The deficiency of 5-methylcytosine (5mC) and its ramification in the occurrence and prognosis of colon cancer.

The incidence and mortality of colon cancer are increasing, and effective biomarkers for its diagnosis are limited. 5-methylcytosine (5mC), a vital DNA methylation marker, plays important roles in gene expression, genomic imprinting, and transposon inhibition. This study aimed to identify the predictors of colon cancer prognosis and lay the foundation for research on therapeutic targets by detecting the levels of 5mC, 5-hydroxymethylcytosine (5hmC), 5-formyl cytosine (5fC), and 5-carboxylcytosine (5caC) in colon cancer and adjacent non-tumor tissues. A tissue microarray including 100 colon cancer tissue samples and 60 adjacent non-tumor tissue samples was used. The expression levels of 5mC and its ramifications were assessed by immunohistochemistry. According to the expression levels, patients were divided into moderately positive and strongly positive groups, and the correlation between clinicopathological characteristics and methylation marks was assessed using 2-sided chi-square tests. The prognostic values of 5mC, 5hmC, 5fC, and 5caC were tested using Kaplan-Meier analyses. Compared with adjacent non-tumor tissues, the overall levels of DNA methylation were lower in colon carcinoma lesions. However, the clinical parameters were not significantly associated with these methylation markers, except for 5hmC, which was associated with the age of cancer patients (P value = .043). Kaplan-Meier analysis disclosed that moderate positive group had a significantly shorter disease specific survival than strong positive group for patients with different levels of 5mC (65.2 vs 95.2 months, P = .014) and 5hmC (71.2 vs 97.5 months, P = .045). 5mC and its ramifications (5hmC, 5fC, and 5caC) can serve as biomarkers for colon cancer. 5mC and 5hmC are stable predictors and therapeutic targets in colon cancer. However, further understanding of its function will help to reveal the complex tumorigenic process and identify new therapeutic strategies.

Serum and peritoneal biomarkers for the early prediction of symptomatic anastomotic leakage in patients following laparoscopic low anterior resection: A single-center prospective cohort study.

BACKGROUND: Anastomotic leakage (AL) is one of the common complications after rectal cancer surgery. This study aimed to evaluate the combination of biomarkers for the early prediction of symptomatic AL after surgery. METHODS: A prospective cohort study evaluated the serum and peritoneal biomarkers of patients who underwent laparoscopic low anterior resection (Lap LAR) from November 1, 2021, to May 1, 2022. Multivariate-penalized logistic regression was performed to explore the independent biomarker with a P-value <.1, and receiver operating characteristic (ROC) curve was used to analyze the area under the curve (AUC), sensitivity, and specificity of the independent biomarkers. A predictive model for symptomatic AL was built based on the independent biomarkers and was visualized with a nomogram. The calibration curve with the concordance index (c-index) was further applied to evaluate the efficacy of the predictive model. RESULTS: A total of 157 patients were included in this study, and 7 (4.5%) were diagnosed with symptomatic AL. C-reactive protein/album ratio (CAR) on postoperative day 1 and systemic immune-inflammation index (SII) and peritoneal interleukin-6 (IL-6) on postoperative day 3 were proven to be independent predictors for the early prediction of symptomatic AL. The optimal cutoff values of CAR, SII, and peritoneal IL-6 were 1.04, 916.99, and 26430.09 pg/ml, respectively. Finally, the nomogram, including these predictors, was established, and the c-index of this nomogram was 0.812, indicating that the nomogram could be used for potential clinical reference. CONCLUSION: The combination of CAR, SII, and peritoneal IL-6 might contribute to the early prediction of symptomatic AL in patients following Lap LAR. Given the limitations of this study and the emergence of other novel biomarkers, multicenter prospective studies are worthy of further exploration.

Effect of the transanal drainage tube on preventing anastomotic leakage after laparoscopic surgery for rectal cancer: a systematic review and meta-analysis.

PURPOSE: Anastomotic leakage (AL) is a common postoperative complication of rectal cancer, and transanal drainage tube (TDT) efficacy is still contentious. This study aimed to evaluate the TDT effect on AL prevention. METHODS: All relevant papers were searched by using a predefined search strategy (two randomized controlled trials (RCTs), one prospective study, and four retrospective studies). Meta-analysis was conducted to estimate AL and re-operation pooled rates. RESULTS: A total of 7 studies (1556 patients) were included: No significant statistic difference was found between two groups on AL rate (odds ratio (OR) 0.61, P = 0.11) and re-operation rate (OR 0.52, P = 0.10). For subgroup analysis, significant statistic difference was found between two groups on AL rate (OR 0.29, P = 0.002) and re-operation rate (OR 0.15, P = 0.04) in patients without neoadjuvant therapy. As for patients without diverting stoma, the AL rate (OR 0.35, P = 0.002) was significantly lower than that in patients without TDT. CONCLUSIONS: TDT may reduce AL morbidity and re-operation rate for patients without high risk of AL, but may be useless for those in high-risk situations.

Comparison of neoadjuvant chemotherapy followed by surgery vs. surgery alone for locally advanced gastric cancer: a meta-analysis.

BACKGROUND: The neoadjuvant chemotherapy is increasingly used in advanced gastric cancer, but the effects on safety and survival are still controversial. The objective of this meta-analysis was to compare the overall survival and short-term surgical outcomes between neoadjuvant chemotherapy followed by surgery (NACS) and surgery alone (SA) for locally advanced gastric cancer. METHODS: Databases (PubMed, Embase, Web of Science, Cochrane Library, and Google Scholar) were explored for relative studies from January 2000 to January 2021. The quality of randomized controlled trials and cohort studies was evaluated using the modified Jadad scoring system and the Newcastle-Ottawa scale, respectively. The Review Manager software (version 5.3) was used to perform this meta-analysis. The overall survival was evaluated as the primary outcome, while perioperative indicators and post-operative complications were evaluated as the secondary outcomes. RESULTS: Twenty studies, including 1420 NACS cases and 1942 SA cases, were enrolled. The results showed that there were no significant differences in overall survival (P = 0.240), harvested lymph nodes (P = 0.200), total complications (P = 0.080), and 30-day post-operative mortality (P = 0.490) between the NACS and SA groups. However, the NACS group was associated with a longer operation time (P < 0.0001), a higher R0 resection rate (P = 0.003), less reoperation (P = 0.030), and less anastomotic leakage (P = 0.007) compared with SA group. CONCLUSIONS: Compared with SA, NACS was considered safe and feasible for improved R0 resection rate as well as decreased reoperation and anastomotic leakage. While unbenefited overall survival indicated a less important effect of NACS on long-term oncological outcomes.

Peritoneal Cytokines as Early Biomarkers of Colorectal Anastomotic Leakage Following Surgery for Colorectal Cancer: A Meta-Analysis.

BACKGROUND: Postoperative colorectal anastomotic leakage (CAL) is a devastating complication following colorectal resection. However, the diagnosis of anastomotic leakage is often delayed because the current methods of identification are unable to achieve 100% clinical sensitivity and specificity. This meta-analysis aimed to evaluate the predictive value of peritoneal fluid cytokines in the detection of CAL following colorectal surgery. METHODS: A comprehensive search was conducted on PubMed, Embase, Cochrane Library, and Web of Science before June 2021 to retrieve studies regarding peritoneal fluid cytokines as early markers of CAL. Pooled analyses of interleukin (IL)-1ß, IL-6, IL-10, and tumor necrosis factor (TNF) were performed. The means (MD) and standard deviations (SD) of the peritoneal fluid cytokines were extracted from the included studies. Review Manager Software 5.3 was used for data analysis. RESULTS: We included eight studies with 580 patients, among which 85 (14.7%) and 522 (44.5%) were evaluated as the CAL and non-CAL groups, respectively. Compared to the non-CAL group, the CAL group had significantly higher peritoneal IL-6 levels on postoperative day (POD) 1-3 (P = 0.0006, 0.0002, and 0.002, respectively) and slightly higher TNF levels on POD 4 (P = 0.0002). Peritoneal levels of IL-1ß and IL-10 were not significantly different between the two groups in this study. CONCLUSION: Peritoneal IL-6 levels can be a diagnostic marker for CAL following colorectal surgery, whereas the value of TNF needs further exploration in the future. SYSTEMATIC REVIEW REGISTRATION: [https://www.crd.york.ac.uk/prospero/#myprospero], PROSPERO (CRD42021274973).

Extralevator abdominoperineal excision versus abdominoperineal excision for low rectal cancer: a meta-analysis.

BACKGROUND: Extralevator abdominoperineal excision (ELAPE) has become a popular procedure for low rectal cancer as compared with abdominoperineal excision (APE). No definitive answer has been achieved whether one is superior to the other. This study aimed to evaluate the safety and efficacy of ELAPE for low rectal cancer with meta-analysis. METHODS: The Web of Science, Cochrane Library, Embase, and PubMed databases before September 2019 were comprehensively searched to retrieve comparative trials of ELAPE and APE for low rectal cancer. Pooled analyses of the perioperative variables, surgical complications, and oncological variables were performed. Odds ratio (OR) and mean differences (MD) from each trial were pooled using random or fixed effects model depending on the heterogeneity of the included studies. A subgroup analysis or a sensitivity analysis was conducted to explore the potential source of heterogeneity when necessary. RESULTS: This meta-analysis included 17 studies with 4049 patients, of whom 2248 (55.5%) underwent ELAPE and 1801 (44.5%) underwent APE. There were no statistical differences regarding the circumferential resection margin positivity (13.0% vs. 16.2%, OR = 0.69, 95% CI = 0.42-1.14, P = 0.15) and post-operative perineal wound complication rate (28.9% vs. 24.1%, OR = 1.21, 95% CI = 0.75-1.94, P = 0.43). The ELAPE was associated with lower rate of intraoperative perforation (6.6% vs. 11.3%, OR = 0.50, 95% CI = 0.39-0.64, P < 0.001) and local recurrence (8.8% vs. 20.5%, OR = 0.29, 95% CI = 0.21-0.41, P < 0.001) when compared with APE. CONCLUSIONS: The ELAPE was associated with a reduction in the rate of intra-operative perforation and local recurrence, without any increase in the circumferential resection margin positivity and post-operative perineal wound complication rate when compared with APE in the surgical treatment of low rectal cancer.

[Application of transorally inserted anvil (OrVil(TM)) in laparoscopic-assisted radical resection for Siewert type II adenocarcinoma of the esophagogastric junction].

OBJECTIVE: To study the safety and feasibility of transorally inserted anvil (OrVil(TM)) in laparoscopic-assisted radical resection for Siewert type II adenocarcinoma of the esophagogastric junction (AEG). METHODS: Clinical data (operative time, rate of thoracotomy, residual cancer in the proximal margin, and postoperative recovery) of 72 patients suffered from Siewert type II AEG were analyzed retrospectively, including 46 cases of applying OrVil(TM) in digestive tract reconstruction for laparoscopic-assisted radical resection and 26 cases of applying pouch clamp embedding anvil, between May 2009 and August 2012 in Department of Minimally Invasive Gastrointestinal Surgery at the Peking University Cancer Hospital and Institute. RESULTS: The length between proximal margin and superior border of tumor was (2.5±1.5) cm in OrVil(TM) group, significantly longer than that in the traditional group [(1.6±1.1) cm, P<0.01]. Moreover, the intraoperative frozen pathological positive incidence of cancer remnant was 2.2% (1/46), and rate of thoracotomy was 0, both of which were significantly lower as compared to the traditional group [23.1% (6/26) and 15.4% (4/26) respectively, both P<0.01]. However, intraoperative blood loss and postoperative complications did not differ between the two groups (both P>0.05). CONCLUSIONS: As for laparoscopic-assisted Siewert type II AEG radical resection, application of OrVil(TM) in digestive tract reconstruction is a safe surgical procedure, and can effectively reduce the rate of intra-operative thoracotomy, which is beneficial to postoperative recovery.

D2 dissection in laparoscopic and open gastrectomy for gastric cancer.

AIM: To evaluate the radicalness and safety of laparoscopic D2 dissection for gastric cancer. METHODS: Clinicopathological data from 209 patients with gastric cancer, who underwent radical gastrectomy with D2 dissection between January 2007 and February 2011, were analyzed retrospectively. Among these patients, 131 patients underwent laparoscopy-assisted gastrectomy (LAG) and 78 underwent open gastrectomy (OG). The parameters analyzed included operative time, blood loss, blood transfusion, morbidity, mortality, the number of harvested lymph nodes (HLNs), and pathological stage. RESULTS: There were no significant differences in sex, age, types of radical resection [radical proximal gastrectomy (PG + D2), radical distal gastrectomy (DG + D2) and radical total gastrectomy (TG + D2)], and stages between the LAG and OG groups (P > 0.05). Among the two groups, 127 cases (96.9%) and 76 cases (97.4%) had 15 or more HLNs, respectively. The average number of HLNs was 26.1 ± 11.4 in the LAG group and 24.2 ± 9.3 in the OG group (P = 0.233). In the same type of radical resection, there were no significant differences in the number of HLNs between the two groups (PG + D2: 21.7 ± 7.5 vs. 22.4 ± 9.3; DG + D2: 25.7 ± 11.0 vs. 22.3 ± 7.9; TG + D2: 30.9 ± 13.4 vs. 29.3 ± 10.4; P > 0.05 for all comparisons). Tumor free margins were obtained in all cases. Compared with OG group, the LAG group had significantly less blood loss, but a longer operation time (P < 0.001). The morbidity of the LAG group was 9.9%, which was not significantly different from the OG group (7.7%) (P = 0.587). The mortality was zero in both groups. CONCLUSION: Laparoscopic D2 dissection is equivalent to OG in the number of HLNs, regardless of tumor location. Thus, this procedure can achieve the same radicalness as OG.