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Liver fibrosis progressing to cirrhosis is a major risk factor for liver cancer, impacting surgical treatment and survival. Our study focuses on the role of extracellular nicotinamide adenine dinucleotide (eNAD+) in liver fibrosis, analyzing liver disease patients undergoing surgery. Additionally, we explore NAD+'s therapeutic potential in a mouse model of extended liver resection and in vitro using 3D hepatocyte spheroids. eNAD+ correlated with aspartate transaminase (AST) and bilirubin after liver resection (AST: r = 0.2828, p = 0.0087; Bilirubin: r = 0.2584, p = 0.0176). Concordantly, post-hepatectomy liver failure (PHLF) was associated with higher eNAD+ peaks (n = 10; p = 0.0063). Post-operative eNAD+ levels decreased significantly (p < 0.05), but in advanced stages of liver fibrosis or cirrhosis, this decline not only diminished but actually showed a trend towards an increase. The expression of NAD+ biosynthesis rate-limiting enzymes, nicotinamide phosphoribosyltransferase (NAMPT) and nicotinamide mononucleotide adenylyltransferase 3 (NMNAT3), were upregulated significantly in the liver tissue of patients with higher liver fibrosis stages (p < 0.0001). Finally, the administration of NAD+ in a 3D hepatocyte spheroid model rescued hepatocytes from TNFalpha-induced cell death and improved viability (p < 0.0001). In a mouse model of extended liver resection, NAD+ treatment significantly improved survival (p = 0.0158) and liver regeneration (p = 0.0186). Our findings reveal that eNAD+ was upregulated in PHLF, and rate-limiting enzymes of NAD+ biosynthesis demonstrated higher expressions under liver fibrosis. Further, eNAD+ administration improved survival after extended liver resection in mice and enhanced hepatocyte viability in vitro. These insights may offer a potential target for future therapies. An analysis on liver disease patients suggests that extracellular Nicotinamide adenine dinucleotide (eNAD + ) correlates with liver fibrosis and post-hepatectomy liver failure, with NAD+ administration improving survival and liver regeneration in mice and hepatocyte viability in vitro. [ABSTRACT FROM AUTHOR]

Introduction Material and Methods Results Conclusions Uterus transplantation has revolutionized reproductive medicine for women with absolute uterine factor infertility, resulting in more than 40 reported successful live births worldwide to date. Small animal models are pivotal to refine this surgical and immunological challenging procedure aiming to enhance safety for both the mother and the child.We established a syngeneic bicornuate uterus transplantation model in young female Lewis rats. All surgical procedures were conducted by an experienced and skilled microsurgeon who organized the learning process into multiple structured steps. Animals underwent meticulous preoperative preparation and postoperative care. Transplant success was monitored by sequential biopsies, monitoring graft viability and documenting histological changes long‐term.Bicornuate uterus transplantation were successfully established achieving an over 70% graft survival rate with the passage of time. The bicornuate model demonstrated safety and feasibility, yielding outcomes comparable to the unicornuate model in terms of ischemia times and complications. Longitudinal biopsies were well‐tolerated, enabling comprehensive monitoring throughout the study.Our novel bicornuate rat uterus transplantation model provides a distinctive opportunity for sequential biopsies at various intervals after transplantation and, therefore, comprehensive monitoring of graft health, viability, and identification of potential signs of rejection. Furthermore, this model allows for different interventions in each horn for comparative studies without interobserver differences contrary to the established unicornuate model. By closely replicating the clinical setting, this model stands as a valuable tool for ongoing research in the field of uterus transplantation, promoting further innovation and deeper insights into the intricacies of the uterus transplant procedure. [ABSTRACT FROM AUTHOR]

Background: Body composition alterations are frequent in patients with cancer or chronic liver disease, but their prognostic value remains unclear in many cancer entities. Objective: We investigated the impact of disease aetiology and body composition after surgery for intrahepatic cholangiocarcinoma (iCCA), a rare and understudied cancer entity in European and North American cohorts. Methods: Computer tomography‐based assessment of body composition at the level of the third lumbar vertebra was performed in 173 patients undergoing curative‐intent liver resection for iCCA at the Department of Surgery, Charité – Universitätsmedizin Berlin. Muscle mass and ‐composition as well as subcutaneous and visceral adipose tissue quantity were determined semi‐automatically. (Secondary) sarcopenia, sarcopenic obesity, myosteatosis, visceral and subcutaneous obesity were correlated to clinicopathological data. Results: Sarcopenia was associated with post‐operative morbidity (intraoperative transfusions [p = 0.027], Clavien–Dindo ≥ IIIb complications [p = 0.030], post‐operative comprehensive complication index, CCI [p < 0.001]). Inferior overall survival was noted in patients with myosteatosis (33 vs. 23 months, p = 0.020). Fifty‐eight patients (34%) had metabolic (dysfunction)‐associated fatty liver disease (MAFLD) and had a significantly higher incidence of sarcopenic (p = 0.006), visceral (p < 0.001) and subcutaneous obesity (p < 0.001). Patients with MAFLD had longer time‐to‐recurrence (median: 38 vs. 12 months, p = 0.025, log‐rank test). Multivariable cox regression analysis confirmed only clinical, and not body, composition parameters (age > 65, fresh frozen plasma transfusions) as independently prognostic for overall survival. Conclusion: This study evidenced a high prevalence of MAFLD in iCCA, suggesting its potential contribution to disease aetiology. Alterations of muscle mass and adipose tissue were more frequent in patients with MAFLD. [ABSTRACT FROM AUTHOR]

Context: Alcoholic liver cirrhosis is a significant risk factor for the development of hepatocellular carcinoma (HCC). The importance of tumour-associated cirrhosis in the development or progression of HCC is not understood. MiRNAs are important regulators for HCC development, but their role in HCC due to alcoholic liver cirrhosis is unclear. Objective: The aim of this study is the detection of miRNA expression in alcoholic liver cirrhosis, tumour-associated cirrhosis, and HCC. Materials and methods: We analysed the differences in the miRNA profiles of HCC, tumour-associated cirrhosis, and cirrhosis without HCC samples from 30 patients who underwent liver transplantation because of alcoholic liver disease. Results: Microarray analyses revealed 40 significantly differentially expressed miRNAs between HCC tissue and tumour-associated cirrhosis tissue. Furthermore, the microarray analysis discovered 56 differentially expressed miRNAs in tumour-associated cirrhosis and cirrhosis without HCC. Discussion: The differences of miRNA profile in alcoholic liver cirrhosis with and without HCC could improve understanding of HCC development, as well as lead to a new diagnostic tool in HCC screening. Conclusion: We were able to show for the first time, the differences of miRNA profile as promising biomarker in HCC, tumour-associated cirrhosis, and cirrhosis without HCC in context of alcoholic liver disease [ABSTRACT FROM AUTHOR]

Background: Data on the typical time point of occurrence of anastomotic leak (AL) after esophagectomy for esophageal cancer are currently scarce. Therefore, the usefulness of routine radiocontrast agent studies (RRCS) for testing proper healing of the anastomosis after esophagectomy remains unclear. Furthermore, preferred available tools to diagnose postoperative AL and therapeutic options are still under debate. Methods: We present a retrospective analysis of 328 consecutive patients who underwent esophagectomy for esophageal cancer between 2005 and 2015. A RRCS has been performed to date in our center on the fifth postoperative day (POD), before returning to normal oral intake. Results: In total, 49 of 328 patients developed AL after esophagectomy (15%). A total of 11 patients (23%) developed AL before the RRCS and 34 patients (69%) after an unremarkable RRCS; and 4 patients (8%) with AL were diagnosed by RRCS, resulting in overall sensitivity of 16%. The median time point of occurrence of AL was POD 9, the majority of AL (84%) occurred between POD 1 and 19. Computed tomography led to the diagnosis of AL in 41% of patients. The most frequent therapy of AL was stenting in 47% of patients. Endoscopic vacuum therapy was used in 4 patients. Conclusions: The majority of AL occurred within the first 3 weeks after esophagectomy without a typical time point. In our series, RRCS on the fifth POD had a low sensitivity of 16%. Therefore, standardized RRCS and fasting till the examination cannot be generally recommended. In case of clinical suspicion of AL, computed tomography of the chest and abdomen with oral contrast agent should be performed, followed by endoscopy. Endoscopic stent placement remains the standard therapy of AL in our center. Endoscopic vacuum therapy evolves as it is an interesting alternative therapeutic option and can be combined with stenting in selected cases. [ABSTRACT FROM AUTHOR]

Background: Obesity is generally considered to be associated with increased postoperative morbidity and mortality following intraabdominal cancer surgery. However, recent reports showed that overweight patients may have a lower risk for adverse postoperative outcomes and this observation has been described as the 'obesity paradox'. Therefore, we aimed to analyze the impact of obesity on outcomes after resection for gastric cancer. Methods: Data of patients who underwent resection for gastric cancer between 2005 and 2012 were assessed. Patient characteristics, postoperative outcomes and long-term survivals were compared between patients with body mass index (BMI) ⩾ 30 and <30. Results: Resection for gastric cancer was performed in 249 patients. BMI ⩾ 30 was identified in 49 patients. Obese patients with BMI ⩾ 30 were more frequently diagnosed with diabetes (31 vs. 16%, p = 0.015). Resection for gastric cancer in obese patients was significantly associated with longer duration of surgery (278 vs. 243 min, p < 0.001), longer duration of hospital stay (18 vs. 16 days, p = 0.028), increased postoperative morbidity (49 vs. 33%, p = 0.037), and increased postoperative mortality (10 vs. 3%, p = 0.028). There was no significant difference in overall survival (OS) between patients with BMI ⩾ 30 and patients with BMI <30 (5-year OS rate: 59 vs. 62%, p = 0.587). Conclusion: Obesity may complicate resection for gastric cancer increasing the duration of surgical procedure, hospital stay and postoperative morbidity and mortality. However, BMI did not predict OS in our patients. Consequently, BMI may be too simple as a parameter to evaluate sophisticated interactions between different body fat compartments and inflammatory and immune responses and thus to predict long-term oncologic outcomes. [ABSTRACT FROM AUTHOR]

Background: Extrahepatic bile duct injuries remain severe complications during cholecystectomies and often require reconstruction by bilioenteric anastomosis (i.e., hepaticojejunostomy), which comes with further long-term complications (e.g., recurring ascending cholangitis, secondary biliary cirrhosis). In the case of inherent extrahepatic biliary atresia or during liver transplant, artificial or engineered bile ducts could allow novel surgical strategies without the need for hepaticojejunostomy. Methods: We present data on the implantation of in vitro-generated neo-bile ducts in 5 domestic pigs. The neo-bile ducts were engineered through decellularization of allogeneic blood vessels and recellularization with autologous cholangiocytes. On postoperative days 0, 1, 7, and 14, blood samples were taken and analyzed (aspartate aminotransferase, alanine aminotransferase, bilirubin, alkaline phosphatase, creatinine, and leukocytes). Magnetic resonance cholangiopancreatography was performed on postoperative day 14 on 1 pig. Fourteen days after implantation, the pigs were sacrificed and the bile ducts were explanted. Results: All pigs survived the complete study period without severe complications. None of the pigs showed signs of biliary leakage or peritonitis. The neo-bile ducts were infiltrated by neutrophils, and neoangiogenesis was observed around and into the implanted tissue. Conclusion: We present a novel strategy for extrahepatic bile duct replacement by implantation of an autologous neo-bile duct generated ex vivo. Whether the presented technique allows the long-term replacement of native bile ducts must be further evaluated. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

It is the goal of this section to publish material that provides information regarding specific issues, aspects of artificial organ application, approach, philosophy, suggestions, and/or thoughts for the future. Proposal of a New Electromechanical Total Artificial Heart: The TAH Serpentina A new type of energy converter for an electromechanical total artificial heart (TAH) based on the principle of a unidirectional moving motor is described. Named the TAH Serpentina, the concept consists of 2 major parts, a pendulum shaped movable element fixed on one side using a joint bearing and a special shaped drum cam. Pusher plates are mounted flexibly to the crossbar of the pendulum. A motor drives the special shaped drum cam linked to the pendulum through a ball bearing. The circular motion of the unidirectional moving brushless DC motor is transferred into the linear motion of the pendulum to drive the pusher plates. Using a crossbar with a variable length, the stroke of the pendulum and therefore the displaced blood volume is alterable. To achieve a variable length, an electric driven screw thread or a hydraulic system is possible. Comparable to the natural heart, cardiac output would be determined by frequency and stroke volume. [ABSTRACT FROM AUTHOR]

Context: The development of pancreatic tissue outside the confines of the main gland represents a congenital abnormality referred to as heterotopic pancreas. This is a rare pathological and surgical entity which remains mostly asymptomatic., Case Report: We present the case of a 28-year-old male, who was admitted to hospital because of a history of blood in bowel movements. After a normal gastroscopy and colonoscopy, Tc99m-tagged red blood cells scintigraphy showed enrichment in the right lower abdomen. At double-balloon endoscopy, a intraluminal polypoid mass 8 cm in diameter was revealed 120 cm from the ileocecal valve. The initial macroscopic diagnosis was a gastrointestinal stromal tumor. During surgery, the diagnosis of heterotopic pancreas with lipoma and fibromatosis was made. To our knowledge this is the first case of ileal heterotopic pancreatic tissue and lipoma described to date in the literature., Conclusion: Ileal heterotopic pancreas is a rare entity with potentially life-threatening complications, local excision being the appropriate indicated treatment.