No abstract

Microsatellite instability (MSI)‐mutator phenotype variably targets microsatellite‐like sequences in coding regions of cancer‐related genes. Intratumor histological heterogeneity of gastric carcinoma with MSI was evaluated and found to be linked with the topographical distribution of MSI‐associated mutations. One hundred fifty tumor sites derived from 51 gastric cancer patients were microdissected with respect to histological and topographical clonality. We found 11 gastric carcinomas with a high frequency of MSI, which were characterized by marked intratumor genetic heterogeneity arising from the progressive MSI‐phenotype that was associated with frameshift mutations on multiple cancer‐related genes. The 11 MSI‐tumor cases manifested the MSI‐phenotype in 34 of 36 tumor sites tested, but not in the remaining 2 sites. Most (88.2%, 30 of 34) MSI‐positive sites and most (96.2%, 25 of 26) tumor sites harboring the frameshift mutations in transforming growth factor‐β receptor type II gene exhibited intestinal‐type histology, whereas the 2 MSI‐negative sites were found to be of diffuse‐type histology without accompanying frameshift mutations. In 2 of 5 cases harboring E2F‐4 frameshift mutations, glandular structures of intestinal‐type tumor were likely to be variably differentiated in relation to the extent of the mutation, i.e., the number of mutated alleles and the size of deleted or inserted base pairs. Overall, the intratumor histological heterogeneity of gastric carcinoma with MSI was associated with the progressive frameshift mutations in transforming growth factor‐β receptor type II and E2F‐4 genes. Int. J. Cancer 82:782–788, 1999. © 1999 Wiley‐Liss, Inc.

We report a large study about cutaneous cGVHD in Asian patients. Cutaneous cGVHD presented with a wide spectrum of clinical and histological manifestations.

Background Limited data are available on the clinical impact of healthy lifestyle behaviors on the risk of dementia in patients with new‐onset atrial fibrillation (AF). Here, we aimed to evaluate the association between a combination of healthy lifestyle behaviors and the risk of incident dementia in patients with AF. Methods and Results Using the Korean National Health Insurance database between 2009 and 2016, we identified 199 952 adult patients who were newly diagnosed as AF without dementia. Patients were categorized into 4 groups by healthy lifestyle behavior score (HLS) with 1 point each being assigned for no current smoking, alcohol abstinence, and regular exercise. The HLS 0, 1, 2, and 3 groups included 4.4%, 17.4%, 53.4%, and 24.8% of the patients, respectively. We performed an inverse probability of treatment weighting to balance covariates between HLS groups. The HLS 1, 2, and 3 groups were associated with a lower risk of dementia compared with the HLS 0 group (hazard ratio [HR], 0.769; 95% CI, 0.704–0.842 for HLS 1; HR, 0.770; 95% CI, 0.709–0.836 for HLS 2; and HR, 0.622; 95% CI, 0.569–0.679 for HLS 3). The risk of dementia showed a tendency to decrease with an increase in HLS ( P ‐for‐trend <0.001). Conclusions A clustering of healthy lifestyle behaviors was associated with a significantly lower risk of dementia in patients with new‐onset AF. These findings support the promotion of a healthy lifestyle within an integrated care approach to AF patient management.

IMPORTANCEGuidelines recommend that all risk factors for early-onset atrial fibrillation, including lifestyle factors, be proactively managed, considering the poor prognosis of the disease. Not much is known about the association of cumulative alcohol intake with the risk of atrial fibrillation in young adults aged 20 to 39 years, especially among heavy drinkers. OBJECTIVETo explore the association of alcohol consumption with the risk of incident atrial fibrillation in young adults. DESIGN, SETTING, AND PARTICIPANTSUsing the National Health Insurance Service database, a nationwide population-based cohort study of adults aged 20 to 39 years without prior atrial fibrillation who underwent 4 serial annual health examinations between 2009 and 2012 was conducted. The cumulative alcohol consumption burden over 4 years was calculated by assigning 1 point to more than moderate drinking (Ն105 g of alcohol per week) each year. Additionally, a semiquantitative cumulative burden was calculated by assigning 0, 1, 2, and 3 points to non, mild (<105 g per week), moderate (105-210 g per week), and heavy (Ն210 g per week) drinking, respectively. Data were analyzed from May to June 2021. EXPOSURE Amount of alcohol intake in 4 years. MAIN OUTCOMES AND MEASURESThe primary outcome was incident atrial fibrillation during the follow-up period.RESULTS A total of 1 537 836 participants (mean [SD] age 29.5 [4.1] years, 1 100 099 [71.5%] male) were included in the final analysis. According to the 4-year cumulative burden of alcohol consumption stratified by moderate to heavy drinking, 889 382 participants (57.8%) were in the burden 0 group, 203 374 participants (13.2%) in the burden 1 group, 148 087 participants (9.6%) in the burden 2 group, 144 023 participants (9.4%) in the burden 3 group, and 152 970 participants (9.9%) in the burden 4 group. During a median (IQR) follow-up of 6.13 (4.59-6.48) years, atrial fibrillation was newly diagnosed in 3066 participants (0.36 per 1000 person-years). Participants with a cumulative burden of 4 points who continued more than moderate drinking for 4 years showed a 25% higher risk of atrial fibrillation compared with 0-point participants who kept non-tomild drinking over 4 years (adjusted HR, 1.25; 95% CI, 1.12-1.40). In a semiquantitative analysis, participants who sustained heavy drinking for 4 consecutive years were associated with a 47% higher atrial fibrillation risk than those who remained nondrinkers over 4 years (aHR, 1.47,. CONCLUSIONS AND RELEVANCEPersistent moderate to heavy drinking and higher cumulative alcohol consumption burden might increase the risk of atrial fibrillation even in young adults aged 20 to 39 years.