Aberrant phosphorylation of human LRH1 at serine 510 is predictable of hepatocellular carcinoma recurrence.

We previously identified the AKT-phosphorylation sites in nuclear receptors and showed that phosphorylation of S379 in mouse retinoic acid γ and S518 in human estrogen receptor α regulate their activity independently of the ligands. Since this site is conserved at S510 in human liver receptor homolog 1 (hLRH1), we developed a monoclonal antibody (mAb) that recognized the phosphorylation form of hLRH1S510 (hLRH1pS510) and verified its clinicopathological significance in hepatocellular carcinoma (HCC). We generated the anti-hLRH1pS510 mAb and assessed its selectivity. We then evaluated the hLRH1pS510 signals in 157 cases of HCC tissues by immunohistochemistry because LRH1 contributes to the pathogenesis of diverse cancers. The developed mAb specifically recognized hLRH1pS510 and worked for immunohistochemistry of formalin-fixed paraffin-embedded tissues. hLRH1pS510 was exclusively localized in the nucleus of HCC cells, but the signal intensity and positive rates varied among the subjects. According to the semi-quantification, 45 cases (34.9%) showed hLRH1pS510-high, and the remaining 112 cases (65.1%) exhibited hLRH1pS510-low. There were significant differences in the recurrence-free survival (RFS) between the two groups, and the 5-year RFS rates in the hLRH1pS510-high and hLRH1pS510-low groups were 26.5% and 46.1%, respectively. In addition, high hLRH1pS510 was significantly correlated with portal vein invasion, hepatic vein invasion, and high levels of serum alpha-fetoprotein (AFP). Furthermore, multivariable analysis revealed that hLRH1pS510-high was an independent biomarker for HCC recurrence. We conclude that aberrant phosphorylation of hLRH1S510 is a predictor of poor prognosis for HCC. The anti-hLRH1pS510 mAb could provide a powerful tool to validate the relevance of hLRH1pS510 in pathological processes such as tumor development and progression.

Long-Term Feasibility of Rescue Reconstruction for Isolated Bile Ducts With Using Cystic Duct in Living Donor Liver Transplantation.

BACKGROUND: The isolated bile duct is sometimes observed in the right liver graft of living donor liver transplantation (LDLT). Even though, as a rescue option, it is known to use the recipient's cystic duct (CyD) for duct-to-duct anastomosis, the long-term feasibility of rescue duct-to-CyD (D-CyD) anastomosis remains unclear. METHODS: We prospectively collected data in the right liver-LDLT cohort and compared rescue D-CyD anastomosis (n = 4) with standard duct-to-hepatic duct (D-HD, n = 45) anastomosis (D-CyD group, n = 4). RESULTS: The observation period was over 5 years (range, 68-171 mo) after LDLT. The D-CyD group included the following anastomosis procedures: anastomosis between the intrahepatic bile duct of the graft and the CyD of the recipient and anastomosis between the posterior HD and the CyD. Surgical outcomes between the 2 groups are similar, excluding the time for the biliary reconstruction (D-CyD, 116 ± 13 min vs D-HD, 57 ± 3 min). During the period, one recipient in the D-CyD group exhibited postoperative biliary stricture and biliary stone, and 6 recipients underwent those complications in the D-HD group (D-CyD, 25.0% vs D-HD, 13.3%) All recipients in the D-CyD group are presently alive and have not experienced liver dysfunction. CONCLUSIONS: Our findings suggest that rescue D-CyD anastomosis for an isolated bile duct in a right liver LDLT is acceptable as a life-saving option in terms of long-term feasibility.

Annual report on National Clinical Database 2020 for gastroenterological surgery in Japan.

Aim: The National Clinical Database (NCD) of Japan is a nationwide data entry system for surgery, and it marked its 10th anniversary in 2020. The aim was to present the 2020 annual report of gastroenterological surgery of the NCD. Methods: The data of the surgical procedures stipulated by the training curriculum for board-certified surgeons of the Japanese Society of Gastroenterological Surgery in the NCD from 2011 to 2020 were summarized. Results: In total, 5 622 845 cases, including 593 088 cases in 2020, were extracted from the NCD. The total number of gastroenterological surgeries increased gradually in these 10 years, except for the year 2020 due to the COVID-19 pandemic. The annual number of surgeries of each organ, except the pancreas and liver, decreased by 0.4%-13.1% in 2020 compared to 2019. The surgical patients were consistently aging, with more than 20% of all gastroenterological surgeries in 2020 involving patients aged 80 years or older. The participation of board-certified surgeons increased for each organ (75.9%-95.7% in 2020). The rates of endoscopic surgery also increased constantly. Although the incidences of postoperative complications of each organ increased by 0.7%-7.9% in these 10 years, postoperative mortality rates decreased by 0.2%-1.5%. Conclusions: We present here the short-term outcomes of each gastroenterological operative procedure in 2020. This review of the 10-years of NCD data of gastroenterological surgery revealed a consistent increase of the number of surgeries (except for in 2020), especially endoscopic procedures, and aging of the Japanese population. The good safety of Japanese gastroenterological surgeries was also indicated.

Tissue-Engineered Hepatocyte Sheets Supplemented with Adipose-Derived Stem Cells.

The ability to engineer biologically viable hepatocytes and tissue matrices with long-term functional maintenance has attracted considerable interest in the fields of hepatocyte transplantation and liver tissue engineering. Here, newly developed hepatocyte sheets supplemented with adipose-derived stem cells (ADSCs) were evaluated to assess the effects of ADSCs on hepatocyte function and engraftment into the subcutaneous space. Eight-week-old male C57BL/6J mice were used as donors, and 6-week-old male C.B-17/Icr-scid/scid mice were used as recipients. Hepatocyte-ADSC composite sheets were developed using temperature-responsive culture dishes. Hepatocyte viability in the hepatocyte-ADSC composite sheets was evaluated in an in vitro assay, and the outcome of subcutaneous transplantation of the sheet was evaluated. Hepatocyte viability was sustained in the hepatocyte-ADSC composite sheets in vitro. Albumin secretion was significantly higher (p = 0.015) in the hepatocytes of the hepatocyte-ADSC composite sheets (70.5 µg/mL) than in hepatocyte-only sheets (24.0 µg/mL). Cytokine assays showed that hepatocyte growth factor and interleukin-6 were contributed by ADSCs and not hepatocytes, which were not capable of constitutively secreting them. Immunohistochemically, phosphorylated STAT3 and c-MET expression in hepatocytes in the hepatocyte-ADSC composite sheets was significantly higher than that in the hepatocyte-only sheets. Engraftment of the transplanted hepatocyte-ADSC composite sheets was significantly enhanced without pretreatment of the subcutaneous tissue to induce a vascular network. In the hepatocyte-ADSC composite sheets, the viability of the hepatocytes was significantly maintained as the co-cultured ADSCs provided cytokines, enhancing pivotal cell signaling necessary for hepatocyte activity. Impact statement Hepatocyte transplantation is a safe, less invasive bridge treatment for liver transplantation, but its effectiveness is low and transitory. Herein, we introduce newly developed hepatocyte-adipose-derived stem cell composite sheets with improved strength, easier transplantation, and increased hepatocyte viability in the subcutaneous transplantation compared with hepatocyte-only sheets.

Case report: Unusual development of hepatocellular carcinoma during immunosuppressive treatments against rheumatoid arthritis overlapping Sjögren's syndrome; cirrhotic steatohepatitis with liver inflammation and fibrosis lurks in autoimmune disorders.

The sequential progression from chronic liver disease to cirrhosis may be a risk factor for hepatocellular carcinoma (HCC) development. Although HCC originates from hepatitis B virus- or hepatitis C virus-associated liver cirrhosis, it has recently been reported in patients with non-alcoholic steatohepatitis (NASH) with advanced fibrosis. However, little is known about the pathophysiological mechanisms linking HCC to rheumatic disorders, including rheumatoid arthritis (RA). Herein, we describe the case of HCC with NASH complicated by RA and Sjögren's syndrome (SS). A fifty-two-year-old patient with RA and diabetes was referred to our hospital for further examination of a liver tumor. She received methotrexate (4 mg/week) for 3 years and adalimumab (40 mg/biweekly) for 2 years. On admission, laboratory data showed mild thrombocytopenia and hypoalbuminemia, with normal hepatitis virus markers or liver enzymes. Anti-nuclear antibodies were positive with high titers (x640), and anti-SS-A/Ro (187.0 U/ml; normal range [NR]: ≤6.9 U/mL) and anti-SS-B/La (320 U/ml; NR: ≤6.9 U/mL) antibodies were also high. Abdominal ultrasonography and computed tomography revealed liver cirrhosis and a tumor in the left lobe (S4) of the liver. She was diagnosed with HCC based on imaging findings, and elevated levels of protein induced by vitamin K absence- II (PIVKA-II) were detected. She underwent laparoscopic partial hepatectomy, and histopathological examination revealed steatohepatitis HCC with background liver cirrhosis. The patient was discharged on the 8th day post-operation without any complications. At the 30 months follow-up, no significant evidence of recurrence was observed. Our case suggests that clinical screening for HCC is needed in patients with RA who are at a high risk of NASH, as they may progress to HCC even without elevated liver enzymes.

Achieving clinically optimal balance between accuracy and simplicity of a formula for manual use: Development of a simple formula for estimating liver graft weight with donor anthropometrics.

In developing a formula for manual use in clinical settings, simplicity is as important as accuracy. Whole-liver (WL) mass is often estimated using demographic and anthropometric information to calculate the standard liver volume or recommended graft volume in liver transplantation. Multiple formulas for estimating WL mass have been reported, including those with multiple independent variables. However, it is unknown whether multivariable models lead to clinically meaningful improvements in accuracy over univariable models. Our goal was to quantitatively define clinically meaningful improvements in accuracy, which justifies an additional independent variable, and to identify an estimation formula for WL graft weight that best balances accuracy and simplicity given the criterion. From the Japanese Liver Transplantation Society registry, which contains data on all liver transplant cases in Japan, 129 WL donor-graft pairs were extracted. Among the candidate models, those with the smallest cross-validation (CV) root-mean-square error (RMSE) were selected, penalizing model complexity by requiring more complex models to yield a ≥5% decrease in CV RMSE. The winning model by voting with random subsets was fitted to the entire dataset to obtain the final formula. External validity was assessed using CV. A simple univariable linear regression formula using body weight (BW) was obtained as follows: WL graft weight [g] = 14.8 × BW [kg] + 439.2. The CV RMSE (g) and coefficient of determination (R2) were 195.2 and 0.548, respectively. In summary, in the development of a simple formula for manually estimating WL weight using demographic and anthropometric variables, a clinically acceptable trade-off between accuracy and simplicity was quantitatively defined, and the best model was selected using this criterion. A univariable linear model using BW achieved a clinically optimal balance between simplicity and accuracy, while one using body surface area performed similarly.

A multicenter comparative study of endoscopic ultrasound-guided fine-needle biopsy using a Franseen needle versus conventional endoscopic ultrasound-guided fine-needle aspiration to evaluate microsatellite instability in patients with unresectable pancreatic cancer.

BACKGROUND/AIMS: Immune checkpoint blockade has recently been reported to be effective in treating microsatellite instability (MSI)-high tumors. Therefore, sufficient sampling of histological specimens is necessary in cases of unresectable pancreatic cancer (UR-PC). This multicenter study investigated the efficacy of endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) using a Franseen needle for MSI evaluation in patients with UR-PC. METHODS: A total of 89 patients with UR-PC who underwent endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) or EUS-FNB using 22-G needles at three hospitals in Japan (2018-2021) were enrolled. Fifty-six of these patients (FNB 23 and FNA 33) were followed up or evaluated for MSI. Patient characteristics, UR-PC data, and procedural outcomes were compared between patients who underwent EUS-FNB and those who underwent EUS-FNA. RESULTS: No significant difference in terms of sufficient tissue acquisition for histology was observed between patients who underwent EUS-FNB and those who underwent EUS-FNA. MSI evaluation was possible significantly more with tissue samples obtained using EUS-FNB than with tissue samples obtained using EUS-FNA (82.6% [19/23] vs. 45.5% [15/33], respectively; p<0.01). In the multivariate analysis, EUS-FNB was the only significant factor influencing the possibility of MSI evaluation. CONCLUSION: EUS-FNB using a Franseen needle is desirable for ensuring sufficient tissue acquisition for MSI evaluation.

[A Case of Pancreatic Cancer That Developed Peritoneal Recurrence after Radical Surgery following Neoadjuvant Chemoradiation Therapy(NACRT)with Pathological Complete Response(pCR)].

A 71-year-old woman was diagnosed with a tumor in the pancreatic head on CT imaging, which was performed as a close examination of an exacerbation of diabetes mellitus. The pancreatic tumor was diagnosed as resectable pancreatic cancer, and after preoperative adjuvant chemoradiotherapy, pancreatoduodenectomy was performed as a radical surgery. There were no residual tumor cells in the resected specimen histopathologically, and the patient was judged to have a pathological complete response(pCR). Six months of postoperative adjuvant chemotherapy was administered, but peritoneal recurrence was observed at 20 months postoperatively, and the patient is currently undergoing treatment for recurrence. There have been other reports of recurrence even after pCR was achieved with preoperative treatment, so it is important to follow up carefully, keeping in mind that pancreatic cancer is a latent systemic disease.

Screening for hilar biliary invasion in ampullary cancer patients.

BACKGROUND: The treatment for ampullary cancer is pancreatoduodenectomy or local ampullectomy. However, effective methods for the preoperative investigation of hilar biliary invasion in ampullary cancer patients have not yet been identified. AIM: To determine the necessity of and an appropriate method for investigating hilar biliary invasion of ampullary cancer. METHODS: Among 43 ampullary cancer patients, 34 underwent endoscopic treatment (n = 9) or surgery (n = 25). The use of imaging findings (thickening and enhancement of the bile duct wall on contrast-enhanced computed tomography, irregularity on endoscopic retrograde cholangiography, thickening of the entire bile duct wall on intraductal ultrasonography (IDUS), and partial thickening of the bile duct wall on IDUS) and biliary biopsy results for diagnosing hilar biliary invasion of ampullary cancer was compared. RESULTS: Hilar invasion was not observed in every patient. Among the patients who did not undergo biliary stent insertion, the combination of partial thickening of the bile duct wall on IDUS and biliary biopsy results showed the highest accuracy (100%) for diagnosing hilar biliary invasion. However, each imaging method and biliary biopsy yielded some false-positive results. CONCLUSION: Although some false-positive results were obtained with each method, the combination of partial thickening of the bile duct wall on IDUS and biliary biopsy results was useful for diagnosing hilar biliary invasion of ampullary cancer. However, hilar invasion of ampullary cancer is rare; therefore, the investigation of hilar biliary invasion of ampullary cancer might be unnecessary.

Two cases of pancreaticoduodenal aneurysm with median arcuate ligament syndrome treated with coil embolization and median arcuate ligament incision.

Median arcuate ligament syndrome is a clinical condition in which the median arcuate ligament causes compression and narrowing of the celiac artery. It has been reported that collateral pathways, which is developed by the decrease of blood flow from the celiac artery, facilitates the formation of aneurysms. Aneurysms around the pancreas in particular require aggressive therapeutic intervention, because a rupture can be fatal. We herein report two cases of pancreaticoduodenal aneurysms associated with median arcuate ligament syndrome treated by coil embolization and median arcuate ligament incision. Case 1 required a hybrid procedure in which median arcuate ligament incision and coil embolization were performed simultaneously. In Case 2, the median arcuate ligament incision was performed about 3 months after emergency endovascular hemostasis for hemorrhagic duodenal ulcer. In both cases, there were no major postoperative complications and no recurrence of aneurysm. Median arcuate ligament incision may be effective to prevent organ ischemia and aneurysm recurrence after coil embolization of intra-abdominal aneurysms associated with median arcuate ligament syndrome.

Cost of postoperative complications of lower anterior resection for rectal cancer: a nationwide registry study of 15,187 patients.

PURPOSE: To assess the increase in hospital costs associated with postoperative complications after lower anterior resection (LAR) for rectal cancer. METHODS: The subjects of this retrospective analysis were patients who underwent elective LAR surgery between April, 2015 and March, 2017, collected from a Japanese nationwide gastroenterological surgery registry linked to hospital-based claims data. We evaluated total and category-specific hospitalization costs based on the level of postoperative complications categorized using the Clavien-Dindo (CD) classification. We assessed the relative increase in hospital costs, adjusting for preoperative factors and hospital case volume. RESULTS: We identified 15,187 patients (mean age 66.8) treated at 884 hospitals. Overall, 71.8% had no recorded complications, whereas 7.6%, 10.8%, 9.0%, 0.6%, and 0.2% had postoperative complications of CD grades I-V, respectively. The median (25th-75th percentiles) hospital costs were $17.3 K (16.1-19.3) for the no-complications group, and $19.1 K (17.3-22.2), $21.0 K (18.5-25.0), $27.4 K (22.4-33.9), $41.8 K (291-618), and $22.7 K (183-421) for the CD grades I-V complication groups, respectively. The multivariable model identified that complications of CD grades I-V were associated with 11%, 21%, 61%, 142%, and 70% increases in in-hospital costs compared with no complications. CONCLUSIONS: Postoperative complications and their severity are strongly associated with increased hospital costs and health-care resource utilization. Implementing strategies to prevent postoperative complications will improve patients' clinical outcomes and reduce hospital care costs substantially.

Efficacy of a novel large-cell Niti-S stent with a slim delivery system for hilar biliary obstruction: a preliminary study.

OBJECTIVES: The large-cell Niti-S stent is useful for multiple stenting in patients with malignant hilar biliary obstruction (MHBO). Recently, a novel uncovered self-expandable metallic stent (USEMS) (a Niti-S large-cell SR slim delivery system) was developed. In this study, we aimed to evaluate the efficacy of this USEMS slim delivery system in MHBO patients. MATERIALS AND METHODS: Outcomes related to USEMS placement, the clinical course, and the period to recurrent biliary obstruction (RBO) were evaluated in MHBO patients who received multiple USEMSs with the Niti-S large-cell SR slim delivery system. RESULTS: Twenty-two MHBO patients underwent the placement of multiple USEMSs, including the novel slim-delivery stent. Six patients had a past history of upper gastrointestinal reconstruction (Billroth I: 1, Billroth II: 4, Roux-en-Y: 1). The number of USEMSs placed in each patient was 2-6. Three procedures were reinterventions. The new slim delivery system was placed as the first stent in ten patients and as an additional stent in the remaining patients. Seven patients were drained using only Niti-S large-cell SR slim delivery stents. The technical and clinical success rates were both 100%. CONCLUSIONS: Placing multiple USEMSs in patients with a past history of abdominal surgery or in reintervention is difficult. Although difficult cases were included in this study, stent-in-stent placement with the novel Niti-S large-cell SR slim delivery system was useful in treating MHBO patients. In addition, this novel stent might be the first choice for MHBO patients.KEY MESSAGESEndoscopic multistenting for MHBO is challenging. In addition, reintervention or multistenting for MHBO patients with a past history of abdominal surgery becomes more difficult.The novel Niti-S large-cell SR slim delivery USEMS is useful as an additional stent because the delivery system is thin and suitable for a 0.025 guidewire. In addition, the novel stent is of the braided type and has a large mesh. Therefore, the novel stent is expected to have strong radial force and can be used as the first SEMS.The Niti-S large-cell SR slim delivery stent is long enough to be used in patients with upper gastrointestinal reconstruction. Although this study included patients with reintervention or a past history of upper gastrointestinal reconstruction, the technical success rate of multiple stenting for MHBO patients was 100%. The slim-delivery stent might overcome several difficulties of endoscopic multistenting.

How is transfusion-associated graft-versus-host disease similar to, yet different from, organ transplantation-associated graft-versus-host disease?

Graft-versus-host disease (GVHD) is a rare, usually fatal complication following blood transfusion or organ transplantation, namely transfusion-associated GVHD (TA-GVHD) and organ transplantation-associated GVHD (OA-GVHD). The dominant mechanism of GVHD is exposure to viable donor lymphocytes that are not recognized as foreign by, but able to respond to, the recipient. The clinical features and relative risk factors of either TA-GVHD or OA-GVHD are yet to be fully understood. The current review article aims to discuss and summarize the similarities and differences between TA-GVHD and OA-GVHD to gain a deeper understanding of the pathogenesis. It is evident that the shared human leukocyte antigens (HLA) between donor and recipient and immunocompromised status of the recipient are the two main risk factors for the development of both TA-GVHD and OA-GVHD. In particular, the homozygous donor with donor-dominant one-way matching at the three loci HLA-A, -B, and -DR has a high risk of developing GVHD following liver transplantation, and such donors should be excluded to prevent it. However, the development of GVHD is thought to be related to a combination of several risk factors, and the contribution of each risk factor remains unknown. Further studies are warranted to determine the important contributing factors that lead to an accurate prediction of GVHD development.

Geriatric Risk Prediction Models for Major Gastroenterological Surgery Using the National Clinical Database in Japan: A Multicenter Prospective Cohort Study.

OBJECTIVES: To investigate the effect of geriatric variables on 5 newly added outcomes and create risk models for predicting these outcomes. SUMMARY OF BACKGROUND DATA: Because there is a current lack of geriatric research focusing on geriatric outcomes using a national surgical database in Japan, there is a need to investigate outcomes associated with major gastro-enterological surgery using these data. METHODS: This multicenter prospective cohort study was conducted at 26 surgery departments across 21 institutions in Japan using the NCD surgical registry. in total, 22 new geriatric variables were imported from the ACS National Surgical Quality Improvement Program geriatric pilot study. The following 5 geriatric outcomes were defined: (1) postoperative delirium, (2) physical function on postoperative day 30, (3) fall risk on discharge, (4) discharge other than home with social service, and (5) functional decline on discharge, and geriatric risk prediction models for major gastroenterological surgery were created. RESULTS: Between January 2018 and December 2018, data on 3981 procedures from 7 major gastroenterological surgeries were collected and analyzed. Older age and preoperative geriatric variables (Origin status from home, History of dementia, Use of mobility aid, fall history, and not competent on admission) were strongly associated with postoperative outcomes. Geriatric risk prediction models for these outcomes were created, with C-statistic values ranging from 0.74 to 0.90, demonstrating model validity and sufficiency of fit. CONCLUSIONS: The risk models for the newly defined 5 geriatric outcomes that we created can be used in the decision-making process or provision of care in geriatric patients.

National survey of hepatobiliary and pancreatic surgery in hemophilia patients in Japan.

BACKGROUND: Approximately 8300 hemophiliacs are registered in Japan, but no comprehensive reports on hepatobiliary and pancreatic surgery (HBPS) have been conducted. This report investigates the current status of HPBS in hemophilia patients in Japan. METHODS: The subjects were hemophiliac patients seen between January 1 2007, and December 31 2017, at facilities participating in this study among the facilities for performing high-difficulty cases nationwide designated by the Japanese Society for HBPS. A retrospective examination of short-term outcomes in 49 cases was conducted to assess patient background, disease, surgical procedure, and complications. RESULTS: The types of hemophilia were A: 43 cases, B: four cases, and von Willebrand disease: two cases (hemophilia severity: mild 32, moderate seven, severe 10). The target malignant diseases for surgery were hepatocellular carcinoma (HCC) in 20 cases, intrahepatic cholangiocellular carcinoma (CCC) in four cases, combined HCC-CCC in two cases, hilar CCC in two cases, and pancreatic cancer in four cases. As for the surgical procedure, limited resection (subsegmentectomy and partial hepatectomy) was performed in 16 cases of HCC even with normal liver function tests. Pancreaticoduodenectomy and distal pacreatectomy were performed for pancreatic cancers as in the standard procedure. Postoperative complications were postoperative bleeding in two cases after hepatectomy and one after pancreatectomy in one case. When compared with Japanese National Clinical Data base, the complication rates after hepatectomy and pancreatectomy were not conspicuous in hemophilic patients. CONCLUSIONS: As long as they are performed in qualified centers, complication rate is not increased in hemophilic patients undergoing HBPS.

What is the optimal surgical treatment for hepatocellular carcinoma beyond the debate between anatomical versus non-anatomical resection?

The optimal type of hepatectomy for hepatocellular carcinoma (HCC)-anatomical or non-anatomical resection-remains controversial despite numerous comparative studies. There are common fundamental issues in published studies comparing anatomical resection with non-anatomical resection: (1) confounding by indication, (2) setting primary outcomes, and (3) a lack of a clear definition of non-anatomical resection. This degrades the quality of the comparison of the two types of surgery. To measure the therapeutic effect of hepatectomy, it is essential to understand the accumulated knowledge underlying these issues, such as the mechanism of hepatocellular carcinoma spread, tumor blood flow drainage theory, and the three patterns of hepatocellular carcinoma recurrence: (1) local intrahepatic metastasis, (2) systemic metastasis, and (3) multicentric carcinogenesis recurrence. Based on evidence that the incidence of local intrahepatic metastasis was so low it was almost negligible, the therapeutic effect of anatomical resection on the oncological survival was determined to be similar to that of non-anatomical resection. Recent research progress demonstrating the clinical impact of subclinical dissemination of HCC after surgery may stimulate new debate on the optimal surgical treatment for HCC beyond the comparison of anatomical and non-anatomical resection.

Induction of Immune Tolerance in Islet Transplantation Using Apoptotic Donor Leukocytes.

Allogeneic islet transplantation has become an effective treatment option for severe Type 1 diabetes with intractable impaired awareness due to hypoglycemic events. Although current immunosuppressive protocols effectively prevent the acute rejection associated with initial T cell activation in recipients, chronic rejection has remained an obstacle for achieving long-term allogeneic islet engraftment. The development of donor-specific immune tolerance to the allograft is the ultimate goal given its potential ability to overcome chronic rejection and disregard the need for maintenance immunosuppression, which may be toxic to islet grafts. Recently, a breakthrough in tolerance induction during allogeneic islet transplantation using apoptotic donor lymphocytes (ADLs) in a non-human primate model had been reported. Several studies have suggested that the clonal depletion, anergy, and expansion of the antigen-specific regulatory immune network are the mechanisms for donor-specific tolerance with ADLs, which act synergistically to induce robust transplant tolerance. This achievement represents a huge step forward toward the clinical application of immune tolerance induction. We herein summarize the reported operational induction therapies in islet transplantation using the ADLs. Moreover, a few obstacles for the engraftment of transplanted islets, such as islet immunogenicity and instant blood-mediated response, which need to be resolved in the future, are also discussed.

Surgical outcomes in gastroenterological surgery in Japan: Report of the National Clinical Database 2011-2019.

BACKGROUND: We aimed to present the 2019 annual report of the gastroenterological section of the National Clinical Database (NCD). METHODS: We reviewed 609,589 cases recorded in 2019 and 5,029,764 cases registered from 2011 to 2019 for the 115 selected gastroenterological surgical procedures. RESULTS: The main features of gastroenterological surgery in Japan were similar to those described in the 2018 annual report, namely, that 1) operative numbers gradually increased in all procedures, except gastrectomy and hepatectomy, which decreased in these years; 2) in all eight major gastroenterological surgeries, the age distribution tended toward older patients; 3) the morbidity of esophagectomy, hepatectomy, and pancreaticoduodenectomy increased, but mortality was minimized in all procedures; 4) all eight major gastroenterological procedures have increasingly been performed under laparoscopy; and 5) board-certified surgeons were increasingly involved. These trends in recent years were more prominent in 2019. CONCLUSIONS: Thanks to the continuous cooperation and dedication of the surgeons, medical staff, and surgical clinical reviewers who registered the clinical data into the NCD, it is possible to understand the comprehensive landscape of surgery in Japan and to disclose new evidence in this field. The Japanese Society of Gastroenterological Surgery will continue to promote the value of this database and encourage the use of feedback and clinical studies using the NCD, now and in the future. Generating further approaches to surgical quality improvement are important directions for future research.