Sequential intravesical chemoimmunotherapy with mitomycin C and bacillus Calmette-Guérin and with bacillus Calmette-Guérin alone in patients with carcinoma in situ of the urinary bladder: results of an EORTC genito-urinary group randomized phase 2 trial (30993)

Background

Bacillus Calmette-Guérin (BCG) is the intravesical treatment of choice for carcinoma in situ (CIS).

Objective

Our aim was to assess if sequential mitomycin C (MMC) plus BCG after transurethral resection (TUR) is worthy of further study in non–muscle-invasive bladder cancer patients with CIS.

Design, setting, and participants

In a noncomparative phase 2 study, 96 patients with primary/secondary/concurrent CIS of the urinary bladder were randomized to sequential MMC plus BCG or to BCG alone after TUR.

Intervention

Patients received six weekly instillations of MMC followed by six weekly instillations of BCG or six weekly instillations of BCG, 3 wk rest, and three further weekly instillations of BCG. Complete responders received three weekly maintenance instillations at 6, 12, 18, 24, 30, and 36 mo in accordance with the initial randomization.

Measurements

End points were complete response (CR) rate at the first control cystoscopy 16–18 wk after start of treatment, disease-free interval, overall survival, and side effects.

Results and limitations

Ninety-six patients were randomized, 48 to each treatment group. Ten patients were ineligible, and three did not start treatment. In all randomized patients, CR rates on MMC plus BCG and BCG alone were 70.8% and 66.7%, respectively. In 83 eligible patients who started treatment, CR rates were 75.6% and 73.8%, respectively. Based on a median follow-up of 4.7 yr, 25 patients (52.1%) on MMC plus BCG and 22 patients (45.8%) on BCG alone were disease free. Twelve patients stopped treatment due to toxicity: three during induction (two MMC plus BCG, one BCG) and nine during maintenance (three MMC plus BCG, six BCG).

Conclusions

In the treatment of patients with CIS, sequential chemoimmunotherapy with MMC plus BCG had acceptable toxicity. CR and disease-free rates were similar to those on BCG alone and to previous publications on sequential chemoimmunotherapy.

Trial registration

This study was registered with the US National Cancer Institute clinical trials database (protocol ID: EORTC-30993). http://www.cancer.gov/search/ViewClinicalTrials.aspx?cdrid=68869&;version=HealthProfessional&;protocolsearchid=7920643.     

Impact of oral health care needs on health-related quality of life in adult HIV+ patients

The aim of this work was to determine the social impact of oral conditions on health-related quality of life in adult HIV+ patients and create a predictive model. The oral health impact profile questionnaire OHIP-49 was randomly administered to 200 HIV+ adults patients of any age and either sex at the High Risk Patients Dental Care Unit (CLAPAR I), School of Dentistry, University of Buenos Aires. Argentina. For each of the 49 items, participants indicated their responses on a five point Likert-type frequency scale ranging from "never" to "very often". Oral health needs were assessed through the CCITN (Community Caries Index of Treatment Need) and CPITN (Community Periodontal Index of Treatment Need). The Mann-Whitney test was used to compare the OHIP-49 score between male and female respondents. The Kruskal-Wallis test was used to assess score differences among the OHIP-49 domains. Altogether, 50% of the respondents were male and 50% were female, aged 36.45 +/- 0.70 years and 38.03 +/- 0.78 years respectively. The assessment of oral health care needs revealed a great need for treatment. Mean CCITN was 11.15 +/- 0.35 and CPITN was 2.41 +/- 0.12. The average total OHIP-49 score (83) revealed a high level of social impact, which was higher for female compared to male respondents (Z(T) = 2.08, p = 0.037). The domains concerning functional limitation (domain 1), physical pain (domain 2) and psychological discomfort (domain 3) showed higher levels of social impact (H = 395.06, p < 0.0001). The social impact observed in these domains was higher for female compared to male patients. In the correlation analysis, oral conditions, age, gender and social impact were significantly associated. These results demonstrate that unmet oral health care need impairs the quality of life of HIV+ patients and suggest the need of comprehensive oral health care interventions.     

Patient weight more than body mass index influences total hip arthroplasty long term survival

The effect of obesity on the long-term survival of total hip arthroplasty remains under discussion. Reviewing meta-analyses of large cohort studies a high body mass index has been correlated with a higher incidence of complications but not univocally with a lower implant survival rate. It has been suggested that body weight rather than body mass index might be a better parameter to evaluate prosthesis outcome. We reviewed 27,571 patients retrospectively with primary arthritis as a preoperative diagnosis. Patients were divided into 4 categories based on their body mass index, or into two groups based on the body weight (<80 kg and =80 kg). Implant survivorship was estimated with use of the Cox proportional hazards model with revision for aseptic loosening as the end point. Results were stratified for sex and implant tribology. When body mass index was used the 10 years implant survival in obese versus non-obese patients was not statistically different (p=0.058), but when body weight was used a statistically different implant survivorship was found for men (p=0.009). Therefore, weight rather than than body mass index influences survival of hip prostheses, and should be used as the discriminant parameter for further studies.     

The Remission Clinic approach to halt the progression of kidney disease

Randomized multicenter studies in diabetic and nondiabetic patients with chronic proteinuric nephropathies have clearly demonstrated that renin-angiotensin system (RAS) inhibitors, such as angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) used alone or in combination, effectively retard renal disease progression. Proteinuria reduction, in addition to arterial blood pressure control, largely mediates the nephroprotective effect of RAS inhibitor therapy. Despite RAS inhibition, however, most patients with chronic kidney disease (CKD) progress to end-stage renal disease (ESRD). This highlights the importance of innovative therapies to halt or revert CKD progression in those at risk. Along this line, a multimodal strategy (Remission Clinic) targeting urinary proteins by dual RAS inhibition with ACE inhibitors and ARBs up-titrated to maximum tolerated doses, by intensified blood pressure control, amelioration of dyslipidemia by statins, smoking cessation and healthy lifestyle implementation was safely and effectively applied at our outpatient clinic to normalize urinary proteins and prevent renal function loss in patients otherwise predicted to rapidly progress to ESRD because of nephrotic-range proteinuria refractory to standard antihypertensive dosages of an ACE inhibitor. This approach achieved remission or regression of proteinuria and stabilized kidney function in most cases, and almost fully prevented progression to ESRD. Provided patients are closely monitored and treatment is cautiously up-titrated according to tolerability, this approach might be safely applied in day-by-day hospital practice. Effective prevention of ESRD would reduce costs of renal replacement therapy by dialysis or transplantation and would be life-saving where these are not available for all patients in need.     

Akreos Adapt AO Intraocular Lens Opacification: A Case Report

A 79-year-old hyperglycemic patient was referred to the ‘Santa Maria delle Croci’ Hospital, Ravenna, Italy. He presented with visual impairment in the right eye. Four years ago, he had had an uneventful cataract surgery in the right eye. We observed an opacification of the intraocular lens (IOL) causing significant visual disturbance. The IOL was exchanged. Unfortunately, pathologic analysis was not performed. Patient-related factors such as hyperglycemia and hypertension might have been responsible for the opacification. To our knowledge, there is only one previous report of opacification of the Akreos Adapt AO IOL.Key words: Intraocular lens opacification, Secondary implant, Intraocular lens explantation