Role of Esophageal Metal Stents Placement and Combination Therapy in Inoperable Esophageal Carcinoma: A Systematic Review and Meta-analysis.

INTRODUCTION: More than 50% of patients with esophageal cancer already have inoperable disease at the time of diagnosis. Controversy surrounds the outcomes of patients with advanced esophageal cancer who receive palliative care by either stent alone or stent plus an additional modality. We set out to perform a systematic review and meta-analysis of studies assessing the use of metal stents as treatment options for symptomatic improvement, survival, and adverse events. METHODS: We searched Embase, MEDLINE, and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception until January 14, 2016, as well as other databases for randomized controlled trials (RCTs) comparing esophageal stent versus either esophageal stent plus brachytherapy, radiotherapy, or chemotherapy. For quality assurance purposes throughout the systematic review, multiple independent extractions were performed, and the process was executed as per the standards of the Cochrane collaboration. Primary outcomes were mean change in dysphagia score, overall survival, and quality of life. Secondary outcomes were adverse events including fever, severe pain, aspiration, fistula, stent migration, perforation, and restenosis. RESULTS: Eight RCTs enrolling 732 patients were included with three distinct comparisons: stents combination therapy vs stents alone (5 studies, n = 417), stents alone versus brachytherapy alone (2 studies, n = 274), and stents + brachytherapy vs brachytherapy alone (1 study, n = 41). Stents combination therapy was defined as stents plus radiotherapy, chemotherapy, or both. Mean change in dysphagia scores favored stents combination therapy versus stents alone, and the effect was seen in patients surviving longer than 3 months. Stents combination therapy was also associated with a more favorable overall survival. The risks of stent migration, aspiration pneumonia, and restenosis were lower in the stents combination group compared to stents alone, while the risks of severe pain, hemorrhage, and fistula formation were higher. Changes in dysphagia scores and overall survival did not differ significantly in the brachytherapy-alone vs stents-alone comparison. The risk of fistula formation and hemorrhage were higher in the stents-alone group, while the risk of perforation was lower, compared to brachytherapy alone. Quality of life improvements were seen in all treatment groups, but were not pooled in analysis due to differing methods of measurement. DISCUSSION: While there appears to be no immediate short-term differences, those who live longer than 3 months experience a significant improvement in dysphagia score using a stents combination therapy approach vs stents alone. The combination therapy significantly improves the overall survival as well as showed improvements in quality of life scores. Larger randomized controlled trials are needed to assess improvements in dysphagia score, overall survival, quality of life, and adverse events.

A fatal case of herpes simplex virus hepatitis in a pregnant patient.

We present a middle aged pregnant woman who developed signs and symptoms of acute liver failure and was found to have herpes simplex virus hepatitis. Patient had an emergent delivery and was started on antiviral therapy, but unfortunately due to the severity of her liver failure, she passed away. The importance of reporting this case is to emphasize on the importance of considering herpes simplex infection in pregnant women who present with acute liver failure, and the importance of early administration of antiviral therapy.

Association between serum cotinine level and prevalence of non-alcoholic fatty liver disease: a cross-sectional study from the Third National Health and Nutrition Examination Survey.

The data on the effect of smoking on non-alcoholic fatty liver disease (NAFLD) has been controversial. The aim of this study was to investigate if an association exists between serum cotinine level (a tobacco biomarker) and NAFLD prevalence in the general US population. We conducted a cross-sectional analysis of data from the Third National Health and Nutrition Examination Survey (NHANES III). We included 11,003 adults aged 20-74 years who underwent ultrasonography. Of those, 4036 were identified as having NAFLD and 6967 were recognized as controls. The percentage of current smokers was significantly lower in subjects with NAFLD compared with those in controls (21.5% vs 26.0%, p<0.01). After adjustment for potential confounders, there was no association between current or former smokers with NAFLD. Additionally, no associations were observed between the levels of serum cotinine and NAFLD. No association between serum cotinine levels at each quartile level and NAFLD was observed regardless of smoking status. In this large US population-based study, we did not find an association between NAFLD and self-reported smoking status or measured serum cotinine level.

Association between chronic hepatitis C and hepatitis C/HIV co-infection and the development of colorectal adenomas.

BACKGROUND: Limited knowledge exists about the effects chronic hepatitis C virus (HCV) infection has in the development of colorectal adenomas (CRA). Data regarding the association between chronic HIV infection and the development of CRA is scarce as well. We aim to determine if there is an association between the development of CRA and chronic infection with HCV and HCV/HIV co-infection. METHODS: From July 1, 2009 to March 31, 2011 a total of 2,051 patients that underwent colonoscopy were included in our study. The population was divided into 2 study groups: those patients who tested positive for HCV, and HCV/HIC; the control groups consisted of patients whose results were negative. Fisher's exact χ(2) test for categorical variables and t-test for continuous variables was used to analyze data between groups. Logistic regression was performed to obtain odds ratios (OR). RESULTS: CRA detection was higher in the HCV than in the control group (26.3% vs. 20.2%; P=1.02); Likewise, the incidence of CRA (25.5% vs. 20.8%; P=0.63) was higher in the co-infection group. However, in both of the study groups this difference was non-statistical. CONCLUSIONS: A higher detection rate of CRP was seen in the HCV population; however, it failed to reach statistical significance. Whether co-infection with HIV/HCV increases the incidence of CRA and/or has a synergistic effect remains to be determined. The small sample population and the retrospective single institution nature of our study, as well as other confounders may have contributed to our negative results. However, our findings question whether HCV and HIV/HCV co-infected patients will benefit from screening colonoscopy at an earlier age. This issue merits further investigation with a large multi-center prospective study.

Histamine H2-Receptor Antagonist Use Is Associated With Lower Prevalence of Nonalcoholic Fatty Liver Disease: A Population-based Study From the National Health and Nutrition Examination Survey, 2001-2006.

BACKGROUND & AIM: Recent basic mechanistic studies found that proton-pump inhibitors (PPIs) or histamine antagonists inhibited multiple pathways involved in nonalcoholic fatty liver disease (NAFLD) development. The aim of this study was to investigate an association between PPIs or H1/H2-receptor antagonist (H1RA/H2RA) use and NAFLD prevalence in the general US population. METHODS: We conducted a cross-sectional analysis of data from the National Health and Nutrition Examination Survey, 2001-2006. We included 10,398 adults aged 20 to 74 years who had alanine aminotransferase data; of those, 2058 were identified as having NAFLD and 8340 as controls. PPI or H1RA/H2RA use was defined as use of prescription medications in the preceding month. The length of use was categorized as ≤60 days and >60 days. NAFLD was defined as elevated serum aminotransferases without any indication of other causes of chronic liver disease. RESULTS: In the multivariate unconditional logistic regression analysis, H2RA use was inversely associated with prevalent NAFLD [odds ratio (OR)=0.43, 95% confidence interval (CI), 0.18-0.99], a finding that was primarily limited to men (OR=0.18, 95% CI, 0.04-0.79) and those with insulin resistance (OR=0.22, 95% CI, 0.05-0.95). However, no significant associations were found between PPI or H1RA use and prevalent NAFLD. CONCLUSIONS: These findings, from the first human study to investigate an association of PPI or H1RA/H2RA use with NAFLD, suggest that H2RA use may be associated with a lower prevalence of NAFLD, primarily among men with insulin resistance.

Association between caffeine consumption and nonalcoholic fatty liver disease: a systemic review and meta-analysis.

OBJECTIVES: Caffeine consumption is reported to be associated with reduced hepatic fibrosis in patients with chronic liver diseases. We performed a systematic review and meta-analysis to assess the association between caffeine consumption and prevalence or hepatic fibrosis of nonalcoholic fatty liver disease (NAFLD) in observational studies. METHODS: We searched the literature of all languages from PubMed, EMBASE, and the Cochrane library from 1 January 1980 through 10 January 2015. Total caffeine consumption was defined as the daily intake of caffeine (mg/day) from all caffeine-containing products. Combined and subgroup analyses stratified by study designs, study locations, and type of caffeine intake were performed. RESULTS: Four cross-sectional and two case control studies with a total of 20,064 subjects were included in the meta-analysis. Among these, three studies with 18,990 subjects were included in the analysis for prevalence of NAFLD while the other three studies with 1074 subjects were for hepatic fibrosis. Total caffeine consumption (mg/day) was not significantly associated with either the prevalence [pooled mean difference (MD) 2.36; 95% confidence interval (CI) -35.92 to 40.64] or hepatic fibrosis (higher versus lower stages; pooled MD -39.95; 95% CI -132.72 to 52.82) of NAFLD. Subgroup analyses stratified by study designs and locations were also not significant. However, after stratifying by type of caffeine intake, regular coffee caffeine intake (mg/day) was significantly associated with reduced hepatic fibrosis of NAFLD (pooled MD -91.35; 95% CI -139.42 to -43.27; n = 2 studies). CONCLUSION: Although total caffeine intake is not associated with the prevalence or hepatic fibrosis of NAFLD, regular coffee caffeine consumption may significantly reduce hepatic fibrosis in patients with NAFLD.

Establishing the link between hepatitis B virus infection and colorectal adenoma.

BACKGROUND: Chronic hepatitis B (CHB) infection has been associated with malignancy, most notably hepatocellular carcinoma. Previous research has shown that hepatitis C is associated with increased colorectal adenomas and neoplasia. Currently, there are no studies on the association of CHB and colorectal adenomas. We aimed to identify a possible link between CHB and colorectal adenoma. METHODS: A retrospective chart review was performed on 588 consecutive patients undergoing screening or diagnostic colonoscopy that were previously screened or diagnosed with hepatitis B. Comparisons between categorical variables were analyzed with Chi Square test and t-test for continuous variables. Unconditional logistic regression was used to generate age-, gender-and race-adjusted odds ratios and their 95% confidence intervals (CI) comparing medication users with non-users. Statistical analyses were performed with SAS 9.3 software. RESULTS: A total of 487 patients were analyzed in the control group vs. 71 in the hepatitis B group. The adenoma detection rate was 23.9% in hepatitis B vs. 15.9% in the non-hepatitis B group for all cause colonoscopy; however this did not reach statistical significance. There was a significantly higher number of adenomas present in the distal colon compared to control (OR =2.16; 95% CI, 1.06-4.43; P=0.04). There were no significant findings between hepatitis B infection with size, multiplicity or presence of proximal adenomas. There was a significant difference noted in regards to smoking history, BMI and age between two groups. CONCLUSIONS: Although the adenoma detection rate was higher in hepatitis B population vs. the non-hepatitis B group this did not reach statistical significance. However, we did find an association between CHB infection and the presence of distal colorectal adenomas. Larger prospective studies are needed to strengthen our findings along with future studies examining hepatitis B virus (HBV) and mechanisms inducing colorectal carcinogenesis.

Low bone mineral density linked to colorectal adenomas: a cross-sectional study of a racially diverse population.

BACKGROUND: Epidemiologic studies suggest that lower bone mineral density (BMD) is associated with an increased risk for colorectal adenoma/cancer, especially in postmenopausal women. The aim of this study is to investigate the association between osteopenia and/or osteoporosis and colorectal adenomas in patients from a New York community hospital. METHODS: We performed a cross-sectional observational study on 200 patients who underwent screening colonoscopies and bone density scan (dual-energy X-ray absorptiometry) at Nassau University Medical Center from November 2009 to March 2011. Among these, 83 patients were identified as osteoporosis (T score of -2.5 or below) and 67 were osteopenia (T score between -1.0 and -2.5). Logistic regression model was performed to assess the association between osteopenia and/or osteoporosis and colorectal adenomas. RESULTS: Among the patients with osteopenia and osteoporosis, the mean ages were 59.1 years [standard deviation (SD) =8.9] and 61.5 (SD =8.9), respectively. There were 94.0%, 85.1% and 74.7% women, respectively, in normal BMD, osteopenia and osteoporosis groups. The prevalence of colorectal adenomas was 17.9% and 25.3% in the osteopenia and osteoporosis groups, respectively, and 18.0% in the normal BMD group. After adjustment for potential confounders including age, sex, race, body mass index (BMI), tobacco use, alcohol use, history of diabetes, hypertension, or dyslipidemia, osteoporosis was found to be associated with presence of colorectal adenomas more than 2, compared to the normal BMD group. No significant associations were found for the prevalence, size, and location of adenomas. CONCLUSIONS: Our study suggests that osteoporosis is significantly associated with the presence of multiple colorectal adenomas. Prospective studies with a larger sample size are warranted in the future.

Ethnic disparities in the risk of colorectal adenomas associated with lipid levels: a retrospective multiethnic study.

BACKGROUND: Although data exists showing that uncontrolled lipid levels in white and black patients is associated with colorectal adenomas, there are currently no studies looking only at the Hispanic population. PURPOSE: With the rapid increase in the Hispanic population, we aimed to look at their risk of colorectal adenomas in association with lipid levels. METHODS: We retrospectively analyzed 1473 patients undergoing colonoscopy from 2009 to 2011 at a community hospital. Statistical analysis was performed using Chi-squared for categorical variables and t test for continuous variables with age-, gender-, and race-adjusted odds ratios. Unconditional logistic regression model was used to estimate 95 % confidence intervals (CI). SAS 9.3 software was used to perform all statistical analysis. RESULTS: In our general population, there was an association with elevated triglyceride levels greater than 150 and presence of multiple colorectal adenomas with odds ratio (OR) 1.60 (1.03, 2.48). There was an association with proximal colon adenomas and cholesterol levels between 200 and 239 with OR 1.57 (1.07, 2.30), and low-density lipoprotein (LDL) levels of greater than 130 with OR 1.54 (1.04, 2.30). There was no association between high-density lipoproteins (HDL) levels and colorectal adenomas. The Hispanic population showed no statistical correlation between elevated triglycerides, cholesterol, or LDL with the presence, size, location, or multiplicity of colorectal adenomas. CONCLUSIONS: We found a significant correlation between elevated lipid levels and colorectal adenomas in white and black patients; however, there was no such association in the Hispanic population. This finding can possibly be due to environmental factors such as dietary, colonic flora, or genetic susceptibility, which fosters further investigation and research.

Effects of calcium and vitamin D supplementation on crypt morphology in normal colon mucosa: A randomized clinical trial.

Calcium and vitamin D modify the molecular phenotypic profiles of colon crypts in the normal colorectal mucosa of colorectal adenoma patients, but their effects on crypt morphology (length, perimeter, and area) are unknown. We analyzed data from a previously conducted pilot, randomized, double-blind, placebo-controlled 2 × 2 factorial chemoprevention clinical trial of supplemental calcium 2000 mg/d and vitamin D3 800 IU/d, alone and in combination, versus placebo over 6 mo. Colorectal crypt length, perimeter, and area in the normal-appearing rectal mucosa were quantified by image analysis. The mean crypt length increased by 1% (P=0.92) in the calcium group, and decreased by 2% (P=0.69) and 4% (P=0.40) in the vitamin D and calcium plus vitamin D groups, respectively, relative to the placebo group. The mean crypt perimeter decreased by 2% (P=0.70) and 4% (P=0.40) in the vitamin D and calcium plus vitamin D groups, respectively, relative to the placebo group, but did not change appreciably in the calcium group. The mean crypt area decreased by 2% (P=0.74), 5% (P=0.41) and 7% (P=0.30) in the calcium, vitamin D and calcium plus vitamin D groups, respectively, relative to the placebo group. Calcium and/or vitamin D3 supplementation do not appear to appreciably change crypt morphology in the normal colorectal mucosa of sporadic adenoma patients. These results, taken together with previous findings, support the use of molecular phenotypic over morphologic pre-neoplastic biomarkers of risk for colorectal neoplasms.

Association between nonalcoholic fatty liver disease and colorectal adenoma: a systemic review and meta-analysis.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is considered to be a hepatic manifestation of metabolic syndrome (MetS) and the most common chronic liver disease worldwide. The association between NAFLD and colorectal adenoma has been investigated in multiples studies but the results have been conflicting. We performed a systematic review and meta-analysis to evaluate this in asymptomatic patients who underwent screening colonoscopy. METHODS: We searched the literatures of all languages from PubMed, EMBASE and the Cochrane library from January 1, 1980 through July 15, 2014. Combined and subgroup analyses stratified by study designs, study locations, characteristics of adenoma (location, size, number, and advanced adenoma) were performed. RESULTS: Four cross-sectional and one cohort studies with a total of 6,263 subjects were included in the meta-analysis. NAFLD was significantly associated with colorectal adenoma [pooled odds ratio (OR) 1.74, 95% confidence interval (CI): 1.53-1.97]. The association was more significant in Asian population (pooled OR =1.77, 95% CI: 1.52-2.05, n=3 studies), compared to European/North American population (pooled OR =1.42, 95% CI: 0.75-2.67, n=2 studies). NAFLD was significantly associated with the number of colorectal adenoma (pooled OR =1.78, 95% CI: 1.10-2.86, n=2 studies), but not the location, size, or presence of advanced adenoma. CONCLUSIONS: Our results suggest NAFLD is significantly associated with the presence of colorectal adenoma in asymptomatic patients undergoing screening colonoscopy. This finding provides additional risk stratifications for applying colorectal cancer (CRC) screening strategies. However, more studies of western population are needed to further investigate the ethnic disparity.

The association of H. pylori and colorectal adenoma: does it exist in the US Hispanic population?

BACKGROUND: Although data on the association between colorectal adenomas and Helicobacter pylori (H. pylori) exists in White and Black patients, there is no data on this association in a US Hispanic population. Our aim was to study the association of adenoma detection and biopsy proven H. pylori infection in a cohort of US Hispanics. METHODS: Data were collected from Nassau University Medical Center, a 530-bed tertiary care teaching hospital in East Meadow, New York. Patients who underwent both an esophagogastroduodenoscopy (EGD) and colonoscopy from July 2009 to March 2011 were pulled from an electronic database. A total of 1,737 patients completed colonoscopies during this time with 95 excluded: 17 inflammatory bowel disease, 12 malignancy, 22 prior history of colorectal adenoma, and 44 incomplete. Among the colonoscopies, 799 patients had EGD's performed prior to colonoscopies that were eligible for our study. RESULTS: H. pylori prevalence was highest in Hispanics 40.9%, followed by Blacks 29.1% (OR 0.59, 95% CI: 0.42-0.84), then Whites 7.9% (OR 0.12, 95% CI: 0.06-0.24). The adenoma detection rate was significantly higher in Whites 23.2% and Blacks 21.8% compared to Hispanics 14.5%, P=0.0002 respectively. Smoking and alcohol were lower in the H. pylori group, 18.6% (n=44) vs. 26.1% (n=147) for smoking (P=0.02) and 14.4% (n=34) vs. 19% (n=107) for alcohol (P=0.12), respectively. There was no evidence in the Hispanics for an association between adenoma detection and H. pylori infection. Furthermore size, location, and multiple polyps did not differ between the two groups. CONCLUSIONS: While data has shown an association between H. pylori and colorectal adenomas, we did not find this in our Hispanic population. With the growing population of Hispanics in the U.S, large scale studies are needed to conclusively characterize the role of H. pylori infection in colorectal adenoma and adenocarcinoma in this group of patients.

Ethnic disparities in the risk of colorectal adenomas associated with aspirin and statin use: a retrospective multiethnic study.

BACKGROUND: Although data on the inverse association between colorectal adenomas (CRA) and daily aspirin or statin therapy exists in white and black patients, scarce data exists on these associations in the Hispanic population. With a rapidly increasing Hispanic population in the United States, defining the association in Hispanics is crucial. METHODS: The study sample included 1,843 consecutive patients who underwent a colonoscopy (screening or diagnostic) from 2009 to 2011 at a community hospital in East Meadow, New York. Data was then extracted from patient charts regarding aspirin and/or statin use. Adjusted odds ratios (OR) and their 95% confidence intervals (CI) were calculated to assess the association between colonoscopy findings and aspirin, statin, or aspirin/statin use. RESULTS: In our total population including all races, aspirin user had an increased risk for having two or more adenomas (OR =1.73, 95% CI: 1.00, 2.99, P=0.05) and presence of an adenoma in the proximal colon (OR =1.66, 95% CI: 1.07, 2.58, P=0.02). In the total study population, those who used both statin and aspirin had an increased risk for having two or more adenomas (OR =2.56, 95% CI: 1.21, 5.39, P=0.01). In the Hispanic population, users of both medications had an increased risk for having two or more adenomas (OR =19.04, 95% CI: 1.30, 280.09, P=0.03), adenoma present in the distal colon (OR =5.75, 95% CI: 1.64, 20.21, P=0.01) and largest adenoma in distal colon (OR =5.75, 95% CI: 1.64, 20.21, P=0.01). CONCLUSIONS: Aspirin use and aspirin/statin use was associated with abnormal colonoscopy findings, particularly in the Hispanic population. These findings may be due to environmental factors such as dietary, colonic flora, or genetic susceptibility. The findings warrant further investigational research, particularly in Hispanics.

Resveratrol induces apoptosis and cell cycle arrest of human T24 bladder cancer cells in vitro and inhibits tumor growth in vivo.

Resveratrol, a naturally occurring polyphenolic antioxidant compound present in grapes and red wine, has been reported to hold various biochemical responses. In this preliminary study, we evaluate the chemopreventive potential of resveratrol against bladder cancer and its mechanism of action. Treatment of bladder cancer cells with resveratrol resulted in a significant decrease in cell viability. Resveratrol induced apoptosis through the modulation of Bcl-2 family proteins and activation of caspase 9 and caspase 3 followed by poly(ADP-ribose) polymerase degradation. Treatment with resveratrol led to G(1) phase cell cycle arrest in T24 cells by activation of p21 and downregulation of cyclin D1, cyclin-dependent kinase 4, and phosphorylated Rb. Resveratrol also inhibited the phosphorylation of Akt, whereas the phosphorylation of p38 MAPK was enhanced. In addition, resveratrol treatment decreased the expression of vascular endothelial growth factor and fibroblast growth factor-2, which might contribute to the inhibition of tumor growth on the bladder cancer xenograft model. These findings suggest that reveratrol could be an important chemoprevention agent for bladder cancer.

Langerhans' cell density and degree of keratinization in foreskins of Chinese preschool boys and adults.

BACKGROUND: Recent epidemiological studies have proposed that male circumcision reduces the relative risk of acquiring HIV-1. Here, we evaluated the density of Langerhans' cell and degree of keratinization in the foreskins of Chinese preschool boys and adults. METHODS: Sixty preschool boys and 20 healthy men without infectious history following male circumcisions were included. The keratin thickness and Langerhans' cells were quantified by using keratin staining, immunohistochemistry, and image analysis. RESULTS: The extent of keratinization was much greater in the inner foreskin than in the outer foreskin in adults and boys with infectious history. It was likely to be less keratinized in boys' foreskins compared with those of adults. The density of Langerhans' cells was higher in the outer foreskin than in the inner foreskin of adults and healthy boys. Furthermore, an increased density of Langerhans' cells of inner foreskin was also found in boys with infectious history compared with healthy boys. There was much higher Langerhans' cell density in boys' foreskin compared with those of adults. CONCLUSIONS: These findings suggest that Chinese men may have a different feature of keratin in the foreskin, and a higher Langerhans' cells density in boys' foreskin may be due to it being less keratinized.

Up-regulation of E-cadherin by small activating RNA inhibits cell invasion and migration in 5637 human bladder cancer cells.

Recent studies have reported that chemically synthesized small duplex RNAs complementary to promoters of target genes can specifically induce gene expression in several cancer cell lines. Such dsRNA, referred to as small activating RNA (saRNA), are involved in the recently described phenomenon called RNA activation (RNAa). Recent findings show that saRNA can inhibit cell proliferation and viability via up-regulation of p21(WAF1/CIP1) (p21) in human bladder cancer cells. In the present study, we demonstrate that induction of E-cadherin expression by saRNA leads to suppression of migration and invasion of 5637 human bladder cancer cells in vitro. The elevated E-cadherin expression was confirmed at transcriptional and protein levels after transfection of a 21-nucleotide dsRNA targeting the E-cadherin promoter (dsEcad). Furthermore, this inhibitory effect was associated with relocalization of beta-catenin from the nucleus to the plasma membrane and decreased beta-catenin-mediated transactivation. These data suggest that activation of E-cadherin by saRNA may have a therapeutic benefit for bladder and other types of cancer.

The use of prostate specific antigen (PSA) density in detecting prostate cancer in Chinese men with PSA levels of 4-10 ng/mL.

AIM: To investigate the utility of prostate specific antigen density for detecting prostate cancer in men with serum PSA levels of 4-10 ng/mL. METHODS: Between January 2003 and November 2007, 237 men (aged 48-84 years, median 71) with total PSA levels of 4-10 ng/mL participated in a protocol for prostate cancer screening. Eligible patients were recommended for transrectal ultrasonography (TRUS)-guided prostate biopsies after measuring prostate volumes transrectally. The diagnostic value of PSA levels and the free-to-total PSA ratio (f/tPSA), PSA densities (PSAD) were compared using receiver operating characteristic analysis. RESULTS: Prostate cancer was diagnosed in 44 (18.6%) of the 237 men who had biopsies. There were significant differences between the groups in the prostate volumes determined by TRUS, PSAD, PSA levels and f/tPSA, whereas there was no significant difference in patient age. The area under the curve (AUC) of PSA (0.6786) and PSAD (0.717) was similar and significantly greater than that of f/tPSA (AUC 0.329). PSAD was a significantly better indicator of prostate cancer than f/tPSA. The sensitivity and specificity of PSA density at a cutoff of 0.134 ng/mL(2) was 90 and 33.7%, respectively. CONCLUSION: PSAD was a better predictor of prostate cancer in Chinese men with PSA levels of 4-10 ng/mL, especially those who have had prior ultrasound-determined measurements of prostate volume. Our data suggest that different PSAD cutoffs may need to be defined for Chinese.

Effects of wortmannin on phosphorylation of PDK1, GSK3-beta, PTEN and expression of Skp2 mRNA after ischemia/reperfusion injury in the mouse kidney.

AIM: The aim of this study was to investigate the role of 3-phosphoinositide-dependent protein kinase-1 (PDK1), glycogen synthase kinase-3beta (GSK3-beta) and phosphatase and tensin homologue deleted on chromosome 10 (PTEN), which are the components of the phosphoinositide 3-kinase (PI3K)/Akt pathway, and expression of S-phase kinase-associated protein 2 (Skp2) messenger RNA (mRNA) in renal ischemia/reperfusion. MATERIALS AND METHODS: Three experimental groups, sham-operative mice, vehicle-delivered mice and wortmannin-treated ischemia/reperfusion injury (IRI) mice were designed to examine PDK1, GSK3-beta and PTEN phosphorylation status, as well as expression of Skp2 mRNA at 30 min, 90 min, 24 h and 48 h of reperfusion after ischemia treatment. Wortmannin or its vehicle was given intraperitoneally 4 h before surgery. Expression of Skp2 mRNA was examined by semiquantitative reverse-transcription PCR, and the components of the PI3K/Akt pathway were detected by western blotting in the IRI kidney. RESULTS: Phosphorylation of PDK1(Ser241), GSK3-beta(Ser9) and PTEN(Ser380) was increased after ischemia/reperfusion in the mouse kidney, and phosphorylation of PDK1 was reduced by wortmannin administration. The renal Skp2 mRNA increased after IRI in mouse, which could be inhibited by wortmannin. CONCLUSIONS: Our primary study suggests that the PI3K/Akt signaling pathway plays an important role in regulating the repair following renal IRI. The Skp2 mRNA increased in the IRI kidney and may be regulated by the PI3K/Akt pathway.