Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Parathyroid carcinoma is a rare disease with a frequency of 0.005% of all malignancies [1, 2]. Various aspects of its pathogenesis, diagnosis, and treatment remain poorly understood. Furthermore, cases with secondary hyperparathyroidism are fewer. In this case report, we describe a case of left parathyroid carcinoma with secondary hyperparathyroidism. CASE PRESENTATION: The patient was a 54-year-old woman who had been on hemodialysis since the age of 40 years. At 53 years of age, her calcium levels were high, and she was diagnosed with drug-resistant secondary hyperparathyroidism and was referred to our hospital for surgical treatment. Blood tests revealed calcium levels of 11.4 mg/dL and intact parathyroid hormone (PTH) levels of 1007 pg/mL. Neck ultrasonography revealed a 22-mm large round hypoechoic mass, partially indistinct margins, and D/W ratio > 1 at the left thyroid lobe. Computed tomography scans revealed a 20-mm nodule at the left thyroid lobe. No enlarged lymph nodes or distant metastases were noted. 99mTc-hexakis-2-methoxyisobutylisonitrile scintigraphy revealed an accumulation at the superior pole of the left thyroid lobe. Laryngeal endoscopy revealed paralysis of the left vocal cord, signifying recurrent nerve palsy due to parathyroid carcinoma. Based on these results, a diagnosis of secondary hyperparathyroidism and suspected left parathyroid carcinoma was made, and the patient underwent surgery. Pathology results revealed hyperplasia in the right upper and lower parathyroid glands. The left upper parathyroid gland showed capsular and venous invasion, and the diagnosis was left parathyroid carcinoma. At 4 months post-surgery, calcium levels improved to 8.7 mg/dL and intact PTH levels to 20 pg/mL, with no signs of recurrence. CONCLUSIONS: We report a case of left parathyroid carcinoma associated with secondary hyperparathyroidism. Concomitant secondary hyperparathyroidism may cause mild hypercalcemia compared to parathyroid carcinoma alone due to the added modification of dialysis. Although our patient also presented with mild hypercalcemia, a D/W ratio > 1 on preoperative echocardiography and presence of recurrent nerve palsy on laryngoscopy led to the suspicion and treatment of parathyroid carcinoma preoperatively.

DOI： 10.1186/s12902-023-01370-x

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BACKGROUND/AIM: This study aimed to examine the clinical significance of the protein expression of the cancer stem cell (CSC) markers ALDH1A1, CD133, CD44, and MSI-1 in primary and metastatic tissues of patients with breast cancer (BC). PATIENTS AND METHODS: ALDH1A1, CD133, CD44, and MSI-1 protein expression in pairs of primary and metastatic tissues of 55 patients with BC with metastases treated at Kanagawa Cancer Center between January 1970 and December 2016 were evaluated using immunohistochemical assay and their association with clinicopathological factors and survival was examined. RESULTS: There were no significant differences in CSC marker expression rates between primary and metastatic tissues for any CSC markers. Regarding the relationship between CSC marker expression in primary tissues and survival, patients with high CD133 expression had significantly lower recurrence-free survival (DFS) and overall survival. On multivariate analysis, they were also a poor independent predictor of DFS (hazard ratio=4.993, 95%CI=2.189-11.394, p=0.0001). In contrast, there was no significant association between the expression of any CSC marker in metastatic tissues and survival. CONCLUSION: CD133 expression in the primary BC tissue may be a useful risk factor for recurrence in patients with BC.

DOI： 10.21873/anticanres.16376

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BACKGROUND/AIM: The prognosis of anaplastic thyroid carcinoma (ATC) is poor, and there is currently no established treatment to improve its outcome. We previously reported that enhancer of zeste homolog 2 (EZH2) was highly expressed in ATC, and may be a therapeutic target; however, the effects of EZH2 on ATC growth currently remain unknown. MATERIALS AND METHODS: We investigated the effects of an EZH2 inhibitor (DZNep) on four ATC cell lines (8305C, KTA1, TTA1 and TTA2). We performed a gene panel analysis of all ATC cell lines to identify differences in DZNep sensitivity between the cell lines. To investigate the effects of DZNep on the recovery of differentiation, we assessed changes in thyroid differentiation markers (TDMs) before and after the DZNep treatment using PCR. RESULTS: EZH2 was expressed in all ATC cell lines. The cell-reducing effects of DZNep were detected in all ATC cell lines, and were the strongest in KTA1 cells followed by TTA2 cells. The TTA1 and 8305C cell lines, which showed weak cell-reducing effects, had TP53 mutations. No changes in TDMs were observed in any ATC cell line. CONCLUSION: DZNep, an EZH2 inhibitor, exerted suppressive effects on the growth of ATC cell lines and has potential as a therapeutic strategy; however, its effects may be attenuated in ATC with TP53 mutations.

DOI： 10.21873/anticanres.16252

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SUMMARY: Emergencies due to malignancies usually have a severe clinical course and require urgent treatment. These scenarios are dubbed 'oncologic emergencies'. Parathyroid tumours often cause hypercalcaemia but not oncologic emergencies. We present a case of parathyroid carcinoma with severe hypercalcaemia and pancreatitis, resolved by surgical resection of the tumour assisted by extracorporeal membrane oxygenation (ECMO). A 66-year-old woman presented to our hospital because of haematuria. Laboratory findings were as follows: white blood cell count: 30 000, C-reactive protein: 17.7, calcium: 21.9, creatine kinase: 316, creatine kinase-myoglobin binding: 20, troponin I: 1415.8, amylase: 1046, lipase: 499, blood urea nitrogen: 57, and creatinine: 2.42. ECG was unremarkable. CT revealed a 4-cm low-density irregular tumour in the left lobe of the thyroid gland and severe pancreatitis. We diagnosed hypercalcaemia and pancreatitis due to parathyroid carcinoma. Volume expansion with isotonic saline was started immediately. Calcitonin, followed by denosumab, calcimimetic agents, and continuous hemodiafiltration were administered. The patient's general condition worsened due to uncontrolled hypercalcaemia. Urgent tumour resection was planned, assisted with ECMO for cardiopulmonary support and surgical field venous pressure reduction. Tumour histology was suggestive of parathyroid carcinoma. Hypercalcaemia and the patient's general condition improved gradually postoperatively. Hypercalcaemia is one of the oncologic emergency symptoms, commonly occurring because of lytic bone metastasis. However, reports about parathyroid carcinoma-causing life-threatening hypercalcaemia and pancreatitis are scarce; the fatality of this condition is estimated to be 30-70%. We report a case of survival of hypercalcaemia of malignancy. LEARNING POINTS: Parathyroid carcinoma is relatively rare and sometimes causes emergent conditions such as hypercalcaemia and severe pancreatitis. General therapy for hypercalcaemia including aggressive saline dehydration, administration of furosemide, calcitonin, zoledronic acid, and evocalcet, and dialysis is sometimes ineffective for parathyroid carcinoma. Therefore, careful planning of therapy in case of exacerbation is important. During an emergency, rapid surgical treatment despite high calcium level is the best potential therapeutic strategy.

DOI： 10.1530/EDM-22-0323

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PURPOSE: Anaplastic thyroid cancer (ATC) is a rare and highly aggressive cancer for which effective systemic therapy has long been sought. Here, we assessed the efficacy and safety of lenvatinib in patients with unresectable ATC. PATIENTS AND METHODS: The study was investigator-initiated and conducted under a multicenter, open-label, nonrandomized, phase II design. Eligibility criteria included pathologically proven ATC; unresectable measurable lesion as defined by RECIST 1.1; age 20 years or older; ECOG PS 0-2; and adequate organ function. The primary end-point was overall survival. Secondary end-points were progression-free survival, objective response rate, disease control rate, clinical benefit rate, and safety. RESULTS: Of 52 patients enrolled from 17 institutions, 42 patients who were confirmed to have ATC were included for efficacy analysis, and 50 patients were included for safety analysis. The estimated 1-year overall survival rate was 11.9% (95% CI, 4.4%-23.6%). One patient (2.4%) achieved complete response, four patients (9.5%) partial response, and 26 patients (61.9%) stable disease, including nine patients (21.4%) who demonstrated durable stable disease, giving an objective response rate of 11.9%, disease control rate of 73.8%, and clinical benefit rate of 33.3%. Adverse events of any grade were observed in 45 patients (90.0%), the most common of which of any grade included loss of appetite (48.0%), fatigue (48.0%), hypertension (44.0%), and palmar-plantar erythrodysesthesia syndrome (26.0%). CONCLUSION: Lenvatinib treatment resulted in disappointing survival for unresectable ATC patients. Although the number of responders was small, responses were durable, indicating that lenvatinib may be beneficial for selected patients. Further investigation to identify suitable candidates for lenvatinib monotherapy is needed.

DOI： 10.1016/j.ejca.2022.06.044

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Clinical screening using the National Comprehensive Cancer Network (NCCN) testing criteria may fail to identify all patients with hereditary breast and ovarian cancers. Thus, this study aimed to evaluate the strategy of expanding target patients for genetic testing among Japanese patients. We reviewed the medical records of 91 breast cancer patients who underwent genetic testing. Among 91 patients, eight were diagnosed with pathogenic or likely pathogenic variants: BRCA1 (n = 4) and BRCA2 (n = 4). Among 50 patients meeting the testing criteria of the guidelines, 6 (12%) were diagnosed with pathogenic or likely pathogenic variants. The sensitivity and specificity of screening using the testing criteria were 75% and 47%, respectively. Expanding the NCCN criteria to include all women diagnosed with breast cancer aged ≤65 years achieved 88% sensitivity but 8% specificity. The expansion of the NCCN criteria could benefit Japanese patients; however, larger studies are necessary to change clinical practice.

DOI： 10.3390/ijerph19106182

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Language：Japanese   Publishing type：Research paper (scientific journal)  

CASE: A 37-year-old pregnant woman arrived at our hospital with an abnormal mammogram. MEDICAL HISTORY: Mammography performed in June 2018 revealed an abnormal shadow on the left breast. Cytology from the 6-mm tumor in the left upper-outer quadrant revealed a malignancy. At the same time, a transvaginal echo revealed cysts, and the patient was diagnosed at 5 weeks gestation. Needle biopsy revealed a luminal A-like cStage Ⅰ, cT1bN0M0 invasive ductal carcinoma (IDC). Tumor resection and sentinel lymph node biopsy were performed under local anesthesia at 12 weeks gestation, and post-delivery adjuvant therapy was planned. Histologic examination of the resected tumor revealed that it was HER2-positive( immunohistochemistry score 3+); therefore, we had to reconsider the use of trastuzumab and decided to administer it to the patient after childbirth. The patient gave birth by cesarean section, and weekly paclitaxel plus trastuzumab was initiated 7 months after surgery. The patient is currently alive without recurrence. DISCUSSION: We faced several difficulties during the treatment of this patient. Postoperative adjuvant therapy is recommended to be administered 8 weeks after the surgical resection of the tumor. However, in our case, given that the tumor was HER2-positive, we could administer adjuvant therapy with trastuzumab only after delivery. Although the prevalence of breast cancer in women below the age of 40 years in Japan is currently as low as 4-6%, the incidence of pregnancy-associated breast cancer is predicted to increase as the number of elderly primigravida increases due to later marriage.

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BACKGROUND: Anaplastic thyroid carcinoma (ATC) is a highly aggressive thyroid tumor with a poor prognosis. However, there are limited choices for ATC treatment. Recently, the effectiveness of antibody-drug conjugates has been demonstrated in various carcinomas. Whether the targets of antibody-drug conjugates are expressed in anaplastic thyroid carcinoma remains unclear. METHODS: Fifty-four patients with ATC were enrolled in this study. Tissue microarrays were constructed using the archives of formalin-fixed paraffin-embedded tissue blocks. All sections were stained with the following antibody-drug conjugate targets: human epidermal growth factor receptor 2 (HER2), nectin-4, trophoblast cell surface antigen 2 (TROP-2), glycoprotein non-metastatic B (GPNMB), and B7-H3. RESULTS: HER2 was negative in all tissues, whereas GPNMB and B7-H3 were expressed in most ATC tissues. TROP-2 and nectin-4 were expressed in 65% and 59% of ATC tissues, respectively. TROP-2 was expressed at significantly higher levels in ATC undifferentiated from papillary thyroid carcinoma than in ATC undifferentiated from follicular thyroid carcinoma and de novo ATC. In contrast, nectin-4 expression was markedly higher in patients with de novo ATC than in those with papillary and follicular thyroid carcinoma. CONCLUSIONS: TROP-2 and nectin-4 are potential therapeutic targets for ATC undifferentiated from papillary thyroid carcinoma and de novo ATC, respectively. GPNMB and B7-H3 potential for treating all types of ATC.

DOI： 10.3390/cancers14030579

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BACKGROUND: Pneumatosis intestinalis is a rare disease characterized by gas-filled cysts within the submucosa or serosa of the intestinal tract. In recent years, pneumatosis intestinalis was reported in patients undergoing cancer treatment, and some case reports exist that report that pneumatosis intestinalis occurs during administration of vascular endothelial growth factor inhibitors, such as bevacizumab and sunitinib. Here, we report the first case of pneumatosis intestinalis during lenvatinib treatment. CASE PRESENTATION: A 77-year-old Japanese man presented to our hospital with a chief complaint of numbness in the right leg and weakness of the lower limbs 9 years after right thyroid lobectomy. Computed tomography showed a tumor 90 mm in size from the lumbar spine to the sacrum, causing spinal cord compression. Blood tests showed that the patient's thyroglobulin level was increased to 11,600 ng/ml. We diagnosed him with thyroid cancer with bone metastases. External beam radiotherapy (39 Gy/13 Fr) was performed on the bone metastases, followed by total thyroidectomy and radioactive iodine therapy. Four months after radioactive iodine therapy, lenvatinib was introduced because the symptoms of numbness and weakness recurred. Lenvatinib was introduced at dose of 24 mg, and then it was reduced to 14 mg owing to Common Terminology Criteria for Adverse Event grade 3 paronychia of the right foot. Although no further significant adverse events occurred, a scheduled computed tomography image showed pneumatosis intestinalis of the ascending colon 14 weeks after the introduction of lenvatinib. No abdominal or digestive symptoms were observed; therefore, we selected conservative treatment. We discontinued lenvatinib for a week, but we were required to restart lenvatinib as the numbness in the right leg worsened after withdrawal. Since the introduction of lenvatinib, 3 years and 5 months passed; we continued lenvatinib treatment, and the therapeutic effect remains partial response. There has been no recurrence of pneumatosis intestinalis. CONCLUSIONS: Although rare, it is important to recognize that pneumatosis intestinalis can occur in association with lenvatinib and should be differentiated from intestinal perforation. Pneumatosis intestinalis association with lenvatinib can be improved by withdrawal.

DOI： 10.1186/s13256-021-03158-w

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：MARY ANN LIEBERT, INC  

Background: Analytical information obtained from clinical tissue samples has recently become more important due to recent advancements in the clinical practice of medicine, for example, gene panel testing. However, acquiring and managing the sample quality, which greatly influences the analyses, are not sufficient and hence requires immediate attention. We introduced time stamp (TS) recording and documentation using the Standard PREanalytical Code (SPREC) for breast cancer surgery samples to monitor and control their quality. Materials and Methods: The TS recording used SPREC for quality control of each sample by recording seven factors: type of sample, type of collection, warm ischemia time (WIT), cold ischemia time (CIT), fixation type, fixation time (FT), and long-term storage. The responsibilities to record each factor were assigned among group members (breast surgeons, anesthesiologists, pathologists, operating room nurses, and medical technologists in pathology). Results: Records based on SPREC were recorded for 393 surgical cases of first-time breast cancer patients performed at the Kanagawa Cancer Center from May 2018 to April 2019. The vascular clamp time was defined as when skin flap formation was completed, regardless of the surgical procedure. An anesthesiologist recorded the vascular clamp time and sample collection time, and the pathologist recorded the fixation start time and fixation end time. WIT was 23 (3-116) minutes (breast-conserving surgery, 11 [3-38] minutes; mastectomy, 26 [5-116] minutes; and nipple-sparing mastectomy, 39 [31-43] minutes), CIT was 37 (3-1052) minutes, and FT was 43 (17-115) hours. The median CIT and FT were significantly shortened after introducing the TS system, and the variabilities were reduced. Conclusion: A TS system for quality control of breast cancer surgical sample functions well due to the establishment of highly versatile WIT and a working group consisting of multiple members of different occupations who shared roles.

DOI： 10.1089/bio.2020.0133

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Language：Japanese   Publisher：(一社)日本内分泌外科学会  

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Language：Japanese   Publisher：日本臨床外科学会  

症例は68歳,男性.下腹部に11mm大の紅色結節を認め,近医皮膚科を受診.生検を施行し,原発不明のneuroendocrine carcinomaの診断であった.CTで縦隔肺門部リンパ節の腫脹を認め,VATS(video assisted thoracic surgery)生検を施行し同様の組織所見であった.原発不明癌の精査加療目的に当院へ紹介となった.組織標本の免疫染色でCD56(+),ChromograninA(+),Synaptophysin(+),ER(+),PgR(+),HER2(-),MIB-1 10-20%の結果であり,乳腺原発が疑われたため当科へ紹介となった.視触診,マンモグラフィ,超音波で,乳腺内・腋窩リンパ節には明らかな所見を認めず,CTで肺動脈周囲リンパ節腫大・右鼠径部リンパ節腫大を認めるのみであった.PET(positron emission tomography)では肺動脈周囲リンパ節・右鼠径部リンパ節に集積を認めるものの,他に原発を示唆する所見は明らかではなかった.潜在性乳癌の皮膚転移,肺動脈周囲リンパ節・右鼠径部リンパ節転移の診断でタモキシフェン内服を開始した.現在タモキシフェン内服し4年となるが,再燃を認めていない.男性乳癌の罹患率は女性患者の0.5%程度であり,さらに男性の潜在性乳癌は症例報告が数例あるのみで極めて稀な病態である.今回われわれは,遠隔転移のみ認めた男性潜在性乳癌を経験したため,文献的考察を交えて報告する.(著者抄録)

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We conducted the Neo-LaTH study in which patients were randomized to different lengths of neoadjuvant induction anti-HER2 therapy with lapatinib and trastuzumab followed by weekly paclitaxel plus the anti-HER2 therapy, and in estrogen receptor (ER)-positive patients, with or without concurrent endocrine therapy. The use of endocrine therapy did not affect the response; comprehensive pathological complete response (CpCR) plus ypN0 rate was 57.6% and 30.3% in ER-negative and ER-positive patients, respectively. After surgery, patients received an anthracycline-based regimen based on physician's choice, followed by trastuzumab for 1 year, and in ER-positive patients, endocrine therapy for 5 years. Here, we report the 5-year survival outcomes. Among the followed-up patients (n = 212), the 5-year disease-free survival (DFS), distant DFS, and overall survival rates were 87.8% [95% confidence interval (CI), 82.5-91.6%], 93.7% (95% CI, 89.3-96.3%), and 95.6% (95% CI, 91.7-97.7%), respectively, with no difference between ER-negative and ER-positive patients. The 5-year DFS rate was significantly higher in patients who had a CpCR plus ypN0 after neoadjuvant treatment than in those who did not (91.7% vs. 85.1%; p = 0.0387). The stratified analysis showed better survival outcomes in patients who had CpCRypN0 than in those who did not after neoadjuvant treatment, regardless of use of adjuvant anthracycline therapy.

DOI： 10.3390/cancers13164008

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BACKGROUND: As Asians are more vulnerable to febrile neutropenia (FN) than Caucasians, evaluations of FN incidence and risk factors in Asians are important for the appropriate use of primary pegfilgrastim (PEG-G). PATIENTS AND METHODS: Japanese breast cancer patients receiving standard adjuvant chemotherapies were prospectively enrolled in multicenter institutions from August 2015 to July 2017. FN was evaluated from 2 treatment policies: true FN (T-FN): ≥37.5 °C, grade 4 neutropenia, mandatory hospital visit (visiting); surrogate FN (S-FN): ≥37.5 °C, oral antibiotic, no mandatory visit (non-visiting). PEG-G was used at the physicians' discretion. The primary endpoint was FN incidence during all cycles. Multivariate logistic regression analysis was performed to identify T-FN risk factors. RESULTS: Of 1005 enrolled patients, 980 women treated with FEC, E(A)C, and TC were analyzed. The FN incidence proportions in all patients were 22.5%, 27.5%, and 33.9% for FEC, E(A)C, and TC, respectively. Those of T-FN were 27.7%, 22.4%, and 36.6%; those of S-FN were 17.3%, 32.4%, and 31.5% with more frequent primary PEG-G usage. The relative dose intensity (RDI) of the 3 regimens was ≥0.85 in both groups. In the analysis of risk factors, TC (odds ratio = 2.67), age ≥ 65 years (2.24), and pretreatment absolute neutrophil count (ANC)/1000 μl (0.8) remained significant. CONCLUSIONS: FN incidences were above 20% in the 3 regimens, with TC showing the highest. RDI was maintained at a high level in both visiting and non-visiting groups. Patient-related risk factors were age and pretreatment ANC.

DOI： 10.1016/j.breast.2021.01.005

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Lenvatinib is a multi-tyrosine kinase inhibitor that inhibits angiogenesis and is currently in use for the treatment of refractory thyroid cancer. Therapy using this agent can be prolonged in patients, although serious complications may ensue among those who require surgical procedures. To the best of our knowledge, the safety of invasive surgical procedures in patients undergoing treatment with lenvatinib has not been fully evaluated. A total of 94 patients were treated with lenvatinib for thyroid cancer between June 2015 and August 2019 at the Kanagawa Cancer Center. Of this cohort, 14 invasive procedures were performed on 11 patients. A total of 8 of these procedures were performed under local anesthesia and 6 under general anesthesia; 3 belonging to the latter group were emergency procedures. No primary wound complications were observed among the patients in the cohort; however, one case of delayed healing secondary to placement of a thoracic drain for acute pneumothorax was reported in the present study. Lenvatinib was initially discontinued in this patient, but it was reintroduced 17 days later due to hypoxemia that may have been related to lung metastases. Hypoxemia improved, although wound healing spanned 14 weeks. Therapy was discontinued prior to percutaneous endoscopic gastrostomy in a patient with local progression; while no wound complications were observed, the patient ultimately died from exacerbation of neoplastic disease. In the current study, which focused on surgical interventions performed on patients undergoing lenvatinib treatment, 1 in 14 wound complications improved conservatively. However, it is critical to recognize that disease progression may occur if drugs are withdrawn prior to performing invasive procedures.

DOI： 10.3892/mco.2021.2243

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BACKGROUND: Inflammatory biomarkers have been reported to be associated with anticancer drug efficacy in various cancers. This study aimed to investigate the associations between baseline inflammatory biomarkers or dynamics of neutrophil-to-lymphocyte ratio (NLR) and treatment outcomes of lenvatinib in ATC. METHODS: Twenty ATC patients whose complete blood count were available were included in this study. Patients characteristics, overall survival (OS), and the associations between baseline inflammatory biomarkers or dynamics of NLR and treatment outcomes of lenvatinib were investigated. RESULTS: All 20 patients had a median baseline NLR of 4.5 (range, 1.4-19.7), a median platelet-to-lymphocyte ratio (PLR) of 169.9 (range, 66.8-671.1), and a median lymphocyte-to-monocyte ratio (LMR) of 2.6 (range, 0.5-5.5). The median OS was 4.2 (95% CI: 1.1-10.3) months in patients with baseline NLR ≤4.5 and 3.1 (95% CI: 1.1-8.3) months in patients with baseline NLR >4.5 (P=0.681). The median OS was 4.2 (95% CI: 1.1-7.8) months in patients with baseline PLR ≤169.9 and 3.9 (95% CI: 0.6-8.3) months in patients with baseline PLR >169.9 (P=0.822). The median OS was 3.7 (95% CI: 1.1-9.8) months in patients with baseline LMR ≤2.6 and 4.2 (95% CI: 0.6-5.4) months in patients with baseline LMR >2.6 (P=0.421). NLR was increased more than the standard deviation of the baseline NLR after lenvatinib initiation in two of 16 patients with follow-up NLR data available. The median OS was 2.0 (95% CI: 1.1- not estimable) months in the increased group but was 5.3 (95% CI: 3.1-9.8) months in the non-increased group (P=0.003). CONCLUSIONS: There was seemed to be no association between prognosis or treatment efficacy of lenvatinib and baseline inflammatory biomarker values in our cases with ATC. However, we possibly estimate prognosis for ATC during lenvatinib treatment by observing the dynamics of NLR.

DOI： 10.21037/gs-20-871

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BACKGROUND: Breast cancer is the most common form of cancer in Japan; genetic background and hereditary breast and ovarian cancer (HBOC) are implicated. The key to HBOC diagnosis involves screening to identify high-risk individuals. However, genetic medicine is still developing; thus, many patients who may potentially benefit from genetic medicine have not yet been identified. OBJECTIVE: This study's objective is to develop a chatbot system that uses augmented intelligence for HBOC screening to determine whether patients meet the National Comprehensive Cancer Network (NCCN) BRCA1/2 testing criteria. METHODS: The system was evaluated by a doctor specializing in genetic medicine and certified genetic counselors. We prepared 3 scenarios and created a conversation with the chatbot to reflect each one. Then we evaluated chatbot feasibility, the required time, the medical accuracy of conversations and family history, and the final result. RESULTS: The times required for the conversation were 7 minutes for scenario 1, 15 minutes for scenario 2, and 16 minutes for scenario 3. Scenarios 1 and 2 met the BRCA1/2 testing criteria, but scenario 3 did not, and this result was consistent with the findings of 3 experts who retrospectively reviewed conversations with the chatbot according to the 3 scenarios. A family history comparison ascertained by the chatbot with the actual scenarios revealed that each result was consistent with each scenario. From a genetic medicine perspective, no errors were noted by the 3 experts. CONCLUSIONS: This study demonstrated that chatbot systems could be applied to preliminary genetic medicine screening for HBOC.

DOI： 10.2196/25184

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

Anaplastic thyroid carcinoma (ATC) is one of the most aggressive cancer types; however, the molecular mechanism contributing to the aggressive characteristics remain unclear. Membrane type 1 matrix metalloproteinase (MT1-MMP) plays an important role in cancer invasion and has been associated with a poor prognosis in various malignant neoplasms. In this study, we investigated the relationship between MT1-MMP expression and the proliferation and invasion of ATC cells, along with the association with clinicopathologic factors in patients with ATC. Suppression of MT1-MMP reduced the proliferation and invasion of ATC cells, and suppressed ERK activity, indicating a role in cancer cell proliferation in collagen matrix culture conditions. The expression of MT1-MMP was detected in 29 of 34 (85.3%) surgical specimens from ATC patients. In addition, the expression of MT1-MMP in the tumor lesion was higher than that of normal and stromal tissues. Collectively, these results suggest that elevated MT1-MMP expression plays a role in the pathogenesis of ATC, which may promote its aggressive characteristics such as proliferation and invasion, highlighting a potential new therapeutic target.

DOI： 10.1016/j.bbrc.2020.06.043

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PURPOSE: Fibroblast growth factor receptor 4 (FGFR4) expression has association with tumor malignancy. In thyroid cancers, FGFR4 has been reported to be characteristically expressed in aggressive thyroid tumors, such as anaplastic thyroid carcinoma (ATC). METHODS: We investigated FGFR4 expression in patients with ATC and analyzed their clinical responses to lenvatinib. Primary tumor samples were obtained from 12 patients with ATC who underwent surgery or core needle biopsy. FGFR4 protein expression in all ATC samples was analyzed via immunohistochemistry, and the treatment efficacy of lenvatinib was evaluated. RESULTS: The proportion of FGFR4-positive cells in the samples ranged from 0 to 50%. Four patients had partial responses, and three patients had stable diseases as a best clinical response to lenvatinib. The median PFS durations of patients with none, weak, and moderate intensity were 0.5, 3.2 (95% CI 1.1-not estimable [NE]), and 4.6 (95% CI 1.1-NE) months, respectively (p = 0.003). CONCLUSIONS: Because FGFR4 was expressed in ATC tissues, the FGFR4 expression might be associated with the treatment efficacy of lenvatinib in a part of ATC patients. To clarify whether FGFR4 can serve as a prognostic or predictive factor for lenvatinib therapy, more cases must be accumulated.

DOI： 10.1007/s00228-020-02842-y

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BACKGROUND/AIM: Metaplastic breast carcinoma (MBC) is a rare malignancy, which is often triple-negative for the hormone receptors and human epidermal growth factor receptor 2, and thus, does not benefit from targeted therapy. In this study, we examined the expression of methylation and demethylation enzymes by immunostaining MBC and the adjacent normal tissues or triple-negative ductal carcinoma (TNDC), and identified alterations that may be used as therapeutic targets. MATERIALS AND METHODS: We retrospectively studied surgical specimens from 15 patients who underwent surgery for MBC at Kanagawa Cancer Center between 2005 and 2016, and similarly from 14 patients with TNDC. The frequencies of high methylation/demethylation enzyme expression were compared among them. RESULTS: The frequencies of high enhancer of zeste homolog 2 (EZH2) and multiple myeloma SET domain (MMSET) expression were significantly higher in both MBC and TNDC than in normal tissue. CONCLUSION: EZH2 and MMSET may be useful therapeutic targets in MBC.

DOI： 10.21873/anticanres.14172

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BACKGROUND: The tumor-node-metastasis (TNM) classification system to categorized anaplastic thyroid cancer (ATC) was revised. METHODS: The revised system was evaluated using a large database of ATC patients. RESULTS: A total of 757 patients were analyzed. The proportion and median overall survival values (OS: months) for each T category were T1 (n = 8, 1.1%, 12.5), T2 (n = 43, 5.7%, 10.9), T3a (n = 117, 15.5%, 5.7), T3b (n = 438, 57.9%, 3.9), and T4 (n = 151, 19.9%, 5.0). The OS of the N0 and N1 patients were 5.9 and 4.3, respectively (log-rank p < 0.01). Sixty-three (58.3%) patients migrated from stage IV A to IV B by revision based on the existence of nodal involvement and 422 patients (55.7%) were stratified into stage IV B, without a worsening of their OS (6.1), leaving 45 patients (5.9%) in stage IV A with fair OS (15.8). The hazard ratios for the survival of the patients of stage IV B compared to stage IV A increased from 1.1 to 2.1 by the revision. No change was made for stage IV C (n = 290, 38.8%, 2.8). CONCLUSION: The revised TNM system clearly indicated the prognoses of ATC patients by extracting rare patients with fair prognoses as having stage IV A disease and categorized many heterogeneous patients in stage IV B.

DOI： 10.3390/cancers12030552

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Anaplastic thyroid cancer (ATC) is an orphan disease with extremely poor prognosis. In particular, unresectable stage IVC ATC is extremely difficult to treat and is associated with a survival of only a few months, even when treated with irradiation and/or chemotherapy. In 2015, lenvatinib was approved for the treatment of ATC in Japan. The aim of the present study was to evaluate the efficacy of lenvatinib for stage IVC ATC. A total of 32 patients with pathologically confirmed stage IVC ATC who were treated at the Kanagawa Cancer Center between 2011 and 2018 were included in the present study, of whom 16 patients were treated with lenvatinib (L group). The remaining 16 patients received palliative therapy (P group), of whom 7 were treated with weekly paclitaxel, 2 received external radiation for tumor reduction 5 days per week until treatment completion, and 2 underwent tracheostomy to avoid the risk of asphyxiation. The survival curves of both groups were analyzed using the log-rank test. The median overall survival time of the L and P groups was 4.2 and 2.0 months, respectively. A significant survival benefit was observed in the L group compared with that in the P group (P=0.00298). A reduction in tumor size by ≥30% (clinical partial response) within 1 month after treatment was observed in 5 patients (31.3%) in the L group and in no patients in the P group. Therefore, lenvatinib treatment yielded a median survival benefit of ~2 months compared with palliative therapy in stage IVC ATC. However, although a reduction in tumor size by ≥30% was confirmed in 5 patients who received lenvatinib treatment, 2 of those patients succumbed to massive necrosis and bleeding. These results suggest that an appropriate lenvatinib dose reduction is necessary.

DOI： 10.3892/mco.2019.1964

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Occult thyroid carcinoma preceded by clinical manifestations and findings from extrathyroidal tumors is rare. The lack of malignant findings in the thyroid during the preoperative examination makes diagnosis difficult. We encountered a 71-year-old man with a primary ectopic thyroid carcinoma causing superior vena cava syndrome. Although no malignant findings were found in the thyroid gland, biopsy of bone metastases led to the diagnosis of thyroid cancer. HE staining of bone metastases revealed nuclear features of papillary carcinoma, and immunostaining was positive for thyroglobulin and PAX-8. The second case involved an 84-year-old man with a mediastinal tumor and suspected thyroid cancer because of high thyroglobulin levels in blood. The pathological tumor finding was papillary thyroid cancer. The last case was that of a 56-year-old woman lacking preoperative thyroid examination malignant findings, but with cervical lymph node metastasis. The thyroglobulin level of the lymph node puncture fluid was useful for preoperative diagnosis. We performed total thyroidectomy plus bilateral modified neck dissection. Pathology revealed a 1 mm papillary carcinoma in the left lobe. All of these cases were difficult to diagnose. However, we combined the results of various tests such as radiographic imaging, blood tests, and immunohistological tests to diagnose our patients.

DOI： 10.1155/2020/4249067

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INTRODUCTION: Despite the excellent prognosis associated with pathological complete response (pCR) to neoadjuvant chemotherapy (NAC), some patients still develop recurrence. Here, we investigated the outcomes of breast cancer patients with pCR, as well as the clinical and pathological predictors of cancer recurrence in these patients. MATERIALS AND METHODS: Of the 1599 breast cancer patients treated with NAC, we evaluated 394 patients who achieved pCR between January 2007 and December 2016. pCR was defined as no evidence of invasive cancer in breast. Residual in situ ductal and axillary lymph node diseases were not considered. We analyzed the outcomes using the Kaplan-Meier method. We assessed the association of clinical and pathological predictors with cancer recurrence using the cox proportional hazards regression model. RESULTS: The median follow-up time was 63 months. The 5-year disease-free survival rate was 92.3%. Cancer recurrence was observed in 28 patients (7.1%): local recurrence 8 patients (2.0%), visceral metastasis 10 patients (2.5%), and brain metastasis 10 patients (2.5%). Brain metastases were found in patients with HER2 type breast cancer. The significant predictors of cancer recurrence were HER2 positivity (p = 0.04), clinical tumor size (p < 0.01), and lymph node metastasis (p < 0.01) before NAC on univariate analysis and only lymph node metastasis on multivariate analysis. CONCLUSION: Patients achieving pCR to NAC showed excellent outcomes. Advanced clinical stage, large tumor size, presence of lymph node metastasis, and HER2 positivity before NAC were identified as significant predictors of cancer recurrence. Residual in situ ductal and lymph node diseases after NAC were not significant predictors.

DOI： 10.1016/j.ejso.2019.08.001

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SUMMARY: Anaplastic transformation of a primary thyroid tumor whose process can be followed is rare. The objective this study is to report a case of anaplastic transformation of locally advanced papillary thyroid carcinoma after treatment with lenvatinib. A 74-year-old woman consulted a local physician because of cough and bloody sputum. Thyroid cancer with tracheal invasion was suspected on computed tomography (CT) imaging, and she visited our hospital for treatment. We suspected anaplastic thyroid cancer (ATC) and core needle biopsy was performed. Histologic sections of the core needle biopsy showed that the tumor formed a papillary structure, and we diagnosed papillary thyroid carcinoma. Surgery would have been difficult, and we initiated lenvatinib at a low dose of 8 mg/day. CT on day 40 of lenvatinib treatment revealed that the thyroid tumor had shrunk remarkably. CT on day 111 revealed that tumor regrowth and tracheal invasion had been exacerbated. Core needle biopsy was performed, and histologic sections of the core needle biopsy that was performed after regrowth of the tumor showed that individual cancer cells had large, irregular nuclei, and necrosis was also observed. The immunohistochemical findings were negative for thyroglobulin, and only a few cells were positive for thyroid transcription factor 1, and we diagnosed ATC. Anaplastic transformation of the target lesion may be one of the causes of lenvatinib treatment failure in differentiated thyroid carcinoma. LEARNING POINTS: Anaplastic transformation of a primary thyroid tumor whose process can be followed is rare. The resistance mechanism of lenvatinib in treatment for differentiated thyroid carcinoma has not been clarified. Anaplastic transformation of the target lesion may be one of the causes of lenvatinib treatment failure in differentiated thyroid carcinoma.

DOI： 10.1530/EDM-19-0085

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In 2014/2015, tyrosine kinase inhibitors (TKIs) were introduced as a secondary treatment for refractory differentiated thyroid cancer (DTC) in Japan. While renal dysfunction is an adverse event of TKI, data on this adverse event in TKI-treated DTC remains insufficient. Here, we investigated renal function in patients undergoing TKI treatment for DTC and evaluated the efficacy of dose reduction/withdrawal for cases of renal dysfunction.A total of 73 cases of radioactive iodine-refractory DTC treated with sorafenib (n = 22) or lenvatinib (n = 51) were included. Patient data evaluated were TKI treatment period, estimated glomerular filtration rate (eGFR) before and after TKI therapy, incidence and degree (maximum value at time of TKI treatment) of proteinuria, and albumin levels before and after TKI therapy were compared.The mean ΔeGFR was -6.75% with lenvatinib and +5.90% with sorafenib. It was not significant (P = .15). The mean Δalbumin was -8.90% and -5.85% with lenvatinib and sorafenib, respectively; there was no significant difference between the lenvatinib and sorafenib groups (P = .77). According to our program of TKI dose reduction and withdrawal, all patients except 2 with diabetes were successfully continuing treatment.Overall, the present results demonstrated that renal function is negatively affected by long-term TKI treatment for RAI-refractory DTC. However, heightened proteinuria, decreased eGFR and albumin levels, and significant but apparently reversible renal dysfunction were more frequent with lenvatinib than sorafenib.

DOI： 10.1097/MD.0000000000017588

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SUMMARY: The objective this study is to report two cases of thyroid gland invasion by upper mediastinal carcinoma. Mediastinal tumors are uncommon and represent 3% of the tumors seen within the chest. In reports on mediastinal masses, the incidence of malignant lesions ranged from 25 to 49%. The thyroid gland can be directly invaded by surrounding organ cancers. We report these cases contrasting them to the case of a thyroid cancer with mediastinal lesions. Case 1 was a 73-year-old woman who was diagnosed with papillary thyroid carcinoma, and she underwent surgery and postoperative radioactive iodine. Case 2 was a 74-year-old man who was diagnosed with non-small-cell lung carcinoma, favor squamous cell carcinoma, and he underwent chemoradiotherapy. Case 3 was a 77-year-old man who was diagnosed a thymic carcinoma based on pathological findings and referred the patient to thoracic surgeons for surgical management. The images of the three cases were similar, and the differential diagnoses were difficult and required pathological examination. Primary thyroid carcinoma and invading carcinoma originating from the adjacent organs need to be distinguished because their prognoses and treatment strategies are different. It is important to properly diagnose them by images and pathological findings. UNLABELLED: The thyroid gland in the anterior neck can be directly invaded by surrounding organ cancers. Primary thyroid carcinoma and invading carcinoma originating from the adjacent organs need to be distinguished because their prognoses and treatment strategies are different. It is important to properly diagnose by images and pathological findings.

DOI： 10.1530/EDM-19-0028

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In patients with distant metastasis, treatment for differentiated thyroid cancer (DTC) includes complete total thyroidectomy, followed by radioactive iodine (RAI) therapy for metastatic lesions. Tyrosine kinase inhibitor (TKI) treatment is the final treatment option for metastatic lesions, which is incurable with surgery/RAI therapy. The present study examined whether treatment outcomes for DTC in patients with distant metastasis improved following TKI treatment. This study included 147 patients (median age, 71; range, 33-91 years) who underwent surgery in our hospitals and were diagnosed with distant metastasis. Disease progression was observed in 70 patients, of whom 56 were treated with TKI (TKI group); 14 refused TKI treatment or showed no treatment indication [untreated (UT) group]. Disease progression and treatment outcomes were assessed using imaging evaluations. The present study investigated thyroglobulin doubling time (Tg-DT) and Tg antibody presence/absence and their relation to disease progression. Overall survival following disease progression between the two groups was compared. The study included 22 cases of sorafenib, 49 of lenvatinib, and 15 involving TKIs. The mean dosing period for sorafenib was 153 days and for lenvatinib was 462 days. In the TKI group, 16, 26, and 9 patients exhibited partial responses (PRs), stable disease (SD), and progressive disease (PD), respectively, whereas 5 patients were not evaluable. The disease control rate (DCR) (PR+SD) was 75.0%. A total of 16 patients died in the TKI group, whereas 10/14 patients in the UT group died. Survival curves for the groups were significantly different. TKI treatment improved the prognosis of patients with distant metastasis and PD.

DOI： 10.3892/ol.2019.10180

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Some patients with differentiated thyroid cancer (DTC) may require an initial low dose (LD) of lenvatinib. However, few studies have investigated the efficacy of LD lenvatinib. We compared the efficacy and tolerability of lenvatinib at an initial LD to those of the standard initial dose of 24 mg in patients with DTC.In this cross-sectional study, records of patients with DTC treated with lenvatinib were retrospectively reviewed. Patients were divided into 2 groups based on the initial dose of lenvatinib: a full-dose (FD) group that received an initial dose of 24 mg/d and a LD group that received an initial dose of less than 24 mg/d. Categorical variables were compared with the Fisher exact test and continuous variables with Student t test. A progression-free survival (PFS) curve was constructed with the Kaplan-Meier method. A probability (P) value of < .05 was considered statistically significant.Thirty-six patients with DTC were treated with lenvatinib (30 in the FD group and 6 in the LD group). The response rates were 43% and 33% in the FD and LD groups, respectively. The median PFS duration was 696 [95% confidence interval (CI): 318-not available (NA)] days in the FD group. The median PFS of the LD group was not reached (95% CI: 124-NA) (P = .293). Treatment interruptions were required in 25 (83%) patients in the FD group and 4 (67%) in the LD group (P = .573). Dose reductions were required in 28 (93%) patients in the FD group and 4 (67%) in the LD group (P = .121). There were no significant differences in the incidences of common adverse events between the 2 groups.The LD group also required dose reduction and interruption frequently. Since these findings are only the short-term results of a limited number of cases, a large number of cases and long-term observations are needed to determine whether an initial LD is effective for patients with DTC in poor general condition.

DOI： 10.1097/MD.0000000000014774

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Anaplastic thyroid cancer (ATC) is associated with an extremely poor prognosis and is resistant to the majority of chemotherapies. In 2015, lenvatinib was approved for treating ATC in Japan. The present study aimed to evaluate the overall survival (OS) of patients with ATC treated with lenvatinib. A total of 23 patients with a definitive histological diagnosis of ATC who were treated at Kanagawa Cancer Center (Yokohama, Kanagawa. Japan) were enrolled. Surgical treatment was possible in 10 patients (including one debulking surgery), and lenvatinib treatment was postoperatively started. The remaining 13 patients were not eligible for debulking surgery; thus, lenvatinib was promptly approved as a life-saving treatment. The therapeutic effect was determined according to the Response Evaluation Criteria In Solid Tumors criteria (ver.1.1). The patients exhibited a lenvatinib response rate of 17.4% and a disease control rate of 43.5%. However, lenvatinib was associated with a 100% incidence of treatment-related adverse events (AEs), with hypertension being the most common AE (91.3%). Additionally, dose interruptions and reductions were required due to the development of tumor fistulas or other tumor-related AEs, and 9 (39.1%) patients discontinued treatment due to grade 3 or higher AEs. The median OS time was 166 days. Overall, the present study demonstrated the effectiveness of lenvatinib against ATC, which is often chemotherapy-resistant. Successful treatment of fistulas developing due to tumor necrosis at the site of the primary lesion is crucial for improving the patient outcome. The response to lenvatinib in patients with ATC varies on a case-by-case basis and requires further investigation in future studies.

DOI： 10.3892/ol.2018.9553

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PURPOSE: Angiogenesis plays a crucial role in the development, growth, and metastasis of carcinomas, and studies have reported conflicting evidence regarding the VEGFR expression in anaplastic thyroid cancer. We investigated the expression of VEGFR2 in patients with anaplastic thyroid cancer (ATC) and analyzed the clinical response to the VEGFR inhibitor lenvatinib. METHODS: This cross-sectional study included primary tumor samples obtained from 12 patients with ATC, including 5 males and 7 females (age range 63-89 years) who underwent surgery or core needle biopsy for a thyroid tumor in the Department of Breast and Endocrine Surgery at Kanagawa Cancer Center in Kanagawa, Japan. VEGFR2 protein expression in the ATC samples was analyzed by immunohistochemistry in all patients, and the therapeutic effect of lenvatinib was evaluated in seven patients who underwent tissue biopsy and lesion evaluation. RESULTS: VEGFR expression was not detected in any of the samples from the 12 patients. Four of the 12 patients treated with lenvatinib had partial response, the three patients achieved stable disease, and the five patients were not examined. CONCLUSIONS: There was no correlation between the expression of VEGFR2 in tumor tissue and the clinical response to lenvatinib among patients with ATC. Further studies are necessary to elucidate the mechanism underlying the response to lenvatinib.

DOI： 10.1007/s00280-018-3657-x

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Language：Japanese   Publisher：日本臨床外科学会  

近年,BRCA遺伝子変異と耳下腺腫瘍の関連性を示唆する報告がされている.症例は41歳,女性.家族歴で母方祖母;乳癌・卵巣癌,母;卵巣癌,母方叔母二人に乳癌を認める.32歳時に左乳癌に対して左乳房部分切除+センチネルリンパ節生検を施行し,浸潤性乳管癌,ER(-),PgR(-),HER2(-)の診断であった.当院遺伝カウンセリング受診後の遺伝子検査ではBRCA1変異陽性であり,同年リスク低減卵巣卵管切除術を施行した.続けて,リスク低減乳房切除術を予定していたが,耳下腺癌を認めて右耳下腺摘出術を施行した.病理結果は,粘表皮癌,Histological grade;Intermediate grade(AFIP series 4)/High grade(WHO classification)であった.BRCA1変異陽性乳癌術後に耳下腺癌を合併した1例を経験したので報告する.(著者抄録)

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2018&ichushi_jid=J03156&link_issn=&doc_id=20181004020004&doc_link_id=10.3919%2Fjjsa.79.1825&url=https%3A%2F%2Fdoi.org%2F10.3919%2Fjjsa.79.1825&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

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In the original publication of this article, Table 1 was published incorrectly with rows out of order under "Distant metastasis (n, %)".

DOI： 10.1007/s12282-018-0832-1

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INTRODUCTION: Undifferentiated pleomorphic sarcoma (UPS) constitutes less than of all sarcomas in adults and rarely involves the breast. We herein present a patient with UPS of the breast with lung and bone metastases. This case was treated by eribulin as first chemotherapy, and performed mastectomy for local control. CASE PRESENTATION: A 55-year-old female presented a tumor measuring over 5 cm with pain in the right breast. Pathology of the incisional biopsy specimen led to a diagnosis of UPS. Computed tomography revealed a right tumor, right pubic tumor with osteolysis, and multiple lung metastases. She was started on eribulin; however, the tumor grew in size, indicating progressive disease, and the patient underwent simple mastectomy for local control. Pathological evaluation of the excised tumor was consistent with UPS. The patient elected palliative treatment and died due to respiratory failure caused by multiple lung metastases that exacerbated four months after surgery. DISCUSSION: Soft tissue sarcomas with distant metastases are treated with chemotherapy; however, there are currently no effective chemotherapeutic agents for UPS of the breast. Given the potential efficacy of eribulin in soft tissue tumors and the easy management of associated side effects, the patient was treated with eribulin, which however was insufficient for disease control. CONCLUSION: The prognosis of UPS with distant metastasis remains poor. Treatment approaches including chemotherapy and surgery should be considered based on the patient's general condition, prognosis, and expectations on quality of life.

DOI： 10.1016/j.ijscr.2018.07.049

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A 63-year-old man was diagnosed with multiple lung metastases from anaplastic thyroid cancer and received lenvatinib. Follow-up computed tomography on day 34 of lenvatinib treatment showed pneumothorax. The pneumothorax was temporarily improved with chest drainage. However, pleurodesis was performed to treat a relapse of the pneumothorax. Pneumothorax during chemotherapy for a malignant tumor is considered a relatively rare complication. This case is the first documentation that pneumothorax may develop during lenvatinib treatment. The possible development of pneumothorax should be considered when lenvatinib is used in patients with lung metastasis.

DOI： 10.1155/2018/7875929

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Most substernal goiters can be managed through the transcervical approach, but a sternotomy is required in some cases. This report is about a large substernal goiter, which was resected via a transcervical and full sternotomy approach. The patient was a 57-year-old female, who visited our hospital for surgical treatment for a large substernal goiter. Computed tomography of the neck and chest revealed that the substernal goiter extended to both sides of the thorax and had compressed the trachea. We performed total thyroidectomy safely via a transcervical and full sternotomy approach. No postoperative complications occurred, except transient hypocalcemia. A histopathological examination did not reveal any malignancy, and the lesion was diagnosed as an adenomatous goiter. Most substernal goiters can be managed through the transcervical approach, but a full sternotomy is required when a substernal goiter extends to both sides of the thorax and/or has a larger diameter than the thoracic inlet or airway constriction is revealed. A full sternotomy provides excellent exposure and can help reduce the risk of complications, such as recurrent laryngeal nerve palsy and injuries to major blood vessels.

DOI： 10.1155/2018/6107982

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BACKGROUND/AIM: Enhancer of zeste homolog 2 (EZH2) is a member of the polycomb group of genes, which are key factors in the regulation of cell proliferation and differentiation. EZH2 is overexpressed in many malignancies. We analyzed EZH2 protein expression levels in different histological subtypes of thyroid cancer to examine its utility as a prognostic factor. MATERIALS AND METHODS: We examined EZH2 protein expression by immunohistochemistry in tissue samples from 67 cases of poorly differentiated (PDTC) and 48 cases of anaplastic thyroid carcinoma (ATC), and in samples of adjacent normal and differentiated thyroid carcinoma (DTC). We examined differences in expression of EZH2 among various histological types of thyroid cancer, and the relationship between EZH2 expression and patient outcome. RESULTS: EZH2 protein was expressed in PDTC and ATC, but not in normal thyroid gland or DTC. EZH-positivity increased in the order of DTC, PDTC, and ATC (p<0.01). Higher EZH2 expression correlated with poorer survival in PDTC (p=0.004), and a similar but non-significant trend was observed in ATC (p=0.166). Multivariate analysis identified EZH2 as an independent prognostic factor similar to metastatic status in the Japanese Society of Thyroid Surgery (JSTS) classification of PDTC. CONCLUSION: EZH2 overexpression is associated with malignant potential in thyroid cancer, and may thus be a useful prognostic marker of aggressive thyroid cancer.

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The occurrence of renal tumors originating from thyroid cancer is extremely rare with a few effective treatments for renal metastases. Here, we report the cases of two patients with differentiated thyroid cancer who underwent nephrectomy for a metastatic kidney tumor. Case 1 was a 74-year-old man who was diagnosed with right kidney tumor 10 years after initial surgery for papillary thyroid cancer (PTC). Right nephrectomy was performed, and the pathology was metastatic PTC. Case 2 was a 68-year-old woman who was diagnosed with left kidney tumor 24 years after surgery for follicular thyroid carcinoma (FTC). Left nephrectomy was performed, and the pathology was metastatic FTC. Nephrectomy for single renal metastasis could be considered a treatment option if the patients' general condition is positive.

DOI： 10.1155/2018/7842792

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BACKGROUND: Non-functioning parathyroid carcinoma is a rare disease that is difficult to distinguish from other diseases based on the lack of hyperparathyroidism. This is a report of non-functioning parathyroid carcinoma diagnosed by reverse transcription polymerase chain reaction (RT-PCR) targeting parathyroid hormone (PTH) messenger RNA. CASE PRESENTATION: The patient is a 67-year-old male who visited our hospital for the chief complaint of hoarseness. A 5-cm mass was observed in the right lobe of the thyroid gland, and poorly differentiated thyroid carcinoma was suspected according to the fine-needle biopsy results. The laboratory data for thyroid functions, thyroglobulin, anti-thyroglobulin antibodies, calcium, phosphorus, and intact-PTH were all within the normal range. Right recurrent nerve paralysis was observed preoperatively. The patient was diagnosed with poorly differentiated thyroid carcinoma, and total thyroidectomy and central node dissection with partial resection of the right recurrent nerve and esophageal muscle were performed. The pathological findings revealed atypical cells containing clear cells in solid and alveolar structures with broad fibrosis. Mitosis, focal coagulative necrosis, and vascular and capsular invasions were observed. A slightly positive PTH immunohistochemical stain was noted, whereas the RT-PCR results were positive. We finally diagnosed this tumor as non-functioning PTC. No distant metastasis occurred, and the patient is still alive. CONCLUSIONS: This is a report of a patient with non-functioning parathyroid carcinoma, which is clinically very rare. We diagnosed this tumor as non-functioning parathyroid carcinoma using RT-PCR for PTH mRNA.

DOI： 10.1186/s40792-017-0357-4

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Tokyo  

Background: Surgical biopsy of metastatic lesions followed by pathological confirmation for the investigation of biomarkers is occasionally proposed as an effective strategy in the treatment of metastatic breast cancer. However, few reports have examined Ki-67 immunohistochemical expression in distant metastatic lesions of breast cancer patients. This study aimed to investigate the clinicopathological significance of subtypes and Ki-67 immunohistochemical expression in metastatic breast cancer lesions. Methods: We retrospectively studied surgical specimens of primary breast cancer tumors and their corresponding metastatic lesions from patients (n = 68) who underwent surgery for primary breast cancer tumors between December 1977 and March 2013. Tissue microarrays were constructed using primary and metastatic lesions, and were stained with antibodies against estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, and Ki-67. We also examined the clinicopathological characteristics and outcome measures of patients with metastatic breast cancer using primary and paired metastatic lesions. Results: Compared with the primary lesions, there was no significant difference in subtypes in the metastatic lesions according to metastatic sites. Metastatic lesions of the brain, viscera, and bone exhibited slightly higher levels of Ki-67 immunohistochemical expression compared with primary lesions. A Cox proportional hazards model using multivariate analysis demonstrated that high Ki-67 immunohistochemical expression in distant metastatic lesions was associated with poorer overall survival outcomes after biopsy of recurrence lesion (hazard ratio 2.307
95% confidence interval 1.207–4.407, P = 0.011). Conclusions: High Ki-67 immunohistochemical expression levels in distant metastatic lesions were independently associated with poorer overall survival outcomes after biopsy of recurrence lesion in breast cancer patients.

DOI： 10.1007/s12282-017-0774-z

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：INT INST ANTICANCER RESEARCH  

Background: Thyroid dysfunction is occasionally reported after the administration of nivolumab. We report on the incidence of and risk factors for nivolumab-induced thyroid dysfunction in patients with non-small lung cancer. Patients and Methods: A total of 82 patients who received nivolumab between January 2016 and December 2016 at the Kanagawa Cancer Center were included. Prior to nivolumab treatment, 72 patients had normal thyroid function. Results: Among the 72 patients with normal thyroid function prior to nivolumab treatment, the incidence of thyroid dysfunction was 19.5%. There were no significant differences between patients in whom thyroid dysfunction had occurred regarding sex, age, nivolumab dose, or thyroid function prior to nivolumab administration. However, the total number of doses of nivolumab was significantly greater in patients who developed thyroid dysfunction after nivolumab treatment (p=0.03). Conclusion: The total number of doses administered may be a risk factor for the development of thyroid dysfunction after nivolumab therapy.

DOI： 10.21873/invivo.11195

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BACKGROUND: We present the cases of 2 patients with invasive thyroid cancer, who underwent reconstructive surgery using a deltopectoral flap. Although the overall rate of extrathyroidal extension in patients with thyroid cancer is quite low, skin invasion is the most common pattern observed. Reconstructive surgery, involving local skin flaps, is required in these patients. The deltopectoral flap relies on the blood supply from intercostal perforators of the internal thoracic artery and usually requires skin grafting to the donor site. The internal thoracic artery is rarely sacrificed in these cases, even in an advanced surgery such as in patients with invasive thyroid cancer. CASE PRESENTATION: A 55-year-old man with a distended thyroid gland presented to our hospital. He underwent advanced surgery, including skin excision, because we suspected that his tumor was thyroid cancer. The defect was covered with an ipsilateral deltopectoral flap via transposition of the flap, without skin grafting. In the second case, a 67-year-old woman with thyroid cancer that metastasized to her neck lymph nodes presented to our institution. Although the ipsilateral internal thoracic artery was sacrificed near its origin during tumor resection, the deltopectoral flap was raised in the usual manner without any complications. The skin defect caused by the tumor resection was covered with the flap. The patient had an uneventful clinical course for more than 2 years of follow-up. These 2 cases show the effectiveness of using the deltopectoral flap as a reconstructive option for patients with thyroid cancer who underwent radical surgery, resulting in a skin defect. The first case shows that this flap does not always require skin grafting to the donor site. To our knowledge, the second case may be the first report of a deltopectoral flap that was safely raised and applied with resection of the bifurcation of the ipsilateral internal thoracic artery. CONCLUSIONS: Although thyroid cancer surgery with surrounding skin excision is a rare procedure, we found that the deltopectoral flap was useful and should be the first choice for patients undergoing reconstructive surgery, whether the bifurcation of the ipsilateral internal thoracic artery is sacrificed.

DOI： 10.1186/s12893-017-0297-8

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The 208 trial showed that lenvatinib has a significant antitumor effect on unresectable anaplastic thyroid cancer(ATC). Herein, we present a retrospective review of data from 7 patients with unresectable ATC who received lenvatinib in our hospital between May 2015 and October 2016. Two patients were men and 5 were women. The median age was 78(range, 72-85)years, and 1 patient had Stage IV A disease, 1 had Stage IV B, and 5 had Stage IV C at diagnosis, respectively. Three patients experienced a partial response and 1 patient experienced stable disease. The response rate was 43%, and the disease control rate was 57%. The median progression-free survival(PFS)was 4.1(range, 1.1-12.2)months. Grade 3 and Grade 4 gastrointestinal hemorrhage were observed in 2patients and Grade 3 anorexia was observed in 1 patient. Further clinical research seems to be needed to establish a treatment strategy involving lenvatinib for ATC.

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BACKGROUND: In metastatic breast cancer, the status of the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), as well as the Ki-67 index sometimes change between primary and metastatic lesions. However, the change in expression levels of enhancer of zeste homolog 2 (EZH2) between primary and metastatic lesions has not been determined in metastatic breast cancer. METHODS: Ninety-six metastatic breast cancer patients had biopsies or resections of metastatic lesions between September 1990 and February 2014 at the Kanagawa Cancer Center. We evaluated ER, PR, HER2, Ki-67, and EZH2 in primary lesions and their corresponding metastatic lesions using immunohistochemistry. We examined the change in expression of EZH2 between primary and metastatic lesions, the correlation between the expression of EZH2 and the expression of other biomarkers, and the relationship between EZH2 expression and patient outcome in metastatic breast cancer. RESULTS: EZH2 expression was significantly higher in metastatic lesions compared with primary lesions. EZH2 expression was highly correlated with Ki-67 expression in primary and metastatic lesions. High-level expression of EZH2 was associated with poorer disease-free survival (DFS) outcomes in patients with primary lesions (P < 0.001); however, high-level expression of EZH2 was not associated with poorer DFS outcomes in patients with metastatic lesions (P = 0.063). High-level expression of EZH2 was associated with poorer overall survival (OS) postoperatively in patients with primary (P = 0.001) or metastatic lesions (P = 0.005). High-level expression of EZH2 was associated with poorer OS outcomes after recurrence in patients with metastatic lesions (P = 0.014); however, high-level expression of EZH2 was not associated with poorer OS outcomes after recurrence in patients with primary lesions (P = 0.096). High-level expression of EZH2 in metastatic lesions was independently associated with poorer OS outcomes after recurrence. CONCLUSIONS: EZH2 expression was significantly increased in metastatic lesions compared with primary lesions. High-level expression of EZH2 in metastatic lesions was associated with poorer OS outcomes after primary surgery and recurrence.

DOI： 10.1186/s12885-017-3154-3

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Overall survival remains unsatisfactory in stage II/III gastric cancer, even after curative surgery and adjuvant chemotherapy. Platelet-derived growth factor receptor-β (PDGFR-β) is associated with the proliferation of cancer cells. The present study therefore investigated the association of PDGFR-β gene expression with patient outcome in 134 stage II/III gastric cancer patients who received adjuvant chemotherapy with S-1. Relative PDGFR-β gene expression was measured in surgical cancer tissue and adjacent normal mucosa specimens by reverse transcription-quantitative polymerase chain reaction. The PDGFR-β gene expression levels were found to be significantly higher in the cancer tissues compared with the adjacent normal mucosa. A high level of PDGFR-β gene expression was associated with a significantly poorer 5-year overall survival rate compared with a low level of PDGFR-β expression. Upon multivariate analysis, PDGFR-β gene expression was found to be an independent predictor of survival. Overall, the study indicates that PDGFR-β overexpression in gastric cancer tissues is a useful independent predictor of outcome in patients with stage II/III gastric cancer who receive adjuvant chemotherapy with S-1.

DOI： 10.3892/ol.2016.5494

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BACKGROUND: Several studies from other countries have reported that patients with screen-detected breast cancer have better survival than those with symptomatic breast cancer. However, no such comparison has been performed in Japan. Therefore, we aimed to compare the clinicopathological characteristics and survival rates between symptomatic and screen-detected breast cancer in Japanese women. METHODS: From January 2000 to December 2004, 977 and 182 women with symptomatic or screen-detected breast cancer, respectively, underwent surgery at a single Japanese hospital. We retrospectively reviewed these patients' clinicopathological data. Likelihood of death was estimated using the Kaplan-Meier method and the log-rank test. Multivariate analysis including mode of detection, tumor size, lymph node status, hormone receptor status, and adjuvant therapy administration was performed using the Cox proportional hazards model. RESULTS: Screen-detected breast cancer was associated with increased rate of breast-conserving surgery, non-invasive carcinoma, smaller tumor size, decreased lymph node involvement, increased hormone receptor positivity, and decreased adjuvant chemotherapy administration. Compared to women with symptomatic tumors, those with screen-detected tumors had improved overall and breast cancer-specific survival rates. Factors associated with survival in univariate analysis were screen detection, tumor size, lymph node status, progesterone receptor status, and adjuvant chemotherapy administration. CONCLUSIONS: Breast cancer screening in Japanese women has led to increases in the rates of breast-conserving surgery, hormone receptor positivity, and survival rates along with reductions in axillary lymph node dissection and adjuvant chemotherapy administration.

DOI： 10.1007/s12282-016-0678-3

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BACKGROUND: Anaplastic thyroid cancer (ATC) is a rare and extremely aggressive malignancy, with a median survival of less than 6 months due to rapid progression and resistance to multimodal therapies. Effective treatment strategies have not been identified. A prospective clinical study was performed to objectively evaluate outcomes of treatment with paclitaxel. METHODS: An investigator-initiated, multicenter, nonrandomized, open-label, single-arm study to evaluate the feasibility and efficacy of weekly paclitaxel (80 mg/m(2)) administration for patients with pathologically confirmed ATC was conducted in a nationwide organization. RESULTS: Feasibility was analyzed in 56 patients. More than one course of treatment was performed in 52 (93%) patients retaining sufficient dose intensity (>84%). No patient had to terminate the treatment because of an adverse event. The median overall survival was 6.7 months [confidence interval 4.4-9.0]. The 6-month survival was 54%. Among the 42 patients with an evaluable lesion, none demonstrated complete remission, 9 (21%) showed partial remission, 22 (52%) achieved stable disease, and 8 (19%) exhibited progressive disease; 3 did not complete the initial treatment course. The objective response rate was 21%, and the clinical benefit rate was 73%. The median time to progression was 1.6 months. Statistically, no additional effect of concomitant radiation was demonstrated in 6 patients receiving combined therapy. Eight patients, in whom a complete post-treatment surgical removal of the tumor was feasible, survived significantly longer (median 7.6 months [CI 8.1-23.0]) than the other 34 patients in whom the tumor could not be completely removed after chemotherapy (5.4 months [CI 3.0-7.8], p = 0.018). SUMMARY: The study demonstrates objective and accurate information concerning the feasibility and efficacy of a standardized treatment with weekly paclitaxel administration for ATC patients. CONCLUSIONS: Weekly paclitaxel administration for ATC patients can be of clinical benefit in a neo-adjuvant setting.

DOI： 10.1089/thy.2016.0072

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Language：Japanese   Publisher：横浜市立大学医学会  

乳腺腺様嚢胞癌の1例を経験したので報告する。症例は47歳、閉経前女性。右乳房の有痛性腫瘤を主訴に当院を受診した。右乳房C領域に1cm大の腫瘤を触知した。マンモグラフィーではカテゴリー1、超音波検査では0.7cmの境界明瞭粗そうで内部不均一な低エコー腫瘤として描出された。穿刺吸引細胞診では内部に透明な粘液球様物を伴う細胞集塊を認めた。腫瘍摘出術施行し、病理組織学的に腺様嚢胞癌と診断された。断端陽性のため追加切除の方針となり乳房部分切除、センチネルリンパ節生検を施行した。T1bN0M0、triple negativeであった。術後は温存乳房に対する放射線療法を施行した。薬物療法は施行せず、術後5年6ヵ月経過した現在、無再発生存中である。(著者抄録)

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Language：Japanese   Publisher：日本臨床外科学会  

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Language：English   Publisher：AMER SOC CLINICAL ONCOLOGY  

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Language：Japanese   Publisher：横浜市立大学医学会  

症例は24歳女性。数年前より右乳房に数cm大の腫瘤を自覚。その後徐々に増大し、23歳時、前医(他院乳腺外科)受診。右乳房に巨大腫瘤をみとめ、針生検で線維腺腫と診断された。摘出に伴う変形が危惧され、形成外科での同時再建を目的に当院乳腺外来へ紹介となった。初診時、11cm大の可動性良好、弾性のある腫瘤を認めた。腫瘤による圧迫により皮膚に軽度の発赤を伴っていた。臨床所見からは葉状腫瘍との鑑別が考慮されたが、画像、病理所見から線維腺腫がより疑われたため腫瘍摘出術とした。術中の変形の程度により広背筋弁での形成予定であったが、摘出部の僅かな陥凹のみであり、偏位した乳腺と周囲脂肪織の授動のみで形成可能であった。患側乳房の術後の整容性は良好で健側とほぼ対称である。術後病理検査も線維腺腫の診断であった。本症例は巨大線維腺腫による乳腺の著明な偏位、菲薄化、皮膚伸展のため、摘出術のみでは変形をきたすことが危惧される状況であったが、正常乳腺の温存により乳腺組織のみでの整容性維持が可能であったことを報告する。(著者抄録)

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Language：Japanese   Publisher：横浜市立大学医学会  

術後早期に認められた局所再発巣を切除した後に化学療法を施行したが、奏功せずに急速な転帰をたどった乳腺悪性葉状腫瘍の1例を経験したので報告する。症例は49歳女性。他院で左乳房腫瘤に対して左乳房切除術を施行し悪性葉状腫瘍の診断を受けた。その2ヵ月後、左乳房腫瘤と腰痛を主訴に来院、悪性葉状腫瘍の局所再発と多発骨転移に伴う腰痛と診断した。その後左下肢痛と痺れによる歩行困難が出現してきたため、胸腰椎に対する放射線治療を開始したが、その間に局所再発巣が急速に増大して皮膚が自潰、出血のコントロールが困難となり、放射線治療終了後に局所コントロール目的で胸壁再発巣切除、植皮術を施行した。病理所見では、索状配列を示す紡錘形異型細胞の増殖が認められ、核分裂像が50/10HPF、MIB-1 indexが65%と高値、Vimentin陽性、ER陰性、PgR陰性で悪性葉状腫瘍の局所再発として矛盾しなかった。術後全身化学療法としてTC療法(docetaxel、cyclophosphamide)を行ったが奏功せず、2ヵ月後に肺・肝転移が出現し、来院後約5ヵ月で死亡した。(著者抄録)

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We report a case of rapidly growing malignant phyllodes tumor in a 49-year-old woman. The patient had undergone surgery for a left breast tumor at another hospital and was diagnosed with a malignant phyllodes tumor. Two months later, she visited our hospital because of a recurrent tumor of the left breast and lumbago due to multiple bone metastases. We performed radiation therapy for pain control, but a second operation was needed because the size of the tumor increased rapidly and it was difficult to control bleeding. Systemic chemotherapy (docetaxel 75 mg/m&lt;sup&gt;2&lt;/sup&gt;, cyclophosphamide 600 mg/m&lt;sup&gt;2&lt;/sup&gt;, q3w) and zoledronic acid (4 mg/body, q3w) were started, but multiple lung and liver metastases appeared after 2 cycles.

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We report a case of giant fibroadenoma of the breast. A 23-year-old woman was suspected for giant fibroadenoma of the right breast in another hospital. As poor cosmetic results of an operation were a concern, she was referred to our hospital for simultaneous breast reconstruction. The right breast was filled with a giant tumor, 11 cm in diameter, with slight skin redness. Clinical and pathological findings suggested fibroadenoma rather than phyllodes tumor; we therefore planned tumorectomy. Preoperative imaging showed a marked volume shift, thinning of the mammary gland, and skin extension; therefore, we prepared simultaneous breast reconstruction by a plastic surgeon in case of deformation. However, after tumorectomy with maximal preservation of normal gland, only a slight volume shift was seen, and simple volume displacement was sufficient to obtain good cosmetic results.

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BACKGROUND: Total thyroidectomy is well accepted as initial surgery for papillary thyroid cancer (PTC), but the extent of the thyroidectomy remains a matter of controversy. This study was designed to investigate the long-term clinical outcome of PTC patients who had undergone thyroid lobectomy and to elucidate the indications of lobectomy as initial surgery. METHODS: The cases of 1,088 PTC patients who underwent thyroid lobectomy with curative intent at Ito Hospital between 1986 and 1995 were analyzed retrospectively in this study. None of the patients had received postoperative radioactive iodine (RAI) ablation therapy. The median follow-up period was 17.6 years. All clinical outcomes, including recurrence and death as a result of PTC or other reasons, were evaluated. To establish the indications for lobectomy as initial surgery for PTC, the potential risk factors, such as age, sex, primary tumor size, extrathyroidal invasion, and clinical lymph node metastasis at the time of the initial surgery, were assessed statistically for associations with recurrence and disease-related death. RESULTS: The remnant-thyroid recurrence-free survival (RT-RFS) rate, the regional- lymph-node recurrence-free survival (L-RFS) rate, and the distant-recurrence-free survival (D-RFS) rate as of 25 years after surgery were 93.5, 90.6, and 93.6%, respectively. The cause-specific survival (CSS) rate at 25 years was 95.2%. Univariate and multivariate analyses showed that none of the factors assessed were significantly associated with the RT-RFS rate. Tumor size, clinical lymph node metastasis, and extrathyroidal invasion were significantly associated with the L-RFS rate. The D-RFS and CSS rates were both significantly lower in the group of patients who were aged 45 years old or older, the group whose tumors were larger than 40 mm, and the group with extrathyroidal invasion. Based on the above findings, we classified the patients into four groups according to age <45 or ≥ 45 years, tumor size ≤ 40 or >40 mm, whether clinical lymph node metastasis was present, and whether extrathyroidal invasion was present. None of the patients without any of these four risk factors died of PTC. On the other hand, 22 patients who died of PTC were positive for one or more of these four factors. CONCLUSIONS: The long-term clinical outcome of the PTC patients who had been treated by lobectomy without RAI ablation was excellent. Based on the above results, we concluded that lobectomy is a valid alternative to total thyroidectomy for the treatment of PTC patients who are younger than aged 45 years, whose tumor diameter is 40 mm or less, and who do not have clinical lymph node metastasis or extrathyroidal invasion.

DOI： 10.1007/s00268-013-2224-1

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We retrospectively investigated the efficacy and toxicity of lapatinib plus capecitabine in 45 HER2-positive breast cancer patients. The median number of treatment courses was 6(1-22). Brain metastasis developed in 18 cases(40%), and 19 cases(42.2%)had received previous capecitabine treatment for metastatic breast cancer. The objective response rate(ORR=CR+PR)was 22.2%(10/45), and clinical benefit rate(CR+PR+long SD=24w)was 46.7%(21/45).The median time to progression(TTP)was 24.9 weeks(95% CI: 15.2 -34.6 ), and the median overall survival(OS)was 78.1 weeks(95% CI: 55.7 -100.5)in all 45 cases. The median TTP was significantly longer in patients who had not received capecitabine previously(30 vs 16 weeks, 95% CI: 16.3 -43.7, p=0.0051 ). There was no statistical difference in median OS associated with previous capecitabine exposure(42.7 weeks, 95% CI: 21.4 -64, p=0.057 ). The median TTP was significantly longer in patients who received less than 2 treatment regimens with trastuzumab for MBC rather than 3 regimens more(27.3 vs 16 weeks, p=0.0257 ), but there was no statistical difference in median OS(81 vs 40.9 weeks, p=0.26 ). Lapatinib in combination with capecitabine is likely more useful in patients who are naive to capecitabine, who received less than two regimens for metastatic breast cancer.

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Herein, we report two extremely rare cases of differentiated thyroid carcinoma (DTC) with extended tumor thrombus or mediastinum lymph node metastasis (LNM) involving the superior vena cava (SVC), causing SVC syndrome. Both of these patients were successfully treated with radical resection and reconstruction of the SVC using autologous tissue instead of an expanded polytetrafluoroethylene (ePTFE) graft. The left brachiocephalic vein was used to reconstruct the SVC in a papillary thyroid carcinoma patient with mediastinum LNM and a pericardial patch was used in a follicular thyroid carcinoma patient with tumor thrombus. Our search of the English-language literature found sporadic reports of SVC resection with reconstruction by vascular graft (ePTFE), interposed between the brachiocephalic vein and the right atrium. However, SVC reconstruction using autologous tissue in thyroid carcinoma has not been reported to date. To our knowledge, this is the first report describing such an unusual technique in DTC patients.

DOI： 10.1186/1477-7819-7-75

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INTRODUCTION: The distant metastases from differentiated thyroid carcinomas are often untreatable. In particular, bone metastasis is significantly related to poor prognosis since radioactive iodine therapy is generally less effective. Therefore, surgical resection is considered one of the treatments for patients with bone metastases. We report chest wall resection and reconstruction using titanium micromesh covered with polypropylene mesh (Marlex mesh) for metastatic rib bones as a result of follicular thyroid carcinoma. CASE PRESENTATION: A 51-year-old man was referred to our institution with a painful chest wall tumor. He presented with a 15 x 10 cm bony swelling on the left chest wall and multiple small lung nodules from follicular thyroid carcinoma. Completion total thyroidectomy, chest wall resection and reconstruction using titanium micromesh covered with Marlex mesh were performed. There were no critical complications associated with surgical treatments and tumor pain disappeared during the postoperative period. Then, he received radioactive iodine therapy and the uptake of radioactive iodine was well observed in bilateral lung fields. CONCLUSION: Reconstruction using titanium micromesh covered with Marlex mesh is possible for repairing the wide chest wall resection required for thyroid carcinoma metastasis. This technique would help to enhance treatment efficacy in the combination therapy of radioactive iodine and surgery in patients with large thyroid carcinoma metastasis in the chest wall.

DOI： 10.4076/1752-1947-3-7259

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An 83-year-old man was admitted to our hospital with jaundice. At the age of 79, he had undergone distal gastrectomy with Roux-Y reconstruction and cholecystectomy due to early gastric cancer and gall bladder carcinoma. CT and MRI revealed severe dilatation from the common bile duct (CBD) to the intra-hepatic bile duct. Blood tests showed high serum levels of bilirubin and CA19-9. Cytology of the bile juice was Class V. Percutaneous transhepatic bile duct drainage was performed. Curative surgical resection was not indicated due to his age and general condition. Neither percutaneous nor endscopical fistulization were successful. Finally magnetic compression anastomosis was performed. Under general anesthesia, the first magnet was placed in the CBD through a cutaneous fistula. The second one was placed in the duodenum through the jejunum. The two magnets attached the walls of the CBD and duodenum. Three weeks after the maneuver, the anastomosis was completed with only a slight fever.

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BACKGROUND: Although all tumor, node, metastasis system (TNM) stage IVA papillary thyroid carcinomas (PTCs) do not seem to behave equivalently as a result of various tumor and node stages, to our knowledge, subclass evaluation has never been attempted. METHODS: We reviewed 119 stage IVA PTC patients who underwent initial thyroidectomy with modified neck dissection as curative surgery at our institution (33 male patients, 86 female patients; age 61.6 years; follow-up 87.7 months). These patients were divided into groups A (T1-3N1b; n = 79), B (T4aN0-1a; n = 9), and C (T4aN1b; n = 31). Outcomes were compared between the groups. RESULTS: The rates of recurrence (P < .05) and disease mortality (P < .001) were 13.9% and 1.3%, 0% and 0%, and 35.5% and 19.4% in groups A, B, and C, respectively. The 10-year disease-free survival (DFS) and disease-specific survival (DSS) were 73.4% and 97.9%, 100% and 100%, and 54.9% and 69.7% in groups A, B, and C, respectively. DFS and DSS curves differed significantly between group A + B and group C (P < .005 and P < .0005, respectively). The relative risks of DFS and DSS in group C were 2.8-fold and 14.9-fold, respectively, compared with group A (P < .05), and 3.2-fold and 17.5-fold compared with group A + B (P < .01). Thus, outcomes were worse in group C. In multivariate analysis, esophageal invasion and lymphadenopathy were independent risk factors for both DFS and DSS in stage IVA PTC patients. CONCLUSIONS: Outcomes in stage IVA are not equivalent, and patients with T4aN1b are at greater risk for worse prognosis. Therefore, we recommend subclass evaluation for TNM stage IVA PTCs.

DOI： 10.1245/s10434-008-9837-x

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Lung cancer associated with Sweet's syndrome is extremely rare. There are only seven reports of such cases. As far as could be determined from a comprehensive search, there is no reported operative case of lung cancer with this syndrome in the world literature. A 75-year-old Japanese man was diagnosed as having Sweet's syndrome. A chest computed tomography (CT) scan to screen for malignant lesions associated with this syndrome revealed an abnormal shadow in the lung. Although [(18)F]2-fluoro-2-deoxy-D: -glucose positron emission tomography showed no abnormal uptake, lung cancer was most strongly suspected by chest CT. His erythema improved rapidly with steroid therapy and he underwent a segmentectomy (S(6)) of the right lower lobe. A pathological examination revealed lung adenocarcinoma (pT1N0M0: Stage Ia). The patient was discharged from the hospital without any worsening of Sweet's syndrome. We herein report a first operative case of an early stage lung adenocarcinoma with this syndrome.

DOI： 10.1007/s00595-007-3683-5

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BACKGROUND: The mitotic spindle assembly checkpoint (MSAC) genes are responsible for preventing chromosome missegregation. MSAC gene expressions have been reported to be associated with tumor cell proliferation or unfavorable cancer behavior. The present study was conducted to preliminary investigate the MSAC gene expressions in thyroid neoplasms. MATERIALS AND METHODS: Expression levels of MSAC genes (hBUB1, hBUBR1, hBUB3 and hMAD2) were evaluated in 9 follicular thyroid adenomas (FAs), 9 follicular thyroid carcinomas (FTCs), 21 papillary thyroid carcinomas (PTCs), 5 anaplastic (undifferentiated) thyroid carcinomas (ATCs) and 3 adjacent normal thyroid tissues (NTs) by real-time quantitative RT-PCR. These gene expressions were compared between undifferentiated thyroid carcinomas (ATCs) and differentiated thyroid carcinomas (DTCs) and between advanced DTCs and non-advanced DTCs. DTCs included PTCs and FTCs. Advanced DTCs were defined as carcinoma with aggressive nature such as extrathyroid extension, distant metastasis, recurrence or death from the disease. RESULTS: MSAC gene expressions varied in different thyroid tumors and fell in the order of ATC, DTC (PTC and FTC), FA and NT Carcinomas had higher expression compared to adenoma or normal tissue. hBUB1, hBUBR1 and hMAD2 expressions in ATCs were significantly higher than those in DTCs (p<0.005). hBUBR1 and hMAD2 expressions in advanced DTCs were significantly higher than those in non-advanced DTCs (p<0.05). CONCLUSION: The MSAC genes were overexpressed in thyroid carcinomas with aggressive nature. Further studies are required to clarify the relationship between the MSAC gene expressions and thyroid cancer behavior.

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AIM: The aim of this study was to evaluate microscopic nodal status in papillary thyroid carcinoma (PTC) with and without lymphadenopathy and its relation to outcomes. MATERIALS AND METHODS: We retrospectively analyzed 134 patients with PTC who underwent initial thyroidectomy. Forty-two patients with lymphadenopathy underwent therapeutic modified neck dissection (MND) and 92 without lymphadenopathy underwent prophylactic MND. The frequencies, numbers, and percentages of lymph node metastasis (LNM) were determined to evaluate nodal status; then, whether each nodal status influence to outcomes was analyzed. Disease-free survival (DFS) and disease-specific survival (DSS) were assessed (Kaplan-Meier method and log-rank test). RESULTS: Lymphadenopathy was significantly related to local recurrence and DFS, but not DSS. The frequency (100 vs 67.4%), number (15.8 vs 2.7), and percentage (49.7 vs 17.8%) were significantly higher in patients with lymphadenopathy than in those without lymphadenopathy (p < 0.0001). Similarly, these were significantly higher in patients who developed recurrence than in those who did not. Recurrence was frequent in older patients with lymphadenopathy. The frequency, number, and percentage were also higher in older patients who developed local recurrence. CONCLUSIONS: Lymphadenopathy and microscopic nodal status are significantly related to recurrence. Only a few nodes seem to be involved pathologically when no lymphadenopathy.

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OBJECTIVE: To investigate the differences in the pattern of glucose transporter (GLUT) gene expression between normal and tumour tissues and among histological subtypes of renal cell carcinomas (RCCs), as malignant cells are characterized by increased glucose uptake and use. MATERIALS AND METHODS: Enhanced glucose uptake probably depends on the overexpression of GLUT, usually GLUT1 and/or GLUT3, but there are few comprehensive studies to evaluate the relative expression pattern and level of GLUT in normal and tumour kidney tissues, especially of the recently identified GLUT genes. In all, 71 kidney surgical samples were evaluated using reverse transcriptase-polymerase chain reaction (RT-PCR) for GLUT1-14 in normal and tumour (clear cell, papillary and chromophobe RCC, and oncocytoma) tissues. The expression levels for GLUT1-5, 9, 10 and 12 were quantified by real-time quantitative PCR. RESULTS: The RT-PCR results showed that normal kidney tissue expresses all the GLUT isoforms. In clear cell RCC GLUT1 expression increased (P<0.001) while GLUT4, 9 and 12 decreased (P<0.001). In papillary RCC there were no significant increases in GLUT expression, with only GLUT12 significantly expressed at lower levels (P<0.001). In chromophobe RCC the expression of GLUT4 increased (P<0.05), and GLUT2 and 5 decreased (P<0.01), whereas in oncocytoma tissue there were no significant changes in the expression of GLUT1 (P<0.01), 2, 5, 9 (P<0.001) and 10 (P<0.05). CONCLUSIONS: These results suggest that high-affinity GLUTs might have a major role in enhanced glucose uptake in kidney tumours, and that histopathological types are characterized by specific patterns of GLUT expression.

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OBJECTIVE: This study aimed to analyse whether age, metastasis, extrathyroidal invasion and size (AMES) risk definition is valuable for Japanese patients with differentiated thyroid carcinoma (DTC). METHODS: Two hundred and fifteen Japanese DTC patients (43 men, 172 women; mean age, 51.0 years; mean follow-up, 102 months) treated surgically at our institutions between 1981 and 2001 were retrospectively analysed. Clinicopathological features were compared between high-risk and low-risk patients by AMES criteria. Various risk factors were also evaluated for each group of patients. RESULTS: There were 57 high-risk and 158 low-risk patients. Recurrence and mortality rates were 43.9% and 24.6% in high-risk patients and 7.6% and 0.6% in low-risk patients, respectively (p < 0.0001). Disease-specific survival rates at 5, 10 and 15 years were 84.3%, 74.0% and 63.5% in high-risk patients and 100%, 100% and 98.3% in low-risk patients, respectively (p < 0.0001). Univariate analysis revealed that curative resection, local recurrence and distant metastasis were risk factors for mortality in the high-risk group. Multivariate analysis revealed that curative resection (hazard ratio [HR], 4.68; 95% confidence interval [CI], 1.23-17.83; p = 0.024) and distant metastasis (HR, 4.79; 95% CI, 1.24-18.40; p = 0.023) were significantly related to mortality in high-risk patients. CONCLUSION: AMES can identify high-risk and low-risk Japanese patients. Distant metastasis and curative resection are prognostic factors for disease-specific death.

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CONTEXT: The prognostic value of the sixth edition AJCC/UICC TNM classification is currently unclear. OBJECTIVE: The aim was to evaluate the prognostic value of the sixth edition. DESIGN AND PATIENTS: We retrospectively assessed 354 primary differentiated thyroid carcinomas (77 men and 277 women; age, 51.2 yr; follow-up, 107.6 months) between 1964 and 2003. Sixty percent of patients underwent lobectomy, 40% underwent subtotal/total thyroidectomy, and only 2% were given radioiodine. There were 153, 104, 86, and 11 patients in fifth stages I, II, III, and IV, and 175, 76, 14, 68, 10, and 11 patients in sixth stages I, II, III, IVA, IVB, and IVC, respectively. RESULTS: New T1-3 had no significant influence. In Cox proportional hazard analysis, T4a and T4b were significantly related to disease-specific survival (DSS). We separately analyzed 68 patients (age 45 yr or older) with extrathyroid extension. These T4 (fifth) tumors were reclassified as 6 T3, 52 T4a, and 10 T4b tumors. The 10-yr DSS rates were 100, 69.3, and 10.0% for T3, T4a, and T4b, respectively. T4b exhibited worse prognoses compared with T4a (P < 0.0001; hazard ratio, 10.1; 95% confidence interval, 4.1-25.3). Stages I and II in both editions achieved favorable prognoses. The 10-yr DSS rates were 67.0 and 27.3% in fifth stages III and IV, and 100, 74.5, 10.0, and 27.3% in sixth stages III, IVA, IVB, and IVC, respectively. DSS curves differed significantly between all sixth TNM stages (P < 0.0001). CONCLUSION: The sixth edition more accurately predicts different outcomes according to the revised criteria for the degree of extrathyroid extension.

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Microfibril-associated glycoprotein-1 (MAGP1) is found associated with microfibrils in the extracellular matrix (ECM). In humans, MAGP1 is expressed as two alternatively spliced isoforms: MAGP1A, the extracellular microfibril-associated form; and MAGP1B, an exclusively intracellular isoform derived from the skipping of exon 3. The biological function of MAGP1B is unknown. We performed gene expression profiling to study the cellular response to MAGP1B using whole-genome genechips. We found that MAGP1B specifically induces the expression of genes linked to cell adhesion, motility, metabolism, gene expression, development and signal transduction. Versican, a gene product involved in the structure and functional regulation of the ECM, showed the highest up-regulation in response to MAGP1B. These studies suggest a dual role for MAGP1, with extracellular MAGP1A involved in ECM function, and intracellular MAGP1B modulating the expression of genes that function in cell adhesion, migration and control of ECM deposition.

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AIM: The aim of this study is to evaluate the outcome of different modes of resection in papillary thyroid carcinoma (PTC) with laryngotracheal invasion. MATERIALS AND METHODS: Sixty-four primary PTCs with laryngotracheal invasion between 1964 and 2003 were retrospectively analyzed (17 men and 47 women; mean age, 61.6 years; mean follow-up, 92.3 months). Thirteen curative resections included six pharyngolaryngoesophagectomies, two total laryngectomies, and five circumferential resections (complete surgery). Eighteen patients who were candidates for curative resection refused to undergo complete surgery to avoid functional impairment, especially laryngeal function (incomplete surgery). Thirty-three patients with minimal invasion underwent shave or partial resection (conservative surgery). Clinical outcomes were compared between the three groups. The influence of different types of surgery and invasion was also evaluated by Cox proportional hazard analysis. RESULTS: Three (23.1%) complete, 17 (94.4%) incomplete, and 4 (13.8%) conservative surgery patients died of disease (P < 0.0001). The 10-year disease-specific survival (Kaplan-Meier) in complete, incomplete, and conservative surgery patients were 62.9, 11.1, and 87.7%, respectively (log rank test, P < 0.0001). Incomplete surgery related to worse prognosis [p < 0.0001; hazard ratio (HR), 12.9) than complete or conservative surgery. Tracheal deep invasion (p = 0.0019, HR 7.6) and larynx invasion (p < 0.0001, HR 9.9) related to worse prognosis than minimal invasion. CONCLUSION: Curative resection improves clinical outcomes in PTCs with laryngotracheal invasion. Conservative resection for minimal invasion also can achieve favorable prognosis. The degree of tumor invasion is significantly related to survival.

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