Objective: To explore the feasibility, safety and long-term efficacy of laparoscopic total gastrectomy combined with distal pancreaticosplenectomy for the treatment of T4b gastric cancer. Methods: A retrospective cohort study was performed. Clinical data of consecutive patients with T4b gastric cancer invading pancreatic tail undergoing laparoscopic or open total gastrectomy combined with distal pancreaticosplenectomy from January 2010 to December 2014 were analyzed retrospectively. Enrollment criteria: (1) primary gastric cancer confirmed by pathology as T4b adenocarcinoma; (2) chest+abdominal+pelvic enhanced CT indicated cancer invading pancreatic tail without distant metastasis, and R0 resection was evaluated as feasible before operation; (3) physical status was ECOG score 0 to 2, and was tolerant to operation. Patients with peritoneal implant metastasis and tumor invasion of other organs during operation, or changes in surgical methods for other reasons were excluded. All the operations were performed by the same surgical team, which had the experiences of more than 100 cases of laparoscopic and 100 cases of open radical gastrectomy with D2 lymph node dissection. The choice of surgical procedure was discussed by the surgeon and the patient, and decided according to the patient's intension. Patients were divided into the laparoscopic group and open group according to the surgical method. Intraoperative and perioperative findings were compared between the two groups. The 3-year disease-free survival rate were analyzed with Kaplan-Meier survival curve and compared by using log-rank test. Results: A total of 37 consecutive patients were enrolled, including 21 in the laparoscopic group and 16 in the open group, and no one receiving laparoscopic procedure was converted to open surgery. The baseline data of two groups were comparable (all P>0.05). Compared with the open group, the laparoscopic group had significantly longer operation time [(264.0±35.1) minutes vs. (226.6±49.9) minutes, t=2.685, P=0.011], significantly less intraoperative blood loss [(65.7±37.4) ml vs. (182.2±94.6) ml, t=-4.658, P<0.001], significantly shorter time to postoperative flatus [(2.8±0.7) days vs. (4.1±0.7) days, t=-5.776, P<0.001] and significantly shorter postoperative hospital stay [(13.3±2.8) days vs. (16.6±4.3) days, t=-2.822, P=0.008]. Morbidity of postoperative complications, including anastomotic leakage, pancreatic fistula, abdominal abscess, intraperitoneal hemorrhage and duodenal stump leakage, in two groups was similar [19.0% (4/21) vs. 4/16, P=0.705]. There were no cases of anastomotic bleeding or stenosis. The 30-day postoperative mortality was 0 in the laparoscopic group and 1/16 in the open group, respectively (P=0.432). The 3-year disease-free survival rates were 38.1% and 37.5% in the laparoscopic and open group, respectively (P=0.751). Conclusion: Laparoscopic total gastrectomy combined with distal pancreaticosplenectomy performed by experienced surgeons for T4b gastric cancer is safe and effective.
Epigenomic alterations can give rise to various tumor-promoting properties, including therapeutic resistance of cancer cells. Here, we identify an lncRNA, BDNF-AS, whose overexpression is specifically driven by a MEF2A-regulated enhancer in endocrine-resistant and triple-negative breast cancer (TNBC). High levels of BDNF-AS in breast cancer tissues not only feature endocrine resistance in hormone receptor (HR)-positive patients but also correlate with poor outcomes in both HR-positive and TNBC patients. Mechanistically, BDNF-AS acts as a molecular scaffold to promote RNH1 protein degradation via TRIM21-mediated ubiquitination of RNH1 at K225. Subsequently, BDNF-AS abolishes RNH1-regulated and RISC-mediated mTOR mRNA decay, therefore sustaining the activation of mTOR signaling. Importantly, mTOR inhibitor, but not PI3K inhibitor, could reverse tamoxifen resistance induced by the overexpression of BDNF-AS. These results point toward a master regulatory role of an enhancer-activated cascade of BDNF-AS/RNH1/TRIM21/mTOR in endocrine resistance and malignant progression of breast cancer.
Background: The prognostic value of tumor deposit (TD) in gastric cancer is controversial. This study aims to investigate the prognostic value of TD. Methods: The consecutive patients diagnosed with gastric cancer from October 2007 to October 2012 were selected. The patients were divided by whether they suffered TD into two groups. The basic data were comparable between the two groups after propensity score matching (PSM), then survival analysis [overall survival (OS) and cancer-specific survival (CSS)] was applied in two groups. After that, all the patients were divided by pN staging and survival analysis were applied in each subgroup. At last, all patients were divided into TD group, pN1 stage group, pN2 stage group, pN3a, and pN3b stage group, OS and CSS were compared between them. Multivariable competing risk analyses tested association of TD with OS and CSS, before and after PSM. Results: Eight hundred and three patients were concluded. After PSM, 137 patients with TD and 274 patients without TD were selected, the 5-year OS and CSS rates of patients with TD were significantly worse than patients without TD (OS: 19.7% vs. 42.0%, P<0.001; CSS: 22.6% vs. 45.6%, P<0.001). In all patients' survival analysis, the 5-year OS and CSS rates of TD group were comparable with pN3a group (OS: 19.7% vs. 25.3%, P=0.221, CSS: 22.6% vs. 30.1%, P=0.092) and pN3b group (OS: 19.7% vs. 19.6% P=0.349, CSS: 22.6% vs. 23.5%, P=0.452). Meanwhile, on multivariable cox regression analyses, the presence of TD significantly reduces the OS and CSS of patients in gastric cancer. Conclusions: TD has a marked impact on the prognosis of gastric cancer. Even patients with TD had the same prognosis with pN3 stage.
目的:分析研究回肠造口术的方法、适应证及并发症的处理方法.方法:选择2005年8月至2015年8月中山大学孙逸仙纪念医院收治的137例行回肠造口术患者,分析其适应证和并发症,并总结回肠造口术的方法和并发症的处理.结果:预防性回肠造口52例,发生吻合口瘘后治疗性回肠造口85例.发生并发症18例(13.1%):肠造口缺血坏死1例、肠造口肠管狭窄3例、肠管外翻脱出2例、肠造口旁疝1例、肠造口出血4例、转流不完全2例、造口旁皮肤溃烂3例与肠管回缩2例.结论:回肠造口术是预防和治疗吻合口瘘的重要手段,预防和处理回肠造口的并发症极其关键.
目的 探讨过氧化物酶体增殖物激活受体γ辅激活因子1α(PGC1α)在胃癌组织中的表达情况及其临床意义.方法 选取随访资料完整的99例胃癌组织标本,利用免疫组化技术检测胃癌组织中PGC1α的表达情况,并分析PGC1α表达与临床病理特征之间的关系及对生存预后的影响.结果 PGC1α在胃癌患者中的表达水平与肿瘤浸润深度、淋巴结转移、pTNM分期、组织分化程度及Borrmann分型密切相关(P<0.05),而与复发、肿瘤大小、远处转移、性别及年龄无关(P>0.05).COX回归分析结果显示PGC1α的表达水平与总生存预后(OS)及无复发生存预后(RFS)密切相关,差异具有统计学意义(P=0.024),是胃癌患者预后的独立预测因素.结论 PGC1α的表达水平与胃癌患者OS和RFS明显相关,其高表达是胃癌患者预后的独立保护因素.