Awareness of Smoking as a Risk Factor in Bladder Cancer: Results from the Prospective FinnBladder 9 Trial.

BACKGROUND: Data regarding patient education and smoking habits among bladder cancer patients are scarce. OBJECTIVE: To investigate awareness of smoking as a risk factor for bladder cancer among bladder cancer patients. DESIGN, SETTING, AND PARTICIPANTS: This is a substudy of a prospective, randomized, multicenter phase 3 trial (FinnBladder 9, NCT01675219). The data were collected at baseline and after 12 mo of follow-up between 2012 and 2020. INTERVENTION: Patients completed a comprehensive nonvalidated questionnaire on smoking in relation to bladder cancer. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The outcomes measured were patient-reported awareness of smoking as a risk factor for bladder cancer, and the effect of smoking on bladder cancer-related recurrence, progression, and death. Parametric data were compared using Student's t test and proportions using Fischer's exact test. Factors affecting baseline awareness of the effect of smoking cessation on bladder cancer were studied using logistic regression. RESULTS AND LIMITATIONS: Of the 411 patients randomized, 370 completed the baseline questionnaire and were included in the analysis. At baseline, 44% of patients were uncertain if smoking was a risk factor for bladder cancer. Patient awareness of the fact that smoking cessation reduces the risk of bladder cancer recurrence increased from 86% to 92% after 12 mo of follow-up (p = 0.038). Older patients and patients with recurrent bladder cancer had significantly less knowledge about the effect of smoking on bladder cancer recurrence, progression, and mortality. A major limitation is that the response rate was lower at the 12-mo follow-up visit than at baseline. CONCLUSIONS: Awareness of smoking as a bladder cancer risk factor is low. Older patients and patients with recurrent bladder cancer may need special attention regarding education. PATIENT SUMMARY: We looked at outcomes for smoking-related patient education on bladder cancer in a Finnish population. We conclude that older patients and patients with recurrent bladder cancer may need to be educated on this subject.

Symptoms and diagnostic delays in bladder cancer with high risk of recurrence: results from a prospective FinnBladder 9 trial.

PURPOSE: To investigate the symptoms and delays in the clinical pathway of bladder cancer (BC). METHODS: This is a substudy of a prospective, randomized, multicenter phase III study (FinnBladder 9, NCT01675219) where the efficacy of photodynamic diagnosis and 6 weekly optimized mitomycin C instillations are studied in pTa bladder cancer with high risk for recurrence. The data of presenting symptoms and critical time points were prospectively collected, and the effect of factors on delays was analyzed. RESULTS: At the time of analysis, 245 patients were randomized. Analysis included 131 patients with primary bladder cancer and their complete data. Sixty-nine percent had smoking history and 67% presented with macroscopic hematuria. Median patient delay (from symptoms to health-care contact) was 7 days. The median general practice delay (from health-care contact to urology referral) was 8 days. Median time from urology referral to cystoscopy was 23 days and from cystoscopy to TUR-BT 21 days. Total time used in the clinical pathway (from symptom to TUR-BT) was 78 days. Current and former smokers had non-significantly shorter patient-related and general practice delays compared to never smokers. TUR-BT delay was significantly shorter in patients with malignant cytology (16 days) compared to patients with benign cytology (21 days, p = 0.03). CONCLUSIONS: Patient-derived delay was short and most of the delay occurred in the referral centers. The majority had macroscopic hematuria as the initial symptom. Surprisingly, current and past smokers were more prone to contact the health-care system compared to never smokers.

Reindeer BMP extract in the healing of critical-size bone defects in the radius of the rabbit.

BACKGROUND: Native BMP extracts from reindeer effectively induce ectopic new bone formation in vivo, but their bone healing properties have not yet been evaluated. We investigated the effect of reindeer BMP extracts on the healing of long bone defects. METHODS: The implants tested contained 5 mg or 10 mg of unsterilized BMP extract from reindeer and 10 mg of gamma-sterilized BMP extract administered with collagen carrier (Lyostypt, B. Braun, Germany). 70 micro g of rhBMP-2 with collagen carrier (InductOs; Wyeth Europa) served as positive control, and collagen implants (Lyostypt) and untreated defects served as negative controls. New Zealand White rabbits with 1.5 cm of critical-size radius bone defects were used, with 8 weeks of follow-up. RESULTS: Radiographic analysis showed bone formation (BF) to be higher in all groups containing BMPs than in the untreated controls. BF was also higher in the rhBMP-2 group, and marginally higher in the group treated with 10 mg of unsterilized reindeer BMP extract (p = 0.06) as compared to the collagen controls. Bone union (BU) was better in the unsterilized BMP extract groups and rhBMP-2 group than in the untreated controls. BU was also better in the implants with 10 mg of unsterilized reindeer BMP extract and rhBMP-2 than in the collagen-treated implants. The mean area of new bone at the site of the defect proved to be higher in all implants containing BMP than in the untreated defects. It was also higher in the groups with 10 mg of unsterilized reindeer BMP extract and rhBMP-2 than in the collagen-treated controls. Mechanical tests showed torsional stiffness of the bones to be higher in the group with 10 mg of unsterilized BMP extract than in the collagen group. The mean cross-sectional bone area measured by pQCT densitometry was higher in the rhBMP-2 group than in the collagen group. The mean bone density at the defect area was higher in the group with 10 mg of unsterilized BMP than in the rhBMP-2 group. INTERPRETATION: We conclude that both reindeer BMP extract and rhBMP-2 induced improved healing of the rabbit radius bone defects at the doses used. Gamma sterilization of reindeer BMP extract reduced osteoinductivity slightly, but not significantly.

Effect of gamma irradiation on the osteoinductivity of morphogenetic protein extract from reindeer bone.

BACKGROUND: Bone morphogenetic proteins (BMPs), which are capable of stimulating the production of new bone, must be sterilized before preclinical and clinical use to reduce the risk of infections and associated complications. In this study, we investigated the effects of gamma sterilization on the osteoinductivity of native reindeer BMP extract in the Balb/C mouse thigh muscle pouch model. METHODS: 5 mg of native reindeer BMP extract and 5 mg of bovine serum albumin were administered separately either in gelatine capsules or mixed with gelatine as injections. The dose of gamma irradiation was 4.1 Mrad. Unsterile capsules and injections served as controls. New bone formation was evaluated based on the incorporation of Ca45 and also radiographically 3 weeks after implantation. RESULTS: Albumin-containing implants and injections did not induce new bone formation, as monitored in radiographs. Gamma sterilization did not reduce the osteoinductivity of native BMP extract in capsules, but a significant decrease in osteoinductivity--measured as area (50%) and Ca45 incorporation of new bone (27%)--was seen after injection. Gamma sterilization had no effect on the optical density of new bone induced by native BMP extract administered in capsules or by injection. INTERPRETATION: We conclude that, as gamma irradiation did not reduce the osteoinductivity of reindeer BMP extract in gelatine capsules, this method appears to be suitable for sterilization of BMPs to be given in capsule form. Native reindeer BMP extract was more sensitive to irradiation in soluble collagen (gelatine) than BMP in gelatine capsules. This finding must be given serious consideration regarding treatment of patients, but the remaining activity may be sufficient for the induction of bone formation in preclinical and clinical situations.

Osteoinductivity of partially purified native ostrich (Struthio camelus) bone morphogenetic protein: comparison with mammalian species.

Bone morphogenetic proteins (BMPs) are members of the TGF-beta superfamily. They are capable of inducing ectopic bone formation. Until now, the main interest has been focused on mammalian osteoinductive BMPs, and there are no reports of native BMP extracts of birds. In this study, we isolated and characterized native BMPs of ostrich (Struthio camelus) and compared them with identically isolated native bovine (cow) and reindeer BMPs with regard to BMP pattern and osteoinductive capacity. The ostrich BMP pattern differed markedly from that of cow and reindeer BMP in non-reduced SDS-PAGE, reduced SDS-PAGE and Western blot. The differences in isoelectric focusing analysis were smaller. However, the ostrich BMP extract had a peak at pH 5.1, clearly differing from the BMPs of cow and reindeer. The osteoinductive capacity and density of ectopic bone, induced by BMP extracts in a mouse thigh muscle pouch, were determined radiographically. The ostrich BMP extract displayed significantly lower osteoinductive capacity and density of induced bone than the bovine and reindeer BMP extracts. In conclusion, our results indicate that the BMP pattern of birds differs considerably from that of mammals, and that the osteoinductive capacity of BMPs and the density of induced bone are lower in birds than in mammals. They also suggest that the bone metabolism of birds is adapted to make light bones suitable for flying.