Neuroendocrine Tumors Of Pancreas Research Articles

Severe gastroenteritis as presentation of a neuroendocrine tumor of pancreas

Pancreatic neuroendocrine tumors (PanNETs) are a very rare entity, corresponding to 1-2% of all pancreatic neoplasms, although incidence and prevalence are rising. According to hormonal production, they can be functional or nonfunctional, leading to a subset of symptoms. A 45-year-old man, came to our emergency department complaining of vomiting and profuse non-bloody diarrhea for a week, with asthenia and no improvement with medication. He presented with diminished muscular strength and severe electrolytic changes with electrocardiographic repercussion. Patient was admitted to our intensive care unit (ICU) for hypovolemic and distributive shock due to a severe gastroenteritis. Further research studies were carried out which have shown a nodular structure of 5x4cm in the pancreas tail on computed tomography scan. A biopsy was made, and a histopathological exam revealed a pancreatic well differentiated neuroendocrine tumor. Hormonal analysis showed an elevation on vasoactive intestinal polypeptide (VIP). On 68Ga-DOTA-NOC PET/CT, there were 2 nodular lesions with anomalous overexpression of somatostatin receptors, one in the pancreatic tail near splenic hilum and another in the pancreatic head. Patient underwent a total pancreaticoduodenectomy with en bloc splenectomy. Postoperative period was uneventful. Mostly, this kind of pancreatic neuroendocrine tumors are indolent, but till 39% can have an aggressive course, so they have variable prognosis.

APPLICATION OF ENDOSCOPIC ULTRASOUND GUIDED FNAC(EUS-FNAC) IN DIAGNOSING PANCREATIC MASS LESIONS

Introduction: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNAC) has become an important modality for identification of pancreatic masses. It is a minimally invasive procedure that provides excellent cell yield even in deep seated lesions. The preoperative diagnosis of pancreatic mass by EUS-FNAC can help the surgeons in early detection and confirmation of neoplasm as pancreatic mass lesions are highly concerning for pancreatic carcinoma. This study was aimed at application of EUS-FNAC in diagnosing pancreatic mass lesions. Methods: A study was conducted for 20 cases who underwent EUS guided FNAC for pancreatic mass lesions. EUS-FNAC was performed by using a curvilinear array echo endoscope. The technique was carried out by a skilled endoscopist, and the glass slides were used to make smears from fluid that was aspirated containing corpuscular fractions. The slides were air dried before being examined cytopathologically. Results: Out of 20 cases,10 were of pancreatic Ductal adenocarcinoma, 3 of Neuroendocrine tumor of pancreas, 2 of Acinar cell carcinoma, 1 of Solid pseudopapillary tumor, 2 of Serous cystadenoma and 2 of Mucinous cystadenoma. This was confirmed later, on further Immunocytochemical stains. Conclusions:Out of 20 cases, 16 were malignant and 4 were benign. EUS-FNAC can help in early diagnosis and can improve the patient outcome. It is safe, cost-effective and reliable. It not only gives precise cytological diagnosis, but it also allows for the exact site of tiny lesions.

Small pancreas neuroendocrine tumors: How small is small?

Objective: The current study aimed to investigate the issues in contemporary management strategies that focus on small pancreatic neuroendocrine tumors (PNETs). Data Sources and Study Selection: We searched various scientific databases using specific keywords. Results: Surveillance-only strategies were considered for selected patients. The exact cut-off value of small neuroendocrine tumors for surveillance-only strategies needs to be verified with additional high-level evidence. Conclusion: There is no consensus on the size and treatment strategy for small PNETs currently. Patients with small nonfunctioning PNETs require individualized recommendations for surgery versus active surveillance based on tumor size, radiographic characteristics, and patient characteristics, such as age and comorbidities and also patient references.

Categorizing Malignant Small Round Cell Tumors in Aspiration Cytology: An Institutional Experience.

The study aims to categorize malignant small round cell tumors (MSRCTs) originating in various sites of the body with the objective of utilization of cytomorphological features and ancillary techniques. It is a cross-sectional study conducted over a time span of 3 years (2017-2020). 33 cases of tumors with round cell morphology were evaluated by fine needle aspiration cytology (FNAC). The application of cell block preparation supported by immunohistochemistry aided in the categorization of 23 cases with definite diagnosis and the rest were reported as MSRCTs. Among the categorized 23/33 cases, the most common diagnosis was Ewing's sarcoma (7/23) followed by 6 cases of lymphoma. There were 2 cases each of rhabdomyosarcoma and Langerhans cell histiocytosis (LCH) and 1 case each of neuroblastoma, desmoplastic small round cell tumor (DSRCT), myeloid sarcoma, neuroendocrine tumor of pancreas, plasmacytoma, and small cell carcinoma. Histopathology confirmation was available in 24/33 cases. Among the categorized tumors (23/33), biopsy correlation was available in 19 cases, of which concordant result was seen in 17 cases (89.47%), which were 6 cases of lymphoma, 5 cases of Ewing's sarcoma (EWS), 2 of rhabdomyosarcoma, and 1 each of neuroblastoma, small cell carcinoma, DSRCT, and LCH. Discordant result was seen in one case of rhabdomyosarcoma and a case of synovial sarcoma reported as extraskeletal EWS in cytology. Out of the uncategorized cases reported as MSRTCs, histopathology was available in 5 cases which were diagnosed as rhabdomyosarcoma (1 cases), lymphoma (1 case), amelanotic melanoma (1 case), and extraskeletal EWS (2 cases). Categorization of MSRCTs should be done to implement appropriate therapeutic protocol. FNAC provides a rapid diagnosis contributing immensely for the timely management of the patient. Detailed cytomorphological evaluation serves as a guide for further evaluation by ancillary techniques leading to definitive diagnosis.

Nationwide registry for patients with neuroendocrine neoplasm of pancreas, gastrointestinal tract, lungs, bronchi, or thymus in Japan

BackgroundNeuroendocrine neoplasm (NEN) is a comparatively rare tumor that has been considered indolent. Due to these characteristics, detailed epidemiological data have not been analyzed in Japan. To elucidate the present status of NEN diagnosis and treatment in Japan, we started a registry cohort study in January 2015.MethodsPatients pathologically diagnosed with NENs of the pancreas, gastrointestinal tract, lungs, bronchi, or thymus after January 2012 were enrolled in this registry after the date of ethics review committee approval in each hospital or institute. Follow-up was continued for enrolled patients.ResultsDuring 5 years of enrollment between January 2015 and December 2019, a total of 1526 participants from 63 departments were enrolled in this registry (mean, 305.2 participants/year), covering approximately 5.8% of the annual incidence of NENs in Japan. For pancreatic NEN, 41.9% of patients had metastasis and the dominant metastatic site was the liver, at twice the rate of lymph node metastasis in the current registry. In contrast, the frequency of lymph node metastasis from gastrointestinal (GI)-NEN was similar to that of the liver. The distribution of WHO 2019-based grades varied according to the primary site. Low-to-intermediate grade (G1–G2) was dominant for duodenal, jejunal/ileal, rectal, and pancreatic NENs, whereas high grade (G3 or NEC) was dominant for esophageal, stomach, and colon NENs. For PanNENs, G3 and NEC accounted only for 1.6% and 2.9%, respectively.ConclusionsThese cohort data provide crucial information for clinical research to clarify the characteristics of NENs in Japan.

Identification of a VHL gene mutation in atypical Von Hippel-Lindau syndrome: genotype\u2013phenotype correlation and gene therapy perspective

BackgroundClassical von Hippel Lindau (VHL) disease/syndrome includes CNS hemangioblastoma, renal or pancreatic cysts, pheochromocytoma, renal carcinoma and exodermic cystadenoma. The syndrome is caused by mutation of VHL tumor suppressor gene. The most prevalent mutations are present in VHL syndrome. To date, > 500 mutations of gene related to the progression of VHL syndrome have been reported. VHL gene mutation presented in single lung or pancreatic tumor has been reported occasionally, but there is no report of both.MethodsIn this paper, we used CT scan, pathological and genetic examination methods to diagnose a rare atypical VHL syndrome.ResultsWe reported a rare case of atypical VHL syndrome with authenticated VHL mutation at p.Arg167Gln, that was associated with not only bilateral pheochromocytoma but also lung carcinoid and neuroendocrine tumor of pancreas. Based on literature reviews, the patient was recommended to be further subjected to octreotide-based radionuclide therapy.ConclusionsCombined with gene detection and clinical diagnosis, we found the inherent relationship between VHL genotype and phenotype, and constructed the standard diagnosis and treatment process of disease with rare VHL mutation from the perspective of gene therapy.

Abstract 2216: Exploration of the genomic features of pan-neuroendocrine tumors in a Chinese retrospective analysis

Abstract Background: A neuroendocrine tumor (NET) begins in the specialized cells of the body's neuroendocrine system. Most NETs take years to develop and grow slowly. However, some NETs can be fast-growing. NETs can occur in any part of the body, including gastrointestinal (GI) tract (43%), lung (30%), pancreas (7%) and other organs. Here, we reported an analysis of genomic features in 16 GI tract, 45 lung and 13 pancreas NETs. Methods: Patients (pts) with neuroendocrine tumors were enrolled, and surgical tumor tissues or plasma samples were collected. Mutation profiling was performed by next-generation sequencing (NGS). Results: Compared with GI tract NETs patients (Age±SD, 52±11.2), lung NETs patients (Age±SD 62±8.4, P< 0.001) occurred in older patients, and the median age (±SD) of pancreas NETs patients was 58 (±10.8). Mutations were identified in 66 of NETs patients (89.19%), including 12 GI tract (75%), 43 lung (95.56%) and 11 pancreas (84.62%) NETs. Mutations of TP53 (43.85%, 7/16), APC (31.25%, 5/16) and KRAS (25%, 4/16) in GI tract NETs; TP53 (80%, 36/45), LRP1B (24.44%, 11/45) and EGFR (20%, 9/36) in lung NETs and MEN1 (30.77%4/13) in pancreas NETs were observed as the most commonly genetic variations in different type of NETs, which located in different signal pathways and suggested different pathogenesis. Meanwhile, there was no MEN1 mutations and only one LRP1B or EGFR mutation (6.25%, 1/16) occurring in GI tract NETs, one MEN1 mutation (2.22%, 1/44) occurring in lung NETs, and one TP53, KRAS or LRP1B mutation (7.69%, 1/12) and no APC or EGFR mutations occurring in pancreas NETs. In total, although gastrointestinal tract, lung and pancreas NETs all begin in the cells, which have traits of both hormone-producing endocrine cells and nerve cells, the mutation spectrums are very different. On the contrary, the mutations carried by NETs in different locations are related to the organ. Conclusions: In summary, genomic characterization of NETs may offer insights into tumorigenesis and identify potential therapeutic targets in this disease. Citation Format: Jinyan Ye, Weiran Wang, Danhua Wang, Tonghui Ma. Exploration of the genomic features of pan-neuroendocrine tumors in a Chinese retrospective analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2216.

Essential Role of the 14q32 Encoded miRNAs in Endocrine Tumors.

Background: The 14q32 cluster is among the largest polycistronic miRNA clusters. miRNAs encoded here have been implicated in tumorigenesis of multiple organs including endocrine glands. Methods: Critical review of miRNA studies performed in endocrine tumors have been performed. The potential relevance of 14q32 miRNAs through investigating their targets, and integrating the knowledge provided by literature data and bioinformatics predictions have been indicated. Results: Pituitary adenoma, papillary thyroid cancer and a particular subset of pheochromocytoma and adrenocortical cancer are characterized by the downregulation of miRNAs encoded by the 14q32 cluster. Pancreas neuroendocrine tumors, most of the adrenocortical cancer and medullary thyroid cancer are particularly distinct, as 14q32 miRNAs were overexpressed. In pheochromocytoma and growth-hormone producing pituitary adenoma, however, both increased and decreased expression of 14q32 miRNAs cluster members were observed. In the background of this phenomenon methodological, technical and biological factors are hypothesized and discussed. The functions of 14q32 miRNAs were also revealed by bioinformatics and literature data mining. Conclusions: 14q32 miRNAs have a significant role in the tumorigenesis of endocrine organs. Regarding their stable expression in the circulation of healthy individuals, further investigation of 14q32 miRNAs could provide a potential for use as biomarkers (diagnostic or prognostic) in endocrine neoplasms.

Mixed neuroendocrine-non-neuroendocrine neoplasms (MiNEN) of pancreas: a rare entity

Introduction: Mixed neuroendocrine-non-neuroendocrine neoplasms (MiNEN) comprise of both epithelial and neuroendocrine component in which each element has to comprise at least 30% of the tumor. MiNEN usually involve various gastrointestinal organs, however it is very infrequent in pancreas. Case Presentation: We encountered an 81-year-old male patient who presented with pain in upper abdomen since 3 months. He noticed jaundice with cholestatic features for last 15 days which was associated with anorexia and weight loss. Liver function test revealed: Bilirubin-3.8mg/dl; AST- 76 U/L; ALT- 163 U/L; Alkaline phosphatase- 826 IU/L, while carbohydrate antigen 19-9 was 46.9 U/ml. CECT abdomen reported a mass in the pancreatic head with dilated common bile duct and pancreatic duct. He underwent pancreatoduodenectomy (PD) with uneventful post-operative course. Histopathological examination revealed two different tumours: ductal adenocarcinoma admixed with neuroendocrine tumour of pancreas which was confirmed with immunohistochemistry (CK-7, Chromogranin and Synaptophysin positive). He received adjuvant chemotherapy and at the end of six months follow up, he has no recurrence. Conclusion: MiNEN is a rare malignancy of pancreas for which pancreatoduodenectomy was performed and diagnosis confirmed on histopathology with immunohistochemistry. It is important to share all individual experience-based information of such anecdotal cases to get knowledge about their clinical and biological behaviour and to standardize optimal therapy.

Multiple Functional Neuroendocrine Tumors of Pancreas and Duodenum Managed by Robotic Totally Duodenumpancreatectomy

Multiple Functional Neuroendocrine Tumors of Pancreas and Duodenum Managed by Robotic Totally Duodenumpancreatectomy

Out-of-pocket spending (OOPS) and financial toxicity survey for neuroendocrine tumor (NET) patients.

632 Background: Incidence and prevalence of neuroendocrine tumors (NETs) are on the rise. However, with the increasing burden of the disease, there is a need to understand financial toxicity associated with NET management. Especially the out of pocket spending or expenses made by patients and family members, which affects the management and treatment adherence. We report results of our prospective online survey based study looking into determinants and the burden of financial toxicity in NET patients. Methods: We collaborated with NCAN (Neuroendocrine Cancer Awareness Network) a national NET patient support group for our prospective online questionnaire-based survey. After IRB approval, NCAN disseminated online link to the survey on their webpage. The survey had twenty-one questions with the goal of at least 200 complete responses. Results: We received 215 responses before we decided to stop the survey for analysis. The average age of the respondents was 58.4 years. 75% of respondents were females with most repsondents of the survey (37%) being graduates. About 41% of respondents had small bowel NET while 27% had pancreas NET as their NET diagnosis. The median income of the respondents was $65000/year. Median oncology visits were reported to be 4 per year. Median co-pay for the NET specialist visit was found to be $30. The median spending on travel for the physician`s appointment was $250 per visit to see NET specialists. Median monthly insurance premium was $300. Study participants reported spending $75 out of pocket on NET related care every month on top of insurance premiums. More than half of the respondents were on Somatostatin analogues only as their main treatment. About 21% mentioned that they were not able to get required treatment due to cost related issues. Conclusions: The preliminary analysis of the survey gave us an insight into financial toxicity related to NET management. Although most NETs are indolent, the chronic nature of disease and associated, symptom management is often time and resource-intensive. Many patients mentioned having issues with the coverage of insurance and having to travel a long distance to see a NET specialist, which demonstrate a lack of access to NET specialists.

Neuroendocrine tumor of Pancreas: Which modality is better, 320-MDCT or 3T-MRI?

Background: Significant improvement in the spatial and temporal resolution of CT have been made over the past decade, with advent of multidetector row CT (MDCT). Also, the increased spatial resolution of the 3T-MRI allows for high-quality abdominal imaging. Therefore, neuroendocrine tumors of pancreas (PNET) and their metastasis are increasingly diagnosed on imaging studied performed for unrelated purposes. Our purpose of this study is to find out the good modality to detect PNETs. Material and Methods: We selected 11 PNETs. Four of the 11 PNETs were diagnosed as NET G2, and seven of the 11 PNETs were diagnosed as NET G1. We took both 320-MDCT and 3T-MRI for all patients before surgery. We used pancreatic protocol CT with and without intravenous contrast. We made 5 kind of CT image such as non-contrast image, early-arterial phase (25sec), late-arterial phase (40sec), portal phase (70sec) and venous phase(180sec). All CT slices were made of 1mm. About 3T-MRI, we selected 2 kind of images, diffusion-weighted image (DWI) and T2 weighted image (T2WI). Slice thickness of both DWI and T2 weighted image was 3mm. We compared CT image with DWI and T2WI. Results: Seven of the 11 PNETS were diagnosed on both CT, DWI and T2WI. All 7 PNETs showed well-enhanced on late-arterial phase on CT and high signal intensity on both DWI and T2WI. Three of the 11 PNETs were able to detect on CT and DWI. All 3 PNET showed iso-signal intensity as compared to the normal pancreas. One of the 11 PNET was able to detect on DWI and T2WI. The PNET showed the same enhancement as the normal pancreatic parenchyma on all phase CT. Conclusion: DWI was the most sensitive image to detect PNET. High cell density PNETs with moderate vascularity may show atypical PNETs on CT and MRI.

Solving up the jigsaw puzzle: Necrolytic Migratory Erythema Associated with Multifocal Neuroendocrine Tumor of Pancreas, A case report.

Introduction: Necrolytic migratory erythema (NME) is a disorder that is recognized by reddish, migrating areas of blistering that heal with pigmentation. It is a characteristic rash that is often recognized by its distinct appearance and history. It has strong association with glucagonoma, a pancreatic neuroendocrine tumor arising from the alpha type islet cells. In such cases NME presents as a paraneoplastic manifestation of the disease. The diagnosis of this rare tumor depends on high index of suspicion on the basis of history and examination and relevant pathological and radiological investigations. This tumor is potentially curable by surgery. Case Presentation: In this article the authors describe a 36 years old female patient with NME and a multifocal pancreatic neuroendocrine tumor with clinical features of glucagonoma syndrome. After investigations she underwent total pancreatectomy and within a few days her skin lesions and clinical symptoms started improving. Conclusion: Prompt diagnosis and management are of paramount importance in the management of glucagonoma. It is possible if there is high index of suspicion and the management is done appropriately.

68Ga]Ga-NOTA-MAL-Cys39-exendin-4, a potential GLP-1R targeted PET tracer for the detection of insulinoma

Glucagon-like peptide-1 receptor (GLP-1R) is a kind of G protein coupled receptor which regulates the insulin secretion and serves as potential target in the diagnosis of functional pancreas neuroendocrine tumor. The aim of this study was to evaluate the feasibility of GLP-1R targeted tracer [68Ga]Ga-NOTA-MAL-Cys39-exendin-4 in the detection of insulinoma. MethodsNOTA-MAL-Cys39-exendin-4 was synthesized and then radiolabeled with gallium-68 in iQS® Ga-68 Fluidic Labeling Module. The in vitro binding affinity and cell uptake studies were evaluated in INS-1 cells. The in vivo micro-PET/CT imaging and biodistribution studies were performed on INS-1 xenograft tumor models. Results[68Ga]Ga-NOTA-MAL-Cys39-exendin-4 can be efficiently radiolabelled with a yield of about 85% (non-decay corrected) and radiochemical purity of >95% with a favorable stability. The molar activity was at least 145.5 GBq/μmol. The affinity (IC50) for [68Ga]Ga-NOTA-MAL-Cys39-exendin-4 was 12.99 ± 0.81 nM. Micro-PET/CT images showed intense tumor uptake with good contrast to background. Biodistribution study showed the predominant uptake was in the kidney, followed by pancreas, and the liver and spleen just showed mild uptake in the blood-pool phase with rapid clearance. At 1 h post- injection, the tumor to blood, muscle and pancreas ratios were 30.64, 40.21 and 6.46, respectively. Blocking studies showed significantly decreased tumor uptake, which further confirmed binding affinity of [68Ga]Ga-NOTA-MAL-Cys39-exendin-4 to GLP-1R. Conclusion[68Ga]Ga-NOTA-MAL-Cys39-exendin-4 was easily synthesized with high yield, favorable biodistribution and high affinity to islet tumor cell, making the tracer may have great potential in the detection of GLP-1R positive tumor such as an insulinoma.

Uniform and Robust Nuclear Expression of HES1 in Neuroendocrine Neoplasms.

Introduction. Neuroendocrine neoplasms (NENs) are neoplasms that most commonly arise from gastrointestinal tract, pancreas, and lung. HES1 is a downstream target of Notch signaling pathway. The current literature about HES1 expression in NENs is sparse and inconsistent. Methods. In this study, we evaluated HES1 expression by immunohistochemistry in a total of 32 cases of NENs, including 13 well-differentiated neuroendocrine tumors from gastrointestinal tract, 10 cases of well-differentiated neuroendocrine tumors of pancreas, 9 cases from lung, including 4 cases of typical carcinoid, 1 case of atypical carcinoid, and 4 cases of neuroendocrine carcinoma. The intensity of the stain was scored from - to +++, and the distribution of the staining of HES1 was evaluated. Results. HES1 demonstrates uniform robust (+++) nuclear staining pattern in the tumor cells of all the NENs (32/32), regardless of the origin of the system and the grade of the tumor. Conclusions. HES1 is uniformly expressed in NENs with robust nuclear expression pattern. Our finding suggests that NOTCH1 or HES1 inhibitor is a potential therapeutic choice for neuroendocrine neoplasms.

Validation of the 8th AJCC Cancer Staging System for Pancreas Neuroendocrine Tumors Using Korean Nationwide Surgery Database.

PurposeThe 8th edition of the American Joint Committee on Cancer (AJCC) staging system for pancreatic neuroendocrine tumor (PNET) included several significant changes. We aim to evaluate this staging system compared to the 7th edition AJCC staging system and European Neuroendocrine Tumors Society (ENETS) system.Materials and MethodsWe used Korean nationwide surgery database (2000-2014). Of 972 patients who had undergone surgery for PNET, excluding patients diagnosed with ENETS/World Health Organization 2010 grade 3 (G3), only 472 patients with accurate stage were included.ResultsPoor discrimination in overall survival rate (OSR) was noted between AJCC 8th stage III and IV (p=0.180). The disease-free survival (DFS) curves of 8th AJCC classification were well separated between all stages. Compared with stage I, the hazard ratio of II, III, and IV was 3.808, 13.928, and 30.618, respectively (p=0.007, p < 0.001, and p < 0.001). The curves of OSR and DFS of certain prognostic group in AJCC 7th and ENETS overlapped. In ENETS staging system, no significant difference in DFS between stage IIB versus IIIA (p=0.909) and IIIA versus IIIB (p=0.291). In multivariable analysis, lymphovascular invasion (p=0.002), perineural invasion (p=0.003), and grade (p < 0.001) were identified as independent prognostic factors for DFS.ConclusionThis is the first large-scale validation of the AJCC 8th edition staging system for PNET. The revised 8th system provides better discrimination compared to that of the 7th edition and ENETS TNM system. This supports the clinical use of the system.

Ultrastructural comparative analysis of neuroendocrine tumors of pancreas

Detection of ultrastructural distinctions of tumor cells and cell-to-cell cooperation in insulinomas and nonfunctioning neuroendocrine tumors of pancreas. Ultrastructural study of 38 insulinomas and 35 nonfunctioning neuroendocrine tumors of pancreas of the patients treated at Vishnevskiy Surgery Institute from 2010 to 2015. Insulinomas are characterized by high differentiation of intracellular organelles and specific secretory granules. In insulinomas the number of immature endocrine granules exceeded the number of mature granules. The tumor cells were often joined together and held with desmosomes ensuring very tight connection. Desmosome complexes were characterized by their extended length. Such ultrastructural changes were not followed by destruction of tumor cells. There was formation of specific syncytium-like structures consisting of cells connected by cytoplasmic channels with the common cytoplasm with cell organelles. In nonfunctioning tumors the most of the granules were distinguished by polymorphism and had no specific ultrastructure indicating the synthesized hormone. In large areas there were loss of plasmolemma integrity, up to its complete absence, which led to unification of cytoplasmic contents of the cells. Common junctions dominated in nonfunctioning tumors. Desmosomes were rare, poorly developed, and in the form of immature and reduced junctions. Complex cellular junctions are well developed in the cells, ensuring tight connection of tumor cells, reducing their invasive and metastatic potential. Nonfunctioning neuroendocrine tumors on the contrary are characterized by underdevelopment of cellular organelles and immaturity of secretory granules. Predominance of weak direct cell junctions, rupture of membranes of neighboring cells with simultaneous reduction of desmosomes facilitate the migration of individual tumor cells and formation of metastases.

The short-term outcomes of primary tumor resection with synchronous metastases from pancreas neuroendocrine tumors: an analysis of the ACS-NSQIP registry

Background: The incidence of pancreatic neuroendocrine tumors (PNET) is rising worldwide, with many patients developing metastatic disease. Resection of the primary tumor despite of unresectable metastases is suggested to improve long-term oncologic outcomes. Assessments of the morbidity of this approach are scarce and limited to small, single-institutional studies. We sought to determine the patient characteristics and short-term outcomes of pancreatectomy for metastatic (M1) PNET, and compare them to non-metastatic (M0) PNET. The comparison was undertaken to provide a reference with which providers are familiar – i.e. outcomes of pancreatectomy for M0 disease, to better appreciate the burden of complications with M1. Methods: We conducted a retrospective cohort study using the ACS-NSQIP targeted pancreatectomy registry. We included all adults undergoing pancreatectomy for PNET between 2014-2016, with complete staging information. M1 and M0 PNET groups were created. Primary outcomes were 30-day major morbidity, mortality, and prolonged length of stay (>75th percentile). The characteristics and outcomes of M1 and M0 groups were compared using Pearson Chi square, Fisher exact test, and Student t test, as appropriate. A propensity score was created with the following potential confounders defined a priori: age, sex, body mass index, ASA classification, T and N stage, surgical procedure, open approach, and functional histology. The association between M1 and outcomes was adjusted for the propensity score using logistic binomial regression. Results: Of 1,381 included patients, 148 (12%) had M1 disease. Patients with M1 were more likely to be younger, have lower hematocrit, higher ASA class, lower body mass index, and have pre-operative weight loss, than M0 patients (all p < 0.05). T1/2 (75.7% vs. 28.8%, p < 0.01), node positive (72.3% vs. 25.9%, p < 0.01), and functional (29.7% vs. 22.1%, p = 0.04) tumors were more common in the M1 group. There were no differences in the type of pancreatectomy (distal pancreatectomy 60.1% Vs. 57.3%, p = 0.46), but there were more open resections (78.4% vs. 55.5%, p < 0.01) and longer median operating time (322.5 vs. 261 minutes, p < 0.01) for M1. No significant difference was detected in overall 30-day major morbidity (38.5% vs. 39.7%, p = 0.77) and mortality (2.7% vs. 1.0%, p = 0.06) between groups. Prolonged length of stay was more common with M1 (35.1% vs. 25.8%, p = 0.01). Adjusted regression analysis revealed no independent association between M1 and 30-day morbidity (relative risk 0.90, 95% confidence interval: 0.71–1.14), or prolonged length of stay (relative risk 2.89, 95% confidence interval: 0.78–10.7). Regression was not conducted on mortality due to too few events. Conclusion: In a multi-institutional analysis of prospectively collected data, resection of the primary tumor for M1 PNET was not associated with different post-operative morbidity and mortality than for M0 disease. The knowledge of short-term outcomes provided herein is important to weigh perioperative risks against the potential benefits of PNET primary tumor resection in the setting of M1 disease. This can support both decision-making and patient counselling.

Median Pancreatectomy

Summary: Surgical resections traditionally involves pancreaticoduodenectomy and distal pancreatectomy, leading to substantial loss of unaffected endocrine and exocrine tissue of pancreas. They are also associated with significant morbidity (diabetes). To minimize the loss of normal pancreatic tissue, limited resections in the form of central (median) pancreatectomy may be done alternatively. We would hereby like to submit the surgical video of this procedure. Case: A 62 yr female without comorbidities, and being symptomatic with intermittent pain abdomen of 45 days duration. Patient was evaluated with ultrasound and CT abdomen which revealed heterogenous enhancing solid lesion in pancreatic neck. Endoscopic ultrasound was done which was suggestive of pancreatic head mass. Needle aspiration cytology revealed neuroendocrine tumour. After pre-operative work up, patient underwent Open Median(Central) pancreatectomy. Intra-operatively a 1.5x1.5 cm firm mass was found at the neck of pancreas. Rest of abdominal findings were normal. Pancreatic duct was dilated. Continuity of distal pancreas was established using a Roux en Y jejunal limb which was anastomosed with pancreatic duct. Blood loss of 250 ml. Immediate perioperative period was uneventful. As an institutional protocol, feeding jejunostomy was placed in the jejunum. Feeds were started on post-operative day(POD)-3 through feeding jejunostomy and was progressively tapered as oral ingestion improved satisfactorily. Histopathological report was suggestive of Grade I, Neuroendocrine tumour of pancreas. Patient had grade II complication according to Clavien Dindo grading system. Follow-up till 16 months patient is alive having an event free survival. Conclusion: Limited pancreatic resections such as central (median) pancreatectomy may be done in selected cases with pancreatic neuro-endocrine and benign tumors affecting neck and body of pancreas with advantages of retaining uninvolved portions of pancreas.

Pancreas Neuroendocrine Tumor and Its Mimics: Review of Cross-Sectional Imaging Findings for Differential Diagnosis

Pancreas Neuroendocrine Tumor and Its Mimics: Review of Cross-Sectional Imaging Findings for Differential Diagnosis