Level of mitoses in non-muscle invasive papillary urothelial carcinomas (pTa and pT1) at initial bladder biopsy is a simple and powerful predictor of clinical outcome: a multi-center study in South Korea.

BACKGROUND: Histologic grade is the most important predictor of the clinical outcome of non-muscle invasive (Ta, T1) papillary urothelial carcinoma (NMIPUCa), but its ambiguous criteria diminish its power to predict recurrence/progression for individual patients. We attempted to find an objective and reproducible histologic predictor of NMIPUCa that correlates well with the clinical outcome. METHODS: A total of 296 PUCas were collected from the Departments of Surgical Pathology of 11 institutions in South Korea. The clinical outcome was grouped into no event (NE), recurrence (R), and progression (P) categories. All 25 histological parameters were numerically redefined. The clinical pathology of each case was reviewed individually by 11 pathologists from 11 institutions based on the 2004 WHO criteria and afterwards blindly evaluated by two participants, based on our proposed parameters. Univariate and multivariate logistic regression analyses were performed using the R software package. RESULTS: The level of mitoses was the most reliable parameter for predicting the clinical outcome. We propose a four-tiered grading system based on mitotic count (> 10/10 high-power fields), nuclear pleomorphism (smallest-to-largest ratio of tumor nuclei >20), presence of divergent histology, and capillary proliferation (> 20 capillary lumina per papillary core). CONCLUSIONS: The level of mitoses at the initial bladder biopsy and transurethral resection (TUR) specimen appeared to be an independent predictor of the Ta PUCa outcome. Other parameters include the number of mitoses, nuclear pleomorphism, divergent histology, and capillary proliferation within the fibrovascular core. These findings may improve selection of patients for a therapeutic strategy as compared to previous grading systems.

Low levels of circulating microRNA-26a/29a as poor prognostic markers in patients with hepatocellular carcinoma who underwent curative treatment.

BACKGROUND/AIMS: We evaluated the prognostic implication of circulating microRNA (miR)-21, miR-26a, and miR-29a in hepatocellular carcinoma (HCC) patients who underwent curative treatment. METHODS: The study included 120 hepatitis B virus-related HCC patients who underwent hepatic resection (n=63) or radiofrequency ablation (n=57). MiR-21, miR-26a, and miR-29a expression levels in pretreatment plasma and several clinical variables were analyzed to identify prognostic bio-markers. RESULTS: Old age, low albumin level, low platelet count, advanced tumor stage (modified Union for International Cancer Control stages III, IV), low miR-26a (hazard ratio [HR]=1.72; 95% confidence interval [CI]=1.04-2.83; P=0.035), and low miR-29a (HR=1.75; 95% CI=1.04-2.94; P=0.035) were identified as independent risk factors for predicting poor disease-free survival. Low miR-21, miR-26a, and miR-29a were associated with poor liver transplantation (LT)-free survival in the univariate analysis. Multivariate Cox regression analysis showed that low miR-26a (HR=3.41; 95% CI=1.32-8.82; P=0.011) and low miR-29a (HR=2.75; 95% CI=1.10-6.85; P=0.030), low platelet count, and advanced tumor stage were significantly associated with poor LT-free survival. Remarkable correlation was found between miR-26a and miR-29a (Spearman's rho=0.734, P<0.001). CONCLUSION: Pretreatment levels of circulating miR-26a and miR-29a are independent prognostic markers for poor disease-free survival and LT-free survival in hepatitis B virus-related HCC patients.

[Mathematical modeling of the novel influenza A (H1N1) virus and evaluation of the epidemic response strategies in the Republic of Korea].

OBJECTIVES: The pandemic of novel influenza A (H1N1) virus has required decision-makers to act in the face of the substantial uncertainties. In this study, we evaluated the potential impact of the pandemic response strategies in the Republic of Korea using a mathematical model. METHODS: We developed a deterministic model of a pandemic (H1N1) 2009 in a structured population using the demographic data from the Korean population and the epidemiological feature of the pandemic (H1N1) 2009. To estimate the parameter values for the deterministic model, we used the available data from the previous studies on pandemic influenza. The pandemic response strategies of the Republic of Korea for novel influenza A (H1N1) virus such as school closure, mass vaccination (70% of population in 30 days), and a policy for anti-viral drug (treatment or prophylaxis) were applied to the deterministic model. RESULTS: The effect of two-week school closure on the attack rate was low regardless of the timing of the intervention. The earlier vaccination showed the effect of greater delays in reaching the peak of outbreaks. When it was no vaccination, vaccination at initiation of outbreak, vaccination 90 days after the initiation of outbreak and vaccination at the epidemic peak point, the total number of clinical cases for 400 days were 20.8 million, 4.4 million, 4.7 million and 12.6 million, respectively. The pandemic response strategies of the Republic of Korea delayed the peak of outbreaks (about 40 days) and decreased the number of cumulative clinical cases (8 million). CONCLUSIONS: Rapid vaccination was the most important factor to control the spread of pandemic influenza, and the response strategies of the Republic of Korea were shown to delay the spread of pandemic influenza in this deterministic model.