External validation of the French alpha-fetoprotein model for hepatocellular carcinoma liver transplantation in a recent unicentric cohort - a retrospective study.

Prognostic models of liver transplantation (LT) for hepatocellular carcinoma (HCC) mainly derive from LT cohorts with numerous hepatitis C virus (HCV) patients. The AFP model, which is currently used in France to select LT candidates, was derived from a cohort of LT performed between 1988 and 2001, including a majority of HCV-positive recipients. The emergence of new direct-acting antiviral therapies and subsequent decrease of HCV incidence may change the generalizability of such models. We performed an external validation of the AFP model in a cohort of recipients transplanted between 2005 and 2018. Although multivariable analysis identified all three model's factors (AFP level, largest tumor size, number of nodules) as predictors of tumor recurrence, the AFP model showed poor discrimination and calibration in the present cohort. This poor performance could be related to significant differences between the derivation and the present cohort in terms of etiology, severity of underlying liver disease, tumor burden and differentiation, and use of neoadjuvant treatments. The present findings suggest that the decline of HCV-induced HCC among LT candidates may compromise the generalizability of the AFP model in more recent LT cohorts. Further studies are required for updating or building more robust prognostic models.

Impact of 2016 Enhanced Recovery After Surgery (ERAS) Recommendations on Outcomes after Hepatectomy in Cirrhotic and Non-Cirrhotic Patients.

BACKGROUND: The Enhanced Recovery After Surgery (ERAS) society published new recommendations for hepatectomy in 2016. Few studies have assessed their clinical impact. The aim of this monocentric study was to assess the impact of those guidelines on outcomes after liver surgery with a special focus on cirrhotic patients. METHOD: Postoperative outcomes of patients undergoing hepatectomy 30 months before and after ERAS implementation according to the 2016 ERAS guidelines were compared after inverse probability of treatment weighting (IPTW). Primary endpoint was 90-day morbidity. RESULTS: From 2015 to 2020, 430 patients underwent hepatectomy including 226 procedures performed before and 204 after ERAS implementation. After IPTW, overall morbidity (42.5% vs. 64.7%, p < 0.001), Comprehensive Complication Index (CCI) score (14.3 vs. 20.8, p = 0.004), length of stay (10.4 vs. 13.7 days, p = 0.001) and textbook outcome (50% vs. 40.2%, p = 0.022) were significantly improved in the ERAS group, while mortality and severe complications were similar in both groups. In the non-cirrhosis subgroup (n = 321), these results were confirmed. However, in the cirrhosis subgroup (n = 105), no difference appeared on outcomes after hepatectomy with an overall morbidity (47.5% vs. 65.2%, p = 0.069) and a length of stay (8 vs. 9 days, p = 0.310) which were not significantly different. The compliance rate to ERAS guidelines was 60% in both cirrhotic and non-cirrhotic subgroups. CONCLUSION: Perioperative ERAS program for hepatectomy results in improved outcomes with decreased rate of non-severe morbidity. Although those guidelines are not deleterious for cirrhotic patients, they probably require revisions to be more effective in this patient population.

Strategies for liver transplantation during the SARS-CoV-2 outbreak: Preliminary experience from a single center in France.

Liver transplantation (LT) during the ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is challenging given the urgent need to reallocate resources to other areas of patient care. Available guidelines recommend reorganizing transplant care, but data on clinical experience in the context of SARS-CoV-2 pandemic are scarce. Thus, we report strategies and preliminary results in LT during the peak of the SARS-CoV-2 pandemic from a single center in France. Our strategy to reorganize the transplant program included 4 main steps: optimization of available resources, especially intensive care unit capacity; multidisciplinary risk stratification of LT candidates on the waiting list; implementation of a systematic SARS-CoV-2 screening strategy prior to transplantation; and definition of optimal recipient-donor matching. After implementation of these 4 steps, we performed 10 successful LTs during the peak of the pandemic with a short median intensive care unit stay (2.5 days), benchmark posttransplant morbidity, and no occurrence of SARS-CoV-2 infection during follow-up. From this preliminary experience we conclude that efforts in resource planning, optimal recipient selection, and organ allocation strategy are key to maintain a safe LT activity. Transplant centers should be ready to readapt their practices as the pandemic evolves.

Cholangitis lenta: An underdiagnosed lesion associated with severe cholestasis following liver transplantation.

BACKGROUND: Cholangitis lenta (CL) represents a specific histological lesion associated with severe cholestasis and related to sepsis. Despite being well known by pathologists, CL has been poorly studied in liver transplantation (LT). METHODS: We performed a retrospective 12-year analysis of the incidence, risk factors, and outcome of CL in LT recipients. Biopsy samples performed within 3 months after LT underwent blinded rereading to identify recipients with CL. RESULTS: Among 587 LT performed, 45 (7.7%) developed CL. Of these, 7 (15.6%) had no signs of clinical sepsis at the time of biopsy, but further investigations revealed positive cultures. Independent factors associated with CL were sepsis at the time of LT (OR = 3.62 [95%CI = 1.63-8.06]), donor age (OR = 1.05 [1.03-1.08]), and operative time (OR = 1.23 [95%CI = 1.02-1.48]). Cholangitis lenta was associated with increased severe morbidity (71.1% vs 33.0%, P < .001), 90-day mortality (24.4% vs 5.9%, P < .001) and decreased one-year graft (62.1% vs 89.4%, P < .001) and patient survival (55.6% vs 87.9%, P < .001). CONCLUSION: Cholangitis lenta represents a possible lesion associated with cholestasis after LT, which strongly affects its outcome. In the event of an unexplained post-transplant cholestasis, the diagnosis of CL must be considered, even in the absence of clinically evident sepsis.

Primary angioplasty or stenting for hepatic artery stenosis treatment after liver transplantation.

BACKGROUND: Endovascular treatment (EVT) by percutaneous transluminal angioplasty (PTA) or stent is the first-line treatment for hepatic artery stenosis (HAS) after liver transplantation, but there are no guidelines to help choose between PTA and stent. METHODS: Retrospective review of HAS EVT after liver transplantation, between 1999 and 2017. HAS was treated by PTA or stent. We report EVT primary effectiveness, arterial patency after 1 year of follow-up, complications, HAS recurrence rate; comparing PTA to stent. RESULTS: Fifty-two HAS were diagnosed in 42 patients. We performed 51 EVT; 34 PTA (66.7%) and 16 stents (31.4%). Global primary EVT effectiveness was 86.3%: 82.3% after PTA and 100% after stent (P = 1.00 after propensity score matching). Recurrent HAS was found in 22.0% of cases: 29.4% after PTA and 6.2% after stenting, (P = .053 after propensity score matching). Patency rate without recurrent HAS or HAT at 12 months was 73.5% with PTA and 93.8% with stent (P = .09), and globally this was 92.8%. There were 7.8% complications: 2.9% after PTA, 12.5% after stenting (P = .23). CONCLUSION: Primary effectiveness was the same for PTA and stenting. There was a strong trend toward more HAS recurrence after PTA than after stenting suggesting that HAS should benefit from primary stenting.

Neoadjuvant conformal radiotherapy before liver transplantation for hepatocellular carcinoma: a propensity score matched analysis of postoperative morbidity and oncological results.

Aim: To assess neoadjuvant conformal radiotherapy (CRT) before orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC) not suitable for standard locoregional treatments. Methods: Patients undergoing OLT for HCC with or without prior CRT were compared using 1:3 propensity score matching. Results: After propensity score matching, 23 patients with CRT were compared with 66 control subjects. Severe morbidity rate was 34.8 versus 24.2% in the CRT and non-CRT groups (p = 0.289). Complete pathological response was observed in 47.8% of CRT-targeted nodules. The 1-/3-/5-year disease-free survivals were 77.3, 77.3 and 68.7% in the CRT group versus 85.4, 68.0 and 61.7% in the non-CRT group (p = 0.829). Conclusion: Conformal radiotherapy represents a satisfactory neoadjuvant therapy for OLT candidates not suitable for standard HCC locoregional therapies.

No-touch multibipolar radiofrequency ablation vs. surgical resection for solitary hepatocellular carcinoma ranging from 2 to 5 cm.

BACKGROUND & AIMS: No-touch multibipolar radiofrequency ablation (NTM-RFA) represents a novel therapy that surpasses standard RFA for hepatocellular carcinoma (HCC), but it has not been compared to surgical resection (SR). We aimed to compare the outcomes of NTM-RFA and SR for intermediate-sized HCC. METHODS: Between 2012 and 2016, 141 patients with solitary HCC ranging from 2 to 5 cm were treated by NTM-RFA or SR at a single-center. The outcomes of 128 patients were compared after using inverse probability of treatment weighting (IPTW). RESULTS: Seventy-nine patients had NTM-RFA and 62 had SR. After IPTW, the two groups were well-balanced for most baseline characteristics including tumor size, location, etiology, severity of underlying liver disease and alpha-fetoprotein level. Morbidity was higher (67.9% vs. 50.0%, p = 0.042) and hospital stay was longer (12 [IQR 8-13] vs. 7 [IQR 5-9] days, p <0.001) after SR. Local recurrence rates at one and three years were 5.5% and 10.0% after NTM-RFA and 1.9% and 1.9% after SR, respectively (p = 0.065). The rates of systematized recurrence (within the treated segment or in an adjacent segment within a 2 cm distance from treatment site) were higher after NTM-RFA (7.4% vs. 1.9% at one year, 27.8% vs. 3.3% at three years, p = 0.008). Most patients with recurrence were eligible for rescue treatment, resulting in similar overall survival (86.7% after NTM-RFA, 91.4% after SR at three years, p = 0.954) and disease-free survival (40.8% after NTM-RFA, 56.4% after SR at three years, p = 0.119). CONCLUSION: Compared to SR, NTM-RFA for solitary intermediate-sized HCC was associated with less morbidity and more systematized recurrence, while the rate of local recurrence was not significantly different. Most patients with intrahepatic recurrence remained eligible for rescue therapies, resulting in equivalent long-term oncological results after both treatments. LAY SUMMARY: Outcomes of patients treated for intermediate-sized hepatocellular carcinoma by surgical resection or no-touch multibipolar radiofrequency ablation were compared. No-touch multibipolar radiofrequency ablation was associated with a lower overall morbidity and a higher rate of systematized recurrence within the treated segment or in an adjacent segment within a 2 cm distance from the initial tumor site. Most patients with intrahepatic recurrence remained eligible for rescue curative therapy, enabling them to achieve similar long-term oncological results after both treatments.

Evaluation of postoperative ascites after somatostatin infusion following hepatectomy for hepatocellular carcinoma by laparotomy: a multicenter randomized double-blind controlled trial (SOMAPROTECT).

BACKGROUND: The majority of patients undergoing hepatectomy for hepatocellular carcinoma (HCC) suffer from underlying liver disease and are exposed to the risk of postoperative ascites, which is favored by an imbalance between portal venous inflow and a diminished hepatic volume. Finding a reversible, non-invasive method for modulating the portal inflow would be of interest as it could be used temporarily during the early postoperative course. Somatostatin, a well-known drug already used in several indications, may limit the risk of postoperative ascites and liver failure by decreasing portal pressure after hepatectomy for HCC in patients with underlying liver disease. We aimed to evaluate the impact of somatostatin postoperative infusion on the incidence of ascites following hepatectomy by laparotomy for HCC in patients with underlying liver disease. METHODS/DESIGN: The SOMAPROTECT study is a multicenter randomized double-blind placebo controlled phase III trial comparing two arms of patients with underlying liver disease undergoing hepatectomy for HCC by open approach. All patients will have primary abdominal drainage before closure. Patients in the experimental arm will receive a postoperative intravenous infusion of somatostatin during 6 days. Patients in the control group will receive a placebo infusion for the same duration. The primary endpoint will be the presence or absence of postoperative ascites occurring during the 90-day postoperative course, defined as ≥500 ml/24 h of fluid in the drains during at least 3 days or any ascites requiring an invasive procedure comprising percutaneous puncture or drainage. Secondary endpoints will be duration and total volume of ascites, postoperative 90-day mortality and morbidity, liver failure, acute renal failure, length of stay in intensive care unit and hospital stay. The total number of patients to be enrolled was calculated to be 152. DISCUSSION: Postoperative ascites remains a major issue after hepatectomy for HCC as it is associated with increased morbidity, liver and renal failure, the need for specific treatments and prolonged hospital stay. This study represents the first randomized controlled trial to assess the benefits of somatostatin on the risk of postoperative ascites after surgery for HCC. TRIAL REGISTRATION: NCT02799212 (ClinicalTrials.gov identifier). Registered prior to conducting the research on 9 June 2016.

Bleeding Recurrence and Mortality Following Interventional Management of Spontaneous HCC Rupture: Results of a Multicenter European Study.

BACKGROUND: The incidence of spontaneous rupture of hepatocellular carcinoma (HCC) is low in Europe, at less than 3%. HCC rupture remains a life-threatening complication, with mortality reported between 16 and 30%. The risk of bleeding recurrence has never been clearly evaluated in such clinical situation. The objectives of this study were to evaluate the current risk of mortality related to HCC rupture and to focus on the risk of bleeding recurrence following interventional management. METHODS: All patients admitted to 14 French-Italian surgical centers for spontaneous rupture of HCC between May 2000 and May 2012 were retrospectively included. Clinical data, imaging features, relevant laboratory data, treatment strategies, and prognoses were analyzed. RESULTS: Overall, 58 of the 138 included patients (42%) had cirrhosis. Thirty-five patients (25%) presented with hemorrhagic shock, and 19% with organ(s) dysfunction. Bleeding control was obtained by interventional hemostasis, emergency liver resection, and conservative medical management in 86 (62%), 24 (18%), and 21 (15%) patients, respectively. Best supportive care was chosen for 7 (5%) patients. The mortality rate following rupture was 24%. The bleeding recurrence rate was 22% with related mortality of 52%. In multivariate analysis, a bilirubin level >17 micromol/L (HR 3.768; p = 0.006), bleeding recurrence (HR 5.400; p < 0.0001), and ICU admission after initial management (HR 8.199; p < 0.0001) were associated with in-hospital mortality. CONCLUSION: This European, multicenter, large-cohort study confirmed that the prognosis of ruptured HCC is poor with an overall mortality rate of 24%, despite important advances in endovascular techniques. Overall, the rate of bleeding recurrence was more than 20%, with a related high risk of mortality.

A systematic review of the anatomical findings of multiple gallbladders.

BACKGROUND: Multiple gallbladders (MG) are a rare malformation, with no clear data on its clinical impact, therapeutic indications or risk for malignancy. METHODS: A systematic review of all published literature between 1990 and 2017 was performed using the PRISMA guidelines. RESULTS: Data of 181 patients extracted from 153 studies were reviewed. MG were diagnosed during the treatment of a gallstone-related disease in 83% of patients, of which 13% had previous cholecystectomy and had a recurrence of biliary stone disease. The sensitivity of ultrasound scan was 66%, and that of magnetic resonance imaging cholangio-pancreatography, 97%. The cystic duct was common to both gallbladders (type1) in 43% and separated (type 2) in 50% of patients. In the latter case, there was no way to differentiate preoperatively an accessory gallbladder from a Todani II bile duct cyst. Cholecystectomy was performed in 129 patients by laparotomy (43%) or laparoscopy (56%). MG was undiagnosed before surgery in 24% of the patients. The postoperative biliary leakage rate was 0.7%. In two patients, gallbladder cancers were detected. CONCLUSION: MG are difficult to diagnose and share a common natural history with single gallbladders, without evidence of increased risk for malignancy. Excision of both gallbladders is indicated in symptomatic stone disease. However, prophylactic cholecystectomy must be considered for type 2 MG, since it cannot be preoperatively differentiated from a Todani II bile duct cyst, which is associated with a risk of malignant transformation.

Direct-acting antiviral therapy decreases hepatocellular carcinoma recurrence rate in cirrhotic patients with chronic hepatitis C.

BACKGROUND AND AIMS: Arrival of direct-acting antiviral agents against hepatitis C virus with high-sustained virological response rates and very few side effects has drastically changed the management of hepatitis C virus infection. The impact of direct-acting antiviral exposure on hepatocellular carcinoma recurrence after a first remission in patients with advanced fibrosis remains to be clarified. METHODS: 68 consecutive hepatitis C virus patients with a first hepatocellular carcinoma diagnosis and under remission, subsequently treated or not with a direct-acting antiviral combination, were included. Clinical, biological and virological data were collected at first hepatocellular carcinoma diagnosis, at remission and during the surveillance period. RESULTS: All patients were cirrhotic. Median age was 62 years and 76% of patients were male. Twenty-three patients (34%) were treated with direct-acting antivirals and 96% of them achieved sustained virological response. Median time between hepatocellular carcinoma remission and direct-acting antivirals initiation was 7.2 months (IQR: 3.6-13.5; range: 0.3-71.4) and median time between direct-acting antivirals start and hepatocellular carcinoma recurrence was 13.0 months (IQR: 9.2-19.6; range: 3.0-24.7). Recurrence rate was 1.7/100 person-months among treated patients vs 4.2/100 person-months among untreated patients (P=.008). In multivariate survival analysis, the hazard ratio for hepatocellular carcinoma recurrence after direct-acting antivirals exposure was 0.24 (95% confidence interval: 0.10-0.55; P<.001). CONCLUSIONS: Hepatocellular carcinoma recurrence rate was significantly lower among patients treated with direct-acting antivirals compared with untreated patients. Given the potential impact of our observation, large-scale prospective cohort studies are needed to confirm these results.

Splenectomy during whole liver transplantation: a morbid procedure which does not adversely impact long-term survival.

BACKGROUND: Indications for splenectomy (SP) during whole liver transplantation (LT) remain controversial and SP is often avoided because of common complications. We aimed to evaluate specific complications of these combined procedures. METHODS: Data were retrospectively analysed. Splenectomy was performed in patients with splenorenal shunt and/or splenic artery aneurysms or hypersplenism. Patients undergoing simultaneous transplantation and splenectomy (LTSP group) were matched to a non-splenectomy group (LT group). RESULTS: Between 1994 and 2013, we included 47 and 94 patients in LTSP and LT groups, respectively. The LTSP patients had a higher rate of pre-LT portal vein thrombosis (PVT). The LTSP group had a longer operative time and greater blood loss. Mean follow-up was 101 months and 5-year survivals were identical (LTSP 85% vs LT 88%, p = 0.831). Hospital morbidity and rejection incidence were comparable, whereas de novo PVT (34% vs 2%, p < 0.0001) and infection (47% vs 25%, p = 0.014) rates were higher after SP. CONCLUSION: Splenectomy during LT is technically demanding and exposes recipients to a higher thrombosis rate, therefore portal vein patency must be specifically assessed postoperatively. In selected recipients, SP can be performed without increased mortality but at the price of worsening outcome as evidenced by greater risk of infection and PVT.

Traumatic biliary neuroma after orthotopic liver transplantation: a possible cause of "unexplained" anastomotic biliary stricture.

BACKGROUND: Traumatic biliary neuromas (TBNs) represent a rare cause of biliary stricture (BS) after orthotopic liver transplantation (OLT). Diagnosis is challenging preoperatively and is most often made at pathology after resection. Herein, we report a 20-year experience of TBN-related BS. PATIENTS AND METHODS: Medical records of 1030 adult patients undergoing OLT from 1991 to 2014 were reviewed. Patients with histologically proven TBN were identified among those presenting a BS. RESULTS: Over the study period, 52 patients developed an anastomotic BS. Of these, 17 had repeat surgery and specimen examination identified TBN in five instances. All five patients with TBN had a duct-to-duct biliary reconstruction during OLT. Median delay from OLT to onset of symptoms was 69 months (range 4-239). Preoperative imaging showed a compressive mass in one patient. Four patients underwent TBN resection combined with hepaticojejunostomy and had an uneventful postoperative course. One patient underwent TBN resection and duct-to-duct reconstruction; he died from acute pancreatitis on postoperative day 21. After a median follow-up of 40.5 months (range 10-54), no recurrent BS occurred. CONCLUSION: Traumatic biliary neuromas represent a possible diagnosis for unexplained anastomotic BS after OLT. Surgical excision combined with hepaticojejunostomy is effective, allows histological diagnosis, and prevents from recurrence.

Conformal radiotherapy as a bridge to liver transplantation for hepatocellular carcinoma: is it safe?

AIM: To report a preliminary experience of conformal radiotherapy (CRT) as bridge to orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC). METHODS: Data of 12 patients undergoing CRT for HCC followed by OLT between 2012 and 2014 were reviewed. RESULTS: CRT was used in a neoadjuvant or downstaging setting in nine and three patients, respectively. No radiation-related systemic toxicity was observed. Median blood loss and operating time were 1450 ml (600-4000) and 420 min (240-510), respectively. Four patients had diaphragmatic injury. Complete histological response was observed in six patients, and partial response in five. Seven patients developed severe postoperative morbidity including five anastomosis-related complications and one death. CONCLUSION: CRT for HCC provides satisfactory histological response but may compromise OLT safety.

Patients with acute liver failure listed for superurgent liver transplantation in France: reevaluation of the Clichy-Villejuif criteria.

In France, decisions regarding superurgent (SU) liver transplantation (LT) for patients with acute liver failure (ALF) are principally based on the Clichy-Villejuif (CV) criteria. The aims of the present study were to study the outcomes of patients registered for SU LT and the factors that were predictive of spontaneous improvement and to determine the usefulness of the CV criteria. All patients listed in France for SU LT between 1997 and 2010 who were 15 years old or older with ALF were included. In all, 808 patients were listed for SU transplantation: 22% with paracetamol-induced ALF and 78% with non-paracetamol-induced ALF. Of these 808 patients, 112 improved spontaneously, 587 underwent LT, and 109 died or left the waiting list because of a worsening condition. The 1-year survival rate according to an intention-to-treat analysis and the survival after LT were 66.3% [interquartile range (IQR), 62.7%-69.7%] and 74.2% (IQR, 70.5%-77.6%), respectively. The factors that were predictive of a spontaneous recovery with ALF-related paracetamol hepatotoxicity were as follows: hepatic encephalopathy grade 0, 1, or 2 [odds ratio (OR), 4.8; 95% confidence interval (CI), 1.99-11.6]; creatinine clearance≥60 mL/minute/1.73 m2 (OR, 4.77; 95% CI, 1.96-11.63), a bilirubin level<200 µmol/L (OR, 21.64; 95% CI, 1.76-265.7); and a factor V level>20% (OR, 5.79; 95% CI, 1.66-20.29). For ALF-related nonparacetamol hepatotoxicity, the factor that was predictive of a spontaneous recovery was a bilirubin level<200 µmol/L (OR, 10.38; 95% CI, 4.71-22.86). The sensitivity, specificity, and positive and negative predictive values for the CV criteria were 75%, 56%, 50%, and 79%, respectively, for ALF due to paracetamol and 69%, 50%, 64%, and 55%, respectively, for ALF not related to paracetamol. The performance of current criteria for SU transplantation could be improved if paracetamol-induced ALF and non-paracetamol-induced ALF were split and 2 other items were included in this model: the bilirubin level and creatinine clearance.

Subtotal hepatectomy in swine for studying small-for-size syndrome and portal inflow modulation: is it reliable?

BACKGROUND: Small-for-size syndrome (SFSS) is a feared complication of extended liver resection and partial liver transplantation. Swine models of extended hepatectomy have been developed for studying SFSS and its different treatment options. Although portal inflow modulation (PIM) by splenectomy or splenic artery ligation (SAL) has been proposed in humans to prevent SFSS, such procedures have not yet been evaluated in swine. OBJECTIVES: The present study was designed to evaluate modifications in splanchnic haemodynamics yielded by extended hepatectomy with and without PIM in swine. METHODS: Nineteen animals underwent 70% hepatectomy (H70, n = 7), 90% hepatectomy (H90, n = 7) or sham laparotomy (H0, n = 5). Haemodynamic measurements were performed at baseline, after hepatectomy and after PIM by SAL and splenectomy. RESULTS: Portal vein flow increased after both H70 (273 ml/min/100 g versus 123 ml/min/100 g; P = 0.016) and H90 (543 ml/min/100 g versus 124 ml/min/100 g; P = 0.031), but the hepatic venous pressure gradient (HVPG) increased only after H90 (10.0 mmHg versus 3.7 mmHg; P = 0.016). Hepatic artery flow did not significantly decrease after either H70 or H90. In all three groups, neither splenectomy nor SAL induced any changes in splanchnic haemodynamics. CONCLUSIONS: Subtotal hepatectomy of 90% in swine is a reliable model for SFSS inducing a significant increase in HVPG. However, in view of the relevant differences between swine and human splanchnic anatomy, this model is inadequate for studying the effects of PIM by SAL and splenectomy.

Impact of neoadjuvant chemoradiotherapy on postoperative outcomes after esophageal cancer resection: results of a European multicenter study.

OBJECTIVES: To assess the impact of neoadjuvant chemoradiotherapy (NCRT) on anastomotic leakage (AL) and other postoperative outcomes after esophageal cancer (EC) resection. BACKGROUND: Conflicting data have emerged from randomized studies regarding the impact of NCRT on AL. METHODS: Among 2944 consecutive patients operated on for EC between 2000 and 2010 in 30 European centers, patients treated by NCRT after surgery (n=593) were compared with those treated by primary surgery (n=1487). Multivariable analyses and propensity score matching were used to compensate for the differences in some baseline characteristics. RESULTS: Patients in the NCRT group were younger, with a higher prevalence of male sex, malnutrition, advanced tumor stage, squamous cell carcinoma, and surgery after 2005 when compared with the primary surgery group. Postoperative AL rates were 8.8% versus 10.6% (P=0.220), and 90-day postoperative mortality and morbidity rates were 9.3% versus 7.2% (P=0.110) and 33.4% versus 32.1% (P=0.564), respectively. Pulmonary complication rates did not differ between groups (24.6% vs 22.5%; P=0.291), whereas chylothorax (2.5% vs 1.2%; P=0.020), cardiovascular complications (8.6% vs 0.1%; P=0.037), and thromboembolic events (8.6% vs 6.0%; P=0.037) were higher in the NCRT group. After propensity score matching, AL rates were 8.8% versus 11.3% (P=0.228), with more chylothorax (2.5% vs 0.7%; P=0.030) and trend toward more cardiovascular and thromboembolic events in the NCRT group (P=0.069). Predictors of AL were high American Society of Anesthesiologists scores, supracarinal tumoral location, and cervical anastomosis, but not NCRT. CONCLUSIONS: Neoadjuvant chemoradiotherapy does not have an impact on the AL rate after EC resection (NCT 01927016).

Surgical management of liver hydatid disease: subadventitial cystectomy versus resection of the protruding dome.

BACKGROUND: The aim of this study was to compare postoperative outcome and long-term results after management of liver hydatid cysts (LHC) by subadventitial cystectomy (SC) and resection of the protruding dome (RPD) in two tertiary liver surgery centers. METHODS: Medical records of 52 patients who underwent SC in one center, and 27 patients who underwent RPD in another center between 1991 and 2011 were reviewed. Patients underwent long-term follow-up, including serology tests and morphological examinations. RESULTS: Postoperative mortality was nil. The rate of severe morbidity was 7.7 and 22% (p = 0.082), while the rate of serological clearing-up was 20 and 13.3% after SC and RPD, respectively (p = 1.000). After a mean follow-up of 41 months (1-197), four patients developed a long-term cavity-related complication (LTCRC) after RPD (including one recurrence) and none after SC (p = 0.012). All LTCRCs occurred in patients with hydatid cysts located at the liver dome; three required an invasive procedure by either puncture aspiration injection re-aspiration (N = 1) or repeat surgery (N = 2). CONCLUSIONS: RPD exposes to specific LTCRC, especially when hydatid cysts are located at the liver dome, while SC allows ad integrum restoration of the operated liver. Therefore, SC should be considered as the standard surgical treatment for LHC in experienced hepato-pancreato-biliary centers.

Surgical management of congenital intrahepatic bile duct dilatation, Caroli's disease and syndrome: long-term results of the French Association of Surgery Multicenter Study.

OBJECTIVE: To assess clinical presentation and long-term results of surgical management of congenital intrahepatic bile duct dilatation (IHBDD) (Caroli disease and syndrome) in a multicenter setting. BACKGROUND: Congenital IHBDD predisposes to biliary stasis, resulting in intrahepatic lithiasis, septic complications, and cholangiocarcinoma. Although liver resection (LR) is considered to be the treatment of choice for unilobar disease extent into the liver, the management of bilobar disease and/or associated congenital hepatic fibrosis remains challenging. METHODS: From 1978 to 2011, a total of 155 patients (median age: 55.7 years) were enrolled from 26 centers. Bilobar disease, Caroli syndrome, liver atrophy, and intrahepatic stones were encountered in 31.0%, 19.4%, 27.7%, and 48.4% of patients, respectively. A complete resection of congenital intrahepatic bile ducts was achieved in 90.5% of the 148 patients who underwent surgery. RESULTS: Postoperative mortality was nil after anatomical LR (n = 111) and 10.7% after liver transplantation (LT) (n = 28). Grade 3 or higher postoperative morbidity occurred in 15.3% of patients after LR and 39.3% after LT. After a median follow-up of 35 months, the 5-year overall survival rate was 88.5% (88.7% after LT), and the Mayo Clinic score was considered as excellent or good in 86.0% of patients. The 1-year survival rate was 33.3% for the 8 patients (5.2%) who presented with coexistent cholangiocarcinoma. CONCLUSIONS: LR for unilobar and LT for diffuse bilobar congenital IHBDD complicated with cholangitis and/or portal hypertension achieved excellent long-term patient outcomes and survival. Because of the bad prognosis of cholangiocarcinoma and the sizeable morbidity-mortality after LT, timely indication for surgical treatment is of major importance.

Recurrence after liver transplantation for hepatocellular carcinoma according to up-to-seven criteria.

BACKGROUND/AIMS: The Up7 criteria for HCC have recently emerged to identify potential candidates for OLT. The aim of this study was to assess the validity of the Up7 criteria according to the pathological analysis of the explanted livers. METHODOLOGY: For recurrence risk calculation 669 HCC transplanted patients were classified according to both the pathological Milan and Up7 criteria. In order to identify potential predictors of recurrence, selected biological tumor markers and morphological features were then tested by Cox regression. RESULTS: The 5-year HCC recurrence rate for the Milan out/Up7 in subgroup (n=87), was significantly higher than patients meeting Milan criteria (n=299), 15.8% vs. 9.4% (p=0.0290). For patients within the Up7 criteria (n=383), only pre-OLT AFP level >1000ng/mL and microvascular invasion were significant predictors for recurrence, and for those beyond the Up7 criteria (n=286), pre-OLT AFP level >1000ng/mL, poor differentiation grade and microvascular invasion remained significant. CONCLUSIONS: Compared to the current Milan staging system, HCC patients within the pathological Up7 criteria were associated with a higher, but acceptable risk of recurrence after OLT, and along with tumor burden, other parameters can potentially be used for further refinement of HCC staging, such as AFP levels and microvascular invasion.