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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: In pediatric liver transplantation (pLT), hepatic artery thrombosis (HAT) is associated with inferior transplant outcome. Hepatic artery reconstruction (HAR) using an operating microscope (OM) is considered to reduce the incidence of HAT. Methods: HAR using an OM was compared to a historic cohort using surgical loupes (SL) in pLT performed between 2009 and 2020. Primary endpoint was the occurrence of HAT. Secondary endpoints were 1‐year patient and graft survival determined by Kaplan–Meier analysis and complications. Multivariate analysis was used to identify independent risk factors for HAT and adverse events. Results: A total of 79 pLTs were performed [30 (38.0%) living donations; 49 (62.0%) postmortem donations] divided into 23 (29.1%) segment 2/3, 32 (40.5%) left lobe, 4 (5.1%) extended right lobe, and 20 (25.3%) full‐size grafts. One‐year patient and graft survival were both 95.2% in the OM group versus 86.2% and 77.8% in the SL group (p =.276 and p =.077). HAT rate was 0% in the OM group versus 24.1% in the SL group (p =.013). One‐year patient and graft survival were 64.3% and 35.7% in patient with HAT, compared to 93.9% and 92.8% in patients with no HAT (both p <.001). Multivariate analysis revealed HAR with SL (p =.022) and deceased donor liver transplantation (DDLT) (p =.014) as independent risk factors for HAT. The occurrence of HAT was independently associated with the need for retransplantation (p <.001) and biliary leakage (p =.045). Conclusion: In pLT, the use of an OM is significantly associated to reduce HAT rate, biliary complications, and graft loss and outweighs the disadvantages of delayed arterial perfusion and prolonged warm ischemia time (WIT). [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]

Vascular surgery faces a critical demand for novel vascular grafts that are biocompatible and thromboresistant. This urgency particularly applies to bypass operations involving small caliber vessels. In the realm of tissue engineering, the development of fully vascularized organs holds great promise as a solution to organ shortage for transplantation. To achieve this, it is imperative to (re-)construct a biocompatible and non-thrombogenic vascular network within these organs. In this systematic review, we identify, classify and discuss basic principles and methods used to perform in vitro/ex vivo dynamic thrombogenicity testing of perfusable tissue engineered organs and tissues. We conducted a pre-registered systematic review of studies published in the last 23 years according to PRISMA-P Guidelines, comprising a systematic data extraction, in-depth analysis and risk of bias assessment of 116 included studies. We identified shaking (n=28), flow loop (n=17), ex vivo (arterio-venous shunt, n=33) and dynamic in vitro models (n=38) as main approaches for thrombogenicity assessment. This comprehensive review unveils a prevalent lack of standardization and serves as a valuable guide in the design of standardized experimental setups.

Background, Objectives: In recent years, ERAS treatment pathways have found their way into many surgical fields, as they reduce complications and accelerate postoperative recovery. For thoracic surgery, the first ERAS guidelines were published by the ERAS Society and the European Society of Thoracic Surgeons (ESTS) in 2019. We have now evaluated how ERAS-items are implemented in clinical practice by using an online survey., Material and Methods: An online survey was conducted from 12/5/2021 until 1/6/2021. The survey consisted of 22 questions focusing on the key elements of an ERAS program according to the published ERAS guidelines. Results were summarised, descriptively analysed and put into context with the current literature., Results: Of 155 thoracic surgeons, 32 responded to the survey. In 28.1% (n = 9) of the hospitals, an ERAS core unit was established, and a database to record the ERAS items existed in 15.6% (n = 5). Only 3.1% (n = 1) kept an ERAS-diary preoperatively. A so-called Carboloading was conducted at 15.6% (n = 5) of surgeons. Standard PONV prophylaxis was administered to 59.4% (n = 19) of the patients. In most cases (84.4%, n = 29), a single drain was inserted into the pleural cavity during anatomic resections. In 3% (n = 1) of the centres two drains, in 12.5% (n = 4) no drainage was placed. The most commonly applied initial suction was -10 cmH 2 O (75%, n = 24). Suction ≤ 2 cmH 2 O was used by only two of those interviewed. Drainage removal took place in 50% (n = 16) of cases between the 1st or 2nd POD, in 34.4% of cases (n = 11) between the 3rd and 4th POD and in 9.4% (n = 3) the drain remained longer than the 4th POD. The first postoperative mobilisation took place in 71.9% (n = 23) of the centres on the day of the operation., Conclusions: The implementation of ERAS guidelines varies in Germany between centres. Certain perioperative processes are covered sufficiently, but the implementation of key features of ERAS is yet to be fully established in clinical practice. The first steps in this direction have already been taken and lay the foundation for cooperation across centres., Competing Interests: Marco Nicolas Andreas, Tomasz Dziodzio und Jens Neudecker sind als Referenten für Medela Medizintechnik GmbH & Co. Handels KG tätig und erhalten finanzielle Unterstützung diesbezüglich. Jens Neudecker erhält finanzielle Unterstützung von Medtronic GmbH sowie von Becton Dickinson GmbH. Sonstige Interessenkonflikte bestehen nicht. Für diesen Artikel wurden weder Studien an Menschen noch an Tieren durchgeführt. Für die angeführten Studien gelten die jeweiligen Ethik-Richtlinien., (Thieme. All rights reserved.)

Background: The new COVID-19 pandemic has an impact on routine thoracic surgery. Various concepts and recommendations are being pursued to protect patients and hospital staff. However, the implementation of these recommendations may depend on the existing infrastructure, local conditions and in-house procedural instructions., Material and Method: Between 11th May and 26th May 2020, an anonymous online survey on the topic of COVID-19 was conducted among thoracic surgeons in Germany. The survey consisted of 16 questions on the local COVID-19 case numbers, protective measures, procedural instructions and treatment concepts. The results were summarised, descriptively analysed and discussed., Results: The response rate of 42.6% (n = 66), included replies from 23 (34.8%) specialised hospitals, 18 (27.3%) maximum care hospitals and 14 (21.2%) university clinics. COVID-19-positive patients were treated in 65 (99%) clinics and 37.9% of the clinics also performed surgery on COVID-19-positive patients. Nasopharyngeal swabs were the main instrument for COVID-19 patient testing (in 95.4% of the clinics). Test results influenced decisions on treatment in 71.2% of the clinics. In 59.1% of clinics, safety equipment was supplemented with FFP2 masks and eye protection during thoracic surgeries due to the COVID-19 pandemic., Discussion: Almost all thoracic surgeons reported that they had treated patients with COVID-19 and half of them also had performed surgery on COVID-19-positive patients. The applied procedural instructions as well as the effects of COVID-19 on treatment decisions and patient-doctor contact differed between the reporting clinics., Competing Interests: Alle Autoren geben an, dass kein Interessenkonflikt besteht. Für diesen Beitrag wurden von den Autoren keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien., (Thieme. All rights reserved.)