Publications by authors named "Hiromi Nagata"

30 Publications

  • Page 1 of 1

Clinical Relevance of Tissue and Serum Human Epidermal Growth Factor Receptor 2 Expression in Patients With Esophageal Squamous Cell Carcinoma.

J Surg Res 2022 Jan 25;269:189-200. Epub 2021 Sep 25.

Department of Surgery, National Defense Medical College, Tokorozawa, Japan.

Background: Serum and tissue human epidermal growth factor receptor 2 (HER2) levels were evaluated in resected esophageal squamous cell carcinoma (SCC) specimens to assess the relationship between HER2 expression and long-term prognosis.

Methods: We included 95 patients who underwent esophagectomy for esophageal SCC. The serum HER2-extracellular domain (sHER2-ECD) levels were measured using an ELISA kit. A time-dependent receiver operating characteristics curve for censored survival outcomes was constructed to estimate the optimal cut-off value of sHER2-ECD (set at 4211 pg/mL). Immunohistochemical (IHC) staining was performed for HER2, and specimens were classified based on low (0 or 1+) or high HER2-IHC expression (2+ or 3+).

Results: Patients with low sHER2-ECD levels showed poorly differentiated tumors, nodal involvement, and larger tumor size more frequently compared to patients with high sHER2-ECD levels. There were no differences in clinicopathological features based on HER2-IHC expression. Between patients with high and low HER2-IHC expression, the former group showed significantly higher sHER2-ECD levels. Patients with high sHER2-ECD levels had significantly favorable relapse-free survival (RFS) and overall survival (OS) compared to those with low sHER2-ECD levels. Conversely, patients with high HER2-IHC expression had significantly poorer RFS than did patients with low HER2-IHC expression, although no difference was observed in OS. Additionally, patients with high sHER2-ECD levels and low HER2-IHC expression had the highest OS and RFS among the patients studied.

Conclusions: The correlation among sHER2-ECD levels, HER2-IHC expression, and prognosis was demonstrated. Prospective studies are required to validate the impact of serum and tissue HER2 expression in esophageal SCC prognosis.
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http://dx.doi.org/10.1016/j.jss.2021.07.046DOI Listing
January 2022

An Open-label Phase I/IIa Clinical Trial of 11β-HSD1 Inhibitor for Cushing's Syndrome and Autonomous Cortisol Secretion.

J Clin Endocrinol Metab 2021 09;106(10):e3865-e3880

Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka-city, Japan.

Context: 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitors demonstrate antimetabolic and antisarcopenic effects in Cushing's syndrome (CS) and autonomous cortisol secretion (ACS) patients.

Objective: To confirm the efficacy and safety of S-707106 (11β-HSD1 inhibitor) administered to CS and ACS patients.

Design: A 24-week single-center, open-label, single-arm, dose-escalation, investigator-initiated clinical trial on a database.

Setting: Kyushu University Hospital, Kurume University Hospital, and related facilities.

Patients: Sixteen patients with inoperable or recurrent CS and ACS, with mildly impaired glucose tolerance.

Intervention: Oral administration of 200 mg S-707106 after dinner, daily, for 24 weeks. In patients with insufficient improvement in oral glucose tolerance test results at 12 weeks, an escalated dose of S-707106 (200 mg twice daily) was administered for the residual 12 weeks.

Main Outcome Measures: The rate of participants responding to glucose tolerance impairment, defined as those showing a 25% reduction in the area under the curve (AUC) of plasma glucose during the 75-g oral glucose tolerance test at 24 weeks.

Results: S-707106 administration could not achieve the primary endpoint of this clinical trial (>20% of responsive participants). AUC glucose decreased by -7.1% [SD, 14.8 (90% CI -14.8 to -1.0), P = 0.033] and -2.7% [14.5 (-10.2 to 3.4), P = 0.18] at 12 and 24 weeks, respectively. S-707106 administration decreased AUC glucose significantly in participants with a high body mass index. Body fat percentage decreased by -2.5% [1.7 (-3.3 to -1.8), P < 0.001] and body muscle percentage increased by 2.4% [1.6 (1.7 to 3.1), P < 0.001].

Conclusions: S-707106 is an effective insulin sensitizer and antisarcopenic and antiobesity medication for these patients.
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http://dx.doi.org/10.1210/clinem/dgab450DOI Listing
September 2021

AGEs inhibit scavenger receptor class B type I gene expression via Smad1 in HUVECs.

J Mol Endocrinol 2021 03;66(3):223-231

Department of Endocrinology and Metabolism, Faculty of Medicine, Kagawa University, Miki-cho, Kagawa, Japan.

Vascular complications are the main cause of morbidity and mortality in diabetic patients, and advanced glycation end products (AGEs) play a critical role in promoting diabetic vascular dysfunction. The human homolog of scavenger receptor class B type I (SR-BI), CD36, and LIMPII analog-1 (hSR-BI/CLA-1) facilitates the cellular uptake of cholesterol from HDL. In endothelial cells, HDL activates endothelial nitric oxide synthase (eNOS) via hSR-BI/CLA-1. In this study, we elucidated the effects of AGEs on hSR-BI/CLA-1 expression in human umbilical vein endothelial cells (HUVECs). HSR-BI/CLA-1 expression was examined by real-time PCR, western blot analysis, and reporter gene assay in HUVECs incubated with AGEs. eNOS activity was assessed by detecting the phosphorylation (Ser 1179) of eNOS. Our results showed that AGEs decreased the endogenous expression of hSR-BI/CLA-1. AGEs also inhibited the activity of the hSR-BI/CLA-1 promoter and its mRNA expression via receptor RAGE. We identified the binding site for Smad1 on the hSR-BI/CLA-1 promoter: Smad1 bound to its promoter. AGE treatment stimulated the transcriptional activity of Smad1, and mutation of the Smad1 binding site inhibited the effect of AGEs on the hSR-BI/CLA-1 promoter. HDL-treatment enhanced the phosphorylation of eNOS at Ser 1179, but pretreatment with AGEs inhibited the phosphorylation of eNOS Ser 1179. These results suggested that AGEs downregulate the expression of the endothelial hSR-BI/CLA-1 via the Smad1 pathway, which may be a therapeutic target for diabetic endothelial dysfunction.
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http://dx.doi.org/10.1530/JME-20-0177DOI Listing
March 2021

Differences Between Laparoscopic and Open Gastrectomy on the Impact of Postoperative Infectious Complications on Prognosis.

Anticancer Res 2020 Dec;40(12):7109-7117

From the Department of Surgery, National Defense Medical College, Tokorozawa, Japan.

Background/aim: The aim of this study was to evaluate the impact of laparoscopic gastrectomy (LG) for gastric cancer on long-term survival in patients with postoperative infectious complications (PIC).

Patients And Methods: A total of 608 patients who underwent gastrectomy were classified into two groups based on the surgical approach: LG (385 patients) and open gastrectomy (OG: 211 patients). Long-term survival after gastrectomy was compared between patients with and without PIC in both LG and OG groups.

Results: Although the patients with PIC in OG group tended to have worse overall survival (OS) than those without PIC, the OS was not significantly different between the patients with and without PIC in LG group. Although multivariate analysis demonstrated that nodal involvement and PIC were significantly associated with OS in OG group, age and tumor depth, and not PIC, were associated with OS in LG group.

Conclusion: PIC were negative predictors of clinical outcomes in patients with gastric cancer, particularly those who underwent OG, and long-term prognosis may be impacted less by PIC in patients undergoing LG.
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http://dx.doi.org/10.21873/anticanres.14740DOI Listing
December 2020

Preoperative fall risk assessment score as a prognostic factor in gastric cancer patients after gastrectomy.

Jpn J Clin Oncol 2021 Apr;51(4):569-576

Department of Surgery, National Defense Medical College, Tokorozawa, Japan.

Objective: Falls are related to frailty, which is known as an unfavorable prognosticator of gastric cancer. In this study, we investigated the influence of the fall risk assessment score on short- and long-term prognoses in patients with gastric cancer after gastrectomy.

Methods: A total of 430 patients who underwent gastrectomy for gastric cancer were included in this retrospective study. The fall risk assessment score was scored by nursing staffs on admission. We investigated the relationships between the fall risk assessment score and clinicopathological findings, postoperative outcomes and prognoses. We assigned patients with a fall risk assessment score ≥7 to the high-risk group (92 cases, 21.4%) and those with a fall risk assessment score <6 to the low-risk group (338 cases, 78.6%).

Results: There were no significant differences between the two groups in pathological stage of gastric cancer and postoperative complications, but the high-risk group had significantly longer postoperative hospital stays than the low-risk group (P < 0.001). The overall and the relapse-free survival rates in the high-risk group were significantly lower than those in the low-risk group. The high-risk group was one of the independent poor prognostic factors for overall survival, with a hazard ratio of 2.91 (P ≤ 0.001) in univariate analysis and a hazard ratio of 2.74 (P = 0.008) in multivariate analysis.

Conclusions: While the fall risk assessment score is an objective and easy-to-use method to assess fall risk and frailty, it may present a prognostic factor in gastric cancer.
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http://dx.doi.org/10.1093/jjco/hyaa224DOI Listing
April 2021

Significance of Discordant Results Between Confirmatory Tests in Diagnosis of Primary Aldosteronism.

J Clin Endocrinol Metab 2021 01;106(2):e866-e874

Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Context: Current clinical guidelines recommend confirmation of a positive result in at least one confirmatory test in the diagnosis of primary aldosteronism (PA). Clinical implication of multiple confirmatory tests has not been established, especially when patients show discordant results.

Objective: The aim of the present study was to explore the role of 2 confirmatory tests in subtype diagnosis of PA.

Design And Setting: A retrospective cross-sectional study was conducted at two referral centers.

Participants And Methods: We identified 360 hypertensive patients who underwent both a captopril challenge test (CCT) and a saline infusion test (SIT) and exhibited at least one positive result. Among them, we studied 193 patients with PA whose data were available for subtype diagnosis based on adrenal vein sampling (AVS).

Main Outcome Measure: The prevalence of bilateral subtype on AVS according to the results of the confirmatory tests was measured.

Results: Of patients studied, 127 were positive for both CCT and SIT (double-positive), whereas 66 were positive for either CCT or SIT (single-positive) (n = 34 and n = 32, respectively). Altogether, 135 were diagnosed with bilateral subtype on AVS. The single-positive patients had milder clinical features of PA than the double-positive patients. The prevalence of bilateral subtype on AVS was significantly higher in the single-positive patients than in the double-positive patients. (63/66 [95.5%] vs 72/127 [56.7%], P < .01). Several clinical parameters were different between CCT single-positive and SIT single-positive patients.

Conclusion: Patients with discordant results between CCT and SIT have a high probability of bilateral subtype of PA on AVS.
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http://dx.doi.org/10.1210/clinem/dgaa812DOI Listing
January 2021

Significance of aldosterone gradient within left adrenal vein in diagnosing unilateral subtype of primary aldosteronism.

Clin Endocrinol (Oxf) 2021 01 19;94(1):24-33. Epub 2020 Sep 19.

Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Context: The success rate of cannulation of the right adrenal vein is limited. The aldosterone gradient within the same adrenal vein branch is specific for aldosterone-producing adenoma.

Objective: This study was performed to investigate whether the absolute aldosterone gradient within the left adrenal vein (left-AV absolute aldosterone gradient) indicates unilateral excess aldosterone.

Design And Setting: A retrospective cross-sectional study in a single referral centre.

Patients And Methods: In total, 123 consecutive patients with primary aldosteronism who had successful adrenal vein sampling (AVS) data were examined. The left-AV absolute aldosterone gradient was considered significant when a gradient of >4:1 in the aldosterone-to-cortisol ratio between the common trunk vein and central vein was found.

Main Outcome Measure: The prevalence of the unilateral subtype in patients with a significant left-AV absolute aldosterone gradient.

Results: The prevalence of the unilateral subtype was higher in patients with than without a significant left-AV absolute aldosterone gradient (88.2% [15/17] vs 21.7% [23/106], P < .001). Of 60 patients with spontaneous hypokalemia, left unilateral disease on computed tomography, or both, a significant left-AV absolute aldosterone gradient was present only in patients with the unilateral subtype on AVS (42.9% [15/35]), but not in those with the bilateral subtype (0.0% [0/25]). These data were validated in an external cohort.

Conclusion: The presence of a significant left-AV absolute aldosterone gradient can be used to diagnose the left unilateral subtype of primary aldosteronism on AVS in patients with spontaneous hypokalemia, left unilateral disease on computed tomography or both.
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http://dx.doi.org/10.1111/cen.14320DOI Listing
January 2021

Impact of Antiplatelet and Anticoagulant Therapies on Platelet-related Prognostic Markers in Patients With Esophageal Cancer.

In Vivo 2020 Jul-Aug;34(4):1941-1949

Department of Surgery, National Defense Medical College, Saitama, Japan.

Background/aim: In recent years, platelet-related markers were recognized as useful prognostic factors in various malignancies. We investigated the relationship between platelet-related prognostic markers and anti-platelet or anti-coagulant therapies for survival outcomes in esophageal squamous cell carcinoma.

Patients And Methods: Preoperative platelet-related prognostic markers were evaluated from peripheral blood testing and statistical analyses were performed to evaluate the prognostic value of these markers and reveal the effects of antiplatelets and/or anticoagulants regarding their prognostic relevance.

Results: In all 176 patients, preoperative platelet-to-lymphocyte ratio (PLR) was not found to be a predictor of overall survival (OS). However, in patients without antiplatelet or anticoagulant therapies, PLR was significantly associated with a poor OS (p=0.03). Although platelet large cell ratio (P-LCR) was not associated with the prognosis in patients with antiplatelet and/or anticoagulant therapies, higher P-LCR was associated with a poor prognosis in patients without antiplatelet or anticoagulant therapies (p<0.0001).

Conclusion: Researching detailed antiplatelet and anticoagulant therapies could reinforce the prognostic value of platelet-related prognostic markers in ESCC.
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http://dx.doi.org/10.21873/invivo.11991DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7439896PMC
June 2021

Successful surgical drainage with intraoperative ultrasonography for amebic liver abscess refractory to metronidazole and percutaneous drainage: a case report.

BMC Surg 2020 May 24;20(1):112. Epub 2020 May 24.

Department of Surgery, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan.

Background: Metronidazole (MNZ) has been clearly established as a medication for amebic liver abscess. In uncomplicated cases, surgical drainage should be avoided. We report a case of amebic liver abscess refractory to MNZ that was successfully treated using preoperative computed tomography (CT) and percutaneous and surgical drainage with intraoperative ultrasonography (IOUS).

Case Presentation: A 53-year-old man with high-grade fever was diagnosed with a cystic lesion on his right hepatic lobe using CT. Percutaneous drainage was performed, and antibacterial drugs were administered. However, the infection and condition of the patient worsened. Entamoeba histolytica was detected from pus within the mediastinal cavity. Hence, the patient was diagnosed with amebic liver abscess. After the diagnosis was established, we administered MNZ for 10 days. Despite this, the patient's physical condition did not improve. Blood tests suggested impending disseminated intravascular coagulation (DIC). We performed surgical intervention to drain the amebic liver abscess refractory to conservative treatment. During surgery, imaging information from preoperative CT and IOUS enabled us to recognize the anatomical structures and determine the incision lines of the hepatic capsule and hepatic tissue. The patient's DIC immediately regressed after surgery. Unfortunately, malnutrition and disuse syndrome contributed to the patient's long recovery period. He was discharged 137 days post-surgery.

Conclusions: We reported a case of amebic liver abscess refractory to conservative treatment. Surgical drainage with preoperative CT and IOUS allowed us to safely and effectively perform complex abscess decompression.
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http://dx.doi.org/10.1186/s12893-020-00776-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7247227PMC
May 2020

A patient with a pancreatic neuroendocrine tumor and multiple liver metastases achieved a long-term partial response to third-line streptozocin treatment.

Int Cancer Conf J 2020 Jan 28;9(1):45-49. Epub 2019 Nov 28.

1Department of Surgery, National Defense Medical College, 3-2 Namiki, Tokorozawa, 359-8513 Saitama Japan.

The Japanese guideline for gastroenteropancreatic neuroendocrine tumor treatment recommends everolimus or sunitinib as first-line treatment for unresectable pancreatic neuroendocrine tumors (PNETs). Streptozocin (STZ) is recommended as an alternative. We encountered a patient with PNET who had multiple liver metastases and who showed a remarkable response to third-line STZ. The patient was a 50-year-old man with a pancreatic head tumor 32 mm in diameter. We planned to perform subtotal stomach-preserving pancreaticoduodenectomy, but abandoned resecting the pancreas during the surgery upon discovering a small liver tumor 3 mm in diameter, examination of frozen sections of which revealed a poorly differentiated adenocarcinoma. However, the final pathological examination revealed that the liver nodule was a PNET; hence, we completed the subtotal stomach-preserving pancreaticoduodenectomy 5 weeks after the first laparotomy. The patient received no adjuvant chemotherapy after surgery. Twenty-one months later, we discovered 20 scattered liver metastases via computed tomography; these were considered unresectable. Therefore, we administered everolimus for 7 months, but the patient developed interstitial pneumonia and experienced metastatic progression. Subsequent sunitinib administration for 6 months was ineffective. Finally, we chose STZ (1000 mg/m, weekly) as a third-line treatment, which produced a partial response for 10 months. The patient remains alive 38 months after the detection of recurrence. As the order in which anti-cancer drugs should be administered to treat PNET has not been determined, additional predictors of their therapeutic efficacy should be investigated.
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http://dx.doi.org/10.1007/s13691-019-00391-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6942608PMC
January 2020

Pheochromocytoma and paraganglioma: An emerging cause of secondary osteoporosis.

Bone 2020 04 13;133:115221. Epub 2020 Jan 13.

Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. Electronic address:

Context: Pheochromocytoma (PHEO) and paraganglioma (PGL) (PHEO and PGL: PPGLs) are catecholamine-producing neuroendocrine tumors, which are known to be associated with low bone mineral density (BMD). However, it remains unknown whether PPGLs are associated with high prevalence of osteoporotic fracture and if so, whether their surgical resection improves BMD has been addressed.

Objective: To evaluate the risk of vertebral fracture (VF) in PPGLs and the improvement of BMD after surgery.

Design And Settings: A retrospective cross-sectional study in a single referral center.

Participants: This study included the following patients: 1) 49 patients with PPGLs and 61 patients with non-functional AT who were examined radiograph of the spine, 2) 23 patients with PPGLs who were examined BMD at follow-up.

Intervention: 1) The prevalence of VF was evaluated between PPGLs and non-functional AT. 2) In PPGLs, BMD was evaluated at baseline and after surgery.

Results: PPGLs had a higher prevalence of VF (43% [21/49]) than non-functional AT (16% [10/61]; p = 0.002). PPGLs were associated with VF after adjusting for age and sex (odds ratio, 4.47; 95% confidence interval, 1.76-11.3; p = 0.001). In PPGLs, BMD at the lumber spine was improved (before: 0.855 ± 0.198 g/cm, after: 0.888 ± 0.169 g/cm, mean of the difference: 0.032 g/cm, p = 0.026), with 3.8% increase.

Conclusion: This study demonstrates that PPGLs was associated with VF and that their surgical resection contributes to the improvement of BMD in the trabecular bone. These observations support the notion that PPGLs are an emerging cause of secondary osteoporosis.
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http://dx.doi.org/10.1016/j.bone.2020.115221DOI Listing
April 2020

Mixed adenoneuroendocrine carcinoma with loss of HER2 positivity after trastuzumab-based chemotherapy for HER2-positive gastric cancer: a case report.

Surg Case Rep 2020 Jan 8;6(1). Epub 2020 Jan 8.

Department of Surgery, National Defense Medical College, 3-2 Namiki, Tokorozawa, 359-8513, Japan.

Background: Trastuzumab (T-mab)-based chemotherapy is a standard regimen for human epithelial growth factor 2 (HER2)-positive gastric cancer. However, some patients have demonstrated a change in HER2 status after T-mab-based treatment of breast cancer. We report a rare case of mixed adenoneuroendocrine carcinoma with loss of HER2 positivity after T-mab-based chemotherapy for HER2-positive gastric cancer.

Case Presentation: A 60-year-old man presented with a mass of the upper abdomen, which was diagnosed as adenocarcinoma with a HER2 score of 3+ by endoscopic biopsy. He received seven cycles of combination chemotherapy with capecitabine, cisplatin, and T-mab. Subsequently, he underwent open total gastrectomy, distal pancreatosplenectomy, and extended left hepatic lobectomy as a conversion surgery. The surgically resected specimen demonstrated both adenocarcinoma and neuroendocrine components; therefore, it was diagnosed as HER2-negative mixed adenoneuroendocrine carcinoma. Although the patient received additional chemotherapy, multiple liver metastases appeared at 3 months postoperatively and he died at 6 months postoperatively because of the rapidly progressing metastatic tumor.

Conclusions: We encountered a rare case of rapidly progressive mixed adenoneuroendocrine carcinoma that was negative for HER2 expression after T-mab treatment combined with chemotherapy.
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http://dx.doi.org/10.1186/s40792-020-0774-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6949340PMC
January 2020

Unilateral primary aldosteronism as an independent risk factor for vertebral fracture.

Clin Endocrinol (Oxf) 2020 03 19;92(3):206-213. Epub 2020 Jan 19.

Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Context: Primary aldosteronism (PA) is known to increase vertebral fracture (VF), although the detailed mechanism remains to be elucidated. We hypothesized that the PA subtype is associated with VF.

Objective: To evaluate whether unilateral PA is associated with the prevalence of VF.

Design: This was a retrospective cross-sectional study in a single referral centre.

Patients: We identified 210 hypertensive patients whose clinical data were available for case-detection results. One hundred and fifty-two patients were diagnosed with PA using captopril challenge tests.

Measurements: We measured the prevalence of VF, according to PA subtype.

Results: One hundred thirteen patients with PA were subtype classified by adrenal vein sampling. Of these, 37 patients had unilateral PA, 76 patients had bilateral PA, 58 patients had non-PA; 39 patients with PA were not subtype-classified. Patients with PA had a higher prevalence of VF (29%, 44/152) than those with non-PA (12%, 7/58; P = .011). Moreover, unilateral PA had a higher prevalence of VF (46%, 17/37) than bilateral PA (20%, 15/76; P = .021). There was no significant difference in the prevalence of VF between bilateral PA and non-PA. Unilateral PA was an independent risk factor for VF after adjusting for age and sex (OR: 3.16, 95% confidence interval: 1.12-8.92; P = .017). Among patients with unilateral PA, serum cortisol concentrations after 1-mg dexamethasone suppression test were higher in those with VF (1.32 ± 0.67 g/dL) than those without (0.96 ± 0.33 g/dL; P = .048).

Conclusions: Unilateral PA is an independent risk factor for VF.
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http://dx.doi.org/10.1111/cen.14145DOI Listing
March 2020

Nutritional benefit of laparoscopic jejunostomy during neoadjuvant chemotherapy for obstructing esophageal cancer.

Mol Clin Oncol 2019 Dec 16;11(6):612-616. Epub 2019 Oct 16.

Department of Surgery, National Defense Medical College, Tokorozawa, Saitama 359-8513, Japan.

Neoadjuvant chemotherapy (NAC) confers a survival benefit in esophageal carcinoma, but it is difficult to perform in patients who cannot receive enteral feeding due to an esophageal obstruction. In the current study, the nutritional benefit of laparoscopic jejunostomy (Lap-J) was evaluated in patients with NAC for obstructing esophageal cancer. A total of 91 patients with esophageal cancer who received NAC between 2009 and 2017 were included in the present study. Lap-J was performed prior to NAC in 15 patients (16.5%) with an obstructing tumor. Patients with NAC without Lap-J were used as the control group (n=76). Nutritional parameters and surgical outcomes of the two groups were compared retrospectively. In the patients with Lap-J, 14 of the 15 patients (93.3%) did not experience any procedure-associated complications. No mortalities were associated with Lap-J. Significant decreases in total serum protein, albumin, hemoglobin concentrations and prognostic nutritional index (PNI) occurred following NAC in the control but not in the Lap-J group. Serum albumin and the improved modified Glasgow prognostic score increased significantly after NAC in the Lap-J group but not in the control group. In conclusion, perioperative nutritional support with Lap-J was safe and effective in patients with NAC for obstructing esophageal cancer.
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http://dx.doi.org/10.3892/mco.2019.1938DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6826271PMC
December 2019

Role of Aldosterone and Potassium Levels in Sparing Confirmatory Tests in Primary Aldosteronism.

J Clin Endocrinol Metab 2020 04;105(4)

Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Context: The current clinical guidelines suggest that confirmatory tests for primary aldosteronism (PA) may be excluded in some of patients who have elevated plasma aldosterone concentration (PAC) under plasma renin suppression. However, this has low-priority evidence and is under debate in use of serum potassium.

Objective: This study aimed to investigate an appropriate setting for sparing confirmatory tests in PA.

Design And Setting: A retrospective cross-sectional study in a single referral center.

Participants: This study included 327 patients who had hypertension under plasma renin suppression and underwent the captopril challenge test (CCT) between January 2007 and April 2019. CCT results were used to diagnose PA.

Main Outcome Measure: Diagnostic value of PAC and serum potassium in confirmation of PA.

Results: Of the studied patients, 252 of 327 (77%) were diagnosed with PA. All 61 patients with PAC > 30 ng/dL were diagnosed with PA. In patients with PAC between 20 and 30 ng/dL, 44 of 55 (80%) were diagnosed with PA, while all 26 with PAC between 20 to 30 ng/dL who had spontaneous hypokalemia were diagnosed with PA. The proportion of unilateral PA determined by adrenal vein sampling (AVS) was higher in patients who had PAC > 30 ng/dL or those with spontaneous hypokalemia who had PAC between 20 and 30 ng/dL than those who did not meet the criteria (76% vs. 17%, P < .001).

Conclusion: Confirmatory tests in PA could be spared in patients who have typical features of PA and these patients had a high probability of unilateral PA on AVS.
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http://dx.doi.org/10.1210/clinem/dgz148DOI Listing
April 2020

Risk factors for nonalcoholic fatty liver disease after gastrectomy for gastric cancer.

Gastric Cancer 2020 03 25;23(2):356-362. Epub 2019 Sep 25.

Department of Surgery, National Defense Medical College, Tokorozawa, Japan.

Background: Nonalcoholic fatty liver disease (NAFLD) refers to hepatic steatosis caused by something other than alcoholic liver injury, and often occurs after gastrointestinal surgeries such as pancreatoduodenectomy and gastrectomy. This study aimed to identify the risk factors for NAFLD after gastrectomy for gastric cancer.

Methods: A total of 721 patients who underwent gastrectomy for gastric cancer and plane abdominal computed tomography (CT) preoperatively and 1 year after surgery were included in this study. NAFLD was defined as having a mean hepatic CT attenuation value of < 40 Hounsfield units. We retrospectively examined the relationship between the onset of NAFLD and clinicopathological findings to identify the risk factors associated with the development of NAFLD after gastrectomy.

Results: The incidence of postoperative NAFLD was 4.85% (35/721). The univariate analysis identified the following factors as being significantly associated with the incidence of NAFLD: age, preoperative BMI ≥ 25 kg/m, tumor depth of pT3 ≤, lymph node metastasis grade of pN2 ≤, cholecystectomy, D2 lymphadenectomy, adjuvant chemotherapy, high preoperative cholinesterase serum level, and low grade of preoperative FIB-4 index. Adjuvant chemotherapy (p < 0.001) and high preoperative cholinesterase serum level (p = 0.021) were identified as independent risk factors for NAFLD 1 year after gastrectomy.

Conclusion: Our study showed that adjuvant chemotherapy with S-1 and high level of serum cholinesterase were considered as the risk factors for NAFLD occurring after gastrectomy for gastric cancer.
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http://dx.doi.org/10.1007/s10120-019-01009-8DOI Listing
March 2020

Impact of perioperative high mobility group box chromosomal protein 1 expression on long-term outcomes in patients with esophageal squamous cell carcinoma.

J Gastroenterol Hepatol 2020 May 24;35(5):788-794. Epub 2019 Oct 24.

Department of Surgery, National Defense Medical College, Tokorozawa, Japan.

Background And Aim: High mobility group box chromosomal protein-1 (HMGB-1) is a potential late mediator of sepsis and a possible risk factor for postoperative pulmonary complications after esophagectomy. This study aimed to determine the relationship between HMGB-1 and clinicopathological factors and long-term prognosis after esophagectomy for esophageal cancer.

Methods: We measured perioperative serum HMGB-1 levels using ELISA and HMGB-1 protein by immunohistochemistry expression in resected specimens.

Results: Postoperative serum HMGB-1 levels were significantly higher than preoperative levels. Preoperative serum HMGB-1 levels were significantly higher in patients with more intraoperative bleeding, longer intensive care unit stays, and postoperative pneumonia. Postoperative serum HMGB-1 levels were significantly higher in older patients and those with longer operation time and more intraoperative bleeding. There were significant differences in long-term outcomes according to postoperative but not preoperative serum HMGB-1 levels. Multivariate analysis demonstrated that advanced pathological stage, postoperative pulmonary complications, and higher postoperative serum HMGB-1 levels were independently associated with relapse-free survival and overall survival. Preoperative serum HMGB-1 levels were significantly higher in patients with high HMGB-1 expression than those with low HMGB-1 expression by immunohistochemistry, whereas such statistical differences were not observed in postoperative serum HMGB-1. There were no differences in relapse-free survival and overall survival according to HMGB-1 expression by immunohistochemistry. Serum HMGB-1 levels were significantly increased after esophagectomy for esophageal cancer.

Conclusion: Elevated postoperative serum HMGB-1, which was associated not only with poor long-term but also short-term outcomes such as postoperative complications, might serve as a potential marker for prognosis in esophageal cancer.
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http://dx.doi.org/10.1111/jgh.14854DOI Listing
May 2020

Successful resection of a granulocyte colony-stimulating factor-producing carcinoma of the pancreas: A case report.

Mol Clin Oncol 2019 Oct 22;11(4):359-363. Epub 2019 Jul 22.

Department of Surgery, National Defense Medical College, Tokorozawa, Saitama 359-8513, Japan.

Granulocyte colony-stimulating factor (G-CSF) is a naturally occurring glycoprotein that stimulates the proliferation of precursor cells in the bone marrow and their maturation into fully differentiated neutrophils. G-CSF-producing cancers rarely occur in the digestive system, particularly the pancreas. Herein we report the rare case of a G-CSF-producing pancreatic carcinoma associated with severe anemia due to bleeding in the duodenum, which was successfully treated with surgery. A 79 year-old man presented with epigastralgia and anemia at our institution. Esophagogastroduodenoscopy revealed a duodenal tumor, which was diagnosed as a poorly differentiated adenocarcinoma. To control breeding, subtotal stomach-preserving pancreaticoduodenectomy was performed. The excised tumor measured 86×55×54 mm. It was primarily located in the pancreas and compressed the pancreatic parenchyma and main bile duct. It comprised poorly differentiated adenocarcinoma, and prominent neutrophil infiltration was noted around the tumor. Immunohistochemical examination revelaed that the tumor was positive for G-CSF expression. Based on these results, a final diagnosis of G-CSF-producing primary pancreatic cancer was made. At 18 months following surgery, the patient was alive without recurrence.
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http://dx.doi.org/10.3892/mco.2019.1902DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6713937PMC
October 2019

A case of a long-term survival achieved by surgical treatment and chemotherapy for late recurrence of AFP-producing gastric cancer.

Surg Case Rep 2019 Jul 1;5(1):106. Epub 2019 Jul 1.

Department of Surgery, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan.

Background: Alpha-fetoprotein-producing gastric cancer (AFP-GC) is a relatively rare disease, with a dismal prognosis.

Case Presentation: We report the case of a patient with long-term survival after surgery for the recurrence of AFP-GC. A 71-year-old man was diagnosed with gastric cancer and underwent distal gastrectomy with D2 lymphadenectomy (pT3N2M0). Pathological examination of the resected specimen revealed AFP-GC. Fifteen years after the gastrectomy, the patient experienced anorexia and was admitted with a mass located at the mesentery of the small intestine. Following a diagnosis of gastrointestinal stromal tumor of the mesentery, a tumor resection with partial small intestine was performed. The final histopathological diagnosis was AFP-GC's recurrence in the small-bowel mesentery. Two months later, multiple liver metastases were identified, and serum AFP level was found to be extremely high (17,447 ng/mL). Chemotherapy with S-1+CDDP (SP) was initiated for liver metastasis. However, owing to anorexia and fatigue, SP therapy was discontinued following the patient's request at the end of two courses. A CT scan at 1 month after the discontinuation of chemotherapy did not reveal liver metastasis, and serum AFP level decreased to the normal range. He is alive at present with no re-recurrence and no elevation of serum AFP level at 7 years after the second surgery without any chemotherapy.

Conclusion: Even if recurrence of AFP-GC is diagnosed, radical resection and chemotherapy are effective, as noted in the present case.
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http://dx.doi.org/10.1186/s40792-019-0664-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6603113PMC
July 2019

Laparoscopic fenestration for a large ruptured splenic cyst combined with an elevated serum carbohydrate antigen 19-9 level: a case report.

BMC Surg 2019 May 30;19(1):58. Epub 2019 May 30.

Surgery Department, National Defense Medical College, Tokorozawa, Saitama, Japan.

Background: Non-parasitic splenic cysts are associated with elevated serum carbohydrate antigen (CA) 19-9 levels. We report a case in which a 23-year-old female exhibited a large ruptured splenic cyst and an elevated serum CA19-9 level.

Case Presentation: The patient, who experienced postprandial abdominal pain and vomiting, was transferred to our hospital and was found to have a large splenic cyst during an abdominal computed tomography (CT) scan. On physical examination, her vital signs were stable, and she demonstrated rebound tenderness in the epigastric region. An abdominal CT scan revealed abdominal fluid and a low-density region (12 × 12 × 8 cm) with enhanced margins in the spleen. The patient's serum levels of CA19-9 and CA125 were elevated to 17,580 U/mL and 909 U/mL, respectively. A cytological examination of the ascitic fluid resulted in it being categorized as class II. Finally, we made a diagnosis of a ruptured splenic epidermoid cyst and performed laparoscopic splenic fenestration. The patient's postoperative course was uneventful, and she was discharged on postoperative day 5. The cystic lesion was histopathologically diagnosed as a true cyst, and the epithelial cells were positive for CA19-9. Follow-up laboratory tests performed at 4 postoperative months showed normal CA19-9 (24.6 U/L) and CA125 (26.8 U/L) levels. No recurrence of the splenic cyst was detected during the 6 months after surgery.

Conclusion: Laparoscopic fenestration of a ruptured splenic cyst was performed to preserve the spleen, after the results of abdominal fluid cytology and MRI were negative for malignancy.
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http://dx.doi.org/10.1186/s12893-019-0517-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6543565PMC
May 2019

A Case of Acute Exacerbation of Chronic Adrenal Insufficiency Due to Ipilimumab Treatment for Advanced Melanoma.

Am J Case Rep 2019 Jan 25;20:106-110. Epub 2019 Jan 25.

Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka City, Fukuoka, Japan.

BACKGROUND Ipilimumab is a therapeutic human monoclonal antibody that targets the T-cell inhibitory molecule, cytotoxic T-lymphocyte antigen-4 (CTLA-4), and is classified as an immune checkpoint inhibitor that has been shown to improve prognosis in patients with advanced melanoma. However, several immune-related adverse events have been reported to be associated with ipilimumab Treatment. A case of acute exacerbation of chronic adrenal insufficiency is presented that highlights that glucocorticoid dosage for patients undergoing steroid treatment at the time of ipilimumab treatment has yet to be established. CASE REPORT A 50-year-old Japanese woman was diagnosed with malignant melanoma on the sole of her right foot. During her second course of ipilimumab treatment, she developed acute adrenal insufficiency caused by isolated adrenocorticotropic hormone (ACTH) deficiency, which required treatment with oral hydrocortisone. However, the symptoms of her adrenal insufficiency worsened, and she commenced treatment with 12 courses of nivolumab, a therapeutic human monoclonal antibody that blocks programmed cell death protein 1 (PD-1) on the surface of T-cells. She did not require corticosteroid support during nivolumab treatment. CONCLUSIONS This case report highlights the risk of exacerbating adrenal insufficiency during treatment with ipilimumab. The differences in clinical outcome in this patient between ipilimumab and nivolumab treatment might be explained by the different mechanisms between ipilimumab and nivolumab on immune function.
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http://dx.doi.org/10.12659/AJCR.913021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6354724PMC
January 2019

Bilateral Adrenocortical Adenomas along with Virilization and Cushing's Syndrome.

Intern Med 2019 Feb 12;58(3):405-409. Epub 2018 Sep 12.

Department of Endocrinology and Metabolism, Faculty of Medicine, Kagawa University, Japan.

We herein present the case of a 27-year-old woman with clinical and biochemical features of virilism. Imaging studies revealed the presence of a bilateral adrenal tumor. Although the secretion of androgens was remarkable, the autonomous production of cortisol was also evident because of a loss of circadian rhythm and the absence of cortisol suppression by dexamethasone. The surgical excision of both adrenal tumors was performed, and the histological examination showed no malignancy. We also report the successful pregnancy and delivery of the patient who showed evolving adrenocortical insufficiency along with virilization and Cushing's syndrome and who continued to receive glucocorticoid replacement therapy during pregnancy.
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http://dx.doi.org/10.2169/internalmedicine.0790-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6395137PMC
February 2019

Angiotensin II induces cholesterol accumulation and impairs insulin secretion by regulating ABCA1 in beta cells.

J Lipid Res 2018 10 14;59(10):1906-1915. Epub 2018 Aug 14.

Department of Endocrinology and Metabolism, Faculty of Medicine, Kagawa University, 1750-1, Miki-cho, Kita-gun, Kagawa, 761-0793, Japan

In pancreatic β cells, ABCA1, a 254 kDa membrane protein, affects cholesterol homeostasis and insulin secretion. Angiotensin II, as the main effector of the renin-angiotensin system, decreases glucose-stimulated insulin secretion (GSIS). We examined the effect of angiotensin II on ABCA1 expression in primary pancreatic islets and INS-1 cells. Angiotensin II decreased ABCA1 protein and mRNA; angiotensin II type 1 receptor (AT1R) blockade rescued this ABCA1 repression. In parallel, angiotensin II suppressed the promoter activity of , an effect that was abrogated by PD98095, a specific inhibitor of MAPK kinase (MEK). LXR enhanced promoter activity, and angiotensin II decreased the nuclear abundance of LXR protein. On a chromatin immunoprecipitation assay, LXR mediated the transcription of by directly binding to its promoter. Mutation of the LXR binding site on the promoter cancelled the effect of angiotensin II. Furthermore, angiotensin II induced cholesterol accumulation and impaired GSIS; inhibition of AT1R or MEK pathway reversed these effects. In summary, our study showed that angiotensin II suppressed ABCA1 expression in pancreatic islets and INS-1 cells, indicating that angiotensin II may influence GSIS by regulating ABCA1 expression. Additional research may address therapeutic needs in diseases such as diabetes mellitus.
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http://dx.doi.org/10.1194/jlr.M085886DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6168299PMC
October 2018

Impact of reduced skeletal muscle volume on clinical outcome after esophagectomy for esophageal cancer: A retrospective study.

Medicine (Baltimore) 2018 Jul;97(30):e11450

Department of Surgery, National Defense Medical College, 3-2 Namiki, Tokorozawa, Japan.

The aim of the study was to clarify the impact of reduced skeletal muscle volume on the morbidity of patients who underwent esophagectomy for esophageal cancer.Malnutrition and reduced skeletal muscle volume, that is, presarcopenia, are reportedly associated with a high frequency of postoperative complications after esophagectomy. However, it remains unclear whether the reduction of skeletal muscle volume following esophagectomy may affect clinical outcomes including pneumonia occurred beyond the preoperative period.From February 2009 to June 2015, in 123 patients, we retrospectively evaluated the postoperative changes of the psoas muscle index (PI) on computed tomography and assessed their impact on the incidence of pneumonia after esophagectomy.There was a significant reduction in the PI 6 months after surgery compared to the preoperative value. The incidence of pneumonia as of 6 months after surgery was 23.6%, which was higher in patients of advanced age (P = .02), those with a lower body mass index (P = .02), and those with a greater reduction of PI during 6 months after surgery (P = .03). It was not associated with preoperative nutritional data, pulmonary function, operative procedure, and preoperative PI. Multivariate analysis demonstrated that age and postoperative PI reduction were independently associated with the incidence of pneumonia 6 months after surgery (hazard ratio [HR] = 2.92, 95% confidence interval [CI] 1.16-7.32, P = .02; HR = 3.25, 95% CI 1.15-9.15, P = .03, respectively). Patients with pneumonia 6 months after surgery had significantly poorer overall survival than those without pneumonia at that time.Postoperative reduction of skeletal muscle volume was independently associated with the occurrence of pneumonia beyond the preoperative period, which might indicate the importance of a postoperative nutritional support after perioperative period in esophageal cancer patients.
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http://dx.doi.org/10.1097/MD.0000000000011450DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6078756PMC
July 2018

Nivolumab-induced thyroid dysfunction lacking antithyroid antibody is frequently evoked in Japanese patients with malignant melanoma.

BMC Endocr Disord 2018 Jun 8;18(1):36. Epub 2018 Jun 8.

Department of Medicine and Bioregulatory Science, Graduate School Of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan.

Background: Nivolumab, an anti-programmed cell death-1 monoclonal antibody, has improved the survival of patients with malignant melanoma. Despite its efficacy, nivolumab inconsistently induces thyroid dysfunction as an immune-related adverse event (irAE). This study aimed to evaluate nivolumab-induced thyroid dysfunction to determine the risks and mechanisms of thyroid irAEs.

Methods: After excluding 10 patients, data of 24 patients with malignant melanoma (aged 17-85 years; 54% female) were retrospectively analyzed.

Results: Thyroid irAEs were observed in seven patients (29%). Three patients had hypothyroidism after preceding transient thyrotoxicosis, and the other four patients had hypothyroidism without thyrotoxicosis. Levothyroxine-Na replacement was required in three patients. Antithyroid antibody (ATA) titer was elevated in one of four assessable patients. The average (±SD) time to onset of thyroid irAE was 33.6 (±21.9) weeks. The administration period of nivolumab was longer in patients with thyroid irAEs than in those without thyroid irAEs (P < 0.01). There were no significant differences between patients with and without thyroid irAEs regarding age, sex, tumor stage, response to nivolumab therapy, baseline thyroid function, antithyroid peroxidase antibody (anti-TPO Ab) and antithyroglobulin antibody (anti-Tg Ab).

Conclusions: Thyroid dysfunction was a common irAE of nivolumab in malignant melanoma. Neither anti-TPO Ab nor anti-Tg Ab was associated with the risk for nivolumab-induced thyroid dysfunction. A conventional ATA-independent mechanism might be involved in thyroid irAEs. Further studies are required to clarify the mechanism and identify the predictive factors of thyroid irAEs.
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http://dx.doi.org/10.1186/s12902-018-0267-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5994101PMC
June 2018

A case of pneumatosis intestinalis during neoadjuvant chemotherapy with cisplatin and 5-fluorouracil for esophageal cancer.

J Surg Case Rep 2017 Nov 21;2017(11):rjx227. Epub 2017 Nov 21.

Department of Surgery, National Defense Medical College, 3-2 Namiki, Tokorozawa 359-8513, Japan.

Pneumatosis intestinalis (PI) is a relatively rare disease. A 70-year-old man with stage II squamous cell carcinoma of the middle thoracic esophagus was administered cisplatin plus 5-fluorouracil (CF) therapy as neoadjuvant chemotherapy. On Day 14 of the first course of CF therapy, he complained of acute abdominal pain. Computed tomography (CT) revealed PI of the entire colon and a small air bubble in the mesentery. A colonoscopy revealed that there was no finding suggestive of ischemia. Because there was no sign of peritoneal irritation, conservative treatment was selected. On Day 7 after PI diagnosis, CT indicated the disappearance of PI. The patient underwent a radical esophagectomy. Intraoperative laparoscopic findings showed the serosa of the colon to be intact. The patient was discharged without any complications. It is important to take into account that CF therapy may cause PI and that PI can be treated conservatively.
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http://dx.doi.org/10.1093/jscr/rjx227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5697399PMC
November 2017

Perioperative sequential monitoring of hemodynamic parameters in patients with pheochromocytoma using the Non-Invasive Cardiac System (NICaS).

Endocr J 2014 13;61(6):571-5. Epub 2014 Mar 13.

Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.

Surgical treatment of pheochromocytoma is associated with a high risk of hemodynamic instability. To reduce the risk of perioperative complications, adequate medical treatment to normalize blood pressure and restore blood volume is required. Accurate evaluation of the circulating blood volume (CBV) in perioperative patients with pheochromocytoma is clinically important. In the present study, we adopted whole-body bioimpedance monitoring technique using the Non-Invasive Cardiac System (NICaS), which can non-invasively measure cardiac output (CO) values. NICaS-derived CO values were evaluated in eight preoperative patients with pheochromocytoma and were compared with simultaneous CBV values measured by a conventional indicator dilution method using (131)I-labeled human serum albumin. In these patients with pheochromocytoma, the NICaS-derived CO values were significantly correlated with the CBV values measured by (131)I-labeled human serum albumin (4.86 ± 1.05 L/min vs 4.79 ± 1.02 L; r = 0.906; P = 0.002). Sequential NICaS-derived CO values confirmed that CBV increased after preoperative treatment with an α-blocker, with or without volume loading. The results of this study indicate that NICaS can be used to accurately and non-invasively evaluate the hemodynamic status. By sequential monitoring of NICaS-derived CO values, we are able to confirm whether adequate CBV in a patient with pheochromocytoma is obtained by preoperative medical treatment with α-blockers or volume loading, to avoid perioperative complications.
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http://dx.doi.org/10.1507/endocrj.ej13-0471DOI Listing
April 2015

Triploid bridge and role of parthenogenesis in the evolution of autopolyploidy.

Am Nat 2004 Jul 7;164(1):101-12. Epub 2004 Jun 7.

Center for Ecological Research, Kyoto University, Kamitanakami Hiranocho, Otsu 520-2113, Japan.

Autopolyploidization is considered to play an important role in plant evolution. In polyploidization, the polyploid evolves from the original diploid cytotype, in which the triploid state is considered to mediate the process (triploid bridge). Nevertheless, the fitness of triploid individuals seems to be too low to facilitate the polyploidization process (triploid block). The evolutionary condition of autopolyploidy was analyzed using a mathematical model focusing on the role of parthenogenesis in triploid and tetraploid individuals. In addition, offspring were assumed to arise by sexual reproduction by conjugations between haploid, diploid, and triploid gametes produced by diploid, tetraploid, and triploid individuals. According to the analysis, even if triploid block suppresses the fitness of sexually produced triploids, the polyploidization process can proceed when parthenogenesis occurs frequently. If only triploids frequently reproduce parthenogenetically, the evolutionary consequences tend to depend on the fitness of the tetraploid individuals. On the basis of a predetermined parameter set, if tetraploid fitness is relatively low, all three ploidies can coexist. Otherwise, tetraploidization occurs. In this case, triploid parthenogenesis promotes not only triploidization but also tetraploidization. However, if both triploids and tetraploids frequently reproduce parthenogenetically, the ploidy levels with the highest fitness are likely to dominate in the population through direct competition among cytotypes.
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http://dx.doi.org/10.1086/421356DOI Listing
July 2004

Differences in oligosaccharide pattern of a sample of polar bear colostrum and mid-lactation milk.

Comp Biochem Physiol B Biochem Mol Biol 2003 Dec;136(4):887-96

Department of Animal Science, Obihiro University of Agriculture and Veterinary Medicine, Inada cho, Hokkaido, Obihiro 080-8555, Japan.

Although the concentrations of carbohydrate in the colostrum and in the mid-lactation milk of polar bear (Ursus maritimus) were similar, the oligosaccharide patterns differed. The colostrum sample contained Neu5Ac(alpha2-3)Gal(beta1-4)Glc (3'-N-acetylneuraminyllactose), GalNAc(alpha1-3)[Fuc(alpha1-2)]Gal(beta1-4)Glc (A-tetrasaccharide), Fuc(alpha1-2)Gal(beta1-4)Glc (2'-fucosyllactose) and Gal(beta1-4)Glc (lactose). The mid-lactation milk contained Gal(alpha1-3)[Fuc(alpha1-2)]Gal(beta1-4)[Fuc(alpha1-3)]Glc (B-pentasaccharide), GalNAc(alpha1-3)[Fuc(alpha1-2)]Gal(beta1-4)[Fuc(alpha1-3)]Glc (A-pentasaccharide), Gal(alpha1-3)[Fuc(alpha1-2)]Gal(beta1-4)Glc (B-tetrasaccharide), A-tetrasaccharide, Gal(alpha1-3)Gal(beta1-4)[Fuc(alpha1-3)]Glc (3-fucosylisoglobotriose), Gal(alpha1-3)Gal(beta1-4)Glc (isoglobotriose) and lactose. The dominant saccharides in the colostrum were 3'-N-Acetylneuraminyllactose and lactose, whereas isoglobotriose was the dominant saccharide in the mid-lactation milk in which lactose was only a minor component. Isoglobotriose, which had previously been found to be a dominant saccharide in mature milk from the Ezo brown bear, the Japanese black bear and the polar bear, was not found in the polar bear colostrum.
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http://dx.doi.org/10.1016/j.cbpc.2003.09.001DOI Listing
December 2003

Abrupt onset of sensorineural hearing loss and tinnitus in a patient with capillary telangiectasia of the pons.

Ann Otol Rhinol Laryngol 2002 Sep;111(9):855-9

Department of Otorhinolaryngology, Kobe Postal Services Agency Hospital, Japan.

Capillary telangiectasia is often found incidentally on magnetic resonance imaging and may be associated with minor neurologic symptoms, but there has been little evidence about whether such lesions are responsible for these symptoms. Here we report a case of capillary telangiectasia of the right mid pons, which was associated with the abrupt onset of tinnitus and sensorineural hearing loss. Examination of the auditory brain stem responses showed abnormalities of waves III and IV on the left and bilateral prolongation of the interwave intervals. Optokinetic nystagmus showed slight left-right asymmetry.
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http://dx.doi.org/10.1177/000348940211100917DOI Listing
September 2002
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