RARE DISEASE
Ileal neuroendocrine tumor
Ileal neuroendocrine tumor
Ileal neuroendocrine tumor
Synonyms: Ileal neuroendocrine neoplasm
Synonyms: Ileal neuroendocrine neoplasm
Synonyms: Ileal neuroendocrine neoplasm
Drug discovery
1
drug
With orphan designation
Overview
Ileal neuroendocrine tumors (I-NETs), the most common small bowel NETs, arise from serotonin-producing enterochromaffin cells. These tumors frequently present at advanced stages (71% with metastases) due to nonspecific symptoms like abdominal pain or obstruction. Surgical resection remains first-line for localized disease, while systemic therapies—somatostatin analogs, peptide receptor radionuclide therapy (PRRT), and mTOR inhibitors—manage advanced/metastatic cases. Prognosis correlates with tumor grade and stage, with 5-year survival rates exceeding 88% for localized disease but declining with metastasis [1][2][4][12].
Burden
Metastatic spread: 40-64% present with distant metastases (commonly liver) [1][12][17]
Survival: 5-year cancer-specific survival 95% (localized) vs. 54% (distant) [1][17]
Comorbidities: Carcinoid syndrome (6-30% with liver metastases), cardiac fibrosis, and bowel obstruction [4][12][13]
Quality of life: Chronic diarrhea, flushing, and treatment-related side effects (e.g., interferon-induced fatigue) [3][14]
Therapies
Localized disease: Surgical resection (e.g., right hemicolectomy) with lymph node dissection [1][16][17]
Advanced disease:
- First-line: Somatostatin analogs (octreotide/lanreotide) for tumor control and symptom management [3][13][16]
- Second-line: PRRT (177Lu-DOTATATE), mTOR inhibitors (everolimus), or interferon-α [3][13][20]Metastatic liver disease: Hepatic resection, ablation, or embolization [3][16]
Categories: rare endocrine diseases, rare gastroenterological diseases, rare neoplastic diseases, rare transplant-related disorders
Research Papers
331 drug discovery papers about Ileal neuroendocrine tumor, with 3 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
331 drug discovery papers about Ileal neuroendocrine tumor, with 3 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-04-22 | Real-world presentation and outcomes of gastroenteropancreatic neuroendocrine neoplasms in Italy: findings from the nationwide Itanet prospective database.
The incidence of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) is increasing, but population registries seldom capture detailed clinical data. The Italian Association for Neuroendocrine Tumours (Itanet) established a nationwide prospective database to describe presentation, diagnostic pathways, management, and outcomes of newly diagnosed GEP-NENs in Italy. This multicentre prospective observational study enrolled 2138 consecutive patients with newly diagnosed GEP-NENs across 38 Italian centres (2019-2024). Clinical, pathological, imaging, and treatment data were prospectively collected and centrally validated. Descriptive and survival analyses were performed; Ki-67 was modelled as a continuous variable. Median age was 60.6 years, and 55.9% (1195/2138) were male. Tumours were well-differentiated NETs in 90.8% of patients (1942/2138), mainly of pancreatic (41.4%, 886/2138) or ileal (19.7%, 422/2138) origin. Median Ki-67 was 2%. An incidental diagnosis occurred in 58.6% (1254/2138) of cases. Among symptomatic patients, the mean diagnostic delay was 197 days (224 for pancreatic vs 184 for small bowel; p = 0.039). 68Ga-DOTA-peptide PET showed higher diagnostic yield than CT or MRI in small-bowel primaries (93.7% vs 83.1% vs 67.4%), whereas performance was similar in pancreatic tumours. Data on first-line treatment were available for 2050 patients. Initial management included surgery in 36.4% (746/2050), watchful waiting in 19.7% (404/2050), endoscopic resection in 7.7% (158/2050). Overall, 30.6% (627/2050) of patients received systemic therapy, most commonly somatostatin analogues in 23.7% (487/2050). Over a median follow-up of 271 days (IQR 121-530), 62 deaths were observed (event rate 4.9%). Overall survival differed markedly according to metastatic status and tumour grade. Ki-67 was prognostic when modelled continuously (p < 0.001), and a 15% cutoff identified poorer outcomes. This nationwide prospective study delineates real-world diagnostic and therapeutic patterns of GEP-NENs in Italy, confirms Ki-67 as a continuous prognostic biomarker, and identifies a 15% threshold associated with worse survival, providing a benchmark for outcome assessment and future clinical research. None.
2026-03-16 | Malignant Small Bowel Neoplasms: A 20-Year Retrospective Analysis in a Tertiary Center.
Malignant small bowel neoplasms are rare entities, and knowledge about them remains limited due to their histological diversity and the challenges associated with their investigation. However, their rising incidence has generated increasing clinical and research interest. This study aimed to describe the demographic and clinical characteristics of patients with malignant neoplasms of small bowel and the evolution in their diagnosis over 20 years in a tertiary center. Single-center retrospective study of data of patients with malignant small bowel neoplasms diagnosed between 2001 and 2020 in a tertiary hospital was performed. Statistical analysis was performed with SPSS version 29.0 (significance level ≤0.05). Out of 135 patients included, 57% were male. Eighty-nine neoplasms (65.9%) were found in the jejunum/ileum. Adenocarcinomas were the most frequently diagnosed neoplasms (31.1%), followed by neuroendocrine tumors (28.1%). At the time of diagnosis, the majority of patients (80.7%) were symptomatic, with severe complications - including obstruction, hemorrhage, or perforation - occurring in 55.4% of cases. Diagnosis typically involved CT scan (40.7%) or upper digestive endoscopy (22.2%); notably, 22.2% patients still required surgery for diagnosis. Diagnoses were mainly made between 2011 and 2020 (65.9%). Between 2001 and 2010, the most common diagnosed tumors were adenocarcinomas (37.0%), whereas between 2011 and 2020, the most frequently diagnosed malignant neoplasms were neuroendocrine tumors (37.1%). The distribution of histological types differed significantly over the years (p = 0.016). Adenocarcinoma had a higher mortality rate (54.8%) compared to neuroendocrine tumors (7.9%). Given the rarity of these tumors, the cohort of malignant small bowel neoplasms collected at this tertiary center over a 20-year period represents a substantial sample. More than half of patients were symptomatic at diagnosis, despite diagnostic advances over the years. In the last 10 years of the study, there has been an increase in incidence as well as in 5-year survival rates, possibly due to the higher incidence of neuroendocrine tumors and the lower incidence of adenocarcinomas. Notably, the diagnosis of each histological neoplasm type differed significantly statistically over the years, with neuroendocrine tumors being the most diagnosed in recent years.
2026-03-13 | Multivalvular Cardiac Involvement from Giant Hepatic Metastases of an Ileal Neuroendocrine Tumor.
Intestinal neuroendocrine tumors (NETs) are rare, slow-growing neoplasms arising from enterochromaffin cells, capable of secreting vasoactive substances that may cause carcinoid syndrome (CS) and clinically significant valvular heart disease. These tumors are often diagnosed at advanced stages due to nonspecific gastrointestinal symptoms, and distant metastases, particularly to the liver and lymph nodes, are common at presentation. Hormonal dysregulation can lead to chronic diarrhea, flushing, and bronchospasm, while carcinoid heart disease (CHD) contributes substantially to morbidity and mortality, typically affecting right-sided valves, with left-sided involvement being uncommon and more frequently associated with intracardiac shunts than exceptionally high serotonin exposure. Recent advances in management emphasize a multidisciplinary approach integrating systemic therapy, surgery, and targeted radionuclide treatment. Somatostatin analog therapy remains the cornerstone for controlling hormonal symptoms and slowing tumor progression. Aggressive cytoreductive surgery to achieve hormonal stabilization prior to surgical valve replacement has been associated with improved survival, symptomatic relief, and cardiac function. Targeted peptide receptor radionuclide therapy provides additional treatment for residual or metastatic disease, enhancing biochemical and radiological control. We report the case of a 61-year-old woman with chronic diarrhea, weight loss, and recurrent flushing, diagnosed with a well-differentiated ileal NET with extensive hepatic metastases and severe right-sided valvular disease with mild left-sided involvement. She underwent somatostatin analog therapy to control hormonal symptoms, cytoreductive surgery, and surgical replacement of the pulmonary and tricuspid valves. Subsequent targeted peptide receptor radionuclide therapy further reduced tumor burden and stabilized biochemical markers. This combined multimodal strategy resulted in sustained clinical improvement, normalization of neuroendocrine markers, and long-term oncologic stability, as the patient remains asymptomatic and oncologically stable after four years of follow-up from initial presentation. This case highlights the importance of early recognition, comprehensive evaluation, and a multidisciplinary strategy in advanced NETs. Coordinated care integrating endocrinology, oncology, cardiology, nuclear medicine, and surgery can significantly improve survival, hormonal control, and quality of life in patients with complex metastatic disease.
2026-04-22 | Real-world presentation and outcomes of gastroenteropancreatic neuroendocrine neoplasms in Italy: findings from the nationwide Itanet prospective database.
The incidence of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) is increasing, but population registries seldom capture detailed clinical data. The Italian Association for Neuroendocrine Tumours (Itanet) established a nationwide prospective database to describe presentation, diagnostic pathways, management, and outcomes of newly diagnosed GEP-NENs in Italy. This multicentre prospective observational study enrolled 2138 consecutive patients with newly diagnosed GEP-NENs across 38 Italian centres (2019-2024). Clinical, pathological, imaging, and treatment data were prospectively collected and centrally validated. Descriptive and survival analyses were performed; Ki-67 was modelled as a continuous variable. Median age was 60.6 years, and 55.9% (1195/2138) were male. Tumours were well-differentiated NETs in 90.8% of patients (1942/2138), mainly of pancreatic (41.4%, 886/2138) or ileal (19.7%, 422/2138) origin. Median Ki-67 was 2%. An incidental diagnosis occurred in 58.6% (1254/2138) of cases. Among symptomatic patients, the mean diagnostic delay was 197 days (224 for pancreatic vs 184 for small bowel; p = 0.039). 68Ga-DOTA-peptide PET showed higher diagnostic yield than CT or MRI in small-bowel primaries (93.7% vs 83.1% vs 67.4%), whereas performance was similar in pancreatic tumours. Data on first-line treatment were available for 2050 patients. Initial management included surgery in 36.4% (746/2050), watchful waiting in 19.7% (404/2050), endoscopic resection in 7.7% (158/2050). Overall, 30.6% (627/2050) of patients received systemic therapy, most commonly somatostatin analogues in 23.7% (487/2050). Over a median follow-up of 271 days (IQR 121-530), 62 deaths were observed (event rate 4.9%). Overall survival differed markedly according to metastatic status and tumour grade. Ki-67 was prognostic when modelled continuously (p < 0.001), and a 15% cutoff identified poorer outcomes. This nationwide prospective study delineates real-world diagnostic and therapeutic patterns of GEP-NENs in Italy, confirms Ki-67 as a continuous prognostic biomarker, and identifies a 15% threshold associated with worse survival, providing a benchmark for outcome assessment and future clinical research. None.
2026-03-16 | Malignant Small Bowel Neoplasms: A 20-Year Retrospective Analysis in a Tertiary Center.
Malignant small bowel neoplasms are rare entities, and knowledge about them remains limited due to their histological diversity and the challenges associated with their investigation. However, their rising incidence has generated increasing clinical and research interest. This study aimed to describe the demographic and clinical characteristics of patients with malignant neoplasms of small bowel and the evolution in their diagnosis over 20 years in a tertiary center. Single-center retrospective study of data of patients with malignant small bowel neoplasms diagnosed between 2001 and 2020 in a tertiary hospital was performed. Statistical analysis was performed with SPSS version 29.0 (significance level ≤0.05). Out of 135 patients included, 57% were male. Eighty-nine neoplasms (65.9%) were found in the jejunum/ileum. Adenocarcinomas were the most frequently diagnosed neoplasms (31.1%), followed by neuroendocrine tumors (28.1%). At the time of diagnosis, the majority of patients (80.7%) were symptomatic, with severe complications - including obstruction, hemorrhage, or perforation - occurring in 55.4% of cases. Diagnosis typically involved CT scan (40.7%) or upper digestive endoscopy (22.2%); notably, 22.2% patients still required surgery for diagnosis. Diagnoses were mainly made between 2011 and 2020 (65.9%). Between 2001 and 2010, the most common diagnosed tumors were adenocarcinomas (37.0%), whereas between 2011 and 2020, the most frequently diagnosed malignant neoplasms were neuroendocrine tumors (37.1%). The distribution of histological types differed significantly over the years (p = 0.016). Adenocarcinoma had a higher mortality rate (54.8%) compared to neuroendocrine tumors (7.9%). Given the rarity of these tumors, the cohort of malignant small bowel neoplasms collected at this tertiary center over a 20-year period represents a substantial sample. More than half of patients were symptomatic at diagnosis, despite diagnostic advances over the years. In the last 10 years of the study, there has been an increase in incidence as well as in 5-year survival rates, possibly due to the higher incidence of neuroendocrine tumors and the lower incidence of adenocarcinomas. Notably, the diagnosis of each histological neoplasm type differed significantly statistically over the years, with neuroendocrine tumors being the most diagnosed in recent years.
2026-03-13 | Multivalvular Cardiac Involvement from Giant Hepatic Metastases of an Ileal Neuroendocrine Tumor.
Intestinal neuroendocrine tumors (NETs) are rare, slow-growing neoplasms arising from enterochromaffin cells, capable of secreting vasoactive substances that may cause carcinoid syndrome (CS) and clinically significant valvular heart disease. These tumors are often diagnosed at advanced stages due to nonspecific gastrointestinal symptoms, and distant metastases, particularly to the liver and lymph nodes, are common at presentation. Hormonal dysregulation can lead to chronic diarrhea, flushing, and bronchospasm, while carcinoid heart disease (CHD) contributes substantially to morbidity and mortality, typically affecting right-sided valves, with left-sided involvement being uncommon and more frequently associated with intracardiac shunts than exceptionally high serotonin exposure. Recent advances in management emphasize a multidisciplinary approach integrating systemic therapy, surgery, and targeted radionuclide treatment. Somatostatin analog therapy remains the cornerstone for controlling hormonal symptoms and slowing tumor progression. Aggressive cytoreductive surgery to achieve hormonal stabilization prior to surgical valve replacement has been associated with improved survival, symptomatic relief, and cardiac function. Targeted peptide receptor radionuclide therapy provides additional treatment for residual or metastatic disease, enhancing biochemical and radiological control. We report the case of a 61-year-old woman with chronic diarrhea, weight loss, and recurrent flushing, diagnosed with a well-differentiated ileal NET with extensive hepatic metastases and severe right-sided valvular disease with mild left-sided involvement. She underwent somatostatin analog therapy to control hormonal symptoms, cytoreductive surgery, and surgical replacement of the pulmonary and tricuspid valves. Subsequent targeted peptide receptor radionuclide therapy further reduced tumor burden and stabilized biochemical markers. This combined multimodal strategy resulted in sustained clinical improvement, normalization of neuroendocrine markers, and long-term oncologic stability, as the patient remains asymptomatic and oncologically stable after four years of follow-up from initial presentation. This case highlights the importance of early recognition, comprehensive evaluation, and a multidisciplinary strategy in advanced NETs. Coordinated care integrating endocrinology, oncology, cardiology, nuclear medicine, and surgery can significantly improve survival, hormonal control, and quality of life in patients with complex metastatic disease.
Access all drug discovery articles and probability of success in trials forecasts:
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Drug Discovery Landscape
1 orphan drug designation for Ileal neuroendocrine tumor.
1 orphan drug designation for Ileal neuroendocrine tumor.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
human adenovirus C serotype 5 with E1 gene controlled by chromogranin A promoter and hexon modified with protein transduction domain motif | gene therapies | FDA | 2024-12-18 | — | Elicera Therapeutics AB |
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