scholarly journals Identification of Lynch Syndrome Carriers among Patients with Small Bowel Adenocarcinoma

Cancers ◽  
2021 ◽  
Vol 13 (24) ◽  
pp. 6378
Author(s):  
Ariadna Sánchez ◽  
Luis Bujanda ◽  
Miriam Cuatrecasas ◽  
Alex Bofill ◽  
Cristina Alvarez-Urturi ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Small Bowel ◽  
Lynch Syndrome ◽  
Mismatch Repair ◽  
Small Bowel Adenocarcinoma ◽  
Tumor Characteristics ◽  
Spanish Study ◽  
Demographical Data ◽  
Germline Testing

Background: Small bowel adenocarcinoma (SBA) is a rare disease which can be associated with Lynch syndrome (LS). LS tumors are characterized by the presence of microsatellite instability (MSI) and/or the loss of mismatch repair (MMR) protein expression. In SBA, the frequency of MMR deficient (MMRd) tumors varies from 5% to 35%. This study aims to describe the prevalence of LS carriers among patients with MMRd small bowel adenocarcinomas. Methods: A multicenter retrospective study with identification and MMR testing of all consecutive SBA between 2004 and 2020 in a multicenter Spanish study. Demographical data, tumor characteristics, follow-up and survival information were collected. Germline testing was driven by identification of MMRd tumors. Results: A total of 94 individuals diagnosed with SBA were recruited. We observed 20 (21.3%) MMRd tumors. In 9/15 (60%) patients with MMRd tumors, a pathogenic variant was identified (three MLH1, four MSH2, one MSH6 and one PMS2). Accordingly, the prevalence of LS among all SBA cases was 10.1%. Conclusions: More than one-fifth of SBA display MMRd and in more than a half is due to LS. Our data supports the implementation of universal MMR tumor testing among SBA for the identification of LS families.

scholarly journals Pembrolizumab for Microsatellite Instability-High or Mismatch Repair Deficient Small Bowel Adenocarcinoma or Appendiceal Adenocarcinoma

2021 ◽  
Vol 1 (10) ◽  
Author(s):  
Keeley Farrell ◽  
Jennifer Horton
Keyword(s):  
Small Bowel ◽  
Microsatellite Instability ◽  
Mismatch Repair ◽  
Progression Free Survival ◽  
Clinical Effectiveness ◽  
Complete Response ◽  
Small Bowel Adenocarcinoma ◽  
Appendiceal Adenocarcinoma ◽  
The Cost ◽  
Evidence Based Guidelines

Some adult patients with microsatellite instability-high (MSI-H)/mismatch repair deficient (dMMR) small bowel adenocarcinoma might benefit from pembrolizumab in controlling the disease (i.e., some patients achieved a partial or complete response after treatment). These findings are based on 2 single-arm studies (i.e., no comparator) with fewer than 20 patients in each study, which limits the certainty of the findings. The longer-term benefit of pembrolizumab is unclear, as some outcomes (e.g., progression-free survival, overall survival) were not reached at the time of data analysis. The safety of pembrolizumab in patients with MSI-H/dMMR small bowel adenocarcinoma is unknown (no evidence was found for this population). No evidence was identified regarding the clinical effectiveness of pembrolizumab monotherapy for patients with MSI-H/dMMR appendiceal adenocarcinoma. No evidence was identified regarding the cost-effectiveness of pembrolizumab monotherapy for patients with MSI-H/dMMR small bowel adenocarcinoma or appendiceal adenocarcinoma. No evidence-based guidelines were identified regarding pembrolizumab monotherapy for patients with MSI-H/dMMR appendiceal adenocarcinoma. One guideline was identified that recommends pembrolizumab as an option for initial or subsequent therapy in patients with advanced or metastatic MSI-H/dMMR small bowel adenocarcinoma.

The role of defective mismatch repair in small bowel adenocarcinoma in celiac disease

2004 ◽  
Vol 199 (3) ◽  
pp. 86
Author(s):  
D.Dean Potter ◽  
Joseph Murray ◽  
John Donohue ◽  
Lawrence Burgart ◽  
David Nagorney ◽  
...  
Keyword(s):  
Celiac Disease ◽  
Small Bowel ◽  
Mismatch Repair ◽  
Small Bowel Adenocarcinoma ◽  
Defective Mismatch Repair

scholarly journals Characterization and Clinical Outcomes of DNA Mismatch Repair Deficient (MMR-D) Small Bowel Adenocarcinoma

2020 ◽  
pp. clincanres.2892.2020
Author(s):  
Alicia Latham ◽  
Jinru Shia ◽  
Zalak Patel ◽  
Diane L Reidy-Lagunes ◽  
Neil H Segal ◽  
...  
Keyword(s):  
Small Bowel ◽  
Mismatch Repair ◽  
Clinical Outcomes ◽  
Dna Mismatch Repair ◽  
Small Bowel Adenocarcinoma ◽  
Dna Mismatch

Tumor site discordance in mismatch repair deficiency in synchronous endometrial and ovarian cancers

2020 ◽  
Vol 30 (12) ◽  
pp. 1951-1958
Author(s):  
Soyoun Rachel Kim ◽  
Alicia Tone ◽  
Raymond Kim ◽  
Matthew Cesari ◽  
Blaise Clarke ◽  
...  
Keyword(s):  
Lynch Syndrome ◽  
Microsatellite Instability ◽  
Mismatch Repair ◽  
Ovarian Tumor ◽  
Tumor Site ◽  
Mismatch Repair Deficiency ◽  
Ovarian Cancers ◽  
Repair Deficiency ◽  
Endometrial Tumor ◽  
Germline Testing

ObjectivesFor synchronous endometrial and ovarian cancers, most centers rely on mismatch repair testing of the endometrial cancer to identify Lynch syndrome, and neglect the ovarian tumor site completely. We examined the mismatch repair immunohistochemistry and microsatellite instability results from the endometrium and ovary to assess discordance between the tumor sites and between tests.Methods30 women with newly diagnosed synchronous endometrial and ovarian cancer were prospectively recruited from three cancer centers in Ontario, Canada. Both tumor sites were assessed for mismatch repair deficiency by immunohistochemistry and microsatellite instability test; discordance in results between tumor sites and discordance between test results at each site was examined. Cases with discordant results had tumors sequenced with a targeted panel in order to reconcile the findings. All women underwent mismatch repair gene germline testing.ResultsOf 30 patients, 11 (37%) were mismatch repair deficient or microsatellite instable at either tumor site, with 5 (17%) testing positive for Lynch syndrome. Mismatch repair immunohistochemistry expression was discordant between endometrial and ovarian tumor sites in 2 of 27 patients (7%) while microsatellite instability results were discordant in 2 of 25 patients (8%). Relying on immunohistochemistry or microsatellite instability alone on the endometrial tumor would have missed one and three cases of Lynch syndrome, respectively. One patient with Lynch syndrome with a PMS2 pathogenic variant was not detected by either immunohistochemistry or microsatellite instability testing. The rate of discordance between immunohistochemistry and microsatellite instability test was 3.8% in the ovary and 12% in the endometrium.ConclusionsThere was discordance in immunohistochemistry and microsatellite instability results between tumor sites and between tests within each site. Endometrial tumor testing with mismatch repair immunohistochemistry performed well, but missed one case of Lynch syndrome. Given the high incidence of Lynch syndrome (17%), consideration may be given to germline testing in all patients with synchronous endometrial and ovarian cancers.

Pharmacogenetic dosing by UGT1A1 genotype as first-line therapy for advanced small-bowel adenocarcinoma: A North Central Cancer Treatment Group (NCCTG) trial.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 314-314 ◽  
Author(s):  
Robert R. McWilliams ◽  
Michelle R. Mahoney ◽  
Benjamin T. Marchello ◽  
Aminah Jatoi ◽  
Keith D. Krewer ◽  
...  
Keyword(s):  
Small Bowel ◽  
Small Bowel Adenocarcinoma ◽  
First Line ◽  
Prospective Data ◽  
North Central ◽  
First Line Therapy ◽  
Dosing Strategy ◽  
Prolonged Response ◽  
Ugt1a1 Genotype

314 Background: Small bowel adenocarcinoma (SB-ACA) is rare, having little prospective data guiding management. A prior phase I study evaluated UGT1A1 genotype specific dosing of oxaliplatin, irinotecan, and capecitabine. Our prospective, multicenter clinical trial assessing tumor response in pts having metastatic SB-ACA, used a similar dosing strategy. Methods: Genotypes were determined via central lab. Previously untreated pts were dosed by UGT1A1*28 genotypes 6/6, 6/7, and 7/7 receiving 100/85/85 mg/m2 oxaliplatin d1, 150/150/75 mg/m2 irinotecan d1, and 1600/400/200 mg/m2 capecitabine (BID) d2-15 of 21 days. The study design was such that 1 confirmed response in 16 pts expanded enrollment to 33 pts, with 7 required for demonstrating efficacy. Results: 28 pts (13-6/6, 10-6/7, 5-7/7) have been enrolled [75% male, mean age 62.5 (range 41-77)]. Location of primary included: duodenum (63%), jejunum (26%), and ileum (7%), with pts having >1 metastatic site (abdominal-41%, bone-7%, liver-56%, lung-30%, nodal-52%, subcutaneous-4%, other-19%). Gr 3+ treatment related toxicity was not significantly different by genotype (50%-6/6, 44%-6/7, 20%-7/7, p=0.48) and included (pts): diarrhea(5), vomiting(5), leukopenia(5), neutropenia(7), and nausea(6). 57% (13 of 23) pts achieved responses during therapy, with a confirmed response rate of 39% (95% CI 0-58%). 18 have died, with a median follow-up of 8.3 mos (range 0-43). Conclusions: UGT1A1 genotype directed dosing with oxaliplatin, irinotecan, and capecitabine appears to result in prolonged response in this population. Larger studies are needed to determine comparability to CapeOx alone or if response/toxicity differs among genotypes. Supported by NIH Grant CA25224, Sanofi-Aventis, and Pfizer. [Table: see text]

A retrospective study of anti-EGFR antibody therapy in small bowel adenocarcinoma.

2018 ◽  
Vol 36 (15_suppl) ◽  
pp. e16264-e16264 ◽  
Author(s):  
Victoria Serpas ◽  
Kanwal Pratap Singh Raghav ◽  
Gauri R. Varadhachary ◽  
Robert A. Wolff ◽  
Michael J. Overman
Keyword(s):  
Retrospective Study ◽  
Small Bowel ◽  
Antibody Therapy ◽  
Small Bowel Adenocarcinoma ◽  
Egfr Antibody

Tumors of the Stomach and Small Bowel

2020 ◽  
Author(s):  
Jeffrey D. Wayne ◽  
L. Mark Knab ◽  
David J. Bentrem
Keyword(s):  
Risk Factors ◽  
Helicobacter Pylori ◽  
Small Bowel ◽  
Recurrent Disease ◽  
Malignant Tumors ◽  
Gastric Lymphoma ◽  
Small Bowel Adenocarcinoma ◽  
Cancer Death ◽  
The Past

The overall incidence of gastric carcinoma has decreased in the past few decades, but it remains the second leading cause of cancer death worldwide. Malignant tumors of the small intestine are rare, and account for fewer than 5% of all gastrointestinal tract malignancies. This review details the classification, risk factors, clinical evaluation, investigative studies, staging, management, and follow-up and management of recurrent disease in gastric adenocarcinoma; in addition, it examines nonadenocarcinomatous gastric malignancies and small bowel malignancies.  This review contains 7 figures, 16 tables, and 92 references. Keywords:Gastric adenocarcinoma, gastrointestinal stromal tumor, gastric lymphoma, Helicobacter pylori, small bowel adenocarcinoma, surgical resection, staging, chemotherapy, radiation therapy

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