Neuroendocrine neoplasms (NENs) are rare tumors, making up 0.5 % of all cancers, with around 65 % found in the gastroenteropancreatic (GEP) system, with increasing occurrence globally in recent years. The World Health Organization (WHO) classifies GEP-NENs into two main groups: neuroendocrine tumors and neuroendocrine carcinomas according to the new 2022 classification. To provide updated epidemiological data on GEP-NENs diagnosed at a tertiary referral center in Beirut, Lebanon, using the WHO 2022 classification, and to describe changes in incidence, demographics, and tumor characteristics compared with previously reported data. This retrospective study included patients treated at Hotel Dieu de France, from January 2013 to June 2024, with histologically confirmed GEP-NENs and complete medical records available. GEP-NENs were categorized based on their primary site and pathology reports reanalyzed according to the WHO 2022 classification. Data were then collected on patient demographics, primary tumor site, tumor grade and presence of metastasis at diagnosis. Among 194 NENs diagnosed during the study period, 74 were GEP-NENs (25.2 %). The mean age at diagnosis was 59.8 years, with a male-to-female ratio of 1.61. Of patients with available grading data, 39.0 % were classified as NET G1, 34.4 % as NET G2, and 26.6 % as high-grade disease (NET G3 and NEC combined). Compared with data from the previous decade, a lower proportion of G1 tumors and higher proportions of G2 and G3 tumors were observed, along with higher frequencies of pancreatic and hepatic primaries and lower rates of colonic and duodenal primaries. NET G3 and NECs were most frequently located in the liver, ampulla of Vater, and colon. All colorectal GEP-NENs identified were metastatic at diagnosis. GEP-NENs in this cohort were more frequently diagnosed with higher histological grades and metastatic disease compared to the previous decade, a pattern observed during a period marked by major socioeconomic disruption and the COVID-19 pandemic.

Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are common tumors of the digestive system. Although their histological diagnosis is usually straightforward, the differential diagnosis between neuroendocrine tumors G3 (NET G3) and neuroendocrine carcinomas (NECs) may be challenging at times due to a similar immunophenotype and morphology in a small number of cases. The objective of this study was to assess the expression and diagnostic value of PAX5 in GEP-NENs. Immunohistochemical (IHC) analysis for PAX5 was carried out in a large cohort of GEP-NENs, including 39 GEP-NECs and 62 GEP-NETs. Using a semi-quantitative scoring method, PAX5 was shown to be expressed in 30 of 39 GEP-NECs (77%), with 27 of 39 cases (69%) having positivity ≥ 10% in the cells. In particular, GEP-NECs with a high proliferative index had more PAX5-positive cells. None of the cases of GEP-NET G1 and G2 expressed PAX5, while only 2/12 cases of GEP-NET G3 (17%) were positive for PAX5, with PAX5 positivity observed in 1–10% and 10–50% of cells, respectively. The difference in PAX5 expression between GEP-NETs and GEP-NECs was statistically significant (3% vs. 77%, P < 0.001). PAX5 can be used as a complementary diagnostic IHC marker for GEP-NECs. In addition, PAX5 can be considered in cases when it is difficult to distinguish between GEP-NECs and GEP-NET G3.

Colorectal cancer (CRC), gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN), and cholangiocarcinoma (CCA) exhibit high rates of morbidity and mortality once metastasized to the liver. Liver transplantation (LT) is a viable therapeutic approach for these cancers in highly selected patients; however, their invasive nature at late stages causes many patients to be delisted from transplantation or to require further downstaging. Immunotherapy with immune checkpoint modulators has revolutionized cancer research. Immune checkpoint inhibitors (ICI) leverage the chronic inflammatory state and the overexpression of cytotoxic T lymphocyte antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1)/programmed cell death-ligand 1 (PD-L1) by malignant cells and regulatory T cells, to block immune checkpoints and counteract tumor's ability to evade the immune system. However, the interaction between allograft PD-L1 and PD-1 on infiltrating T cells functions as a means of graft tolerance in cases of LT. Therefore, the application of ICIs might block this protective effect and induce graft rejection, a phenomenon particularly observed in PD-1/PD-L1 inhibiting ICIs. The risk of post-LT graft rejection can be mitigated by applying advanced biomarkers and specifying certain mutations that enhance patient selection criteria for pre-LT ICI use. Furthermore, the determination of optimal intervals of ICI administration pre- and post-LT, identification of ICI indications in de novo malignancies occurring after LT, and investigation of biomarkers for early rejection detection, pave the way for more promising LT outcomes in patients with CRC, GEP-NEN, or CCA. Therefore, this review aims to illustrate a comprehensive overview of the role of ICI therapy in the management of non-hepatocellular carcinoma transplant oncology cancers by demonstrating the potential for its application in both pre-and post-LT states, and pathways to reduce or timely detect ICI-associated graft rejection.

Effective therapeutic strategies for advanced gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) remain challenging, including a lack of response to therapy and post-treatment relapse. The rapid development of targeted radionuclide therapy (TRT) offers promising data for patients with somatostatin receptor (SSTR)-expressing tumors. This approach exhibits more advantages than somatostatin analog (SSA) therapy, which is primarily effective for well-differentiated and slow-growing GEP-NENs. Fortunately, some clinical studies on peptide receptor radionuclide therapy (PRRT) labeled with α-emitting radionuclides for GEP-NENs patients showed effective results for those with more advanced GEP-NENs, or those with malignant metastasis. For the improvement of clinical efficacy and the decline in the incidence of treatment-related relapse, recent progress in developing novel techniques and effective disease management strategies for optimal targeting has led to the emergence of targeted alpha therapy (TAT) in GEP-NENs patients. For instance, labeled technology and combination therapy could contribute to significantly improved long-term outcomes. However, the exact dosimetry for precision oncology, the shortage of radionuclides, and the stability of disease control are still under careful consideration. More high-quality, large-scale prospective studies are essential for obtaining valuable evidence on challenging problems and for further exploration.

Gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN) is a rare tumor, but with increasing global prevalence. However, data on epidemiology and survival in Latin America are sparse. To describe clinical characteristics and survival in GEP-NEN treated at the Instituto Nacional de Cancerología in Bogotá, Colombia. This retrospective observational study included patients diagnosed with GEP-NEN between January 1, 2008 and January 1, 2020. Clinical and pathological data were extracted from medical records. Survival analysis was conducted using Kaplan-Meier estimators and Cox proportional hazards models. A total of 204 patients were included. Median age was 55 years (range: 19-83); 61.3% were women. Most tumors (95.6%) were well-differentiated gastroenteropancreatic neuroendocrine tumors (NETs), and 55.9% of patients presented with stage IV disease. The most common primary tumor sites were the pancreas (25.5%) and the small intestine (23.5%). Median interval from symptom onset to diagnosis was 12 months, with 25% of patients requiring ≥ 2 years for diagnosis. Median follow-up was 105 months (95% of CI: 87.6-115.2). Median overall survival was not reached. Poorer survival was significantly associated with higher tumor grade (P<0.001), age > 65 years (P=0.035), and metastatic disease at diagnosis (P<0.001). In contrast, surgical treatment was significantly associated with better overall survival (P=0.006). This study provides real-world evidence on outcomes in GEP-NEN in Latin America. Tumor grade, age, surgical treatment and metastasis at diagnosis were identified as key prognostic factors, highlighting the importance of early diagnosis and timely intervention.