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  

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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

PubMed

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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

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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

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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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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

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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

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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

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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

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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.

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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.

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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.

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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：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

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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  

DOI： 10.5604/01.3001.0012.7866

Scopus

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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

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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

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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  

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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.

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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  

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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：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：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.

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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.

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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.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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)  

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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  

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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）  

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）  

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  

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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  

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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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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  

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）  

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  

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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  

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）  

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）  

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）  

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）  

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）  

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  

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）  

DOI： 10.3748/wjg.v22.i22.5237

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記述言語：英語  

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）  

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）  

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  

DOI： 10.1200/jco.2016.34.4_suppl.529

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記述言語：英語  

DOI： 10.1200/jco.2016.34.4_suppl.502

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記述言語：英語  

DOI： 10.1200/jco.2016.34.4_suppl.297

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記述言語：英語  

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.  

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  

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  

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  

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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）  

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  

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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）  

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  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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）  

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  

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）  

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）  

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  

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記述言語：英語  

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）  

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）  

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）  

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  

DOI： 10.1038/bjc.2014.253

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PubMed

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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）  

DOI： 10.5754/hge14154

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記述言語：英語  

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  

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）  

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）  

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）  

DOI： 10.1007/s12094-013-1079-0

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記述言語：英語  

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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）  

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）  

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）  

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  

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  

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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）  

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  

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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）  

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）  

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記述言語：英語  

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  

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）  

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）  

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  

DOI： 10.1158/1538-7445.AM2011-1519

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記述言語：英語  

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）  

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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/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）  

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記述言語：英語  

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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）  

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.  

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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/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）  

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）  

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）  

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）  

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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）  

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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：英語   掲載種別：研究論文（学術雑誌）  

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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.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）  

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）  

DOI： 10.1007/s00384-009-0733-z

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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  

DOI： 10.5833/jjgs.42.1728

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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/s10434-008-0168-8

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記述言語：英語  

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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/s10434-008-9884-3

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