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.

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).

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.

The Impact of Intraoperative Re-Resection of a Positive Bile Duct Margin on Clinical Outcomes for Hilar Cholangiocarcinoma.

BACKGROUND: The impact of re-resection of a positive intraoperative bile duct margin on clinical outcomes for resectable hilar cholangiocarcinoma (HCCA) remains controversial. We sought to define the impact of re-resection of an initially positive frozen-section bile duct margin on outcomes of patients undergoing surgery for HCCA. METHODS: Patients who underwent curative-intent resection for HCCA between 2000 and 2014 were identified at 10 hepatobiliary centers. Short- and long-term outcomes were analyzed among patients stratified by margin status. RESULTS: Among 215 (83.7%) patients who underwent frozen-section evaluation of the bile duct, 80 (37.2%) patients had a positive (R1) ductal margin, 58 (72.5%) underwent re-resection, and 29 ultimately had a secondary negative margin (secondary R0). There was no difference in morbidity, 30-day mortality, and length of stay among patients who had primary R0, secondary R0, and R1 resection (all p > 0.10). Median and 5-year survival were 22.3 months and 23.3%, respectively, among patients who had a primary R0 resection compared with 18.5 months and 7.9%, respectively, for patients with an R1 resection (p = 0.08). In contrast, among patients who had a secondary R0 margin with re-resection of the bile duct margin, median and 5-year survival were 30.6 months and 44.3%, respectively, which was comparable to patients with a primary R0 margin (p = 0.804). On multivariable analysis, R1 margin resection was associated with decreased survival (R1: hazard ratio [HR] 1.3, 95% confidence interval [CI] 1.0-1.7; p = 0.027), but secondary R0 resection was associated with comparable long-term outcomes as primary R0 resection (HR 0.9, 95% CI 0.4-2.3; p = 0.829). CONCLUSIONS: Additional resection of a positive frozen-section ductal margin to achieve R0 resection was associated with improved long-term outcomes following curative-intent resection of HCCA.

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.

Oncologic effects of preoperative biliary drainage in resectable hilar cholangiocarcinoma: Percutaneous biliary drainage has no adverse effects on survival.

BACKGROUND AND OBJECTIVES: The objective of the current study was to define long-term survival of patients with resectable hilar cholangiocarcinoma (HCCA) after preoperative percutaneous transhepatic biliary drainage (PTBD) versus endoscopic biliary drainage (EBD). METHODS: Between 2000 and 2014, 240 patients who underwent curative-intent resection for HCCA were identified at 10 major hepatobiliary centers. Postoperative morbidity and mortality, as well as disease-specific survival (DSS) and recurrence-free survival (RFS) were analyzed among patients. RESULTS: The median decrease in total bilirubin levels after biliary drainage was similar comparing PTBD (n = 104) versus EBD (n = 92) (mg/dL, 4.9 vs 4.9, P = 0.589) before surgery. There was no difference in baseline demographic characteristics, type of surgical procedure performed, final AJCC tumor stage or postoperative morbidity among patients who underwent EBD only versus PTBD (all P > 0.05). Patients who underwent PTBD versus EBD had a comparable long-term DSS (median, 43.7 vs 36.9 months, P = 0.802) and RFS (median, 26.7 vs 24.0 months, P = 0.571). The overall pattern of recurrence relative to regional or distant disease was also the same among patients undergoing PTBD and EBD (P = 0.669) CONCLUSIONS: Oncologic outcomes including DSS and RFS were similar among patients who underwent PTBD versus EBD with no difference in tumor recurrence location.

Defining Early Recurrence of Hilar Cholangiocarcinoma After Curative-intent Surgery: A Multi-institutional Study from the US Extrahepatic Biliary Malignancy Consortium.

BACKGROUND: Time to tumor recurrence may be associated with outcomes following resection of hepatobiliary cancers. The objective of the current study was to investigate risk factors and prognosis among patients with early versus late recurrence of hilar cholangiocarcinoma (HCCA) after curative-intent resection. METHODS: A total of 225 patients who underwent curative-intent resection for HCCA were identified from 10 academic centers in the USA. Data on clinicopathologic characteristics, pre-, intra-, and postoperative details and overall survival (OS) were analyzed. The slope of the curves identified by linear regression was used to categorize recurrences as early versus late. RESULTS: With a median follow-up of 18.0 months, 99 (44.0%) patients experienced a tumor recurrence. According to the slope of the curves identified by linear regression, the functions of the two straight lines were y = -0.465x + 16.99 and y = -0.12x + 7.16. The intercept value of the two lines was 28.5 months, and therefore, 30 months (2.5 years) was defined as the cutoff to differentiate early from late recurrence. Among 99 patients who experienced recurrence, the majority (n = 80, 80.8%) occurred within the first 2.5 years (early recurrence), while 19.2% of recurrences occurred beyond 2.5 years (late recurrence). Early recurrence was more likely present as distant disease (75.1% vs. 31.6%, p = 0.001) and was associated with a worse OS (Median OS, early 21.5 vs. late 50.4 months, p < 0.001). On multivariable analysis, poor tumor differentiation (HR 10.3, p = 0.021), microvascular invasion (HR 3.3, p = 0.037), perineural invasion (HR 3.9, p = 0.029), lymph node metastases (HR 5.0, p = 0.004), and microscopic positive margin (HR 3.5, p = 0.046) were independent risk factors associated with early recurrence. CONCLUSIONS: Early recurrence of HCCA after curative resection was common (~35.6%). Early recurrence was strongly associated with aggressive tumor characteristics, increased risk of distant metastatic recurrence and a worse long-term survival.

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.

Outcomes After Mastectomy and Lumpectomy in Elderly Patients with Early-Stage Breast Cancer.

INTRODUCTION: Survival in elderly patients undergoing mastectomy or lumpectomy has not been specifically analyzed. METHODS: Patients older than 70 years of age with clinical stage I invasive breast cancer, undergoing mastectomy or lumpectomy with or without radiation, and surveyed within 3 years of their diagnosis, were identified from the Surveillance, Epidemiology, and End Results and medicare health outcomes survey-linked dataset. The primary endpoint was breast cancer-specific survival (CSS). RESULTS: Of 1784 patients, 596 (33.4 %) underwent mastectomy, 918 (51.4 %) underwent lumpectomy with radiation, and 270 (15.1 %) underwent lumpectomy alone. Significant differences were noted in age, tumor size, American Joint Committee on Cancer (AJCC) stage, lymph node status (all p < 0.0001) and number of positive lymph nodes between the three groups (p = 0.003). On univariate analysis, CSS for patients undergoing lumpectomy with radiation [hazard ratio (HR) 0.61, 95 % confidence interval (CI) 0.43-0.85; p = 0.004] was superior to mastectomy. Older age (HR 1.3, 95 % CI 1.09-1.45; p = 0.002), two or more comorbidities (HR 1.57, 95 % CI 1.08-2.26; p = 0.02), inability to perform more than two activities of daily living (HR 1.61, 95 % CI 1.06-2.44; p = 0.03), larger tumor size (HR 2.36, 95 % CI 1.85-3.02; p < 0.0001), and positive lymph nodes (HR 2.83, 95 % CI 1.98-4.04; p < 0.0001) were associated with worse CSS. On multivariate analysis, larger tumor size (HR 1.89, 95 % CI 1.37-2.57; p < 0.0001) and positive lymph node status (HR 1.99, 95 % CI 1.36-2.9; p = 0.0004) independently predicted worse survival. CONCLUSIONS: Elderly patients with early-stage invasive breast cancer undergoing breast conservation have better CSS than those undergoing mastectomy. After adjusting for comorbidities and functional status, survival is dependent on tumor-specific variables. Determination of lymph node status remains important in staging elderly breast cancer patients.

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.

Quality of life of older African American breast cancer survivors: a population-based study.

INTRODUCTION: Factors associated with lower health-related quality of life (HRQOL) among older African American (AA) breast cancer survivors (BCS) have not been elucidated. METHODS: Using the Surveillance, Epidemiology, and End Results-Medicare Health Outcome Survey linked dataset, all resected AA BCS over 65 were identified. Using the most recent survey after diagnosis, individuals with a VR12 physical (PCS) or mental (MCS) component score 10 points lower than the median were categorized as having poor HRQOL. Univariate and multivariate (MV) analyses identified predictors of poor HRQOL. RESULTS: Of 373 AA BCS (median age 74.6), median time from diagnosis to survey was 68.4 months with median follow-up of 138.6 months. Median PCS was 35.9 (IQR 28.5-44.5) with 76 (20.1%) reporting poor PCS. Median MCS was 50.6 (IQR 41.3-59.1) with 101 (27.1%) reporting poor MCS. Predictors of poor PCS included advanced age, larger tumor size, ≥2 comorbidities, inability to perform >2 of 6 activities of daily living (ADLs), modified/radical mastectomy, infiltrating lobular carcinoma, and stage III or IV disease (all p < 0.05). Comorbidities ≥2 and inability to perform >2 of 6 ADLs (p < 0.05) predicted poor MCS. Inability to perform >2 of 6 ADLs was the only independent predictor of poor PCS (OR 10.9, 95% CI 3.0-39.3; p < 0.001) and MCS (OR 7.6, 95% CI 4.3-13.3; p < 0.001). CONCLUSION: In elderly AA BCS, poor HRQOL was not associated with socioeconomic status or tumor-specific factors but rather impairment in ADLs. Physical and mental HRQOL in African American breast cancer survivors is not dependent on socioeconomic or tumor-related characteristics, but rather on inability to perform ADLs.

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.

Conditional Survival After Cytoreductive Surgery with Heated Intraperitoneal Chemotherapy for Low- and High-Grade Appendiceal Primaries.

INTRODUCTION: Survival of patients after cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy for appendiceal neoplasms is projected by conventional overall survival (OS) curves that do not address the survival time a patient has already accrued. We sought to study the conditional survival (CS) after CRS, contingent on patients surviving a fixed duration of time after surgery. METHODS: A retrospective analysis of 493 appendiceal cancer patients from a prospective database was performed. OS was calculated for patients who achieved a complete CRS. CS was estimated based on Kaplan-Meier curves to determine what the patient's long-term survival (3-, 5-, 7-, or 10-year) would be if they were alive at 1, 2, or 3 years from surgery. RESULTS: OS at 5 and 10 years for 137 low-grade patients with complete resections was 83.3 and 74.2 %, respectively. For low-grade patients still alive at 3 years, 5- and 10-year CS was 93.4 and 83.2 %, respectively. For the 35 high-grade patients with complete CRS who survived to 3 years, CS at 10 years was 41.7 %, while their 10-year conventional OS was 24.6 %. CONCLUSIONS: Conventional analysis underestimates OS due to unpredictable variations in tumor biology. When adjusted for time already elapsed since surgery, improvements in survival estimates are more pronounced with high-grade tumors. CS outcomes can be used in determining the optimal frequency of long-term follow-up of these patients.

Routine Admission to Intensive Care Unit After Cytoreductive Surgery and Heated Intraperitoneal Chemotherapy: Not Always a Requirement.

BACKGROUND: Routine postoperative intensive care unit (ICU) observation of patients undergoing cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) is driven by historically reported morbidity and mortality data. The validity of this practice and the criteria for ICU admission have not been elucidated. METHODS: A prospectively maintained database of 1146 CRS/HIPEC procedures performed from December 1991 to 2014 was retrospectively analyzed. Patients with routine postoperative ICU admission were compared with patients sent directly to the surgical floor. To test the safety of non-ICU care practice, patients with less than 48 h ICU admission were compared with patients directly admitted to the floor. Demographics, primary tumor site, comorbidities, estimated blood loss (EBL), extent of CRS, Eastern Cooperative Oncology Group (ECOG) status, and overall survival were analyzed. RESULTS: Complete data were available for 1064 CRS/HIPEC procedures, of which 244 cases (22.93 %) did not require ICU admission. Multivariate logistic regression identified age [odds ratio (OR) 1.024; p = 0.02], EBL (OR 1.002; p < 0.0001), number of resected organs (OR 1.308; p = 0.01) and ECOG > 2 (OR 6.387; p = 0.003) as predictive variables of postoperative ICU admission. The cohort directly admitted to the floor demonstrated less minor grade I/II morbidity (29 vs. 47 %; p < 0.0001) and similar grade III/IV major morbidity (16.5 vs. 13.4 %; p = 0.3) than the patients admitted to the ICU for less than 48 h. CONCLUSIONS: ICU observation is not routinely required for all patients treated with CRS/HIPEC. Selective ICU admission based on ECOG status, nutritional status, age, EBL, and CRS extent is safe, with potential implications for hospitalization cost for these complex cases.

Quality-of-Life Evaluation After Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND: Cytoreductive surgery (CS) with hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal metastases can alleviate symptoms and prolong survival at the expense of morbidity and quality of life (QoL). This study aimed to monitor QoL and outcomes before and after HIPEC. METHODS: A prospective QoL trial of patients who underwent HIPEC for peritoneal metastases from 2000 to 2015 was conducted. The patients completed the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36), the Functional Assessment of Cancer Therapy + Colon Subscale (FACT-C), the Brief Pain Inventory, the Center for Epidemiologic Studies Depression scale, and the Eastern Cooperative Oncology Group (ECOG) performance status at baseline, then 3, 6, 12, and 24 months after HIPEC. The trial outcome index (TOI) was analyzed. Proportional hazards modeled the effect of baseline QoL on survival. RESULTS: The 598 patients (53.8 % female) in the study had a mean age of 53.3 years. The overall 1-year survival rate was 76.8 %, and the median survival period was 2.9 years. The findings showed a minor morbidity rate of 29.3 %, a major morbidity rate of 21.7 %, and a 30-day mortality rate of 3.5 %. The BPI (p < 0.0001) and worst pain (p = 0.004) increased at 3 months but returned to baseline at 6 months. After CS + HIPEC, FACT-C emotional well-being, SF-36 mental component score, and emotional health improved (all p < 0.001). Higher baseline FACT-General (hazard ratio [HR], 0.92; 95 % confidence interval [CI], 0.09-0.96), FACT-C (HR, 0.73; 95 % CI 0.65-0.83), physical well-being (HR, 0.71; 95 % CI 0.64-0.78), TOI (HR, 0.87; 95 % CI 0.84-0.91), and SF-36 vitality (HR, 0.88; 95 % CI 0.83-0.92) were associated with improved survival (all p < 0.001). Higher baseline BPI (HR, 1.1; 95 % CI 1.05-1.14; p < 0.0001), worst pain (HR, 1.06; 95 % CI 1.01-1.10; p = 0.01), and ECOG (HR, 1.74; 95 % CI 1.50-2.01; p < 0.0001) were associated with worse survival. CONCLUSIONS: Although HIPEC is associated with morbidity and detriments to QoL, recovery with good overall QoL typically occurs at or before 6 months. Baseline QoL is associated with morbidity, mortality, and survival after HIPEC.

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.

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.