A prospective cohort study on the clinical value of pelvic peritoneal reconstruction in laparoscopic anterior resection for middle and low rectal cancer / 中华胃肠外科杂志

Objective: To investigate the safety and efficacy of pelvic peritoneal reconstruction and its effect on anal function in laparoscopy-assisted anterior resection of low and middle rectal cancer. Methods: A prospective cohort study was conducted. Consecutive patients with low and middle rectal cancer who underwent laparoscopy-assisted transabdominal anterior resection at Naval Military Medical University Changhai Hospital from February 2020 to February 2021 were enrolled. Inclusion criteria: (1) the distance from tumor to the anal verge ≤10 cm; (2) laparoscopy-assisted transabdominal anterior resection of rectal cancer; (3) complete clinical data; (4) rectal adenocarcinoma diagnosed by postoperative pathology. Exclusion criteria: (1) emergency surgery; (2) patients with a history of anal dysfunction or anal surgery; (3) preoperative diagnosis of distant (liver, lung) metastasis; (4) intestinal obstruction; (5) conversion to open surgery for various reasons. The pelvic floor was reconstructed using SXMD1B405 (Stratafix helical PGA-PCL, Ethicon). The first needle was sutured from the left anterior wall of the neorectum to the right. Insertion of the needle was continued to suture the root of the sigmoid mesentery while the Hemo-lok was used to fix the suture. The second needle was started from the beginning of the first needle, after 3-4 needles, a drainage tube was inserted through the left lower abdominal trocar to the presacral space. Then, the left peritoneal incision of the descending colon was sutured, after which Hemo-lok fixation was performed. The operative time, perioperative complications, postoperative Wexner anal function score and low anterior resection syndrome (LARS) score were compared between the study group and the control group. Three to six months after the operation, pelvic MRI was performed to observe and compare the pelvic floor anatomical structure of the two groups. Results: A total of 230 patients were enrolled, including 58 who underwent pelvic floor peritoneum reconstruction as the study group and 172 who did not undergo pelvic floor peritoneum reconstruction as the control group. There were no significant differences in general data between the two groups (all P>0.05). The operation time of the study group was longer than that of control group [(177.5±33.0) minutes vs. (148.7±45.5) minutes, P<0.001]. There was no significant difference in the incidence of perioperative complications (including anastomotic leakage, anastomotic bleeding, postoperative pneumonia, urinary tract infection, deep vein thrombosis, and intestinal obstruction) between the two groups (all P>0.05). Eight cases had anastomotic leakage, of whom 2 cases (3.4%) in the study group were discharged after conservative treatment, 5 cases (2.9%) of other 6 cases (3.5%) in the control group were discharged after the secondary surgical treatment. The Wexner score and LARS score were 3.1±2.8 and 23.0 (16.0-28.0) in the study group, which were lower than those in the control group [4.7±3.4 and 27.0 (18.0-32.0)], and the differences were statistically significant (t=-3.018, P=0.003 and Z=-2.257, P=0.024). Severe LARS was 16.5% (7/45) in study group and 35.5% (50/141) in control group, and the difference was no significant differences (Z=4.373, P=0.373). Pelvic MRI examination 3 to 6 months after surgery showed that the incidence of intestinal accumulation in the pelvic floor was 9.1% (3/33) in study group and 46.4% (64/138) in control group (χ(2)=15.537, P<0.001). Conclusion: Pelvic peritoneal reconstruction using stratafix in laparoscopic anterior resection of middle and low rectal cancer is safe and feasible, which may reduce the probability of the secondary operation in patients with anastomotic leakage and significantly improve postoperative anal function.

Molecular classification of colorectal carcinoma based on integration of gene expression profile and copy number variation / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To classify colorectal carcinoma (CRC) by TNM staging integrated with the gene expression profile and copy number variation (CNV).</p><p><b>METHODS</b>Profile data of gene expression and CNV of CRC were downloaded from public database and processed with batch bias adjustment, quartile normalization, missing value estimation and feature filtration. The processed profiles of mRNA and CNV were introduced into the codes of Bayesian consensus clustering (BCC) method and were used to calculate the subclasses of CRC. With the follow-up information of disease free survival of CRC patients, the prognostic values of the subclasses was investigated and the software of function enrichment analysis was employed to discover the major pathway signaling to each interesting subclass. All statistic analyses were performed under R-3.0.1 environment or by using SPSS 16.0 software.</p><p><b>RESULTS</b>Profile data of gene expression and corresponding CNV from 335 CRC patients with TNM stage Ⅱ-Ⅲ and followed-up information were obtained. After feature filtering, the profiles contained 1578 probes of mRNA and 345 location of CNV. Four CRC subclasses were identified by the integrative analysis with BCC, and the concordances of BCC subclasses and each of gene-based subclasses (Cramer's V=0.49), CNV-based subclasses (Cramer's V=0.51) and Marisa's subclasses (Cramer's V=0.32) were statistically significant (Ps<0.001). Among BCC subclasses, BCC-I had a favorable prognosis, while BCC-Ⅳ had more unfavorable prognosis. The differences of prognosis were significant among BCC-I, BCC-(Ⅱ+Ⅲ) and BCC-Ⅳ with an overall log-rank P<0.001. The top enriched function was DNA damage and repair signaling when BCC-I compared to BCC-Ⅳ, and the new subgroups classified by the genes associated with enriched signaling had the better prognostic value than BCC subclasses but both of them were significantly correlated (Cramer's V=0.39, P<0.001).</p><p><b>CONCLUSION</b>BCC method is effective to integrate multi-type genomic data for molecular classification of colorectal carcinoma, and the BCC-Ⅳ subclass has poor prognosis, which may be associated with the decreased repairing function of DNA damage.</p>

Gene methylation in stool for the screening of colorectal cancer and pre-malignant lesions / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To evaluate association between DNA methylation of MAL, CDKN2A, and MGMT in stool and development of colorectal cancer, and to evaluate the screening value of these biomarkers in colorectal cancer and pre-malignant lesions.</p><p><b>METHODS</b>Morning stool specimens were collected from 69 patients with colorectal cancer, 24 with colon adenoma, 19 with hyperplastic polyps, and 26 healthy controls. DNA was extracted and treated with bisulfite. Methylation-specific PCR(MSP) was performed for methylation analysis of MAL, CDKN2A and MGMT in DNA samples. Associations between clinicopathological features and gene methylation were analyzed. The sensitivity of diagnosis by combining three methylation markers was compared with fecal occult blood test(FOBT).</p><p><b>RESULTS</b>The methylation frequencies of MAL, CDKN2A and MGMT were 78.3%, 52.5% and 55.1% in colorectal cancer, 58.3%, 41.7% and 37.5% in colon adenomas, 26.3%, 15.8% and 10.5% in hyperplastic polyps, and 3.8%, 0 and 3.8% in healthy controls, respectively. Significant differences in three genes were found between colorectal cancer and hyperplastic polyp, colorectal cancer and healthy control, colon adenoma and hyperplastic polyp, colon adenoma and healthy control(all P<0.05). The diagnostic sensitivity by combining three methylation markers was 92.8% in colorectal cancer, 70.8% in colon adenomas, significantly higher than FOBT examination (29.0% in colorectal cancer and 25.0% in colon adenomas, all P<0.05). No significant associations existed between three genes methylation of the three genes and clinical characteristic including sex, age, tumor location, lymph node metastases and TNM stage (all P>0.05).</p><p><b>CONCLUSION</b>DNA methylations levels of MAL, CDKN2A, and MGMT in stools are significantly higher in colorectal cancer and colon adenoma, which may serve as an noninvasive approach for the screening of colorectal cancer and pre-malignant lesions.</p>

Could tumor characteristics identified by colonoscopy predict the locally advanced rectal carcinoma? / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Neoadjuvant chemoradiation is now considered the standard care for locally advanced rectal carcinoma (T3-4 or/and N1-2 lesions), but the accuracy of staging examinations including endorectal ultrasonography (ERUS) and MRI is far from excellent. In addition, the above staging equipment or professionals who perform the examinations may not be available in some hospitals, while preoperative colonoscopy and biopsy are usually obtainable in most hospitals. The objective of the present study was to investigate the clinical and pathological characteristics of locally advanced rectal carcinoma and identify candidates for neoadjuvant chemoradiation.</p><p><b>METHODS</b>This was a retrospective study. Patients who were treated for rectal cancer at Changhai Hospital from January 1999 to July 2008 were identified from our prospectively collected database. Statistical analysis was performed using SPSS Software System (version 15.0). The Mann-Whitney test, chi-square test and multivariate Logistic regression analysis were performed.</p><p><b>RESULTS</b>A total of 1005 cases were included in this research, of which 761 cases were identified as locally advanced rectal carcinoma depending on postoperative TNM staging. The results of multivariate Logistic regression analysis indicated seven independent risk factors that could be used to predict a locally advanced rectal carcinoma independently: a high grade (including poor differentiation and undifferentiation) (OR: 3.856; 95% CI: 2.064 to 7.204; P = 0.000); large tumor size (OR: 2.455; 95% CI: 1.755 to 3.436; P = 0.000); elevated preoperative serum CEA level (OR: 1.823; 95% CI: 1.309 to 2.537; P = 0.000); non-polypoid tumor type (OR: 1.758; 95% CI: 1.273 to 2.427; P = 0.001); the absence of synchronous polyps (OR: 1.602; 95% CI: 1.103 to 2.327; P = 0.013); the absence of blood in stool (OR: 1.659; 95% CI: 1.049 to 2.624; P = 0.030); and a greater circumferential tumor extent (OR: 1.813; 95% CI: 1.055 to 3.113; P = 0.031). Based on these findings, a Logistic equation was established, the accuracy of which was 64% according to the information of the additional 50 cases.</p><p><b>CONCLUSIONS</b>Some independent risk factors related with locally advanced rectal carcinoma were identified, based on which it is possible to establish a Logistic equation as a tool to predict candidates of neoadjuvant chemoradiation. Further research about optimization of the equation is warranted.</p>

Lymph node metastasis and its risk factors in T1-2 staging invasive rectal carcinoma / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the lymph node metastasis and its risk factors in T1-2 staging invasive rectal carcinoma.</p><p><b>METHODS</b>The data of 1116 patients with rectal cancer treated with total mesorectal excision (TME) technique from January 2000 to April 2009 was analyzed retrospectively. The clinicopathological factors analyzed included gender, age, primary symptom type, number of symptoms, duration of symptom, synchronous polyps, preoperative serum carcino-embryonic antigen level, preoperative serum CA19-9 level, the distance of tumor from the anal verge, tumor size, tumor morphological type, tumor circumferential extent, tumor differentiation and tumor T staging. Statistical analysis was performed by using Logistic regression analysis and Chi-square test.</p><p><b>RESULTS</b>A total of 1116 patients were enrolled, and 358 cases (32.1%) were classified as with T1-2 staging tumor. Two cases (5.6%, 2/36) in patients with a T1 staging tumor were found with lymph node metastasis, and 75 cases (23.3%, 75/322) in patients with a T2 staging tumor, respectively. Compared with patients with T3-4 staging tumor, lymph node metastasis rate of the patients with T1-2 staging tumor was significantly lower [21.5% (77/358) vs. 51.6% (391/758), P < 0.05]. Only the tumor T staging was found as the independent risk factor for the lymph node metastasis in patients with T1-2 staging tumor on multivariate Logistic regression analysis (odds ratio: 5.162; 95%CI: 1.212 to 21.991; P = 0.026).</p><p><b>CONCLUSIONS</b>A substantial proportion of T1-2 staging rectal cancers harbor metastatic lymph nodes and the clinicopathological features except for T staging fail to predict the lymph node metastasis. Further research is warranted to identify the risk factors and guide the clinical practice in patient with T1-2 staging tumor.</p>