Diagnostic performance of preoperative CT in differentiating between benign and malignant origin of suspicious gallbladder lesions

Purpose: To determine diagnostic performance of preoperative CT in differentiating between benign and malignant suspicious gallbladder lesions and to develop a preoperative risk score. Method: All patients referred between January 2007 and September 2018 for suspicion of gallbladder cancer (GBC) or incidentally found GBC were retrospectively analyzed. Patients were excluded when preoperative CT or histopathologic examination was lacking. Two radiologists, blinded to histopathology results, independently reviewed CT images to differentiate benign disease from GBC. Multivariable analysis and internal validation were used to develop a risk score for GBC. Model discrimination, calibration, and diagnostic performance were assessed. Results: In total, 118 patients with 39 malignant (33 %) and 79 benign (67 %) lesions were included. Sensitivity of CT for diagnosing GBC was 90 % (95 % confidence interval [CI]: 76?97). Specificity rates were 61 % (95 % CI: 49?72) and 59 % (95 % CI: 48?70). Three predictors of GBC (irregular lesion aspect, absence of fat stranding, and locoregional lymphadenopathy) were included in the risk score ranging from -1 to 4. Adequate performance was found (AUC: 0.79, calibration slope: 0.89). In patients allocated >0 points, the model showed higher performance in excluding GBC than the radiologists (sensitivity 92 % [95 % CI: 79?98]). Moreover, when allocated >3 points, the risk score was superior in diagnosing GBC (specificity 99 % [95 % CI: 93?100]). Conclusions: Sensitivity rates of CT for differentiation between benign and malignant gallbladder lesions are high, however specificity rates are relatively low. The proposed risk score may facilitate differentiation between benign and malignant suspicious gallbladder lesions

Gallbladder Cancer:Current Insights in Genetic Alterations and Their Possible Therapeutic Implications

SIMPLE SUMMARY: Knowledge of genetic alterations in gallbladder cancer (GBC) continues to increase. This systematic review provides an overview of frequently occurring genetic alterations in GBC and describes their possible therapeutic implications. We detected three frequently (>5%) altered genes (ATM, ERBB2 and PIK3CA) for which targeted therapies are available in other cancer types. For solid cancers with microsatellite instability or a high tumor mutational burden pembrolizumab is FDA-approved. Altogether, these five biomarkers might be used in future molecular panels to enable precision medicine for patients with GBC. We found only nine clinical trials evaluating targeted therapies in GBC directed at frequently altered genes (ERBB2, ARID1A, ATM and KRAS). This underlines the challenges to perform such clinical trials in this rare, heterogeneous cancer type and emphasizes the need for multicenter clinical trials. ABSTRACT: Due to the fast progression in molecular technologies such as next-generation sequencing, knowledge of genetic alterations in gallbladder cancer (GBC) increases. This systematic review provides an overview of frequently occurring genetic alterations occurring in GBC and their possible therapeutic implications. A literature search was performed utilizing PubMed, EMBASE, Cochrane Library, and Web of Science. Only studies reporting genetic alterations in human GBC were included. In total, data were extracted from 62 articles, describing a total of 3893 GBC samples. Frequently detected genetic alterations (>5% in >5 samples across all studies) in GBC for which targeted therapies are available in other cancer types included mutations in ATM, ERBB2, and PIK3CA, and ERBB2 amplifications. High tumor mutational burden (TMB-H) and microsatellite instability (MSI-H) were infrequently observed in GBC (1.7% and 3.5%, respectively). For solid cancers with TMB-H or MSI-H pembrolizumab is FDA-approved and shows an objective response rates of 50% for TMB-H GBC and 41% for MSI-H biliary tract cancer. Only nine clinical trials evaluated targeted therapies in GBC directed at frequently altered genes (ERBB2, ARID1A, ATM, and KRAS). This underlines the challenges to perform such clinical trials in this rare, heterogeneous cancer type and emphasizes the need for multicenter clinical trials

Delta peritoneal cancer index (Delta PCI):A new dynamic prognostic parameter for survival in patients with colorectal peritoneal metastases

Background: The peritoneal cancer index (PCI) calculated during exploratory laparotomy is a strong prognostic factor for overall survival (OS) in patients with colorectal peritoneal metastases (PM) who undergo cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS + HIPEC). Progression of the PCI between diagnostic laparoscopy (DLS) and potential CRS + HIPEC (Delta PCI) might be a more dynamic prognostic factor for OS after CRS + HIPEC. Materials and methods: Between 2012 and 2018, all colorectal PM patients who underwent an exploratory laparotomy for potential CRS + HIPEC after DLS were retrospectively identified from a prospectively maintained database. Patients were divided into stable disease (Delta PCI 0-3), mild progression (Delta PCI 4-9), or severe progression (Delta PCI >= 10). Kaplan-Meier analysis and a multivariate Cox regression were performed. Results: Eighty-four patients (Delta PCI 0-3, n = 35; Delta PCI 4-9, n = 34; and Delta PCI >= 10, n = 15) were analysed. Median OS after CRS + HIPEC was significantly decreased in patients with a Delta PCI of 4-9 (35.1 [95% CI 25.5-44.6]) or Delta PCI >= 10 (24.1 [95% CI 11.7-36.5]) compared to patients with a Delta PCI of 0-3 (47.9 [95% CI 40.0-55.7], p = 0.004). In multivariate regression analysis, Delta PCI remained an independent risk factor for OS: Delta PCI 4-9 HR 3.1 (95% CI 1.4-7.2, p = 0.007) and Delta PCI >= 10 HR 4.4 (95% CI 1.5-13.1, p = 0.007). Conclusion: A high Delta PCI is an independent dynamic prognostic factor for OS and might reflect a more aggressive tumour biology in patients with colorectal PM. HIPEC surgeons should be aware of a high-Delta PCI-associated diminished prognosis and should reconsider CRS + HIPEC when confronted with a Delta PCI >= 10. (C) 2019 Elsevier Ltd, BASO - The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved

Should jaundice preclude resection in patients with gallbladder cancer? Results from a nation-wide cohort study

Background: It is controversial whether patients with gallbladder cancer (GBC) presenting with jaundice benefit from resection. This study re-evaluates the impact of jaundice on resectability and survival. Methods: Data was collected on surgically explored GBC patients in all Dutch academic hospitals from 2000 to 2018. Survival and prognostic factors were assessed. Results: In total 202 patients underwent exploration and 148 were resected; 124 non-jaundiced patients (104 resected) and 75 jaundiced patients (44 resected). Jaundiced patients had significantly (P < 0.05) more pT3/T4 tumors, extended (≥3 segments) liver- and organ resections, major post-operative complications and margin-positive resection. 90-day mortality was higher in jaundiced patients (14% vs. 0%, P < 0.001). Median overall survival (OS) was 7.7 months in jaundiced patients (2-year survival 17%) vs. 26.1 months in non-jaundiced patients (2-year survival 39%, P < 0.001). In multivariate analysis, jaundice (HR1.89) was a poor prognostic factor for OS in surgically explored but not in resected patients. Six jaundiced patients did not develop a recurrence; none had liver- or common bile duct (CBD) invasion on imaging. Conclusion: Jaundice is associated with poor survival. However, jaundice is not an independent adverse prognostic factor in resected patients. Surgery should be considered in patients with limited disease and no CBD invasion on imaging

Impact of Synchronous Versus Metachronous Onset of Colorectal Peritoneal Metastases on Survival Outcomes After Cytoreductive Surgery (CRS) with Hyperthermic Intraperitoneal Chemotherapy (HIPEC): A Multicenter, Retrospective, Observational Study

Background. Careful selection of patients with colorectal peritoneal metastases (PM) for cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is crucial. It remains unknown whether the time of onset of colorectal PM (synchronous vs metachronous) influences surgical morbidity and survival outcomes after CRS with HIPEC. Methods. Patients with histologically proven colorectal PM who underwent CRS with HIPEC between February 2006 and December 2017 in two Dutch tertiary referral hospitals were retrospectively included from a prospectively maintained database. The onset of colorectal PM was classified as synchronous (PM diagnosed at the initiationalpresentation with colorectal cancer) or metachronous (PM diagnosed after initial curative colorectal resection). Major postoperative complications (Clavien-Dindo grade >= 3), overall survival (OS), and disease-free survival (DFS) were compared between patients with synchronous colorectal PM and those with metachronous colorectal PM using Kaplan-Meier analyses, proportional hazard analyses, and a multivariate Cox regression analysis. Results. The study enrolled 433 patients, of whom 231 (53%) had synchronous colorectal PM and 202 (47%) had metachronous colorectal PM. The major postoperative complication rate and median OS were similar between the patients with synchronous colorectal PM and those with metachronous colorectal PM (26.8% vs 29.7%; p=0.693 and 34 vs 33months, respectively; p=0.819). The median DFS was significantly decreased for the patients with metachronous colorectal PM and those with synchronous colorectal PM (11 vs 15months; adjusted hazard ratio, 1.63; 95% confidence interval, 1.18-2.26). Conclusions. Metachronous onset of colorectal PM is associated with early recurrence after CRS with HIPEC compared with synchronous colorectal PM, without a difference in OS or major postoperative complications. Time to onset of colorectal PM should be taken into consideration to optimize patient selection for this major procedure

Should jaundice preclude resection in patients with gallbladder cancer? Results from a nation-wide cohort study

Background: It is controversial whether patients with gallbladder cancer (GBC) presenting with jaundice benefit from resection. This study re-evaluates the impact of jaundice on resectability and survival. Methods: Data was collected on surgically explored GBC patients in all Dutch academic hospitals from 2000 to 2018. Survival and prognostic factors were assessed. Results: In total 202 patients underwent exploration and 148 were resected; 124 non-jaundiced patients (104 resected) and 75 jaundiced patients (44 resected). Jaundiced patients had significantly (P < 0.05) more pT3/T4 tumors, extended (≥3 segments) liver- and organ resections, major post-operative complications and margin-positive resection. 90-day mortality was higher in jaundiced patients (14% vs. 0%, P < 0.001). Median overall survival (OS) was 7.7 months in jaundiced patients (2-year survival 17%) vs. 26.1 months in non-jaundiced patients (2-year survival 39%, P < 0.001). In multivariate analysis, jaundice (HR1.89) was a poor prognostic factor for OS in surgically explored but not in resected patients. Six jaundiced patients did not develop a recurrence; none had liver- or common bile duct (CBD) invasion on imaging. Conclusion: Jaundice is associated with poor survival. However, jaundice is not an independent adverse prognostic factor in resected patients. Surgery should be considered in patients with limited disease and no CBD invasion on imaging

Should jaundice preclude resection in patients with gallbladder cancer? Results from a nation-wide cohort study

Background: It is controversial whether patients with gallbladder cancer (GBC) presenting with jaundice benefit from resection. This study re-evaluates the impact of jaundice on resectability and survival. Methods: Data was collected on surgically explored GBC patients in all Dutch academic hospitals from 2000 to 2018. Survival and prognostic factors were assessed. Results: In total 202 patients underwent exploration and 148 were resected; 124 non-jaundiced patients (104 resected) and 75 jaundiced patients (44 resected). Jaundiced patients had significantly (P < 0.05) more pT3/T4 tumors, extended (≥3 segments) liver- and organ resections, major post-operative complications and margin-positive resection. 90-day mortality was higher in jaundiced patients (14% vs. 0%, P < 0.001). Median overall survival (OS) was 7.7 months in jaundiced patients (2-year survival 17%) vs. 26.1 months in non-jaundiced patients (2-year survival 39%, P < 0.001). In multivariate analysis, jaundice (HR1.89) was a poor prognostic factor for OS in surgically explored but not in resected patients. Six jaundiced patients did not develop a recurrence; none had liver- or common bile duct (CBD) invasion on imaging. Conclusion: Jaundice is associated with poor survival. However, jaundice is not an independent adverse prognostic factor in resected patients. Surgery should be considered in patients with limited disease and no CBD invasion on imaging