Prognostic factors of patients with gastroenteropancreatic neuroendocrine neoplasms

There is an increasing trend in the incidence of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) worldwide. The aim of the present study was to identify the prognostic factors of patients with GEP-NENs. A cross-sectional, retrospective chart review study was conducted among patients with pathologically proven GEP-NENs between January 2003 and December 2016 at Kaohsiung Chung-Gung Memorial Hospital. A total of 97 patients who met the inclusion criteria were included (male/female = 56/41, age: 57.7 ± 15.4 years). The presentation, clinical characteristics, and disease outcomes were reviewed and analyzed. The most common primary site of the GEP-NENs was the rectum (49.5%), followed by the pancreas (17.5%), duodenum (11.3%), stomach (10.3%), colon (6.2%), and appendix (5.2%), and most GEP-NENs were hormonally nonfunctional (94.8%). There were 56 tumors classified as G1 neuroendocrine tumors (NETs), 9 as G2 NETs, and 14 as G3 neuroendocrine carcinoma (NEC). Metastasis was found in 15 patients (15%). Curative treatments, such as surgery or endoscopic resection, were performed in 83.5% of patients (n = 81). The mean overall survival duration was 107.2 ± 7.8 months. The estimated 3- and 5-year overall survival rates for all patients were 84% and 82%, respectively. Logistic regression analysis showed that large tumor size, non-rectal NENs, high histopathological grading, lymphatic metastases and distant metastases were associated with poor survival. This study suggested that the presence of lymphatic or distant metastases at diagnosis is an independent risk factor for poor prognosis in patients with GEP-NENs.     

Diagnosis,treatment, and current concepts in the endoscopic management of gastroenteropancreatic neuroendocrine neoplasms

Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are rare tumors derived from the neuroendocrine cell system, which that have increased in incidence and prevalence in recent years. Despite improvements in radiological and metabolic imaging, endoscopy still plays a pivotal role in the number of GEP-NENs. Tumor detection, characterization, and staging are essential in management and treatment planning. Upper and lower gastrointestinal (GI) endoscopy is essential for correct localization of the primary tumor site of GI NENs. Endoscopic ultrasonography (EUS) has an important role in the imaging and tissue acquisition of pancreatic NENs and locoregional staging of GI neuroendocrine tumors. Correct staging and histological diagnosis have important prognostic implications. Endoscopic operating techniques allow the removal of small GI NENs in the early stage of mucosal or submucosal invasion of the intestinal wall. Preoperative EUS-guided techniques may help the surgeon locate small and deep tumors, thus avoiding formal pancreatic resections in favor of parenchymal-sparing surgery. Finally, locoregional ablative treatments have been proposed in recent studies with promising results in selected patients.     

Immunotherapies for well-differentiated grade 3 gastroenteropancreatic neuroendocrine tumors: A new category in the World Health Organization classification

According to the 2019 World Health Organization (WHO) classification, well-differentiated grade 3 (G3) gastroenteropancreatic (GEP) neuroendocrine tumors (NETs) are a new category of cancer of the digestive system. G3 GEP-NET research and treatment are not as robust as those of lower grade (G1/2) NETs and poorly differentiated neuroendocrine carcinomas (NECs). Previously, the management of high-grade NETs was mainly based on NEC therapies, as high-grade NETs were classified as NECs under the previous WHO classification. Despite this, G3 GEP-NETs are significantly less responsive to platinum-based chemotherapy regimens than NECs, due to their distinct molecular pathogenesis and course of pathological grade transition. Patients with advanced G3 GEP-NETs, who have progressed or are intolerant to chemotherapy regimens such as capecitabine plus temozolomide, have limited treatment choices. Immunotherapy has helped patients with a variety of cancers attain long-term survival through the use of immune checkpoint inhibitors. Immunotherapies, either alone or in combination with other therapies, do not have a clear function in the treatment of G3 GEP-NETs. Currently, the majority of immunotherapy studies, both prospective and retrospective, do not reliably differentiate G3 GEP-NETs from NECs. By contrast, a significant number of studies include non-GEP neuroendocrine neoplasms (NENs). Therefore, there is an urgent need to summarize and evaluate these data to provide more effective therapeutic approaches for patients with this rare tumor. The purpose of this mini-review was to screen and summarize information on G3 GEP-NETs from all studies on NENs immunotherapy.     

Neuroendocrine carcinomas arising in ulcerative colitis： Coincidences or possible correlations？

Patients with inflammatory bowel disease （IBD） are at increased risk of colorectal malignancies. Adenocarcinoma is the commonest type of colorectal neoplasm associated with ulcerative colitis （UC） and Crohn＇s disease, but other types of epithelial and non-epithelial tumors have also been described in inflamed bowel. With regards to non-epithelial malignancies, lymphomas and sarcomas represent the largest group of tumors reported in association with IBD, especially in immunosuppressed patients. Carcinoids and in particular neuroendocrine neoplasms other than carcinoids （NENs） are rare tumors and are infrequently described in the setting of IBD. Thus, this association requires further investigation. We report two cases of neoplasms arising in mild left-sided UC with immuno- histochemical staining for neuroendocrine markers： a large cell and a small cell neuroendocrine carcinoma of the rectum. The two patients were different in age （35 years vs 77 years） and disease duration （11 years vs 27 years）, and both had never received immunosuppressant drugs. Although the patients underwent regular endoscopic and histological follow-up, the two neoplasms were locally advanced at diagnosis. One of the two patients developed multiple liver metastases and died 15 mo after diagnosis. These findings confirm the aggressiveness and the poor prognosis of NENs compared to colorectal adenocarcinoma. While carcinoids seem to be coincidentally associated with IBD, NENs may also arise in this setting. In fact, long-standing inflammation could be directly responsible for the development of pancellular dysplasia involving epithelial, goblet, Paneth and neuroendocrine cells. It has yet to be established which IBD patients have a higher risk of developing NENs.     

胃肠道神经内分泌肿瘤的内镜下诊断与治疗

目的探讨胃肠道神经内分泌肿瘤(neuroendocrine neoplasms,NENs)的内镜下诊断及治疗方法。方法对50例经内镜及病理学证实的NENs进行回顾性分析,分析其内镜下表现及治疗方法。结果胃肠道NENs的发病部位以直肠(38/50)和胃(8/50)最为常见,直肠NENs在内镜下有一定特征性表现,但胃、食管、十二指肠NENs在内镜下表现形式多样,无特定典型表现。部分患者经内镜下黏膜切除术(endoscopic mucosal resection,EMR)、内镜下黏膜剥离术(endoscopic submucosal dissection,ESD)或胃镜与腹腔镜双镜联合治疗,其中1例胃NENs表现为胃体6枚息肉样隆起,活检病理示炎性改变,遂行EMR切除,其病理回报NET 2级(G2),肿瘤紧靠基底及侧切缘,遂行二次ESD分别切除胃内NENs病灶残根。所有患者均完整切除瘤体,无术中及术后迟发性出血发生。随访内镜下治疗的患者目前均无复发及转移。结论胃肠道NENs主要通过内镜及病理学检查确诊,对于部分位于黏膜深层或黏膜下层、直径≤1 cm的瘤体可通过ESD在内镜下切除。     

Lung and digestive neuroendocrine neoplasms. From WHO classification to biomarker screening: Which perspectives?

The recent classifications of lung and digestive neuroendocrine neoplasms (NENs) make a fundamental distinction between well- and poorly-differentiated neoplasms. Well-differentiated NENs are termed carcinoids in the lung and neuroendocrine tumors in the gastroenteropancreatic sphere; their risk of malignancy is highly variable; histological grading is used to stratify patients into prognostically significant groups. Poorly-differentiated NENs are termed neuroendocrine carcinoma in both the lung and the digestive sphere; they constantly are of high grade of malignancy; two types are recognized on the basis of tumor cell morphology, the small cell and the large cell types. Recent studies have largely uncovered the genetic landscape of several subsets of well-differentiated NENs (lung, pancreas, small intestine) and of poorly-differentiated NENs. Some molecular markers may help to the differential diagnosis between highly proliferative neuroendocrine tumors and neuroendocrine carcinomas, especially in the pancreas. In well-differentiated tumors, MGMT status is proposed as a predictive marker of the response to temozolomide, but remains to be validated. In poorly-differentiated neoplasms, large cell neuroendocrine carcinoma has been shown to be a heterogeneous category, with some cases presenting the same molecular signature than small cell carcinoma and others the same signature than adenocarcinomas of the same body site. Rb protein has been recently shown to be a potential marker of response to platinum salts in neuroendocrine carcinoma. Much remains to be done to translate the rapid progress in the molecular understanding of NENS into diagnostic, prognostic or predictive markers.     

Neuroendocrine tumor disease: an evolving landscape

Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) represent a heterogenous group of tumors arising from a variety of neuroendocrine cell types. The incidence and prevalence of GEP-NENs have markedly increased over the last three decades. Symptoms are often absent in early disease, or vague and nonspecific even in advanced disease. Delayed diagnosis is thus common. Chromogranin A is the most commonly used biomarker but has limitations as does the proliferative marker Ki-67%, which is often used for tumor grading and determination of therapy. The development of a multidimensional prognostic nomogram may be valuable in predicting tumor behavior and guiding therapy but requires validation. Identification of NENs that express somatostatin receptors (SSTR) allows for SSTR scintigraphy and positron emission tomography imaging using novel radiolabeled compounds. Complete surgical resection of limited disease or endoscopic ablation of small lesions localized in stomach or rectum can provide cure; however, the majority of GEP-NENs are metastatic (most frequently the liver and/or mesenteric lymph nodes) at diagnosis. Selected patients with metastatic disease may benefit from advanced surgical techniques including hepatic resection or liver transplantation. Somatostatin analogs are effective for symptomatic treatment and exhibit some degree of antiproliferative activity in small intestinal NENs. There is a place for streptozotocin, temozolomide, and capecitabine in the management of pancreatic NENs, while new agents targeting either mTOR (everolimus) or angiogenic (sunitinib) pathways have shown efficacy in these lesions.     

A Clinical Perspective on Gastric Neuroendocrine Neoplasia

The incidence of gastric neuroendocrine tumors (NETs) has increased exponentially based on widespread use of endoscopy and a greater pathological awareness of the condition. A key concern is the potential association with hypergastrinemia induced by proton pump inhibitor administration. Previous confusion regarding diagnosis and therapy has been diminished by a series of international consensus statements defining the biology and management strategies for the disease. Overall, gastric NETs are categorized as well-differentiated or poorly differentiated neoplasms. Well-differentiated gastric NETs are enterochromaffin-like (ECL) cell tumors subclassified into three types based on their relationship to gastrin, a key regulator of ECL cell neoplastic transformation. The treatment of type 1 and type 2 tumors depends on the size and invasiveness of the tumor, whereas type 3 tumors and poorly differentiated neuroendocrine carcinomas warrant aggressive surgical resection. The disease-specific 5-year survival ranges from about 95% in type 1 gastric carcinoids to about 25% in poorly differentiated gastric NECs. Elucidation of the precise biology of a gastric NET is critical to diagnosis and delineation of a type-specific management strategy.     

Neuroendocrine tumors of the small bowels are on the rise: Early aspects and management

Neuroendocrine tumors of the small bowel are on the rise. In the US they have increased by 300%-500% in the last 35 years. At the same time their prognosis is much improved. Today, most neuroendocrine tumors (NETs) of the duodenum are detected "incidentally" and therefore recognized at an early stage. Duodenal NETs which are well differentiated, not larger than 10 mm and limited to the mucosa/submucosa can be endoscopically resected. The management of duodenal NETs ranging between 10 and 20 mm needs an interdisciplinary discussion. Endoscopic ultrasound is the method of choice to determine tumor size and depth of infiltration. Surgery is recommended for well-differentiated duodenal NET tumors greater than 20 mm, for localized sporadic gastrinomas (of any size) and for localized poorly differentiated NE cancers. Surgery is recommended for any ileal NET. Advanced ileal NETs with a carcinoid syndrome are treated with long-acting somatostatin analogs. This treatment significantly improves (progression-free) survival in patients with metastatic NETs of the ileum. For optimal NET management, tumor biology, type, localization and stage of the neoplasm, as well as the patient's individual circumstances have to be taken into account.     

Management of gastric and duodenal neuroendocrine tumors

Gastrointestinal neuroendocrine tumors(GI-NETs) are rare neoplasms, like all NETs. However, the incidence of GI-NETS has been increasing in recent years. Gastric NETs(G-NETs) and duodenal NETs(D-NETs) are the common types of upper GI-NETs based on tumor location. G-NETs are classified into three distinct subgroups: type?Ⅰ, Ⅱ, and Ⅲ. Type?Ⅰ?G-NETs, which are the most common subtype(70%-80% of all G-NETs), are associated with chronic atrophic gastritis, including autoimmune gastritis and Helicobacter pylori associated atrophic gastritis. Type Ⅱ G-NETs(5%-6%) are associated with multiple endocrine neoplasia type 1 and Zollinger-Ellison syndrome(MEN1-ZES). Both type?Ⅰ?and Ⅱ G-NETs are related to hypergastrinemia, are small in size, occur in multiple numbers, and are generally benign. In contrast, type Ⅲ G-NETs(10%-15%) are not associated with hypergastrinemia, are large-sized single tumors, and are usually malignant. Therefore, surgical resection and chemotherapy are generally necessary for type Ⅲ G-NETs, while endoscopic resection and followup, which are acceptable for the treatment of most type?Ⅰ?and Ⅱ G-NETs, are only acceptable for small and well differentiated type Ⅲ G-NETs. D-NETs include gastrinomas(50%-60%), somatostatin-producing tumors(15%), nonfunctional serotonin-containing tumors(20%), poorly differentiated neuroendocrine carcinomas( 3%), and gangliocytic paragangliomas( 2%). Most D-NETs are located in the first or second part of the duodenum, with 20% occurring in the periampullary region. Therapy for D-NETs is based on tumor size, location, histological grade, stage, and tumor type. While endoscopic resection may be considered for small nonfunctional D-NETs(G1) located in the higher papilla region, surgical resection is necessary for most other D-NETs. However, there is no consensus regarding the ideal treatment of D-NETs.     

Classification and pathology of gastroenteropancreatic neuroendocrine neoplasms

Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are composed of cells with a neuroendocrine phenotype. The old and the new WHO classifications distinguish between well-differentiated and poorly differentiated neoplasms. All well-differentiated neoplasms, regardless of whether they behave benignly or develop metastases, will be called neuroendocrine tumours (NETs), and graded G1 (Ki67 <2%) or G2 (Ki67 2-20%). All poorly differentiated neoplasms will be termed neuroendocrine carcinomas (NECs) and graded G3 (Ki67 >20%). To stratify the GEP-NETs and GEP-NECs regarding their prognosis, they are now further classified according to TNM-stage systems that were recently proposed by the European Neuroendocrine Tumour Society (ENETS) and the AJCC/UICC. In the light of these criteria the pathology and biology of the various NETs and NECs of the gastrointestinal tract (including the oesophagus) and the pancreas are reviewed.     

The novel WHO 2010 classification for gastrointestinal neuroendocrine tumours correlates well with the metastatic potential of rectal neuroendocrine tumours

BACKGROUND: Approximately 10-15% of gastroenteropancreatic neuroendocrine tumours (NETs, carcinoids) occur in the rectum, some of which are potentially able to metastasize. The new WHO 2010 classification of NETs applies to all gastroenteropancreatic NETs, but no reports have studied its correlation with the prognosis of rectal NETs. PATIENTS AND METHODs: We retrospectively classified 73 rectal NETs according to the novel WHO 2010 and the previous WHO 2000 classifications. The aim was to assess the validity of the classifications in distinguishing indolent rectal NETs from metastasising tumours. RESULTs: Using the WHO 2010 criteria, we identified 61 G1 tumours, none of which had metastasised during follow-up. Of 11 G2 tumours, 9 had shown distant metastases. The only G3 neuroendocrine carcinoma that occurred had been disseminated at initial presentation. CONCLUSION: Our results show that rectal NETs classified as G1 according to the WHO 2010 classification have an indolent clinical course, whereas G2 NETs often metastasise. The WHO 2010 classification of NETs predicts the metastatic potential of rectal NETs better than the WHO 2000 classification.     

Gastrointestinal hemorrhage needing blood transfusion as the first manifestation of small bowel carcinoid tumor

Carcinoid tumors arise from enterochromaffin or enterochromaffin-like cells that are present in the gastrointestinal tract, ovaries, and lungs. Over 90% of carcinoids originate in the gastrointestinal tract with the most common sites in order of frequency being the appendix, terminal ileum, rectum, and the remainder of the colon. Gastroduodenal and pancreatic carcinoids are infrequent. Carcinoid syndrome is associated with small intestine carcinoids in about 40%. Common symptoms include intermittent intestinal obstruction with crampy abdominal pain and vomiting, and weight loss. Upper gastrointestinal bleeding with melaena or hematochezia is a relatively rare early symptom of patients with small intestine carcinoid tumors. We report on a 69-year-old man, treated with acenocoumarol for previous thromboembolic complications of hereditary protein S deficiency. He was admitted to hospital because of an acute episode of hematochezia followed by melaena. Endoscopic evaluation of esophagus, stomach, duodenum and colonoscopy revealed no apparent source of bleeding. Selective angiographic evaluation of mesenterial arteries showed pathologic vasculature approximately in mid jejunum. Laparotomy revealed bleeding from a small submucosal malignant carcinoid tumor in small intestine and multiple large metastases within mesenteric tissue. Segmental resection of small intestine and exstirpation of the metastatic masses was performed. Postoperative period was uneventful. Cytotoxic chemotherapy in this adjuvant setting has not been recommended. Small intestinal carcinoid tumor has to be considered as a rare cause of gastrointestinal bleeding with melaena or hematochezia. Nevertheless, bleeding is a relatively rare early symptom of patients with small intestine carcinoid tumor.     

Carcinoid of the ampulla of Vater

Endocrine neoplasms only rarely occur at the ampulla of Vater, comprising mostly carcinoids and malignant carcinoids, as well as few cases of poorly differentiated endocrine carcinomas (small cell carcinomas). Only 105 cases are reported in the literature, most as single case reports. For many years, the neoplasms of the disseminated neuroendocrine cell system of the gastrointestinal tract have been subsumed as 'carcinoids'. Instead, in the latest World Health Organization (WHO) classification published in 2000, it is recommended to distinguish between (i) well-differentiated endocrine tumors (carcinoids); (ii) well-differentiated endocrine carcinomas (malignant carcinoids); and (iii) poorly differentiated endocrine carcinomas (small cell carcinomas). Patients with carcinoid tumors of the ampulla of Vater are very often free of clinical and laboratory findings that belong to the carcinoid syndrome. Approximately 26% of all patients with carcinoid tumor reported in the literature had neurofibromatosis. Besides endoscopic retrograde cholangiopancreatography, endosonography, computed tomography or magnetic resonance imaging may complete the staging approach of this tumor. The Kausch-Whipple procedure or pylorus-preserving pancreaticoduodenectomy is considered the treatment of choice for ampullary, well-differentiated carcinoids >2.0 cm and for ampullary neuroendocrine carcinomas. However, it should be considered that long-term survival of patients with ampullary carcinoids is also reported after local tumor excision (5-year survival rate of 90%). The dilemma is that the differentiation of neuroendocrine tumors cannot be assessed intraoperatively in most cases. Therefore, considering that the 5-year survival rate in patients with neuroendocrine carcinomas of the ampulla of Vater is very low without radical resection, neuroendocrine tumors of the ampulla of Vater without definite histological differentiation should undergo extended surgery.     

Somatostatin-producing neuroendocrine tumors of the duodenum and pancreas: incidence, types, biological behavior, association with inherited syndromes, and functional activity

Somatostatin-producing neuroendocrine tumors (SOM-NETs) of the duodenum and pancreas appear to be heterogeneous. To determine their clinicopathological profiles, respective data were analyzed on a series of 82 duodenal and 541 pancreatic NETs. In addition, the clinical records of 821 patients with duodenal or pancreatic NETs were reviewed for evidence of a somatostatinoma syndrome. Predominant or exclusive expression of somatostatin was found in 21 (26%) duodenal and 21 (4%) pancreatic NETs. They were classified as sporadic (n=31) or neurofibromatosis type 1 (NF1)-associated duodenal NETs (n=3), gangliocytic paragangliomas (GCPGs; n=6), or poorly differentiated neuroendocrine carcinomas (pdNECs; n=2). In addition, five duodenal and four pancreatic SOM-NETs were found in five patients with multiple endocrine neoplasia type 1 (MEN1). Metastases occurred in 13 (43%) patients with sporadic or NF1-associated SOM-NETs, but in none of the duodenal or pancreatic MEN1-associated SOM-NETs or GCPGs. Sporadic advanced (stage IV) SOM-NETs were more commonly detected in the pancreas than in the duodenum. None of the patients (including the 821 patients for whom only the clinical records were reviewed) fulfilled the criteria of a somatostatinoma syndrome. Our data show that somatostatin expression is not only seen in sporadic NETs but may also occur in GCPGs, pdNECs, and hereditary NETs. Surgical treatment is effective in most duodenal and many pancreatic SOM-NETs. MEN1-associated SOM-NETs and GCPGs follow a benign course, while somatostatin-producing pdNECs are aggressive neoplasms. The occurrence of the so-called somatostatinoma syndrome appears to be extremely uncommon.     

Clinicopathological characteristics of biliary neuroendocrine neoplasms: a multicenter study

Objectives: This study assessed the clinicopathological features, therapeutic approaches, and prognosis of patients with biliary neuroendocrine neoplasm (NENs).

Materials and methods: Multicenter retrospective study of patients with biliary tract NENs in the gallbladder, the extrahepatic bile duct, or the ampulla of Vater between 2005 and 2014.

Results: Total of 43 patients were included in the study. The median age was 62 years (range: 29–84 years) and 58.1% of the patients were male. The tumors occurred in the gallbladder (n?=?11), the extrahepatic bile duct (n?=?5) or the ampulla of Vater (n?=?27). The liver was the most common metastatic site. Based on the 2010 World Health Organization classification, more patients with gallbladder NENs (11/11 (100%)) had neuroendocrine carcinoma G3 than those with NENs in the ampulla of Vater (10/27 (37.1%)). The median progression free survival time (39.3 vs 5.1 months, p?=?0.001) and median overall survival time (46.9 vs 7.9 months, p?<?0.001) were significantly longer in patients with ampulla of Vater NENs than gallbladder NENs. A 2010 World Health Organization classification of neuroendocrine carcinoma G3 was independently related to poor overall survival (hazard ratio (HR), 27.1; 95% confidence intervals (CI), 2.81-260.68; p?=?0.004).

Conclusion: The 2010 World Health Organization classification of neuroendocrine carcinoma G3 was the only factor related to poor prognosis in patients with biliary neuroendocrine neoplasms.     

Diagnostic role and prognostic value of tumor markers in high-grade gastro-enteropancreatic neuroendocrine neoplasms

ObjectivesHigh-grade gastro-enteropancreatic neuroendocrine neoplasms (GEP-NENs) are a heterogeneous group of rare tumors of two different types: well differentiated neuroendocrine tumors grade 3 (NETs G3) and poorly differentiated neuroendocrine carcinomas (NECs). This study aimed to explore the value of eight common preoperative markers in differentiating NETs G3 from NECs and the prognosis prediction of high-grade GEP-NENs.MethodsSeventy-two patients diagnosed with high-grade GEP-NENs who underwent surgery at our institution were recruited for this study. Demographic and clinicopathological characteristics, preoperative serum tumor markers, and survival data were collected and analyzed. Kaplan–Meier methods were used to analyze survival rates, and a Cox regression model was used to perform multivariate analyses.ResultsSerum carcinoembryonic antigen (CEA) was dramatically higher in NECs than in NETs G3 (P = 0.025). After follow-up, 57 of the 72 patients remained for survival analysis. Elevated serum carbohydrate antigen 19-9 (CA19-9), CEA, cancer antigen 125 and sialic acid (SA) levels indicated poorer survival of high-grade GEP-NEN patients. Only CA19-9 (HR: 6.901, 95% CI: 1.843 to 25.837, P = 0.004) was regarded as an independent risk factor for overall survival. Serum CA19-9 (HR: 4.689, 95% CI: 1.127 to 19.506, P = 0.034) was also regarded as an independent factor for overall survival in NECs.ConclusionsSerum CEA levels can be used to distinguish NETs G3 from NECs. Preoperative CA19-9, CEA, cancer antigen 125 and SA levels have predictive value in the prognosis of high-grade GEP-NENs. Preoperative CA19-9, neuron-specific enolase, and SA levels can predict the prognosis of NECs.     

Neuroendocrine gastric carcinoma. A case report and review of current management

Neuroendocrine or carcinoid tumors of the gastrointestinal tract considered previously extremely rare, are diagnosed at present with increased frequency due to the better capacity to identify neuroendocrine system cells in normal and pathologic conditions. Occasionally, these tumors secrete a great variety of vasoactive substances, producing the carcinoid syndrome. Gastric carcinoids are classified, according to their degree of differentiation into well differentiated and poorly differentiated tumors, also called neuroendocrine carcinomas. Neuroendocrine gastric carcinomas or poorly differentiated gastric carcinoids are seen in 5-15% of all gastric carcinoids, mainly in older male patients. Generally they are large, very aggressive tumors with extensive local infiltration. Due to poor differentiation, they are not frequently associated with an endocrine syndrome. They can be located in any part of the stomach but are mainly seen in antrum. These tumors have an aggressive behavior and must be treated in a radical manner; recurrences are not uncommon. We report the case of a patient with a neuroendocrine gastric carcinoma treated with an en bloc subtotal gastrectomy and colectomy.     

Pedunculated rectal carcinoid removed by endoscopic mucosal resection： A case report

Carcinoid tumors generally appear as yellow/gray or tan submucosal nodules. We experienced a case of pedunculated rectal carcinoid showing a mushroom-like appearance. The case was a forty years old woman who was admitted to our hospital due to rectal bleeding. Colonoscopy revealed a pedunculated polyp presenting a mushroom-shaped appearance measuring 13 mm in diameter in the rectum. The histological diagnosis of specimens obtained by biopsy was adenocarcinoma and transanal ultrasonography revealed the tumor localization within the submucosal layer in the rectum. Endoscopic mucosal resection (EMR) was performed. Histopathological examination established the diagnosis of carcinoid tumor in the rectum. Frequencies of the pedunculated type in rectal carcinoids were reported to be 2.4% to 7.1% in the literature. Because of its rarity, pedunculated configuration may confuse the endoscopic diagnosis of carcinoids. Treatment for carcinoids of 1 to 1.5 cm in size remains controversial. Although such tumors are technically respectable by EMR, careful attention must be paid in dealing with these tumors because there may be unexpected behaviors of the tumors.