Gastric cancer is a heterogeneous cancer, making treatment responses difficult to predict. Here we show that we identify two distinct molecular subtypes, mesenchymal phenotype (MP) and epithelial ...phenotype (EP), by analyzing genomic and proteomic data. Molecularly, MP subtype tumors show high genomic integrity characterized by low mutation rates and microsatellite stability, whereas EP subtype tumors show low genomic integrity. Clinically, the MP subtype is associated with markedly poor survival and resistance to standard chemotherapy, whereas the EP subtype is associated with better survival rates and sensitivity to chemotherapy. Integrative analysis shows that signaling pathways driving epithelial-to-mesenchymal transition and insulin-like growth factor 1 (IGF1)/IGF1 receptor (IGF1R) pathway are highly activated in MP subtype tumors. Importantly, MP subtype cancer cells are more sensitive to inhibition of IGF1/IGF1R pathway than EP subtype. Detailed characterization of these two subtypes could identify novel therapeutic targets and useful biomarkers for prognosis and therapy response.
The long-term course of Crohn's disease (CD) has never been evaluated in non-Caucasian population-based cohorts. The aim of the present study was to evaluate the longterm prognosis of Korean CD ...patients in the well-defined population-based Songpa-Kangdong inflammatory bowel disease cohort.
Outcomes of disease and their predictors were evaluated for 418 patients diagnosed with CD between 1986 and 2015.
During a median of 123 months, systemic corticosteroids, thiopurines, and anti-tumor necrosis factor (TNF) agents were administered to 58.6%, 81.3%, and 37.1% of patients, respectively. Over time, the cumulative probability of starting corticosteroids significantly decreased (p=0.001), whereas that of starting thiopurines and anti-TNFs significantly increased (both p<0.001). The cumulative probability of behavioral progression was 54.5% at 20 years, and it significantly decreased during the anti-TNF era. Intestinal resection was required for 113 patients (27.0%). The cumulative probabilities of intestinal resection at 1, 5, 10, 20, and 25 years after CD diagnosis were 12.7%, 16.5%, 23.8%, 45.1%, and 51.2%, respectively. Multivariable Cox regression analysis identified stricturing behavior at diagnosis (adjusted hazard ratio aHR, 2.70; 95% confidence interval CI, 1.55 to 4.71), penetrating behavior at diagnosis (aHR, 11.15; 95% CI, 6.91 to 17.97), and diagnosis of CD during the anti-TNF era (aHR, 0.51; 95% CI, 0.35 to 0.76) as independently associated with intestinal resection. The standardized mortality ratio among CD patients was 1.36 (95% CI, 0.59 to 2.68).
The long-term prognosis of Korean patients with CD is at least as good as that of Western CD patients, as indicated by the low intestinal resection rate. Moreover, behavioral progression and intestinal resection rates have decreased over the past 3 decades.
Photoresponsive transistor memories that can be erased using light-only bias are of significant interest owing to their convenient elimination of stored data for information delivery. Herein, we ...suggest a strategy to improve light-erasable organic transistor memories, which enables fast “photoinduced recovery” under low-intensity light. CdSe quantum dots (QDs) whose surfaces are covered with three different organic molecules are introduced as photoactive floating-gate interlayers in organic transistor memories. We determine that CdSe QDs capped or surface-modified with small molecular ligands lead to efficient hole diffusion from the QDs to the conducting channel during “photoinduced recovery”, resulting in faster erasing times. In particular, the memories with QDs surface-modified with fluorinated molecules function as normally-ON type transistor memories with nondestructive operation. These memories exhibit high memory ratios over 105 between OFF and ON bistable current states for over 10 000 s and good dynamic switching behavior with voltage-driven programming processes and light-assisted erasing processes within 1 s. Our study provides a useful guideline for designing photoactive floating-gate materials to achieve desirable properties of light-erasable organic transistor memories.
Background Gastric adenocarcinoma is an aggressive disease with frequent lymph node (LN) metastases for which lymphadenectomy results in a survival benefit. In the US, the National Comprehensive ...Cancer Network guidelines recommend D2 lymphadenectomy or a minimum of 15 LNs retrieved. However, retrieval of only 15 LNs is considered by most international guidelines as inadequate. We sought to evaluate the survival benefits associated with a more complete lymphadenectomy. Study Design An international database was constructed by combining gastric cancer cases from the Surveillance, Epidemiology, and End Results program database (n = 13,932) and the Yonsei University Gastric Cancer database (n = 11,358) (total n = 25,289). Kaplan-Meier survival analysis was performed along with Joinpoint analysis to obtain the optimal number of LNs to retrieve based on survival. Prognostic significance of number of nodes retrieved was then confirmed with univariate and multivariate analyses. Results Analysis for both mean and median survival yielded 29 LNs removed as the Joinpoint. This was confirmed with multivariate analysis, where 15 retrieved LNs cutoff fell out of the model and 29 retrieved LNs remained intact, with a hazard ratio of 0.799 (95% CI 0.759 to 0.842; p < 0.001). Stage-stratified Kaplan-Meier analysis for a cutoff point of 29 LNs also demonstrated a statistically significant improvement in survival. Conclusions Joinpoint analysis has allowed for the creation of a model demonstrating the point at which additional dissection would not provide additional benefit. This large international dataset analysis demonstrates that the maximal survival advantage is seen by performing a lymphadenectomy with a minimum of 29 LNs retrieved.
Background
Although various liver-directed treatment modalities, such as liver resection and radiofrequency ablation (RFA), have been applied to treat liver metastases from gastric cancer, optimal ...management of them remains controversial. In patients with liver metastasis from gastric cancer, we investigated the short- and long-term outcomes of liver resection and RFA and analyzed factors influencing survival.
Methods
A total of 98 gastric cancer patients with liver metastasis and no extrahepatic disease were treated by liver resection (
n
= 68) or RFA (
n
= 30). Short- and long-term outcomes were evaluated retrospectively for each of the liver-directed treatments.
Results
Severe complication rates did not differ between liver resection (18 %) and RFA (10 %) (
p
= 0.333). Only one treatment-related mortality occurred in the liver resection group. No statistically significant difference in survival was noted between the treatment groups. Median overall survival after liver resection was 24 months, with 3-year overall and progression-free survival rates of 40.6 % and 30.4 %, respectively. Median overall survival after RFA was 23 months, with 3-year overall and progression-free survival rates of 43.0 % and 37.4 %, respectively. Only the size of the metastases was shown to be an independent prognostic factor for gastric cancer patients with liver metastasis.
Conclusions
In select patients with liver metastasis from gastric cancer, liver resection and RFA showed satisfactory and comparable short- and long-term results. Thus, systemic chemotherapy may not be the only therapeutic option for patients with liver metastasis, and possible liver-directed treatment options for such patients should be considered on an individual basis.
The presence of ulcer in early gastric cancer (EGC) is important for the feasibility of endoscopic resection, only a few studies have examined the clinicopathological implications of endoscopic ulcer ...in EGC.
To determine the role of endoscopic ulcer as a predictor of clinical behaviors in EGC.
Data of 3,270 patients with EGC who underwent surgery between January 2005 and December 2012 were reviewed. Clinicopathological characteristics were analyzed in relation to the presence and stage of ulcer in EGC. Based on endoscopic findings, the stage of ulcer was categorized as active, healing, or scar. Logistic regression analysis was performed to analyze factors associated with lymph node metastasis (LNM).
2,343 (71.7%) patients had endoscopic findings of ulceration in EGC. Submucosal (SM) invasion, LNM, lymphovascular invasion (LVI), perineural invasion, and undifferentiated-type histology were significantly higher in ulcerative than non-ulcerative EGC. Comparison across different stages of ulcer revealed that SM invasion, LNM, and LVI were significantly associated with the active stage, and that these features exhibited significant stage-based differences, being most common at the active stage, and least common at the scar stage. The presence of endoscopic ulcer and active status of the ulcer were identified as independent risk factors for LNM.
Ulcerative EGC detected by endoscopy exhibited more aggressive behaviors than non-ulcerative EGC. Additionally, the endoscopic stage of ulcer may predict the clinicopathological behaviors of EGC. Therefore, the appearance of ulcers should be carefully evaluated to determine an adequate treatment strategy for EGC.
The purpose of this study is to compare the effect of diabetes control induced by Roux-en-Y gastrojejunostomy(RY) vs Billroth-I reconstruction(BI) after distal gastrectomy in patients with early ...gastric cancer(EGC) and type 2 diabetes(T2DM). Forty EGC patients with T2DM, aged 20-80 years, who were expected to undergo curative distal gastrectomy were randomized 1:1 to RY(n = 20) or BI(n = 20). Diabetes medication status, biochemical and hormonal data including blood glucose, HbA1c, insulin, C-peptide, HOMA-IR, ghrelin, leptin, GLP-1, PYY, and GIP were evaluated for 12 months after surgery. Although pre- and postoperative 12-month fasting and postprandial glucose levels did not show a significant difference, HbA1c, C-peptide, and HOMA-IR levels were significantly improved at 12 months after surgery in both BI and RY groups. Sixty percent of RY patients and 20% of BI patients decreased their medication satisfying FBS<126 mg/dL and HbA1c<6.5% and 5% of BI patients stopped their medication satisfying the criteria of FBS<126 mg/dL and HbA1c<6.0%. The improvement patterns were more sustainable with less fluctuation in RY than in BI. On hormonal analysis, ghrelin and leptin levels were decreased and PYY and GIP levels were increased at 12 months after surgery in both groups without significant difference according to the reconstruction type and diabetic improvement status except ghrelin. In gastric cancer surgery, RY reconstruction showed better and more durable diabetes control compared to BI during the first year after surgery. Gastric cancer surgery led to decreased ghrelin and leptin and increased PYY and GIP, which might have a role in improving insulin resistance and glucose homeostasis.
Background Little is known about the clinical and oncologic outcomes of endoscopic submucosal dissection (ESD) compared with surgery in elderly patients with early gastric cancer (EGC). Objective To ...evaluate the clinical and oncologic outcomes of ESD compared with surgery in elderly patients with EGC of an expanded indication. Design Retrospective study with propensity-matched analysis. Setting University-affiliated tertiary-care hospital, Seoul, South Korea. Patients A total of 518 patients 70 years of age or older with initial-onset EGC. Interventions ESD and surgery. Main Outcome Measurements Clinical outcomes, disease-free survival, and overall survival. Results In a propensity-matched analysis of 132 pairs, the length of hospital stay of the ESD group was shorter than that of the surgery group (median interquartile range, 4 3–4 vs 9 7–11 days; P < .001). Intensive care unit admission occurred in the surgery group only (7 patients 5.3%). Two surgery-related deaths occurred in the surgery group (1 splenic artery bleeding and 1 anastomosis site leakage). During follow-up, metachronous lesions developed more often in the ESD group than in the surgery group (12 vs 2 lesions, P = .004). All recurred lesions were successfully treated endoscopically except for 3 patients who refused additional treatment. Overall survival did not differ between the 2 groups ( P = .280). Limitations Nonrandomized, retrospective study. Conclusions ESD is a safe procedure in elderly patients with EGC. Although the risk of metachronous lesions is higher in patients who undergo ESD than in those who undergo surgery, overall survival did not differ between the patients who undergo ESD and surgery.
Genomic profiling can provide prognostic and predictive information to guide clinical care. Biomarkers that reliably predict patient response to chemotherapy and immune checkpoint inhibition in ...gastric cancer are lacking. In this retrospective analysis, we use our machine learning algorithm NTriPath to identify a gastric-cancer specific 32-gene signature. Using unsupervised clustering on expression levels of these 32 genes in tumors from 567 patients, we identify four molecular subtypes that are prognostic for survival. We then built a support vector machine with linear kernel to generate a risk score that is prognostic for five-year overall survival and validate the risk score using three independent datasets. We also find that the molecular subtypes predict response to adjuvant 5-fluorouracil and platinum therapy after gastrectomy and to immune checkpoint inhibitors in patients with metastatic or recurrent disease. In sum, we show that the 32-gene signature is a promising prognostic and predictive biomarker to guide the clinical care of gastric cancer patients and should be validated using large patient cohorts in a prospective manner.
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