Publications by authors named "Tsuyoshi Kobayashi"

269 Publications

Risk Factors for Hepatocellular Carcinoma After Splenectomy in Liver Cirrhotic Patients.

Am Surg 2021 Aug 30:31348211041562. Epub 2021 Aug 30.

Department of Gastroenterological and Transplant Surgery, 12803Hiroshima University, Hiroshima, Japan.

Background: Splenectomy is sometimes indicated for portal hypertension caused by cirrhosis, which is a risk for hepatic carcinogenesis. This study aimed to identify risk factors for hepatocellular carcinoma (HCC) development after splenectomy.

Methods: This retrospective study included 65 patients who underwent splenectomy for portal hypertension between 2009 and 2017. Cox regression analyses were performed to identify factors related to HCC development after splenectomy. The predictive index for HCC development was constructed from the results of multivariate analysis, and 3 risk-dependent groups were defined. Discrimination among the groups was estimated using Kaplan-Meier curves and the log-rank test.

Results: Post-splenectomy, 36.9% of patients developed HCC. In the univariate analysis, the etiology of cirrhosis (hepatitis C virus antibody, = .005, and hepatitis B surface antigen, = .008, referring to non-B and non-C patients, respectively), presence of HCC history ( < .001), and preoperative hemoglobin level ( = .007) were related to HCC development, and the presence of HCC history ( = .002) and preoperative hemoglobin level ( = .022) were independent risk factors. The predictive index classified three groups at risk; the hazards in each group were significantly different (low vs middle risk, = .035, and middle vs high risk, = .011).

Discussion: The etiology of cirrhosis, presence of HCC history, and hemoglobin level were associated with HCC development after splenectomy. The predictive model may aid in HCC surveillance after splenectomy for patients with portal hypertension.
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http://dx.doi.org/10.1177/00031348211041562DOI Listing
August 2021

Non-contact heart rate variability monitoring using Doppler radars located beneath bed mattress: a case report.

Eur Heart J Case Rep 2021 Aug 9;5(8):ytab273. Epub 2021 Aug 9.

Graduate School of Systems Design, Tokyo Metropolitan University, 6-6, Asahigaoka, Hino, Tokyo 191-0065, Japan.

Background: Heart rate variability (HRV) has been investigated previously in autonomic nervous system-related clinical settings. In these settings, HRV is determined by the time-series heartbeat peak-to-peak intervals using electrocardiography (ECG). To reduce patient discomfort, we designed a Doppler radar-based autonomic nervous activity monitoring system (ANMS) that allows cardiopulmonary monitoring without using ECG electrodes or spirometry monitoring.

Case Summary: Using our non-contact ANMS, we observed a bedridden 80-year-old female patient with terminal phase sepsis developed the daytime Cheyne-Stokes respiration (CSR) associated with the attenuation of the low frequency (LF) and high frequency (HF) of HRV components 20 days prior to her death. The patient developed a marked linear decrease in the LF and the HF of HRV components for over 3 days in a row. Furthermore, after the decrease both the LF and the HF showed low and linear values. Around the intersection of the two lines, the decreasing LF and HF lines and the constant LF and HF lines, the ANMS automatically detected the daytime CSR pathogenesis. The attenuation rate of HF (1340 ms/day) was higher than that of LF (956 ms/day). Heart rate increased by ∼10 b.p.m. during these 3 days.

Discussion: We detected CSR-associated LF and HF attenuation in a patient with terminal phase sepsis using our ANMS. The proposed system without lead appears promising for future applications in clinical settings, such as remote cardiac monitoring of patients with heart failure at home or in long-term acute care facilities.
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http://dx.doi.org/10.1093/ehjcr/ytab273DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8350353PMC
August 2021

Usefulness and safety of midline incision for right-sided hepatectomy: Cohort study.

Ann Med Surg (Lond) 2021 Jul 13;67:102498. Epub 2021 Jun 13.

Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan.

Background: While the adoption rates of laparoscopic hepatectomy are increasing, most patients still undergo open hepatectomy. Open hepatectomies use inverted L-shaped or Mercedes incisions for right-sided liver tumor. To decrease procedural invasiveness, we performed midline incisions in such cases, excluding those of laparoscopic hepatectomy. This retrospective study examined the effects of this change in treatment policy on overall patient surgical outcomes.

Materials And Methods: From 2012 to 2018, 374 patients who underwent hepatectomy for right-sided hepatocellular carcinoma were enrolled, and short-term patient outcomes were compared following stratification into the 1st (n = 157) or 2nd (n = 217) Era group based on whether procedures occurred before or after the policy change, respectively.

Results: Short-term outcomes were mostly comparable between the two groups, with significantly increased postoperative aspartate aminotransferase maximum values found in the 2nd Era group relative to the 1st Era group (median: 393 vs. 331, p < 0.05). Pain scores at rest during postoperative day 1 and while moving on postoperative days 1, 2, and 3 were significantly lower in the 2nd Era group than in the 1st Era group (p < 0.05, <0.01, <0.05, <0.01, respectively).

Conclusions: Utilization of midline incisions may provide some benefits in postoperative outcomes for right-sided open hepatectomy cases.
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http://dx.doi.org/10.1016/j.amsu.2021.102498DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8246149PMC
July 2021

Complete Response for Advanced Hepatocellular Carcinoma by Conversion Surgery Therapy Following a Good Response of Regorafenib Despite Rapid Progressive Disease with Sorafenib.

Intern Med 2021 1;60(13):2047-2053. Epub 2021 Jul 1.

Department of Gastroenterology and Metabolism, Research Institute for Radiation Biology and Medicine, Graduate School of Biomedical and Health Science, Hiroshima University Hospital, Japan.

A 68-year-old man with hepatocellular carcinoma (HCC) visited his previous hospital due to abdominal pain and was diagnosed with ruptured HCC. Before visiting our hospital, he underwent HCC treatment at his previous hospital, but his tumors did not improve. Although he started treatment with sorafenib, the tumors rapidly grew. Subsequently, regorafenib was given, and the tumors shrank. After 22 months being treated with regorafenib, HCC reoccurred, with a new lung metastasis and a contrast-enhanced nodule on the peritoneal dissemination appearing. He underwent conversion surgery and survived for 4.5 years after his HCC was diagnosed.
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http://dx.doi.org/10.2169/internalmedicine.5870-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8313913PMC
July 2021

Effect of increased blood flow rate on renal anemia and hepcidin concentration in hemodialysis patients.

BMC Nephrol 2021 Jun 15;22(1):221. Epub 2021 Jun 15.

Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan.

Background: Increasing the blood flow rate (BFR) is a useful method for increasing Kt/V and the clearance for low molecular solutes. Hemodialysis patients are often anemic due to hypoerythropoiesis and their chronic inflammatory state. Hepcidin, a hormone that regulates iron homeostasis, is considered as an indicator of iron deficiency in patients with end-stage renal disease. This study aimed to investigate the effects of an increased BFR during hemodialysis on serum hepcidin levels and anemia.

Methods: Between April 2014 and March 2016, 22 chronic dialysis patients (11 men [50.0 %]; mean [± standard deviation] age, 72 ± 12 years) undergoing maintenance hemodialysis treatment, thrice weekly, were enrolled and followed prospectively for 24 months. In April 2014, the BFR was 200 mL/min; in April 2015 this was increased to 400 mL/min, which was within acceptable limits. The dialysate flow rate remained stable at; 500mlL/min. Blood samples were collected in March 2015 and 2016. The primary endpoint was the comparison of the amounts of erythropoiesis-stimulating agent (ESA) required.

Results: The increased BFR increased the Kt/V and contributed to significantly decreased urea nitrogen (UN) (p = 0.015) and creatinine (Cr) (p = 0.005) levels. The dialysis efficiency was improved by increasing the BFR. Ferritin (p = 0.038), hepcidin (p = 0.041) and high-sensitivity interleukin-6 (p = 0.038) levels were also significantly reduced. The ESA administered was significantly reduced (p = 0.004) and the Erythropoietin Resistant Index (ERI) significantly improved (p = 0.031). The reduction rates in UN (p < 0.001), Cr (p < 0.001), and beta-2 microglobulin (p = 0.017) levels were significantly greater post the BFR increase compared to those prior to the BFR increase. However, hepcidin was not affected by the BFR change.

Conclusions: Increasing BFR was associated with hemodialysis efficiency, and led to reduce inflammatory cytokine interleukin-6, but did not contribute to reduce C-reactive protein. This reduced hepcidin levels, ESA dosage and ERI. Hepcidin levels were significantly correlated with ferritin levels, and it remains to be seen whether reducing hepcidin leads to improve ESA and iron availability during anemia management.
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http://dx.doi.org/10.1186/s12882-021-02426-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8204539PMC
June 2021

Significance of liver resection for intermediate stage hepatocellular carcinoma according to subclassification.

BMC Cancer 2021 Jun 5;21(1):668. Epub 2021 Jun 5.

Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima City, Hiroshima, 734-8551, Japan.

Background: Patients diagnosed with Barcelona Clinic Liver Cancer (BCLC) intermediate stage hepatocellular carcinoma (HCC) encompass a broad clinical population. Kinki criteria subclassifications have been proposed to better predict prognoses and determine appropriate treatment strategies for these patients. This study validated the prognostic significance within the Kinki criteria substages and analyzed the role of liver resection in patients with intermediate stage HCC.

Methods: Patients with intermediate stage HCC (n = 378) were retrospectively subclassified according to the Kinki criteria (B1, n = 123; B2, n = 225; and B3, n = 30). We analyzed the overall survival (OS) and treatment methods.

Results: The OS was significantly different between adjacent substages. Patients in substage B1 who underwent liver resection had a significantly better prognosis than those who did not, even after propensity score matching (PSM). Patients in substage B2 who underwent liver resection had a significantly better prognosis than those who did not; however, there was no difference after PSM. There was no difference in prognosis based on treatments among patients in substage B3.

Conclusions: The Kinki criteria clearly stratify patients with intermediate stage HCC by prognosis. For substage B1 HCC patients, liver resection provides a better prognosis than other treatment modalities. In patients with substage B2 and B3, an alternative approach is required.
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http://dx.doi.org/10.1186/s12885-021-08421-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8180017PMC
June 2021

A multicenter randomized controlled trial comparing administration of antithrombin III after liver resection (HiSCO-05 trial).

Surgery 2021 Apr 26. Epub 2021 Apr 26.

Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan.

Background: Posthepatectomy liver failure is a poor prognostic factor after hepatectomy. Various preventive treatments have been tried; however, there are no clinical trials that use posthepatectomy liver failure as the primary endpoint, and the clinical effects of posthepatectomy liver failure have not been fully verified. The aim of this study was to investigate whether administration of antithrombin III can prevent posthepatectomy liver failure in patients with coagulopathy after hepatectomy. This study also evaluated the safety of AT-III administration after hepatectomy.

Methods: The current study enrolled 141 patients diagnosed with coagulopathy after hepatectomy between October 2015 and September 2018 at 7 hospitals in Hiroshima, Japan (HiSCO group). Patients were randomized to undergo either administration of antithrombin III (n = 64) or non-administration (n = 77). The primary endpoint was the incidence of posthepatectomy liver failure. This randomized controlled trial was registered with the University Medical Information Network Clinical Trial Registry (UMIN000018852).

Results: Treatment for postoperative coagulopathy was performed safely without adverse events. The incidence of posthepatectomy liver failure was similar in both treatment groups (nonadministration of antithrombin III group, 28.5%, versus administration of antithrombin III group, 28.1%; P = .953) The rate of morbidity was higher in the administration group than the non-administrated group (17.2% vs 11.7%, P = .351). Following the multivariate analysis of the whole study group, body mass index ≥25, total bilirubin ≥1.5 mg/dL, and the disseminated intravascular coagulation score ≥5 postoperatively were the independent risk factors for posthepatectomy liver failure.

Conclusion: This study showed that the administration of antithrombin III resulted in no significant difference in preventing posthepatectomy liver failure, possibly through suppressing coagulopathy.
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http://dx.doi.org/10.1016/j.surg.2021.03.057DOI Listing
April 2021

Long-term survival by repeat resection for metastases from primary retroperitoneal leiomyosarcoma: A case report.

Int J Surg Case Rep 2021 May 15;82:105891. Epub 2021 Apr 15.

Department of Surgery, Onomichi General Hospital, Onomichi, Hiroshima, Japan. Electronic address:

Backgound: Retroperitoneal (RP) leiomyosarcoma (LMS) is a rare type of cancer, accounting for 0.1% of all malignancies. The gold-standard treatment for sarcoma is complete resection, and a 50% 5-year overall survival (OS) rate can be achieved by curative surgery. The survival benefits of radiotherapy and systemic chemotherapy for recurrence are not as good as those of surgical resection. To the best of our knowledge, there are a few reports that aggressive radical surgery significantly prolonged the survival period as our case. This case was reported in accordance with the SCARE 2020 Guideline (Ref).

Case Presentation: An 84-year-old woman was referred to our hospital for treatment of a primary RP tumour. At the age of 52-year-old, she underwent complete resection of an RP mass in 1991. Twenty-four years after the primary resection, metachronous recurrences occurred within the soft tissues, which were repeatedly resected. From 2015-2019, liver resections were performed thrice, and the patient survived with no signs of recurrence 1 year after the last surgery.

Conclusion: Long-term survival of 29 years was achieved after undergoing over 20 surgical resections. Herein, we report the long-term survival of a patient who underwent repeated aggressive surgical resections for RP LMS recurrence anda literature review.
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http://dx.doi.org/10.1016/j.ijscr.2021.105891DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082084PMC
May 2021

Evaluation of renal tubulointerstitial damage as a residual renal risk factor for adverse cardiac events in patients with myocardial infarction.

J Cardiol 2021 Aug 5;78(2):114-119. Epub 2021 Apr 5.

Department of Internal Medicine II, Faculty of Medicine, University of Yamanashi, 1110 Shimokato, Chuo 409-3898, Yamanashi, Japan.

Background: Renal dysfunction, defined as a lower estimated glomerular filtration rate (eGFR), has been shown to be related to cardiovascular events in patients with myocardial infarction (MI). However, the contribution of renal tubulointerstitial damage to the predictive value for cardiovascular events has not been established. The aim of this study was to elucidate whether renal tubulointerstitial damage is associated with the occurrence of cardiac death and recurrence of MI in patients who have had MI.

Methods And Results: Urinary β2-microglobulin (β2MG) was measured in 681 consecutive patients with MI in our hospital. All patients were followed up for <12 years or until the occurrence of cardiac death and MI. During a median follow-up period of 6 years, the cumulative cardiac death rate was 5.4%, and the MI rate was 3.1%. When outcomes were divided into two groups according to the β2MG levels, cardiac death and MI rates were lower in patients with lower levels of β2MG (<0.319 mg/gCre: determined by receiver operating characteristic analyses) than in those with β2MG ≥0.319 mg/gCre (5.9% versus 17.1%, p<0.01). When outcomes were stratified according to the β2MG levels in combination with eGFR levels, Kaplan-Meier analyses showed that cardiac death and MI rates increased depending on an increase in the β2MG levels (p<0.05). Moreover, multivariate Cox analyses revealed that high levels of β2MG were a significant independent predictor of adverse events (hazard ratio: 1.956; 95% confidence interval: 1.014-3.774; p = 0.045). The addition of high levels of β2MG to conventional risk factors, including eGFR and urinary albumin, improved the net reclassification improvement (NRI) and integrated discrimination improvement (IDI) (NRI 0.5447, p = 0.0002; IDI 0.0126, p = 0.0454).

Conclusion: Renal tubulointerstitial damage, as assessed by urinary β2MG, is associated with the occurrence of cardiac death and recurrence of MI independent of renal glomerular function in patients with MI.
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http://dx.doi.org/10.1016/j.jjcc.2021.02.006DOI Listing
August 2021

Efficacy of upfront hepatectomy without neoadjuvant chemotherapy for resectable colorectal liver metastasis.

World J Surg Oncol 2021 Apr 5;19(1):97. Epub 2021 Apr 5.

Department of Surgery, Onomichi General Hospital, 1-10-23 Hirahara Onomichi, Hiroshima, 722-8508, Japan.

Background: Hepatectomy for resectable colorectal liver metastasis (CRLM) is recommended. However, the efficacy of upfront hepatectomy without neoadjuvant chemotherapy (NAC) is unclear due to the uncertainty of perioperative systemic chemotherapy. Moreover, it is crucial to predict the prognosis when considering perioperative chemotherapy. This study evaluated the impact of neoadjuvant chemotherapy on the prognosis of patients with resectable CRLM and assessed the usefulness of Beppu's nomogram for predicting prognosis.

Methods: This retrospective study identified 88 consecutive inpatients who underwent primary hepatic resection for CRLM; 58 received neoadjuvant chemotherapy and 30 underwent upfront surgery. Factors associated with recurrence-free survival were identified via univariate and multivariate analysis. Furthermore, propensity score analysis using inverse probability of treatment weighting (IPTW) was performed.

Results: On univariate analysis, poor recurrence-free survival was associated with multiple tumors, advanced primary tumor stage, vascular invasion by the primary tumor, a Beppu's nomogram score ≥ 6, and neoadjuvant chemotherapy. On multivariate analysis, a Beppu's nomogram score ≥ 6 and neoadjuvant chemotherapy were independent risk factors for recurrence. Neoadjuvant chemotherapy recipients had a higher incidence of lymph node metastasis and vascular invasion than non-recipients. Propensity score analysis revealed no significant difference in the recurrence-free survival rate between these groups.

Conclusions: Our results show that upfront hepatectomy without neoadjuvant chemotherapy can be considered for resectable CRLM treatment. Beppu's nomogram score can be a tool for predicting the prognosis of patients with CRLM.
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http://dx.doi.org/10.1186/s12957-021-02210-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8022388PMC
April 2021

Improved safety of induced pluripotent stem cell-derived antigen-presenting cell-based cancer immunotherapy.

Mol Ther Methods Clin Dev 2021 Jun 5;21:171-179. Epub 2021 Mar 5.

Division of Cancer Immunotherapy, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa 277-8577, Japan.

The tumorigenicity and toxicity of induced pluripotent stem cells (iPSCs) and their derivatives are major safety concerns in their clinical application. Recently, we developed granulocyte-macrophage colony-stimulating factor (GM-CSF)-producing proliferating myeloid cells (GM-pMCs) from mouse iPSCs as a source of unlimited antigen-presenting cells for use in cancer immunotherapy. As GM-pMCs are generated by introducing and into iPSC-derived MCs and are dependent on self-produced GM-CSF for proliferation, methods to control their proliferation after administration should be introduced to improve safety. In this study, we compared the efficacy of two promising suicide gene systems, herpes simplex virus-thymidine kinase (HSV-TK)/ganciclovir (GCV) and inducible caspase-9 (iCasp9)/AP1903, for safeguarding GM-pMCs in cancer immunotherapy. The expression of HSV-TK or iCasp9 did not impair the fundamental properties of GM-pMCs. Both of these suicide gene-expressing cells selectively underwent apoptosis after treatment with the corresponding apoptosis-inducing drug, and they were promptly eliminated . iCasp9/AP1903 induced apoptosis more efficiently than HSV-TK/GCV. Furthermore, high concentrations of GCV were toxic to cells not expressing HSV-TK, whereas AP1903 was bioinert. These results suggest that iCasp9/AP1903 is superior to HSV-TK/GCV in terms of both safety and efficacy when controlling the fate of GM-pMCs after priming antitumor immunity.
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http://dx.doi.org/10.1016/j.omtm.2021.03.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994724PMC
June 2021

Echolucency of carotid plaque is useful for selecting high-risk patients with chronic coronary artery disease who benefit from intensive lipid-lowering therapy.

J Cardiol 2021 Jun 23;77(6):590-598. Epub 2021 Jan 23.

Department of Internal Medicine II, University of Yamanashi, Faculty of Medicine, Chuo, Yamanashi, Japan. Electronic address:

Background: Ultrasound assessment of the carotid artery provides prognostic information on coronary events. This study examined whether ultrasound assessments of plaque echolucency of the carotid artery are useful for identifying patients with coronary artery disease (CAD) who are at high risk but could benefit from lipid-lowering therapy for secondary prevention.

Methods: Ultrasound assessment of carotid plaque echolucency with integrated backscatter (IBS) analysis was performed in 393 chronic CAD patients with low-density lipoprotein cholesterol (LDL-C) levels <100 mg/dL on statin therapy. All patients were prospectively followed up for a maximum of 96 months or until the occurrence of one of the following coronary events: cardiac death, nonfatal myocardial infarction, or unstable angina pectoris requiring unplanned revascularization.

Results: During the follow-up period, 45 coronary events occurred. Patients were stratified by IBS (≤-16.3 or >-16.3 dB, median value) and LDL-C level (<70 or 70-99 mg/dL). Multivariate Cox proportional hazards analysis showed that patients with lower IBS and LDL-C 70-99 mg/dL had significantly higher probabilities of coronary events compared with those with higher IBS and LDL-C <70 mg/dL, after adjustment for a baseline model of risk factors (hazard ratio 5.15; 95% confidence interval 1.21-22.0, p = 0.03). In contrast, patients with lower IBS and LDL-C <70 mg/dL had an improved prognosis comparable with those with higher IBS. Addition of LDL-C levels to the baseline model of risk factors improved net reclassification improvement (NRI) and integrated discrimination improvement (IDI) in patients with lower IBS (NRI, 0.44, p = 0.04; and IDI, 0.035, p < 0.01), but not in those with higher IBS.

Conclusions: Evaluation of echolucency of the carotid artery was useful for selecting CAD patients at high risk of secondary coronary events but who could benefit from lipid-lowering therapy.
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http://dx.doi.org/10.1016/j.jjcc.2021.01.002DOI Listing
June 2021

Generation of GM-CSF-producing antigen-presenting cells that induce a cytotoxic T cell-mediated antitumor response.

Oncoimmunology 2020 09 6;9(1):1814620. Epub 2020 Sep 6.

Division of Cancer Immunotherapy, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa, Japan.

Immunotherapy using dendritic cells (DCs) is a promising treatment modality for cancer. However, the limited number of functional DCs from peripheral blood has been linked to the unsatisfactory clinical efficacies of current DC-based cancer immunotherapies. We previously generated proliferating antigen-presenting cells (APCs) by genetically engineering myeloid cells derived from induced pluripotent stem cells (iPSC-pMCs), which offer infinite functional APCs for broad applications in cancer therapy. Herein, we aimed to further enhance the antitumor effect of these cells by genetic modification. GM-CSF gene transfer did not affect the morphology, or surface phenotype of the original iPSC-pMCs, however, it did impart good viability to iPSC-pMCs. The resultant cells induced GM-CSF-dependent CD8 T cell homeostatic proliferation, thereby enhancing antigen-specific T cell priming . Administration of the tumor antigen-loaded GM-CSF-producing iPSC-pMCs (GM-pMCs) efficiently stimulated antigen-specific T cells and promoted effector cell infiltration of the tumor tissues, leading to an augmented antitumor effect. To address the potential tumorigenicity of iPSC-derived products, irradiation was applied and found to restrict the proliferation of GM-pMCs, while retaining their T cell-stimulatory capacity. Furthermore, the irradiated cells exerted an antitumor effect equivalent to that of bone marrow-derived DCs obtained from immunocompetent mice. Additionally, combination with immune checkpoint inhibitors increased the infiltration of CD8 or NK1.1 effector cells and decreased CD11b/Gr-1 cells without causing adverse effects. Hence, although GM-pMCs have certain characteristics that differ from endogenous DCs, our findings suggest the applicability of these cells for broad clinical use and will provide an unlimited source of APCs with uniform quality.
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http://dx.doi.org/10.1080/2162402X.2020.1814620DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7781730PMC
September 2020

Induced hepatic stellate cell integrin, α8β1, enhances cellular contractility and TGFβ activity in liver fibrosis.

J Pathol 2021 04 19;253(4):366-373. Epub 2021 Feb 19.

Integrin-Matrix Biomedical Science, Translational Research Center, Hiroshima University, Hiroshima, Japan.

No effective therapy exists for fatal fibrosis. New therapeutic targets are needed for hepatic fibrosis because the incidence keeps increasing. The activation and differentiation of fibroblasts into myofibroblasts that causes excessive matrix deposition is central to fibrosis. Here, we investigated whether (and which) integrin receptors for matrix proteins activate hepatic stellate cells (HSCs). First, integrin α-subunits were investigated systematically for their expression over the course of HSC activation and their distribution on fibroblasts and other systemic primary cells. The most upregulated in plate culture-activated HSCs and specifically expressed across fibroblast linages was the α8 subunit. An anti-α8 neutralizing mAb was evaluated in three different murine fibrosis models: for cytotoxic (CCl treatment), non-alcoholic steatohepatitis-associated and cholestatic fibrosis. In all models, pathology and fibrosis markers (hydroxyproline and α-smooth muscle actin) were improved following the mAb injection. We also CCl -treated mice with inducible Itga8-/-; these mice were protected from increased hydroxyproline levels. Furthermore, ITGA8 was upregulated in specimens from 90 patients with liver fibrosis, indicating the relevance of our findings to liver fibrosis in people. Mechanistically, inhibition or ligand engagement of HSC α8 suppressed and enhanced myofibroblast differentiation, respectively, and HSC/fibroblast α8 activated latent TGFβ. Finally, integrin α8β1 potentially fulfils the growing need for anti-fibrotic drugs and is an integrin not to be ignored. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.
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http://dx.doi.org/10.1002/path.5618DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7986747PMC
April 2021

Improvement in Brachial Endothelial Vasomotor Function and Brachial-Ankle Pulse Wave Velocity Reduces the Residual Risk for Cardiovascular Events after Optimal Medical Treatment in Patients with Coronary Artery Disease.

J Atheroscler Thromb 2020 Nov 20. Epub 2020 Nov 20.

Department of Internal Medicine II, University of Yamanashi, Faculty of Medicine.

Aim: To examine whether improvement in flow-mediated endothelium-dependent dilatation (FMD) of the brachial artery and brachial-ankle pulse wave velocity (baPWV) has an additive effect on achieving optimal goals of traditional risk factors to reduce cardiovascular risk in patients with coronary artery disease (CAD).

Methods: We assessed 323 patients with CAD and impaired vascular function, defined as an impaired FMD of the brachial artery (<5.5%) and increased baPWV (>1,440 cm/sec). After FMD and baPWV measurements at 24 weeks of optimal medical treatment (OMT), the study patients were followed up for <60 months or until a composite of cardiac death, nonfatal myocardial infarction (MI), unstable angina, or ischemic stroke occurs.

Results: During the median follow-up period of 35 months, cardiovascular events occurred in 72 patients. Multivariate Cox hazards analysis showed that patients with an improvement in FMD and baPWV had the lowest probability of future cardiovascular events. In addition, the improvement in FMD and baPWV had a significant incremental effect on the predictive value of the achievement of optimal goals for blood pressure (BP), low-density lipoprotein cholesterol (LDL-C), and hemoglobin A1c (HbA1c) using net reclassification improvement (NRI) and integrated discrimination improvement (IDI).

Conclusions: The improvement in FMD and baPWV had additive effects on risk reduction of the achievement of the optimal goals of traditional risk factors in patients with CAD. Thus, serial measurements of FMD and baPWV may be useful for identifying CAD patients at residual risk for adverse cardiovascular events following OMT.
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http://dx.doi.org/10.5551/jat.57562DOI Listing
November 2020

Impact of persistent endothelial dysfunction in an infarct-related coronary artery on future major adverse cardiovascular event occurrence in STEMI survivors.

Heart Vessels 2021 Apr 16;36(4):472-482. Epub 2020 Nov 16.

Department of Internal Medicine II, Faculty of Medicine, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi, 409-3898, Japan.

Although coronary endothelial vasomotor dysfunction predicts future coronary events, few human studies have shown the relationship between persistent endothelial vasomotor dysfunction and major adverse cardiovascular events (MACE) using serial assessments in the same coronary artery. This study examined whether persistent endothelial vasomotor dysfunction is related to MACE occurrence in the infarct-related coronary artery (IRA) of ST-segment elevation myocardial infarction (STEMI) survivors using serial assessments of the coronary vasomotor response to acetylcholine (ACh). This study included 169 consecutive patients with a first acute STEMI due to left anterior descending coronary artery (LAD) occlusion and successful reperfusion therapy with percutaneous coronary intervention. Vasomotor response to ACh in the LAD was measured within 2 weeks of acute myocardial infarction (AMI) (first test) and repeated 6 months (second test) after AMI under optimal anti-atherosclerotic therapy. MACE was defined as the composite of all-cause death, non-fatal MI, angina recurrence requiring percutaneous intervention or surgical bypass, and hospitalization for heart failure. We followed up 126 patients for a period of ≤ 60 months until MACE occurrence after second test. Nineteen MACEs occurred during the follow-up. The log-rank test, Kaplan-Meier curves and univariate Cox proportional hazards regression analysis showed that MACE occurrence was significantly associated with the persistent impairment of epicardial coronary artery dilation and coronary blood flow increases in response to ACh (log-rank test, p < 0.001 and p < 0.001, respectively) (Hazard ratio, p = 0.001 and p = 0.002, respectively). Persistent impairment of endothelial vasomotor function in the infarct-related conduit arterial segment and resistance arteriole were the significant predictor of future MACE occurrence in STEMI survivors.
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http://dx.doi.org/10.1007/s00380-020-01723-9DOI Listing
April 2021

Generation of human induced pluripotent stem cell-derived liver buds with chemically defined and animal origin-free media.

Sci Rep 2020 10 21;10(1):17937. Epub 2020 Oct 21.

Division of Regenerative Medicine, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, 108-8639, Japan.

Advances in organoid technology have broadened the number of target diseases and conditions in which human induced pluripotent stem cell (iPSC)-based regenerative medicine can be applied; however, mass production of organoids and the development of chemically defined, animal origin-free (CD-AOF) media and supplements are unresolved issues that hamper the clinical applicability of these approaches. CD-AOF media and supplements ensure the quality and reproducibility of culture systems by lowering lot-to-lot variations and the risk of contamination with viruses or toxins. We previously generated liver organoids from iPSCs, namely iPSC-liver buds (iPSC-LBs), by mimicking the organogenic interactions among hepatocytes, endothelial cells (ECs), and mesenchymal cells (MCs) and recently reported the mass production of iPSC-LBs derived entirely from iPSCs (all iPSC-LBs), which should facilitate their large-scale production for the treatment of liver failure. However, in previous studies we used media originating from animals for differentiation except for the maintenance of undifferentiated iPSCs. Therefore, we developed a CD-AOF medium to generate all iPSC-LBs. We first developed a CD-AOF medium for hepatocytes, ECs, and stage-matched MCs, i.e., septum transversum mesenchyme (STM), in 2D cultures. We next generated all iPSC-LBs by incubating individual cell types in ultra-low attachment micro-dimple plates. The hepatic functions of all iPSC-LBs generated using the CD-AOF medium were equivalent to those of all iPSC-LBs generated using the conventional medium both in vitro and in vivo. Furthermore, we found that this CD-AOF medium could be used in several cell culture settings. Taken together, these results demonstrate the successful development of a CD-AOF medium suitable for all iPSC-LBs. The protocol developed in this study will facilitate the clinical applicability of all iPSC-LBs in the treatment of liver diseases.
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http://dx.doi.org/10.1038/s41598-020-73908-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7578079PMC
October 2020

Impact of low skeletal muscle mass index and perioperative blood transfusion on the prognosis for HCC following curative resection.

BMC Gastroenterol 2020 Oct 7;20(1):328. Epub 2020 Oct 7.

Department of Surgery, Onomichi General Hospital, 1-10-23 Hirahara, Onomichi, Hiroshima, Japan.

Background: This study aimed to assess the prognostic factors including low skeletal muscle mass index (SMI) and perioperative blood transfusion for patients with hepatocellular carcinoma (HCC) following curative surgery.

Methods: This study included 139 patients with HCC who underwent hepatectomy between 2005 and 2016. Univariate and multivariate analyses were performed to identify variables associated with overall survival (OS) and recurrence-free survival (RFS).

Results: Low SMI was significantly related with poor OS, while blood transfusion had a strong impact on RFS. The male ratio and body mass index in the low SMI group were significantly higher than those in the high SMI group. There were no significant differences in age, virus etiology, laboratory data, liver function, tumor makers, and operative variables between the groups. Tumor factors such as tumor diameter, tumor number, poor differentiation, and intrahepatic metastasis (IM) did not significantly differ between the two groups. Operation time, intraoperative blood loss volume, and recurrence ratio were significantly higher in the blood transfusion group than in the non-transfusion group. IM was associated with poor OS and RFS.

Conclusions: Low SMI and blood transfusion were independently related with long-term prognosis in patients with HCC following curative surgery.
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http://dx.doi.org/10.1186/s12876-020-01472-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7539410PMC
October 2020

Intrahepatic cholangiocarcinoma with clear cell type following laparoscopic curative surgery.

Surg Case Rep 2020 Oct 7;6(1):264. Epub 2020 Oct 7.

Department of Surgery, Onomichi General Hospital, 1-10-23, Hirahara, Onomichi, Hiroshima, 722-8508, Japan.

Background: Intrahepatic cholangiocarcinoma (ICC) is the second most common malignancy of primary liver cancer. Among the several pathological types of ICC, only five cases of the clear cell type have been reported, including the one presented below. Here we report a unique case of clear cell type ICC following laparoscopic hepatectomy.

Case Presentation: A 67-year-old woman had a history of hepatitis B virus. Computed tomography revealed a ring-like enhanced mass 35 mm in diameter at segment 7 in the early phase. The enhancement was prolonged to the late phase through the portal phase, while the shape was irregular. Ethoxybenzy magnetic resonance imaging revealed that the tumor had a low signal intensity on T1-weighted imaging and a high signal intensity on T2-weighted imaging. Diffusion-weighted images identified that the tumor had remarkably high signal intensity. Tumor enhancement was not detected throughout the tumor in the hepatocyte phase. Upon ICC diagnosis, a laparoscopic S7 subsegmentectomy was performed. The patient's postoperative course was uneventful. An immunohistochemical examination revealed that the cells tested positive for cytokeratin 7 (CK7), CK19, and CD56 and negative for CK20, CD10, α-fetoprotein, thyroid transcription factor-1. At 2 years after surgery, the patient remains alive without recurrence.

Conclusions: Here we presented a case of clear cell ICC that was treated by laparoscopic hepatectomy. Immunological analysis, especially by CD56 and several CK markers, is helpful for diagnosing this disease.
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http://dx.doi.org/10.1186/s40792-020-01041-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7539241PMC
October 2020

Efficacy of the physiobiological parameter-based grading system for predicting the long-term prognosis after curative surgery for resectable pancreatic cancer.

Eur J Surg Oncol 2021 03 16;47(3 Pt B):613-619. Epub 2020 Sep 16.

Department of Surgery, Onomichi General Hospital, Onomichi, Hiroshima, Japan; Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.

Background: Several prognostic scoring systems based on cancer-related inflammation have been developed. We aimed to evaluate the efficacy of a novel physiobiological parameter-based grading system (PGS) for predicting the long-term prognosis after curative-intent surgery for pancreatic ductal adenocarcinoma.

Methods: One-hundred fifty-nine consecutive patients with pancreatic ductal adenocarcinoma were enrolled. Univariate and multivariate analyses were performed to identify variables associated with overall survival and recurrence-free survival. Patients were stratified according to the PGS score with a cut-off value of 40.5 being estimated by receiver-operating characteristic curve analysis. Propensity score matching analysis (PSM) was performed to compare between patients with low and high scores in the physiobiological parameter-based grading system.

Results: Univariate analysis showed that CEA elevation (p = 0.032), tumor size ≥20 mm (p < 0.001), lymph node metastasis (p < 0.001), high-PGS (p < 0.001), CA19-9 elevation (p < 0.001), Prognostic nutritious index (PNI) ≤40 (p = 0.002) and positive Glasgow prognostic score (GPS) (p = 0.001) were risk factors for poor overall survival. CEA elevation (p = 0.006), Tumor size ≥20 mm (p < 0.001), lymph node metastasis (p < 0.001), high-PGS (p < 0.001), CA19-9 elevation (p < 0.001), PNI ≤40 (p = 0.017) and positive GPS (p < 0.001) were identified as risk factors for poor recurrence-free survival. The multivariate analysis revealed that tumor size ≥20 mm (p = 0.007, p = 0.008, respectively) and high PGS score (p = 0.041, p = 0.018, respectively) were independently associated with poor overall survival and recurrence-free survival. Patients with high-PGS showed a significantly worse long-term prognosis even after PSM.

Conclusion: The PGS is a novel nomogram that could effectively predict long-term outcomes following curative surgery in patients with pancreatic ductal adenocarcinoma.
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http://dx.doi.org/10.1016/j.ejso.2020.09.008DOI Listing
March 2021

Impact on biliary complications of donor abdominal aortic calcification among living donor liver transplantation: a retrospective study.

Transpl Int 2020 12 21;33(12):1745-1753. Epub 2020 Oct 21.

Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.

Abdominal aortic calcification (AAC) was reported as a poor prognostic factor among liver transplantation. However, donor AAC is not enough discussed. We analyzed the impact of the donor AAC level on graft function on outcomes following living donor liver transplantation (LDLT). A total of 133 consecutive patients who had undergone LDLT were divided into two groups (non-AAC group and AAC group) according to their donor AAC level by plain computed tomography. The rate of postoperative biliary complications (BC) was significantly higher in AAC group (N = 17) than in non-AAC group (N = 116; HR, 2.77; 95% CI, 1.32-5.83; P = 0.0008). The Cox proportional hazards regression model revealed that donor AAC (HR, 4.15; 95% CI, 1.93-8.97; P = 0.0003) and right lobe graft (HR, 2.81; 95% CI, 1.41-5.61; P = 0.003) increased the risk of BC. Conversely, splenectomy (HR, 0.39; 95% CI, 0.16-0.92; P = 0.03) decreased the risk of BC after LDLT independently. The long-term survival was also significantly worse in AAC group than in non-AAC group (HR, 2.25; 95% CI, 1.04-4.89; P = 0.04). Donor AAC was an independent prognostic factor for BC among patients undergoing LDLT. Although further investigations are needed to verify our results, the levels of donor AAC could be a useful tool to identify the risks of BC and predict better outcomes following LDLT.
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http://dx.doi.org/10.1111/tri.13748DOI Listing
December 2020

Antithrombin attenuates the progression of hepatocellular carcinoma by regulating neutrophil/interleukin-8 signaling.

Hepatol Res 2020 Nov 7;50(11):1284-1296. Epub 2020 Sep 7.

Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Kasumi, Hiroshima, Japan.

Aim: Inflammation plays an important role in hepatocellular carcinoma (HCC) progression. Here, we examined whether antithrombin (AT) plays a role in attenuating HCC progression, via its anti-inflammatory effects.

Methods: HCCs were developed in AT-insufficient (AT ) mice and wild-type (AT ) mice treated with diethyl nitrosamine and carbon tetrachloride. AT was administered to AT mice. The development of HCC was compared between the three groups. In vitro study, migration assay was performed. The association of the prognosis of patients with HCC and plasma AT values was clinically examined.

Results: AT suppressed the release of interleukin (IL)-8 from lipopolysaccharide (LPS)-stimulated human neutrophils in vitro. Huh-7 cells that were co-cultured with neutrophils and stimulated with LPS showed significantly enhanced migration; however, Huh-7 cells co-cultured with LPS/AT-stimulated neutrophils showed significantly decreased migration. Moreover, the addition of anti-IL-8 antibodies to LPS-stimulated Huh-7 cells co-cultured with neutrophils also suppressed migration. AT mice (AT plasma activity: 64%) promoted liver cancer, as compared with wild-type mice (AT plasma activity: 135%); AT administration attenuated liver cancer in AT mice. Patients with HCC with a preoperative AT level of ≥70% showed better outcomes after liver resection, as compared with those with an AT level of <70%. IL-8 expression and neutrophil infiltration in HCC tissues were negatively correlated with the AT level.

Conclusions: AT attenuates HCC progression by regulating neutrophil/IL-8 signaling.
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http://dx.doi.org/10.1111/hepr.13558DOI Listing
November 2020

De novo hepatocellular carcinoma in living donor liver grafts: A Japanese multicenter experience.

Hepatol Res 2020 Dec 27;50(12):1365-1374. Epub 2020 Sep 27.

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

Aim: Direct-acting antivirals for hepatitis C virus have reduced the decompensation risk. Immunosuppressants for transplantation raise the risk of occurrence of de novo malignancies. We assessed the probabilities of and risk factors for de novo hepatocellular carcinoma (HCC) development post-living donor liver transplantation (LDLT).

Methods: We retrospectively evaluated the data of developed HCC in a graft including metastatic HCC post-LDLT from 2779 adult cases collected from nine major liver transplantation centers in Japan.

Results: Of 2779 LDLT adult recipients, 34 (1.2%) developed HCCs in their grafts. Of 34, five HCCs appeared to be de novo because of a longer period to tumor detection (9.7 [6.4-15.4] years) and no HCC within the native liver of the two recipients. The donor origin of three of five de novo HCCs was confirmed using microsatellite analysis in resected tissue. Primary disease of all five was hepatitis C virus-related cirrhosis, of which two were treated with direct-acting antivirals. Four of five developed HCC de novo in the hepatitis B core antibody-positive grafts. De novo HCCs had favorable prognosis; four of five were cured with complete remission. However, recurrent HCC (n = 29) in the graft had a poorer outcome, especially in patients with neutrophil to lymphocyte ratio scores above 4 (median survival time, 262 [19-463] days).

Conclusion: Analysis of the database from major liver transplantation institutes in Japan revealed that de novo HCCs determined by microsatellite analysis were rarely detected, but the majority were successfully treated. LDLT recipients with higher risks of de novo HCC, including those with hepatitis B core antibody-positive grafts, should be carefully followed by surveillance of the liver graft.
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http://dx.doi.org/10.1111/hepr.13565DOI Listing
December 2020

Preoperative anthropomorphic and nutritious status and fistula risk score for predicting clinically relevant postoperative pancreatic fistula after pancreaticoduodenectomy.

BMC Gastroenterol 2020 Aug 8;20(1):264. Epub 2020 Aug 8.

Department of Surgery, Onomichi General Hospital, 1-10-23, Onomichi, Hiroshima, 722-8508, Japan.

Background: Postoperative pancreatic fistula (POPF) is a life-threatening postoperative complication. The aim of this study was to evaluate the efficacy of the fistula risk score (FRS) and preoperative body composition factors for predicting the occurrence of clinically relevant POPF (CR-POPF) after pancreaticoduodenectomy (PD).

Methods: In this study, 136 consecutive patients who underwent PD between 2006 and 2018 were enrolled. The risk factors of CR-POPF (grades B and C) were analyzed. Preoperative visceral adipose tissue area (VATA), skeletal mass index (SMI), and subcutaneous adipose tissue area (SATA) were calculated from computed tomography data.

Results: The overall 30-day mortality and morbidity rates were 0.7 and 38%, respectively. The incidence rates of grade B and C CR-POPF were 27 and 4%, respectively. A univariate analysis revealed that male sex, habitual smoking, prognostic nutritional index (PNI) < 45, VATA ≥90, VATA/SATA ≥0.9, VATA/SMI ≥ 1.4, and FRS > 4 were significantly associated with the incidence of CR-POPF. A multivariate analysis revealed that PNI < 45, VATA/SMI ≥ 1.4 and FRS > 4 were the independent risk factors of CR-POPF.

Conclusions: Preoperative anthropomorphic imbalance, PNI, and FRS were independent risk factors for CR-POPF. Patients with high-risk factors should be closely monitored during the postoperative period.
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http://dx.doi.org/10.1186/s12876-020-01397-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7414683PMC
August 2020

Obliteration of a Portosystemic Shunt by Hybrid Interventional Radiology Using a Transmesenteric Approach Under Minilaparotomy After Liver Transplantation: A Case Report.

Transplant Proc 2020 Nov 16;52(9):2762-2766. Epub 2020 Jul 16.

Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.

Hepatic encephalopathy that occurs long after liver transplantation (LT) is an uncommon condition. Here, we describe the successful case of a 65-year-old patient who underwent interventional radiology (IVR) using a transmesenteric approach under minilaparotomy for hepatic encephalopathy because of a portosystemic shunt 11 years after ABO-incompatible living donor LT with splenectomy. Enhanced computed tomography confirmed a huge portosystemic shunt and left gastric vein (LGV)-esophageal-azygos vein, which was not treated during LT. Liver stiffness measurements based on transient elastography did not show severe fibrosis in the liver graft. Since the hyperammonemia could not be managed with conventional medical treatment, balloon-occluded retrograde transvenous obliteration (BRTO) was indicated. However, it was difficult to perform because the drainage vein could not be approached from the inferior vena cava (IVC). Surgical shunt ligation was also difficult because of the history of multiple laparotomies. Although intraperitoneal adhesion was severe, the portosystemic shunt was successfully embolized with metallic coils and a plug by IVR using a transmesenteric approach under minilaparotomy. No complications occurred during the operation. His symptoms improved after the operation. The ammonia level and portal flow by ultrasound also improved. He was discharged 14 days after surgery without any complications.
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http://dx.doi.org/10.1016/j.transproceed.2020.06.014DOI Listing
November 2020

Identification of risk factors for open conversion from laparoscopic cholecystectomy for acute cholecystitis based on computed tomography findings.

Surg Today 2020 Dec 5;50(12):1657-1663. Epub 2020 Jul 5.

Department of Surgery, Onomichi General Hospital, 1-10-23 Hirahara, Onomichi, Hiroshima, Japan.

Purpose: Laparoscopic cholecystectomy (LC) is performed widely for acute cholecystitis (AC). This study was conducted to identify the predictors for conversion cholecystectomy (CC) for AC.

Methods: The subjects of this study were 395 patients who underwent emergency surgery for AC between 2011 and 2019. Univariate and multivariate analyses were performed to establish the significance of the risk factors for CC in patients with grades II and III AC.

Results: There were 162 TG18 GII and GIII patients in the LC group and 31 in the CC group. Univariate analysis revealed significant differences in performance status (p = 0.039), C-reactive protein levels (p = 0.016), albumin levels (p = 0.002), gallbladder (GB) wall thickness (p = 0.045), poor contrast of the GB wall (p = 0.035), severe inflammation around the GB (p < 0.001), enhancement of the liver bed (p = 0.048), and duodenal edema (p < 0.001) between the groups. Multivariate analysis identified hypoalbuminemia (p = 0.043) and duodenal edema (p = 0.014) as independent risk factors for CC.

Conclusions: Most patients with grade I AC underwent LC and had better surgical outcomes than those with grades II and III AC. The most appropriate surgical procedure should be selected based on preoperative imaging of the GB and the neighboring organs and by the presence of hypoalbuminemia.
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http://dx.doi.org/10.1007/s00595-020-02069-5DOI Listing
December 2020

PD1 gene polymorphism is associated with a poor prognosis in hepatocellular carcinoma following liver resection, cohort study.

Int J Surg 2020 Aug 29;80:84-90. Epub 2020 Jun 29.

Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan; Research Center for Hepatology and Gastroenterology, Hiroshima University, Hiroshima, Japan.

Background: This study examined whether single nucleotide polymorphism (SNP) in programmed cell death protein (PD)-1 is related to the postoperative prognosis of patients with hepatocellular carcinoma (HCC). The immune checkpoint protein PD-1 is an important inhibitor of T cell responses. SNP in the promoter region of PD-1 -606 G/A has been reported to result in high activation and expression of PD-1 associated with cancer risk.

Materials And Methods: We analyzed 321 patients with HCC who underwent hepatectomy between 2010 and 2015. PD-1 SNP was analyzed by polymerase chain reaction, and the prognosis after surgical treatment of patients with HCC was analyzed.

Results: The PD-1 SNP statuses were as follows: 90 AA (28.1%), 163 GA (50.8%), 68 GG (21.2%). The baseline parameters did not statistically differ between the three groups. The overall survival (OS) of patients with the GG genotype was significantly lower than that of those with the other genotypes (P = 0.031). The GG genotype was an independent risk factor for OS (P = 0.009; HR 2.201). There was no significant difference between the GG genotype and other genotypes in recurrent-free survival. The extrahepatic recurrence (EHR) rate of those with the GG genotype was significantly higher than that of those with the other genotypes (P = 0.036). The GG genotype was an independent risk factor for EHR (P = 0.008; HR 2.037).

Conclusions: The PD-1 SNP GG genotype is associated with poor survival and increased EHR in HCC. Furthermore, the GG genotype is an independent predictive factor for OS and EHR.
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http://dx.doi.org/10.1016/j.ijsu.2020.05.007DOI Listing
August 2020

A novel model for predicting posthepatectomy liver failure based on liver function and degree of liver resection in patients with hepatocellular carcinoma.

HPB (Oxford) 2021 Jan 18;23(1):134-143. Epub 2020 Jun 18.

Department of Gastroenterological and Transplant Surgery, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, Japan.

Background: The permissible liver resection rate for preventing posthepatectomy liver failure (PHLF) remains unclear. We aimed to develop a novel PHLF-predicting model and to strategize hepatectomy for hepatocellular carcinoma (HCC).

Methods: This retrospective study included 335 HCC patients who underwent anatomical hepatectomy at eight institutions between 2013 and 2017. Risk factors, including volume-associated liver-estimating parameters, for PHLF grade B-C were analyzed in a training set (n = 122) via multivariate analysis, and a PHLF prediction model was developed. The utility of the model was evaluated in a validation set (n = 213).

Results: Our model was based on the three independent risk factors for PHLF identified in the training set: volume-associated indocyanine green retention rate at 15 min, platelet count, and prothrombin time index (the VIPP score). The areas under the receiver operating characteristic curve of the VIPP scores for severe PHLF in the training and validation sets were 0.864 and 0.794, respectively. In both sets, the VIPP score stratified patients at risk for severe PHLF, with a score of 3 (specificity, 0.92) indicating higher risk.

Conclusion: Our model facilitates the selection of the appropriate hepatectomy procedure by providing permissible liver resection rates based on VIPP scores.
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http://dx.doi.org/10.1016/j.hpb.2020.05.008DOI Listing
January 2021

Treatment outcomes after splenectomy with gastric devascularization or balloon-occluded retrograde transvenous obliteration for gastric varices: a propensity score-weighted analysis from a single institution.

J Gastroenterol 2020 Sep 12;55(9):877-887. Epub 2020 Jun 12.

Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.

Background: Although balloon-occluded retrograde transvenous obliteration (BRTO) is often selected to treat gastric varices caused by portal hypertension, data comparing BRTO and splenectomy with gastric devascularization (Sp + Dev) are limited.

Methods: From January 2009 to February 2018, 100 patients with gastric varices caused by portal hypertension who underwent Sp + Dev (n = 45) or BRTO (n = 55) were included. Overall survival (OS) and the rebleeding rate were calculated using the inverse probability of a treatment weighting-adjusted log-rank test. Independent risk factors were identified by Cox regression analysis. Changes in liver function and adverse events after the procedures were analyzed.

Results: Patients in the Sp + Dev group tended to have lower platelet counts than those in the BRTO group, but liver function did not differ between these groups. The 5-year OS rates for the Sp + Dev and BRTO groups were 73.4 and 50.0% (p = 0.005), respectively. There were no significant differences in rebleeding rates between the two groups. Multivariate analysis showed that serum albumin level ≤3.6 g/dL, prothrombin time% activity (PT%) ≤80%, and serum creatinine level ≥0.84 mg/dL were poor prognostic factors. Although the Sp + Dev group had more short-term complications after procedures, Sp + Dev tended to be more effective in improving liver function than BRTO.

Conclusions: Sp + Dev showed better OS and improvement of liver function compared with BRTO for the treatment of gastric varices caused by portal hypertension.
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http://dx.doi.org/10.1007/s00535-020-01693-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7289714PMC
September 2020
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