RARE DISEASE
Rare carcinoma of small intestine
Rare carcinoma of small intestine
Rare carcinoma of small intestine
Synonyms: Rare carcinoma of small bowel
Synonyms: Rare carcinoma of small bowel
Synonyms: Rare carcinoma of small bowel
Drug discovery
0
drugs
With orphan designations
Overview
Rare carcinomas of the small intestine (incidence <6/100,000/year) [4] are aggressive malignancies, primarily adenocarcinomas (35%-42% of cases) [6], often diagnosed late due to nonspecific symptoms [9]. Prognosis depends on tumor resectability, with 5-year survival dropping from 65% in localized adenocarcinoma to 4% in metastatic disease [5]. Key risk factors include Crohn’s disease, genetic syndromes (Lynch/FAP), and dietary factors [1][14].
Burden
Represents 3.8% of digestive system malignancies [7]; ≤32% present with metastatic disease [3]
5-year survival ranges from 4% (metastatic adenocarcinoma) to 95% (localized carcinoids) [5][6]
High healthcare utilization due to diagnostic delays, complex multimodal therapy, and 30%-40% recurrence rates [1][9]
Therapies
Surgical resection: Primary treatment for localized disease [1][7]; HIPEC considered for limited peritoneal metastases [3][11]
Systemic therapy: FOLFOX/CAPOX first-line chemotherapy (median OS 15-20 months) [3]; FOLFIRI second-line [7]
Emerging approaches: Immune checkpoint inhibitors for MSI-H tumors [3]; tyrosine kinase inhibitors for GISTs [15]
Categories: rare gastroenterological diseases, rare neoplastic diseases, rare transplant-related disorders
Research Papers
155 drug discovery papers about Rare carcinoma of small intestine, with 1 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
155 drug discovery papers about Rare carcinoma of small intestine, with 1 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-08-12 | Advanced local jejunal carcinoma treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC): a case report and review of the literature.
Jejunal carcinoma, a rare subset of small bowel adenocarcinomas, is characterized by its aggressive nature and nonspecific clinical presentation. The prognosis becomes particularly poor when peritoneal carcinomatosis is present. Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) has emerged as a treatment performed with curative intent for select patients with gastrointestinal cancers, particularly those with limited peritoneal metastases. A 51-year-old female presented with progressive symptoms of small bowel obstruction and gastrointestinal bleeding, diagnosed as jejunal adenocarcinoma with limited peritoneal carcinomatosis. She underwent CRS combined with HIPEC. Postoperative recovery was uneventful, with imaging studies and pathological analysis confirming complete tumor resection. HIPEC and CRS have shown potential in managing peritoneal carcinomatosis. However, their efficacy in rare cancers, such as jejunal carcinoma, remains underexplored. Studies show encouraging outcomes for small bowel adenocarcinoma treated with CRS and HIPEC, emphasizing patient selection and multidisciplinary management.
2026-07-21 | WIN-MTB-2024017 - WIN International Molecular Tumor Board: A 48-year-old female with multiple primary cancers.
Copyright: © 2026 El-Deiry et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Multiple primary cancers (MPC), the occurrence of two or more distinct malignancies in the same patient, pose significant clinical challenges due to their complexity and the need for individualized treatment strategies. This case, discussed at the WIN Consortium International Molecular Tumor Board, illustrates the clinical journey of a 48-year-old female with a BRCA1 germline mutation who developed multiple primary cancers: breast, skin, high-grade serous carcinoma of the ovary, colon and small bowel cancers. Her treatment history included doxorubicin and cyclophosphamide for breast cancer, Mohs surgery for basal cell carcinoma, and carboplatin and paclitaxel for ovarian cancer. After participating in the PRIMA trial with niraparib, she was diagnosed with PIK3CA-mutated colon cancer, leading to resection and CAPOX chemotherapy. A subsequent diagnosis of small bowel adenocarcinoma, molecularly resembling her colon cancer, along with a unique BRCA1-STARD3 fusion in inguinal lymph nodes prompted a comprehensive MTB review. The panel discussed several precision strategies, including combinations of cetuximab, niraparib, and temsirolimus; FOLFIRI with anti-EGFR inhibitors; anti-CTLA-4 and anti-PD-1 (botensilimab and balstilimab); regorafenib with anti-CTLA-4 and anti-PD-1 (ipilimumab and nivolumab); trifluridine/tipiracil with bevacizumab; regorafenib alone; aspirin for potential benefits in patients with PIK3CA mutations; therapies targeting PIK3CA and EGFR alterations; regular imaging and liquid biopsies assessments for monitoring disease progression and guide future treatment decisions; and vaccines targeting PIK3CA, STARD3 and TP53. This case underscores the complexity of managing MPC and highlights the essential role of international molecular tumor boards in generating innovative, tailored treatment recommendations for patients with rare and multifaceted disease courses.
2026-04-15 | Efficacy of targeted therapies for metastatic small bowel adenocarcinoma treatment: A retrospective study by AGEO.
Small bowel adenocarcinoma (SBA) is a rare malignancy with poor prognosis. In metastatic disease, evidence regarding the efficacy of chemotherapy (CT) combined with bevacizumab or anti-EGFR agents is limited to small studies. This study aimed to assess, in real-world practice, the effectiveness of first-line CT combined with targeted therapies (TT)-either antiangiogenic (AA) or anti-EGFR-compared with CT alone in patients with metastatic SBA (mSBA) and proficient mismatch repair/microsatellite stable (pMMR/MSS) status. This retrospective multicentre study included all patients receiving at least one cycle of CT with or without TT for mSBA. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), objective response rate (ORR), and safety. Analyses used inverse probability of treatment weighting (IPTW) in univariable Cox models to account for potential confounding factors that were unbalanced between groups. A total of 255 patients were included: 153 received CT alone, 45 CT+AA, and 16 CT+anti-EGFR as first-line therapy. Median PFS was 8.0 months with CT alone versus 11.9 months with CT+AA (IPTW HR=0.38; 95% CI: 0.29-0.49; p < 0.0001). Median OS was 15.9 versus 23.1 months (IPTW HR=0.38; 95% CI: 0.28-0.51; p < 0.0001). ORR did not differ significantly (33.8% vs 43.2%; p = 0.26). Among 78 patients with RAS wild-type tumours, outcomes did not significantly differ between CT alone and CT+anti-EGFR groups. Adding antiangiogenic therapy to CT significantly improved PFS and OS in first-line treatment of mSBA, warranting confirmation through prospective randomized trials.
2026-02-13 | Rare, Yet Targetable: New Perspectives on Ampullary Carcinomas.
Ampullary carcinoma (AC) is a rare gastrointestinal malignancy with dual intestinal and pancreatobiliary differentiation, complicating diagnosis, staging, and treatment. This review synthesizes current epidemiology, pathology, and multi-omic data to outline a pragmatic care pathway: lineage-first at presentation, mutation-fast at progression. Histology remains the primary classifier: the intestinal subtype generally aligns with colorectal regimens, whereas pancreatobiliary and mixed subtypes favor pancreaticobiliary therapy. In selected fit patients, modified FOLFIRINOX may address mixed phenotypes. Next-generation sequencing adds precision by identifying therapeutically relevant alterations, including ERBB2/HER2 amplifications, MSI-high/dMMR, BRAF V600E, and rare NTRK or RET fusions, while KRAS mutations are enriched in pancreatobiliary tumors. We recommend early application of a rapid-core panel (KRAS/BRAF, MSI/dMMR, ERBB2/HER2, RNA-based fusions) to capture high-impact targets, followed by comprehensive profiling at first progression. Liquid biopsy, plasma circulating tumor DNA (ctDNA), or bile-derived DNA may complement tissue and help identify the dominant lineage. Research priorities include ampulla-enriched umbrella trials, explicit AC subcohorts in tissue-agnostic studies, and ctDNA-informed endpoints. This lineage-first, mutation-fast paradigm supports precision care and evidence generation in AC.
2026-01-31 | Prognostic Factors and the Impact of Adjuvant S-1 Chemotherapy in Resected Ampulla of Vater Carcinoma: A Single-institution Retrospective Study.
Ampulla of Vater carcinoma is a rare malignancy with limited survival after resection, and the role of adjuvant therapy remains unclear. S-1 (oral prodrug of 5-FU with modulators gimeracil and oteracil) has been adopted as an adjuvant treatment for biliary cancers in Japan, but its benefit in ampullary carcinoma is uncertain. We aimed to identify prognostic factors and evaluate the impact of adjuvant S-1 in resected ampullary carcinoma. We retrospectively reviewed 53 patients who underwent pancreatoduodenectomy for ampullary carcinoma at a single institution (2005-2023). Clinicopathologic data and use of adjuvant S-1 were collected. Cancer-specific survival (CSS) and relapse-free survival (RFS) were estimated by the Kaplan-Meier method and compared by the log-rank test. Cox proportional hazards models identified independent prognostic factors. Outcomes with versus without adjuvant S-1 were compared within the node-positive (N+) subset of patients. The 5-year CSS and RFS for all patients were 70.8% and 66.2%, respectively. On multivariate analysis, lymph node metastasis (N+) was the only independent predictor of worse CSS (p=0.04) and RFS (p=0.001). Among N+ patients (n=20), 5-year CSS (51.4% vs. not reached) and RFS (18.0% vs. 18.7%) were similar with adjuvant S-1 (n=11) or surgery alone (n=9) (p=0.5 and 0.4). Adjuvant S-1 did not improve survival in node-positive patients. Lymph node status is a major prognostic factor in ampullary carcinoma. Adjuvant S-1 chemotherapy conferred no significant survival benefit for node-positive patients, underscoring the need for more effective adjuvant strategies.
antibodies
2026-05-27 | [Diagnosis, treatment and prognosis of patients with small bowel adenocarcinoma in Landspítali University Hospital 2002-2021].
Small intestine adenocarcinoma is a rare cancer with poor prognosis. The only curative treatment is surgery to remove the tumor. If the tumor is located in the duodenum, a pancreaticoduodenectomy is recommended, while partial resection of the small intestine is advised for tumors located more distally. Data was obtained from the medical records system at Landspítali. Variables were recorded in Excel, and descriptive statistics along with survival calculations were performed using the statistical software R. A total of 47 patients were diagnosed with small intestine adenocarcinoma, 32 in the duodenum and 15 more distally. Curative surgery was performed on 25 patients. Severe complications (≥3 on the Clavien-Dindo scale) occurred in 32% of cases. The recurrence rate was 24%. One-year survival for patients undergoing surgery was 80%, while five-year survival rate was 56%. Five-year survival was higher for tumors originating in the duodenum (70,6%) compared to other parts of the small intestine (25,0% p>0,05). Small intestine adenocarcinoma is a rare condition, with few patients diagnosed during the study period. A high proportion of patients underwent surgery, but one out of every four was diagnosed with recurrence during follow-up. No previous results for small intestine cancer in Iceland have been published, making comparisons with other countries difficult due to the low incidence of this cancer.
2026-04-06 | SWI/SNF complex alteration and dMMR in primary small bowel undifferentiated tumor: a rare case further complicated by synchronous low-grade endometrioid adenocarcinoma
The 2019 World Health Organization Classification of Digestive Tumors recognizes undifferentiated rhabdoid tumors, driven by switch/sucrose non-fermentable (SWI/SNF) chromatin-remodeling complex alterations such as SMARCA4, SMARCA2, SMARCB1, and ARID1A under the undifferentiated carcinoma category. SMARCA4 -mutated undifferentiated tumors, first described in thoracic sites, are increasingly recognized in extrathoracic locations including the gastrointestinal tract. These tumors are high-grade epithelial neoplasms characterized by loss of differentiation and SMARCA4 expression. We report a 53-year-old woman presenting with severe anemia secondary to heavy vaginal bleeding. Imaging revealed a large ileal mass with hepatic hypodensities. She underwent ileocolic and hepatic wedge resections and hysterectomy. Histopathology revealed two separate tumors: a low-grade, mismatch repair (MMR) intact endometrioid endometrial carcinoma and a SMARCA4 -mutated undifferentiated ileal neoplasm with epithelioid/rhabdoid morphology and liver metastasis. The ileal tumor was positive for vimentin and showed p53 overexpression with preserved SMARCB1 expression. It displayed microsatellite instability (MSI). Next-generation sequencing detected loss-of-function variants in SMARCA4 and ARID1A . The endometrial carcinoma differed in morphology and MMR status, supporting two independent primaries. SMARCA4 -mutated undifferentiated tumor of the small intestine is exceedingly rare. To our knowledge, concurrent SMARCA4 and ARID1A mutations with MSI have not been documented in a primary ileal tumor. This case underscores the diagnostic challenges of SWI/SNF-mutated tumors, particularly in distinguishing synchronous primaries from metastatic carcinoma with rhabdoid tumor-like evolution. SWI/SNF assessment in undifferentiated small bowel tumors, especially with rhabdoid morphology, is warranted. Future studies should explore predictive value for immunotherapy and targeted approaches in MSI-high, ARID1A -deficient tumors.
2026-03-16 | Anti-Hu paraneoplastic syndrome with gastrointestinal dysmotility associated with nasopharyngeal squamous cell carcinoma and small bowel adenocarcinoma.
Anti-Hu paraneoplastic syndrome is a rare autoimmune complication most associated with small cell lung cancer. This case describes a man in his mid-60s with metastatic small bowel adenocarcinoma and nasopharyngeal squamous cell carcinoma who developed confusion, severe dysphagia and progressive weakness. Neurologic evaluation revealed hallucinations, disorientation and lower extremity weakness. Serum and cerebrospinal fluid were positive for anti-Hu (ANNA-1) antibodies, confirming the diagnosis. Anti-Hu disease is associated with a poor prognosis, and despite treatment with high-dose corticosteroids and intravenous immunoglobulin, his neurologic and swallowing deficits persisted. He died within 2 months from progression of his cancer and paraneoplastic disease. This case highlights a rare association of anti-Hu with non-small cell nasopharyngeal and gastrointestinal cancers, expands the spectrum of underlying malignancies linked to this antibody and emphasises the importance of early recognition and timely management of paraneoplastic syndromes in patients presenting with unexplained neurological decline and severe dysphagia.
2026-02-20 | Extrapancreatic Gastrointestinal Tract Grade 3 Well-Differentiated Neuroendocrine Tumors Behave Aggressively Compared With Lower-Grade Tumors Despite Similar Morphology.
The WHO 2019 classification of digestive tract tumors introduced a high-grade (G3) category for well-differentiated neuroendocrine tumors (NETs). These neoplasms appear to have a better prognosis than poorly differentiated neuroendocrine carcinomas (NECs) and may not respond to platinum-based chemotherapy, which is the treatment of choice for NECs, justifying the creation of this new category. Most existing data on G3 NETs are derived from pancreatic neuroendocrine neoplasms, as the majority of G3 neuroendocrine neoplasms (NENs) arise there. G3 NETs are rare at extrapancreatic sites, and their prognosis and behavior are not well studied. We collected and analyzed a multi-institutional cohort of 24 extrapancreatic primary gastrointestinal G3 NETs based on mitotic rate and/or Ki67 index (5 gastric, 13 small bowel, 6 colorectal/anal). Mean Ki67 index was 29.3% (range: 10.5% to 50.2%). Cases generally showed typical well-differentiated NET morphology. Nodal metastases were present in 17/17 (100%) patients; 13/24 (45%) had distant metastases at initial presentation, and 7 patients developed them on follow-up. With a median of 29 months of follow-up, only 2 patients (8%) were alive without disease. Outcomes of G3 NETs were compared with a separate cohort of 125 extrapancreatic G1/G2 gastrointestinal NETs. G3 tumors presented at a higher pT-category stage ( P <0.001) and overall stage ( P =0.002), and patients with G3 disease were more likely to die than those with G1/G2 disease ( P <0.001). Our data show that, like pancreatic G3 NETs, rare extrapancreatic gastrointestinal G3 NETs exhibit aggressive behavior compared with their G1/G2 counterparts (although small bowel NETs tend to recur irrespective of grade). In most cases, the G3 designation is driven by Ki67 index, though exceptions exist, emphasizing the need for reviewing mitotic count in every case.
2026-02-05 | Conversion surgery after pembrolizumab for initially unresectable MSI-H small bowel adenocarcinoma: a case report and brief analysis.
Small-bowel adenocarcinoma (SBA) is rare and often diagnosed at an advanced stage. We report the case of a 61-year-old man with locally advanced unresectable upper jejunal SBA secondary to metastatic lymph nodes involving the superior mesenteric artery. Initial chemotherapy with FOLFOX (oxaliplatin, fluorouracil, and folinic acid) was initiated; however, a microsatellite instability-high (MSI-H) status was identified, and the treatment was promptly switched to pembrolizumab. After four cycles, marked regression of the metastatic lymph nodes was observed, and conversion surgery was performed. Partial jejunectomy with lymphadenectomy was performed to achieve an R0 resection. Pathological examination revealed a moderately differentiated adenocarcinoma with extensive fibrosis in the metastatic lymph nodes, indicating a substantial response to immunotherapy. The patient remained disease-free for 9 months postoperatively. Additionally, a brief meta-analysis of 10 studies comprising 72 patients with MSI-H/mismatch repair-deficient SBA revealed an objective response rate to immune checkpoint inhibitors of 65.3%. This case highlights the potential of pembrolizumab for the curative resection of an initially unresectable MSI-H SBA.
small molecules
2026-08-12 | Advanced local jejunal carcinoma treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC): a case report and review of the literature.
Jejunal carcinoma, a rare subset of small bowel adenocarcinomas, is characterized by its aggressive nature and nonspecific clinical presentation. The prognosis becomes particularly poor when peritoneal carcinomatosis is present. Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) has emerged as a treatment performed with curative intent for select patients with gastrointestinal cancers, particularly those with limited peritoneal metastases. A 51-year-old female presented with progressive symptoms of small bowel obstruction and gastrointestinal bleeding, diagnosed as jejunal adenocarcinoma with limited peritoneal carcinomatosis. She underwent CRS combined with HIPEC. Postoperative recovery was uneventful, with imaging studies and pathological analysis confirming complete tumor resection. HIPEC and CRS have shown potential in managing peritoneal carcinomatosis. However, their efficacy in rare cancers, such as jejunal carcinoma, remains underexplored. Studies show encouraging outcomes for small bowel adenocarcinoma treated with CRS and HIPEC, emphasizing patient selection and multidisciplinary management.
2026-07-21 | WIN-MTB-2024017 - WIN International Molecular Tumor Board: A 48-year-old female with multiple primary cancers.
Copyright: © 2026 El-Deiry et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Multiple primary cancers (MPC), the occurrence of two or more distinct malignancies in the same patient, pose significant clinical challenges due to their complexity and the need for individualized treatment strategies. This case, discussed at the WIN Consortium International Molecular Tumor Board, illustrates the clinical journey of a 48-year-old female with a BRCA1 germline mutation who developed multiple primary cancers: breast, skin, high-grade serous carcinoma of the ovary, colon and small bowel cancers. Her treatment history included doxorubicin and cyclophosphamide for breast cancer, Mohs surgery for basal cell carcinoma, and carboplatin and paclitaxel for ovarian cancer. After participating in the PRIMA trial with niraparib, she was diagnosed with PIK3CA-mutated colon cancer, leading to resection and CAPOX chemotherapy. A subsequent diagnosis of small bowel adenocarcinoma, molecularly resembling her colon cancer, along with a unique BRCA1-STARD3 fusion in inguinal lymph nodes prompted a comprehensive MTB review. The panel discussed several precision strategies, including combinations of cetuximab, niraparib, and temsirolimus; FOLFIRI with anti-EGFR inhibitors; anti-CTLA-4 and anti-PD-1 (botensilimab and balstilimab); regorafenib with anti-CTLA-4 and anti-PD-1 (ipilimumab and nivolumab); trifluridine/tipiracil with bevacizumab; regorafenib alone; aspirin for potential benefits in patients with PIK3CA mutations; therapies targeting PIK3CA and EGFR alterations; regular imaging and liquid biopsies assessments for monitoring disease progression and guide future treatment decisions; and vaccines targeting PIK3CA, STARD3 and TP53. This case underscores the complexity of managing MPC and highlights the essential role of international molecular tumor boards in generating innovative, tailored treatment recommendations for patients with rare and multifaceted disease courses.
2026-04-15 | Efficacy of targeted therapies for metastatic small bowel adenocarcinoma treatment: A retrospective study by AGEO.
Small bowel adenocarcinoma (SBA) is a rare malignancy with poor prognosis. In metastatic disease, evidence regarding the efficacy of chemotherapy (CT) combined with bevacizumab or anti-EGFR agents is limited to small studies. This study aimed to assess, in real-world practice, the effectiveness of first-line CT combined with targeted therapies (TT)-either antiangiogenic (AA) or anti-EGFR-compared with CT alone in patients with metastatic SBA (mSBA) and proficient mismatch repair/microsatellite stable (pMMR/MSS) status. This retrospective multicentre study included all patients receiving at least one cycle of CT with or without TT for mSBA. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), objective response rate (ORR), and safety. Analyses used inverse probability of treatment weighting (IPTW) in univariable Cox models to account for potential confounding factors that were unbalanced between groups. A total of 255 patients were included: 153 received CT alone, 45 CT+AA, and 16 CT+anti-EGFR as first-line therapy. Median PFS was 8.0 months with CT alone versus 11.9 months with CT+AA (IPTW HR=0.38; 95% CI: 0.29-0.49; p < 0.0001). Median OS was 15.9 versus 23.1 months (IPTW HR=0.38; 95% CI: 0.28-0.51; p < 0.0001). ORR did not differ significantly (33.8% vs 43.2%; p = 0.26). Among 78 patients with RAS wild-type tumours, outcomes did not significantly differ between CT alone and CT+anti-EGFR groups. Adding antiangiogenic therapy to CT significantly improved PFS and OS in first-line treatment of mSBA, warranting confirmation through prospective randomized trials.
2026-02-13 | Rare, Yet Targetable: New Perspectives on Ampullary Carcinomas.
Ampullary carcinoma (AC) is a rare gastrointestinal malignancy with dual intestinal and pancreatobiliary differentiation, complicating diagnosis, staging, and treatment. This review synthesizes current epidemiology, pathology, and multi-omic data to outline a pragmatic care pathway: lineage-first at presentation, mutation-fast at progression. Histology remains the primary classifier: the intestinal subtype generally aligns with colorectal regimens, whereas pancreatobiliary and mixed subtypes favor pancreaticobiliary therapy. In selected fit patients, modified FOLFIRINOX may address mixed phenotypes. Next-generation sequencing adds precision by identifying therapeutically relevant alterations, including ERBB2/HER2 amplifications, MSI-high/dMMR, BRAF V600E, and rare NTRK or RET fusions, while KRAS mutations are enriched in pancreatobiliary tumors. We recommend early application of a rapid-core panel (KRAS/BRAF, MSI/dMMR, ERBB2/HER2, RNA-based fusions) to capture high-impact targets, followed by comprehensive profiling at first progression. Liquid biopsy, plasma circulating tumor DNA (ctDNA), or bile-derived DNA may complement tissue and help identify the dominant lineage. Research priorities include ampulla-enriched umbrella trials, explicit AC subcohorts in tissue-agnostic studies, and ctDNA-informed endpoints. This lineage-first, mutation-fast paradigm supports precision care and evidence generation in AC.
2026-01-31 | Prognostic Factors and the Impact of Adjuvant S-1 Chemotherapy in Resected Ampulla of Vater Carcinoma: A Single-institution Retrospective Study.
Ampulla of Vater carcinoma is a rare malignancy with limited survival after resection, and the role of adjuvant therapy remains unclear. S-1 (oral prodrug of 5-FU with modulators gimeracil and oteracil) has been adopted as an adjuvant treatment for biliary cancers in Japan, but its benefit in ampullary carcinoma is uncertain. We aimed to identify prognostic factors and evaluate the impact of adjuvant S-1 in resected ampullary carcinoma. We retrospectively reviewed 53 patients who underwent pancreatoduodenectomy for ampullary carcinoma at a single institution (2005-2023). Clinicopathologic data and use of adjuvant S-1 were collected. Cancer-specific survival (CSS) and relapse-free survival (RFS) were estimated by the Kaplan-Meier method and compared by the log-rank test. Cox proportional hazards models identified independent prognostic factors. Outcomes with versus without adjuvant S-1 were compared within the node-positive (N+) subset of patients. The 5-year CSS and RFS for all patients were 70.8% and 66.2%, respectively. On multivariate analysis, lymph node metastasis (N+) was the only independent predictor of worse CSS (p=0.04) and RFS (p=0.001). Among N+ patients (n=20), 5-year CSS (51.4% vs. not reached) and RFS (18.0% vs. 18.7%) were similar with adjuvant S-1 (n=11) or surgery alone (n=9) (p=0.5 and 0.4). Adjuvant S-1 did not improve survival in node-positive patients. Lymph node status is a major prognostic factor in ampullary carcinoma. Adjuvant S-1 chemotherapy conferred no significant survival benefit for node-positive patients, underscoring the need for more effective adjuvant strategies.
antibodies
2026-05-27 | [Diagnosis, treatment and prognosis of patients with small bowel adenocarcinoma in Landspítali University Hospital 2002-2021].
Small intestine adenocarcinoma is a rare cancer with poor prognosis. The only curative treatment is surgery to remove the tumor. If the tumor is located in the duodenum, a pancreaticoduodenectomy is recommended, while partial resection of the small intestine is advised for tumors located more distally. Data was obtained from the medical records system at Landspítali. Variables were recorded in Excel, and descriptive statistics along with survival calculations were performed using the statistical software R. A total of 47 patients were diagnosed with small intestine adenocarcinoma, 32 in the duodenum and 15 more distally. Curative surgery was performed on 25 patients. Severe complications (≥3 on the Clavien-Dindo scale) occurred in 32% of cases. The recurrence rate was 24%. One-year survival for patients undergoing surgery was 80%, while five-year survival rate was 56%. Five-year survival was higher for tumors originating in the duodenum (70,6%) compared to other parts of the small intestine (25,0% p>0,05). Small intestine adenocarcinoma is a rare condition, with few patients diagnosed during the study period. A high proportion of patients underwent surgery, but one out of every four was diagnosed with recurrence during follow-up. No previous results for small intestine cancer in Iceland have been published, making comparisons with other countries difficult due to the low incidence of this cancer.
2026-04-06 | SWI/SNF complex alteration and dMMR in primary small bowel undifferentiated tumor: a rare case further complicated by synchronous low-grade endometrioid adenocarcinoma
The 2019 World Health Organization Classification of Digestive Tumors recognizes undifferentiated rhabdoid tumors, driven by switch/sucrose non-fermentable (SWI/SNF) chromatin-remodeling complex alterations such as SMARCA4, SMARCA2, SMARCB1, and ARID1A under the undifferentiated carcinoma category. SMARCA4 -mutated undifferentiated tumors, first described in thoracic sites, are increasingly recognized in extrathoracic locations including the gastrointestinal tract. These tumors are high-grade epithelial neoplasms characterized by loss of differentiation and SMARCA4 expression. We report a 53-year-old woman presenting with severe anemia secondary to heavy vaginal bleeding. Imaging revealed a large ileal mass with hepatic hypodensities. She underwent ileocolic and hepatic wedge resections and hysterectomy. Histopathology revealed two separate tumors: a low-grade, mismatch repair (MMR) intact endometrioid endometrial carcinoma and a SMARCA4 -mutated undifferentiated ileal neoplasm with epithelioid/rhabdoid morphology and liver metastasis. The ileal tumor was positive for vimentin and showed p53 overexpression with preserved SMARCB1 expression. It displayed microsatellite instability (MSI). Next-generation sequencing detected loss-of-function variants in SMARCA4 and ARID1A . The endometrial carcinoma differed in morphology and MMR status, supporting two independent primaries. SMARCA4 -mutated undifferentiated tumor of the small intestine is exceedingly rare. To our knowledge, concurrent SMARCA4 and ARID1A mutations with MSI have not been documented in a primary ileal tumor. This case underscores the diagnostic challenges of SWI/SNF-mutated tumors, particularly in distinguishing synchronous primaries from metastatic carcinoma with rhabdoid tumor-like evolution. SWI/SNF assessment in undifferentiated small bowel tumors, especially with rhabdoid morphology, is warranted. Future studies should explore predictive value for immunotherapy and targeted approaches in MSI-high, ARID1A -deficient tumors.
2026-03-16 | Anti-Hu paraneoplastic syndrome with gastrointestinal dysmotility associated with nasopharyngeal squamous cell carcinoma and small bowel adenocarcinoma.
Anti-Hu paraneoplastic syndrome is a rare autoimmune complication most associated with small cell lung cancer. This case describes a man in his mid-60s with metastatic small bowel adenocarcinoma and nasopharyngeal squamous cell carcinoma who developed confusion, severe dysphagia and progressive weakness. Neurologic evaluation revealed hallucinations, disorientation and lower extremity weakness. Serum and cerebrospinal fluid were positive for anti-Hu (ANNA-1) antibodies, confirming the diagnosis. Anti-Hu disease is associated with a poor prognosis, and despite treatment with high-dose corticosteroids and intravenous immunoglobulin, his neurologic and swallowing deficits persisted. He died within 2 months from progression of his cancer and paraneoplastic disease. This case highlights a rare association of anti-Hu with non-small cell nasopharyngeal and gastrointestinal cancers, expands the spectrum of underlying malignancies linked to this antibody and emphasises the importance of early recognition and timely management of paraneoplastic syndromes in patients presenting with unexplained neurological decline and severe dysphagia.
2026-02-20 | Extrapancreatic Gastrointestinal Tract Grade 3 Well-Differentiated Neuroendocrine Tumors Behave Aggressively Compared With Lower-Grade Tumors Despite Similar Morphology.
The WHO 2019 classification of digestive tract tumors introduced a high-grade (G3) category for well-differentiated neuroendocrine tumors (NETs). These neoplasms appear to have a better prognosis than poorly differentiated neuroendocrine carcinomas (NECs) and may not respond to platinum-based chemotherapy, which is the treatment of choice for NECs, justifying the creation of this new category. Most existing data on G3 NETs are derived from pancreatic neuroendocrine neoplasms, as the majority of G3 neuroendocrine neoplasms (NENs) arise there. G3 NETs are rare at extrapancreatic sites, and their prognosis and behavior are not well studied. We collected and analyzed a multi-institutional cohort of 24 extrapancreatic primary gastrointestinal G3 NETs based on mitotic rate and/or Ki67 index (5 gastric, 13 small bowel, 6 colorectal/anal). Mean Ki67 index was 29.3% (range: 10.5% to 50.2%). Cases generally showed typical well-differentiated NET morphology. Nodal metastases were present in 17/17 (100%) patients; 13/24 (45%) had distant metastases at initial presentation, and 7 patients developed them on follow-up. With a median of 29 months of follow-up, only 2 patients (8%) were alive without disease. Outcomes of G3 NETs were compared with a separate cohort of 125 extrapancreatic G1/G2 gastrointestinal NETs. G3 tumors presented at a higher pT-category stage ( P <0.001) and overall stage ( P =0.002), and patients with G3 disease were more likely to die than those with G1/G2 disease ( P <0.001). Our data show that, like pancreatic G3 NETs, rare extrapancreatic gastrointestinal G3 NETs exhibit aggressive behavior compared with their G1/G2 counterparts (although small bowel NETs tend to recur irrespective of grade). In most cases, the G3 designation is driven by Ki67 index, though exceptions exist, emphasizing the need for reviewing mitotic count in every case.
2026-02-05 | Conversion surgery after pembrolizumab for initially unresectable MSI-H small bowel adenocarcinoma: a case report and brief analysis.
Small-bowel adenocarcinoma (SBA) is rare and often diagnosed at an advanced stage. We report the case of a 61-year-old man with locally advanced unresectable upper jejunal SBA secondary to metastatic lymph nodes involving the superior mesenteric artery. Initial chemotherapy with FOLFOX (oxaliplatin, fluorouracil, and folinic acid) was initiated; however, a microsatellite instability-high (MSI-H) status was identified, and the treatment was promptly switched to pembrolizumab. After four cycles, marked regression of the metastatic lymph nodes was observed, and conversion surgery was performed. Partial jejunectomy with lymphadenectomy was performed to achieve an R0 resection. Pathological examination revealed a moderately differentiated adenocarcinoma with extensive fibrosis in the metastatic lymph nodes, indicating a substantial response to immunotherapy. The patient remained disease-free for 9 months postoperatively. Additionally, a brief meta-analysis of 10 studies comprising 72 patients with MSI-H/mismatch repair-deficient SBA revealed an objective response rate to immune checkpoint inhibitors of 65.3%. This case highlights the potential of pembrolizumab for the curative resection of an initially unresectable MSI-H SBA.
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