[Nasal endoscopy-assisted bulboprostatic anastomosis for posterior urethral stricture].

OBJECTIVE: To study the clinical value and operation skills of nasal endoscopy-assisted bulboprostatic anastomosis in the treatment of posterior urethral stricture. METHODS: Between January 2012 and November 2014, we performed nasal endoscopy-assisted bulboprostatic anastomosis for 12 male patients with posterior urethral stricture. We recorded the operation time, blood loss, exposure of operation visual field, and success rate of anastomosis and summarized the operation skills. RESULTS: Eight of the patients experienced first-stage recovery. Two underwent a urethral dilation at 3 months postoperatively, 1 received 10 urethral dilations within 5 months after surgery, and 1 underwent internal urethrotomy after failure in urethral dilation, but all the 4 cases were cured. CONCLUSION: Nasal endoscopy can significantly improve the operation field exposure, elevate the precision, reduce the difficulty, and enhance the efficiency of bulboprostatic anastomosis in the treatment of posterior urethral stricture.

Efficacy of neonatal HBV vaccination on liver cancer and other liver diseases over 30-year follow-up of the Qidong hepatitis B intervention study: a cluster randomized controlled trial.

BACKGROUND: Neonatal hepatitis B vaccination has been implemented worldwide to prevent hepatitis B virus (HBV) infections. Its long-term protective efficacy on primary liver cancer (PLC) and other liver diseases has not been fully examined. METHODS AND FINDINGS: The Qidong Hepatitis B Intervention Study, a population-based, cluster randomized, controlled trial between 1985 and 1990 in Qidong, China, included 39,292 newborns who were randomly assigned to the vaccination group in which 38,366 participants completed the HBV vaccination series and 34,441 newborns who were randomly assigned to the control group in which the participants received neither a vaccine nor a placebo. However, 23,368 (67.8%) participants in the control group received catch-up vaccination at age 10-14 years. By December 2013, a total of 3,895 (10.2%) in the vaccination group and 3,898 (11.3%) in the control group were lost to follow-up. Information on PLC incidence and liver disease mortality were collected through linkage of all remaining cohort members to a well-established population-based tumor registry until December 31, 2013. Two cross-sectional surveys on HBV surface antigen (HBsAg) seroprevalence were conducted in 1996-2000 and 2008-2012. The participation rates of the two surveys were 57.5% (21,770) and 50.7% (17,204) in the vaccination group and 36.3% (12,184) and 58.6% (17,395) in the control group, respectively. Using intention-to-treat analysis, we found that the incidence rate of PLC and the mortality rates of severe end-stage liver diseases and infant fulminant hepatitis were significantly lower in the vaccination group than the control group with efficacies of 84% (95% CI 23%-97%), 70% (95% CI 15%-89%), and 69% (95% CI 34%-85%), respectively. The estimated efficacy of catch-up vaccination on HBsAg seroprevalence in early adulthood was 21% (95% CI 10%-30%), substantially weaker than that of the neonatal vaccination (72%, 95% CI 68%-75%). Receiving a booster at age 10-14 years decreased HBsAg seroprevalence if participants were born to HBsAg-positive mothers (hazard ratio [HR]  = 0.68, 95% CI 0.47-0.97). Limitations to consider in interpreting the study results include the small number of individuals with PLC, participants lost to follow-up, and the large proportion of participants who did not provide serum samples at follow-up. CONCLUSIONS: Neonatal HBV vaccination was found to significantly decrease HBsAg seroprevalence in childhood through young adulthood and subsequently reduce the risk of PLC and other liver diseases in young adults in rural China. The findings underscore the importance of neonatal HBV vaccination. Our results also suggest that an adolescence booster should be considered in individuals born to HBsAg-positive mothers and who have completed the HBV neonatal vaccination series. Please see later in the article for the Editors' Summary.

Dramatic reduction of liver cancer incidence in young adults: 28 year follow-up of etiological interventions in an endemic area of China.

Qidong City, China, has had high liver cancer incidence from endemic hepatitis B virus (HBV) infection and dietary exposure to aflatoxin. Based on etiologic studies, we began interventions in 1980 to reduce dietary aflatoxin and initiate neonatal HBV vaccination. We studied trends in liver cancer incidence rates in the 1.1 million inhabitants of Qidong and examined trends in aflatoxin exposure, staple food consumption, HBV infection markers and annual income. Aflatoxin exposure declined greatly in association with economic reform, increased earnings and educational programs to shift staple food consumption in the total population from moldy corn to fresh rice. A controlled neonatal HBV vaccination trial began in 1983 and ended in November, 1990, when vaccination was expanded to all newborns. Liver cancer incidence fell dramatically in young adults. Compared with 1980-83, the age-specific liver cancer incidence rates in 2005-08 significantly decreased 14-fold at ages 20-24, 9-fold at ages 25-29, 4-fold at ages 30-34, 1.5-fold at ages 35-39, 1.2-fold at ages 40-44 and 1.4-fold at ages 45-49, but increased at older ages. The 14-fold reduction at ages 20-24 might reflect the combined effects of reduced aflatoxin exposure and partial neonatal HBV vaccination. Decrease incidence in age groups >25 years could mainly be attributable to rapid aflatoxin reduction. Compared with 1980-83, liver cancer incidence in 1990-93 significantly decreased 3.4-fold at ages 20-24, and 1.9-fold at ages 25-29 when the first vaccinees were <11 years old.

Therapeutic efficacy of trehalose eye drops for treatment of murine dry eye induced by an intelligently controlled environmental system.

PURPOSE: To determine whether eye drop instillation of the disaccharide trehalose (TT) alleviates ocular surface damage in a dry eye murine model. METHODS: Dry eye was induced in mice using an intelligently controlled environmental system (ICES). After 21 days housed in the ICES without topical treatment, the mice were randomly divided into three groups: no eye drops (ICES) for three weeks, four times a day with PBS 0.01 M 10 µl/eye bilaterally (ICES+PBS), or with TT 87.6 mM 10 µl/eye bilaterally (ICES+TT). Another mice group that was not exposed to the ICES and received no treatment served as a control group (UT). The ocular surface integrity, in each group, was evaluated using Oregon Green dextran (OGD) and fluorescein staining. The expression and distribution of occludin, involucrin, and small proline-rich protein 2 were determined with immunohistology analysis on whole mounted corneas. Heat shock protein 70 (HSP70) and matrix metalloproteinase 9 (MMP-9) expression was estimated with immunohistology. Ocular surface inflammation associated with each treatment was estimated with real time-PCR of interleukin-1ß (IL-1ß), IL-2, IL-6, IL-17, and tumor necrosis factor-alpha in the conjunctiva. RESULTS: OGD staining in the cornea epithelium was lower in the ICES+TT group than in the ICES and ICES+PBS groups. Corneal epithelial occludin staining was markedly more homogenous in the ICES+TT group than in ICES and ICES+PBS groups, and there were no desquamating apical epithelial cells. Involucrin and small proline-rich protein 2 labeling of whole mounted corneas revealed upregulation of their expression in the groups, which received no treatment or PBS instillation compared to the ICES+TT group. HSP70 and MMP-9 immunolabeling revealed a marked increase in corneal epithelial expression in response to the ICES. The group treated with trehalose showed a similar profile expression of HSP70 and MMP-9 as the control group (UT). Conjunctival IL-1ß, IL-2, IL-6, IL-17, tumor necrosis factor-alpha (TNF-α), and MMP-9 mRNA expression was lower in the ICES+TT group than in the ICES or ICES+PBS group. CONCLUSIONS: Trehalose application restored ocular surface integrity, suppressed inflammatory and proteolytic MMP-9 and HSP70 expression, and keratinization in mice with dry eye damaged by a desiccative model.

[Risk features of HBV in human hepatocarcinogenesis: a nested case-controlled study].

OBJECTIVE: To identify the association strength of the prevalence of HBeAg, covalently closed circular DNA (cccDNA) and 1762/1764 nucleotide mutations of hepatitis B virus (HBV) with the occurrence of hepatocellular carcinoma (HCC) in Qidong high risk male cohort. METHODS: A cohort of 377 middle aged HBV infected men in Qidong was followed from January 1989 to December 2002. Incident HCC cases were carefully registered. A matched case-controlled study was conducted on 32 pairs of inherent HCC cases with their matched non-HCC controls. Serum HBeAg was measured by ELISA. cccDNA was detected by primer selected PCR. 1762/1764 nucleotide mutations of HBV was identified by PCR of X gene segment spanning the mutation region. Standard statistical comparison between the prevalence of each HBV marker in HCC versus in control group provided the odds ratio with P value to evaluate its association strength with HCC occurrence. RESULTS: Serum HBeAg prevalence was 53.1% (17/32) in HCC group versus and 15.6% (5/32) in controls (OR = 6.12, P < 0.01). Prevalence of serum cccDNA was detected in 62.5% (21/32) of HCC cases but in 25.0% (8/32) of controls (OR = 5.73, P < 0.01). Sequence of detected cccDNA was repeatedly found to be over 90% homologous with HBV. However, the mutation rate of nucleotide 1762/1764 was not found to be statistically higher in the HCC group versus its controls (OR = 1.54, P = 0.425). CONCLUSIONS: The Qidong male case-controlled cohort had shown that serum HBeAg and cccDNA prevalence were tightly associated with hepatocellular carcinoma occurrence in HBV infected men. These biomarkers may have predictive value in earlier diagnosis and therapeutic effect monitoring.

Tight association of hepatocellular carcinoma with HBV infection in North China.

BACKGROUND: Hepatocellular carcinoma (HCC) is the second most common cancer in China. Hepatitis B and C viruses (HBV and HCV) and aflatoxins are known risk factors for HCC, but the etiological status of these factors in HCC development is not clear. This study was undertaken to define the absolute importance of HBV in hepatocarcinogenesis of North China. METHODS: A consecutive series of 119 patients with pathologically proven HCC were collected from North China during January 1998 to December 2000 by the Cancer Hospital of the Chinese Academy of Medical Sciences, Beijing. Serum HBsAg, anti-HBc and anti-HCV were negative HBV sero-markers. The HBV X gene was analyzed for its expression by PCR, DNA sequencing, and immunohistochemistry. RESULTS: In the 119 HCC patients, 82.4% (98/119) were HBsAg seropositive. When a comprehensive set of HBV markers were detected, the HBV infection rate in these HCC patients was 99.2% (118/119). Of the patients, 11.8%(14/119) were found to be anti-HCV positive. But all the anti-HCV positive HCC patients were co-infected with HBV. CONCLUSIONS: HBV infection is virtually ubiquitous in HCC patients in North China. The tight association of HBV with HCC strongly suggests the dominant role of HBV infection in causing hepatocellular carcinoma. About 11.8% of HCC patients being HCV-related are co-infected with HBV.

Dominant role of hepatitis B virus and cofactor role of aflatoxin in hepatocarcinogenesis in Qidong, China.

We assessed the separate and combined effects of hepatitis B virus (HBV), hepatitis C virus (HCV), and aflatoxin in causing hepatocellular carcinoma (HCC) in Qidong, China. A consecutive series of 181 pathologic-diagnosed HCC cases were studied for hepatitis B surface antigen (HBsAg), anti-HBc, HBV X gene sequence, anti-HCV, the 249ser-p53 mutation, and chronic hepatitis pathology. Each of the 181 incident HCC cases had markers for HBV infection and hepatitis pathology; only 6 of 119 cases were coinfected with HCV. The 249ser-p53 mutation was found in 54% (97/181) of HCC cases and in all 7 cases with tissue for analysis from the hepatitis cohort but in none of 42 matched cases from Beijing. The estimated cumulative dose of aflatoxin B1 in these 7 cases ranged from 0.13 to 0.49 mg/kg. Follow-up data through 13.25 years on a cohort of 145 men with chronic HBV hepatitis showed that the relative risk from aflatoxin exposure was 3.5 (1.5-8.1). A similar relative risk was found using 249ser-p53 mutation as a marker for aflatoxin exposure. In conclusion, HBV hepatitis is ubiquitous in Qidong HCC cases, whereas HCV contributes little to its risk. The 249ser-p53 mutation appears to result from coexposure to aflatoxin and HBV infection. Even modest levels of aflatoxin exposure tripled the risk of HCC in HBV-infected men.