Prediction of survival in patients with colorectal liver metastases- development and validation of a prognostic score model.

BACKGROUND: Metastatic spread of colorectal cancer to the liver impacts prognosis. Advances in chemotherapy have resulted in increased resectability rates and thereby improved survival in patients with colorectal liver metastases (CRLM). However, criteria are needed to ensure that patients selected for hepatic resection benefit from the invasive therapy. The study aimed to construct a predictive model for overall survival (OS) in patients with CRLM, based on preoperatively available information. METHODS: The retrospective cohort study reviewed all patients with CRLM discussed at multidisciplinary team conference at Karolinska University Hospital, Stockholm, Sweden, 2013-2018. Independent prognostic factors for OS were identified, based on which a score model was generated. The model was validated on patients treated for CRLM at Hôpital Universitaire Paul Brousse, Villejuif, France, 2007-2018. Calibration and discrimination methods were used for internal and external validation. RESULTS: The Swedish development cohort included 1013 patients, the French validation cohort 391 patients. Poor OS was significantly associated with age>60years (hazard ratio (HR) 3.57 (95%CI 2.18-9.94)), number of CRLM (HR 4.59 (2.83-12.20)), diameter of largest CRLM>5 cm (HR 2.59 (1.74-5.03)), right-sided primary tumour (HR 2.98 (2.00-5.80)), extrahepatic disease (HR 4.14 (2.38-15.87)) and non-resectability (HR 0.77 (0.66-0.90)). The C-statistic for prediction of OS was .74, in the development cohort and 0.69 in the validation cohort. CONCLUSION: The presented predictive score model can adequately predict OS for patients at the initial diagnosis of CRLM. The prognostic model could be of clinical value in the management of all patients with CRLM, by predicting individualized survival and thereby facilitating treatment recommendations.

TGR5 controls bile acid composition and gallbladder function to protect the liver from bile acid overload.

BACKGROUND & AIMS: As the composition of the bile acid (BA) pool has a major impact on liver pathophysiology, we studied its regulation by the BA receptor Takeda G protein coupled receptor (TGR5), which promotes hepatoprotection against BA overload. METHODS: Wild-type, total and hepatocyte-specific TGR5-knockout, and TGR5-overexpressing mice were used in: partial (66%) and 89% extended hepatectomies (EHs) upon normal, ursodeoxycholic acid (UDCA)- or cholestyramine (CT)-enriched diet, bile duct ligation (BDL), cholic acid (CA)-enriched diet, and TGR5 agonist (RO) treatments. We thereby studied the impact of TGR5 on: BA composition, liver injury, regeneration and survival. We also performed analyses on the gut microbiota (GM) and gallbladder (GB). Liver BA composition was analysed in patients undergoing major hepatectomy. RESULTS: The TGR5-KO hyperhydrophobic BA composition was not directly related to altered BA synthesis, nor to TGR5-KO GM dysbiosis, as supported by hepatocyte-specific KO mice and co-housing experiments, respectively. The TGR5-dependent control of GB dilatation was crucial for BA composition, as determined by experiments including RO treatment and/or cholecystectomy. The poor TGR5-KO post-EH survival rate, related to exacerbated peribiliary necrosis and BA overload, was improved by shifting BAs toward a less toxic composition (CT treatment). After either BDL or a CA-enriched diet with or without cholecystectomy, we found that GB dilatation had strong TGR5-dependent hepatoprotective properties. In patients, a more hydrophobic liver BA composition was correlated with an unfavourable outcome after hepatectomy. CONCLUSIONS: BA composition is crucial for hepatoprotection in mice and humans. We indicate TGR5 as a key regulator of BA profile and thereby as a potential hepatoprotective target under BA overload conditions. LAY SUMMARY: Through multiple in vivo experimental approaches in mice, together with a patient study, this work brings some new light on the relationships between biliary homeostasis, gallbladder function, and liver protection. We showed that hepatic bile acid composition is crucial for optimal liver repair, not only in mice, but also in human patients undergoing major hepatectomy.

Personalized Preoperative Nomograms Predicting Postoperative Risks after Resection of Perihilar Cholangiocarcinoma.

INTRODUCTION: Curative treatment of perihilar tumors requires major hepatectomy responsible for high morbidity and mortality. Current nomograms are based on definitive pathological analysis, not usable for patient selection. Our aim was to propose preoperative predictors for severe morbidity (Dindo-Clavien ≥3) and mortality at sixth month after resection of perihilar tumors. PATIENTS AND METHODS: We reviewed perioperative data of 186 patients operated with major hepatectomy for perihilar tumors between 2012 and 2018 in two high-volume centers. Univariate and multivariate analysis were performed to determine the preoperative predictors of morbidity and mortality. A stepwise regression in forward direction was developed to select variables for definitive models. Hosmer-Lemeshow test, Akaike information criteria and area under the ROC curves were calculated to validate both nomograms. RESULTS: Resections were indicated for perihilar and intrahepatic cholangiocarcinoma in 125 and 61 cases, respectively. Severe complications occurred in 76 patients (40.8%). Nineteen patients (10.2%) deceased before the sixth postoperative month. The predictors of severe morbidity were: male gender, portal vein embolization, planned biliary resection, low psoas muscle area/height2 and low hemoglobinemia. The predictors of early mortality were: age, high bilirubinemia, hypoalbuminemia, biliary drainage and long drainage-to-surgery interval. For both models, the p values of Hosmer-Lemeshow tests were of 0.9 and 0.99, respectively, the Akaike information criteria were of 35.5 and 37.7, respectively, and area under the curves was of 0.73 and 0.86, respectively. CONCLUSION: We developed two accurate and practical nomograms based on exclusively preoperative data to predict early outcomes following the resection of perihilar tumors. If validated in larger series, these tools could be integrated in the decision-making process for patient selection.

Debulking surgery for colorectal liver metastases: Foolish or chance?

Even with the recent advances of surgical techniques and systemic therapies, we are often facing patients with multinodular bilateral disease for whom neither R0 nor R1 resection appears possible to perform. For such extensive cases, the tumor debulking approaches might provide a survival benefit, provided that an objective tumor response is obtained with chemotherapy. Here, we review all the arguments which may defend this strategy and propose some recommendations.

Predictors of unresectability after portal vein embolization for centrally located cholangiocarcinoma.

BACKGROUND: The curative treatment of perihilar cholangiocarcinomas and centrally located intrahepatic cholangiocarcinomas often requires major hepatectomy preceded by portal vein embolization. This strategy, however, is associated with a high rate of dropouts before operation or failure of resection at the time of operative exploration. We aimed to identify predictors of unresectability (dropout or failure of resection) after portal vein embolization for centrally located cholangiocarcinoma, including perihilar cholangiocarcinomas and intrahepatic cholangiocarcinomas. METHOD: All patients undergoing portal vein embolization for a planned resection of a centrally located cholangiocarcinoma between 2000 and 2018 in our center were evaluated retrospectively. Predictors of unresectability were determined under intention-to-treat conditions, based on clinical, biologic, and radiologic data collected before portal vein embolization. RESULTS: Eighty-eight consecutive patients scheduled for portal vein embolization before operative exploration were included, 56 of whom (64%) underwent curative resection and 32 (36%) of whom were not resected, including those who did not undergo exploration (n = 11) and those operated on but not resected (n = 21). The most common cause of unresectability was tumor progression (62%). A psoas muscle index <500 mm2/m2 (P = .04), high body mass index (P = .023), and low serum albumin level (P = .007) were associated with unresectabilty on multivariate analysis. A composite score including these variables (cutoffs determined after receiver operating characteristic curve analysis) was proposed and achieved accurate discrimination regarding unresectability (area under the curve = 0.82, P < .001). CONCLUSION: Predictors of unresectability after portal vein embolization for centrally located cholangiocarcinoma were identified, with sarcopenic overweight patients having a greater risk of unresectability. This preoperative score enables a fairly accurate prediction of unresectability in a given patient. These simple, objective, and inexpensive parameters should be considered in all patients with centrally located cholangiocarcinoma scheduled to undergo portal vein embolization.

Management and Outcome of Borderline Common Bile Duct with Stones: A Prospective Randomized Study.

INTRODUCTION: Management of common bile duct stones (CBDS) in patients with borderline CBD presents a surgical challenge. The aim of this study was to compare conservative treatment with endoscopic stone extraction for the treatment of borderline CBD with stones. PATIENTS AND METHODS: This prospective randomized controlled trial includes patients with CBDS in borderline CBD (CBD <10 mm) associated with gallbladder stones who were treated with conservative treatment or endoscopic stone extraction followed by laparoscopic cholecystectomy (LC) and intraoperative cholangiogram (IOC). The primary outcome was successful CBD clearance. The secondary outcomes were the overall complications, cost, and hospital stay. RESULTS: LC and IOC revealed complete clearance of CBDS in 48 (96%) cases in the endoscopic retrograde cholangiopancreatography (ERCP) group (52% of patients by ERCP, and 44% of patient passed the stone spontaneously), and in the remaining two patients, the CBDS was removed by transcystic exploration. In the conservative group, LC and IOC revealed complete clearance of CBDS in 90% of cases, and in the remaining 10% of patients, the CBDS was removed by transcystic exploration. Post-ERCP pancreatitis (PEP) is noticed significantly in the ERCP group (2 [4%] versus 8 [16%]; P = .04). The average net cost was significantly higher in the ERCP group. Recurrent biliary symptoms developed significantly in the ERCP group after 1 year (10% versus 0%; P = .02) in the form of recurrent cholangititis and recurrent CBDS. CONCLUSIONS: Management of CBDS in patients with borderline CBD represents a surgical challenge. Borderline CBD increases the technical difficulty of ERCP and increases the risk of PEP. Conservative management of CBDS in borderline CBD not only avoids the risks inherent in ERCP and unnecessary preoperative ERCP, but it is also effective in clearing CBDS. The hepatobiliary surgeon should consider a conservative line of treatment in CBDS in borderline CBD in order to decrease the cost and avoid unnecessary ERCP.

Right adrenal gland neuroblastoma infiltrating the liver and mimicking mesenchymal hamartoma: A case report.

INTRODUCTION: Neuroblastoma is the most common extracranial solid pediatric malignancy. The most common site is abdomen with predominance of suprarenal medulla. Infiltration of the tumour to the liver is rare. No cases were reported in the literature about the misdiagnosis of neuroblastoma as mesenchymal hamartoma in the liver. PRESENTATION OF CASE: We represent a rare case of neuroblastoma misdiagnosed as mesenchymal hamartoma in liver in a six-month-old female infant presented with fever and abdominal mass. Abdominal computed tomography (CT) revealed large cystic lesion occupying most of the right liver enchroaching upon right suprarenal region and displacing the right kidney inferior suggestive for mesenchymal hamartoma. Right adrenalectomy with en-bloc resection of the adjacent liver segments was done. Postoperative pathology revealed neuroblastoma with positive specific immunohistochemistry (IHC). DISCUSSION: Although neuroblastoma is the second most common pediatric abdominal malignancy with specific diagnostic modalities, a misdiagnosis of a case with neuroblastoma as mesenchymal hamartoma is rare. Histopathological diagnosis of neuroblastoma with positive IHC is essential as shown in our case. CONCLUSION: We represent a rare case of neuroblastoma which arose from the right adrenal gland and infiltrated the adjacent liver substance mimicking mesenchymal hamartoma of the liver. Neuroblastoma is rarely presented with pyrexia of unknown origin. Neuroblastoma should be considered in differential diagnosis of abdominal mass in all infants and children.

Long-term follow-up of 120 patients after hepaticojejunostomy for treatment of post-cholecystectomy bile duct injuries: A retrospective cohort study.

BACKGROUND: Long-term follow-up is essential for assessment of success of the surgical repair of post-cholecystectomy bile duct injuries (BDI). Factors affecting the long-term outcome and satisfactory length of follow-up have been little reported in the literature. The aim of this study is long-term evaluation of hepaticojejunostomy regarding clinical, radiological, laboratory and quality of life assessment. METHOD: Between January 1992 to December 2007, 120 patients with postcholecystectomy bile duct injury surgically treated by hepaticojejunostomy Roux-en-Y were followed up for 20 years in Mansoura Gastro-enterology Center. Long-term outcomes and quality of life (QOL) were evaluated for all patients. Univariate and multivariate analyses were done for detection of factors affecting long-term outcome. RESULTS: The median follow up period was 149 months, range (70-246 months). Successful long-term outcome was detected in 106 (88.3%) patients. Long-term complications were detected in 35 (29%) patients. Fourteen (11.6%) patients developed anastomotic stricture within different follow up intervals up to 17 years, of which. Seventeen (14.2%) patients developed recurrent episodes of cholangitis at median interval 48 months, range (2-156 months). Post-ERCP pancreatitis, number of anastomosis, operative time, post-operative early complications, and post-operative bile leak were predictors for poor outcome. Physical component was much more affected than mental component in QOL. CONCLUSION: Management of BDI in specialized centers is highly recommended. Longer time for follow-up of the patients of surgical repair of bile duct injury up to 20 years should be adopted to ensure successful outcome. Quality of life assessment is essential component of long-term follow-up.