Specimen extraction through natural orifices with Cai tubes in gastrointestinal surgery: a single-institute series of 234 cases / 中华胃肠外科杂志

Objective: To investigate the feasibility of Cai tube-assisted natural orifice specimen extraction surgery (NOSES) in gastrointestinal surgery. Methods: This was a descriptive case-series study. Inclusion criteria: (1) colorectal or gastric cancer diagnosed by preoperative pathological examination or redundant sigmoid or transverse colon detected by barium enema; (2) indications for laparoscopic surgery; (3) body mass index <30 kg/m2 (transanal surgery) and 35 kg/m2 (transvaginal surgery); (4) no vaginal stenosis or adhesions in female patients undergoing transvaginal specimen extraction; and (5) patients with redundant colon aged 18-70 years and a history of intractable constipation for more than 10 years. Exclusion criteria: (1) colorectal cancer with intestinal perforation or obstruction, or gastric cancer with gastric perforation, gastric hemorrhage, or pyloric obstruction; (2) simultaneous resection of lung, bone, or liver metastases ; (3) history of major abdominal surgery or intestinal adhesions; and (4) incomplete clinical data. From January 2014 to October 2022, 209 patients with gastrointestinal tumors and 25 with redundant colons who met the above criteria were treated by NOSES utilizing a Cai tube (China invention patent number:ZL201410168748.2) in the Department of Gastrointestinal Surgery, Zhongshan Hospital, Xiamen University. The procedures included eversion and pull-out NOSES radical resection in 14 patients with middle and low rectal cancer, NOSES radical left hemicolectomy in 171 patients with left-sided colorectal cancer, NOSES radical right hemicolectomy in 12 patients with right-sided colon cancer, NOSES systematic mesogastric resection in 12 patients with gastric cancer, and NOSES subtotal colectomy in 25 patients with redundant colons. All specimens were collected by using an in-house-made anal cannula (Cai tube) with no auxiliary incisions. The primary outcomes included 1-year recurrence-free survival (RFS) and postoperative complications. Results: Among 234 patients, 116 were male and 118 were female. The mean age was (56.6±10.9) years. NOSES was successfully completed in all patients without conversion to open surgery or procedure-related death. The negative rate of circumferential resection margin was 98.8% (169/171) with both two positive cases having left-sided colorectal cancer. Postoperative complications occurred in 37 patients (15.8%), including 11 cases (4.7%) of anastomotic leakage, 3 cases(1.3%) of anastomotic bleeding, 2 cases (0.9%) of intraperitoneal bleeding, 4 cases (1.7%) of abdominal infection, and 8 cases (3.4%) of pulmonary infection. Reoperations were required in 7 patients (3.0%), all of whom consented to creation of an ileostomy after anastomotic leakage. The total readmission rate within 30 days after surgery was 0.9% (2/234). After a follow-up of (18.3±3.6) months, the 1-year RFS was 94.7%. Five of 209 patients (2.4%) with gastrointestinal tumors had local recurrence, all of which was anastomotic recurrence. Sixteen patients (7.7%) developed distant metastases, including liver metastases(n=8), lung metastases(n=6), and bone metastases (n=2). Conclusion: NOSES assisted by Cai tube is feasible and safe in radical resection of gastrointestinal tumors and subtotal colectomy for redundant colon.

Comparison between laparoscopic-assisted natural orifice specimen extraction surgery and conventional laparoscopic surgery for left colorectal cancer: a randomized controlled study with 3-year follow-up results / 中华胃肠外科杂志

Objective: To evaluate the mid-term efficacy of laparoscopic-assisted natural orifice specimen extraction surgery (NOSES) colectomy using the Cai tube in the treatment of left colorectal cancer. Methods: A prospective randomized control trial (China Clinical Trials Registration Number: ChiCTR-OOR-15007060) was performed. Sixty patients with left colorectal cancer at Department of Gastrointestinal Surgery of Zhongshan Hospital from September 2015 to August 2017 were prospectively enrolled. Case inclusion criteria: (1) left colorectal adenocarcinoma (rectal cancer with distance ≥ 8 cm from tumor low margin to anal edge, sigmoid colon cancer, descending colon cancer and left transverse colon cancer) confirmed by preoperative pathology; (2) satisfactory conditions of conventional laparoscopic surgery; (3) maximum diameter of the tumor < 4.5 cm confirmed by preoperative abdominal and pelvic CT or MRI; (4) BMI < 30 kg/m2. Case exclusion criteria: (1) benign lesions, mucinous adenocarcinoma, signet-ring cell carcinoma and other special pathological types of tumors confirmed by preoperative pathological examination; (2) multiple or recurrent cancers; (3) with a history of neoadjuvant chemoradiotherapy; (4) obvious regional infiltration or distant metastasis indicated by preoperative imaging examination; (5) intestinal obstruction, intestinal perforation, etc. Participants were randomly assigned to NOSES group (using the Cai tube) and conventional laparoscopy (CL) group by random number table method. Clinical data between two groups were compared and analyzed, including perioperative conditions, tumor exfoliation cell detection and bacterial culture results of intraperitoneal lavage fluid, postoperative complications (Clavien-Dindo grading), postoperative pain [visual simulation scoring (VAS) assessment], anal function (Kirwan anal function grading assessment), and postoperative 3-year disease-free survival (DFS), overall survival (OS), overall recurrence rate, and local recurrence rate. Results: A total of 60 patients were enrolled, with 30 in the NOSES group and 30 in the CL group. All the patients in the NOSES group successfully completed operation with Cai tube. Baseline data between the two groups were not significantly different (all P>0.05). There were no statistically significant differences between two groups in conversion rate to open surgery, number of lymph node harivested, proximal and distal resection margin of tumor, negative rate of circumferential margin, operation time, blood loss, inflammatory indexes, postoperative anal function, postoperative hospital stay, hospitalization cost, morbidity of postoperative complications (Clavien-Dindo grade II or above) (all P>0.05). Compared to the CL group, the NOSES group had lower maximum postoperative VAS score (2.5±0.3 vs. 5.1±0.4, t=3.187, P<0.01), and fewer use of additional postoperative analgesia [6.7% (2/30) vs. 33.3% (10/30),χ2=6.670, P=0.02]. The postoperative time to gas passage was shorter in the NOSES group [(2.2±1.4) days vs. (3.1±1.2) days,P=0.026]. No tumor cells and bacterial contamination were found in abdominal lavage fluid before and after operation in either group. The anal function at postoperative 3-month of all the patients in the NOSES group was Kirwan grade I to II, while in the CL group, anal function of 2 cases (6.7%) was Kirwan grade III, and of 28 cases was also Kirwan grade I to II, whose difference was not statistically significant (P>0.05). In the NOSES group and the CL group, 3-year DFS was 96.7% and 83.3% (P=0.090), OS was 100% and 90% (P=0.096), overall recurrence rate was 3.3% and 10.0% (P=0.166), and local recurrence rate was 3.3% and 3.3% (P=0.999), respectively, whose differences were not statistically significant (all P>0.05). Conclusions: In the treatment of left colorectal cancer, compared with conventional laparoscopic colectomy, NOSES colectomy using Cai tube exhibits less scar, less postoperative pain, shorter recovery of gastrointestinal function, and similar mid-term outcomes. Given proper surgical indications, the surgical procedure is safe and feasible.

Relationship between the expression level of miR-29c and biological behavior of gastric cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To study the function and clinicopathological significance of RNA-29c (miR-29c) in the carcinogenesis and development of gastric cancer.</p><p><b>METHODS</b>MicroRNA microarray was applied to assess the miRNAs expression profile of gastric cancer. Quantitative real-time PCR was used to detect the expression of miR-29c in 64 cases of gastric cancer tissues and corresponding normal gastric epithelium, as well as cell lines GES-1, BGC-823 and SGC-7901 cells. MTT assay and flow cytometry were applied to detect the effects of forced expression of miR-29c in gastric cancer BGC-823 cells including cell proliferation, apoptosis, cell cycle and drug sensitivity. Quantitative real-time PCR, Western blot and luciferase reporter assay were used to explore the targeted relationship between miR-29c and myeloid cell leukemia-1 (Mcl-1).</p><p><b>RESULTS</b>Compared with normal gastric epithelium, seven microRNAs (miR-374b*, miRPlus-E1212, miR-338-5p, miR-297, miR-21, miR-135b, miR-18a) were significantly up-regulated more than 2-folds, and nine microRNAs (miR-29b-2*, miR-1260, miRPlus-E1241, miR-S1-5p, miR-148a, miR-29c, miR-647, miR-196b*, ebv-miR-BART5) were significantly down-reguated in gastric cancer tissues. The average expression level of miR-29c in gastric cancer tissues was 0.70 ± 0.34 and in corresponding normal epithelium was 1.00 ± 0.06 (P < 0.05). miR-29c expression was related to tumor size, lymph node metastasis, clinical stage, Laurén classification, Borrmann classification and Ming classification (P < 0.05). The poorer differentiation degree of gastric cell lines, the lower was miR-29c expression level (P < 0.05). Overexpression of miR-29c in gastric cancer BGC-823 cells suppressed cell proliferation, stimulated cell apoptosis, induced cell cycle arrest in S phase and increased the chemotherapy sensitivity to drug docetaxel (all were P < 0.05). The average expression level of Mcl-1 mRNA in gastric cancer tissues was 3.47 ± 1.34 and corresponding epithelialium was 1.00 ± 0.20 (P < 0.05). The expression level of miR-29c was negatively related with that of Mcl-1 mRNA in gastric cancer tissues. miR-29c directly targeted to regulation of Mcl-1 expression.</p><p><b>CONCLUSIONS</b>There are special miRNA expression profile in gastric cancer. The expression of miR-29c is closely related to biological behavior of human gastric cancer. miR-29c is involved in targeted regulation of Mcl-1, and may be one of mechanisms of the carcinogenesis of gastric cancer.</p>

Frequent promoter hypermethylation of several tumor suppressor genes in gastric carcinoma and foveolar epithelium / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To study the promoter hypermethylation of several tumor suppressor genes in gastric carcinoma (GC) tissue and adjacent normal gastric foveolar epithelium (GFE).</p><p><b>METHODS</b>Methylation specific PCR (MSP) was used to examine the promoter methylation of tumor suppressor genes E-cadherin, hMLH1, APC and MGMT in paraffin-embedded gastric cancer tissue and adjacent normal foveolar epithelium in 106 cases.</p><p><b>RESULTS</b>The positive rate of genes promoter methylation was 44.3% (47/106 cases) and 72.6% (77/106 cases) at one or more genes tested in the normal GFE and GC tissue, respectively. There was a significant difference in the positive rates of gene promoter methylation between normal GFE and GC tissue (P = 0.0001). There was a significant association with Laurén classification, degree of differentiation and pTNM staging in GC (P < 0.05), but no significant association with Ming's classification (P > 0.05).</p><p><b>CONCLUSION</b>Tumor suppressor genes promoter methylation is frequently present in GC and adjacent normal gastric foveolar epithelium, especially in Laurén diffuse type GC, poorly differentiated GC, mucus-secreting (signet ring) cell GC and pTNM stage III and IV GC. Our findings indicate that the gene promoter methylation is a common and early event in GC carcinogensis.</p>