Publications by authors named "Nobuyasu Suganuma"

47 Publications

Inflammatory biomarkers and dynamics of neutrophil-to-lymphocyte ratio in lenvatinib treatment for anaplastic thyroid carcinoma.

Gland Surg 2021 Mar;10(3):852-860

Department of Surgery, Yokohama City University School of Medicine, Fukuura, Kanazawa-ku, Yokohama City, Kanagawa, Japan.

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.
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http://dx.doi.org/10.21037/gs-20-871DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033089PMC
March 2021

Invasive procedures in patients undergoing treatment with lenvatinib for thyroid cancer.

Mol Clin Oncol 2021 Apr 26;14(4):81. Epub 2021 Feb 26.

Departments of Breast and Thyroid Surgery, Yokohama City University Medical Center, Yokohama, Kanagawa 232-0024, Japan.

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.
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http://dx.doi.org/10.3892/mco.2021.2243DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947953PMC
April 2021

Prospective cohort study of febrile neutropenia in breast cancer patients administered with neoadjuvant and adjuvant chemotherapies: CSPOR-BC FN study.

Breast 2021 Apr 16;56:70-77. Epub 2021 Feb 16.

Division of Oncology/Hematology, National Cancer Center Hospital East, Chiba, Japan.

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.
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http://dx.doi.org/10.1016/j.breast.2021.01.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7907535PMC
April 2021

Preliminary Screening for Hereditary Breast and Ovarian Cancer Using a Chatbot Augmented Intelligence Genetic Counselor: Development and Feasibility Study.

JMIR Form Res 2021 Feb 5;5(2):e25184. Epub 2021 Feb 5.

Department of Genetic Medicine, Kanagawa Cancer Center, Yokohama, Kanagawa, Japan.

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.
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http://dx.doi.org/10.2196/25184DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7895643PMC
February 2021

Membrane type 1 matrix metalloproteinase regulates anaplastic thyroid carcinoma cell growth and invasion into the collagen matrix.

Biochem Biophys Res Commun 2020 09 4;529(4):1195-1200. Epub 2020 Aug 4.

Organoid Biology Unit, Kanagawa Cancer Center Research Institute, Yokohama, Japan. Electronic address:

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.
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http://dx.doi.org/10.1016/j.bbrc.2020.06.043DOI Listing
September 2020

Occult Thyroid Carcinoma without Malignant Thyroid Gland Findings during Preoperative Examination: Report of Three Cases.

Case Rep Endocrinol 2020 10;2020:4249067. Epub 2020 Apr 10.

Department of Surgery, Yokohama City University School of Medicine, Yokohama, Japan.

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.
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http://dx.doi.org/10.1155/2020/4249067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7171659PMC
April 2020

EZH2 and MMSET Were Identified as Potentially Useful Therapeutic Targets in Metaplastic Breast Carcinoma.

Anticancer Res 2020 Apr;40(4):2133-2139

Department of Surgery, Yokohama City University, Yokohama, Japan.

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.
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http://dx.doi.org/10.21873/anticanres.14172DOI Listing
April 2020

Evaluation of the 8th Edition TNM Classification for Anaplastic Thyroid Carcinoma.

Cancers (Basel) 2020 Feb 27;12(3). Epub 2020 Feb 27.

Anaplastic Thyroid Carcinoma Research Consortium of Japan, Tokyo 113-8603, Japan.

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 ( = 8, 1.1%, 12.5), T2 ( = 43, 5.7%, 10.9), T3a ( = 117, 15.5%, 5.7), T3b ( = 438, 57.9%, 3.9), and T4 ( = 151, 19.9%, 5.0). The OS of the N0 and N1 patients were 5.9 and 4.3, respectively (log-rank < 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 ( = 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.
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http://dx.doi.org/10.3390/cancers12030552DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139873PMC
February 2020

Expression of fibroblast growth factor receptor 4 and clinical response to lenvatinib in patients with anaplastic thyroid carcinoma: a pilot study.

Eur J Clin Pharmacol 2020 May 7;76(5):703-709. Epub 2020 Feb 7.

Department of Surgery, Yokohama City University School of Medicine, 3-9 Fukuura, Kanazawaku, Yokohama City, Kanagawa, Japan.

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.
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http://dx.doi.org/10.1007/s00228-020-02842-yDOI Listing
May 2020

Lenvatinib vs. palliative therapy for stage IVC anaplastic thyroid cancer.

Mol Clin Oncol 2020 Feb 13;12(2):138-143. Epub 2019 Dec 13.

Department of Breast and Thyroid Surgery, Yokohama City University Medical Center, Yokohama, Kanagawa 232-0024, Japan.

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.
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http://dx.doi.org/10.3892/mco.2019.1964DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6951241PMC
February 2020

Clinical and pathological predictors of recurrence in breast cancer patients achieving pathological complete response to neoadjuvant chemotherapy.

Eur J Surg Oncol 2019 Dec 2;45(12):2289-2294. Epub 2019 Aug 2.

Department of Breast Oncology and Surgery, Tokyo Medical University Hospital, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan. Electronic address:

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.
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http://dx.doi.org/10.1016/j.ejso.2019.08.001DOI Listing
December 2019

Renal dysfunction in patients with radioactive iodine-refractory thyroid cancer treated with tyrosine kinase inhibitors: A retrospective study.

Medicine (Baltimore) 2019 Oct;98(42):e17588

Department of Breast and Thyroid Surgery, Yokohama City University Medical Center, Yokohama City, Japan.

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.
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http://dx.doi.org/10.1097/MD.0000000000017588DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6824644PMC
October 2019

Anaplastic thyroid carcinoma diagnosed after treatment of lenvatinib for papillary thyroid carcinoma.

Endocrinol Diabetes Metab Case Rep 2019 Oct 1;2019. Epub 2019 Oct 1.

Department of Surgery, Yokohama City University School of Medicine, Yokohama City, Kanagawa, Japan.

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.
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http://dx.doi.org/10.1530/EDM-19-0085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6790905PMC
October 2019

Two cases of thyroid gland invasion by upper mediastinal carcinoma

Endocrinol Diabetes Metab Case Rep 2019 Jun 30;2019(1). Epub 2019 Jun 30.

Department of Surgery, Yokohama City University School of Medicine, Yokohama, Japan

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.

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.
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http://dx.doi.org/10.1530/EDM-19-0028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6589857PMC
June 2019

Treatment outcomes of differentiated thyroid cancer with distant metastasis improve by tyrosine kinase inhibitors.

Oncol Lett 2019 Jun 21;17(6):5292-5300. Epub 2019 Mar 21.

Department of Breast and Thyroid Surgery, Yokohama City University Medical Center, Yokohama, Kanagawa 232-0024, Japan.

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.
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http://dx.doi.org/10.3892/ol.2019.10180DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6507323PMC
June 2019

Efficacy and tolerability of initial low-dose lenvatinib to treat differentiated thyroid cancer.

Medicine (Baltimore) 2019 Mar;98(10):e14774

Department of Surgery, Yokohama City University School of Medicine, Yokohama City, Kanagawa, Japan.

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.
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http://dx.doi.org/10.1097/MD.0000000000014774DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6417556PMC
March 2019

Lenvatinib as a novel treatment for anaplastic thyroid cancer: A retrospective study.

Oncol Lett 2018 Dec 5;16(6):7271-7277. Epub 2018 Oct 5.

Department of Breast and Endocrine Surgery, Kanagawa Cancer Center, Yokohama, Kanagawa 241-8515, Japan.

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.
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http://dx.doi.org/10.3892/ol.2018.9553DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6256365PMC
December 2018

Nephrectomy for Metastatic Kidney Tumor in Patients with Differentiated Thyroid Cancer: A Report of Two Cases.

Case Rep Endocrinol 2018 11;2018:7842792. Epub 2018 Nov 11.

Department of Surgery, Yokohama City University School of Medicine, Yokohama, Japan.

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.
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http://dx.doi.org/10.1155/2018/7842792DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6252184PMC
November 2018

A Large Substernal Goiter that Extended to Both Sides of the Thorax.

Case Rep Surg 2018 5;2018:6107982. Epub 2018 Nov 5.

Department of Surgery, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa 236-0004, Japan.

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.
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http://dx.doi.org/10.1155/2018/6107982DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6247568PMC
November 2018

A case of undifferentiated pleomorphic sarcoma of the breast with lung and bone metastases.

Int J Surg Case Rep 2018 16;51:143-146. Epub 2018 Aug 16.

Department of Surgery, Yokohama City University School of Medicine, Yokohama, Japan. Electronic address:

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.
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http://dx.doi.org/10.1016/j.ijscr.2018.07.049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6117951PMC
August 2018

Expression of vascular endothelial growth factor receptor 2 and clinical response to lenvatinib in patients with anaplastic thyroid cancer.

Cancer Chemother Pharmacol 2018 10 26;82(4):649-654. Epub 2018 Jul 26.

Department of Surgery, Yokohama City University School of Medicine, 3-9 Fukuura, Kanazawaku, Yokohama City, Kanagawa, Japan.

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.
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http://dx.doi.org/10.1007/s00280-018-3657-xDOI Listing
October 2018

A Case of Pneumothorax after Treatment with Lenvatinib for Anaplastic Thyroid Cancer with Lung Metastasis.

Case Rep Endocrinol 2018 28;2018:7875929. Epub 2018 Mar 28.

Department of Surgery, Yokohama City University School of Medicine, Yokohama, Japan.

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.
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http://dx.doi.org/10.1155/2018/7875929DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5896288PMC
March 2018

Correction to: A comparison of clinicopathological characteristics and long-term survival outcomes between symptomatic and screen-detected breast cancer in Japanese women.

Breast Cancer 2018 03;25(2):257-258

Department of Surgery, Yokohama City University, 39 Fukuura, Kanazawa-ku, Yokohama, Japan.

In the original publication of this article, Table 1 was published incorrectly with rows out of order under "Distant metastasis (n, %)".
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http://dx.doi.org/10.1007/s12282-018-0832-1DOI Listing
March 2018

EZH2 Overexpression as a Useful Prognostic Marker for Aggressive Behaviour in Thyroid Cancer.

In Vivo 2018 Jan-Feb;32(1):25-31

Molecular Pathology and Genetics Division, Kanagawa Cancer Center Research Institute, Yokohama, Japan.

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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http://dx.doi.org/10.21873/invivo.11200DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5892628PMC
August 2018

Potential Risk Factors for Nivolumab-induced Thyroid Dysfunction.

In Vivo 2017 Nov-Dec;31(6):1225-1228

Department of Surgery, Yokohama City University School of Medicine, Yokohama, Japan.

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.
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http://dx.doi.org/10.21873/invivo.11195DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5756657PMC
June 2018

Deltopectoral flap revisited for reconstruction surgery in patients with advanced thyroid cancer: a case report.

BMC Surg 2017 Sep 15;17(1):101. Epub 2017 Sep 15.

Department of General Surgery, Yokohama City University Hospital, Yokohama, Japan.

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.
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http://dx.doi.org/10.1186/s12893-017-0297-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5603086PMC
September 2017

[Efficacy and Safety of Lenvatinib for Unresectable Anaplastic Thyroid Cancer].

Gan To Kagaku Ryoho 2017 Aug;44(8):695-697

Dept. of Breast and Endocrine Surgery, Kanagawa Cancer Center.

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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August 2017

Non-functioning parathyroid carcinoma: a case report.

Surg Case Rep 2017 Dec 19;3(1):81. Epub 2017 Jul 19.

Yokohama City University, Yokohama, Japan.

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.
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http://dx.doi.org/10.1186/s40792-017-0357-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5517387PMC
December 2017

Clinicopathological and prognostic significance of Ki-67 immunohistochemical expression of distant metastatic lesions in patients with metastatic breast cancer.

Breast Cancer 2017 Nov 19;24(6):748-755. Epub 2017 Apr 19.

Department of Surgery, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.

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.
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http://dx.doi.org/10.1007/s12282-017-0774-zDOI Listing
November 2017

Clinical significance of platelet-derived growth factor receptor-β gene expression in stage II/III gastric cancer with S-1 adjuvant chemotherapy.

Oncol Lett 2017 Feb 14;13(2):905-911. Epub 2016 Dec 14.

Department of Surgery, Yokohama City University, Yokohama, Kanagawa 236-0004, Japan.

Overall survival remains unsatisfactory in stage II/III gastric cancer, even after curative surgery and adjuvant chemotherapy. Platelet-derived growth factor receptor-β (-β) is associated with the proliferation of cancer cells. The present study therefore investigated the association of -β gene expression with patient outcome in 134 stage II/III gastric cancer patients who received adjuvant chemotherapy with S-1. Relative -β gene expression was measured in surgical cancer tissue and adjacent normal mucosa specimens by reverse transcription-quantitative polymerase chain reaction. The -β gene expression levels were found to be significantly higher in the cancer tissues compared with the adjacent normal mucosa. A high level of -β gene expression was associated with a significantly poorer 5-year overall survival rate compared with a low level of -β expression. Upon multivariate analysis, -β gene expression was found to be an independent predictor of survival. Overall, the study indicates that -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.
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http://dx.doi.org/10.3892/ol.2016.5494DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5351282PMC
February 2017