Yield of Lynch Syndrome Surveillance for Patients With Pathogenic Variants in DNA Mismatch Repair Genes

Patients with Lynch syndrome are offered the same colorectal cancer (CRC) surveillance programs (colonoscopy every 2 years), regardless of the pathogenic DNA mismatch repair gene variant the patient carries. We aimed to assess the yield of surveillance for patients with these variants in MLH1, MSH2, MSH6, and PMS2.
Source: Clinical Gastroenterology and Hepatology - Category: Gastroenterology Authors: Source Type: research

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We present a 47-year-old woman with an MLH1 gene mutation (G133X 397G>T) who presented with menorrhagia. Eleven family members have this mutation, 6 with carcinoma: 5 colorectal and 1 with a gynecologic primary of unknown type. Colonoscopy and endoscopy were unremarkable. Positron emission and computed tomography revealed a 3 cm anterior dome bladder mass without additional extrauterine disease or uterine connection. She underwent partial cystectomy, laparoscopic hysterectomy, bilateral salpingo-oophorectomy, and lymphadenectomy. The uterus demonstrated a dedifferentiated endometrioid adenocarcinoma, immunohistochemical...
Source: Applied Immunohistochemistry and Molecular Morphology - Category: Chemistry Tags: Online Articles: Case Reports Source Type: research
AbstractThe hallmark of Lynch syndrome (LS)-associated neoplasia is DNA mismatch repair protein (MMR) deficiency. Recent studies have demonstrated that histologically normal colonic crypts in patients with LS can exhibit deficient MMR expression. The aim of this study was to determine the feasibility of detecting MMR deficient crypts in random colonoscopic biopsies of normal mucosa in patients with and without LS. Forty-nine patients, including 33 with LS, 12 without LS, and 4 with germline MMR gene variants of uncertain significance (VUS), were prospectively and blindly evaluated by immunohistochemistry for MMR deficient ...
Source: Familial Cancer - Category: Cancer & Oncology Source Type: research
Authors: Lappalainen J, Holmström D, Lepistö A, Saarnio J, Mecklin JP, Seppälä T Abstract Background: Lifetime incidence of colorectal cancer (CRC) especially in carriers of MLH1 and MSH2 pathogenic germline variants in mismatch repair genes is high despite ongoing colonoscopy surveillance. Lynch syndrome (LS) registries have been criticized for not reporting colonoscopy quality adequately.Methods: Prospective follow-up data from the national registry were combined with a retrospective assessment of the colonoscopy reports from Helsinki University Hospital electronic patients records in 2004-201...
Source: Scandinavian Journal of Gastroenterology - Category: Gastroenterology Tags: Scand J Gastroenterol Source Type: research
CONCLUSION:  LS colonic and extracolonic clinical management, surveillance and therapy are complex and several aspects remain unclear. In the future, surveillance and clinical management need to be more tailored to gene and gender. Future prospective trials are needed. PMID: 31739377 [PubMed - in process]
Source: Zeitschrift fur Gastroenterologie - Category: Gastroenterology Authors: Tags: Z Gastroenterol Source Type: research
AbstractBackgroundWe previously reported that in pathogenic mismatch repair (path_MMR) variant carriers, the incidence of colorectal cancer (CRC) was not reduced when colonoscopy was undertaken more frequently than once every 3 years, and that CRC stage and interval since last colonoscopy were not correlated.MethodsThe Prospective Lynch Syndrome Database (PLSD) that records outcomes of surveillance was examined to determine survival after colon cancer in relation to the time since previous colonoscopy and pathological stage. Onlypath_MMR variants scored by the InSiGHT variant database as class 4 or 5 (clinically actionable...
Source: Hereditary Cancer in Clinical Practice - Category: Cancer & Oncology Source Type: research
CONCLUSIONS: Universal tumour testing strategies for guiding germline genetic testing of people with incident CRC for LS in Australia are likely to be cost-effective compared with no testing. Universal germline gene panel testing would not currently be cost-effective. PMID: 31595523 [PubMed - as supplied by publisher]
Source: Medical Journal of Australia - Category: General Medicine Tags: Med J Aust Source Type: research
Conclusions: The CRC stage and interval since last colonoscopy were not correlated, which is in conflict with the accelerated adenoma-carcinoma paradigm. We have previously reported that more frequent colonoscopy is not associated with lower incidence of CRC in path_MMR carriers as was expected. In contrast, point estimates showed a higher incidence with shorter intervals between examinations, a situation that may parallel to over-diagnosis in breast cancer screening. Our findings raise the possibility that some CRCs in path_MMR carriers may spontaneously disappear: the host immune response may not only remove CRC precurso...
Source: Clinical Genitourinary Cancer - Category: Cancer & Oncology Authors: Tags: Hered Cancer Clin Pract Source Type: research
ConclusionsThe CRC stage and interval since last colonoscopy were not correlated, which is in conflict with the accelerated adenoma-carcinoma paradigm. We have previously reported that more frequent colonoscopy is not associated with lower incidence of CRC inpath_MMR carriers as was expected. In contrast, point estimates showed a higher incidence with shorter intervals between examinations, a situation that may parallel to over-diagnosis in breast cancer screening. Our findings raise the possibility that some CRCs inpath_MMR carriers may spontaneously disappear: the host immune response may not only remove CRC precursor le...
Source: Hereditary Cancer in Clinical Practice - Category: Cancer & Oncology Source Type: research
We report here a 16-year-old patient who presented initially with symptoms characteristic of appendicitis. Following a CT scan suggesting perforated appendicitis, the patient was treated with intravenous antibiotics with a scheduled interval appendectomy three months later. Pathology reports from the interval appendectomy showed that the specimen contained a well-to-moderately differentiated adenocarcinoma. The patient then underwent robot assisted right hemicolectomy as definitive management, which demonstrated that the tumor originated in the cecum with invasion into the submucosa and focally infiltrating the muscularis ...
Source: Journal of Pediatric Surgery Case Reports - Category: Surgery Source Type: research
Conclusion: A proinflammatory potential of the diet does not seem to be significantly associated with CRT risk in persons with LS.
Source: American Journal of Clinical Nutrition - Category: Nutrition Authors: Tags: Research Need: Role of Nutrition in Medical Management Cancer Source Type: research
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