A pilot study of antimicrobial effects and ototoxicity of a Norway spruce (Picea abies) resin-based canine otic rinse product.

BACKGROUND: Norway spruce (Picea abies) resin-based products are used in human medicine. A resin-based otic rinse also could be useful in supportive care of canine otitis externa (COE), yet information on its antimicrobial effect against canine pathogens or ototoxicity is lacking. OBJECTIVES: To investigate the antimicrobial properties and ototoxicity of a commercial resin-based otic product. MATERIALS AND METHODS: Antimicrobial effect was evaluated using a standardised challenge test on Staphylococcus pseudintermedius, Corynebacterium auriscanis, Pseudomonas aeruginosa, Escherichia coli, Malassezia pachydermatis, and Streptococcus halichoeri strains to measure reduction in growth after 24 h exposure to the product. Effect on cell morphology was investigated by exposing S. pseudintermedius, C. auriscanis, P. aeruginosa and M. pachydermatis to the product in 20% and 100% (v/v) concentrations for 6, 24 and 48 h, and evaluating cells by transmission (TEM) and scanning (SEM) electron microscopy. An in vitro microbial kill-rate assay also was performed. Auditory brain stem response test, clinical evaluation and postmortem histological evaluation of ear canals were undertaken on experimental guinea pigs treated with the test product or saline controls. RESULTS: The product showed >log 5 growth reduction for all strains in the challenge test. TEM and SEM images showed clear changes in the cells' inner structures and deterioration of cells, and 100% (v/v) test product exposure induced microbial killing in 1-2 h. Ototoxicity was not detected in guinea pigs. CONCLUSIONS AND CLINICAL RELEVANCE: The product may be an option in supportive care of COE because of antimicrobial effects and lack of ototoxic properties in a guinea pig model.

Comparison of Bacillus Calmette-Guérin Maintenance Therapy with Monthly Instillations and the Southwest Oncology Group Protocol in the Treatment of Non-muscle-invasive Bladder Cancer.

BACKGROUND: Bacillus Calmette-Guérin (BCG) therapy using the Southwest Oncology Group (SWOG) maintenance protocol is the standard in non-muscle-invasive bladder cancer (NMIBC). Maintenance with monthly instillations is also widely used, but evidence comparing the two maintenance protocols is scarce. OBJECTIVE: To compare monthly and SWOG instillation schedules in maintenance BCG therapy. DESIGN, SETTING, AND PARTICIPANTS: We retrospectively identified patients with NMIBC treated with maintenance BCG according to either the monthly or the SWOG instillation regimen in two tertiary care centers in Finland between 2009 and 2019. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We compared discontinuation rates of the monthly and SWOG maintenance protocols due to toxicity, and recurrence and progression rates by protocols. Baseline characteristics were compared with the Wilcoxon rank sum test, chi-square test, and Fisher's exact test. The Kaplan-Meier method and Cox proportional hazards model were used to evaluate the discontinuation of BCG due to toxicity and oncological efficacy. RESULTS AND LIMITATIONS: We identified 723 patients, of whom 545 (75%) and 178 (25%) received maintenance according to the monthly and SWOG protocols, respectively. The median follow-up time was 66 (interquartile range: 45-99) mo. In the monthly and SWOG groups, 131 (24%) and 50 (28%) patients, respectively, discontinued BCG due to toxicity, with no difference in a univariate or multivariate analysis (hazard ratio 1.01, 95% confidence interval [CI]: 0.73-1.40, p = 0.940). The 5-yr recurrence-free survival rates in the monthly and SWOG groups were 65% (95% CI: 61-69%) and 71% (95% CI: 64-79%, p = 0.370), respectively. The 5-yr progression-free survival rates were 89% (95% CI: 86-92%) and 91% (95% CI: 86-96%, p = 0.240), respectively. CONCLUSIONS: Monthly maintenance is a comparable alternative to the SWOG protocol. PATIENT SUMMARY: In this study, we compared two schedules of intravesical bacillus Calmette-Guérin (BCG) treatment used in the treatment of non-muscle-invasive bladder cancer. We found that there were no significant differences between the two instillation schedules in terms of tolerability or efficacy.

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.

Incidence of and mortality from Bacille Calmette-Guérin (BCG) infections after BCG instillation therapy.

OBJECTIVES: To investigate the incidence of and mortality associated with Bacille Calmette-Guérin (BCG) infections in a Finnish population of patients with bladder cancer treated with BCG instillations. MATERIALS AND METHODS: We conducted a nationwide register study and identified patients with BCG infections in Finland during 1996 to 2016 using the Finnish Cancer Registry and the Finnish National Infectious Diseases Register. We estimated the number of patients treated with BCG instillations based on data on national consumed BCG doses used to treat patients with bladder cancer, and calculated the annual incidence proportion of BCG infections. We further performed a detailed medical chart review to describe the clinical features and outcomes of the treated BCG infections. RESULTS: In total, 87 patients with BCG infection after BCG treatment of bladder cancer were identified. The incidence proportion increased gradually, yielding a cumulative incidence proportion of 2.5% during the latter half of the study period. BCG infections led to significant mortality, with 10% overall mortality and 17.5% mortality from systemic infections, which is notably higher than previously reported. CONCLUSION: The incidence proportion of BCG infections among bladder cancer patients treated with BCG has increased in Finland up to 2.5% at a nationwide level, with a notably higher mortality rate than previously reported.

Repeated 5-aminolevulinic Acid Instillations During Follow-up in Non-muscle-invasive Bladder Cancer: A Randomized Study.

BACKGROUND/AIM: Non-muscle invasive bladder carcinoma (NMIBC) is highly recurrent. We studied if 5-aminolevulinic acid (5-ALA) instillations before transurethral resection of bladder tumours (TURBT) and cystoscopy extend the time to recurrence during follow-up with NMIBC patients. PATIENTS AND METHODS: A prospective multicenter study enrolled 328 NMIBC patients. All TURBTs and control cystoscopies during the one-year study period were done with or without 5-ALA instillations. The primary endpoint was time to recurrence. The secondary endpoints were time to recurrence after 7.5, 10.5, and 13.5 months and the number of patients with progressive disease. RESULTS: The overall median follow-up time was 80.4 and 87.0 months for the control and study groups, respectively. There was no statistical difference in time to first recurrence between the two groups. CONCLUSION: We could not obtain significant differences between the control and 5-ALA groups in tumour recurrence among patients with NMIBC.

Serum tumour associated trypsin inhibitor, as a biomarker for survival in renal cell carcinoma.

OBJECTIVE: Tumour associated trypsin inhibitor (TATI) is a peptide that is a marker for several tumours. TATI may also behave as an acute phase reactant in severe inflammatory disease. Overexpression of TATI predicts an unfavourable outcome for many cancers. This study aimed to evaluate the prognostic value of pre- and postoperative concentration of TATI in serum (S-TATI) of patients with renal cell carcinoma (RCC). MATERIALS AND METHODS: S-TATI was determined by time resolved immunofluorometric assay in preoperative and postoperative samples that were collected from 132 RCC patients, who underwent partial or complete nephrectomy in Helsinki University Hospital from May 2005 to July 2010. RESULTS: Preoperative S-TATI was significantly associated with tumour stage, lymph-node involvement, metastatic stage, Chronic Kidney Disease Stage (CKD grade), and preoperative C-reactive protein level (p < 0.05). Postoperative S-TATI was significantly associated only with CKD grade (p < 0.001). Multivariate Cox regression analysis of postoperative S-TATI, as a continuous variable, was an independent prognostic factor for overall survival (HR = 1.01, 95% CI = 1.00-1.01, p = 0.03) and cancer-specific survival (CSS) (HR = 1.01, 95% CI = 1.00-1.02, p = 0.004). CONCLUSIONS: Our data suggest that elevated postoperative S-TATI may be associated with adverse prognosis in RCC patients.

Disease aetiology-based design of multifunctional microemulsion eye drops for moderate or severe dry eye: a randomized, quadruple-masked and active-controlled clinical trial.

PURPOSE: To assess the safety and efficacy of multi-ingredient sacha inchi microemulsion (SIME) eye drops designed to target (1) tear film instability, (2) tear hyperosmolarity, and (3) ocular surface damage and inflammation in moderate or severe dry eye. METHODS: This randomized, quadruple-masked, active-controlled parallel study in 64 adult patients comprised three parts. Part 1 (n = 3): one eye was treated with SIME for one day. Part 2 (n = 9): randomized eyes were treated with SIME and 0.2% hyaluronic acid (HA) control eye drops 3 times a day for 10 days. Part 3 (n = 26 + 26): randomized treatment was applied on both eyes 3 times a day for 30 days. OSDI change was tested for superiority of SIME over HA. Ocular assessments were performed at baseline and after the last dose. RESULTS: Both treatments were well tolerated without adverse device effects. Tear film break-up time (p = 0.0025) and ocular protection index (p = 0.0026; change vs. HA, p = 0.047) increased significantly with SIME after 30 days. Tear osmolarity decreased more in SIME than in the HA group and significantly with both eye drops in hyperosmolar subgroups. Corneal (p = 0.014) and nasal conjunctival staining (p = 0.043) were reduced with SIME in per-protocol patients (n = 24). Conjunctival (p = 0.001) and lid redness (p = 0.012) decreased with SIME in all patients (n = 26). Symptoms decreased by about 25 OSDI units with both treatments (p < 0.0001) and with nonsignificant difference between treatments. CONCLUSIONS: Sacha inchi microemulsion (SIME) proved safe and efficacious in improving each aetiologic factor for dry eye as revealed through objective tests. Hyperosmolar stress dominating blink cycles must be disrupted by biophysical protection of the ocular surface to facilitate resolution of cellular damage and inflammation, and relief of ocular symptoms.

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.

A retrospective study on tolerability and complications of bacillus Calmette-Guérin (BCG) instillations for non-muscle-invasive bladder cancer.

Objectives: The objective was to evaluate the tolerability of BCG treatment and to evaluate the effects of interruption on treatment outcomes. The incidence and characteristics of severe complications were observed. Methods: From hospital records, all bladder carcinoma patients treated with BCG instillations in the institution from 2009-2015 were retrospectively identified. The reasons for interruption, treatment outcome, number of instillations, and diagnosis of BCG infection were recorded. Results: Of the 418 patients who started BCG instillation therapy, 176 (42.1%) interrupted BCG treatment. Of those, 23 (5.5%) patients interrupted because of suspected BCG infection. Systemic BCG infection was found in seven (1.7%), and local infection in five (1.2%) patients. Interruption of treatment was due to other adverse effects in 71 patients (17.0%), BCG failure in 46 patients (11.0%), and other reasons in 36 patients (8.6%). Fifty percent of interruptions due to adverse effects occurred within the first 6 months. The probabilities of tumor recurrence (20.0% vs 10.7%, p = 0.014, OR = 2.077, CI95% = 1.149-3.753) and disease progression (5.4% vs 1.2%, p = 0.018, OR = 4.534, CI95% = 1.152-17.840) were higher among patients whose BCG treatment was interrupted. Conclusions: Severe complications were encountered in only <5% of patients. Adverse effects requiring treatment interruption were more likely to happen within the first year of treatment. Interrupting BCG treatment due to adverse effects increased the risk of disease progression and tumor recurrence.

Perioperative management of radical cystectomy in the Nordic countries.

Objective: Radical cystectomy is performed in all of the Nordic countries, but the current practice patterns remain unclear. This study explored current perioperative care and adherence to the Early Recovery After Cystectomy (ERAC) protocol and EAU guidelines by cystectomy surgeons in the Nordic countries. Materials and methods: The study was performed as a survey including 47 centers performing cystectomies in Norway, Sweden, Finland, Iceland and Denmark. The survey addressed surgical volume, complications, preoperative imaging, use of chemotherapy, multidisciplinary conferences and current practice for perioperative and postoperative care. The survey was dispersed electronically and data was collected between November 2016 and October 2017. Results: The response rate was 55%, with a 78% completion rate of the 58 main questions. Most centers performed 10-50 cystectomies annually. Of responding centers, 96% had preoperative multidisciplinary conferences. Bowel preparation was avoided in 95% of centers and 92% did not use nasogastric tubes. All centers offered neoadjuvant chemotherapy, prescribed prophylactic antibiotics, used urinary drainage and did in-department follow-up. None of the responders waited for proof of bowel function before restarting oral diet and 96% had a standard plan for early mobilization. Conclusion: This study found a high degree of implementation of ERAC and EAU guidelines and similar practice patterns regarding perioperative management of Radical cystectomy among Nordic countries.

Evolving Clinical Picture of Renal Cell Carcinoma: A Population-Based Study from Helsinki.

BACKGROUND: There is a lack of detailed population-based data for renal cell carcinoma (RCC). OBJECTIVES: The study aimed to examine the contemporary changes in the clinical picture and treatment of RCC. METHODS: A total of 1,719 consecutive patients living in the Helsinki metropolitan area with a solid or cystic renal mass (Bosniak 3-4) ≥10 mm were identified. Data from medical records was evaluated for clinical characteristics and treatments in the periods I (2006-2008), II (2009-2011), III (2012-2014), and IV (2015-2016). RESULTS: The proportions of patients with comorbidities (Charlson index ≥2) and frailty (Eastern Co-operative Oncology Group classification ≥2) increased significantly during the study period. The percentage of clinical stage I patients, cystic tumors and use of needle biopsies increased significantly. Use of observation increased from 9% (I) to 32% (IV; p < 0.001). First-line oncological treatments within 6 months were given to 47% of 262 patients with metastases and -cytoreductive nephrectomy (CN) was delivered to 54% of those patients. CONCLUSIONS: The size of renal tumors continued to decrease, while the percentage of patients with significant comorbidity or frailty increased. Active surveillance emerged as the initial strategy. Tyrosine kinase inhibitors with CN remained the primary option in patients with metastatic RCC.

Effects of a sea buckthorn oil spray emulsion on dry eye.

PURPOSE: To investigate the effects of a sea buckthorn oil and sodium hyaluronate-containing eyelid spray emulsion (SB spray) on dry eye. METHODS: A randomized controlled study was carried out. Adults (25-70 years) with Ocular Surface Disease Index (OSDI) ≥20 and moderate or severe dryness, burning or grittiness of the eyes were included. In study part one (n = 2), SB spray was used on both closed eyelids four times in one day. In part two (n = 10), SB spray was used on one randomized eyelid, and a commercial reference spray on the other for nine days. In part three (n = 40), eyes were randomized to one eye receiving SB spray and an untreated control for 1.5 months. Dry eye tests were carried out at baseline, during, and at the end of each study section. Symptoms were recorded in questionnaires and daily logs. RESULTS: In part one, the SB spray was well tolerated. In part two, OSDI decreased significantly (P = 0.022) in the SB spray eye compared to the reference spray, indicating a beneficial effect on symptoms. In part three, OSDI in the SB spray eye decreased significantly compared to the untreated control (P = 0.0007). The scores for dryness at the study end were lower in the SB spray eye compared to control (P = 0.0070). Symptom sums and frequencies of dryness (sum P = 0.0046, frequency P = 0.0016) and watering (sum P = 0.0003, frequency P = 0.013) in the daily logs were lower in the eye treated with SB spray. CONCLUSIONS: SB spray on closed eyelids relieved the symptoms of dry eye.

Surgery for metastases of renal cell carcinoma: outcome of treatments and preliminary assessment of Leuven-Udine prognostic groups in the targeted therapy era.

AIM: This study was conducted to evaluate the efficacy of surgical treatment for metastases accompanied by modern targeted therapies and to evaluate the performance of the Leuven-Udine (L.U.) prognostic groups model. METHODS: This retrospective analysis included 97 consecutive patients with metastatic renal cell carcinoma (mR.C.C.) who underwent surgery for metastases at Helsinki University Hospital between 2006 and 2017. The endpoints were overall survival (O.S.), cancer-specific survival (C.S.S.), recurrence-free survival (R.F.S.) and interval from diagnosis to oncological treatment. RESULTS: The median follow-up time was 46 months (interquartile range, I.Q.R. = 24-74). The estimated median O.S. was 67 months (I.Q.R. = 30-130). A radical surgical result at metastasectomy was achieved in 46 of 97 patients (47%). Of those 46 patients, 28 (61%) experienced recurrence after complete metastasectomy. Median R.F.S. after complete metastasectomy was 10 months (I.Q.R. = 3-37). Five-year O.S. was 59% for patients with complete metastasectomy and 44% for patients with non-complete metastasectomy (p = .035). The median interval from diagnosis to the initiation of targeted oncological treatment was 19 months for patients with non-complete metastasectomy and has hitherto not been reached for patients with complete metastasectomy (p = .006). A statistically significant validation of the prognostic value of the L.U. prognostic groups for predicting C.S.S. was not obtained (p = .420). CONCLUSIONS: Metastasectomy is an option for selected patients with mR.C.C. Complete resection should be attempted when feasible. The data failed to support the prognostic significance of the L.U. model in patients with mR.C.C.

Outcome of surgery for patients with renal cell carcinoma and tumour thrombus in the era of modern targeted therapy.

OBJECTIVE: This study evaluated the clinical outcome of patients with renal cell carcinoma (RCC) with tumour thrombus (TT) after surgical management. MATERIALS AND METHODS: In total, 142 consecutive RCC patients with TT who were operated on in Helsinki University Hospital between 2006 and 2014 were analysed. Eighty-eight (62%) of these patients had been operated on with radical intention and 54 (38%) with cytoreductive intention. A total of 73 patients (51%) received postoperative targeted therapy. The primary endpoint was cancer-specific survival (CSS). RESULTS: The 5 year CSS for level of involvement of TT in the renal vein, subdiaphragmatic vena cava and supradiaphragmatic vena cava was 60% (81 patients), 43% (52 patients) and 51% (nine patients), respectively (p = .42). The median CSS for lymph-node involvement was 63 months for patients with no lymph-node involvement but 10 months for patients with lymph-node involvement (p < .01). The median CSS for metastasis status was 63 months for patients with no metastases compared with 18 months for patients with metastases (p < .01). Among several factors examined, WHO performance status (p = .04), tumour necrosis (p = .05), presence of distant metastases (p = .04) and tumour histology (p = .05) were associated with CSS in the multivariate analysis. CONCLUSIONS: Operative treatment for RCC with TT is associated with good prognosis when there is no lymph-node involvement or distant metastases.

Intravesical Bacillus Calmette-Guérin Versus Combination of Epirubicin and Interferon-α2a in Reducing Recurrence of Non-Muscle-invasive Bladder Carcinoma: FinnBladder-6 Study.

BACKGROUND: Patients with non-muscle-invasive bladder cancer (NMIBC) belonging to the intermediate-risk group should be treated with intravesical instillations to prevent recurrence and progression. OBJECTIVE: We compared the outcome of a monthly maintenance bacillus Calmette-Guérin (BCG) regimen with that of epirubicin (EPI) and interferon-α2a (IFN) in patients with NMIBC. DESIGN, SETTING, AND PARTICIPANTS: Our prospective randomized multicenter study comprised 229 eligible patients with frequently recurrent TaT1 grade 1-2 or low-grade NMIBC enrolled between 1997 and 2008. INTERVENTIONS: The four-arm study involved a single perioperative instillation of EPI plus five weekly instillations of BCG or EPI/IFN, followed by 11 monthly instillations in the 1-yr BCG or EPI/IFN maintenance arms, further followed by four additional quarterly instillations in the two 2-yr maintenance arms. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Time to recurrence, progression, disease-specific survival, and overall mortality were analyzed using the Kaplan-Meier and cumulative incidence analyses plus the Cox and proportional subdistribution hazards models. RESULTS AND LIMITATIONS: The median follow-up time was 7.5 and 7.4 yr in the BCG and EPI/IFN groups, respectively. The probability of recurrence was significantly lower in the BCG group than in the EPI/IFN group. The probability was 39% versus 72% at 7.4 yr, respectively (hazard ratio [HR]: 0.41; 95% confidence interval [CI], 0.28-0.60; p<0.001). There was no significant difference in the probability of progression or in overall survival. However, there was a significant difference in disease-specific mortality in favor of the BCG group (HR: 0.20; 95% CI, 0.04-0.91; p=0.04). CONCLUSIONS: The monthly maintenance BCG regimen showed excellent efficacy and was significantly better in preventing recurrence than a similar regimen of EPI/IFN-α2a. PATIENT SUMMARY: A monthly bacillus Calmette-Guérin (BCG) regimen showed excellent efficacy and was significantly better in preventing recurrence than a similar regimen of epirubicin and interferon-α2a. TRIAL REGISTRATION: Registration was not considered necessary at this stage of the follow-up because the study was initiated as early as in 1997, before the current requirements concerning study registrations were implemented.

Hand-assisted laparoscopic versus open partial nephrectomy in patients with T1 renal tumor: Comparative perioperative, functional and oncological outcome.

OBJECTIVE: Studies comparing hand-assisted laparoscopic partial nephrectomy (HALPN) and open partial nephrectomy (OPN) for T1 kidney tumors are scarce. This study investigated the perioperative, functional and oncological outcomes of these methods. MATERIALS AND METHODS: A prospective institutional kidney tumor register was used to identify patients between January 2006 and May 2014 undergoing HALPN (n = 139) or OPN (n = 165) for tumors 7 cm or smaller with non-absolute indication for nephron-sparing surgery. The outcomes were compared using univariate and multivariate statistical methods. RESULTS: HALPN and OPN groups were similar with regard to tumor characteristics but HALPN patients were 2 years younger (p = 0.001) and had less comorbidity. Fewer intraoperative complications were encountered in HALPN than in OPN patients (7.2% vs 12.7%, p = 0.043). HALPN patients had less all-grade postoperative 30 day complications than OPN patients (27% vs 41%, p = 0.037), but there was no significant difference in Clavien 3-5 complications. Glomerular filtration rate 3 months after operation was lower in the HALPN than in the OPN group (7.1 ± 12.7% vs 10.0 ± 12.4%, p = 0.054). There was no difference in overall survival or recurrence-free survival during the median follow-up of 35 months. CONCLUSIONS: HALPN is a feasible method to achieve equal perioperative, functional and oncological outcomes compared to OPN in patients with tumors 7 cm or smaller in diameter.

Long-term outcome of patients with frequently recurrent non-muscle-invasive bladder carcinoma treated with one perioperative plus four weekly instillations of mitomycin C followed by monthly bacillus Calmette-Guérin (BCG) or alternating BCG and interferon-α2b instillations: prospective randomised FinnBladder-4 study.

BACKGROUND: Recurrent TaT1 non-muscle-invasive bladder cancer (NMIBC) patients should be treated with immediate instillation of chemotherapy after transurethral resection of bladder tumour followed by instillation therapy. OBJECTIVE: To present long-term results of a study exploring the effect of initial mitomycin C (MMC) instillations followed by two types of immunotherapy for patients with frequently recurring NMIBC. DESIGN, SETTING, AND PARTICIPANTS: Between 1992 and 1996, 236 patients with frequently recurring TaT1 grade 1-2 NMIBC were enrolled in the prospective randomised multicentre FinnBladder-4 study. INTERVENTION: One perioperative plus four weekly instillations of MMC followed by monthly bacillus Calmette-Guérin (BCG) or alternating BCG and interferon (IFN)-α2b instillations for up to 1 yr. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary end points were time to first recurrence and time to progression. Secondary end points were disease-specific mortality and overall survival. The principal statistical methods were the proportional subdistribution hazards model and Cox proportional hazards model plus cumulative incidence and Kaplan-Meier analyses. RESULTS AND LIMITATIONS: The median follow-up was 10.3 yr (maximum: 19.8 yr) in the MMC-BCG group and 8.6 yr (maximum: 19.8 yr) in the MMC-BCG/IFN group. The probability of recurrence was significantly lower in the MMC-BCG group than in the MMC-BCG/IFN group (43% vs 78% at 10 yr and 45% vs 80% at 15 yr, respectively; hazard ratio: 2.86; 95% confidence interval, 1.98-4.13; p<0.001). There were no significant differences in the probability of progression, disease-free mortality, or overall survival. CONCLUSIONS: Perioperative plus four weekly MMC instillations followed by monthly BCG, instead of alternating BCG and IFN-α2b instillations, significantly reduce long-term recurrence. PATIENT SUMMARY: We demonstrated in non-muscle-invasive bladder cancer patients with exceptionally frequent recurrences that the risk of long-term recurrence was reduced from 78-80% to 43-45% if one perioperative plus four weekly mitomycin C instillations were followed by monthly bacillus Calmette-Guérin (BCG) instillations for 1 yr instead of alternating instillations of BCG and interferon-α2b. TRIAL REGISTRATION: The registration was not considered necessary at this stage of the follow-up because the study was initiated as early as in 1992 and the last randomisation took place in 1996, before the current requirements concerning study registrations were implemented.

Screening of microbes for novel acidic cutinases and cloning and expression of an acidic cutinase from Aspergillus niger CBS 513.88.

Isolates from gardening waste compost and 38 culture collection microbes were grown on agar plates at pH 4.0 with the cutinase model substrate polycaprolactone as a carbon source. The strains showing polycaprolactone hydrolysis were cultivated in liquid at acidic pH and the cultivations were monitored by assaying the p-nitrophenyl butyrate esterase activities. Culture supernatants of four strains were analyzed for the hydrolysis of tritiated apple cutin at different pHs. Highest amounts of radioactive hydrolysis products were detected at pHs below 5. The hydrolysis of apple cutin by the culture supernatants at acidic pH was further confirmed by GC-MS analysis of the hydrolysis products. On the basis of screening, the acidic cutinase from Aspergillus niger CBS 513.88 was chosen for heterogeneous production in Pichia pastoris and for analysis of the effects of pH on activity and stability. The recombinant enzyme showed activity over a broad range of pHs with maximal activity between pH 5.0 and 6.5. Activity could be detected still at pH 3.5.