Value of ctDNA methylation biomarkers in diagnosis of colorectal tumors.

Tweetable abstract DNA methylation alterations have been identified as promising biological markers for early-stage colorectal cancer detection. Here, the authors highlight some recent advances in DNA methylation and its role in the early diagnosis and overall disease course management of colorectal tumors. New insights into DNA methylation biomarkers for colorectal cancer early diagnosis and management are discussed.

Screening and validation of a novel T stage-lymph node ratio classification for operable colon cancer.

BACKGROUND: Lymph node ratio (LNR) has advantages in predicting prognosis compared with American Joint Committee on Cancer (AJCC) pathological N stage. However, the prognostic value of a novel T stage-lymph node ratio (TLNR) classification for colon cancer combining LNR and pathological primary tumor stage (T stage) is currently unknown. METHODS: We included 62,294 patients with stage I-III colon cancer from the Surveillance, Epidemiology, and End Results Program as a training cohort. External validation was performed in 3,327 additional patients. A novel LNR stage was established and combined with T stage in a novel TLNR classification. Patients with similar survival were grouped according to T and LNR stages, with T1LNR1 as a reference. RESULTS: We developed a novel TLNR classification as follows: stages I (T1LNR1-2, T1LNR4), IIA (T1LNR3, T2LNR1-2, T3LNR1), IIB (T1LNR5, T2LNR3-4, T3LNR2, T4aLNR1), IIC (T2LNR5, T3LNR3-4, T4aLNR2, T4bLNR1), IIIA (T3LNR5, T4aLNR3-4, T4bLNR2), IIIB (T4aLNR5, T4bLNR3-4), and IIIC (T4bLNR5). In the training cohort, the novel TLNR classification had better prognostic discrimination (area under receiver operating characteristic curve, 0.621 vs. 0.608, two-sided P<0.001), superior model-fitting ability for predicting overall survival (Akaike information criteria, 561,129 vs. 562,052), and better net benefits compared with the AJCC 8th tumor/node/metastasis classification. Similar results were found in the validation cohort for predicting both overall and disease-free survival. CONCLUSIONS: This novel TLNR classification may provide better prognostic discrimination, model-fitting ability, and net benefits than the AJCC 8th TNM classification, for potentially better stratification of patients with operable stage I-III colon cancer; however, further studies are required to validate the novel TLNR classification.

Harvest of at least 18 lymph nodes is associated with improved survival in patients with pN0 colon cancer: a retrospective cohort study.

PURPOSE: To investigate the correlation between number of retrieved lymph nodes (rLNs) and prognosis and further ascertain the optimal number of rLNs with a beneficial survival impact in patients with pN0 colon cancer. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was searched for pN0 colon cancer cases. X-Tile software and Kaplan-Meier survival analysis were applied to determine the optimal number of rLNs based on the minimal probability (P) value and the largest χ2 value. Univariate analyses and Cox proportional hazard regression model were used to investigate the relationship between rLN number and overall survival. Multiple analyses were conducted to assess the prognostic predictive ability of the identified optimal rLN cut-off value under different stratifications. Nomograms were established based on the independent prognostic factors selected by the multivariate analysis to predict 3- and 5-year overall survival rates of pN0 patients. RESULTS: A total of 6269 pN0 colon cancer patients who underwent surgical therapy were finally included for analysis. Harvest of at least 18 lymph nodes was determined as the optimal rLN number. This cut-off rLN value (< 18 versus ≥ 18) was identified as an independent prognostic factor (P < 0.001) of overall survival via multivariate analysis. Similar findings were obtained in patients with retrieval of at least 12 lymph nodes (18 > rLNs ≥ 12 versus rLNs ≥ 18) stratified into several groups. CONCLUSIONS: The number of rLNs was identified as an independent prognostic factor for pN0 colon cancer. Retrieval of at least 18 lymph nodes was associated with favorable prognosis in patients with pN0 colon cancer, and should, therefore, be regarded as an alternative cut-off value for survival analysis.

Survival benefits of metformin for colorectal cancer patients with diabetes: a systematic review and meta-analysis.

BACKGROUND: Several studies suggest that metformin has the potential effect of reducing cancer risk. However, its survival benefit in patients with colorectal cancer (CRC) and diabetes is unknown. The aim of our study is to address the effect of metformin on outcomes for CRC based on a systematic review and meta-analysis. METHODS AND FINDINGS: We searched EMBASE and MEDLINE databases from inception through August, 2013, using search terms related to metformin, diabetes, colorectal cancer, and prognostic outcome. The outcome measures were hazard ratios (HRs) with 95% CIs comparing CRC survival in diabetic patients using metformin and without using metformin. The primary end points were overall survival (OS) and CRC specific survival (CS). A total of six cohort studies including 2,461 patients met full eligibility criteria. The pooled HR favoring metformin users was 0.56 for OS (95% CI, 0.41 to 0.77) and 0.66 for CRC-specific survival (95% CI, 0.50 to 0.87). Thus metformin therapy reduced the risk of all cause of death by 44% and the risk of CRC specific death by 34% in CRC patients compared to those in non-users. However, evidence of heterogeneity and possible publication bias was noted for OS. CONCLUSIONS: Patients with CRC and diabetes treated with metformin appear to have an improved survival outcome. Prospective study should be warranted to examine the association between metformin exposure intensity as well as some other confounding variables and survival outcome in diabetic CRC patients.

[Integrity evaluation of resected mesentery specimen after total mesorectal excision by methylene blue perfusion via superior rectal artery].

OBJECTIVE: To evaluate the integrity of the resected mesentery specimen after total mesorectal excision (TME) for low rectal cancer using methylene blue perfusion via the superior rectal artery. METHODS: Twenty patients with low rectal cancer were randomly divided into the methylene blue group (n=10) and the control group (n=10). All the patients received TME and macroscopic examination of the mesorectal surface was performed to evaluate the quality of the surgical specimen. The methylene blue was injected into the specimen postoperatively via superior rectal artery. RESULTS: The mesorectal surface of all the specimens was intact on macroscopic examination. However, after methylene blue perfusion, 2 specimens were found to be incomplete. The number of lymph nodes in the methylene blue group were significantly larger (17.3+/-2.4 vs 12.4+/-5.4, P=0.016). CONCLUSIONS: Integrity evaluation of TME specimen is necessary. Methylene blue perfusion is a convenient and effective method to identify subtle incompleteness of specimen and can improve the detection of lymph node.