Prostate and bladder cancer screening.
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Adult↗
Biomedical subjects
E M Messing
Publications and source records attributed to E M Messing.
Loss of the CDKN2A/p16 locus detected in bladder irrigation specimens by fluorescence in situ hybridization.
PURPOSE: We measured the CDKN2A/p16 tumor suppressor gene locus in bladder irrigation specimens and correlated the measurement with the clinical status of patients with bladder cancer. MATERIALS AND METHODS: Irrigation specimens were obtained at cystoscopy from 10 normal controls, 21 patients with bladder cancer in whom no concurrent bladder tumor was seen and 23 patients with bladder tumors. Deoxyribonucleic cytometry and fluorescence in situ hybridization measurements were made. One fluorescence in situ hybridization probe was specific to the chromosome 9 centromere and the other, COSp16, targeted the CDKN2A/p16 region on chromosome 9p21. Three rates were calculated, including the hyperdiploid fraction from deoxyribonucleic acid cytometry, disomic fraction from the 9 centromere count and COSp16F, the frequency of COSp16 in association with 9 centromere. Specimens were classified as positive or negative for each of these rates using cutoff points based on previous studies and the distribution of values obtained for the normal control specimens. RESULTS: Hyperdiploid fraction values were positive (greater than 8%) in 1 normal and 1 nontumor specimen. Ten specimens from patients with tumor showed elevated hyperdiploid fraction values. In 4 nontumor and 13 tumor irrigation specimens the chromosome 9 disomic fraction values were positive (less than 80%). COSp16F was positive (less than 83%) for 18 nontumor irrigation specimens and 18 tumor irrigation specimens. One normal, and 39 of 44 nontumor and tumor irrigation specimens were positive by at least 1 test. CONCLUSIONS: COSp16 loss is measurable in irrigation specimens and it correlates with clinical status. This assay may prove useful in screening for and managing bladder cancer.
DNA, Neoplasm↗
Pelvic pain following radical retropubic prostatectomy: a prospective study.
OBJECTIVES: To evaluate subacute and chronic pelvic pain after radical retropubic prostatectomy (RRP) performed for clinically localized prostate cancer. METHODS: Twenty-four consecutive patients undergoing RRP completed pain, quality-of-life, and incontinence questionnaires. They also wore pads for 24 hours to measure urine loss objectively before and after surgery. RESULTS: Three patients had pelvic pain preoperatively. Thirteen, 7, and 5 patients had pelvic pain at 1, 3, and 6 months, respectively, after RRP. At 6 months, none of the 5 patients with pelvic pain required analgesic medication. There was a strong relationship between pain and cancer worry, as well as between pain and incontinence. CONCLUSIONS: Many patients have subacute pelvic pain after RRP but improve over time. Severe chronic pain is unlikely after RRP.
Acute Disease↗
Bladder cancer in renal transplant recipients.
OBJECTIVES: To determine if there is an increased rate of occurrence of bladder cancer in renal transplant recipients. METHODS: We reviewed the records of 3130 consecutive renal transplant recipients at the University of Wisconsin Hospital from 1980 to 1994. We then compared the rate of occurrence of bladder cancer in this population with that of the general population of Wisconsin. Using an age-specific hazard model based on the rate of bladder cancer in the general population of Wisconsin, we predicted the expected number of bladder cancer cases in this renal transplant population. RESULTS: Using this model, one would expect 1.81 cases of bladder cancer in the renal transplant data set, as opposed to the observed 6, resulting in a relative risk of 3.31 of developing bladder cancer as a result of renal transplantation. CONCLUSIONS: There is a higher incidence of bladder cancer in renal transplant recipients. Therefore, despite a higher incidence of hematuria in this population, each noninfected patient with microscopic (or gross) hematuria should undergo a careful urologic evaluation.
Adult↗
A prospective study of quantification of urinary incontinence and quality of life in patients undergoing radical retropubic prostatectomy.
OBJECTIVES: To prospectively evaluate the level of urinary incontinence and its impact on quality of life in patients undergoing radical retropubic prostatectomy. METHODS: Patients completed a 24-hour pad test together with an incontinence and quality-of-life questionnaire before and after surgery. RESULTS: Patients were followed up for an average of 7.6 months (range 4.7 to 12.5) after radical prostatectomy. The 24-hour pad test demonstrated that 87% of patients had some incontinence at 1 month and 63% at 6 months after surgery. The median volume of urine leakage was 34 mL at the last follow-up visit; 55% of patients indicated substantial bother from incontinence at the 1-month follow-up visit and 29% at the 6-month follow-up visit. For most patients, there was a substantial discrepancy between the reported and the measured level of incontinence. Patient-reported bother regarding incontinence correlated best to the actual amount of urine loss. CONCLUSIONS: Patients become incontinent after surgery but improve over time. Seventeen percent of patients still experienced leakage of more than 150 mL daily at the last follow-up visit. The questionnaire utilized in this study identifies the presence of incontinence but was not accurate in estimating the amount of urine loss. Initially, quality of life was reduced by surgery but improved over time and nearly returned to the preoperative level.
Aged↗
Urinary nuclear matrix protein as a marker for transitional cell carcinoma of the urinary tract.
PURPOSE: The purpose of this trial was to evaluate an immunoassay for urinary nuclear matrix protein, NMP22, as an indicator for transitional cell carcinoma of the urinary tract. MATERIALS AND METHODS: Three groups of subjects participated in this trial of NMP22: 1-175 with transitional cell carcinoma, 2-117 with benign urinary tract conditions and 3-375 healthy volunteers. Each subject provided a single (3 voids) urine sample for analysis at the time of study entry. Each sample was assayed for the level of NMP22. RESULTS: In normal healthy volunteers and in subjects with benign conditions median NMP22 levels were 2.9 and 3.3 units per ml., respectively. Median urinary NMP22 levels in patients with transitional cell carcinoma were significantly greater than in comparison subjects. Patients with active transitional cell carcinoma had significantly greater median urinary NMP22 levels than those with no evidence of disease (6.04 versus 4.11 units per ml., p = 0.027, 1-tailed Mann-Whitney U test). We noted no effect of tumor grade, extent of disease or exposure to intravesical therapy on urinary NMP22 levels. CONCLUSIONS: NMP22 is a promising urinary tumor marker for monitoring transitional cell carcinoma. Nuclear matrix proteins are a new class of tumor markers that represent the basis for the development of assays with increased efficacy for the detection and treatment of cancer.
Aged↗
Toxicity evaluation of difluoromethylornithine: doses for chemoprevention trials.
This intergroup trial was developed to determine the toxicity of relatively low doses of difluoromethylornithine (DFMO) administered to humans for 1 year. The goal was to find an appropriate DFMO dose for use in human chemoprevention trials. Patients with resected superficial bladder cancers were studied. Following stratification, they were randomized to daily DFMO doses of 0.125, 0.25, 0.5, or 1.0 g/day for a planned period of 1 year. Patients were followed closely for evidence of drug toxicity. Seventy-six patients were evenly randomized (19 per group) to receive each dose of DFMO. Forty-nine patients received DFMO for more than 200 days while 35 received the drug for > or = 350 days. No substantial drug-related toxicity was observed at any dose. DFMO doses of > or = 1 g/day for periods up to 1 year appear to be without significant toxicity in most patients. This dose range may be appropriate for use in future human cancer chemoprevention trials.
Antineoplastic Agents↗
Hematuria home screening: repeat testing results.
To determine at what interval screening should be repeated to detect bladder cancer before it becomes muscle invasive 856 men who had 14 negative daily home tests for hematuria with a chemical reagent strip 9 months previously performed repeat tests. Of these men 50 (5.8%) had at least 1 positive test during the second 14-day screening period and 38 were evaluated, 15 of whom (39.5%) had significant urological pathological conditions, including 8 with malignancies. Bladder cancer was noted in 7 men, with no tumor invading the muscularis propria. The finding of 7 bladder cancers in 856 men (0.82%) who had a negative test 9 months previously indicates that bladder cancer has a brief preclinical duration and that testing must be repeated at least annually for screening to detect bladder cancer consistently before invasion occurs.
Adenocarcinoma↗
Comparison of bladder cancer outcome in men undergoing hematuria home screening versus those with standard clinical presentations.
OBJECTIVES: Because repetitive hematuria home screening with a chemical reagent strip can detect early stage bladder cancer (BC) in asymptomatic middle-aged and elderly men, the ability of this screening to effect earlier detection and reduce BC mortality was investigated. METHODS: Grades, stages, and outcomes of BCs detected by hematuria screening in 1575 men were compared with those of all newly diagnosed BCs in men age 50 years or older reported to the Wisconsin cancer registry in 1988. BC grades and stages were assigned by review of all pathology slides/blocks, and causes of deaths were determined from cancer registry records. As an additional control group, outcomes of BC cases diagnosed in men solicited to take part in screening, who declined, were also determined. RESULTS: The proportions of low-grade (grades 1 and 2) superficial (Stages Ta and T1) versus high-grade (grade 3) or invasive (Stage T2 or higher) cancers in cases detected by hematuria screening (screened cases) and those reported to the tumor registry (unscreened cases) were not significantly different (52.4% versus 47.7% in 21 screened and 56.8% versus 43.3% in 511 unscreened cases) (P > 0.20). Of the high-grade or invasive cases, however, the proportion of late stage (T2 or higher) tumors was significantly lower in the screening-detected BCs compared to unscreened ones (P = 0.007). No screened case has died of BC (3- to 9-year follow-up), whereas 16.4% of unscreened cases have within 2 years of diagnosis (P = 0.025). Twenty-three of 1940 (1.2%) men who were solicited but chose not to participate in screening were diagnosed with BC within 18 months after what would have been their last home screening date, compared with 1.3% of participants having BC detected by screening. Thus, screening participants and those who were solicited and declined had similar likelihoods of developing BC. CONCLUSIONS: Hematuria home screening detects high-grade cancers before they become muscle invading and significantly reduces BC mortality.
Aged↗
Living related and unrelated donors for kidney transplantation. A 28-year experience.
OBJECTIVE: The objective of this study was to analyze a single center's 28-year experience with 1000 living donor transplants. SUMMARY BACKGROUND DATA: The number of potential renal transplant recipients far exceeds the number of cadaveric donors. For this reason, living related donors (LRDs) and, more recently, living unrelated donors (LURDs) have been used to decrease the cadaveric donor shortage. METHODS: From November 15, 1966, until August 5, 1994, 1000 living donor transplants were performed; 906 were living related and 94 were living unrelated transplants. Results were divided into precyclosporine (1966-1986, era I) and cyclosporine (1986-1994, era II) eras. Patient and graft survivals were compared between diabetic and nondiabetic recipients, between LRDs and LURDs, and according to human leukocyte antigen (HLA) matching. Donor mortality, morbidity, and postoperative renal function were also analyzed. RESULTS: The 5-, 10-, and 20-year graft survivals were 78.8%, 64.8%, and 43.4%, respectively. Patient and graft survival improved in era II (patient = 87.0% vs. 81.7%, p = 0.03; graft = 72.9% vs. 67.7%, p = 0.04). Nondiabetic patient and graft survivals were better than diabetic patient survivals in both eras. However, diabetic patient survival improved in era II (78.0% vs. 66.9%, p = 0.04). In era II, HLA-identical recipients had better graft survival than haploidentical or mismatched recipients (91.7% vs. 67.3% and 66.1%, p = 0.01). No difference between haploidentical LRDs and LURDs was seen. One donor death occurred in 1970, and 17% of donors developed postoperative complications. CONCLUSION: Living related and unrelated renal donation continues to be an important source of kidneys for patients with end-stage renal disease.
Adult↗
Proliferation-independent growth factor modulation of the radiation sensitivity of human prostate cells.
The survival of human prostatic epithelial cells irradiated in different physiological states is reported. Exponentially growing cells and contact-inhibited cells grown and irradiated in the presence of the growth factors epidermal growth factor (EGF) and bovine pituitary extract (bPE) had overlapping radiation dose-cell survival curves. However, when EGF and bPE were removed from exponentially growing cells before irradiation, an increase in radiosensitivity was observed if the cells were replated into medium containing growth factors (EGF and bPE) immediately after irradiation. Treating cells with the nonspecific growth factor receptor antagonist suramin had similar effects as did growth factor deprivation. In contrast, when growth factor-deprived cells were maintained in this same medium for 12 h postirradiation, an increase in radiation survival was observed. This increase in survival is attributed to the repair of potentially lethal damage (PLD). Both the increase in radiosensitivity induced by deprivation of growth factor before irradiation and the repair of PLD caused by deprivation of growth factor after irradiation were independent of changes in cellular proliferation.
Animals↗
Intravesical recombinant tumor necrosis factor in the treatment of superficial bladder cancer: an Eastern Cooperative Oncology Group study.
We tested and proved the safety of recombinant human tumor necrosis factor given intravesically weekly for 11 weeks (dwell time 2 hours) for the treatment of superficial bladder cancer in 8 men and 1 woman 46 to 87 years old (mean age 69 years). Cohorts of 3 patients received 200, 400 and 1,000 micrograms. recombinant human tumor necrosis factor. The maximal tolerated dose was not achieved. There were 9 episodes of urological symptoms, 8 of flu-like symptoms, 4 of headache and 3 of chest tightness. Hematological and gastrointestinal toxicities were minor, and no renal toxicity was encountered. Recombinant human tumor necrosis factor was safe to administer at doses up to 1,000 micrograms. We hope that recombinant human tumor necrosis factor in conjunction with other antitumor agents will lead to a new, effective treatment for superficial bladder cancer.
Administration, Intravesical↗
Recovery of epidermal growth factor in voided urine of patients with bladder cancer.
Epidermal growth factor (EGF), a potent mitogen and tumor promoter, is excreted in urine permitting it to incubate with urothelial cells. We have previously shown that the distribution of receptors for EGF (EGF-Rs) on malignant urothelium changes to favor contact between EGF-Rs and intraluminal EGF. OBJECTIVES. To determine if concentrations of EGF in voided urine are different in patients with transitional cell carcinoma (TCC) of the bladder than in those without this condition. METHODS. EGF was measured by radioimmunoassay in the urine of 54 patients with newly diagnosed TCC (16 with grade 1, Stage Ta lesions, and 38 with grade 3, Stage T > or = 2 lesions) and 66 pathologic and normal controls without TCC. Subjects were matched for age and good renal function. RESULTS. EGF concentrations were significantly reduced in patients with TCC compared with controls either when uncorrected (p < 0.0001) or corrected (p < 0.000000002) for urinary creatinine excretion. CONCLUSIONS. The reduced concentration of EGF in voided urine supports previous evidence that the urinary EGF/urothelial EGF-R interaction is important for TCC development and growth, and has the potential to serve as a marker of tumor persistence, recurrence, and therapeutic response.
Age Factors↗
Sequelae of definitive radiation therapy for prostate cancer localized to the pelvis.
OBJECTIVES: To evaluate sequelae and estimate quality of life utilizing a survey instrument in 133 consecutive patients who have undergone definitive radiation therapy for localized prostate cancer. METHODS: All patients reported on have been followed for 14 to 60 months (median, 31 months) after radiation therapy and only patients with definitive prostate radiation therapy are included. Of the patients still alive at time of follow-up, 115 were mailed the questionnaire. Data regarding tumor grade and stage as well as treatment were extracted from patient files. RESULTS: Of the 91% of patients who returned the questionnaire, 11% used a pad and 13% leaked more than a few drops of urine daily. Of all the respondents, 9% stated that incontinence was a problem, and 31% found urinary leaking significantly worsened after radiation therapy compared with before their diagnosis of prostate cancer. With respect to sexual function, 77% recalled being able to have full or partial erections prior to radiation therapy. At some time after radiation therapy, 22% of previously potent respondents were able to have a full erection and 41% were able to have a partial erection. Twenty-nine percent of all patients who were able to establish an erection prior to radiation therapy reported that impotence was a problem at the time of follow-up. Forty-nine percent of patients had abdominal pain, diarrhea, or abdominal cramping during or after radiation therapy and 31% of all patients still had some intestinal symptoms at the time of follow-up. Eighteen percent of all patients were significantly bothered by one or more of these bowel problems. Overall, 31% of all patients reported a persistent degree of physical discomfort that they believed was secondary to their prostate cancer or the effect of treatment. Eighty-one percent were satisfied with radiation therapy and 97% of the patients said they would have radiation therapy again if faced with the decision. CONCLUSIONS: Utilizing a sensitive questionnaire on patients who had definitive radiation therapy for prostate cancer, we found the incidence of patients bothered by incontinence to be surprisingly frequent and higher than previously reported. The frequency of impotence is similar to previous studies. However, when our incontinence and impotence data were compared to Medicare patients who had undergone radical prostatectomy, the frequencies after radiation therapy were significantly lower. Despite the rates of sequelae, the patients were generally satisfied with the decision to undergo radiation therapy and with the medical treatment received.
Aged↗
Expression of N-acetyltransferase (NAT) in cultured human uroepithelial cells.
To determine which of the N-acetyltransferase (NAT) alleles [monomorphic (NAT1) or polymorphic (NAT2)] are expressed in the target cells for arylamine carcinogenesis, namely normal human uroepithelial cells, cDNA was prepared from cellular RNA and amplified by polymerase chain reaction (PCR), using upstream primer 1 comprising the 5' end (nt 47-68) and either downstream primers 2 (nt 908-889) or 3 (nt 953-931) corresponding with the 3' end. With primers 1 and 2, selective for NAT1, a characteristic 861 bp DNA fragment was obtained, whereas with primers 1 and 3, selective for NAT2, a characteristic 907 bp fragment was formed. Similarly, the PCR-amplified cDNA products from the SV40-immortalized human uroepithelial cell line were also found to contain both NAT1 and NAT2. Restriction fragment length polymorphism (RFLP) analysis with HincII (digesting NAT2 to produce 659 bp and 248 bp fragments) and HindIII (digesting NAT1 to produce a 786 bp fragment) further confirmed the authenticity of the NAT alleles. Furthermore, the NAT genotypes of 38 individuals were determined by PCR amplification of lymphocyte DNA and subsequent RFLP analysis using TaqI, KpnI and BamHI. The genotypes were compared to their in vivo acetylator phenotypes which were determined by measuring 5-acetylamino-6-formylamino-3-methyluracil and 1-methylxanthine in urine following administration of caffeine. A good correlation between the genotype and phenotype was obtained in the study population and the frequency of NAT2 allele distribution was M1 > wild-type > M2 > M3. These results suggest that susceptibility to arylamine-induced bladder cancer might be influenced by both hepatic and bladder NAT and that the NAT genotype might be a useful biomarker for screening high risk individuals for bladder cancer resulting from exposure to arylamines.
Acetylation↗
Sequelae of radical prostatectomy.
OBJECTIVE: To evaluate the sequelae of radical prostatectomy, using a survey instrument. PATIENTS AND METHODS: Ninety-three consecutively treated patients who had undergone radical prostatectomy and who had been followed-up for between 12 and 48 months (mean 22.5) were sent a questionnaire by post. Of these, 86 (92%) completed and returned the questionnaire. The mean age of the patients at time of surgery was 64 years (range 49-75) and at time of follow-up was 66 years (range 50-77). RESULTS: Of the 86 patients who responded, 47% used a pad and 59% leaked urine daily. Thirty per cent dripped more than a few drops of urine daily and 34% found their incontinence bothersome. Eighty-four per cent of patients recalled that they had erectile potency before surgery. At follow-up, 9% were able to have a full erection and 38% were able to have a partial erection. Fifty-one per cent reported a substantial problem with reduced or absent erection. Twenty per cent had undergone treatment for bladder neck contracture and more than half of these had had more than one intervention. In all, 24% of the patients reported some persisting degree of physical unpleasantness which they believed to be secondary to their prostate cancer or the effects of treatment. Despite this, 74% were satisfied with their surgery and 88% said they would undergo surgery again. CONCLUSIONS: Using this survey instrument, we found adverse sequelae of radical prostatectomy to be surprisingly high. However, patients were generally satisfied with their decision to undergo surgery.
Aged↗
Role of lymphadenectomy in the treatment of renal cell carcinoma.
We evaluated the role of lymphadenectomy (LND) in the prevention of local recurrence following radical nephrectomy for renal cell carcinoma (RCC) by two retrospective studies. In one, the relative importance of various tumor characteristics to the subsequent development of local recurrence was investigated in 37 patients who underwent radical nephrectomy and later progressed. In 29 evaluable patients, only nodal metastasis was predictive of local recurrence, which developed in 6 of 7 node-positive patients. In our second study the records of 69 consecutive patients with RCC who underwent radical nephrectomy with or without simultaneous LND (N = 42 and 27, respectively) were reviewed. Local control after LND was excellent in node-positive disease; in no node-positive patient with unilateral RCC has a local recurrence developed (N = 5). LND did not extend hospitalization or add to the morbidity of radical nephrectomy.
Carcinoma, Renal Cell↗