Restrictive model of compensated carbon tetrachloride-induced cirrhosis in rats

AIM: To develop a simplified and quick protocol to induce cirrhosis and standardize models of partial liver resection in rats.METHODS: In Fischer F344 rats two modified protocols of phenobarbital-carbon tetrachloride (CCl4) (dilution 50%) gavage to induce cirrhosis (frequency adjusted according to weight, but each subsequent dose was systematically administered) were tested, i.e. the rapid and slow protocols. Prothrombin time (PT) and total bili-rubin (TB) were also evaluated. Animals from the rapid group underwent 15% hepatectomy and animals from the slow group underwent 70% hepatectomy.RESULTS: Rapid protocol: This corresponded to 1 ga-vage/4 d over 6 wk (mortality 30%). Mean PT was 35.2 ± 2.8 s (normal: 14.5 s), and mean TB was 1.8 ± 0.2 mg/dL (normal: 0.1 mg/dL). Slow protocol: This cor-responded to 1 gavage/6 d over 9 wk (mortality 10%). Mean PT was 11.8 ± 0.2 s (normal: 14.5 s), and mean TB was 0.4 ± 0.04 mg/dL (normal: 0.1 mg/dL). Patho-logical analyses were performed in both protocols which showed persistent cirrhosis at 3 mo. Rat mortality in the rapid gavage group who underwent 15% hepatectomy and in the slow gavage group who underwent 70% hepatectomy was 50% and 70%, respectively.CONCLUSION: Our modified model is a simplified method to induce cirrhosis which is rapid (6 to 9 wk), efficient and stable up to 3 mo. Using this method, "Child Pugh A" or "Child Pugh BC" cirrhotic rats were obtained. Our models of cirrhosis and hepatectomy can be used in various situations focusing on postoperative survival.

Metabolic syndrome and non-alcoholic fatty liver disease in liver surgery: The new scourges?

The aim of this topic highlight is to review relevant evidence regarding the influence of the metabolic syndrome(MS) and its associated liver manifestation, non-alcoholic fatty liver disease(NAFLD), on the development of liver cancer as well as their impact on the results of major liver surgery. MS and NAFLD, whose incidences are significantly increasing in Western countries, are leading to a changing profile of the patients undergoing liver surgery. A MEDLINE search was performed for relevant articles using the key words "metabolic syndrome", "liver resection", "liver transplantation", "non alcoholic fatty liver disease", "non-alcoholic steatohepatitis" and "liver cancer". On one hand, the MS favors the development of primary liver malignancies(hepatocellular carcinoma and cholangiocarcinoma)either through NAFLD liver parenchymal alterations(steatosis, steatohepatitis, fibrosis) or in the absence of significant underlying liver parenchyma changes. Also, the existence of NAFLD may have a specific impact on colorectal liver metastases recurrence. On the other hand, the postoperative period following partial liver resection and liver transplantation is at increased risk of both postoperative complications and mortality. These deleterious effects seem to be related to the existence of liver specific complications but also higher cardio-vascular sensitivity in a setting of MS/NAFLD. Finally, the long-term prognosis after curative surgery joins that of patients operated on with other types of underlying liver diseases. An increased rate of patients with MS/NAFLD referred to hepatobiliary units has to be expected. The higher operative risk observed in this subset of patients will require specific improvements in their perioperative management.

Consequences of metabolic syndrome on postoperative outcomes after pancreaticoduodenectomy

AIM To analyze immediate postoperative outcomes after pancreaticoduodenectomy regarding metabolic syndrome.METHODS In two academic centers, postoperative outcomes of patients undergoing pancreaticoduodenectomy from 2002 to 2014 were prospectively recorded. Patients presenting with metabolic syndrome [defined as at least three criteria among overweight(BMI ≥ 28 kg/m2), diabetes mellitus, arterial hypertension and dyslipidemia] were compared to patients without metabolic syndrome.RESULTS Among 270 consecutive patients, 29(11%) presented with metabolic syndrome. In univariable analysis, patients with metabolic syndrome were significantly older(69.4 years vs 62.5 years, P = 0.003) and presented more frequently with soft pancreas(72% vs 22%, P = 0.0001). In-hospital morbidity(83% vs 71%) and mortality(7% vs 6%) did not differ in the two groups so as pancreatic fistula rate(45% vs 30%, P = 0.079) and severity of pancreatic fistula(P = 0.257). In multivariable analysis, soft pancreas texture(P = 0.001), pancreatic duct diameter < 3 mm(P = 0.025) and BMI > 30 kg/m2(P = 0.041) were identified as independent risk factors of pancreatic fistula after pancreaticoduodenectomy, but not metabolic syndrome.CONCLUSION In spite of logical reasoning and appropriate methodology, present series suggests that metabolic syndrome does not jeopardize postoperative outcomes after pancreaticoduodenectomy. Therefore, definition of metabolic syndrome seems to be inappropriate and fatty pancreas needs to be assessed with an international consensual histopathological classification.

Robotic versus laparoscopic liver resection for huge (≥10 cm) liver tumors: an international multicenter propensity-score matched cohort study of 799 cases

Background:The use of laparoscopic(LLR)and robotic liver resections(RLR)has been safely performed in many institutions for liver tumours.A large scale international multicenter study would provide stronger evidence and insight into application of these techniques for huge liver tumours≥10 cm.Methods:This was a retrospective review of 971 patients who underwent LLR and RLR for huge(≥10 cm)tumors at 42 international centers between 2002-2020.Results:One hundred RLR and 699 LLR which met study criteria were included.The comparison between the 2 approaches for patients with huge tumors were performed using 1:3 propensity-score matching(PSM)(73 vs.219).Before PSM,LLR was associated with significantly increased frequency of previous abdominal surgery,malignant pathology,liver cirrhosis and increased median blood.After PSM,RLR and LLR was associated with no significant difference in key perioperative outcomes including media operation time(242 vs.290 min,P=0.286),transfusion rate rate(19.2%vs.16.9%,P=0.652),median blood loss(200 vs.300 mL,P=0.694),open conversion rate(8.2%vs.11.0%,P=0.519),morbidity(28.8%vs.21.9%,P=0.221),major morbidity(4.1%vs.9.6%,P=0.152),mortality and postoperative length of stay(6 vs.6 days,P=0.435).Conclusions:RLR and LLR can be performed safely for selected patients with huge liver tumours with excellent outcomes.There was no significant difference in perioperative outcomes after RLR or LLR.

Prognostication algorithm for non-cirrhotic non-B non-C hepatocellular carcinoma-a multicenter study under the aegis of the French Association of Hepato-Biliary Surgery and liver Transplantation

Background:Liver resection and local ablation are the only curative treatment for non-cirrhotic hepatocellular carcinoma(HCC).Few data exist concerning the prognosis of patients resected for non-cirrhotic HCC.The objectives of this study were to determine the prognostic factors of recurrence-free survival(RFS)and overall survival(OS)and to develop a prognostication algorithm for non-cirrhotic HCC.Methods:French multicenter retrospective study including HCC patients with non-cirrhotic liver without underlying viral hepatitis:F0,F1 or F2 fibrosis.Results:A total of 467 patients were included in 11 centers from 2010 to 2018.Non-cirrhotic liver had a fibrosis score of F0(n=237,50.7%),F1(n=127,27.2%)or F2(n=103,22.1%).OS and RFS at 5 years were 59.2%and 34.5%,respectively.In multivariate analysis,microvascular invasion and HCC differentiation were prognostic factors of OS and RFS and the number and size were prognostic factors of RFS(P<0.005).Stratification based on RFS provided an algorithm based on size(P=0.013)and number(P<0.001):2 HCC with the largest nodule≤10 cm(n=271,Group 1);2 HCC with a nodule>10 cm(n=176,Group 2);>2 HCC regardless of size Conclusions:We developed a prognostication algorithm based on the number(≤or>2)and size(≤or>10 cm),which could be used as a treatment decision support concerning the need for perioperative therapy.In case of bifocal HCC,surgery should not be a contraindication.

Minimally invasive liver resection for huge(≥10cm)tumors:an international multicenter matched cohort study with regression discontinuity analyses

Background:The application and feasibility of minimally invasive liver resection(MILR)for huge liver tumours(≥10 cm)has not been well documented.Methods:Retrospective analysis of data on 6,617 patients who had MILR for liver tumours were gathered from 21 international centers between 2009-2019.Huge tumors and large tumors were defined as tumors with a size≥10.0 cm and 3.0-9.9 cm based on histology,respectively.1:1 coarsened exact-matching(CEM)and 1:2 Mahalanobis distance-matching(MDM)was performed according to clinically-selected variables.Regression discontinuity analyses were performed as an additional line of sensitivity analysis to estimate local treatment effects at the 10-cm tumor size cutoff.Results:Of 2,890 patients with tumours≥3 cm,there were 205 huge tumors.After 1:1 CEM,174 huge tumors were matched to 174 large tumors;and after 1:2 MDM,190 huge tumours were matched to 380 large tumours.There was significantly and consistently increased intraoperative blood loss,frequency in the application of Pringle maneuver,major morbidity and postoperative stay in the huge tumour group compared to the large tumour group after both 1:1 CEM and 1:2 MDM.These findings were reinforced in RD analyses.Intraoperative blood transfusion rate and open conversion rate were significantly higher in the huge tumor group after only 1:2 MDM but not 1:1 CEM.Conclusions:MILR for huge tumours can be safely performed in expert centers It is an operation with substantial complexity and high technical requirement,with worse perioperative outcomes compared to MILR for large tumors,therefore judicious patient selection is pivotal.

A Japanese multi-institutional randomized controlled trial(ND-Trial)

We read with great interest the recently(Annals of Surgery,Feb,2021)published article by Arita and collaborators(1)about the clinical impact of a no-drain policy in liver resections.The aforementioned study(ND-trial)is the first multi-institutional randomized controlled trial(RCT)assessing the impact of a drain placement after liver resection on the severe postoperative complication rate.

Comment on:Failure to rescue in patients with distal pancreatectomy:a nationwide analysis of 10,632 patients

We read with great interest the article recently published by Lequeu et al.(1)based on the French national administrative prospective database for hospital care(PMSI:Programme de Médicalisation des Systèmes d’Information)containing all discharge reports from both private and public hospitals in France.This series aimed at evaluating the influence of hospital volume on failure to rescue after distal pancreatectomy(DP)with or without splenectomy by open and minimally invasive surgery.Collecting number of deaths among patients who experienced major postoperative complication,failure to rescue(FTR)represents the inability for a center to manage these complications and to avoid postoperative deaths.Indeed,FTR appears to be a relevant indicator of quality of care after surgical procedures related to postoperative morbidity and its management.