Distinct effects of surgical denervation on hepatic perfusion, bowel ischemia, and oxidative stress in brain dead and living donor porcine models.

The liver function and perfusion following brain death is mainly influenced by the sympathetic nerves and hormones. We examined the specific influence of surgical liver denervation on systemic and hepatic perfusion parameters, bowel ischemia and oxidative stress in hemodynamically stable BD and control (living donor [LD]) pigs. Brain death was induced in 8 pigs via saline infusion into the balloon of an epidural Tieman-catheter (1 mL/15 minutes) and compared to the control group (n = 6) over 4 hours. At 2 hours postoperatively, complete liver denervation was initiated. We analyzed systemic cardiocirculatory parameters (mean arterial pressure, aortic flow, bowel ischemia (endotoxin, and endotoxin-neutralizing capacity) and oxidative stress (total glutathione in erythrocytes [tGSH(E)]) and compared them to local/hepatic perfusion parameters (hepatic artery and portal venous flow, liver blood flow index, and microperfusion), local bowel ischemia (intramucosal pH [pHi] of stomach [pHi(S)]/colon[pHi(C)]), and liver oxidative stress (glutathione [rGSH(L), GSSG(L)]). Following brain death, the parameters including mean arterial pressure, aortic flow, pHi, endotoxin, and tGSH(E) showed no significant changes at 2 hours. Portal venous flow and microperfusion were decreased significantly and hepatic arterial buffer response was ineffective. Hepatic oxidative stress was increased in BD animals (decrease rGSH(L), increase GSSG(L)). Surgical denervation/manipulation increased portal venous flow significantly, hepatic arterial buffer response became effective, and stomach pHi decreased (BD and LD groups). Hepatic oxidative stress was reduced in the BD group (increase rGSH(L)/GSSG(L); P < 0.001) while it was increased in the LD group (decrease rGSH(L)/GSSG(L); P < 0.001). In conclusion, denervation reduces hepatic oxidative stress in BD only in contrast to the LD. The reciprocal effect of denervation depends on the state of neural activation and postulates a potential benefit of surgical denervation before organ harvesting in brain death.     

Prevention of hepatitis B virus recurrence after liver transplantation

Abstract:  Liver transplantation for hepatitis B virus (HBV)-related liver disease has changed from a contraindication to outcomes comparable with non-HBV-related liver transplantations during the last two decades. Mainly the implementation of immunoprophylaxis with hepatitis B immunoglobulin (HBIG) and the use of nucleoside analogs such as lamivudine and adefovir account for this dramatic change. The standard of care in most centers today consists of lamivudine treatment in replicating hepatitis B pre-orthotopic liver transplantation (OLT) and a combination regimen of lamivudine and HBIG post-OLT. With adefovir, a potent antiviral drug became available in recent years that allows for the treatment of patients with lamivudine-resistant tyrosine-methionine-aspartate-aspartate (YMDD)-mutant HBV. In the transplantation setting, first studies indicate that a triple prophylactic therapy consisting of lamivudine, adefovir, and HBIG will become the standard of care for YMDD-mutant-related hepatitis B. With new drugs emerging for the treatment of chronic HBV, there is optimism for new options also in the transplant setting.     

The Liver Retransplantation Risk Score: a prognostic model for survival after adult liver retransplantation

High-risk combinations of recipient and graft characteristics are poorly defined for liver retransplantation (reLT) in the current era. We aimed to develop a risk model for survival after reLT using data from the European Liver Transplantation Registry, followed by internal and external validation. From 2006 to 2016, 85 067 liver transplants were recorded, including 5581 reLTs (6.6%). The final model included seven predictors of graft survival: recipient age, model for end-stage liver disease score, indication for reLT, recipient hospitalization, time between primary liver transplantation and reLT, donor age, and cold ischemia time. By assigning points to each variable in proportion to their hazard ratio, a simplified risk score was created ranging 0–10. Low-risk (0–3), medium-risk (4–5), and high-risk (6–10) groups were identified with significantly different 5-year survival rates ranging 56.9% (95% CI 52.8–60.7%), 46.3% (95% CI 41.1–51.4%), and 32.1% (95% CI 23.5–41.0%), respectively (P < 0.001). External validation showed that the expected survival rates were closely aligned with the observed mortality probabilities. The Retransplantation Risk Score identifies high-risk combinations of recipient- and graft-related factors prognostic for long-term graft survival after reLT. This tool may serve as a guidance for clinical decision-making on liver acceptance for reLT.     

PI3K/AKT/mTOR and TLR4/MyD88/NF-κB Signaling Inhibitors Attenuate Pathological Mechanisms of Allergic Asthma

Inflammation - Asthma is an inflammatory airway disease wherein bronchoconstriction, airway inflammation, and airway obstruction during asthma attacks are the main problems. It is recognized that...     

Comparison of two different transection techniques in liver surgery—an experimental study in a porcine model

Aims

Postoperative morbidity and mortality after liver resection is closely related to the degree of intraoperative blood loss; the majority of which occurs during transection of the liver parenchyma. Many approaches and devices have therefore been developed to limit bleeding, but none has yet achieved perfect results up to now. The aim of this standardized chronic animal study was to compare the safety and efficacy of the LigaSure? Vessel Sealing System (LVSS) with the stapler technique, which is one of the modern techniques for transecting the parenchyma in liver surgery.

Methods

Sixteen pigs underwent a left liver resection (LLR). Eight pigs received a LLR by means of an Endo GIA, whereas the other eight pigs underwent liver parenchymal transection followed by simultaneous sealing by the LVSS. The operating time, transection time, blood loss during transection, and time of hemostasis were measured on the day of LLR (postoperative day 0/POD 0). Animals were re-explored on postoperative day 7 (POD 7) and the transection surface of remnant liver was observed for fluid collection (hematoma, biloma, and abscess), necrosis, and other pathologies. A biopsy was taken from the area of transection for histopathological examination.

Results

All animals survived until POD 7. Operating time and transection time of the liver parenchyma on POD 0 was significantly shorter in the stapler group. There was no significant difference between the two groups in terms of blood loss during transection, time of hemostasis and number of sutures for hemostasis on POD 0, morbidity rate, as well as the histopathological examination on POD 7. Furthermore, the material costs were significantly higher in the stapler group than in the LVSS group.

Conclusion

In this standardized chronic animal study concerning transection of the parenchyma in liver surgery, LVSS seems not only to be safe, but also comparable with the stapler technique in terms of morbidity and mortality. Additionally, LVSS significantly reduces material costs. However, the transection time is significantly longer for LVSS than for the stapler resection technique.     

Robotic-assisted paraesophageal hernia repair—a case–control study

Aims

The da Vinci® telemanipulation system offers a wide range of precise movements and 3D visualization with depth perception and magnification effect. Such a system could be useful for improving minimally invasive procedures—as in the case of large hiatal hernia with paraesophageal involvement (PEH) repair. Studies reporting on the robotic-assisted PEH repair are scarce, and a comparison to the standard operation techniques is lacking. Therefore, we decided to investigate the feasibility and safety of robotic-assisted surgery (RAS) compared to conventional laparoscopic (CLS) and open surgery (OS) for the first time.

Methods

We investigated 42 patients for the perioperative outcome after PEH repair. Twelve patients were operated on with RAS, 17 with CLS, and 13 with OS. Operating time, intraoperative blood loss, intra- and postoperative complications, mortality, and duration of hospital stay were analyzed in each method.

Results

On average, operating time in the RAS group was 38 min longer, and the intraoperative blood was loss 217 ml lower compared to OS. Both results were similar to the CLS group. The intraoperative complication rate was similar in all groups. The postoperative complication rate in the RAS group was significantly lower than the OS group, though again similar to the CLS group. The hospital stay was 5 days shorter in the RAS group than the OS group and once again similar to the CLS group.

Conclusion

The results show that RAS is feasible and safe. It appears to be an alternative to OS due to lower intraoperative blood loss and potentially fewer postoperative complications, as well as shorter hospital stay. Though, RAS is not superior to CLS.     

Hepatic Hemodynamic Changes Following Stepwise Liver Resection

Aim

Extended liver resection has increased during the last decades. However, hepatic hemodynamic changes after resection and the consequent complications like post hepatectomy liver failure are still a challenging issue. The aim of this study was to systematically evaluate the role of stepwise liver resection on hepatic hemodynamic changes.

Methods

To evaluate this effect we performed 25, 50, and 75 % sequential liver resections in 10 pigs. Before and after each resection, the hepatic artery flow and portal vein flow in relation to the remnant liver volume (RLV) as well as hepatic vascular pressures were measured and compared between the groups.

Results

Following sequential liver resection, the hepatic artery flow /100 g decreases and the portal vein flow increases up to 17 and 167 % following extended liver resection (75 %), respectively. Also, during stepwise liver resection, the portal vein pressure increases gradually up to 33 % following extended hepatectomy (75 %).

Conclusion

Sequential decrease in the RLV decreases the hepatic artery flow /100 g and increases the portal vein flow /100 g and portal vein pressure. As the consequence, the liver goes under more poor-oxygenated blood supply and higher pressure. This may be one of the most important mechanisms of the post hepatectomy liver failure in case of extended liver resection.