ABSTRACT
PURPOSE: To assess cost-effectiveness of routine screening for Lynch Syndrome (LS) in endometrial cancer (EC) patients ≤70years of age. METHODS: Consecutive EC patients ≤70years of age were screened for LS by analysis of microsatellite instability, immunohistochemistry and MLH1 hypermethylation. Costs and health benefit in life years gained (LYG) included surveillance for LS carriers among EC patients and relatives. We calculated incremental cost-effectiveness ratios (ICERs) comparing LS screening among EC patients ≤70years with ≤50years and the revised Bethesda guidelines. RESULTS: Screening for LS in 179 EC patients identified 7 LS carriers; 1 was ≤50 and 6 were 51-70years. Per age category 18 and 9 relatives were identified as LS carrier. Screening resulted in 74,7 LYG (45,4 and 29,3 LYG per age category). The ICER for LS screening in EC patients ≤70 compared with ≤50years was 5,252/LYG. The revised Bethesda guidelines missed 4/7 (57%) LS carriers among EC patients. The ICER for LS screening in EC patients ≤70years of age compared with the revised Bethesda guidelines was 6,668/LYG. Both ICERs remained <16,000/LYG in sensitivity analyses. CONCLUSION: Routine LS screening in EC patients ≤70years is a cost-effective strategy, allowing colorectal cancer prevention in EC patients and their relatives.
Subject(s)
DNA Methylation , DNA Mismatch Repair/genetics , Endometrial Neoplasms/genetics , Genetic Testing/economics , Lynch Syndrome II/diagnosis , Microsatellite Instability , Adult , Age Factors , Aged , Colorectal Neoplasms/diagnosis , Cost-Benefit Analysis , DNA Mutational Analysis , Early Detection of Cancer , Family , Female , Genetic Counseling/economics , Humans , Immunohistochemistry , Lynch Syndrome II/genetics , Mass Screening , Middle Aged , MutL Protein Homolog 1/geneticsABSTRACT
OBJECTIVE: Lynch syndrome (LS) is a hereditary syndrome that predisposes to multiple malignancies including endometrial cancer (EC). We aimed to evaluate a diagnostic strategy for LS based on routine analysis of microsatellite instability (MSI) and immunohistochemical (IHC) staining for mismatch repair (MMR) proteins in tumour tissue of all newly diagnosed EC patients ≤ 70 years. METHODS: Consecutive EC patients ≤ 70 years were included prospectively in eight Dutch centres. EC specimens were analysed for MSI, IHC of four MMR proteins, MMR gene methylation status and BRAF-mutations. tumours were classified as; 1) likely to be caused by LS, 2) sporadic MSI-H, or 3) microsatellite stable (MSS). RESULTS: Tumour specimens of 179 patients (median age 61 years, IQR 57-66) were analysed. In our study 92% of included patients were over 50 years of age. Eleven EC patients were found likely to have LS (6%; 95% CI 3-11%), including 1 patient suspected of an MLH1, 2 of an MSH2, 6 of an MSH6 and 2 of a PMS2 gene defect. Germline mutation analyses revealed 7 MMR gene germline mutations. Ten patients likely to have LS (92%) were older than 50 years. In addition, 31 sporadic MSI-H tumours with MLH1 promoter hypermethylation (17%; 95% CI 13-24%) were identified. CONCLUSIONS: Molecular screening for LS in patients with EC diagnosed ≤ 70 years, leads to identification of a profile likely to have LS in 6% of cases. New screening guidelines for LS are needed, including recommendations for EC patients older than 50 years of age.
Subject(s)
Colorectal Neoplasms, Hereditary Nonpolyposis/diagnosis , Endometrial Neoplasms/genetics , Endometrial Neoplasms/metabolism , Adenosine Triphosphatases/genetics , Aged , Carcinoma, Endometrioid/genetics , Carcinoma, Endometrioid/metabolism , Colorectal Neoplasms, Hereditary Nonpolyposis/genetics , Colorectal Neoplasms, Hereditary Nonpolyposis/metabolism , DNA Repair Enzymes/genetics , DNA-Binding Proteins/genetics , Female , Germ-Line Mutation , Humans , Immunohistochemistry , Microsatellite Instability , Middle Aged , Mismatch Repair Endonuclease PMS2 , Prospective Studies , Proto-Oncogene Proteins B-raf/geneticsABSTRACT
BACKGROUND: The objective of this study was to compare the cosmetic outcome of two different closing techniques for lower midline abdominal incisions: a continuous intracutaneous suture versus interrupted Donati stitches. METHODS: Eighty patients undergoing gynecological surgery through a lower midline abdominal incision were randomized. The cosmetic outcome of the scar was assessed by independent observers and the patients at 8 days and 4-6 months after the operation using visual analog scales and a validated scoring system for hypertrophy, width, color, and cross-hatching. Patients also completed a visual analog scale for postoperative pain on both occasions. The accumulated data were statistically evaluated using two-sided chi 2, Student's t, or Mann-Whitney tests with a confidence interval of 95%. RESULTS: Closing a lower midline abdominal laparotomy wound with an absorbable intracutaneous suture did not take more time than using Donati stitches. Laparotomy scores were only significantly better in the intracutaneous group at the first assessment, one week after the operation. The cosmetic visual analog scale scores by both independent observers and patients were slightly better in the intracutaneous group but the difference was not statistically significant. There was also no significant difference between visual analog scale scores for pain felt around the scar. CONCLUSIONS: This study shows that in the opinion of both independent observers and patients, scar cosmetics are not significantly different when using Donati skin sutures or an intracutaneous suture to close a lower midline laparotomy wound. The two methods do not differ either in time-consuming aspects or postoperative pain perception.
