Publications by authors named "Masanori Yamazaki"

54 Publications

[A Case of Unresectable Recurrent Colorectal Cancer with Regorafenib Treatment and Long-Term Survival].

Gan To Kagaku Ryoho 2021 Dec;48(13):1670-1672

Dept. of Surgery, Shizuoka City Shimizu Hospital.

This paper reports a case in which the patient has survived for 5 years and 6 months after recurrence of colorectal cancer by chemotherapy, and especially in regorafenib as fourth-line therapy has obtained stable disease(SD)for 2 years and 6 months. A man in his 70s underwent left hemicolectomy in the diagnosis of descending colon cancer. Four years and 4 months after the operation, abdominal CT revealed paraaortic lymph node metastasis. When SOX plus bevacizumab was performed as first-line therapy, partial response(PR)was obtained, and PR was maintained for a long time. After progressive disease(PD), IRIS was performed as second-line therapy, but the effect was not obtained. Panitumumab was started as third-line therapy, and PR was temporarily recognized, but since it became PD again, regorafenib was introduced as fourth- line therapy. After regorafenib administration, reduction of paraaortic lymph nodes and lowering of CEA are recognized, and long SD can be maintained. This case can be said to be 1 case in which the usefulness of regorafenib was shown as a salvage- line for unresectable colorectal cancer.
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December 2021

Extra-endocrine phenotypes at infancy in multiple endocrine neoplasia type 2B: A case series of six Japanese patients.

Clin Pediatr Endocrinol 2021 1;30(4):195-200. Epub 2021 Oct 1.

Department of Surgery, Noguchi Thyroid Clinic and Hospital Foundation, Oita, Japan.

Multiple endocrine neoplasia type 2B (MEN2B) is an extremely rare disease, most often caused by a p.Met918Thr mutation. Medullary thyroid carcinoma of MEN2B has a good prognosis if diagnosed by one year of age. However, diagnosis of MEN2B within the first year of life is markedly challenging owing to its high occurrence and lack of clarity in terms of extra-endocrine symptoms that could aid early diagnosis. Herein, we present six cases of Japanese children with MEN2B harboring the p.Met918Thr variant. Exploratory data extraction was conducted using a questionnaire. The patients underwent thyroidectomy at a median age of 11 yr (range, 6-19 yr). Four of the six patients underwent neonatal hospitalization at birth without complications, and three tested positive for neuroblastoma screening at infancy. The patients presented at least one MEN2B-associated symptom before one year of age, including ganglioneuromas, pseudo-Hirschsprung disease, alacrima, bumpy lips, sucking disability, or decreased muscle tone, along with other suspected comorbidities, such as Williams or Prader-Willi syndrome. This case series demonstrates that MEN2B manifests through several extra-endocrine symptoms by the age of one year.
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http://dx.doi.org/10.1297/cpe.30.195DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8481076PMC
October 2021

Changes in serum uric acid levels as a predictor of future decline in renal function in older adults with type 2 diabetes.

Medicine (Baltimore) 2021 Oct;100(40):e27420

Division of Diabetes, Endocrinology and Metabolism, Department of Internal Medicine, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Japan.

Abstract: Given that factors affecting renal function remain unknown, this study aimed to identify key predictors of estimated glomerular filtration rate (eGFR) deterioration, which is a representative of renal function decline in older adults with type 2 diabetes (T2DM). In an exploratory prospective observational study, we enrolled 268 Japanese people with T2DM aged ≥20 years who were followed up at Shinshu University Hospital. Among those, 112 eligible individuals aged ≥65 years were included in the present study. Factors associated with 3-year changes in eGFR (ΔeGFR) and eGFR deterioration (ΔeGFR < 0) were identified using bivariate and multivariable analyses. Regarding baseline values of the subjects, the mean age was 73.5 years, mean blood pressure was 131/74 mm Hg, mean hemoglobin A1c was 7.1%, mean eGFR was 62.0 mL/min/1.73 m2, mean urinary albumin excretion was 222.6 mg/gCre, and mean serum uric acid (UA) was 5.5 mg/mL. In bivariate analysis, the 3-year change in UA (ΔUA) levels was significantly correlated with ΔeGFR (r = -0.491, P < .001), but the baseline UA was not (r = 0.073, P = .444). Multiple linear regression analysis revealed that ΔUA was a significant negative predictor of ΔeGFR in the model that included sex, age, body mass index, serum albumin, and ΔUA as explanatory variables. Moreover, multiple logistic regression analysis demonstrated that ΔUA had a positive association with ΔeGFR <0 (odds ratio 2.374; 95% confidence interval 1.294-4.357). Thus, future renal function decline can be predicted by ΔUA but not by baseline UA in older adults with T2DM. Further research is needed to determine whether lowering the serum UA level can prevent eGFR decline.
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http://dx.doi.org/10.1097/MD.0000000000027420DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8500559PMC
October 2021

[A Case of Duodenal Adenocarcinoma in the Third Portion Treated with Partial Duodenectomy].

Gan To Kagaku Ryoho 2021 Feb;48(2):291-293

Dept. of Surgery, Shizuoka City Shimizu Hospital.

A 85-year-old man was admitted due to vomiting. Abdominal CT showed the remarkable expansion of the stomach and the stenotic lesion in the third portion of the duodenum. Duodenal endoscopy showed a circular tumor of the third potion of the duodenum, and biopsy disclosed tubular adenocarcinoma. Operation was performed on the basis of a diagnosis of primary duodenal cancer of the third portion. Liver metastasis, peritoneal dissemination, and apparent lymph node enlargement were not observed. The tumor was present in the third portion of the duodenum and partial duodenectomy was performed. Reconstruction was achieved by side to side anastomosis of the duodenum and the jejunum. Histopathological diagnosis was well differentiated tubular adenocarcinoma, SS, ly1, v1. Primary duodenal cancer is a relatively rare disease, and there are few cases of third portion. If pancreatic invasion and lymph node metastasis are not observed as in this case, it is necessary to examine the indication of partial duodenectomy.
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February 2021

[Multimodal Therapy for Stage Ⅳ Gallbladder Carcinoma Achieved Long-Term Survival-A Case Report].

Gan To Kagaku Ryoho 2020 Dec;47(13):2290-2292

Dept. of Surgery, Shizuoka City Shimizu Hospital.

A 75-year-old man with a chief complaint of abdominal pain visited our hospital and was diagnosed with Stage Ⅳ gallbladder carcinoma that infiltrated the transverse colon with distant lymph node metastases. He received gemcitabine plus cisplatin chemotherapy, which led the primary lesion to shrink. However, transverse colon obstruction occurred, and semi- urgent right hemicolectomy and extended cholecystectomy were performed. A year and 2 months after first diagnosis, an inferior pancreatic head lymph node swelling was detected. Chemoradiotherapy was performed using S-1, and the lymph node swelling was reduced. Despite continuous S-1 therapy, the lymph node gradually started to swell again, which led to duodenum obstruction by compression. He underwent gastrojejunal bypass; however, his general condition gradually worsened, and he died 2 years and 6 months after the first diagnosis. Even in cases of unresectable gallbladder carcinoma, multimodal therapy, such as surgery, chemoradiotherapy, and palliative gastrointestinal bypass, may archive a long prognosis of 2 years and 6 months.
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December 2020

[A Case of Intraductal Papillary Mucinous Carcinoma of the Pancreas Extending Widely within the Pancreas Resected by Total Pancreatectomy].

Gan To Kagaku Ryoho 2020 Dec;47(13):1771-1773

Dept. of Surgery, Shizuoka City Shimizu Hospital.

A 78-year-old woman visiting our hospital with the chief complaint of abdominal pain was diagnosed with ischemic colitis. CT pointed out pancreatic enlargement, so detailed pancreatic examination was conducted in parallel with treatment. In enhanced CT and MRI, the main pancreatic duct significantly extended over the entire length, and mural nodules scattered in the main pancreatic duct were observed. It was diagnosed with main duct intraductal papillary mucinous neoplasm (IPMN), which is likely to be intraductal papillary mucinous carcinoma(IPMC), and total pancreatectomy was performed. Pathological findings showed diffuse dilation of the main pancreatic duct, non-invasive IPMC progressed over approximately the entire length of the main pancreatic duct, mucinous carcinoma-tubular adenocarcinoma was widely infiltrated in pancreatic tissues around mural nodules. The cancer remained in the pancreas and was eventually diagnosed with IPMC, invasive, pT2, pN0, and pStage ⅠB. This case was an IPMN with high-risk stigmata, and it was an adaptive case of total pancreatectomy because mural nodules extended to the entire pancreas. In recent years, total pancreatectomy has come to be expected good results by the progress of diabetes treatment and the development of pancreatic enzyme agents, it is necessary to carefully judge each case for adaptation.
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December 2020

Pancreatic undifferentiated carcinoma with osteoclast-like giant cells curatively resected after pembrolizumab therapy for lung metastases: a case report.

BMC Gastroenterol 2020 Jul 11;20(1):220. Epub 2020 Jul 11.

Department of Surgery, Shizuoka City Shimizu Hospital, 1231 Miyakami, Shimizu-ku, Shizuoka, 424-8636, Japan.

Background: Therapy targeting programmed death-1 or programmed death-1 ligand-1 (PD-1/PD-L1) has been developed for various solid malignant tumors, such as melanoma and non-small-cell lung cancer (NSCLC), but this approach has little effect in the treatment of pancreatic cancer. Pancreatic undifferentiated carcinoma with osteoclast-like giant cells (UCOGC) is a rare pancreatic malignancy having unique morphology and is considered a variant of pancreatic ductal adenocarcinoma (PDAC). Although UCOGC has been reported to have better prognosis than conventional PDAC, the optimal treatment for UCOGC with distant metastases has not been determined.

Case Presentation: A 66-year-old man was initially diagnosed with NSCLC with multiple intrapulmonary metastases and abdominal lymph node metastasis in the tail of the pancreas, and bronchial biopsy and diagnostic imaging were performed. Pathologic examination of the lung showed poorly differentiated adenocarcinoma cells expressing epithelial marker and PD-L1. Therefore, pembrolizumab monotherapy for NSCLC was given. The pulmonary lesions shrank markedly and were in complete remission after 8 months of anti-PD-1 therapy, though no therapeutic effect was observed in the pancreatic site. Distal pancreatectomy was then performed, and histopathological examination showed that the tumor was UCOGC originating from the pancreas. The histologic findings of the resected specimen mimicked those of the lung biopsy specimen, leading to the final assessment that the lung tumors were metastatic foci that migrated from the UCOGC, and only the metastatic lesions benefited from pembrolizumab therapy.

Conclusion: Immune checkpoint inhibitors have limited therapeutic effects on primary lesions of pancreatic cancer, but they may exert antitumor effects on pulmonary metastases of UCOGC.
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http://dx.doi.org/10.1186/s12876-020-01362-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7353752PMC
July 2020

[Short-Term and Long-Term Outcomes of Colonic Stenting as a Bridge to Surgery for Obstructive Colorectal Cancer].

Gan To Kagaku Ryoho 2019 Dec;46(13):2002-2004

Dept. of Surgery, Shizuoka City Shimizu Hospital.

We examined the short-term and long-term outcomes in 50 patients who underwent stenting as a bridge to surgery(BTS) for obstructive colorectal cancer. The patients comprised 30 men and 20 women, with a mean age of 74.0 years. Stenting and decompression were successful in all patients, and the mean time to oral intake after stenting was 2.4 days. No serious complications related to stenting occurred. Colonoscopy after stenting was important for the preoperative diagnosis of coexisting lesions and planning of the extent of resection. Elective and one-stage surgeries could be performed in all patients after stenting. Regarding long-term outcomes, the 5-year overall survival rate and disease-free survival rate in the BTS patients with Stage Ⅱ plus Ⅲ cancer were 73.1% and 55.7%, respectively. The results of this study suggest that BTS for obstructive colorectal cancer is an effective treatment strategy for not only short-term but also long-term outcomes.
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December 2019

[A Case of Resection of Intraductal Papillary Mucinous Carcinoma Detected Due to Acute Pancreatitis].

Gan To Kagaku Ryoho 2019 Dec;46(13):2255-2257

Dept. of Surgery, Shizuoka City Shimizu Hospital.

A 67-year-old man visiting our hospital with the chief complaint of sudden upper abdominal pain was diagnosed with acute pancreatitis. Based on computed tomography findings, intraductal papillary mucinous neoplasm(IPMN)was suspected as the cause of the pancreatitis and detailed examination was conducted following its alleviation. Endoscopic retrograde and magnetic resonance cholangiopancreatography showed marked dilation of the main pancreatic duct, with a mural nodule inside the main pancreatic duct at the pancreatic head. Main duct IPMN was diagnosed and pancreaticoduodenectomy was performed 3 months after the onset of acute pancreatitis. The histopathological findings showed a tumor proliferating in a mold pattern in the lumen of the dilated main pancreatic duct, resulting in a diagnosis of intraductal papillary mucinous carcinoma(IPMC). The presence of IPMN should be considered as a cause of acute pancreatitis; if findings suggestive of IPMN are found on imaging, detailed examinations and treatment are needed in consideration of the potential for malignancy following alleviation of pancreatitis.
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December 2019

[Four Cases of Ileocolic Intussusception Associated with Malignant Lymphoma of the Ileum].

Gan To Kagaku Ryoho 2018 Dec;45(13):1886-1888

Dept. of Surgery, Shizuoka City Shimizu Hospital.

We report the cases we encountered in our department involving 4 patients with malignant ilial lymphoma that caused ileocolic intussusception. The patients were 2 male and 2 female, aged 65-76 years. All patients' chief complaint was abdominal pain. Computed tomography revealed target signs characteristic of intussusception. Colonoscopy showed a tumor that escaped into the colon, leading to the diagnosis of ileocolic intussusception due to an ileal tumor. However, definitive diagnosis could not be achieved from biopsy. Thus, ileocecal resection or right hemicolectomy was performed. Macroscopically, all tumors were polypoid type and were present within 25 cm from the valve of Bauhin. Histological diagnoses were diffuse large B-cell lymphoma(DLBCL)in 2 patients, T-cell lymphoma in one, and follicular lymphoma in one. Postoperative chemotherapy was performed in patients with DLBCL and T-cell lymphoma. Tumors are commonly the cause of intussusception in adults; therefore, emergent surgery is imperative. When malignant lymphoma is diagnosed, a multidisciplinary approach that includes postoperative chemotherapy is necessary.
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December 2018

[A Case of Advanced Gallbladder Cancer with Paraaortic Lymph Node Metastases Successfully Treated by Chemotherapy and Conversion Surgery].

Gan To Kagaku Ryoho 2018 Dec;45(13):2117-2119

Dept. of Surgery, Shizuoka City Shimizu Hospital.

The patient was a 76-year-old man who was admitted to our hospital with a diagnosis of ileus. A gallbladder tumor was found incidentally on CT, and it was diagnosed as gallbladder cancer. Enlargement of multiple lymph nodes, including the paraaortic lymph nodes, was observed, and PET-CT further showed FDG uptake in the lymph nodes. Based on these findings, the patient was diagnosed with Stage ⅣB gallbladder cancer with paraaortic lymph node metastases. Since surgical resection was not possible, chemotherapy with gemcitabine and cisplatin(GEM plus CDDP)was started. After completion of 4 courses of GEM plus CDDP, the enlarged lymph nodes were decreased in size on CT, and there was no FDG uptake on PET-CT. These findings indicated downstaging to Stage Ⅱ; thus, conversion surgery with extended cholecystectomy and lymph node dissection was performed. The pathological diagnosis confirmed that the patient had Stage Ⅱ cancer(pT2N0M0). A case of unresectable gallbladder cancer that was treated with GEM plus CDDP and subsequent conversion surgery is reported, along with a literature review.
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December 2018

Effects of Sitagliptin on Pancreatic Beta-Cells in Type 2 Diabetes With Sulfonylurea Treatment: A Prospective Randomized Study.

J Clin Med Res 2019 Jan 3;11(1):15-20. Epub 2018 Dec 3.

Department of Diabetes, Endocrinology and Metabolism, Division of Internal Medicine, Shinshu University School of Medicine, Matsumoto, Japan.

Background: This prospective randomized, multicenter, open-label, comparative study was performed to analyze the effects of sitagliptin on glycemic control and maintenance of beta-cell function in patients with poorly controlled type 2 diabetes treated with low-dose glimepiride.

Methods: Forty-one patients with type 2 diabetes mellitus treated with low-dose glimepiride (≤ 2 mg/day) were prospectively enrolled in this study (age: 20 - 75 years; hemoglobin A1c (HbA1c): 7.4- 9.4%). The patients were randomized into two groups: the glimepiride (G) group, in which glimepiride dose was increased gradually to 6 mg/day, and the sitagliptin (S) group, in which sitagliptin was added at a dose of 50 mg/day.

Results: HbA1c level was significantly decreased after 24 weeks, but not 12 weeks, in the G group, while a significant decrease was seen after 12 weeks in the S group. Although there were no significant differences in HbA1c level at 24 weeks between the two groups (P = 0.057). The overall trend of changes in HbA1c level suggested that the glucose-lowering effects were superior in the S group. Furthermore, a significant change in fasting glucose was seen in the S group, but not in the G group. Glycemic control target was achieved in 36.7% and 16.7% patients in the S group and the G group, respectively. The proinsulin/insulin (P/I) ratio was significantly increased in the G group, whereas it tended to decrease in the S group. After 24 weeks of treatment, no significant difference was observed in the P/I ratio between the two groups, whereas a significant difference was noted in the ΔP/I (amount of change). Albuminuria tended to increase in the G group compared with the S group.

Conclusion: The results of the present study suggested that sitagliptin effectively lowered hyperglycemia and that it may have a protective effect on pancreatic beta-cells when combined with a low dose of glimepiride. Therefore, sitagliptin may represent a useful combination therapy with low-dose sulfonylurea, not only for achieving glycemic control but also for protection of pancreatic beta-cells.
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http://dx.doi.org/10.14740/jocmr3632DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6306137PMC
January 2019

Implications of thyroid autoimmunity in infertile women with subclinical hypothyroidism in the absence of both goiter and anti-thyroid antibodies: lessons from three cases.

Endocr J 2019 Feb 18;66(2):193-198. Epub 2018 Dec 18.

Department of Diabetes, Endocrinology and Metabolism, Division of Internal Medicine, Shinshu University School of Medicine, Matsumoto 390-8621, Japan.

There is a great deal of research interest regarding the underlying causes of slightly elevated TSH values in patients with subclinical hypothyroidism (SH) without abnormal findings on ultrasonography or anti-thyroid antibodies. Twelve infertile women with thyroglobulin antibody (TGAb) and thyroid peroxidase antibody (TPOAb)-negative nongoitrous SH were referred to our department of endocrinology between September 2007 and September 2015. None had been diagnosed with autoimmune thyroid disease or had any possible causes of SH. In all cases, LT4 was prescribed to bring TSH value below 2.5 mIU/L. Among those with infertility treatments, six (50%) became pregnant and gave birth to infants. Here, we report three of these six women who successfully became pregnant with infertility treatments and were found to have thyroid autoimmunity on data obtained during the postpartum period. Two developed postpartum thyroiditis, and the remaining one woman was temporarily weakly positive for TPOAb at 9 months postpartum. We describe three infertile subclinically hypothyroid women without goiter or anti-thyroid antibodies with potential thyroid autoimmunity. Thyroid autoimmunity is one of the most important issues for management of pregnant women, and thus, our findings are noteworthy for the care of infertile women with SH. This report provides valuable insights into the presence of autoimmunity in nongoitrous thyroid-associated antibody-negative SH patients.
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http://dx.doi.org/10.1507/endocrj.EJ18-0350DOI Listing
February 2019

Prediction of lowest nocturnal blood glucose level based on self-monitoring of blood glucose in Japanese patients with type 2 diabetes.

J Diabetes Complications 2018 12 13;32(12):1118-1123. Epub 2018 Sep 13.

Department of Diabetes, Endocrinology and Metabolism, Division of Internal Medicine, Shinshu University School of Medicine, Matsumoto, Japan.

Aims: Continuous glucose monitoring (CGM) is not available for all patients with type 2 diabetes (T2D) at risk of nocturnal hypoglycemia (NH). This study was performed to predict the lowest nocturnal blood glucose (LNBG) levels.

Methods: An LNBG prediction formula was developed by multivariate analysis using the data including self-monitoring of blood glucose from a formula making (FM) group of 29 insulin-treated T2D patients with CGM. The validity of the formula was assessed by nonparametric regression analysis of actual and predicted values in a formula validation group consisting of 21 other insulin-treated patients. The clinical impact on prediction was evaluated using a Parkes error grid.

Results: In the FM group with a median age of 64.0, the following formula was established: Predicted LNBG (mg/dL) = 127.4-0.836 × Age (y) + 0.119 × Self-monitored fasting blood glucose (mg/dL) + 0.717 × Basal insulin dose (U/day) (standard error of calibration 17.2 mg/dL). Based on the validation results, standard error of prediction was 31.0 mg/dL. All predicted values fell within zones A (no effect on clinical action) and B (little or no effect on clinical outcome) on the grid.

Conclusions: LNBG could be predicted, and may be helpful for NH prevention.
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http://dx.doi.org/10.1016/j.jdiacomp.2018.09.007DOI Listing
December 2018

[Findings from Total Colonoscopy in Obstructive Colorectal Cancer Patients Who Underwent Stent Placement as a Bridge to Surgery(BTS)].

Gan To Kagaku Ryoho 2017 Nov;44(12):1238-1240

Dept. of Surgery, Shizuoka City Shimizu Hospital.

We clinically investigated 34 patients with obstructive colorectal cancer who underwent placement of a colonic stent as a bridge to surgery(BTS), focusing on endoscopic findings after stent placement.Twenty -nine patients(85.3%)underwent colonoscopy after stent placement, and the entire large intestine could be observed in 28(96.6%).Coexisting lesions were observed in 22(78.6%)of these 28 patients.The lesions comprised adenomatous polyps in 17 patients(60.7%), synchronous colon cancers in 5 patients(17.9%), and obstructive colitis in 3 patients(10.7%), with some overlapping cases.All patients with multiple cancers underwent one-stage surgery, and all lesions were excised at the same time.Colonoscopy after colonic stent placement is important for preoperative diagnosis of coexisting lesions and planning the extent of resection. These considerations support the utility of colonic stenting for BTS.
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November 2017

[Results of Preoperative Colon Stent Placement for Obstructive Colorectal Cancer].

Gan To Kagaku Ryoho 2017 Nov;44(12):1229-1231

Dept. of Surgery, Shizuoka City Shimizu Hospital.

We examined short-term outcomes in 34 patients who had stenting as a bridge to surgery(BTS)for obstructive colorectal cancer during the 5-year period between April 2012 and March 2017.T he patients were 22 men and 12 women with a mean age of 72.6 years. Stenting and decompression were successful in all patients, and the mean time to oral intake after stenting was 2.5 days.No serious complications related to stenting occurred.Elective surgery could be performed in all patients after stenting.The mean number of days to surgery was 24.7 days.Laparoscopic surgery was performed in 14 patients.Postoperative complications included minor leakage in 1 patient, an abdominal wall abscess due to tumor invasion of the abdominal wall in 1 patient, and heart failure and pneumonia, as serious complications, in 1 patient each.Colorectal stenting in patients with obstructive colorectal cancer is a safe and relatively simple procedure.This is an effective treatment strategy in which preoperative colorectal decompression enables a one-stage resection.
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November 2017

[A Case of Retroperitoneal Liposarcoma That Required Three Times Surgical Resections during Four Years].

Gan To Kagaku Ryoho 2017 Nov;44(12):1158-1160

Dept. of Surgery, Shizuoka City Shimizu Hospital.

The patient was a 64-year-old man, who had undergone surgical resection for a right retroperitoneal giant tumor. The histopathological diagnosis was a well-differentiated liposarcoma. Two years and 4 months after the initial surgery, 3 recurrent lesions were found on the dorsal side of the colon hepatic flexure, and resection was performed. One year and 1 month after the secondary surgery, the tumor recurred again, and invaded the right abdominal wall and right transverse colon. Tumor was completely resected macroscopically. All resected tumors were well-differentiated liposarcoma. There have not been any signs of recurrence until 1 year and 6 months after the last operation. For retroperitoneal liposarcoma, complete surgical resection is the only established treatment, but the tumor often recurs. Aggressive resection against recurrent cases is known to contribute to life prognosis, but there is a possibility of the degeneration to a highly malignant dedifferentiated tumor while recurrence is repeated. Therefore, sufficient follow-up observation is needed.
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November 2017

Careful readings for a flash glucose monitoring system in nondiabetic Japanese subjects: individual differences and discrepancy in glucose concentrarion after glucose loading [Rapid Communication].

Endocr J 2017 Aug 25;64(8):827-832. Epub 2017 Jul 25.

Department of Diabetes, Endocrinology and Metabolism, Division of Internal Medicine, Shinshu University School of Medicine, Matsumoto, Japan.

The FreeStyle Libre Flash Glucose Monitoring System (FGM), which can continuously measure glucose concentration in the interstitial fluid glucose (FGM-ISFG), has been in clinical use worldwide. However, it is not clear how accurately FGM-ISFG reflects plasma glucose concentration (PG). In the present study, we examined the clinical utility of FGM by oral glucose tolerance test (OGTT). In eight healthy volunteers (3 males; mean age, 41.8 y) wearing FGM sensors for 14 days, OGTT was performed during days 1-7 and days 8-14, and then both FGM-ISFG and PG were compared. Parkes error grid analysis indicated that all of 65 FGM-ISFG values were within Zone A (no effect on clinical action) and Zone B (little or no effect on clinical outcome). However, in OGTT, the mean FGM-ISFG was higher than the mean actual PG at 30, 60, and 90 minutes after loading (155.5 vs. 139.2 mg/dL, 166.2 vs. 139.2 mg/dL, 149.5 vs. 138.2 mg/dL, respectively; p<0.05). Moreover, the area under the curve of FGM-ISFG was also significantly larger than that of PG (17,626.2 vs. 15,195.0 min·mg/dL; p<0.05). In four of eight subjects, FGM-ISFG tended to be higher than PG in both OGTTs, and the greatest difference between the two values was 58 mg/dL. FGM is useful for glycemic control, whereas it is not appropriate to change therapeutic regimens based on the judgment of nocturnal hypoglycemia and postprandial hyperglycemia by FGM-ISFG. Careful attention is required for proper application of FGM.
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http://dx.doi.org/10.1507/endocrj.EJ17-0193DOI Listing
August 2017

[Long-Term Complete Response by S-1 Chemotherapy for Gastric Cancer with Para-Aortic Lymph Node Metastases].

Gan To Kagaku Ryoho 2016 Nov;43(12):2231-2233

Dept. of Surgery, Shizuoka City Shimizu Hospital.

We describe a 67-year-old man with long-term CR by S-1 chemotherapy for gastric cancer with para-aortic lymph node metastases after reduction surgery. The patient presented at our hospital with epigastric pain. He was diagnosed with gastric cancer with para-aortic lymph node metastases. We performed gastrectomy and D1 lymphadenectomy without any resection of the para-aortic lymph node metastases. We treated the patient with oral S-1 chemotherapy. The initial treatment schedule was 100mg/body/day, twice daily for 4weeks with 2weeks of rest. Grade 1 neutropenia developed at the end of the second course of treatment. The regimen was changed to 2 weeks of administration, with 1 week of rest. The para-aortic lymph node metastases immediately responded to the chemotherapy. Abdominal CT showed almost complete regression of the lymph node metastases 10 months postoperatively. The patient has received S-1 chemotherapy and remained in remission for more than 5 years 6 months.
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November 2016

[Cases of Obstructive Colon Cancer for Which Elective Surgery Was Performed after Colonic Stent Placement].

Gan To Kagaku Ryoho 2015 Nov;42(12):2239-41

Dept. of Surgery, Shizuoka City Shimizu Hospital.

The present study investigated the short-term outcomes of 20 patients with obstructive colon cancer who underwent colonic stent placement as a bridge to surgery (BTS) during the 3-year period between April 2012 and March 2015. Subjects comprised 13 men and 7 women, with a mean age of 68.3 years. Placement and decompression were successfully achieved in all of the patients. Oral ingestion became possible from a mean of 2.7 days after placement. No serious complications associated with placement were encountered. Total colonoscopy was performed after placement in 17 patients (85%), and independent advanced cancer was seen in the proximal portion of the colon in 1 patient. Elective surgery was performed for all of the patients after placement. Excluding the 2 patients for whom preoperative chemotherapy or treatment of another disease was prioritized, the mean interval to surgery for the remaining 18 patients was 23.2 days. The operative procedure performed was laparoscopic surgery in 8 patients (40%). Although minor leakage (n=1) and abdominal wall abscess (n=1) were observed as postoperative complications, the patients generally had an uneventful course. Colonic stent placement for obstructive colon cancer is relatively easy and safe, and may be considered as an effective treatment method that enables favorable intestinal decompression preoperatively and one-stage resection.
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November 2015

[Case Report of a Splenic Abscess Due to Colon Cancer].

Gan To Kagaku Ryoho 2015 Nov;42(12):2227-9

Dept. of Surgery, Shizuoka City Shimizu Hospital.

The patient was a 63-year-old man with a chief complaint of fever and abdominal pain. He was admitted with the diagnosis of splenic abscess on enhanced abdominal computed tomography. After improvement of general condition, we planned a colonoscopy. However, the symptoms were not relieved, so we decided to perform splenectomy. The operative findings included a bulky mass at the splenic flexure, which involved the spleen and the pancreatic tail. Therefore, partial colectomy, splenectomy, and distal pancreatectomy were performed. The pathological examination revealed that the splenic abscess had not developed as a direct extension of the colon cancer but the cancer spread to the splenic hilus. Surgical resection is the first choice in the therapy of splenic abscess developing from colon cancer.
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November 2015

Early-onset, severe, and recurrent primary hyperparathyroidism associated with a novel CDC73 mutation.

Endocr J 2015 8;62(7):627-32. Epub 2015 May 8.

Department of Diabetes, Endocrinology and Metabolism, Shinshu University School of Medicine, Matsumoto, 390-8621, Japan.

Hyperparathyroidism-jaw tumor syndrome (HPT-JT) is a rare autosomal dominant hereditary tumor syndrome characterized by synchronous or metachronous occurrence of primary hyperparathyroidism (PHPT), ossifying fibroma of the maxilla and/or mandible, renal tumor and uterine tumors. Early diagnosis of this syndrome is essential because it is associated with increased risk of parathyroid cancer. A 30-year-old man with urolithiasis had severe hypercalcemia (15.0 mg/dL after correction) induced by inappropriate parathyroid hormone (PTH) secretion (intact PTH 1390 pg/mL), indicating severe PHPT. An underlying parathyroid tumor was surgically removed and was histologically confirmed to be an adenoma. However, PHPT due to another parathyroid tumor reoccurred two years after the surgery. Although no HPT-JT-associated manifestations other than PHPT were detected, HPT-JT was strongly suspected based on the exclusion of multiple endocrine neoplasia (MEN) and the young age of disease occurrence. Genetic analysis revealed a novel nonsense mutation (p.Arg91X; c.271C>T) in exon 3 of the causative gene, CDC73, which encodes the tumor suppressor protein parafibromin. The residual parathyroid glands were all removed without autotransplantation of parathyroid gland taking into consideration prospective parathyroid carcinogenesis. The resected parathyroid tumor was also an adenoma. The present case highlights that HPT-JT should be considered and CDC73 mutation analysis should be performed, especially in cases of early-onset PHPT, recurrent PHPT, PHPT with polyglandular parathyroid involvement, and PHPT presenting with severe hypercalcemia even if there is no positive family history.
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http://dx.doi.org/10.1507/endocrj.EJ15-0057DOI Listing
May 2016

Clustering of CARMA1 through SH3-GUK domain interactions is required for its activation of NF-κB signalling.

Nat Commun 2015 Jan 20;6:5555. Epub 2015 Jan 20.

Laboratory for Cell Signaling, RIKEN Center for Integrative Medical Sciences, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.

CARMA1-mediated NF-κB activation controls lymphocyte activation through antigen receptors and survival of some malignant lymphomas. CARMA1 clusters are formed on physiological receptor-mediated activation or by its oncogenic mutation in activated B-cell-diffuse large B-cell lymphomas (ABC-DLBCLs) with constitutive NF-κB activation. However, regulatory mechanisms and relevance of CARMA1 clusters in the NF-κB pathway are unclear. Here we show that SH3 and GUK domain interactions of CARMA1 link CARMA1 clustering to signal activation. SH3 and GUK domains of CARMA1 interact by either intra- or intermolecular mechanisms, which are required for activation-induced assembly of CARMA1. Disruption of these interactions abolishes the formation of CARMA1 microclusters at the immunological synapse, CARMA-regulated signal activation following antigen receptor stimulation as well as spontaneous CARMA1 clustering and NF-κB activation by the oncogenic CARMA1 mutation in ABC-DLBCLs. Thus, the SH3-GUK interactions that regulate CARMA1 cluster formations are promising therapeutic targets for ABC-DLBCLs.
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http://dx.doi.org/10.1038/ncomms6555DOI Listing
January 2015

[Study of S-1 and oxaliplatin(SOX) plus bevacizumab as first-line therapy in patients with unresectable colorectal cancer].

Gan To Kagaku Ryoho 2014 Dec;41(13):2583-6

Dept. of Surgery, Shizuoka City Shimizu Hospital.

We examined the safety and efficacy of S-1 and oxaliplatin plus bevacizumab (SOX+BV)as first-line therapy for advanced/recurrent unresectable colorectal cancer. The subjects were 14 patients with colorectal cancer who received ≥3 courses of SOX+BV therapy in our department.The dosing regimen for 1 course was as follows: BV (7.5 mg/kg) and oxaliplatin (130 mg/m(2)) were administered via intravenous drip infusion on the first day of the course, and S-1 was orally administered twice a day for 2 weeks, repeated every 3 weeks. All patients completed the study treatment, and the median number of courses completed was 9 courses (range: 3-17 courses). In terms of anti-tumor efficacy, complete remission (CR) was observed in 1 patient (7.1%); partial remission (PR), in 9 patients (64.3%); stable disease (SD), in 3 patients (21.4%); and progressive disease (PD), in 1 patient (7.1%), with a response rate of 71.4% and a disease control rate of 92.9%. The median relapse-free survival based on baseline PD was 12 months, and the median relapse-free survival based on PD according to the Response Evaluation Criteria in Solid Tumors (RECIST) was 10 months.The most common adverse events observed included peripheral sensory neuropathy (100%), fatigue (68.3%), anorexia (57.1%), and leukopenia/neutropenia (35.7%); however, almost all adverse events were Grade≤2 and could be managed.The SOX+BV therapy demonstrated an antitumor efficacy similar to that observed with oxaliplatin, fluorouracil, and folinic acid (FOLFOX)+BV therapy without the use of a central venous port.Therefore, the SOX+BV therapy may be among the effective option as first-line therapy for advanced/recurrent colorectal cancer.
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December 2014

A newly identified missense mutation in RET codon 666 is associated with the development of medullary thyroid carcinoma.

Endocr J 2014 15;61(11):1141-4. Epub 2014 Oct 15.

Division of Diabetes, Endocrinology and Metabolism, Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto 390-8621, Japan.

A 38-year-old woman with a thyroid nodule measuring approximately 2 cm was suspected to have medullary thyroid carcinoma (MTC) because of markedly elevated serum calcitonin and carcinoembryonic antigen levels. There were no signs of pheochromocytoma, whereas primary hyperparathyroidism was suspected based on the findings of inappropriate hypersecretion of parathyroid hormone although no parathyroid tumor was detected with imaging studies. RET mutation analysis revealed a novel germline missense mutation in codon 666, c.1997A>G (p.K666R). She underwent total thyroidectomy with lymphadenectomy and simultaneous total parathyroidectomy with autotransplantation of parathyroid tissue. She was given calcium lactate and alfacalcidol to prevent postoperative hypocalcemia. Pathological findings of the thyroid tumor were compatible with MTC, but the resected parathyroid glands were intact. To our knowledge, c.1997A>G (p.K666R) is a new RET mutation. This is a minor variant, but it is significant because of the possible pathogenicity in tumor formation. It is often difficult to determine whether MTC is generated as part of MEN2-related disease or familial MTC when it is a unique manifestation. In addition, it is still unclear whether all missense mutations in this codon reported previously will lead to the same clinical course and prognosis. Further careful observations of clinical presentation are required to determine the clinical features associated with this variant.
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http://dx.doi.org/10.1507/endocrj.ej14-0334DOI Listing
January 2015

An ITAM-Syk-CARD9 signalling axis triggers contact hypersensitivity by stimulating IL-1 production in dendritic cells.

Nat Commun 2014 May 7;5:3755. Epub 2014 May 7.

Division of Molecular and Cellular Immunoscience, Department of Biomolecular Sciences, Saga Medical School, 5-1-1 Nabeshima Saga, Saga 849-8501, Japan.

A variety of reactive organic compounds, called haptens, can cause allergic contact dermatitis. However, the innate immune mechanisms by which haptens stimulate dendritic cells (DCs) to sensitize T cells remain unclear. Here we show that the coupling of ITAM-Syk-CARD9 signalling to interleukin-1 (IL-1) secretion in DCs is crucial for allergic sensitization to haptens. Both MyD88 and Caspase recruitment domain-containing protein 9 (CARD9) signalling are required for contact hypersensitivity (CHS). Naïve T cells require signals received through IL-1R1-MyD88 for effector differentiation, whereas DCs require CARD9 and spleen tyrosine kinase (Syk) signalling for hapten-induced IL-1α/β secretion and their ability to prime T cells. DC-specific deletion of CARD9, DAP12, Syk or NLRP3, but not MyD88, is sufficient to abolish CHS. All tested haptens, but not irritants, can induce Syk activation, leading to both the CARD9/BCL10-dependent pro-IL-1 synthesis (signal1) and reactive oxygen species-mediated NLRP3 inflammasome activation (signal2), required for IL-1 secretion. These data unveil an innate immune mechanism crucial for allergic contact sensitization to chemical compounds.
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http://dx.doi.org/10.1038/ncomms4755DOI Listing
May 2014

Occurrence of IgG4-related hypophysitis lacking IgG4-bearing plasma cell infiltration during steroid therapy.

Intern Med 2014 1;53(7):753-7. Epub 2012 Mar 1.

Division of Diabetes, Endocrinology and Metabolism, Department of Internal Medicine, Shinshu University School of Medicine, Japan.

Eight years after an episode of multiple IgG4-related disease, a pituitary mass with panhypopituitarism and a visual disturbance developed in a 70-year-old man under low-dose steroid therapy. A pituitary biopsy revealed findings of lymphocytic hypophysitis with the absence of IgG4-positive plasma cell infiltration. The serum IgG4 level was unremarkable. Although performing a pituitary biopsy and measuring the serum IgG4 level is crucial for making a diagnosis of IgG4-related hypophysitis, it is occasionally difficult to diagnose the disease in patients treated with steroid therapy, as observed in the present case. Based on a review of the diagnosis, conducting a careful assessment is required, especially in men and elderly patients thought to have solitary hypophysitis.
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http://dx.doi.org/10.2169/internalmedicine.53.0714DOI Listing
May 2015

Efficacy of combination therapy with sitagliptin and low-dose glimepiride in Japanese patients with type 2 diabetes.

J Clin Med Res 2014 Apr 6;6(2):127-32. Epub 2014 Feb 6.

Department of Internal Medicine, Division of Diabetes, Endocrinology and Metabolism, Shinshu University School of Medicine, Japan.

Background: We examined the effects of combination therapy with 50 mg/day of sitagliptin and low-dose glimepiride (1 mg/day) in patients with type 2 diabetes.

Methods: Twenty-six patients with poorly controlled type 2 diabetes currently taking high-dose glimepiride (≥ 2 mg/day) were enrolled in the study. The dose of glimepiride was reduced to 1 mg/day and 50 mg/day of sitagliptin was added without changing the doses of any other antihyperglycemic agents. The patients were divided into two groups: the low-dose group (2 or 3 mg glimepiride decreased to 1 mg: n = 15) and the high-dose group (4 or 6 mg glimepiride decreased to 1 mg: n = 11).

Results: Combination therapy significantly lowered HbA1c after 24 weeks of treatment in both groups. In the low-dose group, 8.1 ± 0.2% decreased to 7.0 ± 0.1%; in the high-dose group, 8.4 ± 0.1% decreased to 7.3 ± 0.2%. The time course of the degree of HbA1c reduction in the high-dose group was almost superimposable on that in the low-dose group. There were no changes in body weight and no hypoglycemia and in either group during the study period. In conclusion, our results suggested that the combination therapy used in the study is both well tolerated and effective.

Conclusion: This study indicated the usefulness of dipeptidyl peptidase (DPP)-4 inhibitors in Japanese patients with type 2 diabetes, and also reinforces the importance of low doses of sulfonylurea for effective glycemic management.
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http://dx.doi.org/10.14740/jocmr1701wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3935521PMC
April 2014

Laparoscopic partial hepatectomy of focal nodular hyperplasia.

Case Rep Gastroenterol 2012 Sep 8;6(3):720-5. Epub 2012 Nov 8.

Department of Surgery, Shizuoka City Shimizu Hospital, Shizuoka, Japan.

Focal nodular hyperplasia is a benign liver lesion incidentally discovered with increasing frequency because of the proliferation of imaging studies. Radiographic characterization can diagnose this pathologic lesion and nonoperative therapy is the standard of care. However, surgical resection may be required for diagnostic reasons or symptomatic patients. Depending on the anatomic location of the lesion, biopsy and/or resection can be performed laparoscopically. We herein report the case of a 26-year-old Japanese woman with a hepatic tumor who required a medical examination. Her medical history was negative for alcohol abuse, oral contraceptive administration and trauma. Clinical examination showed no significant symptoms. Ultrasonography, computed tomography and magnetic resonance imaging showed a mass located in the left lateral segment of the liver with a diameter of about 40 mm. It was difficult to diagnose the tumor definitively from these imaging studies, so we performed laparoscopic partial hepatectomy with successive firing of endoscopic staplers. The histopathological diagnosis was focal nodular hyperplasia. Surgical procedures and postoperative course were uneventful and the patient was discharged from the hospital on postoperative day 5.
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http://dx.doi.org/10.1159/000345392DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3506082PMC
September 2012
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