A multi-center retrospective study of perioperative chemotherapy for gastric cancer based on real-world data / 中华胃肠外科杂志

Objective: To explore the effect of perioperative chemotherapy on the prognosis of gastric cancer patients under real-world condition. Methods: A retrospective cohort study was carried out. Real world data of gastric cancer patients receiving perioperative chemotherapy and surgery + adjuvant chemotherapy in 33 domestic hospitals from January 1, 2014 to January 31, 2016 were collected. Inclusion criteria: (1) gastric adenocarcinoma was confirmed by histopathology, and clinical stage was cT2-4aN0-3M0 (AJCC 8th edition); (2) D2 radical gastric cancer surgery was performed; (3) at least one cycle of neoadjuvant chemotherapy (NAC) was completed; (4) at least 4 cycles of adjuvant chemotherapy (AC) [SOX (S-1+oxaliplatin) or CapeOX (capecitabine + oxaliplatin)] were completed. Exclusion criteria: (1) complicated with other malignant tumors; (2) radiotherapy received; (3) patients with incomplete data. The enrolled patients who received neoadjuvant chemotherapy and adjuvant chemotherapy were included in the perioperative chemotherapy group, and those who received only postoperative adjuvant chemotherapy were included in the surgery + adjuvant chemotherapy group. Propensity score matching (PSM) method was used to control selection bias. The primary outcome were overall survival (OS) and progression-free survival (PFS) after PSM. OS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the last effective follow-up or death. PFS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the first imaging diagnosis of tumor progression or death. The Kaplan-Meier method was used to estimate the survival rate, and the Cox proportional hazards model was used to evaluate the independent effect of perioperative chemo therapy on OS and PFS. Results: 2 045 cases were included, including 1 293 cases in the surgery+adjuvant chemotherapy group and 752 cases in the perioperative chemotherapy group. After PSM, 492 pairs were included in the analysis. There were no statistically significant differences in gender, age, body mass index, tumor stage before treatment, and tumor location between the two groups (all P>0.05). Compared with the surgery + adjuvant chemotherapy group, patients in the perioperative chemotherapy group had higher proportion of total gastrectomy (χ(2)=40.526, P<0.001), smaller maximum tumor diameter (t=3.969, P<0.001), less number of metastatic lymph nodes (t=1.343, P<0.001), lower ratio of vessel invasion (χ(2)=11.897, P=0.001) and nerve invasion (χ(2)=12.338, P<0.001). In the perioperative chemotherapy group and surgery + adjuvant chemotherapy group, 24 cases (4.9%) and 17 cases (3.4%) developed postoperative complications, respectively, and no significant difference was found between two groups (χ(2)=0.815, P=0.367). The median OS of the perioperative chemotherapy group was longer than that of the surgery + adjuvant chemotherapy group (65 months vs. 45 months, HR: 0.74, 95% CI: 0.62-0.89, P=0.001); the median PFS of the perioperative chemotherapy group was also longer than that of the surgery+adjuvant chemotherapy group (56 months vs. 36 months, HR=0.72, 95% CI:0.61-0.85, P<0.001). The forest plot results of subgroup analysis showed that both men and women could benefit from perioperative chemotherapy (all P<0.05); patients over 45 years of age (P<0.05) and with normal body mass (P<0.01) could benefit significantly; patients with cTNM stage II and III presented a trend of benefit or could benefit significantly (P<0.05); patients with signet ring cell carcinoma benefited little (P>0.05); tumors in the gastric body and gastric antrum benefited more significantly (P<0.05). Conclusion: Perioperative chemotherapy can improve the prognosis of gastric cancer patients.

Research progression of extralevator abdominoperineal excision / 中华胃肠外科杂志

The application of extralevator abdomino-perineal excision (ELAPE) and total mesorectal excision has improved the prognosis of rectal cancer. However, compared with anterior resection for rectal cancer, the circumferential resection margin (CRM) positive rate and intraoperative perforation (IOP) rate are still high. The ELAPE can reduce the CRM positive rate and IOP rate, therefore reduce postoperative local recurrence rate and increase the survival rate of patients. The disadvantage of its trauma, longer operative time, and higher perineum complication in ELAPE is controversial. This review mainly discusses the key points of operative procedure, advantages and disadvantages, research status and development prospects of ELAPE.

Inhibitory effect of silencing of HMGB1 gene expression on the invasive and metastatic abilities of MGC-803 gastric cancer cells / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the effect of high mobility group box-1 (high mobility group box B 1, HMGB1) on the invasive and metastatic abilities of gastric cancer cell line MGC-803 and analyze the possible mechanisms.</p><p><b>METHODS</b>HMGB1 gene targeting siRNA was designed and synthesized, and HMGB1 siRNA oligonucleotides were transfected into the MGC-803 cells with Lipofectamine 2000. The invasive and migratory abilities were detected by transwell assay and scratch assay. The Matrigel matrix glue adhesive ability of MGC-803 cells was evaluated by MTT assay. NF-κB activity was detected by electrophoretic mobility shift assay. The mRNA and protein levels of HMGB1 and MMP-9 were determined by RT-PCR and Western blot, respectively.</p><p><b>RESULTS</b>The siRNA down-regulated the levels of HMGB1 mRNA and protein. Compared with that of the control group, the number of invasive (142.7 ± 3.4 /view vs. 303.5 ± 4.3/view) and migratory (293.7 ± 4.4/view vs. 445.5 ± 5.6/view) cells was significantly increased (P < 0.05) and the adhesive ability of MGC-803 cells to Matrigel was significantly elevated (33.4 ± 0.03% vs. 57.4 ± 4.2%, P < 0.05). In addition, silencing of HMGB1 gene significantly inhibited the activity of NF-κB and the relative expression folds of mRNA (0.2 ± 0.1 vs. 1.4 ± 0.4, P < 0.05)and protein (0.4 ± 0.1 vs. 2.3 ± 0.7, P < 0.05) of MMP-9.</p><p><b>CONCLUSION</b>Silencing of HMGB1 can effectively inhibit the invasion and migration of gastric cancer cells and this effect of HMGB1 may be partly due to its regulation of NF-κB and MMP-9 expressions.</p>

Correlation of VEGF and Ki67 expression with sensitivity to neoadjuvant chemoradiation in rectal adenocarcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the correlation of expression of vascular endothelial growth factor (VEGF) and proliferating cell nuclear antigen (Ki67) with sensitivity to neoadjuvant chemoradiation in rectal adenocarcinoma.</p><p><b>METHODS</b>Samples of pretreatment biopsies and the resected specimens after neoadjuvant therapy in 32 patients with rectal adenocarcinoma were collected, and the expression of Ki67 and VEGF were detected by immunohistochemistry using specific antibodies. The correlation of Ki67 and VEGF expression with clinicopathological factors were analyzed.</p><p><b>RESULTS</b>The level of VEGF expression was significantly correlated with lymph node metastasis (P = 0.033), depth of tumor invasion (P = 0.007) and TNM stage (P = 0.016), but not with histological type, tumor size, age and gender of the patients (P > 0.05). However, VEGF expression was found to be negatively and significantly correlated with the sensitivity to neoadjuvant chemoradiation (P = 0.016), and a transient increase of VEGF expression was detected in the resected specimens after neoadjuvant therapy (P = 0.035). Ki67 labeling index (Ki67-LI) was found to be significantly correlated with lymph node metastasis (P = 0.028), but not with tumor size, age and gender of the patients (P > 0.05). It was also found that tumors with lower Ki67-LI expression were more sensitive to neoadjuvant therapy than that with higher expression of Ki67-LI (P = 0.032). In contrast with VEGF, the Ki67 expression level decreased after neoadjuvant therapy, but no statistical significance was found between pretreatment and posttreatment specimens (P > 0.05).</p><p><b>CONCLUSION</b>The preliminary results of this study demonstrate that the expression of VEGF and Ki67 in pretreatment biopsy of rectal adenocarcinoma may be used as a biomarker to predict tumor response to neoadjuvant chemoradiation.</p>

Manganese superoxide dismutase gene transfection of mouse small intestinal epithelial cells protects them from radiation injury / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the protective effect of manganese superoxide dismutase (MnSOD) gene transfer to small intestinal epithelial cells from radiation injury.</p><p><b>METHODS</b>Herpes simplex virus (HSV) vector containing both the human MnSOD and GFP genes was introduced into mouse small intestine. Expression of MnSOD by the intestinal villi was confirmed by nested RT-PCR, immunofluorescence and enzyme activity assay. Mice were then given various doses of irradiation over the abdomen. The height of intestinal villi was measured on histopathology sections by SZ-PT optical system before irradiation, 24 h and 72 h post-irradiation. All comparisons were performed by one-way analysis of variance using the SPSS statistical software to analyze the significance between groups.</p><p><b>RESULTS</b>Nested RT-PCR, immunofluorescence and enzyme activity assay of MnSOD demonstrated overexpression and increased activity of MnSOD in the inoculated intestine of mice. Control (sham inoculated) irradiated mice showed decreased villi height by 40.1%-59.3% on day 1 and 44.2%-65.1% on day 3 (7.5-15 Gy). Treatment of mice with HSV-MnSOD prior to radiation led to statistically significant radioprotection of the small bowel with mean villi height decreased by only 3.1%-12.4% on day 1 and 6.3%-29.1% on day 3.</p><p><b>CONCLUSION</b>The results demonstrate that overexpression of human MnSOD via a replication defective herpes simplex viral vector is an effective method to protect the small intestine from damage caused by ionizing radiation.</p>