Portal vein arterialization as a salvage procedure in hepatopancreatobiliary surgery: a systematic review.

Background: Portal vein arterialization (PVA) is a possible option when hepatic artery reconstruction is impossible during liver resection. The aim of this study was to review the literature on the clinical application of PVA in hepatopancreatobiliary (HPB) surgery. Methods: We performed a systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We systematically searched the PubMed, Embase and Web of Science databases until December 2019. Experimental (animal) studies, review articles and letters were excluded. Results: Twenty studies involving 57 patients were included. Cholangiocarcinoma was the most common indication for surgery (40 patients [74%]). An end-to-side anastomosis between a celiac trunk branch and the portal vein was the main PVA technique (35 patients [59%]). Portal hypertension was the most common longterm complication (12 patients [21%] after a mean of 4.1 mo). The median followup period was 12 (range 1-87) months. The 1-, 3- and 5-year survival rates were 64%, 27% and 20%, respectively. Conclusion: Portal vein arterialization can be considered as a rescue option to improve the outcome in patients with acute liver de-arterialization when arterial reconstruction is not possible. To prevent portal hypertension and liver injuries due to thrombosis or overarterialization, vessel calibre adjustment and timely closure of the anastomosis should be considered. Further prospective experimental and clinical studies are needed to investigate the potential of this procedure in patients whose liver is suddenly de-arterialized during HPB procedures.

Contexte: L'artérialisation de la veine porte (AVP) est une option envisageable lorsqu'il est impossible de reconstruire l'artère hépatique au moment d'une résection du foie. Le but de cette étude était de faire le point sur la littérature concernant l'application clinique de l'AVP en cours de chirurgie hépatopancréatobiliaire (HPB). Méthodes: Nous avons procédé à une revue systématique selon les directives PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). Nous avons interrogé systématiquement les bases de données PubMed, Embase et Web of Science jusqu'à décembre 2019. Les études expérimentales (chez l'animal), les articles de synthèse et les lettres ont été exclus. Résultats: Vingt études regroupant 57 patients ont été incluses. Le cholangiocarcinome était la plus fréquente indication de la chirurgie (40 patients [74 %]). L'anastomose terminolatérale d'une branche du tronc cæliaque avec la veine porte a été la principale technique d'AVP (35 patients [59 %]). L'hypertension portale a été la plus fréquente complication (12 patients [21 %] après une moyenne de 4,1 mois). Le suivi médian a été de 12 mois (éventail, 1­87 mois). Les taux de survie moyens à 1, 3 et 5 ans ont été de 64 %, 27 % et 20 %, respectivement. Conclusion: L'artérialisation de la veine porte peut être considérée comme une option de dernier ressort pour améliorer l'état des patients victimes d'une désartérialisation hépatique aiguë lorsque la reconstruction artérielle est impossible. Pour prévenir l'hypertension portale et les lésions au foie dues à la thrombose ou à l'hyperartérialisation, il faut veiller à ajuster le calibre vasculaire et fermer rapidement l'anastomose. D'autres études expérimentales et cliniques prospectives s'imposent afin d'analyser le potentiel de cette intervention chez les patients dont le foie se trouve subitement désartérialisé durant une chirurgie HPB.

Broccoli sprout supplementation in patients with advanced pancreatic cancer is difficult despite positive effects-results from the POUDER pilot study.

Pancreatic ductal adenocarcinoma is a highly aggressive malignancy with short survival and limited therapeutic options. Broccoli sulforaphane is a promising new treatment due to the results of recent epidemiological, experimental and patient studies. Upon approval from the ethics committee and registration at ClinicalTrials.gov, 40 patients with palliative chemotherapy were placed into a placebo and treatment group in an unblinded fashion. Fifteen capsules with pulverized broccoli sprouts containing 90 mg/508 µmol sulforaphane and 180 mg/411 µmol glucoraphanin or methylcellulose were administered daily for up to 1 year. Twenty-nine patients were included in the treatment group and 11 patients were in the placebo group; these patients were followed for up to 1 year. The patient characteristics, overall survival and feasibility were assessed. Compared to those of the placebo group, the mean death rate was lower in the treatment group during the first 6 months after intake (day 30: 0%/18%, day 90: 0%/25%, and day 180: 25%/43%), and Kaplan-Meier analysis revealed a higher survival rate. There was a high drop-out rate (72% in the treatment group and 55% in the placebo group) after 1 year. We concluded from the Karnofsky index that the broccoli sprouts did not impact patient's self-care and overall abilities severely. The intake of 15 capsules daily was difficult for some patients, and the broccoli sprouts sometimes increased digestive problems, nausea and emesis. We did not obtain statistically significant results (p = 0.291 for the endpoint at day 180), but the knowledge about the feasibility is the basis for the development of new sulforaphane drugs.

A fast and easy-to-learn technique for liver resection in a porcine model.

OBJECTIVE: Despite the recent advances in surgical techniques and perioperative care, liver resection (especially extended hepatectomy) is still a high-risk procedure with considerable morbidity and mortality. Experimental large animal models are the best option for studies in this regard. The present study was performed to present an easy-to-learn, fast, and multipurpose model of liver resection in a porcine model. METHOD: Stepwise liver resections (resection of segments II/III, IVa/IVb, and VIII/IV) were performed in eight pigs with intraoperative monitoring of hemodynamic parameters. The technical aspects, tips, and tricks of this method are explained in detail. RESULTS: Based on the specific anatomical characteristics of the porcine liver, all resection types including segmental resection, hemihepatectomy, and extended hepatectomy could be performed in one animal in an easy-to-learn and fast technique. All animals were hemodynamically stable following stepwise liver resection. CONCLUSION: Stepwise liver resection using stapler in a porcine model is a fast and easy-to-learn method with which junior staff and research fellows can perform liver resection up to extended hepatectomy under stable conditions.

Oral Preconditioning of Donors After Brain Death With Calcineurin Inhibitors vs. Inhibitors of Mammalian Target for Rapamycin in Pig Kidney Transplantation.

Background: The systemic inflammatory cascade triggered in donors after brain death enhances the ischemia-reperfusion injury after organ transplantation. Intravenous steroids are routinely used in the intensive care units for the donor preconditioning. Immunosuppressive medications could be potentially used for this purpose as well. Data regarding donor preconditioning with calcineurin inhibitors or inhibitors of mammalian target for Rapamycin is limited. The aim of this project is to investigate the effects of (oral) donor preconditioning with a calcineurin inhibitor (Cyclosporine) vs. an inhibitor of mammalian target for Rapamycin (Everolimus) compared to the conventional administration of steroid in the setting of donation after brain death in porcine renal transplantation. Methods: Six hours after the induction of brain death, German landrace donor pigs (33.2 ± 3.9 kg) were randomly preconditioned with either Cyclosporine (n = 9) or Everolimus (n = 9) administered via nasogastric tube with a repeated dose just before organ procurement. Control donors received intravenous Methylprednisolone (n = 8). Kidneys were procured, cold-stored in Histidine-Tryptophane-Ketoglutarate solution at 4°C and transplanted in nephrectomized recipients after a mean cold ischemia time of 18 h. No post-transplant immunosuppression was given to avoid confounding bias. Blood samples were obtained at 4 h post reperfusion and daily until postoperative day 5 for complete blood count, blood urea nitrogen, creatinine, and electrolytes. Graft protocol biopsies were performed 4 h after reperfusion to assess early histological and immunohistochemical changes. Results: There was no difference in the hemodynamic parameters, hemoglobin/hematocrit and electrolytes between the groups. Serum blood urea nitrogen and creatinine peaked on postoperative day 1 in all groups and went back to the preoperative levels at the conclusion of the study on postoperative day 5. Histological assessment of the kidney grafts revealed no significant differences between the groups. TNF-α expression was significantly lower in the study groups compared with Methylprednisolone group (p = 0.01) Immunohistochemistry staining for cytochrome c showed no difference between the groups. Conclusion: Oral preconditioning with Cyclosporine or Everolimus is feasible in donation after brain death pig kidney transplantation and reduces the expression of TNF-α. Future studies are needed to further delineate the role of oral donor preconditioning against ischemia-reperfusion injury.

Mechanical strength of biliary defect closure after topical sealing: Comparison of four sealants in a porcine model.

BACKGROUND/OBJECTIVE: Biliary leakage is a potential complication of liver resection and is still a concern. The aim of the present study was to evaluate the effectiveness of four routinely used sealants in preventing bile leakage under pressure from an induced perforation of the gallbladder in a porcine model. METHODS: Forty Landrace pigs were randomly assigned to one of five groups. These included a control group (n = 8) and one group each for the sealants TachoSil®, TissuCol Duo®, Coseal®, and FloSeal® (n = 8 per group). In the control group, the perforation was left unsealed. To evaluate the biliostatic potential of the sealants, we measured the pressure that was needed to induce leakage (mmHg) and the gallbladder volume (cc) at the time of leakage in each group. RESULTS: A significantly higher mean pressure was required to induce leakage in the sealant groups compared with the control group. However, the biliostatic effects were heterogeneous among the sealant groups. Sealants with the highest to lowest effectiveness were TachoSil, Coseal, TissuCol, and FloSeal. The mean gallbladder volume at the time of leakage also varied between sealant groups. CONCLUSION: Biliostatic properties are markedly improved by the use of modern sealants compared with using no sealant. However, the advantages and disadvantages of using sealants should be carefully considered in each clinical situation. The effectiveness of the sealants should be evaluated in chronic and clinical studies.

Simultaneous Serial Transverse Enteroplasty (STEP) in Size Mismatch Small Bowel Transplantations.

BACKGROUND: Small bowel transplantation (SBTX) in children receiving larger grafts from adults can be challenging because of size mismatch. The aim of the present study was to assess whether a simultaneous serial transverse enteroplasty (STEP) can address the problem of size mismatch. METHODS: Three different size ratio groups between donors and recipients were compared in a porcine model with a 14-day follow-up. The groups were size matched, size mismatched (1:3.8 weight ratio), and size mismatched + STEP (each n = 8). RESULTS: It was technically feasible to simultaneously perform a STEP and SBTX of a mismatched intestinal segment. The postoperative clinical course was uneventful. No signs of bleeding, leakage, stenosis, or ileus were observed and the intestinal segment was well perfused at relaparotomy. Body weight decreased in all groups, but the percentage decrease was lowest in the mismatched + STEP group. Vital enterocyte masses were similar in all the groups (citrulline levels) and the nutritional status was best in the STEP group (transferrin levels, p = 0.04). CONCLUSIONS: We have demonstrated that a simultaneous STEP and SBTX procedure is technically feasible and clinically useful in overcoming the challenges associated with size mismatched SBTX. Our short-term findings justify further investigation in a larger series to elucidate the long-term outcomes of this procedure.

Histopathological effects of modern topical sealants on the liver surface after hepatectomy: an experimental swine study.

The present study aimed to determine the impact of different sealant materials on histopathological changes to the liver surface after liver resection. Thirty-six landrace pigs underwent left anatomical hemihepatectomy and were assigned to a histopathological control group (HPC, n = 9) with no bleeding control, a clinically simulated control group (CSC, n = 9) with no sealant but bipolar cauterization and oversewing of the liver surface, and two treatment groups (n = 9 each) with a collagen-based sealant (CBS) or a fibrinogen-based sealant (FBS) on resection surface. After postoperative day 6, tissue samples were histologically examined. There were no significant differences in preoperative parameters between the groups. Fibrin production was higher in sealant groups compared with the HPC and CSC groups (both p < 0.001). Hepatocellular regeneration in sealant groups was higher than in both control groups. A significantly higher regeneration was seen in the FBS group. Use of sealants increased the degree of fibrin exudation at the resection plane. Increased hepatocellular necrosis was seen in the CBS group compared with the FBS group. The posthepatectomy hepatocellular regeneration rate was higher in the FBS group compared with the CBS group. Randomized studies are needed to assess the impact of sealants on posthepatectomy liver regeneration in the clinical setting.

Hemostatic efficiency of modern topical sealants: Comparative evaluation after liver resection and splenic laceration in a swine model.

Parenchymal transection during hepatobiliary surgery can disrupt small vasculature or bile ducts, which could be managed difficultly. Sealants are helpful tools to achieve better hemostasis. The aim of this study is to analyze the hemostatic efficiency of four modern sealants in a porcine model. In this study, 40 landrace pigs were assigned equally to the control (without sealant) and four sealant groups. Standardized liver resection and splenic lesions were performed and left without using sealant (control) or treated with one of the following sealants: TachoSil® , Tissucol Duo® , Coseal® , and FloSeal® . We measured relative and absolute bleeding times (seconds) as well as total blood loss (g) in a maximum observation time of 300 s. Sealants could show a significantly improved hemostasis comparing to the control group. However, hemostasis was heterogeneous among the sealant groups (liver resection: 60%-100%, spleen injury: 70%-100%). The mean blood loss decreased significantly using sealants comparing to control group (liver resection: 6-120 fold, spleen injury: 2.5-36 fold). The hemostatic time in groups that achieved complete hemostasis was different in each sealant group (liver resection: 30-166 s, spleen injury: 60-180 s). We conclude that the hemostatic efficacy of modern sealants is impressive but heterogeneous in liver resection or splenic lesion. To maximize the effectiveness of these tools, the indication of each sealant should be carefully considered in individual settings by the surgeons. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1307-1316, 2018.