CTNNB1 exon 3 mutations in metastatic solid pseudopapillary neoplasm of the pancreas.

BACKGROUND AND OBJECTIVES: Solid pseudopapillary neoplasm (SPN) of the pancreas demonstrates an indolent disease course; however, some patients present with a "malignant" phenotype, including distant metastases resistant to chemotherapy. This analysis identifies molecular drivers of metastatic SPN using the world's largest clinicogenomics database. METHODS: The American Association for Cancer Research Project Genomics Evidence Neoplasia Information Exchange was queried for primary and metastatic SPN samples. Sample-level genomic alterations were compared. A pan-pancreatic cancer analysis assessed relevant mutations among all metastatic pancreatic malignancies. RESULTS: Among 28 SPN samples identified (n = 17 primary, n = 11 metastatic), the most commonly mutated gene was CTNNB1, (24/28 samples; 85.7%). Most mutations were missense (21/24; 87.5%) or in-frame deletions (3/24; 12.5%). The most common CTNNB1 mutations in primary SPN were exon 3 S37F/C missense mutations (6/16 profiled patients, 37.5%), contrasting exon 3 D32N/Y/H missense mutations in metastatic samples (6/11 profiled patients, 54.5%). Metastatic SPN had higher rates of CTNNB1 mutations than metastases from pancreatic ductal adenocarcinoma (72.7% vs. 1.1%; q < 0.0001), pancreatic neuroendocrine tumor (72.7% vs. 2.5%; q < 0.0001), and pancreatic acinar cell carcinoma (72.7% vs. 11.5%; q = 0.0254). CONCLUSIONS: Missense mutations along exon 3 of CTNNB1 predominate metastatic SPN, differentiating these patients from those with metastases from analogous pancreatic malignancies.

Perioperative cyclooxygenase inhibition and postoperative pancreatic fistula after pancreatoduodenectomy: A systematic review and meta-analysis of comparative studies.

BACKGROUND: Nonsteroidal anti-inflammatory drug (NSAID) use has been investigated as a modifiable risk factor for postoperative pancreatic fistula (POPF) after pancreatoduodenectomy (PD). This study comprises a systematic review and meta-analysis examining the impact of perioperative NSAID use on rates of POPF after PD. METHODS: A Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020-compliant systematic review was performed. Pooled mean differences (MD), odds ratios (OR), and risk ratios with 95% CIs were calculated. RESULTS: Seven studies published from 2015 to 2021 were included, reporting 2851 PDs (1372 receiving NSAIDs and 1479 not receiving NSAIDs). There were no differences regarding blood loss (MD -99.40 mL; 95% CI, -201.71 to 2.91; P = .06), overall morbidity (OR 1.05; 95% CI, 0.68-1.61; P = .83), hemorrhage (OR 2.35; 95% CI, 0.48-11.59; P = .29), delayed gastric emptying (OR 0.98; 95% CI, 0.60-1.60; P = .93), bile leak (OR 0.68; 95% CI, 0.12-3.89; P = .66), surgical site infection (OR 1.02; 95% CI, 0.33-3.22; P = .97), abscess (OR 0.99; 95% CI, 0.51-1.91; P = .97), clinically relevant POPF (OR 1.18; 95% CI, 0.84-1.64; P = .33), readmission (OR 0.94; 95% CI, 0.61-1.46; P = .78), or reoperation (OR 0.82; 95% CI, 0.33-2.06; P = .68). NSAID use was associated with a shorter hospital stay (MD -1.05 days; 95% CI, -1.39 to 0.71; P < .00001). CONCLUSION: The use of NSAIDs in the perioperative period for patients undergoing PD was not associated with increased rates of POPF.

Malignant Solid Pseudopapillary Neoplasm of the Pancreas: An Orthogonal Analysis.

BACKGROUND: Pancreatic solid pseudopapillary neoplasms (SPN) are generally indolent; however, some patients present with "malignant" SPN. An orthogonal analysis of multiple datasets was performed to investigate the utility of complete surgical resection (CSR) for malignant SPN. METHODS: A systematic review was performed for cases of malignant SPN, defined as T4, N1, and/or M1. Malignant SPN was analyzed within the National Cancer Database (NCDB) and compared with T1-3N0M0 SPN. Predictors of malignant SPN were assessed, and treatments were analyzed by using survival analysis. RESULTS: The systematic review yielded 164 cases of malignant SPN. Of 31 children, only one died due to malignant SPN. Among adults, CSR was associated with improved disease-specific survival (DSS) (P = 0.0002). Chemotherapy did not improve malignant SPN DSS, whether resected (P = 0.8485) or not (P = 0.2219). Of 692 adults with SPN within the NCDB, 93 (13.4%) had malignant SPN. Pancreatic head location (odds ratio [OR] 2.174; 95% confidence interval [CI] 1.136-4.166; P = 0.0186) and tumor size (OR 1.154; 95% CI 1.079-1.235; P < 0.0001) associated with the malignant phenotype. Malignant SPN predicted decreased overall survival (OS) compared with T1-3N0M0 disease (P < 0.0001). Resected malignant SPN demonstrated improved OS (P < 0.0001), including resected stage IV malignant SPN (P = 0.0003). Chemotherapy did not improve OS for malignant SPN, whether resected (P = 0.8633) or not (P = 0.5734). Within a multivariable model, resection was associated with decreased hazard of death (hazard ratio 0.090; 95% CI 0.030-0.261; P < 0.0001). CONCLUSIONS: Approximately 13% of patients with SPN present with a malignant phenotype. Pediatric cases may be less aggressive. Resection may improve survival for malignant SPN, which does not appear chemosensitive.

Surgical versus non-surgical management for patients with malignant bowel obstruction (S1316): a pragmatic comparative effectiveness trial.

BACKGROUND: Malignant small bowel obstruction has a poor prognosis and is associated with multiple related symptoms. The optimal treatment approach is often unclear. We aimed to compare surgical versus non-surgical management with the aim to determine the optimal approach for managing malignant bowel obstruction. METHODS: S1316 was a pragmatic comparative effectiveness trial done within the National Cancer Trials Network at 30 hospital and cancer research centres in the USA, Mexico, Peru, and Colombia. Participants had an intra-abdominal or retroperitoneal primary cancer confirmed via pathological report and malignant bowel disease; were aged 18 years or older with a Zubrod performance status 0-2 within 1 week before admission; had a surgical indication; and treatment equipoise. Participants were randomly assigned (1:1) to surgical or non-surgical treatment using a dynamic balancing algorithm, balancing on primary tumour type. Patients who declined consent for random assignment were offered a prospective observational patient choice pathway. The primary outcome was the number of days alive and out of the hospital (good days) at 91 days. Analyses were based on intention-to-treat linear, logistic, and Cox regression models combining data from both pathways and adjusting for potential confounders. Treatment complications were assessed in all analysed patients in the study. This completed study is registered with ClinicalTrials.gov, NCT02270450. FINDINGS: From May 11, 2015, to April 27, 2020, 221 patients were enrolled (143 [65%] were female and 78 [35%] were male). There were 199 evaluable participants: 49 in the randomised pathway (24 surgery and 25 non-surgery) and 150 in the patient choice pathway (58 surgery and 92 non-surgery). No difference was seen between surgery and non-surgery for the primary outcome of good days: mean 42·6 days (SD 32·2) in the randomised surgery group, 43·9 days (29·5) in the randomised non-surgery group, 54·8 days (27·0) in the patient choice surgery group, and 52·7 days (30·7) in the patient choice non-surgery group (adjusted mean difference 2·9 additional good days in surgical versus non-surgical treatment [95% CI -5·5 to 11·3]; p=0·50). During their initial hospital stay, six participants died, five due to cancer progression (four patients from the randomised pathway, two in each treatment group, and one from the patient choice pathway, in the surgery group) and one due to malignant bowel obstruction treatment complications (patient choice pathway, non-surgery). The most common grade 3-4 malignant bowel obstruction treatment complication was anaemia (three [6%] patients in the randomised pathway, all in the surgical group, and five [3%] patients in the patient choice pathway, four in the surgical group and one in the non-surgical group). INTERPRETATION: In our study, whether patients received a surgical or non-surgical treatment approach did not influence good days during the first 91 days after registration. These findings should inform treatment decisions for patients hospitalised with malignant bowel obstruction. FUNDING: Agency for Healthcare Research and Quality and the National Cancer Institute. TRANSLATION: For the Spanish translation of the abstract see Supplementary Materials section.

Lymph node metastases in young patients with gastrointestinal stromal tumor: A nationwide analysis.

BACKGROUND: Children, adolescents, and young adults (CAYA) (age ≤39 years) with GIST have high rates of LNM, but their clinical relevance is undefined. This study analyzed the impact of LNM on overall survival (OS) for CAYA with GIST. METHODS: The National Cancer Database was queried for patients with resected GIST and pathologic nodal staging data from 2004-2019. Factors associated with LNM were identified. Survival was assessed stratified by presence of LNM. RESULTS: Of 4420 patients with GIST, 238 were CAYA (5.4%). When compared to older adults, CAYA more often had small intestine primaries (51.8% vs. 36.6%, p < 0.0001), T4 tumors (30.7% vs. 24.5%, p = 0.0275) and pN1 disease (11.3% vs. 4.7%, p < 0.0001). Within a multivariable Cox proportional hazards regression model adjusting for age, comorbid disease, mitotic rate, tumor size, and primary site, LNM were associated with increased hazard of death for older adults (hazard ratio [HR]: 1.83; confidence interval [CI]: 1.35-2.42; p < 0.0001), but not CAYA (HR: 3.38; CI: 0.50-14.08; p = 0.13). For CAYA, only high mitotic rate predicted mortality (HR: 4.68; CI: 1.41-18.37: p = 0.02). CONCLUSIONS: LNM are more commonly identified among CAYA with resected GIST who undergo lymph node evaluations, but do not appear to impact OS as observed in older adults. High mitotic rate remains a predictor of poor outcomes for CAYA with GIST.

Nationwide analysis of unplanned conversion during minimally invasive distal pancreatectomy for pancreatic adenocarcinoma.

BACKGROUND: Utilization of minimally-invasive distal pancreatectomy (MIDP) for pancreatic adenocarcinoma has increased. While unplanned conversion to an open procedure during MIDP is associated with inferior short-term outcomes, the long-term consequences of conversion have not been adequately examined. METHODS: Patients with pancreatic adenocarcinoma undergoing MIDP were selected from the National Cancer Database (2010-2015) and subdivided based on the occurrence of unplanned conversion. Post-operative outcomes and overall survival (OS) were examined. Conversion was additionally compared to a matched group of planned open resections. RESULTS: Among 592 patients undergoing attempted MIDP, unplanned conversion occurred in 23.1%. Despite increased 90-day mortality among patients experiencing conversion, there was no difference in median OS between groups (25.0 vs 27.8 months, p = 0.095). For patients undergoing conversion, post-operative outcomes and long-term survival were similar when compared to a propensity-matched group of patients undergoing planned open resection. On multivariable analysis, treatment at an academic facility (OR 0.63) and a robotic approach (OR 0.50) were both significantly associated with completed MIDP. CONCLUSION: Despite inferior post-operative outcomes compared to successful MIDP, unplanned conversion did not result in significantly reduced long term survival. MIDP can be attempted selectively but treatment at experienced centers via a robotic approach should be considered.

Pancreatic carcinosarcoma: An orthogonal analysis.

BACKGROUND: Pancreatic carcinosarcoma is a rare subtype of pancreatic cancer. There are no consensus guidelines regarding its treatment. The current study is an orthogonal analysis of multiple datasets to evaluate prognostic features. METHODS: A modified Preferred Reporting Items for Systematic reviews and Meta-Analyses 2020 systematic review was performed for reported cases of pancreatic carcinosarcoma. All cases of pancreatic carcinosarcoma in the National Cancer Database were identified for analysis. Analyses were compared to previously published data from the Surveillance, Epidemiology, and End Results database to increase validity. RESULTS: Seventy-one cases of pancreatic carcinosarcoma were reported in the literature. Reports of pancreatic carcinosarcoma increased over time (P = .0075). Tumor size >5.0 cm, metastatic disease, and relapse were associated with decreased disease-specific survival (all log-rank P < .05). Ninety-nine cases of pancreatic carcinosarcoma were analyzed within the National Cancer Database. Pancreatic carcinosarcoma incidence increased over time (P = .0371). Resection + chemotherapy, pathologic lymph node examination, and treatment at an academic center were associated with improved overall survival (all log-rank P < .05), whereas harboring ≥2 positive lymph nodes was associated with decreased overall survival (log-rank P = .0171). Within a multivariable model adjusting for age, sex, comorbid disease, and disease stage, resection + chemotherapy was associated with a decreased hazard of death (hazard ratio .036; confidence Interval .004-.298; P = .0022). Published data from the Surveillance, Epidemiology, and End Results database supported the current analysis regarding the incidence of pancreatic carcinosarcoma, resection, lymph node evaluation, and the impact of metastatic disease. CONCLUSION: Pancreatic carcinosarcoma is exceedingly rare, with a poor prognosis. Long-term survival is possible with curative resection in the absence of relapse. The number of positive lymph nodes appears to impact prognosis.

Segmental bile duct resection versus pancreatoduodenectomy for middle and distal third bile duct cancer. A systematic review and meta-analysis of comparative studies.

INTRODUCTION: Data regarding oncologic outcomes of segmental bile duct resection (SBDR) versus pancreatoduodenectomy (PD) for bile duct cancers (BDC) are conflicting. We compared SBDR and PD for BDC utilizing pooled data analysis. MATERIALS AND METHODS: A comprehensive PRISMA 2020 systematic review was performed. Studies comparing SBDR with PD for BDC were included. Pooled mean differences (MD), odds ratios (OR), and risk ratios (RR) with 95% confidence intervals (CI) were calculated. Subgroup analyses were performed. Study quality, bias, heterogeneity, and certainty were analyzed. RESULTS: Twelve studies from 2004 to 2021 were included, comprising 533 SBDR and 1,313 PD. SBDR was associated with positive proximal duct margins (OR 1.56; CI 1.11-2.18; P = .01), and distal duct margins (OR 43.25; CI 10.38-180.16; P < .01). SBDR yielded fewer lymph nodes (MD -6.93 nodes; CI -9.72-4.15; P < .01) and detected fewer nodal metastases (OR 0.72; CI 0.55-0.94; P = .01). SBDR portended less perioperative morbidity (OR 0.31; CI 0.21-0.46; P < .01), but not mortality (OR 0.52; CI 0.20-1.32; P = .17). SBDR was associated with locoregional recurrences (OR 1.88; CI 1.01-3.53; P = .02), and lymph node recurrences (OR 2.13; CI 1.42-3.2; P = .04). SBDR yielded decreased 5-year OS (OR 0.75; CI 0.65-0.85; P < .01). CONCLUSIONS: Despite decreased perioperative morbidity, SBDR appears to provide inferior oncologic control for BDC.

Cholecystoappendiceal Fistula From Appendiceal Adenocarcinoma Requiring a Right Hemicolectomy With Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy.

Bilioenteric fistulae are rare and difficult to manage complications of chronic cholecystitis. While cholecystoduodenal and cholecystocolic fistulae are more common, a cholecystoappendiceal fistula is an extremely rare finding. We report the presentation and operative management of a 59-year-old male with cholecystoappendiceal fistula and associated abscess in the gallbladder fossa. The patient was appropriately resuscitated, the abscess drained by interventional radiology, and after a complete workup, underwent a laparoscopic appendectomy and cholecystectomy. Pathology revealed moderately differentiated appendiceal adenocarcinoma requiring a right hemicolectomy with cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC). He has recovered well postoperatively with no complications. This case highlights the importance of having a very high index of suspicion for underlying malignancy when managing a fistula of any kind. To the best of our understanding, this is only the second reported case of a cholecystoappendiceal fistula.

Peritoneal metastases from primary appendiceal and colorectal carcinomas demonstrate distinct molecular identities on comprehensive tumor analysis.

BACKGROUND AND OBJECTIVES: Published data comparing peritoneal metastases from appendiceal cancers (pAC) and colorectal cancers (pCRC) remain sparse. We compared pAC and pCRC using comprehensive tumor profiling (CTP). METHODS: CTP was performed, including next-generation sequencing and analysis of copy number variation (CNV), microsatellite instability (MSI) and tumor mutational burden (TMB). RESULTS: One hundred thirty-six pAC and 348 pCRC samples underwent CTP. The cohorts' age and gender were similar. pCRC demonstrated increased pathogenic variants (PATHs) in APC (48% vs. 3%, p < 0.01), ARID1A (12% vs. 2%, p < 0.01), BRAF (12% vs. 2%, p < 0.01), FBXW7 (7% vs. 2%, p < 0.01), KRAS (52% vs. 41%, p < 0.05), PIK3CA (15% vs. 2%, p < 0.01), and TP53 (53% vs. 23%, p < 0.01), and decreased PATHs in GNAS (8% vs. 31%, p < 0.01). There was no difference in CNV, fusion rate, or MSI. Median TMB was higher in pCRC (5.8 vs. 5.0 mutations per megabase, p = 0.0007). Rates of TMB-high tumors were similar (pAC 2.1% vs. pCRC 9.0%, p = 0.1957). pCRC had significantly more TMB-high tumors at lower thresholds. CONCLUSIONS: Despite a reduced overall TMB, pAC demonstrated mutations distinct from those seen in pCRC. These may serve as discrete biomarkers for future study.

International Center-Level Variation in Utilization of Completion Lymph Node Dissection and Adjuvant Systemic Therapy for Sentinel Lymph Node-Positive Melanoma at Major Referral Centers.

OBJECTIVE: The aim of this study was to determine overall trends and center-level variation in utilization of completion lymph node dissection (CLND) and adjuvant systemic therapy for sentinel lymph node (SLN)-positive melanoma. SUMMARY BACKGROUND DATA: Based on recent clinical trials, management options for SLN-positive melanoma now include effective adjuvant systemic therapy and nodal observation instead of CLND. It is unknown how these findings have shaped practice or how these contemporaneous developments have influenced their respective utilization. METHODS: We performed an international cohort study at 21 melanoma referral centers in Australia, Europe, and the United States that treated adults with SLN-positive melanoma and negative distant staging from July 2017 to June 2019. We used generalized linear and multinomial logistic regression models with random intercepts for each center to assess center-level variation in CLND and adjuvant systemic treatment, adjusting for patient and disease-specific characteristics. RESULTS: Among 1109 patients, performance of CLND decreased from 28% to 8% and adjuvant systemic therapy use increased from 29 to 60%. For both CLND and adjuvant systemic treatment, the most influential factors were nodal tumor size, stage, and location of treating center. There was notable variation among treating centers in management of stage IIIA patients and use of CLND with adjuvant systemic therapy versus nodal observation alone for similar risk patients. CONCLUSIONS: There has been an overall decline in CLND and simultaneous adoption of adjuvant systemic therapy for patients with SLN-positive melanoma though wide variation in practice remains. Accounting for differences in patient mix, location of care contributed significantly to the observed variation.

The Impact of an Enhanced Recovery Protocol in a High-Risk Population Undergoing Colon Cancer Surgery.

OBJECTIVE: Enhanced Recovery ERP protocols (ERP) have improved surgical outcomes in patients undergoing elective colon cancer (CC) surgery; however, efficacy in different populations may vary. We examined the impact of an ERP in a population with high rates of obesity and multiple comorbidities. METHODS: We performed a retrospective analysis of factors associated with postoperative complications (PoC) and length of stay (LOS) following CC surgery from 2011 to 2019 in a 5-hospital healthcare system which serves a population with higher rates of obesity (body mass index ≥30kg/m2) and multi-comorbidities, as compared to published studies. Univariable and multivariable analyses were performed. RESULTS: A total of 408 elective CC surgery patients with complete oncologic surgical data were identified. Of these, 191 (46.81%) were under ERP. Factors independently associated with PoC included obesity (OR=1.66, P=.029), laparoscopic (OR=.52, P=.020), and hybrid (OR=.38, P=.012) versus open surgery and ASA (American Society of Anesthesiologists) class ≥3 (OR=1.98, P=.006). ERP did not impact PoC but was associated with a reduction in LOS (ß=-1.02 days, 95%CI: -1.75 - -.30, P=.006). ERP had an impact on LOS in both the non-obese and obese groups (P<.001 and P=.034, respectively). PoC significantly increased LOS (ß=6.67 days, 95%CI: 5.41-7.03, P<.001). CONCLUSIONS: Following elective CC surgery, obesity and medical comorbidities were associated with increased PoC and in turn, as expected, increased LOS. ERP was associated with a reduction in LOS in both obese and non-obese patients. In high-risk populations, application of ERP may be particularly important to optimize surgical outcomes following CC surgery.

Impact of Social Determinants of Health on Outcomes Following Resection for Hepatocellular Carcinoma.

BACKGROUND: We sought to determine the impact of social determinants of health (SDoH) on outcomes of patients undergoing resection for hepatocellular carcinoma (HCC). PATIENTS AND METHODS: Patients with HCC in the National Cancer Database who underwent resection from 2009 to 2018 were identified. SDoH associated with length of stay (LOS), 30-day readmission, and 30-day mortality were analyzed using regression analyses adjusted for confounding variables. RESULTS: Among 9235 patients, the median age (range) was 65.0 (18-90) years, 72.1% were male, and 57.9% were White. A total of 3% were uninsured, 11.1% had Medicaid, 21% resided in regions with a median household income within the lowest quartile of the US population, and 27.0% resided in regions within the lowest quartile of education level. The odds for having longer LOS were lower among patients with the highest regional education level compared with those with the lowest level [odds ratio (OR) 0.86, 95% confidence interval (CI) 0.77-0.97]. The risk of readmission was lower among patients with Medicare (OR 0.52; 95% CI 0.33-0.81), Medicaid (OR 0.52; 95% CI 0.31-0.87), or private insurance (OR 0.56; 95% CI 0.35-0.88) compared with uninsured patients. Thirty-day overall mortality was less likely among patients with Medicare (OR 0.45; 95% CI 0.27-0.75), Medicaid (OR 0.53; 95% CI 0.30-0.93), or private insurance (OR 0.40; 95% CI 0.24-0.66), and among patients with high regional income (OR 0.58; 95% CI 0.44-0.77). CONCLUSIONS: Adjusted regression analyses identified SDoH that were associated with HCC outcomes. Increased awareness of how SDoH relate to outcomes may inform strategies that attempt to account for these associations and improve patient outcomes.

Gracilis Flap Reconstruction After Proctocolectomy for Malignancy and Inflammatory Bowel Disease.

BACKGROUND: Gracilis flap reconstruction (GFR) following abdominoperineal resection (APR) or proctocolectomy (PC) can reduce pelvic wound complications but has not been adequately assessed in the setting of immunosuppression, fistulous disease, and neoadjuvant chemoradiation. METHODS: Patients undergoing APR/PC with GFR were retrospectively analyzed with regard to perioperative characteristics, and morbidity was assessed. RESULTS: Patients underwent GFR for rectal cancer (n = 28), anal cancer (n = 3), inflammatory bowel disease (n = 13), or benign fistulizing disease (n = 1). 22.2% were chronically immunosuppressed, and 66.7% underwent preoperative chemoradiation. Twenty (44.4%) patients had minor wound complications, all treated nonoperatively. Nine patients had major complications with 4 patients requiring reoperation. The 4 threatened flaps were unilateral, and all were salvaged. Donor site morbidity was minimal. Patients with major complications were older (56 vs. 71 years, P = .030), and less likely to have pelvic drains (P = .018). CONCLUSION: In high-risk perineal wounds, GFR offers durable reconstruction with acceptably low morbidity.

Lymph Node Metastases in Gastrointestinal Stromal Tumors: an Uncommon Event.

BACKGROUND: Lymph node (LN) metastases are uncommon among gastrointestinal stromal tumors (GISTs), and their presence has not been utilized in disease prognostication. This study was designed to examine factors associated with GIST nodal metastases and their impact on survival. PATIENTS AND METHODS: Patients undergoing surgical resection of GIST with nodal evaluation were selected from the National Cancer Database. Logistic regression was utilized to evaluate factors associated with LN metastases. Survival was assessed for patients with and without nodal involvement and Cox regression was used to evaluate the impact of LN metastases while adjusting for other prognostic factors. RESULTS: Out of 5018 patients, 301 (6.0%) had LN involvement. Nodal metastases occurred most frequently among tumors of the stomach (49.5%), followed by the small bowel (43.2%), colorectum (6.0%), and esophagus (1.3%). On multivariable analysis, male sex (OR 1.34), high mitotic rate (OR 2.10), tumor size (OR 1.02), and a primary tumor located in the small bowel (OR 1.36) were all significantly associated with nodal metastases. LN metastases were significantly associated with decreased overall survival (OS) for tumors arising in the small bowel (log-rank p < 0.01) and the colorectum (log-rank p < 0.01). Within a multivariable model adjusting for established prognostic factors, LN metastases remained independently associated with decreased survival (HR 1.60, p < 0.001). CONCLUSIONS: For GISTs, LN metastases occur more often in males and were associated with tumor size and mitotic activity. Nodal involvement is associated with decreased survival, independent of other well-established prognostic factors.