Search Results (97)

Background and Clinical Significance: Carcinoid tumors are rare, slow-growing neuroendocrine cell neoplasms that typically affect the gastrointestinal tract. While metastasis may occur, it most commonly occurs in the liver, and orbital metastasis is extremely rare, especially while on systemic somatostatin suppression. Case Presentation: A 57-year-old man with a history of gastrointestinal carcinoid tumor treated with lanreotide for 5 years presented with a left proptotic, red eye and double vision for several months. Clinical examination revealed left proptosis, supraduction deficit, lower lid retraction, and dilated episcleral vessels inferiorly. Magnetic resonance imaging demonstrated a 1.8 cm enhancing lesion centered within the left inferior rectus muscle. Left orbitotomy and biopsy were performed, which confirmed metastatic carcinoid tumor. He will undergo localized orbital radiation and substitution of lanreotide with systemic chemotherapy. Conclusions: Orbital metastasis of carcinoid tumor is extremely uncommon. Given its rarity, diagnosis may be challenging. In patients presenting with ocular complaints including chronic red eye, double vision, proptosis, and mass effect with a prior history of neuroendocrine cancer, a high index of suspicion for orbital metastasis is necessary with timely workup and treatment even if the disease has been otherwise well-controlled with somatostatin analogs. Full article

Background/Objectives: The 2019 WHO classification redefined high-grade gastrointestinal neuroendocrine neoplasms (GI NENs), encompassing not only poorly differentiated neuroendocrine carcinomas (NECs), but also well-differentiated grade 3 neuroendocrine tumors (NETs G3). Since both subtypes share a Ki-67 index > 20%, distinguishing them based solely on morphology is challenging. Prior studies have shown TP53 alterations in NECs but not in NETs. This study aimed to evaluate clinico-morphological parameters and the immunohistochemical (IHC) expression of p53 in high-grade GI NENs to identify relevant correlations. Methods: Tumors were stratified by Ki-67 index into two groups: >20–50% and >50%. p53 IHC expression was assessed as “wild-type” (1–20% positive tumor cells) or “non-wild-type” (absence or >20% positivity). Correlations were analyzed between Ki-67, p53 status, and various pathological features. Results: Significant correlations were found between the Ki-67 index and maximum tumor size, pT stage, lymphovascular invasion, perineural infiltration, and diagnostic classification. Similarly, p53 immunohistochemical status was significantly associated with lymphovascular invasion, lymph node metastasis, and tumor classification (NET G3 versus NEC, including NEC components of MiNENs). Conclusions: The findings support the value of Ki-67 and p53 as complementary biomarkers in the pathological evaluation of high-grade GI NENs. Their significant associations with key morphological parameters support their utility in differentiating NETs G3 from NECs, particularly in cases showing overlapping histological features. The immunohistochemical profile of p53 may serve as a useful diagnostic adjunct in routine practice. Full article

Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are rare tumors with different clinical and biological characteristics. Ki-67 staining and mitotic counts are the most commonly used prognostic markers, but these methods are time-consuming and lack reproducibility, highlighting the need for innovative approaches that improve histological evaluation and prognosis. In our previous study, we observed that the microRNA (miRNA) expression profile of GEP-NENs correlates with the three grades of GEP-NENs. This study aimed to characterize a group of miRNAs that discriminate well-differentiated GEP-NENs grading 1 (G1) and grading (G2). Fifty formalin-fixed and paraffin-embedded tissue specimens from well-differentiated GEP-NENs G1 and G2 tissues were used for this study. The expression levels of 21 miRNAs were examined using qRT-PCR, while FGFR2 and FGF1 protein expression were evaluated through immunohistochemistry (IHC). We identified four miRNAs (hsa-miR-133, hsa-miR-150-5p, hsa-miR-143-3p and hsa-miR-378a-3p) that are downregulated in G2 GEP-NENs compared to G1. Bioinformatic analysis revealed that these miRNAs play a key role in modulating the FGF/FGFR signaling pathway. Consistent with this observation, we found that fibroblast growth factor receptor 2 (FGFR2) expression is markedly higher in G2 NENs patients, whereas its expression remains low in G1 NENs. Our findings highlight the potential use of miRNAs to confirm the histological evaluation of GEP-NENs by employing them as biomarkers for improving histological evaluation and tumor classification. Full article

Prompt and accurate identification of liver metastases from neuroendocrine tumors, arising from the gastrointestinal system and from the pancreas, through the means of both anatomical and functional diagnostic imaging techniques is mandatory. A patient’s prognosis and treatment planning are dependent on these diagnostic procedures. The aim of this narrative review is to depict the common appearance of liver metastases, as well as to depict atypical imaging patterns. Moreover, this review will cover the differential diagnosis between liver metastases from neuroendocrine tumors and other primary and secondary malignant liver lesions, as well as benign liver lesions. Full article

Background: Functioning gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are rare tumors that secrete biologically active hormones, leading to complex clinical syndromes such as carcinoid syndrome, VIPoma, glucagonoma, gastrinoma, insulinoma, and somatostatinoma. These syndromes frequently induce profound metabolic, gastrointestinal, and nutritional disturbances. Objective: This review aims to provide a comprehensive overview of the physiopathology of malnutrition in functioning GEP-NENs and to highlight nutritional and supportive care strategies, including how medical, surgical, and locoregional treatments can indirectly improve nutritional outcomes. Methods: We analyzed the current literature and clinical guidelines to identify key mechanisms of malnutrition across different functioning syndromes and their clinical manifestations. Nutritional recommendations and the impact of treatment modalities on nutritional status were summarized. Results: The pathophysiology of malnutrition in functioning NENs is multifactorial and syndrome-specific. Hormonal hypersecretion may cause diarrhea, electrolyte imbalances, catabolic states, steatorrhea, or hypoglycemia, among other effects. These lead to nutrient loss, malabsorption, or altered intake. Tailored dietary interventions, micronutrient supplementation (e.g., niacin, calcium, vitamin B12), and symptom-guided nutritional support are essential. Somatostatin analogs, PRRT, and cytoreductive approaches often contribute to symptom control, thereby enhancing nutritional status and patient quality of life. Conclusions: Malnutrition in functioning GEP-NENs is a significant clinical issue that requires early recognition and a multidisciplinary, individualized management plan. Integrating nutrition into the comprehensive care of these patients is essential to improve outcomes and quality of life. Full article

Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are a varied group of tumors that originate from neuroendocrine cells found throughout the gastrointestinal tract. These tumors encompass a broad spectrum of biological behaviors, ranging from slow-growing, well-differentiated neuroendocrine tumors (GEP-NETs) to aggressive and poorly differentiated neuroendocrine carcinomas (GEP-NECs), complicating their accurate classification and effective treatment. While advances in molecular research have refined our understanding of these tumors, their complexity, unpredictable progression, and differential response to therapies remain major clinical hurdles. A significant clinical challenge is the accurate grading and diagnosis of GEP-NENs, which is traditionally reliant on subjective methods. However, innovative technologies, such as artificial intelligence-based diagnostics, multi-omics approaches, and precision oncology, are now offering solutions for more precise and reliable classification. Meanwhile, emerging therapies aiming to activate the immune response or modify the tumor environment present promising avenues for improved outcomes. Realizing the full potential of these advances will require a thoughtful integration of molecular insights with standardized diagnostic practices and evolving therapeutic strategies, ensuring that progress in research meaningfully informs and enhances patient care across diverse clinical settings. This review discusses new advancements and explores future directions toward personalized and effective treatments for GEP-NENs. Full article

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are a family of tumors that arise throughout the gastrointestinal tract. These tumors are heterogeneous, with complex clinical symptoms and tumor behaviors, and demonstrate rising incidence rates worldwide. In addition to their nature, GEP-NETs possess limited diagnostic and therapeutic options, which results in poor survival rates for patients with metastatic tumors. Given these findings, a further analysis of these tumors’ biology is needed to determine new therapeutic strategies. The tumor microenvironment (TME) consists of several residual cell populations and non-cellular components whose altered behavior creates a tumor-supportive niche. Studies from other cancers demonstrate the TME’s significance in tumor initiation, progression, and spread. In this review, we discuss efforts to characterize the TME in GEP-NETs. Preliminary studies of the immune system in GEP-NETs have led to several major clinical trials, with limited success. Efforts to target signaling crosstalk between cancer-associated fibroblasts, vascular endothelial cells, and tumor cells has led to major discoveries and multiple approved therapies. Finally, alterations to the extracellular matrix may lead towards an improved understanding of GEP-NET development, behavior, and improved detection methods. While research has rapidly expanded our knowledge within the last decade, further work is needed to bring our understanding of the GEP-NET TME in line with other rare cancers. Full article

Background/Objectives: Small bowel tumors (SBTs) encompass a diverse range of tumor types, with benign tumors being the most prevalent. However, the incidence of malignant SBTs is increasing, particularly small bowel adenocarcinoma; this poses a diagnostic challenge for clinicians and radiologists due to the varied and nonspecific clinical and radiological presentations associated with SBTs. In fact, SBTs can present differently in emergencies, often mimicking inflammatory diseases or manifesting as complications such as intussusception, small bowel obstruction (SBO), intestinal ischemia, perforation, gastrointestinal bleeding, or metastatic disease. These tumors can remain asymptomatic for extended periods. Methods: We present a pictorial review on the role of imaging in evaluating SBTs, focusing on the emergency setting where diagnosis can be incidental. We also include some representative cases that may be useful for radiologists and residents in clinical practice. Results: Despite these challenges, contrast-enhanced computed tomography (CECT) is usually the best modality to use in emergencies for evaluating SBTs, and in some cases, a diagnosis can be made incidentally. However, when possible, multimodal imaging through cross-sectional imaging remains crucial for the non-invasive diagnosis of SBTs in stable patients, as endoscopic procedures may also be impractical. A complementary CT study with distension using negative oral contrast media, such as water, polyethylene glycol, or mannitol solutions, can improve the characterization of SBTs and rule out multiple SBT locations, particularly in small bowel neuroendocrine tumor (NET) and gastrointestinal tumor (GIST) localization. Positive water-soluble iodine-based oral contrast, such as Gastrografin (GGF), can be used to evaluate and monitor the intestinal lumen during the nonsurgical management of small bowel obstruction (SBO) or in suspected cases of small bowel perforations or the presence of fistulas. Magnetic resonance enterography (MRE) can aid in improving the characterization of SBTs through a multiplanar and multisequence study. Positron emission tomography combined with CT is generally an essential modality in evaluating metastatic disease and staging and assessing tumor prognosis, but it has limitations for indolent lymphoma and small NETs. Conclusions: Therefore, the integration of multiple imaging modalities can improve patient management and provide a preoperative risk assessment with prognostic and predictive indicators. In the future, radiomics could potentially serve as a “virtual biopsy” for SBTs, allowing for better diagnosis and more personalized management in precision medicine. 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/Objective: Identifying patterns of diagnostic imaging workflow parallel to the influence of certain variables, such as pathology guidelines over time, provides valuable insight for clinical decision making. This study presents a recurring trend of initial imaging orders and follow-ups, up to the diagnosis of pancreatic neuroendocrine tumors (pNETs), across two decades, with scans which led to pathological investigation. Methods: Three readers evaluated common conventional imaging among initial and follow-up studies for lesion detection and localization. Inter-reader and intra-reader analyses were controlled as contributing factors to the imaging diagnostic trend. Results: Our results show that CT was the prominent initial scan in pNET workup, likely due to their wide availability, high spatial resolution, and rapid acquisition, with a sufficient detection rate throughout both decades, regardless of technical advances. However, MRI scans also gained soaring popularity, especially among syndromic patients, likely due to follow-up and anatomical surgery precision. Conclusions: Newer modalities may be eventually useful and only requested for pNETs staging and further treatment. Full article

Transplant oncology integrates a wide variety of fields, such as surgery, oncology, and transplant medicine, intending to increase the range of studies and treatments for hepatobiliary cancers and other liver-related malignant lesions. Liver transplantation (LT) has proven to be an effective treatment for hepatocellular carcinoma. While the Milan criteria are still the gold standard, several new, more inclusive criteria have been proposed, and hepatocellular carcinoma has become a major indication for liver transplantation. The continuous evolution of diagnostic technologies supported this with higher image quality and more accurate staging. This review describes the current applications of transplant oncology in hepatocellular carcinoma, cholangiocarcinoma, neuroendocrine tumors, and liver metastatic disease from colorectal cancer and discusses the path that led to the development of transplant oncology as an organized approach to managing gastrointestinal malignancies through transplantation. More importantly, the significance of a multidisciplinary approach and criteria in the selection of suitable candidates are discussed. In addition, newer aspects of transplant oncology, such as immunotherapy, circulating tumor DNA (ctDNA), novel surgical techniques, and the utilization of artificial intelligence, are presented. Finally, the opportunities and challenges involved in the field’s future, as well as the evolution of the criteria used over the years and insightful thoughts for the future of the criteria, are discussed. 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

The Eastern Canadian Gastrointestinal Cancer Consensus Conference was an annual meeting that was held in St. John’s, Newfoundland and Labrador, from 26 to 28 September 2024. This included experts in medical oncology, radiation oncology, surgical oncology, nuclear medicine, and general practitioners in oncology (GPO) from across the eastern Canadian provinces who are involved in the management of patients with gastrointestinal malignancies. This consensus statement generated by the conference addresses multiple topics, including the management of localized rectal cancer, liver-limited colorectal cancer, systemic therapy for advanced biliary tract cancers, radioligand therapy for gastroenteropancreatic neuroendocrine tumors (GEP-NETs), systemic therapy for pancreatic and midgut well-differentiated NETs, and systemic therapy for HER2-positive gastroesophageal cancers. Full article

Neuroendocrine tumors (NETs) of the liver are a rare entity. NETs are often poorly recognized, with diagnostic difficulties and differential challenges between primary tumors of the liver and metastases from other organs, mainly from the gastrointestinal tract. Multidisciplinary and multi-technical diagnosis is mandatory to properly treat these tumors. This case describes the complex history and the treatment course of a 68-year-old man with a history of NET onset after liver transplantation. Liver transplantation is the treatment of choice for patients with advanced liver disease or acute liver failure, but careful pre- and post-transplant patient monitoring is required. Liver transplant patients receive immunosuppressive therapy, and donor livers should be screened to exclude potential malignancies. This clinical case, in addition to emphasizing the diagnostic and therapeutic difficulty of hepatic NET, underlines the role of post-transplant immunosuppressive therapy and pre-transplant screening, which includes a thorough evaluation of donor and recipient history, physical examination, and laboratory tests. Moreover, post-transplant immunosuppressive therapy is essential to maintain the viability of the transplanted organ, but it is not free from potential risks, including an increased risk of cancer. Therefore, close monitoring of therapy is necessary to optimize long-term results and the patient’s quality of life. Full article

Background: Gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs) are the most prevalent subgroup among NETs and include heterogeneous tumors characterized by different clinical behavior and prognosis. The NETest is a tool based on real-time PCR combined with deep learning strategies to specifically identify tumors with a neuroendocrine genotype. Despite the promising results achieved regarding its utility in the field of GEP-NETs, the NETest has not yet entered into routine clinical practice. Methods: We performed a systematic review aimed at summarizing available evidence on the application of the NETest in both the diagnosis and the prognostic stratification of GEP-NETs. Results: We identified five studies evaluating the diagnostic role of the NETest and nine studies evaluating its prognostic value. The NETest emerged as a reliable biomarker for GEP-NET diagnosis with an accuracy higher than 90%, regardless of tumor stage and grade. However, according to some studies, the NETest showed a low specificity, mainly attributed to interferences with other gastro-intestinal malignancies. In terms of prognostic value, the NETest correlated with the detection of residual disease after surgery in six studies. The NETest was also associated with patients’ survival outcomes, namely progression-free survival (PFS) and overall survival (OS) in three studies. Conclusions: According to current systematic review, the value of the NETest both for diagnosis and for prognosis of GEP-NET emerged as robust across different studies. Further prospective analysis on larger GEP-NET series is encouraged to validate this tool, improving patients’ diagnosis, management, and follow-up. Full article