Small Bowel Tumors Research Articles

Solitary Loss of PMS2 in a patient with Colon carcinoma

Abstract Introduction/Objective In the United States, there are about 150,000 new cases of Colorectal cancer (CRC) and about 50,000 CRC related deaths each year. Hereditary nonpolyposis colorectal cancer (Lynch Syndrome) accounts for 2% - 4% of CRC. It is characterized by germline mutations in mismatch repair (MMR) genes - MLH1, MSH2, MSH6 and PMS2. Patients with Lynch syndrome have up to an 80% lifetime risk (LTR) of CRC and up to 60% LTR of endometrial cancer. Lynch syndrome patients also have an associated LTR of ovarian cancer (38%), upper urologic tract cancer (18%), gastric cancer (13%), small bowel cancer (6%), hepatobiliary tract cancer (4%), and brain tumors (3% - usually glioblastoma). Methods/Case Report A 76-year-old man with history of moderately differentiated colorectal adenosarcoma involving the transverse colon and a recently diagnosed grade group 5 (Gleason 4 + 5) prostate adenocarcinoma, currently being managed at an outside hospital. The case was sent to UAB for DNA MMR/microsatellite instability (MSI) status evaluation testing. Immunostaining showed loss of PMS2 and intact expression of MLH1, MSH2 and MSH6. These results were confirmed by the IdyIIa MSI assay which detected microsatellite instability in 5 of 7 markers and negative for BRAF V600E variant confirming microsatellite instable tumor. Results (if a Case Study enter NA) NA Conclusion Solitary loss of PMS2 in colonic adenocarcinoma is uncommon and may be caused by an underlying germline mutation of MLH-1 or PMS2, thus could represent Lynch Syndrome. Our patient’s age doesn’t favor Lynch syndrome. Next step would be to perform MLH-1 promoter methylation to confirm sporadic nature of carcinoma. Somatic methylation of the MLH1 promoter occurs in approximately 80% of CRC with defective MMR. Prostate cancer is not currently considered a part of Lynch syndrome.

Rare findings of capsule endoscopy. Clinical observation

The article provides a brief overview of the frequency, prevalence of use, and results of video capsule endoscopy in patients with various indications after undergoing CT/MRI enterography or barium sulfate enterography. A clinical case is presented where a patient with symptoms of gastrointestinal bleeding underwent video capsule endoscopy, revealing a small bowel tumor, followed by surgical treatment. This non-invasive technique enables obtaining more accurate data for decision-making regarding further treatment strategies.

Nutrition Rehabilitation in Oncopathology: Opportunities and Prospects

Nutritional corrective support is an integral component of rehabilitation programs in the perioperative period for oncological pathology. The aim of this study was to evaluate the effectiveness of including remaxol in the rehabilitation treatment regimen for gastroenterological cancer patients. Material and methods. The treatment results of 42 patients with gastric outlet tumors and small intestine tumors were retrospectively analyzed. Remaxol was included in the adjuvant therapy for patients in the main (I, N=22) group: intravenously 400 ml at a rate of 40–80 drops/min (2–4 ml/min) once a day for 10 days. Patients in the comparison group (II, N= 20) received traditional nutritional therapy. The study used both traditional clinical diagnostic methods and methods for assessing the risks of nutritional deficiency and the rehabilitation potential of the body, its adaptive capabilities, and disease prognosis. Results. All patients showed signs of severe nutritional deficiency, endotoxemia, intoxication, and hepatotoxicity. Liver detoxification parameters were better in patients who received remaxol as an adjuvant therapy than in the comparison group. Conclusions. Cancer patients with a high nutritional risk and moderate to high nutritional deficiency are at a higher risk of developing toxic complications requiring adjuvant therapy. The inclusion of remaxol in adjuvant therapy reduced the severity of hepatotoxic reactions in these patients. The data obtained made it possible to recommend its inclusion in treatment regimens for patients with this pathology.

B-092 Effect of the Increased Specificity in a Recombinant anti-tTG Assay on a Celiac Disease Diagnostic Algorithm

Abstract Background Celiac disease is an autoimmune disease where ingestion of gluten results in damage in the small intestine. Celiac disease is estimated to affect 1 in 100 people worldwide, but only 30% of individuals are correctly diagnosed. If celiac disease is neither diagnosed nor treated, this can lead to additional health problems such as type 1 diabetes, multiple sclerosis, short stature, coronary artery disease and small intestine cancers. The celiac disease diagnostic algorithm at our institution begins with determination of IgA levels in the patient. If the patient is not IgA deficient (IgA > 7 mg/dL), an anti-tissue transglutaminase (anti-tTG) IgA level is determined. In patients who have anti-tTG IgA ≥ 4U/mL, an endomysial antibodies (EMA) IgA is performed by indirect immunofluorescence (IFA). Inova Diagnostics updated the reagent from human-derived native antigen to a more specific assay containing a recombinant antigen. We investigated the impact of this change on the downstream testing in our algorithm. Methods The new assay was implemented in August of 2023, and the monthly test counts and percentage of abnormal results were counted for both anti-tTG IgA and EMA IFA before and after the new assay was implemented. Results As shown in Figure 1., switching to the new recombinant anti-tTG reagent resulted in a decrease in the number of anti-tTG IgA results that were classified as abnormal. Subsequently, the abnormal samples that advanced in the algorithm for EMA IFA testing had a higher percentage of abnormal results, while the number of tests performed was lower. Conclusions Use of a more specific anti-tTG assay results in reduction of false positive results, and tests that continue through the celiac disease algorithm are more likely to represent a true diagnosis of celiac disease.

Multifaceted modeling of small intestinal neuroendocrine tumors

Small intestinal neuroendocrine tumors, siNETs, are a group of rare cancers that arise from neuroendocrine cells in the lining of the jejunum and ileum, which are either classified as tumors, siNETs, or carcinomas, siNECs. Current treatment strategies for low grade tumors include surgical resection, peptide radionucleotide receptor therapy, and somatostatin analogues, while high grade and recurrent tumors may receive cytotoxic chemotherapy. These limited treatment options are linked to the lack of representative models that can both reflect the biology of the tumor and are amenable to mid-to-high throughput experimentation. Cell line generation is challenging considering the indolent nature of primary lesions, although some attempts have been successful using a variety of methods and include the primary P-STS line and those derived from metastatic lesions including GOT1, CNDT2.5 and HC45. Patient-derived modeling, including organoids and xenografting, have allowed for multicellular and three-dimensional representations of the original tumor. These specific models allow for multicellular populations derived from the tumor, providing better tumor representation for use in drug screening and in vitro assays. Currently, there are limited, although increasing, published models of siNETs implanted as xenografts in mice and zebrafish. As these cellular and animal models provide insights on siNET biology, theragnostic modeling has provided key information on the clinical progression and treatment of this disease. Significant strides toward more representative models have been made throughout the last decade. In this review, details of these attempts as well as future directions and strategies for more robust models will be addressed.

EL14 Chemotherapy for colorectal cancer and small bowel cancer

EL14 Chemotherapy for colorectal cancer and small bowel cancer

Should we perform regular surveillance capsule endoscopies in patients following small-bowel adenocarcinoma resection? A case report and discussion.

Because small-bowel tumors are rare, prospective data on the utility of video capsule endoscopy (VCE) for their detection are limited. Current guidelines do not advocate for surveillance VCEs in patients following small-bowel tumor resection, which is mostly due to a lack of data. Here, we report an 81-year-old male patient who had undergone curative segmental ileal adenocarcinoma resection 15 years ago and another segmental jejunal adenocarcinoma resection (TNM-Classification: pT2 pN0 (0/2) G2M0) 7 years ago. He now presents with melena, progressive dyspnea, and decreased hemoglobin levels. VCE revealed local intestinal recurrence of the previously resected jejunal adenocarcinoma, leading to a second segmental jejunal resection (TNM-Classification: pT3 L1 pN0 (0/5) G2 M0). We believe that regular surveillance VCEs after the first jejunal adenocarcinoma resection might have facilitated earlier detection of tumor recurrence in this patient's case. Therefore, we suggest considering regular surveillance VCEs, at least in patients with recurrent small-bowel malignancies. However, future prospective studies are warranted to validate our findings.

S2244 Risk of Small Intestine Cancer in Inflammatory Bowel Disease: Results From A Large Multi-Center Database

S2244 Risk of Small Intestine Cancer in Inflammatory Bowel Disease: Results From A Large Multi-Center Database

Investigating causal links between gallstones, cholecystectomy, and 33 site-specific cancers: a Mendelian randomization post-meta-analysis study

Background and aimThe association between gallstones/cholecystectomy and cancer remains inconclusive in the current literature. This study aimed to explore the causal connections between gallstones/cholecystectomy and cancer risk by utilizing a bidirectional two-sample multivariable Mendelian randomization approach with Genome-Wide Association Studies data.MethodsUtilizing Genome-Wide Association Studies data from the UK Biobank and FinnGen, this research employed multivariable Mendelian randomization analyses to explore the impact of gallstones and cholecystectomy on the risk of 33 distinct cancer types. Instrumental variables for gallstones and cholecystectomy were carefully selected to ensure robust analyses, and sensitivity and heterogeneity tests were conducted to verify the findings’ validity.ResultsMultivariable Mendelian randomization analysis, incorporating data from more than 450,000 individuals for gallstones and cholecystectomy, revealed nuanced associations with cancer risk. Cholecystectomy was associated with a significantly increased risk of nonmelanoma skin cancer (OR = 1.59, 95% CI: 1.21 to 2.10, P = 0.001), while gallstones were linked to a decreased risk of the same cancer type (OR = 0.63, 95% CI: 0.47 to 0.84, P = 0.002). Interestingly, the analysis also suggested that cholecystectomy may lower the risk of small intestine tumors (OR = 0.18, 95% CI: 0.043 to 0.71, P = 0.015), with gallstones showing an inverse relationship, indicating an increased risk (OR = 6.41, 95% CI: 1.48 to 27.80, P = 0.013).ConclusionsThe multivariable Mendelian randomization analysis highlights the differential impact of gallstones and cholecystectomy on cancer risk, specifically for nonmelanoma skin cancer and small intestine tumors. These results underscore the importance of nuanced clinical management strategies and further research to understand the underlying mechanisms and potential clinical implications of gallstone disease and cholecystectomy on cancer risk.

Computed tomography radiomics models of tumor differentiation in canine small intestinal tumors.

Radiomics models have been widely exploited in oncology for the investigation of tumor classification, as well as for predicting tumor response to treatment and genomic sequence; however, their performance in veterinary gastrointestinal tumors remains unexplored. Here, we sought to investigate and compare the performance of radiomics models in various settings for differentiating among canine small intestinal adenocarcinoma, lymphoma, and spindle cell sarcoma. Forty-two small intestinal tumors were contoured using four different segmentation methods: pre- or post-contrast, each with or without the inclusion of intraluminal gas. The mesenteric lymph nodes of pre- and post-contrast images were also contoured. The bin settings included bin count and bin width of 16, 32, 64, 128, and 256. Multinomial logistic regression, random forest, and support vector machine models were used to construct radiomics models. Using features from both primary tumors and lymph nodes showed significantly better performance than modeling using only the radiomics features of primary tumors, which indicated that the inclusion of mesenteric lymph nodes aids model performance. The support vector machine model exhibited significantly superior performance compared with the multinomial logistic regression and random forest models. Combining radiologic findings with radiomics features improved performance compared to using only radiomics features, highlighting the importance of radiologic findings in model building. A support vector machine model consisting of radiologic findings, primary tumors, and lymph node radiomics features with bin count 16 in post-contrast images with the exclusion of intraluminal gas showed the best performance among the various models tested. In conclusion, this study suggests that mesenteric lymph node segmentation and radiological findings should be integrated to build a potent radiomics model capable of differentiating among small intestinal tumors.

Food antigens suppress small intestinal tumorigenesis.

Food components suppressing small intestinal tumorigenesis are not well-defined partly because of the rarity of this tumor type compared to colorectal tumors. Using Apcmin/+ mice, a mouse model for intestinal tumorigenesis, and antigen-free diet, we report here that food antigens serve this function in the small intestine. By depleting Peyer's patches (PPs), immune inductive sites in the small intestine, we found that PPs have a role in the suppression of small intestinal tumors and are important for the induction of small intestinal T cells by food antigens. On the follicle-associated epithelium (FAE) of PPs, microfold (M) cells pass food antigens from lumen to the dendritic cells to induce T cells. Single-cell RNA-seq (scRNA-seq) analysis of immune cells in PPs revealed a significant impact of food antigens on the induction of the PP T cells and the antigen presentation capacity of dendritic cells. These data demonstrate the role of food antigens in the suppression of small intestinal tumorigenesis by PP-mediated immune cell induction.

Small bowel neuroendocrine tumors: Unique features and low lethality compared with small bowel adenocarcinoma.

Population-based studies comparing clinical characteristics and survival disparities between patients with small bowel adenocarcinoma (SBA) and small bowel neuroendocrine tumors (SBNETs) in the United States are limited. Data for patients with SBA or SBNETs, obtained from the Surveillance, Epidemiology, and End Results database for the years between 2000 and 2018 were analyzed. Between 2000 and 2018, the age-adjusted incidence of SBA experienced a marginal increase whereas SBNETs demonstrated a significant increase, emerging as the predominant subtype of small bowel cancer (SBC). Diagnoses peaked at ages 65-69years for SBA and 60-64years for SBNETs, with the latter exhibiting a heightened age-specific incidence and maintaining equilibrium in gender distribution. Clinicopathologic disparities revealed SBA's duodenal predilection, larger tumor size, and advanced stages, contrasting with SBNETs' ileal predilection, early-stage presentation, and superior outcomes. SBNETs patients underwent surgery more frequently but received less chemotherapy and radiation than SBA patients. Factors intricately correlated with a diagnosis of SBNETs included female gender, White race, advanced age, marital status, recent diagnoses, superior tumor differentiation, smaller size, distal location, and early-stage presentation. Survival analysis unveiled a remarkable 79% reduction in the mortality risk for SBNETs compared with SBA. Subgroup analysis further confirmed the consistently favorable survival advantages of SBNETs, highlighting the clinical relevance of histological classification in prognostication. Compared with SBA, SBNETs exhibited distinctive clinicopathological features characterized by a higher inclination toward low-grade and early-stage manifestations, thereby contributing to superior survival outcomes.

A case of inflammatory myofibroblastic tumor of small intestine, presented as intussusception

A case of inflammatory myofibroblastic tumor of small intestine, presented as intussusception

Incidence, survival, and prognostic nomogram of patients with small intestinal neuroendocrine tumors: A SEER population-based study.

Small intestinal neuroendocrine tumors (SI-NETs) are a group of rare and significantly heterogeneous tumors with limited research currently available. This study aimed to investigate the incidence, survival, and prognostic factors of SI-NETs. We selected data from the surveillance, epidemiology, and end results (SEER) database between 2000 and 2019 and evaluated the incidence trend of SI-NETs during this period. We utilized the Kaplan-Meier method to examine the association between clinical variables and survival rates. Based on the multivariable Cox regression analysis results, we developed a nomogram to predict the 1-, 2-, and 3-year cancer-specific survival (CSS) of SI-NETs patients. We evaluated the consistency, accuracy, and clinical utility of the nomogram by drawing calibration curves, receiver operating characteristic (ROC) curves, and decision curve analysis (DCA) curves. The incidence of SI-NETs showed an upward trend in recent years. Age, grade, T stage, M stage, and primary tumor surgery were independent risk factors for CSS in SI-NETs patients. The nomogram model based on these risk factors showed high accuracy and clinical benefit. SI-NETs are rare tumors with an increasing incidence rate. The nomogram model is expected to be an effective tool for personalized prognosis prediction in SI-NETs patients, which may benefit clinical decision-making.

Experiences and Fundamental Care Needs in Patients With Small Intestinal Neuroendocrine Tumours-An Interview Study in a Surgical Context.

The study aimed to describe patients' fundamental care needs and their experiences of nursing care, throughout surgical treatment of small intestinal neuroendocrine tumours. A qualitative descriptive study was performed. Patients' interviews (n = 19) were conducted in Sweden from May 2021 to January 2022 and analysed using directed qualitative content analysis guided by the Fundamentals of Care framework. The results are presented in three descriptive categories chronologically throughout the care chain. In the preoperative phase of care, the category was 'Feeling safe but lonely and frightened, and struggling with existential thoughts'; experiences in the postoperative phase of care resulted in the category 'Feeling cared for but suffering from physical symptoms and feelings of loneliness'; and the category in the discharge phase was 'Lacking self-care information and feeling worried about the future'. There were deficiencies in the delivery of fundamental care for patients with a rare tumour diagnosis throughout surgical treatment. Nursing care is mostly task focused and fragmented, and there is a lack of psychosocial and relational care across the care chain. Registered nurses and nursing managers need to take responsibility for their leadership in nursing care to fulfil patients' fundamental care needs. The Fundamentals of Care framework could be used for work improvements to include all aspects of nursing care. High-quality nursing care is needed throughout the care chain, including self-care after discharge, for patients with this rare tumour diagnosis. A higher awareness of patients' experiences and the importance of psychosocial support is warranted. Registered nurses and nursing managers must revise and improve routines to support patients' psychosocial needs. Registered nurses need to take responsibility for their leadership in nursing care to fulfil patients' fundamental care needs. What problem did the study address? This study highlights patients' fundamental care needs and experiences of nursing care throughout surgical treatment of small intestinal neuroendocrine tumours. What were the main findings? There are deficiencies in fulfilling patients' fundamental care needs across the care chain and in all dimensions of the Fundamental of Care framework throughout surgical treatment of small intestinal neuroendocrine tumours. Patients struggled with loneliness and existential thoughts, as well as worries about the future. Patients experienced a lack of information about plans for the day, self-care, and follow-ups. Where and on whom will the research have an impact? For clinicians to develop an understanding of, and improve, fundamental care needs for patients with small intestinal neuroendocrine tumours in a surgical context. For registered nurses to understand the importance of their leadership and nursing responsibility to fulfil fundamental care needs. The consolidated criteria for reporting qualitative research (COREQ): a 32-item checklist for interviews and focus groups. The patients shared their experiences during the interviews, which has contributed to a deeper knowledge and understanding of the phenomena under study.

Gastrointestinal Cancers in Hospitalized Patients with Cystic Fibrosis: A Nationwide Study, 2010-2020.

As life expectancy in cystic fibrosis (CF) patients has increased, so has the incidence of cancers. We aimed to investigate and describe gastrointestinal cancers in CF hospitalized patients from 2010 to 2020. Utilizing the National Inpatient Sample, we extracted cases of CF-associated hospitalizations and gastrointestinal cancers as well as demographic and clinical data. We compared our CF cohort to age, sex, and race/ethnicity-matched controls. Trends were analyzed by Poisson regression. We identified a total of 902 hospitalizations of CF with gastrointestinal cancer; among them, 539 (59.8%) were colorectal, 139 (15.4%) were liver, 105 (11.6%) were pancreatic, 54 (6.0%) were small bowel, 35 (3.9%) were gastric, and 30 (3.3%) were esophageal cancers. The median age of hospitalization for gastrointestinal cancers ranged from 39 years in liver cancer to 65 years in small bowel cancer. Mortality ranged from 9.5% in pancreatic to 0.0% in small bowel cancer. Colorectal cancer (IRR: 1.09; p = 0.005), pancreatic cancer (IRR: 1.17; p = 0.023), gastric cancer (IRR: 1.41; p = 0.003), and esophageal cancer (IRR: 1.50; p = 0.023) hospitalization rates have been increasing over time. Rates of colorectal (p = 0.037) cancer were significantly higher in our CF cohort compared to controls. Colorectal cancers are the major gastrointestinal cancers in CF patients, and the incidence of these hospitalizations is increasing.

ThP2.12 - Evaluation of hand-assisted laparoscopic surgery of small intestine neuroendocrine tumors as an alternative surgical treatment for open surgery

Abstract Aims Small intestinal neuroendocrine tumor (SI-NETs) is the most common malignancy of the small bowel. Curative treatment is exclusively operative and explorative laparotomy is still considered to be the standard procedure. The purpose of this retrospective cohort study was to assess the outcome of minimally invasive surgery in patients with SI-NETs, at our endocrine surgery unit in 2019, compared to the open approach. Methods Patients who underwent surgery for SI-NETs between 2013 and 2023 were included. Descriptive variables such as operative time, length of hospital stay, use of analgesia and radiciality were compared primarily between groups of patients operated before and after 2019 and secondarily between open and hand-port assisted laparoscopic surgery (HALS). Results Of 97 patients with SI-NET included in the study, 58 (59.8 %) had an open and 39 (40.2 %) minimal invasive surgery. While difference in the operative time, 121 min (91.3-150.3) vs 108 min (83-141), the length of hospital stay, 6 days (4-7) vs 5 days (4-8) and surgical radicality in patients with stage II-III, 79.3% vs 85%, (p-value 0.313) was not significant, 86.2% of patients with explorative laparotomy required epidural analgesia compared to 23.1% with HALS (p-value = <0.001). Conclusion Hand-port assisted laparoscopic surgery of SI-NETs was assessed to be a feasible approach without compromising radical resection and enhancing postoperative recovery with lower amount of required analgesia postoperatively.

Small bowel cancers: A population-based analysis of epidemiology, treatment and outcomes in Ontario, Canada from 2005-2020

IntroductionSmall bowel cancers are uncommon malignancies comprised of several histologies with variable treatments and prognoses. The current study describes the epidemiology, treatment, and outcomes of a large, population-based cohort of patients with small bowel cancers. MethodsWe performed a retrospective cohort study using linked administrative healthcare data from Ontario, Canada. Patients diagnosed with a small bowel cancer between 2005–2020 were included. Trends in incidence, treatments, and survival were explored by histology (adenocarcinoma, neuroendocrine tumors (NET), gastrointestinal stromal tumors (GIST), and lymphoma). ResultsA total of 5306 patients with small bowel cancers were identified. The most common histologies were NET (40.5 %) and adenocarcinoma (31.6 %). Over the study period the annual incidence of small bowel cancers increased from 1.54 to 2.78 per 100 000 and the likelihoods of receiving surgery and systemic therapy within one year of diagnosis both increased for all histologic subtypes except lymphoma. Median overall survival from diagnosis was 1.0 year for adenocarcinoma, 13.2 years for NET, 14.2 years for GIST, and 10.1 years for lymphoma. There was no trend towards improved median survival for adenocarcinoma by year of diagnosis; 0.94 years (2005–2010), 1.07 years (2011–2015), and 0.98 years (2016–2020). DiscussionSmall bowel cancers are increasing in incidence, with increasing use of surgery and systemic therapies. While survival is favourable for many small bowel cancers, it remains poor for adenocarcinoma. Better availability of cancer stage data and detailed histopathology within the database would facilitate future research. SynopsisThis study of small bowel cancer in Ontario from 2005 to 2020 demonstrated increasing incidence, use of surgery, and systemic treatments. The most common histologies are neuroendocrine tumors and adenocarcinoma, with median survivals of 13.2 and 1.0 years respectively.

Emergency surgery influences oncological outcome in small intestinal neuroendocrine tumors.

Patients with small intestinal neuroendocrine tumors (siNETs) frequently present emergently due to bowel ischemia or bowel obstruction. The influence of emergency surgery on the prognosis of siNET remains controversial. The aim of this study was to investigate the association between type of presentation (emergency/elective) and oncological outcome. Clinicopathological data of patients who underwent bowel resection and were treated due to siNET at the Charité - Universitätsmedizin Berlin, Germany were analyzed retrospectively. A total of 165 patients underwent bowel resection for siNET. Of these, 22.4% (n = 37) were emergency and 77.6% (n = 128) were elective procedures. A preoperative known diagnosis was less common in patients with emergency surgery (48.6% vs 85.2%; p < 0.001) and complete resections of all tumor manifestations were performed less often (32.4% vs 50.8%; p = 0.049), while more completion operations had to be performed (24.3% vs 11.1%; p = 0.049). Overall survival (OS) and progression-free survival (PFS) of emergently operated patients were reduced (5-year OS: 85.2% vs 89.5% (p = 0.023); 5-year PFS: 26.7% versus 52.5% (p = 0.018)). In addition, emergency surgery was negatively associated with OS after multivariable regression analysis. Emergency surgery in siNET patients is associated with adverse oncological outcomes including shorter OS and PFS. Prevention of emergency conditions should be emphasized in advanced disease.

Risk of Gastric and Small Intestinal Cancer in Patients With Lynch Syndrome: Data From a Large, Community-Based US Population.

Risk of gastric and small intestinal cancer in Lynch syndrome (LS) remains poorly understood. We investigated the risk of gastric and small intestinal cancer in patients with LS in a large, community-based population. This retrospective cohort study included all patients diagnosed with LS between January 1, 1997, and December 31, 2020, at Kaiser Permanente Northern California. Cumulative incidence of gastric cancer and small intestinal cancer was calculated using competing risk methodology. Among 1,106 patients with LS with a median follow-up of 19.3 years (interquartile range [IQR] 9.4-24.0 years), 11 developed gastric cancer (8 MSH2 , 2 MLH1 and 1 PMS2 ) with a median diagnosis age of 56 years (IQR 42-63 years) and 11 developed small intestinal cancer (6 MSH2 , 3 MLH1 , 1 MSH6 and 1 PMS2 ) with a median diagnosis age of 57 years (IQR 50-66 years). Cumulative incidence by age 80 years was 7.26% (95% confidence internal [CI], 1.80-18.03%) for men and 3.43% (95% CI, 0.50-11.71%) for women for gastric cancer and 7.28% (95% CI, 3.19-13.63%) for men and 2.21% (95% CI, 0.23-9.19%) for women for small intestinal cancer. Pathogenic variant carriers of MSH2 and MLH1 had the highest risk of gastric and small intestinal cancer. History of Helicobacter pylori infection was associated with increased risk of gastric cancer (adjusted odds ratio 5.52; 95% CI, 1.72-17.75). Patients with LS, particularly MSH2 and MLH1 pathogenic variant carriers, had significantly increased lifetime risk of gastric and small intestinal cancer. Testing and treatment of H. pylori infection should be considered for all patients with LS.