S3056 Small Bowel Neuroendocrine Tumor

Introduction: Neuroendocrine tumors (NETs) have been increasing in incidence due to higher rates of endoscopic evaluation. They constitute 2% of all gastrointestinal malignancies. They are more prevalent in females. NETS most commonly develop in the small intestine. They are mostly non-functional, although a considerable proportion secrete gastric acid and in turn, can cause duodenal ulceration. Carcinoid syndrome is rare in duodenal NETs and mostly occurs in the setting of hepatic metastases. Case Description/Methods: A 78-year-old man with a history of hypertension, hyperlipidemia, diabetes mellitus, paroxysmal atrial fibrillation on apixaban, and left lower extremity weakness due to childhood polio presented to the emergency department following an episode of syncope. He reported intermittent melena for the past 2-3 months but denied hematemesis or hematochezia. Initial labs showed stable hemoglobin (14.3 g/dL) and platelets (249,000/μL), but he had hypokalemia (2.8 mmol/L) and atrial fibrillation with rapid ventricular response on EKG. Given his melena and anticoagulation use, gastroenterology was consulted for further evaluation. During upper endoscopy, a 6 cm x 6 cm polyp was found in the duodenal bulb. Its appearance was benign, but due to the size and location being atypical, a biopsy was obtained. Biopsy confirmed a well-differentiated duodenal neuroendocrine tumor (DNET), with staining positive for synaptophysin, chromogranin, CD56 and focally AE 1/3. Imaging showed no distant metastases. Initially, the patient's syncope was attributed to arrhythmia secondary to hypokalemia rather than DNET. Given his age and comorbidities, he was managed conservatively along with close surveillance and was given follow-up with an advanced endoscopist and hematology/oncology. Discussion: This case highlights an unusual presentation of NET in an elderly patient with multiple comorbidities, emphasizing the importance of endoscopic evaluation in unexplained gastrointestinal bleeding, even in the absence of anemia. Occupational risk factors, including smoking and coal mine exposure, may have contributed to his malignancy. Further studies are needed to explore NETs in elderly populations.

Intestinal neuroendocrine tumors (NETs) constitute a heterogeneous group with duodenal, small intestinal, colonic and rectal NETs. They constitute more than half of all NETs, with the highest frequencies in the rectum, small intestine, and colon. The tumor biology varies with the location of the primary tumor as well as with the grade and staging of the tumor. Small intestinal NETs usually present low proliferation and are treated in the first line with somatostatin analogs according to current guidelines. If progression occurs, one can add interferon alpha or change the treatment to everolimus. Peptide receptor radionuclide therapy (PRRT) with Lutetium¹⁷⁷-DOTATATE can be an option in the future after registration of the compound. Rectal tumors are usually small when they metastasize; they can be treated with somatostatin analogs but more so with PRRT, while another option is of course everolimus. Colonic NETs are more aggressive than the rest of intestinal NETs and will be treated with everolimus, sometimes in combination with somatostatin analogs based on positive scintigraphy. Another option is a cytotoxic agent such as streptozotocin plus 5-fluorouracil (5-FU) or temozolomide plus capecitabine. The most aggressive tumors, i.e. neuroendocrine carcinoma G3, are treated with a platin-based therapy plus etoposide; if they present with a lower proliferation, i.e. <50%, temozolomide plus capecitabine plus bevacizumab can also be attempted. Duodenal NETs are mostly treated similar to pancreatic NETs, either with cytotoxic agents, streptozotocin plus 5-FU, or temozolomide plus capecitabine, or with targeted agents such as everolimus.

1993). The initial management of NET comprises surgical excision of the primary tumour (aimed at reducing as much as possible of the tumour mass); additionally, in patients who are not cured by surgery alone, medical therapy is used for the control of symptoms and humoral syndromes with agents such as somatostatin analogues and/or a-interferon. Specific therapy with radiopharmaceuticals using radio-labelled substances such as meta-iodobenzylguanidine (MIBG) or somatostatin analogues appears promising for some tumours which show diagnostic uptake, and is the first-line systemic management for sensitive cases. Hepatic artery ligation and/or chemoembolization is also used in patients with excessive hepatic tumour load and uncontrollable symptoms. The control of tumour growth with chemotherapeutic agents is currently mainly reserved for patients with recurrent and/or progressive disease and where other therapeutic modalities have failed. Chemotherapy may be particularly helpful for selected cases of advanced NET, especially pancreatic or poorly differentiated NET. This review deals with the general role of chemotherapy in the management of malignant NET, its integration with other modes of therapy, and the specific protocols which have been used. Histological classification and differentiation of NET

Su1277 THE RESULTS OF ENDOSCOPIC MUCOSAL RESECTION WITH A LIGATION DEVICE FOR DUODENAL NEUROENDOCRINE TUMORS

The incidence of duodenal neuroendocrine tumors (D-NETs) has been steadily rising. Endoscopic resection has become the preferred treatment option for smaller, localized lesions. We aimed to corroborate the efficacy and safety of endoscopic resection of D-NETs in a Western population and to evaluate treatment durability and disease course by examining long-term outcomes after resection. This was a retrospective cohort study of patients who underwent endoscopic resection of a nonampullary D-NET from 2012 through 2020 at a single institution in the United States. Demographic, clinical, and procedural data were abstracted in duplicate and independent fashion. Outcomes were assessed through medical records review and follow-up phone calls. Over the study period, 58 patients underwent endoscopic resection of 59 D-NETs. Follow-up data were available in 85% of patients with a median follow-up duration of 23 months. Almost all D-NETs were located in the duodenal bulb, and all were biologically indolent. The mean size 6.6mm (range: 1 to 27mm). The most common resection technique was cap- or band-assisted endoscopic mucosal resection (73%). Negative resection margins were achieved in 78% of the sample. Delayed hemorrhage and perforation occurred in 5 and 6 patients, respectively; all but one were managed endoscopically. The presence of residual or recurrent neoplasm was identified at follow-up endoscopy in 10 patients and did not appear to be associated with resection margin status or endoscopic removal technique. No patients required surgical resection of a NET, were diagnosed with metastatic NET, or died as the result of their neuroendocrine tumor during follow-up. Endoscopic resection appears to be reasonably safe and durably effective in treating localized duodenal neuroendocrine tumors, but attention to endoscopic rescue of adverse events and to follow-up is necessary.

BackgroundAlthough the status of lymph node metastasis (LNM) is crucial in determining treatment strategy for duodenal neuroendocrine tumors (D-NETs), robust evidence for their potential LNM risk remains lacking. This systematic review aimed to summarize the prevalence and risk factors of LNM in D-NETs.MethodsThis systematic review of electronic databases identified eligible case–control and cohort studies for D-NET resected either endoscopically or surgically, published from 1990 to 2023. The primary outcome was the pooled prevalence of LNM in D-NETs. Secondary outcomes included the pooled prevalence of LNM according to tumor location and functionality, as well as identifying pathological risk factors for LNM. Meta-analysis was performed.ResultsWe identified 36 studies that involved 1,396 patients with D-NETs, including 326 with LNM. The pooled prevalence of LNM in D-NETs was 22.7% (95% confidence interval [CI] 17.3–29.2%). The prevalence was high in ampullary/peri-ampullary D-NETs and functional D-NETs (46.8 and 53.3%, respectively), whereas it was low in non-functional, non-ampullary D-NETs (NAD-NETs) (9.5%). Pathological risk factors for LNM in NAD-NETs included tumor size > 10 mm (odds ratio [OR] 7.31 [95% CI 3.28–16.31]), tumor invasion into the muscularis propria or deeper (OR 7.79 [3.65–16.61]), lymphovascular invasion (OR 5.67 [2.29–14.06]), and World Health Organization grading of G2 (OR 2.47 [1.03–5.92]).ConclusionApproximately one-fourth of the patients with D-NETs had LNM. Endoscopic resection might be acceptable for non-functional NAD-NETs with diameters of 10 mm or less, but additional surgical resection with lymphadenectomy may be recommended for cases exhibiting pathological risk factors.

630 Background: Neuroendocrine tumors (NET) are heterogeneous in terms of prognosis based on location, grade, and stage. In this study we report causes of deaths (COD) in patients with NET. Methods: We used the Surveillance, Epidemiology, and End Results (SEER) Program to query data of NET patients diagnosed between 2000 and 2016 and report COD following NET diagnosis. Results: We reviewed 94,399 NET cases of which 38,692 died during the follow-up period. The highest number of deaths (5,721) occurred within less than a year following grade 3 (G3) NET diagnosis while most deaths in grade 1/2 (G1/G2) cases occurred within 1-5 years of diagnosis (1,889 and 987, respectively). During the first year of diagnosis, most deaths were from NETs (73%), followed by other cancers (11.2%) and cardiac diseases (CD) (4.6%). As time passed, NET deaths decreased to be responsible for 24.3% of deaths after &gt; 10 years of diagnosis, while other cancers (14%) and CD (19.7%) became more common. When dividing NET cases by grade, NETs were responsible for 42.8%, 63.4%, and 81.2% of deaths in G1, G2, and G3, respectively, while other cancers were responsible for 16.2%, 11.8%, and 7.2% of deaths, respectively and CDs were responsible for 12.3%, 7.2%, and 3.2% of deaths, respectively. For G1 localized NET: non-NET cancers (22.2%) was the most common COD followed by NET (19.7 %) and CD (16.8%). For G2 localized NET, NET was COD in 31.1% of cases followed by non-NET cancers (22.4%) and CD (13.8%). In metastatic disease, NET was the most common COD regardless of grade. Conclusions: In G1 and G2 localized NET, deaths were mostly secondary to non-NET causes. Therefore, counseling patients regarding survivorship with cancer-screening and focusing on prevention from non-cancer deaths is important. On the other hand, NET is responsible for most deaths in metastatic NET regardless of grade. Further advances in systemic therapies are needed to improve the outcomes of advanced disease.

Mutations and Allelic Deletions of the MEN1 Gene Are Associated with a Subset of Sporadic Endocrine Pancreatic and Neuroendocrine Tumors and Not Restricted to Foregut Neoplasms

Su1666 Clinical Outcomes for Neuroendocrine Tumors of the Duodenum and Ampulla of Vater: A Population-Based Study

Chronic venulectasias secondary to persistent flushing in the setting of a metastatic well-differentiated neuroendocrine tumor

Neuroendocrine neoplasms (NEN) encompass a diverse set of malignancies with limited precision therapy options. Recently, therapies targeting DLL3 have shown clinical efficacy in aggressive NENs, including small cell lung cancers and neuroendocrine prostate cancers. Given the continued development and expansion of DLL3-targeted therapies, we sought to characterize the expression of DLL3 and identify its clinical and molecular correlates across diverse neuroendocrine and non-neuroendocrine cancers. Here, we interrogated paired DNA and RNA-sequencing from 1,589 NENs across 29 sites, as well as 203,252 tumors across 47 cancer types. We found that high transcriptomic levels of DLL3 correlated with more aggressive histologic and mutational patterns in NENs, with adverse survival outcomes being reflected in NENs originating from the lung, pancreas, stomach, and small bowel. The heterogeneity in DLL3 expression across NENs was largely explained by site of origin, with lung, prostate, and bladder NENs exhibiting relatively high levels of DLL3, whereas gastroenteropancreatic NENs displayed relatively low expression levels. Although the therapeutic targeting of DLL3 may be less applicable for gastroenteropancreatic NENs, we did find an upregulation of alternative targets such as SEZ6, CELSR3, and SSTR2 in these settings. Lastly, expanding our investigation into non-neuroendocrine cancers, we detected an enrichment of DLL3 in both low-grade and high-grade gliomas, Merkel cell carcinomas, medulloblastomas, and melanomas, with such enrichment being associated with prolonged overall survival in gliomas, but worse overall survival in melanomas. Altogether, we demonstrate that DLL3 represents an attractive target for subsets of neuroendocrine and non-neuroendocrine cancers and uncover opportunities for future therapeutic strategies.Significance:DLL3-targeted therapies have recently shown robust clinical efficacy in aggressive neuroendocrine cancers, positioning them to fulfill a great unmet need in these settings. Here, we examine the clinical and biological correlates of DLL3 expression in both neuroendocrine and non-neuroendocrine cancers. Our findings may stimulate the development and application of DLL3-targeted therapies, as well as other precision therapies, in neuroendocrine cancers and beyond.

Neuroendocrine tumors (NET) that develop at the second portion of the duodenum are rare, although most of NET at the duodenum is the first portion. We resected a duodenal NET by using a laparoscopic and endoscopic cooperative surgery (LECS) technique. A 33-year-old man underwent esophagogastroduodenoscopy that revealed a 6 mm, gently raising tumor on the opposite side of the ampulla of vater at the second portion of the duodenum. We performed a full-thickness local excision using the LECS technique. The tumor was confirmed and endoscopically marked along the resection line. After a full-thickness excision, using endoscopic and laparoscopy, closure using a liner stapler was performed laparoscopically. We demonstrated that LECS is a safe and feasible procedure for duodenal G1 NET at the second portion of the duodenum.

Introduction: Neuroendocrine neoplasms of the small intestine (SI-NENs), although rare, are the most prevalent primary neoplasms of this organ. Acromegaly is characterized by excessive secretion of growth hormone (GH), typically due to a pituitary neuroendocrine tumor but, in rare cases, it can result from ectopic secretion of growth hormone-releasing hormone (GHRH) by non-pituitary tumors, particularly neuroendocrine neoplasms (NENs) of the lung or pancreas. We reported a case of concurrent acromegaly and SI-NENs. Case Presentation: A 68-year-old male with a history of severe restrictive pulmonary syndrome secondary to thoracic kyphoscoliosis was referred for evaluation of iron-deficiency anemia and colorectal polyps. Video capsule endoscopy revealed an ulcerative-vegetative lesion in the distal ileum. Computed tomography (CT) enterography demonstrated multiple hypervascular lesions in the ileum, consistent with NENs. A 68Ga-DOTA-NOC PET/CT scan identified several foci of abnormal uptake, consistent with multiple intestinal NENs and suspected lymph node metastasis. Increased uptake was also observed in the pituitary gland. The patient was referred for endocrinology evaluation, where an acromegaloid phenotype was noted. Laboratory findings showed elevated levels of insulin-like growth factor 1 (IGF1) (454 ng/mL; reference range [RR] <225), GH (66 µg/L; RR ≤3), and chromogranin A (625 ng/mL; RR ≤102). Brain CT scan suggested a pituitary adenoma (the patient could not tolerate MRI). No pathogenic variants were detected in the MEN1 and CDKN1B genes. Given the concurrent diagnoses of acromegaly and SI-NENs, the extent of the disease, the high surgical risk, and the patient’s preference, long-acting octreotide therapy was initiated. Conclusion: The association between SI-NENs and acromegaly is rarely reported in the literature and remains unclear. Proposed mechanisms include the coexistence of independent tumors, the development of NENs in response to excessive IGF1 stimulation, and induction of acromegaly through ectopic GHRH secretion by NENs.

Neuroendocrine tumors (NETs) are a heterogeneous group of neoplasms constituting about 0.5 % of all cancer cases. In recent years, there has been a significant increase in the incidence of NETs, which is primarily due to the active development and improvement of medical imaging technologies. Successful treatment and prognosis for patients with NETs strongly depend on the stage of the disease. One of the effective methods of visualization and staging NETs in nuclear medicine is somatostin receptor scintigraphy (SRS), which is based on the use of partial somatostatin receptor agonists labeled with radioactive isotopes. The article presents an analysis of 55 patients with NETs of various localizations who underwent scintigraphy and SPECT/CT. Radiopharmaceutical was used as a tracer for SRS. It was prepared on the basis of a lyophilisate developed by Polatom (Poland) — Tektrotyd, labeled with 99mTc. According to the results of the study SRS with 99mTc-Tektrotyd is informative in the topical diagnosis of NETs, especially when PET/CT scan with 68Ga-labeled peptides is not available. Sensitivity varies depending on the NET localization. It is necessary to continue researches on the diagnostic value of SRS with 99mTc-Tektrotyd for tumors, in the pathogenesis of which somatostatin receptors play a significant role.

Duodenal neuroendocrine tumors (NETs) are rare. Historically, when feasible a less aggressive surgical approach is considered. The aim of this study was to identify factors associated with prognosis and the necessity for more aggressive surgical procedures. All patients who underwent surgery for duodenal NETs between September 2005 and June 2014 were identified retrospectively. Data collected included clinical presentation, operative findings, and histopathological data. Eighteen patients underwent surgical management for duodenal NETs. Two patients underwent transduodenal excision (11%), two patients had partial duodenal resection (11%), two patients had antrectomy including 1st part of duodenum (D1) resection (33%), and eight underwent pancreaticoduodenectomy [PD (44%)]. On analysis, 2nd part of duodenum (D2) location was the most common site of duodenal NETs (n = 9, 50%). The odds of having a PD were 10 times higher when the lesion was in D2 location. The odds of having a positive lymph node are nine times higher when the lesion is in D2 region. The odds of having a positive lymph node are three times higher when lesion is greater than T1. D2 location of NETs is associated with higher odds of lymph node positivity and need for more extensive procedures like PD.