Clinical Significance of Epstein-Barr Virus and Helicobacter pylori Infection in Gastric Carcinoma.

Background/Aims: Epstein-Barr virus (EBV) and Helicobacter pylori (HP) coinfection may synergistically induce severe inflammatory responses in the stomach tissue, increasing the risk of developing gastric cancer. We aimed to analyze the effect of EBV and HP coinfection on the clinicopathologic features and prognosis of gastric cancer, as well as to evaluate the role of EBV infection in non-gastric carcinoma with lymphoid stroma (non-GCLS). Methods: Overall, 956 patients who underwent surgery for gastric cancer between September 2014 and August 2015 were eligible and divided into groups, according to GCLS morphology, EBV infection, and HP infection. Clinicopathologic characteristics and oncologic outcomes were analyzed retrospectively. Results: EBV and HP coinfection was significantly associated with male sex, proximal location, GCLS morphology, and equivocal p53 expression (p<0.001). Multivariate analysis revealed that EBV infection alone (hazard ratio [HR], 0.362; 95% CI, 0.131 to 0.996; p=0.049) and lower third location (HR, 0.624; 95% CI, 0.413 to 0.943; p=0.025) were inversely correlated with overall survival. During median follow-up period of 72 months, overall survival rate was not significantly different between the EBV and HP coinfection group and others (97.6% vs 86.8%; log-rank p=0.144). In non-GCLS patients (n=920), overall survival rate was not significantly different between the EBV infection group and others (96.9% vs 86.4%; log-rank p=0.126). Conclusions: EBV and HP coinfection is not an independent prognostic factor for gastric cancer. EBV infection status, regardless of HP infection, affects the clinicopathologic features of all types of gastric cancer. However, it does not lead to a significant difference in overall survival of non-GCLS patients.

Gene Expression of Prox-1 and Hif-1a in Primo Vessels Inside Lymph Vessels of the Rabbit.

The gene expression of Prox-1 and Hif-1a for the isolated primo vessels (PVs) and composite lymphatic vessels (LVs) containing PVs (LVs + PVs) was investigated by RNA-sequencing (Seq) and quantitative polymerase chain reaction (qRT-PCR) analysis. RNA-Seq on the passed 10 samples on RNA-QC for two experimental groups with PVs and PVs + LVs proceeded to the library construction stage automatically and analyzed differentially expressed genes (DEGs). From the real-time qRT-PCR analysis data, we found the marker genes of Prox-1 and Hif-1a were enriched and decreased in an isolated PVs compared to LVs, respectively. Based on mRNA transcriptional data, Prox-1 and Hif-1a were increased and decreased in PVs compared to LVs + PVs under lipopolysaccharide (LPS) treatment and relieved by acupuncture electric stimulation (AES), respectively. This finding indicates that high and low levels of Prox-1 and Hif-1a may be involved in the function of PVs and that pathophysiological and physiological condition could progress into inflamed lymphatic endothelial cells expanding the PV within the LV.

Analysis and Differential Expression of Primo Genes Using RNA-Seq and qRT-PCR Experiments.

Although the existence of the primo vasculature system has been shown in many species, including mice, rats, rabbits and humans, the biological role of this system, including expression of genes and proteins, has not yet been investigated. Especially the transcriptional action by mRNA, which is required for biological action, needs to be studied in primo vasculature biology. Differentially expressed genes in both isolated primo vessels and lymphatic vessels of rabbits were analyzed by RNA sequencing experiments. Primer efficiency and RNA purity of the primo vessels under lipopolysaccharides were confirmed prior to performing real-time qRT-PCR analysis following RNA extraction. We demonstrated that FLT4 was enriched in primo vessels and that several genes, including HSPH1 and EPHB2, were highly expressed in primo vessels compared with lymphatic vessels. Our data show that almost all genes, except HSPA4, were increased or sustained in isolated primo vessels compared with lymphatic vessels (FLT4 2.58 fold, HSPH1 1.83 fold, EPHB2 1.52 fold; whereas HSPA4 decreased 0.50 fold), suggesting primo vessels as a central regulator in diverse physiology. This implies that FLT4, HSPH1, and EPHB2 in high amounts may be involved in the functional activity of primo vessels. Our experimental data show that several genes are highly enriched in primo vessels in the lymphatic vessels of the rabbit.

Does Radiofrequency Ablation Induce Neoplastic Changes in Benign Thyroid Nodules: A Preliminary Study.

BACKGROUND: To evaluate the clinical feasibility of radiofrequency ablation (RFA) of benign thyroid nodules along with cytomorphological alteration, and any malignant transformation through biopsy. METHODS: The data were retrospectively collected between April 2008 and June 2013 and core needle biopsy (CNB) was performed on 16 benign thyroid nodules previously treated using RFA. The parameters of the patients were compared, between the time of enrollment and the last follow-up examination, using linear mixed model statistical analysis. RESULTS: No atypical cells or neoplastic transformation were detected in the undertreated peripheral portion of treated benign nodules on the CNB specimen. RFA altered neither the thyroid capsule nor the thyroid tissue adjacent to the treated area. On histopathological examinations, we observed 81.2% acellular hyalinization, which was the most common finding. After a mean follow-up period of over 5 years, the mean volume of thyroid nodule had decreased to 6.4±4.2 mL, with a reduction rate of 81.3%±5.8% (P<0.0001). CONCLUSION: RFA is a technically feasible treatment method for benign thyroid nodules, with no carcinogenic effect or tissue damage of the normal thyroid tissue adjacent to the RFA-treated zone.

Expression of Genes in Primo Vasculature Floating in Lymphatic Endothelium Under Lipopolysaccharide and Acupuncture Electric Stimulation.

It is known that the primo vascular system (PVS) includes the primo nodes and vessels. However, the relevant genes in the PVS system for both pathologic and physiologic condition are poorly understood. Here, we first examined the gene expression in primo vessels (PVs) floating in lymphatic endothelium by isolation of PVS and lymphatic vessels (LVs) containing PVS. To investigate therapeutic effects, both PVs and LVs containing PVS were isolated after lipopolysaccharide injection and acupuncture electric stimulation at two acupoints Joksamni (ST36) and Hapgok (LI04) following lipopolysaccharide injection. We used reverse transcriptase-polymerase chain reaction to examine expression of lymphatic endothelial cell markers and inflammatory related genes. We found that lymphatic endothelial cell markers such as fms-related tyrosine kinase 4 (Flt4), lymphatic vessel endothelial receptor (Lyve-1), prospero homeobox protein 1 (Prox-1), and podoplanin (Pdpn) were highly expressed in PV compared to that of lymphatic endothelium, suggesting pivotal roles of PV in LV under inflammation. Furthermore, lymphatic-related genes including metal-response element-binding transcription factor 2 (Mtf2), hypoxia inducible factor (Hif1a), angiotensin II type 1 receptor (Agtr1), and angiotensin II type 2 receptor (Agtr2) were also overall increased in PV, and remarkably increased and these genes except peroxisome proliferator-activated receptor gamma (Pparg) after acupuncture electric stimulation in two acupoints implying central role of PV by gene activation.

Differential Gene Expression by RNA-Seq Analysis of the Primo Vessel in the Rabbit Lymph.

For the connectome of primo vascular system, some long-type primo vessels dyed with Alcian blue injected into inguinal nodes, abdominal node, and axially nodes were visualized, which passed over around the vena cava of the rabbit. The Alcian blue dye revealed primo vessels and colored blue in the rabbit lymph vessels. The length of long-type primo vessels was 18 cm on average, of which diameters were about 20-30 µm, and the lymph vessels had diameters of 100-150 µm. Three different tissues of pure primo vessel, mixed primo + lymph vessel, and only lymph vessel were made to undergo RNA-Seq analysis by next-generation sequencing. We also analyzed differentially expressed genes (DEGs) from the RNA-Seq data, in which 30 genes of the primo vessels, primo + lymph vessels, and lymph vessels were selected for primo marker candidates. From the plot of DEG analysis, 10 genes had remarkably different expression pattern on the Group 1 (primo vessel) vs Group 3 (lymph vessel). With Fragments Per Kilobase of exon per Million the cutoff p-value for each gene was < 0.05. Fragments Per Kilobase of exon per Million of the 10 genes such as IGHM, HLA-DRA, HIST1H41, LPL, CD36, SRGN, DGAT2, SNCG, CD48, and GPD1 for primo vessels compared with those of lymph vessels increased twice or thrice. These results suggest that the selected genes could be used for the specific marker to construct primo connectome of circuit system in the rabbit.

A Case of Primary Small Bowel Melanoma Diagnosed by Single-Balloon Enteroscopy.

Although metastasis from cutaneous malignant melanoma to the small intestine is not uncommon, primary small bowel melanoma (SBM) is extremely rare. This case report describes a rare case of primary SBM, diagnosed by single-balloon enteroscopy. A 74-year-old man presented with recurrent melena. Upper endoscopy and colonoscopy were unremarkable. Abdominal computed tomography (CT) revealed an ileal mass with ileo-ileal intussusception. Subsequent single-balloon enteroscopy identified an ileal tumor, which was histologically diagnosed as melanoma. Extensive clinical examination did not reveal any primary cutaneous lesions. To the best of our knowledge, this is the first case of primary SBM in South Korea.

Assessment of hepatocellular carcinoma risk based on peg-interferon plus ribavirin treatment experience in this new era of highly effective oral antiviral drugs.

In this new era of highly effective oral antiviral drugs for chronic hepatitis C virus (HCV), indications for antiviral treatment may be extendable. This study undertaken to identify suitable candidates for peg-interferon plus ribavirin (PEG-IFN/RBV) treatment by evaluating hepatocellular carcinoma (HCC) risk in patients with chronic HCV treated or not with PEG-IFN/RBV.This large-scale retrospective study was conducted on 1176 patients with chronic HCV without a history of HCC (treatment group [n = 489] and no-treatment group [n = 687]). In the treatment group, patients treated with PEG-IFN/RBV were dichotomized based on the achievement of sustained virologic response (SVR) into SVR (+) and SVR (-) groups.Median follow-up for all study subjects was 31 months (range 6-144 months). Three-year cumulative HCC development rates in the SVR (+) (1.1%) and SVR (-) (8.6%) subgroups were significantly lower than in the no-treatment group (13.5%) (P < 0.01 and P < 0.01, respectively). In all study subjects, presence of cirrhosis (hazard ratio [HR], 9.92, P < 0.01), age (HR 1.03, P < 0.01), SVR (-) (HR 7.02, P < 0.01), and no-treatment (HR 6.76, P < 0.01) were found to be independent risk factors of HCC development. In the treatment group, age, the presence of cirrhosis, and SVR (-) were predictors of HCC development. In the no-treatment group, age, male, and the presence of cirrhosis were independent predictors for HCC development.HCC risk increased in patients with chronic HCV with older age, cirrhosis, SVR (-) after PEG-IFN/RBV treatment, and no PEG-IFN/RBV treatment. Active antiviral therapy based on highly effective oral drugs needs to be considered in these patients.

Vascular enhancement pattern of mass in computed tomography may predict chemo-responsiveness in advanced pancreatic cancer.

INTRODUCTION: Chemo-responsiveness in pancreatic cancer is known to be dependent on fibrosis and vascularity. The purpose of this study was to assess vascular enhancement in advanced pancreatic adenocarcinoma with or without liver metastasis in computed tomography (CT) and to analyze the correlation between enhancement patterns and chemo-responsiveness. METHODS: Patients were assigned to either a responder group (partial response or stable disease) or a non-responder group (progressive disease) according to chemo-responsiveness assessed by CT before and after gemcitabine-based chemotherapy. Hounsefield unit (HU) was measured in pancreatic mass and the largest metastatic liver mass using region of interest (ROI). HU differences (ΔHU) between arterial and pre-contrast phase were calculated. RESULTS: Of the 101 study subjects, 78(77.2%) were assigned to the pancreas responder group {mean ΔHU (±SD), 36.7(±21.6)} and 23(22.8%) to the pancreas non-responder group {mean ΔHU (±SD), 20.6(±9.9)} (p = 0.001 for ΔHUs). Of the 46 study subjects with liver metastasis, 25(54.3%) were assigned to the liver metastasis responder group {mean ΔHU (±SD), 36.9(±21.0} and 21(45.7%) to the liver metastasis non-responder group {mean ΔHU (±SD), 17.1 (±24.0)}, (p = 0.005 for ΔHUs). CONCLUSION: CT determined mass vascular enhancement patterns may predict chemoresponse in advanced pancreatic cancer.

Refractory pseudomembranous colitis that was treated successfully with colonoscopic fecal microbial transplantation.

Pseudomembranous colitis (PMC) is a nosocomial and opportunistic infection caused by Clostridium difficile. PMC is related to the use of antibiotics leading to intestinal dysbiosis and an overgrowth of C. difficile. Metronidazole or vancomycin is considered to be the standard therapy for the management of PMC. However, PMC has a 15%-30% recurrence rate and can be refractory to standard treatments, resulting in morbidity and mortality. Here we describe a patient who experienced refractory PMC who was treated with fecal microbiota transplantation. A 69-year-old woman was admitted to the hospital with consistent abdominal pain and diarrhea, which had been present for 5 months. She was diagnosed with PMC by colonoscopy and tested positive for C. difficile toxin. Even though she took metronidazole for 10 days, followed by vancomycin for 4 weeks, her symptoms did not improve. Because of her recurrent and refractory symptoms, we decided to perform fecal microbiota transplantation. Fifty grams of fresh feces from a donor were obtained on the day of the procedure, mixed with 500 mL of normal saline, and then filtered. The filtered solution was administered to the patient's colon using a colonoscope. After the procedure, her symptoms rapidly improved and a follow-up colonoscopy showed that the PMC had resolved without recurrence.

Abdominal Obesity and Mortality in Continuous Ambulatory Peritoneal Dialysis Patients.

BACKGROUND: The relationship between abdominal obesity (AO) and mortality in peritoneal dialysis (PD) patients is controversial. METHODS: The prevalence of AO in 84 PD patients was assessed in a cross-section manner and followed up for 9 years at a single center. AO was defined as a waist circumference (WC) of more than 90 cm in males or more than 80 cm in females. The patients were classified as either with AO(AO group) or without AO(nAO group). RESULTS: The AO group was older, contained more diabetics, more females, and had higher Charlson comorbidity index (aCCI) scores, BMI, and triglyceride and lower serum creatinine than the non-AO subjects. The follow-up duration was 53.2±34.4 months. At the end of the follow-up, eighteen patients (21.4%) were dead; 9 died of cardiovascular causes. The five year survival rate was 40.8%. Kaplan-Meier analysis revealed that both all-cause and cardiovascular-cause mortalities were similar in the AO and nAO groups. Multivariate analysis revealed the presence of AO not to be an independent risk factor of all-cause and cardiovascular-cause mortality. CONCLUSION: AO itself might not be a risk factor for mortality in PD patients. Nevertheless, further prospective studies with a large number of patients will be needed to prove this.

Heavily Doped, Charge-Balanced Fluorescent Organic Light-Emitting Diodes from Direct Charge Trapping of Dopants in Emission Layer.

We studied the effect of direct charge trapping at different doping concentrations on the device performance in tris(8-hydroxyquinoline) aluminum (Alq3):10-(2-benzothiazolyl)-2,3,6,7-tetrahydro-1,1,7,7-tetramethyl-1H,5H,11H-(1)-benzopyropyrano(6,7-8-i,j)quinolizin-11-one (C545T) as a host-dopant system of a fluorescent organic light-emitting diode. With increasing C545T doping concentration, trap sites could lead to the promotion of hole injection and the suppression of electron injection due to the electron-transport character of Alq3 host for each carriers, as confirmed by hole- and electron-only devices. Direct charge injection of hole carriers from the hole transport layer into C545T dopants and the charge trapping of electron carriers are the dominant processes to improve the charge balance and the corresponding efficiency. The shift of the electroluminescence (EL) spectra from 519 nm to 530 nm was confirmed the exciton formation route from Förster energy transfer of host-dopant system to direct charge trapping of dopant-only emitting systems. Variation in the doping concentration dictates the role of the dopant in the fluorescent host-dopant system. Even though concentration quenching in fluorescent dopants is unavoidable, relatively heavy doping is necessary to improve the charge balance and efficiency and to investigate the relationship between direct charge trapping and device performance. Heavy doping at a doping ratio of 6% also generates heavy exciton quenching and excimer exciton, because of the excitons being close enough and dipole-dipole interactions. The optimum device performance was achieved with a 4%-doped device, retaining the high efficiency of 12.5 cd/A from 100 cd/m(2) up to 15,000 cd/m(2).

Metformin-associated lactic acidosis: predisposing factors and outcome.

BACKGROUND: Metformin is considered the first choice oral treatment for type 2 diabetes patients in the absence of contraindications. Rarely, life-threatening complications associated with metformin treatment are seen in some patients with underlying diseases. The aim of this study was to further investigate the clinical profiles and risk factors for metformin-associated lactic acidosis (MALA) and the treatment modalities according to survival. METHODS: To identify MALA, we performed a retrospective study in seven diabetic patients who were taking metformin and had been diagnosed with lactic acidosis at Inha University Hospital between 1995 and 2012. For each patient, we recorded the age, sex, daily metformin dosage, laboratory test results, admission diagnosis, and risk factors. Also, concurrent conditions, treatment modalities, and outcomes were evaluated. RESULTS: Six patients had risk factors for lactic acidosis before admission. All patients had renal impairment on admission as a precipitating risk factor. Five patients survived and two patients died despite early renal replacement therapy. Older patients tended to have a poorer prognosis. CONCLUSION: Renal function must be monitored in elderly type 2 diabetes mellitus patients with underlying diseases and conditions causing renal impairment who begin metformin treatment. Accurate recognition of MALA and initiation of renal replacement are essential for treatment.

A Case of Post-radiotherapy Urethral Stricture with Spontaneous Bladder Rupture, Mimicking Obstructive Uropathy due to Cancer Metastasis.

Non-traumatic, spontaneous urinary bladder rupture is a rare complication of urethral stricture. Furthermore, its symptoms are often nonspecific, and misdiagnosis is common. The authors experienced a case of urethral stricture with spontaneous bladder rupture and bilateral hydronephrosis, mimicking obstructive uropathy attributed to cancer metastasis. A 55-year-old woman was admitted with abdominal pain and distension, oliguria, and an elevated serum creatinine level. She had undergone radical hysterectomy for uterine cervical cancer and received post-operative concurrent chemoradiation therapy 13 years previously. Non-contrast enhanced computed tomography showed massive ascites and bilateral hydronephrosis. The initial diagnosis was acute kidney injury due to obstructive uropathy caused by malignant disease. After improvement of her renal function by bilateral percutaneous nephrostomy catheterization, contrast-enhanced computed tomography and a cytologic examination of ascites showed no evidence of malignancy. However, during retrograde pyelography, a severe urethral stricture was found, and subsequent cystography showed leakage of contrast into the peritoneal cavity and cystoscopy revealed a defect of the posterior bladder wall. After urethral dilatation and primary closure of the bladder wall, acute kidney injury and ascites were resolved.

Family medicine clerkship web sites: the state of the art.

BACKGROUND AND OBJECTIVES: The use of on-line syllabi to acquire information about a course, clerkship, or rotation is growing. This study investigated the number of existing family medicine clerkship Web sites with syllabi and determined their completeness and usability. METHODS: In sping 1999, all schools with third-year family medicine clerkship Web sites were identified (n = 71) using Association of American Medical Colleges and American Academy of Family Physicians clerkship directories to identify required family medicine clerkships, followed by a Web search to identify any associated Web sites. A checklist with 11 content and 5 technical categories was developed and pilot tested. All sites were evaluated by at least two investigators. Two identifiable checklist characteristics were required to be present for a site to be identified as an on-line syllabus and included in the study. RESULTS: Of the 71 sites initially identified, 40 were included in the study, 22 were excluded, and 9 required further review by an additional evaluator. A total of 44 sites were included in the study. The most common content features identified were instructor information, goals, overview, and requirements. Less-common features included objectives, learning resources, schedule, and grading policy. CONCLUSIONS: A minority of family medicine clerkships have on-line syllabi. Most sites have basic information, but other relevant clerkship information is absent. New and revised family medicine clerkship on-line syllabus development would benefit from using the checklist to guide the creation of instructionally sound educational resources.