https://ogma.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:45110  3.5 years since last colonoscopy were 36, 93, 56 and 33, respectively. Among these, 16.7, 19.4, 9.9 and 15.1% were stage III–IV, respectively (p = 0.34). The cancers detected more than 2.5 years after the last colonoscopy were not more advanced than those diagnosed earlier (p = 0.14). 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 precursor lesions in path_MMR carriers, but may remove infiltrating cancers as well. If confirmed, our suggested interpretation will have a bearing on surveillance policy for path_MMR carriers.]]> Wed 26 Oct 2022 14:12:41 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:23155 Wed 24 Aug 2016 15:58:37 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:36129 Wed 17 Nov 2021 16:30:50 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:51759  70 years). Of 38 patients with high-risk tumour test results and genetics services referral, diagnostic testing was carried out for 25 (89%) and identified a LS pathogenic/likely pathogenic variant for 11 patients (44% of 25; 0.7% of 1,624 patients). Conclusions: Given the LS testing and referral gaps, further work is needed to identify strategies for successful integration of LS testing into clinical care, and provide a model for hereditary cancers and broader genomic medicine. Standardised reporting may help clinicians interpret tumour test results and initiate further actions.]]> Wed 13 Mar 2024 08:10:01 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:10386 Wed 11 Apr 2018 17:00:11 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:27601 Wed 11 Apr 2018 15:11:09 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:19784 Wed 11 Apr 2018 13:29:49 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:10691 Wed 11 Apr 2018 12:41:02 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:6851 Wed 11 Apr 2018 10:50:17 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:34658 A in MLH1 gene and c.942+3A > T in MSH2, the deletion mutation encompassing EPCAM is one of the most common causative changes responsible for LS in Poland.]]> Wed 09 Feb 2022 15:54:51 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:34524 Wed 06 Apr 2022 13:58:28 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:53291 Tue 21 Nov 2023 11:48:09 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:51614 Tue 12 Sep 2023 13:49:19 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:44981 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. Methods: The 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. Only path_MMR variants scored by the InSiGHT variant database as class 4 or 5 (clinically actionable) were included in the analysis. Results: Ninety-nine path_MMR carriers had no cancer prior to or at first colonoscopy, but subsequently developed colon cancer. Among these, 96 were 65 years of age or younger at diagnosis, and included 77 path_MLH1, 17 path_MSH2, and 2 path_MSH6 carriers. The number of cancers detected within < 1.5, 1.5–2.5, 2.5–3.5 and at > 3.5 years after previous colonoscopy were 9, 43, 31 and 13, respectively. Of these, 2, 8, 4 and 3 were stage III, respectively, and only one stage IV (interval 2.5–3.5 years) disease. Ten-year crude survival after colon cancer were 93, 94 and 82% for stage I, II and III disease, respectively (p < 0.001). Ten-year crude survival when the last colonoscopy had been < 1.5, 1.5–2.5, 2.5–3.5 or > 3.5 years before diagnosis, was 89, 90, 90 and 92%, respectively (p = 0.91). Conclusions: In path_MLH1 and path_MSH2 carriers, more advanced colon cancer stage was associated with poorer survival, whereas time since previous colonoscopy was not. Although the numbers are limited, together with our previously reported findings, these results may be in conflict with the view that follow-up of path_MMR variant carriers with colonoscopy intervals of less than 3 years provides significant benefit.]]> Thu 27 Oct 2022 09:15:48 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:31439 MLH1 promoter locus for dual MLH1/PMS2 negative tumours. On the basis of these results, genetic counselling and targeted germline mutation testing is then offered to patients considered at high risk of LS. From 1 August 2013 to 31 December 2015, 124 patients were screened (mean age 64.6 years). Thirty-six (29.0%) demonstrated abnormal MMR IHC: 26 (72.2%) showed dual loss of MLH1/PMS2, five (13.9%) dual loss of MSH2/MSH6, three (8.3%) isolated loss of MSH6, and two (5.6%) isolated loss of PMS2. Twenty-five of 26 (96.1%) patients with dual MLH1/PMS2 loss demonstrated MLH1 promoter methylation. Therefore, 11 (8.9%) patients screened were classified as high risk for LS, of whom nine (81.8%) accepted germline mutation testing. Three (2.4% of total screened) were confirmed to have LS, two with germline PMS2 and one with germline MSH2 mutation. Massive parallel sequencing of tumour tissue demonstrated somatic mutations which were concordant with the IHC results in the remainder. Interestingly, the one MLH1/PMS2 IHC negative but not hypermethylated tumour harboured only somatic MLH1 mutations, indicating that universal cascade methylation testing in MLH1/PMS2 IHC negative tumours is very low yield and could be reconsidered in a resource-poor setting. In conclusion, universal screening for LS in patients presenting with gynaecological malignancy using the algorithm described above identified LS in three of 124 (2.4%) of our population. Only three of nine (33.3%) patients considered at high risk for LS by combined IHC and hypermethylation analysis were proven to have LS. Only one of the LS patients was less than 50 years of age and none of these patients would have been identified had more restrictive Amsterdam or Bethesda criteria been applied.]]> Thu 27 Jan 2022 15:57:55 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:8477 Sat 24 Mar 2018 08:41:59 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:13923 Sat 24 Mar 2018 08:24:50 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:19920 Sat 24 Mar 2018 08:03:46 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:20280 Sat 24 Mar 2018 07:59:53 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:26262 Sat 24 Mar 2018 07:40:14 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:24769 Pathology.]]> Sat 24 Mar 2018 07:14:07 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:53956 Mon 22 Jan 2024 17:02:37 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:20652 Mon 14 Dec 2020 14:04:44 AEDT ]]>