Improved survival prediction and comparison of prognostic models for patients with hepatocellular carcinoma treated with sorafenib

BACKGROUND: The 'Prediction Of Survival in Advanced Sorafenib-treated HCC' (PROSASH) model addressed the heterogeneous survival of patients with hepatocellular carcinoma (HCC) treated with sorafenib in clinical trials, but requires validation in daily clinical practice. This study aimed to validate, compare and optimize this model for survival prediction. METHODS: Patients treated with sorafenib for HCC at 5 tertiary European centres were retrospectively staged according to the PROSASH model. In addition, the optimized PROSASH-II model was developed using the data of 4 centres (training set) and tested in an independent dataset. These models for overall survival (OS) were then compared with existing prognostic models. RESULTS: The PROSASH model was validated in 445 patients, showing clear differences between the 4 risk groups (OS 16.9-4.6 months). A total of 920 patients (n=615 in training set, n=305 in validation set) were available to develop PROSASH-II. This optimized model incorporated fewer and less subjective parameters: the serum albumin, bilirubin and alpha-fetoprotein, and macrovascular invasion, extrahepatic spread and largest tumour size on imaging. Both PROSASH and PROSASH-II showed improved discrimination (C-index 0.62 and 0.63, respectively) compared with existing prognostic scores (C-index ≤0.59). CONCLUSIONS: In HCC patients treated with sorafenib, individualized prediction of survival and risk group stratification using baseline prognostic and predictive parameters with the PROSASH model was validated. The refined PROSASH-II model performed at least as good with fewer and more objective parameters. PROSASH-II can be used as a tool for tailored treatment of HCC in daily practice and to define pre-planned subgroups for future studies

Endoscopic and Percutaneous Preoperative Biliary Drainage in Patients with Suspected Hilar Cholangiocarcinoma

INTRODUCTION: Controversy exists over the preferred technique of preoperative biliary drainage (PBD) in patients with hilar cholangiocarcinoma (HCCA) requiring major liver resection. The current study compared outcomes of endoscopic biliary drainage (EBD) and percutaneous transhepatic biliary drainage (PTBD) in patients with resectable HCCA. METHODS: One hundred fifteen consecutive patients were explored for HCCA between 2001 and July 2008 and assigned by initial PBD procedure to either EBD or PTBD. RESULTS: Of these patients, 101 (88%) underwent PBD; 90 patients underwent EBD as primary procedure, and 11 PTBD. The technical success rate of initial drainage was 81% in the EBD versus 100% in the PTBD group (P = 0.20). Stent dislocation was similar in the EBD and PTBD groups (23% vs. 20%, P = 0.70). Infectious complications were significantly more common in the endoscopic group (48% vs. 9%, P < 0.05). Patients in the EBD group underwent more drainage procedures (2.8 vs. 1.4, P < 0.01) and had a significantly longer drainage period until laparotomy (mean 15 weeks vs. 11 weeks in the PTBD group; P < 0.05). In 30 patients, EBD was converted to PTBD due to failure of the endoscopic approach. CONCLUSIONS: Preoperative percutaneous drainage could outperform endoscopic stent placement in patients with resectable HCCA, showing fewer infectious complications, using less procedure

Value of risk scores in the decision to palliate patients with ruptured abdominal aortic aneurysm

Background: The aim of this study was to develop a 48-h mortality risk score, which included morphology data, for patients with ruptured abdominal aortic aneurysm presenting to an emergency department, and to assess its predictive accuracy and clinical effectiveness in triaging patients to immediate aneurysm repair, transfer or palliative care. Methods: Data from patients in the IMPROVE (Immediate Management of the Patient With Ruptured Aneurysm: Open Versus Endovascular Repair) randomized trial were used to develop the risk score. Variables considered included age, sex, haemodynamic markers and aortic morphology. Backwards selection was used to identify relevant predictors. Predictive performance was assessed using calibration plots and the C-statistic. Validation of the newly developed and other previously published scores was conducted in four external populations. The net benefit of treating patients based on a risk threshold compared with treating none was quantified. Results: Data from 536 patients in the IMPROVE trial were included. The final variables retained were age, sex, haemoglobin level, serum creatinine level, systolic BP, aortic neck length and angle, and acute myocardial ischaemia. The discrimination of the score for 48-h mortality in the IMPROVE data was reasonable (C-statistic 0·710, 95 per cent c.i. 0·659 to 0·760), but varied in external populations (from 0·652 to 0·761). The new score outperformed other published risk scores in some, but not all, populations. An 8 (95 per cent c.i. 5 to 11) per cent improvement in the C-statistic was estimated compared with using age alone. Conclusion: The assessed risk scores did not have sufficient accuracy to enable potentially life-saving decisions to be made regarding intervention. Focus should therefore shift to offering repair to more patients and reducing non-intervention rates, while respecting the wishes of the patient and family

Hepatocellular carcinoma: Dutch guideline for surveillance, diagnosis and therapy

Hepatocellular carcinoma (HCC) is rare in the Netherlands, even though the incidence has increased quite sharply in recent years. Standard treatment options consist of surgery, orthotopic liver transplantation, radiofrequency ablation, transarterial chemoembolisation (TACE) and systemic therapy with sorafenib. The consensus-based Dutch HCC guideline, established in 2013, serves to guide surveillance, diagnosis and treatment options: Surveillance should be performed by ultrasound at six-month intervals in well-defined cirrhotic patients and in selected high-risk hepatitis B carriers; A nodule > 1 cm in cirrhotic patients with arterial hypervascularity and venous or delayed phase washout at four-phase CT or MRI scan establishes the diagnosis of HCC; In patients with HCC without underlying cirrhosis, resection should be considered regardless of tumour size; In cirrhotic HCC patients, tumour stage, severity of underlying cirrhosis, and performance status determine treatment options. The algorithm of the Barcelona Clinic Liver Cancer (BCLC) staging system should be followed; Patients with Child-Pugh A-B cirrhosis (CP < 8 points) and performance status 0-2 are candidates for any active treatment other than transplantation; In early stage HCC (BCLC stage 0 or A, compensated cirrhosis without portal hypertension) surgical resection, liver transplantation, or radiofrequency ablation should be considered; In intermediate stage HCC (BCLC stage B) TACE and/or radiofrequency ablation should be considered; In advanced stage HCC (BCLC stage C) sorafenib should be considered. Conclusion: The Dutch HCC guideline offers advice for surveillance, diagnosis and treatment of HCC

Preoperative endoscopic versus percutaneous transhepatic biliary drainage in potentially resectable perihilar cholangiocarcinoma (DRAINAGE trial): design and rationale of a randomized controlled trial

Background: Liver surgery in perihilar cholangiocarcinoma (PHC) is associated with high postoperative morbidity because the tumor typically causes biliary obstruction. Preoperative biliary drainage is used to create a safer environment prior to liver surgery, but biliary drainage may be harmful when severe drainage-related complications deteriorate the patients' condition or increase the risk of postoperative morbidity. Biliary drainage can cause cholangitis/cholecystitis, pancreatitis, hemorrhage, portal vein thrombosis, bowel wall perforation, or dehydration. Two methods of preoperative biliary drainage are mostly applied: endoscopic biliary drainage, which is currently used in most regional centers before referring patients for surgical treatment, and percutaneous transhepatic biliary drainage. Both methods are associated with severe drainage-related complications, but two small retrospective series found a lower incidence in the number of preoperative complications after percutaneous drainage compared to endoscopic drainage (18-25% versus 38-60%, respectively). The present study randomizes patients with potentially resectable PHC and biliary obstruction between preoperative endoscopic or percutaneous transhepatic biliary drainage. Methods/Design: The study is a multi-center trial with an "all-comers" design, randomizing patients between endoscopic or percutaneous transhepatic biliary drainage. All patients selected to potentially undergo a major liver resection for presumed PHC are eligible for inclusion in the study provided that the biliary system in the future liver remnant is obstructed (even if they underwent previous inadequate endoscopic drainage). Primary outcome measure is the total number of severe preoperative complications between randomization and exploratory laparotomy. The study is designed to detect superiority of percutaneous drainage: a provisional sample size of 106 patients is required to detect a relative decrease of 50% in the number of severe preoperative complications (alpha = 0.95; beta = 0.8). Interim analysis after inclusion of 53 patients (50%) will provide the definitive sample size. Secondary outcome measures encompass the success of biliary drainage, quality of life, and postoperative morbidity and mortality. Discussion: The DRAINAGE trial is designed to identify a difference in the number of severe drainage-related complications after endoscopic and percutaneous transhepatic biliary drainage in patients selected to undergo a major liver resection for perihilar cholangiocarcinoma