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W A See

Publications and source records attributed to W A See.

At least 55 records · Page 3Linked to original sources

Diversity and modulation of plasminogen activator activity in human transitional carcinoma cell lines.

Baseline cellular plasminogen activator (PA) activity, the cellular proteins responsible for variations in PA activity and the effect of cellular PA activity on cellular adherence to and lysis of fibrin substrate were evaluated in three human transitional carcinoma cell lines. Net PA activity in the cell lines 253J, 639V and 647V was measured using a chromogenic substrate assay. These lines were then analyzed to determine the specific protein(s) responsible for differences in PA activity. mRNA and protein levels of cellular uPA, tPA, PAI1 and PAI2 were measured using Northern blot analysis and ELISA assays. Intact cells were used in an in vitro fibrinolysis assay so as to correlate cell biology with protein and mRNA level observations. Net cellular PA activity in the three cell lines varied over a 20-fold range (253J > 639V > 647V). Net PA activity demonstrated a direct correlation with mRNA transcript and protein levels of uPA/low levels of tPA mRNA were detected in the 253J line. However, tPA protein was not detectable in any of the lines. Both PAI1 and PAI2 were detected in varying amounts in each of the three cell lines. In vitro assays demonstrated a direct correlation between net PA activity and plasminogen dependent fibrin substrate lysis. Cellular adherence to fibrin varied as an inverse function of net PA activity. These findings suggest that variations in cellular uPA levels are principally responsible for variations in PA activity between cell lines. Variations in net PA activity are in turn reflected at the cellular level by differences in ECMP substrate lysis and cellular adherence to fibrin.

Carcinoma, Transitional Cell↗

Predictors of laparoscopic complications after formal training in laparoscopic surgery.

OBJECTIVE: To evaluate the relationship between laparoscopic complication rates and surgeon-dependent variables following a laparoscopic training course. DESIGN: Participants were surveyed regarding their interval laparoscopic experience 3 months and 12 months after the course. PARTICIPANTS: Course participants/survey respondents represented a cross section of urologic surgeons in the United States. A total of 181 individuals (61% of 297 participants) completed and returned the 3-month questionnaire. A total of 128 surgeons responded to the 12-month questionnaire (78.5% of 163 participants). MAIN OUTCOME MEASURE: Logistic regression analysis tested the relationship between surgeons' complication rates and study variables. RESULTS: At 3 months, surgeons who performed clinical procedures without additional training were 3.39 times more likely to have at least one complication compared with surgeons who sought additional training (P = .03). At 12 months, surgeons who had attended the training course alone, were in solo practice, or performed laparoscopic surgery with a variable assistant were 4.85, 7.74, and 4.80 times more likely, respectively, to have had a complication than their counterparts who attended the course with a partner, were in group practice, or operated with the same assistant (P = .004, P = .0008, and P = .0015, respectively). At both 3 and 12 months, laparoscopic complication rates of individual surgeons demonstrated a significant inverse correlation with the number of laparoscopic procedures performed. CONCLUSIONS: The rate of complications associated with the clinical learning curve can be decreased by additional education following an initial course in laparoscopy. An ongoing clinical association with surgeons performing similar procedures decreases long-term complication rates.

Clinical Competence↗

Alpha-fetoprotein half-life as a predictor of residual testicular tumor. Effect of the analytic strategy on test sensitivity and specificity.

BACKGROUND: Alpha-fetoprotein (AFP) serum values after orchiectomy for testicular cancer can be used to predict the residual disease status. However, the optimal strategy for postorchiectomy marker analysis has not been studied. This article evaluated different analytic methods in an effort to identify the approach that provided the greatest sensitivity and specificity for occult residual disease. METHODS: Statistical information on the AFP half-life (t1/2) derived from a clinical data set of 24 patients with AFP-secreting clinical Stage A testicular cancer and pathologically defined nodal status was incorporated into a mathematic model of postorchiectomy marker values as a function of residual tumor volume and time. The model was used to test the effect of various analytic strategies on detecting the residual tumor. The clinical data set then was analyzed to measure the effect of different analytic methods on the predictive value of the AFP t1/2. RESULTS: In the model, the AFP t1/2 calculated from a single set of serum measurements obtained from the initial serum t1/2 was a poor predictor of disease status in patients with up to 40% residual tumor volume. Determined by the sequential addition of serum values obtained at normal t1/2 intervals, the AFP t1/2 improved in sensitivity but required up to seven serial values (35 days) to detect an abnormal t1/2 in patients with 10% residual tumor. By contrast, changes in the most recent interval t1/2 relative to the initial calculated t1/2 predicted the disease status in patients with 10% residual tumor after four t1/2 (20 days) and in patients with 1% residual volume after 35 days. CONCLUSIONS: The use of this last strategy in the clinical data set improved both the sensitivity and specificity of the AFP t1/2 in predicting residual tumor relative to the other methods.

Half-Life↗

Chest staging in testis cancer patients: imaging modality selection based upon risk assessment as determined by abdominal computerized tomography scan results.

We compared chest computerized tomography (CT) to chest x-ray as chest staging modalities in testis cancer patients on the basis of abdominal CT findings. We identified 92 patients who presented with negative staging abdominal CT scans and 52 with abnormal abdominal CT scans. Of these patients 42 and 32, respectively, underwent a chest x-ray and chest CT concurrently as part of the initial staging evaluation. Dictated x-ray reports were used to compare study findings. Findings on chest x-ray and chest CT were considered concordant if both studies identified similar chest abnormalities. Findings were considered discordant if either study failed to identify an abnormality noted on the other test. Patient outcome during followup, response to therapy or chest pathology was used to discriminate benign from malignant radiological abnormalities. Radiographic chest abnormalities (chest x-ray and/or chest CT) were identified in 12 of the 42 patients with negative abdominal CT scans. Three of these 12 studies represented metastasis with the remainder being benign. Imaging results were concordant in all 3 patients with chest metastasis and 5 of 9 with benign chest disease. Chest x-ray identified abnormalities not observed on chest CT in 1 patient, with chest CT identifying abnormalities not observed on chest x-ray in 3. Radiographic chest abnormalities (chest x-ray and/or chest CT) were identified in 15 of 32 patients who had a positive abdominal CT. All chest lesions identified in these patients were believed to represent metastatic disease. Chest x-ray failed to identify abnormalities present on chest CT in 4 of the 15 patients. The use of chest CT as a staging modality in abdominal CT negative patients failed to increase diagnostic sensitivity relative to chest x-ray alone. However, in 32 patients with abnormal abdominal CT scans the use of chest x-ray alone would have missed intrathoracic metastatic disease in 4. These data suggest that chest x-ray may be the preferred initial chest staging study for testis cancer patients with negative abdominal CT, while chest CT is mandated in patients with abnormal abdominal CT.

Abdomen↗

Plasminogen activators: regulators of tumor cell adherence to sites of lower urinary tract surgical trauma.

Tumor cell adherence (TCA) to sites of surgical injury is a requisite step in implantation-mediated tumor recurrence. This study examined the relationship between tumor-associated plasminogen activator (PA) and the ability of tumor cells to remain adherent to surgical injury sites. High (1E8) and low (3A9) PA producing clones from the murine transitional carcinoma cell line 4909 were selected using an in vitro 125I fibrinolysis assay. Net cellular PA activity of each clone was determined from cell lysates using a chromogenic substrate assay. In vitro TCA and fibrin substrate lysis as a function of time were simultaneously measured using a tetrazolium dye assay in combination with an 125I fibrinolysis assay. In vivo TCA to in situ cautery-injured rat bladders was measured 30 minutes (n = 12 animals/cell line) and 24 hours (n = 18 animals/cell line) following tumor exposure with a radiolabeled TCA assay. In vitro and in vivo competitive binding assays evaluated the relative adherence of mixtures of the 1E8 and 3A9 clones. Cellular PA activity was 0.022, 0.014 and 0.007 units per mg. protein for the 1E8, 4909 and 3A9 cell lines. In vitro TCA to fibrin in the presence of plasminogen was significantly different for each cell line and demonstrated an inverse relationship with both plasminogen-dependent fibrin lysis and cellular PA activity (p < 0.0001). The in vivo assay showed that the percentage of 1E8 cells remaining adherent 24 hours after tumor exposure was significantly less than that of the 3A9 cells (p = 0.01). Both in vitro and in vivo competitive binding assays demonstrated preferential adherence of the 3A9 cell line. Cellular PA production appears to be a tumor-intrinsic variable that modulates TCA to surgical injury sites.

Animals↗

Inverted V peritoneotomy significantly improves nodal yield in laparoscopic pelvic lymphadenectomy.

We compared the nodal yield and volume of target tissue removed in 3 groups of patients undergoing laparoscopic pelvic lymphadenectomy as a staging procedure for carcinoma of the prostate. With the exception of the type of peritoneotomy used to expose the obturator fossa, surgical management of all patients was identical. Results were evaluated in patients undergoing linear peritoneotomy (40), inverted V peritoneotomy (14) or both procedures (28, 1 approach on each side). Significantly more tissue was removed from patients in the inverted V group (16.3 +/- 8.3 cm.3) compared to the linear peritoneotomy group (7.2 +/- 5.7 cm.3, p = 0.004). This resulted in a significant increase in nodal yield in patients in the inverted V group (11.0 +/- 4.1) relative to the linear peritoneotomy group (6.8 +/- 5.2, p = 0.003). In terms of the volume of tissue removed and the number of nodes obtained, combination patients had values intermediate to those in the other groups (11.6 +/- 10.5 cm.3 and 8.8 +/- 5.6 nodes, respectively). The right-to-left ratio of nodes and tissue volume was reversed in the combination group relative to the other 2 groups. Operative time was significantly decreased for the inverted V technique compared to the linear peritoneotomy approach (p = 0.01). No difference in operative blood loss of complications was identified. The improved exposure obtained with this technique appears to result in a more complete lymphadenectomy without increased risk of complications.

Humans↗

Laparoscopic surgical training: effectiveness and impact on urological surgical practice patterns.

Urological interest in laparoscopic surgical techniques has dramatically increased during the last several years. However, the extent to which these methods are being used and the impact of training courses on clinical use are unclear. We assessed urologist practice patterns subsequent to a formal training course in urological laparoscopic surgery. On 5 dates between January and October 1991, a total of 163 urologists participated in a 2-day, university sponsored, laparoscopic surgery training seminar. Instruction consisted of 8 hours of didactic lectures including 2 live video cases, 4.5 hours of simulation and 4.5 hours in a live animal laboratory. Three months after the course the participants were mailed a questionnaire inquiring as to the interval laparoscopic surgery experience. Practice demographics, additional training, equipment availability, number of laparoscopic surgery candidates identified, percentage of overall surgical case load, patient inquiries, cases performed and complications were assessed by the questionnaire. Descriptive and correlative information was then derived from the data set. A total of 105 course participants (64%) responded to the questionnaire and 64 had engaged in some form of additional training following the course. During the 3 months since course completion respondents had identified an average of 4 candidates for laparoscopic surgery, which represented a mean of 2.5% of the total case load. Specific patient inquiries averaged less than 1 per physician within 3 months. During this same interval respondents had performed a total of 156 laparoscopic procedures (1.7 per urologist). Of the participants 45% had not performed their first case and 32% had performed more than 1 laparoscopic procedure. A total of 11 complications was reported (7.2%) and in 7 instances the surgeon was required to convert to an open approach. Veress needle placement was perceived as the most difficult aspect of the technique (22% of the respondents). Training subsequent to the course was the best predictor of clinical use. Of those who responded 88% believed that their future use of laparoscopy would increase. This survey suggests that subsequent to training, laparoscopic techniques are being rapidly and safely used by urologists. However, in the current state of development the impact of laparoscopic surgery on global urological practice patterns appears to be small.

Education, Medical, Continuing↗

Granulomatous inflammation in bladder wash specimens after intravesical bacillus Calmette-Guerin therapy for transitional cell carcinoma of the bladder.

The authors retrospectively reviewed a series of bladder wash cytologic specimens and concurrently available bladder biopsy samples to evaluate granulomatous inflammation in patients receiving intravesical bacillus Calmette-Guerin (BCG) immunotherapy for transitional cell carcinoma of the bladder. Comparisons were made during the 2-month period following six weekly BCG instillations in 25 patients and during the 1-year period following the last dose of BCG in 23 patients. At some point during the 2-month follow-up period, cytologic specimens contained free histiocytes in 64%, histiocyte aggregates (resembling fragments of granulomas) in 76%, and multinucleated histiocytic giant cells in 56% of patients. Similarly, concurrent biopsy samples contained granulomas in 78% and multinucleated giant cells in 56% of patients. During the 1-year period following the last dose of BCG, inflammatory changes peaked within the first 3 months and gradually resolved at 9-12 months. In none of these instances were the cytologic features of granulomatous inflammation misinterpreted as malignant. It was concluded that the cytologic findings after intravesical BCG are more specific than previously realized and closely parallel the histologic changes seen in corresponding bladder biopsy specimens.

Adult↗

Regional chemotherapy for bladder neoplasms using continuous intravesical infusion of doxorubicin: impact of concomitant administration of dimethyl sulfoxide on drug absorption and antitumor activity.

BACKGROUND: One objective of regional chemotherapy is to achieve the therapeutic drug levels in local tissues and primary nodal drainage fields, while minimizing systemic drug toxicity. The composition of the drug-delivery vehicle may influence local drug absorption and thereby modulate both tissue drug levels and systemic toxicity. PURPOSE: We evaluated the effect of dimethyl sulfoxide (DMSO) as a drug-delivery vehicle on regional and systemic levels of doxorubicin (DOX) and on the cytotoxicity of DOX following continuous intravesical administration in an invasive rat transitional cell bladder carcinoma model. METHODS: F344 rats received continuous intravesical DOX infusion for a 7-day period using a regional drug administration system. A constant dose of DOX was administered in one of three DMSO concentrations (0%, 10%, or 50%) to groups of animals (N = 20 per group). These concentrations corresponded to target urinary concentrations of 0%, 0.1%, and 0.5%, respectively. DOX levels in urine, serum, muscle, liver, bladder wall, and retroperitoneal lymph nodes were measured using a fluorescence assay on experimental days 0, 2, 4, 6, and 8 (N = four animals/group per day). In vitro assays evaluated the effect of DMSO concentration on the cytotoxicity of DOX against six transitional cell carcinoma cell lines. A final experiment on rats with established bladder tumors compared the cytoreductive effect of continuous intravesical infusion of DOX in 50% DMSO with that of DOX alone and with that in a sham-treated control group; there were 20 rats in each group. RESULTS: Mean and peak tissue and serum levels of DOX increased as a direct function of DMSO concentration. Compared with the results in controls, mean concentrations of DOX in the bladder were increased 7.1-fold and 12.1-fold in the groups given 10% and 50% DMSO, respectively. Average drug concentrations in the lymph nodes were increased 9.6-fold and 9.3-fold in the groups given 10% and 50% DMSO, respectively. In vitro, DMSO synergistically enhanced the cytotoxicity of DOX in two of the six cell lines studied. Solubilizing the test agent in 5% DMSO reduced the IC50 (drug concentration required to reduce cell viability to 50% of control values) to an average of 56% +/- 41% (+/- SD) of control values; 10% DMSO further decreased the average IC50 to 20% +/- 18% (+/- SD) of control values. The mean bladder tumor weight of animals treated with the combination of DOX and DMSO was 0.52 g. This compared with a mean tumor-bearing bladder weight of 2.69 g in the control group (P = .012) and 0.80 g in the group treated with DOX alone (P = .0544). CONCLUSIONS: These results suggest that the use of DMSO as a solvent vehicle for DOX improves drug absorption while simultaneously potentiating DOX cytotoxicity. The use of DMSO as a drug carrier merits further evaluation as a way of enhancing the efficacy of regional chemotherapy regimens.

Administration, Intravesical↗

Intravesical recombinant tissue plasminogen activator for the prevention of implantation-mediated bladder tumor recurrence.

The mechanism by which intravesical recombinant tissue plasminogen activator (rTPA) prevents tumor cell adherence to injured bladder surfaces, and the optimal parameters for the in vivo use of rTPA for adherence prevention, were evaluated. Intravesical rTPA decreased tumor cell adherence to sites of urothelial injury as a direct function of drug concentration in the intravesical fluid. Recombinant TPA concentrations of 1 mg/ml and 0.1 mg/ml significantly decreased tumor cell adherence relative to the control group. The efficacy of rTPA in removing adherent cells was time-dependent with maximal activity occurring at 15 min or later following intravesical administration. Intravesical rTPA effectively reduced the size of the tumor inoculum when administered either concomitant with, or subsequent to, tumor cell exposure. The relative efficacy of these two approaches was dependent upon the presence of serum in the intravesical fluid. Administration of rTPA concomitant with tumor cell exposure proved more effective in the absence of serum, while postadherence administration was more effective in the presence of 10% fetal calf serum. The addition of exogenous plasminogen to the rTPA solution did not increase anti-adherence activity relative to rTPA alone. However, blockade of endogenous plasminogen conversion with systemically administered epsilon-amino-caproic acid reversed the anti-adherence activity of exogenous rTPA. In vitro experiments evaluating cellular adherence to fibrin substrate confirmed that rTPA's anti-adherence activity was dependent on the presence of plasminogen. Exogenous rTPA administered immediately following tumor cell adherence decreased tumor cell implantation in animals receiving low to moderate tumor inoculums. These data suggest that rTPA prevents cellular adherence as a result of plasminogen activation and subsequent fibrinolysis. Intravesical rTPA administered in sufficient concentration for relatively short periods of time effectively reduces the adherent tumor inoculum and alters implantation as an inverse function of the tumor inoculum. This approach represents a novel strategy which may prove applicable for the prevention of implantation-mediated tumor recurrence at sites of surgical trauma.

Administration, Intravesical↗

Urinary trypsin levels observed in pancreas transplant patients with duodenocystostomies promote in vitro fibrinolysis and in vivo bacterial adherence to urothelial surfaces.

This study evaluated the role of activated urinary trypsin in mediating the increased incidence of infectious and hemorrhagic lower urinary tract complications in pancreas transplant patients with pancreatico-duodenocystostomies (PDC). The effect of trypsin concentrations corresponding to those observed in the urine of PDC patients were studied using an in vitro assay of clot lysis and an in vivo assay of bacterial-urinary tract adherence. Results were compared with those of parallel assays performed using urine from a pancreas transplant patient with a duodenocystostomy and control human urine. All trypsin concentrations studied demonstrated fibrinolytic activity. Fibrinolysis increased as a direct function of both trypsin concentration and duration of substrate exposure (P < 0.0001). Fibrin lysis resulting from the urine of the transplant patient was 4.6 times greater than that predicted based upon assays of total trypsin content in the sample. Fibrinolytic activity in control urine specimens was 0.16% of that observed in transplant urine specimens. Exposure of the rat urinary bladder to 200 micrograms/ml trypsin concentrations, or transplant urine, resulted in a significant increase in bacterial adherence over that seen in control urine from treated animals (P < 0.05). These findings demonstrate a significant effect of urinary trypsin on physiologic processes involved in hemostasis and the prevention of urinary tract infection. Active urinary trypsin may play an etiologic role in hemorrhagic and infectious lower urinary tract complications observed in patients with a PDC.

Animals↗

In vitro particulate adherence to fibronectin: correlation with in vivo particulate adherence to sites of bladder injury.

This study examined the role of fibronectin in promoting particulate attachment to sites of urothelial injury. Variables influencing adherence of the rat transitional carcinoma cell line 4909 and "non-cellular" styrene-divinylbenzene microspheres to fibronectin were studied in an in vitro system. A soluble synthetic peptide fragment (Gly-Arg-Gly-Asp-Ser [GRGDS]) duplicating the receptor binding domain of fibronectin (RGD) was used to determine whether cell adherence could be inhibited by fibronectin receptor blockade. In vitro findings were correlated with an in vivo assay of both cellular and non-cellular particulate adherence to injured urothelium. Time, plated cell density, substrate concentration, GRGDS concentration, and cell viability, were all found to be significant independent variables influencing in vitro cellular adherence (p less than 0.0001). Receptor blockade with GRGDS significantly decreased in vitro tumor cell adherence to fibronectin. In vitro microsphere binding increased as a direct function of fibronectin concentration but was not time dependent (p less than 0.0001 and p = 0.14 for fibronectin concentration and time respectively). The in vivo adherence of both tumor cells and microspheres was significantly increased in injured bladders compared to controls (p less than 0.01). Receptor blockade with GRGDS failed to inhibit in vivo cell adherence to sites of urothelial injury. Microspheres proved to be competitive inhibitors of cellular adherence in competitive binding assays. In vitro microsphere binding demonstrated a pH dependence with maximal binding at pH 7.2. These data suggest that in vitro tumor cell adherence to fibronectin differs from in vivo tumor cell adherence to sites of urothelial injury. Manipulations which inhibit in vitro adherence, specifically fibronectin receptor blockade and cell death, fail to effect in vivo binding to the extreme that non-cellular particulate appears to bind to the same site, and with similar affinity, as cellular particles.

Animals↗

The impact of iatrogenic urothelial trauma on urinary levels of transforming growth factor-alpha.

Growth factors are important regulators of epithelial cell biology. We postulated that iatrogenic bladder manipulations may alter urinary growth factor levels and thereby influence both normal and neoplastic urothelium. Using a rat model we studied the effects of various types of urothelial injury, corresponding to bladder catheterization, cystoscopy, fulguration, and chronic indwelling catheterization (Groups B, C, D, and E respectively) on levels of urinary transforming growth factor-alpha (uTGFa). Urine samples collected circa the time of transurethral bladder manipulation were analyzed for protein, creatinine (Cr), and TGFa. Results in experimental groups were compared to control values (group A). Peak concentrations of uTGFa uniformly occurred on the day of surgery and represented 176%, 196%, 726%, 461% and 916% increases relative to pre-operative values in groups A, B, C, D and E respectively. Total uTGFa (nM/mg. Cr) was maximal on experimental day 0 in groups A, B, C, D and day 2 in group E (102%, 114%, 227%, 290% and 976% change from baseline respectively). Compared to control, levels of uTFGFa were significantly elevated on day 0 in the fulguration group, and day 0 and 2 in the chronic catheterization animals (p less than .05). Nonsignificant elevations of uTGFa relative to control were based in all groups through day 7. The chronic catheterization levels remained significantly elevated, compared to control, over the duration of the study (ANOVA, p less than .05). Urinary protein levels correlated with the severity of the injury and showed a strong positive correlation with uTGFa (p = .0001). This study demonstrated a clear impact of iatrogenic urothelial trauma on urinary levels of TGFa.

Animals↗

Staging of advanced bladder cancer. Current concepts and pitfalls.

Data presented in the preceding paragraphs should highlight to the reader several important features of clinical bladder cancer staging. Irrespective of the staging level being addressed, the available techniques uniformly have limitations, as well as advantages and disadvantages with respect to each other. A common shortcoming of both plain and cross-sectional techniques employing conventional X-rays is their lack of specificity. Every radiographic finding has an associated differential diagnosis in which neoplasia-related change is but one of many possibilities. Solitary abnormalities on bone scan or chest film serve as an excellent examples of this dilemma. The specificity of conventional imaging techniques is further compromised by attempts to increase sensitivity. As long as nonspecific anatomic changes are used as discriminating criteria, increases in test sensitivity will always occur at the price of specificity. It is hoped that advances in PET scanning and the use of isotope-labeled, tumor-selective monoclonal antibodies will overcome the limitations of currently available techniques. The significance of the limitations of a given test depends to some degree on whether the test is being used for clinical decision making or for patient stratification in a clinical trial. As an example, an aggressive transurethral resection of bladder tumors provides excellent information for clinical management but may introduce bias into multicenter studies in which this technique is not uniformly practiced. Similarly, the results of bimanual examination under anesthesia are important in the reference framework of the managing physician but are a poor quantifier of disease extent in multi-investigator clinical trials. Which staging studies are indicated and their optimal sequence for performance are influenced by pre-existing clinical information. Recognizing this, the staging algorithm in Figure 6 is intended to serve only as a guide to assist the clinician in the evaluation of patients with bladder neoplasms. As clarifications, several points concerning this algorithm merit mention. The literature suggests that as a single study, transurethral ultrasonography provides excellent local staging information. However, given that it is not widely available, the authors have chosen not to incorporate it into the staging schema. Optimally, it would be used immediately prior to transurethral resection of bladder tumors and bimanual examination. In addition, the algorithm lists MRI interchangeably with CT. While MRI appears to have slightly better sensitivity and specificity for both local and regional tumor stage relative to CT, its benefits are to some degree offset by its greater cost and the need to image the patient in multiple planes for lengthy intervals.(ABSTRACT TRUNCATED AT 400 WORDS)

Algorithms↗

Tumors of the kidney, ureter, and bladder.

Neoplastic diseases of the kidneys and urinary collecting system are relatively common, but when detected early, they have an excellent prognosis. Because gross or microscopic hematuria may be an early harbinger of genitourinary pathology, the primary care physician and internist play an integral role in diagnosing these diseases. A high index of suspicion together with a thorough history, physical examination, and appropriate diagnostic studies will enable the correct diagnosis and improved patient management in most cases.

Humans↗

Single-dose preoperative systemic cyclophosphamide for the prevention of bladder tumor implantation in F344 rats.

An implantable rat bladder tumor model using the rat transitional carcinoma cell line 4909 was used to evaluate the effect of single-dose, preoperative, systemic chemotherapy on the risk of intravesical tumor implantation. To simulate the clinical setting in which drug levels would be present in both the tumor and the site of implantation, both tumor donor animals and tumor recipients were given a single dose of cyclophosphamide (CY) 1 h prior to tumor harvest and implantation. This protocol resulted in a significant reduction in the incidence of tumor implantation, in tumor volume, and in the incidence of nodal metastases relative to control animals. Dose-response experiments demonstrated that 10 of 139 (7%) animals treated with single doses of CY ranging from 2.5-100 mg/kg developed tumors as compared to 46 of 66 (70%) animals with tumors in the control groups (P less than 0.001). CY doses below 2.5 mg/kg were associated with an increased incidence of tumor implantation (19 of 45, 42%). No lethal toxicity was seen at doses of 50 mg/kg or less. Peak antitumor activity occurred when the CY was administered 1 h prior to tumor implantation as compared to 48 or 24 h before or 1 or 24 h after tumor implantation. Preoperative "chemoprophylaxis" may be an effective strategy for preventing bladder tumor recurrences resulting from tumor implantation.

Animals↗