Publications by authors named "Satoru Yamaguchi"

164 Publications

A Pilot Study Analyzing the Clinical Utility of Comprehensive Genomic Profiling Using Plasma Cell-Free DNA for Solid Tumor Patients in Japan (PROFILE Study).

Ann Surg Oncol 2021 Mar 28. Epub 2021 Mar 28.

Department of Precision Cancer Medicine, Center for Innovative Cancer Treatment, Tokyo Medical and Dental University, Tokyo, 113-8510, Japan.

Background: The clinical utility of plasma cell-free DNA in precision cancer medicine has not been established. A pilot study was conducted to investigate the clinical utility of comprehensive genomic profiling by liquid biopsy in a Japanese population.

Methods: In this PROFILE study, 102 patients with advanced solid tumors who showed progression with standard systemic therapy underwent liquid biopsy between August 2017 and February 2020. Liquid biopsy was performed using Guardant360.

Results: Of the 102 patients, 56 were women, and the median age was 65 years. Regarding the types of cancer, 31 were hepatobiliary and pancreatic cancer, 17 were gastrointestinal cancer, and 13 were breast cancer. Frequently altered genes were TP53 (53.9%, 46/102), KRAS (25.5%, 26/102), PIK3CA (19.6%, 20/102), and EGFR (17.6%, 18/102). At least one genetic aberration was detected in 92 patients (90.2%). Actionable mutation was discovered in 88 patients (86.3%), and 67 patients (65.7%) were clinical trial candidates. Of the 102 patients, 22 (21.6%) were able to receive biomarker-matched therapy. Their best responses were as follows: 1 complete response, 3 partial responses, 7 stable diseases, and 11 progressive diseases. Additionally, the treated patients were divided on the basis of matching scores (≥ 50% vs. < 50%). The patients were divided into high and low groups. The high group had a higher disease control rate (DCR) of 75% compared with 20% in the low group (P = 0.010).

Conclusions: The results indicate that liquid biopsy is useful for identifying actionable mutations associated with the clinical response of selected patients.
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http://dx.doi.org/10.1245/s10434-021-09856-5DOI Listing
March 2021

The updated five-year overall survival and long-term oxaliplatin-related neurotoxicity assessment of the FACOS study.

Surg Today 2021 Feb 14. Epub 2021 Feb 14.

Department of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical University, Kawagoe, Japan.

Purpose: We previously reported the first evidence of oncological benefits from a Japanese phase II trial of oxaliplatin-based adjuvant chemotherapy in patients with stage III colon cancer (the FACOS study). We herein report the long-term survival and persistent oxaliplatin-related peripheral sensory neuropathy (PSN) for patients enrolled in this trial.

Methods: Patients were scheduled to receive the mFOLFOX6 or CAPOX regimen in the adjuvant setting. The five-year overall survival (OS) rate and persistent PSN were evaluated.

Results: A total of 130 patients (mFOLFOX6, n = 73; CAPOX, n = 57) were eligible. The 5-year OS rate was 91.4%. No significant difference in the OS rate was observed between regimens (mFOLFOX6, 94.4%; CAPOX, 87.4%; P = 0.25). The incidence of PSN during adjuvant treatment was 55.4% in grade 1 (G1), 30.0% in G2, and 4.6% in G3. No patients showed G3 PSN at 12 months, but G1 or G2 residual PSN after 5 years was observed in 21.8% (G1, 20%; G2, 1.8%).

Conclusions: Updated results from the FACOS study support the benefits of oxaliplatin-based adjuvant chemotherapy in terms of the long-term survival among Japanese patients with stage III colon cancer. However, long-term persistent PSN occurs in about 20% of survivors, counterbalancing the favorable OS.
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http://dx.doi.org/10.1007/s00595-021-02230-8DOI Listing
February 2021

Association of Daily Home-Based Hot Water Bathing and Glycemic Control in Ambulatory Japanese Patients with Type 2 Diabetes Mellitus During the COVID-19 Pandemic: A Multicenter Cross-Sectional Study.

Diabetes Metab Syndr Obes 2020 22;13:5059-5069. Epub 2020 Dec 22.

Kato Clinic of Internal Medicine, Tokyo, Japan.

Purpose: To clarify the relationship between daily hot water bathing (HWB) at home and glycemic control in middle-aged and elderly ambulatory patients with type 2 diabetes mellitus (T2DM).

Methods: We defined hemoglobin A1c (HbA1c) as the main outcome. We set 7.0% based on the mean value of the dependent variable as the cut-off point for analysis. Frequency of HWB was an explanatory variable. A two-sample -test was used to compare between groups with continuous variables. Multiple logistic regression analysis was performed for frequency, adjusted age, sex, BMI, T2DM duration (Model 1), and other confounding factors (Model 2). Odds ratio (OR) and 95% confidence interval (95% CI) were calculated.

Results: Among 838 patients, there was a significant difference (p<0.001) in age between males (n=528, 62.8±8.7 years) and females (n=310, 65.0±8.1 years). In Model 1, compared with participants who used HWB more than seven times a week, those with poorly controlled HbA1c were significantly associated with low frequency of HWB: four to six times a week (OR 1.32, 95% CI 0.87-1.99) and less than three times a week (OR 1.43, 95% CI 0.98-2.10); p-value for overall trend was 0.041. In Model 2, p-value for overall trend was 0.138.

Conclusion: A higher frequency of HWB was moderately associated with a decreased risk of poor glycemic control in middle-aged and elderly ambulatory patients with T2DM.
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http://dx.doi.org/10.2147/DMSO.S279270DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7764630PMC
December 2020

Questionnaire-Based Survey on Epidemiology of Functional Gastrointestinal Disorders and Current Status of Gastrointestinal Motility Testing in Asian Countries.

Digestion 2020 Dec 16;102(1):73-89. Epub 2020 Dec 16.

SinoUnited Health, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Background/aims: Functional gastrointestinal disorders (FGIDs) are diagnosed and classified using the latest Rome IV criteria, released in 2016. Epidemiology of FGID diagnosed by the Rome IV criteria and current clinical application of gastrointestinal motility testing in Asian countries are not well known. The aims of this survey are to elucidate the present situation of epidemiology and diagnostic tests of FGID in clinical practice in some East and Southeast Asian countries.

Methods: The questionnaire focusing on current situation of FGID diagnosis and gastrointestinal motility testing was distributed to members of the International Gastroenterology Consensus Symposium study group and collected to be analyzed.

Results: The prevalence rates of subtypes of both functional dyspepsia (FD) and irritable bowel syndrome (IBS) are relatively similar in all Asian countries. In these countries, most patients underwent both upper endoscopy and Helicobacter pylori test to diagnose FD. Colonoscopy was also frequently performed to diagnose IBS and chronic constipation. The frequency of gastrointestinal motility testing to examine gastric emptying and colonic transit time varied among Asian countries.

Conclusions: This survey revealed epidemiology of FGIDs and current status of gastrointestinal motility testing in some East and Southeast Asian countries.
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http://dx.doi.org/10.1159/000513292DOI Listing
December 2020

Evaluation of improvement in quality of life after acupuncture in a patient with cervical dystonia: a case report.

Acupunct Med 2020 Dec 16:964528420958721. Epub 2020 Dec 16.

Department of Neurology, Saitama Medical University, Saitama, Japan.

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http://dx.doi.org/10.1177/0964528420958721DOI Listing
December 2020

Combination of TAS-102 and bevacizumab as third-line treatment for metastatic colorectal cancer: TAS-CC3 study.

Int J Clin Oncol 2021 Jan 21;26(1):111-117. Epub 2020 Oct 21.

Department of Surgery, Teikyo University Chiba Medical Center, Chiba, Japan.

Background: TAS-102 improved the overall survival of metastatic colorectal cancer (CRC) patients with a median progression-free survival (PFS) in the RECOURSE trial. Subsequently, the combination of TAS-102 and bevacizumab was shown to extend the median PFS (C-TASK FORCE study). However, the study included patients who received second- and third-line treatment. Our study exclusively examined patients receiving this combination as a third-line treatment to investigate the clinical impact beyond cytotoxic doublets.

Methods: This investigator-initiated, open-label, single-arm, multi-centered phase II study was conducted in Japan. Eligible CRC patients were refractory or intolerant to fluoropyrimidine, irinotecan, and oxaliplatin in first- and second-line therapy. TAS-102 (35 mg/m) was given orally twice daily on days 1-5 and 8-12 in a 4-week cycle, and bevacizumab (5 mg/kg) was administered by intravenous infusion every 2 weeks. The primary endpoint was PFS and the secondary endpoints were time-to-treatment failure, response rate, overall survival (OS), and safety.

Results: Between June 2016 and August 2017, 32 patients were enrolled. All patients previously received bevacizumab. The median PFS was 4.5 months; the median overall survival was 9.3 months. Partial response was observed in two patients. The most common adverse events above grade 3 were neutropenia followed by thrombocytopenia. There were no non-hematological adverse events above grade 3 and no treatment-related deaths occurred.

Conclusions: This study met its primary endpoint of PFS, which is comparable to the results of the C-TASK FORCE study. The TAS-102 and bevacizumab combination has the potential to be a therapeutic option for third-line treatment of metastatic CRC.
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http://dx.doi.org/10.1007/s10147-020-01794-8DOI Listing
January 2021

Histopathological evaluation of the effectiveness of oral Eppikajutsuto treatment for lymphatic malformation.

J Pediatr Surg 2020 Sep 17. Epub 2020 Sep 17.

Department of Pathology, Graduate School of Medicine, Dokkyo Medical University, Tochigi, Japan. Electronic address:

Background: Lymphatic malformation (LM) is a congenital disease caused by lymphatic vessel malformation. Although standard therapies for LMs are sclerotherapy and/or surgical excision, a new therapy using Japanese herbal medicine Eppikajutsuto (TJ-28) has been recently reported as clinically effective. We aimed to experimentally confirm the therapeutic effectiveness of TJ-28 for LMs.

Methods: LM lesions were generated in the mesentery and peritoneum of mice by intraperitoneal injection of Freund's incomplete adjuvant. Mice with LMs were treated by gavage or dietary administration of TJ-28 for 2 months. Formalin-fixed paraffin-embedded tissue sections of mesentery and peritoneum tissues were histologically and immunohistochemically examined by focusing on lymph nodes and perinodal lymph vessels.

Results: Multiple Freund's incomplete adjuvant-associated foreign-body granulomas were formed in the mesentery and peritoneum, resulting in congestion of lymph fluid and dilatation of lymph vessels. The numbers and sizes of lymph nodes were not significantly different between TJ-28-treated and control groups. However, the luminal areas of lymphatic vessels were reduced significantly in the TJ-28 treatment group by both gavage and dietary administrations.

Conclusion: TJ-28 conspicuously reduced congestion of lymph fluid. This is the first histopathological evaluation of LM model mice to study the effectiveness of oral TJ-28 treatment.
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http://dx.doi.org/10.1016/j.jpedsurg.2020.09.007DOI Listing
September 2020

Management of Gastroesophageal Reflux Disease in Asian Countries: Results of a Questionnaire Survey.

Digestion 2020 4;101(1):66-79. Epub 2019 Dec 4.

Faculty of Medicine, Oita University, Oita, Japan.

Introduction: The Asia-Pacific consensus on the management of gastroesophageal reflux disease (GERD) and the GERD treatment guidelines of 2015 drawn up by the Japanese Society of Gastroenterology were proposed, and GERD management in Asian regions was assumed to be performed based on these consensuses. In this environment, the current status of GERD management in clinical practice among Asian regions is less well-known.

Objective: This questionnaire-based consensus survey was performed to clarify the current status of management of GERD in clinical practice in Asian regions.

Methods: A questionnaire related to management of GERD was distributed to members of the International Gastroenterology Consensus Symposium Study Group. We analyzed the questionnaire responses and compared the results among groups.

Results: The frequencies of erosive GERD (ERD), non-ERD, uninvestigated GERD, and Barrett's esophagus varied significantly among Asian countries. The most important factor in diagnosing GERD was the presence of symptoms in all countries. A proton pump inhibitor was the most commonly prescribed drug to treat GERD in all countries. Endoscopic surveillance for GERD was performed regularly.

Conclusion: This questionnaire survey revealed the current status of management of GERD in clinical practice in various Asian countries.
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http://dx.doi.org/10.1159/000504749DOI Listing
August 2020

Nutritional status predicts adjuvant chemotherapy outcomes for stage III colorectal cancer.

J Anus Rectum Colon 2019 25;3(2):78-83. Epub 2019 Apr 25.

First Department of Surgery, Dokkyo Medical University, Tochigi, Japan.

Objectives: Previously, adjuvant chemotherapy using oxaliplatin was a standard treatment for patients with node-positive colorectal cancer (CRC) who underwent curative surgery. The factor predicting adverse events and therapeutic effect have not yet been established.

Methods: A retrospective cohort of 42 patients diagnosed with stage III CRC between April 2009 and March 2013 in our institution were included in this study. The indicators of host nutritional status were body weight (BW), body mass index (BMI), serum albumin, Onodera's prognostic nutritional index (OPNI), and Glasgow Prognostic Score (GPS). The indicators of host immunocompetence was total lymphocyte counts, total neutrophil counts, granulocytes/lymphocytes ratio (G/L ratio).

Results: The overall recurrence rate was 26.1%. Patients who had a recurrence were more likely to be older. The recurrence was not associated with type of regimen or adverse events. The cases with a few cumulative doses and relative dose intensity of oxaliplatin experienced significantly more recurrence. Nutritional status indicators, such as the serum albumin level, OPNI, and the modified Glasgow prognostic score (mGPS) were associated with the adjuvant chemotherapy outcome. Our study results indicated worse nutritional status induced worse disease-free survival (DFS) and more recurrence.

Conclusion: The host's nutritional status associated with outcomes in stage III CRC patients.
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http://dx.doi.org/10.23922/jarc.2018-031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6752120PMC
April 2019

Treatment strategy for brain metastases from esophageal cancer.

Tumori 2020 Apr 28;106(2):109-114. Epub 2019 Aug 28.

First Department of Surgery, Dokkyo Medical University, Mibu-machi, Tochigi, Japan.

Background: This study aimed to examine the treatment outcomes of patients with brain metastases from esophageal cancer. Brain metastases from esophageal cancer are rare and have a poorer prognosis than brain metastases from lung and breast cancer.

Methods: This study included patients who were diagnosed with and treated for esophageal cancer in our department and subsequently developed brain metastases between April 2010 and December 2014. We examined the differences in survival in patients based on receiving chemotherapy.

Results: In total, 8 patients (7 men and 1 woman) with a mean age of 65 years (range 51-73) were included. Seven presented with neurologic symptoms. Two were diagnosed via computed tomography (CT), 5 via magnetic resonance imaging, and 1 via positron emission tomography/CT. They were treated using whole-brain irradiation or with a gamma knife. In 5 patients, chemotherapy was administered after treatment of the brain metastases. The mean survival from the start of treatment was 358 days (range 31-1196).

Conclusion: The relatively successful local control of brain metastases in these patients indicates that long-term survival may be attainable via concomitant chemotherapy.
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http://dx.doi.org/10.1177/0300891619869518DOI Listing
April 2020

Relationship of daily hot water bathing at home and hot water spa bathing with underlying diseases in middle-aged and elderly ambulatory patients: A Japanese multicenter cross-sectional study.

Complement Ther Med 2019 Apr 10;43:232-239. Epub 2019 Feb 10.

Department of Oriental Medicine, Saitama Medical University, Japan.

The purpose of this study was to clarify the relationship of daily hot water bathing at home (DHW) and hot water spa bathing (HSPA) with the number of underlying diseases in middle-aged and elderly ambulatory patients. We defined the number of underlying diseases as the main outcome and dependent (criterion) variable. The frequency and time of DHW and the frequency of HSPA were set as explanatory variables. Multiple logistic regression analysis was performed for each frequency and time, adjusted age and sex. Odds ratio (OR) and 95% confidence interval (95% CI) were calculated. Among the 1261 patients who participated, there was no significant difference in age between males (n = 508, 72.8 ± 6.8 years) and females (n = 753, 73.5 ± 6.9 years). There was also no significant age difference between males (number of diseases: 2.7 ± 2.0 pts.) and females (number of diseases: 2.7 ± 2.1 pts.) in the occurrence of underlying diseases. Frequency and time of DHW were not associated with the occurrence of underlying diseases. However, compared with participants who utilized hot water spa at least once a week, the occurrence of underlying diseases was significantly associated with bathing frequency: one to three times per month (OR 2.72, 95% CI 1.63-4.52); twice or five times a year (OR 1.92, 95% CI 1.25-2.94). In conclusion, lower frequency of HSPA was significantly associated with increased risk of the occurrence of underlying diseases in middle-aged and elderly ambulatory patients. However, the relationship between proactive use of hot water spa and patients' mental and physical support should be clarified by well-designed cohort studies. The present study was registered as UMIN000033018 by the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) in Japan (refer: https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000037643).
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http://dx.doi.org/10.1016/j.ctim.2019.02.003DOI Listing
April 2019

Questionnaire-Based Survey on Management of Ulcerative Colitis-Associated Cancer in East Asian Countries.

Digestion 2019 14;99(1):86-94. Epub 2018 Dec 14.

Sino United Health Clinic, Gopher Medical Center, Rui Jing Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background/aims: To elucidate the current management of ulcerative colitis (UC)-associated cancer, a questionnaire-based survey was conducted to gather current opinions on colitis-associated cancer in different East Asian countries.

Methods: The questionnaire, based on physicians, contains 9 questions focused on UC management and cancer surveillance. In addition, the questionnaire based on neoplastic cases, which contains 17 questions, was collected and analyzed.

Results: With regard to the diagnosis of UC-associated cancer, most respondents started surveillance colonoscopy within 10 years from onset, favored targeted biopsies, and thought advanced imaging was useful. As for morphology, the frequency of elevated lesion and type 4 lesions was most common in early and advanced cancer, respectively. Peritoneal metastasis was frequently observed, and undifferentiated tumor was frequently developed. Laparoscopic surgery was widely used because it is less invasive. The prognostic outcome was poor, particularly in stage III and undifferentiated type.

Conclusions: The current survey elucidated the current management in Asian countries and characteristics of colitis-associated cancer in these countries.
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http://dx.doi.org/10.1159/000494419DOI Listing
April 2019

[A Case of Advanced Gastric Cancer with Multiple Bone Metastases, Virchow Lymph Node and Para-Aortic Lymph Node Metastases That Responded to Combined Modality Therapy and Underwent Conversion Surgery].

Gan To Kagaku Ryoho 2018 Oct;45(10):1453-1456

First Dept. of Surgery, Dokkyo Medical University.

A 41-year-old woman with type 3 advanced gastric cancer and Virchow lymph node, para-aortic lymph node, and multiple bone metastases was diagnosed with U-less cType 3 cT4aN3M1, cStage IV. We administered docetaxel, cisplatin, and S-1 (DCS)therapy for unresectable gastric cancer. After 11 courses of DCS, we confirmed that the distant lymph node metasta- ses were significantly reduced. We performed radiotherapy(30 Gy/10 Fr)on the thoracic lumber vertebrae. Because the patient was successfully downstaged, we performed total gastrectomy with Roux-en-Y reconstruction. The histopathological diagnosis was ypT3N2M0, ypStage III A. In this case, DCS therapy successfully treated gastric cancer with distant metastases, including multiple bone metastases.
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October 2018

Salvage esophagectomy combined with partial aortic wall resection following thoracic endovascular aortic repair.

Gen Thorac Cardiovasc Surg 2018 Dec 15;66(12):736-743. Epub 2018 Sep 15.

Fukushima Medical University, Fukushima, Japan.

Objective: Definitive chemoradiotherapy is useful for locally advanced esophageal cancer. However, salvage esophagectomy is required when residual or recurrent tumor is evident after chemoradiotherapy. We performed salvage esophagectomy combined with partial aortic wall resection after thoracic endovascular aortic repair for aortic invasion, and we evaluated the results.

Methods: Four patients underwent esophagectomy combined with aortic wall resection after thoracic endovascular aortic repair because the lesion was diagnosed as stage T4b. We evaluated short-term outcomes, including duration of thoracic surgery, blood loss, duration of intubation, intensive care unit stay, and postoperative morbidity, as well as survival after salvage surgery.

Results: Lesions were resected with no intraoperative procedural adverse events. Mean thoracic operation time was 444 min, and mean thoracic blood loss was 506 g. In all patients, complete resection of the lesion was possible with no intraoperative adverse events. All patients were extubated on postoperative day 0, and all were discharged from the intensive care unit on postoperative day 1. One patient experienced grade II wound pain (bilateral chest pain), and another patient experienced difficult sputum expectoration (grade IIIA). The mean follow-up time was 19.8 months, and two patients were alive with no disease recurrence at the time of this report. However, the remaining two patients had died secondary to lymph node metastasis.

Conclusions: Salvage esophagectomy combined with partial aortic wall resection after thoracic endovascular aortic repair provides acceptable short-term outcomes. Future studies are needed to evaluate long-term survival and patient selection criteria.
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http://dx.doi.org/10.1007/s11748-018-1013-zDOI Listing
December 2018

Waardenburg syndrome with isolated deficiency of myenteric ganglion cells at the sigmoid colon and rectum.

Pediatr Rep 2018 May 24;10(2):7500. Epub 2018 May 24.

First Department of Surgery.

Waardenburg syndrome (WS) has the characteristic clinical features caused by the embryologic abnormality of neural crest cells. WS patients sometimes suffer from functional intestinal obstruction. When it is Hirschsprung disease (HD), the WS is diagnosed as type 4 WS. We report a case of WS which did not have myenteric ganglion cells in the sigmoid colon and rectum. Whether to diagnosis this case as type 1 or 4 WS is controversial. Moreover, this is the third report which has peristalsis failure caused by abnormal myenteric plexus. In all three cases, the eosinophils had aggregated in the myenteric layer of the transition zone. During embryonic life, enteric ganglion cells migrate to the myenteric layer from the proximal to the distal side sequentially and, subsequently, to the submucosal layer through the circular muscle. Therefore, we hypothesize that myenteric ganglion cells that had already migrated were eliminated by an eosinophil-mediated mechanism in these three cases. We believe this report may be helpful to elucidate the pathogenesis of some types of HD.
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http://dx.doi.org/10.4081/pr.2018.7500DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6050473PMC
May 2018

F-Fluorodeoxyglucose positron emission tomography can be used to determine the indication for endoscopic resection of superficial esophageal cancer.

Cancer Med 2018 08 28;7(8):3604-3610. Epub 2018 Jun 28.

First Department of Surgery, Dokkyo Medical University, Mibu, Tochigi, Japan.

F-Fluorodeoxyglucose positron emission tomography (FDG-PET) is a useful imaging modality that reflects the tumor activity. However, FDG-PET is mainly used for advanced cancer, not superficial cancer. In this study, we investigated the relationship between the superficial tumor depth of esophageal cancer and the FDG uptake to determine the indications for endoscopic resection (ER). From 2009 to 2017, 444 patients with esophageal cancer underwent esophagectomy or endoscopic submucosal dissection (ESD), and 195 patients were pathologically diagnosed with superficial cancer. Among them, 146 patients were examined by FDG-PET before esophagectomy or ESD. In these 146 patients, the relationship between the pathological tumor depth and FDG uptake was analyzed. The mean maximum standardized uptake value in pT1a-EP/LPM tumors was 1.362 ± 0.890, that in pT1a-MM/pT1b-SM1 tumors was 2.453 ± 1.872, and that in pT1b-SM2/SM3 tumors was 4.265 ± 3.233 (P < .0001). Among 51 pT1a-EP/LPM tumors, 10 (19.6%) showed positive detection of FDG. For pT1a-MM/pT1b-SM1 and pT1b-SM2/SM3 tumors, the detection rate was 52.9% (18/34) and 82.0% (50/61), respectively. The detection rate of pT1a-EP/LPM was significantly lower than in the other two groups (P < .0001). Among 10 FDG-PET-positive lesions, only 1 had no apparent reason for PET positivity; however, 9 of 10 had a suitable reason for detectability by PET and inadequacy for ER. Negative detection of superficial esophageal squamous cell carcinoma by FDG-PET is useful to determine the indication for ER when the tumor depth cannot be diagnosed even after performing magnifying endoscopy with narrow band imaging and endoscopic ultrasonography. When FDG uptake is recognized, a therapeutic modality other than ER should be considered.
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http://dx.doi.org/10.1002/cam4.1628DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6089148PMC
August 2018

Predictive model for macrosomia using maternal parameters without sonography information.

J Matern Fetal Neonatal Med 2019 Nov 10;32(22):3859-3863. Epub 2018 Jul 10.

b Department of Clinical Epidemiology and Health Economics , School of Public Health, The University of Tokyo , Tokyo , Japan.

We aimed to develop new predictive models for excluding macrosomia using only maternal physical parameters, without sonographic examination. The present study retrospectively analyzed the medical records of pregnant women who delivered singleton infants at term at one obstetric hospital in an urban area in Japan from May 2005 to April 2017. We performed logistic regression analysis to predict macrosomia and created an integer risk scoring system based on the significant predictors. We also developed an alternative predictive regression model using machine learning with the random forest algorithm. There were 203 cases of macrosomia among 15,263 eligible women. Although our scoring system had low specificity and positive predictive value, the negative predictive value for screening macrosomia was very high (0.996-1.000). The other model, using machine learning with the random forest algorithm to predict macrosomia, showed a negative predictive value of 0.99, which was similar to the results of our scoring system. Our integer scoring system is an easy and useful method for excluding macrosomia among pregnant women without sonographic examination.
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http://dx.doi.org/10.1080/14767058.2018.1484090DOI Listing
November 2019

Laparoscopic surgery for a Bochdalek hernia triggered by pregnancy in an adult woman: A case report.

Int J Surg Case Rep 2018 1;48:10-15. Epub 2018 May 1.

First Department of Surgery, Dokkyo Medical University, Tochigi, Japan.

Introduction: A Bochdalek hernia (BH) is a type of congenital diaphragmatic hernia. We herein describe an adult woman with a BH triggered by pregnancy and treated by laparoscopic surgery.

Presentation Of Case: A 26-year-old woman was referred to our hospital because of abdominal pain and dyspnea resulting from a left diaphragmatic hernia. She was diagnosed with a BH and underwent laparoscopic surgery. Her postoperative progress was satisfactory, and no recurrence was found at follow-up approximately 1 year later.

Discussion: A recently published study reviewing detailed cases of laparoscopic and/or thoracoscopic repair of adult BH from 1999 to 2016 identified 30 cases. A laparoscopic approach for treatment of BH has recently attracted increasing interest.

Conclusion: Laparoscopic surgery can be safely performed on adults with BH without complications.
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http://dx.doi.org/10.1016/j.ijscr.2018.04.028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6066472PMC
May 2018

Pathological and Clinical Pathological Changes Induced by Four-week, Repeated-dose, Oral Administration of the Wood Preservative Chromated Copper Arsenate in Wistar Rats.

Toxicol Pathol 2018 04 27;46(3):312-323. Epub 2018 Mar 27.

1 The Institute of Environmental Toxicology, Joso-shi, Ibaraki, Japan.

Chromated copper arsenate (CCA) is used as a wood preservative worldwide. Exposure to it may adversely affect human health. Some events have increased human exposure to CCA, including the Great East Japan Earthquake, which generated a large amount of lumber debris from CCA-treated woods. We elucidated the toxicity due to daily exposure to CCA over a 4-week period at doses of 0, 8, 40, and 80 mg/kg/day in Wistar Hannover rats. Chromium (Cr) and arsenic (As), but not copper, were detected in the plasma samples of rats treated with various doses of CCA. Males and females showed sedation, and males had poor body weight gain. The clinical pathologies observed in both sexes included hypochromic and microcytic anemia, hepatic and renal dysfunction, and changes in lipid and glucose levels. Histopathologically, males and females showed forestomach hyperkeratosis, mucosal epithelial hyperplasia in the small intestine, rectal goblet cell hypertrophy, and lipofuscin deposition in the proximal renal tubule. Females showed diffuse hepatocellular hypertrophy with increased 8-hydroxydeoxyguanosine levels. These results indicated that oral administration of CCA mainly affected hematopoietic, gastrointestinal, hepatic, and renal systems owing to the toxic effects of As and/or Cr. Major toxic effects were observed in both sexes receiving 40 and 80 mg/kg/day.
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http://dx.doi.org/10.1177/0192623318765392DOI Listing
April 2018

Minimally Invasive Salvage Operations for Esophageal Cancer after Definitive Chemoradiotherapy.

Digestion 2018 1;97(1):64-69. Epub 2018 Feb 1.

Department of General Surgical Science, Gunma University, Graduate School of Medicine, Maebashi, Japan.

Background/aims: Because salvage surgery after definitive chemoradiotherapy for esophageal cancer is associated with high postoperative mortality and morbidity, minimally invasive methods are desirable. We analyzed the validity of minimally invasive salvage operations (MISO).

Methods: Twenty-five patients underwent salvage operation between 2010 and 2016 in our institution, 10 having undergone right transthoracic salvage esophagectomy (TTSE group), 6 transhiatal salvage esophagectomy (THSE), 6 salvage lymphadenectomy (SLA), and 3 salvage endoscopic submucosal dissection (SESD). Patients who had undergone THSE, SLA, or SESD were categorized as the MISO group. Short- and long-term outcomes were assessed.

Results: The mean duration of surgery was significantly shorter in the SLA groups than in the TTSE group (p = 0.0248). Blood loss was significantly less in the SLA than the TTSE group (p = 0.0340). Intensive care unit stay was shorter in the THSE than the TTSE group (p = 0.0412). There was no significant difference in postoperative mortality between the MISO and THSE groups. Postoperative hospital stay was significantly shorter in the SLA than the TTSE group (p = 0.0061). Patients' survivals did not differ significantly between the MISO and TTSE groups (p = 0.752). Multivariate analysis revealed that residual disease (R0; HR 4.872, 95% CI 1.387-17.110, p = 0.013) was the only independent factor influencing overall survival.

Conclusion: MISO is preferable because short-term outcomes are better and long-term outcomes do not differ from those of TTSE.
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http://dx.doi.org/10.1159/000484034DOI Listing
September 2018

Adverse Prognostic Factors of Advanced Esophageal Cancer in Patients Undergoing Induction Therapy with Docetaxel, Cisplatin and 5-Fluorouracil.

Anticancer Res 2018 02;38(2):911-918

First Department of Surgery, Dokkyo Medical University, Tochigi, Japan.

Background/aim: The purpose of this study was to identify adverse prognostic factors for patients with advanced esophageal cancer undergoing chemotherapy with docetaxel, cisplatin and 5-fluorouracil (DCF).

Patients And Methods: The study cohort comprised of 45 patients with advanced esophageal cancer who underwent induction DCF therapy followed by esophagectomy or chemoradiotherapy. Treatment outcomes and factors affecting early recurrence and death were analyzed.

Results: Overall 3-year survival was 61.4%, and 3-year disease-free survival was 44.7%. Clinically evident lymph node metastasis and clinical stage were associated with recurrence within 1 year and death within 2 years. Low maximum standardized uptake value (SUV) after induction DCF therapy and small decreases in SUV from pre- to post-DCF therapy were also predictors of recurrence and poor prognosis.

Conclusion: Induction DCF therapy may be ineffective for advanced-stage esophageal cancer and clinical lymph node metastasis (≥N2, ≥stage IIIB). Moreover, small decreases in SUV DCF therapy are associated with early disease relapse and death.
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http://dx.doi.org/10.21873/anticanres.12302DOI Listing
February 2018

Evaluation of blood adsorption onto dialysis membranes by time-of-flight secondary ion mass spectrometry and near-field infrared microscopy.

Anal Bioanal Chem 2017 Nov 25;409(27):6387-6396. Epub 2017 Aug 25.

Nipro Corporation, 3-9-3 Honjo-Nishi Kita-Ku, Osaka, 531-8510, Japan.

Blood adsorption onto the inside surface of hollow fiber dialysis membranes was investigated by means of time-of-flight secondary ion mass spectrometry (TOF-SIMS) and near-field infrared microscopy (NFIR) in order to evaluate the biocompatibility and permeability of dialysis membranes. TOF-SIMS is useful for the imaging of particular molecules with a high spatial resolution of approximately 100 nm. In contrast, infrared spectra provide quantitative information and NFIR enables analysis with a high spatial resolution of less than 1 μm, which is close to the resolution of TOF-SIMS. A comparison was made of one of the most widely used dialysis membranes made of polysulfone (PSf), that has an asymmetric and inhomogeneous pore structure, and a newly developed asymmetric cellulose triacetate (ATA) membrane that also has an asymmetric pore structure, even though the conventional cellulose triacetate membrane has a symmetric and homogeneous pore structure. As a result, it was demonstrated that blood adsorption on the inside surface of the ATA membrane is more reduced than that on the PSf membrane. Graphical abstract Analysis of blood adsorption on inside surface of hollow fiber membrane.
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http://dx.doi.org/10.1007/s00216-017-0578-1DOI Listing
November 2017

Validity of neoadjuvant chemotherapy with docetaxel, cisplatin, and S-1 for resectable locally advanced gastric cancer.

Med Oncol 2017 Aug 13;34(8):139. Epub 2017 Jul 13.

First Department of Surgery, Dokkyo Medical University, Kitakobayashi 880, Mibu, Tochigi, 321-0293, Japan.

Gastrectomy with D2 lymphadenectomy plus postoperative chemotherapy is the standard treatment for resectable locally advanced gastric cancer in Japan. However, the prognosis of patients with serosa-positive tumors remains unsatisfactory because of peritoneal recurrence. This study aimed to investigate the validity of neoadjuvant therapy with docetaxel, cisplatin, and S-1 (DCS) in patients with locally advanced gastric cancer. Thirty patients with locally advanced gastric cancer underwent neoadjuvant DCS therapy at Dokkyo Medical University Hospital between June 2013 and October 2015. Gastrectomy and D2 lymphadenectomy were performed after two cycles of preoperative DCS therapy. The clinical responses of the primary gastric tumors based on endoscopic findings were partial response in 17 patients (57%) and stable disease in 13 patients (43%). Analysis of pathological response in the primary gastric lesions showed grade 1a in five patients (17%), grade 1b in nine patients (30%), grade 2 in 11 patients (37%), and grade 3 in five patients (17%). Twenty-four patients (80%) remained alive after a median follow-up period of 31 months. The 2- and 3-year overall survival rates in all patients were 89 and 70%, respectively. The 2-year overall survival rate in pathological responders (grade 1b-3) was 96%, compared with 50% in pathological non-responders (grade 1a) (P = 0.00187). Pathological responders had a significantly higher survival rate than non-responders. These results indicate that neoadjuvant DCS therapy may improve the prognosis in patients with serosa-positive locally advanced gastric cancer.
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http://dx.doi.org/10.1007/s12032-017-0997-zDOI Listing
August 2017

Possible cleavage sites of glutelin partial degradation confirmed by immunological analysis in globulin-less mutants of rice (Oryza sativa L.).

Electrophoresis 2017 10 1;38(20):2622-2630. Epub 2017 Aug 1.

Graduate School of Agriculture, Kyoto University, Kitashirakawa, Kyoto, Japan.

Proteolytic cleavage or partial degradation of proteins is one of the important post-translational modifications for various biological processes, but it is difficult to analyze. Previously, we demonstrated that some subunits of the major rice (Oryza sativa L.) seed storage protein glutelin are partially degraded to produce newly identified polypeptides X1-X5 in mutants in which another major seed storage protein globulin is absent. In this study, the new polypeptides X3 and X4/X5 were immunologically confirmed to be derived from GluA3 and GluA1/GluA2 subunits, respectively. Additionally, the new polypeptides X1 and X2 were at least in part the α polypeptides of the GluB4 subunit partially degraded at the C-terminus. Simulated 2D-PAGE migration patterns of intact and partially degraded α polypeptides based on the calculation of their MWs and pIs enabled us to narrow or predict the possible locations of cleavage sites. The predicted cleavage sites were also verified by the comparison of 2D-PAGE patterns between seed-extracted and E. coli-expressed proteins of the intact and truncated α polypeptides. The results and methodologies demonstrated here would be useful for analyses of partial degradation of proteins and the structure-function relationships of rice seed protein bodies.
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http://dx.doi.org/10.1002/elps.201700195DOI Listing
October 2017

HSP105 prevents depression-like behavior by increasing hippocampal brain-derived neurotrophic factor levels in mice.

Sci Adv 2017 May 31;3(5):e1603014. Epub 2017 May 31.

Department of Life Science, Okayama University of Science, 1-1 Ridai-cho, Kita-ku, Okayama, Japan.

Heat shock proteins (HSPs) are stress-induced chaperones that are involved in neurological disease. Although increasingly implicated in behavioral disorders, the mechanisms of HSP action, and the relevant functional pathways, are still unclear. We examined whether oral administration of geranylgeranylacetone (GGA), a known HSP inducer, produced an antidepressant effect in a social defeat stress model of depression in mice. We also investigated the possible molecular mechanisms involved, particularly focusing on hippocampal neurogenesis and neurotrophic factor expression. In stressed mice, hippocampal HSP105 expression decreased. However, administration of GGA increased HSP105 expression and improved depression-like behavior, induced hippocampal cell proliferation, and elevated brain-derived neurotrophic factor (BDNF) levels in mouse hippocampus. Co-treatment with GGA and the BDNF receptor inhibitor K252a suppressed the antidepressant effects of GGA. HSP105 knockdown decreased mRNA levels in HT22 hippocampal cell lines and hippocampal tissue and inhibited the GGA-mediated antidepressant effect. These observations suggest that GGA administration is a therapeutic candidate for depressive diseases by increasing hippocampal BDNF levels via HSP105 expression.
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http://dx.doi.org/10.1126/sciadv.1603014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5451194PMC
May 2017

Intravenous injection of umbilical cord-derived mesenchymal stromal cells attenuates reactive gliosis and hypomyelination in a neonatal intraventricular hemorrhage model.

Neuroscience 2017 07 11;355:175-187. Epub 2017 May 11.

Department of Cell Processing and Transfusion, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan. Electronic address:

Intraventricular hemorrhage (IVH) is a frequent complication of preterm newborns, resulting in cerebral palsy and cognitive handicap as well as hypoxic ischemic encephalopathy and periventricular leukomalacia. In this study, we investigated the restorative effect on neonatal IVH by umbilical cord-derived mesenchymal stromal cells (UC-MSCs) cultured in serum-free medium (RM medium) for clinical application. UC-MSCs were cultured with αMEM medium supplemented with FBS or RM. A neonatal IVH mouse model at postnatal day 5 was generated by intraventricular injection of autologous blood, and mice were intravenously administered 1×10 UC-MSCs two days after IVH. Brain magnetic resonance imaging was performed at postnatal day 15, 22 and neurological behavioral measurements were performed at postnatal day 23, accompanied by histopathological analysis and cytokine bead assays in serum after IVH with or without UC-MSCs. Both UC-MSCs cultured with αMEM and RM met the criteria of MSCs and improved behavioral outcome of IVH mice. Moreover the RM group exhibited significant behavioral improvement compared to the control group. Histopathological analysis revealed UC-MSCs cultured with RM significantly attenuated periventricular reactive gliosis, hypomyelination, and periventricular cell death observed after IVH. Furthermore, human brain-derived neurotrophic factor and hepatocyte growth factor were elevated in the serum, cerebrospinal fluid and brain tissue of neonatal IVH model mice 24h after UC-MSCs administration. These results suggest UC-MSCs attenuate neonatal IVH by protecting gliosis and apoptosis of the injured brain, and intravenous injection of UC-MSCs cultured in RM may be feasible for neonatal IVH in clinic.
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http://dx.doi.org/10.1016/j.neuroscience.2017.05.006DOI Listing
July 2017

Effective Mediastinal Lymphadenectomy for Esophageal Cancer Using Slender Tracheal Forceps in Prone Position Thoracoscopic Esophagectomy.

In Vivo 2016 11-12;30(6):893-898

Department of Surgery I, Dokkyo Medical University, Mibu, Japan.

Background/aim: Adequate mediastinal lymphadenectomy during thoracoscopic esophagectomy (TE) requires an extensive operating field. In order to rectify this problem, we developed slender tracheal forceps that can pass through a 12-mm trocar.

Patients And Methods: TE in the prone position was performed in 58 patients with esophageal cancer using slender tracheal forceps. Perioperative and postoperative clinical data were compared against those of 61 patients who underwent transthoracic open esophagectomy (OE).

Results: The mean duration of thoracic manipulation was significantly longer in the TE than OE group: 226.2 versus 171.3 minutes (p<0.0001). Mean blood loss was significantly lower in the TE than OE group: 39.9 versus 176.8 g (p<0.0001). A mean of 23.4 mediastinal lymph nodes were dissected in the TE group and 25.1 in the OE group. The timing of extubation tended to be earlier in the TE group. Postoperative morbidity did not differ between groups.

Conclusion: Slender tracheal forceps are acceptable for fine mediastinal lymphadenectomy in thoracoscopic surgery for esophageal cancer, and the technique could contribute to development of minimally invasive surgery.
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http://dx.doi.org/10.21873/invivo.11010DOI Listing
January 2018