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To date, few reports have investigated the genetic alterations and clinicopathological features in gastric cancer (GC) according to sex. In total, 2673 GC patients receiving curative surgery were enrolled. Among the 2673 GC patients, 1979 (74.0%) patients were male. After propensity-score matching, 846 patients were enrolled for the analysis, including 423 males and 423 females. There was no significant difference in the clinicopathological features between the sexes. Regarding the initial recurrence pattern, the males were more likely to develop tumor recurrence and liver metastasis than the females, especially in stage III GC. Regarding the molecular analysis, the males had higher PD-L1 expression than the females, especially in stage III GC. In addition, the patients aged ≥ 65 years had higher PD-L1 expression than the patients younger than 65 years. The multivariate analysis demonstrated that sex was among the independent prognostic factors affecting overall survival (OS) and disease-free survival (DFS). Among the patients with liver metastases, PD-L1 expression was more common among the aged male patients. The males were associated with more tumor recurrence and higher PD-L1 expression than the females, especially in stage III GC. For GC patients with liver metastases, PD-L1 testing is recommended, especially among aged male patients.

Various reconstruction methods have been performed following distal gastrectomy; however, each reconstruction method has its own advantages and disadvantages. This study aims to compare the long-term outcomes between Billroth-I (B-I) and Roux-en-Y (RY) reconstruction after distal gastrectomy for gastric cancer. A total of 459 patients who underwent distal gastrectomy (B-I: 166, RY: 293) were included. Postoperative endoscopic findings and biliary tract stone formation were compared between the two groups. At 1 year and 2 years postoperatively, gastric residue was more common in the RY group, gastritis was similar between groups, and bile reflux was more common in the B-I group. At 5 years postoperatively, gastric residue was similar between the groups, while gastritis and bile reflux were more common in the B-I group. Gastroesophageal reflux was more common in the B-I group at 1 year postoperatively, but gastroesophageal reflux became not significantly different between the groups at 2 and 5 years postoperatively. Gallstone formation was more common in the RY group and in patients aged ≥ 65 years. During long-term follow-up, RY reconstruction was associated with lower incidence of bile reflux and gastritis, and higher incidence of gallstone formation than B-I reconstruction. The incidence of gastric residue was more common in the RY reconstruction group in the early postoperative period and became not significantly different between the two groups over time. For aged patients with RY reconstruction, cholecystectomy is recommended concurrently as gastrectomy.

Objective The Lauren classification is an important histologic classification of gastric cancer (GC) with different biological behaviors between histologic types. Background To date, there are few reports on the genetic alterations and survival differences between different histologic types according to the Lauren classification. Methods In total, 433 GC patients undergoing surgery were enrolled. The clinicopathologic features, prognoses, and genetic alterations of the different Lauren types were compared. Results Diffuse-type GC was associated with a younger age, female predominance, more Borrmann type 3 and 4 tumors, more advanced pathologic tumor (T) and node (N) categories, more tumor recurrences (especially peritoneal recurrence), and worse 5-year overall survival and disease-free survival rates than intestinal-type GC and mixed-type GC. Regarding genetic alterations, mixed-type GC was associated with more TP53 mutations than intestinal-type GC and diffuse-type GC. Multivariate analysis demonstrated the following independent prognostic factors: age, Lauren classification, and pathologic T and N categories. Regarding mixed-type GC, diffuse-type major tumors were associated with more lymphovascular invasion, a more advanced N category and tumor, node, metastasis stage, and fewer PI3K/AKT pathway mutations than intestinal-type major tumors. Conclusions Diffuse-type GC had unfavorable clinicopathologic features and a worse prognosis than intestinal-type GC. For mixed-type GC, the clinicopathologic features and genetic alterations were different between intestinal-type major tumors and diffuse-type major tumors.

Background/aim Cervical cancer is one of the most common cancers worldwide and a major cause of cancer-related mortality among women. Previous studies have reported that microRNA-miR-187*, which is one of the non-coding parts of the genome producing small conserved ribonucleic acids, is associated with various cancers. In this study, we explored the function of miR-187* in cervical cancer cells. Materials and methods miR-187* mimic, WWOX reporter constructs, siRNA and overexpression constructs were transfected into SiHa cells to investigate the function and regulatory mechanisms of miR-187*. Results Exogenous miR-187* was found to increase the oncogenic phenotypes of SiHa cells. The tumor suppressor gene WWOX is a novel target of miR-187* in SiHa cells. WWOX siRNA suppressed endogenous WWOX expression and increased the oncogenic phenotypes of SiHa cells. Exogenous WWOX expression was able to suppress the oncogenic phenotypes of SiHa cells and rescue cells from miR-187*-induced migration. Conclusion miR-187* seems to enhance SiHa cervical cancer cell oncogenicity via suppression of the WWOX pathway.

Background Mucinous gastric carcinoma (MGC) is rare and often associated with an advanced stage. The clinicopathological features and prognosis of MGC and non-MGC (NMGC) are controversial. Methods In total, 2637 gastric cancer (GC) patients receiving curative surgery were enrolled. The clinicopathological features and genetic alterations were compared between patients with MGC and NMGC. Results Among the 2637 GC patients, 92 (3.5%) had MGC. After propensity score matching, compared to patients with NMGC, patients with MGC had more poorly differentiated tumors, medullary stromal reaction-type tumors, tumors with infiltrating Ming's classification, diffuse-type tumors, more abnormal preoperative serum carbohydrate antigen 19-9 levels, and more advanced T categories. After propensity score matching, there were no significant differences between MGC and NMGC regarding the initial recurrence patterns, 5-year overall survival (OS), and disease-free survival (DFS) rates. Multivariate analysis demonstrated that the MGC cell type is not an independent prognostic factor of OS and DFS. No significant differences in microsatellite instability status, Epstein-Barr virus infection, Helicobacter pylori infection, or genetic mutations were observed between MGC and NMGC. The expression of programmed death-ligand 1 (PD-L1) was significantly higher in MGC than that in NMGC. MGC was diagnosed at a more advanced stage compared with NMGC. Conclusion MGC itself was not an independent prognostic factor of worse survival. MGC was correlated with higher PD-L1 expression than NMGC, which may have a clinical impact on the treatment of MGC in the future.

The role of lncRNAs in the regulation of glutamate metabolism and metabolic reprogramming of pancreatic cancer (PC) during nutrient deprivation is largely unknown. Our study found that alpha-ketoglutarate (aKG) levels were significantly reduced in the absence of XLOC_006390. We subsequently confirmed that the decrease in aKG was mainly due to the downregulation of glutamate dehydrogenase 1 (GDH1) at the mRNA level. Therefore, we first screened transcription factors targeting the GDH1 gene promoter and confirmed that c-Myc regulates GDH1 transcription. c-Myc binds to the promoter of GDH1 and activates its transcription. Downregulation of GDH1 mRNA levels by XLOC_006390 deletion could be rescued by overexpression of c-Myc. Overexpression of XLOC_006390 promoted the protein stability of c-Myc by blocking its ubiquitination. Clinically, XLOC_006390 was positively correlated with the mRNA level of GDH1, and c-Myc positively regulated GDH1 gene expression, which was tightly associated with PC patient prognosis. The dysregulated lncRNA/c-Myc axis increased glutamate metabolism, promoting PC progression to a higher stage. Therefore, XLOC_006390/c-Myc may be a potential target for PC, and its abnormal activation also indicates the progression of PC.

BackgroundTo date, few reports have investigated genetic alterations and clinicopathological features in cardia and noncardia gastric cancer (GC).MethodsIn total, 435 GC patients receiving curative surgery were included. The clinicopathological features, recurrence patterns, prognoses and genetic alterations were compared between cardia and noncardia GC patients.ResultsAmong the 435 enrolled patients, 47 (10.8%) had cardia GC. Compared with noncardia GC, cardia GC was associated with more intestinal-type tumors and similar initial recurrence patterns and 5-year overall survival (OS; 50.8% vs. 50.5%, P = 0.480) and disease-free survival (DFS; 48.6% vs. 48.9%, P = 0.392) rates. For both intestinal-type GC and diffuse-type GC, the clinicopathological features and 5-year OS and DFS rates were not significantly different between the cardia and noncardia GC patients. Multivariable analysis showed that cardia GC was not an independent prognostic factor. Compared with noncardia GC, cardia GC was associated with increased PIK3CA amplification than in patients with intestinal-type GC and was associated with increased HER2 expression in patients with diffuse-type GC.ConclusionsCardia GC is not an independent prognostic factor. In cardia GC patients with intestinal-type GC, PIK3CA amplification was more common, and in those with diffuse-type GC, HER2 expression was more common. Targeted therapy may be beneficial for these patient subgroups.

Background: Epstein&ndash, Barr virus (EBV)-associated gastric cancer (GC) is one of four major gastric cancer types and is traditionally considered to be related to lymphoepithelioma-like GC. Few studies have investigated the clinical significance of EBV infection in intestinal/solid type, diffuse (poorly cohesive) type, and lymphoepithelioma-like GC. Methods: A total of 460 GC patients receiving curative surgery were enrolled. The clinicopathological features, genetic alterations and prognoses were compared between patients with and without EBV infection. Results: EBV-positive GC patients (n = 43) had more tumors located in the upper and middle stomach, more common in lymphoepithelioma-like carcinoma, more lymphoid stroma, fewer Helicobacter pylori infections, and higher programmed death-ligand 1 (PD-L1) expression than EBV-negative GC patients. For intestinal/solid type GC, EBV-positive tumors were more likely to be located in the upper and middle stomach, have more lymphoid stroma, fewer Helicobacter pylori infections, higher PD-L1 expression, and more liver metastases than EBV-negative tumors. For diffuse (poorly cohesive) type GC, EBV-positive tumors were more likely to be located in the upper stomach, and have more lymphoid stroma than EBV-negative tumors. For lymphoepithelioma-like GC, EBV-positive tumors had more PI3K/AKT pathway mutations than EBV-negative tumors. Conclusions: Intestinal/solid type GC patients with EBV-positive tumors were associated with higher PD-L1 expression and more liver metastases, while lymphoepithelioma-like GC patients with EBV-positive tumors had more PI3K/AKT pathway mutations. Immunotherapy and targeted therapy may be beneficial for these groups of patients. Routine EBV survey is recommended in GC.

Background Helicobacter pylori (HP) can induce epithelial cells and intestinal metaplasia with genetic damage that makes them highly susceptible to the development of gastric cancer (GC). Materials and Methods Between 2005 and 2010, 356 patients with gastric cancer who received curative surgery were enrolled. Analysis of HP, Epstein-Barr virus (EBV) infection, PIK3CA amplification, and mutation analysis of 68 mutations in eight genes using a mass spectrometric single-nucleotide polymorphism genotyping technology was conducted. The clinicopathological characteristics of patients with or without HP infection were compared. Results Among the 356 patients, 185 (52.0%) had HP infection. For intestinal-type GC, patients with HP infection were more likely to be younger and had fewer PI3K/AKT pathway genetic mutations than those without HP infection. For diffuse-type GC, patients with HP infection were characterized by less male predominance, less lymphoid stroma, fewer microsatellite instability-high tumors, and fewer PI3K/AKT pathway genetic mutations than those without HP infection. Patients with HP infection had less tumor recurrence and a better 5-year overall survival (87.7% vs. 73.9%, p = .012) and disease-free survival (64.1% vs. 51.3%, p = .013) than those without HP infection, especially for intestinal-type GC. For EBV-negative GC, patients with HP infection had fewer PI3K/AKT pathway mutations and a better 5-year overall survival and disease-free survival than those without HP infection. Multivariate analysis demonstrated that HP infection was an independent prognostic factor regarding overall survival and disease-free survival. Conclusion Patients with GC with HP infection were associated with fewer PI3K/AKT pathway genetic mutations and better survival than those without HP infection, especially for EBV-negative and intestinal-type GC. Implications for Practice Patients with gastric cancer with Helicobacter pylori (HP) infection had fewer PI3K/AKT pathway genetic mutations, less tumor recurrence, and better survival than those without HP infection, especially for Epstein-Barr virus (EBV)-negative and intestinal-type gastric cancer. HP infection is an independent prognostic factor regarding overall survival and disease-free survival. Future in vivo and in vitro studies of the correlation among HP infection, PI3K/AKT pathway, and EBV infection in gastric cancer are required.

Objective: The tumor suppressor gene phosphatase and tensin homolog (PTEN) was reported to inhibit the growth and invasion of gastric cancer (GC) via the downregulation of focal adhesion kinase (FAK). To date, the clinical implication of PTEN and FAK expression in GC has not been well addressed. Methods: A total of 200 GC patients receiving curative surgery were enrolled. The clinicopathologic features according to the expression of PTEN and FAK protein using immunohistochemical staining were compared among patients. Results: Patients with high PTEN expression were more likely to have smaller tumor size, more well- and moderately differentiated tumors, a more superficial gross appearance, less scirrhous stromal reactions, more likely to have high FAK expression, and have less advanced pathologic tumor (T) category, node (N) category, and tumor, node, metastasis (TNM) stage and more distant metastases than patients with low PTEN expression. Multivariate analysis showed that PTEN/FAK expression status is an independent prognostic factor affecting overall survival (OS) and disease-free survival (DFS). Patients with PTEN(high)/FAK(low) had better OS and DFS, followed by those with PTEN(high)/FAK(high), those with PTEN(low)/FAK(low), and those with PTEN(low)/FAK(high) (OS: 83.3% versus 58.0% versus 46.2% versus 26.5%, respectively, P < 0.001; DFS: 83.3% versus 55.8% versus 30.8% versus 24.4%, respectively, P < 0.001). Conclusions: GC patients with high PTEN expression were more likely to have fewer tumor recurrences and a better prognosis than those with low PTEN expression. PTEN and FAK may have opposing effects on GC patient survival. Our results may have clinical impact on treatment of GC patients.

BACKGROUND Lymph node (LN) metastasis is one of the independent prognostic factors of gastric cancer (GC). The difference in survival rates and initial recurrence patterns in patients with node-positive GC with retrieved LN numbers greater than or less than 16 is worthy of further study. METHODS A total of 1314 patients with node-positive GC were enrolled. The clinicopathological characteristics, retrieved LN numbers, adjuvant chemotherapy, initial recurrence patterns, and survival differences between serosa-negative and serosa-positive GC were investigated. RESULTS For serosa-negative GC, patients with retrieved LN numbers ≥16 were associated with fewer tumor recurrences, locoregional recurrences, distant metastases, and better 5-year overall survival (OS) rates and disease-free survival (DFS) rates. For serosa-positive GC, patients with retrieved LN numbers ≥16 were associated with similar locoregional and distant metastasis and similar 5-year OS and DFS rates compared with those with retrieved LN numbers

Few reports have investigated different genetic alterations according to age in various cancers. In total, 1749 GC patients receiving curative surgery were enrolled. The clinicopathological features, and prognoses were compared between younger (

In this work, through utilizing the mixed-ligand synthesis method, two coordination polymers (CPs) based on Co(II), namely, {[Co(μ-ppda)(μ-pbmeix)]·H2O}n (2) and [Co(μ-opda)(μ-pbmeix)0.5]n (1), have been triumphantly formed from 1,4-bis(2-methylimidazol-1-ylmethyl)benzene (pbmeix), a semi-rigid ligand with Co(II) nitrate salts and distinct carboxylic acid co-ligands (o/ppda = 1,2-/1,4-phenylenediacetate). For treatment of pancreatic cancer, the as-generated compounds’ inhibitory activity against the viability of cancer cell was determined by the Cell Counting Kit-8 (CCK-8) assay. The above compounds’ suppression effect against the cells invasion and migration ability was investigated by the trans-well detection. The real time reverse transcription-polymerase chain reaction (RT-PCR) subsequently was employed to test the VEGF signaling pathway activation. Eventually, the cancer cells apoptosis levels after treating with above compound were assessed via detecting the BCL-2 protein expression level. Furthermore, results from molecular docking simulation indicate that complex 1 not only exhibits relatively lower affinity energy, but also forms more binding interactions in comparison to complex 2 when binding to a given target protein. Complex 1 was much superior to complex 2 on treating pancreatic cancer via suppressing the cancer cell invasion, migration and viability ability.

Background Aberrant DNA methylation is involved in gastric carcinogenesis and may serve as a useful biomarker in the diagnosis and detection of gastric cancer (GC) recurrence. Results A total of 157 patients who received surgery for GC were enrolled in the present study. A genome-wide methylation analysis was performed in tumor and adjacent normal tissues for the discovery set of 16 GC patients; the top three hypermethylated CpG sites of DNA promoters were selected for validation in tissue and plasma samples for the validation set of 141 GC patients. The frequencies of the top three hypermethylated genes in available patient tissues (n = 141) and plasma samples (n = 106) were 41.8% and 38.7%, respectively, for ADAM19; 40.4% and 42.5%, respectively, for FLI1; and 56.7% and 50.9%, respectively, for MSC. In both tissue and plasma samples, FLI1 hypermethylation was associated with more advanced GC and liver and distant lymphatic metastasis, and ADAM19 hypermethylation was associated with more stage IV GC. In plasma samples, MSC hypermethylation was more common in non-superficial type GC than samples without MSC hypermethylation. In both tissue and plasma samples, patients with methylation of all the three genes had significantly more liver metastases, distant lymphatic metastases, and paraaortic lymph node metastases than patients with two or fewer hypermethylated genes. The survival analysis showed that only for stage III GC, patients with hypermethylation of two or three genes had a worse 5-year disease-free survival rate than those with hypermethylation of one or none of the three genes. Subgroup analysis showed that FLI1 hypermethylation in both tissue and plasma samples was associated with liver metastasis in MSI−/EBV− GC, and MSC hypermethylation in tissue samples was correlated with liver metastasis in MSI+ or EBV+ GC. Patients with FLI1 hypermethylation in plasma samples had a significantly worse 5-year disease-free survival rate than those without FLI1 hypermethylation in MSI−/EBV− GC. FLI1 hypermethylation was an independent prognostic factor affecting the overall survival and disease-free survival in both tissue and plasma samples. Conclusions DNA methylation is a useful biomarker for predicting tumor recurrence patterns and GC patient survival.

Robot-assisted gastrectomy has been reported to be a safe alternative to both conventional laparoscopy and the open approach for treating early gastric carcinoma. Currently, there are a limited number of published reports on this technique in the literature. We assessed the current status of robotic and laparoscopic surgery in the treatment of gastric cancer and compared the operative outcomes, learning curves, and oncological outcome of the two approaches. Robotic gastrectomy offers benefits that include increased ease of performing D2 lymph node dissection and reduced blood loss compared with laparoscopic gastrectomy. However, the operative time is longer, and robotic gastrectomy is more costly for the patients. Regarding to the operative and oncological outcomes, there appears to be no significant differences between laparoscopic and robotic gastrectomies after the surgeon overcomes the associated learning curves. Sharing the available knowledge regarding laparoscopic and robotic gastrectomies could shorten these learning curves. For elder patients, minimally invasive surgery that decreases the postoperative recovery time should be considered the preferred treatment. Prospective randomized studies are required to compare the surgical and oncological outcomes among laparoscopic, robotic, and open surgeries for both early and advanced gastric cancer.

Signet-ring cell carcinoma (SRC) in advanced gastric cancer (GC) is often associated with more invasiveness and a worse prognosis than other cell types. The genetic alterations associated with gastric carcinogenesis in SRC are still unclear. In this study, 441 GC patients receiving curative surgery for GC between 2005 and 2013 were enrolled. The clinicopathological characteristics and genetic alterations of GC patients with and without SRC were compared. Among the 441 GC patients, 181 had SRC. For early GC, patients with SRC had more tumors located in the middle and lower stomach, more infiltrating tumors and better overall survival (OS) rates than those without SRC. For advanced GC, patients with SRC had more scirrhous type tumors, more PIK3CA amplifications, fewer microsatellite instability-high (MSI-H) tumors, more peritoneal recurrences and worse 5-year OS rates than those without SRC. For advanced GC with SRC, patients with peritoneal recurrence tended to have PD-L1 expression. For advanced GC without SRC, patients with liver metastasis tended to have PD-L1 expression, PI3K/AKT pathway mutations, TP53 mutations and MSI-H tumors. For advanced GC, PD-L1 expression was associated with peritoneal recurrence in SRC tumors, while non-SRC tumors with liver metastasis were likely to have PI3K/AKT pathway mutations, TP53 mutations and PD-L1 expression, immunotherapy and targeted therapy may be beneficial for these patients.

With the progression of molecular techniques, the detection of circulating plasma DNA (cpDNA) is clinically feasible. However, the role of the cpDNA levels in gastric cancer is not well understood. This study assessed the mutational profile in primary tumors and clarified the clinical utility of quantitative and qualitative cpDNA alterations in 277 patients with advanced gastric cancer. The concentrations of cpDNA were measured by TaqMan qPCR, and 68 mutations in 8 genes were studied for cpDNA mutations. The median cpDNA concentrations in patients with stages I, II, and III gastric cancer were 3979, 3390 and 4278 copies/mL, respectively, and increased to 11,380 copies/mL in patients with Stage IV gastric cancer (p < 0.001). Among the 35 patients harboring cpDNA mutations, Stage IV patients (100%) were more likely to display high cpDNA levels than were Stage I (33.3%), II (75%) and III patients (66.7%) (p = 0.037). Patients displaying high cpDNA levels were more likely to experience peritoneal recurrence and exhibited significantly lower 5-year overall survival rates (39.2% vs. 45.8%, p = 0.039) than did patients displaying low cpDNA levels. Only for late stage (Stages III or IV) gastric cancer, patients harboring cpDNA mutations were more likely to experience vascular invasion (20% vs. 2.4%, p = 0.036) and exhibited a lower 5-year overall survival rate than did those lacking cpDNA mutations (5.6% vs. 31.5%, p = 0.028). High cpDNA levels are associated with peritoneal recurrence and poor prognosis in patients with advanced gastric cancer; harboring cpDNA mutations is associated with poor prognosis among patients with late stage gastric cancer.

Atrial fibrillation (AF) is currently recognized as one of the most common cardiac arrhythmias worldwide, with the increasing prevalence that has been estimated to be as high as 9% among the elderly. Health-related quality of life (HRQoL) has become an important patient-centered health outcome measurement, but the impacts created by AF and other arrhythmias with similar symptoms, such as frequent atrial and ventricular premature contractions (APCs and VPCs, defined as ≥ 3 beats/5 minutes), have not been extensively evaluated. The Yilan Study is a population-based community health survey, which in part aims to evaluate the prevalence and impacts of these arrhythmias on the HRQoL in a community dwelling elderly population. A total of 1,732 citizens from the Yilan, Taiwan, aged 65 years or older (45.8% male) were enrolled and visited at their homes, where HRQoL was measured utilizing the Short Form-12 Health Survey. Each participant's heart rhythm was recorded with an electrocardiographic monitor for 5 minutes. The results disclosed that the prevalence of AF of this aged population was 5.8%, similar to the mean global prevalence. Besides, the prevalence of frequent APCs and frequent VPCs in these elderly people were 7.1% and 5.5%, respectively. After multiple regression analysis, elderly people with AF had lower scores in the physical component of HRQoL, while those elderly people with frequent VPCs had lower scores in the mental component. Ultimately, these findings can provide additional useful and population-specific information about AF, and assist medical professionals in designing more effective strategies for cardiac arrhythmia treatments.

// Wen-Liang Fang 1, 2 , Kuo-Hung Huang 1, 2, 3 , Yuan-Tzu Lan 2, 4 , Chien-Hsing Lin 5 , Shih-Ching Chang 2, 4, * , Ming-Huang Chen 2, 6 , Yee Chao 2, 6 , Wen-Chang Lin 7, 8 , Su-Shun Lo 2, 9 , Anna Fen-Yau Li 2, 10 , Chew-Wun Wu 1, 2 , Shih-Hwa Chiou 3, 11, 12 , Yi-Ming Shyr 1, 2, * 1 Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei City, Taiwan 2 School of Medicine, National Yang-Ming University, Taipei City, Taiwan 3 Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei City, Taiwan 4 Division of Colon & Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei City, Taiwan 5 Genome Research Center, National Yang-Ming University, Taipei City, Taiwan 6 Division of Hematology and Oncology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan 7 Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan 8 Institute of Biotechnology in Medicine, National Yang-Ming University, Taipei, Taiwan 9 National Yang-Ming University Hospital, Yilan City, Taiwan 10 Department of Pathology, Taipei Veterans General Hospital, Taipei City, Taiwan 11 Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei City, Taiwan 12 Institute of Pharmacology, National Yang-Ming University, Taipei City, Taiwan * These authors have contributed equally to this work Correspondence to: Shih-Ching Chang, e-mail: changsc@vghtpe.gov.tw Yi-Ming Shyr, e-mail: ymshyr@vghtpe.gov.tw Keywords: PI3K/AKT pathway, PIK3CA amplifications, recurrence pattern, diffuse-type, prognosis Received: August 08, 2015 Accepted: December 05, 2015 Published: December 17, 2015 ABSTRACT Mutations in genes involved in the PI3K/AKT pathway and amplifications of the PIK3CA gene in gastric cancer and their associations with clinicopathological characteristics and EBV infection were analyzed in this study. A total of 431 patients with gastric adenocarcinomas were enrolled, and 39 mutation hotspots were evaluated in these patients using MALDI-TOF mass spectrometry were analyzed. PIK3CA amplifications were analyzed using real-time quantitative PCR. Regarding patients with intestinal-type gastric cancer, those with mutations in PI3K/AKT pathway genes were also more likely to have tumors located in the lower-third of the stomach than were those without mutations. Regarding patients with diffuse-type gastric cancer, those with PI3K/AKT pathway mutations were more likely to have tumors located in the upper-third of the stomach and to have more hematogenous metastases, particularly in the liver and lungs, than were patients without such mutations (22.2% vs. 4.5%). No significant survival difference was observed between patients with vs. without PI3K/AKT pathway mutations. Mutations in PI3K/AKT pathway genes were associated with hematogenous metastasis in patients with diffuse-type gastric cancer. Only when the tumors were located in the middle-third of stomach, tumor with mutations of the PIK3CA gene or mutations of the PI3K/AKT pathway genes were associated with more EBV infection than those without mutations. Patients with PIK3CA amplifications were more likely to have diffuse-type and poorly differentiated gastric cancers and were more likely to experience peritoneal recurrence compared with those without PIK3CA amplifications. Even upon subgroup analysis, PI3KCA amplifications were found to not affect the patients’ outcomes.

Objectives: This study aimed to investigate the long-term risk of stroke in adult patients with spinal deformity. Specifically, the study addressed the possible protective effect of surgery for spinal deformity against stroke. Methods: Using the National Health Insurance Research Database (NHIRD), a monopolistic national database in Taiwan, this retrospective cohort study analyzed the incidence of stroke in patients with adult spinal deformity (ASD) in a 11-year period. A total of 13,503 patients, between 55 and 75 years old, were identified for the diagnosis of ASD. The patients were grouped into two: the surgical group (n = 10,439) who received spinal fusion surgery, and the control group (n = 2124) who received other medical treatment. The incidence rates of all subsequent cerebrovascular accidents, including ischemic and hemorrhagic strokes, were calculated. Hazard ratios for stroke were calculated use a full cohort and a propensity score matched cohort. Adjustments for co-morbidities that may predispose to stroke, including hypertension, diabetes mellitus, arrhythmia and coronary heart disease were conducted. Kaplan-Meier and Cox regression analyses were performed to compare the risk of stroke between the two groups. Results: During the total observation period of 50,450 person-years, the incidence rate of stroke in the surgical group (15.55 per 1000 person-years) was significantly lower than that of the control group (20.89 per 1000 person-years, p &lt, 0.001). Stroke was more likely to occur in the control group than in the surgical group (crude hazard ratio 1.34, p &lt, 0.001, adjusted HR 1.28, p &lt, 0.001, by a propensity score matched model). Conclusions: In this national cohort of more than 13,000 ASD patients covering 10 years, stroke was approximately 25% less likely to happen in patients who underwent spinal fusion surgery than those who received medical management. Therefore, spinal fusion surgery may provide a protective effect against stroke in adult patients with spinal deformity.

Endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) is an effective alternative treatment for early gastric cancer. However, a major concern is the likelihood of lymph node metastasis. From December 1987 to December 2006, 391 patients who underwent curative surgery for gastric cancer with mucosal (T1a, n = 265) or submucosal (T1b, n = 126) invasion and a retrieved lymph node number ≧ 15 were enrolled. The frequency and risk factors of lymph node metastasis were analyzed. The frequency of lymph node metastasis was 4.9 % in T1a lesions and 21.4 % in T1b lesions. Although the depth of submucosal tumor invasion was2 mm, there was a 28.6 % chance of lymph node metastasis. A T1b lesion, i.e., the width of the submucosal tumor invasion was5 mm, resulted in fewer lymph node metastases than lesions5 mm in width. Multivariate analysis demonstrated that Lauren's diffuse type and lymphatic invasion were independent risk factors for lymph node metastasis in T1a lesions, while lymphatic invasion was the strongest risk factor for lymph node metastasis in T1b lesions. EMR/ESD is a good alternative for T1a intestinal type adenocarcinoma without lymphatic invasion. Surgical resection is necessary for patients with T1b gastric cancer with lymphatic invasion.

Adenosquamous carcinoma of the stomach is a very rare disease, consisting of less than 0.4 % of all stomach cancer. From 1991 to 2013, a total of 2800 patients received gastrectomy for gastric cancer at Taipei Veterans General hospital. Among them, seven patients (0.25 %) diagnosed as adenosquamous carcinoma were enrolled. The clinicopathologic characteristics and prognosis were analyzed. The mean age of the seven patients was 62.3 years-old. There were 5 males and 2 females. Six patients were stage III disease and one patient was stage IV disease. Four patients finally died of gastric cancer. Only one patient had no recurrence until death. Among the seven patients, adenocarcinoma component comprises the majority of the metastatic lymph node in 6 patients (85.7 %). The only one patient with major squamous cell carcinoma component in metastatic lymph node had no tumor recurrence till death. Adenosquamous carcinoma of stomach is a rare disease and is associated with a poor prognosis. The component of adenocarcinoma and squamous cell carcinoma in the metastatic lymph node may influence the prognosis.

The disabling pathophysiologic effects of lipid and neuroprotective effects of statins have recently been demonstrated for acute spinal cord injuries in animal models. This large scale population-based study aimed to investigate the effect hyperlipidemia and the use of statins in patients with lumbar spine injury. The National Health Insurance Research Database of Taiwan was used to identify patients with lumbar spine injury. A total of 2844 patients were grouped into three: no hyperlipidemia, hyperlipidemia using low-dose of statins (≤90 of the defined daily dosage (DDD)), and severe hyperlipidemia using high-dose of statins (&gt, 90 DDD). A Cox multiple regression model was used to compare the incidence rates of disability among the three groups. The results showed that patients with hyperlipidemia appeared a higher risk of permanent disability (adjusted HR = 1.38, p = 0.28). In subgroup analysis, patients with severe hyperlipidemia had a higher risk of disability (adjusted HR = 3.1, p &lt, 0.004), whereas hyperlipidemia using low-dose statins had a similar risk of permanently disability (adjusted HR = 0.83, p = 0.661). Hyperlipidemia adversely affected the neurological outcomes of lumbar spinal injury. Statins may have the potential to reverse this higher risk of disability. However, this beneficiary effect of statins only existed in patients using a lower dose (≤90 DDD).

Atopic dermatitis is a prevalent dermatologic disease in children. Corticosteroid is an important treatment but side effects caused by long-term and excessive use heavily concern patients. Traditional Chinese medicine (TCM) is potentially an alternative treatment and might cause less adverse effects. This nationwide retrospective cohort study aimed to examine the hypothesis that TCM use is associated with lower exposure to corticosteroid.Children under 12 years of age with ICD-9 codes 691.8 and 692.x were identified as atopic dermatitis patients from 2007/1/1 to 2007/12/31. Corticosteroid use was compared between TCM users and non-users for one-year follow-up by using a general estimation equation model with propensity-score matching.A total of 9012 TCM users were identified and the use of corticosteroid after treatment was compared with matched TCM non-users. Use of TCM significantly reduced exposure to corticosteroids after 1-year follow-up. Among TCM users, the exposure to any corticosteroids was lower (42.1% reduction in TCM users versus 34.5% increase in TCM non-users, relative risk: 0.36; p-Value0.001), the duration was shorter (relative risk for using corticosteroid more than 14 days: 0.37; p-Value0.001), and the rate of frequent visits with steroid prescription was also lower. CHM was the most commonly used TCM modality (98.5% of all visits) and Xiao-Feng-San was the most commonly used CHM (33% of all prescriptions) with extensive coverage for pathogenesis of atopic dermatitis.Lower use rate of corticosteroid can be found after TCM treatment, which can be considered as an integrative therapy for atopic dermatitis. Further studies are warranted on the basis of this study.

Objectives: Robotic gastrectomy has become increasingly popular in the treatment of gastric cancer, especially in Asian countries. The use of indocyanine green fluorescence has been reported in lymphatic mapping for gastric cancer in laparoscopic gastrectomy; however, there have been few reports regarding the use of indocyanine green in robotic gastrectomy. Methods: From January 2011 to March 2016, a total of 79 patients underwent robotic gastrectomy for gastric cancer. Among them, intraoperative subserosal injection (n = 9) or preoperative submucosal injection (n = 5) of indocyanine green with near-infrared imaging was performed in 14 patients, and the other 65 patients underwent robotic gastrectomy without the use of indocyanine green. Results: There was no significant difference in the operative time, total number of retrieved lymph nodes, operative blood loss, and postoperative hospital stay between the patients who underwent robotic gastrectomy with or without indocyanine green fluorescence. For each lymph node station, there was significantly more number of retrieved lymph nodes in the indocyanine green group than in the no-indocyanine green group at the greater curvature side of the low body (#4d) to the infrapyloric region (#6) of the stomach. Five of the 14 patients who received an indocyanine green injection for lymphatic mapping had lymph node metastasis, and metastatic lymph nodes were located in the lymph node stations as detected by indocyanine green fluorescence during surgery. Conclusion: Indocyanine green fluorescence with near-infrared imaging is feasible and is a promising method of lymphatic mapping in robotic gastrectomy for gastric cancer. In future studies, larger patient numbers and long-term follow-up are required.

Gastric cancer is the second leading cause of cancer-related death worldwide. Herein, we investigated the role of transcription factor Yin Yang 1 (YY1), a multi-functional protein, in tumorigenesis of gastric cancer cells. Results showed that YY1 contributed to gastric carcinogenesis of SC-M1 cells including growth, viability, and abilities of colony formation, migration, invasion, and tumorsphere formation. Levels of pluripotency genes CD44, Oct4, SOX-2, and Nanog were also up-regulated by YY1 in SC-M1 cells. Additionally, the 3'-untranslated region (3'-UTR) of YY1 mRNA was the target of microRNA-34 (miR-34) family consisting of miR-34a, miR-34b, and miR-34c. Overexpression of miR-34 family suppressed carcinogenesis through down-regulation of YY1 in NUGC-3 gastric cancer cells scarcely expressing miR-34 family. Alternatively, knockdown of miR-34 family promoted tumorigenesis via up-regulation of YY1 in SC-M1 and AZ521 gastric cancer cells with higher levels of miR-34 family. The miR-34 family also affected tumorsphere ultra-structure and inhibited the xenografted tumor growth as well as lung metastasis of SC-M1 cells through YY1. Expressions of miR-34a and miR-34c in gastric cancer tissues of patients were lower than those in normal tissues. Taken together, these results suggest that miR-34 family-YY1 axis plays an important role in the control of gastric carcinogenesis.

Bariatric surgery has been adapted to the management of morbid obesity, leading to not only loss of body weight but also improvement of type 2 diabetes mellitus (DM). The goal of our study was to evaluate the effect of gastrectomy in gastric cancer patients with type 2 DM. From 1989 to 2011, a total of 69 gastric cancer patients receiving curative surgery were enrolled in this study. They were diagnosed with type 2 DM preoperatively and all are alive without tumor recurrence. The clinical characteristics were compared between groups with improved or unimproved DM, and groups were also analyzed based on the extent of gastrectomy and different reconstruction methods. Of the 69 patients, 58 received subtotal gastrectomy and 11 received total gastrectomy. The frequency of DM improvement was significantly higher after total gastrectomy than subtotal gastrectomy (81.8 vs. 36.2 %; p = 0.007). Patients with DM duration of less than 5 years tended to experience DM improvement after surgery more frequently than patients with DM duration of more than 5 years (p = 0.028). Roux-en-Y esophagojejunostomy (R-Ye) led to a higher rate of DM improvement than did R-Y gastrojejunostomy (R-Yg), especially in patients with DM duration more than 5 years. Among patients receiving duodenal bypass after gastrectomy, R-Ye was associated with a higher frequency of DM improvement than R-Yg and B-II. The extent of gastrectomy rather than the reconstruction method played an important role in DM improvement after curative surgery for gastric cancer.

Background: Liver trauma is the main cause of death arising from blunt abdominal injury. Nonoperative management (NOM) has been advocated to be a safe option for stable patients who have suffered liver trauma. This study used a population-based dataset to illustrate the incidence of liver trauma, its various causes and treatment, and outcomes. Methods: Information about all patients with any ICD-9-CM coded as liver injury was retrieved as part of a claims dataset for the years 2007 and 2008 from the database maintained in the Bureau of National Health Insurance in Taiwan. Thereafter, statistical analyses were conducted to discover the incidence, mortality rate, percentage of patients receiving NOM, and the association between variables such as age, gender, injury mechanisms, associated injuries, and outcome. Results: A total of 3196 liver trauma patients were admitted in 2007 and 2008, resulting in 264 deaths. The incidence rate is 13.9/100,000 population. The highest incidence rate was in the age 15–24 years group, 25.9/100,000 population; the highest mortality rate was in the age 75–84 years group, 2.1/100,000 population. Additionally, rural residents possessed a higher incidence and mortality rate than urban residents (15.9/100,000 population vs. 12.2/100,000 population and 1.4/100,000 population vs. 1.0/100,000 population). By using logistic regression, the mortality rate was significantly higher in the groups with patients aged >64 years, renal failure or liver cirrhosis, with head or chest, or other abdominal injury. If a patient received a hepatic or abdominal operation, this was retrospectively found to be associated with increased mortality risk (4.731 times, p US$660 were found to have a higher mortality risk (2.209 times, p 64 years group, pedestrians hit in motor-vehicle accidents, renal failure or liver cirrhosis, with head or chest, or other abdominal injury.

Gastric carcinoma is one of the most common malignancies and the second most lethal cancer worldwide. The mechanisms underlying aggressiveness of gastric cancer still remain obscure. c-Myc promoter binding protein 1 (MBP-1) is a negative regulator of c-myc expression and ubiquitously expressed in normal human tissues. It is produced by alternative translation initiation of α-enolase gene. Both MBP-1 and α-enolase are involved in the control of tumorigenesis including gastric cancer. MicroRNAs (miRNAs) are involved in tumorigenesis and could have diagnostic, prognostic and therapeutic potential. In this study, whether miRNAs modulate tumorigenesis of gastric cancer cells through targeting MBP-1 was evaluated. We found that miR-363 targets 3'-untranslated region of human MBP-1/α-enolase messenger RNA. The exogenous miR-363 promotes growth, viability, progression, epithelial-mesenchymal transition and tumorsphere formation of SC-M1 gastric cancer cells through downregulation of MBP-1, whereas the knockdown of endogenous miR-363 suppresses tumorigenesis and progression of SC-M1 cells via upregulation of MBP-1. The miR-363/MBP-1 axis is also involved in the control of carcinogenesis in KATO III and SNU-16 gastric cancer cells. Furthermore, miR-363 induces the xenografted tumor growth and lung metastasis of SC-M1 cells through MBP-1 in vivo. Taken together, these results suggest that miR-363 plays an important role in the increment of gastric carcinogenesis via targeting MBP-1.

The impact of body mass index (BMI) on the outcome of advanced gastric cancer surgery is controversial. Between December 1987 and December 2006, a total of 947 advanced gastric cancer patients receiving curative resection with retrieved lymph node number15 were studied and divided into three groups according to BMI (25, 25-30, and30 kg/m(2)).With regard to comorbidities present prior to surgery, higher BMI patients were more likely to have heart disease, type 2 diabetes, and hypertension than lower BMI patients. Compared with BMI25 kg/m(2), higher BMI patients had longer operative time and more surgery-related morbidity. Multivariate Cox proportional-hazard analysis showed that age, pathological T and N categories, and lymphovascular invasion were independent prognostic factors. The initial recurrence patterns, 5-year overall survival, and cancer-specific survival were similar among the three groups.Only in stage III gastric cancer with BMI less than 25 kg/m(2) patients receiving total gastrectomy had a more advanced pathological N category and a worse prognosis compared to those receiving subtotal gastrectomy. Higher BMI was associated with longer operative time and more surgery-related morbidity than lower BMI. BMI alone is not an independent prognostic factor.

Long-term morbidities can develop after traumatic brain injury (TBI). Some studies have suggested that the risk of stroke is higher after TBI, but the association between concussion and stroke remains unclear. Using a national cohort, the authors analyzed the incidence of both hemorrhagic and ischemic strokes in patients with previous concussion. A representative cohort of approximately one million people was followed up for four years. Patients with new-onset concussion were identified (n = 13,652) as the concussion group. Subsequently, the incidence rates of later stroke events in the concussion group were compared to a sex-, age- and propensity score–matched comparison group (n = 13,652). The overall incidence rate of stroke in the concussion group was higher than that of the comparison group (9.63 versus 6.52 per 1000 person-years, p < 0.001). Significantly higher stroke risk was observed in the concussion group than in the comparison group (crude hazard ratio 1.48, p < 0.001; adjusted HR 1.65, p < 0.001). In the concussion group, the cumulative incidence rates of both ischemic stroke and hemorrhagic stroke were higher than those of the comparison group (8.9% vs. 5.8% and 2.7% vs. 1.6%, respectively, both p < 0.001). Concussion is an independent risk factor for both ischemic and hemorrhagic strokes. Prevention and monitoring strategies of stroke are therefore suggested for patients who have experienced concussion.

The association between osteoporosis and cardiovascular diseases has been demonstrated. Higher cardiovascular risk has also been correlated with vertebral fractures. However, the association between osteoporotic vertebral fracture and the possibly higher risk of stroke remains uncertain. This study aimed to evaluate the incidence, risk, and type of stroke in patients with osteoporotic vertebral fracture. Patients with osteoporotic vertebral fracture were identified (n = 380) and 10 age- and sex-matched controls per case (comparison group, n = 3795) were chosen from a nationwide representative cohort of 999,997 people from 1998 to 2005. Both groups were followed-up for stroke events for 3 years, matched by propensity scores with adjustments for covariates such as comorbidities (ie, hypertension, diabetes, arrhythmia, or coronary heart diseases) and exposure to medications (ie, aspirin, lipid lowering drug, or nitrates), and assessed by Kaplan-Meier and Cox regression analyses. The incidence rate of stroke in the osteoporotic vertebral fracture group (37.5 per 1000 person-years; 95% confidence interval [CI], 27.5–51.2) was significantly higher than in the comparison group (14.0 per 1000 person-years; 95% CI, 12.0–16.4, p

Asthma is one of the most common allergic respiratory diseases around the world and places great burden on medical payment. Chinese herbal medicine (CHM) is commonly used for Taiwanese children to control diseases. The aim of this study is to analyze the CHM prescriptions for asthmatic children by using a nationwide clinical database. The National Health Insurance Research Database (NHIRD) was used to perform this study. Medical records from 1997 to 2009 with diagnosis with asthma made for children aged 6 to 18 were included into the analysis. Association rule mining and social network analysis were used to analyze the prevalence of single CHM and its combinations. Ma-Xing-Gan-Shi-Tang (MXGST) was the most commonly used herbal formula (HF) (20.2% of all prescriptions), followed by Xiao-Qing-Long-Tang (13.1%) and Xing-Su-San (12.8%). Zhe Bei Mu is the most frequently used single herb (SH) (14.6%), followed by Xing Ren (10.7%). MXGST was commonly used with Zhe Bei Mu (3.5%) and other single herbs capable of dispelling phlegm. Besides, MXGST was the core formula to relieve asthma. Further studies about efficacy and drug safety are needed for the CHM commonly used for asthma based on the result of this study.

Background As life expectancy continues to increase around the world, the use of minimally invasive surgery (MIS) could be beneficial for octogenarian and older gastric cancer patients. Methods A total of 359 gastric cancer patients who underwent curative surgery between March 2011 and March 2015 were enrolled; 80 of these patients (22.2%) were octogenarians and older. Surgical approaches included MIS (50 laparoscopic and 65 robotic) and open surgery (n = 244). Surgical outcomes of MIS and open surgery in octogenarian and older patients were compared with younger patients. Results Among octogenarian and older patients, relative to open surgery (n = 53), MIS (n = 27) was associated with less operative blood loss, a shorter postoperative hospital stay and similar rates of surgical complications and mortality. For MIS (n = 115), octogenarian and older patients exhibited similar postoperative outcomes to those of younger patients. For open surgery (n = 244), relative to younger patients, octogenarian and older patients experienced longer postoperative hospital stays, a higher rate of wound infection and a higher incidence of pneumonia. Conclusions MIS for gastric cancer is beneficial and can be performed safely in octogenarian and older patients.

BACKGROUND This study aimed to investigate the medical expenses and outcomes of central cord syndrome (CCS), comparing patients who received surgical and non-surgical management. METHODS Using a 14-year nationwide database in Taiwan, this study followed-up all patients of CCS at least 5 years. The incidence rates, medical expenses, permanently disabled spinal cord injury (SCI), and mortality rates were compared for patients who underwent surgery and those who were managed conservatively. All CCS patients were further stratified by the level of injury (C1-4 vs. C5-7) in the cost analysis. RESULTS A total of 1,753 patients with CCS were followed and the incidence of CCS was the highest among males aged between 60 and 70 years, at 42.4 per 1,000,000 person-years. The total medical expenses were higher in the surgery than the non-surgery group (46,586.9 vs. 28,472.4, P

Background Human epidermal growth factor receptor-2 (HER2) is a transmembrane tyrosine kinase receptor that is overexpressed in 25 to 30 % of human breast cancers and is preferentially localized in lipid rafts. Stomatin is a membrane protein that is absent from the erythrocyte plasma membrane in patients with congenital stomatocytosis and is the major component of the lipid raft. Results In a total of 68 clinical cases of HER2-positive breast cancer, the absence of stomatin expression was associated with a decreased 5-year survival (65 % vs. 93 %, p = 0.005) by survival analysis. For stage I-III HER2-positive breast cancer, the absence of stomatin expression was associated with a decreased 5-year disease-free survival (57 % vs. 81 %, p = 0.016) and was an independent prognostic factor by multivariate analysis. Negative stomatin expression predicts distant metastases in a hazard ratio of 4.0 (95 % confidence interval from 1.3 to 12.5). Conclusions These results may suggest that stomatin is a new prognostic indicator for HER2-positive breast cancer.

Background Hospice care has been part of the Taiwan health-care system for 20 years. Detailed information on the place of death for terminal cancer patients is lacking. Impending death discharge (IDD) is unique in Taiwan, and our study aims to compare IDD with in-hospice death among terminal cancer patients under hospice care. Methods This retrospective study used claims data of decedents of cancer from the National Health Insurance Research Database of Taiwan from 2007 to 2010. Results Of the 22,720 cancer decedents enrolled, 6316 had claims data marked with IDD and 16,404 with in-hospice death. Those with IDD were older; had a shorter hospice stay; and higher rates of gastrointestinal, peritoneal, and pulmonary cancers. The mean daily health-care expenditure was higher in those with IDD, however, the total expenditure of terminal hospice admission was lower than those dying in hospices. Patients who were treated at public hospitals had a higher rate of in-hospice death than those treated at private hospitals. Patients with IDD were positively correlated with increasing age and shorter hospice stay. Patients with IDD were positively correlated with private hospitals, especially religious corporation-based hospitals. Male sex, oropharyngeal cancer, bone/connective/breast cancers, and secondary/metastatic cancers were negatively correlated with IDD. Conclusion Patients with IDD have characteristics distinct from those dying in hospices. Advanced age and short hospice stays were common in those with IDD, and in-depth investigations were needed. As a unique predying process in Taiwan, relevant health-care issues regarding IDD are warranted for further investigations.

To investigate the incidence and risk of stroke after lumbar spinal fusion surgery.Study subjects were identified from a nationwide cohort of 1 million people from 2000 to 2005 and were divided into the lumbar spinal fusion group (n = 2,015), who received posterior lumbar spinal fusion surgery, and the comparison group (n = 16,120) composed of age-, sex-, and propensity score-matched control subjects. The matching process was intended to adjust for demographics, comorbidities, and other immeasurable covariates to minimize selection bias. All subjects were followed up for 3 years for stroke, including hemorrhagic and ischemic strokes. Kaplan-Meier and Cox regression analyses were performed.The overall incidence rate of stroke in the cohort was 9.99 per 1,000 person-year. The lumbar spinal fusion group was less likely to have any stroke (adjusted hazard ratio (HR) = 0.83, p = 0.293), hemorrhagic stroke (adjusted HR = 0.74, p = 0.739) and ischemic stroke (adjusted HR = 0.81, p = 0.250) than the comparison group, but without significance.Three years post-operatively, patients who received lumbar spinal fusion had stroke incidence rates similar to those without surgery. Posterior lumbar spinal fusion surgery is not associated with increased risks for any kind of stroke.

Background context Postoperative stroke is a rare complication of spinal fusion surgery, but its relevant risk and incidence remain unclear. Purpose To investigate the incidence and risk of stroke after spinal fusion surgery. Study design Cohort study. Patient sample All study subjects were extracted from a nationwide representative cohort of one million people from 2000 to 2005. Outcome measures Stroke, including hemorrhagic and ischemic, during the study period. Methods An exposure group of 2,249 subjects who received spinal fusion surgery during the study period was compared with 2,203 control subjects matched by age, sex, and propensity score. All were followed up for 3 years for all kinds of stroke. Demographics, comorbidities, and nonmeasurable covariates were matched between the two groups. Kaplan-Meier analyses were performed, with adjustments by Cox regression model. Results There were 4,452 subjects, including 2,249 spinal fusion patients and 2,203 controls, who were followed up for 12,967 person-years. The incidence rates of any, hemorrhagic, and ischemic strokes were 9.95, 1.21, and 8.86, respectively, per 1,000 person-years in the spinal fusion group and 11.5, 1.69, and 9.93, respectively, in the comparison group. Patients who received spinal fusion surgery were less likely to have any stroke (crude hazard ratio [HR]=0.87, p=.393), hemorrhagic stroke (HR=0.72, p=.473), and ischemic stroke (HR=0.89, p=.582) than the comparison group but without statistical significance. After adjusting for demographics, comorbidities, and medications, there were still no significant differences for risks of any, hemorrhagic, and ischemic strokes (adjusted HR=0.89, 1.36, and 0.87; p=.522, .553, and .477, respectively) in the spinal fusion group. Conclusions Patients receiving spinal fusion surgery have similar incidence rates of having a stroke within 3 years postoperation as those without surgery. Risks of any postoperative stroke are similar or insignificantly lower in the spinal fusion group.

Robotic gastrectomy has become more popular in the treatment of gastric cancer, especially in Asian countries. Until now, few studies have compared robotic surgery with open or laparoscopic surgery for gastric cancer patients.Data were prospectively collected between January 2006 and February 2012. A total of 689 patients underwent curative resection of adenocarcinoma of the stomach. Patients were separated into three groups according to the different surgical approaches used (586 open, 64 laparoscopic, and 39 robotic). The clinicopathological characteristics and surgical outcomes of the three groups were compared.The open group was associated with a larger tumor size, more D2 dissection, more advanced tumor stage, and more blood loss than the groups treated with laparoscopic and robotic methods. Robotic gastrectomy was associated with female predominance, less blood loss, shorter hospital stay, and longer operative time than open and laparoscopic gastrectomy. The retrieved lymph node numbers were similar between the open and robotic groups. Postoperative morbidity rates were similar among the three groups. In terms of the learning curve of robotic gastrectomy, operative time and docking time were significantly reduced in the recent robotic group (n=14) compared to the initial robotic group (n=25).Robotic gastrectomy could achieve extended lymph node dissection similar to open surgery. Our results showed a significant learning curve effect in the initial 25 cases of the robotic group.

The benefit of resection of gastric cancer with locoregional invasion is still under debate. This study aimed to investigate the impact of surgery on patients with gastric cancer with locoregional invasion. From January 1988 to December 2009, a total of 2,678 patients with gastric cancer underwent surgery at the Department of Surgery, Taipei Veterans General Hospital. Among these patients, 569 and 295 were diagnosed as T4a (serosa invasion without penetration of visceral peritoneum) and T4b (serosa exposure with invasion of adjacent structure), respectively. Invasion type and prognosis were analyzed in patients with gastric cancer who had either curative or palliative resection. Our results showed that patients with T4a gastric cancer had a better 5-year overall survival than patients with T4b (22.5% vs. 11.5%, P

Hip fracture is an important health care issue in the elderly. Postoperative pulmonary complications occur in 4% of patients after hip fracture surgery. However, previous research is limited regarding pulmonary rehabilitation in this group. In this study, we present clinical evidence regarding the impact of a comprehensive pulmonary rehabilitation program in elderly hip fracture patients after hip surgery. We designed a nonrandomized, Quasi-experimental study, comparing 2 sequential time periods in the same center. Elderly patients (≥65 years) with a new hip fracture from February 1, 2014 to December 31, 2015 and who were willing to undergo a postoperative pulmonary rehabilitation program were enrolled. The pulmonary rehabilitation program started on January 1, 2015. Patients who refused rehabilitation or did not receive a surgical intervention were excluded. Patients received either standard care (standard care group) or standard care plus the postoperative rehabilitation program (intervention group). A total of 240 patients (163 women and 77 men) were enrolled, including 138 in the standard care group and 102 in the intervention group. The intervention group had a significantly lower incidence of pneumonia (6 patients, 5.9%) compared to the standard care group (19 patients, 13.9%). An age >80 years, cancer status, and not undergoing the postoperative pulmonary rehabilitation program were factors associated with a higher risk of pneumonia. In multivariate analysis, age >80 years, history of stroke/cancer, thrombocytopenia, and hyperglycemia (>200 mg/dL) were identified as risk factors for pneumonia. The incidence of pneumonia was lower in the elderly patients with hip fractures who received the postoperative pulmonary rehabilitation program after surgery. This is the first trial to demonstrate the effect of a postoperative pulmonary rehabilitation program in hip surgery patients.

Background Ultrasound-guided percutaneous drainage has been suggested in recent years to be the treatment of choice for breast abscesses. Although MRSA has recently been observed to be a significant causative pathogen in mastitis, reports dealing with ultrasound-guided drainage of breast abscess did not address the bacteriology of these infections. Study Design Between January 1 and December 31, 2007, 129 women were diagnosed with puerperal mastitis at Taipei City Hospital. Data were collected by retrospective chart review. Charts were surveyed for mastitis recurrence for at least 1 year after the initial infection treatment, through December 31, 2008. Results The most commonly identified organism was Staphylococcus aureus, present in 69 of 78 of bacterial isolates (88%). There were 52 of 78 (66%) bacterial isolates that were MRSA. Forty-seven of 52 (90%) women infected by MRSA underwent initial ultrasound-guided percutaneous abscess drainage. Among them, 11 (23%) women underwent subsequent conversion to surgical incision and drainage. Comparing women infected with MRSA and women infected with other pathogens, there was no statistical difference in the duration of treatment, number of outpatient follow-up visits, duration of antibiotics use, or abscess recurrence rates. Conclusions MRSA is the most common bacteria in puerperal breast abscess in our population. When these patients are treated initially by percutaneous abscess drainage followed by repeated ultrasound-guided drainage or surgical incision and drainage, the presence of MRSA may not adversely affect treatment outcomes.

Background and Aim: Prognostic factors of lymph node-negative gastric adenocarcinoma after curative resection have been discussed. Recurrent pattern of advanced lymph node-negative gastric cancer after curative resection has rarely been described. Methods: Recurrent sites and correlated clinicopathological factors of 372 patients with lymph node-negative advanced gastric adenocarcinoma that underwent R0 resection from 1988 to 2005 were analyzed. Results: Recurrence was noted in 51 (13.7%) patients. Recurrent rates according to site of recurrence were 26 peritoneal seeding (51.0%), 26 locoregional (51.0%), 17 hematogenous (33.3%), and 4 lymph node metastasis (7.8%). Clinicopathological factors to predict peritoneal seeding were serosal exposure, lymphovascular invasion, Lauren's diffuse type differentiation and scirrhous stromal reaction. Serosal exposure, tumor size, microscopic infiltrating growth type predicts locoregional recurrence. Tumor had only lymphovascular invasion predict hematogenous spreading. Conclusion: Node-negative advanced gastric cancer has more peritoneal seeding and locoregional recurrence. Aggressive cell behavior predicted the route of tumor cell spreading.

Background: Presence or absence of nodal metastasis influences outcome of gastric cancer patients. This study gives insight into survival predictors and clinicopathological features of node-negative gastric adenocarcinoma. Methods: Between 1988 and 1999, 689 gastric cancer patients without other cancer or gastrectomy for benign disease who underwent curative resection were enrolled in this study. Clinicopathological data in patients with node metastasis were compared with those without. Results: The survival rate at 5 and 10 years for node-negative cases was 91.7% and 89.7%, respectively. On univariate analysis, node-negative patients were characterized by frequent location in the lower two-thirds of the stomach (84.9%), tumor size less than 4 cm (63.5%), grossly superficial type (71.6%), more medullary stromal reaction (50.5%) and intestinal type (67.7%), tumor invasion confined to serosa (78.4%), less poorly differentiated cell type (43.2%), and less lymphovascular invasion (33.4%). Multivariate analysis demonstrated that lymphovascular invasion (relative risk: 5.036) and depth of cancer invasion (relative risk: 4.404) were independent poor prognostic factors. However, lymphovascular invasion and serosal invasion were also correlated (P

Pyloric stenosis usually presents with symptoms, and this may lead patients to consult their physician. We evaluate whether distal gastric cancer patients with pyloric stenosis had a better outcome than those without.A total of 551 distal gastric cancer patients who received curative subtotal gastrectomy between January 1988 and December 2003 at Taipei Veterans General Hospital were analyzed. Among them, 174 patients were sorted into the pyloric stenosis group according to obstructive symptoms. Their clinicopathological features, survival and prognostic factors were evaluated.The 5-year overall and disease-free survival rate of distal third gastric adenocarcinoma for the pyloric stenosis group was significantly lower than those without pyloric stenosis. Multivariate analysis revealed the pyloric stenosis group had deeper cancer invasion (relative to pT1, RR of pT2 3.1, p=0.009; pT3 6.1, p0.001; pT4 16.5, p0.001), and more lymph node metastasis (RR 3.6; p=0.001). The pyloric stenosis group had a tendency to lymph node metastasis toward the hepatoduodenal ligament, but this did not reach statistical difference. However, the pyloric stenosis group had significantly higher lymph node metastasis in the retropancreatic region (5.17% vs. 0.53%; p=0.001).Distal gastric cancers with pyloric stenosis have worse biological behavior than those without, and consequently have a poor outcome.

Heme oxygenase-1 (HO-1) gene, which encodes an oxidative response protein, plays a role in cytoprotection. A (GT)n dinucleotide repeat in HO-1 promoter is polymorphic and modulates the transcriptional activity of the gene. A HO-1 gene promoter polymorphism was reported to be associated with the risks of lung adenocarcinoma and oral squamous cancer. In this study, the correlation between the HO-1 gene promoter polymorphism and the clinicopathological characteristics, along with the risk of gastric cancer, was analyzed.We examined the genotypic frequencies of (GT)n repeats in 183 gastric cancer patients and 250 control subjects by PCR-based genotyping and DNA sequencing. The length polymorphisms of (GT)n repeats were classified into short (S) component (nor= 25), medium (M) component (26or= nor= 30) and long (L) component (nor= 31). The distribution of S, M and L components in patient and control groups were evaluated to determine the correlation with susceptibility and clinicopathological characteristics of gastric adenocarcinoma.Higher frequencies of L-allele, L-allele carrier (S/L, M/L, L/L) and S/L genotype were found in gastric cancer patients. The frequencies of M-allele, M-allele carrier (M/M, M/L, M/S) and M/M genotype were significantly lower in patients with gastric cancer than controls. Furthermore, the frequency of lymphovascular tumor invasion was significantly lower in M-allele carriers compared to non-M-allele carriers (S/S, S/L, L/L) (p = 0.009).These findings suggest that the long (GT)n repeat of HO-1 gene promoter was associated with a higher frequency of gastric adenocarcinoma, and the medium (GT)n repeat might possess protective effect against gastric adenocarcinoma with a lower frequency of lymphovascular invasion in tumors.

The expression of RhoA, a member of the ras homologue family, is reported to be involved in tumorigenesis in some cancers; however, its prognostic value in gastric cancer is controversial. Between April 1988 and January 2005, a total of 206 gastric cancer patients receiving curative surgery were enrolled in this study. Immunohistochemical staining of the RhoA protein was performed, and the clinicopathological characteristics and initial recurrence patterns were compared between low RhoA expression (n = 55) and high RhoA expression (n = 151) gastric cancer patients. For intestinal-type (n = 134) gastric cancer, there is no significant difference between the clinicopathological characteristics and RhoA expression. However, for diffuse-type (n = 82) gastric cancer, high RhoA expression was associated with more advanced pathological N category compared to low RhoA expression. A multivariate analysis revealed that age, pathological T and N categories, and RhoA expression were independent prognostic factors for overall survival after curative surgery. For all patients, the five-year overall survival rates and disease-free survival rates were higher in patients with low RhoA expression compared to those with high RhoA expression, which was observed in diffuse-type gastric cancer, not in intestinal-type gastric cancer. With regard to the initial recurrence pattern, patients with high RhoA expression had more distant metastasis compared to those with low RhoA expression, especially more liver metastasis. RhoA expression is an independent prognostic factor for gastric cancer, especially for diffuse-type. We should be aware of liver metastasis during the follow-up of gastric cancer with high RhoA expression.

Since surgical resection is the principal treatment of gastric cancer, early detection is the only effective strategy against this disease at present. Recently, a new polymorphic gene family, the major histocompatibility complex class I chain-related (MIC) genes located about 40 kb centromeric to HLA-B gene has been proposed. This family consists of five genes (A, B, C, D and E). Among them, MICA has five various alleles (A4, A5, A5.1, A6 and A9), which can be used as a polymorphic marker for genetic mapping and for disease susceptibility. The MICA polymorphism was studied in our gastric cancer patients to see if there is any possible correlation with genetic predisposition and clinicopathological factors. Genomic DNA was extracted from fresh or frozen peripheral blood leukocytes in 107 patients with gastric adenocarcinoma who underwent gastrectomy in our hospital and 351 noncancer controls. MICA polymorphism was analysed by using PCR-based technique. The results showed both phenotypic and allele frequencies of allele A9 in patients with gastric cancer were significantly higher than controls (33 vs 17.6%, P=0.005; 17 vs 9.9%, P=0.02). Gastric adenocarcinoma with allele A9 was associated with less schirrous change than those without (P=0.014). MICA gene A9 allele might confer the risk of gastric cancer and associate with less schirrous change. The mechanisms among them deserve further investigation.