Association of Depression and Antidepressant Use With Driving Behaviors in Older Adults: A LongROAD Study.

Older adults aged 70 and older who drive have higher crash death rates per mile driven compared to middle aged (35-54 years) adults who drive in the US. Prior studies have found that depression and or antidepressant medication use in older adults are associated with an increase in the vehicular crash rate. Using data from the prospective multi-site AAA Longitudinal Research on Aging Drivers Study, this analysis examined the independent and interdependent associations of self-reported depression and antidepressant use with driving behaviors that can increase motor vehicle crash risk such as hard braking, speeding, and night-time driving in adults over age 65. Of the 2951 participants, 6.4% reported having depression and 21.9% were on an antidepressant medication. Correcting for age, race, gender, and education level, participants on an antidepressant had increased hard braking events (1.22 [1.10-1.34]) but self-reported depression alone was not associated with changes in driving behaviors.

Defining the Risk of Early Recurrence Following Curative-Intent Resection for Distal Cholangiocarcinoma.

BACKGROUND: Although multidisciplinary treatments including the use of adjuvant therapy (AT) have been adopted for biliary tract cancers, patients with distal cholangiocarcinoma (DCC) can still experience recurrence. We sought to characterize the incidence and predictors of early recurrence (ER) that occurred within 12 months following surgery for DCC. PATIENTS AND METHODS: Patients who underwent resection for DCC between 2000 and 2015 were identified from the US multi-institutional database. Cox regression analysis was used to identify clinicopathological factors to develop an ER risk score, and the predictive model was validated in an external dataset. RESULTS: Among 245 patients included in the analysis, 67 patients (27.3%) developed ER. No difference was noted in ER rates between patients who did and did not receive AT (28.7% vs. 25.0%, p = 0.55). Multivariable analysis revealed that neutrophil-to-lymphocyte ratio (NLR), peak total bilirubin (T-Bil), major vascular resection (MVR), lymphovascular invasion, and R1 surgical margin status were associated with a higher ER risk. A DIstal Cholangiocarcinoma Early Recurrence Score was developed according to each factor available prior to surgery [NLR > 9.0 (2 points); peak T-bil > 1.5 mg/dL (1 points); MVR (2 points)]. Cumulative ER rates incrementally increased among patients who were low (0 points; 10.6%), intermediate (1-2 points; 26.8%), or high (3-5 points; 57.6%) risk (p < 0.001) in the training dataset, as well as in the validation dataset [low (0 points); 3.4%, intermediate (1-2 points); 32.7%, or high risk (3-5 points); 55.6% (p < 0.001)]. CONCLUSIONS: Among patients undergoing resection for DCC, 1 in 4 patients experienced an ER. Alternative treatment strategies such as neoadjuvant chemotherapy may be considered especially among individuals deemed to be at high risk for ER.

Defining and Predicting Early Recurrence after Resection for Gallbladder Cancer.

BACKGROUND: The optimal time interval to define early recurrence (ER) among patients who underwent resection of gallbladder cancer (GBC) is not well defined. We sought to develop and validate a novel GBC recurrence risk (GBRR) score to predict ER among patients undergoing resection for GBC. PATIENTS AND METHODS: Patients who underwent curative-intent resection for GBC between 2000 and 2018 were identified from the US Extrahepatic Biliary Malignancy Consortium database. A minimum p value approach in the log-rank test was used to define the optimal cutoff for ER. A risk stratification model was developed to predict ER based on relevant clinicopathological factors and was externally validated. RESULTS: Among 309 patients, 103 patients (33.3%) had a recurrence at a median follow-up period of 15.1 months. The optimal cutoff for ER was defined at 12 months (p = 3.04 × 10-18). On multivariable analysis, T3/T4 disease (HR: 2.80; 95% CI 1.58-5.11) and poor tumor differentiation (HR: 1.91; 95% CI 1.11-3.25) were associated with greater hazards of ER. The GBRR score was developed using ß-coefficients of variables in the final model, and patients were classified into three distinct groups relative to the risk for ER (12-month RFS; low risk: 88.4%, intermediate risk: 77.9%, high risk: 37.0%, p < 0.001). The external validation demonstrated good model generalizability with good calibration (n = 102: 12-month RFS; low risk: 94.2%, intermediate risk: 59.8%, high risk: 42.0%, p < 0.001). The GBRR score is available online at https://ktsahara.shinyapps.io/GBC_earlyrec/ . CONCLUSIONS: A novel online calculator was developed to help clinicians predict the probability of ER after curative-intent resection for GBC. The proposed web-based tool may help in the optimization of surveillance intervals and the counselling of patients about their prognosis.

Does Intentional Support of Degree Programs in General Surgery Residency Affect Research Productivity or Pursuit of Academic Surgery? A Multi-Institutional Study.

OBJECTIVE: To determine whether pursuit of an advanced degree during dedicated research time (DRT) in a general surgery residency training program impacts a resident's research productivity. DESIGN: A retrospective, multi-institutional cohort study. SETTING: General surgery residency programs that were approved to graduate more than 5 categorical residents per year and that offered at least 1 year of DRT were contacted for participation in the study. A total of 10 general surgery residency programs agreed to participate in the study. PARTICIPANTS: Residents who started their residency between 2000 and 2012 and spent at least one full year in DRT (n = 511) were included. Those who completed an advanced degree were compared on the following parameters to those who did not complete one: total number of papers, first-author papers, the Journal Citation Reports impact factors of publication (2018, or most recent), and first position after residency or fellowship training. RESULTS: During DRT, 87 (17%) residents obtained an advanced degree. The most common degree obtained was a Master of Public Health (MPH, n = 42 (48.8%)). Residents who did not obtain an advanced degree during DRT published fewer papers (median 8, [interquartile range 4-12]) than those who obtained a degree (9, [6-17]) (p = 0.002). They also published fewer first author papers (3, [2-6]) vs (5, [2-9]) (p = 0.002) than those who obtained a degree. Resident impact factor (RIF) was calculated using Journal Citation Reports impact factor and author position. Those who did not earn an advanced degree had a lower RIF (adjusted RIF, 84 ± 4 vs 134 ± 5, p < 0.001) compared to those who did. There was no association between obtaining a degree and pursuit of academic surgery (p = 0.13) CONCLUSIONS: Pursuit of an advanced degree during DRT is associated with increased research productivity but is not associated with pursuit of an academic career.

Survival benefit of lymphadenectomy for gallbladder cancer based on the therapeutic index: An analysis of the US extrahepatic biliary malignancy consortium.

BACKGROUND: The survival benefit of lymphadenectomy among patients with gallbladder cancer (GBC) remains poorly understood. METHODS: Patients who underwent resection for GBC between 2000 and 2015 were identified from a US multi-institutional database. The therapeutic index (LNM rate multiplied by 3-year overall survival [OS]) was determined to assess the survival benefit of lymphadenectomy. RESULTS: Among 449 patients, less than half had LNM (N = 183, 40.8%). The median number of evaluated and metastatic lymph nodes (LNs) was 3 (interquartile range [IQR]: 1-6) and 1 (IQR: 0-1), respectively. 3-year OS among patients with LNM in the entire cohort was 26.8%. The therapeutic index was lower among patients with T4 (5.9) or T1 (6.0) tumors as well as carbohydrate antigen (CA19-9) ≥200 UI/mL (6.0). Of note, a therapeutic index difference ≥10 was noted relative to CA19-9 (<200: 18.7 vs ≥200: 6.0), American Joint Committee on Cancer T Stage (T1: 6.0 vs T2: 17.8 vs T4: 5.9) and number of LNs examined (1-2: 6.9 vs ≥6: 16.9). Concomitant common bile duct resection was not associated with a higher therapeutic index among patients with either T2 or T3 disease. CONCLUSION: Certain clinicopathological factors including T1 or T4 tumor and CA19-9 ≥200 UI/mL were associated with a low therapeutic index. Resection of six or more LNs was associated with a meaningful therapeutic index benefit among patients with LNM.

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).

Arachidonic acid and colorectal adenoma risk: a Mendelian randomization study.

BACKGROUND: Previous studies have shown a link between increased dietary intake of arachidonic acid (ARA) and colorectal neoplasms. It has been shown that erythrocyte phospholipid membrane concentrations of ARA are strongly determined by genetic variation. Fatty acid desaturase (FADS) controls the rate limiting step in ARA production, and FADS variant rs174537 has been shown to be responsible for up to 18.6% of the variation seen. To determine if a causal association exists between erythrocyte membrane ARA concentrations and colorectal adenomas, we conducted a Mendelian randomization (MR) analysis using rs174537 as an instrumental variable (IV). MR analysis was chosen because it is less susceptible to bias and confounding. PATIENTS AND METHODS: A case-control study was performed using the Tennessee Colorectal Polyps Study. Patients were matched on age, gender, race, facility site, and year of colonoscopy. Cases were defined as any colorectal adenoma on colonoscopy (n=909) and controls were polyp free (n=855). A two-stage logistic regression was conducted using rs174537 as the IV with the dependent variable being the presence of a colorectal adenoma on colonoscopy. RESULTS: Cases were older (59 vs 57 years of age, P<0.0001), and more likely to use alcohol (47.4% vs 19.8%, P=0.001) and to smoke (77.0% vs 66.9%, P<0.0001). There was no statistically significant difference in: age, sex, alcohol use, body mass index (BMI), or NSAID use when stratified by the rs174537 alleles. Genotype was strongly associated with erythrocyte membrane ARA concentrations (P<0.0001). We found no evidence of an association between our IV (rs174537) and colorectal adenomas (P=0.41). CONCLUSION: In our MR study increased erythrocyte ARA concentrations were not associated with the risk of colorectal adenomas.

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.

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.

The Hand-Assisted Laparoscopic Approach to Resection of Pancreatic Mucinous Cystic Neoplasms: An Underused Technique?

Pancreatic mucinous cystic neoplasms (MCNs) are rare tumors typically of the distal pancreas that harbor malignant potential. Although resection is recommended, data are limited on optimal operative approaches to distal pancreatectomy for MCN. MCN resections (2000-2014; eight institutions) were included. Outcomes of minimally invasive and open MCN resections were compared. A total of 289 patients underwent distal pancreatectomy for MCN: 136(47%) minimally invasive and 153(53%) open. Minimally invasive procedures were associated with smaller MCN size (3.9 vs 6.8 cm; P = 0.001), lower operative blood loss (192 vs 392 mL; P = 0.001), and shorter hospital stay(5 vs 7 days; P = 0.001) compared with open. Despite higher American Society of Anesthesiologists class, hand-assisted (n = 46) had similar advantages as laparoscopic/robotic (n = 76). When comparing hand-assisted to open, although MCN size was slightly smaller (4.1 vs 6.8 cm; P = 0.001), specimen length, operative time, and nodal yield were identical. Similar to laparoscopic/robotic, hand-assisted had lower operative blood loss (161 vs 392 mL; P = 0.001) and shorter hospital stay (5 vs 7 days; P = 0.03) compared with open, without increased complications. Hand-assisted laparoscopic technique is a useful approach for MCN resection because specimen length, lymph node yield, operative time, and complication profiles are similar to open procedures, but it still offers the advantages of a minimally invasive approach. Hand-assisted laparoscopy should be considered as an alternative to open technique or as a successive step before converting from total laparoscopic to open distal pancreatectomy for MCN.

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.

Mitotic rate is associated with positive lymph nodes in patients with thin melanomas.

BACKGROUND: The American Joint Commission on Cancer will remove mitotic rate from its staging guidelines in 2018. OBJECTIVE: Using a large nationally representative cohort, we examined the association between mitotic rate and lymph node positivity among thin melanomas. METHODS: A total of 149,273 thin melanomas in the National Cancer Database were examined for their association of high-risk features of mitotic rate, ulceration, and Breslow depth with lymph node status. RESULTS: Among 17,204 patients with thin melanomas with data on Breslow depth, ulceration, and mitotic rate who underwent a lymph node biopsy, there was a strong linear relationship between odds of having a positive lymph node and mitotic rate (R2 = 0.96, P < .0001, ß = 3.31). The odds of having a positive node increased by 19% with each 1-point increase in mitotic rate (odds ratio, 1.19; 95% confidence interval, 1.17-1.21). Cases with negative nodes had a mean mitotic rate of 1.54 plus or minus 2.07 mitoses/mm2 compared with 3.30 plus or minus 3.54 mitoses/mm2 for those with positive nodes (P < .0001). LIMITATIONS: The data collected do not allow for survival analyses. CONCLUSIONS: Mitotic rate was strongly associated with the odds of having a positive lymph node and should continue to be reported on pathology reports.

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.

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.

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.

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.

The Effects of Travel Burden on Outcomes After Resection of Extrahepatic Biliary Malignancies: Results from the US Extrahepatic Biliary Consortium.

BACKGROUND: Surgical resection of extrahepatic biliary malignancies has been increasingly centralized at high-volume tertiary care centers. While this has improved outcomes overall, increased travel burden has been associated with worse survival for many other malignancies. We hypothesized that longer travel distances are associated with worse outcomes for these patients as well. STUDY DESIGN: Data was analyzed from the US Extrahepatic Biliary Consortium database, which retrospectively reviewed patients who received resection of extrahepatic biliary malignancies at 10 high-volume centers. Driving distance to the patient's treatment center was measured for 1025 patients. These were divided into four quartiles for analysis: < 24.5, 24.5-57.2, 57.2-117, and < 117 mi. Cox proportional hazard models were then used to measure differences in overall survival. RESULTS: No difference was found between the groups in severity of disease or post-operative complications. The median overall survival in each quartile was as follows: 1st = 1.91, 2nd = 1.60, 3rd = 1.30, and 4th = 1.39 years. Patients in the 3rd and 4th quartile had a significantly lower median household income (p = 0.0001) and a greater proportion Caucasian race (p = 0.0001). However, neither of these was independently associated with overall survival. The two furthest quartiles were found to have decreased overall survival (HR = 1.39, CI = 1.12-1.73 and HR = 1.3, CI = 1.04-1.62), with quartile 3 remaining significant after multivariate analysis (HR = 1.45, CI = 1.04-2.0, p = 0.028). CONCLUSIONS: Longer travel distances were associated with decreased overall survival, especially in the 3rd quartile of our study. Patients traveling longer distances also had a lower household income, suggesting that these patients have significant barriers to care.

Surgical Site Infection Is Associated with Tumor Recurrence in Patients with Extrahepatic Biliary Malignancies.

BACKGROUND: Surgical site infections (SSI) are one of the most common complications after hepato-pancreato-biliary surgery. Infectious complications may lead to an associated immune-modulatory effect that inhibits the body's response to cancer surveillance. We sought to define the impact of SSI on long-term prognosis of patients undergoing surgical resection of extrahepatic biliary malignancies (EHBM). METHODS: Patients undergoing surgery for EHBM between 2000 and 2014 were identified using a large, multi-center, national cohort dataset. Recurrence free survival (RFS) was calculated and a multivariable Cox proportional hazards model was utilized to identify potential risk factors for RFS including SSI. RESULTS: Seven hundred twenty-eight patients included in the analytic cohort; 236 (32.4%) patients had perihilar cholangiocarcinoma, 241 (33.1%) gallbladder cancer, and 251 (34.5%) distal cholangiocarcinoma. A major resection, liver resection, was performed in 205 (28.3%) patients, while 110 (15.2%) patients had a pancreaticoduodenectomy. The overall incidence of morbidity was 55.8%; among the 397 patients who experienced a complication, 161 patients specifically had an SSI. The SSI occurred as an infection of the surgical site (n = 70, 9.6%) or formation of an abscess in the operative bed (n = 91, 12.5%). SSI was associated with long-term survival as patients who experienced an SSI had a median RFS of 19.5 months compared with 30.5 months for those patients who did not have an SSI (HR 1.40, 95% CI 1.08-1.80; p = 0.01). Among 279 patients who had EHBM that had no associated lymph node metastases, well-to-moderate tumor differentiation, as well as an R0 resection margin, SSI remained associated with worse RFS (HR 1.84, 95% CI 1.03-3.29; p = 0.038), as well as overall survival (HR 1.87, 95% CI 1.18-2.97; p = 0.008). CONCLUSION: SSI was a relatively common occurrence following surgery for EHBM as 1 in 10 patients experienced an SSI. In addition to standard tumor-specific factors, the occurrence of postoperative SSI was adversely associated with long-term survival.

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.