Zhendan Yao

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.

Validation of the Memorial Sloan-Kettering Cancer Center Nomogram to Predict Disease-Specific Survival after R0 Resection in a Chinese Gastric Cancer Population

Background Prediction of disease-specific survival (DSS) for individual patient with gastric cancer after R0 resection remains a clinical concern. Since the clinicopathologic characteristics of gastric cancer vary widely between China and western countries, this study is to evaluate a nomogram from Memorial Sloan-Kettering Cancer Center (MSKCC) for predicting the probability of DSS in patients with gastric cancer from a Chinese cohort. Methods From 1998 to 2007, clinical data of 979 patients with gastric cancer who underwent R0 resection were retrospectively collected from Peking University Cancer Hospital & Institute and used for external validation. The performance of the MSKCC nomogram in our population was assessed using concordance index (C-index) and calibration plot. Results The C-index for the MSKCC predictive nomogram was 0.74 in the Chinese cohort, compared with 0.69 for American Joint Committee on Cancer (AJCC) staging system (P<0.0001). This suggests that the discriminating value of MSKCC nomogram is superior to AJCC staging system for prognostic prediction in the Chinese population. Calibration plots showed that the actual survival of Chinese patients corresponded closely to the MSKCC nonogram-predicted survival probabilities. Moreover, MSKCC nomogram predictions demonstrated the heterogeneity of survival in stage IIA/IIB/IIIA/IIIB disease of the Chinese patients. Conclusion In this study, we externally validated MSKCC nomogram for predicting the probability of 5- and 9-year DSS after R0 resection for gastric cancer in a Chinese population. The MSKCC nomogram performed well with good discrimination and calibration. The MSKCC nomogram improved individualized predictions of survival, and may assist Chinese clinicians and patients in individual follow-up scheduling, and decision making with regard to various treatment options.

GOLPH3 predicts survival of colorectal cancer patients treated with 5-fluorouracil-based adjuvant chemotherapy

BackgroundGolgi phosphoprotein 3 (GOLPH3) has been validated as a potent oncogene involved in the progression of many types of solid tumors, and its overexpression is associated with poor clinical outcome in many cancers. However, it is still unknown the association of GOLPH3 expression with the prognosis of colorectal cancer (CRC) patients who received 5-fluorouracil (5-FU)-based adjuvant chemotherapy.MethodsThe expression of GOLPH3 was determined by qRT-PCR and immunohistochemistry in colorectal tissues from CRC patients treated with 5-FU based adjuvant chemotherapy after surgery. The association of GOLPH3 with clinicopathologic features and prognosis was analysed. The effects of GOLPH3 on 5-FU sensitivity were examined in CRC cell lines.ResultsGOLPH3 expression was elevated in CRC tissues compared with matched adjacent noncancerous tissues. Kaplan-Meier survival curves indicated that high GOLPH3 expression was significantly associated with prolonged disease-free survival (DFS, P = 0.002) and overall survival (OS, P = 0.011) in patients who received 5-FU-based adjuvant chemotherapy. Moreover, multivariate analysis showed that GOLPH3 expression was an independent prognostic factor for DFS in CRC patients treated with 5-FU-based chemotherapy (HR, 0.468; 95%CI, 0.222-0.987; P = 0.046). In vitro, overexpression of GOLPH3 facilitated the 5-FU chemosensitivity in CRC cells; while siRNA-mediated knockdown of GOLPH3 reduced the sensitivity of CRC cells to 5-FU-induced apoptosis.ConclusionsOur results suggest that GOLPH3 is associated with prognosis in CRC patients treated with postoperative 5-FU-based adjuvant chemotherapy, and may serve as a potential indicator to predict 5-FU chemosensitivity.

Downregulated USP3 mRNA functions as a competitive endogenous RNA of SMAD4 by sponging miR-224 and promotes metastasis in colorectal cancer

Increasing evidence shows that competitive endogenous RNAs (ceRNAs) can affect the expression of other transcripts by sequestering common microRNAs (miRNAs), and participate in tumourigenesis. As a potent tumour suppressor in colorectal cancer (CRC), SMAD4 is regulated by many miRNAs. However, the regulation of SMAD4 by ceRNAs has never been examined. In the present study, we found that USP3 modulated SMAD4 expression in a miRNA dependent, and protein-coding gene independent manner. USP3 and SMAD4 were directly targeted by miR-224, and overexpression of the USP3 3′UTR could inhibit metastasis caused by the loss of USP3. The correlation of USP3, SMAD4 and miR-224 expression was further verified in CRC specimens. Additionally, the loss of USP3 was associated with distal metastasis and a poor prognosis. Altogether, our study demonstrates USP3 as a bona fide SMAD4 ceRNA. The results from this study may provide new insights into the prevention and treatment of CRC.

Evaluation of immune responses of gastric cancer patients treated by laparoscopic and open gastrectomy

Laparoscopic surgery has been shown to offer more advantages than open surgery for the treatment of gastric cancer. However, the perioperative immune responses after laparoscopic surgery remain largely unexplored. Here, we analyzed the immunity of gastric cancer patients treated by laparoscopy-assisted gastrectomy (LAG) or open gastrectomy (OG) with D2 dissection. Seventy patients were randomized into LAG and OG groups. The operative details and postoperative outcomes of the two groups were compared. The immune factors were measured preoperatively as well as on the first, third, and seventh postoperative days (POD). Our results indicate that there was no significant difference between two groups in clinical characteristics. The profiles of white blood cells, neutrophils, lymphocytes, as well as the lymphocyte subpopulations, including T lymphocytes, B lymphocytes, CD4+ T cells, and CD8+ T cells were similar in the LAG and the OG groups. Only the natural killer cell counts were significantly higher in LAG-treated patients than in OG-treated ones on POD7. Moreover, no statistical differences were found between the two groups with respect to the levels of perioperative cytokines, including IFN-γ, IL-4, IL-6, and TNF-α. However, compared with the OG group, most of the immune factors in the LAG group had trends to return to preoperative levels on POD7. Our study demonstrates that the immune function of LAG-treated patients showed patterns similar to that of OG-treated patients, although larger prospective multicenter trials are needed to further evaluate the immunological status of LAG.