130 research outputs found
Factors Influencing Oncologic Outcomes after Tumor-specific Mesorectal Excision for Rectal Cancer
Risk factors of circumferential resection margin involvement in the patients with extraperitoneal rectal cancer
The Effects of Tai Chi in Centrally Obese Adults with Depression Symptoms
This study examined the effects of Tai Chi, a low-impact mind-body movement therapy, on severity of depression, anxiety, and stress symptoms in centrally obese people with elevated depression symptoms. In total, 213 participants were randomized to a 24-week Tai Chi intervention program or a wait-list control group. Assessments were conducted at baseline and 12 and 24 weeks. Outcomes were severity of depression, anxiety, and stress symptoms, leg strength, central obesity, and other measures of metabolic symptom. There were statistically significant between-group differences in favor of the Tai Chi group in depression (mean difference = −5.6 units, < 0.001), anxiety (−2.3 units, < 0.01), and stress (−3.6 units, < 0.001) symptom scores and leg strength (1.1 units, < 0.001) at 12 weeks. These changes were further improved or maintained in the Tai Chi group relative to the control group during the second 12 weeks of follow-up. Tai Chi appears to be beneficial for reducing severity of depression, anxiety, and stress and leg strength in centrally obese people with depression symptoms. More studies with longer follow-up are needed to confirm the findings. This trial is registered with ACTRN12613000010796
No difference in penetrance between truncating and missense/aberrant splicing pathogenic variants in mlh1 and msh2: A prospective lynch syndrome database study
Background. Lynch syndrome is the most common genetic predisposition for hereditary cancer. Carriers of pathogenic changes in mismatch repair (MMR) genes have an increased risk of developing colorectal (CRC), endometrial, ovarian, urinary tract, prostate, and other cancers, depending on which gene is malfunctioning. In Lynch syndrome, differences in cancer incidence (penetrance) according to the gene involved have led to the stratification of cancer surveillance. By contrast, any differences in penetrance determined by the type of pathogenic variant remain unknown. Objective. To determine cumulative incidences of cancer in carriers of truncating and missense or aberrant splicing pathogenic variants of the MLH1 and MSH2 genes. Methods. Carriers of pathogenic variants of MLH1 (path_MLH1) and MSH2 (path_MSH2) genes filed in the Prospective Lynch Syndrome Database (PLSD) were categorized as truncating or missense/aberrant splicing according to the InSiGHT criteria for pathogenicity. Results. Among 5199 carriers, 1045 had missense or aberrant splicing variants, and 3930 had truncating variants. Prospective observation years for the two groups were 8205 and 34,141 years, respectively, after which there were no significant differences in incidences for cancer overall or for colorectal cancer or endometrial cancers separately. Conclusion. Truncating and missense or aberrant splicing pathogenic variants were associated with similar average cumulative incidences of cancer in carriers of path MLH1 and path_MSH2.Fil: Dominguez Valentin, Mev. St Mark’s Hospital; Reino Unido. The Norwegian Radium Hospital; Noruega. European Hereditary Tumour Group; Reino UnidoFil: Plazzer, John Paul. St Mark’s Hospital; Reino Unido. The Royal Melbourne Hospital; AustraliaFil: Sampson, Julian R.. European Hereditary Tumour Group; Reino Unido. Cardiff University; Reino UnidoFil: Engel, Christoph. European Hereditary Tumour Group; Reino Unido. Universitat Leipzig; AlemaniaFil: Aretz, Stefan. Universitat Bonn; AlemaniaFil: Jenkins, Mark A.. University of Melbourne; AustraliaFil: Sunde, Lone. Aalborg University; DinamarcaFil: Bernstein, Inge. Aalborg University; DinamarcaFil: Capella, Gabriel. European Hereditary Tumour Group; Reino Unido. St Mark’s Hospital; Reino Unido. Institut Català d’Oncologia; EspañaFil: Balaguer Prunés, Francesc. Universidad de Barcelona; EspañaFil: Macrae, Finlay. European Hereditary Tumour Group; Reino Unido. The Royal Melbourne Hospital; AustraliaFil: Winship, Ingrid M.. University of Melbourne; AustraliaFil: Thomas, Huw. Imperial College London; Reino UnidoFil: Evans, Dafydd Gareth. University of Manchester; Reino UnidoFil: Burn, John. Universidad de Newcastle; Australia. The Royal Melbourne Hospital; Australia. St Mark’s Hospital; Reino UnidoFil: Greenblatt, Marc. University of Vermont; Estados UnidosFil: de Vos tot Nederveen Cappel, Wouter H.. Isala Clinics; Países BajosFil: Sijmons, Rolf H.. University of Groningen; Países Bajos. St Mark’s Hospital; Reino Unido. European Hereditary Tumour Group; Reino UnidoFil: Nielsen, Maartje. Leids Universitair Medisch Centrum; Países BajosFil: Bertario, Lucio. Fondazione IRCCS Istituto Nazionale dei Tumori; ItaliaFil: Bonanni, Bernardo. Fondazione IRCCS Istituto Nazionale dei Tumori; ItaliaFil: Tibiletti, Maria Grazia. Università dell’Insubria; ItaliaFil: Cavestro, Giulia Martina. Vita-Salute San Raffaele University; ItaliaFil: Lindblom, Annika. Karolinska Huddinge Hospital; SueciaFil: Della Valle, Adriana. Hospital Fuerzas Armadas; UruguayFil: Lopez Kostner, Francisco. Clínica Universidad de los Andes; ChileFil: Alvarez, Karin. Clínica Universidad de los Andes; ChileFil: Gluck, Nathan. Universitat Tel Aviv; IsraelFil: Katz, Lior. Sheba Medical Center; IsraelFil: Heinimann, Karl. University Hospital Basel; SuizaFil: Piñero, Tamara Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional e Ingeniería Biomédica - Hospital Italiano. Instituto de Medicina Traslacional e Ingeniería Biomédica.- Instituto Universitario Hospital Italiano de Buenos Aires. Instituto de Medicina Traslacional e Ingeniería Biomédica; ArgentinaFil: Pavicic, Walter Hernan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional e Ingeniería Biomédica - Hospital Italiano. Instituto de Medicina Traslacional e Ingeniería Biomédica.- Instituto Universitario Hospital Italiano de Buenos Aires. Instituto de Medicina Traslacional e Ingeniería Biomédica; Argentin
Cancer risks by gene, age, and gender in 6350 carriers of pathogenic mismatch repair variants: findings from the Prospective Lynch Syndrome Database
Lynch syndrome (LS) results from pathogenic variants in the mismatch repair (MMR) genes and is the most common hereditary cancer syndrome, affecting an estimated 1 in 300 individuals. Pathogenic variants in each of the MMR genes path_MLH1, path_MSH2, path_MSH6, and path_PMS2 result in different risks for cancers in organs including the colorectum, endometrium, ovaries, stomach, small bowel, bile duct, pancreas, and upper urinary tract. Accurate estimates of these risks are essential for planning appropriate approaches to the prevention or early diagnosis of cancers but the robustness of previous studies has been limited by factors including retrospective design,1,2 lack of validation in independent cohorts,3-5 and inconsistent classification of genetic variants. Unexpected findings from previous studies have included path_MLH1 and path_MSH2 carriers appearing to have a lifetime risk of colorectal cancer (CRC) of approximately 50%, despite surveillance colonoscopy,6-8 and that shorter intervals between colonoscopies do not seem to reduce the incidence of CRC in LS.9,10 These findings challenge the assumptions that CRC in LS usually develops from a noninfiltrative adenoma precursor and that CRC can be prevented by colonoscopic detection and removal of adenomas in the colon and rectum. Additionally, previous studies in the Prospective Lynch Syndrome Database (PLSD) have shown no increase in cancer risk in path_PMS2 carriers before 40 years of age and, although observation years were limited in older path_PMS2 carriers, LS-associated cancers other than endometrial and prostate were not observed.6-8 In this study we collected prospective data from a new large cohort of path_MMR carriers to validate previous findings from PLSD. We also updated information on the original cohort to ensure consistent classification of pathogenicity of MMR gene variants. We then combined both data sets, providing larger numbers that allowed us to derive more precise risk estimates for cancers in LS categorized by gene and gender
No Difference in Penetrance between Truncating and Missense/Aberrant Splicing Pathogenic Variants in MLH1 and MSH2:A Prospective Lynch Syndrome Database Study
Background. Lynch syndrome is the most common genetic predisposition for hereditary cancer. Carriers of pathogenic changes in mismatch repair (MMR) genes have an increased risk of developing colorectal (CRC), endometrial, ovarian, urinary tract, prostate, and other cancers, depending on which gene is malfunctioning. In Lynch syndrome, differences in cancer incidence (penetrance) according to the gene involved have led to the stratification of cancer surveillance. By contrast, any differences in penetrance determined by the type of pathogenic variant remain unknown. Objective. To determine cumulative incidences of cancer in carriers of truncating and missense or aberrant splicing pathogenic variants of the MLH1 and MSH2 genes. Methods. Carriers of pathogenic variants of MLH1 (path_MLH1) and MSH2 (path_MSH2) genes filed in the Prospective Lynch Syndrome Database (PLSD) were categorized as truncating or missense/aberrant splicing according to the InSiGHT criteria for pathogenicity. Results. Among 5199 carriers, 1045 had missense or aberrant splicing variants, and 3930 had truncating variants. Prospective observation years for the two groups were 8205 and 34,141 years, respectively, after which there were no significant differences in incidences for cancer overall or for colorectal cancer or endometrial cancers separately. Conclusion. Truncating and missense or aberrant splicing pathogenic variants were associated with similar average cumulative incidences of cancer in carriers of path MLH1 and path_MSH2
Cancer risks by gene, age, and gender in 6350 carriers of pathogenic mismatch repair variants:findings from the Prospective Lynch Syndrome Database
Purpose Pathogenic variants affecting MLH1, MSH2, MSH6, and PMS2 cause Lynch syndrome and result in different but imprecisely known cancer risks. This study aimed to provide age and organ-specific 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 follow-up 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
Radical Resection After IORT-Containing Multimodality Treatment is the Most Important Determinant for Outcome in Patients Treated for Locally Recurrent Rectal Cancer
No Difference in Penetrance between Truncating and Missense/Aberrant Splicing Pathogenic Variants in MLH1 and MSH2: A Prospective Lynch Syndrome Database Study
Background. Lynch syndrome is the most common genetic predisposition for hereditary cancer. Carriers of pathogenic changes in mismatch repair (MMR) genes have an increased risk of developing colorectal (CRC), endometrial, ovarian, urinary tract, prostate, and other cancers, depending on which gene is malfunctioning. In Lynch syndrome, differences in cancer incidence (penetrance) according to the gene involved have led to the stratification of cancer surveillance. By contrast, any differences in penetrance determined by the type of pathogenic variant remain unknown. Objective. To determine cumulative incidences of cancer in carriers of truncating and missense or aberrant splicing pathogenic variants of the MLH1 and MSH2 genes. Methods. Carriers of pathogenic variants of MLH1 (path_MLH1) and MSH2 (path_MSH2) genes filed in the Prospective Lynch Syndrome Database (PLSD) were categorized as truncating or missense/aberrant splicing according to the InSiGHT criteria for pathogenicity. Results. Among 5199 carriers, 1045 had missense or aberrant splicing variants, and 3930 had truncating variants. Prospective observation years for the two groups were 8205 and 34,141 years, respectively, after which there were no significant differences in incidences for cancer overall or for colorectal cancer or endometrial cancers separately. Conclusion. Truncating and missense or aberrant splicing pathogenic variants were associated with similar average cumulative incidences of cancer in carriers of path MLH1 and path_MSH2
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