailed examination of the abdominal cavity during cesarean delivery at 37 weeks revealed that the primary lesion was located in the small bowel. CONCLUSION: It is important to recognize that the small bowel may be the primary site of metastatic ovarian cancer. Detailed and careful examination is necessary to diagnose small bowel cancer during pregnancy.

DOI： 10.1159/000540524

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The risk and prognosis of pancreatobiliary cancer and in patients with autoimmune pancreatitis (AIP) and IgG4-related sclerosing cholangitis (IgG4-SC) remain unclear. Therefore, we retrospectively investigated the risk of pancreatobiliary cancer and prognosis in patients with AIP and IgG4-SC. METHODS: Patients with AIP and IgG4-SC at seven centers between 1998 and 2022 were investigated. The following data were evaluated: (1) the number of cancers diagnosed and standardized incidence ratio (SIR) for pancreatobiliary and other cancers during the observational period and (2) prognosis after diagnosis of AIP and IgG4-SC using standardized mortality ratio (SMR). RESULTS: This study included 201 patients with AIP and IgG4-SC. The mean follow-up period was 5.7 years. Seven cases of pancreatic cancer were diagnosed, and the SIR was 8.11 (95% confidence interval [CI]: 7.29-9.13). Three cases of bile duct cancer were diagnosed, and the SIR was 6.89 (95% CI: 6.20-7.75). The SMR after the diagnosis of AIP and IgG4-SC in cases that developed pancreatobiliary cancer were 4.03 (95% CI: 2.83-6.99). CONCLUSIONS: Patients with autoimmune pancreatitis and IgG4-SC were associated with a high risk of pancreatic and bile duct cancer. Patients with AIP and IgG4-SC have a worse prognosis when they develop pancreatobiliary cancer.

DOI： 10.1002/jhbp.1404

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Elmer Press, Inc.  

DOI： 10.14740/wjon1694

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記述言語：英語   出版者・発行元：(一社)日本癌学会  

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記述言語：英語  

Since the popularization of cancer screening and an improvement in treatment over the last two decades, multiple primary malignant neoplasms (MPMNs) have been increasingly reported. We report a patient who developed metachronous MPMNs in the breast, the endometrium, and the pancreas over a period of 13 years. A 42-year-old woman was first diagnosed with breast cancer and underwent breast-conserving surgery with adjuvant radiation therapy and endocrine therapy. Four years after breast surgery, she was diagnosed with endometrial cancer and underwent a laparoscopic modified radical hysterectomy with bilateral oophorectomy with pelvic lymph node dissection followed by adjuvant chemotherapy. However, there was peritoneal dissemination of endometrial cancer 1 year after surgery, which could be removed laparoscopically followed by adjuvant chemotherapy. Ten years after breast cancer surgery, pleural metastasis of breast cancer was diagnosed and treated by endocrine therapy. Thirteen years after breast cancer surgery, a pancreatic tumor with multiple liver masses emerged. It was difficult to diagnose whether primary or metastasis cancer by the results of the pathological analysis. Finally, we diagnosed primary pancreatic cancer with liver metastasis by clinical examination with the BRCA2-pathogenic variant. These tumors were well responded to chemotherapy and the patient survived during a follow-up period of 8 months. According to MPMNs, breast cancer patients should be followed-up carefully for the possibility of BRCA pathogenic variant and development of different primary malignant neoplasms.

DOI： 10.14740/wjon1658

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記述言語：日本語   出版者・発行元：日本消化器病学会-関東支部  

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記述言語：日本語   出版者・発行元：(一社)日本外科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Aberrant glycosylation is a prominent feature of cancer, that can be used as targets to improve the existing cancer biomarkers, and help to assess metastasis risks, and therapeutic effects. We developed a targeted O-glycoproteomics method using serum specimens, and evaluated its utility in identifying advanced colorectal cancer (CRC) markers. To this end, we combined consecutive lectin affinity purification using Maclura pomifera lectin (MPL), jacalin, and Sambucus nigra lectin, which have affinities for the following O-glycans, that have received attention as cancer-related antigens, Tn (GalNAc-Ser/Thr), Sialyl Tn (Siaα2-6GalNAc-Ser/Thr), T (Galβ1-3GalNAc-Ser/Thr), Sialyl T (Siaα2-3Galβ1-GalNAc-Ser/Thr), and di-Sialyl T (Siaα2-3Galβ1-3[Siaα2-6] GalNAc-Ser/Thr), with a unique O-glycoproteomics approach. A total of 2,068 O-glycoforms derived from 265 proteins were identified in healthy individuals and patients with advanced CRC, of which 44 CRC-specific O-glycoforms were extracted. Particularly, five glycoproteins with T, Sialyl T, and di-Sialyl T antigens in specific peptide regions were evaluated quantitatively and statistically. We found that fibulin-2 (FBLN2) (aa330-349)/T antigen (area under the curve [AUC] = 0.92); macrophage colony-stimulating factor 1 (CSF1) (aa370-395)/(T + di-Sialyl T) (AUC = 0.94); macrophage mannose receptor 1 (MRC1) (aa1083-1101 and aa1215-1229)/T (AUC = 0.96 and 0.99); fibrinogen alpha chain (FGA) (aa354-367, aa511-527 and aa559-573)/Sialyl T (AUC = 0.98, 0.90 and 0.94); and complement component C7 (C7) (aa692-701)/di-Sialyl T (AUC = 1.00), can have high diagnostic efficacy to strategically predict advanced CRC groups. Hence, they could be promising markers for detection of advanced CRC, and provide new clinical test indicators along with lectins, such as MPL and jacalin. Our O-glycoproteomics platform provides a novel tool and resource, for researchers and clinicians seeking to better understand and treat advanced CRC.

DOI： 10.3389/fonc.2023.1104936

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND/AIM: The prognosis of recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) is poor, although immune checkpoint inhibitors (ICIs), such as nivolumab, have been shown to prolong survival. We investigated the factors that predict the efficacy of nivolumab when selecting an appropriate treatment strategy for patients with R/M SCCHN. PATIENTS AND METHODS: Forty-four Japanese patients with R/M SCCHN treated with nivolumab between May 2017 and October 2021 were analyzed. The primary endpoint of the study was overall survival (OS). We defined pre-treatment tumor size (PTS) as the sum of the size of all measurable lesions, and tumor growth rate (TGR) as the total growth rate of the largest tumor diameter on CT scans taken to determine treatment response, divided by the interval between CT scans. Receiver operating characteristic (ROC) curves were used to identify the cutoff points of PTS and TGR for OS. Cox proportional hazards regression analysis was performed to examine the relationships between various factors, including patient characteristics, PTS, and TGR, as well as treatment outcomes. RESULTS: In multivariate analysis, Eastern Cooperative Oncology Group (ECOG) performance status (PS) score ≥1, progressive disease (PD) as best overall response (BOR), and TGR >0.60%/day were independent risk factors for poor OS in patients with R/M-SCCHN. CONCLUSION: Higher TGR, poor PS, and PD as BOR may be prognostic factors in patients with R/M SCCHN.

DOI： 10.21873/invivo.13378

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The clinical outcomes of everolimus rechallenge in patients with pancreatic neuroendocrine neoplasms (PNENs) are unknown. This study aimed to investigate the treatment outcomes and safety of everolimus rechallenge treatment with PNENs. METHODS: Clinical data of everolimus-treated patients with PNENs at two institutions were collected. Patients who underwent everolimus rechallenge were included in the study. We analyzed the progression-free survival (PFS) and treatment response associated with everolimus rechallenge and the adverse events. RESULTS: Between 2008 and 2020, 117 patients received initial treatment with everolimus, of which 14 patients received everolimus rechallenge. With regard to the grade of PNENs, there were 2 cases of G1, 11 cases of G2, and 1 case of G3. The median rechallenge PFS was 5.7 months. The objective response rate was 21.4%. the disease control rate was 71.4%. The only major grade 3 or 4 adverse event was neutropenia (n = 1, 7.1%). No other severe adverse event was observed. CONCLUSION: The outcomes and safety of everolimus rechallenge were verified, and it was deemed an acceptable treatment. Everolimus rechallenge may provide a new drug therapy for patients with advanced PNENs for whom no other drug treatment option is available.

DOI： 10.3390/cancers14225669

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記述言語：日本語   出版者・発行元：(公社)日本生化学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND/AIM: This Japanese single-center retrospective cohort study aimed to evaluate the real-world therapeutic outcomes of pembrolizumab or pembrolizumab plus chemotherapy (pembrolizumab regimen) as first-line therapy for patients with recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). PATIENTS AND METHODS: Thirty-two Japanese patients with R/M SCCHN treated with the pembrolizumab regimen between January 2020 and January 2022 were analyzed. The primary endpoint of the study was overall survival. RESULTS: The median follow-up duration was 9.8 months (range=1.6-25.1 months). Fourteen patients received pembrolizumab alone, whereas the others received pembrolizumab with chemotherapy. The 1-year overall and progression-free survival rates were 64.5% (95% CI=38.9-81.6) and 54.9% (95% CI=33.9-71.8), respectively. The objective response rate was 56.2%. The Kaplan-Meier analysis showed that patients with favorable objective responses and an Eastern Cooperative Oncology Group performance status of 0 had longer survival. Immune-related adverse events (irAEs) occurred in 16 out of 32 patients (50.0%) during treatment; however, there were no irAEs greater than grade 4. CONCLUSION: The observed therapeutic efficacy and safety of pembrolizumab in real-world clinical practice was consistent with the data of the KEYNOTE-048 trial.

DOI： 10.21873/anticanres.15948

PubMed

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記述言語：英語   出版者・発行元：(一社)日本癌学会  

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

Peptide receptor radionuclide therapy(PRRT)is a pioneer drug in the rapid development of radio-theranostics, and a paradigm-shifting approach to treat neuroendocrine tumor( NET). The NETTER-1 trial for NETs of the midgut is currently the only global phase Ⅲ prospective clinical trial demonstrating the efficacy and safety of PRRT. In Japan, phase Ⅰ and Ⅰ/Ⅱ trials for lung and gastroenteropancreatic NETs were also conducted, and regulatory approval was granted in June of 2021. Although regulatory approval was obtained in Japan without specifying the primary organ or the history of treatment, there is limited evidence at this time, and guidelines recommend use after the second-line for midgut NETs and in the last phase for all other NETs. PRRT is expected to be utilized as upfront therapy, and the results of ongoing prospective clinical trials are awaited. The effect of PRRT is corelated with accumulation rate of somatostatin receptor scintigraphy(SRS). Sometime accumulation rate of SRS is not constant among multiple tumors in even one patient, then effective use of PRRT is depending on detailed exploration for result of SRS of each tumor. In order to perform this treatment in Japan, a special ward dedicated to radionuclide therapy or at least" a special measures patient room" prescribed by laws and regulations is necessary." A special measures patient room" is a general patient room with temporary isolation and taking radiation protection countermeasure, instead of the special exhaust and drainage systems of radionuclide therapy ward. On the other hand, in order to operate the rooms, it is necessary to set up and decontaminate the rooms for each treatment, which requires specialized knowledge and manpower. Since there is a growing demand for radionuclide therapies, it is important to promote the appropriate introduction of this therapy and to establish a collaborative network for this purpose.

PubMed

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記述言語：日本語   出版者・発行元：(株)癌と化学療法社  

ペプチド受容体放射性核種療法(PRRT)は、今後急速に進むといわれるradio-theranostics発展の序章となる薬剤であり、神経内分泌腫瘍(NET)治療のパラダイムシフトアプローチでもある。中腸原発のNETを対象としたNETTER-1試験は、現時点で唯一の国際共同第III相試験であり、その有効性と安全性を示している。国内でも膵・消化管と肺NETを対象としたphase IとI/II試験が施行され、2021年6月に薬事承認を得た。日本では原発臓器も他治療とのタイミングも特定しない形で薬事承認が得られてはいるが、現時点ではエビデンスが少なく、ガイドライン上は中腸原発では二次治療以降として、それ以外すべての原発臓器では既承認薬無効例の代替治療として使用が推奨されている。今後はupfrontでの治療が期待されており、現在行われている前向き臨床試験の結果が待たれる。PRRTの効果には、ソマトスタチン受容体シンチグラフィー(SRS)の集積量が相関すると考えられるが、同一腫瘍であってもその集積が経時的に変化し、また同一患者でも腫瘍ごとに集積が異なることが知られており、SRS集積を詳細に評価検討することは、PRRTを効果的に使用するために重要なことであると考えられる。日本で本治療を実施するためには、放射線治療病室または特別措置病室が必要となる。特別措置病室は、放射線治療病室のような専用の排気排水設備を設置せずとも、一般病室に特別な防護措置および汚染拡大防止措置を講じることで一時管理区域とすることができる。一方で、治療1回ごとに設営と除染が必要になるため、専門的な知識と手間が必要になる。核医学治療のニーズの高まりがあるので、適切な導入の促進と連携のネットワーク作りが肝要であると考えられる。(著者抄録)

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2022&ichushi_jid=J00296&link_issn=&doc_id=20220823400003&doc_link_id=%2Fab8gtkrc%2F2022%2F004908%2F003%2F0813-0820%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fab8gtkrc%2F2022%2F004908%2F003%2F0813-0820%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: Approximately 60% of patients with chronic constipation (CC) have a significantly higher rate of loss of defecation desire (LODD). Bile acids are expected to have a restorative effect on defecation desire (DD) because they lower the rectal sensory threshold, which is an objective index of DD. Elobixibat (EXB) specifically inhibits the ileal bile acid transporter/apical sodium-dependent bile acid transporter, which is a transporter involved in the reabsorption of bile acids in the terminal ileum. This study aims to investigate the LODD improvement rate in patients with CC after 4 weeks of EXB treatment. Methods: A total of 40 adult patients with CC who meet the eligibility criteria will be enrolled. Patients will receive oral EXB (10 mg/day) for 4 weeks. A patient diary will be provided daily at 4 weeks after treatment. The primary endpoint will be the percentage LODD improvement at week 4 of the treatment period from week 2 of the observation period using questionnaires. Ethics and dissemination: Ethical approval was obtained from the Yokohama City University Certified Institutional Review Board prior to participant enrolment (approval number: CRB21-008). The results of this study will be submitted for publication in international peer-reviewed journals, and key findings will be presented at international scientific conferences. Participants desiring the results of this study will be directly contacted for data dissemination. Trial registration: This trial was registered at ClinicalTrials.gov (NCT05165199). Protocol version: 1.0, September 21, 2021.

DOI： 10.1016/j.conctc.2022.100958

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Neuroendocrine carcinoma (NEC) is a rare subtype of malignant gallbladder tumor. Although surgical resection is the only potentially curative therapy for gallbladder NEC, most cases are surgically unresectable because of advanced stage disease and/or biologically aggressive behavior. The standard palliative treatment for malignant gallbladder tumors is chemotherapy; however, the efficacy of chemoradiotherapy in the treatment of gallbladder tumors is controversial. Here, we report a case of gallbladder NEC that showed a durable response to chemoradiotherapy. A 68-year-old Japanese man presented with a huge gallbladder tumor with liver and duodenal invasion. Pathological findings revealed poorly differentiated NEC of the gallbladder. After seven cycles of chemotherapy comprising cisplatin and irinotecan, computed tomography (CT) revealed remarkable tumor shrinkage, but an enlarged portal lymph node. The patient was treated with 50.4 Gy in 28 fractions with two cycles of cisplatin and etoposide. After chemoradiotherapy, the enlarged lymph node also decreased in size. Maximum standardized uptake value of fluorodeoxyglucose-positron emission tomography/CT(FDG-PET/CT) changed from 8.2 to physiological accumulation. We defined this condition as a complete response on both enhanced CT and FDG-PET/CT; therefore, we did not perform systemic treatment and only observed his condition. This patient remained healthy with no recurrence at 3 years after chemoradiotherapy.

DOI： 10.1007/s12328-022-01645-1

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Peptide receptor activation therapy (PRRT) is a promising treatment option for metastatic neuroendocrine tumors (NETs). However, predicting tumor shrinkage before treatment is challenging. We analyzed the shrinkage rate of each metastatic tumor lesion to identify predictive factors related to shrinkage. Patients with metastatic NET who underwent PRRT were included in this retrospective study. For each patient, between one to five metastatic lesions were selected in descending order of size, and the change in the maximum tumor diameter after treatment was defined as the shrinkage rate per lesion (L-SR). We analyzed the relationship between pretreatment clinicopathological factors and L-SR. The median L-SR of all 75 lesions in 20 patients was 20% (95% CI: 4.8-26.1%). While previous treatment with cytotoxic agents (34.4%, p &lt; 0.05) and primary tumor of the pancreas (27.8%, p &lt; 0.05) were significantly favorable factors, a primary tumor of the rectum was significantly more resistant to shrinkage (-20.5%, p &lt; 0.001). Therefore, lesion-based analysis of PRRT for NETs showed that pancreatic NET and previous treatment with cytotoxic agents were favorable factors for tumor shrinkage; however, rectal NET was a factor associated with resistance to shrinkage.

DOI： 10.3390/cancers14143317

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記述言語：日本語   出版者・発行元：(NPO)日本緩和医療学会  

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記述言語：日本語   出版者・発行元：(NPO)日本緩和医療学会  

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記述言語：日本語   出版者・発行元：(NPO)日本緩和医療学会  

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記述言語：日本語   出版者・発行元：(NPO)日本緩和医療学会  

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記述言語：日本語   出版者・発行元：(NPO)日本緩和医療学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Objective The effectiveness of everolimus for the management of pancreatic neuroendocrine neoplasms (PNENs), including the G3/NEC types, remains unclear. We therefore investigated the effectiveness of the drug for the management of PNENs. Methods We analyzed the progression-free survival (PFS) and overall survival (OS) associated with everolimus and factors influencing the PFS and OS. Results One hundred patients were evaluated. The PFS associated with the G1/G2 types tended to be significantly longer than that associated with the G3/NEC types (hazard ratio [HR], 0.45; p =0.005). A multivariate analysis showed that the significant factors influencing the PFS were age (<65 years old; HR, 0.44; p =0.002), grade (G1/G2; HR, 0.42; p =0.006), everolimus treatment line (≤2nd; HR, 0.55; p =0.031), and presence of treatment with metformin (yes; HR, 0.29; p =0.044). The median OS was 63.8 months. In the multivariate analysis, the significant factors influencing the OS were grade (G1/G2; HR, 0.21; p <0.001), volume of liver metastasis (≤25%; HR, 0.27; p <0.001), everolimus treatment line (≤2nd; HR, 0.27; p <0.001), and presence of primary tumor resection (yes; HR, 0.33; p =0.005). Conclusions The effectiveness of everolimus in the management of G3/NEC types and prognoses tended to be poorer than those associated with the G1/G2 types. Everolimus combined with metformin and early-line treatment with everolimus may be effective for managing advanced PNENs.

DOI： 10.2169/internalmedicine.9416-22

PubMed

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

DOI： 10.3769/radioisotopes.71.135

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記述言語：日本語   出版者・発行元：(株)アークメディア  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

INTRODUCTION: Chronic constipation (CC) is a functional disorder that negatively impacts the quality of life of patients. This is a protocol for a multicentre, 12-week, randomised, double-blind, placebo-controlled study to test the efficacy and safety of elobixibat (EXB) versus placebo in patients with CC. METHODS AND ANALYSIS: This will be a multicentre, double-blind, placebo-control, randomised controlled trial. A total of 100 adult patients with CC, diagnosed based on Rome IV criteria, who fulfil the inclusion/exclusion criteria will be enrolled. The patients will be randomly assigned to receive EXB (10 mg) or placebo treatment (n=50 per group). Blood tests and stool sampling will be performed 12 weeks following initiation of treatment and questionnaires will be issued to participants. The primary outcome will be the change in complete spontaneous bowel movements after 12 weeks of administration. The secondary outcomes will include the change in Japanese Patient Assessment of Constipation Quality of Life and absolute serum and faecal bile acid. ETHICS AND DISSEMINATION: Ethics approval has been obtained from Yokohama City University Certified Institutional Review Board before participant enrolment. The results of this study will be submitted for publication in international peer-reviewed journals and the key findings will be presented at international scientific conferences. PROTOCOL VERSION: V.3.0, 15 June 2021. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (number NCT04784780).

DOI： 10.1136/bmjopen-2021-060704

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：MDPI  

Simple Summary Opioids are used in cancer pain management, however, their continuous use may not be tolerable owing to adverse effects such as constipation, sleepiness, nausea, and respiratory depression. Opioid-induced constipation reduces the quality of life of patients, and osmotic laxatives are conventionally recommended for preventing opioid-induced constipation. Recently, naldemedine, a peripherally acting mu-opioid receptor antagonist, can be used to safely and effectively treat opioid-induced constipation based on its etiological mechanism, without affecting central analgesia. In this study, we compared the effectiveness of magnesium oxide with that of naldemedine in preventing opioid-induced constipation. Naldemedine significantly prevented deterioration in the quality of defecation (the Japanese Patient Assessment of Constipation Quality of Life and complete spontaneous bowel movement) and reduced gastrointestinal adverse effects, mainly nausea, compared with magnesium oxide during 12-week administration. Opioid-induced constipation (OIC) may occur in patients receiving opioid treatment, decreasing their quality of life (QOL). We compared the effectiveness of magnesium oxide (MgO) with that of naldemedine (NAL) in preventing OIC. This proof-of-concept, randomized controlled trial (registration number UMIN000031891) involved 120 patients with cancer scheduled to receive opioid therapy. The patients were randomly assigned and stratified by age and sex to receive MgO (500 mg, thrice daily) or NAL (0.2 mg, once daily) for 12 weeks. The change in the average Japanese version of Patient Assessment of Constipation QOL (JPAC-QOL) from baseline to 2 weeks was assessed as the primary endpoint. The other endpoints were spontaneous bowel movements (SBMs) and complete SBMs (CSBMs). Deterioration in the mean JPAC-QOL was significantly lower in the NAL group than in the MgO group after 2 weeks. There were fewer adverse events in the NAL group than in the MgO group. Neither significant differences in the change in SBMs between the groups nor serious adverse events/deaths were observed. The CSBM rate was higher in the NAL group than in the MgO group at 2 and 12 weeks. In conclusion, NAL significantly prevented deterioration in constipation-specific QOL and CSBM rate compared with MgO.

DOI： 10.3390/cancers14092112

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Opioid-induced constipation (OIC) may occur in patients receiving opioid treatment, decreasing their quality of life (QOL). We compared the effectiveness of magnesium oxide (MgO) with that of naldemedine (NAL) in preventing OIC. This proof-of-concept, randomized controlled trial (registration number UMIN000031891) involved 120 patients with cancer scheduled to receive opioid therapy. The patients were randomly assigned and stratified by age and sex to receive MgO (500 mg, thrice daily) or NAL (0.2 mg, once daily) for 12 weeks. The change in the average Japanese version of Patient Assessment of Constipation QOL (JPAC-QOL) from baseline to 2 weeks was assessed as the primary endpoint. The other endpoints were spontaneous bowel movements (SBMs) and complete SBMs (CSBMs). Deterioration in the mean JPAC-QOL was significantly lower in the NAL group than in the MgO group after 2 weeks. There were fewer adverse events in the NAL group than in the MgO group. Neither significant differences in the change in SBMs between the groups nor serious adverse events/deaths were observed. The CSBM rate was higher in the NAL group than in the MgO group at 2 and 12 weeks. In conclusion, NAL significantly prevented deterioration in constipation-specific QOL and CSBM rate compared with MgO.

DOI： 10.3390/cancers14092112

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND/PURPOSE: The detection ability and role of different imaging modalities to detect pancreatic neuroendocrine neoplasms (PNENs) including small lesions is unclear. This study aimed to compare the ability of endoscopic ultrasound (EUS) and computed tomography (CT) to detect PNENs. METHODS: Data of patients who underwent EUS and contrast-enhanced CT and were diagnosed with PNENs were analyzed. The detection rates of pancreatic lesions with EUS and CT based on tumor size and influencing factors were investigated. RESULTS: For 256 PNEN lesions, the detection rate of EUS was better than that of CT (94.5% vs. 86.3%; p < 0.001). EUS was significantly superior to CT for PNENs ≤ 5 mm (58.3% vs 16.7%; p = 0.006) and 5-10 mm (97.7% vs 79.5%; p = 0.008). There was no significant difference in the detection rate between EUS and CT for PNENs > 10 mm (98.4% vs 96.4%; p = 0.375). Size (≤ 5 mm) and insulinoma were independent factors associated with poor EUS and CT detection rates. CONCLUSIONS: EUS exhibited better detection ability than CT, with an excellent detection rate for PNENs > 5 mm, except for insulinomas. CT could detect PNENs > 10 mm, which are amenable to treatment.

DOI： 10.1002/jhbp.1144

PubMed

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記述言語：日本語   出版者・発行元：(公社)日本超音波医学会  

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記述言語：日本語   出版者・発行元：(公社)日本超音波医学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Theranostics is a term coined by combining the words "therapeutics" and "diagnostics," referring to single chemical entities developed to deliver therapy and diagnosis simultaneously. Neuroendocrine tumors are rare cancers that occur in various organs of the body; and they express neuroendocrine factors such as chromogranin A and somatostatin receptor. Somatostatin analogs bind to somatostatin receptor, and when combined with diagnostic radionuclides, such as gamma-emitters, are utilized for diagnosis of neuroendocrine tumor. Somatostatin receptor scintigraphy when combined with therapeutic radionuclides, such as beta-emitters, are effective in treating neuroendocrine tumor as peptide receptor radionuclide therapy. Somatostatin receptor scintigraphy and peptide receptor radionuclide therapy are some of the most frequently used and successful theranostics for neuroendocrine tumor. In Japan, radiopharmaceuticals are regulated under a complex law system, creating a significant drug lag, which is a major public concern. It took nearly 10 years to obtain the approval for somatostatin receptor scintigraphy and peptide receptor radionuclide therapy use by the Japanese government. In 2021, 111 Lu-DOTATATE (Lutathera®), a drug for peptide receptor radionuclide therapy, was covered by insurance in Japan. In this review, we summarize the history of the development of neuroendocrine tumor theranostics and theranostics in general, as therapeutic treatment for cancer in the future. Furthermore, we briefly addressed the Japanese point of view regarding the development of new radiopharmaceuticals.

DOI： 10.1111/cas.15327

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The appropriate delivery of death pronouncements potentially affects bereaved families' wellbeing positively. Although younger physicians need to learn the competencies and entrustable professional activities (EPAs) to conduct death pronouncement independently, both of which have not been clarified. Therefore, this study aimed to develop a list of competencies and EPAs necessary for death pronouncement practice, which resident physicians need to acquire by the end of their residency training (postgraduate year 2). METHODS: An anonymous modified Delphi study was conducted with a panel of 31 experts. The experts were invited online from general wards in hospitals with resident physicians across Japan to participate in the study using the purposive and snowball sampling method. A non-anonymous web conference was held with three additional external evaluators to finalize the item list. The consensus criterion was defined as a mean response of at least 4 points on a 5-point Likert scale for each competency and EPA item and a rating of 4 or 5 points by at least 80% of the participants. RESULTS: Consensus was achieved, with consistently high levels of agreement across panel members, on 11 competencies and 9 EPA items. Additionally, a correspondence matrix table between competencies and EPAs was developed. CONCLUSIONS: This study clarified the standardized educational outcomes as competencies in death pronouncement practice and the unit of professional practice of physicians who can perform this independently (EPAs), serving as a blueprint to aid the development of an educational model and evaluation method for clinical educational institutions and developers of medical school curriculums.

DOI： 10.1186/s12909-022-03149-5

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Neuroendocrine neoplasm (NEN) is a comparatively rare tumor that has been considered indolent. Due to these characteristics, detailed epidemiological data have not been analyzed in Japan. To elucidate the present status of NEN diagnosis and treatment in Japan, we started a registry cohort study in January 2015. METHODS: Patients pathologically diagnosed with NENs of the pancreas, gastrointestinal tract, lungs, bronchi, or thymus after January 2012 were enrolled in this registry after the date of ethics review committee approval in each hospital or institute. Follow-up was continued for enrolled patients. RESULTS: During 5 years of enrollment between January 2015 and December 2019, a total of 1526 participants from 63 departments were enrolled in this registry (mean, 305.2 participants/year), covering approximately 5.8% of the annual incidence of NENs in Japan. For pancreatic NEN, 41.9% of patients had metastasis and the dominant metastatic site was the liver, at twice the rate of lymph node metastasis in the current registry. In contrast, the frequency of lymph node metastasis from gastrointestinal (GI)-NEN was similar to that of the liver. The distribution of WHO 2019-based grades varied according to the primary site. Low-to-intermediate grade (G1-G2) was dominant for duodenal, jejunal/ileal, rectal, and pancreatic NENs, whereas high grade (G3 or NEC) was dominant for esophageal, stomach, and colon NENs. For PanNENs, G3 and NEC accounted only for 1.6% and 2.9%, respectively. CONCLUSIONS: These cohort data provide crucial information for clinical research to clarify the characteristics of NENs in Japan.

DOI： 10.1007/s10147-022-02130-y

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: In addition to the direct power of anticancer drugs, the effectiveness of anticancer therapy depends on the host immune function. The present study investigated whether or not the reduction rate and histological response of preoperative chemotherapy were related to the immune microenvironment surrounding a primary tumor of the rectum. METHODS: Sixty-five patients received preoperative chemotherapy followed by resection from 2012 to 2014; all of these patients were retrospectively analyzed. CD3, CD8, and FoxP3 were immunohistochemically examined as markers for T lymphocytes, cytotoxic T lymphocytes, and regulatory T lymphocytes (Treg), respectively. The correlation between the tumor-infiltrating lymphocyte composition and the tumor reduction rate and histological response to neoadjuvant chemotherapy was investigated. RESULTS: The average tumor reduction rate was 41.5% ± 18.8%. According to RECIST, 47 patients (72.3%) achieved a partial response (PR), and 1 patient (1.5%) achieved a complete response (CR). Eight patients (12.3%) showed a grade 2 histological response, and 2 (3.1%) showed a grade 3 response. A multivariate analysis demonstrated that a low Treg infiltration in stromal cell areas was significantly associated with the achievement of a PR or CR [odds ratio (OR) 7.69; 95% confidence interval (CI) 1.96-33.33; p < 0.01] and a histological grade 2 or 3 response (OR 11.11; 95% CI 1.37-98.04; p = 0.02). CONCLUSION: A low Treg infiltration in the stromal cell areas may be a marker of a good response to neoadjuvant chemotherapy in patients with locally advanced rectal cancer.

DOI： 10.1007/s00595-021-02311-8

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The present prospective phase 1/2 study aimed to elucidate the efficacy and safety of 177 Lu-DOTATATE (four cycles of 7.4 GBq) in Japanese patients with unresectable, progressive neuroendocrine tumors (NETs). METHODS: From April 2018 to October 2020, 15 patients with advanced NETs (five midgut, eight pancreatic, and two lung NETs) were enrolled. Objective response rate (ORR), progression-free survival (PFS), and adverse events (AEs) were evaluated. Pharmacokinetics and dosimetry were also evaluated in three midgut patients. RESULTS: The mean absorbed doses of 177 Lu-DOTATATE to the kidneys (20.7 Gy/29.6 GBq) and the bone marrow (0.631 Gy/29.6 GBq) were within the radiation tolerance doses. The ORR of the whole population was 53% (90% CI, 30%-76%). ORRs of the midgut and non-midgut NETs were 60% (90% CI, 19%-92%) and 50% (90% CI, 22%-78%), respectively. There was no difference in the maximum reduction rate of the sum of the target lesion diameters between patients with midgut and non-midgut NET. The median PFS was not reached; the PFS rate at 52 weeks was 80% (90% CI, 56.1%-91.7%). AEs of Grade 3 or higher were lymphopenia (47%) and leukopenia (7%). CONCLUSION: 177 Lu-DOTATATE demonstrated remarkable tumor shrinkage and tolerability in Japanese patients with advanced NETs.

DOI： 10.1002/jhbp.1101

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

INTRODUCTION: Tapentadol has analgesic effects comparable to those of conventional opioids and is associated with fewer side effects, including gastrointestinal symptoms, drowsiness, and dizziness, than other opioids. However, the safety of tapentadol in the Japanese population remains unclear; the present multicentre study aimed to examine the safety of tapentadol and the characteristics of patients likely to discontinue this treatment owing to adverse events. METHODS: The safety of tapentadol was assessed retrospectively in patients with any type of cancer treated between August 18, 2014 and October 31, 2019 across nine institutions in Japan. Patients were examined at baseline and at the time of opioid discontinuation. Multivariate analysis was performed to identify factors associated with tapentadol discontinuation owing to adverse events. RESULTS: A total of 906 patients were included in this study, and 685 (75.6%) cases were followed up until tapentadol cessation for any reason. Among patients who discontinued treatment, 119 (17.4%) did so because of adverse events. Among adverse events associated with difficulty in taking medication, nausea was the most common cause of treatment discontinuation (4.7%), followed by drowsiness (1.8%). Multivariate analysis showed that those who were prescribed tapentadol by a palliative care physician (odds ratio [OR] 2.60, 95% confidence interval [CI] 1.36-4.99, p = 0.004), patients switching to tapentadol due to side effects from previous opioids (OR 2.19, 95% CI 1.05-4.56, p = 0.037), and patients who did not use naldemedine (OR 5.06, 95% CI 2.47-10.37, p < 0.0001) had an increased risk of treatment discontinuation owing to adverse events. CONCLUSIONS: This study presents the safety profile of tapentadol and the characteristics of patients likely to discontinue this treatment owing to adverse events in the Japanese population. Prospective controlled trials are required to evaluate the safety of tapentadol and validate the present findings. TRIAL REGISTRATION NUMBER: UMIN 000044282 (University Hospital Medical Information Network).

DOI： 10.1007/s40122-021-00327-z

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: Peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTA0-Tyr3-octreotate (177Lu-DOTATATE) is one of the most reliable treatments for unresectable, progressive neuroendocrine tumors (NETs) with somatostatin receptor expression. We have, for the first time, reported the results of the tolerability, safety, pharmacokinetics, dosimetry, and efficacy of this treatment for Japanese patients with NET. METHODS: Patients with unresectable, somatostatin receptor scintigraphy (SRS)-positive NETs were enrolled in this phase I clinical trial. They were treated with 29.6 GBq of 177Lu-DOTATATE (four doses of 7.4 GBq) combined with amino acid solution infusion plus octreotide long-acting release (LAR) 30 mg. The primary objective of this study was to evaluate the tolerability, safety, pharmacokinetics, and dosimetry of a single administration of this treatment in patients with SRS-positive NETs. RESULTS: Six Japanese patients (three men and three women; mean age 61.5 years; range 50-70 years) with SRS-positive unresectable NETs were recruited. 177Lu-DOTATATE was eliminated from the blood in a two-phase manner. Cumulative urinary excretion of radioactivity was 60.1% (range 49.0%-69.8%) within the initial 6 h. The cumulative renal absorbed dose for 29.6 GBq of 177Lu-DOTATATE was 16.8 Gy (range 12.0-21.2 Gy), and the biological effective dose was 17.0 Gy (range 12.2-21.5 Gy). Administration of 177Lu-DOTATATE was well tolerated, with no dose-limiting toxicities. Grade 3 lymphopenia occurred in two (33.3%) cases, but there were no other severe toxicities. Four patients achieved partial response (objective response rate, 66.7%), one patient had stable disease, and one patient had progressive disease. CONCLUSION: PRRT with 177Lu-DOTATATE was well-tolerated and showed good outcomes in Japanese patients with unresectable NETs. Peptide receptor radionuclide therapy, 177Lu-DOTA0-Tyr3-octreotate .

DOI： 10.1007/s12149-021-01674-9

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記述言語：日本語   出版者・発行元：(株)癌と化学療法社  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: Real-world outcomes of nivolumab treatment for gastric cancer and associated prognostic factors remain unclear; the present study aimed to evaluate both items. Methods: A total of 278 consecutive patients treated with nivolumab for gastric cancer during 2017-2019 were enrolled in this multi-institutional retrospective cohort study. The impact of laboratory findings, immune-related adverse events (irAEs), and clinicopathological factors on long-term survival was evaluated using the Cox proportional hazards model. Results: The response rate was 11.7% in patients with measurable lesions. The overall and progression-free survival estimates were 6.77 and 2.53 months, respectively. The incidence of irAEs was 30.6% (6.8% for grade ≥3). There were no treatment-related deaths. Multivariate analysis revealed that C-reactive protein level of ≤0.5 mg/dL (hazard ratio = 0.476, P < .001), irAE occurrence (hazard ratio = 0.544, P < .001), albumin level of >3.5 g/dL (hazard ratio = 0.688, P = .045), performance status 0 (hazard ratio = 0.711, P = .028), lymphocyte count >1000/μL (hazard ratio = 0.686, P = .027), and differentiated histological type (hazard ratio = 0.740, P = .046) were independently associated with improved survival. The median survival of patients with four or more good prognostic factors was 18.3 months. Conclusion: Nivolumab showed safety and survival benefits in patients with previously treated unresectable or recurrent gastric cancer. Low C-reactive protein level, irAE occurrence, high albumin level, high lymphocyte count, and differentiated histological type may affect outcomes. The presence of four or more good prognostic factors may help identify likely long-term survivors.

DOI： 10.1002/ags3.12489

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記述言語：日本語   出版者・発行元：(有)科学評論社  

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記述言語：英語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Constipation is a common, distressing complication in patients with cancer receiving palliative care. Elobixibat is a novel inhibitor of the ileal bile acid transporter that is used to treat chronic constipation by stimulating bowel function. However, its efficacy in patients with cancer has not been examined. This study investigated the drug's effectiveness in patients with cancer with chronic constipation. PATIENTS AND METHODS: This prospective-sampling, single-center, observational study included hospitalized patients with cancer diagnosed, using the Rome IV criteria, with chronic constipation. Within 2 weeks of hospitalization, each participant was administered elobixibat (5-15 mg) daily until discharge. Spontaneous bowel movements (SBMs), complete spontaneous bowel movements (CSBMs), Bristol stool form scale (BSFS) scores, and the Patient Assessment of Constipation Quality of Life questionnaire (PAC-QOL) scores were assessed before and after elobixibat administration. We also evaluated the relationship between the amount of food consumed and the SBM frequency. RESULTS: Among the 83 participants, the mean pre- and post-treatment frequencies of daily SBMs were 0.3 and 1.2 (p < .0001) and those of CSBMs were 0.1 and 0.6 (p < .0001), respectively. The mean pretreatment BSFS score was 1.6, whereas the post-treatment value was 3.5 (p < .0001); the mean PAC-QOL score (overall) improved from 1.01 to 0.74 (p = .01). There was no significant change in the daily SBM frequency between fasting and feeding states (1.2 vs. 1.3; p = .8), and there was no correlation between the amount of food intake and the SBM frequency after elobixibat administration (r = .03). Serious adverse events were not observed. CONCLUSION: This study showed that elobixibat is safe and effective for patients with cancer with chronic constipation, regardless of the food intake amount. IMPLICATIONS FOR PRACTICE: Elobixibat was effective at relieving chronic constipation in patients with various cancers. Serious adverse events were not observed, and the relief of constipation was independent of variation in food intake.

DOI： 10.1002/onco.13879

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The incidence and risk factors of severe anaphylaxis by intravenous anti-cancer drugs are unclear, whereas those of milder reactions have been reported. STUDY DESIGN: Electronic medical charts of cancer patients who have undergone intravenous chemotherapy between January 2013 and October 2020 in a university hospital were retrospectively reviewed. Non-epithelial malignancies were also included in the analysis. "Severe anaphylaxis" was judged using Brown's criteria: typical presentation of anaphylaxis and one or more of hypoxia, shock, and neurologic compromise. (UMIN000042887). RESULTS: Among 5584 patients (2964 males [53.1%], 2620 females [46.9%], median age 66 years), 88,200 person-day anti-cancer drug administrations were performed intravenously, and 27 severe anaphylaxes were observed. The causative drugs included carboplatin (14 cases), paclitaxel (9 cases), and cisplatin, docetaxel, trastuzumab, and cetuximab (1 case each). The person-based lifetime incidence of severe anaphylaxis for patients who received at least one intravenous chemotherapy was 0.48% (27/5584, 95% confidence interval (CI) 0.30%-0.67%) and the administration-based incidence was 0.031% (27/88,200, 95% CI 0.019%-0.043%). Among 124 patients who received at least 10 carboplatin administrations, 10 patients experienced carboplatin-induced severe anaphylaxis (10/124, 8.1%, 95% CI 3.0%-13.1%). Carboplatin caused severe anaphylaxis after at least 9-min interval since the drip started. Thirteen out of 14 patients experienced carboplatin-induced severe anaphylaxis within a 75-day interval from the previous treatment. Paclitaxel infusion caused severe anaphylaxis after a median of 5 min after the first drip of the day at a life-long incidence of 0.93% (9/968, 95% CI 0.27%-1.59%). CONCLUSION: We elucidated the high-risk settings of chemotherapy-induced severe anaphylaxis.

DOI： 10.1002/cam4.4252

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記述言語：英語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：英語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Peptide receptor radionuclide therapy (PRRT) with radiolabeled somatostatin analogs is an innovative treatment for advanced somatostatin-positive neuroendocrine tumors (NETs). PRRT cannot be performed in Japan because there is no approval or insurance cover so far. METHODS: We relied on foreign institutions to perform PRRT for Japanese patients with NETs. We retrospectively evaluated the safety and efficacy of PRRT. The inclusion criteria were pathologically confirmed well-differentiated NET and visible tumor uptake on pre-therapeutic somatostatin receptor scintigraphy. 177 Lu-DOTA-TOC was used as the standard treatment, and patients received three infusions every 8 weeks. Until the end of 2017, combination treatment with 90 Y and 177 Lu-DOTA-TOC was performed using the same protocol. RESULTS: Thirty-five patients were evaluated, and the primary lesions were pancreas, rectum, small intestine, stomach, and other locations. The partial response rate was 42.9%. Progression-free survival (PFS) was 12.8 months and overall survival was 42.8 months. There was no significant difference in PFS between front-line and late-line PRRT (11.0 months vs 28.0 months; P = .383). Severe adverse events included lymphocytopenia (20.0%) and thrombocytopenia (5.7%). Myelodysplastic syndrome occurred in one case. CONCLUSION: PRRT was effective and safe for Japanese patients with advanced NETs. PRRT was equally effective as front-line and late-line treatment.

DOI： 10.1002/jhbp.1014

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Sentinel lymph node (SLN) biopsy has been the standard modality for breast cancer patients with clinically node negative disease. In patients who undergo axillary lymph node dissection (ALND) due to SLN metastasis, the harvested nodes (non-SLNs) often contain no metastasis. Here, we evaluated the predictive factors associated with non-SLN metastasis in breast cancer patients. MATERIALS AND METHODS: This was a retrospective study of patients with operable cT1-3, cN0 invasive breast cancer who underwent SLN biopsy followed by ALND due to SLN metastasis. The clinicopathologic factors and predictive factors of non-SLN metastasis were analyzed. The optimal cutoff for the Ki67 index and the number of positive and negative SLNs that were predictive of non-SLN metastasis were evaluated using receiver operating characteristic curves. RESULTS: The median number of SLN and non-SLN was 3 and 11, respectively. Of the 150 patients, 52 (35.0%) had metastases in non-SLNs. The optimal cutoffs for the Ki67 index and the number of positive and negative SLNs were of 12%, 2, and 1, respectively. In the univariate analysis, the Ki67 index and the number of positive SLNs≥2 and negative SLNs≤1 were higher in the non-SLN + group than that in the non-SLN - group. The number of negative SLNs was as a predictive factor for non-SLNs metastasis in the multivariate analysis. CONCLUSIONS: The number of negative SLNs predicts the risk of non-SLN metastasis in breast cancer. When deciding on whether to omit ALND, the number of positive and negative SLNs should be considered.

DOI： 10.1016/j.jss.2021.01.047

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIM: To evaluate the association between bromodomain-containing protein 4 (BRD4) expression and clinicopathological factors and prognosis in human breast cancer specimens. PATIENTS AND METHODS: We used tissue microarrays constructed from samples of patients (n=183) who underwent surgery. We validated the association between BRD4 expression and prognosis in solid tumours, including breast cancer, using The Cancer Genome Atlas (TCGA) database. RESULTS: Immunohistochemical staining showed that BRD4 was widely distributed in breast cancer tissues. BRD4 was strongly expressed in 19.7% of patients but BRD4 staining intensity was not correlated with other clinicopathological factors. Most importantly, patients with a strong BRD4 expression had a significantly longer disease-specific survival than those with a weak BRD4 expression (100.0% vs. 91.3% at 5 years, p=0.027). mRNA expression analysis showed similar results (91.2% vs. 80.2% at 6 years, p=0.047). CONCLUSION: Strong BRD4 expression was associated with a significantly better prognosis in breast cancer tumours.

DOI： 10.21873/anticanres.15148

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND/PURPOSE: The relationship between autoimmune pancreatitis (AIP) and malignancy has been reported. However, the potential risk for cancer in patients with immunoglobulin 4 (IgG4)-related sclerosing cholangitis (IgG4-SC) is unclear. The present study aimed to evaluate the incidence of cancer in IgG4-SC patients. METHODS: We retrospectively collected clinical data for 121 patients diagnosed with IgG4-SC from 7 hospitals. We calculated the standardized incidence ratio (SIR) of cancer in IgG4-SC patients based on the national cancer rates. The SIR of the period after the diagnosis of IgG4-SC were calculated. RESULTS: The mean follow-up period was 6.4 years, with 121 IgG4-SC patients. During the follow-up period, 26 patients had cancer, and 29 cancers were diagnosed. The SIR of cancer after the diagnosis of IgG4-SC was 1.90 (95% confidence interval [CI] 1.67-2.21). The SIR of pancreatic and bile duct cancer was 10.30 and 8.88, respectively. The SIR of cancer in <1 year, 1-5 years, and >5 years after diagnosis of IgG4-SC were 2.58, 1.01, and 2.44, respectively. CONCLUSIONS: IgG4-SC patients have a high risk of cancer including pancreatic and bile duct cancer. The risk of cancer was high less <1 year and >5 years after diagnosis of IgG4-SC. Therefore, IgG4-SC patients may require careful long-term follow-up.

DOI： 10.1002/jhbp.957

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記述言語：日本語   出版者・発行元：(NPO)日本緩和医療学会  

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記述言語：日本語   出版者・発行元：(NPO)日本緩和医療学会  

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記述言語：日本語   出版者・発行元：(NPO)日本緩和医療学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Extrapulmonary neuroendocrine carcinoma (EPNEC) is a lethal disease with a poor prognosis. Platinum-based chemotherapy is used as the standard first-line treatment for unresectable EPNEC. Several retrospective studies have reported the results of the utilization of temozolomide (TMZ) as a drug for the second-line treatment for EPNEC. Patients with unresectable EPNEC that were resistant to platinum-based combination chemotherapy were recruited for a prospective phase II study of TMZ monotherapy. A 200 mg/m2 dose of TMZ was given from day 1 to day 5, every 4 weeks. Response rate (RR) was evaluated as the primary end-point. The presence of O6 -methylguanine DNA methyltransferase (MGMT) in EPNEC patients was also evaluated as exploratory research. Thirteen patients were enrolled in this study. Primary lesions were pancreas (n = 3), stomach (n = 3), duodenum (n = 1), colon (n = 1), gallbladder (n = 1), liver (n = 1), uterus (n = 1), bladder (n = 1), and primary unknown (n = 1). Each case was defined as pathological poorly differentiated neuroendocrine carcinoma from surgically resected and/or biopsied specimens. The median Ki-67 labeling index was 60% (range, 22%-90%). The RR was 15.4%, progression-free survival was 1.8 months (95% confidence interval [CI], 1.0-2.7), overall survival (OS) was 7.8 months (95% CI, 6.0-9.5), and OS from first-line treatment was 19.2 months (95% CI, 15.1-23.3). No grade 3 or 4 hematological toxicity had occurred and there was one case of grade 3 nausea. One case presented MGMT deficiency and this case showed partial response. Temozolomide monotherapy is a feasible, modestly effective, and safe treatment for patients with unresectable EPNEC following platinum-based chemotherapy, especially those with MGMT deficiency.

DOI： 10.1111/cas.14811

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Objective Neuroendocrine neoplasms (NENs) are rare and indolent diseases, but the efficacy of treatment without surgical resection is temporary and limited. Targeted immunotherapy is an important treatment strategy in several cancers. However, the tumor and host immune reactions in the NEN microenvironment are poorly understood. Therefore, we investigated the immune checkpoint system and host immune response in pathological NEN specimens. Methods The expression of the mismatch repair proteins MSH2, MSH6, PMS2, and MLH1 was immunohistochemically detected in archival tissue samples obtained from 20 patients with gastroenteropancreatic NENs. We additionally assessed the expression of programmed death (PD)-1, PD-L1, and the tumor-infiltrating lymphocyte (TIL) markers CD8 and family of transcription factor P3 (FOXP3). Results All 20 NENs expressed the mismatch repair proteins MSH2, MSH6, PMS2, and MLH1. The PD-L1 and/or PD-1 expression in the tumor cells and/or TILs was confirmed in 75% of the cases. PD-1-, CD8-, and FOXP3-positive TILs were more frequently associated with PD-L1-positive tumors than with PD-L1 negative tumors (PD-1: 19.5 vs. 7.3, CD8: 18.1 vs. 7.1, FOXP3: 13.2 vs. 3.2, p=0.438, p=0.419, P=0.603, respectively). The number of cells positive for PD-1 tended to gradually increase in increasing grade of NENs but did not reach significance (Grade 1: 5.8, Grade 2: 10.2, NEC: 18.1, p=0.903). Conclusion NENs consistently express mismatch repair proteins but have a high expression of PD-L1 and/or PD-1 in the tumor microenvironment. NEC and PD-L1-positive NENs may be immunologically "hot" tumors, so an immunological approach may be an appropriate treatment strategy for these tumors.

DOI： 10.2169/internalmedicine.5648-20

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND/AIM: This study aimed to investigate the efficacy of first-line gemcitabine monotherapy for metastatic breast cancer (MBC) and its effect on health-related quality of life (HRQoL) compared with treatment of physician's choice (TPC). PATIENTS AND METHODS: We enrolled 96 patients into the first-line gemcitabine group (n=47) or other treatment of physician's choice (TPC) group (n=49) from May 2010 to April 2013. HRQoL was evaluated every 4 weeks. RESULTS: There was no significant difference in the median time to treatment failure (5.3 vs. 4.6 months, hazard ratio=0.87, p=0.546) and the incidence rates of grade 3/4 haematological toxicity (10.6% vs. 8.1%, p=0.677) and grade 3/4 non-haematological toxicity (4.2% vs. 8.1%, p=0.429) between the gemcitabine and TPC groups. Changes in HRQoL from baseline to 12 weeks were not significantly different. CONCLUSION: Gemcitabine achieves similar efficacy and HRQoL benefit to other chemotherapy and can be used as first-line treatment for MBC.

DOI： 10.21873/anticanres.14930

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Lateral lymph node dissection (LLND) has been considered as the standard treatment strategy for locally advanced lower rectal cancer in Japan. Controversy remains around whether all patients require LLND. This study aims to examine the long-term outcomes of patients in which LLND was performed and clarify the value of LLND. METHOD: Consecutive 458 patients with lower rectal cancer who underwent total mesorectal excision (TME) plus LLND from 1992 to 2012 were included. The long-term outcomes and risk factors for recurrent in patients performed TME + LLND were examined. We assessed the impact of LLND on survival using an estimated therapeutic index. RESULTS: The incidence of LLNM was 15.5%. The 5-year RFS and OS rates of patients with LLNM were 40.9% and 47.7%, while patients without LLNM had a good prognosis. The 5-year local recurrence (LR) rate was 9.2%, and independent risk factors for LR were T4 and LLNM. The LR rate of patients with LLNM was high (22.8%). The LLNM rate of the groups with 0, 1, 2, 3, or 4 risk factors (male, tumor location < 4 cm from anal verge, T4, and MLNM) was 3.8%, 9.2%, 18.1%, and 50.0%. The 5-year OS of the groups was 96.2%, 86.1%, 69.7%, and 48.5%. CONCLUSION: Although patients with locally advanced lower rectal cancer who received LLND had a good prognosis, LLND alone was insufficient to control local recurrence in patients with metastatic lateral nodes.

DOI： 10.1007/s00384-020-03760-2

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND/AIM: We previously presented the real-world treatment outcomes of the EXTREME regimen as a first-line therapy for recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). This study aimed to evaluate the prognostic significance of pretreatment inflammatory biomarkers in patients with R/M-SCCHN treated with the EXTREME regimen as first-line therapy as a supplementary study of our previous retrospective cohort study. PATIENTS AND METHODS: The treatment outcomes of 100 patients with R/M-SCCHN treated with the EXTREME regimen as first-line therapy were compared according to patient characteristics and pretreatment inflammatory biomarkers using a Cox proportional hazards regression model. Survival was evaluated using the Kaplan-Meier method. RESULTS: In multivariate analysis, a lymphocyte-to-monocyte ratio (LMR) of <1.944 and Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 1 were independent risk factors for poor overall and progression-free survival. Furthermore, we found that the PS-LMR score based on the ECOG PS and LMR could stratify patients to extract the poor prognostic characteristics of R/M-SCCHN patients treated with the EXTREME regimen as first-line therapy. CONCLUSION: Further evaluation is warranted to study the reliability and applicability of this novel scoring system in predicting the prognosis of R/M-SCCHN patients in the future.

DOI： 10.21873/cdp.10047

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND/AIM: Aldehyde dehydrogenase 1 (ALDH1) is known as a breast cancer stem cell (CSC) marker. This study aimed to identify genes associated with ALDH1. MATERIALS AND METHODS: ALDH1-positive and -negative breast cancer cells were isolated using laser capture microdissection from five tissue samples of ALDH1-positive breast cancer patients. Messenger RNA expression levels were compared between ALDH1-positive and -negative cells. RESULTS: We found 104 differentially expressed genes between ALDH1-positive and -negative cells. Gene ontology and pathway analysis revealed that these genes were correlated with CSC functions and pathways. Network analyses identified 10 genes that were closely associated with ALDH1. We validated these 10 genes utilizing The Cancer Genome Atlas and the Molecular Taxonomy of Breast Cancer International Consortium cohort, and found that they were associated with ALDH1 expression and correlated with Wnt pathway signaling. CONCLUSION: The 10 genes we identified could be potential targets for CSC therapy of breast cancer.

DOI： 10.21873/anticanres.14696

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: Although the effectiveness of antiemetic therapy for colorectal cancer chemotherapy has improved with further drug development, some patients still suffer from chemotherapy-induced nausea and vomiting (CINV) even with only 5-hydroxytryptamine-3 receptor antagonist and dexamethasone. The present study investigated the risk factors of CINV in patients who received chemotherapy for colorectal cancer and clarified which patients need additional neurokinin 1 receptor antagonist. METHODS: Patients with colorectal cancer receiving moderate-emetic-risk chemotherapy (MEC) were enrolled in this prospective single-arm study with intravenous palonosetron 0.75 mg and dexamethasone 9.9 mg before chemotherapy and with paroral dexamethasone 8 mg on days 2 and 3. The primary endpoint was the complete response (CR) rate for delayed-phase CINV. RESULTS: A total of 179 patients were eligible for this study. The delayed CR rate was 84.9% (152/179). There were no significant differences in any risk factors, but women with a low body mass index (BMI) (a combination of "female sex" and "BMI < 20") showed a significantly lower rate of CC (complete control) (odds ratio [OR] = 0.45, 95% confidence interval [CI] = 0.17-1.13; p = 0.039), and young patients with a low BMI (combination of "age < 65" and "BMI < 20") showed a significantly lower rate of CR (OR = 0.34, 95% CI = 0.13-0.88; p = 0.022) than the other patients. CONCLUSIONS: This study failed to identify any single risk factors associated with delayed CINV in patients who received chemotherapy for advanced colorectal cancer. However, combinations of "thin and women" or "young and thin patients" might be possible predictive conditions, thus, candidates for NK1 receptor antagonist administration in MEC. Further investigations are required to develop criteria for the supplementation of NK1 receptor antagonist.

DOI： 10.1007/s00384-020-03731-7

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Nipple-areola complex (NAC) reconstruction is a technique used in breast reconstructive surgery, which is performed during the final stage of breast reconstruction after total mastectomy of primary breast cancer. Composite nipple grafts utilizing the contralateral NAC are common; however, to our knowledge, there are no reports of new primary invasive ductal carcinoma development within the graft. Here, we describe one such case for the first time. CASE PRESENTATION: A 54-year-old woman was referred to us by the Department of Plastic and Reconstructive Surgery in our medical center for further evaluation of right nipple erosion. She had undergone total mastectomy of the right breast following a breast cancer diagnosis 15 years ago, at which time tumor biological profiling revealed the following: estrogen receptor (ER), positive; progesterone receptor (PgR), negative; and human epidermal growth factor receptor 2 (HER2), undetermined. She received adjuvant chemotherapy and endocrine therapy. She defaulted endocrine therapy for a few years, and 7 years after surgery, she underwent autologous breast reconstruction with a deep inferior epigastric perforator (DIEP) flap. In the following year, NAC reconstruction was performed using a composite graft technique. Seven years after the NAC reconstruction, erosion appeared on the nipple grafted from its contralateral counterpart; scrape cytology revealed malignancy. The skin on the right side of her chest around the NAC and subcutaneous fat tissue consisted of transferred tissue from the abdomen, as the DIEP flap and grafted nipple were located on the graft skin. The right nipple carcinoma arose from the tissue taken from the left nipple. Magnetic resonance imaging (MRI) or computed tomography showed no malignant findings in the left breast. As the malignant lesion seemed limited to the area around the grafted right nipple on MRI, surgical resection with sufficient lateral and deep margins was performed around the right nipple. Pathological findings revealed invasive ductal carcinoma with comedo ductal components infiltrating the graft skin and underlying adipose tissue. Immunohistochemistry revealed positive for ER, PgR, and HER2. CONCLUSIONS: To our knowledge, this is the first case involving the development of invasive ductal carcinoma in a nipple graft constructed on the skin of a DIEP flap, with the origin from the contralateral breast's nipple.

DOI： 10.1186/s40792-020-00962-2

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記述言語：日本語   出版者・発行元：(NPO)日本緩和医療学会  

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記述言語：日本語   出版者・発行元：(NPO)日本緩和医療学会  

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記述言語：日本語   出版者・発行元：(一社)日本膵臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本膵臓学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Patients taking opioids are known to develop opioid-induced constipation (OIC), which reduces their quality of life. The aim of this study is to compare magnesium oxide with naldemedine and determine which is more effective in preventing OIC. METHODS: This proof-of-concept, prospective, randomized controlled trial commenced in Japan in March 2018. Initially, a questionnaire-based survey will be conducted targeting adult patients with cancer who concomitantly commenced opioid treatment and OIC prevention treatment. Patients will then be randomly allocated to a magnesium oxide group (500 mg thrice daily) or a naldemedine group (0.2 mg once daily). Each drug will be orally administered for 12 weeks. The primary endpoint is defined as any improvement in scores on the Japanese version of Patient Assessment of Constipation Quality of Life questionnaire (JPAC-QOL) from baseline to 2 weeks of treatment. DISCUSSION: The primary endpoint is change in JPAC-QOL score from baseline to 2 weeks of intervention. The key secondary endpoint will be change in spontaneous bowel movements at 2 and 12 weeks of intervention. This study will determine whether magnesium oxide or naldemedine is more effective for the prevention of OIC. TRIAL REGISTRATION: University Hospital Medical Information Network (UMIN) Clinical Trials Registry, UMIN000031891. Registered March 25, 2018.

DOI： 10.1186/s13063-020-04385-0

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Eppikajututo (TJ-28, a Kampo medicine) is effective against rheumatoid arthritis and eczema. We conducted a randomized comparative trial to assess the efficacy of TJ-28 for preventing hand-foot syndrome (HFS) as a complication of adjuvant chemotherapy using capecitabine. METHODS: The present study was a multi-institutional randomized-controlled trial (UMIN000005899). Colorectal cancer patients scheduled to receive capecitabine chemotherapy as adjuvant therapy were randomly assigned to receive TJ-28 (7500 mg/day) or oral pyridoxine (60 mg/day). Patients were monitored for the development of grade ≥ 2 HFS according to the National Cancer Institute Common Toxicity Criteria until chemotherapy completion. RESULTS: Twenty-two patients were enrolled in this study. The relative dose intensity of capecitabine was 76.2% in the TJ-28 group and 68.2% in the pyridoxine group. Grade ≥ 2 HFS developed in 6 (50.0%) of 12 TJ-28 patients and in 4 (40.0%) of 10 pyridoxine patients. Chemotherapy treatment failure was observed in seven patients, mainly due to HFS, liver dysfunction, diarrhea, and neutropenia. Chemotherapy treatment failure due to HFS occurred in none of the TJ-28 group and 2 patients (20.0%) in the pyridoxine group (p = 0.114). CONCLUSION: Capecitabine-associated HFS was not markedly prevented by TJ-28 compared with pyridoxine. However, TJ-28 might support the continuation of chemotherapy with capecitabine. Further studies are warranted to clarify the benefits of TJ-28.

DOI： 10.1007/s12664-020-01039-6

PubMed

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記述言語：日本語   出版者・発行元：(一社)日本膵臓学会  

60代女性。2002年膵頭十二指腸切除術が施行され高分化神経内分泌癌と診断された。2003年に肝転移再発をきたし陽子線治療や化学療法が施行されたが肝転移の増悪を認めた。病理学的再評価で、膵神経内分泌腫瘍(NET Grad2 Ki67 6%)、免疫染色でソマトスタチン受容体の強陽性が確認された。ペプチド受容体放射性核種療法(PRRT)の適応と考えられ、2011年バーゼル大学にて、177Lu-DOTATOCによるPRRTが施行されCTで肝転移の縮小が認められた。2013年再度肝転移が増大しPRRTが再度施行され、CTで腫瘍の再縮小が認められた。2016年に再増大をきたしPRRTによる再々治療が施行されたが肝転移は増大し2017年に肝不全にて死亡した。本症では膵神経内分泌腫瘍多発肝転移がPRRTのみで6年にわたり制御された。PRRTは、切除不能膵神経内分泌腫瘍に極めて有用な治療法である。(著者抄録)

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2020&ichushi_jid=J02025&link_issn=&doc_id=20200512360011&doc_link_id=%2Fcq0pancr%2F2020%2F003501%2F019%2F0097-0103%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcq0pancr%2F2020%2F003501%2F019%2F0097-0103%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：英語   掲載種別：研究論文（学術雑誌）  

The pancreatic cancer microenvironment is crucial in cancer development, progression and drug resistance. Cancer-stromal interactions have been recognized as important targets for cancer therapy. However, identifying relevant and druggable cancer-stromal interactions is challenging due to the lack of quantitative methods to analyze the whole cancer-stromal interactome. Here we studied 14 resected pancreatic cancer specimens (8 pancreatic adenocarcinoma (PDAC) patients as a cancer group and 6 intraductal papillary-mucinous adenoma (IPMA) patients as a control). Shotgun proteomics of the stromal lesion dissected with laser captured microdissection (LCM) was performed, and identified 102 differentially expressed proteins in pancreatic cancer stroma. Next, we obtained gene expression data in human pancreatic cancer and normal pancreatic tissue from The Cancer Genome Atlas database (n = 169) and The Genotype-Tissue Expression database (n = 197), and identified 1435 genes, which were differentially expressed in pancreatic cancer cells. To identify relevant and druggable cancer-stromal-interaction targets, we applied these datasets to our in-house ligand-receptor database. Finally, we identified 9 key genes and 8 key cancer-stromal-interaction targets for PDAC patients. Furthermore, we examined FN1 and ITGA3 protein expression in pancreatic cancer tissues using tissue microarrays (TMAs) of 271 PDAC cases, and demonstrated that FN1-ITGA3 had unfavorable prognostic impact for PDAC patients.

DOI： 10.1016/j.canlet.2019.10.031

PubMed

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記述言語：英語  

Background: Neuroendocrine tumors (NETs) are rare, but their worldwide incidence is gradually increasing. NETs are generally heterogeneous; however, in rare cases, they have been shown to change their phenotype (i.e., nonfunctional to functional or one functional phenotype to the addition of another functional phenotype). Here, we present two cases of liver metastatic NETs with phenotype transformation at the advanced stage that led to life-threatening events. Case presentation: A 73-year-old woman had a small intestinal nonfunctional NET with liver metastasis. After uncontrollable liver metastasis at the advanced stage, she developed duodenal perforation with hypergastremia. The patient was treated with octreotide and proton pump inhibitors and underwent endoscopic closure for duodenal perforation, but her general condition gradually deteriorated, and she died 2 weeks after duodenal perforation. Another patient, a 50-year-old man, had a functional NET (gastrinoma) with liver metastasis and duodenal ulcer. After uncontrollable liver metastasis at the advanced stage, he developed hypoglycemia. Although octoreotide and diazoxide were administrated for hyperalimentation, his hypoglycemia was uncontrollable, and he died after 4 months owing to general deterioration. Conclusion: The present cases show that advanced NETs with treatment-uncontrollable liver metastasis can transform their phenotype, specifically from a nonfunctional NET into a functional NET, and from one functional NET into the addition of another functional NET. These experiences suggest that the presence of treatment-resistant liver metastasis might be a hallmark of the potential to gain novel functions.

DOI： 10.3389/fonc.2020.555963

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND/AIM: This Japanese multiple-center retrospective study aimed to examine the real-world treatment outcomes of the EXTREME regimen as a first-line therapy for recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). PATIENTS AND METHODS: A total of 100 R/M SCCHN patients treated with the EXTREME regimen as first-line therapy were analyzed. The treatment outcomes were evaluated to compare patient and treatment characteristics with overall survival. RESULTS: Patients treated with carboplatin-based EXTREME regimen showed similar overall survival with less adverse effects compared to that of patients using cisplatin. The post-progression survival was significantly longer in patients treated with second-line treatment following the EXTREME regimen than in those without second-line treatment. CONCLUSION: The carboplatin-based EXTREME regimen was more feasible with similar treatment outcomes compared to cisplatin-based EXTREME regimen. In addition, subsequent lines of therapy contributed to improvement of survival for R/M SCCHN patients.

DOI： 10.21873/anticanres.13898

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.4172/2167-0870.1000384

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：英語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: It is important to determine whether anthracycline-containing regimens or taxane-containing regimens are more effective in individual patients. The present study compared the efficacy of six cycles of docetaxel and cyclophosphamide (TC6) with that of three cycles of 5-fluorouracil, epirubicin and cyclophosphamide followed by docetaxel (FEC-D) in Japanese patients with hormone receptor (HR)-negative breast cancer (BC) to identify subtypes requiring anthracycline treatment. METHODS: The study included 103 patients with operable HR-negative BC. Of these patients 53 received FEC-D and 50 received TC6. The primary endpoint was pathological complete response (pCR). The secondary endpoints were safety, breast-conserving surgery, disease-free survival (DFS) and overall survival (OS). The predictive factors for each regimen were evaluated. RESULTS: Of the 103 patients, 97 completed the study (FEC-D, 50 patients; TC6, 47 patients). The pCR rate was higher with FEC-D (36%) than with TC6 (25.5%); however, the difference was not significant (P = 0.265). TC6 was safer than FEC-D, as the adverse events with docetaxel in the FEC-D regimen were similar to those with the TC6 regimen. Among patients with basal BC, the pCR rate was significantly higher with FEC-D (42.9%) than with TC6 (13.6%; P = 0.033). Among patients with triple-negative breast cancer (TNBC), the DFS and OS were significantly better with FEC-D than with TC6 (P = 0.016 and P = 0.034, respectively). CONCLUSION: TC6 was not as effective as FEC-D for treating HR-negative BC, as TC6 was not sufficient to treat TNBC, particularly the basal subtype. Our findings suggest that anthracyclines are better treatment options than taxanes for basal BC.

DOI： 10.1016/j.breast.2019.06.003

PubMed

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記述言語：日本語   出版者・発行元：(公社)神奈川県医師会  

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記述言語：日本語   出版者・発行元：(一社)日本膵臓学会  

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記述言語：日本語   出版者・発行元：(NPO)日本緩和医療学会  

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

Approximately 20-30% of cancers are associated with hypercalcemia, and this is a complication often encountered in cancer care. Hypercalcemia causes disorders such as disturbance of consciousness and, in severe cases, kidney failure and even death. In this report, we present a case of malignant ameloblastoma associated with uncontrollable hypercalcemia followed by a life-threatening disease course. In this case, hypercalcemia shortened the period of home care, and the medical staff could have extended this period by acquiring knowledge that leads to early detection and better control of hypercalcemia. In addition, the choice of the place for end-of-life care may have been expanded by considering the treatment of not only the malignant tumor but also hypercalcemia as its complication.

PubMed

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

Although many patients with terminal cancers desire to be cared for at home, frequently, such patients cannot be shifted to home care due to their unstable symptoms. In severe cases, emergency hospitalizations may be frequently required after introducinghome medical care. We report a case of makinghome medical care difficult due to repeated emergency hospitalizations despite of the patient's deep desire. Interviews were conducted with both the oncologist in charge of the case and a home physician, and their viewpoints were compared. For patients and their families to achieve desired livingconditions, it was considered necessary to give supportive medical care that meet their desires until the end of their lives as mutual viewpoints are taken in a good balance.

PubMed

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

Chemical coping also has an idea that it is an early stage of abuse and dependence of opioids, it is important to grasp the frequency, complaints, and risk factors of chemical coping. In this study, observational research was performed backwardly with 549 people using opioids who were newly requested to the palliative care team. Results revealed that 13 of 549 patients (2.4%)were diagnosed with chemical coping. In terms of a breakdown of the complaint, and it was following rate and reasons, 6 people(46%)felt easy, 2 people(15%)were anxious, 2 people(15%)could sleep, 2 people(15%)had unknown reasons, and 1(8%)was calm. Characteristics of each patient diagnosed with chemical coping included frequent psychiatric symptoms such as life expectancy of 3 months, opioid oral administration period of 1 year or more, disease incidence period of 1 year or more, anxiety, delirium, and depression. One benign disease also confirmed the transition to opioid dependence.

PubMed

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記述言語：日本語   出版者・発行元：(株)癌と化学療法社  

がん末期において療養先として自宅を希望する患者が多いが、症状が安定せず在宅へ移行できない症例も多く経験する。症状が強い場合には在宅医療導入後も緊急入院を必要とすることが多い。今回在宅療養を希望したにもかかわらず、当院への緊急入院を繰り返し在宅導入が困難であった症例を経験したので報告する。また、症例にかかわったがん治療医と在宅医にインタビューを行い両者の視点を比較した。患者・家族の望む生活を実現するには、互いの視点をバランスよく取り入れながら最期まで揺れる希望にそった形での医療のサポートを行う必要があると考えられる。(著者抄録)

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記述言語：日本語   出版者・発行元：日本消化器病学会-関東支部  

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：(有)科学評論社  

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記述言語：日本語   出版者・発行元：金原出版(株)  

111Inペンテトレオチドを用いたソマトスタチン受容体シンチグラフィ(SRS)を行った神経内分泌腫瘍(NET)55症例(男女比24/31)を対象として、SRSの実施状況と、病理組織検査との対比について検討した。内訳は消化管NET 11例、膵NET 26例、その他NET 4例、その他の疾患14例で、施行目的は初期診断16例、ステージング10例、経過観察3例、ソマトスタチン受容体発現の確認26例であり、SRSによる病変指摘率は87.8%、SRS陽性と病理におけるソマトスタチン受容体2a発現の一致率は93.1%であった。SRSは比較的高率に病変を指摘することができ、病理組織におけるソマトスタチン受容体の発現を適切に反映していることも確認できた。しかし、一部の症例ではSRSの画像所見と病理所見が一致せず、SRSの感度がその主たる原因と考えられた。

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2019&ichushi_jid=J01565&link_issn=&doc_id=20190322140012&doc_link_id=10.18888%2Frp.0000000782&url=https%3A%2F%2Fdoi.org%2F10.18888%2Frp.0000000782&type=%E5%8C%BB%E6%9B%B8.jp_%E3%82%AA%E3%83%BC%E3%83%AB%E3%82%A2%E3%82%AF%E3%82%BB%E3%82%B9&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: Application of next-generation DNA sequencing (NGS) has recently become increasingly common in the field of clinical oncology in several countries around the world. In Japan also, a system for applying NGS to routine clinical practice is gradually being established. During this process, we introduced in Japan the tumor-profiling MSK-IMPACT (Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets) assay. Methods: We present here our initial experience with the use of MSK-IMPACT in 68 patients selected from two institutions in Japan between June 2016 and October 2017. Results: MSK-IMPACT sequencing was successful and yielded results in specimens obtained from 64 of the 68 patients, representing an overall assay success rate of 94.1%. The top three cancer types tested were endometrial cancer (17.2%), pancreatic cancer (15.6%) and colorectal cancer (12.5%). Evaluation of the clinical actionability of the genetic alterations revealed that 25.0% of patients (n = 16) harbored at least one actionable alteration. However, enrolling the patients in a genomically matched clinical trial was difficult, mainly because most clinical trials are limited to tumors arising from a specific organ/site. One patient with microsatellite instability-high status, as determined by MSK-IMPACT, was treated with pembrolizumab and showed partial response. Conclusions: Although tumor profiling by NGS and administration of genomically matched therapy is a promising strategy, because of its high cost, we need to consider how we can fit it into the Japanese medical system. Towards this end, we believe that it is important to share our initial experience for furthering precision medicine in Japan.

DOI： 10.1093/jjco/hyy173

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Fundacion Clinica Medica Sur  

Introduction and aim. We developed a rat model of portal vein ligation (PVL) with venous congestion (PVL+C) to investigate beneficial effect PVL plus congestion for regeneration of intact liver segments. Materials and methods. In the PVL group, portal vein branches were ligated except the caudate lobe (CL). In the PVL + C group, the left lateral hepatic vein was ligated in addition to PVL. Chronological changes in the following variables were compared among the groups: CL weight to body weight ratio (CL/BW), embolized liver weight to body weight ratio (EL/BW), histological findings of the embolized/non-embolized liver, and expression of several mediators that affect liver regeneration in the non-embolized liver. Results. Weight regeneration of CL continued up to postoperative day (POD)7 in PVL + C, but terminated at POD2 in PVL. CL/BW at POD7 was significantly higher in PVL + C than in PVL (2.41 ± 0.33% vs. 1.22 ± 0.18%, P &lt
0.01). In contrast, EL/BW continued to decrease up to POD7 in PVL + C but reached nadir at POD2 in PVL. Furthermore, EL/BW at POD7 was significantly smaller in PVL + C than in PVL (0.35 ± 0.03% vs. 0.67 ± 0.08%, P &lt
0.01). Histologically-proven injury in the embolized liver was more severe in PVL + C than in PVL. Expression of Ki-67, IL-6, TNF-α, and HGF were greater and/or more prolonged in PVL + C than in PVL. Conclusions. Our rat model of PVL + C was considered useful for investigating the beneficial effect of congestion in addition to PVC. PVL + C caused increased devastation of the embolized liver, and higher and more prolonged expression of factors promoting liver regeneration in the non-embolized liver than in PVL.

DOI： 10.5604/01.3001.0012.7866

Scopus

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.pan.2018.11.001

Web of Science

PubMed

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記述言語：日本語   出版者・発行元：(株)アークメディア  

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記述言語：英語   出版者・発行元：(一社)日本核医学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s10549-018-4793-z

Web of Science

PubMed

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記述言語：日本語   出版者・発行元：(一社)日本消化器外科学会  

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記述言語：日本語   出版者・発行元：(株)日本メディカルセンター  

＜文献概要＞111Inペンテトレオチドを用いたソマトスタチン受容体シンチグラフィー(somatostatin receptor scintigraphy;SRS)は,ソマトスタチン受容体を有する神経内分泌腫瘍に集積し,可視化することで,その存在診断と質的診断の双方の役割を担うmolecular imagingである.SRSは,ペプチド受容体放射性核種療法(peptide receptor radio-nucleotide therapy;PRRT)を施行するうえでの必須の検査である.SRSによる集積部位は,PRRTによる治療標的部位そのものであり,PRRTは,ソマトスタチン受容体を有する神経内分泌腫瘍細胞のみを選択的に攻撃する標的治療といえる.SRSとPRRTの関係は,診断と治療の融合を意味する新たな診断治療体系であるTheranosticsのモデルケースとしても注目されている.

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

Superselective intra-arterial chemoradiation therapy for oral cancer induces the complication of mucositis. Although the associated pain is controlled using opioids, major questions from patients in clinical practice are as follows:(1)the mean number of days from the completion of superselective intra-arterial chemoradiation therapy to the discontinuation of opioid administration, and(2)patient factors enabling the discontinuation of opioids. The purpose of this study was to clarify these points. A retrospective follow-up study was conducted from April 2016 to March 2017 on patients who underwent superselective intra-arterial chemoradiation therapy at our department of oral surgery. The patients were divided into 2 groups:one who discontinued opioids, and the other who did not. Clinical backgrounds and data were compared between the 2 groups. The mean number of days from the completion of superselective intra-arterial chemoradiation therapy to the discontinuation of opioid administration was 51±34.4 days. The absence of diabetes and deliria during treatment were determined as factors contributing to the discontinuation of opioids.

PubMed

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

Superselective intra-arterial chemoradiation therapy for locally advanced oral cancer induces complications such as mucositis, which impedes oral intake. Thus, at our hospital, a gastrostomy is performed in almost all patients during the treatment period to ensure the presence of an alternative administration route for nutrition and drugs. The purpose of this study was to calculate the mean number of days from completion of superselective intra-arterial chemoradiation therapy to the decannulation of gastrostomy, and extract patient factors for the decannulation. A retrospective follow-up study was conducted from April 2016 to March 2017 on patients who underwent superselective intra-arterial chemoradiation therapy at our department of oral surgery. The patients were divided into 2 groups:one who was decannulated and the other who did not. Clinical backgrounds and data were compared between the 2 groups. In the group with the decannulation, the mean period from treatment completion to the decannulation was 132±51.6 days. Heavy alcohol consumption, absence of haphalgesia before treatment, and possible securement of the opening with the breadth of 3 fingers, were determined as factors contributing to the decannulation of gastrostomy tube.

PubMed

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記述言語：日本語   出版者・発行元：(株)癌と化学療法社  

症例は52歳、女性。乳がん胸椎転移に伴う難治性疼痛に対してアセトアミノフェン、NSAIDs、オキシコドンを内服していたが疼痛コントロール不良であった。鎮痛補助薬としてプレガバリンやガバペンチンを使用したが副作用のため継続できなかった。タペンタドールのノルアドレナリン再取り込み阻害作用に注目し、タペンタドールとオキシコドンによる併用療法を導入したところ、患者の満足のいく疼痛コントロールを得ることができた。オピオイド併用による副作用の出現はなかった。神経障害性疼痛を合併した難治性疼痛に対して、モルヒネ、オキシコドン、フェンタニルなどのμオピオイド受容体作動薬とノルアドレナリン再取り込み阻害作用をもつタペンタドールを併用することが、疼痛緩和に有効である可能性が示唆された。(著者抄録)

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記述言語：日本語   出版者・発行元：(株)癌と化学療法社  

口腔癌における超選択的偽注化学放射線療法は、治療により粘膜炎の合併症を引き起こす。その症状緩和にオピオイドを用いた疼痛コントロールを行っているが、臨床現場で患者側からの質問として、(1)超選択的動注化学放射線療法終了後からオピオイド中止までの平均日数、(2)オピオイド中止が可能となった患者側の因子の問い合わせが多い。本検討ではこれらを解明することを目的とする。方法として2016年4月〜2017年3月の間、当院口腔外科で超選択的動注化学放射線療法を施行した患者を対象とし、後方視的に観察研究を行い、オピオイド中止が可能な患者群、不可能であった患者群を2群に分類し臨床的背景や臨床データとの比較検討を行った。その結果、オピオイド中止が可能な群では、治療終了後からオピオイド中止までの期間の平均は51(±34.4)日であった。非糖尿病患者と治療中のせん妄ない群がオピオイド中止に寄与する因子として抽出された。(著者抄録)

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記述言語：日本語   出版者・発行元：(株)癌と化学療法社  

局所進行口腔癌に対する超選択的動注化学放射線療法は、粘膜炎などの合併症を引き起こし、経口摂取や内服が不可能となる。そのため当院では治療期間中にほぼ全例に胃瘻造設を施行し、栄養および薬剤投与ルートの確保を行っている。本検討では超選択的動注化学放射線療法終了後から胃瘻抜去までの平均日数の算出と、胃瘻抜去が可能な因子を抽出することを目的とした。方法は2016年4月〜2017年3月までの間、当院口腔外科で超選択的動注化学放射線療法を施行した患者を対象とし、後方視的に観察研究を行った。胃瘻抜去が可能であった患者群、不可能であった患者群の2群に分類し、臨床的背景や臨床データの比較検討を行った。その結果、胃瘻抜去可能群において、治療終了後から胃瘻抜去までの平均期間は132(±51.6)日であった。胃瘻抜去が可能な患者因子として、アルコール摂取量が多い、治療前の接触時痛がない、開口3横指確保可能といった因子が抽出された。(著者抄録)

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

A 52-year-old woman had been prescribed oral medication of acetaminophen, non-steroidal anti-inflammatory drugs (NSAIDs), and oxycodone for intractable pain associated with thoracic metastasis of breast cancer. However, the pain control was poor. Although pregabalin and gabapentin were used as supplementary analgesics, they could not be continued because of their side effects. Based on the noradrenalin reincorporation-inhibiting action of tapentadol, a combination therapy of tapentadol and oxycodone was introduced and satisfactory pain control was achieved. No side effects from the combined opioids were observed. This finding indicates the potential of administrating a combination therapy of m-opioid receptor agonists(such as morphine, oxycodone, and fentanyl)with tapentadol, which has a noradrenaline reincorporation-inhibiting action, as an effective remedy for alleviating intractable pain complicated with neuropathic pain.

PubMed

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

Akathisia is a condition wherein sitting calmly and quietly is impossible, with a representative complaint of restless legs. It is generally assumed to be caused by anti-dopamine activity. In severe cases, it has been known to result in suicide attempt. We reported a case of drug-induced akathisia with difficulty in oral intake, in which fentanyl citrate sublingual tablets were found to be effective in relieving symptoms. The patient was a female aged 50's who had a gastric cancer with peritoneal dissemination causing pain and vomiting. Palliative care was requested for management of symptoms. Metoclopramide and haloperidol were administered for vomiting. However, because of the complaints of restless legs, the case was diagnosed as drug-induced akathisia. Fentanyl citrate sublingual tablets were then administered for pain management, resulting in temporary improvement of akathisia symptoms.

PubMed

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

We investigated the usefulness of suvorexant for complicated delirium in patients with cancer who experience sleep disturbance during hospitalization. Nine patients with malignant tumors complicated with symptoms of delirium and insomnia were included in this study; their palliative care was managed by the palliative care team of our hospital for a period of one year from April 2016 to March 2017. A retrospective follow-up study was then conducted. The Japanese version of DRS-R98 was used to evaluate the severity of the patient's delirium. The total severity score of DRS-R98 significantly decreased after the administration of suvorexant when compared to the score before its administration(6.66±1.73 vs 10±3.20, p=0.0031). In addition, suvorexant did not exhibit any harmful effects. Our results indicate that suvorexant was useful in alleviating delirium symptoms in cancer patients who experience sleep disturbance.

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY  

The present study determined the effect of the tumor-targeting strain Salmonella typhimurium A1-R (S. typhimurium A1-R) on CD8(+) tumor-infiltrating lymphocytes (TILs) in a syngeneic pancreatic-cancer orthotopic mouse model. The effect of tumor-targeting S. typhimurium A1-R on CD8(+) TILs was determined on the Pan02 murine pancreatic-adenocarcinoma implanted orthotopically in the pancreatic tail of C57BL/6 immunocompromised mice. Three weeks after orthotopic implantation, mice were randomized as follows G1: untreated control group (n=8); and G2: S. typhimurium A1-R-treatment group (n=8, 1x10(7) colony forming units [CFU]/body, iv, weekly, 3 weeks). On the 22nd day from initial treatment, all mice were sacrificed and tumors were harvested. The tumor-volume ratio was defined as ratio of tumor volume on the 22nd day relative to the 1st day. The tumor volume ratio was significantly lower in the S. typhimurium A1-R-treated group (G2) (3.0 +/- 2.8) than the untreated control (G1) (39.9 +/- 30.7, P&lt;0.01). Hematoxylin and easin (H&E) staining on tumor sections was performed to evaluate tumor destruction which was classified according to the Evans grading system and found to be much greater in the S. typhimurium A1-R-treated mice (G2). Six mice in G1 had peritoneal dissemination, whereas no mice showed peritoneal dissemination in G2 (P&lt;0.01). Immunohistochemical staining with anti-mouse CD8(+) antibody was performed in order to detect TILs determined by calculating the average number of CD8(+) cells in three high power fields (200x) in the treated and untreated tumors. The TIL score was significantly higher in G2 (133.5 +/- 32.2) than G1 (45.1 +/- 19.4, P&lt;0.001). The present study demonstrates that S. typhimurium A1-R promotes CD8(+) T cell infiltration and inhibition of tumor growth and metastasis. J. Cell. Biochem. 119: 634-639, 2018. (c) 2017 Wiley Periodicals, Inc.

DOI： 10.1002/jcb.26224

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記述言語：日本語   出版者・発行元：医学図書出版(株)  

111Inペンテトレオチドを用いたソマトスタチン受容体シンチグラフィー(SRS)が本邦で使用可能となって間もなく2年が経過する。本検査は、膵をはじめとする神経内分泌腫瘍(NET)の初期診断、術前診断、経過観察、ソマトスタチン受容体(SSTR)の発現の確認など臨床のさまざまな場面で使用され、その有用性が報告されてきた。しかしながら、SSTRは、NET以外にもさまざまな腫瘍で発現しSRSでの集積が確認されていること、SSTRを発現していないNETではSRSの集積を認めないこと、また膵頭部領域でSRSの集積が報告されているように、生理的集積にも注意が必要である。SRSの機能的画像としての特徴を理解し、その他のモダリティーと合わせた総合的な診断が必要と考えられる。また新規の治療法である、PRRT(ペプチド受容体放射線核種治療)の適応確認のための重要性が今後ますます高まることが予想される。(著者抄録)

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記述言語：日本語   出版者・発行元：横浜市立大学医学会  

正確な病状に関する情報共有は患者・家族と医療者が協力し診療を行うために必須である。しかし、当事者にとって「悪いニュース」であるがん告知は、患者・家族の心情に重大な影響を及ぼす場合があり、十分な配慮の下で行うことが求められる。がんと診断された時からの緩和ケアを推進する国のがん対策推進基本計画に基づき、がん診療拠点病院の指定要件として「がん告知や予後告知を行う際のコミュニケーションに関するマニュアルの作成」が求められることになった。そこで横浜市立大学附属病院においても、スタッフががん告知に関する理解やスキルを高め、必要な場合に適切な部署と連携することを目的にがん告知マニュアルを作成した。作成に従事したのは院内のがん診療に携わる複数の専門職であり、さらに院外の医療倫理、がんサバイバーシップなどに造詣のある研究者の助言を得た。がん総合医療センター運営会議での内容確認と承認を得た上で平成29年3月8日に院内配布された。作成にあたっては国立がんセンターの「がん告知マニュアル」(1996年)を基盤に現在の社会状況と当院の現状を加味し、臨床現場で問題となる「がん告知を希望しない患者への対応」、「自己決定能力のない患者への対応」、「小児へのがん告知」についても記述を加えた。このマニュアルが当院のみならず多くの医療者に貢献することを期待し、臨床部長会の承認を得て本稿を公開する。(著者抄録)

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2017&ichushi_jid=J01499&link_issn=&doc_id=20180213290008&doc_link_id=https%3A%2F%2Fycu.repo.nii.ac.jp%2Frecords%2F1348&url=https%3A%2F%2Fycu.repo.nii.ac.jp%2Frecords%2F1348&type=%E6%A8%AA%E6%B5%9C%E5%B8%82%E7%AB%8B%E5%A4%A7%E5%AD%A6%EF%BC%9A%E6%A8%AA%E6%B5%9C%E5%B8%82%E7%AB%8B%E5%A4%A7%E5%AD%A6%E5%AD%A6%E8%A1%93%E6%A9%9F%E9%96%A2%E3%83%AA%E3%83%9D%E3%82%B8%E3%83%88%E3%83%AA&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F80205_3.gif

記述言語：日本語   出版者・発行元：(一社)日本核医学会  

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記述言語：日本語   出版者・発行元：(NPO)日本核医学技術学会  

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記述言語：日本語   出版者・発行元：(一社)日本核医学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER JAPAN KK  

My arguments regarding postmastectomy radiotherapy (PMRT) for this case are based on the following 4 reasons: (1) high rate of local recurrence in the no PMRT group in the Early Breast Cancer Trialists' Collaborative Group meta-analysis on which the present guideline is based, (2) stage migration by sentinel node biopsy, (3) possible adverse events of radiotherapy, and (4) problems on extrapolation of data from western countries.

DOI： 10.1007/s12282-016-0749-5

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記述言語：日本語   出版者・発行元：(一社)日本消化器外科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

Background: This study aimed to determine the maximum tolerated dose (MTD), dose-limiting toxicity, and efficacy of second-line chemotherapy with FOLFIRINOX after gemcitabine (GEM)-based chemotherapy failure in metastatic pancreatic cancer (MPC).
Methods: We studied 18 histopathologically proven MPC patients. The schedule was 85 mg/m(2) oxaliplatin, irinotecan, and 400 mg/m2 leucovorin, followed by 400 mg/m(2) 5-fluorouracil (5-FU) as a bolus on day 1 and 2400 mg/m(2) 5-FU as a 46-hour continuous infusion biweekly. The dose of irinotecan was defined as follows: level 0: 100 mg/m(2), level 1: 125 mg/m(2), level 2: 150 mg/m(2), and level 3: 180 mg/m(2). The doses of other drugs were fixed. The primary endpoint of phase II study was the response rate (RR).
Results: We initially evaluated 6 patients in a phase I study. One patient developed neutropenia and 1 patient developed hyperglycemia and severe infection. Accordingly, level 1 was chosen as the MTD. According to a phase II study, the RR was 22.2% and the disease control rate was 61.1%. The progression-free survival and overall survival were 2.8 (range, 0.7-19.1) and 9.8 (2.4-19.8) months, respectively. The most common severe adverse event was neutropenia (66.7%). Febrile neutropenia occurred in 1 (5.6%) case.
Conclusion: The recommended dose was 85 mg/m(2) oxaliplatin, 100 mg/m(2) irinotecan, and 400 mg/m(2) leucovorin, followed by 400 mg/m(2) 5-FU as a bolus on day 1 and 2400 mg/m(2) 5-FU as a 46-hour continuous infusion. These results indicate that second-line FOLFIRINOX is a marginally effective treatment for GEM-based chemotherapy failure cases.

DOI： 10.1097/MD.0000000000006769

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記述言語：日本語   出版者・発行元：日本内分泌外科学会・日本甲状腺外科学会  

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記述言語：日本語   出版者・発行元：(株)メジカルビュー社  

当院では2011年より,バーゼル大学と提携し27人の日本在住の切除不能NET患者のPRRTを行ってきた。海外の医療機関との臨床情報の共有と事前の準備は,海外での治療を実現するために必要である。当院でのこれまでの試みを報告する。(著者抄録)

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2017&ichushi_jid=J01843&link_issn=&doc_id=20170404240008&doc_link_id=%2Fap4ringc%2F2017%2F003304%2F009%2F0461-0467%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fap4ringc%2F2017%2F003304%2F009%2F0461-0467%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：日本語   出版者・発行元：(株)メジカルビュー社  

＜Point＞20年以上前より欧米で使用されていた、111In-ペンテトレオチドを用いたソマトスタチン受容体シンチグラフィー(somatostatin receptor scintigraphy;SRS/商品名:オクトレオスキャンR)がわが国で保険収載され、実臨床で運用が開始された。これまでの海外でのデータの集積を基に、神経内分泌腫瘍に対して、初期診断、病期診断、術前診断、経過観察、またソマトスタチン受容体(somatostatinreceptor;SSTR)発現の確認など、さまざまな用途での使用が検討されている。新規の治療法である、PRRT(peptide receptorradionuclide therapy;ペプチド受容体放射線核種療法)の適応確認のための重要性が今後高まることが予想される。(著者抄録)

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記述言語：日本語   出版者・発行元：(一社)日本消化器外科学会  

目的:教室における下部直腸・肛門管腺癌の鼠径リンパ節郭清(inguinal node dissection;以下,INDと略記)症例の治療成績を明らかにする.対象と方法:1992年から2009年までの,腫瘍下縁がPまたはEの下部直腸・肛門管腺癌手術症例の内,INDを施行した16例(同時性転移7例,異時性転移9例)を対象とし,術後長期成績について検討した.結果:術後合併症はリンパ漏を13例(81.3%),surgical site infection(SSI),下肢の浮腫をそれぞれ3例(18.8%)認めた.平均在院日数は27日だった.術後補助化学療法は6例(37.5%)に施行された.同時性転移7例の5年無再発生存率は28.6%,5年全生存率(overall survival;以下,OSと略記)は28.6%だった.異時性転移9例の初回手術後から鼠径リンパ節転移までの期間は中央値11ヵ月で,IND後4年以内に全例再発を認めたが,5年OSは33.3%だった.IND後の再発例は13例(81.3%)で,初回再発部位は骨盤内が3例,肺,肝臓,対側鼠径リンパ節,大動脈周囲リンパ節,皮膚がそれぞれ2例だった.結語:鼠径リンパ節単独転移を伴う下部直腸・肛門管腺癌に対するINDは,長期生存の可能性もあり施行する意義があるかもしれないが,遠隔再発率は高くIND後の集学的治療の開発が必要であると考えられた.(著者抄録)

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2017&ichushi_jid=J01117&link_issn=&doc_id=20170323300003&doc_link_id=10.5833%2Fjjgs.2015.0113&url=https%3A%2F%2Fdoi.org%2F10.5833%2Fjjgs.2015.0113&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

記述言語：英語   出版者・発行元：AMER ASSOC CANCER RESEARCH  

DOI： 10.1158/1538-7445.SABCS16-P5-16-04

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：KARGER  

Background/Aims: Somatostatin receptor (SSTR) scintigraphy (SRS) is the standard imaging modality for evaluation of gastroenteropancreatic neuroendocrine tumor (GEP-NET) in Western countries. However, this modality was not approved in Japan until recently. The purpose of this study was to evaluate the clinical efficacy of SRS for detecting GEP-NET in Japanese patients. Methods: Japanese patients with advanced GEP-NET were enrolled and evaluated by the SRS and CT. We also compared SRS and immunohistochemical expression of SSTRtype 2a (SSTR2a). Results:We enrolled 16 patients and the primary sites were the pancreas in 9, the stomach in 1, the small intestine in 2, the colon in 3, and unknown in 1. SRS showed positive findings in 3 (100%) of grade 1 (G1) and in 12 (92.3%) of grade 2 (G2) lesions. In the liver, SRS and CT detected lesions in 13 and 14 cases, respectively. The concordance rate of SSTR2a expression with SRS findings was 93.8% in the whole body and 92.9% in the liver. Conclusions: SRS could detect almost all of G1 and G2. SRS could be useful to detect lesions, with a high concordance rate with CT and pathological findings. We confirmed that SRS is a useful and reliable modality for Japanese patients. (C) 2017 S. Karger AG, Basel

DOI： 10.1159/000470838

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Medical Association of Yokohama City University  

Recently, along with the globalization and development of information communication technology, remote classes (e-learning) have been actively utilized at universities. E-leaming refers to classes provided by means of information technology using electronic media. In the first- And second-phase training plans for cancer professionals carried out at Yokohama City University, we (1) developed a total system considering diversity, sustainable education, and globalization, (2) improved the system considering the dignity of life, and (3) formed a harmonized educational foundation of multimodal cancer treatment through e-learning, thus bringing benefits to cancer care. In July 2017, the third-phase training plan for cancer professionals responding to multiple needs was accepted. The three continued programs contribute to the development of a base of cooperation among universities throughout Japan and human resources of multiple professions, and act as a bridge to realize beyond the limitations of the various professions. In this article, the outline of the third-phase training plan for cancer professionals and examples of e-learning for harmonized education at Yokohama City University are explained.

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Japanese Society of Gastroenterological Surgery  

Purpose: The outcomes of patients with lower rectal and anal canal adenocarcinoma who underwent inguinal node dissection (IND) were evaluated. Subject and Method: In the period of 1992 to 2009, 16 patients who underwent curative resection with IND for lower rectal and anal canal adenocarcinoma were investigated for long-term outcome. Result: The postoperative complications were 13 cases (81.3%) for lymphorrhea, 3 cases each 3 (18.8%) for surgical site infection and leg edema. Postoperative hospital stay was 27 days. Adjuvant chemotherapy was performed for 6 cases (37.5%). In the 7 cases of synchronous inguinal node metastasis, 5 year relapse-free-survival (RFS) was 28.6% and 5 year overall-survival (OS) was 28.6%. In the 9 cases of metachronous metastasis, all patients had relapsed within 4 years. However, 5 year OS of the metachronous cases is 33.3%. The median period from the initial surgery to inguinal node metastasis was 11 months. Recurrence of post IND is 13 cases (81.3%). In the first relapse site, pelvic was 3 cases and lung, liver, contralateral inguinal node, paraaortic node and skin were 2 cases each. Conclusion: IND might improve the long-term outcome of the patients who have lower rectal and anal canal adenocarcinoma with inguinal node metastasis. However, it is necessary to develop the multidisciplinary treatment after IND because of high recurrence rate.

DOI： 10.5833/jjgs.2015.0113

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：TAYLOR & FRANCIS INC  

Pancreatic cancer is a recalcitrant malignancy, partly due to desmoplastic stroma which stimulates tumor growth, invasion, and metastasis, and inhibits chemotherapeutic drug delivery. Transforming growth factor- (TGF-) has an important role in the formation of stromal desmoplasia. The present study describes the ability of color-coded intravital imaging to demonstrate the efficacy of a TGF- inhibitor to target stroma in an orthotopic mouse model of pancreatic cancer. The BxPC-3 human pancreatic adenocarcinoma cell line expressing green fluorescent protein (GFP), which also has a high TGF- expression level, was used in an orthotopic model in transgenic nude mice ubiquitously expressing red fluorescent protein (RFP). Fourteen mice were randomized into a control group (n = 7, vehicle, i.p., weekly, for 3weeks) and a treated group (n = 7, SB431542 [TGF- receptor type I inhibitor] 0.3mg, i.p., weekly, for 3weeks). Stromal cells expressing RFP and cancer cells expressing GFP were observed weekly for 3weeks by real-time color-coded intravital imaging. The RFP fluorescence area from the stromal cells, relative to the GFP fluorescence area of the cancer cells, was significantly decreased in the TGF--inhibitor-treatment group compared to the control group. The present study demonstrated color-coded imaging in an orthotopic pancreatic-cancer cell-line mouse model can readily detect the selective anti-stromal-cell targeting of a TGF- inhibitor.

DOI： 10.1080/15384101.2017.1315489

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：IMPACT JOURNALS LLC  

Patient-derived xenograft (PDX) mouse models of cancer are emerging as an important component of personalized precision cancer therapy. However, most models currently offered to patients have their tumors subcutaneously-transplanted in immunodeficient mice, which rarely metastasize. In contrast, orthotopic-transplant patient-derived models, termed patient-derived orthotopic xenografts (PDOX), usually metastasize as in the patient. We demonstrate in the present report why orthotopic models are so important for the patient, since primary and metastatic tumors developed in an orthotopic model can have differential chemosensitivity, not detectable in standard subcutaneous tumor models. A subcutaneous nude mouse model of HER-2 expressing cervical carcinoma was not sensitive to entinostat (a benzamide histone deactylase inhibitor), which also did not inhibit primary tumor growth in a PDOX model of the same tumor. However, in the PDOX model, entinostat alone significantly reduced the metastatic tumor burden, compared to the control. Thus, only the PDOX model could be used to discover the anti-metastatic activity of entinostat for this patient. The results of the present report indicate the importance of using mouse models that can recapitulate metastatic cancer for precisely individualizing cancer therapy.

DOI： 10.18632/oncotarget.12322

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：INT COLLEGE OF SURGEONS  

The aim of this study was to evaluate the long-term prognosis of patients who underwent colectomy for familial adenomatous polyposis. The clinical data of 29 familial adenomatous polyposis patients who underwent colectomy were retrospectively reviewed. Five patients died of causes that included colorectal cancer (CRC), desmoid tumor, cancer of the small intestine, and pancreatitis. The 30-year survival rate was 72%. Among the 15 patients who had CRC at primary surgery, the 5-year survival rate was 100% in stages 0, I, and II, and 75% in stage IIIA. Stage I desmoid tumor showed slow or no growth, whereas a stage IV tumor showed rapid growth and was fatal. Extracolonic malignancies were seen in the small intestine, stomach, duodenum, thyroid, kidney, breast, and ovary. Among 8 patients with ileorectal anastomosis, 4 had a second primary rectal cancer and 6 had a salvage reoperation. None of the patients who underwent either stapled or handsewn ileal pouch-anal anastomosis had second primary rectal cancers. The stage of primary CRC at colectomy is the most important prognostic factor. But in addition to second primary CRC, the management of desmoid tumors and extracolonic malignancies is important for long-term survival regardless of the anastomotic technique used.

DOI： 10.9738/INTSURG-D-16-00046.1

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ACADEMIC PRESS INC ELSEVIER SCIENCE  

Background: The standard of care for elderly women with breast cancer remains controversial. The aim of this study was to clarify the management of elderly breast cancer patients who undergo surgery.
Materials and methods: This retrospective single-center cohort study included 2276 breast cancer patients who underwent surgery between 1993 and 2014. The patients were divided into three groups according to age: &lt;= 64 y (young), 65-74 y (older), and &gt;= 75 y (elderly).
Results: The elderly had more advanced stage disease at diagnosis (stage III and IV, 16.2%, 17.5%, and 22.1% for the young, older, and elderly groups, respectively). The elderly were more likely to undergo mastectomy (43.3%, 41.4%, and 50.7%, respectively), omit axillary operation (0.6%, 1.1%, and 9.3%, respectively), and skip radiotherapy after breast-conserving surgery (93.1%, 86.8%, and 29.1%, respectively). Endocrine therapy was widely used in all the groups (94.4%, 93.8%, and 90.1%, respectively), but frequency of chemotherapy was lower in the elderly regardless of hormone receptor (HR) status (40.8%, 25.5%, and 9.3% in HR(+), 87.2%, 75.3%, and 39.5% in HR(-), respectively). Although the locoregional recurrence rate was higher in the elderly (4.2%, 3.4%, and 7.0% at 5 y, respectively; P = 0.028), there were no differences among groups in distant metastasis-free survival or breast cancerespecific survival.
Conclusions: Although elderly patients had more advanced stages of cancer and received less treatment, there were no differences in survival. Omission of axillary dissection, radiation, and chemotherapy after operation may be an option for breast cancer patients aged &gt;= 75 y. (C) 2016 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.jss.2016.05.031

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記述言語：英語  

With the increasing use of adjuvant chemotherapy for treating early breast cancer, febrile neutropenia management has become crucial. Guidelines for febrile neutropenia management are mostly based on a Caucasian population survey although ethnic differences are reported in terms of adverse events. We survey the current status of febrile neutropenia and risk factors in Japanese female breast cancer patients receiving neoadjuvant and adjuvant chemotherapy regimens potential for febrile neutropenia. Subsequently, we plan to conduct a multicenter prospective cohort study involving 1000 patients with operable breast cancer. With the current state of oral antibiotics being routinely prescribed without hematology tests, we survey febrile neutropenia based on two different definitions, namely, true febrile neutropenia: ≥37.5°C and Grade 4 neutropenia, and surrogate febrile neutropenia: ≥37.5°C and oral antibiotic and antipyretic intake. The comparison of true febrile neutropenia and surrogate febrile neutropenia incidences is anticipated to provide information on the safety and feasibility of chemotherapy management without performing blood tests.

DOI： 10.1093/jjco/hyw045

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCI LTD  

Aim: Triple negative breast cancer (TNBC) is a heterogeneous disease and is associated with the cancer stem cell (CSC), basal-like, and BRCA1 function deficient (BRCAness) subtypes. We examined these 3 subtypes in TNBC and compared their chemosensitivity against anthracycline or taxane with a special attention to BRCAness.
Methods: Sixty-six TNBC cases were obtained from a randomized phase II trial comparing TCx6 (TC6) with PEC-Docetaxel (FEC-D) as neoadjuvant chemotherapy. The core needle specimens before chemotherapy were used for subtyping. The basal-like and CSC subtypes were identified by immunohistochemistry; CK5/6 and EGFR staining for the basal-like subtype and ALDH1 staining for the CSC subtype. The BRCAness subtype was examined by Multiplex Ligation-dependent Probe Amplification (MLPA). Correlations between subgroups and pCR rates according to each regimen and subtype were examined.
Results: The basal-like and BRCAness subtypes were significantly associated (p = 0.010) with the other subtypes, but not the CSC subtype. The pCR rates were higher with 1-EC-D than with TC6 in the basal-like (54.5% vs 14.3%, p = 0.081) and BRCAness (56.2% vs 16.7%, p = 0.030) subtypes. Both were not effective in the CSC subtype (18.2% vs 11.8%, p = 1.00).
Conclusion: BRCAness identified by MLPA was practically useful for treatment selection for avoiding taxane. ALDH1 may be considered as a marker for the CSC subtype requiring novel agents. (C) 2016 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.ejso.2016.02.246

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

A 70-year-old man with left abdominal pain was referred to our hospital, and was diagnosed with type 1 advanced gastric cancer with lymph node metastasis. Neoadjuvant chemotherapy(NAC)with docetaxel and S-1 combination was administered. After 2 courses of chemotherapy, total gastrectomy with D2 lymph node dissection, splenectomy, and cholecystectomy were performed. Pathologically, viable cancer cells were not evident in the primary lesion and lymph nodes. The pathological response of NAC was judged to be Grade 3. On immunohistochemical analysis of the biopsy specimens obtained before treatment, the cancer cells were positive for class III b-tubulin and negative for TS, DPD, and ERCC1. The anti-tumor effect of S-1 may have led to the pCR.

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記述言語：英語   出版者・発行元：AMER ASSOC CANCER RESEARCH  

DOI： 10.1158/1538-7445.AM2016-4894

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BAISHIDENG PUBLISHING GROUP INC  

AIM: To investigate the long-term oncologic outcomes and prognostic factors in patients with obstructive colorectal cancer (CRC) at multiple Japanese institutions.
METHODS: We identified 362 patients diagnosed with obstructive colorectal cancer from January 1, 2002 to December 31, 2012 in Yokohama Clinical Oncology Group's department of gastroenterological surgery. Among them, 234 patients with stage I/II disease who had undergone surgical resection of their primary lesions were analyzed, retrospectively. We report the long-term outcomes, the risk factors for recurrence, and the prognostic factors.
RESULTS: The five-year disease free survival and cancer-specific survival were 50.6% and 80.3%, respectively. A multivariate analysis showed the ASAPS (HR = 2.23, P = 0.026), serum Albumin &lt;= 4.0 g/dL (HR = 2.96, P = 0.007), T4 tumor (HR = 2.73, P = 0.002) and R1 resection (HR = 6.56, P = 0.02) to be independent risk factors for recurrence. Furthermore, poorly differentiated cancers (HR = 6.28, P = 0.009), a T4 tumor (HR = 3.46, P = 0.011) and R1 resection (HR = 6.16, P = 0.006) were independent prognostic factors in patients with obstructive CRC.
CONCLUSION: The outcomes of patients with obstructive CRC was poor. T4 tumor and R1 resection were found to be independent prognostic factors for both recurrence and survival in patients with obstructive CRC.

DOI： 10.3748/wjg.v22.i22.5237

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記述言語：英語   出版者・発行元：AMER SOC CLINICAL ONCOLOGY  

DOI： 10.1200/JCO.2016.34.15_suppl.10019

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER  

This study was designed to evaluate the diagnostic accuracy of magnetic resonance imaging (MRI) for lateral pelvic lymph-node metastasis.
Eighty-four patients with primary lower rectal cancer were examined by MRI and subsequently underwent radical surgery with lateral pelvic lymph-node dissection, without preoperative treatment. Lateral lymph-node metastases were assessed preoperatively by MRI, and the results were compared with the histopathological findings. The criterion for lateral lymph-node metastasis was any recognizable lymph node in the pelvic wall, regardless of diameter.
Lateral pelvic lymph-node metastasis was diagnosed on preoperative MRI in 16 patients (19.9 %). The overall patient-based sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of MRI were 75, 69.1, 36.4, 92.2, and 70.2 %, respectively. When a cut-off value of 10 mm was used for diagnosis, the corresponding values were 43.8, 98.5, 87.5, 88.1, and 88.1 %, respectively. The mean diameter of metastatic nodes (14.7 mm) was significantly larger than that of negative nodes (5.7 mm; P &lt; 0.01).
MRI is an effective technique for predicting lateral pelvic node involvement and thus may facilitate preoperative decision-making in rectal cancer treatment. A cut-off value of 10 mm is useful for avoiding unnecessary lateral lymph-node dissection.

DOI： 10.1007/s00268-015-3299-7

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記述言語：日本語   出版者・発行元：横浜市立大学医学会  

本邦でのがん対策は，2006年6月にがん対策基本法が施行されてから10年目を迎えている．がんプロフェショナル養成基盤推進プランは文部科学省の大学におけるがん医療人の養成の取組みのひとつである．がんプロフェッショナル養成基盤推進プラン事業とがん診療拠点病院は相互補完的な関係であり，がん教育・診療・研究の基盤強化が行われている．大学病院におけるがん専門医療人の育成の推進は，がん診療の均霑化に大きな役割を果たすと考えられる． 本稿では，新しいがん教育の取組みと，成果を踏まえながら，これからの新しいがん教育の方向性を述べて行く．

DOI： 10.15015/00000509

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その他リンク： http://id.nii.ac.jp/1246/00000509/

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER  

Aldehyde dehydrogenase 1 (ALDH1) has been identified as a breast cancer stem cell marker, but its value as a predictor of prognosis and chemoresistance is controversial. This study investigated the effect of ALDH1 on prognosis and chemoresponse by breast cancer subtype. We immunohistochemically analyzed 653 invasive breast cancer specimens and evaluated correlations among clinicopathological factors, survival status, response to neoadjuvant chemotherapy, and ALDH1 expression. Of 653 specimens, 139 (21.3 %) expressed ALDH1 in tumor cells. ALDH1 expression was correlated significantly with larger tumor size, node metastasis, higher nuclear grade, and with HER2(+) and progesterone/estrogen receptor (HR)(-) subtypes. ALDH1 expression was significantly observed in HER2 type and triple-negative breast cancer (TNBC). Patients with ALDH1(+) cancers had significantly shorter disease-free survival (P &lt; 0001) and overall survival (P = 0.044). ALDH1 expression significantly affected prognosis of luminal types, but not TNBC and HER2-enriched types. For the 234 patients treated with neoadjuvant chemotherapy, pathological complete response (pCR) rate was significantly lower in ALDH1(+) cases (13.5 vs. 30.3 %, P = 0.003). pCR and ALDH1 expression were significantly correlated in TNBC patients (P = 0.003). ALDH1(+) breast cancers tended to be aggressive, with poor prognoses. Although ALDH1(+) TNBC showed higher chemoresistance, ALDH1 had significant impact on prognosis in the luminal type but not in TNBC.

DOI： 10.1007/s10549-016-3738-7

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記述言語：日本語   出版者・発行元：医学図書出版(株)  

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記述言語：英語   出版者・発行元：AMER SOC CLINICAL ONCOLOGY  

DOI： 10.1200/jco.2016.34.4_suppl.529

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記述言語：英語   出版者・発行元：AMER SOC CLINICAL ONCOLOGY  

DOI： 10.1200/jco.2016.34.4_suppl.502

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記述言語：英語   出版者・発行元：AMER SOC CLINICAL ONCOLOGY  

DOI： 10.1200/jco.2016.34.4_suppl.297

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記述言語：英語   出版者・発行元：AMER SOC CLINICAL ONCOLOGY  

DOI： 10.1200/jco.2016.34.4_suppl.703

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SAGE Publications Inc.  

Late recurrence of malignant tumors in the heart more than 10 years after surgery is quite rare, especially for colorectal carcinoma. Here, we report a case of late cardiac metastasis from a primary colorectal carcinoma, which occurred more than 15 years after the initial surgery. To our knowledge, this is the first such reported case.

DOI： 10.1177/0218492314539950

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Japanese Society of Clinical Pharmacology and Therapeutics  

Background: Cytochrome P450 2A6 (CYP2A6) is an enzyme responsible for the metabolism of tobacco-specific nitrosamines leading to the generation of the ultimate carcinogenic forms and the metabolism of nicotine. We here report that the genetic polymorphism of human CYP2A6 involving whole-gene deletion, CYP2A6∗4, is associated with primary lung cancer and the overall survival of patients. Methods: We prepared genomic DNA samples from 387 Japanese patients with primary lung cancer and analyzed the whole-gene deletion genotype CYP2A6∗4 using a rapid genetic testing method we developed in this study. We analyzed the association of CYP2A6∗4 and NRF2 with overall survival. Results: Patients harboring wild-type CYP2A6 genotype (∗]/∗] or∗]/∗4) and CYP2A6∗4∗4 numbered 380 (98.2°o) and 7 (1 .800), respectively. In a univariate analysis of factors that correlate with clinicopathological features, the frequency of the CYP2A6∗4/∗4 genotype was significantly higher in males than in females (P = 0.025), in patients with adenocarcinoma than in those with non-adenocarcinoma (P =0.001), and in nonsmokers than in smokers (P = 0.007). In a multivariate logistic analysis, the CYP2A6∗4/∗4 genotype was not associated with gender or smoking behavior. Interestingly, lung cancer patients carrying CYP2A6∗4/∗4 genotype and NRF2 SNP heterozygous (c.-617 C/A) or wild-type homozygous (c.-617C C) alleles exhibited remarkable survival (85 .700) of over 1 ,500 days after surgical operation. Analysis of male smokers showed that CYP2A6∗4/∗4 was associated with favorable survival outcome in patients with adenocarcinoma. Conclusions: These results suggest that the CYP2A6∗4 is associated with lung cancer among Japanese population and is a potential prognostic biomarker for assessing overall survival of patients with lung cancer undergoing resection.

DOI： 10.3999/jscpt.47.183

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：S. Karger AG  

A 49-year-old Japanese man had multiple huge masses (max. size 60 mm diameter) in his liver. These tumors were pathologically diagnosed by tumor biopsy as epithelioid hemangioendotheliomas of the liver. In this case, multiple liver tumors existed in both lobes. Also this patient did not agree to receive surgical resection including liver transplantation. Chemotherapy with sorafenib at a dose of 400 mg/body twice a day was started. About 6 months later, CT findings revealed that these tumors were shrinking slightly
33 months later, the tumors obviously showed a partial response in accordance with the Response Evaluation Criteria in Solid Tumors (RECIST). Also 60 months later, the partial response continued with sorafenib monotherapy.

DOI： 10.1159/000443986

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Medical Association of Yokohama City University  

With the introduction of the Cancer Control Act in 2007, accessibility to uniform cancer-related medical care has been promoted. We have held joint seminars using a video conference system and simultaneous relay to remote areas since February 2013 as part of the "Promotion Plan for the Platform of Human Resource Development for Cancer" supported by the Ministry of Education, Culture, Sports, Science and Technology (participating universities: The University of Tokyo, Yokohama City University, Toho University, and Jichi Medical University). The participating universities can simultaneously join in public seminars in real time. They also promote accessibility to uniform cancer-related medical care and the education and training of oncology specialists, through collaboration among universities. Since August 2016, we have participated in an academic authentication federation called GakuNin developed by the National Institute of Informatics to promote a seamless video conference system. We started providing remote lectures at several locations using the video conference system and federation authenticated multipoint control units (FaMCUs). In this paper, the outline and authentication system of GakuNin, a video conference system using multipoint control units (MCUs), and its future possible applications are discussed.

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DOI： 10.1007/s00384-015-2340-5

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記述言語：英語   出版者・発行元：(一社)日本癌学会  

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記述言語：日本語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：日本語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：日本語   出版者・発行元：(一社)日本核医学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER  

S-1, a novel oral prodrug of 5-fluorouracil (5-FU), and irinotecan with or without bevacizumab is known to be effective in metastatic colorectal cancer (mCRC). However, it is not clear whether S-1 and irinotecan confers benefits compared to 5-FU and leucovorin plus oxaliplatin (FOLFOX) in patients with mCRC. Our aim was to compare the efficacy and safety of these regimens.We analyzed 187 patients with previously untreated mCRC who were enrolled in four phase II studies: SIR (S-1 and irinotecan, n = 40), SIRB (S-1 and irinotecan with bevacizumab, n = 51), FOLFOX (5-FU and leucovorin plus oxaliplatin, n = 46), and STOX (stop-and-go strategy of modified FOLFOX-6 with bevacizumab, n = 50). We evaluated efficacy and safety between SIR/SIRB and FOLFOX/STOX.Baseline characteristics were similar in the two groups composed of SIR/SIRB (n = 91) and FOLFOX/STOX (n = 96). The overall response rates were not significantly different between the two groups (65 % in SIR/SIRB vs. 52 % in FOLFOX/STOX, p = 0.125). The median progression-free survival was 10.9 months in SIR/SIRB versus 12.1 months in FOLFOX/STOX (p = 0.59). The median overall survival was 27.3 months in SIR/SIRB versus 26.8 months in FOLFOX/STOX (p = 0.97). Gastrointestinal adverse events were the most common toxicities in SIR/SIRB, while neutropenia and sensory neuropathy were the most common toxicities in FOLFOX/STOX.S-1 and irinotecan with or without bevacizumab was well tolerated and showed similar response rates and survival compared to the FOLFOX regimen. This combination should be considered as an experimental first-line treatment for mCRC.

DOI： 10.1007/s00280-015-2834-4

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その他リンク： http://orcid.org/0000-0001-8454-1995

DOI： 10.1158/1538-7445.AM2015-4247

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DOI： 10.1158/1538-7445.AM2015-219

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DOI： 10.1371/journal.pone.0130472

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DOI： 10.1158/1538-7445.SABCS14-P2-06-16

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DOI： 10.1016/j.pan.2015.02.008

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記述言語：日本語   出版者・発行元：(一社)日本膵臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本膵臓学会  

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記述言語：英語   出版者・発行元：AMER ASSOC CANCER RESEARCH  

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DOI： 10.1016/j.jss.2014.10.048

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCI LTD  

Background: We compared clinical outcomes of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) against those of classical 2-stage hepaectomy in treating metastatic liver disease.
Methods: Short-term outcomes, serial changes in volume of the future liver remnant (FLR), functional FLR volume, and tumor growth activity during the treatment period, were compared between our first 11 consecutive patients treated with ALPPS and 54 patients treated with classical 2-stage hepatectomy.
Results: Mortality in the ALPPS group (9%) tended to be higher than in the classical 2-stage group (2%, P = 0.341). The FLR hypertrophy ratio (FLR volume after vs. before the procedure) 1 week after the first operation in the ALPPS group (1.54 +/- 0.18) exceeded that in the classical 2-stage group (1.19 +/- 0.29, P = 0.005), being similar to the ratio at 3 weeks after the first procedure in the classical 2-stage group (1.40 +/- 0.43). However, functional volume of the FLR in the ALPPS group 1 week after the first procedure (52.1%) tended to be smaller than that in the classical group 3 weeks after the first procedure (59.2%).
Conclusions: ALPPS should be used with extreme caution, giving special attention to postoperative complications and grade of functional liver regeneration. (C) 2015 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.ejso.2015.01.031

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DOI： 10.1007/s00795-014-0071-2

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DOI： 10.1007/s00384-015-2129-6

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DOI： 10.1371/journal.pone.0117417

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1186/s12876-015-0233-2

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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記述言語：日本語   出版者・発行元：(株)北隆館  

非密封RIを用いるRI内用療法は、現状では高コストな特別なRI治療専用病棟の必要性、病院経営における不採算性、放射線防護に関わる法規制などの制約があり、広く知られ普及している治療法とは言えない。しかしながら、近年研究開発が進められている分子イメージング技術、抗体医薬を用いた分子標的治療の普及などを背景に、RI内用療法がもつイメージング診断と治療を融合したTheranosticsの概念を具現化できる将来性のある治療法である。(著者抄録)

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

AimThe indications for intersphincteric (ISR) anterior resection are not clearly defined. The aim of this study was to evaluate vertical extension of T2 or T3 low rectal cancer treated by rectal amputation to optimize patient selection for ISR.
MethodThe abdominoperineal excision specimens of T2 or T3 low rectal cancer from 53 patients treated between 1992 and 2004 were retrospectively reviewed. Vertical invasion was quantified by measuring the shortest distance between the tumour and the striated muscle (T-SM), assuming that this represented the surgical margin that would have be achieved had an ISR been performed.
ResultsInvolvement of the dentate line (DL) and intramural distal spread were independent risk factors for T-SM 2mm. The T-SM was less when the inferior border of the tumour was on the distal side of the DL (r=0.572, P&lt;0.001). The probability of involvement of the DL, intramural distal spread or either one of these being associated with T-SM2mm was 43, 46 and 43%, respectively. All patients without both intramural distal spread and involvement of the DL had T-SM&gt;2.
ConclusionWe recommend that ISR should only be performed for patients with T2 or T3 low rectal cancer in whom the lowest edge of the tumour is above the DL and there is no intramural distal spread. Such patients are relatively unlikely to have a T-SM 2mm.

DOI： 10.1111/codi.12769

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：H G E UPDATE MEDICAL PUBLISHING S A  

Background/Aims: Anastomotic leakage is major complication of colorectal surgery Total parenteral nutrition (TPN) and fasting are conservative treatments for leakage in the absence of peritonitis in Japan. Elemental diet (ED) jelly is a completely digested formula and is easily absorbed without secretion of digestive juices. The purpose of this study was to assess the safety of ED jelly in management of anastomotic leakage. Methodology: Six hundred and two patients who underwent elective surgery for left side colorectal cancer from January 2008 to December 2011 were included in the study. Pelvic drainage was performed for all patients. Sixty-three (10.5%) patients were diagnosed with an anastomotic leakage, and of these, 31 (5.2%) without diverting stoma were enrolled in this study, Results: Sixteen patients received TPN (TPN group) and 15 patients received ED jelly (ED group). The duration of intravenous infusion was significantly shorter in the ED group than in the TPN group (15 days versus 25 days, P= 0.008). In the TPN group, catheter infection was occurred in 2 patients who required re-insertion of the catheter. Conclusion: Conservative management of anastomotic leakage after colorectal surgery with ED jelly appears to be a safe and useful approach.

DOI： 10.5754/hge13469

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DOI： 10.1016/j.ejso.2014.09.001

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1159/000370253

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記述言語：日本語   出版者・発行元：日本外科系連合学会  

症例は54歳，女性．胸部上部食道癌に対しD2郭清を伴う右開胸開腹食道亜全摘，胃管再建が施行された．術後病期はT2，N1，M0，fStage Ⅱであり補助化学療法としてFP療法を２コース施行した．術後11カ月で頸部リンパ節再発を認めたため治療的抗癌剤としてFP療法を再開した．４コース目day7より，構語障害，小脳性運動失調を認め，脳MRIにて白質脳症と診断された．薬剤の中断により数日で症状は軽快しMRI所見でも白質脳症に伴う変化はほぼ消失した．以後レジメンを変更し，神経症状の再発なく現在も化学療法継続中である．薬剤性白質脳症は様々な抗悪性腫瘍薬で発症が報告されており，5-FU，cisplatinも原因薬剤になりえる．白質脳症を発症した場合は早期診断，治療が重要であり，化学療法を再開する際には，レジメン変更を検討する必要があると考えられた．

DOI： 10.4030/jjcs.40.668

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：W.B. Saunders Ltd  

Background: Although sentinel lymph node biopsy (SLNB) is a standard staging method for assessing nodal status of breast cancer patients, SLNB after neoadjuvant chemotherapy (NAC) remains controversial. The aim of this study was to validate the practicality and accuracy of SLNB by our modified Indigocarmine blue dye methods following NAC. Methods: One hundred consecutive cases with breast cancers treated by NAC were enrolled in this study. After NAC, all patients underwent SLNB performed by our modified Indigocarmine blue dye methods without radioisotope, followed by back-up axillary lymph node dissection (ALND). Results: Sentinel nodes (SNs) were identified in 94 cases (identification rate, 94%)
the accuracy was 94.7% (89/94 cases)
and the false negative rate (FNR) 13.5% (5/37 cases). For cases with vs. without clinically evident metastatic nodes before NAC, the identification rate was 92.4% (61/66 cases) vs. 97.1% (33/34 cases)
the accuracy 91.8% (56/61 cases) vs. 97.0% (32/33 cases) and the FNR 16.1% (5/31 cases) vs. 0% (0/6 case), respectively. There were six patients without identified SNs, three of them had metastatic nodes. False negatives occurred in five cases
in four, fewer than two sentinel nodes had been removed. Conclusion: Following NAC, the accuracy of SLNB by modified Indigocarmine blue dye methods is adequate compared with other tracers. In patients in whom no SNs have been identified, lymphatic metastasis is likely and therefore ALND is recommended. For patients with cN0 prior to NAC, SLNB by modified Indigocarmine blue dye methods is clinically feasible, though controversial for patients with positive nodes.

DOI： 10.1016/j.ejso.2014.10.066

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PUBLIC LIBRARY SCIENCE  

The aim of this study is to determine the efficacy of neoadjuvant chemotherapy (NAC) with gemcitabine (GEM) in combination with fluorescence-guided surgery (FGS) on a pancreatic cancer patient derived orthotopic xenograft (PDOX) model. A PDOX model was established from a CA19-9-positive, CEA-negative tumor from a patient who had undergone a pancreaticoduodenectomy for pancreatic adenocarcinoma. Mice were randomized to 4 groups: bright light surgery (BLS) only; BLS+NAC; FGS only; and FGS+NAC. An anti-CA19-9 or anti-CEA antibody conjugated to DyLight 650 was administered intravenously via the tail vein of mice with the pancreatic cancer PDOX 24 hours before surgery. The PDOX was brightly labeled with fluorophore-conjugated anti-CA19-9, but not with a fluorophore-conjugated anti-CEA antibody. FGS was performed using the fluorophore-conjugated anti-CA19-9 antibody. FGS had no benefit over BLS to prevent metastatic recurrence. NAC in combination with BLS did not convey an advantage over BLS to prevent metastatic recurrence. However, FGS+NAC significantly reduced the metastatic recurrence frequency to one of 8 mice, compared to FGS only after which metastasis recurred in 6 out of 8 mice, and BLS+NAC with metastatic recurrence in 7 out of 8 mice (p=0.041). Thus NAC in combination with FGS can reduce or even eliminate metastatic recurrence of pancreatic cancer sensitive to NAC. The present study further emphasizes the power of the PDOX model which enables metastasis to occur and thereby identify the efficacy of NAC in combination with FGS on metastatic recurrence.

DOI： 10.1371/journal.pone.0114310

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：IMPACT JOURNALS LLC  

The aim of the present study was to examine the efficacy of tumor-targeting Salmonella typhimurium A1-R treatment following anti-vascular endothelial growth factor (VEGF) therapy on VEGF-positive human pancreatic cancer. A pancreatic cancer patient-derived orthotopic xenograft (PDOX) that was VEGF-positive and an orthotopic VEGF-positive human pancreatic cancer cell line (MiaPaCa-2-GFP) as well as a VEGF-negative cell line (Panc-1) were tested. Nude mice with these tumors were treated with gemcitabine (GEM), bevacizumab (BEV), and S. typhimurium A1-R. BEV/GEM followed by S. typhimurium A1-R significantly reduced tumor weight compared to BEV/GEM treatment alone in the PDOX and MiaPaCa-2 models. Neither treatment was as effective in the VEGF-negative model as in the VEGF-positive models. These results demonstrate that S. typhimurium A1-R following anti-angiogenic therapy is effective on pancreatic cancer including the PDOX model, suggesting its clinical potential.

DOI： 10.18632/oncotarget.2641

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: HER2-positive breast cancer sensitivity to anthracyclines is enhanced when topoisomerase IIα (TOP2A) is co-amplified under both adjuvant and metastatic settings. However, the relationship between anthracycline sensitivity and TOP2A amplification in HER2-positive breast cancers in neoadjuvant settings is not known. METHODS: The TOP2A gene status was examined by FISH in biopsies from 18 patients who received anthracycline and cyclophosphamide before surgery. RESULTS: The TOP2A gene was amplified in 6/17 patients and was significantly associated with pathological response to the chemotherapy regimen. CONCLUSIONS: TOP2A amplification could predict anthracycline-sensitivity. Thus, the HER2/TOP2A co-amplified subtype may be effectively treated by anthracycline-containing regimens alone.

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DOI： 10.1007/s12282-013-0447-5

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記述言語：英語   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

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記述言語：英語   出版者・発行元：AMER ASSOC CANCER RESEARCH  

DOI： 10.1158/1538-7445.AM2014-CT318

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：H G E UPDATE MEDICAL PUBLISHING S A  

Background/Aims: Endoscopic treatment for postoperative benign bile duct stricture (BBS) is a therapeutic challenge. No previous studies have compared endoscopic treatments for BBS and malignant bile duct stricture (MBS). The aim of this study was to compare endoscopic treatments for postoperative BBS and MBS. Methodology: This study enrolled 22 consecutive patients with a diagnosis of postoperative BBS and 110 patients diagnosed with MBS. Cases involving digestive tract reconstruction were excluded. We compared the length of the bile duct strictures, the success rate of endoscopic treatment, and the incidence of complications. Results: The following results were obtained for the postoperative BBS and MBS groups, respectively: length of bile duct stricture, 6.50 mm vs. 24.3 mm (P&lt;0.0001).; success rate of endoscopic treatment, 90.9% vs. 93.6% (P=0.6551). Post-ERCP pancreatitis occurred after 11 sessions (10.7%) vs. 7 sessions (1.83%) (P=0.0002) and post-ERCP cholangitis occurred after 7 sessions (6.80%) vs. 4 sessions (1.04%) (P=0.0021). BBS was a significant risk factor for post-ERCP pancreatitis and cholangitis based on a multivariate analysis (OR 10.732; P=0.0,022; OR, 6.443; P=0.0260). Conclusion. Post-ERCP-related complications were more frequent after postoperative BBS than after MBS. The need for careful endoscopic treatment may be greater for postoperative BBS cases than for MBS cases.

DOI： 10.5754/hge13136

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER JAPAN KK  

The use of preoperative endocrine therapy for breast cancer has increased during the last decade. Although several studies have reported favorable response rates in postmenopausal women, its effectiveness in premenopausal women remains unknown. This study therefore aimed to evaluate the potential benefits of preoperative endocrine therapy in premenopausal women.
Fifty-three patients with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative invasive breast cancer were included in this study. Preoperative endocrine therapy with goserelin acetate and tamoxifen was administered for 3 months. Clinical evaluations were performed by ultrasonography before and after endocrine therapy. Pathological evaluations were performed using core biopsy and surgical specimens. Immunohistochemical evaluations of ER, progesterone receptor (PgR), HER2, and Ki-67 were performed before and after endocrine therapy.
Partial response (PR) was observed in 23 % (12/53) and progressive disease (PD) in 2 % (2/53) of patients. Significant suppression of Ki-67 was observed following endocrine therapy in 90 % (47/52) of patients (P &lt; 0.0001). Significant downregulation of PgR was observed after endocrine therapy (P = 0.0002), which tended to be correlated with clinical response (P = 0.058).
Three months of preoperative endocrine therapy with goserelin acetate and tamoxifen was safe and effective in premenopausal patients with invasive breast cancer, with a 23 % PR rate. Changes in PgR and Ki-67 expression might be promising markers for endocrine responsiveness.

DOI： 10.1007/s12282-012-0429-z

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記述言語：日本語   出版者・発行元：(一財)日本消化器病学会  

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記述言語：日本語   出版者・発行元：日本Acute Care Surgery学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PUBLIC LIBRARY SCIENCE  

We previously defined macrophages harvested from the peritoneal cavity of nude mice with subcutaneous human pancreatic tumors as "tumor-educated-macrophages'' (Edu) and macrophages harvested from mice without tumors as "naive-macrophages'' (Naive), and demonstrated that Edu-macrophages promoted tumor growth and metastasis. In this study, Edu- and Naive-macrophages were compared for their ability to enhance pancreatic cancer malignancy at the cellular level in vitro and in vivo. The inhibitory efficacy of Zoledronic acid (ZA) on Edu-macrophage-enhanced metastasis was also determined. XPA1 human pancreatic cancer cells in Gelfoam co-cultured with Edu-macrophages proliferated to a greater extent compared to XPA1 cells cultured with Naive-macrophages (P = 0.014). XPA1 cells exposed to conditioned medium harvested from Edu culture significantly increased proliferation (P = 0.016) and had more migration stimulation capability (P &lt; 0.001) compared to cultured cancer cells treated with the conditioned medium from Naive. The mitotic index of the XPA1 cells, expressing GFP in the nucleus and RFP in the cytoplasm, significantly increased in vivo in the presence of Edu-compared to Naive-macrophages (P = 0.001). Zoledronic acid (ZA) killed both Edu and Naive in vitro. Edu promoted tumor growth and metastasis in an orthotopic mouse model of the XPA1 human pancreatic cancer cell line. ZA reduced primary tumor growth (P = 0.006) and prevented metastasis (P = 0.025) promoted by Edu-macrophages. These results indicate that ZA inhibits enhanced primary tumor growth and metastasis of human pancreatic cancer induced by Edu-macrophages.

DOI： 10.1371/journal.pone.0103382

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Nature Publishing Group  

Background:CD133 and CD44 are putative cancer stem cell (CSC) markers in colorectal cancer (CRC). However, their clinical significance is currently unclear. Here, we evaluated primary CRC cell isolates to determine the significance of several CSC markers, including CD133 and CD44, as predictors of tumourigenesis and prognosis.Methods:CD133-and CD44-positive cells from fresh clinical samples of 77 CRCs were selected by flow cytometric sorting and evaluated for tumourigenicity following subcutaneous transplantation into NOD/SCID mice. Cancer stem cell marker expression was examined in both xenografts and a complementary DNA library compiled from 167 CRC patient samples.Results:CD44 +, CD133 + and CD133 + CD44 + sub-populations were significantly more tumourigenic than the total cell population. The clinical samples expressed several transcript variants of CD44. Variant 2 was specifically overexpressed in both primary tumours and xenografts in comparison with the normal mucosa. A prognostic assay using qRT-PCR showed that the CD44v2 high group (n=84, 5-year survival rate (5-OS): 0.74) had a significantly worse prognosis (P=0.041) than the CD44v2 low group (n=83, 5-OS: 0.88).Conclusions: CD44 is an important CSC marker in CRC patients. Furthermore, CRC patients with high expression of CD44v2 have a poorer prognosis than patients with other CD44 variants. © 2014 Cancer Research UK.

DOI： 10.1038/bjc.2014.253

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記述言語：日本語   出版者・発行元：(一社)日本乳癌学会  

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記述言語：日本語   出版者・発行元：(一社)日本乳癌学会  

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記述言語：日本語   出版者・発行元：(一社)日本癌治療学会  

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DOI： 10.1245/s10434-014-3549-1

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：H G E UPDATE MEDICAL PUBLISHING S A  

Background/Aims: To determine the effect of the pyridoxine for prevention of hand- foot syndrome in colorectal cancer patients with adjuvant chemotherapy using capecitabine. Methodology: Colorectal cancer patients scheduled for capecitabine chemotherapy as adjuvant setting were randomly assigned to with or without concurrent oral pyridoxine (60 mg/d) groups. Patients were monitored whether being a development of National Cancer Institute Common Toxicity Criteria grade 2 or worse HFS until chemotherapy ended. Results: Sixty patients were enrolled in this study. Relative dose intensity was 89.5% in total. The median number of chemotherapy cycles to grade 2 or worse HFS was four in both groups. Grade 2 or worse HFS developed in 18 (60.0%) of 30 control patients and in 18 (60.0%) of 30 pyridoxine patients. The cumulative dose of capecitabine to grade 2 or worse HFS I was not different between the two groups. Conclusions: Pyridoxine is not effective in prevention of capecitabine-associated HFS.

DOI： 10.5754/hge14154

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記述言語：英語   出版者・発行元：AMER SOC CLINICAL ONCOLOGY  

DOI： 10.1200/jco.2014.32.15_suppl.e12013

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.surg.2013.12.030

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記述言語：英語   出版者・発行元：AMER SOC CLINICAL ONCOLOGY  

DOI： 10.1200/jco.2014.32.15_suppl.e20695

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

Introduction:
Although surgeons have tried to reduce the number of ports in order to achieve better cosmesis and less postoperative pain, it may lead to increased risk for complications. Herein, we introduce a technique, "laparoscopic bowel-lifting (LBL) technique," which helps to reduce ports without additional trocars.
Methods:
The mesocolon is pierced near the line of transaction using the pair of dissecting forceps. A 1-0 Vicryl suture is introduced into the abdominal cavity using a grasping needle and passed through the mesocolon. The colon is retracted using the suture and fixed to the abdominal wall using a pair of forceps. Thereafter, traction is placed on the main nutrient artery. Mobilization of the rectum is performed after moving the traction to the cranial side by using a grasping needle. As the rectal tube was pulled toward the cranial side, it is possible to identify the mesorectum with a good visual field.
Results:
We performed this procedure in 100 consecutive patients with rectal cancer who underwent curative laparoscopic low anterior resection (Lap-LAR) between November 2001 and March 2010. The median duration of follow-up after Lap-LAR was 53.2 months. The tumor was located in the middle rectum in 75 patients and in the lower rectum in 25 patients. The stage grouping on the basis of the TNM classification was as follows: stage 0, 6; stage I, 46; stage II, 18; and stage III, 30. The number of trocars used in the LBL group was 3 or 4. No LBL cases used 5 trocars. No operative complications were attributable to this technique. The overall rates of anastomotic leakage and morbidity were 10.0% and 33.0%, respectively. The 5-year relapse-free and 5-year overall survival rates were stage 0, 100/100; stage I, 93.3/96.8; stage II, 81.5/88.5; and stage III, 74.5/75.7.
Conclusions:
LBL technique is feasible for performing Lap-LAR. This method reduces the number of ports and might help to introduce a single-incisional surgery.

DOI： 10.1097/SLE.0b013e318293c478

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER  

Although obesity is considered as a risk factor for postoperative morbidity in abdominal surgery, its effect on the outcomes of laparoscopic-assisted colectomy (LAC) is still unclear. The technical difficulty and risk factor for postoperative complication in LAC are thought to be influenced by visceral obesity. The aim of this prospective study was to evaluate the impact of visceral fat on the surgical outcomes of LAC.
Between April 2005 and December 2010, consecutive patients with preoperatively diagnosed colon cancer, excluding medium and low rectal cancer, who underwent LAC, were enrolled. Their visceral fat area (VFA) and body mass index (BMI) were prospectively collected. The VFA was assessed by Fat Scan software. The patients were classified into two groups as follows: VFA nonobese with VFA &lt; 100 cm(2) (VNO) and VFA obese with VFA a parts per thousand 100 cm(2) (VO). The predictive factors for surgical complications of LAC were evaluated by univariate and logistic regression analyses.
A total of 338 consecutive patients were enrolled in this study. Of the 338 patients, 194 (57.4 %) and 138 (42.6 %) were classified into the VNO and VO groups, respectively. Logistic regression analysis showed that high BMI (a parts per thousand 25 kg/m(2)) and VO independently predicted the incidence of overall postoperative complications (p = 0.040 and 0.007, respectively). VO was more highly related to the incidence of overall postoperative complications, anastomotic leakage (p = 0.021), and surgical site infection (SSI) (p = 0.013) than high BMI.
VFA is a more useful parameter than BMI in predicting surgical outcomes after LAC.

DOI： 10.1007/s00384-013-1803-9

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記述言語：日本語   出版者・発行元：(一社)日本外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本外科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER-VERLAG ITALIA SRL  

Regulatory T cells (Tregs) play a role in the immunosuppressive state in pancreatic cancer patients. We aimed to evaluate the changes of immune cells population including Tregs caused by gemcitabine (GEM)-based chemotherapy.
Fifty-three patients with pancreatic cancer were enrolled in this study, of which 32 received GEM- based chemotherapy. Blood samples were collected before and at least 2 weeks after the last dose of chemotherapy. The peripheral blood mononuclear cells (PBMCs) were subjected to flow cytometry analysis after labeling with anti-CD4, anti-CD25, and anti-Foxp3 antibodies. Other lymphocytes and NK cell markers were also measured. The proliferative capacity of PBMCs stimulated with anti-CD3 was analyzed using H-3 thymidine.
The percentage and number of Tregs were significantly decreased after chemotherapy (p = 0.032, p = 0.003, respectively). The other immune cells and the proliferative capacity did not change.
This study showed that GEM-based chemotherapy produced an immunomodulatory effect via the depletion of Tregs.

DOI： 10.1007/s12094-013-1079-0

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記述言語：英語   出版者・発行元：ELSEVIER SCI LTD  

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記述言語：日本語   出版者・発行元：(一社)日本外科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER  

This report presents a rare case of intrahepatic cholangiocarcinoma (IHCC) arising 28 years after excision of a type IV-A congenital choledochal cyst. The patient underwent excision of a congenital choledochal cyst (Todani's type IV-A) at 12 years of age, with Roux-en-Y hepaticojejunostomy reconstruction. She received a pancreaticoduodenectomy (PD) using the modified Child method for an infection of a residual congenital choledochal cyst in the pancreatic head at the age of 18. She was referred to this department with a liver tumor 22 years later. Left hemihepatectomy with left-side caudate lobectomy was performed and the tumor was pathologically diagnosed to be IHCC. The cause of the current carcinogenesis was presumed to be reflux of pancreatic juice into the residual intrahepatic bile duct during surgery. This case suggests that a careful long-term follow-up is important for patients with congenital choledochal cysts, even if a separation-operation was performed at a young age, and especially after PD.

DOI： 10.1007/s00595-012-0387-2

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER  

Background. Little is known about the immunological effect of neoadjuvant chemoradiotherapy (NACRT) in the tumor microenvironment of pancreatic ductal adenocarcinoma. The objective of this study was to examine the immunological modifications induced by NACRT in patients with pancreatic cancer.
Methods. Fifty-two patients with pancreatic cancer who underwent surgical resection were enrolled in this study. NACRT was administered to 22 patients, whereas the other 30 patients underwent surgical resection without NACRT. The resected tumor specimens were analyzed for the presence of tumor-infiltrating lymphocytes by using immunohistochemical staining for CD4, CD8, CD68, CD163, Foxp3, and major histocompatibility complex class I (MHC class I) antigen.
Results. The number of CD4+ and CD8+ lymphocytes was significantly higher in patients who received NACRT than in those who did not receive NACRT. No significant difference in MHC class I expression was observed between the groups. In the NACRT group, patients with a high accumulation of CD8+ cells experienced longer overall survival than those with a low number of CD8+ cells.
Conclusions. NACRT may induce the accumulation of CD4+ and CD8+ cells in the tumor microenvironment and a high accumulation of CD8+ cells might be a good prognostic marker for pancreatic cancer treated with NACRT.

DOI： 10.1245/s10434-013-3390-y

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER  

Background In surgical treatment of elderly patients, securing the safety of surgery and radical cure must be balanced. Our purpose was to verify the safety and validity of laparoscopic surgery for the treatment of colorectal cancer in elderly patients.
Methods Patients with cTis-T4a colorectal cancer who were 75 years or older were randomized to receive open or laparoscopic surgery. Exclusion criteria were patients who had a bulky tumor, rectal cancer that required pelvic side wall lymphadenectomy, and history of colon resection. Patients were divided according to tumor location (right colon, left colon, and rectum). The short-term outcomes were compared between the two groups.
Results One hundred patients (right 43, left 28, and rectum 29) were registered in each group from August 2008 to August 2012. There were no differences in patient characteristics between the two groups. Three patients were converted from laparoscopic to open, because of bleeding, excision of peritoneum metastasis, and patient's desire, respectively. In the short-term results (open:laparoscopic), there were significant differences in the rates of complications (36:23 %) and ileus (12:4 %), amount of blood loss (157:63 mL), and duration of surgery (150:172 min). There were no significant differences in the pathological margins, and the number of dissected lymph nodes. In the subgroup analysis according to the tumor location, there were significant differences in the rate of complications (39.4:22.5 %), amount of blood loss (135:42 mL), duration of surgery (139:160 min), and length of postoperative stay (13.0:10.0 days) in the colon cancer. There were no significant differences in short-term results in the rectal cancer.
Conclusions Laparoscopic surgery in elderly colorectal cancer patients did not result in a difference in radical cure compared with open surgery, and the short-term results except the duration of surgery were excellent. It is an effective procedure for elderly patients with colorectal cancer, especially colon cancer.

DOI： 10.1007/s00464-013-3223-x

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DOI： 10.3892/ol.2014.2271

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その他リンク： http://orcid.org/0000-0002-1294-5269

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記述言語：英語   出版者・発行元：AMER ASSOC CANCER RESEARCH  

DOI： 10.1158/0008-5472.SABCS13-P3-14-08

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記述言語：日本語   出版者・発行元：(株)篠原出版新社  

53歳女性、主訴は左乳房腫瘤。USで左ED領域に7.2cmの低エコー腫瘤を認め、マンモグラフィでは同部にカテゴリー4の腫瘤を認めた。Core needle biopsyで組織型はMPC、ER(-)、PgR(-)、HER2(-)、NG=3、Ki67=69%、AE1/AE3(+)、vimentin(+)、T3N1M0 cStage IIIAの診断で術前化学療法(FEC100×4-DOC75×2)施行しcPR。Bt+Ax(I+II)施行、組織学的治療効果はGrade 2a、pN0(0/14)であった。MPCのほとんどはTriple negative乳癌だが術前化学療法施行症例の報告は少ない。文献的考察を加え報告する。(著者抄録)

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DOI： 10.1245/s10434-012-2491-3

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DOI： 10.5754/hge.13459

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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記述言語：日本語   出版者・発行元：日本臨床外科学会  

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記述言語：日本語   出版者・発行元：日本臨床外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PUBLIC LIBRARY SCIENCE  

Purpose: The transcription factor NRF2 plays a pivotal role in protecting normal cells from external toxic challenges and oxidative stress, whereas it can also endow cancer cells resistance to anticancer drugs. At present little information is available about the genetic polymorphisms of the NRF2 gene and their clinical relevance. We aimed to investigate the single nucleotide polymorphisms in the NRF2 gene as a prognostic biomarker in lung cancer.
Experimental Design: We prepared genomic DNA samples from 387 Japanese patients with primary lung cancer and detected SNP (c.-617C&gt;A; rs6721961) in the ARE-like loci of the human NRF2 gene by the rapid genetic testing method we developed in this study. We then analyzed the association between the SNP in the NRF2 gene and patients' overall survival.
Results: Patients harboring wild-type (WT) homozygous (c.-617C/C), SNP heterozygous (c.-617C/A), and SNP homozygous (c.-617A/A) alleles numbered 216 (55.8%), 147 (38.0%), and 24 (6.2%), respectively. Multivariate logistic regression models revealed that SNP homozygote (c.-617A/A) was significantly related to gender. Its frequency was four-fold higher in female patients than in males (10.8% female vs 2.7% male) and was associated with female non-smokers with adenocarcinoma. Interestingly, lung cancer patients carrying NRF2 SNP homozygous alleles (c.-617A/A) and the 309T (WT) allele in the MDM2 gene exhibited remarkable survival over 1,700 days after surgical operation (log-rank p = 0.021).
Conclusion: SNP homozygous (c.-617A/A) alleles in the NRF2 gene are associated with female non-smokers with adenocarcinoma and regarded as a prognostic biomarker for assessing overall survival of patients with lung adenocarcinoma.

DOI： 10.1371/journal.pone.0073794

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記述言語：日本語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：日本語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器外科学会  

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出版者・発行元：Elsevier {BV}  

DOI： 10.1016/j.pan.2013.07.169

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記述言語：日本語   出版者・発行元：(一社)日本膵臓学会  

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記述言語：日本語   出版者・発行元：(一社)日本乳癌学会  

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記述言語：日本語   出版者・発行元：(一社)日本乳癌学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: To estimate the radiation dose and biodistribution of (18)F-5-fluorouracil ([(18)F]-5-FU) from positron emission tomography/computed tomography (PET/CT) data, and to extrapolate mouse data to human data in order to evaluate cross-species consistency. METHODS: Fifteen cancer patients (head and neck cancer (n=11), colon cancer (n=4)) were enrolled. Sequential PET/CT images were acquired for 2h after intravenous administration of [(18)F]-5-FU, and the percent of the injected dose delivered to each organ was derived. For comparison, [(18)F]-5-FU was administered to female BALB/cAJcl-nu/nu nude mice (n=19), and the percent of the injected dose delivered to mouse organs was extrapolated to the human model. Absorbed radiation dose was calculated using OLINDA/EXM 1.0 software. RESULTS: In human subjects, high [(18)F]-5-FU uptake was seen in the liver, gallbladder and kidneys. The absorbed dose was highest in the gallbladder wall. In mice, the biodistribution of [(18)F]-5-FU corresponded to that of humans. Estimated absorbed radiation doses for all organs were moderately correlated, and doses to organs (except the gallbladder and urinary bladder) were significantly correlated between mice and humans. The mean effective [(18)F]-5-FU dose was higher in humans (0.0124mSv/MBq) than in mice (0.0058mSv/MBq). CONCLUSION: Biodistribution and radiation dosimetry of [(18)F]-5-FU were compared between humans and mice: biodistribution in mice and humans was similar. Data from mice underestimated the effective dose in humans, suggesting that clinical measurements are needed for more detailed dose estimation in order to ensure radiation safety. The observed effective doses suggest the feasibility of [(18)F]-5-FU PET/CT for human studies.

DOI： 10.1016/j.apradiso.2013.01.014

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DOI： 10.1158/1538-7445.AM2013-4675

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記述言語：日本語   出版者・発行元：(一社)日本外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本外科学会  

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記述言語：日本語   出版者・発行元：Japan Surgical Association  

症例は65歳，女性．右乳房腫瘤を自覚しマンモグラフィ（MMG）で要精査となり当科紹介受診．触診で右C領域に2.5×2.0cmの境界明瞭で可動性良好の腫瘤を触知，MMGで同領域に多形性で不均一な石灰化の集簇を伴う直径2cmの高濃度腫瘤を認めた．乳房超音波検査（US）では，長径2cm大の内部に石灰化を伴う低エコー腫瘤を認めた．腫瘤の境界はMMGでほぼ境界明瞭だが乳頭側で一部鋸歯状を呈し，USでも腫瘤の乳頭側境界は不明瞭であった．針生検を施行したところ背景に乳腺線維腺腫を伴う浸潤性乳管癌の診断であった．術前診断T2N0M0にて右乳房全摘術，センチネルリンパ節生検術を行った．病理組織診断では2.2×1.6×1.1cm大の腫瘍結節を認め，組織学的には乳腺線維腺腫に併存した浸潤性乳管癌であった．今回われわれは，乳腺線維腺腫に併存した浸潤性管乳癌を経験したので文献的考察を加えて報告する．

DOI： 10.3919/jjsa.74.371

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その他リンク： http://search.jamas.or.jp/link/ui/2013217428

DOI： 10.1007/s10549-012-2398-5

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DOI： 10.1111/cas.12066

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DOI： 10.1016/j.surg.2012.06.026

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記述言語：日本語   出版者・発行元：The Japan Society of Coloproctology  

高齢者に対する手術では根治性と同時に主要臓器機能低下を考慮した合併症対策が必要である．著者らは，80歳以上の大腸癌症例の手術成績と長期予後を検討した．1992年から2010年の間の大腸癌切除例3,267例を80歳以上（O群），80歳未満（Y群）に分け治療成績を比較した．O群238例，Y群3,029例で，O群に補助化学療法施行例と腹腔鏡手術例が少なかった．術中出血量はY群で多く，手術時間はY群で長かった．術後合併症では，呼吸器合併症がO群に多かった．O群における合併症発生に関連する因子の多変量解析では，腹腔鏡手術例で合併症が少なかった．長期成績では全生存率はStage IIIbを除く各StageでY群が良好であったが，無再発生存率ではStage IIIaのみで差があった．再発に対する治療では，O群で緩和ケアが多く，切除術施行例が少なかった．総体的にみてO群の短期成績は良好であり，腹腔鏡手術が合併症減少に有用であることが示唆された．

DOI： 10.3862/jcoloproctology.66.221

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その他リンク： http://search.jamas.or.jp/link/ui/2013197943

記述言語：日本語   出版者・発行元：Japan Surgical Association  

症例は41歳の女性，検診で右乳房腫瘤を指摘され当院を受診した．29歳と36歳時に右乳房E領域の乳腺多形腺腫に対して，他院で腫瘍摘出術を施行されている．身体所見では，右乳房EAB領域に境界不明瞭な2.3cmの腫瘤を触知し，針生検では，乳腺多形腺腫の再発が疑われた．病理学的に明らかな悪性所見は認めなかったため，整容性を考慮して乳頭温存乳房部分切除術を施行した．術後2年，明らかな局所再発は認めていない．多形腺腫は唾液腺に多く認める良性腫瘍であるが，乳腺原発の報告は少ない．不十分な切除に起因する局所再発や悪性転化が報告されているため，術前に乳腺多形腺腫と診断された場合は，十分な切除断端距離を確保し，腫瘍被膜を損傷しないように切除する必要がある．

DOI： 10.3919/jjsa.73.3052

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その他リンク： http://search.jamas.or.jp/link/ui/2013118278

DOI： 10.3978/j.issn.2072-1439.2012.10.17

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.jss.2012.03.020

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記述言語：日本語   出版者・発行元：(NPO)日本乳癌検診学会  

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記述言語：日本語   出版者・発行元：日本臨床外科学会  

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記述言語：英語   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

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記述言語：英語   出版者・発行元：(一社)日本癌学会  

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DOI： 10.1007/s00268-012-1578-0

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Fluorouracil (5-FU) plus irinotecan combined with bevacizumab has significant activity in metastatic colorectal cancer (mCRC), but S-1 has become a substitute for continuous infusion of 5-FU and has a very low incidence of hand-foot syndrome. With the S-1 plus irinotecan regimen (SIR), the response rate was 62.5%, and the progression-free survival was 8.0 months. We report here on an update of efficacy and safety of the SIR plus bevacizumab (SIRB) regimen as first line treatment for mCRC patients. Fifty-one eligible patients with histologically confirmed advanced or recurrent colorectal cancer received this treatment. S-1 was administered orally on days 1-14 of a 21-day cycle. Patients were assigned on the basis of body surface area (BSA) to receive one of the following oral doses twice daily: 40 mg, 50 mg, or 60 mg. Irinotecan (150 mg/m 2) plus bevacizumab (7.5 mg/kg) were administered by intravenous infusion on day 1. Safety analysis identified a grade 3/4 neutropenia rate of 26%. Other grade 3/4 toxicities were diarrhea (8%), nausea (6%), vomiting (2%), and hypertension (8%). The response rate was 67% and the median progression-free survival time was 373 days. The SIRB regimen appears to be highly active and well tolerated as first-line treatment for mCRC. © Springer Science+Business Media, LLC 2011.

DOI： 10.1007/s10637-011-9743-0

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記述言語：日本語   出版者・発行元：The Japan Society of Coloproctology  

DOI： 10.3862/jcoloproctology.65.294

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その他リンク： http://search.jamas.or.jp/link/ui/2012224895

DOI： 10.1007/s00464-011-2047-9

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DOI： 10.1158/1538-7445.AM2012-2425

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DOI： 10.1158/1538-7445.AM2012-3693

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記述言語：日本語   出版者・発行元：The Japan Society of Coloproctology  

目的：後期高齢者大腸癌手術における改訂長谷川式簡易知能評価スケール（HDS-R）を用いた術後せん妄発生予測の有用性を明らかにする．対象と方法：大腸癌手術を施行した75歳以上の症例のうち，術前にHDS-Rが行われた71症例．失見当識，幻視，幻聴，異常興奮，ルートの自己抜去のいずれかを生じたとき術後せん妄ありとした．術後せん妄発生率と術前HDS-Rの値，術前因子，術中術後因子について検討した．結果：術後せん妄は71例中16例（22.5％）に発生した．単変量解析ではHDS-R＜25点，BMI，脳血管疾患の有無，眠剤常用歴が術後せん妄発生の有意な予測因子であり，多変量解析では眠剤常用歴，HDS-R＜25点が有意な術後せん妄発生予測因子（odds ratio=6.42,7.313，p=0.049,0.022）であった．結論：後期高齢者大腸癌手術例において，HDS-Rは術後せん妄発症予測に有用である．

DOI： 10.3862/jcoloproctology.65.43

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その他リンク： http://search.jamas.or.jp/link/ui/2012134192

DOI： 10.1097/SLE.0b013e318242ec97

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記述言語：日本語   出版者・発行元：日本大腸肛門病学会  

We report two cases of port site recurrence after laparoscopic colectomy for colorectal cancer.&lt;BR&gt;Case 1: A 61-year old woman was diagnosed with port site recurrence by CT and PET-CT, thirty-one months after a laparoscopic assisted low anterior resection for rectal cancer. The patient had a wide en bloc excision of abdominal wall tumor and resection of peritoneal dissemination. The patient was subsequently diagnosed with Virchow lymph node metastasis and received chemotherapy. Forty-eight months after the first operation, the patient passed away.&lt;BR&gt;Case 2: A 60-year old man was diagnosed with port site recurrence and liver metastasis by CT and PET-CT, twelve months after laparoscopic assisted colectomy for transverse colon cancer. The patient had a wide en bloc excision of abdominal wall tumor and extended posterior sectionectomy of the liver. The patient was subsequently diagnosed with lymph node metastasis, liver metastasis and lung metastasis and has been undergoing chemotherapy.&lt;BR&gt;Port site recurrence is frequently associated with systematic metastasis and poor outcomes.

DOI： 10.3862/jcoloproctology.65.31

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DOI： 10.5754/hge10010

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DOI： 10.3727/096504012X13473664562565

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

The clinical behavior and operative indications for branch duct intraductal papillary mucinous neoplasms (iPMNs) of the pancreas are controversial problems. Patients and Methods: We retrospectively identified and analyzed 249 patients with branch duct IPMNs in oui institution between 1997 and 2011. Forty-one patients who underwent surgical resection were evaluated by preoperative endoscopic ultrasonographic (EUS) findings and divided into two groups by postoperative pathological findings: low risk (low-grade dysplasia or moderate dysplasia) and high risk (high-grade dysplasia or carcinoma).All patients were evaluated by imaging examinations twice a year and disease progression and development of pancreatic ductal adenocarcinoma was analyzed. Results: The mural nodule diameter of the papillary protrusions (4.3 mm vs. 16.4 mm, p&lt
0.0001) and the width diameter of the mural nodule (5.7 mm vs. 23.2 mm, p&lt
0.0001) evaluated by EUS findings were significantly correlated with low risk and high risk Malignant disease progression of branch duct IPMNs occurred in only one case (0.4%). On the other hand, development of ductal adenocarcinoma in other pancreatic lesions occurred in five cases (2%). Male sex (n=4),elder patients over 75 (n=3), and past history of surgical resection of the pancreas (n=3) were risk factors for development of pancreatic ductal adenocarcinoma. Conclusions: The malignant disease progression of branch duct IPMNs was very rare, but development of ductal adenocarcinoma in other pancreatic lesions was not so rare. The mural nodule diameter using EUS was a reliable preoperative diagnostic finding. Careful attention should be paid to mural nodules at initial diagnosis and to development of ductal adenocarcinoma in other pancreatic lesions during follow-up.

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記述言語：英語   出版者・発行元：AMER ASSOC CANCER RESEARCH  

DOI： 10.1158/0008-5472.SABCS11-P5-13-23

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記述言語：日本語   出版者・発行元：(一社)日本消化器外科学会  

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記述言語：英語   出版者・発行元：SPRINGER TOKYO  

Liver surgery has been known to cure metastatic colorectal cancer in a small proportion of patients. However, advances in procedural technique and chemotherapy now allow more patients to have safe, potentially curative surgery. Here we review surgery for unresectable colorectal liver metastases using an expert multidisciplinary approach. With multidisciplinary management of patients with effective chemotherapy that can downstage metastases, more patients with previously inoperable disease can benefit from surgery. Portal vein embolization results in hypertrophy of the future liver remnant; on occasions, combining embolization with staged liver resection permits potentially curative surgery for patients previously unable to survive resection. However, increasing use of chemotherapy has raised awareness of potential hepatotoxicity and other deleterious effects of cytotoxic agents. Prolonged prehepatectomy chemotherapy therefore can reduce resectability even using a 2-stage procedure. Suitable timing of surgery for unresectable liver metastases during chemotherapy is critical. Because of advances in chemotherapy, colorectal cancer, like ovarian cancer, can now show survival benefit from maximum surgical debulking. Benefit from such maximum hepatic debulking surgery for metastatic colorectal disease is uncertain, but likely. Surgery in isolation may be approaching technical limits, but is now likely to help more patients because of the success of complementary strategies, particularly newer chemotherapy and targeted therapy. Expert individualized multidisciplinary treatment planning and problem-solving is essential.

DOI： 10.1007/s10147-011-0291-6

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

In July 2003, a 63-year-old man received a low anterior resection for rectal cancer. In February 2006, he underwent a right hepatectomy for a solitary metastatic liver tumor
the liver tumor had not invaded the bile duct, and a curative resection was performed. In August 2008, an enhanced computed tomography examination revealed a massive focal lesion at the point of the common bile duct. Endoscopic ultrasonography clearly revealed a hyperechoic polypoid lesion that had spread laterally on the surface of the slightly dilated bile duct and had a smooth outer hyperechoic layer. No lymph nodes were present in this region. Endoscopic retrograde cholangiopancreatography revealed an irregular stricture, and a biopsy was performed through the scope. Microscopic examination revealed a tumor characterized as a moderately differentiated adenocarcinoma resembling the liver tumor. We diagnosed the intrabiliary tumor as a metachronous metastatic bile duct tumor from rectal cancer without involvement of the liver parenchyma. This is a very rare case, with recurrence only in an extrahepatic bile duct after the complete resection of a metastatic liver tumor. This is the first clinical, pathological, and radiological description of this rare condition. © Springer 2011.

DOI： 10.1007/s12328-011-0240-y

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ACADEMIC PRESS INC ELSEVIER SCIENCE  

Background. We developed 90%-hepatectomized mice that were the fatal model, and analyzed the gene expression profiles using a complementary DNA (cDNA) microarray to clarify the mechanisms of hepatic failure after excessive hepatectomy.
Materials and Methods. Ribonucleic acid (RNA)s from the remnant hepatic tissue of 70%- and 90%-hepatectomized mice were labeled with fluorescent dyes, and hybridized to the Riken set of 39,168 full-length enriched mouse cDNA arrays. The gene expression profiles in 90%- and 70%-hepatectomized mice were analyzed by scanning date for fluorescent dye signals.
Results. The down-regulated genes in 90%-hepatectomized mice were genes activating extracellular matrix (ECM) remodeling (matrix metalloproteinases, laminins, and integrins), genes related to cytokines (tumor necrosis factor alpha converting enzyme, and Janus kinase 3) that were related to the priming, genes related to growth factor (heparin-binding epidermal growth factor-like growth factor and others), and genes promoting cell cycle progression (cyclin D1, D2, and E2) that were related to the progression of hepatocytes. The up-regulated genes were genes inhibiting ECM remodeling [plasminogen activator inhibitors (PAIs)].
Conclusions. Hepatic failure after hepatectomy was characterized by the inhibition of hepatic cell cycle priming and progression both induced by ECM remodeling in liver regeneration. Particularly, the overexpression of PAIs was thought to play the major role in the first step of inhibition of ECM remodeling. (C) 2011 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.jss.2009.11.722

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DOI： 10.1158/1538-7445.AM2011-304

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記述言語：英語   出版者・発行元：AMER ASSOC CANCER RESEARCH  

DOI： 10.1158/1538-7445.AM2011-1519

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記述言語：英語   出版者・発行元：AMER ASSOC CANCER RESEARCH  

DOI： 10.1158/1538-7445.AM2011-5210

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：INT INST ANTICANCER RESEARCH  

Aim: To evaluate the validity of surgical therapy for isolated hepatic and pulmonary colorectal metastases. Patients and Methods: Among 256 patients with liver resection for colorectal cancer metastases, 31 patients underwent resection for lung metastases synchronously or following liver resection. Results: Twenty-nine patients (93.5%) underwent pulmonary resection for lung metastases after hepatectomy. Two patients (6.5%) with synchronously identified liver and lung metastases underwent staged liver and lung resection. The 5-, and 10-year overall survival rates were 77.5% and 39.5% after the initial liver resection and were 44.7% and 38.2% after the pulmonary resection, respectively. By multivariate analysis, the presence of three or more pulmonary metastases (risk ratio=3.692, 95% confidence interval C I=1.039-13.118, p=0.043) was an independent adverse prognostic factor. Conclusion: Surgical resection for both hepatic and pulmonary metastases from colorectal cancer appears feasible and efficacious in patients with &lt; 3 pulmonary metastases.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER  

Background This study evaluates the clinical characteristics of rectal cancer involving the anal canal.
Methods A total of 346 consecutive patients with primary low rectal cancer located below the peritoneal reflection were reviewed in this study. Patients were divided into two groups according to whether the lower edge of the tumor came in contact with the anal canal (P group, n=78) or not (Rb group, n=268). Clinical and pathological parameters, recurrence rates, and survival rates were compared between the two groups.
Results The occurrence of uncommon histological types of tumor was significantly higher in the P group than in the Rb group. P group patients also had a significantly higher lateral pelvic node metastasis rate (p &lt; 0.001), lower 5-year overall survival rate (p=0.0491), and higher 5-year local recurrence rate (p=0.0171) than Rb group patients. Multivariate analysis revealed that tumor location was a significant risk factor for local recurrence. In the P group, multivariate analysis showed that uncommon histological tumor types were a significant prognostic factor.
Conclusion Rectal cancer involving the anal canal should be treated with special care, considering the particularly high lateral pelvic lymph node metastasis rate and high local recurrence rate.

DOI： 10.1007/s11605-010-1393-6

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：H G E UPDATE MEDICAL PUBLISHING S A  

Background/Aims: Recent technical developments have enabled solo surgery in laparoscopic surgery. Our experience of solo surgery using the voice-guided robotic arm in laparoscopic colectomy for colorectal cancer was analyzed.
Methodology: The colon-lifting method was used in this study. The laparoscope was handled by AESOP3000 (TM). The colon was retracted anteriorly by the thread that passed through the mesocolon. This method enables lymphadenectomy by stretching of feeding vessels and obviates the need for an assistant. The short-term outcomes and survival between robotic arm and human scopist in a series of laparoscopic colectomies were compared with a case-matched control study.
Results: The numbers of both group patients were 11 respectively. There was no conversion to open surgery in both groups. The operation time (Robotic vs. Human=269 min. vs. 265) and laparoscopic time (209 us. 212) were not significant differences. There were also no significant differences in the bleeding, the morbidity rate and the numbers of dissected lymph nodes between the two groups. The five-year overall (81.8% vs. 72.7%) and disease-free (72.7% vs. 62.3%) survivals showed no significant differences.
Conclusions: Laparoscopic solo-surgery in colectomy is safe and feasible, without any deterioration of the curative potential of the procedure.

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記述言語：英語   出版者・発行元：SPANDIDOS PUBL LTD  

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DOI： 10.1007/s00384-010-0981-y

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: The use of radioisotopes (RIs) is regulated and not all institutions have nuclear medicine facilities for sentinel node biopsy (SNB). We previously reported blue dye-assisted four-node axillary sampling (4NAS/dye) to be a suitable method for detecting sentinel nodes (SNs) without RIs. Here, we present an interim report on an observational study of this technique. Methods: From May 2003 to June 2008, 234 early breast cancer patients underwent SNB with 4NAS/dye. Lymphatic mapping was performed by injection of patent blue, and axillary sampling was performed until 4 SNs were detected. Patients with metastatic SNs underwent axillary lymph node dissection (ALND) at levels I and II, while SN-negative patients did not undergo further axillary procedures. Results: The SN identification rate was 99%. In total, 44 patients were diagnosed with metastatic disease by using the 4NAS/dye technique and underwent ALND
the remaining 189 patients did not undergo ALND (the SNB group). After a median follow-up period of 54 months, only 1 patient (0.5%) in the SNB group developed axillary recurrence. For the 4NAS/dye procedure, blue SNs were harvested in 220 patients (94%) and only unstained SNs were harvested in 13 patients (6%). Among the 44 patients with SN metastases, foci were found in blue SNs in 37 patients (84%), while they were found in only unstained SNs in 7 patients (16%). Conclusions: SNB with 4NAS/dye is a safe and reliable technique for treatment of early breast cancer patients. This technique may be particularly useful for surgeons who do not have access to radioisotope facilities. © 2010 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.ejso.2010.06.011

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DOI： 10.1093/jjco/hyq020

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DOI： 10.1158/1538-7445.AM10-830

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Japanese Journal of Cancer and Chemotherapy Publishers Inc.  

A 35-year-old woman with recurrent breast cancer with liver metastasis was treated with classical CMF because they had been resistant to anthracycline, taxane and vinorelbine. A remarkable response was achieved, FDG-PET demonstrated that FDG accumulation disappeared in the liver metastasis. Toxicities were tolerable and classical CMF could be continued on an outpatient basis without compromising quality of life. Our experience suggested that classical CMF was a useful regimen for recurrent metastatic breast cancer refractory to treatment with new agents.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

We report a case of a gastrointestinal stromal tumor (GIST) with strong and faint KIT protein staining, respectively, at two different sites. A single point mutation (c1727 T&gt
C) was detected in DNA extracted from both sites, and a further deletion mutation (c1678-1680 del GTT) was detected in DNA from the site with strong KIT protein staining. Cloning analysis indicated that the point mutation and the deletion were present on different alleles. © Springer 2010.

DOI： 10.1007/s00595-008-4029-7

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background Many studies have focused on laparoscopic techniques for the treatment of colon cancer, but such work is more limited for the treatment of rectal cancer, largely because of concerns for safety issues. This report presents an effective method of anal lavage and excision in laparoscopic low anterior resection. Methods The authors developed clamp forceps for intestinal lavage and a Y-shaped vinyl hood that can be operated under pneumoperitoneum for airproof surgery. These devices enabled secure clamping and cleansing of the area and use of automatic suture instruments for open laparotomy through a minilaparotomy wound. The authors called this technique the Y-Hood method and compared its short-term results from May 2005 to October 2008 (n = 28) with those for double-stapling technique surgical cases between September 2000 and October 2008 in which automatic suture instruments were used more than once (n = 107). A multivariate analysis of risk factors for anastomotic leakage also was performed. Results No difference in background factors such as patient sex, age, and tumor node metastasis (TNM) staging were detected. Anastomotic leakage was found in 12 cases that used multiple stapling for rectal transection (11.2%) and 2 cases that used the Y-Hood (7.1%). The cost for rectectomy was 92,505 yen for multiple stapling and 53,107 yen for the Y-Hood (p&lt
0.0001). As risk factors for anastomotic leakage, multivariate analysis identified the number of times stapling for rectal transection was performed and the height of the anastomotic region. Conclusion The Y-Hood method enables operations to be performed within the interior of the pelvis without reducing the number of ports because the instruments can be accessed using minilaparotomy. Because the use of stapling for rectal transection is minimized, this method is effective in avoiding anastomotic leakage and also cost efficient. The Y-Hood method allows for thorough intestinal lavage and safe laparoscopic low anterior resection. Copyright © 2009 Springer Science+Business Media, LLC.

DOI： 10.1007/s00464-009-0564-6

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1245/s10434-009-0708-x

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Axonal transport plays a crucial role in neuronal morphogenesis, survival, and function. Despite its importance, however, the molecular mechanisms of axonal transport remain mostly unknown because a simple and quantitative assay system for axonal transport has been lacking. In order to better characterize the molecular mechanisms involved in axonal transport, we here developed a computer-assisted monitoring system. Using lipophilic fluorochrome chloromethylbenzamido dialkylcarbocyanine (CM-DiI) as a labeling dye, we have successfully labeled membranous organelles in cultured chick dorsal root ganglia neurons. We confirmed that sodium azide, an ATPase inhibitor, and nocodazole, a microtubule-destabilizing agent, markedly suppressed anterograde and retrograde axonal transport of CM-DiI-labeled particles. We further tested the effects of several anti-neoplastic drugs on axonal transport. Paclitaxel, vincristine, cisplatin, and oxaliplatin, all of which are known to be neurotoxic and to cause neurological symptoms, suppressed anterograde and retrograde axonal transport. Another series of anti-neoplastic drugs, including methotrexate and 5-fluorouracil, did not affect the axonal transport. This is the first report of an automated monitoring system for axonal transport. This system will be useful for toxicity assays, characterizing axonal transport, or screening drugs that may modify neuronal functions. © 2010 The Japanese Pharmacological Society.

DOI： 10.1254/jphs.09352FP

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記述言語：日本語   出版者・発行元：Japanese College of Surgeons  

下血を繰り返し手術に至った，NSAIDsが誘因と考えられる多発小腸潰瘍の１例を経験したので報告する．症例は59歳，男性．C型慢性肝炎によるHCCに対して肝動脈塞栓術を施行した．術後の発熱に対し非ステロイド系消炎鎮痛剤（NSAIDs）を投与した．第10病日に下血し緊急下部消化管内視鏡検査を施行したところ，回腸末端に浅い多発潰瘍を認めた．第16病日，再度下血し出血性ショックに陥ったので緊急開腹術を施行した．回腸末端の潰瘍からの出血と判断し回盲部切除術を施行した．UＬ-IからIVの潰瘍が多発し，種々の程度の線維化，出血，血管増生を伴っていたがNSAIDsによる潰瘍として診断された．

DOI： 10.4030/jjcs.34.1057

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その他リンク： http://search.jamas.or.jp/link/ui/2010209623

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCI LTD  

Aims: To compare enhanced pathology with serial sectioning and the transcription-reverse transcription concerted reaction (TRC) for detecting sentinel node (SN) metastasis in breast cancer cases.
Methods: In total, 115 SN samples from 32 breast cancer cases were investigated by pathological examination with 2.0-mm serial sectioning and by quantitative analysis of carcinoembryonic antigen messenger RNA with the TRC.
Results: The results were concordant in 98.3% of these cases. Two histologically metastatic nodes tested negative by TRC. whereas none tested positive by TRC alone.
Conclusion: Pathological examination with 2-mm sectioning showed superior performance to TRC Under the study conditions. (C) 2008 Published by Elsevier Ltd.

DOI： 10.1016/j.ejso.2008.10.008

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: We retrospectively evaluated the efficacy of weekly paclitaxel therapy as second-line treatment for patients with advanced gastric cancer that was refractory to S-1. Patients and Methods: In total, 33 patients received intravenous paclitaxel (80 mg m-2) on days 1, 8 and 15 as part of a 4-week cycle. Results: Eight patients showed a partial response, 11 showed stable disease and 14 showed disease progression. In total, 171 courses (mean=5.2
range=3-16) were administered. Thirteen cases subsequently underwent third-line treatment. The median survival time and time to progression from the time of second-line treatment was 8.0 months and 4.2 months, respectively. The most common haematological toxicities were leukopenia and neutropenia. Non-haematological toxicities were generally mild to moderate and controllable. Conclusion: This study showed favourable therapeutic outcomes for advanced gastric cancer patients. However, it will be necessary to confirm the advantages of paclitaxel treatment for S-1-refractory advanced gastric cancer in a larger population.

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DOI： 10.1016/j.jss.2008.07.001

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background/Aims: This study examines the efficacy of a bioresorbable sodium hyaluronate-carboxy-methylcellulose-based membrane (HA/CMC membrane) in reducing postoperative abdominal adhesion and ileus after intestinal resection. Also, this study attempts to identify the possible factors that influence effectiveness through qualitative analysis of an individual patient case. Methodology: Bioresorable membranes were applied just prior to abdominal closure in 121 patients who underwent abdominal surgery. The incidence of adhesion-related postoperative ileus was compared between the treatment and control group. Severity and extent of adhesions were also examined in 27 patients who underwent follow-up laparotomy. Results: The incidence of postoperative ileus was low in the treatment group. For the partial colectomies with lymph node dissection for colorectal cancers, there was no difference between the treatment and control group in the incidence of postoperative ileus. In patients who underwent a second operation, the incidence and severity of adhesions were significantly lower for the treated area compared with the untreated area. Conclusions: HA/CMC membrane was effective in reducing postoperative abdominal adhesions. The incidence of adhesion-related postoperative ileus after colorectal cancer surgery was unchanged. The results of qualitative analysis imply that further improvement of application may allow HA/CMC membrane to be more effective in reducing postoperative ileus. © H.G.E. Update Medical Publishing S.A.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：INT INST ANTICANCER RESEARCH  

The feasibility and efficacy of adriamycin or epirubicin in combination with cyclophosphamide followed by weekly paclitaxel (AC/EC-weekly PAC) as adjuvant chemotherapy for breast cancer was investigated. Patients and Methods: Node-positive breast cancer was treated with AC/EC-weekly PAC, namely AC at 60/600 mg/m(2) or EC at 90/600 mg/m(2) x 4 at three-week intervals, followed by weekly PAC (80 mg/m(2)) x 12, namely four cycles of single weekly administration for three weeks followed by a one-week rest (3x4 PAC) or single weekly administration for 12 consecutive weeks (12 PAC). Results: One hundred and three of 109 consecutive patients enrolled were analyzed, of whom 96 (93.2%) completed the regimen. Grade 314 neutropenia occurred in 52.4% receiving AC/EC, and 10.9% of 55 receiving 12 PAC but only 2.1% of 48 receiving 3x4 PAC. Neuropathy disorders occurred in more than half receiving PAC, which did not improve after one-week rest in 3x4 PAC. Conclusion: AC/EC-weekly PAC is feasible and without serious complications.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：H G E UPDATE MEDICAL PUBLISHING S A  

Background/Aims: To evaluate surgery for local recurrence after rectal cancer resection.
Methodology: In total, 76 patients with local recurrence after rectal cancer resection were enrolled between 1978 and 1998. Of these, 61 underwent curative resection. Outcomes were assessed according to treatment. Recurrence was classified as visceral or parietal based on preoperative computed tomography or magnetic resonance imaging.
Results: The 5-year survival rates were 17.8%, 25.9%, and 36.9% for patients who underwent total pelvic exenteration, abdomino-perineal resection, and local resection, respectively. Of the 61 patients who underwent curative resection, 18 (29.5%) showed visceral recurrence and 43 (70.5%) showed parietal recurrence. Among patients with visceral recurrence, 9 (50%) underwent total pelvic exenteration, 6 (33.3%) underwent abdomino-perineal resection, and 3 (16.7%) underwent local resection. Among patients with parietal recurrence, 27 (62.8%) underwent total pelvic exenteration, 4 (9.3%) underwent abdomino-perineal resection, and 12 (27.9%) underwent local resection. Mucinous adenocarcinomas were most common among patients with parietal recurrence. Overall 5-year survival rates were 64.9% and 14.0% for patients with visceral and parietal recurrence, respectively.
Conclusions: Curative resection was effective in rectal cancer patients with visceral recurrence. Novel systemic chemical radiotherapy should be considered for patients with parietal recurrence.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: To investigate the function of tumor necrosis factor-alpha (TNF-α) during hepatocyte proliferation, we studied liver regeneration following partial hepatectomy in mice lacking type 1 TNF receptor (TNFR-1). Materials and methods: TNFR-1 knockout (KO) and wild-type mice were subjected to partial (two-thirds) hepatectomy. Liver regeneration was evaluated by assessing liver weights and Ki67 immunohistochemistry. Riken complementary DNA microarray analysis was performed for liver samples from mice undergoing partial hepatectomy to better compare different mouse partial hepatectomy models (TNFR-1 KO mice, KO group
and wild-type mice, W group). Results: Liver weight was regained after 14 days in the KO group, and after 7 days in the W group. Genes including lipopolysaccharide, toll-like receptor 4 precursor, mitogen-activated protein kinase kinase kinase 4, mitogen-activated protein kinase kinase kinase kinase 4, and mitogen-activated protein kinase 8-interacting protein were up-regulated in the KO group. As for the cell-cycle-regulated genes, the levels of cyclin D1, nuclear factor-kappa B light chain, and TNF receptor super family membrane 1a were down-regulated in the KO group. Microarray analysis showed decreased activities of the hexokinase- and phospho-fructokinase-related glycolytic pathways in the KO group. Conclusions: These results contribute to the better understanding of the mechanisms of liver regeneration after partial hepatectomy in TNFR-1 KO mice. © 2009 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.jss.2007.12.785

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

While the pre-treatment status of cancer is generally correlated with outcome, little is known about microenvironmental change caused by anti-cancer treatment and how it may affect outcome. For example, treatment may lead to induction of gene expression that promotes resistance to therapy. In the present study, we attempted to find a gene that was both induced by irradiation and associated with radioresistance in tumors. Using single-color oligo-microarrays, we analyzed the gene expression profiles of two murine squamous cell carcinomas, NR-S1, which is highly radioresistant, and SCCVII, which is radiosensitive, after irradiation with 137-Cs gamma rays or carbon ions. Candidate genes were those differentially regulated between NR-S1 and SCCVII after any kind of irradiation. Four genes, Efna1 (Ephrin-A1), Sprr1a (small proline-rich protein 1A), Srgap3 (SLIT-ROBO Rho GTPase activating protein 3) and Xrra1 [RIKEN 2days neonatethymusthymiccells (NOD)cDNAclone E430023D08 3′], were selected as candidate genes associated with radiotherapy-induced radioresistance. We focused on Efnal, which encodes a ligand for the Eph receptor tyrosine kinase known to be involved in the vascular endothelial growth factor (VEGF) pathway. We used immunohistochemical methods to detect expression of Ephrin-A1, VEGF, and the micro-vascular marker CD31 in radioresistant NR-S1 tumor cells. Ephrin-A1 was detected in the cytoplasm of NR-S1 tumor cells after irradiation, but not in SCCVII tumor cells. Irradiation of NR-S1 tumor cells also led to significant increases in microvascular density, and up-regulation of VEGF expression. Our results suggest that radiotherapy-induced changes in gene expression related with angiogenesis might also modulate microenvironment and influence responsiveness of tumors. Copyright © 2009 by the Society for Experimental Biology and Medicine.

DOI： 10.3181/0806-RM-189

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DOI： 10.1007/s00268-008-9807-2

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Purpose: The aim of this study was to assess the usefulness of intraperitoneal lavage cytology (lavage Cy) status before the resection of colorectal cancer as a predictive factor of peritoneal recurrence. Materials and methods: The lavage Cy-positive [lavage Cy (+)] rate, peritoneal recurrence rate, and 5-year survival rate were examined in 298 cases of colorectal cancer in relation to various clinicopathological factors. Results: The overall lavage Cy (+) rate was 6.0%. The lavage Cy (+) rate within the group with peritoneal and hepatic metastases was significantly higher than that in the group without metastases (46.7% vs. 3.9% and 26.9% vs. 4.0%, respectively). The lavage Cy (+) rate was not significantly associated with any of the clinicopathological factors examined. The peritoneal recurrence rate was higher in the lavage Cy (+) group than in the lavage Cy-negative [lavage Cy (+)] group, although the difference was not statistically significant. There was no significant difference in survival, regardless of the lavage Cy status, among the 263 patients who underwent curative resection. Conclusion: The lavage Cy status before resection was not a useful predictive factor of peritoneal recurrence in cases of colorectal cancer. © Springer-Verlag 2009.

DOI： 10.1007/s00384-009-0733-z