Non-functional pancreatic neuroendocrine tumours: ATRX/DAXX and alternative lengthening of telomeres (ALT) are prognostically independent from ARX/PDX1 expression and tumour size.

OBJECTIVE: Recent studies have found aristaless-related homeobox gene (ARX)/pancreatic and duodenal homeobox 1 (PDX1), alpha-thalassemia/mental retardation X-linked (ATRX)/death domain-associated protein (DAXX) and alternative lengthening of telomeres (ALT) to be promising prognostic biomarkers for non-functional pancreatic neuroendocrine tumours (NF-PanNETs). However, they have not been comprehensively evaluated, especially among small NF-PanNETs (≤2.0 cm). Moreover, their status in neuroendocrine tumours (NETs) from other sites remains unknown. DESIGN: An international cohort of 1322 NETs was evaluated by immunolabelling for ARX/PDX1 and ATRX/DAXX, and telomere-specific fluorescence in situ hybridisation for ALT. This cohort included 561 primary NF-PanNETs, 107 NF-PanNET metastases and 654 primary, non-pancreatic non-functional NETs and NET metastases. The results were correlated with numerous clinicopathological features including relapse-free survival (RFS). RESULTS: ATRX/DAXX loss and ALT were associated with several adverse prognostic findings and distant metastasis/recurrence (p<0.001). The 5-year RFS rates for patients with ATRX/DAXX-negative and ALT-positive NF-PanNETs were 40% and 42% as compared with 85% and 86% for wild-type NF-PanNETs (p<0.001 and p<0.001). Shorter 5-year RFS rates for ≤2.0 cm NF-PanNETs patients were also seen with ATRX/DAXX loss (65% vs 92%, p=0.003) and ALT (60% vs 93%, p<0.001). By multivariate analysis, ATRX/DAXX and ALT status were independent prognostic factors for RFS. Conversely, classifying NF-PanNETs by ARX/PDX1 expression did not independently correlate with RFS. Except for 4% of pulmonary carcinoids, ATRX/DAXX loss and ALT were only identified in primary (25% and 29%) and NF-PanNET metastases (62% and 71%). CONCLUSIONS: ATRX/DAXX and ALT should be considered in the prognostic evaluation of NF-PanNETs including ≤2.0 cm tumours, and are highly specific for pancreatic origin among NET metastases of unknown primary.

Lacking Advanced Degrees are not a Barrier to Entry into Academic Surgery Leadership.

BACKGROUND: Undergraduate and graduate medical education offerings continue to create opportunities for medical students to pursue MD+ degree education. These educational endeavors provide formal education in fields related to surgery, which gives trainees and surgeons diverse perspectives on surgical care. This study sought to assess current prevalence of additional advanced degrees among leaders in academic surgery to assess the relationship between dual degree attainment and holding various leadership positions within surgical departments. METHODS: The Association for Program Directors in Surgery database was used to identify academic surgical programs, which comprised our study population. Each department of surgery website in the APDS database was interrogated for departmental leaders and their reported academic degrees. RESULTS: Among 3223 identified surgeon leaders, 14.6% (470/3223) were found to possess MD+ degrees. Most common degrees possessed included MBA, MPH, and PhD. In comparing different types of surgeon leaders such as chairs, program directors, and division chiefs, no group was found to have a significantly higher prevalence of MD+ degrees than others. CONCLUSION: Prevalence of MD+ degrees among current academic surgery leaders is low, and the lack of an advanced degree should not be considered a barrier to entry into leadership positions. We hypothesize that these findings are likely to evolve as larger proportions of trainees obtain MD+ degrees during medical school and academic development time throughout residency.

Formal robotic training diminishes the learning curve for robotic pancreatoduodenectomy: Implications for new programs in complex robotic surgery.

INTRODUCTION: The learning curve associated with robotic pancreatoduodenectomy (RPD) is a hurdle for new programs to achieve optimal results. Since early analysis, robotic training has recently expanded, and the RPD approach has been refined. The purpose of this study is to examine RPD outcomes for surgeons who implemented a new program after receiving formal RPD training to determine if such training reduces the learning curve. METHODS: Outcomes for consecutive patients undergoing RPD at a single tertiary institution were compared to optimal RPD benchmarks from a previously reported learning curve analysis. Two surgical oncologists with formal RPD training performed all operations with one surgeon as bedside assistant and the other at the console. RESULTS: Forty consecutive RPD operations were evaluated. Mean operative time was 354 ± 54 min, and blood loss was 300 ml. Length of stay was 7 days. Three patients (7.5%) underwent conversion to open. Pancreatic fistula affected five patients (12.5%). Operative time was stable over the study and lower than the reported benchmark. These RPD operative outcomes were similar to reported surgeon outcomes after the learning curve. CONCLUSION: This study suggests formal robotic training facilitates safe and efficient adoption of RPD for new programs, reducing or eliminating the learning curve.

Integrating next-generation sequencing to endoscopic retrograde cholangiopancreatography (ERCP)-obtained biliary specimens improves the detection and management of patients with malignant bile duct strictures.

OBJECTIVE: Despite improvements in imaging, serum CA19-9 and pathological evaluation, differentiating between benign and malignant bile duct strictures remains a diagnostic conundrum. Recent developments in next-generation sequencing (NGS) have opened new opportunities for early detection and management of cancers but, to date, have not been rigorously applied to biliary specimens. DESIGN: We prospectively evaluated a 28-gene NGS panel (BiliSeq) using endoscopic retrograde cholangiopancreatography-obtained biliary specimens from patients with bile duct strictures. The diagnostic performance of serum CA19-9, pathological evaluation and BiliSeq was assessed on 252 patients (57 trainings and 195 validations) with 346 biliary specimens. RESULTS: The sensitivity and specificity of BiliSeq for malignant strictures was 73% and 100%, respectively. In comparison, an elevated serum CA19-9 and pathological evaluation had sensitivities of 76% and 48%, and specificities of 69% and 99%, respectively. The combination of BiliSeq and pathological evaluation increased the sensitivity to 83% and maintained a specificity of 99%. BiliSeq improved the sensitivity of pathological evaluation for malignancy from 35% to 77% for biliary brushings and from 52% to 83% for biliary biopsies. Among patients with primary sclerosing cholangitis (PSC), BiliSeq had an 83% sensitivity as compared with pathological evaluation with an 8% sensitivity. Therapeutically relevant genomic alterations were identified in 20 (8%) patients. Two patients with ERBB2-amplified cholangiocarcinoma received a trastuzumab-based regimen and had measurable clinicoradiographic response. CONCLUSIONS: The combination of BiliSeq and pathological evaluation of biliary specimens increased the detection of malignant strictures, particularly in patients with PSC. Additionally, BiliSeq identified alterations that may stratify patients for specific anticancer therapies.

Surgical Resection Does Not Improve Survival in Multifocal Intrahepatic Cholangiocarcinoma: A Comparison of Surgical Resection with Intra-Arterial Therapies.

BACKGROUND: Multifocal intrahepatic cholangiocarcinoma (ICC) has traditionally been treated with surgical resection when amenable. Intra-arterial therapy (IAT) for multifocal ICC has not been directly compared with surgical resection. METHODS: A single-center, retrospective review of consecutive patients treated for multifocal ICC was conducted. Patients with distant metastases or treatment with systemic chemotherapy alone were excluded. Patients were divided into two groups: surgical resection versus IAT; IAT included transarterial chemoembolization (TACE), transarterial radioembolization (TARE), and hepatic arterial infusion (HAI) pump therapy. Subjects were also analyzed by surgical resection, TACE, and HAI pump therapy. RESULTS: Overall, 116 patients with multifocal ICC were studied, 57 in the surgical resection group and 59 in the IAT group (TACE = 41, HAI pump = 16, TARE = 2). The IAT group was characterized by a higher incidence of bilobar disease (88.1% vs. 47.4%, p < 0.001), larger tumors (median 10.6 vs. 7.5 cm, p = 0.004), higher incidence of macrovascular invasion (44.1% vs. 24.6%, p = 0.027), and higher rate of nodal metastases (57.6% vs. 28.6%, p = 0.002). Median overall survival for surgical resection was 20 months versus 16 months for IAT (p = 0.627). Multivariate analysis found that macrovascular invasion [hazard ratio (HR) 2.52, 95% confidence interval (CI) 1.56-4.09] and non-receipt of systemic chemotherapy (HR 3.81, 95% CI 2.23-6.52) were independent poor prognostic risk factors. Surgical resection was not associated with a survival advantage over IAT on multivariate analysis (p = 0.242). CONCLUSION: Despite selection bias for use of surgical resection compared with IAT, no survival advantage was conferred in the treatment of multifocal ICC.

Minimally invasive liver resection for primary and metastatic liver tumors: influence of age on perioperative complications and mortality.

BACKGROUND: As minimally invasive technique becomes more popular, an increasing number of elderly patients were considered for minimally invasive liver resection (MILR). Limited physiologic reserve remains a major concern, which frequently leads surgeons to recommend nonresectional alternatives. We sought to evaluate complications and outcomes of elderly patients undergoing MILR. METHODS: Eight hundred and thirty-one patients who underwent MILR were classified into groups A, B, and C based on age [(< 70, n = 629), (70-79, n = 148), (≥ 80, n = 54) years old, respectively]. RESULTS: Gender distribution, BMI, and cirrhotic status were comparable among all groups. Groups B and C had higher MELD (p = 0.047) and ASA (p = 0.001) scores. Operative time (170, 157, 152 min; p = 0.64) and estimated blood loss (145, 130, 145 ml; p = 0.95) were statistically equal. Overall postoperative complications were greater in groups B and C (12.9 and 9.3 vs. 6.5%, respectively). Complications in group C were all minor. Clavien-Dindo grade III-IV complications were higher in group B when compared to group A (6.8 vs. 2.7%, p = 0.43). There was no significant difference in cardiopulmonary complications, thromboembolic events, ICU admissions, and transfusion rates seen in groups B and C when compared to group A. Duration of hospital stay was statistically longer in groups B and C (3.6, 3.5 vs. 2.5 days, p = 0.0012). 30- and 90-day mortality rates were comparable among the groups, irrespective of age. CONCLUSIONS: In spite of greater preoperative comorbidities and ASA score, there was no significant increase in postoperative morbidity after minimally invasive liver resection in patients ≥ 70 years of age.

Laparoscopic liver resection for hepatocellular carcinoma in early and advanced cirrhosis.

BACKGROUND: Laparoscopic liver resection for hepatocellular carcinoma is well described in early cirrhosis. Less is known regarding outcomes with more advanced cirrhosis, and this study aimed to compare these groups. METHODS: A retrospective review of resections at a high-volume hepatobiliary center over a 15-year period was performed. Primary end-points were 30 and 90-day mortality. Secondary end-points included complications and survival. RESULTS: 80 early (Child's A) were compared to 26 advanced (20 Child's B and 6 Child's C) patients. Baseline patient and tumor characteristics were similar except for parameters indicating degree of cirrhosis. Only early cirrhotic patients underwent anatomic hepatectomies (six cases) and median operative times were longer (151 vs 99 min, p = 0.03). Intraoperative blood loss, conversion, R0 resection, length-of-stay and perioperative complications were comparable. 30 and 90-day mortality were statistically similar (2.5 vs 0%, OR 1.69, 95% CI 0.08-36.19 and 2.5 vs 7.7%, OR 0.31 95% CI 0.04-2.30). There was a trend toward longer survival in the early cirrhotic group but this did not reach significance (50 vs 21 months, p = 0.077). CONCLUSIONS: In carefully selected advanced cirrhotic patients, laparoscopic liver resection may be performed with acceptable outcomes. Though this is not yet well established, further trials may be warranted.

Pediatric liver transplantation for hepatocellular cancer and rare liver malignancies: US multicenter and single-center experience (1981-2015).

A tenth of all pediatric liver transplantations (LTs) are performed for unresectable liver malignancies, especially the more common hepatoblastoma (HBL). Less understood are outcomes after LT for the rare hepatocellular carcinoma, nonhepatoblastoma embryonal tumors (EMBs), and slow growing metastatic neuroendocrine tumors of childhood. Pediatric LT is increasingly performed for rare unresectable liver malignancies other than HBL. We performed a retrospective review of outcomes after LT for malignancy in the multicenter US Scientific Registry of Transplant Recipients (SRTR; n = 677; 1987-2015). We then reviewed the Children's Hospital of Pittsburgh (CHP; n = 74; 1981-2014) experience focusing on LT for unresectable hepatocellular cancer (HCC), EMBs, and metastatic liver tumors (METS). HBL was included to provide reference statistics. In the SRTR database, LT for HCC and HBL increased over time (P < 0.001). Compared with other malignancies, the 149 HCC cases received fewer segmental grafts (P < 0.001) and also experienced 10-year patient survival similar to 15,710 adult HCC LT recipients (51.6% versus 49.6%; P = 0.848, not significant [NS], log-rank test). For 22 of 149 cases with incidental HCC, 10-year patient survival was higher than 127 primary HCC cases (85% [95% confidence interval (CI), 70.6%-100%] versus 48.3% [95% CI, 38%-61%]; P = 0.168, NS) and similar to 3392 biliary atresia cases (89.9%; 95% CI, 88.7%-91%). Actuarial 10-year patient survival for 17 EMBs, 10 METS, and 6 leiomyosarcoma patients exceeded 60%. These survival outcomes were similar to those seen for HBL. At CHP, posttransplant recurrence-free and overall survival among 25 HCC, 17 (68%) of whom had preexisting liver disease, was 16/25 or 64%, and 9/25 or 36%, respectively. All 10 patients with incidental HCC and tumor-node-metastasis stage I and II HCC survived recurrence-free. Only vascular invasion predicted poor survival in multivariate analysis (P < 0.0001). A total of 4 of 5 EMB patients (80%) and all patients with METS (neuroendocrine-2, pseudopapillary pancreatic-1) also survived recurrence-free. Among children, LT can be curative for unresectable HCC confined to the liver and without vascular invasion, incidental HCC, embryonal tumors, and metastatic neuroendocrine tumors. Liver Transplantation 23 1577-1588 2017 AASLD.

Liver Resection After Selective Internal Radiation Therapy with Yttrium-90 is Safe and Feasible: A Bi-institutional Analysis.

BACKGROUND: Treatment with yttrium-90 (Y90) microspheres has emerged as a viable liver-directed therapy for patients with unresectable tumors and those outside transplantation criteria. A select number of patients demonstrate a favorable response and become candidates for surgical resection. METHODS: Patients who underwent selective internal radiation therapy (SIRT) with Y90 microspheres at two institutions were reviewed. Patients who underwent liver resection were included in the study. The data gathered included demographics, tumor characteristics, response to Y90, surgical details, perioperative outcomes, and survival. RESULTS: The inclusion criteria were met by 12 patients. The diagnoses included metastatic disease from colorectal adenocarcinoma (n = 6), neuroendocrine tumor (n = 1), and ocular melanoma (n = 1) in addition to hepatocellular carcinoma (n = 4). The median time from liver disease diagnosis to Y90 treatment was 5.5 months (range 2-92 months). The median time from Y90 treatment to surgery was 9.5 months (range 3-20 months). The surgical approach included right hepatectomy (n = 3), extended right hepatectomy (n = 5), extended left hepatectomy (n = 1), segmentectomy with ablation (n = 2), and segmentectomy with isolated liver perfusion (n = 1). The hospital stay was 7 days (range 4-31 days), and 67% of the patients were discharged home. The readmission rate was 42%. The 90-day morbidity and mortality rates were respectively 42 and 8%. At this writing, the median overall survival has not been reached at 25 months. CONCLUSION: Liver resection after Y90 SIRT is a challenging surgical procedure with high rates of perioperative morbidity and hospital readmission. However, for properly selected patients, potential exists for extending disease-free and overall survival in the current era of multimodal therapy for malignant liver disease.

Initial Treatment of Unresectable Neuroendocrine Tumor Liver Metastases with Transarterial Chemoembolization using Streptozotocin: A 20-Year Experience.

BACKGROUND: The majority of patients with neuroendocrine tumor liver metastases (NELM) present with multifocal disease and are not surgical candidates. We present our 20-year experience with transarterial chemoembolization (TACE) using streptozotocin (STZ) in patients with initially unresectable NELM. METHODS: Patients with unresectable NELM treated with TACE using STZ at a single institution from 1995 to 2015 were identified after institutional board approval. Imaging was independently reviewed by a radiologist to evaluate for RECIST 1.1 responses. RESULTS: Ninety-one patients with NELM who underwent 474 TACE treatments during the past 20 years were identified. Median age was 62 years, and 54 % of the patients were females. Median number of TACE treatments per patient was four (range 1-22). TACE treatment with STZ was very well tolerated with 10.3 % of treatments being associated with side effects, predominantly transient, including hyper/hypotension, bradycardia, or postembolization syndrome. Median overall survival from the start of TACE was 44 months (5-year OS from TACE 40.8 % and 5-year PFS 20.3 %), and 54 % of the patients who had carcinoid syndrome reported improved symptoms after TACE treatments. Age, grade, liver tumor burden, and ability to undergo multiple TACE treatments were independent predictors of overall survival in multivariable analysis. Chromogranin A levels >115 ng/ml were associated with worse overall survival (p < 0.001). CONCLUSIONS: In patients with unresectable NELM, TACE with STZ is well tolerated with minimal toxicity and can lead to diminished carcinoid syndrome and long-term survival. This is a novel, conservative approach for the initial treatment of unresectable NELM.

Performance of prognostic scores and staging systems in predicting long-term survival outcomes after surgery for intrahepatic cholangiocarcinoma.

INTRODUCTION: We sought to validate the commonly used prognostic models and staging systems for intrahepatic cholangiocarcinoma (ICC) in a large multi-center patient cohort. METHODS: The overall (OS) and disease free survival (DFS) prognostic discriminatory ability of various commonly used models were assessed in a large retrospective cohort. Harrell's concordance index (c-index) was used to determine accuracy of model prediction. RESULTS: Among 1054 ICC patients, median OS was 37.7 months and 1-, 3-, and 5-year survival, were 78.8%, 51.5%, and 39.3%, respectively. Recurrence of disease occurred in 454 (43.0%) patients with a median DFS of 29.6 months. One-, 3- and 5- year DFS were 64.6%, 46.5 % and 44.4%, respectively. The prognostic models associated with the best OS prediction were the Wang nomogram (c-index 0.668) and the Nathan staging system (c-index 0.639). No model was proficient in predicting DFS. Only the Wang nomogram exceeded a c-index of 0.6 for DFS (c-index 0.602). The c-index for the AJCC staging system was 0.637 for OS and 0.582 for DFS. CONCLUSIONS: While the Wang nomogram had the best discriminatory ability relative to OS and DFS, no ICC staging system or nomogram demonstrated excellent prognostic discrimination. The AJCC staging for ICC performed reasonably, although its overall discrimination was only modest-to-good.

The effect of preoperative chemotherapy treatment in surgically treated intrahepatic cholangiocarcinoma patients-A multi-institutional analysis.

INTRODUCTION: While preoperative chemotherapy (pCT) is utilized in many intra-abdominal cancers, the use of pCT among patients with intrahepatic cholangiocarcinoma (ICC) remains ill defined. As such, the objective of the current study was to examine the impact of pCT among patients undergoing curative-intent resection for ICC. METHODS: Patients who underwent hepatectomy for ICC were identified from a multi-institutional international cohort. The association between pCT with peri-operative and long-term clinical outcomes was assessed. RESULTS: Of the 1 057 patients who were identified and met the inclusion criteria, 62 patients (5.9%) received pCT. These patients were noticed to have more advanced disease. Median OS (pCT:46.9 months vs no pCT:37.4 months; P = 0.900) and DFS (pCT: 34.1 months vs no pCT: 29.1 months; P = 0.909) were similar between the two groups. In a subgroup analysis of propensity-score matched patients, there was longer OS (pCT:46.9 months vs no pCT:29.4 months) and DFS (pCT:34.1 months vs no pCT:14.0 months); however this did not reach statistical significance (both P > 0.05). CONCLUSION: In conclusion, pCT utilization among patients with ICC was higher among patients with more advanced disease. Short-term post-operative outcomes were not affected by pCT use and receipt of pCT resulted in equivalent OS and DFS following curative-intent resection.

A multi-institutional analysis of elderly patients undergoing a liver resection for intrahepatic cholangiocarcinoma.

BACKGROUND: Little is known regarding postoperative outcomes of elderly patients undergoing liver surgery for intrahepatic cholangiocarcinoma (ICC). METHODS: Five hundred and eighty-four patients undergoing liver resection for ICC between 1990 and 2015 were identified. Perioperative morbidity, mortality, overall survival (OS), and disease-free survival (DFS) were compared between elderly (>70 year, n = 129) and non-elderly (≤70 years, n = 455) patients. RESULTS: Older patients had a higher incidence of complications (elderly vs. non-elderly; 52.7% vs. 42.6%; P = 0.03), as well as major complications (elderly vs. non-elderly; 24.0% vs. 14.9%; P = 0.01); 30-day (0.1% vs. 3.3%; P > 0.05), and 90-day mortality (2.3% vs. 5.5%; P > 0.05) were comparable. Five-year OS and DFS were comparable between the elderly and non-elderly patients (OS, 13.3% vs. 24.4%; and DFS; 7.3% vs. 12.0%; P > 0.05). On propensity score matching, DFS and OS were also comparable among non-elderly versus elderly patients. Poor tumor grade was associated with worse DFS among elderly patients (HR = 1.6, 95%CI 1.0-2.6; P = 0.04), whereas periductal invasion (HR = 1.9, 95% CI 1.1-3.5; P = 0.03) and nodal disease (HR = 2.3, 95% CI 1.3-3.9; P = 0.003) were predictive of shorter DFS among non-elderly patients. CONCLUSION: Elderly patients undergoing liver surgery for ICC demonstrated an increased risk of perioperative complications, but comparable long-term DFS and OS compared with younger patients. Rather, tumor characteristics were more predictive of worse long-term outcomes. J. Surg. Oncol. 2016;113:420-426. © 2016 Wiley Periodicals, Inc.

Decrease in tumor enhancement on contrast-enhanced CT is associated with improved survival in patients with hepatocellular carcinoma treated with Sorafenib.

BACKGROUND: This study investigates whether changes in arterial enhancement of hepatocellular carcinoma (HCC) on contrast-enhanced CT in patients treated with Sorafenib predicts overall survival. METHODS: Thirty-seven HCC patients treated with Sorafenib were identified retrospectively. Up to two target liver lesions were measured on baseline and follow-up contrast-enhanced CT scans. Patients were stratified by whether arterial enhancement decreased by at least 15% and hazard ratio was calculated for all-cause mortality. Patients were then classified as progressive disease, stable disease or partial response using both the modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria and a novel system of enhancement-based response criteria we modeled on mRECIST, but substituting change in arterial enhancement for longest enhancing diameter as the primary measure of tumor response. This response stratification was assessed using survival analysis. RESULTS: Patients with a 15% decrease in arterial enhancement on follow-up contrast-enhanced CT had median overall survival of 1022 days versus 189 days in those without; this corresponded to a significant decrease in risk of all-cause mortality (hazard ratio 0.34; P = 0.04). Response groups created using the enhancement-based criteria showed significant differences in overall survival (P < 0.001) and all response groups were significantly separated from each other on a pair-wise basis. CONCLUSIONS: Decrease in arterial tumor enhancement on follow-up contrast-enhanced CT by at least 15% was associated with improved overall survival in this small sample of HCC patients treated with Sorafenib and shows promise as a possible clinical measure of tumor response in this population.

Robotic and open distal pancreatectomy with celiac axis resection for locally advanced pancreatic body tumors: a single institutional assessment of perioperative outcomes and survival.

BACKGROUND: Distal pancreatectomy with celiac axis resection (DP-CAR) is an option for T4 tumors of the pancreatic body. We examined the perioperative and oncologic outcomes of open and robotic DP-CAR at a high-volume pancreatic center. METHODS: Retrospective review of all consecutive DP-CARs. Patient demographics, 90-day perioperative outcomes, and disease specific survival were collected. RESULTS: 30 DP-CARs were performed (11 Robotic, 19 Open). Both groups had similar preoperative/tumor characteristics, and 27 of 28 PDA patients received neoadjuvant chemotherapy. Robotic DP-CAR was associated with decreased OT (316 vs. 476 min), reduced EBL (393 vs. 1736 ml) and lower rates of blood transfusion (0% vs. 54%) (all p < 0.05). No robotic DP-CAR required conversion. Both groups had similar rates of 90-day mortality, major morbidity, LOS, readmission, and receipt of adjuvant therapy. Similarly, both approaches were associated with high R0 resection rates (82% vs. 79%). At a median follow-up of 33 months, median overall survival for the PDA cohort was 35 months, with no difference in the robotic and open approach (33 and 40 months, p = 0.310). CONCLUSIONS: With a median survival approaching 3 years, DP-CAR represents an effective treatment for select patients with locally advanced pancreatic body cancer, regardless of approach.

Can hepatic resection provide a long-term cure for patients with intrahepatic cholangiocarcinoma?

BACKGROUND: A patient can be considered statistically cured from a specific disease when their mortality rate returns to the same level as that of the general population. In the current study, the authors sought to assess the probability of being statistically cured from intrahepatic cholangiocarcinoma (ICC) by hepatic resection. METHODS: A total of 584 patients who underwent surgery with curative intent for ICC between 1990 and 2013 at 1 of 12 participating institutions were identified. A nonmixture cure model was adopted to compare mortality after hepatic resection with the mortality expected for the general population matched by sex and age. RESULTS: The median, 1-year, 3-year, and 5-year disease-free survival was 10 months, 44%, 18%, and 11%, respectively; the corresponding overall survival was 27 months, 75%, 37%, and 22%, respectively. The probability of being cured of ICC was 9.7% (95% confidence interval, 6.1%-13.4%). The mortality of patients undergoing surgery for ICC was higher than that of the general population until year 10, at which time patients alive without tumor recurrence can be considered cured with 99% certainty. Multivariate analysis demonstrated that cure probabilities ranged from 25.8% (time to cure, 9.8 years) in patients with a single, well-differentiated ICC measuring ≤5 cm that was without vascular/periductal invasion and lymph nodes metastases versus <0.1% (time to cure, 12.6 years) among patients with all 6 of these risk factors. A model with which to calculate cure fraction and time to cure was developed. CONCLUSIONS: The cure model indicated that statistical cure was possible in patients undergoing hepatic resection for ICC. The overall probability of cure was approximately 10% and varied based on several tumor-specific factors. Cancer 2015;121:3998-4006. © 2015 American Cancer Society.

Impact of complications on long-term survival after resection of intrahepatic cholangiocarcinoma.

BACKGROUND: The impact of postoperative complications on the long-term outcomes of patients undergoing surgery for cancer is unclear. The objective of the current study was to define the incidence of complications among patients undergoing surgery for intrahepatic cholangiocarcinoma (ICC) and identify the association between morbidity and long-term outcomes. METHODS: A total of 583 patients undergoing surgery with curative intent for ICC between 1990 and 2013 at 1 of 12 participating institutions were identified. The association between the occurrence and severity of postoperative complications on long-term survival was analyzed. RESULTS: The median age of the patients was 59.9 years and the majority of patients were male (52.3%). A total of 91 patients (15.6%) and 153 patients (26.2%) developed a major and minor postoperative complication, respectively; 18 patients (3.5%) died within 90 days of surgery. Median, 1-year, 3-year, and 5-year recurrence-free survival were 10.0 months, 43.3%, 16.7%, and 11.1%, respectively. Postoperative complications (hazard ratio [HR], 1.37, 95% confidence interval [95% CI], 1.08-1.73 [P = .01]) and severity of complications (major vs none: HR, 1.55; 95% CI, 1.14-2.11 [P = .01]; minor vs none: HR, 1.30; 95% CI, 0.99-1.70 [P = .06]) independently predicted shorter recurrence-free survival. Median, 1-year, 3-year, and 5-year overall survival was 27.8 months, 76.8%, 39.0%, and 23.4%, respectively. Postoperative complications (HR, 1.64; 95% CI, 1.30-2.08 [P<.001]) and severity of complications (major vs none: HR, 1.79; 95% CI, 1.31-2.44 [P<.001]; minor vs none: HR, 1.50; 95% CI, 1.15-1.95 [P<.01]) independently predicted shorter overall survival. CONCLUSIONS: Postoperative complications were found to be independent predictors of worse long-term outcomes. The prevention and management of postoperative complications is crucial to increase both short-term and long-term survival.

The Impact of Surgical Margin Status on Long-Term Outcome After Resection for Intrahepatic Cholangiocarcinoma.

BACKGROUND: The influence of margin status on long-term outcome of patients undergoing liver resection for intrahepatic cholangiocarcinoma (ICC) remains controversial. We sought to study the impact of surgical tumor margin status on recurrence-free survival (RFS) and overall survival (OS) of patients undergoing resection for ICC. METHODS: From a multi-institutional database, 583 patients who underwent hepatic resection for ICC were identified. Demographics data, operative details, pathologic margin status, and long-term outcomes were collected and analyzed. RESULTS: Margin status was positive (R1) in 95 (17.8 %) patients; among patients who underwent an R0 resection (80.9 %), margin width was negative by 1-4 mm in 166 (31.0 %) patients, 5-9 mm in 100 (18.7 %) patients, and ≥1 cm in 174 (32.5 %) patients. Overall, 379 (65.0 %) patients had a recurrence: 61.5 % intrahepatic, 13.5 % extrahepatic, and 25.0 % both intra- and extrahepatic. Median and 5-year RFS and OS was 10.0 months and 9.2 %, and 26.4 months and 23.0 %, respectively. Patients who had an R1 resection had a higher risk of recurrence (hazard ratio [HR] 1.61, 95 % CI 1.15-2.27; p = 0.01) and shorter OS (HR 1.54, 95 % CI 1.12-2.11). Among patients with an R0 resection, margin width was also associated with RFS (1-4 mm: HR 1.32, 95 % CI 0.98-1.78 vs. 5-9 mm: HR 1.21, 95 % CI 0.89-1.66) and OS (1-4 mm: HR 1.95, 95 % CI 0.45-2.63 vs. 5-9 mm: HR 1.21, 95 % CI 0.88-1.68) (referent ≥1 cm; both p ≤ 0.002). Margin status and width remain independently associated with RFS and OS on multivariable analyses. CONCLUSIONS: For patients undergoing resection of ICC, R1 margin status was associated with an inferior long-term outcome. Moreover, there was an incremental worsening RFS and OS as margin width decreased.

Liver transplantation for metastatic neuroendocrine tumors: Outcomes and prognostic variables.

BACKGROUND: Patient selection for liver transplantation for metastatic neuroendocrine tumors remains a topic of debate. There is no established MELD exception, making it difficult to obtain donor organs. METHODS: A multicenter database was created assessing outcomes for liver and multivisceral transplantation for metastatic neuroendocrine tumors and identifying prognostic factors for survival. Demographic, transplant, primary tumor site and management, pathology, recurrent disease and survival data were collected and analyzed. Survival probabilities were calculated using the Kaplan-Meier method. RESULTS: Analysis included 85 patients who underwent liver transplantation November 1988-January 2012 at 28 centers. One, three, and five-year patient survival rates were 83%, 60%, and 52%, respectively; 40 of 85 patients died, with 20 of 40 deaths due to recurrent disease. In univariate analyses, the following were predictors of poor prognosis: large vessel invasion (P < 0.001), extent of extrahepatic resection at liver transplant (P = 0.007), and tumor differentiation (P = 0.003). In multivariable analysis, predictors of poor overall survival included large vessel invasion (P = 0.001), and extent of extrahepatic resection at liver transplant (P = 0.015). CONCLUSION: In the absence of poor prognostic factors, metastatic neuroendocrine tumor is an acceptable indication for liver transplantation. Identification of favorable prognostic factors should allow assignment of a MELD exception similar to hepatocellular carcinoma.

Health-related quality of life as a prognostic factor in patients with advanced cancer.

BACKGROUND: Evidence continues to accumulate regarding the association between health-related quality of life (HRQoL) and survival across chronic diseases. The objectives of the current study were to investigate the prognostic value of HRQoL in patients with hepatocellular carcinoma and cholangiocarcinoma after adjusting for sociodemographics, disease-related factors, and treatment-related factors. METHODS: A total of 321 patients diagnosed with hepatocellular or cholangiocarcinoma were administered the Functional Assessment of Cancer Therapy-Hepatobiliary instrument. Cox regression and Kaplan-Meier survival analyses were performed to test the association between the 5 domains of HRQoL and survival. RESULTS: Using Cox regression, overall HRQoL was found to be significantly associated with survival (P = .003) after adjusting for demographics, disease-specific factors, and treatment. Subscales of the Functional Assessment of Cancer Therapy-Hepatobiliary, including the Physical Well-Being (P = .02) and the Symptoms and Side Effects subscales (P = .05), were also found to be significantly associated with survival after adjusting for demographics, disease-specific factors, and treatment. CONCLUSIONS: HRQoL was found to be prognostic of survival in patients with hepatocellular and cholangiocarcinoma while covarying for demographics, disease-specific factors, and treatment. Stratifying patients based on HRQoL when testing novel treatments may be recommended. Health-related quality of life was found to be prognostic of survival in patients with hepatocellular and cholangiocarcinoma while controlling for demographics, disease-specific factors, and treatment-related factors.