Transarterial chemoembolization followed by moderately hypofractionated radiotherapy in hepatocellular carcinoma: Long-term results of RTF3 regimen.

PURPOSE: In early-stage hepatocellular carcinoma (HCC) patients merely fit for surgery, transarterial chemoembolization (TACE) achieve low long-term disease control. We evaluated the efficacy and safety of its combination with moderately hypofractionated radiotherapy (hRT) using RTF3 regimen. MATERIAL AND METHODS: Between 2006 and 2016, 61 consecutive patients treated in our single expert center for a Barcelona Clinic Liver Cancer (BCLC) A HCC by TACE followed by hRT 3Gy/fraction were retrospectively included. RESULTS: Sixty of the 61 included presented Child-Pugh A cirrhosis (A5, n=41, 67.2%; A6: n=19, 31.1%). Fourteen patients (22.9%) were already treated for a HCC, mainly by radiofrequency (n=12). All patient received a TACE followed by 3Gy per fraction hRT. Mean radiation dose was 54Gy (range: 48-60). After a median follow-up of 118 months, median time-to-progression, progression-free survival (PFS) and overall survival (OS) was 21.3, 18.1, and 31.5 months, respectively. In univariate analysis, PFS was related to dose > 54Gy (HR: 2, P=0.036), and OS was correlated to Child-Pugh A6 or B7 (HR: 1.93, P=0.03) and overall hRT time (HR: 1.06, P=0.015). At progression, orthotopic liver transplantation was performed in 8 patients (13.1%). Severe symptomatic adverse events occurred in 12 patients (19.7%), mainly ascites (n=7). CONCLUSION: In BCLC-A Child-Pugh A HCC patients ineligible to surgery or thermoablation, TACE-hRT is a safe and effective treatment. Prospective studies are needed to compare this association with radioembolization, TACE-stereotactic radiotherapy, and systemic treatments combinations.

Novel strategies in liver graft preservation - The French perspective.

Given the increasing graft shortage, the transplant community is forced to use so called marginal liver grafts with a higher susceptibility to ischemia-reperfusion injury. This exposes the recipient to a higher risk of graft failure and post-transplant complications. While static cold storage remains the gold standard in low-risk transplant scenarios, dynamic preservation strategies may allow to improve outcomes after transplantation of marginal liver grafts. Two dynamic preservation strategies, end-ischemic hypothermic oxygenated perfusion (HOPE) and continuous normothermic machine perfusion (cNMP), have been evaluated in randomized clinical trials. The results show improved preservation of liver grafts after cNMP and reduction of post-transplant biliary complications after HOPE. In comparison to cNMP, HOPE has the advantage of requiring less logistics and expertise with the possibility to return to default static cold storage. Both strategies allow to assess graft viability prior to transplantation and may thus contribute to optimizing graft selection and reducing discard rates. The use of dynamic preservation is rapidly increasing in France and results from a national randomized trial on the use of HOPE in marginal grafts will soon be available. Future applications should focus on controlled donation after circulatory death liver grafts, split grafts and graft treatment during perfusion. The final aim of dynamic liver graft preservation is to improve post-transplant outcomes, increase the number of transplanted grafts and allow expansion of transplant indications.

Hepatopulmonary Syndrome and Post-Liver Transplantation Complications: A Case-Control Study.

BACKGROUND: Although liver transplantation (LT) improves survival in cirrhotic patients with hepatopulmonary syndrome (HPS), few data exist concerning post-operative complications in these patients. OBJECTIVE: To compare complications after LT between patients with and without HPS. METHODS: In a case-control study, we retrospectively analyzed all patients who underwent LT in our center from January 2010 to July 2016. We compared cases of identified HPS to controls matched for age, MELD score, comorbidities, red blood cells transfused, and highest dosage of norepinephrine perfused during transplantation. RESULTS: Among 451 transplanted patients, we identified 71 patients with HPS who could be analyzed. We found a significantly (p<0.001) higher number of post-operative complications in patients with HPS (median 5 vs 3), with more occurrence of cardiac, infectious and surgical complications than in the controls: 39.4% vs 12.7% (p<0.001), 81.7% vs 49.3% (p<0.001), and 59.2% vs 40.1% (p<0.029), respectively. There were also more ICU readmissions at 1 month among HPS patients (10 vs 1, p=0.01). There was no significant difference concerning ventilation data, lengths of ICU or hospital stay (8.5 [range 3-232] and 32 [14-276] days, respectively on the whole cohort) and death in the ICU (4.2% on the whole cohort). The 1-year survival was higher in HPS patients (94.4% vs 81.1%, p=0.034); there was no difference in 5-year survival. CONCLUSION: HPS patients seem to have a higher number of complications in the first month following LT.

Surgical activity during the Covid-19 pandemic: Results for 112 patients in a French tertiary care center, a quality improvement study.

BACKGROUND: After the emergence of Covid-19 in China, Hubei Province, the epidemic quickly spread to Europe. France was quickly hit and our institution was one of the first French university to receive patients infected with Sars-COV2. The predicted massive influx of patients motivated the cancellation of all elective surgical procedures planned to free hospitalization beds and to free intensive care beds. Nevertheless, we should properly select patients who will be canceled to avoid life-threatening. The retained surgical indications are surgical emergencies, oncologic surgery, and organ transplantation. MATERIAL AND METHODS: We describe the organization of our institution which allows the continuation of these surgical activities while limiting the exposure of our patients to the Sars Cov2. RESULTS: After 4 weeks of implementation of intra-hospital protocols for the control of the Covid-19 epidemic, 112 patients were operated on (104 oncology or emergency surgeries and 8 liver transplants). Only one case of post-operative contamination was observed. No mortality related to Covid-19 was noted. No cases of contamination of surgical care personnel have been reported. CONCLUSION: We found that the performance of oncological or emergency surgery is possible, safe for both patients and caregivers.

Impact of cirrhosis in patients undergoing laparoscopic liver resection in a nationwide multicentre survey.

BACKGROUND: The aim was to analyse the impact of cirrhosis on short-term outcomes after laparoscopic liver resection (LLR) in a multicentre national cohort study. METHODS: This retrospective study included all patients undergoing LLR in 27 centres between 2000 and 2017. Cirrhosis was defined as F4 fibrosis on pathological examination. Short-term outcomes of patients with and without liver cirrhosis were compared after propensity score matching by centre volume, demographic and tumour characteristics, and extent of resection. RESULTS: Among 3150 patients included, LLR was performed in 774 patients with (24·6 per cent) and 2376 (75·4 per cent) without cirrhosis. Severe complication and mortality rates in patients with cirrhosis were 10·6 and 2·6 per cent respectively. Posthepatectomy liver failure (PHLF) developed in 3·6 per cent of patients with cirrhosis and was the major cause of death (11 of 20 patients). After matching, patients with cirrhosis tended to have higher rates of severe complications (odds ratio (OR) 1·74, 95 per cent c.i. 0·92 to 3·41; P = 0·096) and PHLF (OR 7·13, 0·91 to 323·10; P = 0·068) than those without cirrhosis. They also had a higher risk of death (OR 5·13, 1·08 to 48·61; P = 0·039). Rates of cardiorespiratory complications (P = 0·338), bile leakage (P = 0·286) and reoperation (P = 0·352) were similar in the two groups. Patients with cirrhosis had a longer hospital stay than those without (11 versus 8 days; P = 0·018). Centre expertise was an independent protective factor against PHLF in patients with cirrhosis (OR 0·33, 0·14 to 0·76; P = 0·010). CONCLUSION: Underlying cirrhosis remains an independent risk factor for impaired outcomes in patients undergoing LLR, even in expert centres.

ANTECEDENTES: El objetivo de este estudio fue analizar el impacto de la cirrosis en los resultados a corto plazo después de la resección hepática laparoscópica (laparoscopic liver resection, LLR) en un estudio de cohortes multicéntrico nacional. MÉTODOS: Este estudio retrospectivo incluyó todos los pacientes sometidos a LLR en 27 centros entre 2000 y 2017. La cirrosis se definió como fibrosis F4 en el examen histopatológico. Los resultados a corto plazo de los pacientes con hígado cirrótico (cirrhotic liver CL) (pacientes CL) y los pacientes con hígado no cirrótico (non-cirrhotic liver, NCL) (pacientes NCL) se compararon después de realizar un emparejamiento por puntaje de propension del volumen del centro, las características demográficas y del tumor, y la extensión de la resección. RESULTADOS: Del total de 3.150 pacientes incluidos, se realizó LLR en 774 (24,6%) pacientes CL y en 2.376 (75,4%) pacientes NCL. Las tasas de complicaciones graves y mortalidad en el grupo de pacientes CL fueron del 10,6% y 2,6%, respectivamente. La insuficiencia hepática posterior a la hepatectomía (post-hepatectomy liver failure, PHLF) fue la principal causa de mortalidad (55% de los casos) y se produjo en el 3,6% de los casos en pacientes CL. Después del emparejamiento, los pacientes CL tendieron a tener tasas más altas de complicaciones graves (razón de oportunidades, odds ratio, OR 1,74; i.c. del 95% 0,92-0,41; P = 0,096) y de PHLF (OR 7,13; i.c. del 95% 0,91-323,10; P = 0,068) en comparación con los pacientes NCL. Los pacientes CL estuvieron expuestos a un mayor riesgo de mortalidad (OR 5,13; i.c. del 95% 1,08-48,6; P = 0,039) en comparación con los pacientes NCL. Los pacientes CL presentaron tasas similares de complicaciones cardiorrespiratorias graves (P = 0,338), de fuga biliar (P = 0,286) y de reintervenciones (P = 0,352) que los pacientes NCL. Los pacientes CL tuvieron una estancia hospitalaria más larga (11 versus 8 días; P = 0,018) que los pacientes NCL. La experiencia del centro fue un factor protector independiente de PHLF (OR 0,33; i.c. del 95% 0,14-0,76; P = 0,010) pacientes CL. CONCLUSIÓN: La presencia de cirrosis subyacente sigue siendo un factor de riesgo independiente de peores resultados en pacientes sometidos a resección hepática laparoscópica, incluso en centros con experiencia.

Low-Phospholipid Associated Cholelithiasis (LPAC) syndrome: A synthetic review.

Low-Phospholipid Associated Cholelithiasis (LPAC) is a genetic disease responsible for the development of intrahepatic lithiasis. It is associated with a mutation of the ABCB4 gene which codes for protein MDR3, a biliary carrier. As a nosological entity, it is defined by presence of two of the three following criteria: age less than 40 years at onset of biliary symptoms, recurrence of biliary symptoms after cholecystectomy, and intrahepatic hyperechogenic foci detected by ultrasound. While the majority of clinical forms are simple, there also exist complicated forms, involving extended intrahepatic lithiasis and its consequences: lithiasis migration, acute cholangitis, intrahepatic abscess. Chronic evolution can lead to secondary sclerosing cholangitis or secondary biliary cirrhosis. In unusual cases, degeneration into cholangiocarcinoma may occur. Treatment is built around ursodeoxycholic acid, which yields dissolution of biliary calculi. Complicated forms may call for interventional, radiological, endoscopic or surgical treatment. This synthetic review illustrates and summarizes the different aspects of this entity, from simple gallbladder lithiasis to cholangiocarcinoma, as well as secondary biliary cirrhosis requiring liver transplant, on the basis of clinical cases and the iconography of patients treated in our ward.

Large hepatocellular carcinoma: Does fibrosis really impact prognosis after resection?

BACKGROUND: Hepatectomy remains the standard treatment for large hepatocellular carcinoma (LHCC) ≥5cm. Fibrosis may constitute a contraindication for resection because of high risk of post-hepatectomy liver failure, but its impact on patient outcome and cancer recurrence remains ill defined. Our aim was to compare predictors of survival in patients with and without cirrhosis following hepatectomy for LHCC. METHODS: The data on consecutive patients undergoing hepatectomy for LHCC in two tertiary centres between 2012 and 2016 were reviewed. The outcomes of cirrhotic (F4) and non-cirrhotic (F0-F3) patients were compared. Patients with perioperative medical (sorafenib) or radiological (transarterial chemoembolization, radiofrequency) treatments were excluded. RESULTS: Sixty patients were included. Preoperative and intraoperative features were identical between both groups. Cirrhotics (n=15) presented more satellite nodules on specimens (73% vs. 44%; P=0.073) but better differentiated lesions than non-cirrhotics (P=0.041). The median overall survival of cirrhotics was 34 vs. 29months for non-cirrhotics (P=0.8), and their disease-free survival was 14 versus 18 months (P=0.9). Fibrosis stage did not impact overall (P=0.2) nor disease-free survivals (P=0.6). CONCLUSION: Hepatectomy for LHCC in cirrhotics can achieve acceptable oncological results when compared to non-cirrhotic patients. Curative resection of LHCC should be attempted if liver function is acceptable, whatever the fibrosis stage.

Risk score to predict biliary leakage after elective liver resection.

BACKGROUND: Biliary leakage remains a major cause of morbidity after liver resection. Previous prognostic studies of posthepatectomy biliary leakage (PHBL) lacked power, population homogeneity, and model validation. The present study aimed to develop a risk score for predicting severe PHBL. METHODS: In this multicentre observational study, patients who underwent liver resection without hepaticojejunostomy in one of nine tertiary centres between 2012 and 2015 were randomly assigned to a development or validation cohort in a 2 : 1 ratio. A model predicting severe PHBL (International Study Group of Liver Surgery grade B/C) was developed and further validated. RESULTS: A total of 2218 procedures were included. PHBL of any severity and severe PHBL occurred in 141 (6·4 per cent) and 92 (4·1 per cent) patients respectively. In the development cohort (1475 patients), multivariable analysis identified blood loss of at least 500 ml, liver remnant ischaemia time 45 min or more, anatomical resection including segment VIII, transection along the right aspect of the left intersectional plane, and associating liver partition and portal vein ligation for staged hepatectomy as predictors of severe PHBL. A risk score (ranging from 0 to 5) was built using the development cohort (area under the receiver operating characteristic curve (AUROC) 0·79, 95 per cent c.i. 0·74 to 0·85) and tested successfully in the validation cohort (AUROC 0·70, 0·60 to 0·80). A score of at least 3 predicted an increase in severe PHBL (19·4 versus 2·6 per cent in the development cohort, P < 0·001; 15 versus 3·1 per cent in the validation cohort, P < 0·001). CONCLUSION: The present risk score reliably predicts severe PHBL. It represents a multi-institutionally validated prognostic tool that can be used to identify a subset of patients at high risk of severe PHBL after elective hepatectomy.

Surgical Management of Large Spontaneous Portosystemic Splenorenal Shunts During Liver Transplantation: Splenectomy or Left Renal Vein Ligation?

OBJECTIVE: Management of splenorenal shunt (SRS) during whole liver transplantation is still controversial. Splenectomy (SP) permits its radical removal, at the price of a specific related morbidity. Left renal vein ligation (LRVL) performs a downstream ligation with potential renal repercussions. This study aimed to compare these techniques regarding portal revascularization and postoperative outcomes. METHODS: From 1994 to 2012, 22 SPs and 7 LRVLs were performed for large SRS (>1 cm) management. RESULTS: There was no difference in operating times or transfusion rates. In both groups, efficient portal flow was initially obtained in all cases. After a median follow-up of 79 months, 2 patients in the SP group presented an altered portal flow owing to persistence of a not disconnected mesentericogonadic or splenorenal shunt. Postoperative morbidity, including infection and portal vein thrombosis, was not significantly different (32% vs 14%). SP allowed a faster correction of the thrombocytopenia. The LRVL group had a moderate and temporary impairment of renal function. CONCLUSIONS: SP and LRVL represent 2 effective procedures to avoid vascular steal in the presence of SRS, but they require a patent portal vein. SP appears to be associated to specific but acceptable intraoperative morbidity, permits treatment of associated splenic artery aneurysm, and enables a faster correction of thrombocytopenia. However, the presence of a remote hilum SRS or another large portosystemic shunt represents a cause of failure of the procedure. LRVL is a safer and less demanding procedure that can suppress portal steal whatever the location of the SRS, but at the price of moderate renal morbidity.

Toward a standard technique for laparoscopic distal pancreatectomy? Synthesis of the 2013 ACHBT Spring workshop.

Laparoscopic distal pancreatectomy is currently a commonly performed procedure. Twenty-five retrospective studies comparing laparotomy and laparoscopy have dealt with the feasibility of this approach for localized benign and malignant tumors. However, these studies report several different techniques. The aim of this review was to determine if a standardized procedure could be proposed. Based on the literature and the experience of surgeons in the French Association of Hepatobiliary Surgery and Liver Transplantation (ACBHT-Association française de chirurgie hépato-biliaire et de transplantation hépatique), we recommend primary control of the splenic artery, use of linear staplers for pancreatic transection, splenic vein control either at its end or its origin, and, depending on local conditions, preservation of the splenic vessels when splenic preservation is envisioned. Current data do not allow establishment of any definitive recommendations as to the ideal site of pancreatic transection, operative patient position, or the direction of dissection, which mainly depends on local practices. Control of the splenic vein remains the critical point of this procedure, and impacts the intra-operative strategy.

Management of bleeding liver tumors.

Liver tumors bleed rarely; management has changed radically during the last 20years, advancing from emergency surgery with poor results to multidisciplinary management. The first steps are the diagnosis and control of bleeding. Abdominopelvic CT scan should be performed as soon as patient hemodynamics allow. When active bleeding is visualized, arterial embolization, targeted as selectively as possible, is preferable to surgery, which should be reserved for severe hemodynamic instability or failure of interventional radiology. When surgery is unavoidable, abbreviated laparotomy (damage control) with perihepatic packing is recommended. The second step is determination of the etiology and treatment of the underlying tumor. Adenoma and hepatocellular carcinoma (HCC) are the two most frequently encountered tumors in this context. Liver MRI after control of the bleeding episode generally leads to the diagnosis although sometimes the analysis can be difficult because of the hematoma. Prompt resection is indicated for HCC, atypical adenoma or lesions at risk for degeneration to hepatocellular carcinoma. For adenoma with no suspicion of malignancy, it is best to wait for the hematoma to resorb completely before undertaking appropriate therapy.