Symptomatic Cholelithiasis: Do Minority Patients Experience Delays to Surgery?

BACKGROUND: Cholecystectomy is one of the most common surgeries and the majority are performed to treat symptomatic cholelithiasis (SC). While surgery is often elective, poor access or delays in care may lead to urgent cases, which are potentially associated with higher complication rates. This study aims to determine if minority patients with SC have higher rates of urgent cholecystectomy and postoperative complications. MATERIALS AND METHODS: Analysis of patients undergoing cholecystectomy for SC utilizing American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) from 2017 to 2019. Primary outcome was acuity of cholecystectomy (i.e., urgent versus elective). Secondary outcomes were any post-operative complication and length of stay. RESULTS: Patients who underwent cholecystectomy for SC between 2017 to 2019 (N: 13,390) were analyzed. Hispanic and non-Hispanic Black patients had higher odds of undergoing urgent surgery as compared to non-Hispanic White patients, and Hispanics had over twice the odds (adjusted odds ratio (aOR), 2.16; 95% CI 1.93-2.43), adjusting for age, sex, and comorbidities. Having urgent surgery was associated with higher odds for developing any postoperative complication and experiencing longer length of stay. After adjusting for urgency of surgery, Non-Hispanic Black and Asian patients were at risk for higher postoperative length of stay. CONCLUSIONS: Hispanic and non-Hispanic Black patients were more likely to undergo urgent cholecystectomy as compared to non-Hispanic White patients for SC. Urgent surgery was independently associated with a higher complication rate and longer length of stay. Further characterization of the delays to surgery that lead to these differences are critical to prevent further treatment disparities.

Trends in Robot-Assisted Procedures for General Surgery in the Veterans Health Administration.

INTRODUCTION: Implementation of robot-assisted procedures is growing. Utilization within the country's largest healthcare network, the Veterans Health Administration, is unclear. METHODS: A retrospective cohort study using data from the Department of Veterans Affairs Corporate Data Warehouse from January 2015 through December 2019. Trends in robot utilization for cholecystectomy, ventral hernia repair, and inguinal hernia repair were characterized nationally and regionally by Veterans Integrated Services Network. Patients, who underwent laparoscopic repairs for these procedures and open hernia repairs, were included to determine proportion performed robotically. RESULTS: We identified 119,191 patients, of which 5689 (4.77%) received a robotic operation. The proportion of operations performed robotically increased from 1.49% to 10.55% (7.08-fold change; slope, 2.14% per year; 95% confidence interval [0.79%, 3.49%]). Ventral hernia repair had the largest growth in robotic procedures (1.51% to 13.94%; 9.23-fold change; slope, 2.86% per year; 95% confidence interval [1.04%, 4.68%]). Regions with the largest increase in robotic utilization were primarily along the Northeast, Midwest, and West Coast. CONCLUSIONS: Robot utilization in general surgery is increasing at different rates across the United States in the Veterans Health Administration. Future studies should investigate the regional disparities and drivers of this approach.

Robot-Assisted General Surgery Procedures at the Veterans Health Administration: A Comparison of Surgical Techniques.

INTRODUCTION: The use of the robot in general surgery has exploded in the last decade. The Veterans Health Administration presents a unique opportunity to study differences between surgical approaches due to the ability to control for health system and insurance variability. This study compares clinical outcomes between robot-assisted and laparoscopic or open techniques for three general surgery procedures. METHODS: A retrospective observational study using the Veterans Affair Surgical Quality Improvement Program database. Operative time, length of stay, and complications were compared for cholecystectomy (robot-assisted versus laparoscopic), ventral, and inguinal hernia repair (robot-assisted versus laparoscopic or open) from 2015 to 2019. RESULTS: More than 80,000 cases were analyzed (21,652 cholecystectomy, 9214 ventral hernia repairs, and 51,324 inguinal hernia repairs). Median operative time was longer for all robot-assisted approaches as compared to laparoscopic or open techniques with the largest difference seen between open and robot-assisted primary ventral hernia repair (unadjusted difference of 93 min, P < 0.001). Median length of stay was between 1 and 4 d and significantly for robot-assisted ventral hernia repairs (versus open, P < 0.01; versus lap for recurrent hernia, P < 0.05). Specific postoperative outcomes of interest were overall low with few differences between techniques. CONCLUSIONS: While the robotic platform was associated with longer operative time, these findings must be interpreted in the context of a learning curve and indications for use (i.e., use of the robot for technically challenging cases). Our findings suggest that at the Veterans Health Administration, the robot is as safe a platform for common general surgery procedures as traditional approaches. Future studies should focus on patient-centered outcomes including pain and cosmesis.

Cumulative GRAS Score as a Predictor of Survival After Resection for Adrenocortical Carcinoma: Analysis From the U.S. Adrenocortical Carcinoma Database.

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare but aggressive malignancy, and many prognostic factors that influence survival remain undefined. Individually, the GRAS (Grade, Resection status, Age, and Symptoms of hormone hypersecretion) parameters have demonstrated their prognostic value in ACC. This study aimed to assess the value of a cumulative GRAS score as a prognostic indicator after ACC resection. METHODS: A retrospective cohort study of adult patients who underwent surgical resection for ACC between 1993 and 2014 was performed using the United States Adrenocortical Carcinoma Group (US-ACCG) database. A sum GRAS score was calculated for each patient by adding one point each when the criteria were met for tumor grade (Weiss criteria ≥ 3 or Ki67 ≥ 20%), resection status (micro- or macroscopically positive margin), age (≥ 50 years), and preoperative symptoms of hormone hypersecretion (present). Overall survival (OS) and disease-free survival (DFS) by cumulative GRAS score were analyzed by the Kaplan-Meier method and log-rank test. RESULTS: Of the 265 patients in the US-ACCG database, 243 (92%) had sufficient data available to calculate a cumulative GRAS score and were included in this analysis. The 265 patients comprised 23 patients (10%) with a GRAS of 0, 52 patients (21%) with a GRAS of 1, 92 patients (38%) with a GRAS of 2, 63 patients (26%) with a GRAS of 3, and 13 patients (5%) with a GRAS of 4. An increasing GRAS score was associated with shortened OS (p < 0.01) and DFS (p < 0.01) after index resection. CONCLUSION: In this retrospective analysis, the cumulative GRAS score effectively stratified OS and DFS after index resection for ACC. Further prospective analysis is required to validate the cumulative GRAS score as a prognostic indicator for clinical use.

Actual 5-Year Survivors After Surgical Resection of Hilar Cholangiocarcinoma.

BACKGROUND: The prevalence and characteristics of actual 5-year survivors after surgical treatment of hilar cholangiocarcinoma (HC) have not been described previously. METHODS: Patients who underwent resection for HC from 2000 to 2015 were analyzed through a multi-institutional registry from 10 U.S. academic medical centers. The clinicopathologic characteristics and both the perioperative and long-term outcomes for actual 5-year survivors were compared with those for non-survivors (patients who died within 5 years after surgery). Patients alive at last encounter who had a follow-up period shorter than 5 years were excluded from the study. RESULTS: The study identified 257 patients with HC who underwent curative-intent resection with an actuarial 5-year survival of 19%. Of 194 patients with a follow-up period longer than 5 years, 23 (12%) were 5-year survivors. Compared with non-survivors, the 5-year survivors had a lower median pretreatment CA 19-9 level (116 vs. 34 U/L; P = 0.008) and a lower rate of lymph node involvement (42% vs. 15%; P = 0.027) and R1 margins (39% vs. 17%; P = 0.042). However, the sole presence of these factors did not preclude a 5-year survival after surgery. The frequencies of bile duct resection alone, major hepatectomy, caudate lobe resection, portal vein or hepatic artery resection, preoperative biliary sepsis, intraoperative blood transfusion, serious postoperative complications, and receipt of adjuvant chemotherapy were comparable between the two groups. CONCLUSIONS: One in eight patients with HC reaches the 5-year survival milestone after resection. A 5-year survival can be achieved even in the presence of traditionally unfavorable clinicopathologic factors (elevated CA 19-9, nodal metastasis, and R1 margins).

Association of Perioperative Transfusion with Recurrence and Survival After Resection of Distal Cholangiocarcinoma: A 10-Institution Study from the US Extrahepatic Biliary Malignancy Consortium.

BACKGROUND: Perioperative allogeneic blood transfusion is associated with poor oncologic outcomes in multiple malignancies. The effect of blood transfusion on recurrence and survival in distal cholangiocarcinoma (DCC) is not known. METHODS: All patients with DCC who underwent curative-intent pancreaticoduodenectomy at 10 institutions from 2000 to 2015 were included. Primary outcomes were recurrence-free (RFS) and overall survival (OS). RESULTS: Among 314 patients with DCC, 191 (61%) underwent curative-intent pancreaticoduodenectomy. Fifty-three patients (28%) received perioperative blood transfusions, with a median of 2 units. There were no differences in baseline demographics or operative data between transfusion and no-transfusion groups. Compared with no-transfusion, patients who received a transfusion were more likely to have (+) margins (28 vs 14%; p = 0.034) and major complications (46 vs 16%; p < 0.001). Transfusion was associated with worse median RFS (19 vs 32 months; p = 0.006) and OS (15 vs 29 months; p = 0.003), which persisted on multivariable (MV) analysis for both RFS [hazard ratio (HR) 1.8; 95% confidence interval (CI) 1.1-3.0; p = 0.031] and OS (HR 1.9; 95% CI 1.1-3.3; p = 0.018), after controlling for portal vein resection, estimated blood loss (EBL), grade, lymphovascular invasion (LVI), and major complications. Similarly, transfusion of ≥ 2 pRBCs was associated with lower RFS (17 vs 32 months; p < 0.001) and OS (14 vs 29 months; p < 0.001), which again persisted on MV analysis for both RFS (HR 2.6; 95% CI 1.4-4.5; p = 0.001) and OS (HR 4.0; 95% CI 2.2-7.5; p < 0.001). The RFS and OS of patients transfused 1 unit was comparable to patients who were not transfused. CONCLUSION: Perioperative blood transfusion is associated with decreased RFS and OS after resection for distal cholangiocarcinoma, after accounting for known adverse pathologic factors. Volume of transfusion seems to exert an independent effect, as 1 unit was not associated with the same adverse effects as ≥ 2 units.

Transplantation Versus Resection for Hilar Cholangiocarcinoma: An Argument for Shifting Treatment Paradigms for Resectable Disease.

OBJECTIVE: To investigate the influence of type of surgery (transplant vs resection) on overall survival (OS) in patients with hilar cholangiocarcinoma (H-CCA). BACKGROUND: Outcomes after resection for H-CCA are poor, yet transplantation is currently only reserved for well-selected patients with unresectable disease. METHODS: All patients with H-CCA who underwent resection from 2000 to 2015 at 10 institutions were included. Three institutions additionally had active H-CCA transplant protocols with similar selection criteria over similar time periods. RESULTS: Of 304 patients with suspected H-CCA, 234 underwent attempted resection and 70 were enrolled in a transplant protocol. Excluding incomplete/R2 resections (n = 43), patients who were enrolled, but did not undergo transplant (n = 24), and transplants without confirmed H-CCA diagnoses (n = 5), 191 patients underwent curative-intent resection and 41 curative-intent transplant. Compared with resection, transplant patients were younger (52 vs 65 years; P < 0.001), and more frequently had primary sclerosing cholangitis (PSC; 61% vs 2%; P < 0.001) and received chemotherapy and/or radiation (98% vs 57%; P < 0.001). Groups were otherwise similar in demographics and comorbidities. Patients who underwent transplant for confirmed H-CCA diagnosis had improved OS compared with resection (3-year: 72% vs 33%; 5-year: 64% vs 18%; P < 0.001). Among patients who underwent resection for tumors <3 cm with lymph-node negative disease, and excluding PSC patients, transplant was still associated with improved OS (3-year: 54% vs 44%; 5-year: 54% vs 29%; P = 0.03). Transplant remained associated with improved survival on intention-to-treat analysis, even after accounting for tumor size, lymph node status, and PSC (P = 0.049). CONCLUSIONS: Resection for hilar cholangiocarcinoma that meets criteria for transplantation (<3 cm, lymph-node negative disease) is associated with substantially decreased survival compared to transplant for the same criteria with unresectable disease. Prospective trials are needed and justified.

A Novel T-Stage Classification System for Adrenocortical Carcinoma: Proposal from the US Adrenocortical Carcinoma Study Group.

BACKGROUND: The 7th AJCC T-stage system for adrenocortical carcinoma (ACC), based on size and extra-adrenal invasion, does not adequately stratify patients by survival. Lymphovascular invasion (LVI) is a known poor prognostic factor. We propose a novel T-stage system that incorporates LVI to better risk-stratify patients undergoing resection for ACC. METHOD: Patients undergoing curative-intent resections for ACC from 1993 to 2014 at 13 institutions comprising the US ACC Group were included. Primary outcome was disease-specific survival (DSS). RESULTS: Of the 265 patients with ACC, 149 were included for analysis. The current T-stage system failed to differentiate patients with T2 versus T3 disease (p = 0.10). Presence of LVI was associated with worse DSS versus no LVI (36 mo vs. 168 mo; p = 0.001). After accounting for the individual components of the current T-stage system (size, extra-adrenal invasion), LVI remained a poor prognostic factor on multivariable analysis (hazard ratio 2.14, 95% confidence interval 1.05-4.38, p = 0.04). LVI positivity further stratified patients with T2 and T3 disease (T2: 37 mo vs. median not reached; T3: 36 mo vs. 96 mo; p = 0.03) but did not influence survival in patients with T1 or T4 disease. By incorporating LVI, a new T-stage classification system was created: [T1: ≤ 5 cm, (-)local invasion, (+/-)LVI; T2: > 5 cm, (-)local invasion, (-)LVI OR any size, (+)local invasion, (-)LVI; T3: > 5 cm, (-)local invasion, (+)LVI OR any size, (+)local invasion, (+)LVI; T4: any size, (+)adjacent organ invasion, (+/-)LVI]. Each progressive new T-stage group was associated with worse median DSS (T1: 167 mo; T2: 96 mo; T3: 37 mo; T4: 15 mo; p < 0.001). CONCLUSIONS: Compared with the current T-stage system, the proposed T-stage system, which incorporates LVI, better differentiates T2 and T3 disease and accurately stratifies patients by disease-specific survival. If externally validated, this T-stage classification should be considered for future AJCC staging systems.

Association of perioperative transfusion with survival and recurrence after resection of gallbladder cancer: A 10-institution study from the US Extrahepatic Biliary Malignancy Consortium.

BACKGROUND AND OBJECTIVES: Perioperative blood transfusion is associated with poor outcomes in several malignancies. Its effect in gallbladder cancer (GBC) is unknown. METHODS: All patients with GBC who underwent curative-intent resection at 10-institutions from 2000 to 2015 were included. The effect of blood transfusion on overall survival (OS) and recurrence-free (RFS) was evaluated. RESULTS: Of 262 patients with curative-intent resection for GBC, 61 patients (23%) received blood transfusions. Radical cholecystectomy was the most common procedure (80%), but major hepatectomy was more frequent in the transfusion versus no-transfusion group (13% vs 4%; P = 0.02). The transfusion group was less likely to have incidentally discovered disease (57% vs 74%) and receive adjuvant therapy (29% vs 48%), but more likely to have preoperative jaundice (23% vs 11%), T3/T4 tumors (60% vs 39%), LVI (71% vs 40%), PNI (71% vs 48%), and major complications (39% vs 12%) (all P < 0.05). Transfusion was associated with lower median OS compared to no-transfusion (20 vs 32 mos; P < 0.001), which persisted on multivariable (MV) analysis (HR:1.9; 95%CI 1.1-3.5; P = 0.035), controlling for comorbidities, serum albumin, INR, preoperative jaundice, major hepatectomy, incidental discovery, margin status, T-Stage, LN status, and major complications. Median RFS of transfused patients was 13mo compared to 49mo for non-transfused patients (P = 0.1). Transfusion, however, was an independent predictor of decreased RFS on MV analysis (HR:2.3; 95%CI 1.1-5.1; P = 0.035). CONCLUSIONS: Perioperative blood transfusion is associated with decreased OS and RFS after resection for GCC, accounting for other adverse factors. Transfusions should thus be administered with well-defined protocols.

Adjuvant therapy is associated with improved survival after curative resection for hilar cholangiocarcinoma: A multi-institution analysis from the U.S. extrahepatic biliary malignancy consortium.

BACKGROUND: Curative-intent treatment for localized hilar cholangiocarcinoma (HC) requires surgical resection. However, the effect of adjuvant therapy (AT) on survival is unclear. We analyzed the impact of AT on overall (OS) and recurrence free survival (RFS) in patients undergoing curative resection. METHODS: We reviewed patients with resected HC between 2000 and 2015 from the ten institutions participating in the U.S. Extrahepatic Biliary Malignancy Consortium. We analyzed the impact of AT on RFS and OS. The probability of RFS and OS were calculated in the method of Kaplan and Meier and analyzed using multivariate Cox regression analysis. RESULTS: A total of 249 patients underwent curative resection for HC. Patients who received AT and those who did not had similar demographic and preoperative features. In a multivariate Cox regression analysis, AT conferred a significant protective effect on OS (HR 0.58, P = 0.013), and this was maintained in a propensity matched analysis (HR 0.66, P = 0.033). The protective effect of AT remained significant when node negative patients were excluded (HR 0.28, P = 0.001), while it disappeared (HR 0.76, P = 0.260) when node positive patients were excluded. CONCLUSIONS: AT should be strongly considered after curative-intent resection for HC, particularly in patients with node positive disease.

Outcomes after vascular resection during curative-intent resection for hilar cholangiocarcinoma: a multi-institution study from the US extrahepatic biliary malignancy consortium.

BACKGROUND: Surgical resection is the cornerstone of curative-intent therapy for patients with hilar cholangiocarcinoma (HC). The role of vascular resection (VR) in the treatment of HC in western centres is not well defined. METHODS: Utilizing data from the U.S. Extrahepatic Biliary Malignancy Consortium, patients were grouped into those who underwent resection for HC based on VR status: no VR, portal vein resection (PVR), or hepatic artery resection (HAR). Perioperative and long-term survival outcomes were analyzed. RESULTS: Between 1998 and 2015, 201 patients underwent resection for HC, of which 31 (15%) underwent VR: 19 patients (9%) underwent PVR alone and 12 patients (6%) underwent HAR either with (n = 2) or without PVR (n = 10). Patients selected for VR tended to be younger with higher stage disease. Rates of postoperative complications and 30-day mortality were similar when stratified by vascular resection status. On multivariate analysis, receipt of PVR or HAR did not significantly affect OS or RFS. CONCLUSION: In a modern, multi-institutional cohort of patients undergoing curative-intent resection for HC, VR appears to be a safe procedure in a highly selected subset, although long-term survival outcomes appear equivalent. VR should be considered only in select patients based on tumor and patient characteristics.

Curative Surgical Resection of Adrenocortical Carcinoma: Determining Long-term Outcome Based on Conditional Disease-free Probability.

OBJECTIVE: To evaluate conditional disease-free survival (CDFS) for patients who underwent curative intent surgery for adrenocortical carcinoma (ACC). BACKGROUND: ACC is a rare but aggressive tumor. Survival estimates are usually reported as survival from the time of surgery. CDFS estimates may be more clinically relevant by accounting for the changing likelihood of disease-free survival (DFS) according to time elapsed after surgery. METHODS: CDFS was assessed using a multi-institutional cohort of patients. Cox proportional hazards models were used to evaluate factors associated with DFS. Three-year CDFS (CDFS3) estimates at "x" year after surgery were calculated as follows: CDFS3 = DFS(x+3)/DFS(x). RESULTS: One hundred ninety-two patients were included in the study cohort; median patient age was 52 years. On presentation, 36% of patients had a functional tumor and median size was 11.5 cm. Most patients underwent R0 resection (75%) and 9% had N1 disease. Overall 1-, 3-, and 5-year DFS was 59%, 34%, and 22%, respectively. Using CDFS estimates, the probability of remaining disease free for an additional 3 years given that the patient had survived without disease at 1, 3, and 5 years, was 43%, 53%, and 70%, respectively. Patients with less favorable prognosis at baseline demonstrated the greatest increase in CDFS3 over time (eg, capsular invasion: 28%-88%, Δ60% vs no capsular invasion: 51%-87%, Δ36%). CONCLUSIONS: DFS estimates for patients with ACC improved dramatically over time, in particular among patients with initial worse prognoses. CDFS estimates may provide more clinically relevant information about the changing likelihood of DFS over time.

A Novel Pathology-Based Preoperative Risk Score to Predict Locoregional Residual and Distant Disease and Survival for Incidental Gallbladder Cancer: A 10-Institution Study from the U.S. Extrahepatic Biliary Malignancy Consortium.

BACKGROUND: This study was designed to develop a more robust predictive model, beyond T-stage alone, for incidental gallbladder cancer (IGBC) for discovering locoregional residual (LRD) and distant disease (DD) at reoperation, and estimating overall survival (OS). T-stage alone is currently used to guide treatment for incidental gallbladder cancer. Residual disease at re-resection is the most important factor in predicting outcomes. METHODS: All patients with IGBC who underwent reoperation at 10 institutions from 2000 to 2015 were included. Routine pathology data from initial cholecystectomy was utilized to create the gallbladder cancer predictive risk score (GBRS). RESULTS: Of 449 patients with gallbladder cancer, 262 (58 %) were incidentally discovered and underwent reoperation. Advanced T-stage, grade, and presence of lymphovascular (LVI) and perineural (PNI) invasion were all associated with increased rates of DD and LRD and decreased OS. Each pathologic characteristic was assigned a value (T1a: 0, T1b: 1, T2: 2, T3/4: 3; well-diff: 1, mod-diff: 2, poor-diff: 3; LVI-neg: 1, LVI-pos: 2; PNI-neg: 1, PNI-pos: 2), which added to a total GBRS score from 3 to 10. The scores were separated into three risk-groups (low: 3-4, intermediate: 5-7, high: 8-10). Each progressive GBRS group was associated with an increased incidence LRD and DD at the time of re-resection and reduced OS. CONCLUSIONS: By accounting for subtle pathologic variations within each T-stage, this novel predictive risk-score better stratifies patients with incidentally discovered gallbladder cancer. Compared with T-stage alone, it more accurately identifies patients at risk for locoregional-residual and distant disease and predicts long-term survival as it redistributes T1b, T2, and T3 disease across separate risk-groups based on additional biologic features. This score may help to optimize treatment strategy for patients with incidentally discovered gallbladder cancer.

Routine port-site excision in incidentally discovered gallbladder cancer is not associated with improved survival: A multi-institution analysis from the US Extrahepatic Biliary Malignancy Consortium.

BACKGROUND: Current data on the utility of port-site excision (PSE) during re-resection for incidentally discovered gallbladder cancer (IGBC) in the US are conflicting and limited to single-institution series. METHODS: All patients with IGBC who underwent curative re-resection at 10 institutions from 2000 to 2015 were included. Patients with and without PSE were compared. Primary outcome was overall survival (OS). RESULTS: Of 449 pts with GBC, 266 were incidentally discovered, of which 193(73%) underwent curative re-resection and had port-site data; 47 pts(24%) underwent PSE, 146(76%) did not. The PSE rate remained similar over time (2000-2004: 33%; 2005-2009: 22%; 2010-2015:22%; P = 0.36). Both groups had similar demographics, operative procedures, and post-operative complications. There was no difference in T-stage (T1: 9 vs. 11%; T2: 52 vs. 52%; T3: 39 vs. 38%; P = 0.96) or LN involvement (36 vs. 41%; P = 0.7) between groups. A 3-year OS was similar between PSE and no PSE groups (65 vs. 43%; P = 0.07). On univariable analysis, residual disease at re-resection (HR = 2.1, 95% CI 1.4-3.3; P = 0.001), high tumor grade, and advanced T-stage were associated with decreased OS. Only grade and T-stage, but not PSE, persisted on multivariable analysis. Distant disease recurrence-rate was identical between PSE and no PSE groups (80 vs. 81%; P = 1.0). CONCLUSION: Port-site excision during re-resection for IGBC is not associated with improved overall survival and has the same distant disease recurrence compared to no port-site excision. Routine port-site excision is not recommended.

Defining the Chance of Statistical Cure Among Patients with Extrahepatic Biliary Tract Cancer.

BACKGROUND: While surgery offers the best curative-intent treatment, many patients with biliary tract malignancies have poor long-term outcomes. We sought to apply a non-mixture cure model to calculate the cure fraction and the time to cure after surgery of patients with peri-hilar cholangiocarcinoma (PHCC) or gallbladder cancer (GBC). METHODS: Using the Extrahepatic Biliary Malignancy Consortium, 576 patients who underwent curative-intent surgery for gallbladder carcinoma or peri-hilar cholangiocarcinoma between 1998 and 2014 at 10 major hepatobiliary institutions were identified and included in the analysis. A non-mixture cure model was adopted to compare mortality after surgery to the mortality expected for the general population matched by sex and age. RESULTS: The median and 5-year overall survival (OS) were 1.9 years (IQR, 0.9-4.9) and 23.9 % (95 % CI, 19.6-28.6). Among all patients with PHCC or GBC, the probability of being cured after surgery was 14.5 % (95 % CI, 8.7-23.2); the time to cure was 9.7 years and the median survival of uncured patients was 1.8 years. Determinants of cure probabilities included lymph node metastasis and CA 19.9 level (p ≤ 0.05). The cure fraction for patients with a CA 19.9 < 50 U/ml and no lymph nodes metastases were 39.0 % versus only 5.1 % among patients with a CA 19.9 ≥ 50 who also had lymph node metastasis. CONCLUSIONS: Examining an "all comer" cohort, <15 % of patients with PHCC or GBC could be considered cured after surgery. Factors such CA 19.9 level and lymph node metastasis independently predicted long-term outcome. Estimating the odds of statistical cure following surgery for biliary tract cancer can assist in decision-making as well as inform discussions around survivorship.

Evaluating the American College of Surgeons National Surgical Quality Improvement project risk calculator: results from the U.S. Extrahepatic Biliary Malignancy Consortium.

BACKGROUND: The objective of this study is to evaluate use of the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) online risk calculator for estimating common outcomes after operations for gallbladder cancer and extrahepatic cholangiocarcinoma. METHODS: Subjects from the United States Extrahepatic Biliary Malignancy Consortium (USE-BMC) who underwent operation between January 1, 2000 and December 31, 2014 at 10 academic medical centers were included in this study. Calculator estimates of risk were compared to actual outcomes. RESULTS: The majority of patients underwent partial or major hepatectomy, Whipple procedures or extrahepatic bile duct resection. For the entire cohort, c-statistics for surgical site infection (0.635), reoperation (0.680) and readmission (0.565) were less than 0.7. The c-statistic for death was 0.740. For all outcomes the actual proportion of patients experiencing an event was much higher than the median predicted risk of that event. Similarly, the group of patients who experienced an outcome did have higher median predicted risk than those who did not. CONCLUSIONS: The ACS NSQIP risk calculator is easy to use but requires further modifications to more accurately estimate outcomes for some patient populations and operations for which validation studies show suboptimal performance.

Survival after resection of perihilar cholangiocarcinoma in patients with lymph node metastases.

BACKGROUND: The aim of this study was to compare patients with PHC with lymph node metastases (LN+) who underwent a resection with patients who did not undergo resection because of locally advanced disease at exploratory laparotomy. METHODS: Consecutive LN+ patients who underwent a resection for PHC in 12 centers were compared with patients who did not undergo resection because of locally advanced disease at exploratory laparotomy in 2 centers. RESULTS: In the resected cohort of 119 patients, the median overall survival (OS) was 19 months and the estimated 1-, 3- and 5-year OS was 69%, 27% and 13%, respectively. In the non-resected cohort of 113 patients, median OS was 12 months and the estimated 1-, 3- and 5-year OS was 49%, 7%, and 3%, respectively. OS was better in the resected LN+ cohort (p < 0.001). Positive resection margin (hazard ratio [HR]: 1.54; 95%CI: 0.97-2.45) and lymphovascular invasion (LVI) (HR: 1.71; 95%CI: 1.09-2.69) were independent poor prognostic factors in the resected cohort. CONCLUSION: Patients with PHC who underwent a resection for LN+ disease had better OS than patients who did not undergo resection because of locally advanced disease at exploratory laparotomy. LN+ PHC does not preclude 5-year survival after resection.

Prognostic Implications of Lymph Node Status for Patients With Gallbladder Cancer: A Multi-Institutional Study.

BACKGROUND: Although the American Joint Committee on Cancer (AJCC) classification is the most accepted lymph node (LN) staging system for gallbladder adenocarcinoma (GBA), other LN prognostic schemes have been proposed. This study sought to define the performance of the AJCC LN staging system relative to the number of metastatic LNs (NMLN), the log odds of metastatic LN (LODDS), and the LN ratio (LNR). METHODS: Patients who underwent curative-intent resection for GBA between 2000 and 2015 were identified from a multi-institutional database. The prognostic performance of various LN staging systems was compared by Harrell's C and the Akaike information criterion (AIC). RESULTS: Altogether, 214 patients with a median age of 66.7 years (interquartile range [IQR] 56.5-73.1) were identified. A total of 1334 LNs were retrieved, with a median of 4 (IQR 2-8) LNs per patient. Patients with LN metastasis had an increased risk of death (hazard ratio [HR] 1.87; 95 % confidence interval [CI] 1.24-2.82; P = 0.003) and recurrence (HR 2.28; 95 % CI 1.37-3.80; P = 0.002). In the entire cohort, LNR, analyzed as either a continuous scale (C-index, 0.603; AIC, 803.5) or a discrete scale (C-index, 0.609; AIC, 802.2), provided better prognostic discrimination. Among the patients with four or more LNs examined, LODDS (C-index, 0.621; AIC, 363.8) had the best performance versus LNR (C-index, 0.615; AIC, 368.7), AJCC LN staging system (C-index, 0.601; AIC, 373.4), and NMLN (C-index, 0.613; AIC, 369.5). CONCLUSIONS: Both LODDS and LNR performed better than the AJCC LN staging system. Among the patients who had four or more LNs examined, LODDS performed better than LNR. Both LODDS and LNR should be incorporated into the AJCC LN staging system for GBA.

Curative Resection of Adrenocortical Carcinoma: Rates and Patterns of Postoperative Recurrence.

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare malignancy. The aim of this study was to determine the incidence and patterns of recurrence after curative-intent surgery for ACC. METHODS: Patients who underwent curative-intent resection for ACC between 1993 and 2014 were identified from 13 academic institutions participating in the United States ACC study group. Patients with metastasis or an R2 margin were excluded. Patterns and rates of recurrence were determined and classified as locoregional and distant recurrence. RESULTS: A total of 180 patients with a median age of 52 years (interquartile range 43-61) were identified. Most patients underwent open surgery (n = 111, 64.5 %) and had an R0 resection margin (n = 117, 75.0 %). At last follow-up, 116 patients (64.4 %) had experienced recurrence (locoregional only, n = 41, 36.3 %; distant only, n = 51, 45.1 %; locoregional and distant, n = 21, 18.6 %). Median time to recurrence was 18.8 months. Several factors were associated with locoregional recurrence, including left-sided ACC location (odds ratio [OR] 2.71, 95 % confidence interval [CI] 1.06-6.89) and T3/T4 disease (reference T1/T2, OR 3.04, 95 % CI 1.19-7.80) (both p < 0.05). Distant recurrence was associated with larger tumor size (OR 1.11, 95 % CI 1.01-1.24) and T3/T4 disease (reference T1/T2, OR 5.23, 95 % CI 1.70-16.10) (both p < 0.05). Patients with combined locoregional and distant recurrence had worse survival (3- and 5-year survival: 39.5, 19.7 %) versus patients with distant-only (3- and 5-year survival 55.1, 43.3 %) or locoregional-only recurrence (3- and 5-year survival 81.4, 64.1 %) (p = 0.01). CONCLUSIONS: Nearly two-thirds of patients experienced disease recurrence after resection of ACC. Although a subset of patients experienced recurrence with locoregional disease only, many patients experienced recurrence with distant disease as a component of recurrence and had a poor prognosis.

Changing Odds of Survival Over Time among Patients Undergoing Surgical Resection of Gallbladder Carcinoma.

BACKGROUND: While survival after malignancies is traditionally reported as actuarial survival, conditional survival (CS) may be more clinically relevant by accounting for "accrued" survival time as time progresses. We sought to compare actuarial and CS among patients with gallbladder carcinoma (GBC) . METHODS: A total of 312 patients who underwent curative intent surgery for GBC between 2000 and 2014 were identified using a multi-institutional database. Overall survival (OS) was estimated using the Kaplan-Meier method. CS was calculated as the probability of surviving an additional 3 years at year "x" after surgery using the formula CS3 = S(x+3)/Sx. RESULTS: Among all patients, the median actuarial OS was 24.8 months (IQR 13.3-88.9). While actuarial survival decreased over time, 3-year CS (CS3) increased, with CS3 at 2 years after surgery noted to be 61.8 % compared with the 5-year actuarial OS of 31.6 %. Factors associated with reduced actuarial OS were positive margin status (HR 3.61, 95 % CI 2.47-5.26), increasing tumor size (HR = 1.02, 95 % CI 1.01-1.02), higher tumor grade (HR 2.98, 95 % CI 1.47-6.04), residual disease at repeat resection (HR = 2.78, 95 % CI 1.49-3.49, p < 0.001), and lymph node metastasis (HR = 1.95, 95 % CI 1.39-2.75, all p < 0.001). The calculated CS3 exceeded the actuarial survival within each high-risk patient subgroup. For example, patients with residual disease at repeat resection had an actuarial survival 23.1 % at 5 years versus a CS3 of 56.3 % in patients alive at 2 years (Δ = 33.2 %). CONCLUSIONS: CS provides a more accurate, dynamic estimate for survival, especially among high-risk patients. CS estimates can be used to accurately predict survival and guide clinical decision making.