Christine Mian

IMMUNOCYT1: A NEW TOOL FOR DETECTING TRANSITIONAL CELL CANCER OF THE URINARY TRACT

PURPOSE The limitations of cytology and the invasiveness of cystoscopy for detecting bladder cancer generate increasing interest in noninvasive, urine bound diagnostic tools. We assessed the diagnostic value of the newly developed immunocytochemical test, Immunocyt, which detects cellular markers specific for transitional cell cancer in the voided urine of patients with bladder cancer. MATERIALS AND METHODS Participating in our prospective study were 264 consecutive patients with a mean age of 65.9 years, including 114 in whom symptoms were suggestive of bladder cancer and 150 who were being followed after complete transurethral resection of superficial transitional cell carcinoma. Voided urine specimens were evaluated by standard cytology and the Immunocyt test, which traces the monoclonal antibodies M344, LDQ10 and 19A211 against transitional cell carcinoma in exfoliated urothelial cells. In all cases cystoscopy was subsequently performed and any suspicious lesion was evaluated by biopsy. RESULTS Histologically proved transitional cell carcinoma was found in 79 patients. Immunocyt with cytology had 89.9% sensitivity overall (84, 88 and 96.5% in grades 1 to 3 disease, respectively). A total of 34 (43%), 3 (3.8%) and 34 (43%) cases were positive on Immunocyt only, cytology only and both evaluations, respectively. In 8 cases (10.1%) both tests were negative. Overall Immunocyt only was 86.1% sensitive (84, 84 and 89.6% in grades 1 to 3 disease, respectively) and 79.4% specific. Overall cytology only was 46.8% sensitive (4, 52 and 79.3% in grades 1 to 3 disease, respectively) and 98.2% specific. CONCLUSIONS Immunocyt is a noninvasive, highly sensitive test for detecting transitional cell carcinoma of all grades and stages. When combined with conventional urinary cytology, it may replace cystoscopy in select patients, especially in followup protocols of low grade transitional cell carcinoma.

The aging lower urinary tract: a comparative urodynamic study of men and women

OBJECTIVES The fact that aging women report similar voiding symptoms as age-matched men prompted us to compare age-related changes of urodynamic parameters in both sexes. METHODS Four hundred thirty-six patients (253 men and 183 women) 40 years of age or older underwent the following investigations: free uroflowmetry, measurement of postvoid residual volume, and full urodynamic testing, including a pressure-flow study (pQs). Additional investigations were a urethral pressure profile in women and quantification of prostate volume by transrectal ultrasonography in men. All men were referred for lower urinary tract symptoms suspicious of bladder outflow obstruction and women predominantly for urinary incontinence. Patients with previous surgery of the lower urinary tract (prostate, bladder, urethra) and those taking medication with a major effect on voiding function (alpha-receptor blockers, 5 alpha-reductase inhibitors, anticholinergic agents) were excluded. RESULTS The mean +/- standard deviation (SD) age in the female (f) population (n = 183) was 59 +/- 16 years (range 40 to 93), in the male population (m) (n = 253) 67 +/- 9 years (range 40 to 90). In both sexes, we observed a statistically significant increase of postvoid residual volume (f: P = 0.0001; m: P = 0.02) and a decrease of peak flow rate (f: P = 0.019; m: P = 0.014), average flow rate (f: P = 0.007; m: P = 0.04), voided volume (f: P = 0.007; m: P = 0.002), and bladder capacity determined by urodynamics (f: P = 0.003; m: P = 0.0004) with progressing age. In both sexes, there were no age-related changes (P >0.05), demonstrable for maximum detrusor pressure and detrusor pressure at peak flow rate. In women, there was a significant decrease of functional urethral length (P = 0.012) and maximum urethral closing pressure (P = 0.0001) with higher age; in men, the prostate volume increased significantly with age (P = 0.0001). With respect to detrusor instability, we observed an increase in men from 23.4% (40 to 60 years) to 46.7% (more than 80 years) (P = 0.004), whereas in women no significant age-related changes were present (P >0.05). CONCLUSIONS These data show that age-associated urodynamic changes in both sexes are comparable for a number of parameters. They provide an explanation for the fact that aging women report comparable voiding symptoms as men and suggest a primary, non-sex-specific aging process of the urinary bladder.

p16INK4a is a useful marker for the diagnosis of adenocarcinoma of the cervix uteri and its precursors: An immunohistochemical study with immunocytochemical correlations

p16INK4a is a tumor suppressor gene that plays a central role in the regulation of the cell cycle. In squamous cervical cancers, overexpression of p16INK4a is induced by HPV and associated with the carcinogenesis of cervical epithelia. The aim of this study was to determine whether immunostaining of p16INK4a is useful in detecting adenocarcinomas of the cervix uteri in histologic and cytologic routine specimens. A total of 45 surgical specimens, including 18 cases of invasive carcinoma, 8 cases of adenocarcinoma in situ, 4 cases of endocervical glandular atypia (cervical glandular intraepithelial neoplasia), and 15 reactive lesions of the endocervical glands were immunostained using a specific anti-human p16INK4a monoclonal antibody (clone E6H4, mtm laboratories AG, Heidelberg, Germany). Furthermore, immunocytochemical analysis was performed on 10 preoperative ThinPrep cytologic samples with abnormal glandular cells and compared with the human papillomavirus status as assessed with the Hybrid Capture II test. p16INK4a was detected immunohistochemically in all 26 cases of adenocarcinoma of the cervix uteri, including 18 invasive and 8 in situ carcinomas. Only a focal expression was evidenced in the four specimens with endocervical glandular atypia, and no reaction was found in reactive lesions. Also, the immunocytochemical analysis on the 10 ThinPrep specimens evidenced a strong expression of p16INK4a in neoplastic endocervical cells. In all cases this was associated with a high-risk HPV-positive typing. p16INK4a is a useful marker for the detection of the adenocarcinoma of the cervix uteri and its precursors. The immunocytochemical detection on ThinPrep specimens may contribute to an early detection of endocervical lesions.

P16INK4a expression and progression risk of low-grade intraepithelial neoplasia of the cervix uteri

The aim of the study was to evaluate the immunohistochemical expression of p16INK4a as a marker of progression risk in low-grade dysplastic lesions of the cervix uteri. p16INK4a immunohistochemistry was performed on 32 CIN1 with proven spontaneous regression of the lesion in the follow-up (group A), 31 (group B) with progression to CIN3 and 33 (group C) that were randomly chosen irrespective of the natural history of the lesion. p16INK4a staining pattern was scored as negative (less than 5% cells in the lower third of dysplastic epithelium stained), as focally positive (≤25%) and as diffuse positive (>25%). A diffuse staining pattern was detected in 43.8% of CIN1 of group A, 74.2% of group B and 56.3% of group C. No p16INK4a staining was detected in 31.3% and 12.9% CIN1 lesions of groups A and B, respectively. Overall, 71.4% and 37.8% of p16INK4a-negative and diffusely positive CIN1 had regressed at follow-up, whereas 28.6% and 62.2% negative and diffusely positive CIN1 were progressed to CIN3, respectively (P<0.05). All CIN3 lesions analyzed during follow-up of group B were diffusely stained for p16INK4a. Although p16INK4a may be expressed in low-grade squamous lesions that undergo spontaneous regression, in this study, CIN1 cases with diffuse p16INK4a staining had a significantly higher tendency to progress to a high-grade lesion than p16INK4a-negative cases. p16INK4a may have the potential to support the interpretation of low-grade dysplastic lesions of the cervix uteri.

Does extended lymphadenectomy increase the morbidity of radical cystectomy

To report the events during and after radical cystectomy and urinary diversion for bladder cancer, in terms of major and minor complications, comparing a minimal with an extended lymphadenectomy, as more lymph nodes obtained during radical cystectomy may improve staging and thus the outcome.

Institutional variability in the accuracy of urinary cytology for predicting recurrence of transitional cell carcinoma of the bladder

To assess the contemporary inter‐institutional accuracy of urinary cytology in predicting the recurrence of transitional cell carcinoma (TCC) of the bladder, in a large multi‐institutional cohort from four continents, as cystoscopy and urinary cytology represent the ‘gold standards’ for surveillance of TCC recurrences, but the ability of cytology to predict recurrence varies.

INTERRELATIONSHIPS OF BLADDER COMPLIANCE WITH AGE, DETRUSOR INSTABILITY, AND OBSTRUCTION IN ELDERLY MEN WITH LOWER URINARY TRACT SYMPTOMS

Data on the interrelationships of bladder compliance (BC), detrusor instability (DI), and bladder outflow obstruction (BOO) in elderly men with lower urinary tract symptoms (LUTS) are scarce and were therefore assessed in this study. Principle inclusion criteria for this study were men aged ⩾50 years suffering from LUTS as defined by an International Prostate Symptoms Score (IPSS) of ⩾7 and a peak flow rate (Qmax) of ⩽15 ml/sec. Patients with previous surgery of the bladder, prostate, or urethra as well as a pathological neurourological status were excluded from this study. The following parameters were studied in all patients: IPSS, prostate volume calculated by transrectal ultrasonography, free uroflow study, post‐void residual volume determined by transurethral catheterization, and a multichannel pressure flow study (pQS). A group of 170 men were included in the analysis. The mean BC in the overall group was 32 ± 2 ml/cm H2O (mean ± standard error of the mean [SEM]; range, 4–100 ml/cm H2O). In 36.5% of patients, BC was significantly reduced (⩽20 ml/cm H2O), and in a further 37.1%, it ranged from 20 to 40 ml/cm H2O. BC decreased statistically significantly (p < 0.05) in patients with advanced age, lower Qmax, higher voiding pressures, and larger prostates. In men with DI (n = 61), mean BC was significantly lower (22 ± 3 ml/cm H2O) compared to those without (37 ± 3 ml/cm H2O; p = 0.001; n = 109). Patients with severe BOO as defined by a linear passive urethral resistance relationship of ⩾3 (n = 109), had a significantly lower BC (23 ± 2 ml/cm H2O) compared to those without or minimal obstruction only (39 ± 3 ml/cm H2O; p = 0.0002; n = 61). Stepwise logistic regression analysis revealed that DI, a low bladder capacity, and a high maximum detrusor pressure were independent predictors of markedly reduced BC (<20 ml/cm H2O). BC is decreased in elderly men with high voiding pressures, BOO, and DI. The mechanism leading to the reduction of BC under these circumstances is largely unknown and could result from cytostructural alterations of the detrusor and changes in detrusor innervation. Neurourol. Urodynam. 18:3–15, 1999.

Detection of upper urinary tract transitional cell carcinoma with ImmunoCyt: a preliminary report.

OBJECTIVES To assess the clinical performance of ImmunoCyt in the detection of upper urinary tract transitional cell carcinoma (UT-TCC). This newly developed immunocytochemical test detects three cellular markers specific for TCC. METHODS Thirty-seven patients with symptoms and/or findings on imaging suggestive of UT tumors were prospectively evaluated. All patients underwent a standard cytologic evaluation and ImmunoCyt testing of voided urine, as well as imaging studies. Urine samples were also obtained from the UT of 32 patients by ureteral catheterization and tested by cytologic analysis and ImmunoCyt. RESULTS Sixteen patients had UT-TCC as documented by the final histologic evaluation. The sensitivity of testing the voided urine from 37 patients was 50% for cytologic analysis, 75% for ImmunoCyt, and 87% for both methods combined. The cytologic evaluation detected no G1, 1 (17%) of 6 G2, and 7 (100%) of 7 G3 tumors. ImmunoCyt detected 1 (33%) of 3 G1, 6 (100%) of 6 G2, and 5 (71%) of 7 G3 tumors. The sensitivity in the 32 urine samples obtained from the UT was 82% for cytologic analysis, 91% for ImmunoCyt, and 100% for both methods combined. Cytologic analysis detected all G2 and G3 (100% sensitivity) and no G1 tumors. ImmunoCyt detected 2 (100% sensitivity) of 2 G1, 4 (100%) of 4 G2, and 4 (80%) of 5 G3 tumors. The test specificity, calculated in 21 patients free of TCC, was 100% for cytologic analysis in voided and ureteral urine specimens and 95% and 100% for ImmunoCyt in voided and ureteral urine samples, respectively. CONCLUSIONS The results of this preliminary study show that ImmunoCyt complements cytologic analysis in detecting UT-TCC, mainly because of its high sensitivity to low-grade TCC. The combination of cytologic testing and ImmunoCyt gives 100% sensitivity in detecting UT-TCC in UT urine samples.

Comparison of complications in three incontinent urinary diversions.

BACKGROUND Few data are available in comparing different incontinent urinary diversions (ICUD). OBJECTIVE To compare early, short-term, and long-term complications in three different forms of ICUD. DESIGN, SETTING, AND PARTICIPANTS 130 high-risk patients undergoing radical cystectomy and ICUD were prospectively enrolled at one institution. The patients were divided into three groups: ileal conduit (IC), colon conduit (CC), and ureteroureterocutaneostomy (UUCS). INTERVENTION All patients underwent radical cystectomy and one form of ICUD. MEASUREMENTS The complications observed were prospectively listed and subsequently compared. Statistical analysis was performed using the Pearsons chi-square test. A p-value < or = 0.05 was considered statistically significant. RESULTS AND LIMITATIONS 130 patients with a median age of 71.0 yr (range 46-81) underwent radical cystoprostatectomy (RCP): n=95 (73%) or anterior pelvic exenteration (APE) n=35 (27%) with lymphadenectomy. An IC was performed in 55, a CC in 34, and a UUCS in 41 patients, respectively. A high comorbidity, mainly diabetes, arteriosclerosis, pulmonary insufficiency, and borderline renal function (creatinine>1.5mg%) was found in 12.7% of group 1, in 35.2% of group 2, and in 48.9% of group 3. Overall median follow-up was 16 mo (range 5-84). Perioperative mortality occurred in 1.5%. The overall perioperative diversion-unrelated complication rate was 23.6%. IC showed the lowest rate with 18.1%, followed by CC with 26.4%, and UUCS with 32%, respectively. In contrast, major diversion-related complications occurred in 18.1% of IC, in 5.8% of CC, and none in UUCS. The same was true for late surgical reintervention, with 20% for IC, 5.8% for CC, and 2.4% for UUCS. CONCLUSIONS Complications are closely related to the method selected. The IC had the highest rate of severe complications as well as surgical reinterventions and late complications in the intestinal tract.

uCyt+/ImmunoCyt in the detection of recurrent urothelial carcinoma: an update on 1991 analyses.

The authors provide an update on the clinical value and role of the uCyt+/ImmunoCyt™ test as a noninvasive tool for the detection of recurrent urothelial carcinoma.