Comparison of Short-term and Three-year Oncological Outcomes Between Robotic and Laparoscopic Gastrectomy for Gastric Cancer: A Large Multicenter Cohort Study.

OBJECTIVE: To compare the short-term and long-term outcomes between robotic gastrectomy (RG) and laparoscopic gastrectomy (LG) for gastric cancer. BACKGROUND: The clinical outcomes of RG over LG have not yet been effectively demonstrated. METHODS: This retrospective cohort study included 3599 patients with gastric cancer who underwent radical gastrectomy at eight high-volume hospitals in China from January 2015 to June 2019. Propensity score matching was performed between patients who received RG and LG. The primary end point was 3-year disease-free survival (DFS). RESULTS: After 1:1 propensity score matching, 1034 pairs of patients were enrolled in a balanced cohort for further analysis. The 3-year DFS in the RG and LG was 83.7% and 83.1% ( P =0.745), respectively, and the 3-year overall survival was 85.2% and 84.4%, respectively ( P =0.647). During 3 years of follow-up, 154 patients in the RG and LG groups relapsed (cumulative incidence of recurrence: 15.0% vs 15.0%, P =0.988). There was no significant difference in the recurrence sites between the 2 groups (all P >0.05). Sensitivity analysis showed that RG had comparable 3-year DFS (77.4% vs 76.7%, P =0.745) and overall survival (79.7% vs 78.4%, P =0.577) to LG in patients with advanced (pathologic T2-4a) disease, and the recurrence pattern within 3 years was also similar between the 2 groups (all P >0.05). RG had less intraoperative blood loss, lower conversion rate, and shorter hospital stays than LG (all P >0.05). CONCLUSIONS: For resectable gastric cancer, including advanced cases, RG is a safe approach with comparable 3-year oncological outcomes to LG when performed by experienced surgeons.

Loss of PTPN4 activates STAT3 to promote the tumor growth in rectal cancer.

Colorectal cancer (CRC) is one of the most common types of malignant tumor. Many genetic factors have been proved to show high association with the occurrence and development of CRC and many mutations are detected in CRC. PTPN4/PTP-MEG1 is a widely expressed non-receptor protein tyrosine phosphatase. Over the past three decades, PTPN4 has been demonstrated in the literature to participate in many biological processes. In this study, we identified a nonsense mutation of PTPN4 with a mutation ratio of 90.90% from 1 case of rectal cancer, leading to loss of function in PTPN4 gene. Several somatic mutations occurred in 5/137 rectal cancer samples from The Cancer Genome Atlas Rectum Adenocarcinoma (TCGA READ) database. Interestingly, we found that PTPN4 negative cytoplasm staining was more prone to lymphatic metastasis (N = 50, P = 0.0153) and low expression of PTPN4 in rectal cancer was highly associated with poor prognosis. Overexpression of PTPN4 suppressed the cell growth, and moreover, the loss of PTPN4 accelerated cell growth and boosted clonogenicity of CRC cells. Furthermore, we revealed that the deletion of PTPN4 promoted the tumor formation of NCM460 cells in vivo. In terms of the molecular mechanism, we demonstrated that PTPN4 dephosphorylates pSTAT3 at the Tyr705 residue with a direct interaction and suppresses the transcriptional activity of STAT3. In summary, our study revealed a novel mechanism that the tumorigenesis of colorectal cancer might be caused by the loss of PTPN4 through activating STAT3, which will broaden the therapy strategy for anti-rectal cancer in the future.

Overexpression of CREPT confers colorectal cancer sensitivity to fluorouracil.

AIM: To investigate expression of cell cycle-related and expression-elevated protein in tumor (CREPT) in colorectal cancer (CRC) and determine its prognostic value in response to 5-fluorouracil (5-FU). METHODS: The relative expression of CREPT in CRC tumor samples was determined using immunohistochemistry. The protein content in cell lines was analyzed by immunoblotting. Cell viability was measured with the CCK-8 assay. Cell cycle and apoptosis analyses were performed with flow cytometry. RESULTS: CREPT was overexpressed in CRC tissues and correlated with histological grade. Clinicopathological analysis indicated that CREPT was positively related to tumor progression. Exogenous expression of CREPT stimulated cell proliferation and accelerated the cell cycle. More importantly, high expression of CREPT sensitized CRC cells to 5-FU treatment. Furthermore, we demonstrated that 5-FU elicited significant apoptosis in CREPT-positive cells. CONCLUSION: Aberrant overexpression of CREPT contributes to tumorigenesis of CRC by promoting cell proliferation and accelerating the cell cycle, and confers sensitivity to 5-FU. CREPT is a potential prognostic biomarker for 5-FU in CRC.

The postoperative clinical outcomes and safety of early enteral nutrition in operated gastric cancer patients.

PURPOSE: This study investigated the impact of early enteral nutrition (EEN) on the clinical outcomes of gastric cancer patients after radical gastrectomy. METHODS: Four hundred gastric cancer patients undergoing radical gastrectomy of any extend with D2 nodal dissection were randomly divided into an experimental and a control group with 200 cases in each group. Patients in the control group received postoperative parenteral nutrition (PN), while patients in the experimental group received postoperative EEN. After treatment, the clinical outcomes, postoperative immune function, and nutritional status of the two groups were evaluated. RESULTS: The postoperative fever time, intestinal function recovery time, anal exhaust time, and the length of hospital stay for patients in the experimental group were significantly shorter than those of the control group. We did not find significant differences in anastomotic leak, postoperative ileus and regurgitation between the two groups. The activities of multiple immune cell types, including CD3⁺, CD4⁺, CD4⁺/CD8⁺, and natural killer (NK) cells, were significantly lower in both groups on postoperative day 1 when compared with the preoperative levels (p<0.05). The level of CD8⁺ was not significantly different between the two groups (p>0.05). After treatment, levels of CD3⁺, CD4⁺, CD4⁺/CD8⁺, and NK cells in the experimental group patients were 35.6 ± 4.2, 42.2 ± 3.0, 1.7 ± 0.3, and 27.3 ± 5.3%, respectively, on postoperative day 7, which were similar to the preoperative levels. The immune cell levels from the control group patients remained significantly lower when compared with preoperative values; in addition, these values were also significantly lower when compared with the EEN patients (p<0.05) CONCLUSION: For gastric cancer patients undergoing radical gastrectomy, the clinical outcome, immune function and nutritional status after EEN were significantly improved. These data suggest the widespread use of EEN in clinical practice.

Microsatellite instability of gastric cancer and precancerous lesions.

OBJECTIVE: To investigate whether microsatellite instability (MSI) of gastric cancer and precancerous lesions were existed and its effect. METHODS: Laser microdissection was used. Gastric, intestinal metaplasia, dysplasia and normal mucosa were collected respectively. Five microsatellite loci were selected and MSI was detected by denaturing high-performance liquid chromatography. RESULTS: In the five microsatellite loci REF-positive phenotype, intestinal metaplasia MSI was 20.7%. Dysplasia MSI was 22.4%. Gastric MSI was 47.9%, and there was no MSI in normal gastric mucosa. CONCLUSION: MSI gradually increased from precancerous lesions to gastric cancer. The early detection of MSI may be a potential early warning indicator for early diagnosis of gastric cancer.

Detection of microsatellite instability in gastric cancer and dysplasia tissues.

OBJECTIVE: We aimed to investigate the association between gastric cancer and microsatellite instability (MSI) in the present study. METHOD: Phenol-chloroform method was employed for DNA extraction from the cancer tissues of 65gastric cancer patients and the dysplasia tissues and normal control tissues of 32 non-gastric cancer patients. The microsatellite loci Bat25, Bat26, D2S123, D5S346 and D17S250 were detected by using PCR-SSCP silver staining technique, and the MSI of the gastric cancer tissues and the precancerous tissues was analyzed. RESULTS: Of 65 gastric cancer cases, MSI was detected in 43 cases, with the detection rate of 66.2%. There were 13 cases showing MSI-H and 30 cases showing MSI-L, accounting for 30.2% and 69.8%, respectively. Among 32 cases of dysplasia tissues, MSI was detected in 10 cases, with the detection rate of 31.3%. Two cases of dysplasia tissues showed MSI-H and 8 cases showed MSI-L, accounting for 20.0% and 80.0%, respectively. CONCLUSION: Gastric cancer patients had a high detection rate of MSI. It is speculated that MSI is another molecular mechanism of carcinogenesis and may serve as a sensitive diagnostic indicator of gastric cancer.

A missense mutation (S3660L) in MLL3 gene influences risk of gastric cancer.

PURPOSE: Several studies indicated that the expression level of MLL3 gene in gastric cancer tissue was associated with prognosis, and previous studies also suggested that genetic polymorphisms of MLL3 were related to the risk for gastric cancer. The present study aimed to investigate the association of a missense mutation (S3660L) in the MLL3 gene with gastric cancer risk in a Chinese population. METHODS: In the present study, we identified a novel missense mutation in MLL3 gene (S3660L) by directly sequencing method in 48 gastric cancer patients. To further explore the relation between gastric cancer and this mutation, we selected 354 gastric cancer patients and 377 healthy control subjects and designed a case-control study. RESULTS: We found that the AG genotype (14.9 vs 6.40%, odds ratio/OR=2.58, 95% CI: 1.33-4.54, p<0.001) and A allele (7.5 vs 3.2%, OR=2.46, 95% CI: 1.55~5.34, p<0.001) were common in the gastric cancer patients than in the control subjects. CONCLUSION: We concluded that this novel missense (S3660L) mutation in MLL3 gene is likely to increase the gastric cancer risk.

Mll3 genetic variants affect risk of gastric cancer in the chinese han population.

It is reported that the expression level of MLL3 in gastric cancer tissue highly correlates with tumor progression. However, whether MLL3 genetic variants are associated with the risk of gastric cancer remains unclear. In this study, we conducted a genotyping analysis for MLL3 in 314 cases of gastric cancer and 322 controls from the Chinese Han population. 4 SNPs (rs6943984, rs4725443, rs3800836, rs6464211) were selected for the present analysis. We found 2 SNPs (rs6943984, rs4725443) of MLL3 gene were significantly associated with the risk of gastric cancer : the rs6943984 with the minor allele A and rs4725443 with the minor allele C revealed strong associations with increased gastric cancer risk [P <0.001, OR=1.97, 95% CI=1.48~2.64 and P <0.001, OR = 2.23, 95% CI = 1.54~3.24]. Haplotype analysis of the four SNPs showed that haplotype A-T-A-C, G-T-G-C, and G-C-A-C increased the risk of gastric cancer (P <0.001, P=0.18, and P<0.001, respectively), while haplotype G-T-A-C significantly reduced the risk of gastric cancer (P <0.001). We concluded that MLL3 variants are significantly associated with gastric cancer risk. Our results for the first time provided new insight into susceptibility factors of MLL3 gene variants in carcinogenesis of gastric cancer of the Chinese Han population.

[Combination of single-port thoracoscopy and laparoscopy for the treatment of esophageal carcinoma: report of 6 cases].

OBJECTIVE: To study the feasibility and early results of radical resection of esophageal carcinoma using single-port thoracoscopy combined with laparoscopy. METHODS: From March 2010 to December 2010, 6 patients with esophageal carcinoma underwent radical resection by single-port thoracoscopy combined with laparoscopy in the General Hospital of People's Liberation Army. With the patients at a supine position, laparoscopy was performed to complete stomach mobilization and abdominal lymph node dissection. Thoracoscopy was then carried out with the patients lying on the left to mobilize the esophagus and dissect thoracic lymph nodes. Finally, the stomach was pulled into the thoracic cavity via the hiatus of the diaphragm to construct a tube-like stomach, which was then anastomosed to the esophagus using the OrVil system. RESULTS: No patient was converted to open surgery during the operation. The total operative time ranged from 200 to 320 min. The mean laparoscopic time was 75(range, 45-90) min, and the mean thoracoscopic time 160(120-240) min. The mean intraoperative blood loss was 220(160-300) ml. The mean lymph node retrieval was 12(9-18). No anastomotic fistula, chylothorax, lung infection were found postoperatively. CONCLUSION: After esophageal resection using single-port thoracoscopic and laparoscopy, reconstruction using OrVil system is safe and feasible.