Search Results (45)

Background/Objectives: Type 1 gastric neuroendocrine tumors (gNET) arise in the setting of autoimmune chronic atrophic gastritis and secondary hypergastrinemia. Vitamin D deficiency (VDD) has been associated with bone impairment and adverse outcomes in patients with neuroendocrine tumor (NET); however, data specifically addressing gNET remain limited. This study aimed to evaluate vitamin D status, supplementation requirements, and bone involvement in patients with type 1 gNET compared with those with entero-pancreatic NET (EP-NET). Methods: This retrospective study included patients with type 1 gNET followed at a tertiary referral center between 2010 and 2025 and an age- and sex-matched EP-NET cohort. VDD prevalence, time and dose required for normalization, supplementation formulations, bone status, and dietary habits were analyzed. Results: Twenty-six patients were included (thirteen gNET and thirteen EP-NET). VDD was significantly more prevalent in the gNET group compared with the EP-NET group (92.3% vs. 46.2%, p = 0.03, OR: 14). gNET required significantly higher daily cholecalciferol doses (3198.9 ± 1629 vs. 1580 ± 1121 IU/day, p = 0.008) and more frequently required multiple supplementation formulations (38.5% vs. 0%, p = 0.04). Multivariable linear regression analysis restricted to VDD patients confirmed that gNET was independently associated with higher daily cholecalciferol dose requirements (p = 0.037). Bone impairment, defined as osteoporosis or osteopenia, was significantly more common in the gNET group (61.5% vs. 15.4%, p = 0.04, OR: 8.8). Dietary adherence did not differ between groups. Conclusions: Type 1 gNET show a higher burden of VDD, increased vitamin D supplementation requirements, and a higher prevalence of bone impairment compared with EP-NET, irrespective of dietary habits. These findings suggest disease-specific mechanisms and support the need for tailored management in these patients. Full article

Purpose: Zollinger–Ellison syndrome (ZES) is the most frequent, functional, malignant pancreatic neuroendocrine tumor syndrome (pNET), which is due to ectopic secretion of gastrin by a pNET/NET (i.e., gastrinomas) resulting in severe, refractory acid-peptic disease (ulcer, GERD). ZES has several unique management features, which lead to a number of unresolved controversies. Areas covered: Whereas both medical and surgical controversies exist, they have not been examined in detail for some time. This review contains an analysis of a number of the main current, medical controversies that are unresolved in ZES patients, including insights into the basis of these controversies and possible insights into their resolution from recent studies in patients with gastrinomas or from recent studies in other pNET syndromes or other neuroendocrine tumors (NETs). These include the following: controversies in the long-term control of acid secretion and acid antisecretory drug side-effects; controversies related to the difficulty in making the diagnosis of ZES; nonsurgical MEN1/ZES controversies related to the management of gastric carcinoids (Type II); nonsurgical MEN1/ZES controversies related to whether genotype–phenotype correlations exist in MEN1 patients including MEN1/ZES patients; nonsurgical MEN1/ZES controversies related to the roles of imaging/tumor localization in MEN1 patients for gastrinomas/pNETs in their initial/follow-up management; controversies related to the role of non-surgical tumor ablation for treatment of ZES/gastrinomas; and controversies related to medical treatment selection for advanced, metastatic disease in patients with ZES/gastrinomas/other malignant pNETs. Conclusions: In this paper, the basis for the development of each of these unique ZES-related controversies is discussed and insights into progress that could lead to their resolution are reviewed. Full article

Background/Objectives: Autoimmune metaplastic atrophic gastritis (AMAG) is a chronic, autoimmune-mediated condition associated with increased risk of malignancy and nutritional deficiencies, yet diagnostic and follow-up processes remain inconsistent and unclear. This study investigates follow-up testing performance in patients with AMAG and neuroendocrine tumors (NET), as well as the correlation between endoscopic impressions and histologic findings. Methods: We retrospectively analyzed 65 gastric biopsies with final diagnoses or comments mentioning the possibility of AMAG, 12 of which included well-differentiated WHO grade 1 NET arising in AMAG. H&E slides were reviewed to assess atrophy severity, the presence or absence of enterochromaffin-like (ECL) cell hyperplasia, and Helicobacter organisms. The final diagnostic line or comments made were scored from 1 to 5, based on the strength of the language used to alert the treating clinician to the likelihood of AMAG. Corresponding endoscopy reports were scored from 1 to 5 based on the likelihood of the reports documenting AMAG features. Data regarding follow-up laboratory testing relevant to AMAG and biopsy performance were collected from the electronic medical records. Results: Endoscopy scores showed no significant associations with the histology comment score or atrophy grade. The histology comment score was positively associated with performing at least a total of three laboratory tests (p = 0.03). No association was found between the presence or absence of follow-up biopsy and histology comment score (p = 0.60). Follow-up biopsy was more common in patients with NET than those with AMAG without NET (p < 0.001). Conclusions: Poor endoscopic–histologic correlation with variable follow-up practices highlights the need for standardized protocols in AMAG management. Enhanced adherence to biopsy guidelines, standardized pathology reporting, and consistent surveillance, particularly for patients with AMAG without NET, are imperative to improve diagnosis and outcomes. Future research should focus on optimizing endoscopic techniques, standardizing serological tests, and establishing evidence-based surveillance protocols for AMAG patients. Full article

A 60-year-old woman with hypertension and hyperlipidemia was referred for an incidentally detected gastric subepithelial mass during screening endoscopy. Esophagogastroduodenoscopy revealed a 10 mm dimple in the antrum, and contrast-enhanced CT showed a 2.5 cm enhancing oval lesion. Laparoscopic partial gastrectomy with intraoperative endoscopic guidance was performed. Gross examination revealed a 3.0 × 2.0 × 1.0 cm pale, firm nodule. Histology showed small round cells arranged in nests and trabeculae within the muscularis propria, with numerous vessels and focal calcification. Immunohistochemistry was negative for CD117, HMB45, and chromogranin A, but demonstrated strong smooth muscle actin positivity, weak synaptophysin reactivity, and focal CD56 staining. The findings confirmed a gastric glomus tumor with neuroendocrine features. Smooth muscle actin immunostaining is essential to distinguish gastric glomus tumors from neuroendocrine tumors when biopsy material is limited, ensuring accurate diagnosis and appropriate management. Full article

Post-operative pancreatic fistula (POPF) is a serious yet far too common complication following distal pancreatectomy (DP), as it affects 20–30% of patients after DP. POPF raises the risk of other complications and causes delays to a patient’s oncologic care. In this review, we present the latest data on patient risk factors for developing POPF, such as obesity, smoking, young age, thick pancreas, lack of epidural anesthesia, hypoalbuminemia, and elevated drain amylase levels. Other risk factors that have been identified with irregular consistency include open surgical approach, non-malignant or neuroendocrine tumor pathology, simultaneous splenectomy, simultaneous vascular resection, and long operative time. We also review the consequences of POPF, which include hemorrhage, infection, delayed gastric emptying, re-operation, re-admission, delays in adjuvant chemotherapy initiation, reduced progression-free survival, and reduced overall survival. Finally, we present strategies that have been studied for avoiding POPF after DP, including reducing pressure at the sphincter of Oddi, the use of sealants and patches, optimizing pancreatic transection, strategies for post-operative drain placement, the use of post-operative somatostatin analogues, and pre-clinical studies of experimental devices and techniques that may inform future trials. This review informs readers on the current state of the art with regard to POPF after DP and sets the stage for future studies to improve patient outcomes. Full article

Background: The glucocorticoid receptor (GR) regulates the transcription of thousands of genes. In cancer, both oncogenic and tumor suppressive roles of GR have been proposed. Methods: A tissue microarray containing 18,527 samples from 147 tumor (sub-)types and 608 samples from 76 normal tissue types was analyzed for GR expression by immunohistochemistry. Results: GR positivity was found in 76.4% of 14,349 interpretable cancers, including 18.5% with weak, 19.6% with moderate, and 38.3% with strong positivity. GR positivity appeared in all 147 tumor types, with at least one strongly positive tumor in 136 types. Of out tumor entities, 77 of the 147 showed GR positivity in 100% of the cases analyzed. Only six tumor types had less than 50% GR-positive cases, including adenomas with low-/high-grade dysplasia (32.5%/21.7%), adenocarcinomas (17%) and neuroendocrine carcinomas (45.5%) of the colorectum, endometrial carcinomas (25.6%), and rhabdoid tumors (25%). Reduced GR staining was associated with grade progression in pTa (p < 0.0001) and with nodal metastasis in pT2-4 (p = 0.0051) urothelial bladder carcinoma, advanced pT stage (p = 0.0006) in breast carcinomas of no special type (NST), and high grade (p = 0.0066), advanced pT stage (p < 0.0001), and distant metastasis (p = 0.0081) in clear cell renal cell carcinoma. GR expression was unrelated to clinico-pathological parameters in gastric, pancreatic, and colorectal adenocarcinoma, and in serous high-grade carcinoma of the ovary. Conclusions: GR expression is frequent across all cancer types. Associations between reduced GR expression and unfavorable tumor features in certain cancers suggest that the functional importance of GR-regulated genes in cancer progression depends on the cell of tumor origin. Full article

Autoimmune gastritis (AIG) has a strong correlation with gastric neuroendocrine tumors (NETs) and gastric cancer, making its timely and accurate diagnosis crucial for tumor prevention. The endoscopic manifestations of AIG differ from those of gastritis caused by Helicobacter pylori (H. pylori) infection in terms of the affected gastric anatomical regions and the pathological characteristics observed in biopsy samples. Therefore, when diagnosing AIG based on endoscopic images, it is essential not only to distinguish between normal and atrophic gastric mucosa but also to accurately identify the anatomical region in which the atrophic mucosa is located. In this study, we propose a patient-based multitask gastroscopy image classification network that analyzes all images obtained during the endoscopic procedure. First, we employ the Scale-Invariant Feature Transform (SIFT) algorithm for image registration, generating an image similarity matrix. Next, we use a hierarchical clustering algorithm to group images based on this matrix. Finally, we apply the RepLKNet model, which utilizes large-kernel convolution, to each image group to perform two tasks: anatomical region classification and lesion recognition. Our method achieves an accuracy of 93.4 ± 0.5% (95% CI) and a precision of 92.6 ± 0.4% (95% CI) in the anatomical region classification task, which categorizes images into the fundus, body, and antrum. Additionally, it attains an accuracy of 90.2 ± 1.0% (95% CI) and a precision of 90.5 ± 0.8% (95% CI) in the lesion recognition task, which identifies the presence of gastric mucosal atrophic lesions in gastroscopy images. These results demonstrate that the proposed multitask patient-based gastroscopy image analysis method holds significant practical value for advancing computer-aided diagnosis systems for atrophic gastritis and enhancing the diagnostic accuracy and efficiency of AIG. Full article

Autoimmune gastritis (AIG) is an uncommon and often underestimated condition in children, characterized by chronic stomach inflammation leading to the destruction of oxyntic glands with subsequent atrophic and metaplastic changes. This condition is associated with hypo-/achlorhydria, impairing iron and vitamin B12 absorption. The pathogenesis involves the activation of helper type 1 CD4+/CD25-T-cells against parietal cells. Clinical manifestations in children are not specific and include abdominal pain, bloating, nausea, vomiting, and iron deficiency anemia (IDA). The disease is also linked to an increased risk of pernicious anemia, intestinal-type gastric cancer, and type I neuroendocrine tumors. AIG is often diagnosed through the presence of autoantibodies in the serum, such as parietal cell (APCA) and intrinsic factor (IF) antibodies. However, therapeutic recommendations for pediatric AIG are currently lacking. We aim to present two clinical cases of pediatric-onset AIG, highlighting the heterogeneous clinical manifestations and the challenges in diagnosis with the support of an updated literature review. A 9-year-old girl presented with refractory IDA, initial hypogammaglobulinemia, and a 12-year-old boy was initially diagnosed with eosinophilic esophagitis. Both cases underline the importance of considering AIG in children with chronic gastrointestinal symptoms and gastric atrophy. Diagnostic workup, including endoscopy and serological tests, is crucial for accurate identification. A better understanding of this condition is imperative for timely intervention and regular monitoring, given the potential long-term complications, including the risk of malignancy. These cases contribute to expanding the clinical spectrum of pediatric AIG and highlight the necessity for comprehensive evaluation and management in affected children. Full article

Background/Objectives: Neuroendocrine tumors (NETs) can arise in any organ and are most commonly found in the lungs and gastroenteropancreatic (GEP) system. GEP-NETs represent a small percentage of gastrointestinal cancers, and therefore, the standard treatment is not well-defined, especially for advanced disease. Our objective is to review GI NETs among veterans and analyze their therapeutic outcomes. Methods: A total of 61 GI NET cases were identified from our institution from 2019–2024. In total, twenty-seven review papers, ten population-based/multicenter/outcome studies, six case reports, and one case series were reviewed for the literature review. Results: The incidence of GI NETs at our institution was higher than the known epidemiology of GI NETs. Small intestine NETs were one of the most common sites of GEP-NETs at our institution, with only one of nineteen cases being grade 3 poorly differentiated neuroendocrine carcinoma. All cases of colonic and rectal NETs had good clinical outcomes consistent with findings from the literature. Most of the gastric NETs were type 1 and had benign courses of disease, except for one case with an intermediate grade and metastatic liver lesions. One case of esophageal neuroendocrine carcinoma (E-NEC) showed a complete response to chemotherapy despite a significant tumor burden on presentation and high-grade pathology, while another case of ENEC had recurrent disease despite systemic therapy. Conclusions: While the role of surgery or endoscopic resection is limited to localized tumors, combined treatment with chemoradiation can significantly improve patient outcomes, especially in high-grade, poorly differentiated tumors. Further studies are needed to establish systemic (i.e., chemotherapy and radiation) treatment strategies for poorly differentiated GI NETs. Full article

Background: Mixed neuroendocrine–non-neuroendocrine neoplasms (MiNENs) of the esophago-gastric junction (EGJ) are rare aggressive malignant neoplasms, with, currently, limited evidence regarding the appropriate therapeutic approach. Methods: Herein, we report multimodal treatment management of a patient with oligometastatic MiNEN of EGJ (Siewert III), discuss the lessons learnt, and provide a review of the literature. Results: A 69-year-old female was diagnosed with a locally advanced EGJ tumor and three liver metastases (cT4, cN+, M1). Although the initial histology from biopsy revealed adenocarcinoma, the histopathology of a lymph node biopsy from staging laparoscopy revealed infiltration of neuroendocrine carcinoma cells. Thus, the diagnosis of a mixed neuroendocrine adenocarcinoma was set, and systemic chemotherapy with etoposide and cisplatin was initiated. A major clinical response led to conversion surgical resection of the primary tumor and metastases, followed by adjuvant therapy with immunotherapy. The patient is free of disease at the 3-year follow-up. A review of the literature on similar cases of EGJ or gastric MiNENs revealed a limited number of cases. Out of the 39 patients, 20 of them (51.3%) suffered from advanced-stage disease. The MiNEN diagnosis typically occurred after surgical resection. Systemic chemotherapy against the neuroendocrine component demonstrated significant response rates, while in cases in which conversion surgery was offered, prolongation of survival was demonstrated. Conclusions: Our case and the existing literature on MiNENs of EGJ underline the need for a personalized treatment approach following thorough interpretation of comprehensive pretherapeutic staging. Conversion radical surgery with curative intent could be considered in cases of major or complete clinical response to induction chemotherapy with potentially favorable outcomes. Full article

Background/Objectives: Neuroendocrine tumors (NETs) are heterogeneous malignancies arising from enterochromaffin cells that can arise from the gastrointestinal (GI) tract and pancreas. Surgical management is the cornerstone of treatment, with the optimal approach tailored by tumor grade, size, location, and presence of metastasis. This review discusses the current strategies for the surgical management of NETs of the gastroenteropancreatic tract. Methods: A review of the available literature was conducted to evaluate surgical approaches to NETs. Consensus guidelines were incorporated to synthesize evidence-based recommendations. Results: For gastric NETs, surgical approach depends on Rindi Classification, WHO grade, and tumor size, with endoscopic approaches favored for smaller and low-grade lesions. Small bowel NETs can be multifocal and thus often require a surgical approach with careful evaluation of the entire intestine. Pancreatic NETs are categorized as functional or non-functional, with enucleation or formal resection strategies based on size, location, functional status, and risk of malignancy. Colorectal NETs are primarily treated with transanal localized or formal surgical resection, depending on lesion size and depth of invasion or presence of lymph node involvement. Appendiceal NETs are either treated with appendectomy or right hemicolectomy, depending on the size, location, and invasiveness of the lesions. For metastatic NETs, cytoreduction, liver transplantation, and targeted therapies offer symptom relief and possible survival benefits. Conclusions: Surgical resection provides curative potential for localized NETs and symptom control in metastatic cases. Future research is essential to refine guidelines for intermediate-risk lesions and multifocal tumors, ensuring optimal outcomes for patients with gastroenteropancreatic NETs. Full article

The protein menin is encoded by the MEN1 gene and primarily serves as a nuclear scaffold protein, regulating gene expression through its interaction with and regulation of chromatin modifiers and transcription factors. While the scope of menin’s functions continues to expand, one area of growing investigation is the role of menin in cancer. Menin is increasingly recognized for its dual function as either a tumor suppressor or a tumor promoter in a highly tumor-dependent and context-specific manner. While menin serves as a suppressor of neuroendocrine tumor growth, as seen in the cancer risk syndrome multiple endocrine neoplasia type 1 (MEN1) syndrome caused by pathogenic germline variants in MEN1, recent data demonstrate that menin also suppresses cholangiocarcinoma, pancreatic ductal adenocarcinoma, gastric adenocarcinoma, lung adenocarcinoma, and melanoma. On the other hand, menin can also serve as a tumor promoter in leukemia, colorectal cancer, ovarian and endometrial cancers, Ewing sarcoma, and gliomas. Moreover, menin can either suppress or promote tumorigenesis in the breast and prostate depending on hormone receptor status and may also have mixed roles in hepatocellular carcinoma. Here, we review the rapidly expanding literature on the role and function of menin across a broad array of different cancer types, outlining tumor-specific differences in menin’s function and mechanism of action, as well as identifying its therapeutic potential and highlighting areas for future investigation. Full article

Autoimmune atrophic gastritis is an immune-mediated disease resulting in autoimmune destruction of the specialized acid-producing gastric parietal cells. As a consequence, in autoimmune atrophic gastritis, gastric acid secretion is irreversibly impaired, and the resulting hypochlorhydria leads to the main clinical manifestations and is linked, directly or indirectly, to the long-term neoplastic complications of this disease. In the last few years, autoimmune atrophic gastritis has gained growing interest leading to the acquisition of new knowledge on different aspects of this disorder. Although reliable serological biomarkers are available and gastrointestinal endoscopy techniques have substantially evolved, the diagnosis of autoimmune atrophic gastritis is still affected by a considerable delay and relies on histopathological assessment of gastric biopsies. One of the reasons for the diagnostic delay is that the clinical presentations of autoimmune atrophic gastritis giving rise to clinical suspicion are very different, ranging from hematological to neurological–psychiatric up to gastrointestinal and less commonly to gynecological–obstetric symptoms or signs. Therefore, patients with autoimmune atrophic gastritis often seek advice from physicians of other medical specialties than gastroenterologists, thus underlining the need for increased awareness of this disease in a broad medical and scientific community. Full article

Objectives: Our aim was to investigate the clinical outcome of patients with well-differentiated gastric, duodenal, and rectal neuroendocrine tumors after treatment with incomplete endoscopic resection due to the finding of microscopic positive resection margins (R1). Methods: This is a retrospective analysis of consecutive patients with type 1 gastric, non-ampullary non-functioning duodenal, or rectal neuroendocrine neoplasms with positive R1 margins after endoscopic resection. The rate of tumor recurrence and progression-free survival were considered to be the study’s main endpoints. Statistical analysis was performed using MedCalc^® v.17 software and a p-value of <0.05 was considered significant. A Cox proportional-hazard regression was performed to identify risk factors for disease recurrence/progression. Results: After evaluating 110 patients, a total of 58 patients were included in the final analysis (15 gastric NENs, 12 duodenal NENs, and 31 rectal NENs). After evidence of endoscopic R1 resection had been gathered, 26 patients (44.8%) underwent an endoscopic/surgical extension of the previous resection. Tumor progression (all local recurrences) occurred in five out of fifty-eight patients (8.6%) with a median PFS of 36 months. There were no tumor-related deaths. G2 grading and the gastric primary tumor site were the only features significantly associated with the risk of recurrence of the disease (HR: 11.97 [95% CI: 1.22–116.99], HR: 12.54 [95% CI: 1.28–122.24], respectively). Conclusions: Tumor progression rarely occurs in patients with microscopic positive margin excision (R1) after endoscopic resection and does not seem to affect patients’ clinical outcomes. Full article

Autoimmune atrophic gastritis (AAG) is a chronic condition characterized by the presence of atrophy in the oxyntic mucosa due to anti-parietal cell antibodies. This review provides a comprehensive and up-to-date overview of autoimmune atrophic gastritis, reporting recent evidence on epidemiology, pathogenesis, diagnosis, clinical presentation, risk of malignancies, and management. The prevalence of AAG has been estimated at between 0.3% and 2.7% in the general population. The diagnosis of AAG is based on a combination of the serologic profile and the histological examination of gastric biopsies. Patients with AAG are often asymptomatic but can also have dyspeptic or reflux symptoms. The atrophy of the oxyntic mucosa leads to iron and vitamin B12 malabsorption, which may result in anemia and neurological affections. Autoimmune atrophic gastritis is associated with an increased risk of type I neuroendocrine tumors (NETs) and gastric cancer, with an incidence rate of 2.8% and 0.5% per person/year, respectively. Management is directed to reinstate vitamins and iron and to prevent malignancies with endoscopic surveillance. In conclusion, atrophic autoimmune gastritis is an infrequent condition, often asymptomatic and misdiagnosed, that requires an early diagnosis for appropriate vitamin supplementation and endoscopic follow-up for the early diagnosis of NETs and gastric cancer. Full article