Percutaneous Preoperative Biliary Drainage for Resectable Perihilar Cholangiocarcinoma: No Association with Survival and No Increase in Seeding Metastases

Background: Endoscopic biliary drainage (EBD) and percutaneous transhepatic biliary drainage (PTBD) are both used to resolve jaundice before surgery for perihilar cholangiocarcinoma (PHC). PTBD has been associated with seeding metastases. The aim of this study was to compare overall survival (OS) and the incidence of initial seeding metastases that potentially influence survival in patients with preoperative PTBD versus EBD. Methods: Between 1991 and 2012, a total of 278 patients underwent preoperative biliary drainage and resection of PHC at 2 institutions in the Netherlands and the United States. Of these, 33 patients were excluded for postoperative mortality. Among the 245 included patients, 88 patients who underwent preoperative PTBD (with or without previous EBD) were compared to 157 patients who underwent EBD only. Survival analysis was done with Kaplan–Meier and Cox regression with propensity score adjustment. Results: Unadjusted median OS was comparable between the PTBD group (35 months) and EBD-only group (41 months; P = 0.26). After adjustment for propensity score, OS between the PTBD group and EBD-only group was similar (hazard ratio, 1.05; 95 % confidence interval, 0.74–1.49; P = 0.80). Seeding metastases in the laparotomy scar occurred as initial recurrence in 7 patients, including 3 patients (3.4 %) in the PTBD group and 4 patients (2.7 %) in the EBD-only group (P = 0.71). No patient had an initial recurrence in percutaneous catheter tracts. Conclusions: The present study found no effect of PTBD on survival compared to patients with EBD and no increase in seeding metastases that developed as initial recurrence. These data suggest that PTBD can safely be used in preoperative management of PHC

FOLFIRINOX Induction Therapy for Stage 3 Pancreatic Adenocarcinoma

ABSTRACT Background. Reports show that FOLFIRINOX therapy for pancreatic ductal adenocarcinoma (PDAC) results in objective response rates two to threefold higher than those of other regimens. This study aimed to assess response and resection rates for locally unresectable (stage 3) patients initially treated with induction FOLFIRINOX. Methods. The institutional cancer database was queried for patients treated with induction FOLFIRINOX therapy between 2010 and 2013. Patients were included in the study if they were treated at the authors' institution for stage 3 PDAC (locally unresectable) that had been adjudicated at a weekly multidisciplinary tumor board. Results. The study identified 101 patients. The median age was 64 years (range 37-81 years), and the median followup period was 12 months (range 3-37 months). The patients received a median of six cycles (range 1-20 cycles) of induction FOLFIRINOX. No grade 4 or 5 toxicity was recorded. At the initial restaging (median of 3 months after diagnosis), 23 patients (23 %) had developed distant metastases, 15 patients (15 %) had undergone resection, and 63 patients (63 %) had proceeded to chemoradiation. In the group of 63 patients who had proceeded to chemoradiation (median of 9 months after diagnosis), an additional 16 patients (16 %) had undergone resection, and 5 patients (5 %) had developed metastases. A partial radiographic response was observed in 29 % of all the patients, which was associated with ability to perform resection (p = 0.004). The median overall survival time was 11 months for the group that progressed with FOLFIRINOX and 26 months for the group that did not progress. Conclusion. Nearly one third of the patients who had been initially identified as having stage 3 pancreatic carcinoma and had been treated with FOLFIRINOX responded radiographically and underwent tumor resection. A recently completed phase 3 randomized trial for stage 4 pancreatic ductal adenocarcinoma (PDAC) identified FOL-FIRINOX as superior to gemcitabine in terms of radiographic response together with improved progression-free and overall survival. 1 Patients who received FOLFIRINOX experienced a 32 % objective response rate (ORR) compared with 9 % in the gemcitabine arm of the study, which correlated with survival benefit (median overall and progression-free survival, 11 and 6 versus 7 and 3 months, respectively). Retrospective studies of patients with both borderline resectable PDAC (stages 1 and 2) and stage 3 disease (locally unresectable) also have suggested an ORR of approximately 30 % with FOLFIRINOX. 2,3 The reported ORR from non-FOLFIRINOX regimens has generally been in the range of 10 %, including the results of a phase

Early liver transplantation for severe alcohol-related hepatitis not responding to medical treatment: a prospective controlled study

peer reviewedBackground: Early liver transplantation for severe alcohol-related hepatitis is an emerging treatment option. We aimed to assess the risk of alcohol relapse 2 years after early liver transplantation for alcohol-related hepatitis compared with liver transplantation for alcohol-related cirrhosis after at least 6 months of abstinence. Methods: We conducted a multicentre, non-randomised, non-inferiority, controlled study in 19 French and Belgian hospitals. All participants were aged 18 years or older. There were three groups of patients recruited prospectively: patients with severe alcohol-related hepatitis who did not respond to medical treatment and were eligible for early liver transplantation according to a new selection scoring system based on social and addiction items that can be quantified in points (early transplantation group); patients with alcohol-related cirrhosis listed for liver transplantation after at least 6 months of abstinence (standard transplantation group); patients with severe alcohol-related hepatitis not responding to medical treatment not eligible for early liver transplantation according to the selection score (not eligible for early transplantation group), this group did not enter any further liver transplantation processes. We also defined a historical control group of patients with severe alcohol-related hepatitis unresponsive to medical therapy and non-transplanted. The primary outcome was the non-inferiority of 2-year rate of alcohol relapse after transplantation in the early transplantation group compared with the standard transplantation group using the alcohol timeline follow back (TLFB) method and a prespecified non-inferiority margin of 10%. Secondary outcomes were the pattern of alcohol relapse, 2-year survival rate post-transplant in the early transplantation group compared with the standard transplantation group, and 2-year overall survival in the early transplantation group compared with patients in the not eligible for early transplantation group and historical controls. This trial is registered with ClinicalTrials.gov, NCT01756794. Findings: Between Dec 5, 2012, and June 30, 2016, we included 149 patients with severe alcohol-related hepatitis: 102 in the early transplantation group and 47 in the not eligible for early transplantation group. 129 patients were included in the standard transplantation group. 68 patients in the early transplantation group and 93 patients in the standard transplantation group received a liver transplant. 23 (34%) patients relapsed in the early transplantation group, and 23 (25%) patients relapsed in the standard transplantation group; therefore, the non-inferiority of early transplantation versus standard transplantation was not demonstrated (absolute difference 9·1% [95% CI –∞ to 21·1]; p=0·45). The 2-year rate of high alcohol intake was greater in the early transplantation group than the standard transplantation group (absolute difference 16·7% [95% CI 5·8–27·6]) The time spent drinking alcohol was not different between the two groups (standardised difference 0·24 [95% CI −0·07 to 0·55]), but the time spent drinking a large quantity of alcohol was higher in the early transplantation group than the standard transplantation group (standardised difference 0·50 [95% CI 0·17–0·82]). 2-year post-transplant survival was similar between the early transplantation group and the standard transplantation group (hazard ratio [HR] 0·87 [95% CI 0·33–2·26]); 2-year overall survival was higher in the early transplantation group than the not eligible for early transplantation group and historical controls (HR 0·27 [95% CI 0·16–0·47] and 0·21 [0·13–0·32]). Interpretation: We cannot conclude non-inferiority in terms of rate of alcohol relapse post-transplant between early liver transplantation and standard transplantation. High alcohol intake is more frequent after early liver transplantation. This prospective controlled study confirms the important survival benefit related to early liver transplantation for severe alcohol-related hepatitis; and this study provides objective data on survival and alcohol relapse to tailor the management of patients with severe alcohol-related hepatitis. Funding: The present study has been granted by the French Ministry of Health—Programme Hospitalier de Recherche Clinique 2010

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Prognosis of resected intrahepatic cholangiocarcinoma

Introduction. Alors qu’elle constitue le seul traitement curatif du cholangiocarcinome intrahépatique (CCIH), la résection reste associée à un taux de récidive supérieur à 60% et un taux de survie réelle à 5 ans inférieur à 20%. Une estimation fiable du pronostic ainsi qu’une meilleure compréhension de la biologie tumorale est essentielle pour améliorer le pronostic.Méthodes. A l’appui des données clinico-biologiques de deux larges cohortes de patients avec CCIH réséqué (MSKCC, n=189 et AFC, n=522), trois objectifs ont été explorés. Tout d’abord, définir quel modèle pronostique publié est le plus performant. Ensuite, définir la fiabilité de l’évaluation pronostique préopératoire à partir de, respectivement, l’imagerie, des microARN (miR) circulants diagnostiques et du profil génomique tumoral. Enfin, évaluer l’impact pronostique de la survenue d’événements périopératoires tels que transfusion et morbidité.Résultats. Premièrement, les nomogrammes apportaient une meilleure estimation pronostique en comparaison à la classification AJCC 7ème édition. Deuxièmement, la taille et la multifocalité tumorale sur l’imagerie préopératoire permettaient de différencier deux groupes de patients de pronostic clairement distincts (p 2) était indépendamment associée à une survie globale plus courte (p=0,002).Conclusion. Alors que les nomogrammes postopératoires apportent une meilleure estimation pronostique, le développement de modèles pronostiques préopératoires est faisable notamment à partir de l’imagerie et de marqueurs biologiques tumoraux complémentaires.Introduction. Complete resection stands as the only curative option for intrahepatic cholangiocarcinoma (IHCC). Still, prognosis remains poor after resection due to a recurrence rate over 60% leading to actual 5-year survival rates below 20%. Reliable prognostic estimation and better understanding of tumor biology would be of interest for improving IHCC prognosis.Methods. Using clinical and biological data from two large cohort of resected IHCC (MSKCC, n=189 and AFC, n=522), three objectives have been explored. First, assessing the performances of different published prognostic models. Second, defining the reliability of preoperative prognostic estimation using imaging, tumoral genomic profiling and circulating tumoral microRNA (miR). Third, evaluating the prognostic impact of perioperative events such as blood transfusion and morbidity.Results. First, nomograms displayed better prognostic accuracy over the AJCC 7th edition staging system. Second, tumor size and multifocality on preoperative imaging allowed patient stratification in groups statistically different regarding prognosis (p 2) was independently associated with shorter overall survival (p=0.002).Conclusion. Nomograms outperform conventional staging sytem. Preoperative prognostic estimation is feasible and reliable using imaging. Identifying new prognostic biomarkers would help refining preoperative prognostic estimation

Pronostic du cholangiocarcinome intrahépatique réséqué

Introduction. Complete resection stands as the only curative option for intrahepatic cholangiocarcinoma (IHCC). Still, prognosis remains poor after resection due to a recurrence rate over 60% leading to actual 5-year survival rates below 20%. Reliable prognostic estimation and better understanding of tumor biology would be of interest for improving IHCC prognosis.Methods. Using clinical and biological data from two large cohort of resected IHCC (MSKCC, n=189 and AFC, n=522), three objectives have been explored. First, assessing the performances of different published prognostic models. Second, defining the reliability of preoperative prognostic estimation using imaging, tumoral genomic profiling and circulating tumoral microRNA (miR). Third, evaluating the prognostic impact of perioperative events such as blood transfusion and morbidity.Results. First, nomograms displayed better prognostic accuracy over the AJCC 7th edition staging system. Second, tumor size and multifocality on preoperative imaging allowed patient stratification in groups statistically different regarding prognosis (p 2) was independently associated with shorter overall survival (p=0.002).Conclusion. Nomograms outperform conventional staging sytem. Preoperative prognostic estimation is feasible and reliable using imaging. Identifying new prognostic biomarkers would help refining preoperative prognostic estimation.Introduction. Alors qu’elle constitue le seul traitement curatif du cholangiocarcinome intrahépatique (CCIH), la résection reste associée à un taux de récidive supérieur à 60% et un taux de survie réelle à 5 ans inférieur à 20%. Une estimation fiable du pronostic ainsi qu’une meilleure compréhension de la biologie tumorale est essentielle pour améliorer le pronostic.Méthodes. A l’appui des données clinico-biologiques de deux larges cohortes de patients avec CCIH réséqué (MSKCC, n=189 et AFC, n=522), trois objectifs ont été explorés. Tout d’abord, définir quel modèle pronostique publié est le plus performant. Ensuite, définir la fiabilité de l’évaluation pronostique préopératoire à partir de, respectivement, l’imagerie, des microARN (miR) circulants diagnostiques et du profil génomique tumoral. Enfin, évaluer l’impact pronostique de la survenue d’événements périopératoires tels que transfusion et morbidité.Résultats. Premièrement, les nomogrammes apportaient une meilleure estimation pronostique en comparaison à la classification AJCC 7ème édition. Deuxièmement, la taille et la multifocalité tumorale sur l’imagerie préopératoire permettaient de différencier deux groupes de patients de pronostic clairement distincts (p 2) était indépendamment associée à une survie globale plus courte (p=0,002).Conclusion. Alors que les nomogrammes postopératoires apportent une meilleure estimation pronostique, le développement de modèles pronostiques préopératoires est faisable notamment à partir de l’imagerie et de marqueurs biologiques tumoraux complémentaires

Robot-Assisted Choledochoduodenostomy: A Safe and Reproducible Procedure for Benign Common Bile Duct Obstruction.

International audienceBACKGROUND:Choledochoduodenostomy (CD) is an option for treating choledocholithiasis and benign biliary obstruction after failure of endoscopic treatment. Nevertheless, this procedure is rarely performed using a mini-invasive approach because of its technical complexity. Robotic assistance could be a safer approach to overcome such technical issues.METHODS:All consecutive patients who underwent a robot-assisted CD for benign biliary obstruction were included.RESULTS:Between 2012 and 2016, 12 patients were operated on, 7 of whom had a body mass index over 25 (58%) and 7 were ASA class 3 (58%). The median age was 73 years (range 49-93). Median operative time was 140 min (range 105-208) and median blood loss was 90 mL (range 5-500). One patient presented with cholangitis 1 month after surgery (treated medically, Clavien-Dindo grade 2). Median length of stay was 7 days (range 3-8). None of the patients experienced severe morbidity after a median follow-up of 15 months.Conclusion:Robot-assisted CD is safe and feasible in benign biliary obstruction. (C) 2017 S. Karger AG, Base

Detecting Hospital Outliers in Post-Pancreatectomy Care Using Funnel Plots from 2009–2018 Based on Nationwide Medico-Administrative Data

International audienceObjectives: Our objective was to identify hospitals with unusual mortality rates for major pancreatectomies over a period of ten years using 30-day mortality data from the French national database. Methods: Data for all patients who underwent pancreatectomy were extracted from the national medico-economic database (Programme de Médicalisation des Systèmes d'Information). To identify quality outliers for each hospital, the observed-to-expected 30-day mortality rates were used as a quality indicator. Results: A total of 19 494 patients underwent a major pancreatectomy in France between January 2009 and December 2018. The overall 30-day mortality rate was 4.8% (n = 944). For the 2009–2014 period, the funnel plot showed that 10 of the 176 hospitals lie outside the central 95% region and 7 lie outside the central 99.8% region. For the 2015–2018 period, out of 176 hospitals, 6 lie outside the central 95% region and 2 lie outside the central 99.8% region. The change in standardized mortality ratios between 2009–2014 and 2015–2018 testing for differences from the overall change, they were there 4 hospitals lie outside the central 95% region and 0 lie outside the central 99.8% region. Conclusion: Over time, the improvement in hospital quality was weak. This study suggests that there is a pressing need to reorganize the supply of care for pancreatic surgery in France