The role of multidetector CT scan in the management of prosthetic aortic valve thrombosis: A case report.

Key Clinical Message: In this case report, the utility of MDCT in elucidating the pathophysiology and etiology of prosthetic aortic valve dysfunction allowed us to distinguish thrombosis from pannus as an etiology of prosthetic valve dysfunction. MDCT also guided the success of therapy. Abstract: The diagnosis and management of prosthetic aortic valve thrombosis (PAVT) is challenging. The accurate diagnosis of this entity and its prompt management is vital to improving the prognosis of PAVT patients. Multidetector CT plays a central role in this effort. We present a case of PAVT in which the use of MDCT was useful in guiding management.

Subchondral Bone Length in Knee Osteoarthritis: A Deep Learning-Derived Imaging Measure and Its Association With Radiographic and Clinical Outcomes.

OBJECTIVE: To develop a bone shape measure that reflects the extent of cartilage loss and bone flattening in knee osteoarthritis (OA) and test it against estimates of disease severity. METHODS: A fast region-based convolutional neural network was trained to crop the knee joints in sagittal dual-echo steady-state magnetic resonance imaging sequences obtained from the Osteoarthritis Initiative (OAI). Publicly available annotations of the cartilage and menisci were used as references to annotate the tibia and the femur in 61 knees. Another deep neural network (U-Net) was developed to learn these annotations. Model predictions were compared to radiologist-driven annotations on an independent test set (27 knees). The U-Net was applied to automatically extract the knee joint structures on the larger OAI data set (n = 9,434 knees). We defined subchondral bone length (SBL), a novel shape measure characterizing the extent of overlying cartilage and bone flattening, and examined its relationship with radiographic joint space narrowing (JSN), concurrent pain and disability (according to the Western Ontario and McMaster Universities Osteoarthritis Index), as well as subsequent partial or total knee replacement. Odds ratios (ORs) and 95% confidence intervals (95% CIs) for each outcome were estimated using relative changes in SBL from the OAI data set stratified into quartiles. RESULTS: The mean SBL values for knees with JSN were consistently different from knees without JSN. Greater changes of SBL from baseline were associated with greater pain and disability. For knees with medial or lateral JSN, the ORs for future knee replacement between the lowest and highest quartiles corresponding to SBL changes were 5.68 (95% CI 3.90-8.27) and 7.19 (95% CI 3.71-13.95), respectively. CONCLUSION: SBL quantified OA status based on JSN severity and shows promise as an imaging marker in predicting clinical and structural OA outcomes.

Cortisol and Dehydroepiandrosterone Response to Adrenocorticotropic Hormone and Frailty in Older Women.

BACKGROUND: The response to adrenocorticotropic hormone (ACTH) is poorly characterized in old-old adults and may provide insight into the physiologic response to stress. METHOD: We performed a standard 250 µg ACTH stimulation test in a home-based substudy of 51 women aged 85-96 years enrolled in the Women's Health and Aging Study II who were not taking corticosteroids. We examined the cortisol and dehydroepiandrosterone (DHEA) responses at 0, 30, 60, and 120 minutes, overall and by frailty status. RESULTS: The peak cortisol response to ACTH could not be determined, with the highest levels at the 120-minute time point. Pre- and post-ACTH stimulated cortisol levels did not differ by frailty status over this time frame, with no difference in the characteristics of the dose-response curves. Pre- and post-ACTH stimulated DHEA levels also did not differ by frailty status, though the dose-response curves suggested divergence after stimulation, with a more rapid DHEA response with increasing frailty. CONCLUSIONS: Our data demonstrate a robust cortisol response to ACTH challenge testing, but inadequate negative feedback in old-old women, resulting in prolonged exposure to cortisol. Future studies should examine dynamic cortisol and DHEA responses in this age group, using a less potent ACTH stimulus and longer collection period.

Colon and Rectal Neuroendocrine Tumors: Are They Really One Disease? A Single-Institution Experience over 15 Years.

Colon and rectal neuroendocrine tumors (NETs) are often studied as one entity. Recent evidence suggests that worse outcomes are associated with colon compared with rectal NETs; direct comparisons are lacking. Our aim was to assess clinicopathologic, treatment, and survival differences between these diseases. All patients who underwent resection of colorectal NETs at one institution from 2000 to 2014 were included and analyzed. Of 29 patients, 12(41%) had colon and 17 (59%) had rectal NETs. Baseline demographics were similar between groups, although colon patients tended to be symptomatic at presentation (67% vs 44%, P = 0.41). Eighty-three per cent of colon patients underwent surgical resection, whereas 77 per cent of rectal patients underwent endoscopic or transanal resection (P = 0.003). Colon patients had larger (3.4 cm vs 0.7 cm, P = 0.03), higher T-stage (T3/T4: 91% vs 14%, P = 0.003), higher grade tumors (42% vs 12%, P = 0.09) with more lymph nodes (58% vs 24%, P = 0.12) and lymphovascular invasion positivity (58% vs 24%, P = 0.32). Five-year disease-specific survival was 53% versus 80 per cent for colon and rectal patients, respectively (P = 0.22). After excluding high-grade tumors, colon NETs were associated with lymphovascular invasion positivity (100% vs 17%, P = 0.05) and advanced T-stage (80% vs 8%, P = 0.01). Colon and rectal 5-year disease-specific survival was 67 versus 80 per cent (P = 0.86). Colon and rectal NETs clinically seem to be distinct entities. Colon tumors have more aggressive clinicopathologic features, which may translate to worse outcomes. These differences in tumor biology may demand distinct management and should be further studied in a multi-institutional setting.

Morbidity and Outcomes Following Axillary Lymphadenectomy for Melanoma: Weighing the Risk of Surgery in the Era of MSLT-II.

BACKGROUND: Limited data exist characterizing complications after axillary lymphadenectomy for melanoma. With high rates of complications reported after dissection for breast cancer and data suggesting that completion lymphadenectomy may have limited therapeutic benefit, this study characterized morbidity to facilitate clinical decision-making. METHODS: Using a broad definition for complications, patients who underwent axillary dissection for melanoma at a single center (from 2003 to 2015) were assessed through retrospective chart review. Patients were stratified by potential risk factors for complications; outcomes were compared. RESULTS: Two hundred fifty-four axillary dissections in 239 patients were identified. Assessed risk factors for complications included age > 55 years (n = 133, 52%), body mass index (BMI) ≥ 30 kg/m2 (n = 90, 40%), diabetes (n = 40, 16%), smoking (n = 81, 32%), extremity primary (n = 71, 28%), therapeutic lymphadenectomy (n = 105, 41%), and adjuvant radiation (n = 33, 13%). Wound complications were observed in 51 patients with 38 (15%) seromas, 3 (1%) dehiscences, and 10 (4%) hematomas. There were 5 (2%) reoperations, all for hematoma. Thirty-day readmission rate was 6% (n = 14). Importantly, lymphedema occurred in only 13 (5%) patients. Wound dehiscence occurred only in smokers (p = 0.03) and was associated with adjuvant radiation (p = 0.04). Twenty-eight (11%) patients developed frozen shoulder, which was related to smoking (p = 0.02). Lymphedema was more likely in patients after therapeutic dissection (p = 0.04). All other risk factors were not associated with increased complications. CONCLUSIONS: This analysis supports historical data that axillary dissection for melanoma is a low-risk procedure, with smoking, therapeutic lymphadenectomy, and adjuvant radiation associated with increased morbidity. Although morbidity of lymphadenectomy is often cited as a reason to alter surgical approach or even forgo intervention, this may be less of a concern for axillary dissection.

The Oncologic Impact of Postoperative Complications Following Resection of Truncal and Extremity Soft Tissue Sarcomas.

INTRODUCTION: Postoperative complications (POCs) negatively impact oncologic outcomes in some malignancies; however, little is known regarding their effect in soft tissue sarcoma (STS). The aim of this study was to determine the impact of POCs on survival after resection of truncal and extremity STS. METHODS: All patients who underwent resection for a primary truncal or extremity STS at a single academic institution from 2000 to 2015 were included and analyzed. Primary outcome was disease-specific survival (DSS). RESULTS: Among 546 STS patients, POCs occurred in 159 (29%) patients; 57% were major and 55% were surgical site infections. Patients with POCs were older (61 vs. 53 years), had more comorbidities (50 vs. 38%), longer operative time (127 vs. 93 min), higher-grade tumors (93 vs. 86%), and were more likely to receive preoperative radiation (42 vs. 33%; all p < 0.05). There was no difference in receipt of postoperative therapy between the POCs and no POCs groups (19 vs. 18%, p = 0.74). Median follow-up for survivors was 37 months, and the 5-year DSS for the entire cohort was 78%. Compared with patients without POCs, patients with POCs had a worse DSS (68% vs. 81%, p = 0.001). Predictors for decreased DSS on univariate analysis included POCs (hazard ratio [HR] 2.12, 95% confidence interval [CI] 1.37-3.28, p = 0.001), advanced age, neurovascular/bone resection, positive margin, high grade, and preoperative and postoperative therapy (all p < 0.05). POCs (HR 1.76, 95% CI 1.08-2.87, p = 0.02) remained an independent predictor for reduced DSS on multivariate analysis, along with age (HR 1.02, p = 0.046) and tumor grade (HR 7.62, p = 0.046). CONCLUSIONS: POCs following resection of truncal and extremity STS are associated with decreased DSS. Efforts to optimize modifiable risk factors and decrease the rate of POCs warrant further investigation.

Pathologic and Prognostic Implications of Incidental versus Nonincidental Gallbladder Cancer: A 10-Institution Study from the United States Extrahepatic Biliary Malignancy Consortium.

Most gallbladder cancers (GBCs) are discovered incidentally after routine cholecystectomy. The influence of timing of diagnosis on disease stage, treatment, and prognosis is not known. Patients with GBC who underwent resection at 10 institutions from 2000 to 2015 were included. Patients diagnosed incidentally (IGBC) and nonincidentally (non-IGBC) were compared. Primary outcome was overall survival (OS). Of 445 patients with GBC, 266 (60%) were IGBC and 179 (40%) were non-IGBC. Compared with IGBC, non-IGBC patients were more likely to have R2 resections (43% vs 19%; P < 0.001), advanced T-stage (T3/T4: 70% vs 40%; P < 0.001), high-grade tumors (50% vs 31%; P < 0.001), lymphovascular invasion (64% vs 45%; P = 0.01), and positive lymph nodes (60% vs 43%; P = 0.009). Receipt of adjuvant chemotherapy was similar between groups (49% vs 49%). Non-IGBC was associated with worse median OS compared with IGBC (17 vs 32 months; P < 0.001), which persisted among stage III patients (12 vs 29 months; P < 0.001), but not stages I, II, or IV. Despite accounting for other adverse pathologic factors (grade, T-stage, lymphovascular invasion, margin, lymph node), adjuvant chemotherapy was associated with improved OS only in stage III IGBC, but not in non-IGBC. Compared with incidental discovery, non-IGBC is associated with reduced OS, which is most evident in stage III disease. Despite being well matched for other adverse pathologic factors, adjuvant chemotherapy was associated with improved survival only in stage III patients with incidentally discovered cancer. This underscores the importance of timing of diagnosis in GBC and suggests that these two groups may represent a distinct biology of disease, and the same treatment paradigm may not be appropriate.

Routine port-site excision in incidentally discovered gallbladder cancer is not associated with improved survival: A multi-institution analysis from the US Extrahepatic Biliary Malignancy Consortium.

BACKGROUND: Current data on the utility of port-site excision (PSE) during re-resection for incidentally discovered gallbladder cancer (IGBC) in the US are conflicting and limited to single-institution series. METHODS: All patients with IGBC who underwent curative re-resection at 10 institutions from 2000 to 2015 were included. Patients with and without PSE were compared. Primary outcome was overall survival (OS). RESULTS: Of 449 pts with GBC, 266 were incidentally discovered, of which 193(73%) underwent curative re-resection and had port-site data; 47 pts(24%) underwent PSE, 146(76%) did not. The PSE rate remained similar over time (2000-2004: 33%; 2005-2009: 22%; 2010-2015:22%; P = 0.36). Both groups had similar demographics, operative procedures, and post-operative complications. There was no difference in T-stage (T1: 9 vs. 11%; T2: 52 vs. 52%; T3: 39 vs. 38%; P = 0.96) or LN involvement (36 vs. 41%; P = 0.7) between groups. A 3-year OS was similar between PSE and no PSE groups (65 vs. 43%; P = 0.07). On univariable analysis, residual disease at re-resection (HR = 2.1, 95% CI 1.4-3.3; P = 0.001), high tumor grade, and advanced T-stage were associated with decreased OS. Only grade and T-stage, but not PSE, persisted on multivariable analysis. Distant disease recurrence-rate was identical between PSE and no PSE groups (80 vs. 81%; P = 1.0). CONCLUSION: Port-site excision during re-resection for IGBC is not associated with improved overall survival and has the same distant disease recurrence compared to no port-site excision. Routine port-site excision is not recommended.

Association of Optimal Time Interval to Re-resection for Incidental Gallbladder Cancer With Overall Survival: A Multi-Institution Analysis From the US Extrahepatic Biliary Malignancy Consortium.

Importance: The current recommendation is to perform re-resection for select patients with incidentally discovered gallbladder cancer. The optimal time interval for re-resection for both patient selection and long-term survival is not known. Objective: To assess the association of time interval from the initial cholecystectomy to reoperation with overall survival. Design, Setting, and Participants: This cohort study was conducted from January 1, 2000, to December 31, 2014 at 10 US academic institutions. A total of 207 patients with incidentally discovered gallbladder cancer who underwent reoperation and had available data on the date of their initial cholecystectomy were included. Exposures: Time interval from the initial cholecystectomy to reoperation: group A: less than 4 weeks; group B: 4 to 8 weeks; and group C: greater than 8 weeks. Main Outcomes and Measures: Primary outcome was overall survival. Results: Of 449 patients with gallbladder cancer, 207 cases (46%) were discovered incidentally and underwent reoperation at 3 different time intervals from the date of the original cholecystectomy: group A: less than 4 weeks (25 patients, 12%); B: 4 to 8 weeks (91 patients, 44%); C: more than 8 weeks (91 patients, 44%). The mean (SD) ages of patients in groups A, B, and C were 65 (9), 64 (11), and 66 (12) years, respectively. All groups were similar for baseline demographics, extent of resection, presence of residual disease, T stage, resection margin status, lymph node involvement, and postoperative complications. Patients who underwent reoperation between 4 and 8 weeks had the longest median overall survival (group B: 40.4 months) compared with those who underwent early (group A: 17.4 months) or late (group C: 22.4 months) reoperation (log-rank P = .03). Group A and C time intervals (vs group B), presence of residual disease, an R2 resection, advanced T stage, and lymph node involvement were associated with decreased overall survival on univariable Cox regression. Only group A (hazard ratio, 2.63; 95% CI, 1.25-5.54) and group C (hazard ratio, 2.07; 95% CI, 1.17-3.66) time intervals (vs group B), R2 resection (hazard ratio, 2.69; 95% CI, 1.27-5.69), and advanced Tstage (hazard ratio, 1.85; 95% CI, 1.11-3.08) persisted on multivariable Cox regression analysis. Conclusions and Relevance: The optimal time interval for re-resection for incidentally discovered gallbladder cancer appears to be between 4 and 8 weeks after the initial cholecystectomy.

A Novel Pathology-Based Preoperative Risk Score to Predict Locoregional Residual and Distant Disease and Survival for Incidental Gallbladder Cancer: A 10-Institution Study from the U.S. Extrahepatic Biliary Malignancy Consortium.

BACKGROUND: This study was designed to develop a more robust predictive model, beyond T-stage alone, for incidental gallbladder cancer (IGBC) for discovering locoregional residual (LRD) and distant disease (DD) at reoperation, and estimating overall survival (OS). T-stage alone is currently used to guide treatment for incidental gallbladder cancer. Residual disease at re-resection is the most important factor in predicting outcomes. METHODS: All patients with IGBC who underwent reoperation at 10 institutions from 2000 to 2015 were included. Routine pathology data from initial cholecystectomy was utilized to create the gallbladder cancer predictive risk score (GBRS). RESULTS: Of 449 patients with gallbladder cancer, 262 (58 %) were incidentally discovered and underwent reoperation. Advanced T-stage, grade, and presence of lymphovascular (LVI) and perineural (PNI) invasion were all associated with increased rates of DD and LRD and decreased OS. Each pathologic characteristic was assigned a value (T1a: 0, T1b: 1, T2: 2, T3/4: 3; well-diff: 1, mod-diff: 2, poor-diff: 3; LVI-neg: 1, LVI-pos: 2; PNI-neg: 1, PNI-pos: 2), which added to a total GBRS score from 3 to 10. The scores were separated into three risk-groups (low: 3-4, intermediate: 5-7, high: 8-10). Each progressive GBRS group was associated with an increased incidence LRD and DD at the time of re-resection and reduced OS. CONCLUSIONS: By accounting for subtle pathologic variations within each T-stage, this novel predictive risk-score better stratifies patients with incidentally discovered gallbladder cancer. Compared with T-stage alone, it more accurately identifies patients at risk for locoregional-residual and distant disease and predicts long-term survival as it redistributes T1b, T2, and T3 disease across separate risk-groups based on additional biologic features. This score may help to optimize treatment strategy for patients with incidentally discovered gallbladder cancer.

Vitamin Variation in Capsicum Spp. Provides Opportunities to Improve Nutritional Value of Human Diets.

Chile peppers, native to the Americas, have spread around the world and have been integrated into the diets of many cultures. Much like their heat content, nutritional content can vary dramatically between different pepper types. In this study, a diverse set of chile pepper types were examined for nutrient content. Some pepper types were found to have high levels of vitamin A, vitamin C, or folate. Correlations between nutrient content, species, cultivation status, or geographic region were limited. Varietal selection or plant breeding offer tools to augment nutrient content in peppers. Integration of nutrient rich pepper types into diets that already include peppers could help combat nutrient deficiencies by providing a significant portion of recommended daily nutrients.

Proposal for a new T-stage classification system for distal cholangiocarcinoma: a 10-institution study from the U.S. Extrahepatic Biliary Malignancy Consortium.

BACKGROUND: Seventh AJCC distal cholangiocarcinoma T-stage classification inadequately separates patients by survival. This retrospective study aimed to define a novel T-stage system to better stratify patients after resection. METHODS: Curative-intent pancreaticoduodenectomies for distal cholangiocarcinoma (1/2000-5/2015) at 10 US institutions were included. Relationships between tumor characteristics and overall survival (OS) were assessed and incorporated into a novel T-stage classification. RESULTS: 176 patients (median follow-up: 24mo) were included. Current AJCC T-stage was not associated with OS (T1: 23mo, T2: 20mo, T3: 25mo, T4: 12mo; p = 0.355). Tumor size ≥3 cm and presence of lymphovascular invasion (LVI) were associated with decreased OS on univariate and multivariable analyses. Patients were stratified into 3 groups [T1: size <3 cm and (-)LVI (n = 69; 39.2%); T2: size ≥3 cm and (-)LVI or size <3 cm and (+)LVI (n = 82; 46.6%); and T3: size ≥3 cm and (+)LVI (n = 25; 14.2%)]. Each progressive proposed T-stage was associated with decreased median OS (T1: 35mo; T2: 20mo; T3: 8mo; p = 0.002). CONCLUSION: Current AJCC distal cholangiocarcinoma T-stage does not adequately stratify patients by survival. This proposed T-stage classification, based on tumor size and LVI, better differentiates patient outcomes after resection and could be considered for incorporation into the next AJCC distal cholangiocarcinoma staging system.

Is there an Optimal Surgical Approach to Neuroendocrine Tumors of the Ampulla? A Single Institution Experience Over 15 Years.

Neuroendocrine tumors (NETs) of the ampulla of Vater are rare neoplasms accounting for a small fraction of gastroenteropancreatic NETs. The optimal surgical approach remains controversial. This study aimed to define the optimal approach in patients with ampullary NETs. Patients who underwent resection of ampullary NETs from 2000 to 2014 were analyzed. Fourteen patients with well-differentiated, nonfunctional NETs were identified. The mean age was 60 ± 15 years, and nine (64%) were male. The mean tumor size was 1.6 ± 0.9 cm and the majority (61%) had an advanced tumor-node-metastasis stage. Eight (57%) patients underwent pancreaticoduodenectomy (PD) and six (43%) underwent transduodenal ampullectomy (TA). Although the mean tumor size was similar (1.7 vs 1.5 cm), the majority (75 vs 20%) of PD patients demonstrated a trend toward more aggressive tumors, characterized by advance T stage in 25 vs 0 per cent, lymph node positivity in 88 vs 17 per cent, and elevated proliferative index (Ki-67) in 25 vs 0 per cent. Complete resection (R0) was achieved in all PD patients versus 75 per cent in TA patients. There was no difference in major complication rate (50 vs 33%). In the TA group, one (17%) patient recurred and two (33%) patients died, whereas only one (13%) patient died in the PD group and no patients recurred. In conclusion, ampullary tumors can be aggressive tumors characterized by high regional lymph node involvement. A transduodenal approach may provide an inadequate oncological resection and thus has the potential to understage ampullary NETs. In the era of increasing therapeutic options for gastroenteropancreatic NETs, accurate staging is crucial and appropriate oncologic resection via PD for ampullary NETs should be considered.

A 15-year experience with gastric neuroendocrine tumors: Does type make a difference?

BACKGROUND: Gastric neuroendocrine tumors (GNETs) are rare and classified into three types by disease etiology and typical behavior. METHODS: The aim was to describe outcomes after GNET resection at a single institution from 2000 to 2014, stratified by tumor type. Given the small patient number, P-values were not assigned. RESULTS: Of 22 patients, 12 patients (55%) had Type 1, none (0%) had Type 2, and 10 (45%) had Type 3 tumors. Compared to Type 3, Type 1 patients were younger (mean age: 52 vs. 59 years) with similar rates of endoscopic resection (25% vs. 20%). Type 1 GNETs often had multiple tumors (60% vs. 10%) and were not poorly differentiated (0% vs. 11%). Only 33% of Type 1 had nodal metastases compared to 71% of Type 3. Type 1 GNETs presented with metastatic disease less often (17% vs. 40%). Three year recurrence-free survival was 33% for Type 1 compared to 86% for Type 3. Disease-specific survival at 3-years was 100% and 75% for Types 1 and 3, respectively. CONCLUSION: Type 1 GNETs are often indolent and multifocal without nodal involvement, but have high recurrence risk. Type 3 is more aggressive with increased nodal involvement; nodal evaluation should be routinely performed. Determination of GNET type is paramount to treating patients with this rare disease. J. Surg. Oncol. 2016;114:576-580. © 2016 Wiley Periodicals, Inc.

Pancreatic neuroendocrine tumors: Preoperative factors that predict lymph node metastases to guide operative strategy.

BACKGROUND: Enucleation and anatomic resection (central, distal, or pancreaticoduodenectomy) are surgical options for pancreatic neuroendocrine tumors. Depending on nodal-status, enucleation alone may not be oncologically appropriate. Preoperative factors predictive of nodal-involvement are not well defined. METHODS: Patients who underwent curative-intent enucleation or resection of non-metastatic, well/moderately differentiated tumors at a single institution (2000-2014) were included. The aim was to determine factors associated with nodal-metastases and recurrence-free survival. RESULTS: Of 195 patients undergoing resection, 164 met inclusion-criteria. Lymphadenectomy was performed in 131 (80%), and 32 (24%) had nodal-metastases. Receiver-operative-characteristics analysis revealed tumor size ≥2 cm was associated with nodal-involvement (AUC: 0.689; Sensitivity: 90%; Specificity: 53%). On multivariable analysis, male gender (OR: 3.16; 95%CI: 1.18-8.46; P = 0.02), head/uncinate location (HR: 5.37; 95%CI: 2.07-13.96; P = 0.001), and size ≥2 cm (HR: 6.52; 95%CI: 1.75-24.30; P = 0.005) were associated with nodal-positivity. Nodal-metastases (HR: 3.04; 95%CI: 1.04-8.91; P = 0.043) and advanced T-stage (HR: 5.39; 95%CI: 1.46-19.95; P = 0.012) were independently associated with decreased recurrence-free survival. Enucleation (n = 17; 10%) had more positive margins and similar complication rates, pancreatic fistula rates, and lengths of stay as anatomic resections. CONCLUSION: For pancreatic neuroendocrine tumors, male gender, head/uncinate location, and size ≥2 cm are associated with nodal-metastases. Nodal involvement is associated with decreased recurrence-free survival. Anatomic resection may be preferred in patients with these characteristics, as enucleation alone may under-stage patients and does not appear to be associated with an improved complication profile. J. Surg. Oncol. 2016;114:440-445. © 2016 Wiley Periodicals, Inc.

Symptomatic presentation as a predictor of recurrence in gastroenteropancreatic neuroendocrine tumors: A single institution experience over 15 years.

BACKGROUND AND OBJECTIVES: The prognostic implication of symptomatic presentation of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) remains unclear. METHODS: Patients who underwent resection of nonfunctional GEP-NETs (2000-2014) were analyzed. Primary outcomes were overall survival (OS) and distant recurrence-free survival (RFS). RESULTS: Symptomatic presentation was seen in 208 (61%) of 339 patients and was associated with younger age (55 vs. 59 yrs, P = 0.001), higher tumor grade (38% vs. 21%, P = 0.027), presence of lymphovascular invasion (58% vs. 33%, P < 0.001), presence of perineural invasion (54% vs. 29%, P = 0.002), and advanced disease (T3/T4/N1/M1 [63% vs. 44%, P = 0.002]), but not tumor size (2.6 vs. 2.5 cm, P = 0.74). Symptomatic presentation was associated with decreased 3-yr distant-RFS (80% vs. 89%, P = 0.012), but not OS. When accounting for adverse features, symptomatic presentation remained independently associated with reduced distant-RFS (HR 3.51, P = 0.007). On subgroup-analysis of advanced disease patients, symptomatology was associated with reduced 3-yr distant-RFS (67% vs. 79%, P = 0.012) and persisted as an independent risk-factor for decreased distant-RFS (HR 3.01, P = 0.027). CONCLUSIONS: Symptomatic presentation of GEP-NETs is associated with aggressive features and worse distant-RFS. Trials assessing adjuvant therapy for advanced GEP-NETs are needed, and symptomatic presentation may be considered as one inclusion criterion. Following resection, symptomatic presentation should be taken into account when planning surveillance. J. Surg. Oncol. 2016;114:163-169. © 2016 Wiley Periodicals, Inc.