Small Bowel Adenocarcinoma Research Articles

650P Genomic profiling of small bowel adenocarcinoma: A pooled analysis

650P Genomic profiling of small bowel adenocarcinoma: A pooled analysis

S1805 Small Bowel Adenocarcinomas Exhibit Worse Mortality Compared to Neuroendocrine Tumors With Modulation by Clinical, Demographic, and Socioeconomic Factors

S1805 Small Bowel Adenocarcinomas Exhibit Worse Mortality Compared to Neuroendocrine Tumors With Modulation by Clinical, Demographic, and Socioeconomic Factors

Taxane-Based Chemotherapy Is Effective in Metastatic Appendiceal Adenocarcinoma.

Appendiceal cancer is a rare, orphan disease with no therapies currently approved by the FDA for its treatment. Given the limited data regarding drug efficacy, these tumors have historically been treated with chemotherapy designed for colon cancer. However, an overwhelming body of molecular data has demonstrated that appendiceal adenocarcinoma is a distinct entity with key molecular differences from colon cancer, notably rare APC mutation. Recognizing that APC loss-of-function is thought to contribute to taxane resistance and that taxanes are effective in the treatment of other gastrointestinal tumors, including gastric, esophageal, and small bowel adenocarcinoma, we completed a single-center retrospective study to assess efficacy. In a cohort of 13 patients with metastatic appendiceal adenocarcinoma, treated with taxane chemotherapy the median overall survival was 8.8 months. Of 10 evaluable patients, we observed 3 responses, 4 patients with stable disease, and 3 with progression (30% response rate, 70% disease control rate). The results of this study showing activity of taxane-based chemotherapy in appendiceal adenocarcinoma support further clinical investigation of taxane therapy in this orphan disease.

S-1 as an alternative treatment after 5-fluorouracil-induced coronary vasospasm in a patient with small bowel adenocarcinoma: a case report.

5-Fluorouracil (5-FU) is a chemotherapeutic agent used worldwide to treat various solid tumors. It may cause adverse cardiotoxic events, the most common of which is coronary vasospasm. Recently, the 2022 European Society for Medical Oncology guidelines for metastatic colorectal cancer recommended S-1 as an alternative therapy after 5-FU-induced cardiotoxicity; however, only limited data on Asian patients are available. Here, we report a case of safe administration of S-1 to a 72-year-old Japanese female patient with metastatic small bowel adenocarcinoma who developed 5-FU-induced coronary vasospasm. While receiving modified FOLFOX6 (5-FU plus leucovorin and oxaliplatin) as palliative chemotherapy, she experienced chest pain with electrocardiographic ST elevation. Chemotherapy was temporarily suspended, but treatment was resumed by switching from modified FOLFOX6 to SOX (S-1 plus oxaliplatin) as the tumor began to worsen. Owing to the adverse event of enteritis, the patient's treatment was switched to S-1 monotherapy after cycle 3, and S-1 monotherapy was continued without any cardiotoxicity. S-1 may be a promising alternative therapy after 5-FU-induced cardiotoxicity.

Mismatch repair deficiency as prognostic factor for stage III small bowel adenocarcinoma: A multicentric international study.

Small bowel adenocarcinoma (SBA) is a rare cancer with an aggressive behavior. No study has specifically addressed the putative prognostic role of mismatch repair status in stage III SBAs. We aimed to investigate whether mismatch repair deficiency is associated with cancer-specific survival in a Western cohort of patients with stage III SBAs. In this retrospective multicentric international cohort study, we enrolled 70 patients who underwent surgically resection for stage III SBAs and we analyzed the frequency of mismatch repair deficiency, tested by immunohistochemistry for mismatch repair proteins and by polymerase chain reaction for microsatellite instability, and its association with cancer-specific survival and other clinic-pathologic factors. We found sixteen (23%) patients with mismatch repair deficient adenocarcinoma, without discordance between immunohistochemical and polymerase chain reaction for microsatellite instability analyses. Mismatch repair deficiency proved to be associated with a better outcome both at univariable analysis (hazard ratio: 0.28, 95% confidence interval: 0.08-0.91, p: 0.035) and in bivariable models adjusted for patient age or gender, tumor site, pT4 stage, tumor budding, and perineural invasion. This study highlights the importance of testing mismatch repair status to improve prognostic stratification in stage III SBAs.

Mismatch repair deficiency, a future biomarker to guide adjuvant chemotherapy in localized small bowel adenocarcinoma?

Mismatch repair deficiency, a future biomarker to guide adjuvant chemotherapy in localized small bowel adenocarcinoma?

Case Report: Primary small bowel adenocarcinoma with peritoneal metastasis responded well to a CapeOX + bevacizumab regimen

BackgroundSmall bowel adenocarcinoma (SBA) is a rare condition often presenting with various non-specific gastrointestinal symptoms, making its diagnosis challenging. Delayed diagnosis is common, as patients may not receive the correct diagnosis until complications arise, necessitating further investigations. Furthermore, the management of SBA patients poses difficulties due to the scarcity of high-quality evidence.Case presentationIn this report, we present the case of an elderly man with SBA in the ileum who arrived at our emergency room with acute abdominal pain. The diagnosis was not made until the SBA caused a perforation, leading to acute abdominal pain. An emergent exploratory laparotomy revealed a 3 cm × 3 cm perforated tumor in the ileum, along with widespread metastatic nodules on the omentum, ascending colon, descending colon, and rectum. Postoperative pathological evaluation confirmed the diagnosis of SBA with peritoneal metastasis (pT4N2M1, stage IV). Following surgery, the patient received palliative systemic chemotherapy, which included the CapeOX regimen and the anti-VEGF monoclonal antibody bevacizumab. Remarkably, the patient responded well to this therapy, displaying good tolerance, and we observed no signs of disease progression. As of now, the patient is in good health and continuing with regular follow-up.ConclusionThe early diagnosis of small bowel adenocarcinoma remains a challenge. Delayed diagnosis can lead to a poor prognosis, underscoring the importance of considering SBA as a potential diagnosis for patients with unexplained abdominal pain and gastrointestinal symptoms. This case also highlights the efficacy of palliative chemotherapy with the CapeOX regimen combined with bevacizumab in controlling SBA.

The Prognostic Utility of the Metastatic Lymph Node Ratio and the Number of Regional Lymph Nodes Removed from Patients with Small Bowel Adenocarcinomas.

Background and Objectives: Small bowel adenocarcinomas (SBAs) are rare tumors of the gastrointestinal system. Lymph node metastasis in patients with curatively resected SBAs is associated with poor prognosis. In this study, we determined the prognostic utility of the number of removed lymph nodes and the metastatic lymph node ratio (the N ratio). Materials and Methods: The data of 97 patients who underwent curative SBA resection in nine hospitals of Turkey were retrospectively evaluated. Univariate and multivariate analyses of potentially prognostic factors including the N ratio and the numbers of regional lymph nodes removed were evaluated. Results: Univariate analysis showed that perineural and vascular invasion, metastatic lymph nodes, advanced TNM stage, and a high N ratio were significant predictors of poor survival. Multivariate analysis revealed that the N ratio was a significant independent predictor of disease-specific survival (DSS). The group with the lowest N ratio exhibited the longest disease-free survival (DFS) and DSS; these decreased significantly as the N ratio increased (both, p < 0.001). There was no significant difference in either DFS or DSS between groups with low and high numbers of dissected lymph nodes (i.e., <13 and ≥13) (both, p = 0.075). Conclusions: We found that the N ratio was independently prognostic of DSS in patients with radically resected SBAs. The N ratio is a convenient and accurate measure of the severity of lymph node metastasis.

A Mysterious Presentation of Small Bowel Stricture

Small bowel adenocarcinoma is a rare malignancy that accounts for a small percentage of gastrointestinal cancers. Diagnosis and management of small bowel adenocarcinoma can be challenging due to its rarity and nonspecific presentation. We present a case of a 51-year-old male with a history of intravenous drug use who presented with worsening abdominal pain and was found to have a small bowel obstruction. Exploratory laparotomy revealed a stricture in the jejunum caused by an intraluminal mass, which was resected. Pathological examination confirmed the diagnosis of intestinal type, moderately differentiated adenocarcinoma. This case highlights the importance of considering small bowel adenocarcinoma as a possible etiology in patients presenting with small bowel obstruction, particularly in high-risk individuals. Early diagnosis and complete resection remain the mainstays of treatment for improved outcomes in small bowel adenocarcinoma.

Exploring the immune microenvironment in small bowel adenocarcinoma using digital image analysis.

Small bowel adenocarcinoma (SBA) is a rare malignancy of the small intestine associated with late stage diagnosis and poor survival outcome. High expression of immune cells and immune checkpoint biomarkers especially programmed cell death ligand-1 (PD-L1) have been shown to significantly impact disease progression. We have analysed the expression of a subset of immune cell and immune checkpoint biomarkers in a cohort of SBA patients and assessed their impact on progression-free survival (PFS) and overall survival (OS). 25 patient samples in the form of formalin fixed, paraffin embedded (FFPE) tissue were obtained in tissue microarray (TMAs) format. Automated immunohistochemistry (IHC) staining was performed using validated antibodies for CD3, CD4, CD8, CD68, PD-L1, ICOS, IDO1 and LAG3. Slides were scanned digitally and assessed in QuPath, an open source image analysis software, for biomarker density and percentage positivity. Survival analyses were carried out using the Kaplan Meier method. Varying expressions of biomarkers were recorded. High expressions of CD3, CD4 and IDO1 were significant for PFS (p = 0.043, 0.020 and 0.018 respectively). High expression of ICOS was significant for both PFS (p = 0.040) and OS (p = 0.041), while high PD-L1 expression in tumour cells was significant for OS (p = 0.033). High correlation was observed between PD-L1 and IDO1 expressions (Pearson correlation co-efficient = 1) and subsequently high IDO1 expression in tumour cells was found to be significant for PFS (p = 0.006) and OS (p = 0.034). High levels of immune cells and immune checkpoint proteins have a significant impact on patient survival in SBA. These data could provide an insight into the immunotherapeutic management of patients with SBA.

P-327 Comparison of clinicopathological and molecular features of two rare entities: Appendiceal carcinoma and small bowel adenocarcinoma

P-327 Comparison of clinicopathological and molecular features of two rare entities: Appendiceal carcinoma and small bowel adenocarcinoma

Gut inflammation and tumorigenesis: every site has a different tale to tell.

Gut inflammation has been correlated with cancerogenesis by disrupting gastrointestinal homeostasis. Numerous chronic inflammatory disorders of the tubular gastrointestinal tract (e.g., gastroesophageal reflux disease, Helicobacter pylori-induced and autoimmune chronic gastritis, celiac disease, and inflammatory bowel diseases) have been variably associated with an increased neoplastic risk. Gastrointestinal inflammation-induced neoplasms include epithelial tumors (esophageal squamous cell carcinoma and adenocarcinoma, gastric adenocarcinoma and neuroendocrine tumors, small bowel adenocarcinoma and neuroendocrine tumors, and colorectal cancer) and lymphomas (such as gastric marginal zone lymphomas and enteropathy-associated T cell lymphoma). In the last decades, numerous studies have investigated the pathogenetic mechanisms and the microenvironmental/microbiome changes that trigger genetic and/or epigenetic alterations eventually leading to tumorigenesis, often through a histologically recognizable inflammation-dysplasia-carcinoma cancerogenic sequence. In the present review, an overview of the current knowledge on the links between inflammatory diseases and neoplasms of the tubular GI tract, applying a site-by-site approach, is provided.

Abstract CT148: Efficacy, safety, and biomarker analysis of combined MEK (Cobimetinib) and PD-L1 (Atezolizumab) inhibition (COTEZO) in advanced small bowel adenocarcinoma (SBA)

Abstract Purpose: Preclinical evidence supporting immunomodulatory effect of MEK inhibition that augments anti-tumor activity of PD-1 inhibitors is a compelling rationale for investigating combined MEK and PD-L1 inhibition in advanced microsatellite-stable (MSS) SBA wherein immune checkpoint inhibitors (ICIs) have little clinical benefit. We conducted a prospective, phase 2 trial evaluating efficacy and safety of COTEZO regimen in treatment refractory SBA. Procedures: Patients aged ≥ 18 years with metastatic MSS SBA, ECOG PS 0 - 2, and disease progression on prior systemic chemotherapy were enrolled and treated with cobimetinib (60 mg orally once daily for days 1 - 21) and atezolizumab (840 mg intravenously every 2 weeks) every 28-day cycle. The primary endpoint was objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1. by independent radiology review. Key pre-specified secondary endpoints were safety, disease control rate (DCR), progression-free (PFS) and overall (OS) survival. Pre/on-treatment biopsies were examined for response biomarkers. Results: Between 4/2017 and 7/2020, 20 patients were enrolled. The confirmed ORR per RECISTv1.1 was 10% [2/20; 95%CI: 1.2 - 31.7] (1 complete response and 1 partial response). Seven patients had stable disease for a DCR of 45% (95%CI: 23.1 - 68.5). Median PFS and OS were 2.4 (95% CI 1.3-3.5) and 8.8 (95% CI 5.6 - 12) months, respectively. Grade 3 treatment-emergent adverse events (no grade 4/5) occurred in 7 (35%) patients; most common being elevated CPK (15%) and vomiting (10%). One (5%) patient had grade 3 vomiting, necessitating treatment discontinuation. There appeared to be a marked difference in OS between patients with increased pre-treatment tumor immune infiltration as compared to those lacking immune infiltration amongst patients with RNASeq data available (n=13). Specifically, increased immune infiltration as assessed by computational deconvolution of RNASeq data pointed to increased macrophage and monocyte infiltration as prognostic factors. This was additionally assessed via application of a global “immune score” algorithm, ESTIMATE. In order to generalize our findings, we expanded our computational deconvolution analysis to include additional small bowel adenocarcinoma patients who received standard-of-care treatment (n=7). For the combined standard-of-care and experimentally treated patients we saw that those with immune infiltration had significantly better OS (9 months vs greater than 3 years, HR 5.7, Padj = 0.017), suggesting that immune infiltration is a prognostic, rather than predictive biomarker. Conclusions: Although our study did not meet its primary endpoint of ORR, we identified tumor immune infiltration as a prognostic biomarker in SBA, which could select patients with better outcomes on immunotherapy. Citation Format: Nicholas Hornstein, John P. Shen, Andrew J. Pellatt, Suyu Liu, Mark Knafl, Anneleis F. Willett, Haifeng Zhu, Dipen M. Maru, Walter Darbonne, Ignacio I. Wistuba, Andy Futreal, James C. Yao, Scott E. Woodman, Michael J. Overman, Kanwal P. Raghav. Efficacy, safety, and biomarker analysis of combined MEK (Cobimetinib) and PD-L1 (Atezolizumab) inhibition (COTEZO) in advanced small bowel adenocarcinoma (SBA) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT148.

Abstract 29: Characterization of a murine intestinal cancer homograft model for therapeutic evaluation

Abstract Introduction: Intestinal cancers are one of the most lethal malignancies and are responsible for a mass of cancer-related deaths. The discovery of new drugs and therapeutic strategies is underway, and to complement this, the development of superior animal models is required for preclinical studies. Genetically engineered mouse models (GEMMs) mimic de novo human tumor growth within an intact tumor microenvironment and are potent immunocompetent models for studying pathogenesis and immuno-oncology of intestinal cancers. GEMMs with dysfunctional DNA mismatch repair (MMR) genes, like MHL1 and MSH2, manifest intestinal tumors related to microsatellite instability (MSI). However, the low incidence and distinct latency among individuals hamper the application of these GEMMs in preclinical research. In this study, a murine intestinal cancer homograft from GEMMs with MMR deficiency is established to enroll larger cohorts of mice for preclinical studies. Methods: MMR-deficient GEMMs were generated by knockout of Mlh1 gene with a CRISPR-Cas9 system. Intestinal cancer development was investigated in 16 GEMMs. The developed tumor in the intestine of GEMM was isolated by surgery and inoculated into C57BL/6 mice subcutaneously to establish a murine homograft model. The tumor homograft was passaged and expanded in vivo, and stable tumor growth was established over consecutive passages. Histopathological studies were conducted for both the original and passaged tumors. Genomic mutations and gene expression were analyzed by whole exome sequencing and RNA-sequencing, and tumor-infiltrating lymphocytes (TILs) were analyzed by flow cytometry. Therapeutic efficacy of chemotherapies and immune checkpoint inhibitors were evaluated in vivo for tumor growth inhibition. Results: The intestinal tumors or lesions were observed in two of the sixteen Mlh1-KO mice with an incidence of 12.5%. A murine homograft model of small bowel adenocarcinoma was successfully established using the tumor located in jejunum of a Mlh1-KO mouse. This model was stably passaged in vivo with semblable pathological features as the original lesion in Mlh1-KO mice. The various degrees of TILs and response to treatments revealed the potential of this model for in vivo investigation of immune response. Conclusion: Our murine intestinal cancer homograft model presented rapid and stable subcutaneous growth in immunocompetent mice, providing an efficient approach for intestinal cancer researchers and a superior preclinical model for new drug discovery. Citation Format: Jinxi Wang, Leilei Chen, Likun Zhang, Jingqian Zhu, Ludovic Bourre, Jingjing Wang. Characterization of a murine intestinal cancer homograft model for therapeutic evaluation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 29.

Small bowel adenocarcinoma in a Crohn's disease patient presenting as small bowel obstruction: a case report

Background: Small bowel adenocarcinoma (SBA) is a rare but dreaded complication of Crohn's disease with a poor prognosis. The evidence has concluded that it is difficult to differentiate between SBA and benign strictures. Intraoperative and pathological diagnosis is the mainstay of treatment. Case presentation: The current case involves a 40-year-old male with a 12-year history of Crohn's disease who presented with symptoms of small bowel obstruction, which were confirmed by an abdominal C.T. scan. An exploratory laparotomy revealed a stricture, which raised the possibility of malignant disease. Histology revealed a well-differentiated adenocarcinoma. Conclusion: The rarity of small bowel adenocarcinoma in Crohn's disease patients necessitates a high index of suspicion in patients presenting with features of small bowel obstruction or strictures.

Preoperative Predictors of Neoplasia in Patients Undergoing Small Bowel Resection for Complicated Crohn's Disease: A Multicentre Case-Control Study.

Crohn's disease (CD) is associated with an increased risk of small bowel neoplasia (SBN). We aimed to assess preoperative predictors of SBN in CD patients. We conducted a retrospective case-control study including CD patients who underwent surgery: cases were diagnosed with SBN on histopathological analysis and controls had no neoplasia. Preoperative cross-sectional imaging was reviewed by a panel of blinded expert radiologists. Fifty cases were matched to one hundred and fifty consecutive controls. In multivariable analysis, predictors of SBN were age ≥ 50 years (OR = 28, 95% CI = 5.05-206), median CD duration ≥ 17.5 years (OR = 4.25, 95% CI = 1.33-14.3), and surgery for stricture (OR = 5.84, 95% CI = 1.27-35.4). The predictors of small bowel adenocarcinoma were age ≥ 50 years (OR = 5.14, 95% CI = 2.12-12.7), CD duration ≥ 15 years (OR = 5.65, 95% CI = 2.33-14.3), and digestive wall thickening > 8 mm (OR = 3.79, 95% CI = 1.45-11.3). A predictive score based on the aforementioned factors was constructed. Almost 73.7% of patients with a high score had SBA. Old age, long small bowel CD duration, and stricture predicted the presence of SBN, particularly adenocarcinoma when patients have digestive wall thickening > 8 mm on preoperative imaging.

Does Small Bowel Adenocarcinoma Have a Worse Prognosis than Colonic Adenocarcinoma? A Propensity Score-matched Comparison Using the National Cancer Database

Does Small Bowel Adenocarcinoma Have a Worse Prognosis than Colonic Adenocarcinoma? A Propensity Score-matched Comparison Using the National Cancer Database

Small Bowel Carcinoma in the Setting of Inflammatory Bowel Disease.

Small bowel carcinomas are rare in the general population, but the incidence is increasing. Patients with inflammatory bowel diseases (IBDs) are at significantly higher risk of small bowel adenocarcinomas than their non-IBD counterparts, with Crohn's patients having at least a 12-fold increased risk and ulcerative colitis patients with a more controversial and modest 2-fold increased risk compared with the general population. IBD patients with small bowel carcinomas present with nonspecific symptoms that overlap with typical IBD symptoms, and this results in difficulty making a preoperative diagnosis. Cross-sectional imaging is rarely diagnostic, and most cancers are found incidentally at the time of surgery performed for an IBD indication. As such, most small bowel carcinomas are found at advanced stages and carry a poor prognosis. Oncologic surgical resection is the treatment of choice for patients with locoregional disease with little evidence available to guide adjuvant therapy. Patients with metastatic disease are treated with systemic chemotherapy, and surgery is reserved for palliation in this population. Prognosis is poor with few long-term survivors reported.

Small Bowel Adenocarcinoma Metastatic to the Ovaries: A Challenging Diagnosis.

Secondary metastatic disease to the ovary, including metastases arising from the gastrointestinal tract, breast, or female genital tract, is rare. An accurate diagnosis is challenging due to the wide range of differential diagnoses, especially in a patient without a prior known history of malignancy. We report a case of a 23-year-old woman with invasive, poorly differentiated small bowel adenocarcinoma metastatic to the ovaries, a rare tumor with a poor prognosis, who presented with worsening pelvic pain and symptomatic anemia.

Synchronous adenocarcinoma of small bowel, appendix and rectum

Synchronous colorectal carcinoma (SCRC) has been relatively a rare case as nature of the disease is not well established, due to limited data regarding the disease. The incident of SCRC showed by ranges from 2.3 to 12.4%, most cases were 2 site pathologies, involving colon and rectum. Due to its rarity, the diagnostic and treatment modalities provide such challenges to clinician. We reported a rare case in which patient had 3 sites synchronous adenocarcinoma of small bowel, appendix and rectum. Diagnosis was made intra-operatively as patient presented with acute small bowel obstruction. Here we discussed regarding the challenges in detecting and managing the synchronous lesion, including the interesting pathobiology of the disease.