Long-term prognosis and DNA damage status after oral mucosal epithelial cell sheet transplantation following esophageal endoscopic submucosal dissection for squamous cell carcinoma: A case series.

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.

Essential updates 2022/2023: A review of current topics in robotic hepatectomy.

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.

Update on endoscopic surgery in Japan: Results of the 16th National Survey of endoscopic surgery by the Japan Society for Endoscopic Surgery.

This article reports the results of the 16th National Survey conducted by the Japan Society for Endoscopic Surgery (JSES) for 2020 and 2021. Laparoscopic cholecystectomy was first introduced to Japan in 1990 and has rapidly become popular because of its minimally invasive nature. Since then, the number of objective organs and indications for laparoscopic surgery have gradually expanded. In 2021, 290 787 patients underwent endoscopic surgery in all surgical domains. Of these, 124 614, 110 757, 23 156, 21 771, 6543, 2614, 535, 465, 247, and 58 underwent abdominal, obstetric and gynecologic, thoracic, urological, pediatric, orthopedic, bariatric, mammary and thyroid gland, cardiovascular, and plastic surgery, respectively. Owing to the impact of the coronavirus disease 2019 (COVID-19) infection spread, the incidence of many surgeries decreased in 2020, and levels are only now gradually recovering. However, despite the impact of COVID-19, robot-assisted surgeries were increasingly applied. The rate of complications did not change significantly, indicating that the procedure was performed safely, even with the spread of COVID-19.

A prospective randomized controlled study evaluating efficacy of Daikenchuto in the treatment of postoperative abdominal pain and bloating following hepatectomy.

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.

Open Abdominal Management for Damage Control in Liver Transplantation: A Single-center Experience.

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 < 0.01), a higher incidence of previous upper abdominal surgery (50% versus 18%, P < 0.01), more pretransplant ICU treatment (31% versus 10%, P = 0.03), and more renal replacement therapy (38% versus 12%, P = 0.01). At the time of the damage control decision, coagulopathy (81%), acidosis (38%), hypothermia (31%), and a high-dose noradrenaline requirement (75%) were observed. The abdominal wall was closed in the second operation in 75% of patients, in the third operation in 19%, and in the fourth operation in 6%. Postoperatively, the frequency of early allograft dysfunction was predominantly higher in the open abdominal management group (69%), whereas the frequency of vascular complications and intra-abdominal infection was the same as in other patients. Conclusions: Open abdominal management can be a crucial option in cases of complex liver transplant complicated by conditions such as hypothermia, acidosis, coagulopathy, and hemodynamic instability. Damage control management minimizes deterioration of the patient's condition during surgery, allowing completion of the planned procedure after stabilizing the patient's overall condition in the ICU.

Generation of human hepatobiliary organoids with a functional bile duct from chemically induced liver progenitor cells.

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-ß 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.

Improved survival of pediatric deceased donor liver transplantation recipients after introduction of the pediatric prioritization system: Analysis of data from a Japanese national survey.

BACKGROUND: In Japan, there has never been a national analysis of pediatric deceased donor liver transplantation (pDDLT) based on donor and recipient factors. We constructed a Japanese nationwide database and assessed outcomes of pDDLT focusing on the pediatric prioritization system introduced in 2018. METHODS: We collected data on pDDLTs (<18 years) performed between 1999 and 2021 from the Japan Organ Transplant Network and Japanese Liver Transplantation Society, identified risk factors for graft survival and compared the characteristics and graft survival in pDDLTs conducted before and after the introduction of the pediatric prioritization system. RESULTS: Overall, 112 cases of pDDLT were included, with a 1-year graft survival rate of 86.6%. Four poor prognostic factors were identified: recipient intensive care unit stay, model for end-stage liver disease/pediatric end-stage liver disease score, donor cause of death, and donor total bilirubin. After the introduction of the system, allografts from pediatric donors were more reliably allocated to pediatric recipients and the annual number of pDDLTs increased. The 1-year graft survival rate improved significantly as did pDDLT conditions indicated by the risk factors. CONCLUSIONS: Under the revised allocation system, opportunities for pDDLT increased, resulting in favorable recipient and donor conditions and improved survival.

Repeated Minimally Invasive Pancreatectomy for Intraductal Papillary Mucinous Neoplasm in the Remnant Pancreas: A Case Report.

BACKGROUND Minimally invasive pancreatectomy has become the standard practice for the management of benign and malignant pancreatic tumors. Techniques such as robotic and laparoscopic approaches are known to reduce morbidity by offering benefits such as less blood loss, reduced pain, shorter hospital stays, and quicker recovery times. The indication for repeated minimally invasive pancreatectomy for recurrent or de novo pancreatic neoplasm after primary pancreatic surgery remains debated. CASE REPORT A 50-year-old woman was admitted to our hospital with a diagnosis of an intraductal papillary mucinous neoplasm in the pancreatic head. In 2010, she underwent laparoscopic single-branch resection for a branch-type tumor in the pancreatic uncinate process. During a 5-year follow-up, a de novo intraductal papillary mucinous neoplasm was detected, showing gradual growth and the presence of a mural nodule over the next 7 years. The patient's CEA level was elevated to 7.0 ng/mL. Considering the tumor's progression and the appearance of a mural nodule, we recommended a robot-assisted Whipple procedure. The operation began with laparoscopic adhesiolysis. After detachment of the adhesions and remobilization of the duodenum using the Kocher maneuver, the operation continued with the Da Vinci surgical system. The postoperative period was uneventful, and the patient was discharged on postoperative day 20. Pathological examination revealed intraductal papillary mucinous carcinoma in situ with negative resection margins. CONCLUSIONS This case verifies the safety and feasibility of performing a robotic Whipple procedure for a newly diagnosed pancreatic neoplasm in patients who have previously undergone minimally invasive pancreatic surgery.

Analysis of Expression Status and Relationship Between Senescence-related Genes and Pancreatic Function-related Genes in Human Islets of Langerhans from Donors of Various Ages.

BACKGROUND/AIM: Although studies on senescence-related genes using human islets of Langerhans have been performed, the expression of senescence-related genes and their association with functional genes in islets remain insufficiently investigated. We aimed to determine whether and what types of senescent-related genes are expressed in islets and identify their correlations with pancreatic function-related genes by using islets isolated for transplantation from individuals of various ages. MATERIALS AND METHODS: Islets from deceased donors of both sexes and different ages were used for analysis. The expression status of senescence-related genes (glutaminase 1, interleukin 6, interleukin 8, cyclin-dependent kinase inhibitor 2A, cyclin-dependent kinase inhibitor 1A, and senescence-associated beta-galactosidase) and pancreatic function-related genes (glucagon and insulin) was examined by reverse transcription-quantitative polymerase chain reaction, and their relationships with age were investigated. RESULTS: We obtained isolated human islets from 18 deceased multiorgan donors. There was no correlation between donor age and expression of any of the senescence-related genes. Regarding correlations between donor age and pancreatic function-related genes, age was positively correlated only with INS (r=0.49, p=0.03). INS expression was not correlated with that of GLS1 (r=0.23, p=0.34), IL6 (r=-0.06, p=0.79), or IL8 (r=-0.1, p=0.12), but positively related with p16 (r=0.89, p<0.0001), p21 (r=0.51, p=0.02), and SA-ß-gal (r=0.52, p=0.02). CONCLUSION: We showed the functional potential even of aged islets, which were originally thought to be functionally impaired. We were unable to identify any senescence-related genes expressed in islets from donors of different ages. Therefore, a new index is needed to evaluate not only actual chronological age but also organ- and cell-specific age.

Clinical Outcomes and Histologic Findings of Patients With Hepatocellular Carcinoma With Durable Partial Response or Durable Stable Disease After Receiving Atezolizumab Plus Bevacizumab.

PURPOSE: Durable partial response (PR) and durable stable disease (SD) are often seen in patients with hepatocellular carcinoma (HCC) receiving atezolizumab plus bevacizumab (atezo-bev). This study investigates the outcome of these patients and the histopathology of the residual tumors. PATIENTS AND METHODS: The IMbrave150 study's atezo-bev group was analyzed. PR or SD per RECIST v1.1 lasting more than 6 months was defined as durable. For histologic analysis, a comparable real-world group of patients from Japan and Taiwan who had undergone resection of residual tumors after atezo-bev was investigated. RESULTS: In the IMbrave150 study, 56 (77.8%) of the 72 PRs and 41 (28.5%) of the 144 SDs were considered durable. The median overall survival was not estimable for patients with durable PR and 23.7 months for those with durable SD. The median progression-free survival was 23.2 months for patients with durable PR and 13.2 months for those with durable SD. In the real-world setting, a total of 38 tumors were resected from 32 patients (23 PRs and nine SDs) receiving atezo-bev. Pathologic complete responses (PCRs) were more frequent in PR tumors than SD tumors (57.7% v 16.7%, P = .034). PCR rate correlated with time from atezo-bev initiation to resection and was 55.6% (5 of 9) for PR tumors resected beyond 8 months after starting atezo-bev, a time practically corresponding to the durable PR definition used for IMbrave150. We found no reliable radiologic features to predict PCR of the residual tumors. CONCLUSION: Durable PR patients from the atezo-bev group showed a favorable outcome, which may be partly explained by the high rate of PCR lesions. Early recognition of PCR lesions may help subsequent treatment decision.