Early portal vein thrombosis after hepatectomy for perihilar cholangiocarcinoma: Incidence, risk factors, and management.

AIM: To study the incidence, risk factors and management of portal vein thrombosis (PVT) after hepatectomy for perihilar cholangiocarcinoma (PHCC). PATIENTS AND METHOD: Single-center retrospective analysis of 86 consecutive patients who underwent major hepatectomy for PHCC, between 2012 and 2019, with comparison of the characteristics of the groups with (PVT+) and without (PVT-) postoperative portal vein thrombosis. RESULTS: Seven patients (8%) presented with PVT diagnosed during the first postoperative week. Preoperative portal embolization had been performed in 71% of patients in the PVT+ group versus 34% in the PVT- group (P=0.1). Portal reconstruction was performed in 100% and 38% of PVT+ and PVT- patients, respectively (P=0.002). In view of the gravity of the clinical and/or biochemical picture, five (71%) patients underwent urgent re-operation with portal thrombectomy, one of whom died early (hemorrhagic shock after surgical treatment of PVT). Two patients had exclusively medical treatment. Complete recanalization of the portal vein was achieved in the short and medium term in the six survivors. After a mean follow-up of 21 months, there was no statistically significant difference in overall survival between the two groups. FINDINGS: Post-hepatectomy PVT for PHCC is a not-infrequent and potentially lethal event. Rapid management, adapted to the extension of the thrombus and the severity of the thrombosis (hepatic function, signs of portal hypertension) makes it possible to limit the impact on postoperative mortality. We did not identify any modifiable risk factor. However, when it is oncologically and anatomically feasible, left±extended hepatectomy (without portal embolization) may be less risky than extended right hepatectomy, and portal vein resection should only be performed if there is strong suspicion of tumor invasion.

Resectable and transplantable hepatocellular carcinoma: Integration of liver stiffness assessment in the decision-making algorithm.

BACKGROUND: Liver resection is a curative treatment for hepatocellular carcinoma (HCC) and an alternative to liver transplantation (LT). However, post-liver resection recurrence rates remain high. This study aimed to determine whether liver stiffness measurement (LSM) correlated with recurrence and to propose a method for predicting HCC recurrence exclusively using pre-liver resection criteria. METHODS: This retrospective monocentric study included patients who had undergone LR liver resection for HCC between 2015 and 2018 and who had (1) preoperative alpha-fetoprotein scores indicating initial transplant viability and (2) available preoperative LSM data. We developed a predictive score for recurrence over time using Cox univariate regression and multivariate analysis with a combination plot before selecting the optimal thresholds (receiver operating characteristic curves + Youden test). RESULTS: Sixty-six patients were included. After an average follow-up of 40 months, the recurrence rate was 45% (n = 30). Three-year overall survival was 88%. Four preoperative variables significantly impacted the time to recurrence: age ≥70 years, LSM ≥11 kPa, international normalized ratio (INR) ≥1.2, and maximum HCC diameter ≥3 cm. By assigning 1 point per positive item, patients with a score <2 (n = 22) demonstrated greater mean overall survival (69.7 vs 54.8 months, P = .02) and disease-free survival (52.2 vs 34.7 months, P = .02) than those with a score ≥2. Patients experiencing early recurrence (<1 year) presented a significantly higher preoperative LSM (P = .06). CONCLUSION: We identified a simple preoperative score predictive of early hepatocellular carcinoma recurrence after liver resection, highlighting the role of liver stiffness. This score could help physicians select patients and make decisions concerning perioperative medical treatment.

The ILLS Laparoscopic Liver Surgery Fellow Skills Curriculum.

INTRODUCTION: Laparoscopy is becoming the standard approach in liver surgery. As the degree of difficulty varies greatly from core skills to advanced procedures, strategies for teaching young surgeons need to be reconsidered. We here aimed to design a skills curriculum for LLR. METHODS: Using the nominal group technique, 22 substeps of LLR were identified by 61 hepatobiliary surgeons. The raters were asked to rate (1) the difficulty of substeps and (2) the minimum number of times that the substep must be performed for mastery of the technique. According to the frequency of defined substeps, being estimated on the basis of high volume center experiences (n = 222 LLR; 1/2017-12/2018), the center's training capacity and defined goals for a 2-year fellowship were calculated. RESULTS: Ten surgical substeps (45%) are routinely performed and can thus be taught sufficiently at centers carrying out ≥50 LLR in 2 years. As the mobilization of the right liver lobe and the dissection of the hepatic artery or portal vein is performed in only 27% and 28% of all LLR, respectively, sufficient training can only be provided at centers with ≥100 LLRs in 2 years. Mastery of complex parenchymal dissection (19%) and hilar lymphadenectomy (8%) can only be achieved in center performing ≥200 LLR in 2 years. CONCLUSION: We here suggest a stepwise approach for training of hepatobiliary fellows in LLR. Based on the estimated complexity of the substeps and the size of the center, not every substep can be learned within 2 years.

Evaluation of a micro-spectrometer for the real-time assessment of liver graft with mild-to-moderate macrosteatosis: A proof of concept study.

BACKGROUND & AIMS: Liver macrosteatosis (MS) is a major predictor of graft dysfunction after transplantation. However, frozen section techniques to quantify steatosis are often unavailable in the context of procurements, and the findings of preoperative imaging techniques correlate poorly with those of permanent sections, so that the surgeon is ultimately responsible for the decision. Our aim was to assess the accuracy of a non-invasive pocket-sized micro-spectrometer (PSM) for the real-time estimation of MS. METHODS: We prospectively evaluated a commercial PSM by scanning the liver capsule. A double pathological quantification of MS was performed on permanent sections. Initial calibration (training cohort) was performed on 35 livers (MS ≤60%) and an algorithm was created to correlate the estimated (PSM) and known (pathological) MS values. A second assessment (validation cohort) was then performed on 154 grafts. RESULTS: Our algorithm achieved a coefficient of determination R2 = 0.81. Its validation on the second cohort demonstrated a Lin's concordance coefficient of 0.78. Accuracy reached 0.91%, with reproducibility of 86.3%. The sensitivity, specificity, positive and negative predictive values for MS ≥30% were 66.7%, 100%, 100% and 98%, respectively. The PSM could predict the absence (<30%)/presence (≥30%) of MS with a kappa coefficient of 0.79. Neither graft weight nor height, donor body mass index nor the CT-scan liver-to-spleen attenuation ratio could accurately predict MS. CONCLUSION: We demonstrated that a PSM can reliably and reproducibly assess mild-to-moderate MS. Its low cost and the immediacy of results may offer considerable added-value decision support for surgeons. This tool could avoid the detrimental and prolonged ischaemia caused by the pathological examination of (potentially) marginal grafts. This device now needs to be assessed in the context of a large-scale multicentre study. LAY SUMMARY: Macro-vacuolar liver steatosis is a major prognostic factor for outcomes after liver transplantation. However, it is often difficult for logistical reasons to get this estimation during procurement. Therefore, we developed an algorithm for a commercial, portable and affordable spectrometer to accurately estimate this content in a real-time fashion. This device could be of great interest for clinical decision-making to accept or discard a potential human liver graft.

Serial volumetric assessment of large for size liver grafts after whole cadaveric liver transplant in adults: do large liver grafts shrink in size?

BACKGROUND: After whole graft orthotopic liver transplantation (OLT), adaptation of the large grafts' volume to recipient weight is widely accepted despite the paucity of evidence on this subject. METHODS: Thirty nine patients with GRWR > 2.5% were included in this study and subsequently divided into two groups with 3 ≥ GRWR > 3%. Patients had CT scans at three predetermined time points after OLT used for measuring the liver volume. The objective of this study is to evaluate the volumetric changes of whole large liver grafts after adult OLT. RESULTS: At LT, the mean graft recipient body weight ratio (GRWR) was 3.1 ± 0.4%. The mean liver weight was 1881 ± 68 g at LT, 2014 ± 99 ml at one week, 1725 ± 126 ml at 3 months, and 1632 ± 117 (ml) at >6 months. There is an initial increase at 1 week after LT and a subsequent decrease of liver volume on later measurements. None of the late volume measurements were significantly different from the initial graft volume at liver transplant in pair wise comparisons ANOVA repeated measures (p > 0.05). Similarly, the mean GRWR did not change significantly between the initial calculation at transplantation date and the subsequent measurements during the different study time points (F = 0.04, p = 0.96) with a mean of 3.1% (95% CI = 2.2-4.2). AUC ROC discriminated a cutoff of 3% for the initial GRWR above which grafts tend to decrease in size over time (c statistics = 0.74, p = 0.036). In a Clustered ANOVA repeated measures, there was no significant difference in the changes of liver volume between both groups. However, patients with GRWR > 3 showed a trend towards a latent reduction in volume over the tracing period. There was a tendency, but none significant; towards a higher bilirubin, AST, ALT levels over the first postoperative days in recipients with GRWR > 3. CONCLUSION: Large grafts do not significantly decrease in size. Nonetheless, grafts weighing >3% of the GRWR show a different trend towards decrease in size over time.

Hepatectomy for hepatocellular carcinoma larger than 10 cm: preoperative risk stratification to prevent futile surgery.

OBJECTIVES: Appropriate patient selection is important to achieving good outcomes and obviating futile surgery in patients with huge (≥10 cm) hepatocellular carcinoma (HCC). The aim of this study was to identify independent predictors of futile outcomes, defined as death within 3 months of surgery or within 1 year from early recurrence following hepatectomy for huge HCC. METHODS: The outcomes of 149 patients with huge HCCs who underwent resection during 1995-2012 were analysed. Multivariate logistic regression analysis was performed to identify preoperative independent predictors of futility. RESULTS: Independent predictors of 3-month mortality (18.1%) were: total bilirubin level >34 µmol/l [P = 0.0443; odds ratio (OR) 16.470]; platelet count of <150 000 cells/ml (P = 0.0098; OR 5.039), and the presence of portal vein tumour thrombosis (P = 0.0041; OR 5.138). The last of these was the sole independent predictor of 1-year recurrence-related mortality (17.2%). Rates of recurrence-related mortality at 3 months and 1 year were, respectively, 6.3% and 7.1% in patients with Barcelona Clinic Liver Cancer (BCLC) stage A disease, 12.5% and 14% in patients with BCLC stage B disease, and 37.8% (P = 0.0002) and 75% (P = 0.0002) in patients with BCLC stage C disease. CONCLUSIONS: According to the present data, among patients submitted to hepatectomy for huge HCC, those with a high bilirubin level, low platelet count and portal vein thrombosis are at higher risk for futile surgery. The presence of portal vein tumour thrombosis should be regarded as a relative contraindication to surgery.

Interest of preoperative immunonutrition in liver resection for cancer: study protocol of the PROPILS trial, a multicenter randomized controlled phase IV trial.

BACKGROUND: Malnutrition is an independent risk factor of postoperative morbidity and mortality and it's observed in 20 to 50% of surgical patients. Preoperative interventions to optimize the nutritional status, reduce postoperative complications and enteral nutrition has proven to be superior to the parenteral one. Moreover, regardless of the nutritional status of the patient, surgery impairs the immunological response, thus increasing the risk of postoperative sepsis. Immunonutrition has been developed to improve the immunometabolic host response in perioperative period and it has been proven to reduce significantly postoperative infectious complications and length of hospital stay in patients undergoing elective gastrointestinal surgery for tumors. We hypothesize that a preoperative oral immunonutrition (ORAL IMPACT®) can reduce postoperative morbidity in liver resection for cancer. METHODS/DESIGN: Prospective multicenter randomized placebo-controlled double-blind phase IV trial with two parallel treatment groups receiving either study product (ORAL IMPACT®) or control supplement (isocaloric isonitrogenous supplement--IMPACT CONTROL®) for 7 days before liver resection for cancer. A total of 400 patients will be enrolled. Patients will be stratified according to the type of hepatectomy, the presence of chronic liver disease and the investigator center. The main end-point is to evaluate in intention-to-treat analysis the overall 30-day morbidity. Secondary end-points are to assess the 30-day infectious and non-infectious morbidity, length of antibiotic treatment and hospital stay, modifications on total food intake, compliance to treatment, side-effects of immunonutrition, impact on liver regeneration and sarcopenia, and to perform a medico-economic analysis. DISCUSSION: The overall morbidity rate after liver resection is 22% to 42%. Infectious post-operative complications (12% to 23%) increase the length of hospital stay and costs and are responsible for a quarter of 30-day mortality. Various methods have been advocated to decrease the rate of postoperative complications but there is no evidence to support or refute the use of any treatment and further trials are required. The effects of preoperative oral immunonutrition in non-cirrhotic patients undergoing liver resection for cancer are unknown. The present trial is designed to evaluate whether the administration of a short-term preoperative oral immunonutrition can reduce postoperative morbidity in non-cirrhotic patients undergoing liver resection for cancer. TRIAL REGISTRATION: Clinicaltrial.gov: NCT02041871.

Non-invasive assessment of liver graft fibrosis by transient elastography after liver transplantation.

BACKGROUND: Liver stiffness measurement (LSM) by transient elastography (TE) (FibroScan) is a validated method of quantifying liver fibrosis in non-transplanted patients with hepatitis C virus (HCV). It could be useful in follow-up after liver transplantation (LT). The aim of this study was to assess the diagnostic accuracy of LSM in evaluating liver fibrosis after LT in patients with and without recurrent HCV. PATIENTS AND METHODS: Forty-three patients (mean age 57.6 ± 9.9 years), 28 (65.1%) HCV-positive patients and 15 (34.9%) HCV-negative patients underwent gold standard liver biopsy and TE 55.8 ± 4.9 months after transplantation. Liver fibrosis was scored on biopsy specimens according to METAVIR (F0-F4). Accuracy of TE and optimal stiffness cut-off values for fibrosis staging were determined by a receiver-operating characteristics (ROC) curve analysis. RESULTS: Median stiffness values were significantly different for METAVIR score less than 2 (5.8 kPa) vs. METAVIR score greater to equal to 2 (9.6 kPa) (P<0.001). The area under the ROC curve was 0.83 for METAVIR score greater to equal to 2 (95%CI: 0.71-0.95). The optimal stiffness cut-off value was 7 kPa for METAVIR scores greater to equal to 2. The results were similar whether the patients had recurrent HCV infection or not. CONCLUSIONS: These results indicate that transient elastography accurately identifies LT recipients with significant fibrosis, irrespective of HCV status. It is a promising non-invasive tool to assess graft fibrosis progression after LT in patients with HCV recurrence, as well as for screening of late graft fibrosis of other etiologies. Transient elastography could reduce the use of invasive protocol biopsies.