The Influence of Hepatitis B Viral Load and Pre-S Deletion Mutations on Post-Operative Recurrence of Hepatocellular Carcinoma and the Tertiary Preventive Effects by Anti-Viral Therapy

Background

Whether or not hepatitis B virus (HBV) genotypes, mutations, and viral loads determine outcomes for patients with HBV-induced hepatocellular carcinoma (HCC) remains controversial.

Aims

To study the influence of HBV viral factors on prognoses for patients with HBV-induced HCC after resection surgery and investigate if antiviral therapy could counteract the adverse effects of viral factors.

Methods

A total of 333 HBV-related HCC patients who underwent tumor resection were enrolled retrospectively. Serum HBV DNA levels, mutations, anti-viral therapy, and other clinical variables were analyzed for their association with post-operative recurrence.

Results

After a median follow-up of 45.9 months, 208 patients had HCC recurrence after resection. The 5-year overall survival and recurrence-free survival rates were 55.4% and 35.3%, respectively. Multivariate analysis showed indocyanine green retention rate at 15 minutes >10%, gamma-glutamyltransferase (GGT) level >60 U/L, macroscopic and microscopic venous invasion, and the absence of anti-viral therapy were significant risk factors for recurrence. Anti-viral therapy could decrease recurrence in patients with early stage HCC, but the effect was less apparent in those with the Barcelona-Clinic Liver Cancer stage C HCC. For patients without antiviral therapy after resection, serum HBV DNA levels >10⁶ copies/mL, GGT >60 U/L, and macroscopic and microscopic venous invasion were significant risk factors predicting recurrence. Among the 216 patients without anti-viral therapy but with complete HBV surface gene mapping data, 73 were with pre-S deletion mutants. Among patients with higher serum HBV DNA levels, those with pre-S deletion had significantly higher rates of recurrence. Moreover, multivariate analysis showed multi-nodularity, macroscopic venous invasion, cirrhosis, advanced tumor cell differentiation, and pre-S deletion were significant risk factors predictive of recurrence.

Conclusions

Ongoing HBV viral replication and pre-S deletion are crucial for determining post-operative tumor recurrence. Anti-viral therapy can help reduce recurrence and improve prognosis, especially for those with early stage HCC.     

Risk Factors and Post-Resection Independent Predictive Score for the Recurrence of Hepatitis B-Related Hepatocellular Carcinoma

Background

Independent risk factors associated with hepatitis B (HBV)-related hepatocellular carcinoma (HCC) after resection remains unknown. An accurate risk score for HCC recurrence is lacking.

Methods

We prospectively followed up 200 patients who underwent liver resection for HBV-related HCC for at least 2 years. Demographic, biochemical, tumor, virological and anti-viral treatment factors were analyzed to identify independent risk factors associated with recurrence after resection and a risk score for HCC recurrence formulated.

Results

Two hundred patients (80% male) who underwent liver resection for HBV-related HCC were recruited. The median time of recurrence was 184 weeks (IQR 52–207 weeks) for the entire cohort and 100 patients (50%) developed HCC recurrence. Stepwise Cox regression analysis identified that one-month post resection HBV DNA >20,000 IU/mL (p = 0.019; relative risk (RR) 1.67; 95% confidence interval (C.I.): 1.09–2.57), the presence of lymphovascular permeation (p<0.001; RR 2.69; 95% C.I.: 1.75–4.12), microsatellite lesions (p<0.001; RR 2.86; 95% C.I.: 1.82–4.51), and AFP >100ng/mL before resection (p = 0.021; RR 1.63; 95% C.I.: 1.08–2.47) were independently associated with HCC recurrence. Antiviral treatment before resection (p = 0.024; RR 0.1; 95% C.I.: 0.01–0.74) was independently associated with reduced risk of HCC recurrence. A post-resection independent predictive score (PRIPS) was derived and validated with sensitivity of 75.3% and 60.6% and specificity of 55.7% and 79.2%, to predict the 1- and 3-year risks for the HCC recurrence respectively with the hazard ratio of 2.71 (95% C.I.: 2.12–3.48; p<0.001). The AUC for the 1- and 3-year prediction were 0.675 (95% C.I.: 0.6–0.78) and 0.746 (95% C.I.: 0.69–0.82) respectively.

Conclusion

Several tumor, virological and biochemical factors were associated with a higher cumulative risk of HCC recurrence after resection. PRIPS was derived for more accurate risk assessment. Regardless of the HBV DNA level, antiviral treatment should be given to patients before resection to reduce the risk of recurrence.     

Risk Factors for Idiopathic Optic Neuritis Recurrence

Background

Approximately 30–50% of idiopathic optic neuritis (ION) patients experience one or multiple episodes of recurrence. The aim of this study was to search for risk factors for ION recurrence.

Methods

Clinical data on hospitalized patients diagnosed with ION between January 2003 and January 2011 at the First Affiliated Hospital of Guangxi Medical University were retrospectively collected. Univariate and multivariate analyses were performed on factors that might cause ION recurrence. In total, 115 ION cases (32 recurrent and 83 non-recurrent cases) with complete data were analyzed. The length of the follow-up period ranged from 12 to 108 months (median: 42 months).

Results

The univariate analysis showed that the recurrence rate for unilateral ION was higher than that for bilateral ION (40% vs. 12%, p = 0.001). Underlying diseases had a significant impact on recurrence (p<0.001): the recurrence rates due to neuromyelitis optica (NMO), multiple sclerosis (MS), demyelinating lesions alone of the central nervous system, and unknown causes were 89%, 70%, 41%, and 8.7%, respectively. The multivariate analysis showed that the factors causing relatively high recurrence rates included NMO (odds ratio [OR], 73.5; 95% confidence interval [CI], 7.3 to 740.9), MS (OR, 33.9; 95% CI, 5.2 to 222.2), and demyelinating lesions alone (OR, 8.9; 95% CI, 2.3 to 34.4), unilateral involvement (OR, 5.7; 95% CI, 1.5 to 21.3), relatively low initial glucocorticoid dosage (equivalent to ≤100 mg prednisone/day) (OR, 4.3; 95% CI, 1.0 to 17.9).

Conclusion

Underlying diseases, laterality (unilateral or bilateral), and initial glucocorticoid dosage are important risk factors of ION recurrence. Clinical physicians are advised to treat ION patients with a sufficient dose of glucocorticoid in the initial treatment stage to reduce the recurrence risk.     

Impact of Squamous and Glandular Differentiation on Oncologic Outcomes in Upper and Lower Tract Urothelial Carcinoma

Purpose

To investigate the prognostic significance of squamous and/or glandular differentiation in urothelial carcinoma (UC).

Materials and Methods

Among 800 consecutive patients who underwent radical cystectomy or nephroureterectomy at our institution from January 1990 to December 2010, 696 patients were included for the analysis. Clinicopathologic variables were compared according to the presence of squamous and/or glandular differentiation and the tumor location.

Results

A total of 51 (7.3%) patients had squamous and/or glandular differentiation. Patients with squamous and/or glandular differentiation had higher pathological T stage (p<0.001) and grade (p<0.001) than those with pure form of UC. After the median follow-up of 55.2 months, 84 (24.6%) and 82 (23.1%) died of upper urinary tract UC and UC of bladder, respectively. Patients with squamous and/or glandular differentiation in upper urinary tract UC showed poorer cancer-specific survival (CSS) (p<0.001) and overall survival (OS) (p<0.001) than those with pure form in upper urinary tract UC (p<0.001), but not in UC of bladder (p = 0.178 for CSS and p = 0.172 for OS). On multivariate Cox regression analysis, squamous and/or glandular differentiation was an independent predictor of CSS (hazard ratio [HR] 1.76; 95% confidence interval [CI] 1.08–2.85, p = 0.023), but it was not associated with OS (HR 1.52; 95% CI 1.00–2.32, p = 0.051).

Conclusions

The presence of variant histology could be associated with poorer survival outcome in patients with UC. Squamous and/or glandular differentiation is associated with features of biologically aggressive disease and an independent predictor of CSS.     

Determinants of Brushite Stone Formation: A Case-Control Study

Purpose

The occurrence of brushite stones has increased during recent years. However, the pathogenic factors driving the development of brushite stones remain unclear.

Methods

Twenty-eight brushite stone formers and 28 age-, sex- and BMI-matched healthy individuals were enrolled in this case-control study. Anthropometric, clinical, 24 h urinary parameters and dietary intake from 7-day weighed food records were assessed.

Results

Pure brushite stones were present in 46% of patients, while calcium oxalate was the major secondary stone component. Urinary pH and oxalate excretion were significantly higher, whereas urinary citrate was lower in patients as compared to healthy controls. Despite lower dietary intake, urinary calcium excretion was significantly higher in brushite stone patients. Binary logistic regression analysis revealed pH>6.50 (OR 7.296; p = 0.035), calcium>6.40 mmol/24 h (OR 25.213; p = 0.001) and citrate excretion <2.600 mmol/24 h (OR 15.352; p = 0.005) as urinary risk factors for brushite stone formation. A total of 56% of patients exhibited distal renal tubular acidosis (dRTA). Urinary pH, calcium and citrate excretion did not significantly differ between patients with or without dRTA.

Conclusions

Hypercalciuria, a diminished citrate excretion and an elevated pH turned out to be the major urinary determinants of brushite stone formation. Interestingly, urinary phosphate was not associated with urolithiasis. The increased urinary oxalate excretion, possibly due to decreased calcium intake, promotes the risk of mixed stone formation with calcium oxalate. Neither dietary factors nor dRTA can account as cause for hypercalciuria, higher urinary pH and diminished citrate excretion. Further research is needed to define the role of dRTA in brushite stone formation and to evaluate the hypothesis of an acquired acidification defect.     

Frequency,Risk Factors and Survival Associated with an Intrasubsegmental Recurrence after Radiofrequency Ablation for Hepatocellular Carcinoma

Background

In the treatment of hepatocellular carcinoma (HCC), hepatic resection has the advantage over radiofrequency ablation (RFA) in terms of systematic removal of a hepatic segment.

Methods

We enrolled 303 consecutive patients of a single naïve HCC that had been treated by RFA at The University of Tokyo Hospital from 1999 to 2004. Recurrence was categorized as either intra- or extra-subsegmental as according to the Couinaud''s segment of the original nodule. To assess the relationship between the subsegments of the original and recurrent nodules, we calculated the kappa coefficient. We assessed the risk factors for intra- and extra-subsegmental recurrence independently using univariate and multivariate Cox proportional hazard regression. We also assessed the impact of the mode of recurrence on the survival outcome.

Results

During the follow-up period, 201 patients in our cohort showed tumor recurrence distributed in a total of 340 subsegments. Recurrence was categorized as exclusively intra-subsegmental, exclusively extra-subsegmental, and simultaneously intra- and extra-subsegmental in 40 (20%), 110 (55%), and 51 (25%) patients, respectively. The kappa coefficient was measured at 0.135 (95% CI, 0.079–0.190; P<0.001). Multivariate analysis revealed that of the tumor size, AFP value and platelet count were all risk factors for both intra- and extra-subsegmental recurrence. Of the patients in whom recurrent HCC was found to be exclusively intra-subsegmental, extra-subsegmental, and simultaneously intra- and extra-subsegmental, 37 (92.5%), 99 (90.8%) and 42 (82.3%), respectively, were treated using RFA. The survival outcomes after recurrence were similar between patients with an exclusively intra- or extra-subsegmental recurrence.

Conclusions

The effectiveness of systematic subsegmentectomy may be limited in the patients with both HCC and chronic liver disease who frequently undergo multi-focal tumor recurrence.     

Nucleot(s)ide Analogues for Hepatitis B Virus-Related Hepatocellular Carcinoma after Curative Treatment: A Systematic Review and Meta-Analysis

Aim

The benefit of nucleot(s)ide analogues (NA) for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after curative treatment has been widely debated due to the relatively weak evidence. The objective of this systematic review was to evaluate the effect of NA on recurrence and survival after curative treatment of HBV-HCC.

Methods

A systematic electronic search was performed. All controlled trials comparing NA versus placebo or no treatment were considered for inclusion. Results were expressed as Hazard Ratio for recurrence and survival with 95% confidence intervals using RevMan 5.2.

Results

We included 13 trials with 6350 patients. There were significant improvements for recurrence-free survival (HR 0.66, 95% CI 0.54–0.80; p<0.0001) and overall survival (HR 0.56, 95% CI 0.43–0.73; p<0.0001) in the adjuvant NA group compared with the control group. Sensitivity analyses confirmed the robustness of the results. There were no serious adverse effects being reported. Lamivudine resistance was from 28.6% to 37.5% but could be rescued by other types of NA or combination therapy.

Conclusion

Our study suggested benefits of adjuvant NA therapy following curative treatment of HBV-HCC. Since the great proven efficacy of NA in improving clinical and viral parameters besides HCC, further studies should be focused on broadening the indications for NA therapy after curative treatment of HBV-HCC.     

Scoring Selection Criteria Including Total Tumour Volume and Pretransplant Percentage of Lymphocytes to Predict Recurrence of Hepatocellular Carcinoma after Liver Transplantation

Aim

The selection criteria for patients with hepatocellular carcinoma (HCC) to undergo liver transplantation should accurately predict posttransplant recurrence while not denying potential beneficiaries. In the present study, we attempted to identify risk factors associated with posttransplant recurrence and to expand the selection criteria.

Patients and Methods

Adult patients with HCC who underwent liver transplantation between November 2004 and September 2012 at our centre were recruited into the current study (N = 241). Clinical and pathological data were retrospectively reviewed. Patients who died during the perioperative period or died of non-recurrence causes were excluded from this study (N = 25). All potential risk factors were analysed using uni- and multi-variate analyses.

Results

Sixty-one recipients of 216 qualified patients suffered from recurrence. Similar recurrence-free and long-term survival rates were observed between living donor liver transplant recipients (N = 60) and deceased donor liver transplant recipients (N = 156). Total tumour volume (TTV) and preoperative percentage of lymphocytes (L%) were two independent risk factors in the multivariate analysis. We propose a prognostic score model based on these two risk factors. Patients within our criteria achieved a similar recurrence-free survival to patients within the Milan criteria. Seventy-one patients who were beyond the Milan criteria but within our criteria also had comparable survival to patients within the Milan criteria.

Conclusions

TTV and L% are two risk factors that contribute to posttransplant recurrence. Selection criteria based on these two factors, which are proposed by our study, expanded the Milan criteria without increasing the risk of posttransplant recurrence.     

Better Long-Term Survival in Young Patients with Non-Metastatic Colorectal Cancer after Surgery,an Analysis of 69,835 Patients in SEER Database

Objective

To compare the long-term survival of colorectal cancer (CRC) in young patients with elderly ones.

Methods

Using Surveillance, Epidemiology, and End Results (SEER) population-based data, we identified 69,835 patients with non-metastatic colorectal cancer diagnosed between January 1, 1988 and December 31, 2003 treated with surgery. Patients were divided into young (40 years and under) and elderly groups (over 40 years of age). Five-year cancer specific survival data were obtained. Kaplan-Meier methods were adopted and multivariable Cox regression models were built for the analysis of long-term survival outcomes and risk factors.

Results

Young patients showed significantly higher pathological grading (p<0.001), more cases of mucinous and signet-ring histological type (p<0.001), later AJCC stage (p<0.001), more lymph nodes (≥12 nodes) dissected (p<0.001) and higher metastatic lymph node ratio (p<0.001). The 5-year colorectal cancer specific survival rates were 78.6% in young group and 75.3% in elderly group, which had significant difference in both univariate and multivariate analysis (P<0.001). Further analysis showed this significant difference only existed in stage II and III patients.

Conclusions

Compared with elderly patients, young patients with colorectal cancer treated with surgery appear to have unique characteristics and a higher cancer specific survival rate although they presented with higher proportions of unfavorable biological behavior as well as advanced stage disease.     

Risk Factors for Small Airway Obstruction among Chinese Island Residents: A Case-Control Study

Background

We investigated the prevalence of and risk factors for small airway obstruction (SAO) among Chinese island residents to establish means to prevent and treat SAO.

Methods

From October 17, 2011 to November 1, 2011, a total of 2,873 residents aged >20 years who lived on the Huangqi Peninsula of Fujian were recruited by random cluster sampling. They were asked to complete a Burden of Obstructive Lung Disease (BOLD) questionnaire and underwent physical examinations and lung function evaluations. SAO was defined as a forced expiratory flow at 50% of vital capacity, Vmax50%, of less than 70% of predicted. Risk factors for SAO were assessed from among demographic and anthropometric variables, blood chemistry results, and questionnaire response items.

Results

A total of 216 (7.52%) Chinese island residents were identified as having SAO (95 males; 121 females). Their survey and test results were compared with 432 age and sex-matched healthy controls (192 males; 240 females) for SAO risk factors. Among numerous factors investigated, only diabetes mellitus (p = 0.039), smoking index (SI, p<0.001 for SI>600), second hand smoke (p = 0.002), and lack of regular exercise (p<0.001) were significant risk factors for SAO.

Conclusions

The risk factors for SAO among Chinese island residents appeared to be similar to those among people who live in high-density urban environments and impoverished rural areas. Public health policies and medical practices directed toward improving respiratory health for island residents should be comparable to those used for urban and rural dwellers.     

Development of Contrast-Induced Acute Kidney Injury after Elective Contrast Media Exposure in Patients with Type 2 Diabetes Mellitus: Effect of Albuminuria

Background

The influence of albuminuria and urinary pH on the development of contrast-induced acute kidney disease (CI-AKI) in patients with type 2 diabetes mellitus (T2DM) after elective coronary angiography (CAG) or percutaneous coronary intervention (PCI) is unknown.

Methods

CI-AKI was defined as an increase in serum creatinine >26.4 µmol/L or ≥50% of baseline value within 48 hours after contrast media exposure. Demographics, traditional risk factors, clinical outcomes and CI-AKI incidence were compared between groups. Univariate analysis and multivariate logistic regression were performed to assess risk factors of CI-AKI.

Results

We observed 597 patients with T2DM after CAG or PCI. Patients were divided into 3 groups based on early morning urinary albumin: negative group (urine dipstick negative, n = 483), trace group (urine dipstick trace, n = 60), and positive group (urine dipstick ≥1+, n = 54). CI-AKI occurred in 33 (5.5%) patients, including 19 (3.9%) in the negativealbuminuria group, 4 (6.7%) in the trace group, and 10 (18.5%) in the positive group (p< 0.001), respectively. After adjusting for potential confounding risk factors, positive albuminuria (OR = 3.8, 95% CI: 1.5 to 9.2, p = 0.004) and urinary pH<6 (OR = 2.4, 95% CI: 1.1 to 5.1, p = 0.020) remained significantly associated with CI-AKI.

Conclusion

Preprocedural albuminuria and urinary pH <6 are independent risk factors of CI-AKI in patients with T2DM undergoing elective cardiac catheterization, and may be used to identify patients at high risk of post-procedural CI-AKI.     

Preoperative Neutrophil-to-Lymphocyte Ratio Is a Predictor of Recurrence following Thermal Ablation for Recurrent Hepatocellular Carcinoma: A Retrospective Analysis

Purpose

The aim of this study is to determine the predictive value of preoperative blood neutrophil-to-lymphocyte ratio (NLR) for recurrence in recurrent hepatocellular carcinoma (RHCC) patients following thermal ablation.

Material and Methods

This retrospective study enrolled 506 RHCC patients who underwent thermal ablation from April 2006 to April 2014. The clinicopathological parameters including NLR were evaluated to identify predictors of recurrence rate after thermal ablation. A Cox multiple regression analysis was performed to determine the parameters that predicted recurrence in RHCC patients. The best cutoff value of NLR was determined with time-dependent receiver operating characteristic (ROC) curve analysis. The recurrence-free survival (RFS) rate was determined in patients with high and low NLR.

Results

The multivariate Cox proportional hazard model analysis showed that NLR was a prognostic factor in recurrence-free survival. NLR ≥2.14 was evaluated (AUROC = 0.824; P<0.001), and 183 of 506 patients (36.2%) had a NLR of more than 2.14. During the follow-up period (12–96 months), the 1-, and 3- year recurrence rates were 20.7% and 31.6% in low NLR group, respectively. These recurrence rates were significantly less than those in the high NLR group (57.9% and 82.5%, respectively) (P<0.001). A recurrence-free survival analyses demonstrated that the RFS in the low NLR group (67.2%) was significantly higher than that in the high NLR group (13.1%) (P<0.001).

Conclusion

Our results show that preoperative NLR is a predictor for re-recurrence after thermal ablation in RHCC patients. Additionally, patients with NLR <2.14 have a lower recurrence rate, which may improve the clinical management of RHCC patients.     

Utilization of Surveillance after Polypectomy in the Medicare Population – A Cohort Study

Background

Surveillance in patients with previous polypectomy was underused in the Medicare population in 1994. This study investigates whether expansion of Medicare reimbursement for colonoscopy screening in high-risk individuals has reduced the inappropriate use of surveillance.

Methods

We used Kaplan-Meier analysis to estimate time to surveillance and polyp recurrence rates for Medicare beneficiaries with a colonoscopy with polypectomy between 1998 and 2003 who were followed through 2008 for receipt of surveillance colonoscopy. Generalized Estimating Equations were used to estimate risk factors for: 1) failing to undergo surveillance and 2) polyp recurrence among these individuals. Analyses were stratified into three 2-year cohorts based on baseline colonoscopy date.

Results

Medicare beneficiaries undergoing a colonoscopy with polypectomy in the 1998–1999 (n = 4,136), 2000–2001 (n = 3,538) and 2002–2003 (n = 4,655) cohorts had respective probabilities of 30%, 26% and 20% (p<0.001) of subsequent surveillance events within 3 years. At the same time, 58%, 52% and 45% (p<0.001) of beneficiaries received a surveillance event within 5 years. Polyp recurrence rates after 5 years were 36%, 30% and 26% (p<0.001) respectively. Older age (≥ 70 years), female gender, later cohort (2000–2001 & 2002–2003), and severe comorbidity were the most important risk factors for failure to undergo a surveillance event. Male gender and early cohort (1998–1999) were the most important risk factors for polyp recurrence.

Conclusions

Expansion of Medicare reimbursement for colonoscopy screening in high-risk individuals has not reduced underutilization of surveillance in the Medicare population. It is important to take action now to improve this situation, because polyp recurrence is substantial in this population.     

Oblique Bile Duct Predisposes to the Recurrence of Bile Duct Stones

Background and Study Aims

Bile stones represent a highly prevalent condition and abnormalities of the biliary tree predispose to stone recurrence due to development of biliary stasis. In our study, we assessed the importance of an altered bile duct course for stone formation.

Patients and Methods

1,307 patients with choledocholithiasis in the absence of any associated hepatobiliary disease who underwent endoscopic retrograde cholangiopancreatography (ERCP) between 2002 and 2009 were analysed. The angle enclosed between the horizontal portion of the common bile duct (CBD) and the horizontal plane was measured (angle α). Oblique common bile duct (OCBD) was defined as a CBD with angle α<45°.

Results

103 patients (7.9%) were found to harbour OCBD and these were compared to 104 randomly selected control subjects. Compared to controls, OCBD patients were (i) significantly older (72±13 vs. 67±13, p<0.00001); (ii) more frequently underwent a cholecystectomy (p = 0.02) and biliary surgery (p = 0.003) prior to the diagnosis and (iii) more often developed chronic pancreatitis (p = 0.04) as well as biliary fistulae (p = 0.03). Prior to and after ERCP, OCBD subjects displayed significantly elevated cholestatic parameters and angle α negatively correlated with common bile duct diameter (r = -0.29, p = 0.003). OCBD subjects more often required multiple back-to-back ERCP sessions to remove bile stones (p = 0.005) as well as more ERCPs later on due to recurrent stone formation (p<0.05).

Conclusion

OCBD defines a novel variant of the biliary tree, which is associated with chronic cholestasis, hampers an efficient stone removal and predisposes to recurrence of bile duct stones.     

S. haematobium as a Common Cause of Genital Morbidity in Girls: A Cross-sectional Study of Children in South Africa

Background

Schistosoma (S.) haematobium infection is a common cause of genital morbidity in adult women. Ova in the genital mucosal lining may cause lesions, bleeding, pain, discharge, and the damaged surfaces may pose a risk for HIV. In a heterogeneous schistosomiasis endemic area in South Africa, we sought to investigate if young girls had genital symptoms and if this was associated with urinary S. haematobium.

Methodology

In a cross-sectional study of 18 randomly chosen primary schools, we included 1057 schoolgirls between the age of 10 and 12 years. We interviewed assenting girls, whose parents had consented to their participation and examined three urines from each of them for schistosome ova.

Principal findings

One third of the girls reported to have a history of genital symptoms. Prior schistosomal infection was reported by 22% (226/1020), this was associated with current genital symptoms (p<0.001). In regression analysis the genital symptoms were significantly associated both with urinary schistosomiasis (p<0.001) and water contact (p<0.001).

Conclusions

Even before sexually active age, a relatively large proportion of the participating girls had similar genital symptoms to those reported for adult genital schistosomiasis previously. Anti-schistosomal treatment should be considered at a young age in order to prevent chronic genital damage and secondary infections such as HIV, sexually transmitted diseases and other super-infections.     

Anatomical Characteristics of Pulmonary Veins for the Prediction of Postoperative Recurrence after Radiofrequency Catheter Ablation of Atrial Fibrillation

Background

The relationship between focal pulmonary vein potential and atrial fibrillation (AF) has been confirmed. Pulmonary vein (PV) isolation and circumferential pulmonary vein ablation have been the most commonly used procedures of radiofrequency ablation. However, few studies have investigated the relationship between anatomical characteristics of PV and AF recurrences after radiofrequency ablation.

Methodology

For 267 AF patients treated by radiofrequency catheter ablation, the anatomic structure characteristics of pulmonary veins were assessed by multi-slice spiral computed tomography while the values of left atrial diameter (LAD) were measured with transesophageal ultrasonic cardiogram. After radiofrequency catheter ablation, postoperative recurrence was evaluated during a 10-month term follow-up.

Principal Findings

During follow-up, postoperative recurrence occurred in 44 patients. The mean diameters of LAD, left superior PV, right superior PV, all left PV, and all superior PV were significantly larger in patients with postoperative recurrence (Recurrence vs. Non-recurrence group; 43.9 ± 6.4 mm vs. 40.7 ± 5.6 mm; 18.4 ± 2.1 mm vs. 17.1 ± 3.1 mm; 18.2 ± 2.8 mm vs. 17.2 mm ± 3.9 mm; 16.4 ± 1.5 mm vs. 15.6 ± 2.5 mm; 18.3 ± 2.1 mm vs. 17.1 ± 3.0 mm; respectively; all P < 0.05). Multivariable survival analysis showed that the type and the course of AF, LAD, and the diameters of all superior PV were the independent risk factors for the postoperative recurrence after radiofrequency catheter ablation.

Conclusions

The enlargements of all superior PV and LAD, long course of diseases, and persistent AF were the independent risk factors for the postoperative recurrence after radiofrequency catheter ablation.     

Intraoperative Blood Loss Independently Predicts Survival and Recurrence after Resection of Colorectal Cancer Liver Metastasis

Background

Although numerous prognostic factors have been reported for colorectal cancer liver metastasis (CRLM), few studies have reported intraoperative blood loss (IBL) effects on clinical outcome after CRLM resection.

Methods

We retrospectively evaluated the clinical and histopathological characteristics of 139 patients who underwent liver resection for CRLM. The IBL cutoff volume was calculated using receiver operating characteristic curves. Overall survival (OS) and recurrence free survival (RFS) were assessed using the Kaplan–Meier and Cox regression methods.

Results

All patients underwent curative resection. The median follow up period was 25.0 months (range, 2.1–88.8). Body mass index (BMI) and CRLM number and tumor size were associated with increased IBL. BMI (P=0.01; 95% CI = 1.3–8.5) and IBL (P<0.01; 95% CI = 1.6–12.5) were independent OSOs predictors. Five factors, including IBL (P=0.02; 95% CI = 1.1–4.1), were significantly related to RFS via multivariate Cox regression analysis. In addition, OSOs and RFS significantly decreased with increasing IBL volumes. The 5-year OSOs of patients with IBL≤250, 250–500, and >500mL were 71%, 33%, and 0%, respectively (P<0.01). RFS of patients within three IBL volumes at the end of the first year were 67%, 38%, and 18%, respectively (P<0.01).

Conclusions

IBL during CRLM resection is an independent predictor of long term survival and tumor recurrence, and its prognostic value was confirmed by a dose–response relationship.     

Risk Factors of Pneumothorax after Endobronchial Ultrasound-Guided Transbronchial Biopsy for Peripheral Lung Lesions

Background

The risk of endobronchial ultrasound-guided transbronchial biopsy-related pneumothorax is a major concern and warrants further studies. The aim of our study was to estimate the risk of pneumothorax after this procedure and identify its risk factors.

Methods

From 2007 to 2011, 399 patients who underwent endobronchial ultrasound-guided transbronchial biopsy for peripheral lung lesions were included in this study. The variables analyzed included patient factors, lesion factors and procedure factors. Multivariate logistic regression analysis was used to identify independent risk factors for pneumothorax.

Results

The incidence of pneumothorax was 3.3% (13/399). Chest tube placement was required for 31% (4/13) of pneumothoraces. Independent risk factors for pneumothorax included pulmonary emphysema (OR, 55.09; 95% CI, 9.37–324.03; p<0.001) and probe position adjacent to the lesion (OR, 17.01; 95% CI, 2.85–101.64; p = 0.002). The number of biopsy specimens, age, sex, history of prior lung surgery and lesion size, location and character did not influence the risk of pneumothorax in our analyses.

Conclusions

The risk of pneumothorax after endobronchial ultrasound-guided transbronchial biopsy is low. To further reduce the risk of pneumothorax, every effort should be made to advance the endobronchial ultrasound probe into the bronchus where it is imaged within the target lesion before embarking on transbronchial biopsy.     

Overexpression of ERG and Wild-Type PTEN Are Associated with Favorable Clinical Prognosis and Low Biochemical Recurrence in Prostate Cancer

Objectives

The aim of this study was to investigate the expression of two commonly altered genes ERG and PTEN in prostate cancer (PC) and evaluate their prognostic significance. Despite conflicting published results, TMPRSS2-ERG gene fusion and PTEN loss are generally considered unfavorable markers for PC progression.

Materials and Methods

Of the 762 prostatic adenocarcinoma specimens obtained from radical prostatectomy, 613 without neoadjuvant hormone therapy were included in tissue microarrays for quantitatively assessment of ERG and PTEN expression via immunohistochemistry. Statistical analysis of the association between such expression and clinicopathological parameters, including clinical prognosis, was performed with a p-value of <0.05 considered significant.

Results

During a median follow-up period of 44.0 months, 132 (21.5%) patients developed biochemical recurrence (BCR). ERG overexpression and PTEN loss were observed in 145 (23.7%) and 253 (41.3%) cases, respectively. BCR-free survival was significantly better in patients with ERG overexpression (p=0.005), but unfavorable among those with PTEN loss (p=0.142). Sub-group analysis revealed that patients with PTEN loss and negative ERG expression had the worst BCR-free survival outcome (p=0.021). Furthermore, multivariate analysis identified prostate-specific antigen level (≥10 ng/mL), Gleason score (>6), pathologic T stage (≥T3), positive surgical margin, and extraprostatic capsule extension as significant risk factors for BCR (p<0.05).

Conclusions

Our results indicated that ERG overexpression was associated with favorable BCR-free survival after radical prostatectomy for PC, whereas PTEN loss was with unfavorable outcomes.     

The 1973 WHO Classification Is More Suitable than the 2004 WHO Classification for Predicting Prognosis in Non-Muscle-Invasive Bladder Cancer

Background

Predicting the recurrence and progression of Non-muscle-invasive bladder cancer(NMIBC) is critical for urologist. Histological grade provides significant prognostic information, especially for prediction of progression. Currently, the 1973 and the 2004 WHO classification co-exist. Which system is better for predicting rumor recurrence and progression still a matter for debate.

Methodology/Principal Findings

348 patients diagnosed with Non-muscle invasive bladder cancer were enrolled in our retrospective study. Paraffin sections were assessed by an experienced urological pathologist according to both the 1973 and 2004 WHO classifications. Tumor recurrence and progression was followed-up in all patients. During follow-up, corresponding 5-year recurrence-free survival rates of G1, G2 and G3 were 82.1%, 55.9%, 32.1% and the 5-year progression-free survival rates were 95.9%, 84.4% and 43.3%, respectively. The 5-year recurrence-free survival rates of papillary urothelial neoplasm of low malignant potential (PUNLMP), low-grade papillary urothelial carcinoma(LGPUC) and high-grade papillary urothelial carcinoma (HGPUC) were 69.8%, 67.1% and 42.0% respectively and the 5-year progression-free survival rates were 100%, 90.9% and 54.8% respectively. In multivariate analysis, the 1973 WHO classification significantly associated with both tumor recurrence and progression(p = 0.010 and p = 0.022, respectively); the 2004 WHO classification correlated with tumor progression(p = 0.019), while was not proved to be a variable that can predict the risk of recurrence(p = 0.547). Kaplan-Meier plots showed that both the 1973 WHO and the 2004 WHO classifications were significantly associated with progression-free survival (p<0.0001, log-rank test). For prediction of recurrence, significant differences were observed between the tumor grades classified using the 1973 WHO grading system (p<0.0001, log-rank test), while a significant overlap was observed between PUNLMP and LG plots using the 2004 WHO grading system(p = 0.616, log-rank test).

Conclusion/Significance

Both the 1973 WHO and the 2004 WHO Classifications are effective in predicting tumor progression in Non-muscle invasive bladder cancer, while the 1973 WHO Classification is more suitable for predicting tumor recurrence.