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Background. Endoscopic resection is considered the treatment of choice for type I gastric neuroendocrine neoplasia (gNEN) given its indolent behaviour; however, the favoured endoscopic technique to remove these tumours is not well established. Aims. This systematic review is aimed at investigating the best endoscopic management for type I gNEN. Methods. PubMed Central/Medline and Scopus were systematically searched for records up to August 31, 2020. Results. After screening the 675 retrieved records, 6 studies were selected for the final analysis. The main endoscopic resection techniques described were endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD). Overall, 112 gNENs were removed by EMR and 77 by ESD. Both techniques showed similar results for complete and en bloc resection (97.4% and 98.7%; 92.3% and 96.3% with ESD and EMR, respectively). ESD was associated with a higher rate of complications than EMR (11.7% vs. 5.4%), but this difference was not statistically significant (p=0.17). The rates of recurrence during follow-up were 18.2% and 11.5% for EMR and ESD, respectively. Conclusions. To date, there are no sufficient data showing superiority of a given endoscopic technique over others. Both ESD and EMR seem to be effective in the management of type I gNEN, with a relatively low rate of recurrence.

Although re-assessment of proliferative activity by K67 evaluation during the course of neuroendocrine neoplasms (NENs) is recommended in selected patients, its impact on patients' management is not clear due to the lack of data supporting this practice. To investigate Ki67 change at time of progressive disease (PD) in entero-pancreatic NENs (EP-NENs). Retrospective analysis of sporadic EP-NENs which received histological re-assessment after PD once radiologically documented. Forty-three patients were evaluated, including 24 pancreatic NENs (PNENs), and 19 small intestine NENs (SI-NENs). At time of initial histological evaluation, 19 patients had grade 1 (G1) NETs (44.2%), and 24 grade 2 (G2) NETs (55.8%), overall median Ki67 being 3% (range 1%-20%). At time of PD, 13 patients had G1 NETs (30.2%), 26 G2 NETs (60.5%), and 4 had grade 3 (G3) NECs (9.3%), thus resulting in a significant median Ki67 increase (8%, range 1%-70%; p = 0.0006), and a G upgrading in 12 patients (27.9%). A statistically significant Ki67 increase and G grading change at time of PD was observed in PNENs (p = 0.0005 and p = 0.028, respectively). Conversely, no statistically significant change occurred in non-PNENs. In PNENs with documented PD, Ki67 increase occurs in a significant proportion of patients, providing useful information necessary to choose appropriate therapeutic options.

Objective The incidental diagnosis of type I gastric neuroendocrine tumors (gNETs) has become increasingly frequent in clinical practice, largely due to the widespread use of upper gastrointestinal endoscopy and improved recognition of these lesions. Although typically indolent, type I gNETs require accurate assessment to ensure appropriate risk stratification, management, and follow‐up. This review provides a practical, evidence‐based guide specifically designed for gastroenterologists and clinicians managing patients with incidentally discovered type I gNETs. Methods Structured in a step‐by‐step format, the review outlines key aspects of diagnosis and management, including endoscopic recognition and differential diagnosis, histological confirmation with a focus on corpus‐restricted atrophic gastritis, initial risk assessment based on tumor characteristics and patient factors, and the use of additional imaging modalities such as endoscopic ultrasound, cross‐sectional imaging, and functional imaging. Results The review emphasizes the importance of referring patients to specialized centers for multidisciplinary evaluation, a strategy shown to improve clinical outcomes and adherence to best practices. Finally, practical recommendations for long‐term surveillance are provided, with clear indications tailored to individual patient risk profiles. Conclusion By integrating current guidelines with practical insights and highlighting critical decision points, this review serves as a concise, user‐friendly tool to support clinicians in optimizing the care of patients with type I gastric NETs. This stepwise approach aims to bridge the gap between complex guideline recommendations and daily clinical practice, offering actionable guidance to ensure safe, effective, and standardized management of these increasingly encountered lesions.

Carcinoid syndrome (CS) is the most common functional syndrome associated with neuroendocrine neoplasia (NEN), particularly in intestinal NEN with extensive liver metastases. Owing to the heterogenous symptomatic scenario present in CS, recognition of these patients may be challenging. In this review, we explore some key clinical factors used to identify patients affected by CS, with particular focus on differential diagnoses of diarrhea, which is the main symptom of CS. Moreover, we highlight the importance of nutritional screening as a clinical indication to prevent malnutrition and to manage the most common nutrient deficiencies present in these patients.

Gastric neuroendocrine neoplasms (g-NENs) are rare tumors arising from the gastric enterochromaffin-like cells. Recent data suggests an increased detection rate, attributed to more frequent esophagogastroduodenoscopies. While type 3 g-NENs were historically deemed aggressive, emerging research indicates potential for conservative management, especially endoscopic resection, in well-differentiated, small tumors. European guidelines now advocate for endoscopic intervention in selected cases, but North American guidelines remain more conservative. Key factors influencing outcomes are tumor size, grading, and depth of gastric wall infiltration. Endoscopic resection has shown promise for tumors confined to submucosal layers without lymphovascular invasion. Given the complexities, a multidisciplinary team approach is essential for management decisions. Current insights are largely based on retrospective studies, underscoring the need for prospective research to optimize endoscopic approaches.

Background/Objectives: Lutathera® ([177Lu]Lu-DOTA-TATE) is the first radiolabelled somatostatin (SST) analog approved for the treatment of patients with well-differentiated (G1 and G2) unresectable or metastatic gastro-entero-pancreatic neuro-endocrine-neoplasms (GEP-NENs). The bone marrow and kidneys are critical organs for RLT with [177Lu]Lu-DOTA-TATE. Our purpose was to evaluate hematological and renal toxicity in 29 patients (18 males, 11 females) treated with Lutathera®. Methods: According to standard protocols, four cycles of (177Lu)Lu-DOTA-TATE were administered every eight/nine weeks. Patients received pre-medication with anti-emetic and anti-acid drugs and a slow amino acid infusion for renal protection. Blood count and serum creatinine data were collected at three time points: before the first cycle, after the second cycle, and at the end of treatment. Results: We found that almost all hematological parameters significantly decreased between the baseline and/or interim and post-therapy evaluation, although without a clinical impact. The presence of total tumor load or bone metastases had no influence on these findings, while male patients showed less hematological toxicity than females. Conversely, creatinine levels did not vary during treatment. Conclusions: Our study confirms that [177Lu]Lu-DOTATATE RLT is safe and well tolerated despite some minor (grade 1) hematological toxicity.

Owing to the rarity and the biological and clinical heterogeneity of gastroenteropancreatic neuroendocrine neoplasia (GEP NEN), the management of these patients may be challenging for physicians. This review highlights the specific features of GEP NEN with particular attention on the role of Ki67 heterogeneity, the potential prognostic role of novel radiological techniques, and the clinical usefulness of functional imaging, including 68Ga-DOTA-SST PET/CT and 18F-FDG PET/CT. Understanding these specific features may help to plan proper and tailored follow-up programs and therapeutic approaches.

Background: The ocular involvement of neuroendocrine neoplasms (NENs) is uncommon and mainly represented by metastases from gastrointestinal and lung neuroendocrine tumors. Primary orbital NENs are even less common and their diagnostic and therapeutic management is a challenge. Methods: A systematic review of the literature was conducted from 1966 to September 2023 on PubMed to identify articles on orbital NENs and to summarize their clinical–pathological features, diagnosis and therapeutic management. Furthermore, we presented a case of a locally advanced retro-orbital primary neuroendocrine tumor that was referred to the certified Center of Excellence of Sant’Andrea Hospital, La Sapienza University of Rome, Italy. Results: The final analysis included 63 records on orbital NENs and 11 records focused on primary orbital NENs. The localization was mostly unilateral and in the right orbit; proptosis or exophthalmos represented the initial symptoms. The diagnostic work-up and therapeutic management was discussed and a diagnostic algorithm for the suspicion of primary orbital NENs was proposed. Conclusions: A multidisciplinary approach is required for the management of primary orbital NENs, emphasizing the importance of early referral to dedicated centers for prompt differential diagnosis, tailored treatment, and an improved quality of life and survival.

Opinion statement Functional pancreatic neuroendocrine neoplasms (pNENs) are rare and heterogeneous diseases in terms of both clinical and pathological aspects. These tumors secrete hormones or peptides, which may cause a wide variety of symptoms related to a clinical syndrome. The management of functional pNENs is still challenging for clinicians due to the need to control both tumor growth and specific symptoms. Surgery remains the cornerstone in the management of local disease because it can definitively cure the patient. However, when the disease is not resectable, a broad spectrum of therapeutic options, including locoregional therapy, somatostatin analogs (SSAs), targeted therapies, peptide-receptor radionuclide therapy (PRRT), and chemotherapy, are available. The present review summarizes the main key issues regarding the clinical management of these tumors, providing a specific highlight on their therapeutic approach.

One of the most unusual complications in cholethiasis is spontaneous cholecystocutaneous fistula, which has only been reported a few times in the literature.  We report the case of a 76 year old man who presented with a right hypochondrium subcutaneous abscess, with pain evoked through palpation.  No comorbidity in the patient's medical history were noted.   Confirmation of cholecystocutaneous fistula was made using the proper diagnostic process, which is computed tomography with contrast media, followed by hepatobiliary MRI. This confirmed the presence of a fistulous pathway between the gallbladder and the skin.  The patient underwent cholecystectomy surgery and open laparotomy with en block aponeurotic muscle, skin and fistula orifice excision.