Publications by authors named "Yasuhiro Miyazaki"

189 Publications

Intra-abdominal desmoid-type fibromatosis successfully resected using laparoscopic fluorescence imaging with indocyanine green after intersphincteric resection for rectal cancer.

Asian J Endosc Surg 2021 Jul 24. Epub 2021 Jul 24.

Department of Gastrointestinal Surgery, Osaka General Medical Center, Osaka, Japan.

Successful resection of intra-abdominal tumors using indocyanine green (ICG) fluorescence imaging has not been reported. Here, we report a rare case of an intra-abdominal desmoid-type fibromatosis successfully resected using this technique after intersphincteric resection (ISR) for rectal cancer. One year after ISR for rectal cancer in a 47-year-old man, computed tomography showed a 50-mm intra-abdominal tumor near the left common iliac vein. Surgical resection was performed. The tumor was located in the mesentery of the remnant rectum after ISR. ICG fluorescence imaging confirmed the blood supply to the mesentery of the distal remnant rectum after tumor excision. The anal canal was successfully preserved without creating a permanent colostomy. The tumor was safely resected with resection margins, diagnosed as desmoid-type fibromatosis. No tumor recurrence was observed 6 months post-resection. This was the first case report to demonstrate the utility of this technique for an intra-abdominal tumor resection.
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http://dx.doi.org/10.1111/ases.12968DOI Listing
July 2021

OSK-0028 in Patients With Esophageal Cancer Undergoing Esophagectomy: A Double-blind, Randomised Controlled Trial.

Anticancer Res 2021 Aug;41(8):3875-3884

Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.

Background/aim: An excessive postoperative inflammatory response is correlated with the development of pneumonia and an unfavourable prognosis in patients undergoing esophagectomy for esophageal cancer. We assessed the influence of OSK-0028, a synthetic human ghrelin on inflammatory response and energy metabolism, on the postoperative course of patients following radical esophagectomy.

Patients And Methods: Esophageal cancer patients were randomly assigned to low-dose (LD; 0.25 μg/kg/h) or high-dose (HD; 0.5 μg/kg/h) intravenous OSK-0028 or placebo for 7 days after esophagectomy. The primary endpoint was serum interleukin-6 level on postoperative day (POD) 3.

Results: A total of 75 patients were enrolled (23 LD, 26 HD, 26 placebo). The median interleukin-6 levels on POD 3 were 40.95, 35.85, and 64.50 pg/ml in the placebo, LD, and HD groups, respectively, with no significant differences (p=0.78). Postoperative complications did not differ between groups. Bodyweight loss was significantly lower in patients receiving OSK-0028 than in those receiving placebo (-0.17% vs. 1.78%, p=0.043).

Conclusion: Although OSK-0028 did not attenuate inflammatory response after esophagectomy, it prevented postoperative bodyweight loss.
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http://dx.doi.org/10.21873/anticanres.15182DOI Listing
August 2021

Background characteristics and diabetes remission after laparoscopic sleeve gastrectomy in Japanese patients with type 2 diabetes stratified by BMI: subgroup analysis of J-SMART.

Diabetol Int 2021 Jul 2;12(3):303-312. Epub 2021 Jan 2.

Center of Diabetes, Endocrine and Metabolism, Toho University Sakura Medical Center, 564-1, Shimoshizu, Sakura-City, Chiba 285-8741 Japan.

Aim: The J-SMART study was the first national survey of Japanese patients undergoing laparoscopic sleeve gastrectomy (LSG). We performed a subgroup analysis of J-SMART focusing on the differences in patient background and diabetes remission between patients with BMI 32-34.9 kg/m and those with higher BMI.

Methods: In this multi-institutional retrospective study at 10 certified bariatric institutions, 203 Japanese with type 2 diabetes (T2D) and BMI of 32 kg/m or higher were analyzed (mean age: 49.2 years, BMI: 43.8 kg/m, HbA1c: 7.6%). Patients were stratified into five groups according to preoperative BMI.

Results: Background characteristics in BMI 32.0-34.9 group were higher adjusted HbA1c, higher visceral/subcutaneous fat area ratio, higher prevalence of diabetic retinopathy, higher frequency of insulin use and lower serum C-peptide. Although 2-year percent total weight loss (21.7%) and diabetes complete remission (CR) rate (52.4%) were lower in BMI 32.0-34.9 group, diabetes improvement rate was 81.0%, and the decrease in HbA1c and number of antidiabetic drugs were comparable or greater than those with higher BMI. Higher BMI and no insulin use were significant independent predictors of diabetes CR. No significant independent predictor was identified for diabetes improvement.

Conclusion: The patients with 32-34.9 kg/m were characterized by more severe visceral obesity, T2D and the complications, and lower intrinsic insulin secretion capacity. LSG should be considered as a treatment option for patients with BMI 32-34.9 kg/m, to improve diabetes control.
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http://dx.doi.org/10.1007/s13340-020-00487-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172703PMC
July 2021

Angiosarkom mit diffuser ödematöser Induration im Gesicht: ein seltenes und atypisches klinisches Merkmal.

J Dtsch Dermatol Ges 2021 Jun;19(6):892-895

Department of Dermatology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.

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http://dx.doi.org/10.1111/ddg.14352_gDOI Listing
June 2021

Pancreas-left gastric artery angle is associated with postoperative inflammation and drain amylase after laparoscopic gastrectomy.

Asian J Endosc Surg 2021 Apr 26. Epub 2021 Apr 26.

Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Japan.

Introduction: The pancreas often interferes with the surgical field during laparoscopic gastrectomy (LG) and its disorders cause severe postoperative complications. This study aimed to evaluate the association between the anatomical location of the pancreas and surgical outcome and to investigate the optimal surgical position in LG.

Methods: We newly defined the angle formed between the supra-pancreatic region and the root of the left gastric artery (LGA) as the pancreas-LGA angle (PLA). The association between PLA and surgical outcomes in 107 consecutive patients who underwent laparoscopic distal gastrectomy (LDG) was investigated. Then, the change in PLA before and after insertion of the back pillow in 30 patients with gastric cancer was examined.

Results: The median PLA was 62° (range, 2°-157°). No differences were found in the patient background between patients with small PLA (PLA < 62°; n = 53) and those with large PLA (PLA ≧ 62°; n = 54). The postoperative inflammation response (white blood cells, neutrophils, and C-reactive protein) and amylase concentration in the drainage fluid (D-AMY) were significantly higher in the small PLA group than large PLA group. Multivariable analyses demonstrated that small PLA was an independent risk factor for high D-AMY. After insertion of a back pillow, PLA was noninvasively increased in all patients, and the median PLA was changed to 92° (range, 8°-151°) from 61° (range, 2°-140°). Of 17 patients with small PLA, nine developed large PLA.

Conclusions: These results suggest that PLA can become one of the indicators of postoperative complications related to anatomical patient factors in LDG.
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http://dx.doi.org/10.1111/ases.12938DOI Listing
April 2021

Angiosarcoma presenting as a diffuse facial edematous induration: a rare and atypical clinical feature.

J Dtsch Dermatol Ges 2021 Jun 16;19(6):892-895. Epub 2021 Apr 16.

Department of Dermatology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.

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http://dx.doi.org/10.1111/ddg.14352DOI Listing
June 2021

Surgical plume from tissue infected with human hepatitis B virus can contain viral substances.

Minim Invasive Ther Allied Technol 2021 Apr 14:1-9. Epub 2021 Apr 14.

Department of Next Generation Endoscopic Intervention, Osaka University Graduate School of Medicine, Osaka, Japan.

Introduction: Evidence on the biological danger associated with surgical plume is lacking. We examined whether surgical plume, generated by the energy devices ultrasonically activated scalpel (US) or electrocautery (EC) contains virus-related substances.

Material And Methods: Tumor mass of a hepatocellular carcinoma line was prepared in a mouse. Surgical plume generated on the mass by US or EC was collected and detection of HBs gene fragment and antigens (HBsAg or AFP) was conducted. : Detection of HBV-DNA and HBsAg was conducted following the collection of surgical plume generated from clinically obtained liver specimens from six HBV-associated hepatocellular carcinoma patients.

Results: HBs gene fragment was detected in the solutions regardless of the device used. HBsAg was detected in US and EC solutions and AFP was also detected in a US solution. HBV-DNA was detected in both devices, in all three cases whose preoperative serum HBV-DNA was positive. In the other serum-negative cases, HBV-DNA was not detected. While serum HBsAg was positive in five of six cases, it was not detected in any solution.

Conclusions: DNA fragments or antigens of virus can exist in the surgical plume generated by EC or US.
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http://dx.doi.org/10.1080/13645706.2021.1910848DOI Listing
April 2021

Oral nutritional supplements versus a regular diet alone for body weight loss after gastrectomy: a phase 3, multicenter, open-label randomized controlled trial.

Gastric Cancer 2021 Apr 9. Epub 2021 Apr 9.

Osaka University Graduate School of Medicine, Osaka, Japan.

Background: Body weight loss (BWL) after gastrectomy is associated with not only a deteriorated quality of life but also a poor prognosis. Oral nutritional supplements (ONS) may be used to minimize BWL, which is observed in the first 3 months after gastrectomy and becomes stable thereafter, although the results of several randomized trials remain controversial.

Methods: We performed a multicenter, open-label randomized controlled trial including 1003 gastric cancer patients undergoing curative gastrectomy. Patients were assigned to the ONS group or the control group. In the former, 400 ml (400 kcal) per day for 12 weeks as enteral nutrition was planned, and the actual intake amount was recorded daily by patients themselves. The primary endpoint was BWL 1 year after gastrectomy.

Results: BWL data were available in 880 patients (ONS 437, control 443). BWL at 3 months was significantly lower in the ONS group than in the control group (7.1 ± 5.6% and 8.5 ± 5.8%, p = 0.0011). However, the difference gradually declined after 6 months and was not significant 1 year after surgery (9.3 ± 8.2% and 9.8 ± 8.7%, p = 0.37). In the ONS group, 50.4% of patients took more than 200 ml/day of ONS (average 301 ml) and showed significantly less BWL (8.2 ± 7.2%) at 1 year than the control (p = 0.0204).

Conclusion: The administration of ONS for 12 weeks after gastrectomy did not improve BWL at 1 year. However, the improvement in BWL remained until 1 year after surgery in patients who took more than 200 kcal/day of ONS.
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http://dx.doi.org/10.1007/s10120-021-01188-3DOI Listing
April 2021

Propranolol suppresses gastric cancer cell growth by regulating proliferation and apoptosis.

Gastric Cancer 2021 Mar 29. Epub 2021 Mar 29.

Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.

Background: Despite improvements in gastric cancer treatment, the mortality associated with advanced gastric cancer is still high. The activation of β-adrenergic receptors by stress has been shown to accelerate the progression of several cancers. Accordingly, increasing evidence suggests that the blockade of β-adrenergic signaling can inhibit tumor growth. However, the effect of β-blockers, which target several signaling pathways, on gastric cancer remains to be elucidated. This study aimed to investigate the anti-tumor effects of propranolol, a non-selective β-blocker, on gastric cancer.

Methods: We explored the effect of propranolol on the MKN45 and NUGC3 gastric cancer cell lines. Its efficacy and the mechanism by which it exerts anti-tumor effects were examined using several assays (e.g., cell proliferation, cell cycle, apoptosis, and wound healing) and a xenograft mouse model.

Results: We found that propranolol inhibited tumor growth and induced G1-phase cell cycle arrest and apoptosis in both cell lines. Propranolol also decreased the expression of phosphorylated CREB-ATF and MEK-ERK pathways; suppressed the expression of matrix metalloproteinase-2, 9 and vascular endothelial growth factor; and inhibited gastric cancer cell migration. In the xenograft mouse model, propranolol treatment significantly inhibited tumor growth, and immunohistochemistry revealed that propranolol led to the suppression of proliferation and induction of apoptosis.

Conclusions: Propranolol inhibits the proliferation of gastric cancer cells by inducing G1-phase cell cycle arrest and apoptosis. These findings indicate that propranolol might have an opportunity as a new drug for gastric cancer.
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http://dx.doi.org/10.1007/s10120-021-01184-7DOI Listing
March 2021

Investigating the Characteristics of Covert Unilateral Spatial Neglect Using the Modified Posner Task: A Single-subject Design Study.

Prog Rehabil Med 2021 6;6:20210014. Epub 2021 Mar 6.

Graduate School of Human Health Sciences, Tokyo Metropolitan University, Tokyo, Japan.

Objectives: Patients identified as asymptomatic for unilateral spatial neglect (USN) based on paper-and-pen tests nonetheless often collide with objects to their left while walking. This study aimed to investigate chronic USN in subjects who experienced collisions while walking.

Methods: Two patients with chronic USN who experienced collisions while walking were evaluated using the Behavioral Inattention Test-conventional (BIT-c). Additionally, the modified Posner task (MPT) was used to evaluate the left and right reaction times. MPT targets randomly appeared either on the side indicated by the cue (valid condition) or on the opposite side (invalid condition). This study used an alternating treatments single-case design. The valid and invalid conditions of the MPT alternated rapidly and randomly to determine differences in reaction time. Statistical analysis compared left and right reaction times using a one-tailed randomization test to study valid and invalid conditions.

Results: The total BIT-c score was in the normal range for both subjects, whereas MPT reaction times were higher on the left side than on the right side for the invalid condition. However, for the valid condition, only Case B had increased reaction times on the left side.

Conclusions: The MPT valid condition evaluates voluntary attention, whereas the invalid condition evaluates the reorientation of attention. Consequently, for Case A, a left reorientation of attention deficit was observed, whereas, for Case B, left voluntary attention and left reorientation of attention deficits were observed. The MPT results revealed the characteristics of covert neglect signs. USN evaluation would benefit from additional research using MPT.
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http://dx.doi.org/10.2490/prm.20210014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937691PMC
March 2021

Clinical significance of surgical intervention for imatinib-resistant gastrointestinal stromal tumors in the era of multiple tyrosine kinase inhibitors.

Surg Today 2021 Feb 11. Epub 2021 Feb 11.

Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2-E2, Yamadaoka, Suita, Osaka, 565-0871, Japan.

Purpose: Imatinib is the standard treatment for unresectable and metastatic GIST. In the late stages, patients undergoing imatinib show drug resistance. Surgical intervention has been occasionally performed for resistant lesions. However, the clinical significance of such intervention remains unclear.

Methods: Between 2006 and 2015, 37 patients were diagnosed with imatinib-resistant GISTs. We performed surgical intervention only for localized resistant lesions. We retrospectively investigated the background characteristics, data on surgical intervention and subsequent treatment, progression-free survival (PFS), and overall survival (OS).

Results: Eighteen patients diagnosed with localized resistance received surgical intervention (S-group) and 19 patients diagnosed with generalized resistance were received other TKIs (M-group). In S-group, no serious complications occurred, and all patients restarted imatinib after resection. The median PFS was 14.5 months. Five patients underwent surgical intervention multiple times followed by the continuation of imatinib, and the median duration of imatinib continuation was 22.2 months. Second-line TKIs were administered to 93% of the patients and the dose-intensity and outcome were similar in both groups. The median OS was 47.2 months after surgery.

Conclusions: Surgical intervention could be performed safely and therefore could be followed by the continuation of TKI therapy. Surgical intervention based on the appropriate criteria of resistance might thus be useful for imatinib-resistant GISTs.
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http://dx.doi.org/10.1007/s00595-021-02241-5DOI Listing
February 2021

Prediction of Long-Term Diabetes Remission After Metabolic Surgery in Obese East Asian Patients: a Comparison Between ABCD and IMS Scores.

Obes Surg 2021 Apr 7;31(4):1485-1495. Epub 2021 Jan 7.

Weight Loss and Metabolic Surgery Center, Yotsuya Medical Cube, Tokyo, Japan.

Purpose: Recently, more than 10 models have been developed to predict remission of type 2 diabetes mellitus (T2DM) after metabolic surgery. The ABCD score was compared to the individualized metabolic surgery (IMS) score in terms of prediction of T2DM remission, but which of the two scoring systems is better remains controversial.

Methods: Patient data from 463 obese East Asian patients who underwent laparoscopic Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (SG), or SG with duodenojejunal bypass (SG-DJB) as a primary operation and were followed for at least 3 years were retrospectively collected from 24 institutions. The correlation between the ABCD and IMS scoring systems and the discrimination power of the models was evaluated. The cut-off point for the IMS stage of T2DM severity was also revised to adjust the scoring system to obese East Asian patients.

Results: The two scoring systems were significantly well correlated. The IMS scoring system showed significant differences in T2DM remission rates between the procedures in the moderate stage, but the ABCD score showed no significant differences in each category. The discrimination power of the IMS score was comparable to that of the ABCD score at both 3 and 5 years. The revised IMS scoring system showed that SG-DJB had significantly higher T2DM remission rates in the moderate stage at 5 years than RYGB or SG.

Conclusion: IMS score may be comparable to ABCD score to predict T2DM remission in obese East Asian patients. The revised IMS scoring system may also select candidates for SG or SG-DJB.
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http://dx.doi.org/10.1007/s11695-020-05151-6DOI Listing
April 2021

Continuous ghrelin infusion attenuates the postoperative inflammatory response in patients with esophageal cancer.

Esophagus 2021 Apr 27;18(2):239-247. Epub 2020 Aug 27.

Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.

Purpose: The aim of this study was to clarify whether ghrelin infusion is useful for suppressing inflammatory responses after esophagectomy.

Methods: A phase I study of ghrelin administration after esophagectomy was performed in 20 patients with esophageal cancer. The anti-inflammatory effect of ghrelin was compared with 20 consecutive patients who did not receive ghrelin infusion. Additionally, 10 patients with intermittent infusion for 10 days were compared with 10 patients with continuous infusion for 5 days. The primary endpoint was the duration of systemic inflammatory response syndrome (SIRS). Secondary endpoints included postoperative complications, serum C-reactive protein (CRP), interleukin-6 (IL-6), and growth hormone (GH) levels.

Results: No adverse events of ghrelin administration occurred. Patients with ghrelin infusion had higher plasma ghrelin levels on postoperative day (POD) 3 (p = 0.003) and shorter SIRS duration (p = 0.007) than patients without ghrelin infusion. Although SIRS duration was similar (p = 0.19), patients with continuous ghrelin infusion had significantly higher plasma ghrelin (p < 0.001) and GH levels (p = 0.002) on POD 3 than patients with intermittent ghrelin infusion. Serum CRP and IL-6 levels on POD 3 tended to be lower in the continuous infusion versus intermittent infusion group.

Conclusions: Ghrelin was safely administered after esophagectomy and may reduce excess postoperative inflammatory responses. Continuous infusion is better for this purpose than intermittent infusion.
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http://dx.doi.org/10.1007/s10388-020-00776-zDOI Listing
April 2021

Laparoscopic surgery for familial multiple gastrointestinal stromal tumors with germ line c-kit gene mutation.

Asian J Endosc Surg 2021 Apr 9;14(2):250-253. Epub 2020 Jul 9.

Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Japan.

Familial gastrointestinal stromal tumor (GIST) is an exceedingly rare disease characterized by mutations in the c-kit and platelet-derived growth factor receptor alpha genes. We report the case of a 73-year-old woman with multiple submucosal tumors (SMTs) in the stomach and small intestine. Her elder sister had previously presented with multiple SMTs on examination and underwent surgery to remove the tumors because they showed a tendency to increase in size during follow-up. The sister's tumors were pathologically diagnosed as GISTs, and a germ line mutation was recognized in exon 17 of c-kit. Subsequently, the patient presented with multiple SMTs and the same germ line mutation as her sister. After 9 years of follow-up, a single tumor was found to have grown in size, and SILS was performed for this SMT, which was also pathologically diagnosed as a GIST. To our knowledge, this is the first report of laparoscopic surgery for a case of familial GIST.
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http://dx.doi.org/10.1111/ases.12837DOI Listing
April 2021

Practical Judgment of Workload Based on Physical Activity, Work Conditions, and Worker's Age in Construction Site.

Sensors (Basel) 2020 Jul 6;20(13). Epub 2020 Jul 6.

Department of Civil Engineering, College of Science and Engineering, Ritsumeikan University, Shiga 525-8577, Japan.

It is important for construction companies to sustain a productive workforce without sacrificing its health and safety. This study aims to develop a practical judgement method to estimate the workload risk of individual construction workers. Based on studies, we developed a workload model comprising a hygrothermal environment, behavioral information, and the physical characteristics of workers). The construction workers' heart rate and physical activity were measured using the data collected from a wearable device equipped with a biosensor and an acceleration sensor. This study is the first report to use worker physical activity, age, and the wet bulb globe temperature (WBGT) to determine a worker's physical workload. The accuracy of this health risk judgment result was 89.2%, indicating that it is possible to easily judge the health risk of workers even in an environment where it is difficult to measure the subject in advance. The proposed model and its findings can aid in monitoring the health impacts of working conditions during construction activities, and thereby contribute toward determining workers' health damage. However, the sampled construction workers are 12 workers, further studies in other working conditions are required to accumulate more evidence and assure the accuracy of the models.
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http://dx.doi.org/10.3390/s20133786DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7374462PMC
July 2020

Laparoscopic gastrectomy for heart failure patients with left ventricular assist devices.

Asian J Endosc Surg 2021 Jan 21;14(1):81-84. Epub 2020 Jun 21.

Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Japan.

Left ventricular assist devices (LVADs) currently play an important role in the treatment of patients with end-stage heart failure who require a bridge to heart transplantation. As the LVAD population increases, the incidence of cancer patients with an LVAD is assumed to be increasing as well. For gastric cancer patients with an LVAD, surgery may be the only curative treatment, especially as chemotherapy is scarcely available. However, we cannot perform an upper-middle incision in these patients because of the LVAD's location and driveline. Furthermore, to reduce the risk of driveline infection, minimally invasive surgery is desirable. Therefore, laparoscopic surgery is, where possible, suitable for achieving a secure approach to the abdominal cavity. However, laparoscopic surgery for patients with LVAD requires careful consideration not only for anesthetic management, but also for the technical procedure. We ingenuously performed laparoscopic gastrectomy for a gastric cancer patient with LVAD to preserve the device and obtain a good surgical view.
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http://dx.doi.org/10.1111/ases.12821DOI Listing
January 2021

A case of diaphragmatic hernia incarceration after a heart transplant operation.

Asian J Endosc Surg 2021 Jan 25;14(1):116-119. Epub 2020 May 25.

Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Japan.

We report a case of a diaphragmatic hernia after a heart transplant operation. A 43-year-old woman, who underwent orthotropic heart transplantation for hypertrophic cadiomyopathy two year earlier, presented with vomiting and epigastric pain. A computed tomography scan showed that the stomach and transverse colon were dislocated in the left thoracic cavity. We diagnosed left diaphragmatic hernia incarceration and performed laparoscopic repair of the diaphragmatic hernia. A 12 × 8 cm diaphragmatic defect was found intraoperatively on the ventrolateral aspect of the left diaphragm, and the stomach with volvulus had herniated into the thorax through the defect. The hernia was considered to be iatrogenic. The diaphragmatic defect was large, and the diaphragm was thinning. We closed the defect by mesh repair. Laparoscopic mesh repair of the diaphragmatic hernia could be performed safely and with minimal invasiveness.
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http://dx.doi.org/10.1111/ases.12811DOI Listing
January 2021

[Laparoscopic Resection of a Huge Gastric Gastrointestinal Stromal Tumor after Neoadjuvant Chemotherapy-A Case Report].

Gan To Kagaku Ryoho 2020 Apr;47(4):670-672

Dept. of Gastroenterological Surgery, Osaka University Graduate School of Medicine.

An 83-year-old woman was hospitalized with abdominal discomfort. Abdominal computed tomography(CT)revealed a hugetumor (size, 15 cm)in thegastric body. Based on thefindings of endoscopic ultrasonography-guided fine-needle aspiration, she was diagnosed with gastrointestinal stromal tumor(GIST). Invasion of thesurrounding viscera and distant metastasis were not observed; however, owing to the tumor size(>10 cm), we initiated neoadjuvant chemotherapy with imatinib. CT performed a month after chemotherapy revealed tumor shrinkage, and CT repeated 6 months after the second CT revealed tumor shrinkage to 8 cm. The patient showed a partial response to chemotherapy. She was deemed suitable to undergo laparoscopic radical resection and subsequently underwent laparoscopic partial gastric resection. Histopathological examination of the resected specimen(measuring 10 cm)revealed hyaline degeneration in most tumor cells and positive ckit expression in only some proportion of tumor cells. Based on histopathological evaluation, the tumor was diagnosed as Grade 2b. The patient showed an uneventful postoperative course. After discharge, she received imatinib as adjuvant chemotherapy and is progressing well without recurrence. Taken together, we reported the case of a huge gastric GIST in a patient who showed significant tumor shrinkage following preoperative neoadjuvant chemotherapy and successfully underwent laparoscopic radical resection.
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April 2020

[A Case of Neuroendocrine Carcinoma Treated with Salvage Surgery after Systemic Chemotherapy].

Gan To Kagaku Ryoho 2020 Feb;47(2):358-360

Dept. of Gastroenterological Surgery, Osaka General Medical Center.

A man in his 50s was admitted to our hospital due to hematemesis.Esophagogastroduodenoscopy revealed an 8 cm type 2 gastric tumor.The tumor was histologically diagnosed as a neuroendocrine carcinoma.CT showed that the tumor had directly infiltrated the liver but there was no distant metastasis.We performed open distal gastrectomy, D2 lymph node dissection, partial hepatectomy, and cholecystectomy.Four months after the surgery, metastases of the right adrenal gland and dorsal part of the inferior vena cava were found.Although a significant tumor reduction was obtained by 12 courses of chemotherapy with CDDP plus CPT-11, this effective treatment was discontinued for the patient's convenience.Fifteen months after the surgery, metastasis of the right adrenal gland and dorsal part of inferior vena cava demonstrated re-growth without any further metastasis.After 4 courses of the same regimen, a partial response was obtained for the recurrences.As a salvage surgery, we performed open right adrenal gland and the lymph nodes of dorsal of IVC resection.The patient is alive without recurrence 1 year after the salvage surgery.
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February 2020

[A Case of Long-Term Disease Control after Administration of Oxaliplatin for Esophagogastric Junction Squamous Cell Carcinoma].

Gan To Kagaku Ryoho 2020 Feb;47(2):310-312

Dept. of Gastroenterological Surgery, Osaka General Medical Center.

There are few reports of using oxaliplatin(L-OHP)for esophageal squamous cell carcinoma.We report a case of long-term disease control after administration of L-OHP for esophagogastric junction squamous cell carcinoma(EG).A woman in her 40s was diagnosed with EG(cT3, cN2, cM0, cStage Ⅲ).She received thoracoscopic, laparoscopic-assisted, subtotal esophagectomy with 3-field dissection after 3 courses of preoperative chemotherapy with DCF(docetaxel hydrate, cisplatin, 5- fluorouracil).Reconstruction was achieved using a retrosternally shifted gastric tube and transesophageal gastro-tubing. Pathological examination showed EG(ypT3, ypN2, ypM0, ypStage Ⅲ)(chemotherapy evaluation: Grade 1a).After 12 months, para-aortic lymph node recurrence(#112aoP, #16a2lat)was observed on a follow-up CT examination.First, we administered 5 courses of chemotherapy with SOX(S-1 100mg/m2 day 1-14 and L-OHP 100 mg/m2 day 1).Recurrent lymph nodes shrunk slightly, and there were no new lesions.Subsequently, there was no other adverse event except for Grade 1 chemotherapy-induced neuropathy.Second, we administered 3 courses of chemotherapy with FOLFOX(5-FU 400mg/m2, L-OHP 85mg/m2, Leucovorin 200 mg/m2 day 1, 5-FU 1,600mg/m2/46 hr)in combination with radiotherapy(total 60 Gy/ 30 Fr).Recurrent lymph nodes shrunk slightly, and there were no new lesions.Subsequently, there was no other adverse event except for Grade 1 chemotherapy-induced neuropathy.No new recurrence was observed 19 months after the first recur- rence.The patient continues to receive weekly nab-PTX(85mg/m2).A regimen that includes L-OHP is useful in the treatment of advanced or recurrent esophageal squamous cell carcinoma.
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February 2020

Impact of preoperative fecal short chain fatty acids on postoperative infectious complications in esophageal cancer patients.

BMC Gastroenterol 2020 Mar 16;20(1):74. Epub 2020 Mar 16.

Department of Surgery, Osaka International Cancer Institute, 3-1-69 Otemae, Osaka, Chuo-ku, 541-8567, Japan.

Background: The intestinal epithelial barrier allows absorption of dietary nutrients and prevents passage of pathogens and toxins into the body. Severe insults have a negative impact on the intestinal environment, which may decrease intestinal barrier function and cause bacterial translocation. Bacterial translocation, which can cause infectious complications, is defined as the passage of microbes from the gastrointestinal tract across the mucosal barrier to extraintestinal sites. The aim of this study was to investigate the correlation between concentrations of preoperative fecal organic acids and the occurrence of postoperative infectious complications in patients with esophageal cancer.

Methods: Fifty-five patients with esophageal cancer who underwent esophagectomy were enrolled in this study. Perioperative synbiotics were administered to all patients. Perioperative clinical characteristics and concentrations of preoperative fecal organic acids were compared between patients with and without postoperative infectious complications.

Results: Postoperative infectious complications occurred in 10 patients. In patients with complications, the concentrations of acetic acid and propionic acid were significantly lower than in patients without complications (p = 0.044 and 0.032, respectively). The concentration of butyric acid was nonsignificantly lower in patients with complications, while the concentration of lactic acid was nonsignificantly higher. The calculated gap between the concentrations of fecal acetic acid plus propionic acid plus butyric acid minus lactic acid was significantly lower in patients with complications. Multivariate analysis revealed that a low gap between acetic acid plus propionic acid plus butyric acid minus lactic acid was an independent risk factor for postoperative infectious complications (p = 0.027).

Conclusions: Preoperative fecal concentrations of organic acids had a clinically important impact on the occurrence of postoperative infectious complications in patients with esophageal cancer. To reduce postoperative infectious complications, it may be useful to modulate the intestinal environment and maintain concentrations of fecal organic acids before surgery.
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http://dx.doi.org/10.1186/s12876-020-01217-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7075004PMC
March 2020

[Long-Term Survival with Multidisciplinary Treatment and Nutritional Therapy for Thoracic Esophageal Cancer with Multiple Liver Metastases-A Case Report].

Gan To Kagaku Ryoho 2019 Dec;46(13):2036-2038

Dept. of Gastroenterological Surgery, Graduate School of Medicine, Faculty of Medicine, Osaka University.

The patient was a 63-year-old man with a chief complaint. Upper endoscopic examination revealed a semicircular type 2 lesion, sized 24-28 cm, on the incisor teeth and a 3 cm sized elevated lesion directly above the EGJ. When biopsy was performed, squamous cell carcinoma(SCC)was detected. In this case, lymph node metastasis and multiple liver metastases were observed, and diagnosis at the first examination was cT3N2M1(HEP), Stage Ⅳ. After 7 months of chemotherapy, he underwent right thoracic esophageal subtotal resection, 3-field lymph node dissection, posterior mediastinal gastric tube reconstruction, and partial hepatectomy. Despite receiving postoperative chemotherapy, he showed recurrence in the liver(S8). Four additional courses of chemotherapy were administered and partial hepatectomy(S8)was performed, without the appearance of new lesions. He was considered to be cured 1 year and 6months after starting the treatment and was followed- up without chemotherapy. However, 4 months later, chemotherapy was resumed when right adrenal and abdominal wall metastases and liver recurrence(S3)were found. After that, the regimen was modified, and he continued treatment. More than 4 years have passed since the start of treatment, but the treatment has been continued without a decline in ADL.
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December 2019

[A Case Report on Larynx-Preserving Surgery with Tracheal Resection of an Advanced Esophageal Cancer with Tracheal Invasion].

Gan To Kagaku Ryoho 2019 Dec;46(13):2530-2532

Dept. of Gastroenterological Surgery, Graduate School of Medicine, Osaka University.

We present the case of a 69-year-old man who was diagnosed with ascending colon cancer. Preoperative CT revealed 2 advanced esophageal cancers, both at T4; thus, a diagnosis of esophageal cancer(Ut-Ce, cT4b[Tr]N2M0, Stage ⅣA/Mt, cT4b[Lt-Br]N2M0, Stage ⅣA)was made. The patient received chemotherapy(DTX/CDDP/5-FU), and as the second-line treatment, he received chemoradiotherapy(40 Gy with DTX/CDDP/5-FU). We performed transthoracoabdominal esophagectomy, laryngeal preservation with tracheal resection, 3-field lymph node dissection, posterior mediastinal gastric tube reconstruction, mediastinal tracheostomy, and pectoralis major myocutaneous flap filling. He had an anterior chest wall subcutaneous abscess without respiratory complications. Pathological examination indicated a complete response. Two months after the surgery for esophageal cancer, radical surgery was performed for the colon cancer. Fifty-five months after esophagus cancer surgery, no recurrence was observed.
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December 2019

[A Case of Pancreatic Head Cancer after Esophagectomy and Gastrectomy Treated with Pancreatoduodenectomy].

Gan To Kagaku Ryoho 2019 Dec;46(13):2464-2466

Dept. of Gastroenterological Surgery, Osaka General Medical Center.

A woman in her 40s was hospitalizedfor jaundice. Six years before, she hadbeen diagnosedwith synchronous esophageal andgastric cancers andhadund ergone subtotal esophagectomy andtotal gastrectomy, accompaniedby reconstruction with the pedicled jejunum. Multimodal imaging revealed a tumor at the pancreatic head, probably pancreatic cancer, which induced severe stenosis of the intrapancreatic bile duct. Scraping cytology findings of the lesion via the percutaneous transhepatic cholangial drainage(PTCD)route strengthenedthe suspicion. In the image, although no obvious invasion of the major vessels or apparent distant metastases were detected, an abnormal shadow was found continuously lining the main tumor andpara -aortic region, which was a contraindication for curative resection. Therefore, we performed neoadjuvant chemotherapy with gemcitabine plus S-1. After 3 courses, the lesion size reduced notably, and pancreatoduodenectomy was performed. The pathological diagnosis was pancreatic cancer(ph, ypT3, ypN1a, ypM0, ypStage ⅡB). Except for pancreatic fistulas(Clavien-Dindo Ⅲa), the postoperative clinical course was uneventful, andshe was dischargedon postoperative day 27. To date, the patient is alive without recurrence and is undergoing adjuvant chemotherapy with S-1.
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December 2019

[Two Cases of Intraductal Papillary Neoplasm of the Bile Duct(IPNB)Resected with Hepatectomy].

Gan To Kagaku Ryoho 2019 Dec;46(13):2398-2400

Dept. of Gastroenterological Surgery, Osaka General Medical Center.

Case 1: A man in his 70s was referred to our hospital for further examination of a liver tumor(S3, 3 cm)detected by ultrasonography. Multimodal image examination showed a cystic lesion with solid papillary components located in the S4 accompanied by dilatation of the surrounding intrahepatic bile duct. Although biliary cytology did not indicate confirmed malignancy, the lesion was thought to be an intraductal papillary neoplasm of bile duct(IPNB)with malignant potential, and a left lobectomy was performed. Histopathological examination revealed a papillary tumor in the intrahepatic bile duct which consisted of atypical epithelial cells of pancreatobiliary type, and the lesion was diagnosed as an IPNB with high-grade intraepithelial neoplasia. Case 2: A woman in her 70s was referred to our hospital because of a liver tumor(S4, 8 cm)detected by ultrasonography. Multimodal image examination showed a cystic lesion localized to the liver(S3, 8 cm), and endoscopic retrograde cholangiopancreatography(ERCP)showed continuity of the cyst and the intrahepatic bile duct. The biliary cytology was positive, and the lesion was thought to be a malignant IPNB. After preoperative drainage of the cystic lesion, a left lobectomy was conducted. Histopathological examination showed that the papillary tumor localized to the bile duct and atypical epithelium cells of pancreatobiliary type were infiltrating into the surrounding matrix. We diagnosed this tumor as an IPNB with an associated invasive carcinoma.
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December 2019

Anti-glypican-1 antibody-drug conjugate is a potential therapy against pancreatic cancer.

Br J Cancer 2020 04 10;122(9):1333-1341. Epub 2020 Mar 10.

Laboratory of Immune Signal, National Institute of Biomedical Innovation, Health and Nutrition, Ibaraki, Japan.

Background: Pancreatic cancer (PDAC) is the most lethal malignancy. New treatment options for it are urgently required. The aim was to develop an antibody-drug conjugate (ADC) targeting glypican-1 (GPC-1) as a new therapy for PDAC.

Methods: We evaluated GPC-1 expression in resected PDAC specimens and PDAC cell lines. We then measured the antitumour effect of anti-GPC-1 monoclonal antibody conjugated with the cytotoxic agent monomethyl auristatin F (MMAF) in vitro and in vivo.

Results: GPC-1 was overexpressed in most primary PDAC cells and tissues. The PDAC cell lines BxPC-3 and T3M-4 strongly expressed GPC-1 relative to SUIT-2 cells. Compared with control ADC, GPC-1-ADC showed a potent antitumour effect against BxPC-3 and T3M-4, but little activity against SUIT-2 cells. In the xenograft and patient-derived tumour models, GPC-1-ADC significantly and potently inhibited tumour growth in a dose-dependent manner. GPC-1-ADC-mediated G2/M-phase cell cycle arrest was detected in the tumour tissues of GPC-1-ADC-treated mice relative to those of control-ADC-treated mice.

Conclusions: GPC-1-ADC showed significant tumour growth inhibition against GPC-1-positive pancreatic cell lines and patient-derived, GPC-1-positive pancreatic cancer tissues. Our preclinical data demonstrated that targeting GPC-1 with ADC is a promising therapy for patients with GPC-1-positive pancreatic cancer.
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http://dx.doi.org/10.1038/s41416-020-0781-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7189381PMC
April 2020

Tracheal resection and anterior mediastinal tracheostomy in the multidisciplinary treatment of esophageal cancer with tracheal invasion.

Dis Esophagus 2020 May;33(5)

Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan.

Combined tracheal resection and anterior mediastinal tracheostomy (AMT) for esophageal cancer with tracheal invasion is a challenging treatment because of its high morbidity and the lack of evidence regarding long-term outcomes. The aim of this study was to assess the short- and long-term outcomes of AMT as part of the multidisciplinary treatment for esophageal cancer with tracheal invasion. This retrospective study included 27 consecutive patients with esophageal cancer with tracheal invasion who underwent combined tracheal resection and AMT in their multidisciplinary treatment for esophageal cancer. We evaluated postoperative complications, body weight loss, and survival and examined the prognostic value of preoperative factors. All patients underwent chemotherapy and/or chemoradiotherapy as prior treatment. R0 resection was achieved in all cases. Clavien-Dindo grade I or greater complications occurred in 17 patients (63%), and grade III or greater complications occurred in 12 (44%). Overall in-hospital mortality was 4%, with one patient dying on postoperative day 48 when the brachiocephalic artery ruptured from tracheal compression. The 30- and 90-day mortality rates were 0% and 4%, respectively. Median weight change in patients without recurrence in the year after surgery was -1.7% (-9.6-21%). All of these patients received nutrition by oral intake and were living independently at home without public assistance. The 3- and 5-year disease-free survival rates were 25.9% and 18.5%, respectively; 3- and 5-year overall survival rates were 38.6% and 25.7%, respectively. Multivariate analysis identified response to prior treatment as an independent prognostic factor in these patients. Combined tracheal resection and AMT may be adapted as part of the multidisciplinary treatment of esophageal cancer with tracheal invasion. Improving AMT safety and optimizing patient selection may improve prognosis among patients with this cancer.
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http://dx.doi.org/10.1093/dote/doz101DOI Listing
May 2020

Clinical significance of chromatin remodeling factor CHD5 expression in gastric cancer.

Oncol Lett 2020 Jan 21;19(1):1066-1073. Epub 2019 Nov 21.

Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.

Chromodomain helicase DNA-binding 5 (), which is a member of the family, has been identified as a tumor suppressor gene in a variety of malignancies. The aim of the current study was to clarify the clinical significance of CHD5 expression in gastric cancer. CHD5 expression was evaluated using immunohistochemistry (IHC) in 154 specimens resected from patients with gastric cancer from January 2011 to December 2013, and assessed its relationships with clinicopathological characteristics and survival. cell proliferation, invasion, and migration assays and western blotting analysis were performed to clarify the role of CHD5 in human gastric cancer cell lines. Of a total of 154 patients, 57 (37.0%) exhibited low CHD5 expression, which was significantly associated with positive lymphatic invasion (P=0.032), advanced pT status (P=0.011), and advanced pStage (P=0.014). Overall survival (OS) in patients with low CHD5 expression was significantly worse compared with patients with high CHD5 expression (hazard ratio, 1.96; 95% confidence interval, 1.09-3.45; log-rank P=0.023). Cox multivariate analysis for OS revealed that CHD5 expression was an independent prognostic factor with age and pN status. , the upregulation of CHD5 in gastric cancer cells with low CHD5 expression significantly decreased cell proliferation, migration and invasion. CHD5 was associated with the regulation of multiple cancer-related targets, including p53 and enhancer of zeste homolog 2 (EZH2) in western blotting analysis. In conclusion, since CHD5 regulated multiple cancer-related targets, its expression may be a useful prognostic biomarker in patients with gastric cancer.
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http://dx.doi.org/10.3892/ol.2019.11138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6924149PMC
January 2020

TAS-116 inhibits oncogenic KIT signalling on the Golgi in both imatinib-naïve and imatinib-resistant gastrointestinal stromal tumours.

Br J Cancer 2020 03 20;122(5):658-667. Epub 2019 Dec 20.

Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Japan.

Background: Despite the effectiveness of imatinib mesylate (IM), most gastrointestinal stromal tumours (GISTs) develop IM resistance, mainly due to the additional kinase-domain mutations accompanied by concomitant reactivation of KIT tyrosine kinase. Heat-shock protein 90 (HSP90) is one of the chaperone molecules required for appropriate folding of proteins such as KIT.

Methods: We used a novel HSP90 inhibitor, TAS-116, which showed specific binding to HSP90α/β with low toxicity in animal models. The efficacy and mechanism of TAS-116 against IM-resistant GIST were evaluated by using IM-naïve and IM-resistant GIST cell lines. We also evaluated the effects of TAS-116 on the other HSP90 client protein, EGFR, by using lung cell lines.

Results: TAS-116 inhibited growth and induced apoptosis in both IM-naïve and IM-resistant GIST cell lines with KIT activation. We found KIT was activated mainly in intracellular compartments, such as trans-Golgi cisternae, and TAS-116 reduced autophosphorylated KIT in the Golgi apparatus. In IM-resistant GISTs in xenograft mouse models, TAS-116 caused tumour growth inhibition. We found that TAS-116 decreased phosphorylated EGFR levels and inhibited the growth of EGFR-mutated lung cancer cell lines.

Conclusion: TAS-116 may be a novel promising drug to overcome tyrosine kinase inhibitor-resistance in both GIST and EGFR-mutated lung cancer.
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http://dx.doi.org/10.1038/s41416-019-0688-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7054534PMC
March 2020

Background characteristics and postoperative outcomes of insufficient weight loss after laparoscopic sleeve gastrectomy in Japanese patients.

Ann Gastroenterol Surg 2019 Nov 26;3(6):638-647. Epub 2019 Aug 26.

Center of Diabetes, Endocrine and Metabolism Toho University Sakura Medical Center Chiba Japan.

Aim: Laparoscopic sleeve gastrectomy (LSG) is becoming popular in Japan, but insufficient weight loss is often observed in patients after LSG. We investigated the effect of LSG on obesity-related comorbidities and identified the background characteristics of Japanese patients with insufficient weight loss after LSG.

Methods: In this multi-institutional retrospective study at 10 certified bariatric institutions, 322 Japanese patients who underwent LSG with a follow-up period of more than 2 years were analyzed. Anthropometry, obesity-related comorbidities and psychosocial background data were collected. Weight loss was expressed as 2-year percent total weight loss (%TWL).

Results: Mean age, body weight, body mass index (BMI) and glycated hemoglobin were 46.9 years, 119.2 kg, 43.7 kg/m and 7.1%, respectively. Prevalence of mental disorders was 26.3%. Mean BMI declined to 30.3 kg/m at 2 years and %TWL was 29.9%. Improvements in the markers and prevalence of obesity-related comorbidities were observed. Remission rates of diabetes, dyslipidemia and hypertension were 75.6%, 59.7% and 41.8%, respectively. %TWL at the respective cut-off level of diabetes remission was 20.8%. Lower remission rates of diabetes in patients with %TWL <20%, and less calorie restriction and higher prevalence of mental disorders (46.9%) in patients with %TWL <15% were observed. Frequencies of %TWL <15% and <20% were 6.5% and 18.5%, respectively.

Conclusion: %TWL 20% was a candidate cut-off point of insufficient weight loss for diabetes remission after LSG, and mental disorders might be relevant to intractable obesity in Japanese patients.
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http://dx.doi.org/10.1002/ags3.12285DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6875950PMC
November 2019
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