Cancer risk and survival in path_MMR carriers by gene and gender up to 75 years of age: a report from the Prospective Lynch Syndrome Database

Background Most patients with path_MMR gene variants (Lynch syndrome (LS)) now survive both their first and subsequent cancers, resulting in a growing number of older patients with LS for whom limited information exists with respect to cancer risk and survival. Objective and design  This observational, international, multicentre study aimed to determine prospectively observed incidences of cancers and survival in path_MMR carriers up to 75 years of age. Results 3119 patients were followed for a total of 24 475 years. Cumulative incidences at 75 years (risks) for colorectal cancer were 46%, 43% and 15% in path_MLH1, path_MSH2 and path_MSH6 carriers; for endometrial cancer 43%, 57% and 46%; for ovarian cancer 10%, 17% and 13%; for upper gastrointestinal (gastric, duodenal, bile duct or pancreatic) cancers 21%, 10% and 7%; for urinary tract cancers 8%, 25% and 11%; for prostate cancer 17%, 32% and 18%; and for brain tumours 1%, 5% and 1%, respectively. Ovarian cancer occurred mainly premenopausally. By contrast, upper gastrointestinal, urinary tract and prostate cancers occurred predominantly at older ages. Overall 5-year survival for prostate cancer was 100%, urinary bladder 93%, ureter 85%, duodenum 67%, stomach 61%, bile duct 29%, brain 22% and pancreas 0%. Path_PMS2 carriers had lower risk for cancer. Conclusion  Carriers of different path_MMR variants exhibit distinct patterns of cancer risk and survival as they age. Risk estimates for counselling and planning of surveillance and treatment should be tailored to each patient's age, gender and path_MMR variant. We have updated our open-access website www.lscarisk. org to facilitate this

Incidence of and survival after subsequent cancers in carriers of pathogenic MMR variants with previous cancer: a report from the prospective Lynch syndrome database

Objective Today most patients with Lynch syndrome (LS) survive their first cancer. There is limited information on the incidences and outcome of subsequent cancers. The present study addresses three questions: (i) what is the cumulative incidence of a subsequent cancer; (ii) in which organs do subsequent cancers occur; and (iii) what is the survival following these cancers? Design Information was collated on prospectively organised surveillance and prospectively observed outcomes in patients with LS who had cancer prior to inclusion and analysed by age, gender and genetic variants. Results 1273 patients with LS from 10 countries were followed up for 7753 observation years. 318 patients (25.7%) developed 341 first subsequent cancers, including colorectal (n=147, 43%), upper GI, pancreas or bile duct (n=37, 11%) and urinary tract (n=32, 10%). The cumulative incidences for any subsequent cancer from age 40 to age 70 years were 73% for pathogenic MLH1 (path_MLH1), 76% for path_MSH2 carriers and 52% for path_MSH6 carriers, and for colorectal cancer (CRC) the cumulative incidences were 46%, 48% and 23%, respectively. Crude survival after any subsequent cancer was 82% (95% CI 76% to 87%) and 10-year crude survival after CRC was 91% (95% CI 83% to 95%). Conclusions Relative incidence of subsequent cancer compared with incidence of first cancer was slightly but insignificantly higher than cancer incidence in patients with LS without previous cancer (range 0.94-1.49). The favourable survival after subsequent cancers validated continued follow-up to prevent death from cancer. The interactive website http://lscarisk.org was expanded to calculate the risks by gender, genetic variant and age for subsequent cancer for any patient with LS with previous cancer

Higher-order aberrations after implantation of iris-fixated rigid or foldable phakic intraocular lenses

PURPOSE: To evaluate higher-order aberrations (HOAs) after implantation of Artiflex phakic intraocular lenses (pIOLs). SETTING: Department of Ophthalmology, Academic Hospital Maastricht, Maastricht, The Netherlands. METHODS: This retrospective comparative case series comprised 27 eyes (14 patients) that had Artiflex pIOL implantation and 22 eyes (13 patients) that had Artisan pIOL implantation. Refractive data, pupil size, IOL decentration, and HOA values were recorded and compared. Laboratory analysis was performed. Follow-up was 1 year. RESULTS: In the Artiflex group, the mean spherical equivalent (SE) changed from -9.95 diopters (D) +/- 1.43 (SD) (range -6.75 to -12.13 D) to -0.30 +/- 0.53 D (range -1.94 to 0.56 D). Postoperatively, trefoil-y increased (increase factor 1.73) and spherical aberration decreased (increase factor 0.55). The mean pIOL decentration was 0.24 +/- 0.12 mm; 96.3% were decentered 0.5 mm or less. There was a significant correlation between pIOL decentration and postoperative spherical aberration and coma-y. In the Artisan group, the mean SE changed from -9.90 +/- 2.74 D (range -4.00 to -14.50 D) to -0.20 +/- 0.42 D (range -0.75 to 0.50 D). Postoperatively, trefoil-y and spherical aberration increased (increase factors 3.32 and 6.84, respectively). Laboratory analysis confirmed the negative and positive spherical aberration profile of the Artiflex pIOL and Artisan pIOL, respectively. CONCLUSIONS: Artiflex pIOL implantation decreased spherical aberration, while Artisan pIOL implantation increased spherical aberration. Trefoil-y increased in both groups. These changes might be explained by incision size differences in relation to trefoil and differences in optic design in relation to spherical aberration