No abstract

Ethyl pyruvate (EP), a stable lipophilic pyruvate derivative, has been shown to exert anti-inflammatory activities through inhibiting the expression of various pro-inflammatory mediators as well as circulating levels of high mobility group box protein 1 (HMGB1) in a variety of in vitro and in vivo model systems. Necrotic cell death triggers an inflammatory response through release of HMGB1 in the extracellular space due to the membrane rupture. In an effort to better understand the pharmacological action mechanism that could explain the anti-inflammatory properties of EP, we examined the effects of EP on necrotic cell death in A549 lung adenocarcinoma cells in response to glucose deprivation (GD), a common characteristic of the tumor microenvironment. Here we show that EP prevented GD-induced necrosis and HMGB1 release and switched the cell death mode to apoptosis through inhibiting GD-induced CuZn superoxide dismutase release and ROS production. These results suggest that the necrosisto-apoptosis switch activity of EP may contribute to its anti-inflammatory action and that EP may suppress tumor development possibly through its activity to induce the cell death mode switch from tumor promoting necrotic cell death to tumor suppressive apoptotic cell death.

We conclude that the liver function alteration after LAG may have been caused by direct liver manipulation or aberrant hepatic artery ligation rather than the CO₂ pneumoperitoneum.

NET patients treated by ER may have a good prognosis if the tumor size is small and histologically low grade without lymphatic invasion.

IMPORTANCEThe long-term safety of laparoscopic distal gastrectomy for locally advanced gastric cancer (AGC) remains uncertain given the lack of 5-year follow-up results.OBJECTIVE To compare the 5-year follow-up results in patients with clinically AGC enrolled in the Korean Laparoendoscopic Gastrointestinal Surgery Study (KLASS)-02 randomized clinical trial who underwent laparoscopic or open distal gastrectomy. DESIGN, SETTING, AND PARTICIPANTSThe KLASS-02, a multicenter randomized clinical trial, showed that laparoscopic surgery was noninferior to open surgery for patients with locally AGC. The present study assessed the 5-year follow-up results, including 5-year overall survival (OS) and relapse-free survival (RFS) rates and long-term complications, in patients enrolled in KLASS-02. From November 21, 2011, to April 29, 2015 aged 20 to 80 years diagnosed preoperatively with locally AGC were enrolled. Final follow-up was on June 15, 2021. Data were analyzed June 24 to September 9, 2021. INTERVENTIONS Patients were treated with R0 resection either by laparoscopic gastrectomy or open gastrectomy as the full analysis set of the KLASS-02 trial. MAIN OUTCOMES AND MEASURES Five-year OS and RFS rates, recurrence patterns, and long-term surgical complications were evaluated. RESULTS This study enrolled a total of 1050 patients. A total of 974 patients were treated with R0 resection; 492 (50.5%) in the laparoscopic gastrectomy group (mean [SD] age, 59.8 [11.0] years; 351 men [71.3%]) and 482 (49.5%) in the open gastrectomy group (mean [SD] age, 59.4 [11.5] years; 335 men [69.5%]). In patients who underwent laparoscopic and open distal gastrectomy, the 5-year OS (88.9% vs 88.7%) and RFS (79.5% vs 81.1%) rates did not differ significantly. The most common types of recurrence were peritoneal carcinomatosis (73 of 173 [42.1%]), hematogenous metastases (36 of 173 [20.8%]), and locoregional recurrence (23 of 173 [13.2%]), with no between-group differences in types of recurrence at each cancer stage. The correlation between 3-year RFS and 5-year OS at the individual level was highest in patients with stage III gastric cancer (ρ = 0.720). The late complication rate was significantly lower in the laparoscopic than in the open surgery group (32 of 492 [6.5%] vs 53 of 482 [11.0%]). The most common type of complication in both groups was intestinal obstruction (13 of 492 [2.6%] vs 24 of 482 [5.0%]). CONCLUSIONS AND RELEVANCEThe 5-year outcomes of the KLASS-02 trial support the 3-year results, which is the noninferiority of laparoscopic surgery compared with open gastrectomy for locally AGC. The laparoscopic approach can be recommended in patients with locally AGC to achieve the benefit of low incidence of late complications.