Prognostic models to predict survival in patients with pancreatic cancer: a systematic review.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) has poor survival. Current treatments offer little likelihood of cure or long-term survival. This systematic review evaluates prognostic models predicting overall survival in patients diagnosed with PDAC. METHODS: We conducted a comprehensive search of eight electronic databases from their date of inception through to December 2019. Studies that published models predicting survival in patients with PDAC were identified. RESULTS: 3297 studies were identified; 187 full-text articles were retrieved and 54 studies of 49 unique prognostic models were included. Of these, 28 (57.1%) were conducted in patients with advanced disease, 17 (34.7%) with resectable disease, and four (8.2%) in all patients. 34 (69.4%) models were validated, and 35 (71.4%) reported model discrimination, with only five models reporting values >0.70 in both derivation and validation cohorts. Many (n = 27) had a moderate to high risk of bias and most (n = 33) were developed using retrospective data. No variables were unanimously found to be predictive of survival when included in more than one study. CONCLUSION: Most prognostic models were developed using retrospective data and performed poorly. Future research should validate instruments performing well locally in international cohorts and investigate other potential predictors of survival.

The AGITG GAP Study: A Phase II Study of Perioperative Gemcitabine and Nab-Paclitaxel for Resectable Pancreas Cancer.

BACKGROUND: While combination therapy with nab-paclitaxel/gemcitabine (nab-gem) is effective in pancreatic ductal adenocarcinoma (PDAC), its efficacy as perioperative chemotherapy is unknown. The primary objective of this multicenter, prospective, single-arm, phase II study was to determine whether neoadjuvant therapy with nab-gem was associated with higher complete resection rates (R0) in resectable PDAC, while the secondary objectives were to determine the utility of radiological assessment of response to preoperative chemotherapy and the safety and efficacy of nab-gem as perioperative therapy. METHODS: Patients were recruited from eight Australian sites, and 42 patients with radiologically defined resectable PDAC and an Eastern Cooperative Oncology Group performance status of 0-2 were enrolled. Participants received two cycles of preoperative nab-paclitaxel 125 mg/m2 and gemcitabine 1000 mg/m2 on days 1, 8, and 15 (28-day cycle) presurgery, and four cycles postoperatively. Early response to chemotherapy was measured with fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) scans on day 15. RESULTS: Preoperative nab-gem was completed by 93% of participants, but only 63% postoperatively. Thirty-six patients had surgery: 6 (17%) were unresectable, 15 (52%) had R0 (≥ 1 mm) resections, 14 (48%) had R1 (< 1 mm) resections, and 1 patient did not have PDAC. Median progression-free survival was 12.3 months and median overall survival (OS) was 23.5 months: R0 patients had an OS of 35 months versus 25.6 months for R1 patients after surgery. Seven patients had not progressed after 43 months. CONCLUSIONS: The GAP trial demonstrated that perioperative nab-gem was tolerable. Although the primary endpoint of an 85% R0 rate was not met, the R0 rate was similar to trials using a > 1 mm R0 resection definition, and survival rates were comparable with recent adjuvant studies.

The Upper Gastrointestinal Cancer Registry (UGICR): a clinical quality registry to monitor and improve care in upper gastrointestinal cancers.

PURPOSE: The Upper Gastrointestinal Cancer Registry (UGICR) was developed to monitor and improve the quality of care provided to patients with upper gastrointestinal cancers in Australia. PARTICIPANTS: It supports four cancer modules: pancreatic, oesophagogastric, biliary and primary liver cancer. The pancreatic cancer (PC) module was the first module to be implemented, with others being established in a staged approach. Individuals are recruited to the registry if they are aged 18 years or older, have received care for their cancer at a participating public/private hospital or private clinic in Australia and do not opt out of participation. FINDINGS TO DATE: The UGICR is governed by a multidisciplinary steering committee that provides clinical governance and oversees clinical working parties. The role of the working parties is to develop quality indicators based on best practice for each registry module, develop the minimum datasets and provide guidance in analysing and reporting of results. Data are captured from existing data sources (population-based cancer incidence registries, pathology databases and hospital-coded data) and manually from clinical records. Data collectors directly enter information into a secure web-based Research Electronic Data Capture (REDCap) data collection platform. The PC module began with a pilot phase, and subsequently, we used a formal modified Delphi consensus process to establish a core set of quality indicators for PC. The second module developed was the oesophagogastric cancer (OGC) module. Results of the 1 year pilot phases for PC and OGC modules are included in this cohort profile. FUTURE PLANS: The UGICR will provide regular reports of risk-adjusted, benchmarked performance on a range of quality indicators that will highlight variations in care and clinical outcomes at a health service level. The registry has also been developed with the view to collect patient-reported outcomes (PROs), which will further add to our understanding of the care of patients with these cancers.

Impact of Jaundice on Outcomes Following Emergency Laparoscopic Cholecystectomy in Patients with Choledocholithiasis.

INTRODUCTION: Traditional teaching dictates that it may not be prudent to take the jaundiced patient to theatre for emergency laparoscopic cholecystectomy as they may experience worse outcomes following surgery. METHODS: A prospective cohort of 104 patients undergoing emergency laparoscopic cholecystectomy was stratified into two groups using a serum total bilirubin of above 50 µmol/L (2.9 mg/dL) to define the jaundiced group. Primary outcomes were morbidity and mortality rate. The Clavien-Dindo classification and the novel Comprehensive Complication Index (CCI) were applied to the grading of surgical complications. Multivariate analysis to identify possible predictors of morbidity and length of stay was also performed. RESULTS: Overall morbidity rate in the jaundiced group was 28 versus 36% (control), p = 0.405. Mean CCI in the jaundiced group was 5.28 versus 8.00 in the control group, p = 0.229. Mean length of stay was shorter in the jaundiced group, 4.65 versus 6.51 days, p = 0.036. There were no peri-operative mortalities or conversions to open surgery. Only male gender and the presence of retained stones were found to be associated with morbidity. Serum total bilirubin was not associated with increased morbidity. CONCLUSION: Amongst patients undergoing laparoscopic cholecystectomy who are found to have choledocholithiasis on IOC, the presence of jaundice does not appear to contribute towards increased morbidity.

Usefulness of early post-operative liver function test monitoring after laparoscopic common bile duct exploration.

BACKGROUND: This study examines the usefulness of early post-operative liver function test (LFT) monitoring in predicting retained choledocholithiasis after laparoscopic common bile duct exploration (LCBDE). METHODS: Data on patients who had LCBDE over a 3-year period were collected retrospectively. Patients who had ongoing choledocholithiasis after unsuccessful LCBDE were considered for the test group and patients who had successful LCBDE were considered for the control group. Preoperative, day 1 post-operative and day 2 post-operative alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), alanine transaminase (ALT) and bilirubin levels were recorded. Proportions of patients who had worsening LFTs were analysed in each group. RESULTS: Proportions of patient who had worsening LFTs on day 1 were not statistically different between two groups and they were statistically equal on equivalence testing (two one-sided tests). On day 2, proportions of patient were again not statistically different. Bilirubin and ALT were statistically equivalent (P = 0.022 and P = 0.025 respectively) but GGT and ALP failed to achieve statistical equivalence (P = 0.062 and P = 0.138 respectively) on day 2. Twelve patients with normal appearing final intraoperative cholangiogram needed reintervention due to retained choledocholithiasis diagnosed subsequently. LFTs progressively improved despite presence of choledocholithiasis in eight of these 12 patients (75%) and only four were diagnosed by worsening post-operative LFTs during index admission. CONCLUSION: LFTs in the early post-operative period are not useful in determining which patients require biliary imaging or intervention after an apparently successful LCBDE.