Intraprostatic ethanol diffusion: comparison of two injection methods using ex vivo human prostates.

BACKGROUND: Intraprostatic injection of ethanol has been previously tested in clinical trials as a potential treatment of BPH, with variable outcomes. As evident from animal studies, the inconsistency was owing to various degrees of ethanol backflow along the needle tract. In acute canine experiments, we previously documented that using convection enhanced delivery (CED) eliminates backflow and improves ethanol distribution. The goal of this study was to compare the diffusion pattern between a microporous hollow fiber catheter (MiHFC) and a standard needle in human prostates from organ donors. METHODS: Prostates were harvested from cadaveric organ donors immediately after removal of organs for transplant. After trimming off excess fat and weighing, prostates were injected with absolute ethanol. The total injected volume was 25% of the calculated prostate volume. One lateral lobe was injected using a single lumen 21-gauge control needle. The contralateral lobe was injected with the same volume but using a MiHFC. Immediately after injection, prostates were fixed en bloc in 10% neutral-buffered formalin, and then sectioned. Three-dimensional reconstruction was performed to determine lesion volume based on hematoxylin- and eosin-stained cross-sections. RESULTS: Three fresh human prostates were harvested and injected. The time from harvest to intraprostatic injection was 15-35 min. The lesion created by the MiHFC was 1.14±0.52 cm(3), whereas that from the control needle was 0.28±0.10 cm(3) (P=0.038). No backflow was observed along the needle tract of the MiHFC. CONCLUSIONS: This study shows that freshly harvested human prostates can be used to evaluate new treatments using intraprostatic injection. Similar to in vivo canine experiments, the ethanol lesion sizes were significantly bigger with the use of a MiHFC when compared with a standard single lumen needle.

Growth of human renal cortical tissue on collagen gel.

A model system for 3-dimensional "native-state" culture of tissues on collagen gels (Proc. Natl. Acad. Sci. USA 86:2013-2017; 1989) has been applied in this study to histologically normal human renal cortical tissue from 11 patients undergoing nephrectomy for renal cell carcinoma elsewhere in the kidney. Microbial contamination occurred in 12/90 cultures, the rest (78) were studied by visual inspection, histology, immunohistochemical analysis for pankeratin (epithelial cell origin), vimentin (mesenchymal cell origin), and p-glycoprotein (associated with proximal tubules), transmission electron microscopy (EM), incorporation of tritiated thymidine (3HTdR). In the first 10 days, explants showed 3HTdR-labeled cells in tubule structures. The surrounding gel was invaded by cells forming tubule structures, sometimes with basement membrane. Some of these cells showed labeling by 3HTdR and immunostaining positive for pankeratin and p-glycoprotein. EM showed well-polarized epithelial cells in tubule structures with tight junctions, interdigitating lateral processes, and microvilli characteristic of proximal and distal convoluted tubules. 3HTdR-labeled cells in tubule structures were observed even 2 mo. after Passage 1, 6 mo. after the initial explantation. Tubule growth was most active and fibroblast proliferation was negligible from 2 to 4 wk postexplantation. The proliferation of tubulelike cells and formation of tubulelike structures in this system represents an opportunity to study human renal cortical tissue in vitro, under conditions more closely resembling in vivo circumstances than are present in other in vitro systems suitable for long-term study. This model has potential use for in vitro toxicology studies and studies of renal physiology.

Drug therapy of prostatic cancer.

While hormonal therapy has been the usual and appropriate treatment of advanced or metastatic prostatic cancer for the past 50 years, the recent development of new therapeutic agents as medical alternatives to orchidectomy has drastically altered the options and perspectives in the treatment of this disease. Estrogens had been the only commonly used drug therapy in the United States. Newer alternatives include androgen synthesis inhibitors, a class of agents termed antiandrogens, and gonadotrophin-releasing hormone (GnRH) [luteinising hormone-releasing hormone (LHRH)] analogues, either alone or in combination. As the result of basic scientific studies and prospective clinical trials which have examined the issue of risk versus benefit, several trends have emerged. In the United States, orchidectomy is waning as the primary treatment option for metastatic prostatic cancer, while estrogen use has declined drastically; GnRH analogues are being prescribed more frequently. Furthermore, combination therapy with GnRH analogues (or orchidectomy, to a lesser extent) and the antiandrogen flutamide is gaining wider acceptance as a primary treatment option. The rationale, advantages, and real or potential disadvantages of these various treatment options are discussed.

In vitro study of the interaction of doxorubicin, thiotepa, and mitomycin-C, agents used for intravesical chemotherapy of superficial bladder cancer.

Several cytotoxic agents have been identified as effective in the treatment of superficial transitional cell carcinoma of the bladder, including doxorubicin, thiotepa and mitomycin-C. An in vitro study was conducted to assess the interactions of these three drugs against a well differentiated human bladder tumor cell line, RT-4, to identify and evaluate synergistic combinations among these agents. Cytotoxicity was evaluated by a colorimetric assay based on the capacity of viable cells to metabolize a tetrazolium dye, MTT, to produce a colored formazan product. The analyses of drug interactions were done by the isobolographic method (construction of isoeffect plots). The combination of doxorubicin and thiotepa was found to be the most synergistic, followed by the combination of doxorubicin and mitomycin-C. The combination of mitomycin C and thiotepa demonstrated an unpredictable effect. These findings suggest the combination of doxorubicin and thiotepa has potential advantage for chemotherapy of superficial bladder tumors.

Locally recurrent endometrioid adenocarcinoma of the prostate after radical prostatectomy.

Endometrioid carcinoma of the prostate is considered a variant of classical prostatic ductal carcinoma. Endometrioid carcinoma variant often has the unique clinical presentation of gross hematuria. The propensity of this tumor to spread within the urothelium makes local failure of curative therapy commonplace. We present 2 representative cases with a review of followup surveillance procedures and treatment options for the local recurrence once identified.

Assessment of human genitourinary tumors and chemosensitivity testing in 3-dimensional collagen gel culture.

A recently described collagen gel culture technique has been modified to evaluate the growth characteristics and chemosensitivity patterns of genitourinary neoplasms. Fresh human surgical explants incorporated radiolabeled DNA precursors [H3)thymidine or deoxyuridine) in 97% of 38 patient specimens (18/19 bladder, 3/3 prostate, 2/2 testis, 13/14 renal), after being maintained for three to 13 weeks/passage, with several specimens reaching their sixth passage (20 months). Control cellular DNA incorporation ranged from five to 90% (#cells labeled/#cells evaluated), with median labeling for bladder 30%, prostate 80%, testis 90%, and renal 80%. Original histopathologic classification was maintained in all cases. Tumor volume and glucose consumption were other measurable parameters. Seventy-three surgical specimen cultures were treated with chemotherapeutic agents after a minimum of four weeks in culture. Single agent exposures were 24 hours at 1X and 10X reported peak plasma concentrations. Combination agents were sequenced as in current clinical protocol for bladder tumors and fourteen day continuous fluorodeoxyuridine (FdURD) exposure for renal tumors. Sensitivity was found in 1/2 prostate and 1/10 renal tumors to Adriamycin, 8/15 bladder and 1/2 testis tumors to cisplatin, 11/28 renal tumors to FdURD and 6/16 bladder tumors to MVAC combination chemotherapy. This culture system offers the advantages of in vivo-like solid tumor growth, a high culture success rate, longevity in culture, maintenance of the primary histopathology and reproducible chemosensitivity response.

Comparing clinical staging plus transrectal ultrasound with surgical-pathologic staging of prostate cancer.

Twenty-five men with histopathologic diagnosis of prostatic adenocarcinoma were staged utilizing traditional staging modalities and transrectal ultrasound of the prostate (TRUSP). A comparison was then done with surgical-pathologic stage. TRUSP accurately predicted the local extent of disease in 84 percent of patients, while digital rectal examination understaged in 64 percent of patients. TRUSP is a valuable adjunct to staging prostate cancer prior to definitive therapy.

Transrectal ultrasound and fine needle aspiration for malacoplakia of the prostate.

Clinically, malacoplakia of the prostate gland may mimic prostatic carcinoma. We report a case of prostatic malacoplakia in which transrectal ultrasound of the prostate was most compatible with carcinoma. However, fine needle aspiration cytology and biopsy revealed the classical histopathological features of malacoplakia so that a correct diagnosis could be made.