Small Bowel Neuroendocrine Tumors Research Articles

The Role of Endoscopy in Small Bowel Neuroendocrine Tumors.

Small bowel neuroendocrine tumors (NETs) represent approximately one-third of NETs of the gastrointestinal tract, and their incidence is increasing. When determining if endoscopic resection is appropriate, endoscopic ultrasound is used to assess the lesion size and depth of invasion for duodenal NETs. A number of techniques, including endoscopic mucosal resection (EMR), band-assisted EMR (band-EMR), endoscopic submucosal dissection (ESD), and over-the-scope clip-assisted endoscopic full-thickness resection (EFTR), have been studied; however, the best technique for endoscopic resection remains unclear. The vast majority of currently available data are retrospective, and prospective studies with longer follow-up times are required. For jejunal and ileal NETs, endoscopic techniques such as video capsule endoscopy (VCE) and balloon enteroscopy (BE) assist in diagnosis. This includes localization of the primary NET in metastatic disease where initial workup has been negative, and the identification of multifocal disease, which may change management and prognostication.

Recurrence Patterns After Surgical Resection of Gastroenteropancreatic Neuroendocrine Tumors: Analysis From the National Comprehensive Cancer Network Oncology Outcomes Database.

Current National Comprehensive Cancer Network guidelines for gastroenteropancreatic neuroendocrine tumors (GEPNETs) recommend complete (R0) surgical resection of the primary tumor and metastases, if feasible. However, large multicenter studies of recurrence patterns of GEPNETs after resection have not been performed. Patients 18 years or older who presented to 7 participating National Comprehensive Cancer Network institutions between 2004 and 2008 with a new diagnosis of a small bowel, pancreas, or colon/rectum neuroendocrine tumor (NET) and underwent R0 resection of the primary tumor, and synchronous metastases, if present, were included in this analysis. Descriptive statistics and Kaplan-Meier estimates were used to calculate recurrence rates and time-associated end points, respectively. Of 294 patients with GEPNETs, 50% were male, 88% were White, and 99% had Eastern Cooperative Oncology Group performance status 0 to 1. The median age was 55 years (range, 20-90). The median follow-up time from R0 resection was 62.1 months. Recurrence rates were 18% in small bowel NETs (n = 110), 26% in pancreatic NETs (n = 141), and 10% in colon/rectum NETs (n = 50). The frequency of surveillance imaging was highly variable. R0 resection was associated with variable risk of recurrence across subtypes. Further research to inform refinement of guidelines for the appropriate duration of surveillance after R0 resection is needed.

A Rare Case of Rectal Adenocarcinoma and Small-Bowel Neuroendocrine Tumor in a Young Patient with Long-Standing Crohn's Disease

Background: The association of adenocarcinoma of the colon and neuroendocrine tumor (NET) of the small bowel has been previously described in Crohn's disease (CD), however the concomitance of both neoplasms is extremely rare. Here, the author reports a rare case of both rectal adenocarcinoma and small-bowel NET in a young male with long-standing CD. Case Report: The patient presented with clinical and radiological features of intestinal obstruction 2 years posttotal colectomy and end ileostomy for rectal cancer and found to have ileal NET. Conclusion: Small-bowel NET symptoms can mimic CD and is a rare entity, but physicians should suspect NETs in CD patients presenting with intestinal obstruction.

Evaluating Nationwide Application of Minimally Invasive Surgery for Treatment of Small Bowel Neuroendocrine Neoplasms

AimOpen resection of small bowel neuroendocrine neoplasms (SB-NEN) is still considered standard-of-care, mainly because of frequently encountered multifocality and central mesenteric masses. The aim of this study was to evaluate surgical approach for SB-NEN at a national level and determine predictors for overall survival.MethodsPatients with SB-NEN who underwent resection between 2005 and 2015 were included from the Netherlands Cancer Registry. Patient and tumor characteristics were compared between laparoscopic and open approach. Overall survival was assessed by Kaplan–Meier and compared with the Log-rank test. Independent predictors were determined by Cox proportional hazards model.ResultsIn total, 482 patients were included, of whom 342 (71%) underwent open and 140 (29%) laparoscopic resection. The open resection group had significantly more multifocal tumors resected (24% vs. 14%), pN2 lymph nodes (18% vs. 7%) and stage IV disease (36% vs. 22%). Overall survival after open resection was significantly shorter compared to laparoscopic resection (3-year: 81% vs. 89%, 5-year: 71% vs. 84%, p = 0.004). In multivariable analysis, age above 60-years (60–75, HR 3.38 (95% CI 1.84–6.23); > 75 years, HR 7.63 (95% CI 3.86–15.07)), stage IV disease (HR 1.86 (95% CI 1.18–2.94)) and a laparoscopic approach (HR 0.51 (95% CI 0.28–0.94)) were independently associated with overall survival, whereas multifocal primary tumor, grade and resection margin status were not.ConclusionLaparoscopic resection was the approach in 29% of SB-NEN at a national level with selection of the more favorable patients. Laparoscopic resection remained independently associated with better overall survival besides age and stage, but residual confounding cannot be excluded.

Evaluation of the prognosis for N2 status in patients with small bowel neuroendocrine tumors

BackgroundThe 8th edition AJCC Staging for small bowel neuroendocrine tumors created a novel N2 classification. This study investigates if it is independently prognostic. MethodsRecords of patients from 2008 to 2019 were reviewed. Survival rates were estimated by Kaplan-Meier method and compared by log-rank. The Cox Proportional Hazards model was used to determine factors associated with overall survival (OS) via multivariate analysis. ResultsAmong 300 patients, 225 were N2 and 60 were N1. No differences were seen in pathologic markers for N1 compared to N2. N2 were more likely to have liver metastases (LM) (p = 0.048) but rates of resectability were similar. Median OS for N1 with >70% liver cytoreduction was not yet reached compared to 121 months for N2 (p = 0.005). On multivariate analysis, LM was associated with shorter survival (p = 0.028), but nodal status was not. ConclusionsUnlike LM, N2 status is not independently prognostic, but a marker for aggressive LM.

Laboratory, Clinical, and Survival Outcomes Associated With Peptide Receptor Radionuclide Therapy in Patients With Gastroenteropancreatic Neuroendocrine Tumors

Peptide receptor radionuclide therapy (PRRT) is approved in the US for treatment of gastroenteropancreatic neuroendocrine tumors (NETs), but data on PRRT outcomes within US populations remain scarce. To analyze the first 2 years of PRRT implementation at a US-based NET referral center. This cohort study was conducted using medical records of patients with metastatic NET receiving PRRT from 2018 through 2020 in a NET program at a tertiary referral center. Included patients were those at the center with metastatic NETs who received at least 1 dose of PRRT over the study period. Laboratory toxic effects were assessed using Common Terminology Criteria for Adverse Events version 5.0. Tumor response was determined using Response Evaluation Criteria in Solid Tumors 1.1. Survival analysis was conducted to identify factors associated with progression-free survival (PFS) and overall survival. Data were analyzed from August 2018 through August 2020. Receiving 4 cycles of lutetium-177-dotatate infusion, separated by 8-week intervals targeted to 7.4 GBq (200 mCi) per dose. Data were compared from before and after PRRT to determine hematologic, liver, and kidney toxic effects and to assess tumor progression and patient survival. Among 78 patients receiving at least 1 dose of PRRT, median (interquartile range) age at PRRT initiation was 59.8 (53.5-69.2) years and 39 (50.0%) were men. The most common primary NET sites included small bowel, occurring in 34 patients (43.6%), and pancreas, occurring in 22 patients (28.2%). World Health Organization grade 1 or 2 tumors occurred in 62 patients (79.5%). Among all patients, 56 patients underwent pretreatment with tumor resection (71.8%), 49 patients received nonsomatostatin analogue systemic therapy (62.8%), and 49 patients received liver-directed therapy (62.8%). At least 1 grade 2 or greater toxic effect was found in 47 patients (60.3%). Median PFS was 21.6 months for the study group, was not reached by 22 months for patients with small bowel primary tumors, and was 13.3 months for patients with pancreatic primary tumors. Having a small bowel primary tumor was associated with a lower rate of progression compared with having a pancreatic primary tumor (hazard ratio, 0.19; 95% CI, 0.07-0.55; P = .01). Median overall survival was not reached. This cohort study of patients with metastatic NETs found that PRRT was associated with laboratory-measured toxic effects during treatment for most patients and an overall median PFS of 21.6 months. Patients with small bowel NETs had longer PFS after PRRT compared with patients with pancreatic NETs.

Tumour grade and primary site predict patterns of recurrence and survival in patients with resected gastroenteropancreatic neuroendocrine tumors

BackgroundPatterns of recurrence help to inform surveillance of patients with resected gastroenteropancreatic neuroendocrine tumors (GEP-NETs). MethodsPatients with GEP-NETs in British Columbia, Canada (2004–2015) were reviewed. Associations between tumor characteristics, recurrence and survival were analyzed. ResultsAmong 759 patients, 41%, 25%, and 17% had grade 1, 2, and 3 disease, respectively. 387 patients had R0/R1 resections, of which 30% recurred (median 25 months). 5-year incidence of recurrence was 22% (grade 1), 46% (grade 2), and 59% (grade 3) (p < 0.001). Grade predicted distant recurrence (Grade 2 HR 1.89, 95% CI 1.16–3.07; p = 0.011; Grade 3 HR 3.29, 95% CI 1.81–5.99; p < 0.001). Compared to small bowel NETs, pancreas NETs had less peritoneal recurrence (OR 0.15, 95% CI 0.03–0.68, p = 0.014). No patients had isolated pulmonary recurrences. ConclusionHigher grade tumors and pancreatic NETs require more frequent surveillance. Evidence is limited for pulmonary surveillance.

Small bowel radiology.

Recent advances in computed tomography (CT), ultrasound (US), magnetic resonance imaging (MRI), and nuclear radiology have improved the diagnosis and characterization of small bowel pathology. Our purpose is to highlight the current status and recent advances in multimodality noninvasive imaging of the small bowel. CT and MR enterography are established techniques for small bowel evaluation. Dual-energy CT is a novel technique that has shown promise for the mesenteric ischemia and small bowel bleeding. Advanced US techniques and MRI sequences are being investigated to improve assessment of bowel inflammation, treatment response assessment, motility, and mural fibrosis. Novel radiotracers and scanner technologies have made molecular imaging the new reference standard for small bowel neuroendocrine tumors. Computational image analysis and artificial intelligence (AI) have the potential to augment physician expertise, reduce errors and variability in assessment of the small bowel on imaging. Advances in translational imaging research coupled with progress in imaging technology have led to a wider adoption of cross-sectional imaging for the evaluation and management of small bowel entities. Ongoing developments in image acquisition and postprocessing techniques, molecular imaging and AI have the strongest potential to transform the care and outcomes of patients with small bowel diseases.

Advanced small-bowel well-differentiated neuroendocrine tumours: An international survey of practice on 3rd-line treatment.

BACKGROUNDSomatostatin analogues are an established first-line therapy for well differentiated small bowel neuroendocrine tumours (Wd-SBNETs), while and peptide receptor radionuclide therapy (PRRT) is frequently used as a second-line therapy. Adequate treatment selection of third-line treatment remains challenging due to the limited prospective data currently available on the best therapeutic sequence. AIMTo understand current practice and rationale for decision-making by physicians in the 3rd-line setting by building an online survey. METHODSWeighted average (WA) of likelihood of usage between responders (1 very unlikely; 4 very likely) was used to reflect the relevance of factors explored.RESULTSReplies from representatives of 28 centers were received (5/8/2020-21/9/2020); medical oncologist (53.6%), gastroenterologist (17.9%); United Kingdom (21.4%), Spain (17.9%), Italy (14.3%). Majority from European Neuroendocrine Tumor Society (ENETS) Centres of Excellence (57.1%), who followed ENETS guidelines (82.1%). Generally speaking, 3rd-line treatment for Wd-SBNETs was: everolimus (EVE) (66.7%), PRRT (18.5%), liver embolization (LE) (7.4%) and interferon-alpha (IFN) (3.7%); chemotherapy (0%); decision was based on clinical trial data (59.3%), or personal experience (22.2%). EVE was most likely used if Ki-67 < 10% (WA 3.27/4) or age < 70 years (WA 3.23/4), in the 3rd-line setting (WA 3.23/4); regardless of presence/absence of carcinoid syndrome (CS), rate of progression or extent of disease. Chemotherapy was mainly utilised only if rapid progression (within 6 mo) (WA 3.35/4), Ki-67 10%-20% (WA 2.77/4), negative somatostatin receptor imaging (WA 2.65/4) or high tumour burden (WA 2.77/4); temozolomide or streptozocin was used with capecitabine or 5-fluorouracil (5-FU) (57.7%), FOLFOX (5-FU combined with oxaliplatin) (23.1%). LE was selected if presence of CS (WA 3.24/4) or Ki-67 < 10% (WA 2.8/4), after progression to other treatments (WA 2.8/4). IFN was rarely used (WA 1.3/4).CONCLUSIONEverolimus was the most frequently used therapeutic option in the third-line setting. The most important factors for decision-making included Ki-67, rate of progression, functionality and tumour burden; since this decision is based on multiple factors, it highlights the need for a multidisciplinary assessment.

Clinical Features, Management, and Molecular Characteristics of Familial Small Bowel Neuroendocrine Tumors.

Small bowel neuroendocrine tumors are rare tumors with an increasing incidence over the last several decades. Early detection remains challenging because patients commonly develop symptoms late in the disease course, often after the tumors have metastasized. Although these tumors were thought to arise from sporadic genetic mutations, large epidemiological studies strongly support genetic predisposition and increased risk of disease in affected families. Recent studies of familial small bowel neuroendocrine tumors have identified several novel genetic mutations. Screening for familial small bowel neuroendocrine tumors can lead to earlier diagnosis and improved patient outcomes. This review aims to summarize the current knowledge of molecular changes seen in familial small bowel neuroendocrine tumors, identify clinical features specific to familial disease, and provide strategies for screening and treatment.

ASO Author Reflections: Indolent Growth and Small Bowel Neuroendocrine Tumor Management.

Surgical treatment is central to management of small bowel neuroendocrine tumors (SBNETs). Current controversies include whether to resect asymptomatic primary tumors in the setting of unresectable metastases, the role of minimally invasive surgery, and how best to incorporate/sequence medical treatments. Low SBNET incidence, long event-times, and variability in disease burden, surgical technique, and institutional treatment preferences remain obstacles to conducting randomized surgical trials for SBNETs. With increasing referral of these patients to high-volume centers, cooperation between experienced SBNET clinicians should allow design of high-quality randomized trials to test new treatments and answer key questions.

Desmoplastic mesenteric lesions do not respond radiographically to peptide receptor radionuclide therapy.

177 Lu-Dotatate treatment is indicated for progressive, well-differentiated, small bowel neuroendocrine tumours) NETs. These tumours often metastasise to mesenteric lymph nodes and produce a desmoplastic reaction, consisting of tumour cells interspersed with fibrotic tissue. We hypothesised that, in patients treated with 177 Lu-Dotatate, mesenteric tumours would remain stable even as liver tumour size changes were observed. We retrospectively reviewed the records of all patients treated with 177 Lu-Dotatate between April 2018 and December 2019. Among patients with desmoplastic mesenteric tumours and liver metastases, we evaluated changes in tumour size of mesenteric and liver lesions based on pre- and post-treatment anatomic scans. As a result of the infrequency of objective radiographic response, any reported changes in tumour size were considered significant. Twenty-one patients met the inclusion criteria: nine had evidence of shrinkage of liver lesion(s), one had mild progression of liver lesions, seven had stable hepatic disease and four had a mixed hepatic response. Two of the patients with hepatic tumour shrinkage met the criteria for a partial response via RECIST 1.1 (https://recist.eortc.org). Desmoplastic mesenteric lesions remained unchanged in size, regardless of the changes detected in liver lesions. In conclusion, 177 Lu-Dotatate does not impact desmoplastic mesenteric tumours which are typically associated with midgut NETs. Patients whose disease is predominantly confined to desmoplastic mesenteric lesions are unlikely to respond radiographically to peptide receptor radionuclide therapy. Moreover, the inclusion of desmoplastic mesenteric lesions as target lesions in RECIST measurements tends to increase rates of disease stability vs response or progression.

Radiographic response of desmoplastic mesenteric lesions to peptide receptor radionuclide therapy (PRRT).

362 Background: 177Lu-dotatate PRRT is indicated in well-differentiated, SSTR+ small bowel NETs. These tumors often metastasize to mesenteric lymph nodes and produce a desmoplastic reaction, consisting of tumor cells mixed with fibrotic tissue. We hypothesized that in patients treated with 177Lu-dotatate, mesenteric tumors would remain stable even as liver tumor size changes were observed. Methods: We retrospectively reviewed the records of all patients treated with 177Lu-dotatate between 4/2018 and 12/2019. Among patients with desmoplastic mesenteric tumors and liver metastases, we evaluated changes in tumor size of mesenteric and liver lesions based on pre and post-treatment radiology reports. Due to the infrequency of objective radiographic response (ORR), any reported changes in tumor size were considered significant. Scans were subsequently reviewed by a radiologist to confirm findings. Results: 21 patients met the inclusion criteria: 9 had evidence of shrinkage of liver lesion(s), 1 report described mild progression of liver lesions, 7 described stable hepatic disease and 4 described mixed hepatic progression/response. 2 of the patients with hepatic tumor shrinkage met criteria for PR by RECIST 1.1. Desmoplastic mesenteric lesions remained unchanged in size, regardless of the changes detected on liver lesions. Conclusions: 177Lu-dotatate does not impact desmoplastic mesenteric tumors typically associated with midgut NETs. Patients whose disease is confined to desmoplastic mesenteric lesions are unlikely to respond radiographically to PRRT. Moreover, the inclusion of desmoplastic mesenteric lesions as target lesions in RECIST measurements increases rates of disease stability versus response or progression.

Fluorescence angiography guided resection of small bowel neuroendocrine neoplasms with mesenteric lymph node metastases

BackgroundSurgery for small bowel neuroendocrine neoplasms (SB-NEN) might result in vascular compromise of the remaining bowel due to resection of lymph node metastases in close proximity to main mesenteric vessels. Fluorescence angiography (FA) has been described as a safe technique to assess perfusion during gastro-intestinal surgery. This study aimed to evaluate the potential value of intraoperative FA during surgery for SB-NEN. MethodsThis study included patients undergoing surgery for SB-NEN of any stage. The planned level of transection was marked by the surgeon, after which FA using indocyanine green (ICG) was performed. The primary study outcome was change in management due to FA. ResultsTen consecutive patients with SB-NEN were included, all with metastatic lymph nodes close to main mesenteric vessels. FA use led to management changes in eight patients (80%); four patients had less bowel resected with a preserved length of 5–35 cm. The other four patients had more extended bowel resections with an additional length varying from 3 to 25 cm. The median postoperative stay was 4 days (interquartile range 4–6). No anastomotic leakage occurred. ConclusionThis is the first known series describing preliminary results of FA during SB-NEN surgery. FA led to a management change in 80% of patients with better tailoring the extent of resection of small bowel. Structural implementation of FA to assess small bowel perfusion after dissection for small bowel NET results in change of management, either by preserving small bowel or resecting ill-perfused small bowel.

The Landmark Series: Management of Small Bowel Neuroendocrine Tumors.

Surgical resection is the foundation for treatment of small bowel neuroendocrine tumors (SBNETs). Guidelines for surgical management of SBNETs rely on retrospective data, which suggest that primary tumor resection and cytoreduction improve symptoms, prevent future complications, and lengthen survival. In advanced NETs, improvement in progression-free survival has been reported in large, randomized, controlled trials of various medical treatments, including somatostatin analogues, targeted therapy, and peptide receptor radionuclide therapy. This review discusses important studies influencing the management of SBNETs and the limitations of current evidence regarding surgical interventions for SBNETs.

Upfront Small Bowel Resection for Small Bowel Neuroendocrine Tumors With Synchronous Metastases: A Propensity-score Matched Comparative Population-based Analysis.

We examined the impact of upfront small bowel resection (USBR) for metastatic small bowel neuroendocrine (SB-NET) compared to nonoperative management (NOM) on long-term healthcare utilization and survival outcomes. The role of early resection of the primary tumor in metastatic SB-NET remains controversial. Conflicting data exist regarding its clinical and survival benefits. This is a population-based retrospective matched comparative cohort study of adults diagnosed with synchronous metastatic SB-NET between 2001 and 2017 in Ontario. USBR was defined as resection within 6 months of diagnosis. Primary outcomes were subsequent unplanned acute care admissions and small bowel-related surgery. Secondary outcome was overall survival. USBR and NOM patients were matched 2:1 using a propensity-score. We used time-to-event analyses with cumulative incidencefunctions and univariate Andersen-Gill regression for primary outcomes. E value methods assessed the potential for residual confounding. Of 1000 patients identified, 785 had USBR. The matched cohort included 348 patients with USBR and 174 with NOM. Patients with USBR had lower 3-year risk of subsequent admissions (72.6% vs 86.4%, P < 0.001) than those with NOM, with hazard ratio 0.72 (95% confidence interval 0.570.91). USBR was associated with lower risk of subsequent small bowel-related surgery (15.4% vs 40.3%, P < 0.001), with hazard ratio 0.44 (95% confidence interval 0.29-0.67). E -values indicated it was unlikely that the observed risk estimates could be explained by an unmeasured confounder. Sensitivity analysis excluding emergent resections to define USBR did not alter the results. USBR for SB-NETs in the presence of metastatic disease was associated with better patient-oriented outcomes of decreased subsequent admissions and interventions, compared to NOM. USBR should be considered for metastatic SB-NETs.

Diagnosis and prognostic significance of extramural venous invasion in neuroendocrine tumors of the small intestine

Extramural venous invasion (EMVI) is an established independent prognostic factor in colorectal carcinoma where it is linked to hematogenous spread (i.e., liver metastases), influencing the decision for adjuvant chemotherapy. However, its prognostic significance in small intestinal neuroendocrine tumors (NETs) has not been studied, nor is it routinely assessed or reported. We reviewed primary small bowel NETs (14 jejunum, 82 ileum, 8 not specified) from 104 patients (52 women; median age 60.5, range: 24–84). EMVI was identified in 58 cases (55.8%), including in 13 of 21 equivocal cases using an elastin stain. In univariate analysis, EMVI was associated with lymphovascular and perineural invasion, tumor stage, and lymph node and distant metastases, whereas in multivariate analysis, only distant metastases remained significant (p < 0.001). Liver metastases were present in 55 cases (52.9%) and were significantly associated in univariate analysis with lymphovascular and perineural invasion, tumor stage, lymph node metastases, and EMVI, whereas in multivariate analysis, only EMVI remained significant (p < 0.001; odds ratio (OR) = 59.42). Eight patients developed metachronous liver metastases during follow-up (mean 22.9 ± 22.0 months, range: 4.7–73.2) and all (100%) were positive for EMVI. In contrast, of 49 patients who never developed liver metastases over significantly longer follow-up (mean 71.0 ± 32.4 months, range: 6.6–150.4; p < 0.001), only 7 (14.3%) had EMVI (p < 0.001). In Kaplan–Meier analysis, 8 of 15 patients with EMVI (53.3%) developed metachronous liver metastases, compared with 0 of 42 patients without EMVI (p < 0.001). In contrast, nonhepatic distant metastases, seen in 26 (25.0%) patients, were not associated with EMVI in multivariate or Kaplan–Meier analyses. Our data demonstrate that EMVI is common in small bowel NETs and strongly correlates with development of liver metastases. Therefore, its evaluation is critical and should be assessed in combination with adjuvant techniques such as elastin staining, if necessary. Moreover, inclusion of EMVI in pathology reporting guidelines should be considered.

Ovarian metastases of ileal neuroendocrine tumor

A 55-year-old, menopausal woman with history of breast carcinoma was referred for recurrent abdominal pain without diarrhea. Physical examination, routine biological investigation, and serum CA15-3 were normal. Abdominal contrast-enhanced computed tomography (CT) found a 15-mm ileal hyper-vascularized lesion with mild intestinal dilation and a mesenteric mass of about 20 mm. Both ovaries were moderately enlarged without radiological overt signs of malignancy. CT findings were consistent with ileal neuroendocrine tumor (ileal-NET) with mesenteric invasion. Serum value of chromogranin A was normal. 18F-Fluorodihydroxyphenylalanine (18F-FDOPA) positron emission tomography (PET)/CT was added to the preoperative work-up 1 Addeo P. Poncet G. Goichot B. et al. The added diagnostic value of 18F-fluorodihydroxyphenylalanine PET/CT in the preoperative work-up of small bowel neuroendocrine tumors. J Gastrointest Surg. 2017; 22: 722-730 Crossref PubMed Scopus (7) Google Scholar and distinctly identified the primary ileal-NET with the mesenteric involvement. Moreover, intense and pathological 18F-FDOPA uptake was shown in both ovaries and 1 peritoneal nodule of a few millimeters in the Douglas space (Fig 1, A), suggesting ovarian metastases with peritoneal carcinomatosis. Surgical exploration found the primary tumor and the mesenteric lesion that were removed by a 20-cm ileal resection and mesenteric lymphadenectomy. Intervention was completed by bilateral salpingo-oophorectomy, omentectomy, and multiple peritoneal biopsies (Fig 1, B). Postoperative course was uneventful, and pathology confirmed a 20-mm, well-differentiated grade-2 ileal-NET (Ki-67: 4%) with mesenteric invasion, ovarian bilateral spread, and pelvic peritoneal metastases as small as a few millimeters in size (pT4N2M1, UICC 2016).

S2830 Hematochezia of Unknown Origin

INTRODUCTION: The estimated incidence of neuroendocrine tumors in the United States ranges from 2.5 to 5 cases per 100,000. Although relatively rare, the most common location for them is the small bowel, specifically the ileum. Rarely do they present with hemodynamically significant bleeding or at a young age. The following case is a rare presentation of substantial hematochezia from a small bowel neuroendocrine tumor in a young, otherwise healthy male. CASE DESCRIPTION/METHODS: The patient is a 26 year old male who presented to hospital complaining of bloody stools.His hemoglobin on admission was 6.9 dg/L. Patient underwent a CTA that was read as 1.6 cm mesenteric mass and right colon extravasation, but subsequent angiography was negative for active bleeding. A follow-up Meckel’s scan was also negative. Within 3 days, the patient had 12 bloody stools and required transfusion of 6 units of blood. An EGD and colonoscopy revealed no sources of acute bleed. Decision was then made to transfer the patient to a higher acuity facility for push enteroscopy and video capsule endoscopy. VCE on transfer was remarkable for 3 areas of fresh blood mixed with mucosa in the distal small bowel. Decision was made for a push enteroscopy the next day, however it revealed a normal small bowel from the ileocecal valve to about 100cm into the ileum. The patient was stabilized and a few weeks later underwent an exploratory laparotomy where a mesenteric mass and 2 lymph nodes were biopsied. There was also appreciable denseness to the mid and distal jejunum. Subsequent biopsies were remarkable for a well-differentiated, G2 neuroendocrine tumor likely representing a metastatic tumor from the adjacent small intestine. Since surgery, the patient reports no further episodes of hematochezia. DISCUSSION: The most common site of small bowel neuroendocrine tumors is the ileum, approximately 60-100cm from the ileocecal valve. While abdominal pain is the most common presentation, GI bleeding is the initial symptom in 23-29 percent of cases. One study of neuroendocrine tumors found it took an average of 2.3 tests before a diagnosis was determined. In this case, the patient underwent multiple imaging and endoscopic evaluation before ascertaining a cause for his bleeding. These tumors are typically found in the 6th or 7th decade of life, which is one of the unusual facets of this case. For a tumor of this size, surgery with extensive lymph node resection is associated with low local recurrence.Figure 1.: Mesenteric tumor pathology report.

S3568 Metastatic Jejunal Carcinoid Masquerading as a Pelvic Mass

INTRODUCTION: Neuroendocrine tumors (NETs), also known as carcinoid tumors, are epithelial neoplasms that arise from enterochromaffin cells and are classified according to their histologic features and confirmed by immunohistochemical staining. NETs most commonly occur in the gastrointestinal tract, pancreas, appendix, rectum and the lungs but they can develop anywhere in the body. Due to their common embryonic origin, neuroendocrine tumors of the jejunum, ileum and appendix are collectively called midgut carcinoid tumors. NETs are now the most common small bowel tumor. Small bowel NETs are difficult to diagnose as they follow an insidious course; early on in the disease, symptoms are vague and nonspecific. Late diagnosis when regional or distant metastasis have already occurred is common. Forty percent of symptomatic patients without carcinoid syndrome present with vague abdominal pain. CASE DESCRIPTION/METHODS: We present a case of a 58 yo female with complaints of abdominal pain. The patient had six months of alternating fevers, chills and fatigue. She was placed on antibiotics but her fevers returned upon completion. Three months thereafter, the patient developed left lower quadrant abdominal pain that was sharp in nature and radiated to her groin. A CT scan of the abdomen and pelvis demonstrated an enhancing soft tissue mass with internal cystic and necrotic changes located in the midline upper pelvis, measuring 2.8 by 2 cm and two adjacent satellite nodules located superior to the mass. The location of this mass made it un-amenable to a percutaneous biopsy. The patient underwent an Endoscopic Ultrasound Guided Fine Needle Aspiration (EUS-FNA) with cytology demonstrating low grade neuroendocrine carcinoma with the malignant cells being positive for chromogranin A and synaptophysin. Endoscopic evaluation was negative. A capsule endoscopy revealed two small areas in the jejunum that were concerning for small bowel tumors. A subsequent octreoscan was positive, showing an abnormal activity in the mid-abdomen. The patient subsequently underwent surgical excision. The surgical pathology confirmed the mesenteric mass finding as metastatic low grade neuroendocrine tumor and identified two distinct small bowel low grade carcinoid tumors. DISCUSSION: Carcinoid tumors can vary in their presentation and delay the time of diagnosis. Early consideration for NETs in the differential for patients with vague undiagnosed abdominal symptoms could lead to more prompt diagnosis and treatment prior to metastatic spread.Figure 1.: Tumor Positive for Chromogranin A.Figure 2.: Tumor Positive for Synaptophysin.