Background: Neuroendocrine neoplasms are a heterogeneous group of tumors that raise challenges in terms of diagnosis, treatment and monitoring. Despite continuous efforts, no biomarker has showed satisfying accuracy in predicting outcome or response to treatment. Methods: We conducted a systematic review to determine relevant circulating biomarkers for angiogenesis in neuroendocrine tumors. We searched three databases (Pubmed, Embase, Web of Science) using the keywords “neuroendocrine” and “biomarkers”, plus specific biomarkers were searched by full and abbreviated name. From a total of 2448 publications, 11 articles met the eligibility criteria. Results: VEGF is the most potent and the most studied angiogenic molecule, but results were highly controversial. Placental growth factor, Angiopoietin 2 and IL-8 were the most consistent markers in predicting poor outcome and aggressive disease behavior. Conclusions: There is no robust evidence so far to sustain the use of angiogenic biomarkers in routine practice, although the results show promising leads.

Background and Aims: Celiac disease is characterized by an inappropriate T-cell-mediated response to gluten in small bowel in genetically predisposed individuals, carriers of the DQ2 and/or DQ8 haplotypes of the human leukocyte antigen. The aim of our study was to asses HLA typing in adult patients with celiac disease, in their first degree relatives and in a healthy control group. Methods: We conducted a prospective observational study on three cohorts: 117 patients diagnosed with celiac disease, 41 first-degree relatives of celiac patients and 57 asymptomatic healthy volunteers. Low resolution HLA typing for DQ alleles was performed in all study subjects with DNA extracted from peripheral blood, using SSP HLA-DQB1 kit (Innotrain Diagnostik GmbH, Germany). Next Generation Sequencing (NGS) was used only in 18 patients for typing confirmation of DQB1 and DQA1 loci and whole gene sequencing. Results: Prevalence of HLA-DQ2 was significantly higher in the CD group compared to the healthy subjects group (95.6% vs 29.8%, p <0.001), with no statistically significant differences in HLA-DQ8 and combined HLA-DQ2/DQ8 prevalences.Several HLA DQA1 and DQB1 alleles (HLA-DQA1* 05:01, HLA-DQB1*02:01, HLA-DQB1*02:02) and haplotypes (DQA1*02:01-DQB1*02:02,DQA1*05:01-DQB1*02:01) were strongly associated with celiac disease in our group: OR 4.28, 4.28, 4.67 and 5.43 and 4.28 respectively. Predominantly, patients presented with typical symptoms and iron deficiency anemia. 95.5% of them had histological Marsh type modifications ≥3a. A relatively poor response to gluten-free diet was observed and 9.4% developed complications (refractory celiac disease, enteropathy-associated T cell lymphoma, intestinal adenocarcinoma), with a death rate of 6.8%. 23% associated other autoimmune diseases.Screening adherence for 1st degree relatives was very low: only 16%. Familial screening diagnosed 4 cases of asymptomatic celiac disease. 32 relatives (78%) had HLA-DQ2 haplotype, 5 carried HLA-DQ8, 4 didn’t carry any risk haplotype. Conclusions: This study demonstrated a higher prevalence of the HLA-DQ2 genotype in patients with celiac disease compared to the healthy population but not of HLA-DQ8 or combined HLA-DQ2/DQ8. Alleles HLA-DQA1* 05:01, HLA-DQB1*02:01, HLA-DQB1*02:02 and haplotypes (DQA1*02:01-DQB1*02:02,DQA1*05:01-DQB1*02:01) were strongly associated with celiac disease in our cohort.

Background and Objectives: Neuroendocrine neoplasms (NENs) require multidisciplinary management, yet access to advanced imaging and therapies is uneven across Europe. We aimed to describe real-world management of NENs in an Eastern Europe referral center. Methods: This retrospective single-center study included 192 NEN patients treated between 2011 and 2026 at a national referral center in Romania. Results: Most tumors were well-differentiated (88%), pancreatic primary (59.9%), and non-functioning (77.1%); 51.0% were metastatic at diagnosis. Overall, 30.7% (n = 59) of patients underwent somatostatin receptor imaging, mainly with locally available 99mTc-HYNIC-TOC scintigraphy (n = 56). Among therapeutic modalities, 68.2% of patients underwent conventional systemic therapy and 69.3% had surgery (R0 resection was achieved in 98.9% of curative-intent surgeries; recurrence rate 40%). Peptide receptor radionuclide therapy (PRRT) was performed in 14.6% (19/130) of metastatic NENs and liver-directed therapy (LDT) in 13.6% (16/118) of NENs with liver metastases. Median time to treatment was 78 days for somatostatin analogs, 29 days for chemotherapy in neuroendocrine carcinoma, 30 days for surgery, 62.5 days for LDT, and 144 days for PRRT. Conclusions: This is one of the few reports on real-world management of NENs in an Eastern European tertiary care referral center, which highlights the available multidisciplinary care but also the challenges in diagnostics and therapeutic access for patients with NEN.