PMS2 cause Lynch syndrome and result in different but imprecisely known cancer risks. This study aimed to provide age and organspecific cancer risks according to gene and gender and to determine survival after cancer. Methods: We conducted an international, multicenter prospective observational study using independent test and validation cohorts of carriers of class 4 or class 5 variants. After validation the cohorts were merged providing 6350 participants and 51,646 followup years. Results: There were 1808 prospectively observed cancers. Pathogenic MLH1 and MSH2 variants caused high penetrance dominant cancer syndromes sharing similar colorectal, endometrial, and ovarian cancer risks, but older MSH2 carriers had higher risk of cancers of the upper urinary tract, upper gastrointestinal tract, brain, and particularly prostate. Pathogenic MSH6 variants caused a sex-limited trait with high endometrial cancer risk but only modestly increased colorectal cancer risk in both genders. We did not demonstrate a significantly increased cancer risk in carriers of pathogenic PMS2 variants. Ten-year crude survival was over 80% following colon, endometrial, or ovarian cancer. Conclusion: Management guidelines for Lynch syndrome may require revision in light of these different gene and gender-specific risks and the good prognosis for the most commonly associated cancers.

Purpose To determine impact of risk-reducing hysterectomy and bilateral salpingo-oophorectomy (BSO) on gynecological cancer incidence and death in heterozygotes of pathogenic MMR (path_MMR) variants. Methods The Prospective Lynch Syndrome Database was used to investigate the effects of gynecological risk-reducing surgery (RRS) at different ages. Results Risk-reducing hysterectomy at 25 years of age prevents endometrial cancer before 50 years in 15%, 18%, 13%, and 0% of path_MLH1, path_MSH2, path_MSH6, and path_PMS2 heterozygotes and death in 2%, 2%, 1%, and 0%, respectively. Risk-reducing BSO at 25 years of age prevents ovarian cancer before 50 years in 6%, 11%, 2%, and 0% and death in 1%, 2%, 0%, and 0%, respectively. Risk-reducing hysterectomy at 40 years prevents endometrial cancer by 50 years in 13%, 16%, 11%, and 0% and death in 1%, 2%, 1%, and 0%, respectively. BSO at 40 years prevents ovarian cancer before 50 years in 4%, 8%, 0%, and 0%, and death in 1%, 1%, 0%, and 0%, respectively. Conclusion Little benefit is gained by performing RRS before 40 years of age and premenopausal BSO in path_MSH6 and path_PMS2 heterozygotes has no measurable benefit for mortality. These findings may aid decision making for women with LS who are considering RRS.

and Marianne Haeusler for their efforts over many years. The CCFR graciously thanks the generous contributions of their study participants and dedication of study staff.

AbstractObjectiveRate of learning is often cited as a deterrent in the use of endoscopic ear surgery. This study investigated the learning curves of novice surgeons performing simulated ear surgery using either an endoscope or a microscope.MethodsA prospective multi-site clinical research study was conducted. Seventy-two medical students were randomly allocated to the endoscope or microscope group, and performed 10 myringotomy and ventilation tube insertions. Trial times were used to produce learning curves. From these, slope (learning rate) and asymptote (optimal proficiency) were ascertained.ResultsThere was no significant difference between the learning curves (p = 0.41). The learning rate value was 68.62 for the microscope group and 78.71 for the endoscope group. The optimal proficiency (seconds) was 32.83 for the microscope group and 27.87 for the endoscope group.ConclusionThe absence of a significant difference shows that the learning rates of each technique are statistically indistinguishable. This suggests that surgeons are not justified when citing ‘steep learning curve’ in arguments against the use of endoscopes in middle-ear surgery.