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Background: The aim of this study was to evaluate the effectiveness and safety of TJ-100 TSUMURA Daikenchuto (DKT) Extract Granules in preventing post-hepatectomy digestive symptoms and the effects on small intestinal mucosal atrophy. Methods: Eligible patients were randomly assigned to the DKT therapy and usual care groups in a 1:1 ratio. The DKT therapy group was administered DKT for 14 days after surgery or until the day of discharge if the patient left the hospital before 14 days, and the usual care group did not receive DKT. We used the numeric rating scale to measure abdominal pain and bloating after surgery and compared the results between the two groups to determine the efficiency of DKT. We also evaluated postoperative small intestinal mucosal atrophy using diamine oxidase (DAO) and glucagon-like peptide-2 (GLP-2) activities in the serum, and postoperative complications. Results: No adverse effects were observed in the DKT group. No significant difference was observed in the area under the curve for postoperative abdominal pain or bloating throughout the study period. No differences were observed in DAO2, GLP2, and other nutrition assessment indicators. Four postoperative infections were observed in three patients (two with intra-abdominal surgical site infections [SSIs] and two with pneumonia). All cases of infection occurred in the control group. Conclusions: Although DKT did not significantly improve postoperative symptoms, such as abdominal pain or bloating, it is widely used in Japan to improve bowel movement and is safely prescribed for patients undergoing hepatectomy with a tendency toward less postoperative infection.

Abstract Aim The Japanese National Clinical Database, which covers more than 95% of the surgeries performed in Japan, is the largest nationwide database. This is the 2021 annual report of the Gastroenterological Section of the National Clinical Database, which aims to present the short‐term outcomes of cases registered in 2021 and discuss significant changes and insights into gastroenterological surgeries observed over the decade. Methods We reviewed the data of patients registered in the National Clinical Database between 2012 and 2021. Results In total, 5 788 093 cases, including 597 780 cases in 2021, were extracted from the National Clinical Database. The number of surgeries resumed its original trend after a uniform decrease due to the coronavirus disease 2019 pandemic. The patient population continues to age, and the proportion of female patients is steadily increasing. The trend of surgeries being conducted in certified institutions with the involvement of board‐certified surgeons is consistently rising. Moreover, the increasing trend of endoscopic surgery rate is still maintained. Although operative mortality is declining, the trend of increasing postoperative complications continues. Surgery on the esophagus, liver, and pancreas has shown substantial improvements in operative mortality, with a high participation rate of board‐certified surgeons. Surgical procedures with a high incidence of emergency surgeries are characterized by low participation rates of board‐certified surgeons, increased morbidity rates, and worse mortality outcomes. Conclusion This overview of surgical patients in Japan, obtained using data extracted from the National Clinical Database, may serve as a critical cornerstone for the future development of gastroenterological surgery.

Abstract This study aimed to address the diagnostic challenges in distinguishing between alcohol-related liver disease (ALD) and metabolic dysfunction-associated steatotic liver disease (MASLD). We utilized whole-slide imaging technology to conduct a comprehensive digital analysis of liver specimens collected from patients undergoing transplantation. This study included 36 and 17 patients with ALD and MASLD cirrhosis, respectively, who underwent transplantation at our institution. Digital slides were analyzed for fibrosis patterns using FibroNest™. Patient background characteristics were comparable between ALD (n = 36) and MASLD (n = 17) groups, except for sex. The ALD group exhibited thicker collagen per strand, longer and more flexural fibrosis, and a more heterogeneous distribution than the MASLD group. In patients with ALD and concomitant metabolic dysfunction, fiber distribution became relatively uniform, resembling MASLD. Application of the phenotypic fibrosis composite score achieved 100% sensitivity and specificity for ALD/MASLD diagnosis. Digital pathological analysis of the fibrosis patterns showed morphological differences between ALD and MASLD. This approach holds promise for histological differentiation, providing valuable insights beyond the current definitions based solely on alcohol intake. This study emphasizes the potential of digital pathology in refining the diagnostic criteria for hepatic disorders.

Abstract The liver requires careful handling intra‐operatively owing to its vital functions and complexity. Traditional open hepatectomy, while standard, is invasive and requires long recovery periods. Laparoscopic hepatectomy is a less invasive option, with its own challenges. The rise of robotic surgery, such as the da Vinci® system, improves precision and control, addressing the limitations of conventional methods, but brings new concerns, such as costs and training. This review focuses on the latest advancements in robotic hepatectomy from 2022/23 articles, delving into topics like “robotic surgery in liver transplantation,” “robotic hepatectomy for hilar cholangiocarcinoma,” “robotic vascular reconstruction following hepatectomy,” “robotic repeat hepatectomy,” and “prospective trials in robotic hepatectomy.” To retrieve articles, a focused literature search was conducted using PubMed for articles from 2022/23 with a 5‐year filter, excluding reviews. Initially, abstracts were screened, and relevant articles on robotic surgery were examined in full for inclusion in this review. Although all the above items are cutting‐edge, and many of the references are necessarily at the level of case reports, recent articles are still accompanied by surgical videos, which are useful to readers, especially surgeons who are considering imitating the procedures. In summary, we examined the recent advancements in robotic liver resection. The inclusion of videos that present new techniques aids in knowledge transfer. We anticipate the continued growth of this field of research.

Background & Aims: Polystyrene microplastics (PS-MPs) are pervasive in our daily life and can be ingested by the human body through bioaccumulation, causing organ damage, especially liver damage. However, the effect of PS-MPs bioaccumulation on human hepatotoxicity and their metabolism remains unclear. Recent studies have demonstrated that PS-MPs cause lipid and bile acid metabolism disorders. The human hepatobiliary organoids (HBOs) regenerated from chemically induced liver progenitor cells converted by mature hepatocytes and the bile duct provides a bioengineering model for liver disease and hepatic metabolism. Approach & Results: Exposure of HBOs to PS-MPs with a diameter of 1 µm for 48 h causes hepatotoxicity, hepatocyte damage, and changes in bile acid metabolism. PS-MPs could be accumulated into the bile ducts of HBOs, which can be promoted by ursodeoxycholic acid, increasing bile flow and volume by activating the bile transporter of BSEP in a dose-dependent manner along with MRP-2. The accumulation of PS-MPs in the bile duct was able to be inhibited by the bile transporter inhibitor of troglitazone that could inhibit the transporters of BSEP and MRP-2, which increased the hepatotoxicity caused by PS-MPs. Conclusions: This study provides insights into the metabolic pathways of PS-MPs in the liver and suggests potential therapeutic strategies to reduce MP-induced liver damage.

Abstract Background Liver disease imposes a significant medical burden that persists due to a shortage of liver donors and an incomplete understanding of liver disease progression. Hepatobiliary organoids (HBOs) could provide an in vitro mini-organ model to increase the understanding of the liver and may benefit the development of regenerative medicine. Methods In this study, we aimed to establish HBOs with bile duct (BD) structures and mature hepatocytes (MHs) using human chemically induced liver progenitor cells (hCLiPs). hCLiPs were induced in mature cryo-hepatocytes using a small-molecule cocktail of TGF-β inhibitor (A-83-01, A), GSK3 inhibitor (CHIR99021, C), and 10% FBS (FAC). HBOs were then formed by seeding hCLiPs into ultralow attachment plates and culturing them with a combination of small molecules of Rock-inhibitor (Y-27632) and AC (YAC). Results These HBOs exhibited bile canaliculi of MHs connected to BD structures, mimicking bile secretion and transportation functions of the liver. The organoids showed gene expression patterns consistent with both MHs and BD structures, and functional assays confirmed their ability to transport the bile analogs of rhodamine-123 and CLF. Functional patient-specific HBOs were also successfully created from hCLiPs sourced from cirrhotic liver tissues. Conclusions This study demonstrated the potential of human HBOs as an efficient model for studying hepatobiliary diseases, drug discovery, and personalized medicine.

Abstract Background Distal pancreatectomy (DP) with lymph node (LN) dissection is the standard procedure for pancreatic ductal adenocarcinoma of the tail (Pt‐PDAC). However, the optimal surgery including extent of LN dissection is still being debated. The present study investigated the incidence and prognostic impact of LN metastasis on patients suffering from Pt‐PDAC. Patients and method This multicenter, retrospective study involved 163 patients who underwent DP for resectable Pt‐PDAC at 12 institutions between 2013 and 2017. The frequency of LN metastasis and the effect of LN dissection on Pt‐PDAC prognosis were investigated. Results There were high incidences of metastases to the LNs along the splenic artery in the patients with Pt‐PDAC (39%). The rate of metastases in the LNs along the common hepatic, left gastric, and celiac arteries were low, and the therapeutic index for these LNs was zero. In pancreatic tail cancer located more distally, there were no metastases to the LNs along the common hepatic artery. Multivariate analysis revealed that tumor size was the only independent factor related to recurrence‐free survival (HR = 2.01, 95% CI = 1.33–3.05, p = 0.001). The level of pancreas division and LN dissection along the common hepatic artery did not affect the site of tumor recurrence or recurrence‐free survival. Conclusions LN dissection along the hepatic artery for Pt‐PDAC has little significance. Distal pancreatic transection may be acceptable in terms of oncological safety, but further examination of short‐term outcomes and preservation of pancreatic function is required.

Autologous oral mucosal epithelial cell sheet (AOMECS) transplantation has recently been applied in human patients to prevent postprocedural stenosis following endoscopic submucosal dissection (ESD) for esophageal squamous cell carcinoma. However, the long-term safety of AOMECS transplantation remains unclear. We evaluated the long-term outcomes of 10 patients who participated in a clinical trial of AOMECS transplantation after esophageal ESD. Additionally, we assessed the local DNA damage response in the esophageal epithelium using p53 binding protein 1 (53BP1) immunofluorescence in post-AOMECS biopsy specimens. The median follow-up period was 118.5 months (range: 46–130 months). Two patients developed primary esophageal cancer near the AOMECS site and successfully underwent additional ESD. One patient developed lymph node metastasis and underwent chemotherapy. None of the patients died from the original disease, although one patient died from unrelated causes. The rate of abnormal 53BP1 nuclear foci, indicative of increased genome instability, increased with the progression of neoplasia in patients post AOMECS. Our case series suggests that AOMECS transplantation provides an acceptable long-term prognosis and 53BP1 foci may serve as a useful marker for assessing DNA instability in the post-AOMECS esophageal epithelium.

Background. Patients undergoing liver transplantation are in a state of coagulopathy before surgery because of liver failure. Intraoperative hemorrhage, massive transfusions, and post–reperfusion syndrome further contribute to coagulopathy, acidosis, and hypothermia. In such situations, temporary cessation of surgery with open abdominal management and resuscitation in the intensive care unit (ICU), which is commonly used as a damage control strategy in trauma care, may be effective. We assessed the outcomes of open abdominal management in liver transplantation and the corresponding complication rates. Methods. We retrospectively reviewed the outcomes of patients undergoing open abdominal management among 250 consecutive liver transplantation cases performed at our institution from 2009 to 2022. Results. Open abdominal management was indicated in 16 patients. The open abdomen management group had higher Model for End-stage Liver Disease scores (24 versus 16, P

Abstract Background The COVID‐19 outbreak made conventional medical care impossible, forcing changes in both healthcare providers and patients. In Japan, COVID‐19 infection began spreading in earnest in 2020 and exploded in 2021. There was concern that the medical impact of COVID‐19 in 2021 would differ from that in 2020. We aimed to clarify the impact of COVID‐19 on mortality and anastomotic leakage in laparoscopic surgery for gastric cancer and rectal cancer in Japan using the National Clinical Database (NCD). Methods We collected data from patients who underwent laparoscopic distal gastrectomy (LDG) and laparoscopic low anterior resection (LLAR) from January 2018 to December 2021 from the NCD, a web‐based surgical registration system in Japan. The number of surgical cases, monthly incidence of mortality and morbidity (anastomotic leakage), standardized mortality ratio (SMR), and standardized morbidity‐leakage ratio (SMLR [ratio of observed patients to expected patients calculated using the risk calculator established in the NCD]) were evaluated. Results The numbers of LDG and LLAR cases continued to decline in the first year of the pandemic in 2020 and were as low in 2021 as in 2020. Although the numbers of robot‐assisted LDG and LLAR cases increased, the growth rate was lower than the rate of increase prior to the pandemic. Mortality and anastomotic leakage, two of the most important complications, as assessed by SMR and SMLR, did not worsen during the pandemic in comparison to the pre‐pandemic period. Conclusions Laparoscopic surgeries were performed safely in Japan and were not affected by the COVID‐19 pandemic.

Abstract Background The detection rate of superficial non-ampullary duodenal epithelial tumors (SNADETs) has recently been increasing. Large tumors may contain malignant lesions and early therapeutic intervention is recommended. Endoscopic mucosal dissection (ESD) is considered a feasible treatment modality, however, the anatomical and physiological characteristics of the duodenum create a risk of postoperative perforation after ESD. Methods To explore whether myoblast sheet transplantation could prevent delayed perforation after ESD, a first-in-human (FIH) clinical trial of laparoscopic autologous myoblast sheet transplantation after duodenal ESD was launched. Autologous myoblast sheets fabricated from muscle tissue obtained seven weeks before ESD were transplanted laparoscopically onto the serous side of the ESD. The primary endpoints were the onset of peritonitis due to delayed perforation within three days after surgery and all adverse events during the follow-up period. Results Three patients with SNADETs ≥ 20 mm in size underwent transplantation of a myoblast sheet onto the serous side of the duodenum after ESD. In case 1, The patient’s postoperative course was uneventful. Endoscopy and abdominal computed tomography revealed no signs of delayed perforation. Despite incomplete mucosal closure in case 2, and multiple micro perforations during ESD in case 3, cell sheet transplantation could prevent the postoperative massive perforation after ESD, and endoscopy on day 49 after transplantation revealed no stenosis. Conclusions This clinical trial showed the safety, efficacy, and procedural operability of this novel regenerative medicine approach involving transplanting an autologous myoblast sheet laparoscopically onto the serosa after ESD in cases with a high risk of delayed perforation. This result indicates the potential application of cell sheet medicine in treating various abdominal organs and conditions with minimal invasiveness in the future. Trial registration jRCT, jRCT2073210094. Registered November 8 2021, https://jrct.niph.go.jp/latest-detail/jRCT2073210094 .

Abstract Aim The aim of this study was to verify the clinical feasibility of tele‐proctoring using our ultra‐low latency communication system with shared internet access. Methods Connections between two multiple remote locations at various distances were established through the TELEPRO® tele‐proctoring system. The server records the latency between the two locations for tele‐proctoring using the annotations. Questionnaires were administered to the surgeons, assistants, and medical staff. Respondents rated the quickness and quality of communication in terms of latency and disturbances in the audio, video, and usefulness of the live telestrations with annotation. Results Seven hospitals tele‐proctored with Sapporo Medical University between January 2021 and September 2022. The median latency of annotation between the two locations ranged from 24.5 to 48.5 ms. No major technological problems occurred, such as streaming interruption, loss of video or audio, poor resolution. The video encoding time was 10 ms, and its decoding time was 0.8 ms. The total latency positively correlated with the distance between two locations (R = 0.55, p

Abstract Aim After pancreaticoduodenectomy, 20–40% of patients develop steatotic liver disease (SLD), and steatohepatitis can be a problem. Although patatin‐like phospholipase domain‐containing 3 protein (PNPLA3) and transmembrane 6 superfamily member 2 (TM6SF2) polymorphisms are involved in SLD and steatohepatitis development, whether this is the case after pancreaticoduodenectomy is unclear. Methods and Results Forty‐three patients with pancreatic cancer who underwent pancreaticoduodenectomy at our hospital between April 1, 2018, and March 31, 2021, were included. We extracted DNA from noncancerous areas of residual specimens after pancreaticoduodenectomy and determined PNPLA3 and TM6SF2 gene polymorphisms using real‐time polymerase chain reaction. SLD was defined as a liver with an attenuation value of ≤40 HU or a liver‐to‐spleen ratio of ≤0.9 on computed tomography. We defined high hepatic fibrosis indexes (HFI) instead of steatohepatitis as a Fibrosis‐4 index of ≥2.67 or nonalcoholic fatty liver disease fibrosis score of ≥0.675 in patients with SLD. The cumulative incidence of SLD (P = 0.299) and high HFI (P = 0.987) after pancreaticoduodenectomy were not significantly different between the PNPLA3 homozygous and minor allele groups. The incidences of high HFI at 1 year after pancreaticoduodenectomy were 16.8% and 27.0% in the TM6SF2 major homozygous and minor allele groups, respectively, with a significant difference in the cumulative incidence (P = 0.046). Conclusion The TM6SF2 minor allele may contribute to steatohepatitis development after pancreaticoduodenectomy.

Abstract Liver metastasis in gastric cancer is incurable. Alpha-fetoprotein-producing gastric cancer has a poor prognosis and is prone to liver metastasis. We investigated the association between preoperative serum alpha-fetoprotein levels, liver metastasis, and expression of primitive enterocyte phenotype markers. We reviewed the medical records of 401 patients with gastric cancer who underwent curative surgical resection and immunohistochemically evaluated the primitive phenotype markers. The preoperative serum alpha-fetoprotein levels were elevated and normal in 8 and 393 patients, respectively. Liver metastasis was more frequent in patients with higher preoperative alpha-fetoprotein levels. The 5-year postoperative recurrence-free survival and overall survival rates were significantly worse in patients with higher preoperative serum alpha-fetoprotein levels. Although alpha-fetoprotein and Glypican3 and Spalt-like transcription factor 4 tended to be stained with high preoperative serum alpha-fetoprotein levels, these markers were also positive in some patients with normal alpha-fetoprotein levels. In summary, patients with gastric cancer and high preoperative serum alpha-fetoprotein levels have a poor prognosis and high incidence of liver metastasis. Alpha-fetoprotein can help detect liver metastasis relating to the primitive enterocyte phenotype.

Abstract Background Thyroid storm can be complicated by liver dysfunction, which may occasionally progress to acute liver failure. We herein report a case of acute liver failure following thyroid storm that was treated with living donor liver transplantation after resuscitation from cardiopulmonary arrest. Case report The patient was a woman in her 40 s who had been diagnosed with an abnormal thyroid function. She suffered from fatigue and vomiting, and was found to have consciousness disorder, a fever, and tachycardia with a neck mass. She was diagnosed with thyroid storm and was referred to our hospital. After arrival, she went into cardiopulmonary arrest and veno-arterial extracorporeal membrane oxygenation was initiated. In addition to treatment for thyroid storm with antithyroid drugs, steroids, and plasma exchange, extracorporeal life support was required for 5 days. However, despite improvements in her thyroid function, her liver function deteriorated. We planned living donor liver transplantation for acute liver failure after ensuring the recovery and control of the thyroid function following total thyroidectomy. The donor was her husband who donated the right lobe of his liver. Although she experienced acute cellular rejection after surgery, and other complications—including intra-abdominal hemorrhaging and ischemic changes in the intestine—her liver function and general condition gradually improved. One year after living donor liver transplantation, the patient was in a good condition with a normal liver function. Conclusions To our knowledge, this is the first report of living donor liver transplantation in a patient with acute liver failure following thyroid storm. Liver transplantation should be recognized as an effective treatment for acute liver failure following thyroid storm.

Recent advances in systemic therapy for hepatocellular carcinoma (HCC) have led to debates about the feasibility of combination therapies, such as systemic therapy combined with surgery or transarterial chemoembolization, for patients with advanced HCC. However, a lack of consensus on the oncological resectability criteria has hindered discussions of “conversion therapy” and the optimal management in patients with HCC. To address this issue, the Japan Liver Cancer Association (JLCA) and the Japanese Society of Hepato-biliary-pancreatic Surgery (JSHBPS) established a working group and discussed the concept of borderline resectable HCC. Herein, we present a consensus statement from this expert panel on the resectability criteria for HCC from the oncological standpoint under the assumption of technically and liver-functionally resectable situations. The criteria for oncological resectability in HCC are classified into three grades: Resectable (R), representing an oncological status for which surgery alone may be expected to offer clearly better survival outcomes as compared with other treatments; Borderline resectable 1 (BR1), representing an oncological status for which surgical intervention as a part of multidisciplinary treatment may be expected to offer survival benefit; and Borderline resectable 2 (BR2), representing an oncological status for which the efficacy of surgery is uncertain and the indication for surgery should be determined carefully under the standard multidisciplinary treatment. These criteria aim to provide a common language for discussing and analyzing the treatment strategies for advanced HCC. It is also expected that these criteria will be optimized, modified, and updated based on further advancements in systemic therapies and future validation studies.

Abstract Background Although the standard therapy for advanced-stage hepatocellular carcinoma (HCC) is systemic chemotherapy, the combination of atezolizumab and bevacizumab (atezo + bev) with a high objective response rate may lead to conversion to resection in patients with initially unresectable HCC. This study aims to evaluate the efficacy of atezo + bev in achieving conversion surgery and prolonged progression-free survival (PFS) for initially unresectable HCC. Methods The RACB study is a prospective, single-arm, multicenter, phase II trial evaluating the efficacy of combination therapy with atezo + bev for conversion surgery in patients with technically and/or oncologically unresectable HCC. The main eligibility criteria are as follows: (1) unresectable HCC without a history of systemic chemotherapy, (2) at least one target lesion based on RECIST ver. 1.1, and (3) a Child‒Pugh score of 5–6. The definition of unresectable tumors in this study includes macroscopic vascular invasion and/or extrahepatic metastasis and massive distribution of intrahepatic tumors. Patients will be treated with atezolizumab (1200 mg/body weight) and bevacizumab (15 mg/kg) every 3 weeks. If the patient is considered resectable on radiological assessment 12 weeks after initial chemotherapy, the patient will be treated with atezolizumab monotherapy 3 weeks after combination chemotherapy followed by surgery 3 weeks after atezolizumab monotherapy. If the patient is considered unresectable, the patient will continue with atezo + bev and undergo a radiological assessment every 9 weeks until resectable or until disease progression. The primary endpoint is PFS, and the secondary endpoints are the overall response rate, overall survival, resection rate, curative resection rate, on-protocol resection rate, and ICG retention rate at 15 min after atezo + bev therapy. The assessments of safety and quality of life during the treatment course will also be evaluated. The number of patients has been set at 50 based on the threshold and the expected PFS rate at 6 months after enrollment of 40% and 60%, respectively, with a one-sided alpha error of 0.05 and power of 0.80. The enrollment and follow-up periods will be 2 and 1.5 years, respectively. Discussion This study will elucidate the efficacy of conversion surgery with atezo + bev for initially unresectable HCC. In addition, the conversion rate, safety and quality of life during the treatment course will also be demonstrated. Trial registration This study is registered in the Japan Registry of Clinical Trials (jRCTs051210148, January 7, 2022).

Abstract Aim This study aimed to evaluate the impact of the coronavirus disease (COVID‐19) pandemic on elective endoscopic surgeries in Japan using the National Clinical Database. Methods We retrospectively analyzed the clinicopathological factors and surgical outcomes of laparoscopic cholecystectomy (LC), laparoscopic distal gastrectomy (LDG), and laparoscopic low anterior resection (LLAR) and compared the monthly numbers of each procedure performed in 2020 with those in 2018 and 2019. The degree of infection in prefectures was classified into low and high groups. Results In 2020, the number of LCs (except for acute cholecystitis) was 76 079 (93.0% of that in 2019), the number of LDGs was 14 271 (85.9% of that in 2019), and the number of LLARs was 19 570 (88.1% of that in 2019). Although the number of robot‐assisted LDG and LLAR cases increased in 2020, the growth rate was mild compared with that in 2019. There was little difference in the number of cases in the degree of infection in the prefectures. The numbers of LC, LDG, and LLAR cases decreased from May to June and recovered gradually. In late 2020, the proportion of T4 and N2 cases of gastric cancer and the number of T4 cases of rectal cancer increased compared with those in 2019. There was little difference between the proportions of postoperative complications and mortality in the three procedures between 2019 and 2020. Conclusion The number of endoscopic surgeries decreased in 2020 as a result of the COVID‐19 pandemic. However, the procedures were performed safely in Japan.

Abstract Aim Liver allografts from brain‐dead donors, which were declined and were eventually not transplanted due to accompanying marginal factors, have never been surveyed in Japan. We surveyed the declined allografts and discussed the graft potential focusing on various marginal factors. Methods We collected data on brain‐dead donors between 1999 and 2019 from the Japan Organ Transplant Network. We divided their liver allografts into declined (nontransplanted) and transplanted ones, and then characterized declined ones focusing on their timepoints of decline and accompanying marginal factors. For each marginal factor, we calculated the decline rate from the number of declined and transplanted allografts, and assessed the 1‐year graft survival rate from transplanted allografts. Results A total of 571 liver allografts were divided into 84 (14.7%) declined and 487 (85.3%) transplanted ones. In the declined allografts, a majority was declined after laparotomy (n = 55, 65.5%), most of which had steatosis and/or fibrosis (n = 52). Out of the moderate steatotic (without F ≥ 2 fibrosis) allografts (n = 33), 21 were declined and 12 were transplanted, leading to a 63.6% decline rate. The latter 12 achieved a 92.9% 1‐year graft survival rate after transplantation. Comparison of donor background showed no significant difference between the declined and transplanted allografts. Conclusion Pathological abnormalities of steatosis/fibrosis seem to be the most common donor factor leading to graft decline in Japan. Allografts with moderate steatosis were highly declined; however, transplanted ones achieved promising outcomes. This national survey highlights the potential utility of liver allografts with moderate steatosis.

Abstract Loss of E-cadherin expression is a poor prognostic factor in patients with breast cancer. Breast cancer cells co-cultured with adipocytes reportedly promote E-cadherin attenuation and tumor progression. The current study aimed to investigate the association of reduced E-cadherin expression with adipose tissue invasion (ATI) and prognosis in breast cancer. Surgical specimens were collected from 188 women with invasive ductal carcinoma of the breast who had undergone surgery without neoadjuvant treatment. We compared E-cadherin expression in ATI and invasive front (IF) using immunohistochemistry with ImageJ. Reduced E-cadherin expression was detected not only in the ATI area but also in the IF, and the degree of reduced E-cadherin expression was positively correlated with both areas. In patients with lymph node metastasis compared to those without, E-cadherin expression was reduced and this reduction was associated with poor recurrence-free survival. We concluded that E-cadherin expression is reduced not only at the ATI area but also at the IF of the tumor. Reduced E-cadherin expression is a clear prognostic factor for breast cancer. Hence, future research is warranted for establishing an objective and quantitative E-cadherin staining assay that will allow clinical use of E-cadherin as a prognostic factor.

We previously reported the efficacy of chemically induced liver progenitors (CLiP) as a source of cells for transplantation in patients with liver disease. This study aimed to characterize CLiP derived from steatotic livers using a pig model for future clinical applications. Livers were removed from miniature pigs with diet-induced steatosis and normal livers by laparoscopic hepatectomy. Mature hepatocytes (MH) isolated from the livers of each group were cultured in differentiation medium composed of Y-27632, A-83-01, and CHIR99021 (YAC medium). The characteristics of CLiP, including liver-specific function, proliferative capacity in vivo, and extracellular vesicles (EVs) production, were evaluated. Although CLiP in both groups expressed hepatic progenitor cell markers (Epithelial cell adhesion molecule and Trophoblast cell surface antigen 2), the proliferative potential was higher for the disease group than the healthy group. In contrast, markers of functional MH after re-differentiation were only detected in the healthy group. Both groups showed high cell viability and the ability to differentiate into albumin-positive cells in vivo. EVs counts were lower in disease-derived CLiP than in the normal group; however, there were no differences in microRNA expression within EVs. Using a pig model, CLiP was successfully produced from a liver that reproduced steatotic liver disease. Although there were slightly fewer EVs from CLiP in the disease group than in the normal liver group, the in vivo proliferative capacity of CLiP was high. Therefore, CLiP induced in the steatotic liver are a promising source for cell therapy in patients with liver disease.

Abstract 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.

Introduction: Cell sheet technology has been applied in the treatment of patients with severe cardiac failure. Although the paracrine effect of cell sheets accelerating angiogenesis is thought to be the intrinsic mechanism for improvement of cardiac function, little is known about how a cell sheet would function in the abdomen. Methods: We used acetic acid-induced gastric ulcer rat model to elucidate the mechanisms of myoblast sheet transplantation in the abdomen. Myoblast sheet was implanted onto the serosal side of the gastric ulcer and the effect of sheet transplantation was analyzed. The maximal diameter of the ulcer and the changes in the gene expression of various growth factors in transplanted site was analyzed. The progenitor marker CD34 was also examined by immunohistochemistry. Results: Cell sheet transplantation accelerated the ulcer healing. qPCR showed that angiogenic growth factors were significantly upregulated around the ulcer in the transplantation group. In addition, at first, HIF-1a and SDF-1 continued to increase from 3 h after transplantation to 72 h, then VEGF increased significantly after 24 h with a slight delay. An immunohistochemical analysis showed a statistically significant increase in CD34 positivity in the tissue around the ulcer in the transplantation group. Conclusion: Myoblast sheet secreted various growth factors and cytokines immediately after transplantation onto the serosal side of artificial ulcer in the abdomen. Autonomous secretion, resulting in the time-dependent and well-orchestrated gene expression of various growth factors, plays a crucial role in the cell sheet function. Cell sheet transplantation is expected to be useful to support angiogenesis of the ischemic area in the abdominal cavity.

Background Can Background be changed from bold to normal text?: Chemically-induced liver progenitors (CLiPs) have promising applications in liver regenerative medicine. We aimed to clarify the efficacy of CLiPs for ameliorating fibrosis in a diet-induced nonalcoholic steatohepatitis rat model, since nonalcoholic fatty liver disease is currently recognized as the most common form of chronic liver disease in developed countries. Methods: Primary mature hepatocytes were isolated from 7-week-old male Wistar rats. To establish CLiPs, isolated hepatocytes were cultured in differentiation medium composed of Y-27632, A-83-01, and CHIR99021 (YAC medium). As an animal model that reproduces NASH pathophysiology, 6-week-old severe combined immunodeficient (SCID) mice were carefully selected and prepared and fed with choline-deficient, L-amino acid-defined, high-fat diet (HFD). After 12 weeks’ HFD feeding, the mice were assigned to continue HFD with or without the administration of rat CLiPs (HFD + CLiPs and HFD-CLiPs, respectively). Rat CLiPs were administered from the spleen. Hepatic fibrosis was semi-quantitatively evaluated according to histology. Liver parenchyma and blood samples were collected for biochemical analyses. Results: Rat CLiPs were positive for CK19 and EpCAM were successfully delivered to the liver. At 8 weeks after CLiPs transplantation, the HFD + CLiPs group showed significantly less positive staining than the HFD-CLiPs group. Alanine aminotransferase significantly improved in the HFD + CLiPs group, as demonstrated by Azan staining and αSMA immunostaining. RT qPCR showed that the liver expression of MMP2 and 9 tended to be higher in the HFD + CLiPs group. Conclusions: The anti-fibrotic effect of CLiPs was demonstrated in the immunodeficient NASH animal model and may have therapeutic applications in humans.

Introduction: Endoscopic submucosal dissection (ESD) is a minimally invasive treatment for early esophageal cancer. However, large mucosal defects after esophageal ESD result in refractory strictures. In the present study, we histologically evaluated the endoscopic transplantation of allogeneic epidermal cell sheets (ECSs) as a feasible therapy for preventing esophageal stricture after circumferential ESD in a porcine model. Methods: Epidermal cells were isolated from the skin tissue of allogeneic pigs and cultured on temperature-responsive cell culture inserts for 2 weeks. Transplantable ECSs were harvested by reducing the temperature and endoscopically transplanting the sheets to ulcer sites immediately after esophageal ESD. The engraftment of transplanted ECSs was then evaluated in two pigs at 7 days after transplantation. Next, ten pigs were divided into two groups to evaluate the endoscopic transplantation of allogeneic ECSs for the prevention of esophageal strictures after ESD. Allogeneic ECSs were transplanted immediately after esophageal ESD in the transplantation group (n = 5), whereas the control group (n = 5) did not undergo transplantation. Results: Most of the transplanted allogeneic ECSs were successfully engrafted at the ulcer sites in the early phase. Fluorescence in situ hybridization analysis revealed that several allogeneic cells were present in the transplanted area at 7 days after ESD. At 14 days after ESD, significant differences in body weight loss, dysphagia scores, and mucosal strictures were observed between the control and transplantation groups. Transplanting allogeneic ECSs after esophageal ESD promotes mucosal healing and angiogenesis and prevents excessive inflammation and granulation tissue formation. Conclusions: Endoscopic and histological analyses revealed that allogeneic ECSs promoted artificial ulcer healing after ESD, preventing esophageal strictures after ESD.

Abstract Background Hospital-acquired disability (HAD) in patients who undergo living donor liver transplantation (LDLT) is expected to worsen physical functions due to inactivity during hospitalization. The aim of this study was to explore whether a decline in activities of daily living from hospital admission to discharge is associated with prognosis in LDLT patients, who once discharged from a hospital. Methods We retrospectively examined the relationship between HAD and prognosis in 135 patients who underwent LDLT from June 2008 to June 2018, and discharged from hospital once. HAD was defined as a decline of over 5 points in the Barthel Index as an activity of daily living assessment. Additionally, LDLT patients were classified into four groups: low or high skeletal muscle index (SMI) and HAD or non-HAD. Univariate and multivariate Cox proportional hazard models were used to evaluate the association between HAD and survival. Results HAD was identified in 47 LDLT patients (34.8%). The HAD group had a significantly higher all-cause mortality than the non-HAD group (log-rank: p

Abstract Aim Using nationwide data collected over the past 20 years, we aimed to investigate deceased donor liver transplantation (DDLT) outcomes to develop a unique risk model that can be used to establish a standard for organ acceptance in Japan. Methods Data were collected for 449 recipients aged ≥18 years who underwent DDLT between 1999 and 2019. Least absolute shrinkage and selection operator (LASSO) regression analysis was utilized to develop an original risk score model for 1‐year graft loss (termed the Japan Risk Index [JRI]). We developed risk indices according to recipient, donor, and surgery components (termed JRI‐R, D, and S, respectively). The JRI was validated via a 5‐fold cross‐validation. We also compared DDLT outcomes and risk indices among Era1 (−2011), Era2 (−2015), and Era3 (−2019). Results The 1‐year graft survival rate was 89.5% and improved significantly, reaching 84.7%, 87.6%, and 93.9% in Era1, Era2, and Era3, respectively. The JRI was calculated as JRI‐R (re‐transplantation, Model for End‐Stage Liver Disease score, medical condition in intensive care unit) × JRI‐D (age, catecholamine index, maximum sodium, maximum total bilirubin) × JRI‐S (total ischemic time) × 0.84. The risk model achieved a mean C‐statistic value of 0.81 in the validation analysis. The risk index was significantly lower in Era3 than in Era2. Conclusion Changes in the risk index over time indicated that avoiding risks contributed to the improved outcomes in Era3. The JRI is unique to adult DDLT in Japan and may be useful as a reference for organ acceptance in the future.

Abstract Liver transplantation (LT) for non‐hepatocellular carcinoma is still a debatable indication. Recently, hilar cholangiocellular carcinoma (hCCC) has attracted interest as a new indication for LT, but LT in this case should be carefully considered. Based on the recent meta‐analysis for intrahepatic CCC (IHCCC) and our results from incidental IHCCC transplanted for other diseases such as primary sclerosing cholangitis, the indication for LT for IHCCC should be limited to a single tumor less than 2 cm. For hCCC, with pre‐transplant chemoradiotherapy and careful selection criteria, long‐term survival after LT could be attained. In order to improve the results of LT for intrahepatic and hCCC, further studies are required on the ingenuity of immunosuppressive therapy combined with chemotherapy, and optimal treatment methods to prevent recurrence, as well as initial case selection.

Background: The intrahepatic bile ducts (BDs) play an important role in the modification and transport of bile, and the integration between the BD and hepatocytes is the basis of the liver function. However, the lack of a source of cholangiocytes limits in vitro research. The aim of the present study was to establish three-dimensional BDs combined with human mature hepatocytes (hMHs) in vitro using chemically induced human liver progenitor cells (hCLiPs) derived from hMHs.Methods: In this study, we formed functional BDs from hCLiPs using hepatocyte growth factor and extracellular matrix. BDs expressed the typical biliary markers CK-7, GGT1, CFTR and EpCAM and were able to transport the bile-like substance rhodamine 123 into the lumen. The established three-dimensional BDs were cocultured with hMHs. These cells were able to bind to the BDs, and the bile acid analog CLF was transported from the culture medium through the hMHs and accumulated in the lumen of the BDs. The BDs generated from the hCLiPs showed a BD function and a physiological system (e.g., the transport of bile within the liver) when they were connected to the hMHs.Conclusion: We present a novel in vitro three-dimensional BD combined with hMHs for study, drug screening and the therapeutic modulation of the cholangiocyte function.

Abstract Background and Aim Treatment for small hepatocellular carcinoma (HCC) is determined based on the results of a liver function test and the tumor location and spread. The present study compared the outcomes among local therapy, hepatic resection (HR), and living‐donor liver transplantation (LDLT) for small HCC in a single institute. Methods We compared the overall survival, recurrence‐free survival, and cancer‐specific survival rates in patients with three HCC nodules

Abstract In Japan, asymptomatic metastatic breast cancer (MBC) is often detected using tumor markers or imaging tests. We aimed to investigate differences in clinicopathological features, prognosis, and treatment between asymptomatic and symptomatic MBCs. Patients with MBC were retrospectively divided into asymptomatic and symptomatic groups to compare their prognosis by breast cancer subtype: luminal, human epidermal growth factor receptor 2 positive, and triple negative. Of 204 patients with MBC (114 asymptomatic, 90 symptomatic), the symptomatic group had a higher frequency of multiple metastatic sites and TN subtype. All cohorts in the asymptomatic group tended to or had longer post-recurrence survival (PRS) than those in the symptomatic group. In contrast, all cohorts and TN patients in the asymptomatic group tended to have or had longer overall survival (OS) than those in the symptomatic group, although no significant difference was observed in the luminal and HER2 subtypes. In the multivariate analysis, TN, recurrence-free survival, multiple metastatic sites, and symptomatic MBC were independently predictive of PRS. Regarding the luminal subtype, the asymptomatic group had longer chemotherapy duration than the symptomatic group, with no significant difference in OS between the groups. Asymptomatic and symptomatic MBCs differ in terms of subtypes and prognosis, and whether they require different treatment strategies for each subtype warrants further investigation.

Abstract Background Obturator hernia (OH) is an extremely rare abdominal wall hernia with risk factors including aging, female sex, emaciation, and increased abdominal pressure. Its symptoms are nonspecific, and diagnosis is often delayed; however, this delay can lead to a fatal course. Therefore, early diagnosis and surgical intervention are necessary to reduce the mortality rate associated with OH. Considering the risk factors for OH, patients currently undergoing hemodialysis (HD) may be particularly vulnerable to OH. Here, we report two cases of OH in patients undergoing HD along with a review of the relevant literature. Case presentation Case 1 included a 76-year-old female undergoing HD due to autosomal dominant polycystic kidney disease. She was hospitalized for upper abdominal pain, vomiting, and diarrhea. On the day of hospitalization, she was diagnosed with OH using computed tomography and underwent emergency surgery. Case 2 included a 90-year-old emaciated female who was admitted to our hospital for projectile vomiting while undergoing HD. She was diagnosed with OH and shock, but surgery was not performed due to shock. Nonetheless, her blood pressure gradually increased, and she completely recovered. Spontaneous reduction in OH was confirmed on the third day of hospitalization. Both patients recovered well. Conclusions The symptoms of OH are non-specific, and certain symptoms such as vomiting and anorexia are often overlooked because they are common in patients undergoing HD. It is important to include OH in the differential diagnosis of digestive organ symptoms in patients undergoing HD, especially in those with risk factors for OH, such as elderly female patients on HD due to autosomal dominant polycystic kidney disease.

Abstract Objectives Anastomotic biliary strictures (ABSs) are common complications following living donor liver transplantation (LDLT). We evaluated the feasibility of a novel removable, intraductal, fully covered, self‐expandable metallic stent (FCSEMS) for the treatment of ABSs following LDLT. Methods Nine patients with duct‐to‐duct ABSs that developed following LDLT were prospectively enrolled in this study. We placed a short FCSEMS with a long lasso and middle waist formation in each patient's ABS above the papilla and removed it 16 weeks later. Results The FCSEMS placements were successful in all nine cases. Four patients experienced mild cholangitis, which was resolved with conservative treatment. Additionally, there was one case of distal migration. The FCSEMSs were successfully removed from all the patients, and the clinical success rate was 100%. Stricture recurrence occurred in one (11.1%) patient during the follow‐up period. Limitations The small number and lack of comparison with other types of FCSEMSs and plastic stents. Conclusions Intraductal placement of FCSEMSs is useful for treating refractory ABSs after LDLT, although further studies are required with larger sample sizes.

Aim: The formation of a secondary liver is expected in ectopic transplants in liver therapy. It is reported that the transplantation of hepatocyte sheets constitutes one of the techniques used to form a secondary liver. Accordingly, we established a subcutaneous transplant for hepatocyte/fibroblast sheets in previous studies. In this development study with hepatocyte/fibroblast sheets, we evaluated the differences in transplantation sites to promote the maturation of transplanted tissue in a liver injury model. Methods: A cocultured hepatocyte sheet of fibroblasts (TIG-118 cells) and human hepatocytes (PXB cells) was prepared on a temperature-responsive culture dish. The prepared cocultured hepatocyte sheet was either transplanted subcutaneously or on the liver surface of a persistent liver injury model (cDNA-uPA/SCID mouse: uPA mouse), and was evaluated by the human albumin concentration in mouse blood. As a control group, hepatocyte cell sheets were used that were transplanted to both areas and compared. Results: Although the cocultured hepatocyte sheet led to functional improvements in the early stages of culture in subcutaneous transplantation, these did not last in the long-term after transplantation. Although coculture effects were not observed in the liver surface transplantation case, long-term functional expressions in mono- and cocultured sheets in the case of liver surface transplantation were exhibited compared with subcutaneous administration. Conclusion: These results suggest that sustained stimulation of liver regenerationvaries depending on the transplant site and is largely involved in the maturation of hepatocyte tissue.

Amniotic membrane is attracting attention as a new material for regenerative medicine. We herein report that the culture of primary rat hepatocytes on human amniotic membrane maintained their morphology and their production of albumin for at least two months. Human amniotic membrane was collected during planned cesarean section and kept frozen until usage. Primary rat hepatocytes were plated on human amniotic membrane. Hepatocytes accumulated as colonies on amniotic membrane, and their rat albumin level was maintained for two months. Their three-dimensional structure on extracellular matrix, which is abundant in amniotic membranes might influence the maintenance of the hepatocyte-specific function.

Introduction: Atezolizumab plus bevacizumab therapy is extremely effective in the treatment of intermediate-stage hepatocellular carcinoma (HCC), with a response rate of 44%, as reported in the IMbrave150 trial. When tumor shrinkage is obtained, achieving complete response (CR) is possible in many cases using curative conversion with resection, ablation, or super selective transarterial chemoembolization (TACE) with curative intent. This concept, i.e., curative conversion by combining systemic therapy and locoregional therapy, has not been reported before. This multicenter proof-of-concept study was conducted to show the value of curative conversion in immunotherapy-treated intermediate-stage HCC meeting TACE-unsuitable criteria. Methods: This study included 110 consecutive Child-Pugh A patients who received atezolizumab plus bevacizumab as first-line treatment for unresectable and TACE-unsuitable intermediate-stage HCC at seven centers in Japan. CR rate, drug-free rate, time to CR, change in liver function, efficacy in positron emission tomography (PET)-positive HCC, progression-free survival (PFS), and overall survival (OS) were assessed in patients who achieved CR using resection, ablation, super selective TACE with curative intent following atezolizumab plus bevacizumab or atezolizumab plus bevacizumab alone. Results: Clinical or pathological CR was achieved in 38 patients (35%) (median observation period: 21.2 months). The modalities of curative conversion in 35 patients were as follows: resection, 7; ablation, 13; and superselective TACE, 15. Three patients achieved clinical CR with atezolizumab plus bevacizumab therapy alone. Among the 38 CR patients, 25 achieved drug-free status. PFS was not reached, and three patients experienced recurrence after reaching CR. Regarding OS, there were no deaths in any of the CR patients. The albumin-bilirubin score did not deteriorate after locoregional therapy or resection. Of seven PET-positive patients who achieved CR with atezolizumab plus bevacizumab followed by curative conversion, five achieved drug-free status. Discussion/Conclusion: The achievement of CR rate by curative conversion in patients treated with atezolizumab plus bevacizumab as the preceding therapy for unresectable and TACE-unsuitable intermediate-stage HCC was 35%. Overall, 23% of patients achieved drug-free status and no recurrence was observed from this patient subgroup with CR and drug free status. Thus, achieving CR and/or drug-free status should be a therapeutic goal for patients with intermediate-stage HCC without vascular invasion or extrahepatic spread.

Portal vein thrombosis following liver transplantation is generally managed by endovascular treatment. Although several techniques are available for portal venous access, trans-splenic access is of interest because it avoids damage to the liver graft. However, the spleen cannot be punctured to access the portal vein after splenectomy. We herein report a case of portal vein thrombosis following living donor liver transplantation with simultaneous splenectomy successfully treated by percutaneous intervention with direct puncture of the retropancreatic splenic vein. The splenic vein was punctured under computed tomography guidance in the prone position. Portal venography revealed a contrast defect due to a thrombus in the extrahepatic to intrahepatic portal vein. The portal vein was reopened after thrombectomy, and the portal vein thrombosis did not recur for 2 y. The technique and advantages of our approach are described.

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.

Background Daikenchuto (DKT) has positive therapeutic effects on improving various gastrointestinal disorders. The present study investigated whether or not DKT has a potential therapeutic effect on chemotherapy-induced acute small intestinal mucositis (CIM) in a rat model. Methods Intraperitoneal injection of 10 mg/kg methotrexate (MTX) every 3 days for a total of 3 doses was used for induction of CIM in a rat model. The MTX and DKT-MTX groups were injected with MTX as above from the first day, and the DKT-MTX and DKT groups were administered 2.7% DKT via the diet at the same time. The rats were euthanized on day 15. Results The DKT-MTX group showed an improvement in the body weight and conditions of gastrointestinal disorders as well as increased levels of diamine oxidase in plasma and in the small intestinal villi. The pathology results showed that small intestinal mucosal injury in the DKT-MTX group was less severe than that in the MTX group. Immunohistochemistry for myeloperoxidase and malondialdehyde and quantitative real-time polymerase chain reaction (RT-qPCR) for TGF-β1 and HIF-1α showed that DKT attenuated peroxidative damage. The crypts in the DKT-MTX group contained more Ki-67-positive cells than MTX group. The zonula occluden-1 and claudin-3 results showed that DKT promoted repair of the mucosal barrier. RT-qPCR for the amino acid transporters EAAT3 and BO+AT also confirmed that DKT promoted mucosal repair and thus promoted nutrient absorption. Conclusion DKT protected against MTX-induced CIM in a rat model by reducing inflammation, stimulating cell proliferation, and stabilizing the mucosal barrier.

Aim We investigated the proportion of bedridden patients after emergency surgery among the elderly ages over 75; defined as the latter‐stage elderly in Japan, the associated factors, and interventions used to prevent it. Methods Eighty‐two latter‐stage elderly patients who underwent emergency surgery for non‐traumatic illness between January 2020 and June 2021 in our hospital were included in the study. Backgrounds and various perioperative factors were compared retrospectively between the groups including patients who became bedridden from Performance Status Scale 0 to 3 before admission (Bedridden group) and those who did not (Keep group). Results Three cases of death and seven patients who were bedridden before admission were excluded. The 72 remaining patients were divided into the Bedridden group (n = 10, 13.9%) and the Keep group (n = 62, 86.1%). There were significant differences in the prevalence of dementia, pre‐ and postoperative circulatory dynamics, renal dysfunction, coagulation abnormality, length of stay in the high care unit/intensive care unit, and number of hospital days, with a relative risk of 13 (1.74–96.71), a sensitivity of 1.00, and a specificity of 0.67 for a preoperative shock index of 0.7 or higher being associated with the Bedridden group. Among patients with a preoperative shock index of 0.7 or higher, there was a significant difference in SI at 24 h postoperatively between the two groups. Conclusion Preoperative shock index may be the most sensitive predictor. Early circulatory stabilization seems to be protective against patients becoming bedridden.

Introduction: The phase III REFLECT trial demonstrated that lenvatinib was superior to sorafenib in terms of progression-free survival (PFS), time to progression, and objective response rate (ORR) for patients with unresectable hepatocellular carcinoma (HCC). This study assessed the efficacy and safety of preoperative lenvatinib therapy for patients with oncologically or technically unresectable HCC. Methods: In this multicenter single-arm phase II trial, patients with advanced HCC and factors suggestive of a poor prognosis (macroscopic vascular invasion, extrahepatic metastasis, or multinodular tumors) were enrolled. Patients with these factors, even with technically resectable HCC, were defined as oncologically unresectable because of the expected poor prognosis after surgery. After 8 weeks of lenvatinib therapy, the patients were assessed for resectability, and tumor resection was performed if the tumor was considered technically resectable. The primary endpoint was the surgical resection rate. The secondary endpoints were the macroscopic curative resection rate, overall survival (OS), ORR, PFS, and the change in the indocyanine green retention rate at 15 min as measured before and after lenvatinib therapy. The trial was registered with the Japan Registry of Clinical Trials (s031190057). Results: Between July 2019 and January 2021, 49 patients (42 oncologically unresectable patients and 7 technically unresectable patients) from 11 centers were enrolled. The ORR was 37.5% based on mRECIST and 12.5% based on RECIST version 1.1. Thirty-three patients underwent surgery (surgical resection rate: 67.3%) without perioperative mortality. The surgical resection rate was 76.2% for oncologically unresectable patients and 14.3% for technically unresectable patients. The 1-year OS rate and median PFS were 75.9% and 7.2 months, respectively, with a median follow-up period of 9.3 months. Conclusions: The relatively high surgical resection rate seen in this study suggests the safety and feasibility of lenvatinib therapy followed by surgical resection for patients with oncologically or technically unresectable HCC.

Summary: Background: Delayed gastric emptying (DGE) is uncomfortable complication after left hepatectomy. The aim of this study is to show our strategy to prevent DGE after living donor left hepatectomy. Methods: The cases were divided into 3 groups as without any prevention (control group), prevented DGE with putting omentum between the liver and pylorus (O group), and with putting a Seprafilm (S group). The incidence of DGE and the CT finding 1 month after surgery were retrospectively compared between the groups. Results: The incidence of DGE was significantly decreased in O and S group than control group (P

Abstract 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.

Abstract The tumour microenvironment (TME) plays an important role in cancer development, progression, and metastasis. Various cytokines are present in the TME in oesophageal cancer. Oesophageal stricture is a major complication of endoscopic submucosal dissection (ESD) for oesophageal cancer, and inflammatory cytokines are closely related to its pathogenesis. However, the cytokine crosstalk involved in the oesophageal cancer TME and post-ESD stricture has not been fully elucidated. This study investigated the comprehensive cytokine dynamics following ESD in patients with oesophageal cancer. In addition, the effect of a novel preventive technique for post-ESD stricture, autologous cell sheet engraftment, on cytokine levels was evaluated. Various pro-inflammatory and anti-tumorigenic cytokines were elevated in patients with oesophageal cancer, and ESD transiently influenced cytokine concentrations. IL-1β and TNF-α, two major pro-inflammatory cytokines that induce oesophageal stricture, were significantly suppressed by cell sheet engraftment. In conclusion, this study revealed the distinct cytokine dynamics after ESD in patients with oesophageal cancer, together with the effect of autologous cell sheet engraftment on cytokine fluctuation. These results can accelerate research on the TME and therapeutic strategies for oesophageal cancer.

Objective: Unusual clinical course Background: In living-donor liver transplantation, biliary complications are considered an Achilles' heel. Consequently, various attempts have been made to reduce their incidence, and multiple innovations in surgical techniques have been reported. We herein report a case involving an intraoperative ultrasound cholangiogram in the recipient's abdominal cavity after reperfusion of the graft. Case Report: A 39-year-old male patient with decompensated alcoholic liver cirrhosis was admitted to our hospital for living-donor liver transplantation. The donor was his younger brother. Preoperative magnetic resonance cholangiopancreatography revealed no evidence of biliary anatomical variance; this could have been problematic when donating the left lobe graft. Intraoperative cholangiography showed that the left hepatic duct was sufficiently long for division, guaranteeing donor safety. Back-table observation of the bile duct revealed 3 orifices; of these, the central orifice was very small, and the corresponding bile duct was not evident on intraoperative cholangiography in donor surgery. After an injection of perfluorobutane microbubbles (Sonazoid) diluted 1000-fold into the small central orifice, the bile duct of segment 4 (B4) was clearly visualized with an intraoperative ultrasound cholangiogram. The off-label use of Sonazoid was approved by Nagasaki University Hospital. Based on this finding, we determined that all 3 openings required reconstruction and reconstructed them using a telescope reconstruction method. Conclusions: We verified that intraoperative ultrasound cholangiogram is useful as a tool to confirm the anatomy of the bile duct when it is not revealed through other evaluation techniques; hence, it is a method that transplant surgeons should be familiar with. [ABSTRACT FROM AUTHOR]

Background/Aim: Owing to underlying diseases and decreased physiological functions, frailty in elderly patients may be associated with adverse postoperative complications and mortality. To date, there are various frailty assessment methods, with the five-item modified frailty index (mFI-5) being an objective and concise evaluation tool. This study aimed to clarify whether mFI-5 scoring, a measure of frailty, can predict postoperative outcomes in elderly patients undergoing laparoscopic colorectal surgery. Patients and Methods: A total of 107 patients aged over 80 years who underwent laparoscopic colorectal surgery at Nagasaki University Hospital between 2011 and 2018 were included in this study. The mFI-5 was used to assess the preoperative condition of each patient, with scores compared against various postoperative outcome measures. Univariate analysis was used to determine between-group differences for pre- and post-operative variables. Results: Of the 107 patients [median age, 83 (80-99) years], 44.9% were male. The mFI-5 score was calculated and patients were divided into three groups: 0 (n=36, 33.6%); 1 (n=44, 41.1%); and 2+ (n=27, 25.3%). The groups were significantly associated with the American Society of Anesthesiology (ASA) classification (p<0.001). Postoperative complications occurred in 43 patients (40.2%), and a higher mFI-5 score was significantly associated with postoperative complications of Clavien-Dindo grade =III and duration of hospital stay. Conclusion: The mFI-5 is an objective and useful tool for predicting postoperative complications of laparoscopic surgery in elderly patients with colorectal cancer. [ABSTRACT FROM AUTHOR]