infection and a family history of gastric cancer are the main risk factors for gastric cancer. Whether treatment to eradicate
can reduce the risk of gastric cancer in persons with a family history of ...gastric cancer in first-degree relatives is unknown.
In this single-center, double-blind, placebo-controlled trial, we screened 3100 first-degree relatives of patients with gastric cancer. We randomly assigned 1838 participants with
infection to receive either eradication therapy (lansoprazole 30 mg, amoxicillin 1000 mg, and clarithromycin 500 mg, each taken twice daily for 7 days) or placebo. The primary outcome was development of gastric cancer. A prespecified secondary outcome was development of gastric cancer according to
eradication status, assessed during the follow-up period.
A total of 1676 participants were included in the modified intention-to-treat population for the analysis of the primary outcome (832 in the treatment group and 844 in the placebo group). During a median follow-up of 9.2 years, gastric cancer developed in 10 participants (1.2%) in the treatment group and in 23 (2.7%) in the placebo group (hazard ratio, 0.45; 95% confidence interval CI, 0.21 to 0.94; P = 0.03 by log-rank test). Among the 10 participants in the treatment group in whom gastric cancer developed, 5 (50.0%) had persistent
infection. Gastric cancer developed in 0.8% of participants (5 of 608) in whom
infection was eradicated and in 2.9% of participants (28 of 979) who had persistent infection (hazard ratio, 0.27; 95% CI, 0.10 to 0.70). Adverse events were mild and were more common in the treatment group than in the placebo group (53.0% vs. 19.1%; P<0.001).
Among persons with
infection who had a family history of gastric cancer in first-degree relatives,
eradication treatment reduced the risk of gastric cancer. (Funded by the National Cancer Center, South Korea; ClinicalTrials.gov number, NCT01678027.).
Circulating tumor DNA (ctDNA) has emerged as a candidate biomarker for cancer screening. However, studies on the usefulness of ctDNA for postoperative recurrence monitoring are limited. The present ...study monitored ctDNA in postoperative blood by employing cancer-specific rearrangements. Personalized cancer-specific rearrangements in 25 gastric cancers were analyzed by whole-genome sequencing (WGS) and were employed for ctDNA monitoring with blood up to 12 months after surgery. Personalized cancer-specific rearrangements were identified in 19 samples. The median lead time, which is the median duration between a positive ctDNA detection and recurrence, was 4.05 months. The presence of postoperative ctDNA prior to clinical recurrence was significantly correlated with cancer recurrence within 12 months of surgery (P = 0.029); in contrast, no correlation was found between cancer recurrence and the presence of preoperative ctDNA, suggesting the clinical usefulness of postoperative ctDNA monitoring for cancer recurrence in gastric cancer patients. However, the clinical application of ctDNA can be limited by the presence of ctDNA non-shedders (42.1%, 8/19) and by inconsistent postoperative ctDNA positivity.
To assess the prognostic roles of BAP1, PBRM1, pS6, PTEN, TGase2, PD-L1, CA9, PSMA, and Ki-67 tissue biomarkers in localized renal cell carcinoma (RCC).
Patients who underwent a nephrectomy during ...1992-2015 and had a primary specimen of their kidney tumor were included. The nine tissue biomarkers were immunohistochemically stained on tissue microarrays of RCC, and the semi-quantitative H-score, including intensity score, was used to grade the sample. The Cox proportional hazards model was used to evaluate tissue markers significant for overall survival (OS), cancer-specific survival (CSS), and recurrence-free survival (RFS) after adjusting for significant clinicopathological parameters.
Samples from 351 RCC patients were included. The mean age of the patients was 53.9 years; the rates of pathologic T1-2/≥T3 stage, Fuhrman 1+2/3+4 grade, recurrence, and death were 269/65(80.5/19.5%), 222/107 (67.5/32.5%), 6.6%, and 10.5%, respectively. Median OS, CSS, and RFS were 220.6, 220.6, and 147.1 months, respectively. The multivariable analysis showed that pathologic T stage and Fuhrman nuclear grade were significantly associated with OS and CSS. Pathologic T stage and tumor size were associated with RFS. After adjusting for these significant prognostic clinicopathological factors, Ki-67 was significantly associated with OS (hazard ratio HR, 2.7), CSS (HR, 3.82), and RFS (HR, 4.85) and pS6 was associated with CSS (HR, 8.63) and RFS (HR, 8.51) in the multivariable model (p<0.05).
pS6 and Ki-67 are significant prognostic factors of RCC; however, BAP1, PBRM1, TGase 2, PD-L1, CA9, PTEN loss, and PSMA markers did not show this association.
Integration of human papillomavirus (HPV) DNA into the host genome is a critical aetiological event in the progression from normal cervix to intraepithelial neoplasm, and finally to invasive cervical ...cancer. However, there has been little work on how HPV integration status relates to treatment outcome for cervical carcinomas. In the current study, HPV E2 and E6 gene copy numbers were measured in 111 cervical cancer tissues using real-time QPCR. Integration patterns were divided into four groups: single copy-integrated with episomal components (group 1), single copy-integrated without episomal components (group 2), multicopy tandem repetition-integrated (group 3), and low HPV (group 4) groups. A relapse-predicting model was constructed using multivariable Cox proportional hazards model to classify patients into different risk groups for disease-free survival (DFS). The model was internally validated using bootstrap resampling. Oligonucleotide microarray analysis was performed to evaluate gene expression patterns in relation to the different integration groups. DFS rate was inferior in the order of the patients in group 4, group 2/3, and group 1. Multivariate analysis showed that histologic grade, clinical stage group, and integration pattern were significant prognostic factors for poor DFS. The current prognostic model accurately predicted the risk of relapse, with an area under the receiver operating characteristic curve (AUC) of 0.74 (bootstrap corrected, 0.71). In conclusion, these data suggest that HPV integration pattern is a potent prognostic factor for tailored treatment of cervical cancer.
To investigate the predictive factors for lateral pelvic lymph node (LPLN) metastasis in patients with locally advanced rectal cancer treated with preoperative chemoradiotherapy (CRT).
Fifty-seven ...patients with locally advanced rectal cancer and LPLNs larger than 5 mm underwent LPLN dissection (LPLD) after preoperative CRT. The MRI findings, including the apparent diffusion coefficient value and LPLN size reduction rate before/after CRT; clinical factors; and pathologic results were evaluated to identify the predictive factors associated with LPLN metastasis.
LPLN metastasis was confirmed in 23 patients (40.4%). Metastasis was significantly higher in LPLNs with multiplicity, short-axis diameter ≥8 mm before CRT, short-axis diameter >5 mm after CRT, size reduction rate ≤33.3%, heterogeneous signal intensity, and irregular margin (P<0.05) on MR. Multivariable analysis showed that pre-CRT short-axis diameter of LPLNs ≥8 mm, size reduction rate ≤33.3%, and heterogeneous signal intensity were independently associated with LPLN metastasis.
The size and signal intensity of LPLN before and after CRT are useful MRI findings to predict LPLN metastasis and are helpful to determine the indications for LPLD.
Heart failure (HF) is a complex clinical syndrome with persistently high mortality. High-throughput proteomic technologies offer new opportunities to improve HF risk stratification, but their ...contribution remains to be clearly defined. We aimed to systematically review prognostic studies using high-throughput proteomics to identify protein signatures associated with HF mortality.
We searched four databases and two clinical trial registries for articles published from 2012 to 2023. HF proteomics studies measuring high numbers of proteins using aptamer or antibody-based affinity platforms on human plasma or serum with outcomes of all-cause or cardiovascular death were included. Two reviewers independently screened articles, extracted data, and assessed the risk of bias. A third reviewer resolved conflicts. We assessed the risk of bias using the Risk Of Bias In Non-randomized Studies-of Exposure tool.
Out of 5131 unique articles identified, nine articles were included in the review. The nine studies were observational; three used the aptamer platform, and six used the antibody platform. We found considerable heterogeneity across studies in measurement panels, HF definitions, ejection fraction categorization, follow-up duration, and outcome definitions, and a lack of risk estimates for most protein associations. Hence, we proceeded with a systematic review rather than a meta-analysis. In two comparable aptamer studies in patients with HF with reduced ejection fraction, 21 proteins were identified in common for the association with all-cause death. Among these, one protein, WAP four-disulfide core domain protein 2 was also reported in an antibody study on HFrEF and for the association with CV death. We proposed standardized reporting criteria to facilitate the interpretation of future studies.
In this systematic review of nine studies evaluating the association of proteomics with mortality in HF, we identified a limited number of proteins common across several studies. Heterogeneity across studies compromised drawing broad inferences, underscoring the importance of standardized approaches to reporting.
Background Extended lymph node dissection in gastric cancer (D3) was proven to have no survival benefit compared with a D2 dissection, but whether adding the superior mesenteric nodes (No. 14v) to ...the dissection provides survival benefit for gastric cancer patients remains controversial. Methods From April 2001 to June 2007, 1,661 patients underwent curative resection for middle or lower third gastric cancer. Patients were grouped according to No. 14v lymphadenectomy (14vD+/14vD-). Clinicopathologic characteristics and treatment-related factors were compared between the groups. Overall survival according to the clinical stage (Union for International Cancer Control tumor–node–metastasis staging 6th edition) was analyzed using the Cox proportional hazard model. Results The incidence of No. 14v lymph node metastasis was 5.0%. There was no difference in morbidity or mortality between the 14vD+ and the 14vD- groups. The proportion of locoregional recurrence was greater in 14vD- group ( P = .018). In clinical stages I and II, 14v lymph node dissection did not affect overall survival; in contrast, 14v lymph node dissection was an independent prognostic factor in patients with clinical stage III/IV gastric cancer (hazard ratio, 0.58; 95% confidence interval, 0.38–0.88; P = .01). Conclusion Extended D2 gastrectomy including No. 14v lymph node dissection seems to be associated with improved overall survival of patients with clinical stage III/IV gastric cancer in the middle or lower third of the stomach.
To evaluate predictive factors for retrograde ureteral stent failure in patients with non-urological malignant ureteral obstruction.
Between 2005 and 2014, medical records of 284 malignant ureteral ...obstruction patients with 712 retrograde ureteral stent trials including 63 (22.2%) having bilateral malignant ureteral obstruction were retrospectively reviewed. Retrograde ureteral stent failure was defined as the inability to place ureteral stents by cystoscopy, recurrent stent obstruction within one month, or non-relief of azotemia within one week from the prior retrograde ureteral stent. The clinicopathological parameters and first retrograde pyelographic findings were analyzed to investigate the predictive factors for retrograde ureteral stent failure and conversion to percutaneous nephrostomy in multivariate analysis with a statistical significance of p < 0.05.
Retrograde ureteral stent failure was detected in 14.1% of patients. The mean number of retrograde ureteral stent placements and indwelling duration of the ureteral stents were 2.5 ± 2.6 times and 8.6 ± 4.0 months, respectively. Multivariate analyses identified several specific RGP findings as significant predictive factors for retrograde ureteral stent failure (p < 0.05). The significant retrograde pyelographic findings included grade 4 hydronephrosis (hazard ratio 4.10, 95% confidence interval 1.39-12.09), irreversible ureteral kinking (hazard ratio 2.72, confidence interval 1.03-7.18), presence of bladder invasion (hazard ratio 4.78, confidence interval 1.81-12.63), and multiple lesions of ureteral stricture (hazard ratio 3.46, confidence interval 1.35-8.83) (p < 0.05).
Retrograde pyelography might prevent unnecessary and ineffective retrograde ureteral stent trials in patients with advanced non-urological malignant ureteral obstruction.
Abstract Objective To evaluate the impact of lower limb lymphedema (LLL) on quality of life (QOL) in cervical, ovarian, and endometrial cancer survivors after pelvic lymph node dissection. Study ...design A cross-sectional case-control study was performed using the Korean version of the Gynecologic Cancer Lymphedema Questionnaire (GCLQ-K) and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30). In total, 25 women with LLL and 28 women without LLL completed both questionnaires. Results The GCLQ-K total symptom score and scores for swelling-general, swelling-limb, and heaviness were significantly higher in the LLL group than in the control group. In the EORTC QLQ-C30, the LLL group reported more financial difficulties compared to the control group (mean score, 16.0 vs. 6.0; P = 0.035). Global health status was poorer in the LLL group with borderline statistical significance (mean score, 62.7 vs. 71.4; P = 0.069). Spearman's correlations suggested that global health status in the EORTC QLQ-C30 correlated with the GCLQ-K total symptom score (in the LLL group, R = −0.64, P = 0.001; in the control group, R = −0.42, P = 0.027). Conclusions QOL decreases due to LLL-related symptoms and financial difficulty in women with LLL. Well-designed prospective studies are required to confirm these findings.
The prognostic significance of inherited genetic variants in advanced-stage non-small cell lung cancer (NSCLC) patients remains unknown. In this study, we genotyped 271 817 single-nucleotide ...polymorphisms in 348 advanced NSCLC patients who received chemotherapy and analyzed their association with prognosis by using Cox proportional hazard regression model adjusted for known prognostic factors. Top candidate single-nucleotide polymorphisms (SNPs) were selected using the bootstrap re-sampling procedure. Median age of patient population was 56 years. Proportions of female, never smokers and adenocarcinoma were 64.9, 67.5 and 80.4%, respectively. We identified 17 top candidate SNPs related to prognosis using cut-off minimum P value of <5.0 × 10(-5) in at least 70% of 1000 bootstrap samples. These SNPs were located in the genomic regions of the FAM154A, ANKS1A, DLST, THSD7B, NCOA2, CDH8, SLC35D2, NALCN and EGF genes. The most significant SNP, rs1571228 (9p22.1:FAM154A), was significantly associated with overall survival in dominant model AG+GG to AA, hazard ratio (HR) of death (95% CI) = 0.53 (0.42-0.67); P = 2.025 × 10(-7). The SNP at 4q25:EGF, rs11098063, for which some genetic variations was previously reported to be associated with prognosis, also showed significant association with overall survival in additive model CC versus CT versus TT, HR (95% CI) = 1.00 versus 0.61 (0.47-0.78) versus 0.39 (0.19-0.79); P = 9.582 × 10(-6). Survival differences according to the genotype of these SNPs were independent of sex, smoking, histology and chemotherapy regimens. These results suggested the variants at multiple genetic loci might contribute to the risk of death in advanced NSCLC patients receiving chemotherapy.
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