Malignant Neuroendocrine Tumors Research Articles

Clinical Evaluation of Response to Octreotide and Chemotherapy in High-Grade Malignant Neuroendocrine Tumors and Promising In Vitro Preclinical Results with Pasireotide.

Background and Objectives: High-grade malignant neuroendocrine tumors (G3 NETs) and neuroendocrine carcinomas (NECs) are characterized by rapid proliferation, high metastatic capacity, and strong expression of somatostatin receptors (SSTRs). We aimed to analyze the presence of SSTRs in NET G3 and NEC, and to correlate their expression with the use of octreotide and pasireotide. Materials and Methods: For this purpose, we first performed a retrospective study of G3 NET and NEC patients, which included the determination of SSTR expression and response to octreotide treatment. Second, we selected the H69 small cell lung cancer cell line to determine the effect of octreotide and pasireotide. Results: Our results showed the traditional somatostatin analog (SSA) octreotide was ineffective in patients with NET G3 and NEC. On the other hand, RT-qPCR showed a high expression of SSTR2 and SSTR5 in H69 cells. Interestingly, while octreotide did not modify H69 cell proliferation, a strong inhibition of proliferation was detected with the use of pasireotide. Conclusions: In view of these results, a clinical trial in NET G3 and NEC patients using pasireotide is necessary to determine the usefulness of this drug in improving patient treatment.

The factors associated with all-cause in-hospital mortality in patients with malignant well-differentiated gastroenteropancreatic neuroendocrine tumors: A retrospective analysis of National Inpatient Survey (NIS) 2020 dataset.

e16292 Background: Neuroendocrine tumors (NET) affect less than 200,000 (52 per 100,000) of the US population, with malignant well-differentiated gastroenteropancreatic (GEP) NETs accounting for about 65% of the cases. Owing to its rarity, the evidence on factors associated with all-cause mortality is limited. To address this gap, this study aims to identify socio-demographic and clinical factors associated with all-cause in-hospital mortality for patients with malignant well-differentiated GEP NET. Methods: We analyzed data from 2020 Nationwide Inpatient Sample survey on patients hospitalized with malignant well-differentiated GEP NET. Using ICD10 code, we identified patients hospitalized with any diagnosis of malignant well-differentiated GEP NET. In-hospital mortality was assessed based on the patient final disposition on discharge and dichotomized. Exposure variables analyzed included age, sex, tumor site, history of essential hypertension, COVID-19, hyperlipidemia, insurance status, length of hospital stay, and number of comorbidities present on the patients record. Multivariable logistic regression was used to assess for factors associated with mortality. Results: Of the 956 patients in this study, most were white (73.43%), male (48.28%) and mean age was 65 years (SD 13.59). Affected sites include small intestine (57.25%), pancreas (13.56%), colon (8.47%), appendix (8.26%), stomach (8.68%) and rectum (3.51%). Our results revealed that females were less likely to die in the hospital compared to their male counterpart hospitalized with malignant well-differentiated GEP NET (aOR = 0.42; 95% CI: 0.19 - 0.95). The presence of hyperlipidemia was significantly associated with in-hospital mortality (aOR = 0.24; 95% CI: 0.08 - 0.75). For every unit increase in the number of comorbidities, there is 12% increased risk of mortality (aOR = 1.12; 95% CI: 1.05 -1.19). The associations of age, race, tumor site, history of hypertension, insurance status or length of stay with in-hospital mortality were not statistically significant. Conclusions: Our study found significant associations of sex, hyperlipidemia, number of comorbidities and in-hospital mortality among patients with malignant well-differentiated GEP NET. Findings from this study highlight that factors such as sex, hyperlipidemia and number of comorbidities may be critical when developing prognostic tools that can be used to determine the risk of mortality among hospitalized patients hospitalized with these tumors.

Exploring effective biomarkers and potential immune related gene in small cell lung cancer

Small cell lung cancer (SCLC) is well known as a highly malignant neuroendocrine tumor. Immunotherapy combined with chemotherapy has become a standard treatment for extensive SCLC. However, since most patients quickly develop resistance and relapse, finding new therapeutic targets for SCLC is important. We obtained four microarray datasets from the Gene Expression Omnibus database and screened differentially expressed genes by two methods: batch correction and “RobustRankAggregation”. After the establishment of a protein–protein interaction network through Cytoscape, seven hub genes (AURKB, BIRC5, TOP2A, TYMS, PCNA, UBE2C, and AURKA) with high expression in SCLC samples were obtained by eight CytoHubba algorithms. The Least Absolute Shrinkage and Selection Operator regression and the Wilcoxon test were used to analyze the differences in the immune cells’ infiltration between normal and SCLC samples. The contents of seven kinds of immune cells were considered to differ significantly between SCLC samples and normal samples. A negative association was found between BIRC5 and monocytes in the correlation analysis between immune cells and the seven hub genes. The subsequent in vitro validation of experimental results showed that downregulating the expression of BIRC5 by siRNA can promote apoptotic activity of SCLC cells and inhibit their vitality, migration, and invasion. The use of BIRC5 inhibitor inhibited the vitality of SCLC cells and increased their apoptotic activity. BIRC5 may be a novel therapeutic target option for SCLC.

LT and SOX9 expression are associated with gene setsthat distinguish Merkel cell polyomavirus (MCPyV)-positive and MCPyV-negative Merkel cell carcinoma.

Merkel cell carcinoma (MCC) is an aggressive malignant neuroendocrine tumour. There are two subsets of MCC, one related to Merkel cell polyomavirus (MCPyV) and the other to ultraviolet radiation (UVR). MCPyV-positive and MCPyV-negative MCCs have been considered to be different tumours, as the former harbour few DNA mutations and are not related to UVR, and the latter usually arise in sun-exposed areas and may be found in conjunction with other keratinocytic tumours, mostly squamous cell carcinomas. Two viral oncoproteins, large T antigen (LT; coded by MCPyV_gp3) and small T antigen (sT; coded by MCPyV_gp4), promote different carcinogenic pathways. To determine which genes are differentially expressed in MCPyV-positive and MCPyV-negative MCC; to describe the mutational burden and the most frequently mutated genes in both MCC subtypes; and to identify the clinical and molecular factors that may be related to patient survival. Ninety-two patients with a diagnosis of MCC were identified from the medical databases of participating centres. To study gene expression, a customized panel of 172 genes was developed. Gene expression profiling was performed with nCounter technology. For mutational studies, a customized panel of 26 genes was designed. Somatic single nucleotide variants (SNVs) were identified following the GATK Best Practices workflow for somatic mutations. The expression of LT enabled the series to be divided into two groups (LT positive, n = 55; LT negative, n = 37). Genes differentially expressed in LT-negative patients were related to epithelial differentiation, especially SOX9, or proliferation and the cell cycle (MYC, CDK6), among others. Congruently, LT displayed lower expression in SOX9-positive patients, and differentially expressed genes in SOX9-positive patients were related to epithelial/squamous differentiation. In LT-positive patients, the mean SNV frequency was 4.3; in LT-negative patients it was 10 (P = 0.03). On multivariate survival analysis, the expression of SNAI1 [hazard ratio (HR) 1.046, 95% confidence interval (CI) 1.007-1.086; P = 0.02] and CDK6 (HR 1.049, 95% CI 1.020-1.080; P = 0.001) were identified as risk factors. Tumours with weak LT expression tend to co-express genes related to squamous differentiation and the cell cycle, and to have a higher mutational burden. These findings are congruent with those of earlier studies.

Peptide Receptor Radionuclide Therapy Is Effective for Clinical Control of Symptomatic Metastatic Insulinoma: A Long-Term Retrospective Analysis.

Metastatic insulinoma is a rare malignant neuroendocrine tumor characterized by inappropriate insulin secretion, resulting in life-threatening hypoglycemia, which is often difficult to treat. There is currently very limited information about the efficacy of peptide receptor radionuclide therapy (PRRT) for clinical control of hypoglycemia. The aim of this long-term retrospective study was to evaluate the therapeutic efficacy of PRRT for improving hypoglycemia, to evaluate the change of medication after PRRT, and to calculate progression-free survival (PFS) and overall survival (OS). Methods: Inclusion criteria were histologically proven somatostatin receptor-positive metastatic malignant insulinoma and at least 2 cycles of [90Y]Y-DOTATOC or [177Lu]Lu-DOTATOC therapy from early 2000 to early 2022. A semiquantitative scoring system was used to quantify the severity and frequency of hypoglycemic episodes under background antihypoglycemic therapy (somatostatin analog, diazoxide, everolimus, corticosteroids): score 0, no hypoglycemic episodes; score 1, hypoglycemic events requiring additional conservative treatment with optimization of nutrition; score 2, severe hypoglycemia necessitating hospitalization and combined medication or history of hypoglycemic coma. Hypoglycemic score before and after PRRT was analyzed. Time of benefit was defined as a time range of fewer hypoglycemic episodes in the observation period than at baseline. Information on antihypoglycemic medication before and after therapy, PFS, and OS was recorded. Results: Twenty-six of 32 patients with a total of 106 [90Y]Y-DOTATOC/[177Lu]Lu-DOTATOC cycles were included. The average observation period was 21.5 mo (range, 2.3-107.4 mo). Before therapy, 81% (n = 21) of the patients had a hypoglycemia score of 2 and 19% (n = 5) had a score of 1. After PRRT, 81% of patients (n = 21) had a decreased score, and the remaining 5 patients showed a stable situation. There was temporary worsening of hypoglycemia just after injection of [90Y]Y-DOTATOC/[177Lu]Lu-DOTATOC in 19% of patients. The average time of benefit in the observation period was 17.2 mo (range, 0-70.2 mo). Antihypoglycemic medication reduction was achieved in 58% (n = 15) of patients. The median OS and PFS after the start of PRRT were 19.7 mo (95% CI, 6.5-32.9 mo) and 11.7 mo (95% CI, 4.9-18.5 mo), respectively. Conclusion: To our knowledge, our study included the largest cohort of patients with malignant insulinoma to be evaluated. Long-lasting symptom control and reduction of antihypoglycemic medications were shown in most patients after late-line PRRT.

All you need to know about VIPoma: Review on the latest studies

Vasoactive intestinal peptide secreting tumor (VIPoma) is a rare mostly malignant neuroendocrine tumor that is characterized by watery diarrhea, hypokalemia and achlorhydria due to the nonregulated increased secretion of VIP. VIPomas ar diagnosed by the presence of the most common symptoms, laboratory analysis of blood and stool, radiological imaging and immunohistochemical findings. Primary treatment includes fluid replacement, electrolyte balance correction, pharmacological treatment with somatostatin analogs, surgical resection and chemotherapy. This review aims to provide an insight into the latest research on VIPoma epidemiology, pathophysiology, diagnostics and treatment.

FRI610 Phosphatidylinositol 3-kinase Inhibition With Alpelisib Is Safe And Effective In Treating Refractory Hypoglycemia Associated With Malignant Insulinoma

Abstract Disclosure: Y. Kang: None. D.A. Rubinson: None. I. Odintsov: None. A. Vaidya: None. J.S. Williams: None. G.K. Adler: None. M.E. McDonnell: None. M. Patti: Advisory Board Member; Self; Fractyl Laboratories. Consulting Fee; Self; AstraZeneca, Hanmi Pharmaceuticals, MBX. Grant Recipient; Self; Dexcom. N.E. Palermo: None. Background: Nonfunctioning malignant pancreatic neuroendocrine tumors (PNETs) can transform to functional PNETs. Transformation into insulin-secreting PNET (ISPNET) is associated with poor overall survival and refractory hypoglycemia, often requiring ICU care. We present a case of refractory hypoglycemia due to ISPNET, which was successfully treated with alpelisib, an inhibitor of phosphatidylinositol 3-kinase (PI3K) currently approved for breast cancer. Clinical Case: A 79-year-old man with a 5-year history of type 2 diabetes and 10-year history of grade II, well-differentiated, non-functioning PNET (Ki67 15%) with hepatic metastasis presented with worsening symptomatic hypoglycemia. He discontinued his antidiabetic agent 3 months ago due to hypoglycemia and was on lanreotide and everolimus as PNET treatment. Evaluation revealed plasma glucose 29 mg/dL, proinsulin >700 pmol/L (reference: 3.6-22), insulin 116 uIU/mL (2.6-24.9), C-peptide 12.0 ng/mL (1.1-4.4), beta-hydroxybutyrate 0.1 mmol/L (<0.3), and negative sulfonylurea panel. Imaging showed extensive progression of hepatic metastases, and debulking hepatectomy was performed. Pathology showed grade III PNET with positive insulin staining and mib-1 index of 22%. After 2 months of euglycemia post-surgery, he was readmitted to the ICU with refractory hypoglycemia. Evaluation showed plasma glucose 91 mg/dL, proinsulin, and insulin levels above-assay (>700 pmol/L and >930.0 uIU/mL, respectively) and C-peptide 71.8 ng/mL; imaging revealed hepatic tumor progression. Severe hypoglycemia as low as 34 mg/dL was noted despite therapy with IV dextrose (30%, up to 100 cc/hr), glucagon infusion (0.6 mg/hr), dexamethasone 20 mg QD, and diazoxide 30 mg TID. Debilitating anasarca developed despite aggressive diuresis, attributed to high-volume IV dextrose, diazoxide, and renal dysfunction. Two hours after 300 mg alpelisib administration, patient exhibited hyperglycemia, allowing discontinuation of dextrose infusion 8 hours later. Glucagon infusion was subsequently discontinued, and he was discharged to home. Within 20 days, the patient was able to discontinue all diuretics, dexamethasone, and cornstarch. Patient had no side effects related to alpelisib and performance status returned to baseline. Glucose ranged between 160-300 mg/dL without any hypoglycemia. On week 4 of alpelisib, plasma glucose was 340 mg/dL, proinsulin >700 pmol/L, insulin 181 uIU/mL, and C-peptide 20.2 ng/mL. Conclusion: To our knowledge, this is the first case demonstrating alpelisib as a safe and effective option in refractory hypoglycemia associated with insulinoma. While it is unclear whether this is mediated by anti-tumor effects or solely by blockade of insulin action, PI3-K inhibition should be considered as a treatment option in patients with ISPNET in whom hypoglycemia has failed to improve with conventional approaches. Presentation: Friday, June 16, 2023

Hedinger Syndrome-Lessons Learnt: A Single-Center Experience.

Hedinger syndrome (HS) or carcinoid heart disease (CD) is a rare and challenging manifestation of malignant neuroendocrine tumours (NETs) involving the heart. We aimed to report our experience with surgical strategies and midterm results in HS patients. Eleven patients (58 ± 11 (range 41 to 79 years); 5 females) with HS who underwent cardiac surgery in our department between 07/2005 and 05/2023 were analysed. All patients showed a New York Heart Association (NYHA) class III-IV and in all the tricuspid valve (TV) was involved. Four patients received a TV replacement, and three TV reconstruction. Recently, to preserve the geometry and function of the compromised right ventricle (RV), we have applied the TV "bio-prosthesis in native-valve" implantation technique with the preservation of the valve apparatus (tricuspid valve implantation: TVI) in four cases. Concomitant procedures included pulmonary valve replacement in four, pulmonary implantation in one, and aortic valve replacement in three cases. To treat RV failure, we adapted a combined TandemHeart®-CytoSorb® haemoperfusion strategy in Patient #10 and venoarterial extracorporeal membrane oxygenation (V-A ECMO) support avoidance, after experiencing an ECMO-induced carcinoid-storm-related death in Patient #8. Mortality at 30 days was 18% (2/11). The median follow up was 2 ± 2.1 years (range 1 month to 6 years) with an overall mortality during the follow-up period of 72.7% (8/11). HS surgery, despite being a high-risk procedure, can efficiently prolong survival, and represents a safe and feasible procedure. However, patient selection seems to be crucial. Further follow up and larger cohorts are needed.

Prognostic factors and clinic-pathologic characteristics of ovarian tumor with different histologic subtypes-a SEER database population study of 41,376 cases.

Ovarian cancer is considered the leading cause of cancer-related deaths among all gynecological malignancies and a significant reason for mortality in women. This cohort study aimed to explore the survival trends of malignant ovarian tumors (MOT), cancer antigen 125 (CA125) level, and clinicopathological prognostic factors of MOT by histological subtype. Using the Surveillance, Epidemiology, and End Results (SEER) database, a total of 41,411 MOT cases diagnosed between January 2005 and December 2014 were extracted. According to the histological classification of MOT, four categories were included: epithelial ovarian carcinoma (EOC), malignant ovarian germ cell tumors (MOGCTs), malignant ovarian sex cord-stromal tumors (MOSCSTs) and ovarian neuroendocrine tumors (ONTs). We analyzed disease-specific survival (DS) and overall survival (OS) among the four categories, and their histological subtypes. Kaplan-Meier method was used to estimate survival curves, and log-rank test was used to evaluate differences between curves. Univariate and multivariate Cox proportional hazards models were applied to evaluate the prognostic impact of MOT. Significant predictors related to improved OS were younger age, low grade, early FIGO stage and localized SEER stage, while positive/elevated CA125 level was a risk factor. For MOGCT and MOSCST, 3-, 5- and 10-year DS rate estimates were all >80%, followed by ONT around 70%. Malignant epithelial cancer showed low DS rate at 3-year (70.7%), 5-year (58.7%), and 10-year (47.3%). EOC patients had the worst outcome, whereas MOGCT cases had the most favorable survival. Positive/elevated CA125 level led to poor prognosis. Furthermore, younger age, low grade, early FIGO stage and localized SEER stage were significant predictors for improved OS.

Primary Small Cell Carcinoma of the Breast: When a Rare Tumour is Real

Background: Extra-pulmonary small-cell neoplasms are rare, and treatment planning is challenging for clinicians. The lack of guideline-based management undermines and isolates patients for whom these cancers are not just rare but also real. Small-cell breast cancer (SCBC) is a rare, aggressive disease that accounts for less than 1% of all invasive breast cancers. Here, we report a case of SCBC and discuss the complexities of case management. Case Presentation: A 46-year-old patient presented with a self-detected right breast lump. Mammogram and ultrasound examination showed a 69x47mm dense lesion in the upper outer aspect of the right breast and a 17mm pathologic node in the inferior right axilla. The triple assessment demonstrated a localised high-grade malignant neuroendocrine neoplasm. Management extrapolated from small cell lung cancer management and case reports, consisted of chemotherapy with carboplatin, and etoposide introduced with concurrent radiotherapy, followed by mastectomy with axillary lymph node dissection. A complete pathological response was obtained. Six months following her surgery, metastatic disease in the brain, chest wall, lymph nodes, and lungs developed. Rechallenge with carboplatin and etoposide led to a brief response, and subsequent immunotherapy was ineffective. Conclusion: This case report highlights the challenges of rare tumour management. Establishing registries for these and other rare tumors would facilitate care, reduce patient uncertainty and assist in founding protocol-based care.

Mixed Neuroendocrine - Non-Neuroendocrine Neoplasm (MiNEN) - A Rare Heterogenous Malignancy of the Pancreas

Introduction: Pancreatic mixed neuroendocrine non-neuroendocrine neoplasms are extremely rare tumours accounting for 0.5% of all the pancreatic malignancies and 5% of all pancreatic neuroendocrine neoplasms. These tumors are rarely diagnosed preoperatively and they have a poor prognosis. Pancreatic MiNEN is characterized by 2 malignant lesions adenocarcinoma and Neuroendocrine tumour with each constituent involving more than 30% of the tumour. We report a case of 57yr old male with dullaching abdominal pain radiating to back. CA 19-9 was mildly elevated. Other laboratory tests are within normal limits. CECT abdomen revealed bulky pancreas with specks of calcification in the head of the pancreas and few tiny non enhancing hypodense areas and a well defined isodense lesion measuring 1.2x1.4cm in the second part of duodenum with enhancement in post contrast images associated with thickness of duodenal wall. The patient underwent Whipple’s pancreaticoduodenectomy with regional lymphadenectomy. Histopathological examination of specimen revealed an infiltrating acinar adenocarcinoma of the pancreas interspersed with a well differentiated neuroendocrine tumour component which made up of more than 45% of the tumour. The features were consistent with Mixed Neuroendocrine Non Neuroendocrine Neoplasm of the pancreas. Keywords: MiNEN, Pancreas, Neuroendocrine, Non neuroendocrine, Adenocarcinoma

Carcinogenicity assessment of tegoprazan in Sprague-Dawley (Crl:CD) rats and ICR (Crl:CD1) mice

Tegoprazan is a novel potassium-competitive acid blocker (P-CAB) that reversibly inhibits the proton pump in gastric parietal cells and has been approved for the treatment of acid-related diseases in Korea. This study aimed to evaluate the carcinogenic potential of tegoprazan in Sprague-Dawley rats and CD-1 mice. Tegoprazan was administered daily by oral gavage to rats for up to 94 weeks and mice for up to 104 weeks. Evidence of carcinogenic potential of tegoprazan was identified in rats only and was limited to benign and/or malignant neuroendocrine cell tumors at exposures >7-fold of the recommended human dose. Glandular stomach findings were considered secondary to the expected pharmacology of tegoprazan, characterized by their location in the fundic and body regions of the stomach. Overall, tegoprazan induced gastric enterochromaffin-like (ECL) cell tumors in SD rats, but did not produce any treatment-related statistically significant increase in the incidence of neoplasms relevant to humans when administered to SD rats and CD-1 mice by gavage at doses up to 300 and 150 mg/kg/day, respectively. Gastric ECL cell tumors are thought to be induced by the exaggerated indirect pharmacological effect of tegoprazan, similar to that reported for proton pump inhibitors (PPIs) and other P-CABs.

P-247 Comparison of overall survival of malignant gastric neuroendocrine tumor with gastric adenocarcinoma: A propensity score matching study

P-247 Comparison of overall survival of malignant gastric neuroendocrine tumor with gastric adenocarcinoma: A propensity score matching study

Bronchial carcinoid misdiagnosed as COVID pneumonia: a case report.

The authors report a case of 55-years-old man who presented with a history of cough for 1 month and was initially diagnosed with a case of COVID-19. Then he was treated as a case of pneumonia as seen on high-resolution computed tomography. Later, contrast-enhanced computed tomography and bronchoscopy-guided biopsy were done which revealed a right lower lobe neuroendocrine tumour (carcinoid), which was successfully resected. The majority of typical carcinoids are located in the central airways leading to bronchial obstruction with recurrent pneumonia, chest pain, and wheezing. During the COVID-19 pandemic, lung cancer patients were at higher risk of being affected by COVID-19. This study emphasizes that early identification and differential diagnosis are extremely difficult in the absence of comprehensive study and workup as the clinical and imaging findings of COVID-19 may resemble lung cancer. Although hilar and mediastinal lymph nodes are the most common metastatic sites for typical carcinoids, most lymphadenopathies are caused by a reactive inflammatory reaction. Bronchial carcinoids are uncommon, malignant neuroendocrine tumours for which the only curative management is complete surgical resection. With full resection, the result of typical carcinoids with lymph node metastases is favourable.

Spleen-Preserving Retrograde Distal Pancreatectomy for Malignant Insulinoma

Introduction: Distal pancreatectomy is performed primarily for malignant and premalignant diseases of the pancreas. Neuroendocrine tumors within the body and tail of the pancreas can be resected or enucleated depending upon the size and relationship of the tumor with the pancreatic duct.1,2 This video presents the technical details of a spleen-preserving laparoscopic distal pancreatectomy using a retrograde dissection (Kimura technique) for malignant pancreatic neuroendocrine tumor treatment. Operative Technique: A 47-year-old woman with medical history of hypertension and hypothyroidism comes to endocrinology presenting 3 months history of lumbar pain and 6 months history of neuroglycopenic symptoms. The work-up demonstrated hyperinsulinemic hypoglycemia produced by a 2.7 cm insulin-producing tumor of the body of the pancreas. A 1 cm cyst of the tail of the pancreas, a 5 mm sellar mass, and an adenoma of one parathyroid gland with elevated parathyroid hormone and calcium are seen as well, indicatory of a multiple endocrine neoplasia type 1.3–5 A five-trocar laparoscopic distal pancreatectomy was performed with one surgeon between the legs and two more surgeons on each side of the patient. The liver was retracted for better visibility and started with the section of splenocolic ligament to release the splenic angle of the colon and move it to the midline. Short gastric vessels of the gastrosplenic ligament are sectioned to address the posterior face of the stomach, through the lesser sac. The stomach was retracted cephalad, allowing for a better exposure of the pancreas. The insulinoma became visible on the anteroinferior margin and was well delimited with intraoperative manipulation. Pancreas is accessed through the retroperitoneum. Splenic vessels are dissected. The splenic artery and vein are identified and referred to be able to dissect along the upper edge of the pancreas, in a retrograde approach to preserve vascular structures. Ligaclips are placed on the branches of the splenic vessels. Transection is performed at the level of the junction of the head and neck of the pancreas, leaving enough space between the mass using a linear stapler capable of 60 mm long cuts and with 3.5 mm open staple height. The integrity of the piece is verified and is extracted with a laparoscopic specimen retrieval bag. In the case of this patient with previous surgery, an existing Pfannenstiel-type scar is used to avoid extension of the laparoscopic scars. Blake-type drain is placed in situ. Results: The postoperative course was uneventful. No postoperative diabetes was observed and no treatment for hypoglycemia was necessary. Early oral feeding postoperatively was well tolerated. The patient was discharged home 3 days after surgery with a placed drain. Histology analysis confirmed the full resection of the intrapancreatic neuroendocrine tumor. No competing financial interests exist. Runtime of video: 9 mins 24 secs

ODP245 Syndrome of Diabetic Ketoalkalosis due to Severe Hypercortisolemia: A Case Series

Abstract Introduction Decompensated diabetes (DM) precoma/comas states are major causes of hospital morbidity and mortality. These commonly include diabetic ketoacidosis (DKA), diabetic hyperglycemic hyperosmolar syndrome (DHHS), diabetic hypoglycemia coma (DHC) and diabetic lactic acidosis (DLA). Another less common decompensated DM precoma/coma state to be aware of is Diabetic ketoalkalosis (DKAL). We present two cases of DKAL due to severe hypercortisolemia (HCS) from ectopic Cushing's syndrome (ECS). Clinical cases; Case 1 was a 61 yr old AA woman with suboptimally managed type 2 DM who had been admitted for DKA 2 months before. She had marked hyperglycemia (blood glucose >500mg/dl) on repeated measures (RMs) and chronic diarrhea with tachypnea and altered mental status (AMS). She had heavy tobacco abuse and work up revealed a right lung mass biopsy of which showed a malignant neuroendocrine tumor presumed to be malignant bronchial carcinoid. Her initial lab tests showed marked metabolic alkalosis with severe hypokalemia and elevated anion gap, ketonemia and ketonuria. Presentation was typical of DKAL and subsequent work up showed ECS with serum cortisol > 110 (n; 4.3-22.4ug/dl) on RMs and serum ACTH 377-480 (n; 0/46pg/ml). Her metabolic derangements were corrected and HCS managed with mild impact using ketaconazole and octreotide but she died within a month of admission with intractable septic shock despite parenteral antimicrobials. Case 2 was a 46 yr old Hispanic man with heavy tobacco abuse admitted on account of AMS, tachypnea and upper abdominal pain. He had severe hyperglycemia (blood glucose >750mg/dl on RMs) though not known to have DM. HBA1c was > 15% indicating undiagnosed DM. Initial lab tests showed marked respiratory and metabolic alkalosis, marked hyponatremia, hypokalemia, hypo-osmolality but with ketonemia and ketonuria. Presentation was consistent with DKAL. Work up showed a left lung lesion with pleural effusion shown to be small cell carcinoma of the lung. He was also found to have profound HCS (serum cortisol >150ug/d; on RMs) confirmed due to ECS with serum ACTH, 1500-1800pg/ml. Metabolic derangements were corrected and he was started on ketoconazole and etomidate to correct HCS with little response. Elective bilateral adrenalectomy was planned but patient abruptly discharged himself AMA. He was readmitted ∼ 3 weeks later with a massive pulmonary embolism and acute respiratory failure from which he never recovered. He died ∼ 2 months later. Discussion + Conclusions DKAL is an uncommon but important potential acute presentation of decompensated DM. Early recognition and management requires close attention to the acid-base and electrolyte derangements that often accompany it. Among the many possible causes of DKAL severe HCS is an important possibility to be consider. Rapid diagnosis and institution of aggressive therapy of HCS is crucial as it often has high morbidity and mortality potential. Presentation: No date and time listed

Prognostic biomarkers and immune cell infiltration characteristics in small cell lung cancer

BackgroundSmall cell lung cancer (SCLC) is a highly malignant and aggressive neuroendocrine tumor. With the rise of immunotherapy, it has provided a new direction for SCLC. However, due to the lack of prognostic biomarkers, the median overall survival of SCLC is still to be improved. This study aimed to explore novel biomarkers and tumor-infiltrating immune cell characteristics that may serve as potential diagnostic and prognostic markers in SCLC. MethodsGene expression profiles from patients with SCLC were downloaded from the Gene Expression Omnibus (GEO) database, and tumor microenvironment (TME) infiltration profile data were obtained using CIBERSORT. The robust rank aggregation (RRA) method was utilized to integrate three SCLC microarray datasets downloaded from the GEO database and identify robust differentially expressed genes (DEGs) between normal and tumor tissue samples. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to explore the functions of the robust DEGs. Subsequently, protein–protein interaction networks and key modules were constructed by Cytoscape, and hub genes were selected from the whole network using the plugin cytoHubba. Survival analysis of hub genes was performed by Kaplan–Meier plotter in 18 patients with extensive-stage SCLC. ResultsA total of 312 robust DEGs, including 55 upregulated and 257 downregulated genes, were screened from 129 SCLC tissue samples and 44 normal tissue samples. GO and KEGG enrichment analyses revealed that the robust DEGs were predominantly involved in human T-cell leukemia virus 1 infection, focal adhesion, complement and coagulation cascades, tumor necrosis factor (TNF) signaling pathway, and ECM-receptor interaction, which are closely associated with the development and progression of SCLC. Subsequently, three DEGs modules and six hub genes (ITGA10, DUSP12, PTGS2, FOS, TGFBR2, and ICAM1) were identified through screening with the Cytoscape plugins MCODE and cytoHubba, respectively. Immune cell infiltration analysis by the CIBERSORT algorithm revealed that resting memory CD4+ T cells were the predominant infiltrating immune cells in SCLC. In addition, Kaplan–Meier plotter revealed that the gene prostaglandin-endoperoxide synthase 2 (PTGS2) was a potential prognostic biomarker of SCLC. ConclusionsHub genes and tumor-infiltrating immune cells may be the molecular mechanisms underlying the development of SCLC, and this finding could contribute to the formulation of individualized immunotherapy strategies for SCLC.

Unresectable Mesenteric Mass Causing Small Bowel Obstruction

Small bowel obstruction (SBO) has a variety of etiologies, including but not limited to adhesions, malignancy, hernia, and inflammatory bowel diseases. Treatment for SBO may be nonoperative or operative, depending on the underlying condition and clinical symptoms. Clinical judgment and radiological findings cooperate in formulating an appropriate assessment and treatment plan. Mass effect due to malignancy is an indication for surgical intervention, as tumor resection is a mainstay of treatment. However, patient safety and chances of vascular compromise must be considered when determining if the tumor is resectable. Reported is a case of a 65-year-old female with severe abdominal pain, nausea, vomiting, and obstipation due to a malignant neuroendocrine tumor within the mesentery adjacent to the aortic bifurcation. Management included surgical intervention to alleviate bowel obstruction and biopsy of the tumor.

TU4.8 An Analysis of Rectal Cancer Patient Treatment and Outcomes in a large NHS Trust

Abstract Introduction Rectal cancer (RC) is a common cancer in the UK. Treatment options include surgery, chemotherapy, radiotherapy or a combination of these in the form of neoadjuvant or adjuvant treatment. Aim To analyse the treatment type and outcomes of our RC patients. Methods We performed an analysis of prospectively collected data on patients diagnosed with RC between Jan-2013 and Dec-2020 in our trust. Details included demographics, histology, staging, treatment and mortality. Twenty patients out of 1202 were excluded due to missing information leaving 1182 for further analysis. Results 404 patients did not receive resectional surgery due to patient choice (30), inoperability of the tumour (259), or co-morbidity (115). A total of 778 patients were found to have operable disease with TNM staging as follows; Stage1–291, Stage2–231, Stage3–217, Stage4–39. Among them 302 went on to receive neo-adjuvant treatment of which 67 (22.2%) had a complete response to treatment (ypT0). The remaining 476 patients received primary surgery; 268 did not require any additional treatment and 199 went on to have adjuvant chemo/radiotherapy. Nine patients had further intervention due to incomplete resection or disease recurrence. The majority of the tumours were adenocarcinomas (97%). Other types included; malignant melanoma, neuroendocrine tumours, and squamous cell carcinomas. The overall 1-year and 5-year mortality for the group receiving primary surgery were 5.0% and 20.4%. In the neoadjuvant group these were 3.6% and 20.9%. Conclusion We present data from a large NHS trust demonstrating a multimodal approach which has enabled us to achieve good overall outcomes.

Gastric Neuroendocrine Tumors With Parietal Cell Atrophy in a Long-term Carcinogenicity Study in Rats.

Malignant neuroendocrine tumors were diagnosed in the stomach of two out of sixty female Sprague-Dawley rats treated for 89 weeks with a high dose of a novel, small molecule, cannabinoid-1 antagonist. The tumors were associated with parietal cell atrophy accompanied by foveolar hyperplasia of the glandular stomach mucosa. Parietal cell atrophy/foveolar hyperplasia was considered test article related at the high dose, given the higher incidence and severity relative to untreated controls, although the precise mechanism of the parietal cell atrophy was undetermined. Spontaneous gastric neuroendocrine tumors are very rare in rats, and the current cases were considered secondary to parietal cell atrophy causing reduced gastric acid secretion and subsequent overstimulation of gastrin release through a feedback loop.