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When a person undergoes a genetic test it can identify a variant(change), but it is unclear whether that variant is actually connected to a health condition for example Lynch Syndrome.

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2825808

Conclusions and Relevance  In this cohort study of individuals undergoing genetic testing, the empirically estimated accuracy of pathogenic, likely pathogenic, benign, and likely benign classifications exceeded the certainty thresholds set by current variant classification guidelines, suggesting the need to reevaluate definitions of these classifications.

The relative contribution of various strategies to resolve VUS, including emerging machine learning–based computational methods, RNA analysis, and cascade family testing, provides useful insights that can be applied toward further improving VC methods, reducing the rate of VUS, and generating more definitive results for patients.

“Today is a day of hope,” said Mater hospital chairman David Begg as it launched an initiative which could mean cancer patients securing access to cutting-edge drug treatments in the State years in advance of when this would otherwise have been the case.

Miriam….“While I did not have the benefit of a clinical trial, I have received new treatments that have come through in the last six to seven years. I am currently stable [but] I have had the last line of treatment. So I am looking for what is coming next.”

https://www.irishtimes.com/health/2024/10/14/a-day-of-hope-irish-hospital-patients-get-access-to-early-phase-cancer-drugs/

Conclusions: Colonoscopy prevented CRC in path_PMS2 carriers but not in the others. Our findings are consistent with colonoscopy surveillance blocking the adenoma-carcinoma pathway by removing identified adenomas which might otherwise become CRCs. However, in the other carriers most CRCs likely arised from dMMR cells in the crypts that have an increased mutation rate with increased stochastic chaotic probabilities for mutations. Therefore, this mechanism, that may be associated with no or only a short sojourn time of MSI tumours as adenomas, could explain the findings in our previous and current reports.

path_MMR:Pathogenic or likely pathogenic variant in one of the MMR genes (MLH1, MSH2, MSH6, or PMS2)

https://pubmed.ncbi.nlm.nih.gov/38741120/

Overall….colonoscopy works either by preventing some cancer, or where this is not biologically possible- by diagnosing cancer early.

There is increasing interest in the use of less-invasive approaches to investigation of at-risk populations, driven in part by the COVID19 pandemic as resources have been increasingly constrained, alongside expanding evidence of clinical effectiveness.

Fecal hemaglobin immunochemical testing(FIT) has been validated in screening and symptomatic populations, is cost-effective, and acceptable to patients.

As a quantitative assay, lower fHb concentration thresholds increase CRC sensitivity albeit with decreased specificity, however FIT has a lower sensitivity for advanced adenomas of around 40-60%2. Therefore a ‘FIT only’ strategy may theoretically result in fewer prevented CRCs, notwithstanding a limited understanding of the natural history of familial CRC. However the estimated reduction in risk by removal of precursor advanced adenomas at colonoscopy provides an opportunity for a less-invasive combined strategy using FIT.

In conclusion the authors have developed a compelling rationale for a combined FIT:colonoscopy strategy where previous data has indicated that FIT alone would not be sufficient. Although their study did not identify differences according to levels of CRC risk, further refinement of risk estimates and investigative strategies may facilitate risk-stratified mixed-modality surveillance strategies.

https://www.gastrojournal.org/article/S0016-5085(24)05458-1/pdf