A nationwide propensity score analysis comparing ablation and resection for hepatocellular carcinoma.

BACKGROUND AND OBJECTIVES: Studies have reported ambiguous results regarding the efficacy of ablation for early-stage hepatocellular carcinoma (HCC). Our study compared outcomes of ablation versus resection for HCC ≤50 mm to identify tumor sizes that would most benefit from ablation in terms of long-term survival. METHODS: The National Cancer Database was queried for patients with stage I and II HCC ≤50 mm who underwent ablation or resection (2004-2018). Three cohorts were created based on tumor size: ≤20, 21-30, and 31-50 mm. A propensity score-matched survival analysis was performed using the Kaplan-Meier method. RESULTS: In total, 36.47% (n = 4263) and 63.53% (n = 7425) of patients underwent resection and ablation, respectively. After matching, resection was associated with a significant survival benefit compared to ablation (3-year survival: 78.13% vs. 67.64%; p < 0.0001) in patients with HCC of ≤20 mm. The impact of resection was even more striking among patients with HCC of 21-30 mm (3-year survival: 77.88% vs. 60.53%; p < 0.0001) and 31-50 mm (3-year survival: 67.21% vs. 48.55%; p < 0.0001). CONCLUSIONS: While resection offers a survival benefit over ablation in the treatment of early-stage HCC ≤50 mm, ablation may provide a feasible bridging strategy in patients awaiting transplantation.

Use of immunotherapy and surgery for stage IV melanoma.

BACKGROUND: Immunotherapy for stage IV melanoma has dramatically changed the overall prognosis and treatment strategies. The aim of this study was to evaluate whether changes in systemic immunotherapy options have significantly altered surgical resection rates for patients with stage IV melanoma. METHODS: The National Cancer Database (2004-2015) was used to perform a difference-in-difference analysis to evaluate whether the rate of surgical resection of metastatic disease for stage IV melanoma differed with the use of immunotherapy in the checkpoint inhibitor era in comparison with the use of immunotherapy in the pre-checkpoint inhibitor era. An adjusted difference-in-difference analysis stratified by facility type was performed. An adjusted Poisson regression analysis evaluated predictors of surgical resection in patients with stage IV melanoma who received immunotherapy. RESULTS: There were 14,433 patients with stage IV melanoma (median age, 66 years [interquartile range, 56-76 years]; female, 31.7%), and of all patients in the checkpoint inhibitor era (n = 7,524), 25% (n = 1,879) received immunotherapy. Patients with stage IV disease who received immunotherapy in the checkpoint inhibitor era were more likely to be younger, be healthier, have private insurance, come from upper income quartiles, and be treated at academic programs. A difference-in-difference analysis revealed similar rates of surgical resection of metastatic disease with the use of immunotherapy in the checkpoint inhibitor era and the pre-checkpoint inhibitor era, regardless of facility type. CONCLUSIONS: The distribution of immunotherapy was unequal among patients with stage IV melanoma. Across all facilities, the rates of surgical resection of metastatic disease for stage IV melanoma did not differ with the use of immunotherapy between the checkpoint inhibitor era and the pre-checkpoint inhibitor era.

The Role of Venous and Arterial Resection in Pancreatic Cancer Surgery.

Pancreatic cancer continues to carry a dismal prognosis with the majority of patients presenting at advanced stages of disease. Complete surgical resection remains essential for prolonging survival and increasing the possibility of cure. However, few patients will be resectable at diagnosis, with a significant portion presenting with borderline or locally advanced disease. The addition of vascular resection and reconstruction at the time of pancreatectomy enables expansion of the patient population able to undergo resection with curative intent and achieve tumor-free margins. This review provides an overview of the literature regarding the role of venous and arterial resection in the treatment of pancreatic cancer, with a focus on outcomes including survival, morbidity, and mortality.

Pathological Margin Clearance and Survival After Pancreaticoduodenectomy in a US and European Pancreatic Center.

BACKGROUND: The optimal definition of a margin-negative resection and its exact prognostic significance on survival in resected pancreatic adenocarcinoma remains unknown. This study was designed to assess the relationship between pathological margin clearance, margin type, and survival. METHODS: Patients who underwent pancreaticoduodenectomy with curative intent at two academic institutions, in Amsterdam, the Netherlands, and Boston, Massachusetts, between 2000 and 2014 were retrospectively evaluated. Overall survival, recurrence rates, and progression-free survival (PFS) were assessed by Kaplan-Meier estimates and multivariate Cox proportional hazards analysis, according to pathological margin clearance and type of margin involved. RESULTS: Of 531 patients identified, the median PFS was 12.9, 15.4, and 24.1 months, and the median overall survival was 17.4, 22.9, and 27.7 months for margin clearances of 0, < 1, and ≥1 mm, respectively (all log-rank p < 0.001). On multivariate analysis, patients with a margin clearance of ≥1 mm demonstrated a survival advantage relative to those with 0 mm clearance [hazard ratio (HR) 0.71, p < 0.01], whereas survival was comparable for patients with a margin clearance of < 1 mm versus 0 mm (HR: 0.93, p = 0.60). Patients with involvement (0 or < 1 mm margin clearance) of the SMV/PV margin demonstrated prolonged median overall survival (25.7 months) relative to those with SMA involvement (17.5 months). CONCLUSIONS: In patients undergoing pancreaticoduodenectomy for pancreatic adenocarcinoma, a margin clearance of ≥1 mm correlates with improved survival relative to < 1 mm clearance and may be a more accurate predictor of a complete margin-negative resection in pancreatic cancer. The type of margin involved also appears to impact survival.

Neoadjuvant therapy affects margins and margins affect all: perioperative and survival outcomes in resected pancreatic adenocarcinoma.

BACKGROUND: Resection margin status is an important prognostic factor in pancreatic cancer; however, the impact of positive resection margins in those who received neoadjuvant therapy remains unclear. The current study investigates the prognostic impact of resection margin status after neoadjuvant therapy and pancreaticoduodenectomy for patients with pancreatic adenocarcinoma. METHODS: Patients who underwent pancreaticoduodenectomy for pancreatic adenocarcinoma between 2006 and 2013 were identified from the National Cancer Database. Multivariable logistic regression analysis was utilized to examine the predictive value of neoadjuvant therapy for resection margin status. Long-term outcomes were compared using a Cox proportional hazards model. RESULTS: 7917 patients were identified in total: 1077 (13.6%) and 6840 (86.4%) patients received neoadjuvant therapy and upfront surgery, respectively. Upfront surgery was independently predictive of a positive margin (25.7% vs. 17.7%; OR, 1.54) compared to neoadjuvant therapy. After receipt of neoadjuvant therapy, positive margins (median overall survival, 18.5 vs. 25.9 months; HR, 1.58) remained significantly associated with poor survival on multivariable analysis. DISCUSSION: While neoadjuvant therapy is associated with decreased R1/R2-resection rates after pancreaticoduodenectomy, the poor prognostic impact of positive margins is not abrogated by neoadjuvant therapy, stressing the need for complete tumor clearance and postoperative treatment even after neoadjuvant therapy.

Unique predictors and economic burden of superficial and deep/organ space surgical site infections following pancreatectomy.

BACKGROUND: Surgical site infections (SSIs) are common following pancreatectomy and associated with significant morbidity and economic burden. We sought to identify distinct predictors for superficial versus deep/organ space SSIs and their effects on surgical outcomes. METHODS: ACS-NSQIP targeted pancreatectomy 2014 and 2015 databases were queried. Univariate and multivariate models were developed for both types of SSI, length of stay (LOS), and readmission. Costs were estimated based on Centers for Medicare & Medicaid Services (CMS) recommendations. RESULTS: Of 8093 patients, there were 422 (5.2%) superficial and 1005 (12.4%) deep/organ space SSIs. On multivariate analyses, preoperative biliary stenting was predictive only for superficial SSI (OR: 2.21), while BMI of 25-29.9 (OR: 1.25) and BMI ≥30 kg/m2 (OR: 1.53), pancreatic duct size <3 mm (OR: 1.30), and intermediate (OR: 1.67) versus hard gland texture were predictors of deep/organ-space SSI. Superficial and deep/organ space SSIs were independent predictors of prolonged LOS (OR: 1.74 vs 1.80) and readmission (OR: 2.59 vs 6.57). Additional readmission costs per patient secondary to superficial SSI and deep/organ space SSI were $7661.37 and $18,409.42, respectively. CONCLUSION: Deep/organ space SSI contributes more profoundly to prolonged hospital stay, readmission, and additional costs, suggesting that strategies should focus on preferential prevention of deep/organ space infections.

Stereotactic body radiotherapy for unresected pancreatic cancer: A nationwide review.

BACKGROUND: The role of conventional radiotherapy in the management of pancreatic cancer has yet to be elucidated. Over the past decade, stereotactic body radiotherapy (SBRT) has emerged as a novel therapeutic option in pancreatic cancer care. This study evaluated the survival impact of SBRT on patients with unresected pancreatic cancer. METHODS: The National Cancer Data Base was queried for unresected patients who received chemotherapy for nonmetastatic pancreatic adenocarcinoma between 2004 and 2012. Four treatment groups were identified: chemotherapy alone, chemotherapy combined with external-beam radiotherapy (EBRT), chemotherapy combined with intensity-modulated radiotherapy (IMRT), and chemotherapy combined with SBRT. Propensity score models predicting the odds of receiving SBRT were created to control for potential selection bias, and patients were matched by propensity scores. The survival analysis was performed with the Kaplan-Meier method. RESULTS: A total of 14,331 patients met the inclusion criteria. Chemotherapy alone was delivered to 5464 patients (38.1%); 6418 (44.8%), 322 (2.3%), and 2127 (14.8%) received chemotherapy along with EBRT, IMRT, and SBRT, respectively. The unadjusted median survival before matching was 9.9, 10.9, 12.0, and 13.9 months for patients treated with chemotherapy, EBRT, IMRT, and SBRT, respectively. In separate matched analyses, SBRT remained superior to chemotherapy alone (log-rank P < .0001) and EBRT (log-rank P = .0180). After matching, survival did not differ between patients receiving IMRT and patients receiving SBRT (log-rank P = .0492). CONCLUSIONS: SBRT is associated with a significantly better outcome than chemotherapy alone or in conjunction with traditional EBRT. These results support the idea that SBRT is a promising treatment approach for patients with unresected pancreatic cancer. Cancer 2017;123:4158-4167. © 2017 American Cancer Society.

Surgical Management of Gallbladder Cancer: Simple Versus Extended Cholecystectomy and the Role of Adjuvant Therapy.

OBJECTIVE: To assess if simple cholecystectomy with adjuvant therapy could provide outcomes comparable to extended cholecystectomy. BACKGROUND: Current guidelines recommend extended/radical cholecystectomy for T2/T3 gallbladder cancer; however, many tumors are discovered incidentally at laparoscopic cholecystectomy. METHODS: The national Cancer Data Base 2004 to 2014 was queried for patients with pT2/T3 gallbladder adenocarcinoma who underwent resection. Adjuvant therapy was defined as chemotherapy, with or without radiotherapy, within 90 days of surgery. Baseline characteristics and overall survival were compared by χ and Kaplan-Meier method, respectively. One-to-one propensity score matching for receipt of adjuvant therapy was used to account for potential selection bias. RESULTS: A total of 6825 patients were identified. Diagnosis was made predominantly (78.9%) at the time of surgery or on pathology; 31.8% (2168) received adjuvant therapy. The majority, 88.8% (6060), had a simple cholecystectomy. Patients who received adjuvant therapy versus surgery alone were more likely to: be younger, privately insured, have no comorbidities, pT3 disease, positive lymph nodes, positive resection margins, and extended cholecystectomy. After matching, median survival was significantly longer for extended cholecystectomy with adjuvant therapy (23.3 months) than cholecystectomy with adjuvant therapy (16.4 months), which was significantly longer than either simple (12.4 months) or extended (10.7 months) cholecystectomy alone (all log-rank P<0.001). CONCLUSIONS: Adjuvant therapy prolongs survival after resection of T2/T3 tumors. Simple cholecystectomy with adjuvant therapy appears to be superior to extended resection alone in the short term and may serve as a potential alternative to re-resection in select high-risk individuals.

Hemorrhage after pancreaticoduodenectomy: does timing matter?

BACKGROUND: Hemorrhage after pancreaticoduodenectomy is a potentially fatal complication. We retrospectively reviewed state-wide data to evaluate incidence, type of hemorrhage, treatment modalities, and outcomes. METHODS: Healthcare Cost and Utilization Project's Florida State Inpatient Database was queried 2007-2011 for patients undergoing pancreaticoduodenectomy. Characteristics and outcomes were compared by χ2. Multivariate logistic regression model was generated for risk of hemorrhage during index visit. RESULTS: Of 2548 patients, 217 (8.5%) developed post-operative hemorrhage during their index visit with 139 (64.0%) requiring angiographic, endoscopic, or operative intervention. Overall mortality during index visit was 5.7% (146) - significantly higher in those patients who had post-operative hemorrhage (24.9%) vs not (4.0%) (p < 0.0001). Mortality was significantly higher when post-operative hemorrhage occurred during the second (POD 8-14) vs first (POD 0-7) week at 15/28 vs 16/74, respectively (p = 0.007). On multivariate analysis, male sex (OR 1.56, p = 0.003), vascular resection (OR 1.88, p = 0.017), very low hospital volume (≤7 PD/year; OR 1.62, p = 0.016), and post-operative intra-abdominal/wound infection (OR 2.31, p < 0.0001) were independent predictors for risk of hemorrhage during index visit. CONCLUSIONS: Hemorrhage following pancreaticoduodenectomy remains common, resulting in significantly increased mortality. Hemorrhage during the second post-operative week carries approximately double the mortality of early bleeding, suggesting different etiologies requiring differing treatment approaches.

Disparities in access to care among patients with appendiceal or colorectal cancer and peritoneal metastases: A medicare insurance-based study in the United States.

Background: Prior studies attempting to identify disparities in the care of patients with appendiceal (AC) or colorectal cancer (CRC) with peritoneal metastasis (PM) are limited to single-institution, highly selected patient populations. This observational cohort study sought to identify factors associated with specialty care for Medicare beneficiaries with AC/CRC-PM. Materials and methods: Patients >65 years old in the United States diagnosed with AC/CRC and isolated PM were identified within the Medicare Standard Analytic File (2013-2017). Mixed-effects analyses assessed patient factors associated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) and outpatient consultation with a peritoneal surface malignancy (PSM) surgeon, and Cox proportional-hazards analysis compared 3-year overall survival (OS) between patients receiving CRS/HIPEC versus systemic therapy alone. Results: Among 7,653 patients, only 250 (3.3%) underwent CRS/HIPEC. Among those individuals who did not undergo CRS/HIPEC (N=7,403), only 475 (6.4%) had outpatient consultation with a PSM surgeon. Patient factors independently associated with lower odds of CRS/HIPEC and PSM surgery consultation included older age, greater comorbidity burden, higher social vulnerability index, and further distance from a PSM center (p<0.05). CRS/HIPEC was independently associated with better 3-year OS compared with systemic therapy alone (HR=0.29, 95%CI=0.21-0.38). Conclusion: An exceedingly small proportion of Medicare beneficiaries with AC/CRC-PM undergo CRS/HIPEC or even have an outpatient consultation with a PSM surgeon. Significant disparities in treatment and access to care exist for patients with higher levels of social vulnerability and those that live further away from a PSM center. Future research and interventions should focus on improving access to care for these at-risk patient populations.

Evolution of delayed resistance to immunotherapy in a melanoma responder.

Despite initial responses1-3, most melanoma patients develop resistance4 to immune checkpoint blockade (ICB). To understand the evolution of resistance, we studied 37 tumor samples over 9 years from a patient with metastatic melanoma with complete clinical response to ICB followed by delayed recurrence and death. Phylogenetic analysis revealed co-evolution of seven lineages with multiple convergent, but independent resistance-associated alterations. All recurrent tumors emerged from a lineage characterized by loss of chromosome 15q, with post-treatment clones acquiring additional genomic driver events. Deconvolution of bulk RNA sequencing and highly multiplexed immunofluorescence (t-CyCIF) revealed differences in immune composition among different lineages. Imaging revealed a vasculogenic mimicry phenotype in NGFRhi tumor cells with high PD-L1 expression in close proximity to immune cells. Rapid autopsy demonstrated two distinct NGFR spatial patterns with high polarity and proximity to immune cells in subcutaneous tumors versus a diffuse spatial pattern in lung tumors, suggesting different roles of this neural-crest-like program in different tumor microenvironments. Broadly, this study establishes a high-resolution map of the evolutionary dynamics of resistance to ICB, characterizes a de-differentiated neural-crest tumor population in melanoma immunotherapy resistance and describes site-specific differences in tumor-immune interactions via longitudinal analysis of a patient with melanoma with an unusual clinical course.

Plasma-derived extracellular vesicle analysis and deconvolution enable prediction and tracking of melanoma checkpoint blockade outcome.

Immune checkpoint inhibitors (ICIs) show promise, but most patients do not respond. We identify and validate biomarkers from extracellular vesicles (EVs), allowing non-invasive monitoring of tumor- intrinsic and host immune status, as well as a prediction of ICI response. We undertook transcriptomic profiling of plasma-derived EVs and tumors from 50 patients with metastatic melanoma receiving ICI, and validated with an independent EV-only cohort of 30 patients. Plasma-derived EV and tumor transcriptomes correlate. EV profiles reveal drivers of ICI resistance and melanoma progression, exhibit differentially expressed genes/pathways, and correlate with clinical response to ICI. We created a Bayesian probabilistic deconvolution model to estimate contributions from tumor and non-tumor sources, enabling interpretation of differentially expressed genes/pathways. EV RNA-seq mutations also segregated ICI response. EVs serve as a non-invasive biomarker to jointly probe tumor-intrinsic and immune changes to ICI, function as predictive markers of ICI responsiveness, and monitor tumor persistence and immune activation.

Is Neoadjuvant Therapy Sufficient in Resected Pancreatic Cancer Patients? A National Study.

BACKGROUND: Despite the increasing use of neoadjuvant treatment, the question of whether preoperatively treated, successfully resected patients should receive additional postoperative adjuvant treatment remains unanswered. We evaluate the impact of adjuvant therapy following neoadjuvant treatment and pancreatectomy in pancreatic cancer patients in a large national study. METHODS: We used the National Cancer Data Base between 2006 and 2013 to identify resected, non-metastatic pancreatic adenocarcinoma patients who received neoadjuvant chemo(radio)therapy followed by pancreatectomy. Kaplan-Meier and multivariate Cox proportional hazard regression analyses were performed to compare survival between groups. RESULTS: In total, 1357 patients were identified. Of the patients, 38.6% (n = 524) were treated with postoperative therapy. There was no difference in unadjusted median overall survival between patients who did and did not receive postoperative therapy (median survival, 27.5 vs. 27.1 months, log-rank p = 0.5409). Postoperative therapy was not significantly associated with favorable prognosis in patients with positive resection margins (log-rank p = 0.6452) or positive lymph nodes (log-rank p = 0.6252). On multivariate analysis, receipt of postoperative therapy was not predictive of survival (hazard ratio 0.972; 95% CI 0.848-1.115; p = 0.6876). CONCLUSIONS: Our results using national data suggest that after receipt of neoadjuvant therapy and pancreatectomy, additional postoperative therapy may not provide additional survival benefit. These data warrant further prospective data collection and consideration for clinical trials.

International Validation of the Eighth Edition of the American Joint Committee on Cancer (AJCC) TNM Staging System in Patients With Resected Pancreatic Cancer.

Importance: The recently released eighth edition of the American Joint Committee on Cancer TNM staging system for pancreatic cancer seeks to improve prognostic accuracy but lacks international validation. Objective: To validate the eighth edition of the American Joint Committee on Cancer TNM staging system in an international cohort of patients with resected pancreatic ductal adenocarcinoma. Design, Setting, and Participants: This international multicenter cohort study took place in 5 tertiary centers in Europe and the United States from 2000 to 2015. Patients who underwent pancreatoduodenectomy for nonmetastatic pancreatic ductal adenocarcinoma were eligible. Data analysis took place from December 2017 to April 2018. Exposures: Patients were retrospectively staged according to the seventh and eighth editions of the TNM staging system. Main Outcomes and Measures: Prognostic accuracy on survival rates, assessed by Kaplan-Meier and multivariate Cox proportional hazards analyses and concordance statistics. Results: A total of 1525 consecutive patients were included (median [IQR] age, 66 (58-72) years; 802 (52.6%) male). Distribution among stages via the seventh edition was stage IA in 41 patients (2.7%), stage IB in 42 (2.8%), stage IIA in 200 (13.1%), stage IIB in 1229 (80.6%), and stage III in 12 (0.8%); this changed with use of the eighth edition to stage IA in 118 patients (7.7%), stage IB in 144 (9.4%), stage IIA in 22 (1.4%), stage IIB in 643 (42.2%), and stage III in 598 (39.2%). With the eighth edition, 774 patients (50.8%) migrated to a different stage; 183 (12.0%) were reclassified to a lower stage and 591 (38.8%) to a higher stage. Median overall survival for the entire cohort was 24.4 months (95% CI, 23.4-26.2 months). On Kaplan-Meier analysis, 5-year survival rates changed from 38.2% for patients in stage IA, 34.7% in IB, 35.3% in IIA, 16.5% in IIB, and 0% in stage III (log-rank P < .001) via classification with the seventh edition to 39.2% for patients in stage IA, 33.9% in IB, 27.6% in IIA, 21.0% in IIB, and 10.8% in stage III (log-rank P < .001) with the eighth edition. For patients who were node negative, the T stage was not associated with prognostication of survival in either edition. In the eighth edition, the N stage was associated with 5-year survival rates of 35.6% in N0, 20.8% in N1, and 10.9% in N2 (log-rank P < .001). The C statistic improved from 0.55 (95% CI, 0.53-0.57) for the seventh edition to 0.57 (95% CI, 0.55-0.60) for the eighth edition. Conclusions and Relevance: The eighth edition of the TNM staging system demonstrated a more equal distribution among stages and a modestly increased prognostic accuracy in patients with resected pancreatic ductal adenocarcinoma compared with the seventh edition. The revised T stage remains poorly associated with survival, whereas the revised N stage is highly prognostic.

Lymphatic versus Hematogenous Melanoma Metastases: Support for Biological Heterogeneity without Clear Clinical Application.

Melanoma demonstrates considerable biological heterogeneity and is associated with several routes of dissemination including lymphatic and hematogenous. Locoregional control via surgery may improve outcomes for patients with limited lymphatic metastases. Once stage IV disease is diagnosed, clinical outcomes are determined by molecular and/or immunologic factors and identification of tumor/microenvironmental features correlating with distant metastases is critical for future prognostic stratification.

Totally Implantable Venous Access Devices: A Review of Complications and Management Strategies.

OBJECTIVE: Totally implantable venous access devices (portacaths, or "ports"), are widely used for intermittent central venous access especially for cancer patients. Although ports have a superior safety margin compared with other long-term venous access devices, there are a number of complications associated with their use. METHODS: This is a narrative review. We searched PubMed and Google Scholar for articles about complications related to the use of portacaths. "Similar articles" feature of PubMed and reference list of the existing literature were also reviewed for additional relevant studies. RESULTS: In this review, we provide the latest evidence regarding the most common ones of these adverse events and how to diagnose and treat them. Immediate complications including pneumothorax, hemothorax, arterial puncture, and air embolism as well as late complications such as port infection, malfunction, and thrombosis are covered in detail. CONCLUSIONS: Physicians should be familiar with port complications and their diagnosis and management.

National Rise of Primary Pancreatic Carcinoid Tumors: Comparison to Functional and Nonfunctional Pancreatic Neuroendocrine Tumors.

BACKGROUND: New guidelines recommend differentiating between carcinoid and pancreatic neuroendocrine tumors (PNETs) during clinical trials. However, little is known about the behavior and incidence of primary pancreatic carcinoid tumors. STUDY DESIGN: We performed a retrospective cohort study using the National Cancer Data Base (NCDB) to identify adults with primary PNETs diagnosed between 2004 and 2013. The Kaplan-Meier method was used to evaluate overall survival, and multivariate Cox proportional hazards model was used to assess the hazard of death in resected patients. RESULTS: Of 10,752 patients, 12.7% were diagnosed with carcinoid tumors, 84.7% with nonfunctional and 2.6% with functional PNETs. Although the number of functional PNETs has remained relatively constant over time, rates of nonfunctional and carcinoid tumors have risen dramatically. Only 36 (5.7%) carcinoid tumors were diagnosed in 2004; this increased to 497 (27.7%) in 2013. Overall survival was significantly longer for carcinoid compared with functional and nonfunctional tumors (log-rank p < 0.0001), with 5-year survival rates of 63.1%, 58.3%, and 52.6%, respectively. For patients having resection, overall survival further improved for carcinoid tumors relative to functional (log-rank p = 0.0011) and nonfunctional (log-rank p < 0.0001) tumors, but the survival difference between functional and nonfunctional tumors disappeared (log-rank p = 0.4579); 5-year survival rates were 89.2%, 76.6%, and 78.7%, respectively. On multivariate Cox regression of the resected cohort, mortality was significantly higher for patients with functional (hazard ratio [HR] 1.81) and nonfunctional (HR 1.40) PNETs compared with carcinoid tumors. CONCLUSIONS: Primary pancreatic carcinoid tumors are increasingly being diagnosed. Differentiating PNET subtypes plays an important role in prognostication. Resection remains a critical component of care.

Upper extremity deep venous thrombosis after port insertion: What are the risk factors?

BACKGROUND: Totally implantable venous access devices (ports) are widely used, especially for cancer chemotherapy. Although their use has been associated with upper extremity deep venous thrombosis, the risk factors of upper extremity deep venous thrombosis in patients with a port are not studied adequately. METHODS: The Healthcare Cost and Utilization Project's Florida State Ambulatory Surgery and Services Database was queried between 2007 and 2011 for patients who underwent outpatient port insertion, identified by Current Procedural Terminology code. Patients were followed in the State Ambulatory Surgery and Services Database, State Inpatient Database, and State Emergency Department Database for upper extremity deep venous thrombosis occurrence. The cohort was divided into a test cohort and a validation cohort based on the year of port placement. A multivariable logistic regression model was developed to identify risk factors for upper extremity deep venous thrombosis in patients with a port. The model then was tested on the validation cohort. RESULTS: Of the 51,049 patients in the derivation cohort, 926 (1.81%) developed an upper extremity deep venous thrombosis. On multivariate analysis, independently significant predictors of upper extremity deep venous thrombosis included age <65 years (odds ratio = 1.22), Elixhauser score of 1 to 2 compared with zero (odds ratio = 1.17), end-stage renal disease (versus no kidney disease; odds ratio = 2.63), history of any deep venous thrombosis (odds ratio = 1.77), all-cause 30-day revisit (odds ratio = 2.36), African American race (versus white; odds ratio = 1.86), and other nonwhite races (odds ratio = 1.35). Additionally, compared with genitourinary malignancies, patients with gastrointestinal (odds ratio = 1.55), metastatic (odds ratio = 1.76), and lung cancers (odds ratio = 1.68) had greater risks of developing an upper extremity deep venous thrombosis. CONCLUSION: This study identified major risk factors of upper extremity deep venous thrombosis. Further studies are needed to evaluate the appropriateness of thromboprophylaxis in patients at greater risk of upper extremity deep venous thrombosis.

Evolution and impact of lymph node dissection during pancreaticoduodenectomy for pancreatic cancer.

BACKGROUND: Insufficient examination of lymph nodes after pancreaticoduodenectomy can lead some pancreatic cancer patients with N1 disease to be misclassified as N0. We examined trends in lymph node dissection throughout time and investigated how these changes affect lymph node status and its prognostic value. METHODS: The National Cancer Data Base was queried for patients with nonmetastatic pancreatic adenocarcinoma (2004-2013) who underwent classic pancreaticoduodenectomy with antrectomy. Logistic regression was performed for odds of node positivity. Kaplan-Meier curves and Cox proportional hazards models were used to assess the impact of lymph node status on overall survival for patients diagnosed during 2-year intervals from 2004-2012. RESULTS: Median number of examined lymph nodes was 10 (interquartile range 6-15) in 2004 vs 17 (interquartile range 12-24) in 2013. Number of lymph nodes examined was a significant predictor of N1 disease (P < .0001), with a plateau at 30 nodes. N1 disease increased from 64.4% to 68.0% (P < .0001). Survival for both N1 and N0 subgroups improved. In successive multivariate models, N0 versus N1 status was consistently protective for overall survival (P < .0001), but there was no change in the magnitude of its hazard ratio over time (overall hazard ratio 0.691; 95% confidence interval 0.660-0.723). CONCLUSION: Contemporary patients have an adequate number of nodes examined during standard pancreaticoduodenectomy. This, along with rising rates of N1 cancer detection and improved survival for both node-positive and node-negative patients, suggest more accurate classification of lymph node status. However, no increased benefit is achieved beyond 30 nodes. Overall, lymph node status remains a strong prognosticator for overall survival.

Neoadjuvant therapy versus upfront surgery for resected pancreatic adenocarcinoma: A nationwide propensity score matched analysis.

BACKGROUND: Neoadjuvant therapy is an emerging paradigm in pancreatic cancer care; however, its role for resectable disease remains controversial in the absence of conclusive randomized controlled trials. The purpose of the present study is to assess the impact of neoadjuvant therapy on survival in resected pancreatic cancer patients by clinical stage. METHODS: A retrospective cohort study using the National Cancer Data Base from 2004 to 2012 including nonmetastatic pancreatic adenocarcinoma patients who underwent pancreatectomy and initiated chemotherapy. Propensity score matching within each stage was used to account for potential selection bias between patients undergoing neoadjuvant therapy and upfront surgery. Overall survival was compared by the Kaplan-Meier method. RESULTS: In the study, 1,541 and 7,159 patients received neoadjuvant therapy followed by surgery and upfront surgery succeeded by adjuvant therapy, respectively. In clinical stage III pancreatic cancer (n = 486), neoadjuvant therapy was associated with significant survival benefit after matching (median survival 22.9 vs 17.3 months; log-rank P < .0001) compared with conventional upfront surgery followed by adjuvant therapy; however, no survival difference was found between the 2 treatment sequences in patients with clinical stage I (n = 3,149; median survival, 26.2 vs 25.7 months; P = .4418) and II (n = 5,065; median survival, 23.5 vs 23.0 months; P = .7751) disease after matching. CONCLUSION: The survival impact of neoadjuvant therapy is stage-dependent. Neoadjuvant therapy does not disadvantage survival compared with conventional upfront surgery followed by adjuvant therapy in any stage, and is associated with a significant survival advantage in stage III pancreatic cancer.