Glioblastoma (GBM) is a devastating and incurable brain tumour, with a median overall survival of fifteen months. Identifying the cell of origin that harbours mutations that drive GBM could provide a fundamental basis for understanding disease progression and developing new treatments. Given that the accumulation of somatic mutations has been implicated in gliomagenesis, studies have suggested that neural stem cells (NSCs), with their self-renewal and proliferative capacities, in the subventricular zone (SVZ) of the adult human brain may be the cells from which GBM originates. However, there is a lack of direct genetic evidence from human patients with GBM. Here we describe direct molecular genetic evidence from patient brain tissue and genome-edited mouse models that show astrocyte-like NSCs in the SVZ to be the cell of origin that contains the driver mutations of human GBM. First, we performed deep sequencing of triple-matched tissues, consisting of (i) normal SVZ tissue away from the tumour mass, (ii) tumour tissue, and (iii) normal cortical tissue (or blood), from 28 patients with isocitrate dehydrogenase (IDH) wild-type GBM or other types of brain tumour. We found that normal SVZ tissue away from the tumour in 56.3% of patients with wild-type IDH GBM contained low-level GBM driver mutations (down to approximately 1% of the mutational burden) that were observed at high levels in their matching tumours. Moreover, by single-cell sequencing and laser microdissection analysis of patient brain tissue and genome editing of a mouse model, we found that astrocyte-like NSCs that carry driver mutations migrate from the SVZ and lead to the development of high-grade malignant gliomas in distant brain regions. Together, our results show that NSCs in human SVZ tissue are the cells of origin that contain the driver mutations of GBM.

LADG for patients with clinical stage I gastric cancer is safe and has a benefit of lower occurrence of wound complication compared with conventional ODG.

Obesity increases the risks of diabetes, hypertension, and cardiovascular diseases, ultimately contributing to mortality. Korean Society for the Study of Obesity (KSSO) was established to improve the management of obesity through research and education; to that end, the Committee of Clinical Practice Guidelines of KSSO reviews systemic evidence using expert panels to develop clinical guidelines. The clinical practice guidelines for obesity were revised in 2018 using National Health Insurance Service Health checkup data from 2006 to 2015. Following these guidelines, we added a category, class III obesity, which includes individuals with body mass index (BMI) ≥35 kg/m 2 . Agreeing with the International Federation for the Surgery of Obesity and Metabolic Disorders, Asian Pacific Chapter consensus, we determined that bariatric surgery is indicated for Korean patients with BMI ≥35 kg/m 2 and for Korean patients with BMI ≥30 kg/m 2 who have comorbidities. The new guidelines focus on guiding clinicians and patients to manage obesity more effectively. Our recommendations and treatment algorithms can serve as a guide for the evaluation, prevention, and management of overweight and obesity.

Objective: The aim of the study was to evaluate the short-term outcomes of KLASS-02-RCT, a multicenter randomized controlled trial comparing laparoscopic distal gastrectomy (LDG) with D2 lymphadenectomy with open distal gastrectomy (ODG). Summary Background Data: Although several benefits of laparoscopic gastric cancer surgery have been reported, strong evidence is still limited, especially in locally advanced gastric cancer which requires extensive lymph node dissection. Methods: Enrollment criteria included histologically confirmed cT2-4a and N0-1 gastric adenocarcinoma. Thirty-day morbidity, 90-day mortality, postoperative pain, and recovery were compared between LDG and ODG groups. Results: A total of 1050 patients were randomly assigned to LDG (n = 526) or ODG group (n = 524) between November 2011 and April 2015. After excluding patients who received bypass or no surgery, 1011 patients were analyzed as actual treatment group. Mean number of totally retrieved lymph nodes was similar in both groups (LDG = 46.6 vs ODG = 47.4, P = 0.451). Early morbidity rate was significantly lower after LDG (16.6%) than after ODG (24.1%; P = 0.003). Postoperative analgesics use and patients’ reported pain score were significantly lower after LDG. First day of flatus was earlier after LDG (3.5 vs 3.7 d, P = 0.025) and postoperative hospital stay was shorter in LDG group (8.1 vs 9.3 d, P = 0.005). Ninety days’ mortality rate was similar in both groups (LDG = 0.4% vs ODG = 0.6%, P = 0.682). Conclusions: Laparoscopic distal gastrectomy with D2 lymphadenectomy for locally advanced gastric cancer shows benefits in terms of lower complication rate, faster recovery, and less pain compared with open surgery.

; for the Korean Laparoendoscopic Gastrointestinal Surgery Study (KLASS) Group IMPORTANCE Laparoscopic distal gastrectomy is gaining popularity over open distal gastrectomy for gastric cancer because of better early postoperative outcomes. However, to our knowledge, no studies have proved whether laparoscopic distal gastrectomy is oncologically equivalent to open distal gastrectomy. OBJECTIVE To examine whether the long-term survival among patients with stage I gastric cancer undergoing laparoscopic distal gastrectomy is noninferior to that among patients undergoing open distal gastrectomy. DESIGN The Korean Laparoendoscopic Gastrointestinal Surgery Study (KLASS) group, which includes 15 surgeons from 13 institutes, conducted a phase 3, multicenter, open-label, noninferiority, prospective randomized clinical trial (KLASS-01) of patients with histologically proven, preoperative clinical stage I gastric adenocarcinoma from January 5, 2006, to August 23, 2010. Survival and recurrence status of the patients was determined in December 2016. INTERVENTIONS Patients were randomly assigned (1:1) to laparoscopic distal gastrectomy (n = 705) or open distal gastrectomy (n = 711). Of these patients, 85 received a surgical approach opposite the one to which they were randomized (63 randomized to the open surgery group and 22 to the laparoscopic group). MAIN OUTCOMES AND MEASURES Difference in 5-year overall survival between the laparoscopic and open distal gastrectomy groups. The noninferiority margin was prespecified as −5% (corresponding hazard ratio of 1.54), with an assumed survival of 90% after 5 years in the open surgery group. RESULTS Among the 1416 patients (mean [SD] age, 57.3 [11.1] years; 940 [66.4%] male) included in the study, the 5-year overall survival rates were 94.2% in the laparoscopic group and 93.3% in the open surgery group (log-rank P = .64). Intention-to-treat analysis confirmed the noninferiority of the laparoscopic approach compared with the open approach (difference, 0.9 percentage points; 1-sided 97.5% CI, −1.6 to infinity). The 5-year cancer-specific survival rates were similar between the 2 groups (97.1% in the laparoscopic group and 97.2% in the open surgery group, log-rank P = .91; difference, −0.03 percentage points; 1-sided 97.5% CI, −1.8 to infinity). Per-protocol analysis results were consistent with the intention-to-treat results for overall and cancer-specific survival rates. CONCLUSIONS AND RELEVANCE The KLASS-01 trial revealed similar overall and cancer-specific survival rates between patients receiving laparoscopic and open distal gastrectomy. Laparoscopic distal gastrectomy is an oncologically safe alternative to open surgery for stage I gastric cancer.