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Biomedical subjects

D J Culkin

Publications and source records attributed to D J Culkin.

At least 19 recordsLinked to original sources
PubMed1999

Cisplatin, methotrexate and bleomycin for the treatment of carcinoma of the penis: a Southwest Oncology Group study.

PURPOSE: We ascertained whether combined cisplatin, methotrexate and bleomycin have efficacy for treating locally advanced or metastatic carcinoma of the penis, and evaluate the toxicity resulting from this regimen. MATERIALS AND METHODS: Patients had biopsy proved locally advanced or metastatic epidermoid carcinoma of the penis. Chemotherapy consisted of 75 mg./m.2 cisplatin infused intravenously on day 1, 25 mg./m.2 intravenous bolus of methotrexate on days 1 and 8, and 10 unit per m.2 intravenous bolus of bleomycin on days 1 and 8 with a cycle length of 21 days. Our study was performed as a standard phase II evaluation with 2 stages of accrual. RESULTS: Enrolled in this study were 45 patients, including 40 who were evaluable for a response. There were 5 complete and 8 partial responses for a 32.5% response rate. Five treatment related deaths occurred and 6 of the 36 remaining patients evaluable for toxicity had 1 or more life threatening toxic episodes. CONCLUSIONS: A regimen of cisplatin, methotrexate and bleomycin appears to have promising results. However, toxicity was prodigious, and an emphasis of future research should be to decrease toxicity.

Adult↗
PubMed1998

Bilateral orchiectomy with or without flutamide for metastatic prostate cancer.

BACKGROUND: Combined androgen blockade for the treatment of metastatic prostate cancer consists of an antiandrogen drug plus castration. In a previous trial, we found that adding the antiandrogen flutamide to leuprolide acetate (a synthetic gonadotropin-releasing hormone that results in medical ablation of testicular function) significantly improved survival as compared with that achieved with placebo plus leuprolide acetate. In the current trial, we compared flutamide plus bilateral orchiectomy with placebo plus orchiectomy. METHODS: We randomly assigned patients who had never received antiandrogen therapy and who had distant metastases from adenocarcinoma of the prostate to treatment with bilateral orchiectomy and either flutamide or placebo. Patients were stratified according to the extent of disease and according to performance status. RESULTS: Of the 1387 patients who were enrolled in the trial, 700 were randomly assigned to the flutamide group and 687 to the placebo group. Overall, the incidence of toxic effects was minimal; the only notable differences between the groups were the greater rates of diarrhea and anemia with flutamide. There was no significant difference between the two groups in overall survival (P=0.14). The estimated risk of death (hazard ratio) for flutamide as compared with placebo was 0.91 (90 percent confidence interval, 0.81 to 1.01). Flutamide was not associated with enhanced benefit in patients with minimal disease. CONCLUSIONS: The addition of flutamide to bilateral orchiectomy does not result in a clinically meaningful improvement in survival among patients with metastatic prostate cancer.

Adenocarcinoma↗
PubMed1998

Wilms' tumor with renal cell carcinoma overgrowth in a 3-year-old child.

Wilms' tumors that contain features of both renal cell carcinoma and classic Wilms' tumor histology are rare. Even though nine such cases have been previously reported in the literature, we report the first case of a Wilms' tumor with an overwhelmingly renal cell carcinoma histologic pattern.

Carcinoma, Renal Cell↗
PubMed1997

Prostate-specific antigen (PSA) and PSA density: racial differences in men without prostate cancer.

BACKGROUND: Many physicians now use serum prostate-specific antigen (PSA) to screen for prostate cancer in asymptomatic men. Whether or not a prostate biopsy should also be performed depends on an accurate definition of what constitutes a normal PSA value. Until recently, studies conducted to establish normal serum PSA values have involved study populations that have included few African-American men. PURPOSE: We sought to compare serum PSA levels and PSA density (i.e., serum PSA level/prostate volume ratio) in African-American and white men without histologic evidence of prostate cancer. METHODS: We reviewed the medical records of 826 consecutive men who underwent one or more prostate biopsies at the Veterans Affairs Medical Center in Shreveport, LA, from January 1993 through December 1995. In this retrospective review, we recorded patient's age, race, serum PSA level, digital rectal examination result, ultrasound-determined prostate volume, indications for biopsy, and biopsy results. Data from a total of 752 consecutive men who were either white or African-American and whose indication for biopsy included a serum PSA of greater than 4.0 ng/mL and/or an abnormal digital rectal examination were analyzed. To examine possible differences in serum PSA level, PSA density, prostate volume, and patient age, the two-sided Student's t test was employed. Multivariate linear regression analysis was used to determine if serum PSA levels were associated with the patient's age, race, or prostate volume in men without prostate cancer. RESULTS: Of the 752 men included in this analysis, 254 had histologic evidence of prostate cancer and 498 did not. Of the 498 men without prostate cancer, 367 (74%) men were white and 131 (26%) were black. There were no racial differences in age or calculated prostate volume. Serum PSA levels and calculated PSA density, however, were significantly (both P < .0001) higher in African-American men that in white men. A multivariate linear regression analysis indicated that race and prostate volume were independent variables associated with serum PSA level. For African-American and white men, serum PSA values of greater than 4 ng/mL were associated with prostate cancer with sensitivities of 89.5% and 81.9%, respectively, and specificities of 38.2% and 52.3%, respectively. CONCLUSION: Among biopsied men without histologic evidence of prostate cancer, African-Americans have a significantly higher PSA level and PSA density than similarly aged white men. IMPLICATIONS: Published criteria for normal PSA level and density have been derived primarily from white men and may not be directly applicable to other populations. Race-specific data are needed to fully optimize PSA as a tumor marker in racial populations that are at high risk for prostate cancer death.

Adult↗
PubMed1997

Influence of hepatic function on serum levels of prostate specific antigen.

PURPOSE: Recent studies have suggested that the primary site of metabolism for prostate specific antigen (PSA) is the liver. We evaluated men undergoing liver transplantation to determine whether chronic hepatic insufficiency affected serum PSA levels and whether improved hepatic function altered serum PSA levels. MATERIALS AND METHODS: Ten men with a mean age of 46 years (range 23 to 67) undergoing liver transplantation were evaluated. Liver function tests, including serum bilirubin, serum glutamic-oxaloacetic transaminase and serum glutamic pyruvic transaminase, as well as serum PSA were determined 1 day before and a mean of 12.6 months (range 4 to 18) after transplantation. RESULTS: Serum bilirubin and serum glutamic-oxaloacetic transaminase declined significantly after liver transplantation. There was no difference in mean serum PSA levels before and after liver transplantation. CONCLUSIONS: Our results suggest that severe hepatic dysfunction does not significantly alter the serum concentration of PSA. These data, combined with recent investigations demonstrating an intrahepatic mechanism for PSA elimination, suggest that the liver has a significant reserve to metabolize the relatively small quantities of PSA in the circulation.

Adult↗
PubMed1996

Prostate specific antigen is metabolized in the liver.

PURPOSE: The site of metabolism of prostate specific antigen (PSA) was determined. MATERIALS AND METHODS: In a prospective study, during clinically indicated left and right heart catheterizations for various cardiac diseases in 12 men (mean age 62.5 +/- 8.3 years, standard deviation), selective blood samples were obtained from the infra-renal, infra-hepatic and supra-hepatic inferior vena cava, renal vein, superior vena cava, pulmonary artery and femoral artery. Mean PSA concentration was calculated for all vascular sites. Using a paired Student t test, the mean difference between the afferent and efferent PSA concentrations across the renal, hepatic, pulmonary and pelvic circulation was calculated. RESULTS: The hepatic gradient between the infra-hepatic and suprahepatic inferior vena cava showed the greatest decrease (0.11 +/- 0.16 ng./ml. or 8.3%) in PSA concentration and was statistically significant (p = 0.04). A smaller decrease across the pulmonary circulation was statistically insignificant. No decrease in the PSA concentration was noted across the renal circulation. The PSA concentration increased significantly (0.19 +/- 0.18 ng./ml. or 16.3%, p = 0.003) across the pelvic circulation, confirming the release of PSA from the prostate. CONCLUSIONS: PSA is released from the prostate. The kidneys and lungs do not have a significant role in elimination of PSA, and the liver appears to be the most likely site of its metabolism. Although our sample size is small and the PSA range is narrow, our results strongly support these conclusions.

Aged↗
PubMed1995

Cellular PSA in benign and malignant prostate.

To determine the relationship of carcinoma of the prostate and cellular production of prostate-specific antigen, cytosol levels of PSA were measured in benign and malignant fresh prostate tissue harvested from radical prostatectomy specimens. Wedge biopsies were taken from benign (N = 21) and malignant (N = 74) prostate tissue and were immediately fixed in liquid nitrogen, and then homogenized and differentially centrifuged, and the cytosol fractions extracted. The remaining specimen was sent for routine pathologic assessment. The Hybritech methodology was used to measure the cytosol PSA and standard protein analysis was used for cytosol protein (CP) measurement. There was a significantly greater concentration of PSA in malignant tissue (P = 0.046). Also, when benign and malignant tissue were available from a single prostate (N = 17), these differences in cytosol PSA were even greater (P = 0.002). In addition, there was no significant difference when serum PSAs from the malignant tissue were ranked according to Gleason score and placed into three different histologic grades (i.e., Gleason scores 2-4, 5-6, and 7-10).

Cytosol↗
PubMed1994

Techniques for bypassing and stenting ureteral obstructions.

The advent of current endourological equipment and combined cystoscopic fluoroscopy allows the urologist to divert and/or stent the majority of benign and malignant ureteral obstructions in either a retrograde or antegrade fashion. We report on our recent experience in managing 105 obstructed renal units to formulate a troubleshooting endourological algorithm for bypassing and stenting ureteral obstructions. The methods described allow for safe and successful stent diversion in the majority of patients with ureteral obstruction requiring initial or primary endourological management. The algorithm presents alternative techniques for bypassing and stenting ureteral obstructions.

Algorithms↗
PubMed1993

Evaluation of the current incidence of nodal metastasis from prostate cancer.

To determine the influences of transrectal ultrasonography, prostate-specific antigen (PSA), and heightened public awareness of prostate cancer stage at diagnosis, we prospectively evaluated our most recent 173 patients who had a pelvic lymphadenectomy from 1987 to 1991. All patients had clinically localized prostate cancer and underwent bilateral limited pelvic lymph node dissections (N = 173); 19 (10.7%) were found to have nodal metastasis. Pathologic tumor stage and grade information was available for 168 patients who had a simultaneous radical prostatectomy. Clinical T-stage data revealed that only one patient had a T3 lesion. Pathologic T stage showed 7.1% to be T1a (12/168), 4.1% to be T1b (7/168), 13.7% to be T2a (23/168), 34.5% to be T2b (58/168), and 40.5% to be T3 lesions (68/168). Metastatic nodal involvement was not seen in any T1a, T1b, or T2a lesions. A Gleason's score of less than 5 lesions was predictive of no nodal metastasis. The clinical stage was upstaged pathologically in none of the T1a, 16.7% of the clinical T1b, 75% of the T2a, and 73% of the T2b lesions. With regard to serum PSA, 27% of those patients with a level > 20 ng/ml had nodal metastasis (6/22) in this series. Although an elevated PSA was not predictive of tumor nodal metastasis, no patient with a normal PSA had nodal metastasis. Although the distribution of pathologic T stages is similar to that reported in the literature, our low incidence of nodal metastasis may suggest that prostate cancer is being diagnosed earlier.

Adult↗
PubMed1992

Evaluation of a new tumor marker for localized prostate cancer.

Adenocarcinoma associated antigen (ACAA) is a large molecular weight protein that is normally found in low serum levels. Recent data have revealed elevations in patients with adenocarcinomas, including prostate cancer. To evaluate the relationship of ACAA levels with prostate cancer, we measured the cytosol content in malignant and nonmalignant prostate tissue and compared these results to those of the standard markers, prostatic acid phosphatase (PAP) and prostatic specific antigen (PSA). Enzyme solid phase immunoassay was used to quantitate PSA and ACAA levels, and the enzymatic method was used to measure PAP. Wedge resection from the right and left posterior lobes of 50 fresh radical retropubic prostatectomy specimens were used for cytosol analysis. All foci of within each prostate gland were carefully mapped by a single pathologist. When all malignant wedges (N = 74) were compared to all the benign wedges (N = 21), only the PSA levels showed significant elevation (p less than 0.02). However, when benign and malignant tissue from the same prostate were available for comparison, both PSA (N = 17) and ACAA (N = 16) showed significant elevations in the cytosol of the malignant tissue (p less than 0.002 and p less than 0.03, respectively). Although not statistically significant, the cytosol PAP did show a consistent trend to be greater in malignant tissue. It appears that there is an association of increased cytosol ACAA and PSA with prostate cancer.

Acid Phosphatase↗
PubMed1992

Ureteral injury in abdominal vascular reconstructive surgery.

Iatrogenic ureteral injuries in vascular reconstructive surgery are rarely reported. We present a case of ureteral transection during repair of an aortic aneurysm in a patient with a previously placed aortobifemoral graft. In reported series of surgical ureteral injuries, 17 of 381 injuries occurred during vascular procedures. A review of the literature and management scheme for ureteral complications in the presence of prosthetic vascular grafts is presented in light of current endourologic materials and techniques.

Abdomen↗
PubMed1992

Acquired immunodeficiency syndrome manifesting as prostate nodule secondary to cryptococcal infection.

We report the first case of acquired immunodeficiency syndrome (AIDS) presenting as prostate nodularity secondary to mycotic granulomatous prostatitis which mimicked prostatic cancer on digital rectal examination. Transrectal ultrasonography revealed hypoechoic areas in the peripheral zone, which on biopsy specimen were found to represent cryptococcal infection. Subsequent serologic evaluation of the patient confirmed human immunodeficiency virus (HIV) positivity and later AIDS developed in the patient.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Anatomic, functional, and pathologic changes from internal ureteral stent placement.

The anatomic, hydrodynamic, functional, and pathologic changes associated with unilateral internal ureteral stenting were evaluated in 20 female canines. Selective glomerular filtration rates (GFR) were measured with technetium 99m diethylenetriamine pentaacetic acid (DTPA) renal scans (N = 14) prior to and several weeks after unilateral internal stent placement. Cystometry and cystography were done at weekly intervals to determine if reflux occurred and to measure the intravesical pressure to produce this reflux (N = 16). Ureteral lumenal capacities of mid 6-cm ureteral segments of stented and unstented ureters were compared. The mid-ureteral lumenal volumes were three times greater in the stented ureters (p < 0.002). There were no significant differences in the selective GFR before and after stenting. Low-pressure vesicoureteral reflux occurred at a mean intravesical pressure of 13.7 cm of water and was present in 84.6 percent (11/13) of the canines whose stents did not migrate or obstruct from encrustation. There were no significant alterations in serum chemistries or blood counts. Fluoroscopic imaging also showed ineffective ureteral peristalsis. This study confirms that internal ureteral stents cause vesicoureteral reflux and significant lumenal dilation without altering renal function.

Animals↗