Calcifications and Cystic Morphology on Preoperative Imaging Predict Survival After Resection of Pancreatic Neuroendocrine Tumors.

BACKGROUND: Radiographic calcifications and cystic morphology are associated with higher and lower tumor grade, respectively, in pancreatic neuroendocrine tumors (PNETs). Whether calcifications and/or cystic morphology could be used preoperatively to predict post-resection survival in patients with PNETs remains elusive. METHODS: Patients undergoing curative-intent resection of well-differentiated PNETs from 2000 to 2017 at eight academic institutions participating in the US Neuroendocrine Tumor Study Group were identified. Preoperative cross-sectional imaging reports were reviewed to identify the presence of calcifications and of a cystic component occupying >50% of the total tumor area. Clinicopathologic characteristics and recurrence-free survival (RFS) were compared. RESULTS: Of 981 patients studied, 18% had calcifications and 17% had cystic tumors. Tumors with calcifications were more commonly associated with Ki-67 ≥3% (47% vs. 33%; p = 0.029), lymph node metastasis (36% vs. 24%; p = 0.011), and distant metastasis (13% vs. 4%; p < 0.001). In contrast, cystic tumors were less commonly associated with lymph node metastasis (12% vs. 30%; p < 0.001). Five-year RFS after resection was most favorable for cystic tumors without calcifications (91%), intermediate for solid tumors without calcifications (77%), and least favorable for any calcified PNET (solid 69%, cystic 67%; p = 0.043). Calcifications remained an independent predictor of RFS on multivariable analysis (p = 0.043) controlling for nodal (p < 0.001) and distant metastasis (p = 0.001). CONCLUSIONS: Easily detectable radiographic features, such as calcifications and cystic morphology, can be used preoperatively to stratify prognosis in patients with PNETs and possibly inform the decision to operate or not, as well as guide the extent of resection and potential use of neoadjuvant therapy.

Conditional Survival Following Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Surface Malignancies: An Analysis from the US HIPEC Collaborative.

INTRODUCTION: The long-term prognosis of patients who undergo cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal surface malignancies (PSM) varies considerably on the basis of histological and operative factors. While overall survival (OS) estimates are used to inform adjuvant therapy and surveillance strategies, conditional survival may provide more clinically relevant estimates of prognosis by accounting for disease-free time elapsed. PATIENTS AND METHODS: All patients from 12 academic institutions who underwent CRS ± HIPEC for PSM from 2000 to 2017 were retrospectively analyzed. OS and disease-free survival (DFS) rates were calculated using the Kaplan-Meier method while conditional overall (COS) and conditional disease-free survival (CDFS) rates were calculated at 1, 2, or 3 years from surgery for different tumor histologies. RESULTS: Overall, 1610 patients underwent CRS ± HIPEC. Among patients with benign appendiceal mucinous tumors (N = 460), 5-year OS and COS at 3 years were 92.1% and 96.3% (Δ4.2%), respectively. For patients with well-differentiated appendiceal cancers (N = 400), 5-year OS and COS at 3 years were 76.3% and 88.3% (Δ12.0%), respectively. For patients with high-grade appendiceal cancers (N = 258), 5-year OS and COS at 3 years were 43.8% and 75.4% (Δ31.6%), respectively. For patients with colorectal cancers (N = 362), 5-year OS and COS at 3 years were 31.8% and 67.3% (Δ35.5%), respectively. For patients with peritoneal mesothelioma (N = 130), 5-year OS and COS at 3 years were 67.6% and 89.7% (Δ22.1%), respectively. Similar trends were observed for DFS/CDFS. CONCLUSION: The conditional survival of patients undergoing CRS ± HIPEC for PSM is associated with tumor histology. COS and CDFS provide a more accurate, dynamic estimate of survival than OS and DFS, especially for patients with more aggressive histologies.

Access Denied: Inequities in Clinical Trial Enrollment for Pancreatic Cancer.

BACKGROUND: The influence of social determinants of health (SDH) on participation in clinical trials for pancreatic cancer is not well understood. In this study, we describe trends and identify disparities in pancreatic cancer clinical trial enrollment. PATIENTS AND METHODS: This is a retrospective study of stage I-IV pancreatic cancer patients in the 2004-2016 National Cancer Database. Cohort was stratified into those enrolled in clinical trials during first course of treatment versus not enrolled. Bivariate analysis and logistic regression were used to understand the relationship between SDH and clinical trial participation. RESULTS: A total of 1127 patients (0.4%) enrolled in clinical trials versus 301,340 (99.6%) did not enroll. Enrollment increased over the study period (p < 0.001), but not for Black patients or patients on Medicaid. The majority enrolled had metastatic disease (65.8%). On multivariate analysis, in addition to year of diagnosis (p < 0.001), stage (p < 0.001), and Charlson score (p < 0.001), increasing age [odds ratio (OR) 0.96, 95% confidence interval (CI) 0.96-0.97], non-white race (OR 0.54, CI 0.44-0.66), living in the South (OR 0.42, CI 0.35-0.51), and Medicaid, lack of insurance, or unknown insurance (0.41, CI 0.31-0.53) were predictors of lack of participation. Conversely, treatment at an academic center (OR 6.36, CI 5.4-7.4) and higher neighborhood education predicted enrollment (OR 2.0, CI 1.55-2.67 for < 7% with no high school degree versus > 21%). DISCUSSION: Age, race, insurance, and geography are barriers to clinical trial enrollment for pancreatic cancer patients. While overall enrollment increased, Black patients and patients on Medicaid remain underrepresented. After adjusting for cancer-specific factors, SDH are still associated with clinical trial enrollment, suggesting need for targeted interventions.

Is Cytoreductive Surgery-Hyperthermic Intraperitoneal Chemotherapy Still Indicated in Patients With Extraperitoneal Disease?

INTRODUCTION: The role of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with extraperitoneal disease (EPD) is controversial. METHODS: Among patients with peritoneal metastases from appendiceal cancer (AC) and colorectal cancer (CRC) who underwent CRS-HIPEC, those with EPD (liver, lung, or retroperitoneal lymph nodes [RP LN]) were retrospectively compared to those without EPD. Overall (OS) and recurrence-free survival (RFS) analyses were performed before/after propensity score matching (PSM). RESULTS: Among 1341 patients with AC (64%) or CRC (36%) who underwent CRS ± HIPEC, 134 (10%) had EPD whereas 1207 (90%) did not. EPD was located in the lungs (47%), RP LN (28%), liver (18%), or multiple (6%). Patients with EPD experienced worse median OS (34 versus 63 mo; P = 0.002) and RFS (12 versus 19 mo; P < 0.001). On a multivariable analysis, EPD was associated with worse RFS (P = 0.003), but not OS (P = 0.071). After PSM, the association of EPD with OS (P = 0.204) and RFS (P = 0.056) was no longer significant. In the multivariable analysis of the PSM cohort, EPD was not associated with OS (P = 0.157) or RFS (P = 0.110). CONCLUSIONS: The findings of this large retrospective multi-institutional study suggest that EPD alone, while a negative prognostic indicator, should not be considered an absolute contraindication to CRS ± HIPEC for otherwise well-selected patients with peritoneal surface malignancies. Further research is needed to delineate whether location of EPD influences OS and RFS following CRS-HIPEC.

Using machine learning to preoperatively stratify prognosis among patients with gallbladder cancer: a multi-institutional analysis.

BACKGROUND: Gallbladder cancer (GBC) is an aggressive malignancy associated with a high risk of recurrence and mortality. We used a machine-based learning approach to stratify patients into distinct prognostic groups using preperative variables. METHODS: Patients undergoing curative-intent resection of GBC were identified using a multi-institutional database. A classification and regression tree (CART) was used to stratify patients relative to overall survival (OS) based on preoperative clinical factors. RESULTS: CART analysis identified tumor size, biliary drainage, carbohydrate antigen 19-9 (CA19-9) levels, and neutrophil-lymphocyte ratio (NLR) as the factors most strongly associated with OS. Machine learning cohorted patients into four prognostic groups: Group 1 (n = 109): NLR ≤1.5, CA19-9 ≤20, no drainage, tumor size <5.0 cm; Group 2 (n = 88): NLR >1.5, CA19-9 ≤20, no drainage, tumor size <5.0 cm; Group 3 (n = 46): CA19-9 >20, no drainage, tumor size <5.0 cm; Group 4 (n = 77): tumor size <5.0 cm with drainage OR tumor size ≥5.0 cm. Median OS decreased incrementally with CART group designation (59.5, 27.6, 20.6, and 12.1 months; p < 0.0001). CONCLUSIONS: A machine-based model was able to stratify GBC patients into four distinct prognostic groups based only on preoperative characteristics. Characterizing patient prognosis with machine learning tools may help physicians provide more patient-centered care.

The Effect of an Enhanced Recovery Protocol on Colorectal Surgery Patients With Diabetes.

BACKGROUND: The effect of an enhanced recovery protocol including preoperative carbohydrate loading on patients with diabetes is unclear. This study investigated the effect of both on perioperative glucose management and postoperative outcomes in patients with diabetes undergoing colorectal surgery. MATERIALS AND METHODS: A retrospective study was conducted on patients undergoing elective colorectal surgery before and after implementation of an enhanced recovery protocol. Ninety-nine patients with type 2 diabetes (DM, 41 control versus 58 enhanced recovery) and 366 patients without diabetes (NDM, 158 control versus 158 enhanced recovery) were included. Multivariate analyses were run to compare mean peak perioperative serum glucose and postoperative outcomes in enhanced recovery and control cohorts with (DM) and without diabetes (NDM). RESULTS: Mean peak preoperative glucose was elevated in DM enhanced recovery compared with DM control patients (192.2 [72.2] versus 139.8 [41.4]; P < 0.001). Mean peak intraoperative (162.3 [43.1] versus 163.8 [39.6]; P = 0.869) and postoperative glucose (207.7 [75.8] versus 217.8 [78.5]; P = 0.523) were similar in DM enhanced recovery compared with DM control group. Enhanced recovery led to decreased LOS in DM (P = 0.001) and NDM enhanced recovery patients (P < 0.000) compared with their control groups. CONCLUSIONS: An enhanced recovery protocol may lead to increased peak preoperative glucose levels and 30-d readmissions in patients with type 2 diabetes undergoing colorectal surgery. However, the ultimate clinical significance of transiently elevated preoperative glucose in DM patients is uncertain. Our results suggest that an enhanced recovery protocol and preoperative carbohydrate loading does not lead to poorer postoperative glycemic control overall in patients with diabetes undergoing colorectal surgery.

Neoadjuvant therapy versus surgery first for ampullary carcinoma: A propensity score-matched analysis of the NCDB.

BACKGROUND: The role of neoadjuvant therapy (NT) for ampullary carcinoma (AC) has not been clearly established. METHODS: Patients who underwent pancreatoduodenectomy for AC between 2004 and 2016 were identified in the National Cancer Database. Overall survival (OS) was compared between those who received NT before resection and those who underwent surgery first (SF). Propensity score matching (PSM) was performed using age, pathologic T and N stage, and tumor differentiation. RESULTS: Among 8688 patients with AC, 175 (2.0%) received NT before surgery. While patients who received NT were younger (p = .022) and more likely to have nodal metastasis (43.3% vs. 35.1%, p < .001), there was no difference in OS on univariate (43 vs. 33 months; hazard ratio [HR]: 1.10, 95% confidence interval [CI]: 0.88-1.37, p = .401) or multivariate (HR: 1.09, 95% CI: 0.88-1.36, p = .416) analysis between groups. After PSM, there remained no difference in OS between NT or SF groups on univariate (37 vs. 32 months; HR: 1.20, 95% CI: 0.87-1.64, p = .350) or multivariate (HR: 0.99, 95% CI: 0.71-1.38, p = .943) analysis. CONCLUSION: NT followed by surgery was not associated with improved survival outcomes compared with SF among patients with localized AC. While NT is an acceptable alternative for patients with advanced disease, SF should remain the standard of care.

Women in hepatopancreaticobiliary surgery: is there a pipeline problem?

BACKGROUND: Women are underrepresented in hepatopancreatobiliary (HPB) surgery. We investigated whether this is a pipeline problem by looking at the percentage of women trainees presenting at Americas Hepato-Pancreato-Biliary Association (AHPBA) and then determining their ultimate career path. METHODS: We extracted gender, level of training, and career path of first authors of abstracts presented at the 2007 and 2012 AHPBA conferences. Chi-square analysis and Fisher's exact test were used to examine gender trends. RESULTS: 85 authors in 2007 and 109 in 2012 met inclusion criteria. 16.5% of presenters were female in 2007 compared to 22.9% in 2012. Just over 50% of authors went into academic medicine in 2007 (55%) and 2012 (59%) which did not differ by gender (p = 0.868 in 2007, p = 0.174 in 2012). 41.2% of first authors from 2007 to 2012 went into an HPB related field which did not differ significantly by gender (p = 0.450 for 2007, p = 0.626 for 2012). CONCLUSION: Similar percentages of men and women who present at AHPBA ultimately obtain an HPB related job, however, more men than women trainees present at AHPBA. More efforts to encourage women to go into HPB surgery early may help eliminate this gender gap.

Textbook Outcomes Among Medicare Patients Undergoing Hepatopancreatic Surgery.

OBJECTIVE: To define and test "Textbook Outcome" (TO)-a composite measure for healthcare quality-among Medicare patients undergoing hepatopancreatic resections. Hospital variation in TO and Medicare payments were analyzed. BACKGROUND: Composite measures of quality may be superior to individual measures for the analysis of hospital performance. METHODS: The Medicare Provider Analysis and Review (MEDPAR) Inpatient Files were reviewed to identify Medicare patients who underwent pancreatic and liver procedures between 2013 and 2015. TO was defined as: no postoperative surgical complications, no prolonged length of hospital stay, no readmission ≤ 90 days after discharge, and no postoperative mortality ≤ 90 days after surgery. Medicare payments were compared among patients who achieved TO versus patients who did not. Multivariable logistic regression was used to investigate patient factors associated with TO. A nomogram to predict probability of TO was developed and validated. RESULTS: TO was achieved in 44% (n = 5919) of 13,467 patients undergoing hepatopancreatic surgery. Adjusted TO rates at the hospital level varied from 11.1% to 69.6% for pancreatic procedures and from 16.6% to 78.7% for liver procedures. Prolonged length of hospital stay represented the major obstacle to achieve TO. Average Medicare payments were substantially higher among patients who did not have a TO. Factors associated with TO on multivariable analysis were age, sex, Charlson comorbidity score, previous hospital admissions, procedure type, and surgical approach (all P > 0.05). CONCLUSIONS: Less than one-half of Medicare patients achieved a TO following hepatopancreatic procedures with a wide variation in the rates of TO among hospitals. There was a discrepancy in Medicare payments for patients who achieved a TO versus patients who did not. TO could be useful for the public reporting of patient level hospital performance and hospital variation.

Minimally Invasive Versus Open Liver Resection for Hepatocellular Carcinoma in the Setting of Portal Vein Hypertension: Results of an International Multi-institutional Analysis.

BACKGROUND: Patients with hepatocellular carcinoma (HCC) and portal vein hypertension assessed with platelet count (PVH-PLT; platelet count < 100,000/mL) are often denied surgery even when the disease is technically resectable. Short- and long-term outcomes of patients undergoing minimally invasive surgery (MIS) versus open resection for HCC and PVH-PLT were compared. METHODS: Propensity score matching (PSM) was used to balance the clinicopathological differences between MIS and non-MIS patents. Univariate comparison and standard survival analyses were utilized. RESULTS: Among 1974 patients who underwent surgery for HCC, 13% had a PVH-PLT and 33% underwent MIS. After 1:1 PSM, 407 MIS and 407 non-MIS patients were analyzed. Incidence of complications and length-of-stay (LoS) were higher among non-MIS versus MIS patients (both p ≤ 0.002). After PSM, among 178 PVH-PLT patients (89 MIS and 89 non-MIS), patients who underwent a non-MIS approach had longer LoS (> 7 days; non-MIS: 55% vs. MIS: 29%), as well as higher morbidity (non-MIS: 42% vs. MIS: 29%) [p <0.001]. In contrast, long-term oncological outcomes were comparable, including 3-year overall survival (non-MIS: 66.2% vs. MIS: 72.9%) and disease-free survival (non-MIS: 47.3% vs. MIS: 50.2%) [both p ≥ 0.08]. CONCLUSION: An MIS approach was associated with improved short-term outcomes, but similar long-term outcomes, compared with open liver resection for patients with HCC and PVH-PLT. An MIS approach for liver resection should be considered for patients with HCC, even those individuals with PVH-PLT.

Specific Growth Rate as a Predictor of Survival in Pancreatic Neuroendocrine Tumors: A Multi-institutional Study from the United States Neuroendocrine Study Group.

BACKGROUND: Pancreatic neuroendocrine tumors (PNETs) are often indolent; however, identifying patients at risk for rapidly progressing variants is critical, particularly for those with small tumors who may be candidates for expectant management. Specific growth rate (SGR) has been predictive of survival in other malignancies but has not been examined in PNETs. METHODS: A retrospective cohort study of adult patients who underwent PNET resection from 2000 to 2016 was performed utilizing the multi-institutional United States Neuroendocrine Study Group database. Patients with ≥ 2 preoperative cross-sectional imaging studies at least 30 days apart were included in our analysis (N = 288). Patients were grouped as "high SGR" or "low SGR." Demographic and clinical factors were compared between the groups. Kaplan-Meier and log-rank analysis were used for survival analysis. Cox proportional hazard analysis was used to assess the impact of various clinical factors on overall survival (OS). RESULTS: High SGR was associated with higher T stage at resection, shorter doubling time, and elevated HbA1c (all P ≤ 0.01). Patients with high SGR had significantly decreased 5-year OS (63 vs 80%, P = 0.01) and disease-specific survival (72 vs 91%, P = 0.03) compared to those with low SGR. In patients with small (≤ 2 cm) tumors (N = 106), high SGR predicted lower 5-year OS (79 vs 96%, P = 0.01). On multivariate analysis, high SGR was independently associated with worse OS (hazard ratio 2.67, 95% confidence interval 1.05-6.84, P = 0.04). CONCLUSION: High SGR is associated with worse survival in PNET patients. Evaluating PNET SGR may enhance clinical decision-making, particularly when weighing expectant management versus surgery in patients with small tumors.

Impact of Insurance Status on Survival in Gastroenteropancreatic Neuroendocrine Tumors.

BACKGROUND: Insurance status predicts access to medical care in the USA. Previous studies have shown uninsured patients with some malignancies have worse outcomes than insured patients. The impact of insurance status on patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) is unclear. PATIENTS AND METHODS: A retrospective cohort study of adult patients with resected GEP-NETs was performed using the US Neuroendocrine Tumor Study Group (USNETSG) database (2000-2016). Demographic and clinical factors were compared by insurance status. Patients ≥ 65 years were excluded, as these patients are almost universally covered by Medicare. Kaplan-Meier and log-rank analyses were used for survival analysis. Logistic regression was used to assess factors associated with overall survival (OS). RESULTS: The USNETSG database included 2022 patients. Of those, 1425 were aged 18-64 years at index operation and were included in our analysis. Uninsured patients were more likely to have an emergent operation (7.9% versus 2.5%, p = 0.01) and less likely to receive postoperative somatostatin analog therapy (1.6% versus 9.9%, p = 0.03). OS at 1, 5, and 10 years was significantly higher for insured patients (96.3%, 88.2%, and 73.8%, respectively) than uninsured patients (87.7%, 71.9%, and 44.0%, respectively) (p < 0.01). On Cox multivariate regression analysis controlling for T/M stage, tumor grade, ASA class, and income level, being uninsured was independently associated with worse OS [hazard ratio (HR) 2.69, 95% confidence interval (CI) 1.32-5.48, p = 0.006]. CONCLUSIONS: Insurance status is an independent predictor of survival in patients with GEP-NETs. Our study highlights the importance of access to medical care, disparities related to insurance status, and the need to mitigate these disparities.

Predictors of Anastomotic Failure After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: Does Technique Matter?

BACKGROUND: Anastomotic failure (AF) after cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) remains a dreaded complication. Whether specific factors, including anastomotic technique, are associated with AF is poorly understood. METHODS: Patients who underwent CRS-HIPEC including at least one bowel resection between 2000 and 2017 from 12 academic institutions were reviewed to determine factors associated with AF (anastomotic leak or enteric fistula). RESULTS: Among 1020 patients who met the inclusion criteria, the median age was 55 years, 43.9% were male, and the most common histology was appendiceal neoplasm (62.3%). The median Peritoneal Cancer Index was 14, and 93.2% of the patients underwent CC0/1 resection. Overall, 82 of the patients (8%) experienced an AF, whereas 938 (92.0%) did not. In the multivariable analysis, the factors associated with AF included male gender (odds ratio [OR], 2.2; p < 0.01), left-sided colorectal resection (OR 10.0; p = 0.03), and preoperative albumin (OR 1.8 per g/dL; p = 0.02).Technical factors such as method (stapled vs hand-sewn), timing of anastomosis, and chemotherapy regimen used were not associated with AF (all p > 0.05). Anastomotic failure was associated with longer hospital stay (23 vs 10 days; p < 0.01), higher complication rate (90% vs 59%; p < 0.01), higher reoperation rate (41% vs 9%; p < 0.01), more 30-day readmissions (59% vs 22%; p < 0.01), greater 30-day mortality (9% vs 1%; p < 0.01), and greater 90-day mortality (16% vs 8%; p = 0.02) as well as shorter median overall survival (25.6 vs 66.0 months; p < 0.01). CONCLUSIONS: Among patients undergoing CRS-HIPEC, AF is independently associated with postoperative morbidity and worse long-term outcomes. Because patient- and tumor-related, but not technical, factors are associated with AF, operative technique may be individualized based on patient considerations and surgeon preference.

Outcomes of neoadjuvant chemotherapy before CRS-HIPEC for patients with appendiceal cancer.

BACKGROUND: Cytoreductive surgery (CRS) with or without hyperthermic intraperitoneal chemotherapy (HIPEC) is indicated for patients with peritoneal dissemination of appendiceal cancer. The role of neoadjuvant chemotherapy (NAC) before CRS-HIPEC remains controversial. METHODS: A retrospective review of adult patients who underwent CRS ± HIPEC for metastatic appendiceal cancer between 2000-2017 was performed. Patients who received NAC followed by surgery were compared with those who underwent surgery first (SF) with and without 1:1 propensity score matching (PSM). RESULTS: Among 803 patients with appendiceal cancer who underwent CRS ± HIPEC, 225 (28%) received NAC, and 578 (72%) underwent SF. After PSM (n = 186), median overall survival (OS) did not differ (NAC: 40 vs SF: 56 months; P = .210) but recurrence-free survival (RFS) was worse among patients who received NAC (14 vs 22 months; P = .007). NAC was independently associated with worse OS (hazards ratio [HR], 1.81; 95% confidence interval [CI], 1.03-3.18) and RFS (HR, 1.93; 95% CI, 1.25-2.99). CONCLUSION: In this multi-institutional retrospective analysis of patients with peritoneal dissemination from appendiceal cancer, the use of NAC before CRS-HIPEC was associated with worse OS and RFS even after PSM and multivariable regression. Immediate surgery should be considered for patients with disease amenable to complete cytoreduction.

Adjuvant therapy following resection of gastroenteropancreatic neuroendocrine tumors provides no recurrence or survival benefit.

BACKGROUND AND OBJECTIVES: Lack of high-level evidence supporting adjuvant therapy for patients with resected gastroenteropancreatic neuroendocrine tumors (GEP NETs) warrants an evaluation of its non-standard of care use. METHODS: Patients with primary GEP NETs who underwent curative-intent resection at eight institutions between 2000 and 2016 were identified; 91 patients received adjuvant therapy. Recurrence-free survival (RFS) and overall survival (OS) were compared between adjuvant cytotoxic chemotherapy and somatostatin analog cohorts. RESULTS: In resected patients, 33 received cytotoxic chemotherapy, and 58 received somatostatin analogs. Five-year RFS/OS was 49% and 83%, respectively. Cytotoxic chemotherapy RFS/OS was 36% and 61%, respectively, lower than the no therapy cohort (P < .01). RFS with somatostatin analog therapy (compared to none) was lower (P < .01), as was OS (P = .01). On multivariable analysis, adjuvant cytotoxic therapy was negatively associated with RFS but not OS controlling for patient/tumor-specific characteristics (RFS P < .01). CONCLUSIONS: Our data, reflecting the largest reported experience to date, demonstrate that adjuvant therapy for resected GEP NETs is negatively associated with RFS and confers no OS benefit. Selection bias enriching our treatment cohort for individuals with unmeasured high-risk characteristics likely explains some of these results; future studies should focus on patient subsets who may benefit from adjuvant therapy.

County Rankings Have Limited Utility When Predicting Liver Transplant Outcomes.

BACKGROUND: Evidence of geographical differences in liver transplantation (LT) outcomes has been proposed as a reason to include community characteristics in risk adjustment of transplant quality metrics. However, consistency and utility of rankings in LT outcomes for counties have not been demonstrated. AIMS: We sought to evaluate the utility of county rankings (county socioeconomic status (SES) or county health scores (CHS)) on outcomes after LT. METHODS: Using the United Network for Organ Sharing Registry, adults ≥ 18 years of age undergoing LT between 2002 and 2014 were identified. County-specific 1-year survival was calculated using the Kaplan-Meier method for counties with ≥ 5 LT performed during this period. Agreement between high-risk designation by 1-year mortality rate and county ranking was calculated using the Spearman correlation coefficient. RESULTS: The analysis included 47,769 LT recipients in 1092 counties. County 1-year mortality rates were not correlated with county CHS (Spearman ρ = 0.01, p = 0.694) or county SES (Spearman ρ = - 0.01, p = 0.734). After controlling for individual-level covariates, a statistically significant variability in mortality hazards across counties (p < 0.001) persisted. Although both CHS and SES measures improved the model fit (p = 0.004 and p = 0.048, respectively), an unexplained residual variation in mortality hazard across counties continued. CONCLUSIONS: There is poor agreement between county rankings on various socioeconomic indicators and LT outcomes. Although there is variability in outcomes across counties, this appears not to be due to county-level socioeconomic indices.

Sequential Versus Combined Heart-Liver Transplantation in the USA.

INTRODUCTION: Combined heart-liver transplantation (CHLT) has resulted in acceptable survival rates compared to orthotopic liver transplantation (OLT) alone and orthotopic heart transplantation alone. Using the US transplant registry, we compared outcomes following sequential and combined HLT. METHODS: We conducted a retrospective cohort study. De-identified data were obtained from the United Network Organ Sharing Registry. The primary outcome was patient survival from the date of OLT. Secondary outcomes included liver allograft survival and heart allograft survival. RESULTS: The study cohort included 301 CHLT recipients and six sequential heart-liver transplantation (SHLT) recipients. Patient survival after CHLT was 88% at 1 year, 84% at 3 years, and 82% at 5 years compared to 83%, 67%, and 50% in the SHLT group (p = 0.010). Liver allograft survival at 1, 3, and 5 years was 88%,83% and 82%, respectively, in the CHLT group compared to 83% and 67%, and 50%, respectively, in the SHLT group (p = 0.009). After OLT, heart allograft survival at 1, 3, and 5 years was 86%, 79%, and 74% in the CHLT group, respectively, compared to 83%, 67%, and 50% in the SHLT group (p = 0.037). CONCLUSIONS: Despite the limited size of the SHLT cohort, we found that CHLT was superior to SHLT in survival rate and graft survival. The better outcomes noted in CHLT may relate to immunoprotection provided by liver transplantation from the same donor.

Travel to a high volume hospital to undergo resection of gallbladder cancer: does it impact quality of care and long-term outcomes?

BACKGROUND: The relationship of volume and travel distance to patient outcomes after resection of gallbladder cancer (GBC) remains poorly defined. METHODS: The 2004-2015 National Cancer Database was used to identify GBC resection patients and examine the impact of travel distance, hospital volume and both on overall survival (OS) and quality of care indicators. RESULTS: Among 10,174 patients undergoing surgery for GBC, the majority of patients were Caucasian (N = 8,175, 80%) and had a Charlson-Deyo comorbidity score of 0 (N = 6,785, 67%). On unadjusted survival analysis increasing travel distance and hospital volume were associated with improved OS (both p < 0.001). After controlling for competing risk factors, the 4th quartile of hospital volume was associated with a decreased hazard of death (HR 0.831, 95% CI 0.751-0.920, p < 0.001). When both hospital volume and travel distance were included, the association with improved OS persisted only for hospital volume (4th quartile HR 0.835, 95% CI 0.753-0.925, p < 0.001), whereas there was no independent association of increasing travel distance with OS. CONCLUSIONS: Both increasing travel distance and hospital volume were associated with improved OS; however, adjusted models demonstrated that the impact of travel distance was mediated through hospital volume.

Hepatic angiomyolipoma: an international multicenter analysis on diagnosis, management and outcome.

BACKGROUND: Hepatic angiomyolipoma (HAML) may easily be misdiagnosed as a malignancy. The study aim was to assess diagnostic dilemmas, clinical management and outcome of this rare tumor. METHODS: This retrospective international multicenter study included all patients with pathologically proven HAML diagnosed between 1997 and 2017. Data on patient characteristics, diagnostic work-up, management and follow-up were analyzed. RESULTS: Thirty-eight patients were included, 32 female. Median age was 56yrs (i.q.r. 43-64) and median HAML-diameter was 57.5 mm (i.q.r. 38.5-95.3). Thirty patients had undergone CT and 27/38 MRI of the liver, diagnostic biopsy was performed in 19/38. Initial diagnosis was incorrect in 15/38 patients, of which 13 were thought to have malignancy. In 84% biopsy resulted in a correct preoperative diagnosis. Twenty-nine patients were managed with surgical resection, 4/38 with surveillance and 3/38 with liver transplantation. Recurrence after resection occurred in two cases. No HAML related deaths or progression to malignancy were documented. CONCLUSION: HAML diagnosis proved problematic even in hepatobiliary expertise centers. Biopsy is indicated and may provide valuable additional information when HAML diagnosis is considered on cross-sectional imaging, especially when surgical resection imposes a risk of complications. Conservative management with regular imaging follow-up might be justified when biopsy confirms (classic type) HAML.

Impact of perioperative blood transfusion on survival in pancreatic neuroendocrine tumor patients: analysis from the US Neuroendocrine Study Group.

BACKGROUND: Packed red blood cell (PRBC) transfusion has been associated with worse survival in multiple malignancies but its impact on pancreatic neuroendocrine tumors (PNETs) is unknown. The aim of this study was to determine the impact of PRBC transfusion on survival following PNET resection. METHODS: A retrospective cohort study of PNET patients was performed using the US Neuroendocrine Tumor Study Group database. Demographic and clinical factors were compared. Kaplan-Meier and log-rank analyses were performed. Factors associated with transfusion, overall (OS), recurrence-free (RFS) and progression-free survival (PFS) were assessed by logistic regression. RESULTS: Of 1129 patients with surgically resected PNETs, 156 (13.8%) received perioperative PRBC transfusion. Transfused patients had higher ASA Class, lower preoperative hemoglobin, larger tumors, more nodal involvement, and increased major complications (all p < 0.010). Transfused patients had worse median OS (116 vs 150 months, p < 0.001), worse RFS (83 vs 128 months, p < 0.01) in curatively resected (n = 1047), and worse PFS (11 vs 24 months, p = 0.110) in non-curatively resected (n = 82) patients. On multivariable analysis, transfusion was associated with worse OS (HR 1.80, p = 0.011) when controlling for TNM stage, tumor grade, final resection status, and pre-operative anemia. CONCLUSION: PRBC transfusion is associated with worse survival for patients undergoing PNET resection.