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Biomedical subjects

E M Messing

Publications and source records attributed to E M Messing.

At least 19 recordsLinked to original sources
PubMed1992

Age as a predictor of an aggressive clinical course for superficial bladder cancer in men.

Tumor grade and stage are two of the strongest predictors for indolent versus aggressive clinical course in bladder cancer. To identify age-related trends in tumor aggressiveness the authors investigated the relationships of age with grade and stage. Pathologic specimens were obtained for 89% (527 of 590) of new bladder cancer cases among men older than 50 years of age reported to the state tumor registry in Wisconsin for 1988. Tumors were grouped as low grade (G1, G2) or high grade (G3), and as superficial (Ta) or invasive (greater than or equal to T1), according to the TNM system. This analysis included 485 transitional cell carcinomas (TCC) for which the authors determined stage-stratified and grade-stratified odds ratios for men 50 through 64 years of age and older than 65 years of age. Men older than 65 years of age with superficial TCC were more than three times as likely to have a high-grade malignancy than men 50 through 64 years of age (P = 0.01); the odds ratio was 3.44 (95% CI = 1.28, 9.26). A relationship was not apparent for invasive TCC. Age and stage were weakly associated for low-grade and high-grade TCC that may be due, in part, to the strong correlation of stage with grade as a prognostic indicator. These data suggest that men in older age groups are at increased risk for superficial bladder cancer of high grade, which portends an aggressive clinical course.

Age Factors↗
PubMed1992

Epidermal growth factor and its receptor: markers of--and targets for--chemoprevention of bladder cancer.

Epidermal growth factor (EGF) is excreted in urine in high concentrations in a biologically active form. Several lines of evidence indicate that EGF plays a role in transitional cell carcinoma (TCC) development and growth. These include: (1) EGF in the normal urine of rats promotes chemically initiated TCC; (2) EGF in normal human urine stimulates the clonal growth of human TCC cells in vitro; (3) EGF stimulates the in vitro growth of human TCC cells, but not normal human urothelial cells; (4) the density and distribution of the EGF receptor (EGF-R) on human urothelial tissues permits significant access of premalignant, dysplastic, and malignant cells to EGF; and (5) the concentration of EGF in the voided urine of patients with TCC is reduced, implying that EGF may be "extracted" from urine by the greater number of EGF-Rs in patients with urothelial malignancy. Abnormal expression of the urothelial EGF-R and/or altered excretion of EGF may well precede overt evidence of TCC and thus may serve as markers of risk or exposure. Similarly, reversion of EGF-R expression or the return of excreted EGF to normal levels may provide a marker of response for preventive and therapeutic strategies. Interference with the EGF/EGF-R interaction through dietary or pharmacological manipulations of the urine, or via targeting strategies employing intravesical administration of conjugated toxins or isotopes is already being employed in experimental and clinical studies. These approaches offer promising new tools in the detection, monitoring, prevention, and management of early stage bladder cancer.

Antineoplastic Agents↗
PubMed1992

A prospective clinical trial of difluoromethylornithine (DFMO) in patients with resected superficial bladder cancer.

Difluoromethylornithine (DFMO) is a promising chemopreventive agent which is excreted unchanged in the urine, is active in vivo against superficial bladder cancer in animal tumor model systems, and has cytotoxic activity in vitro against superficial bladder cancer cells. Thus, DFMO may be particularly efficacious in preventing the development of bladder tumors and/or for the therapy of established superficial bladder cancer. To examine this hypothesis, an intergroup clinical trial is currently accruing patients with cystoscopically resected superficial bladder cancer (who would otherwise simply be observed). While the primary goal of this protocol is to define a daily dose of DFMO having little or no toxicity for use in future randomized chemoprevention trials, the rate of recurrent bladder tumors will also be followed in the hope that DFMO will inhibit the development of recurrent bladder cancers.

Clinical Trials as Topic↗
PubMed1992

Home screening for hematuria: results of a multiclinic study.

The majority of urinary tract tumors cause bleeding in the urine. A program designed to detect hematuria before it is grossly apparent may contribute to earlier detection and more successful treatment of these malignancies. To test this hypothesis a hematuria home screening study was conducted. A total of 1,340 healthy men 50 years old or older used chemical reagent strips for 14 consecutive days to test the urine. Of the men 283 (21.1%) had at least 1 episode of hematuria. Of the 192 hematuria positive men who received a complete urological evaluation 16 (8.3%) had urological cancers and 47 (24.5%) had other hematuria-causing diseases that required immediate treatment. The quantity and frequency of hematuria were not related to disease severity. A hematuria home screening regimen is feasible and economical, and may promote the early detection of urinary tract cancers and other diseases in men more than 50 years old.

Aged↗
PubMed1992

Prostate-specific antigen as a predictor of radiotherapy response and patterns of failure in localized prostate cancer.

PURPOSE: A study of preradiation and postradiation, serial serum prostate-specific antigen (PSA) levels was performed in patients who had clinically localized prostate cancer. The prognostic value of the PSA in pretreatment evaluation and posttreatment follow-up was assessed. PATIENTS AND METHODS: Sixty-three patients who presented with clinically localized prostate cancer and who were treated with external-beam radiation therapy were followed-up for a median of 25 months. A serum PSA and physical examination were performed at 3-month intervals, and a bone scan was done yearly. An increase in PSA triggered an additional metastatic workup. Prostate rebiopsy was performed for new, palpable nodules or for a serial increase in PSA in the context of a negative metastatic workup. RESULTS: Forty-one patients remained recurrence-free and 22 recurred clinically, 15 distantly and seven locally. The PSA was the strongest, independent, pretreatment prognostic indicator (P = .019) among pretreatment PSA, stage, and grade, but lost significance when the serum prostatic acid phosphatase (PAP) status was included. The initial rate of the PSA decrease after radiation (median half-life, 2.6 months) failed to predict outcome. Recurrence-free patients reached postradiation PSA levels that were equivalent to those reported in disease-free male populations; failure of the PSA to reach such normal levels was a multivariate predictor of subsequent failure (P less than .037). All clinicopathologic documentations of failure were preceded by an increase in PSA levels during follow-up. Delayed versus early PSA increase was associated with clinically localized versus metastatic first recurrence. CONCLUSIONS: The serum PSA is an independent pretreatment and posttreatment predictor of outcome. Additionally, for a median follow-up of 25 months, delayed PSA failure is associated with clinically localized rather than metastatic recurrence, a relationship that may help in selection for local salvage therapy.

Aged↗
PubMed1991

Treatment of severe electrical burns of the genitalia and perineum by early excision and grafting.

A patient with severe electrical burns to his perineum and genitalia is presented. Evaluation of such patients necessarily includes local wound exploration, cystourethroscopy and proctoscopy. The principles of early serial debridement and wound closure were applied to all tissues including testis and penis. Removal of non-viable tissue and wound closure was accomplished by postburn day 10 without sacrifice of viable tissue and without wound sepsis. The benefits of early debridement and wound closure are reduction of infection, earlier onset of physiotherapy, quicker recovery of function, and shortened hospital stay.

Accidents, Occupational↗
PubMed1991

Comparison of 15 monoclonal antibodies against tumor-associated antigens of transitional cell carcinoma of the human bladder.

Quantitative urinary immunocytology with our monoclonal antibody (mab) 486p 3/12 proved to be valuable for diagnostic use in bladder-cancer patients' urine, especially in the followup of patients with superficial bladder carcinoma. To evaluate the use of other monoclonal antibodies in bladder cancer, we compared 15 mabs directed against bladder-tumor-associated antigens from seven research groups in a broad panel of cellular and tissue specimens (bladder tumor, prostatic adenoma, and kidney stone). Quantitative evaluation was done in cytocentrifuged preparations and tissue specimens. None of the 15 mabs was bladder-tumor-specific. All 15 stained normal urothelium to some extent and six stained granulocytes. Each of the 15 seemed to identify a different cellular antigen, as can be clearly demonstrated by the staining pattern of different regions in the normal kidney. The sensitivity of quantitative urinary immunocytology in bladder-tumor patients can be improved by using a panel, rather than one mab in bladder-tumor patients, but specificity decreases simultaneously. A main reason for the poor specificity of quantitative urinary immunocytology with all 15 mabs is that false-positive results are obtained with all mabs in kidney-stone patients. Our quantitative urinary immunocytology method is a general tool for the diagnostic use of all mabs in bladder-tumor patients. Mabs that have a high sensitivity might be useful in the followup of patients with superficial bladder carcinoma. None of the 15 mabs (because of their poor specificity) seems to be helpful in quantitative urinary immunocytology for screening a population for bladder carcinoma.

Antibodies, Monoclonal↗
PubMed1990

Clinical implications of the expression of epidermal growth factor receptors in human transitional cell carcinoma.

To evaluate the distribution and density of epidermal growth factor (EGF) receptors (EGF-Rs) on urothelium, immunohistological studies using a monoclonal antibody to the binding portion of the human EGF-R were performed on frozen specimens of normal urothelium (N = 20), urothelium from patients with nonurothelial urological malignancies (N = 15) and inflammatory diseases (N = 8), low grade superficial transitional cell carcinomas (TCC) (N = 13), high grade superficial or invasive TCC (N = 28), and endoscopically normal appearing urothelium from patients with low grade superficial (N = 5) or high grade (N = 21) TCC elsewhere in the bladder (or ipsilateral renal pelvis/ureter). EGF-Rs are found only on the basal layer of epithelial cells (with scattered representation on intermediate cells) in 95% of normal urothelial specimens and 100% of pathological specimens without urothelial malignancy. Alternatively, 92.3% of specimens of low grade superficial TCC and 100% of high grade TCCs had EGF-Rs richly expressed on the superficial as well as the deeper layers of urothelium. This "malignant" distribution of EGF-Rs was also found on all specimens of endoscopically normal appearing urothelium in patients with TCC elsewhere. The density of EGF-Rs correlated closely with tumor grade on both "premalignant" and frankly neoplastic urothelium. We conclude that the expression of EGF-Rs on urothelium favors the interaction of premalignant and malignant tissue with urinary EGF. To determine if altering the physiochemical environment of urine could interfere with this interaction, the effects of pH on the binding of and growth responses to EGF were assessed on four human TCC cell lines. Scatchard plots demonstrated that varying pH from 5.0 to 7.5 did not significantly change the total number of receptors, but EGF-R affinity was reduced approximately 20-fold as pH decreased from 7.5 to 5 in each TCC target. Similarly, significant growth stimulation by EGF at pH 7.5 was abrogated at pH less than or equal to 7.0 while growth rates in the absence of EGF remained unchanged at lower pHs. It thus appears that urinary acidification may hold promise in the management and prevention of recurrent bladder cancer.

Adenocarcinoma↗
PubMed1990

Psychological and mood disturbance associated with the diagnosis and treatment of testis cancer and other malignancies.

Eighty-seven men with testis cancer (TC) and 35 men with other cancers (OC) completed measures of mood (Profile of Mood States) and of personality and psychopathology (Millon Clinical Multiaxial Inventory). Effects of primary disease, phase of diagnosis and treatment, locoregional vs. cytotoxic treatment, age, and marital status on these measures were examined. TC patients appeared more distressed during treatment, particularly during cytotoxic as compared to locoregional treatment, than before or after treatment, and more distressed than OC patients. Being married appeared to buffer the stress of cancer and its treatment. Although treatment, particularly cytotoxic therapy, appeared to result in transient distress, results did not offer strong evidence that cancer and its treatment typically precipitate severe psychopathology.

Adaptation, Psychological↗
PubMed1990

Perioperative methotrexate, vinblastine, doxorubicin and cisplatin (M-VAC) for poor risk transitional cell carcinoma of the bladder: an Eastern Cooperative Oncology Group pilot study.

A total of 18 patients with locally advanced transitional cell carcinoma of the bladder underwent 2 preoperative cycles of chemotherapy with methotrexate, vinblastine, doxorubicin and cisplatin followed by radical cystectomy and 2 postoperative cycles of chemotherapy. Radical cystectomy was performed in 17 of 18 patients (94%) with a pathological partial response in 3 (17%) and a pathological complete response in 2 (11%), for an over-all response rate of 28% (95% confidence limits 10 to 53%). At 23-month median followup 9 patients (50%) remained without evidence of recurrent disease, while 9 (50%) died of metastatic bladder cancer. Average relative dose intensity of all therapy given was 78%. Hematological toxicity was moderate, with no septic deaths or bleeding complications. However, 4 thromboembolic events occurred. While downstaging of the primary bladder tumor can occur with this perioperative schedule our results were not as impressive as some previously reported findings. The incidence of thromboembolic events is worrisome.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Hematuria screening for bladder cancer.

Detection of bladder cancer before deep invasion occurs offers patients a favorable prognosis. Because most bladder cancers, even when noninvasive, produce hematuria, screening asymptomatic persons at risk for bladder cancer for hematuria provides a means of promoting early detection and has the potential to reduce morbidity and mortality. However, bladder cancer-induced hematuria is quite intermittent; thus, repetitive testing is necessary. In a pilot study, 11.4% of asymptomatic men over age 50 who had at least one positive dipstick result were found on urologic work-up to have bladder cancers that were caught early enough to receive purportedly curative treatment. Issues concerning the applicability of this methodology to other high-risk populations are discussed and efforts now underway to confirm and expand upon this screening program are described.

Aged↗
PubMed1989

Urinary tract cancers found by homescreening with hematuria dipsticks in healthy men over 50 years of age.

In a homescreening study 235 asymptomatic men, 50 years of age and older without known causes of hematuria, tested their urine each week with a chemical reagent strip for the presence of blood for 1 year. Forty-four men had hematuria at least once, and 31 had a full urologic evaluation. Of these, eight were found to have urinary cancers and seven had nonmalignant diseases warranting immediate treatment. In six of these 15 men (only two with cancer) hematuria occurred in over 1/3 of the testings, and in four hematuria was found on microscopic urinalysis at the time of urologic evaluation. The degree of hematuria was unrelated to the seriousness of its cause. We conclude that in this population hematuria occurs intermittently and when found, regardless of quantity or symptoms, serious underlying pathology must be ruled out. Furthermore, regular hematuria home testing offers a promising means of detecting urinary cancers and other diseases that warrant therapy in asymptomatic men 50 years of age and older.

Aged↗
PubMed1989

Prostate specific antigen: not detectable despite tumor progression after radical prostatectomy.

Prostate specific antigen was not detectable in 2 men with documented prostate cancer progression after radical prostatectomy. Possible explanations for prostate specific antigen remaining zero in these situations are discussed. We conclude that while monitoring prostate specific antigen is of great value in the followup of patients with prostatic cancer, it has not replaced more standard means of followup.

Acid Phosphatase↗
PubMed1989

High-dose ketoconazole in advanced hormone-refractory prostate cancer: endocrinologic and clinical effects.

High-dose ketoconazole (400 mg orally three times a day) and physiologic replacement doses of glucocorticoids (hydrocortisone, 20 mg 8 AM, 10 mg 4 PM, and 8 PM) were administered to 38 patients with advanced prostatic cancer, refractory to at least initial testicular androgen deprivation. Thirty patients were completely evaluable; six were withdrawn due to possible ketoconazole-related toxicity and were considered drug failures. Two patients were unevaluable due to intercurrent therapy or inability to maintain follow-up. Ketoconazole was generally well tolerated. Mild or moderate nausea and vomiting occurred in 37% of patients, but required dose modification or discontinuation in only three patients; no hepatic damage was seen. Five of 36 patients (14%) responded to ketoconazole as determined by palpable or radiographic tumor mass reduction of 50% or greater and normalization of acid phosphatase or bone scan. Fifty percent of patients entered were stable at 90 days. Plasma androstenedione and dehydroepiandrosterone sulfate (DHEAS) were reduced markedly in almost all patients. Plasma testosterone (T) levels were low and remained unchanged, while gonadotropins were persistently elevated. Mean plasma ketoconazole content was 6.6 micrograms/mL after 28 days of therapy. While ketoconazole with hydrocortisone does suppress plasma androgens in advanced prostatic cancer patients, this infrequently causes regression of cancer that has progressed despite adequate testicular androgen ablation.

Acid Phosphatase↗
PubMed1988

Normal and malignant human urothelium: in vitro response to blockade of polyamine synthesis and interconversion.

To assess the effect of polyamine blockade on urinary epithelium, growth of normal human urothelial cell cultures and human transitional cell carcinoma (TCC) cell lines in the presence of various inhibitors of polyamine synthesis was evaluated. All four human TCC cell lines tested were quite sensitive to the specific inhibitor of ornithine decarboxylase, alpha-difluoromethylornithine (DFMO), requiring less than or equal to 1.0 mM DFMO to double generation time. Alternatively, all three human urothelial cultures tested required 5-20-fold higher DFMO concentrations to achieve similar growth inhibition. The inhibitory effect of DFMO on TCC was found to act synergistically with that of the inhibitor of S-adenosylmethionine decarboxylase, methylglyoxal bis(guanylhydrazone), and additively with that of recombinant beta-serine interferon. Addition of individual polyamines entirely prevented the inhibitory effects of DFMO and/or methylglyoxal bis(guanylhydrazone) but not that of beta-serine interferon. It appears that inhibition of polyamine synthesis and/or interconversion holds promise in the management of TCC and that the in vitro model described will be of value in investigating such clinical applications.

Carcinoma, Transitional Cell↗
PubMed1987

Normal and malignant human urothelium: in vitro effects of epidermal growth factor.

Cultures of human normal urothelial (HU) cells and transitional cell carcinoma (TCC) cell lines were tested for their ability to specifically bind and respond to epidermal growth factor (EGF). The criteria of response investigated were stimulation of growth and induction of ornithine decarboxylase (ODC) activity. All four human TCC cell lines tested were stimulated to grow by EGF (1-100 ng/ml) in a dose related fashion while only one of four HU cell cultures was similarly stimulated, and growth stimulation of this cell line occurred only at early passage. TCC and HU cells bound EGF to similar degrees with Kds of 0.86 nM for TCC and 2.54 nM for HU (P greater than 0.05) and 91637 +/- 9816 (SD) (high affinity) receptors/cell for TCC and 124275 +/- 16841 for HU (P greater than 0.10). Baseline ODC activity was statistically similar in the two TCC and the three HU cell cultures tested. However, EGF induced dose related ODC activity only in the TCC cell lines and not in any of the HU cell cultures. Thus, while both malignant and normal urothelium bind EGF equally well in vitro, only TCC responds to EGF in two parameters relevant to neoplasia: growth and induction of ODC activity.

Carcinoma, Transitional Cell↗
PubMed1987

Method for assuring accuracy of bone biopsy using technetium 99 bone scan.

In the clinical staging of malignancy, radionuclide bone scanning has played an increasingly important role. An area of increased radionuclide uptake on technetium 99 (99Tc) bone scan which is not visualized on skeletal radiographs can present a significant diagnostic dilemma. This can be further compounded by nonrevealing percutaneous or open surgical biopsies. The authors present a method of definitively localizing the appropriate site for bone biopsy in such circumstances. Use of this technique has allowed us to ascertain that isolated rib lesions in two patients with extra-osseous malignancies were not due to metastatic disease.

Aged↗