Publications by authors named "Masahiro Ohira"

120 Publications

Treatment of multiple huge liver cysts in a hybrid operating room: a case report.

Surg Case Rep 2021 Oct 29;7(1):232. Epub 2021 Oct 29.

Department of Gastroenterological Surgery, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.

Background: Liver cysts are common, with most cases being asymptomatic. In symptomatic cases, the disease is amenable to treatment. However, huge or multiple liver cysts with vascular narrowing and associated systemic symptoms are extremely rare. Furthermore, the performance of a reliable and effective surgery in such cases remains a major problem. Here, we report a case of multiple giant liver cysts with impaired blood flow surgically treated in a hybrid operating room.

Case Presentation: A 73-year-old male presented to a previous doctor with leg edema and dyspnea on exertion; computed tomography revealed that the cause complaint was right lung and heart compression and inferior vena cava (IVC) stenosis due to huge liver cysts in the caudal lobe. The patient was referred to our hospital because of disease recurrence despite percutaneous aspiration of the cyst. Multiple liver cysts were observed in addition to the drained cysts, two of which were located on both sides of the IVC and caused IVC stenosis. We performed open surgery for the liver cysts and used the hybrid operating room for intraoperative IVC angiography and measuring the hepatic vein and portal vein (PV) pressure. We performed unroofing of the hepatic cyst and cauterization of the cyst wall on the hepatic side. Angiography was performed before and after unroofing of the liver cysts, and IVC stenosis release was confirmed. IVC pressure measured at the peripheral side of the stenosis and PV pressures were continuously measured during surgery and were confirmed to have decreased during the opening of the liver cysts. The patient had a good postoperative course and was discharged on the 10th postoperative day. No recurrence was observed 6 months postoperatively.

Conclusions: Cyst unroofing surgery using angiography in a hybrid operating room is a useful treatment for deep hepatic lesions in that vascular stenosis improvement can be intraoperatively confirmed. Moreover, in cases wherein the cyst compresses the vasculature, intraoperative monitoring of IVC and PV pressures can be used to prove that the liver cyst is hemodynamically involved.
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http://dx.doi.org/10.1186/s40792-021-01320-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8556466PMC
October 2021

Rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone therapy increases carotid intima-media thickness and plaque score with von Willebrand factor activity elevation in patients with malignant lymphoma.

J Chemother 2021 Oct 18:1-6. Epub 2021 Oct 18.

Center for Diabetes, Metabolism and Endocrinology, Toho University Medical Center Sakura Hospital, Chiba, Japan.

An increased risk for atherosclerosis has been noted in cancer survivors; however, studies that focus on the risk of atherosclerosis in patients treated with chemotherapy are scarce. Therefore, we evaluated 32 patients who received rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) therapy for B-cell malignant lymphoma by analysing the changes in atherosclerosis. Just before each treatment course, plasma levels of von Willebrand Factor (vWF) activity were evaluated, and carotid ultrasonography was performed at baseline and after the final treatment. Throughout the follow-up period, plasma vWF levels showed significantly transient increased by approximately 20%-40%. Both mean carotid intima-media thickness (IMT) and plaque score (PS) significantly increased during the 36.6 ± 26.0 weeks of observation (mean IMT: 0.724 ± 0.118 to 0.767 ± 0.129 mm; PS: 4.31 ± 3.53 to 4.87 ± 3.88,  < 0.001). Our study suggests that R-CHOP therapy promotes atherosclerosis.
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http://dx.doi.org/10.1080/1120009X.2021.1988202DOI Listing
October 2021

Effect of Conventional Medical Therapy or Laparoscopic Sleeve Gastrectomy on Urinary Albumin in Japanese Subjects with Severe Obesity: An Observational Study.

Obes Facts 2021 Oct 14:1-9. Epub 2021 Oct 14.

Center of Diabetes, Endocrinology and Metabolism, Toho University Sakura Medical Center, Sakura-shi, Japan.

Introduction: In patients with severe obesity, albuminuria can be improved by both conventional medical therapy and bariatric surgery. The purpose of this study was to compare the impact of weight loss achieved through conventional medical therapy or laparoscopic sleeve gastrectomy (LSG) on albuminuria in Japanese subjects with severe obesity and identify the factors involved.

Methods: We retrospectively evaluated the clinical characteristics including the urinary albumin/creatinine ratio (UACR) of 340 consecutive subjects with a body mass index ≥35 who received LSG (n = 242) or medical therapy (n = 98) between 2010 and 2018 and were followed for at least 12 months.

Results: The baseline of the UACR was not different between the 2 groups. At the 12-month follow-up, total weight loss (TWL) and decreases in glycosylated hemoglobin (HbA1c) and loge UACR were greater in the LSG group than in the medical therapy group (body weight; -35.7 kg vs. -8.0 kg, p < 0.001, HbA1c; -1.4% vs. -0.7%, p < 0.001, loge UACR; -0.3 vs. 0.9, p < 0.001). The rate of complete remission of diabetes was significantly higher in the LSG group than in the medical therapy group. At 12 and 36 months (n = 111 in the medical therapy group, n = 56 in the LSG group at 36 months), loge UACR increased in the medical therapy group, while it remained unchanged or decreased in the LSG group. In subjects with microalbuminuria and macroalbuminuria, changes in the loge UACR correlated with percent total body weight loss (%TWL) in both groups at 12 months. Percent TWL contributed independently to the change in the loge UACR, irrespective of whether LSG was performed. In receiver-operating characteristic analysis, a weight loss of 7.8% predicted a decrease in the UACR (∆UACR <0 at 12 months).

Conclusion: Our analysis suggests that albuminuria may increase over time if only medical therapy is continued. To improve albuminuria, weight loss may be more important than whether LSG is performed.
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http://dx.doi.org/10.1159/000519156DOI Listing
October 2021

The Relationship between Serum Insulin-Like Growth Factor-1 Levels and Body Composition Changes after Sleeve Gastrectomy.

Obes Facts 2021 Oct 14:1-9. Epub 2021 Oct 14.

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

Introduction: We previously reported that preoperative serum insulin-like growth factor-1 (IGF-1) is a predictor of total weight loss percentage (%TWL) after laparoscopic sleeve gastrectomy (LSG). IGF-1 may suppress muscle loss after surgery. IGF-1 almost accurately reflects the growth hormone (GH) secretion status, and GH has lipolytic effects. Therefore, IGF-1 may influence both the maintenance of skeletal muscle and the reduction of adipose tissue after LSG. The identification of the relationship between preoperative serum IGF-1 and body composition changes after LSG can help in understanding the pathophysiology of obesity.

Methods: We retrospectively reviewed 72 patients with obesity who underwent LSG and were followed up for 12 months. We analyzed the relationship between preoperative serum IGF-1 levels and body composition changes after LSG. A multiple regression model was used.

Results: LSG led to a significant reduction in body weight. Both body fat mass and skeletal muscle mass decreased after LSG. Preoperative serum IGF-1 levels significantly correlated with %TWL, changes in skeletal muscle mass, and body fat mass after LSG. The multiple regression model showed that preoperative serum IGF-1 levels were related to decreased body fat mass and maintaining skeletal muscle mass after LSG.

Discussion/conclusion: Preoperative IGF-1 measurement helps predict not only successful weight loss but also decreases body fat mass and maintains skeletal muscle mass after LSG.
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http://dx.doi.org/10.1159/000519610DOI Listing
October 2021

Decreased Triglyceride and Increased Serum Lipoprotein Lipase Levels Are Correlated to Increased High-Density Lipoprotein-Cholesterol Levels after Laparoscopic Sleeve Gastrectomy.

Obes Facts 2021 Oct 11:1-8. Epub 2021 Oct 11.

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

Introduction: Laparoscopic sleeve gastrectomy (LSG) significantly increases high-density lipoprotein cholesterol (HDL-C) and lipoprotein lipase (LPL) in pre-heparin serum (pre-heparin LPL levels). LPL is a regulator of serum triglyceride (TG) and HDL-C production; this may be the mechanism for HDL-C increase after LSG. This study aimed to elucidate the mechanism of increase in HDL-C levels by examining the relationship between changes in serum HDL-C levels and LPL after LSG.

Methods: We retrospectively reviewed 104 obese patients, who underwent LSG and were followed up for 12 months. We analyzed the relationship between changes in serum HDL-C levels and various clinical parameters after LSG.

Results: A significant decrease was observed in the patients' BMI and serum TG levels after LSG. Conversely, HDL-C levels and pre-heparin LPL levels were significantly increased after LSG. Simple linear regression showed that changes in HDL-C levels were significantly correlated with total weight loss percentage, change in TG levels, abdominal fat areas, and pre-heparin LPL levels. Additionally, the multiple regression model revealed that a decrease in TG levels and an increase in pre-heparin LPL levels were correlated with increased HDL-C levels after LSG.

Discussion/conclusion: These results show that a decrease in TG levels and an increase in LPL are mechanisms for increased HDL-C levels after LSG.
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http://dx.doi.org/10.1159/000519410DOI Listing
October 2021

Association of Plasma Xanthine Oxidoreductase with Arterial Stiffness in Type 2 Diabetes with Liver Dysfunction.

Am J Med Sci 2021 Oct 4. Epub 2021 Oct 4.

Center for Diabetes, Endocrine and Metabolism, Toho University Sakura Medical Center, Chiba, Japan; Chiba Prefectural University of Health Sciences, Chiba, Japan. Electronic address:

Background: Type 2 diabetes is a risk factor for atherosclerosis. Oxidative stress, which is a causative factor in insulin resistance, leads to atherosclerosis in patients with diabetes. Xanthine oxidoreductase (XOR) is an enzyme that catalyzes the oxidation of hypoxanthine to xanthine and xanthine to uric acid and is related to oxidative stress. We aimed to examine the influence of plasma XOR activity on arterial stiffness in patients with type 2 diabetes.

Methods: In total, 458 patients with type 2 diabetes not receiving antihyperuricemic agents were enrolled and their clinical parameters including plasma XOR activity and the cardio-ankle vascular index (CAVI) were measured. Patients were divided into the liver dysfunction and absence of liver dysfunction groups. Multiple regression analysis was performed.

Results: The median plasma XOR activity level was 64.3 pmol/h/mL (33.3-147.3 pmol/h/mL). Plasma XOR activity was correlated significantly and positively with aspartate transaminase and alanine transaminase (ρ > 0.5). The level of plasma XOR activity in the liver dysfunction group was eight-fold higher than that in the absence of liver dysfunction group. A significant positive correlation was observed between plasma XOR activity and the CAVI only in the liver dysfunction group (ρ = 0.3968, P < 0.0043). Multiple regression models demonstrated that plasma XOR activity was an independent predictor of the CAVI in the liver dysfunction group (P = 0.0055).

Conclusions: Our results suggest that plasma XOR activity is associated with arterial stiffness and may have a role in atherosclerosis development in patients with type 2 diabetes and liver dysfunction.
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http://dx.doi.org/10.1016/j.amjms.2021.09.011DOI Listing
October 2021

Determinants of type 2 diabetes remission after bariatric surgery in obese Japanese patients: a retrospective cohort study.

Diabetol Int 2021 Oct 28;12(4):379-388. Epub 2021 Jan 28.

Center for Diabetes, Endocrine and Metabolism, Toho University Sakura Medical Center, 564-1 Shimoshizu, Sakura, Chiba 285-0841 Japan.

Objective: Bariatric surgery (BS) improves glycemic control in type 2 diabetes; however, some patients show insufficient improvement. Understanding the pathophysiology of type 2 diabetes in obese patients can facilitate appropriate treatment for type 2 diabetes after BS. The homeostatic model assessment (HOMA) 2 enables the calculation of the values from C-peptide data and evaluation of insulin users. We aimed to evaluate the pathophysiology of type 2 diabetes using pre- and postoperative parameters and HOMA2 in obese patients who underwent BS.

Methods: We retrospectively reviewed data from 45 obese patients with type 2 diabetes who underwent BS. They were followed-up for 12 months. The relationship between the HOMA2 score and complete remission (CR) of type 2 diabetes after BS was analyzed. Patients with and without CR were assigned to the CR and non-CR groups, respectively. Multiple regression analysis was used to identify factors associated with improvement in type 2 diabetes after BS.

Results: BS significantly improved body weight and glucose metabolism. The preoperative glycosylated hemoglobin A1c level and insulin secretion (HOMA2-%B) significantly differed between the CR and non-CR groups. Postoperative weight reduction and improved insulin sensitivity correlated significantly with CR; multiple regression showed that the preoperative HOMA 2-%B independently predicted CR of type 2 diabetes after BS.

Conclusion: Preoperative insulin secretion, improvement in insulin sensitivity, and weight reduction after BS are related to CR of type 2 diabetes after BS. The results better reveal the pathophysiology of and treatment for type 2 diabetes in obese patients who undergo BS.
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http://dx.doi.org/10.1007/s13340-021-00493-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8413414PMC
October 2021

B cell depletion with anti-CD20 mAb exacerbates anti-donor CD4 T cell responses in highly sensitized transplant recipients.

Sci Rep 2021 09 13;11(1):18180. Epub 2021 Sep 13.

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.

Pretransplant desensitization with rituximab has been applied to preformed donor-specific anti-human leukocyte antigen antibody (DSA)-positive recipients for elimination of preformed DSA. We investigated the impact of pretransplant desensitization with rituximab on anti-donor T cell responses in DSA-positive transplant recipients. To monitor the patients' immune status, mixed lymphocyte reaction (MLR) assays were performed before and after desensitization with rituximab. Two weeks after rituximab administration, the stimulation index (SI) of anti-donor CD4 T cells was significantly higher in the DSA-positive recipients than in the DSA-negative recipients. To investigate the mechanisms of anti-donor hyper responses of CD4 T cells after B cell depletion, highly sensitized mice models were injected with anti-CD20 mAb to eliminate B cells. Consistent with clinical observations, the SI values of anti-donor CD4 T cells were significantly increased after anti-CD20 mAb injection in the sensitized mice models. Adding B cells isolated from untreated sensitized mice to MLR significantly inhibited the enhancement of anti-donor CD4 T cell response. The depletion of the CD5 B cell subset, which exclusively included IL-10-positive cells, from the additive B cells abrogated such inhibitory effects. These findings demonstrate that IL-10 CD5 B cells suppress the excessive response of anti-donor CD4 T cells responses in sensitized recipients.
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http://dx.doi.org/10.1038/s41598-021-97748-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8437972PMC
September 2021

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

Alternative microexon splicing by RBFOX2 and PTBP1 is associated with metastasis in colorectal cancer.

Int J Cancer 2021 11 16;149(10):1787-1800. Epub 2021 Aug 16.

Department of Cell Proliferation, ART, Graduate School of Medicine, Tohoku University, Sendai, Japan.

The splicing of microexons (very small exons) is frequently dysregulated in the brain of individuals with autism spectrum disorder. However, little is known of the patterns, regulatory mechanisms and roles of microexon splicing in cancer. We here examined the transcriptome-wide profile of microexon splicing in matched colorectal cancer (CRC) and normal tissue specimens. Out of 1492 microexons comprising 3 to 15 nucleotides, 21 (1%) manifested differential splicing between CRC and normal tissue. The 21 genes harboring the differentially spliced microexons were enriched in gene ontology terms related to cell adhesion and migration. RNA interference-mediated knockdown experiments identified two splicing factors, RBFOX2 and PTBP1, as regulators of microexon splicing in CRC cells. RBFOX2 and PTBP1 were found to directly bind to microexon-containing pre-mRNAs and to control their splicing in such cells. Differential microexon splicing was shown to be due, at least in part, to altered expression of RBFOX2 and PTBP1 in CRC tissue compared to matched normal tissue. Finally, we found that changes in the pattern of microexon splicing were associated with CRC metastasis. Our data thus suggest that altered expression of RBFOX2 and PTBP1 might influence CRC metastasis through the regulation of microexon splicing.
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http://dx.doi.org/10.1002/ijc.33758DOI Listing
November 2021

High presepsin concentrations in bile and its marked elevation in biliary tract diseases: A retrospective analysis.

Clin Chim Acta 2021 Oct 29;521:278-284. Epub 2021 Jul 29.

Department of Hematology, Toho University Sakura Medical Center, 2858741 Chiba, Japan. Electronic address:

Background: Presepsin is a diagnostic and prognostic biomarker of both bacterial infection and sepsis; however, elevated presepsin levels have also been observed without sepsis. We conducted several analyses to evaluate the clinical laboratory parameters affecting presepsin levels.

Method: We analyzed the association between sequential organ failure assessment (SOFA) scores and plasma presepsin levels and then analyzed clinical laboratory parameters in 567 patients with univariate and multivariate regression analysis and analysis of covariance (ANCOVA). We also determined presepsin in the bile of 11 patients and examined the presepsin immunostaining in liver.

Results: Spearman's rank correlation analysis with log change revealed that presepsin levels were closely associated with log-transformed SOFA score (ρ = 0.541), alkaline phosphatase (ALP); (ρ = 0.454) and gamma-glutamyl transferase; (ρ = 0.505). Multivariate regression analysis revealed that log-transformed SOFA score (β-coefficient = 0.316), ALP level (β-coefficient = 0.380), and creatinine level (β-coefficient = 0.290) independently and significantly affected log presepsin levels. ANCOVA revealed that presepsin levels were significantly higher in patients with hepatobiliary disease. Patients who presented with dilatation of the bile ducts and elevated ALP levels or total bilirubin levels exhibited high presepsin levels in the bile. Presepsin production in liver Kupffer cells was also confirmed by immunostaining.

Conclusion: Presepsin levels is correlated with the elevation of biliary enzymes in patients without renal dysfunction or sepsis. Additionally, presepsin exists with high concentrations in the bile and is positive in Kupffer cells.
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http://dx.doi.org/10.1016/j.cca.2021.07.025DOI Listing
October 2021

Molecular Mismatch Predicts T Cell-Mediated Rejection and De Novo Donor-Specific Antibody Formation After Living Donor Liver Transplantation.

Liver Transpl 2021 11 23;27(11):1592-1602. Epub 2021 Aug 23.

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

Human leukocyte antigen (HLA) molecular mismatch (MM) analysis improves the prediction of clinical outcomes in kidney transplantation compared with prediction via traditional antigen MM. However, it remains unclear whether the level of MM can be used for risk stratification among liver transplantation (LT) recipients. A retrospective observational study of 45 living donor LTs was performed to evaluate eplet MM as a risk factor for both T cell-mediated rejection (TCMR) in the first month and de novo donor-specific antibody (dnDSA) formation. A total of 9 (20%) patients displayed TCMR. HLA-A, HLA-B, HLA-C, and HLA-DRB1 eplet MM numbers were not associated with TCMR. By contrast, HLA-DQB1 eplet MM (DQB1-EpMM) number was significantly high in patients with TCMR. The predicted indirectly recognizable HLA epitopes (PIRCHE-II) score for the HLA-DQB1 locus (DQB1-PIRCHE-II) was also significantly higher in the TCMR group than in the no-TCMR group. There was a high probability for TCMR to occur with either a DQB1-EpMM ≥7 or a DQB1-PIRCHE-II ≥13. Pretransplant mixed lymphocyte response analyses indicated that there were no significant differences between the antidonor T cell proliferation activities of patients with low-number (<7) and high-number (≥7) DQB1-EpMMs. However, the proportion of CD25 expression on proliferating antidonor CD8 T cells, used as a cytotoxic activity marker, was high in DQB1-EpMMs ≥7. Moreover, both DQB1-EpMMs ≥9 and DQB1-PIRCHE-II ≥3 were predictors of dnDSA formation. Thus, MM analysis may be applied toward tailored immunosuppression based on individual risks.
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http://dx.doi.org/10.1002/lt.26238DOI Listing
November 2021

Pilot study to determine the safety and feasibility of deceased donor liver natural killer cell infusion to liver transplant recipients with hepatocellular carcinoma.

Cancer Immunol Immunother 2021 Jul 19. Epub 2021 Jul 19.

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

Liver transplantation (LT) is a viable treatment option for cirrhosis patients with hepatocellular carcinoma (HCC). However, recurrence is the rate-limiting factor of long-term survival. To prevent this, we conducted the phase I study of the adoptive transfer of deceased donor liver-derived natural killer (NK) cells. Liver NK cells were extracted from donor liver graft perfusate and were stimulated in vitro with IL-2. The patient received an intravenous infusion of NK cells 3-5 days after LT. Eighteen LT recipients were treated. There were no severe cell infusion-related adverse events or acute rejection episodes. One patient withdrew from the study because the pathological observation revealed sarcoma instead of HCC. All patients who received this immunotherapy completed the follow-up for at least 2 years without evidence of HCC recurrence (median follow-up, 96 months [range, 17-121 months]). Considering that 9 (52.9%) of the 17 patients pathologically exceeded the Milan criteria, liver NK cell infusion is likely to be useful for preventing HCC recurrence after LT. This is the first-in-human immunotherapy study using deceased donor liver-derived NK cells to prevent HCC recurrence after LT. This treatment was well tolerated and resulted in no HCC recurrence after LT.Clinical trial registration www.clinicaltrials.gov ; NCT01147380; registration date: June 17, 2010.
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http://dx.doi.org/10.1007/s00262-021-03005-3DOI Listing
July 2021

Cognitive-Evaluative Dimension of Pain in Neuropathic Pain Relapse in Sciatica: A Case Report.

Medicina (Kaunas) 2021 Jun 27;57(7). Epub 2021 Jun 27.

Department of Rehabilitation, Faculty of Health Science, Uekusa Gakuen University, Chiba 264-0007, Japan.

The cognitive-evaluative (C-E) dimension of pain is commonly observed in patients with a relatively long duration of pain. However, little is known about the effects of pain relapse on the C-E dimension of pain. Moreover, the improvement process of the C-E dimension of pain following treatment is unknown. The objective of this case report was to (a) demonstrate that the C-E dimension was affected in the acute phase of neuropathic pain in cases of pain relapse, and (b) demonstrate the improvement process of the C-E dimension of pain. A woman was diagnosed with low back pain (LBP) and sciatica. The patient had previously experienced symptoms of LBP and sciatica; thus, this episode was a case of pain relapse. At the beginning of rehabilitation, the C-E dimension of pain was present in addition to the sensory-discriminative (S-D) dimension of pain. It was observed that improvement of the C-E dimension of pain was delayed in comparison with that of the S-D dimension of pain. The C-E dimension of pain was observed with pain relapse even though it was in the acute phase of pain. This case provides a novel insight into the C-E dimension of pain. Moreover, the delay in improving the C-E dimension of pain indicates a difference in the improvement process for each pain dimension.
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http://dx.doi.org/10.3390/medicina57070658DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8305423PMC
June 2021

A randomized controlled trial of two diets enriched with protein or fat in patients with type 2 diabetes treated with dapagliflozin.

Sci Rep 2021 05 31;11(1):11350. Epub 2021 May 31.

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

Sodium-glucose cotranspsorter-2 (SGLT2) inhibitors (SGLT2i) involve loss of skeletal muscle mass, potentially leading to inadequate HbA1c reduction in type 2 diabetes (T2DM), since muscle mass is related to insulin sensitivity. The benefit of protein-enriched diet for improving HbA1c in SGLT2i-treated T2DM patients remains unclear. We conducted a multicenter, double-blind, randomized, controlled, investigator-initiated clinical trial. 130 T2DM patients treated with dapagliflozin (5 mg) were randomized to isoenergic protein-rich formula diet (P-FD) or fat-rich FD (F-FD) (1:1 allocation) to replace one of three meals/day for 24 weeks. Primary outcome was change in HbA1c. Secondary outcomes were changes in serum insulin, body composition and other metabolic parameters. Although HbA1c decreased significantly in both groups [mean (95% confidence interval) - 0.7% (- 0.9 to - 0.5) in P-FD, - 0.6% (- 0.8 to - 0.5) in F-FD], change in HbA1c was not significantly different between the two groups (P = 0.4474). Fasting insulin and body fat mass decreased, while HDL-cholesterol increased significantly in P-FD, and these changes were significantly greater compared with F-FD (all, P < 0.05). In T2DM treated with dapagliflozin, protein-enriched diet does not contribute to HbA1c reduction, although it decreases serum insulin and body fat mass, and increases HDL-cholesterol compared with fat-enriched diet with identical calories and carbohydrate ratio.
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http://dx.doi.org/10.1038/s41598-021-90879-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166978PMC
May 2021

Loss of antibodies to hepatitis E virus in organ transplant patients with hepatitis E.

Hepatol Res 2021 May 6;51(5):538-547. Epub 2021 Apr 6.

Department of Gastroenterological Surgery, Tokyo Medical University Ibaraki Medical Center, Ami, Japan.

Aim: Studies regarding changes in antibodies to hepatitis E virus (HEV) after HEV infection in organ transplant patients are limited. This study aimed to clarify HEV infection trends in organ transplant patients who contracted HEV using data from a previous Japanese nationwide survey.

Methods: This study was undertaken from 2012 to 2019. Among 4518 liver, heart, and kidney transplant patients, anti-HEV immunoglobulin G (IgG) antibodies were positive in 164; data were collected from 106 of these patients, who consented to participate in the study. In total, 32 liver transplant patients, seven heart transplant patients, and 67 kidney transplant patients from 16 institutions in Japan were examined for IgG, IgM, and IgM antibodies to HEV and the presence of HEV RNA in the serum. The χ -test was used to determine the relationship between the early and late postinfection groups in patients with anti-HEV IgG positive-to-negative conversion rates. The Mann-Whitney U-test was used to compare clinical factors.

Results: Anti-HEV IgG positive-to-negative conversion occurred in 25 (23.6%) of 106 organ transplant patients. Of eight patients with hepatitis E who tested positive for HEV RNA, one (14.0%) had anti-HEV IgG positive-to-negative conversion. Twenty-four (24.5%) of 98 patients negative for HEV RNA had anti-HEV IgG positive-to-negative conversion.

Conclusions: This study revealed, for the first time, the changes in HEV antibodies in organ transplant patients. Loss of anti-HEV IgG could often occur unexpectedly in organ transplant patients with previous HEV infection.
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http://dx.doi.org/10.1111/hepr.13637DOI Listing
May 2021

Prevention of Cardiovascular Events with Pitavastatin is Associated with Increased Serum Lipoprotein Lipase Mass Level: Subgroup Analysis of the TOHO-LIP.

J Atheroscler Thromb 2021 Feb 27. Epub 2021 Feb 27.

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

Aim: To clarify the mechanism by which pitavastatin reduced cardiovascular (CV) events more effectively than atorvastatin in the TOHO Lipid Intervention Trial Using Pitavastatin (TOHO-LIP), the changes in (Δ) non-heparinized serum level of lipoprotein lipase mass (LPL mass) during administration of the respective statins were investigated.

Methods: From TOHO-LIP data, 223 hypercholesterolemic patients with any CV risks followed at Toho University Sakura Medical Center were analyzed. The patients were randomized to pitavastatin (2 mg/day) group (n=107) or atorvastatin (10 mg/day) group (n=116), and followed for 240 weeks. In this subgroup study, the primary and secondary end points were the same as those in TOHO-LIP, and 3-point major adverse cardiovascular events (3P-MACE) was added. The relationship between ΔLPL mass during the first year and the incidences of each end point was analyzed.

Results: The lipid-lowering effect was not different between the two statins. Cumulative 240-week incidence of each end point was significantly lower in pitavastatin group (primary: 1.9% vs. 10.3%, secondary: 4.7% vs. 18.1%, 3P-MACE: 0.9% vs. 6.9%). Mean LPL mass (64.9 to 69.0 ng/mL) and eGFR (70.1 to 73.6 ml/min/1.73m) increased in pitavastatin group, but not in atorvastatin group during the first year. Cox proportional-hazards model revealed that ΔLPL mass (1 ng/mL or 1SD) contributed to almost all end points.

Conclusions: Pitavastatin administration reduced CV events more efficaciously than atorvastatin despite similar LDL cholesterol-lowering effect of the two statins. Increased LPL mass during the first year by pitavastatin treatment may be associated with this efficacy.
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http://dx.doi.org/10.5551/jat.62141DOI Listing
February 2021

Analysis of Risk Factors Affecting Incidence of Osteoporosis and Fragility Fractures in Liver Transplant Recipients.

Ann Transplant 2021 Feb 5;26:e925475. Epub 2021 Feb 5.

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

BACKGROUND Fragility fractures caused by osteoporosis are common complications seen in recipients of organ transplantation who survive long term. Although many risk factors have been identified for osteoporosis after organ transplantation, none of them have been recognized as the main cause of development of the condition. Several studies have examined vitamin D receptor (VDR) gene single-nucleotide polymorphisms (SNPs) for their influence on bone mineral density (BMD) and fracture risk, but with variable results. We aimed to elucidate the risk factors that affect incidence of osteoporosis and fragility fractures in liver transplant recipients. MATERIAL AND METHODS In this study, we monitored incidence of fragility fracture and osteoporosis in 45 patients who had been evaluated with dual-energy X-ray absorptiometry (DXA) after liver transplantation. We also analyzed the association between VDR SNPs such as BsmI, ApaI, FokI, and TaqI with osteoporosis and fracture incidence in 27 patients in our cohort in whom SNPs were evaluated and DXA performed after liver transplantation. RESULTS Osteoporosis was diagnosed in 17 of 45 patients in whom BMD was measured after liver transplantation. Of the patients with osteoporosis, 15 (88.2%) subsequently had fragility fractures. The incidence of postoperative osteoporosis was significantly higher in the recipients who had alcoholic liver cirrhosis as their primary disease. Interestingly, there were significantly more patients with a homozygous BsmI GG genotype in the group diagnosed with osteoporosis. CONCLUSIONS Our study suggests that patients who undergo liver transplantation and have alcoholic liver cirrhosis or the BsmI GG genotype may be at increased risk for osteoporosis. Further research is necessary to confirm these findings.
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http://dx.doi.org/10.12659/AOT.925475DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7871462PMC
February 2021

CAVI-Lowering Effect of Pitavastatin May Be Involved in the Prevention of Cardiovascular Disease: Subgroup Analysis of the TOHO-LIP.

J Atheroscler Thromb 2021 Oct 18;28(10):1083-1094. Epub 2020 Dec 18.

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

Aim: In the TOHO Lipid Intervention Trial Using Pitavastatin (TOHO-LIP), a multicenter randomized controlled trial, pitavastatin significantly reduced cardiovascular (CV) events compared to atorvastatin in patients with hypercholesterolemia. To investigate the mechanism by which pitavastatin preferentially prevents CV events, we investigated the relationship between CV events and cardio-ankle vascular index (CAVI) using the TOHO-LIP database.

Methods: For the subgroup analysis, we selected patients from a single center, Toho University Sakura Medical Center. After excluding those who had CV events at baseline or during the first year, 254 patients were enrolled. The primary end point was the same as that of TOHO-LIP, and three-point major cardiac adverse events (3P-MACE) was added as secondary end point.

Results: The cumulative 5-year incidence of 3P-MACE (pitavastatin 1.6%, atorvastatin 6.1%, P=0.038) was significantly lower in pitavastatin group (2 mg/day) than in atorvastatin group (10 mg/day). CAVI significantly decreased only in pitavastatin group during the first year (9.50-9.34, P=0.042), while the change in low-density lipoprotein cholesterol (LDL-C) did not differ between the two groups. The change in CAVI during the first year positively correlated with 3P-MACE and tended to be an independent predictor of 3P-MACE in Cox proportional hazards model (hazard ratio, 1.736; P=0.079). The annual change in CAVI throughout the observation period was significantly higher in subjects with CV events compared to those without.

Conclusions: In this subgroup analysis, the reduction in CV events tended to be associated with the CAVI-lowering effect of pitavastatin, which was independent of the LDL-C-lowering effect.
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http://dx.doi.org/10.5551/jat.60343DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8560841PMC
October 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

Low serum insulin-like growth factor-1 level is a predictor of low total weight loss percentage after sleeve gastrectomy.

Surg Obes Relat Dis 2020 Dec 11;16(12):1978-1987. Epub 2020 Aug 11.

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

Background: Obesity is a leading cause of metabolic disorders and mortality. Laparoscopic sleeve gastrectomy (LSG) confers beneficial effects not only on weight but also on metabolic disorder development. However, some patients show insufficient weight loss after LSG. A total weight loss percentage (%TWL) <20% after LSG is defined as insufficient. The prediction of patients with insufficient weight loss after LSG before the procedure is performed may prove helpful.

Objectives: To determine predictors of %TWL after LSG.

Setting: Longitudinal study in a university hospital.

Methods: We retrospectively reviewed 90 obese patients who underwent LSG and were followed up for 12 months thereafter. We analyzed the relationship between %TWL and preoperative clinical parameters, such as age, sex, body mass index, lipid and glucose metabolism, and some hormones. Patients were divided into 2 groups, %TWL <20% and 20% ≤ %TWL. Multiple regression model and logistic regression models were performed.

Results: LSG led to significant improvements in weight, liver, and kidney function, and lipid and glucose metabolism. The serum insulin-like growth factor-1 (IGF-1) level was significantly lower in patients with %TWL <20%. Sex, diabetes presence, body mass index, and IGF-1 were independent predictors of %TWL. Receiver operating characteristic curve analysis showed that the cutoff value of IGF-1 for %TWL <20% was 100.0ng/mL. Male sex, diabetes presence, lower preoperative BMI, and IGF-1 values were independently associated with lower %TWL (%TWL <20%).

Conclusions: Serum IGF-1 can be used to screen for patients at risk of low %TWL after LSG.
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http://dx.doi.org/10.1016/j.soard.2020.07.033DOI Listing
December 2020

Rapidly Progressive Invasive Urothelial Carcinoma With Flat and Infiltrative Growth Pattern in the Graft Kidney After Living-Related Kidney Transplantation: A Case Report.

Transplant Proc 2020 Nov 24;52(9):2726-2730. Epub 2020 Aug 24.

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

Background: Because immunosuppression is necessary for kidney transplant recipients, malignant tumorigenesis of recipient organs is a concern; however, few studies have discussed the malignant alteration of transplanted grafts that have been functional for a long time. In addition, a urothelial carcinoma (UC) in transplanted kidney graft is a rare disease.

Case Report: A 62-year-old man had end-stage renal failure 31 years ago and received a kidney transplant from his father. Acute renal failure due to obstruction of the transplanted ureter was diagnosed. Ultrasound, ureterogram, and non-enhanced computed tomography scans revealed no obvious evidence of any neoplastic lesion. We treated the obstruction and hydronephrosis with transplant ureter stenting. However, the regional lymph nodes enlarged, and it became necessary to change the ureteral stent frequently because of stent stenosis; therefore, he underwent lower transplant ureteral resection and reconstruction. Histopathology confirmed a UC with a flat and infiltrative growth pattern. The patient then underwent graftectomy including right external iliac vein resection and reconstruction; however, because of numerous metastatic nodules, radical surgery could not be performed. The patient subsequently died because of septic shock after the second surgery.

Conclusion: We report a case of an invasive UC with a flat and infiltrative growth pattern derived from a transplant kidney graft that occurred 31 years after a living-donor transplant that could not be treated immediately and was difficult to diagnose.
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http://dx.doi.org/10.1016/j.transproceed.2020.08.001DOI Listing
November 2020

Strategies for Deliberate Induction of Immune Tolerance in Liver Transplantation: From Preclinical Models to Clinical Application.

Front Immunol 2020 31;11:1615. Epub 2020 Jul 31.

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

The liver exhibits intrinsic immune regulatory properties that maintain tolerance to endogenous and exogenous antigens, and provide protection against pathogens. Such an immune privilege contributes to susceptibility to spontaneous acceptance despite major histocompatibility complex mismatch when transplanted in animal models. Furthermore, the presence of a liver allograft can suppress the rejection of other solid tissue/organ grafts from the same donor. Despite this immune privilege of the livers, to control the undesired alloimmune responses in humans, most liver transplant recipients require long-term treatment with immune-suppressive drugs that predispose to cardiometabolic side effects and renal insufficiency. Understanding the mechanism of liver transplant tolerance and crosstalk between a variety of hepatic immune cells, such as dendritic cells, Kupffer cells, liver sinusoidas endothelial cells, hepatic stellate cells and so on, and alloreactive T cells would lead to the development of strategies for deliberate induction of more specific immune tolerance in a clinical setting. In this review article, we focus on results derived from basic studies that have attempted to elucidate the immune modulatory mechanisms of liver constituent cells and clinical trials that induced immune tolerance after liver transplantation by utilizing the immune-privilege potential of the liver.
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http://dx.doi.org/10.3389/fimmu.2020.01615DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7412931PMC
April 2021

Impact of Mental Health Background and Nutrition Intake on Medium-Term Weight Loss in Japanese Patients Undergoing Laparoscopic Sleeve Gastrectomy.

Obes Facts 2020 18;13(4):371-383. Epub 2020 Aug 18.

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

Objectives: Bariatric surgery is the most effective weight loss therapy, and recently laparoscopic sleeve gastrectomy (LSG) is gaining popularity worldwide. On the other hand, patients undergoing bariatric surgery have a high prevalence of mental disorders. A Japanese nationwide survey reported high prevalence of mental disorders in patients with low percent total weight loss (%TWL) and also in those with high %TWL. The aim of this study was to investigate the relationship of 1-year %TWL with background mental health status, 3-year outcomes, and nutrition intake in Japanese patients after LSG.

Methods: This study was a single-center retrospective database analysis. A total of 89 Japanese patients who underwent LSG and were followed for 3 years were enrolled (mean age 41.9 years, baseline body mass index 44.9, baseline glycosylated hemoglobin, HbA1c, 7.0%). The patients were divided into 3 groups according to 1-year %TWL as follows: ≤19.9% (insufficient group), 20.0-34.9% (average group) and ≥35.0% (excessive group). Psychosocial and nutritional status as well as physical data were collected from all patients.

Results: The prevalence of mental disorders was 51.7%, and 1-year %TWL was 28.1% in all patients. No significant differences were observed in the changes in body weight and HbA1c between patients with and those without mental disorders. The prevalence of mental disorders was particularly high in the insufficient and excessive groups. In the insufficient group, mood disorders and mental retardation/developmental disorders were frequent, and snacking and eating out habits were often observed. In the excessive group, the frequencies of mood disorders and binge eating were high, and a decrease in skeletal muscle mass due to low protein intake was observed. Furthermore, weight regain was shown 12 months after LSG in both groups. In the average group, there were fewer problems in weight loss outcomes, mental health, nutrition intake and body composition.

Conclusions: Psychosocial and nutritional problems were often found not only in patients with insufficient weight loss, but also in those with seemingly "excellent" weight reduction. To improve long-term weight loss outcome and future health, a multidisciplinary approach focusing on mental health and nutrition is essential for patients undergoing bariatric surgery.
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http://dx.doi.org/10.1159/000509342DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7590761PMC
April 2021

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

New Horizons of Arterial Stiffness Developed Using Cardio-Ankle Vascular Index (CAVI).

J Atheroscler Thromb 2020 Aug 26;27(8):732-748. Epub 2020 Jun 26.

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

Arterial stiffness is recognized mainly as an indicator of arteriosclerosis and a predictor of cardiovascular events. Cardio-ankle vascular index (CAVI), which reflects arterial stiffness from the origin of the aorta to the ankle, was developed in 2004. An important feature of this index is the independency from blood pressure at the time of measurement. A large volume of clinical evidence obtained using CAVI has been reported. CAVI is high in patients with various atherosclerotic diseases including coronary artery disease and chronic kidney disease. Most coronary risk factors increase CAVI and their improvement reduces CAVI. Many prospective studies have investigated the association between CAVI and future cardiovascular disease (CVD), and proposed CAVI of 9 as the optimal cut-off value for predicting CVD. Research also shows that CAVI reflects afterload and left ventricular diastolic dysfunction in patients with heart failure. Furthermore, relatively acute changes in CAVI are observed under various pathophysiological conditions including mental stress, septic shock and congestive heart failure, and in pharmacological studies. CAVI seems to reflect not only structural stiffness but also functional stiffness involved in acute vascular functions. In 2016, Spronck and colleagues proposed a variant index CAVI, and claimed that CAVI was truly independent of blood pressure while CAVI was not. This argument was settled, and the independence of CAVI from blood pressure was reaffirmed. In this review, we summarize the recently accumulated evidence of CAVI, focusing on the proposed cut-off values for CVD events, and suggest the development of new horizons of vascular function index using CAVI.
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http://dx.doi.org/10.5551/jat.RV17043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7458785PMC
August 2020

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

Essential updates 2018/2019: Liver transplantation.

Ann Gastroenterol Surg 2020 May 25;4(3):195-207. Epub 2020 Feb 25.

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

Among the recent topics in the field of liver transplantation (LT), one of the significant therapeutic breakthroughs is the introduction of direct-acting antiviral agents (DAAs) against hepatitis C virus (HCV) infection. With cure rates close to 100%, a better proportion of LT candidates and recipients can be cured of HCV infection by DAA therapies that are simple and well-tolerated. Other critical topics include the issue of indication of LT for patients with hepatocellular carcinoma, which has been continuously studied. Several expanded criteria beyond the Milan criteria with acceptable results have been recently reported. The role of donor-specific antibodies (DSAs) in intractable rejection is also an important matter that has been studied. Although long recognized as an important factor in antibody-mediated rejection and even graft survival in renal transplantation, the impact of DSAs on graft and patient survival in LT remains to be elucidated. Including the issues described above, this article focuses on recent advances in LT, management to avoid recurrence of primary diseases, optimization of immunosuppressive treatment, and extended donor criteria.
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http://dx.doi.org/10.1002/ags3.12321DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7240140PMC
May 2020

Fracture Risk Assessment Tool May Not Indicate Bone Fragility in Women With Type 2 Diabetes.

Am J Med Sci 2020 11 11;360(5):552-559. Epub 2020 Apr 11.

Center for Diabetes, Endocrinology, and Metabolism, Toho University Sakura Medical Center, Chiba, Japan. Electronic address:

Background: Diabetes carries a known risk of bone fracture despite high bone mineral density (BMD). The fracture risk assessment tool (FRAX) predicts the 10-year major osteoporotic fracture risk and hip fracture risk. We investigated the effects of clinical parameters on the FRAX score and evaluated the validity of FRAX for evaluating current bone fragility in diabetes subjects.

Materials And Methods: Forty-seven thousand, three hundred eighty-nine Japanese women participated in the Chiba bone survey, a population-based, multicenter, cross-sectional study of postmenopausal osteoporosis; we estimated FRAX scores without BMD and compared scores between subjects with and without type 2 diabetes.

Results: Mean FRAX major osteoporotic fracture risk was significantly higher in the diabetes group. A multiple regression model demonstrated some clinical parameters that affected the FRAX score and, after adjusting for such parameters, the FRAX score was not significantly different between the diabetes and nondiabetes groups, although the type 2 diabetes rate was significantly higher in subjects with a fracture in the past 5 years, which reflected current bone fragility. After adjusting for clinical parameters, the diabetes rate remained significantly higher in subjects with a fracture in the past 5 years, confirming that type 2 diabetes influences current bone fragility. Our study demonstrated that type 2 diabetes truly carries a risk of bone fracture, but adjusted FRAX major osteoporotic fracture risk is not significantly different between subjects with and without type 2 diabetes.

Conclusions: The FRAX major osteoporotic fracture risk without BMD does not correctly indicate current bone fragility in Japanese middle-aged women with type 2 diabetes.
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http://dx.doi.org/10.1016/j.amjms.2020.04.002DOI Listing
November 2020

Posttransplant Management of Recipients Undergoing Liver Transplantation for Hepatocellular Carcinoma. Working Group Report From the ILTS Transplant Oncology Consensus Conference.

Transplantation 2020 06;104(6):1143-1149

Department of Surgery, Erasmus MC-University Medical Center Rotterdam, Rotterdam, The Netherlands.

Although liver transplantation (LT) is the best treatment for patients with localized hepatocellular carcinoma (HCC), recurrence occurs in 6%-18% of patients. Several factors, particularly morphological criteria combined with dynamic parameters, known before LT modify this risk and combined in prediction models may be used to stratify patients at need of variable surveillance strategies. Additional variables though likely explain differences in recurrence rates in patients with the same pre-LT HCC status. One of these variables is possibly immunosuppression (IS). Once recurrence takes place, management is highly heterogenous. Within the International Liver Transplantation Society Consensus Conference on Liver Transplant Oncology, working group 4 aim was to analyze the data regarding posttransplant management of recipients undergoing LT for HCC. Three areas of research were considered: (1) cancer prediction models and surveillance strategies; (2) tailored IS for cancer recipients; and (3) new adjuvant therapies for HCC recurrence. Following formulation of several questions, a literature search was undertaken with abstract review followed by article retrieval and full-data extraction. The grading of recommendations assessment, development and evaluation (GRADE) system was used for evidence rating incorporating strength of recommendation and quality of evidence.
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http://dx.doi.org/10.1097/TP.0000000000003196DOI Listing
June 2020
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