Results of long-term follow-up of patients with superficial bladder carcinoma treated with intravesically applied bacillus Calmette-Guerin vaccine according to the schedule of 6 weekly + 6 monthly instillations

BackgroundThe efficacy of bacillus Calmette-Guerin (BCG) immunotherapy in the prevention of local recurrence and disease progression in patients with superficial bladder cancer is very well documented. This study reports the effect of BCG on disease-specific and overall survival.Patients and methodsIn this retrospective trial, we have analyzed 170 patients with stage Ta and T1 superficial bladder cancer. Patients in the control group (87 patients) we followed-up only (median follow-up of 119 months) and treated surgically or with other oncologic modalities when progression of disease was diagnosed. The BCG group consisted of 83 patients treated with 6 weekly followed by 6 monthly instillations, and they have been followed-up of median 124 months.ResultsPatients receiving BCG had statistically significant better 10-year disease specific survival (83% vs. 69%, P = 0.03). At the same time point, the local recurrence rate was 48 % and the progression rate 19% for patients treated with BCG, while 77% (P < 0.001) and 38% (P = 0.007) were results in control group. Despite numerically better in the BCG group, overall survival is not significantly different in the 2 groups (P = 0.14).ConclusionBCG immunotherapy significantly increases the disease-specific survival in patients with superficial bladder carcinoma.     

Evaluation of genome damage and its relation to oxidative stress induced by glyphosate in human lymphocytes in vitro

In the present study we evaluated the genotoxic and oxidative potential of glyphosate on human lymphocytes at concentrations likely to be encountered in residential and occupational exposure. Testing was done with and without metabolic activation (S9). Ferric‐reducing ability of plasma (FRAP), thiobarbituric acid reactive substances (TBARS) and the hOGG1 modified comet assay were used to measure glyphosate's oxidative potential and its impact on DNA. Genotoxicity was evaluated by alkaline comet and analysis of micronuclei and other nuclear instabilities applying centromere probes. The alkaline comet assay showed significantly increased tail length (20.39 μm) and intensity (2.19%) for 580 μg/ml, and increased tail intensity (1.88%) at 92.8 μg/ml, compared to control values of 18.15 μm for tail length and 1.14% for tail intensity. With S9, tail length was significantly increased for all concentrations tested: 3.5, 92.8, and 580 μg/ml. Using the hOGG1 comet assay, a significant increase in tail intensity was observed at 2.91 μg/ml with S9 and 580 μg/ml without S9. Without S9, the frequency of micronuclei, nuclear buds and nucleoplasmic bridges slightly increased at concentrations 3.5 μg/ml and higher. The presence of S9 significantly elevated the frequency of nuclear instabilities only for 580 μg/ml. FRAP values slightly increased only at 580 μg/ml regardless of metabolic activation, while TBARS values increased significantly. Since for any of the assays applied, no clear dose‐dependent effect was observed, it indicates that glyphosate in concentrations relevant to human exposure do not pose significant health risk. Environ. Mol. Mutagen. 2009. © 2009 Wiley‐Liss, Inc.     

Management of blunt pancreatic trauma in children

Purpose  Blunt abdominal trauma is the major cause of abdominal injury in children. Because of the retroperitoneal location, insidious signs and symptoms and the lack of sensitivity with common imaging modalities often lead to difficulties in making an accurate diagnosis. The most common complication is the formation of a pancreatic fistula, pancreatitis and a pancreatic pseudocyst, which usually manifests within 3 or 4 weeks after injury. Methods  The case records of seven children (4 male, 3 female) treated for blunt pancreatic injury in the department of pediatric surgery, University Hospital, Split were reviewed. Results  The treatment modalities were selected according to the grade of the pancreatic injury, hemodynamic status and associated injuries. Because all of the patients were classified as grade I or II according to the American Association for the Surgery of Trauma (AAST) classification, a conservative treatment was selected for all seven patients. In four patients the conservative treatment resulted in the total regression of the clinical, biochemical and radiological signs within four weeks (AAST grade I). In the other three patients, pancreatic pseudocysts arose within 3 or 4 weeks after the injury (AAST grade II). Conclusions  The status of the main pancreatic duct and the location of the pancreatic injury constitute the basis of the AAST scoring system. This scale should be used as a guide to selecting a surgical or conservative strategy. Based on these data, two factors appear to be the most important determinants of the treatment strategy for children with pancreatic injury: the grade of the pancreatic injury, which is determined according to the status of the main pancreatic duct and the clinical status of the patient.     

Influence of hyperthermal regimes on experimental teratoma development in vitro

We screened for the impact of hyperthermal regimes varying in the cumulative equivalent minutes at 43°C (CEM43°C) and media composition on tumour development using an original teratoma in vitro model. Rat embryos (three germ layers) were microsurgically isolated and cultivated at the air‐liquid interface. During a two week period, ectodermal, mesodermal and endodermal derivatives developed within trilaminar teratomas. Controls were grown at 37°C. Overall growth was measured, and teratoma survival and differentiation were histologically assessed. Cell proliferation was stereologically quantified by the volume density of Proliferating Cell Nuclear Antigen. Hyperthermia of 42°C, applied for 15 minutes after plating (CEM43°C 3.75 minutes), diminished cell proliferation (P ? .0001) and enhanced differentiation of both myotubes (P ? .01) and cylindrical epithelium (P ? .05). Hyperthermia of 43°C applied each day for 30 minutes during the first week (CEM43°C 210 minutes) impaired overall growth (P ? .01) and diminished cell proliferation (P ? .0001). Long‐term hyperthermia of 40.5°C applied for two weeks (CEM43°C 630 minutes) significantly impaired survival (P ? .005). Long‐term hyperthermia of 40.5°C applied from the second day when differentiation of tissues begins (CEM43°C 585 minutes) impaired survival (P ? .0001), overall growth (P ? .01) and cartilage differentiation (P ? .05). No teratomas survived extreme regimes: 43°C for 24 hours (CEM43°C 1440 minutes), hyperthermia in the scant serum‐free medium (CEM43°C 630 minutes) or treatment with an anti‐HSP70 antibody before long‐term hyperthermia 40.5°C from the second day (CEM43°C 585 minutes). This in vitro research provided novel insights into the impact of hyperthermia on the development of experimental teratomas from their undifferentiated sources and are thus of potential interest for future therapeutic strategies in corresponding in vivo models.     

Multivariate analysis of clinical prognostic factors in patients with glioblastoma multiforme treated with a combined modality approach

We investigated the influence of various clinical prognostic factors in patients with glioblastoma multiforme (GBM) treated with a combined modality approach. A total of 175 patients with GBM was treated in four consecutive prospective phase II studies using surgery, hyperfractionated or accelerated hyperfractionated radiotherapy (RT) and either adjuvant or concurrent or pre-irradiation chemotherapy (CHT) between January 1988 and December 1993. The median survival time for all 175 patients was 14 months and 1-3-year survival (OS) rates were 57%, 34% and 24%, respectively. The median time to tumour progression was 12 months, and 1-3-year progression-free survival (PFS) rates were 43%, 11% and 7%, respectively. Survival analysis showed that of all investigated prognostic factors, only gender did not influence survival. Patients 55 years; patients with KPS 80-100 did better than those with KPS 50-70; patients with frontal tumours did better than those with tumours in other locations; patients with tumours up to 4 cm did better than those with larger tumours, as did patients with either subtotal or gross total tumour resection when compared to those undergoing biopsy only. Multivariate analysis showed that gender and tumour location did not independently influence survival. When PFS was used as the endpoint, only gender did not influence PFS, as confirmed by multivariate analysis.     

Urates in exhaled breath condensate as a biomarker of control in childhood asthma

Objective: The aim of this study was to (1) investigate the possibility to use urates in exhaled breath condensate (EBC) as a biomarker of airway inflammation and control in childhood asthma and (2) explore their association with other biomarkers of airway inflammation and clinical indices of asthma control (Asthma Control Test [ACT], quality of life [PAQLQ], lung function, prn beta-agonist use, time from last exacerbation [TLE]. Methods: This cross-sectional study comprised 103 consecutive patients (age 6–18 years) divided in groups of uncontrolled ([NC], n?=?53) and controlled asthma ([C], n?=?50). Measured lung function and biomarkers included: spirometry, eosinophilic cationic protein (ECP), high-sensitivity C-reactive protein (hs-CRP), exhaled NO (F_ENO), pH and urates in EBC and exhaled breath temperature (EBT). Results: Statistically significant differences were found between groups for EBC urates, EBC pH and EBT (NC versus C: EBC urates, median [IQR], µmol/L; 10 [6] versus 45 [29], p?<?0.001; EBC pH, mean [SD], 7.2 [0.17] versus 7.33 [0.16], p?=?0.002; EBT mean [SD], °C; 34.26 [0.83], versus 33.90 [0.60], p?=?0.014). EBC urates showed significant association with TLE and F_ENO (r?=?0.518, p?<?0.001; r?=?0.369, p?=?0.007, respectively) in NC, and EBC pH (r?=?0.351, p?<?0.001), FEV₁ (r?=?0.222, p?=?0.024), ACT (r?=?0.654, p?<?0.001), PAQLQ (r?=?0.686, p?<?0.001) and prn salbutamol use (r?=??0.527, p?<?0.001) in all asthmatics. Conclusion: In our study, EBC urates were found to be the best single predictor of asthma control and underlying airway inflammation. Our results provide evidence supporting the potential utility to use EBC urates as an additional non-invasive biomarker of control in childhood asthma.     

Treatment and secondary prevention of ischemic coronary events in Croatia (TASPIC-CRO study).

AIMS: The objective of this study is to determine the status of major risk factors for coronary heart disease in patients with established coronary heart disease in Croatia and whether the Joint European Societies' recommendations on coronary heart disease prevention are being followed in Croatia and whether secondary prevention practices have improved between 1998 and 2003. METHODS: Five surveys were undertaken in 35 centres covering the geographical area of the whole of Croatia between 1 June, 1998 and 31 March, 2003. Consecutive patients of both sexes were identified after coronary-bypass grafting or a percutaneous transluminal coronary angioplasty or a hospital admission with acute myocardial infarction or ischaemia. Data collection was based on a review of medical records and the methodology used was similar to the one used in the EUROASPIRE study. RESULTS: Fifteen thousand, five hundred and twenty patients were enrolled (64.6% men); 35% of patients smoked cigarettes, 66% had raised blood pressure, 69% elevated serum total cholesterol, 69% elevated serum low-density lipoprotein (LDL) cholesterol, 42% low high-density lipoprotein (HDL) cholesterol, 37% elevated triglycerides, 30% diabetes and 34% family history of coronary heart disease. More men were smokers and had low HDL cholesterol, but more women had elevated total and LDL cholesterol, hypertension and diabetes. More men had Q wave acute myocardial infarction, but more women had angina. Over 5 years, the prevalence of hypercholesterolemia decreased substantially from 82.7 to 65%. Eighty-three percent of patients received aspirin and this percentage did not change during the study. The use of diuretics, calcium antagonists and nitrates did not change either. The reported use of statins, angiotensin-converting enzyme inhibitors and beta-blockers increased significantly. CONCLUSION: This survey shows a high prevalence of modifiable risk factors in Croatian patients with coronary heart disease. Although the higher use of statins, angiotensin-converting enzyme inhibitors and beta-blockers is encouraging, the fact that most coronary heart disease patients are still not achieving the recommended goals remains a concern. There is real potential to reduce the very high coronary heart disease morbidity and mortality in Croatia.