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Sean C. Skeldon Kara Semotiuk Melyssa Aronson Spring Holter Steven Gallinger Aaron Pollett Cynthia Kuk Bas van Rhijn Peter Bostrom Zane Cohen Neil E. Fleshner Michael A. Jewett Sally Hanna Shahrokh F. Shariat Theodorus H. Van Der Kwast Andrew Evans Jim Catto Bharati Bapat Alexandre R. Zlotta 《European urology》2013
Background
Lynch syndrome (LS), or hereditary nonpolyposis colorectal cancer, is caused by mutations in mismatch repair (MMR) genes. An increased risk for upper tract urothelial carcinoma (UTUC) has been described in this population; however, data regarding the risk for bladder cancer (BCa) are sparse.Objective
To assess the risk of BCa in MMR mutation carriers and suggest screening and management recommendations.Design, setting, and participants
Cancer data from 1980 to 2007 were obtained from the Familial Gastrointestinal Cancer Registry in Toronto for 321 persons with known MMR mutations: mutL homolog 1, colon cancer, nonpolyposis type 2 (E. coli) (MLH1); mutS homolog 2, colon cancer, nonpolyposis type 1 (E. coli) (MSH2); mutS homolog 6 (E. coli) (MSH6); and PMS2 postmeiotic segregation increased 2 (S. cerevisiae) (PMS2).Outcome measurements and statistical analysis
Standardized incidence ratios from the Ontario Cancer Registry, using the Surveillance Epidemiology and End Results public database, were used to compare cancer risk in patients with MMR mutations with the Canadian population. Microsatellite instability analysis and immunohistochemistry (IHC) of the MMR proteins were also performed and the results compared with matched sporadic bladder tumors.Results and limitations
Eleven of 177 patients with MSH2 mutations (6.21%, p < 0.001 compared with the Canadian population) were found to have BCa, compared with 3 of 129 patients with MLH1 mutations (2.32%, p > 0.05). Of these 11 tumors, 81.8% lacked expression of MSH2 on IHC, compared with the matched sporadic cases, which all displayed normal expression of MSH2 and MLH1. The incidence of UTUC among MSH2 carriers was 3.95% (p < 0.001), and all tumors were found to be deficient in MSH2 expression on IHC. Mutations in the intron 5 splice site and exon 7 of the MSH2 gene increased the risk of urothelial cancer. Limitations include possible inflated risk estimates due to ascertainment bias.Conclusions
LS patients with MSH2 mutations are at an increased risk for not only UTUC but also BCa and could be offered appropriate screening. 相似文献68.
Anne Lübbeke Axel Finckh Gabor J. Puskas Domizio Suva Alexandre Lädermann Sylvette Bas Daniel Fritschy Cem Gabay Pierre Hoffmeyer 《International orthopaedics》2013,37(10):2071-2079
Purpose
We evaluated whether synovial fluid (SF) leptin concentrations correlate with pain severity in patients with hip or knee endstage osteoarthritis (OA) and whether they mediate the association between increased joint pain and (1) female gender and (2) obesity.Methods
We conducted a cross-sectional study including patients with primary hip and knee OA undergoing joint replacement between January and December 2010. SF leptin concentrations obtained on the day of surgery were assessed. Main outcome was pain severity measured pre-operatively using WOMAC and VAS pain scales.Results
A total of 219 patients were included, 123 hip and 96 knee arthroplasties. Mean age was 72 years, 59 % were women. Mean SF leptin levels were 22.9 (±25.6) ng/ml in women and 5.4 (±5.9) ng/ml in men. Levels >19.6 ng/ml (highest quartile) were significantly associated with increased pain on both WOMAC (mean difference −9.6, 95 % CI −15.1 to −4.0) and VAS scale (mean difference 0.8, 95 % CI 0.2–1.3). Associations remained unchanged after adjusting for age, co-morbidities, contra-lateral arthritic joint, OA site, and disability. The associations observed between increased pain and female gender or obesity were substantially reduced after adjusting for SF leptin.Conclusion
Joint pain is associated with SF leptin concentrations. Increased pre-operative pain observed in women and obese may be related to high intra-articular leptin levels. 相似文献69.
Bas B. Koolen MD Renato A. Valdés Olmos MD PhD Jelle Wesseling MD PhD Wouter V. Vogel MD PhD Andrew D. Vincent PhD Kenneth G. A. Gilhuijs PhD Sjoerd Rodenhuis MD PhD Emiel J. Th. Rutgers MD PhD Marie-Jeanne T. F. D. Vrancken Peeters MD PhD 《Annals of surgical oncology》2013,20(7):2227-2235
Background
If all initially node-positive patients undergo axillary lymph node dissection (ALND) after neoadjuvant chemotherapy (NAC), overtreatment may occur in patients with complete response. Positron emission tomography–computed tomography (PET/CT) during NAC may predict axillary response and select patients appropriate for less invasive treatment after NAC. We evaluated the value of sequential 18F fluorodeoxyglucose (FDG) PET/CTs during NAC for axillary response monitoring in stage II–III breast cancer.Methods
A total of 219 PET/CTs were performed in 80 patients with cytology-proven, node-positive disease at baseline (PET/CT1, n = 80) and twice during NAC (PET/CT2 n = 62, PET/CT3, n = 77). The relative changes in maximum standardized uptake value (SUVmax) of axillary nodes were examined for their ability to assess pathological response. All patients underwent ALND after chemotherapy, and complete axillary response (pCR), defined as absence of isolated tumor cells and of micro- and macrometastases, served as the reference standard.Results
A total of 32 (40 %) patients experienced axillary pCR. The relative decrease in SUVmax was significantly higher in patients with pCR than in those without, both on PET/CT2 (p < 0.001) and PET/CT3 (p = 0.025). The area under the receiver operating characteristic curve values for PET/CT2 and PET/CT3 were 0.80 (95 % confidence interval 0.68–0.92) and 0.65 (95 % confidence interval 0.52–0.79), respectively. A relative decrease of ≥60 % on PET/CT2 had an excellent specificity (35 of 37, 95 %), a high positive predictive value (12 of 14, 86 %), and a sensitivity of 48 %—that is, it accurately identified histologic pCR in 12 of 25 patients with disease that responded to therapy.Conclusions
18F-FDG PET/CT early during NAC is useful for axillary response monitoring in cytology-proven node-positive breast cancer because it identifies pathological response, thus permitting ALND to be spared. 相似文献70.