Growth of human urological tumors on extracellular matrix as a model for the in vitro cultivation of primary human tumor explants.

The goal of this study was to establish an optimal in vitro growth assay system for human urological tumor explants. Bovine corneal endotelial cell extracellular matrix (ECM) coated dishes were evaluated as a growth substrate for tumor cultures. Growth success for different urological carcinomas (prostatic, bladder, kidney, and testicular) was compared after seeding fresh surgical explants onto bovine corneal endothelial cell ECM and plastic culture flasks. Tumor samples were disaggregated enzymatically, and 1 X 10(4) cells were seeded onto the different substrates using RPMI 1640 medium containing 10% fetal calf serum and/or different growth factors, nutrients, and hormones. Cell growth on ECM was quantitated on days 7-15 by [3H]thymidine uptake, cell counting, and total protein. Tumor cells were characterized by flow cytometry and cytology. It was observed that ECM provides superior culture conditions for urological carcinomas. By increasing the initial number of cells plated on ECM and by adding different growth factors or hormones, the growth rate for specific tumor types was increased significantly. Several tumors (11 cases) grown on ECM were examined under the light microscope, and in all cases pre- and post-cytology confirmed malignancy. Tumor cells maintained on ECM and transplanted into nude mide retained their tumorigenic and morphological characteristics. Clinically aggressive tumors were associated with extensive ECM degradation. In addition, the growth of fresh human tumors on ECM provides a biologically relevant model system (for assessing the invasiveness of tumors in vitro) and should also be useful for drug evaluation studies.

Renal artery aneurysms.

Renal artery aneurysms, previously considered to be rare, have been diagnosed more frequently in recent years mainly due to the extensive use of angiography. Fifty-six patients with 67 aneurysms were evaluated, 5 of these were dissecting aneurysms. Most cases were manifestations of medial hyperplasia or atherosclerosis of the renal arteries. Symptomatology is not pathognomonic. Expanding aneurysm, intractable hypertension, hematuria, and renal infarction represent the most common indications for surgical repair. Reconstruction and repair of these aneurysms, with preservation of the kidney, is the preferred treatment. Surgery was performed on 17 patients (30%): 14 patients had primary repair, while 3 patients underwent nephrectomy for associated carcinoma and end-stage kidney disease. Temporary occlusion of the renal artery with hypothermic perfusion allows surgical repair safely to both patient and kidney. Autotransplantation into the ipsilateral iliac fossa was employed for dissecting aneurysms after resection and repair of the diseased segment. Nine of 12 hypertensive patients required no treatment for hypertension following aneurysmal repair, while 3 patients had improved control.

Metastases to both testicles from prostatic carcinoma six years after radiation therapy.

A case is presented of a sixty-nine-year-old man with metastases to both testicles and right epididymis six years after treatment with external beam radiation for Stage C prostatic carcinoma.

The value of cystoscopy, prostate biopsy and frozen-section urethral biopsy prior to orthotopic neobladder substitution.

INTRODUCTION: The traditional criteria for selecting suitability of male patients with bladder cancer for othtopic neobladder substitution includes: patient motivation, negative transurethral (TUR) prostate biopsy prior to cystectomy, and/or tumor-free biopsy of the urethral margin at the time of cystectomy. In this report we evaluate the value of these preoperative and intraoperative biopsies in the cystoscopically normal prostatic urethra. METHODS: During a 5-year period, cystectomies were performed on 54 men and 13 women with invasive bladder cancer. Prior to this procedure, all of the men had TUR biopsy of the prostate. Forty men with cystoscopically normal prostatic fossa had negative prostatic biopsies, and. had orthotopic neobladder substitution. RESULTS: Pathological examination showed that 3 out of these 40 men had transitional cell carcinoma (TCC) involving the prostate. In all 40 patients, the prostatic apical resection margin was negative. To date, none of the patients developed urethro-neobladder recurrence. CONCLUSION: TUR biopsy of the prostatic urethra prior to cystectomy, or biopsy of the prostatic urethral margin at the time of cystectomy in patients with cystoscopically normal, tumor free prostatic urethra has limited value in selecting candidates for orthotopic neobladder substitution.

Impact of pathologic extraprostatic disease on local and systemic progression following radical prostatectomy.

Fifty patients underwent radical prostatectomy for localized prostate cancer (Stages A2, B) between 1977 and 1982. Surgical specimens were examined for tumor grade and extraprostatic extension of the disease. Forty-one of the 50 patients had capsular involvement (82%), 26 (52%) positive margins and 14 (28%) seminal vesicular involvement. Six patients progressed locally, six systematically and three both. Eight patients progressed at five years and an additional seven at ten years. In all 15 progressors tumor involved the capsule yet four patients with capsular involvement alone progressed. Eleven of the 26 patients (42%) with positive margins progressed. Five of the 14 patients (37%) with seminal vesicle involvement progressed, all five had positive margins as well. None of the patients with disease confined within the capsule progressed. Gleason score for non-progressors ranged between three and nine with a median of six while for progressors it ranged between five and nine with a median of seven. Long rank test and Cox Proportional Hazard Model statistical analysis were employed among all the factors: capsular involvement, positive margins, positive seminal vesicles and grade of tumor. Positive margins was the only statistically significant factor affecting local progression of the disease in both univariate and multivariate analysis at a 95% confidence (p=0.04). All factors were statistically insignificant in affecting systemic progression (p>0.5).

Urothelial carcinoma of the vagina six years following cystectomy for invasive cancer. A case report.

A 74-year-old woman presented with vaginal spotting secondary to transitional cell carcinoma six years following cystectomy for invasive, yet localized, transitional cell carcinoma of the bladder. This represents primary, not metastatic, tumor of the vagina.

Late recurrence with malignant degeneration of testicular teratoma. Case report.

Radical orchiectomy was performed on a 25-year-old man for benign mature teratoma. A synchronous without change 3 cm retroperitoneal mass was followed for five years. The mass enlarged and became symptomatic twelve years after orchiectomy. Excision of the mass revealed a non-seminomatous germ cell tumor. Possible explanation is malignant degeneration of the teratomatous elements. Testicular teratomas should be treated as potentially malignant non-seminomatous tumor.

The value of free and total prostate specific antigen in identifying patients for prostatic biopsy and its relationship to Gleason score and number of positive cores.

INTRODUCTION AND OBJECTIVES: The percentage of free over total prostate specific antigen (%F/T PSA) seems to enhance the predictive value of PSA in diagnosing prostate cancer. We evaluated the value of F/T PSA in 50 consecutive patients who underwent prostate needle biopsy, its relationship to the Gleason score and number of positive cores. MATERIAL AND METHODS: 50 patients underwent prostate needle biopsy for abnormal PSA and/or abnormal digital rectal examination (DRE). There were 8 patients with PSA equal or less than 4 ng/ml, 6 with F/T PSA < 20%, group I (GI). 27 patients with PSA between 4.1 ng/ml and 10.0 ng/ml, 20 with F/T PSA < 20%, group II (GII) and 15 patients with PSA > 10.1 ng/ml (13 with F/T PSA < 20%), group III (GIII). At least six needle biopsies were obtained guided by transrectal ultrasound selectively or randomly. Pathological evaluation included Gleason grade and number of cores involved. RESULTS: 21/50 patients (42%) had positive biopsies, 3/8 in GI, 8/27 in GII (6 had negative DRE) and 10/15 in GIII (9 had positive DRE). 19/21 patients with positive biopsies had F/T PSA < 20%. The sensitivity, specificity and positive predictive value of PSA between 4-10 ng/ml and F/T PSA < 20% was 87.5%, 31% and 35% respectively. Stratifying patients with positive biopsies to F/T PSA < 10%, F/T PSA > 10% and the three PSA groups, there was no relationship to either Gleason score or number of positive cores. CONCLUSION: With a cutoff of 20%, F/T PSA seems to be an important parameter in selecting patients with abnormal PSA for biopsy. It will be helpful mostly with PSA 4-10 ng/ml. No relationship was observed between the level of F/T PSA, grade or number of positive cores.

Familial testicular cancer in five members of a cancer-prone kindred.

Of a family of 13 siblings, four brothers have developed testicular neoplasms, one embryonal cell carcinoma and three testicular seminomas. A first cousin once removed on their mother's side of the family (fourth-degree relative) has developed an embryonal carcinoma. After treatment they are all alive and well. Their mother is a dizygous twin and one of ten siblings. Multiple other cancers have been diagnosed among her siblings and their offspring including breast carcinoma at age 30 years in monozygous twin nieces. Associated urogenital abnormalities, concordance of age, and discordance of pathology in the five males with testicular cancer is discussed. Further identification and reporting of this risk factor is encouraged.

Interferon-beta treatment of metastatic prostate cancer.

A limited clinical trial of Interferon-beta (Human Fibroblast Interferon) in the treatment of advanced, hormone-refractory prostate cancer was conducted by the National Prostate Cancer Project (NPCP Protocol 2100). Sixteen patients with metastatic prostate cancer who had failed prior hormone therapy were entered into the study. Treatment consisted of 6 X 10(6) units of Interferon-beta intravenously three times per week for 12 weeks. Chills and fever were seen in ten of the 16 patients (62.5%), and mild hematologic toxicity occurred in four patients. No complete or partial responses were observed. Three patients had stable disease by NPCP criteria for a mean duration of 6.3 months. Progression of disease was seen in 13 of the 16 patients, eight of whom progressed during therapy. The results of this study suggest that Interferon-beta has limited efficacy in the treatment of advanced, hormone-refractory prostate cancer.

Penile replantation.

Amputation of the penis is thankfully an uncommon injury. Because of its rarity, a uniform plan of management to deal with this difficult injury has yet to be agreed on. We describe a man who sustained such an injury and his subsequent clinical course. The relevant history and pertinent anatomy is highlighted. Additionally, a systematic approach to dealing with this devastating injury is presented.

Liposarcoma of the spermatic cord.

In a 57-year-old man, a suspected incarcerated left inguinal hernia proved to be multifocal dedifferentiated liposarcoma of the spermatic cord. Radical orchiectomy and wide excision were performed, but marginal biopsies were positive for tumour. Radiotherapy was given.

Heparin-binding growth factor isolated from human prostatic extracts.

Prostatic tissue extracts from patients with benign prostatic hyperplasia (BPH) and prostatic carcinoma were fractionated using heparin-Sepharose chromatography. The mitogenic activity of eluted fractions on quiescent subconfluent Swiss Albino 3T3 fibroblasts was tested employing a tritiated-thymidine-incorporation assay. Two peaks of activity were consistently noted--one in the void volume and a second fraction which eluted with 1.3-1.6 M NaCl and contained the majority of the mitogenic activity. Both non-heparin- and heparin-binding fractions increased tritiated incorporation into a mouse osteoblast cell line (MC3T3), while only the heparin-binding fractions stimulated a human umbilical vein endothelial cell line (HUV). No increased uptake of thymidine was seen using a human prostatic carcinoma cell line (PC-3). Sodium dodecyl sulfate/polyacrylamide gel electrophoresis (SDS/PAGE) of lyophilized active fractions showed a persistent band at 17,500 daltons. The purified protein demonstrated angiogenic properties using the chick embryo chorioallantoic membrane (CAM) assay. Western blot analysis using antibodies specific to basic fibroblast growth factor (bFGF) or acidic FGF (aFGF) demonstrated that the former, but not the latter, bound to prostatic growth factor (PrGF), and inhibited its mitogenic activity as well. It appears that PrGF shares homology with basic fibroblast growth factors.

The effect of nitrofurantoin on bladder tumor cell lines: in vitro growth and implantation in the cauterized mouse bladder.

Nitrofurans compounds and derivatives demonstrate antineoplastic activity in vitro as well as in vivo. Nitrofurantoin caused in vitro growth inhibition of a FANFT-induced murine bladder tumor (MBT2) and a human transitional cell carcinoma cell line (GIBB) in concentrations of 125 microM, 250 microM and 500 microM. The implantation and growth of MBT2 in the cauterized mouse bladder was inhibited by 250 microM nitrofurantoin. The bladder mucosa of two groups of C3Hf/HeHa female mice was electrically cauterized. In group I, 1 X 10(6) MBT2 cells were injected into the bladders of 42 mice, while in group II 1 X 10(6) MBT2 cells in 250 microM nitrofurantoin solution were injected into the bladders of 51 mice. Positive tumor implantation was seen in 25 bladders (59.5 per cent) of group I as compared to 15 bladders (29.5 per cent) of group II. All tumors in group I were large, occupying more than 50 per cent of bladder cross sectional area with 24 per cent showing extravesical extention. Sixty-six per cent of tumors in groups II were less than 25 per cent of bladder cross sectional area and 13.4 per cent had extravesical extention.

Pelvic exenteration for advanced primary and recurrent adenocarcinoma.

The authors report on 45 patients who have undergone pelvic exenteration for adenocarcinoma since 1979. Three patients underwent exenteration as the initial treatment for their disease but all others had had previous surgery, radiotherapy or chemotherapy. Operating time and blood loss were lower in previously irradiated patients. There were seven in hospital deaths (15.5%). The number of complications and length of postoperative hospital stay have decreased significantly as experience with pelvic exenteration has been acquired. Symptoms have been controlled in a high proportion of patients. Exenterative surgery is an effective method of treatment in selected patients with pelvic adenocarcinoma but should be undertaken only by experienced surgeons who have access to a wide range of supportive facilities for optimal perioperative management.

Growth of human urologic tumors on extracellular matrix.

Surgical specimens of fifty urologic tumors, 19 renal, 19 bladder, nine prostate and three testicular, were disaggregated into a cell suspension by a two step mechanical and enzymatic method. Viability, cytology and flow cytometry (FCM) for DNA ploidy were subsequently determined. Growth of urological tumors on extracellular matrix (ECM) was carried out as follows: 2.5 to 5 X 10(5) cells were placed in plastic T25 flasks in RPMI 1640 + 10 per cent fetal bovine serum (FBS). 1.0 to 5 X 10(4) cells were plated in wells coated with ECM derived from bovine corneal endothelial cells with RPMI 1640 + 10 per cent FBS. Cultures were incubated for seven to 10 days at 37 degrees C. Only one (renal) out of 28 tumors grew on plastic. Forty out of 50 tumors (80 per cent) established primary cultures on ECM as determined by cell counting, protein determination, and/or [3H]thymidine incorporation. Previous experience with 106 urologic tumors grown on double layer agar demonstrated an overall success rate of 48 per cent. On ECM renal tumors showed 95 per cent growth success, prostate 89 per cent, bladder 63 per cent and testicular 67 per cent. Unlike viability by trypan blue exclusion, tumor DNA ploidy and percentage of malignant cells plated on ECM had no effect on growth success. The malignant nature of the cultured cells was confirmed by cytology. Twelve high grade and metastatic tumors caused degradation of the ECM. DNA ploidy was similar in four and different in six tumors before and after culture. Five tumors underwent in vitro drug testing on ECM with significant growth inhibition observed in three cases. The extracellular matrix seems to be a promising model for growing urologic tumors with excellent potential for drug testing in vitro.