ICUD-EAU International Consultation on Bladder Cancer 2012: Non–Muscle-Invasive Urothelial Carcinoma of the Bladder

Context

Our aim was to present a summary of the Second International Consultation on Bladder Cancer recommendations on the diagnosis and treatment options for non–muscle-invasive urothelial cancer of the bladder (NMIBC) using an evidence-based approach.

Objective

To critically review the recent data on the management of NMIBC to arrive at a general consensus.

Evidence acquisition

A detailed Medline analysis was performed for original articles addressing the treatment of NMIBC with regard to diagnosis, surgery, intravesical chemotherapy, and follow-up. Proceedings from the last 5 yr of major conferences were also searched.

Evidence synthesis

The major findings are presented in an evidence-based fashion. We analyzed large retrospective and prospective studies.

Conclusions

Urothelial cancer of the bladder staged Ta, T1, and carcinoma in situ (CIS), also indicated as NMIBC, poses greatly varying but uniformly demanding challenges to urologic care. On the one hand, the high recurrence rate and low progression rate with Ta low-grade demand risk-adapted treatment and surveillance to provide thorough care while minimizing treatment-related burden. On the other hand, the propensity of Ta high-grade, T1, and CIS to progress demands intense care and timely consideration of radical cystectomy.     

Ct2 Bladder Cancer

The patient is an 80-year-old man who presented with gross hematuria. His past medical history indicates he was a cigarette smoker with 50 pack/years. He was successfully treated for carcinoma of the lung 7 years ago. He received chemotherapy, radiation, and surgery. He has mild COPD but has a good performance status. His laboratory studies do not indicate any abnormalities in terms of renal function. He does not have any significant cardiac disease. He has a medium build. He had prostate cancer and underwent a successful radical prostatectomy 10 years ago. His PSA is undetectable. He has some urinary incontinence and wears two pads/day. He underwent the appropriate investigations for gross hematuria. A CT scan of the abdomen and pelvis was normal with the exception of a 4-cm posterior mass in the bladder. There was no hydronephrosis and no enlarged lymph nodes. He underwent a transurethral resection of a solitary bladder tumor performed by another urologist. The tumor was described as large and sessile. It was located on the posterior wall and was approximately 4 cm. The bimanual examination did not reveal a mass. The pathology report stated that the tumor was a high-grade urothelial carcinoma with invasion into the muscularis propria. There was no lymphovascular invasion. I performed a reTURBT, and at that procedure, I did not identify any obvious tumor but the prior resection site was evident. I resected the prior tumor site quite extensively both in depth and width. The pathology revealed only focal carcinoma in situ. There was ample muscle in the specimen and there was some fat as well. As stated, they were free of any cancer. The patient is receptive to any treatment approach.     

Challenging Case: Stones

A 40-year-old woman presents to the emergency department after a motor vehicle accident, and a CT scan revealed no injuries but incidentally notes three non-obstructing stones in the left kidney of 3, 4, and 5 mm in size. She is completely asymptomatic and has no history of urolithiasis.     

Effects of pegylated interferon alfa-2b on the pharmacokinetic and pharmacodynamic properties of methadone: a prospective, nonrandomized, crossover study in patients coinfected with hepatitis C and HIV receiving methadone maintenance treatment

BACKGROUND: Hepatitis C virus (HCV) infection is common among methadone-maintained HIV-positive individuals. Pegylated interferon (pegIFN) used in combination with ribavirin is conventional treatment for HCV. However, pegIFN has been associated with adverse effects (AEs) that may simulate opioid withdrawal and be confused with insufficient methadone dosage. OBJECTIVE: The aim of this study was to determine, using methadone pharmacokinetic properties, whether methadone dosage adjustments are needed on initiation of treatment with pegIFN alfa-2b for HCV in methadone-maintained HIV-positive patients. METHODS: This prospective, nonrandomized, crossover study was conducted at the Albert Einstein College of Medicine and Montefiore Medical Center (Bronx, New York). Patients who were aged > or =18 years, coinfected with chronic HCV and HIV, and had been receiving methadone maintenance treatment (dosage, 40-200 mg/d PO) for at least 8 weeks prior to enrollment were eligible. We determined mean methadone C(max), T(max), Cn,in, AUC, and oral clearance (CL/F) values over a 24-hour period before (baseline) and after the administration of pegIFN alfa-2b 1.5 microg/kg SC (2 doses given 1 week apart). To determine differences in opiate withdrawal symptoms, one of the primary investigators administered the Subjective Opiate Withdrawal Scale (SOWS) and Objective Opiate Withdrawal Scale (OOWS) at baseline and 7, 14, and 21 days after the administration of the first dose. Study participants underwent weekly clinical evaluation for signs and symptoms of methadone withdrawal and for AEs of pegIFN. RESULTS: Nine patients were included in the study (7 men, 2 women; 7 Hispanic, 2 black; mean [SD] age, 41 [8.3] years; mean [SD] weight, 75.0 [12.3] kg). We did not observe any significant changes from baseline in mean C(max), T(max), C(min), AUC, and CL/F values despite 80% power to detect a 30% change in either direction. Changes from baseline in SOWS and OOWS scores were not statistically significant. The only AEs reported were mild and consistent with those expected after pegIFN alfa-2b administration, such as inflammation at the injection site and mild, brief, flu-like symptoms. CONCLUSION: Based on the results of this small, prospective, nonrandomized study, pegIFN alfa-2b did not appear to precipitate opioid withdrawal in this sample of methadone-maintained persons with HIV and chronic HCV coinfection; methadone dosage adjustments were unlikely to be needed.     

A longitudinal immunologic evaluation of hemophiliac patients

Over an average span of one year, we performed a prospective clinical and immunologic evaluation of 30 patients with hemophilia. No patient developed life-threatening opportunistic infection or malignancy; however, the immunologic abnormalities and lymphadenopathy initially present in nine patients (lymphadenopathy group) persisted. In addition, five patients, representing 24% of the initial group without lymphadenopathy, developed generalized lymphadenopathy (converter group). One episode of idiopathic thrombocytopenia (ITP) and one episode of staphylococcal sepsis occurred in this "converter" group; one episode of ITP also occurred in the lymphadenopathy group. Sixteen patients remained asymptomatic. At the time of the follow-up evaluation, those differences in mononuclear cell (MNC) percentages and numbers noted initially among the three hemophiliac groups were no longer present. Natural killer cell function alone or in the presence of biologic response modifiers was not different among hemophiliac and control groups. Before developing lymphadenopathy, the converter group of patients had significantly better lymphocyte mitogenic function than did the other two groups of patients with hemophilia. However, lymphocyte mitogenic responses of all groups of patients with hemophilia significantly deteriorated over the course of the study. The abnormal mitogenic responses noted in these patients was explained in part by higher levels of spontaneous suppressor cell activity in mononuclear cell preparations from patients with hemophilia. We conclude that long-term immunologic studies of this patient population requires both quantitative and qualitative evaluations. Our data show that patients with hemophilia have progressive dysfunction of cell- mediated immunity.     

In vitro characterization of the human recombinant soluble granulocyte- macrophage colony-stimulating factor receptor

We have cloned, expressed, and partially purified a naturally occurring, truncated, soluble form of the human granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor alpha subunit to investigate its biochemical and biologic properties. The soluble receptor species lacks the transmembrane and cytoplasmic domains that are presumably removed from the intact receptor cDNA by a mechanism of alternative splicing. The resulting soluble 55- to 60-kD glycosylated receptor species binds GM-CSF with a dissociation constant (kd) of 3.8 nmol/L. The soluble GM-CSF receptor successfully competes for GM-CSF binding not only with the transmembrane-anchored GM-CSF receptor alpha subunit but also with the native oligomeric high-affinity receptor complex. In addition, in human bone marrow colony-forming assays, the soluble GM-CSF receptor species can antagonize the activity of GM-CSF. Our data suggest that the soluble GM-CSF receptor may be capable of acting in vivo as a modulator of the biologic activity of GM-CSF.