Diffuse parenchymal urine leak after kidney transplantation following degloving injury during donor nephrectomy.

Laparoscopic donor nephrectomy can result in trauma to the kidney which may affect recipient graft function. In this case, the kidney sustained a complete degloving of the capsule during extraction. The kidney was transplanted and had immediate, good renal function, but postoperative course was complicated by a large urinoma that drained through the wound. Exploration was negative for a defined urine leak, but the surface of the denuded kidney was leaking a significant amount of unconcentrated urine. The patient was successfully treated with tissue glue treatment to the kidney surface and peritoneal window.

Comparison of the modified vest and the direct anastomosis for radical retropubic prostatectomy.

OBJECTIVES: This retrospective study was undertaken to compare the efficacy of the Vest and direct vesicourethral anastomosis for radical prostatectomy. METHODS: Five hundred six patients who underwent consecutive radical prostatectomies at our institution were analyzed. Two hundred fifty-nine patients underwent vesicourethral anastomosis using the Vest technique and 247 underwent a direct suture anastomosis. The groups were analyzed relative to time until healing, the occurrence of anastomotic strictures, and the continence rate 1 year after surgery. RESULTS: Approximately twice as many patients who underwent the Vest procedure experienced delayed healing and 8.5% developed anastomotic strictures compared with 1.2% of the direct anastomosis group. The Vest group experienced slightly better urinary continence 1 year postoperatively. CONCLUSIONS: The Vest procedure is a reasonable alternative to direct anastomosis for radical prostatectomy and provides similar results. We suggest specific circumstances when the Vest anastomosis may be particularly useful.

Prospective analysis of multifocality in renal cell carcinoma: influence of histological pattern, grade, number, size, volume and deoxyribonucleic acid ploidy.

In an effort to characterize more fully multifocal renal cell carcinoma, 100 radical nephrectomy specimens with localized renal cell carcinoma were analyzed in a prospective fashion. Analysis of each specimen consisted of preoperative computerized tomography or magnetic resonance imaging, standard pathological examination with frozen section and 3 mm. step sectioning under magnification. Multifocal renal cell carcinoma was found in 16 specimens. Multifocal disease was suspected by preoperative imaging in 7 specimens (44%) and confirmed after standard pathological investigation in 10 (63%). Papillary and mixed histological patterns occurred at a significantly increased rate in specimens with multifocal disease (p = 0.011). Other parameters, such as stage, tumor size and volume, histological grade and deoxyribonucleic acid ploidy were evaluated and did not correlate with the presence or extent of multifocality. The number of secondary tumors per specimen varied from 1 to 50 (median 2) and were of higher grade in 3 (19%) and of lower grade in 2 (12%) when compared with the predominant tumor. In conclusion, information from preoperative and to some degree intraoperative tests (except histological pattern) cannot reliably predict multifocality. The true risk for unknown multifocality in a surgical setting seems to be 6%, which roughly corresponds to the incidence of locally recurrent disease in published large institutional series.

Expression and androgenic regulation of human prostate-specific kallikreins.

In vitro studies suggest that the protease activity of PSA might play a functional role to facilitate the growth and spreading of cancerous prostatic cells. hK2 may have similar properties. Further investigation to prove their in vivo effects is required. Regulation of PSA and hKLK2 gene expression is mediated not only by androgens, but also by a number of autocrine and paracrine factors, suggesting that the control mechanisms for expression of these genes are complex and multifaceted. Such factors may also be integral for the growth and differentiation of prostate cells. Thus PSA and hKLK2 may serve as useful markers to study the regulation of gene expression during cell growth and differentiation of the prostate.

Antagonism of androgen action in prostate tumor cells by retinoic acid.

Recent studies have demonstrated that retinoic acid (RA) can repress the growth of human prostatic epithelial cells. Since the proliferation of prostate cells is highly dependent on androgen stimulation, presumably via its cognate receptor, we investigated the effects of RA on the expression of the androgen receptor and other androgen-regulated genes in the human prostatic adenocarcinoma cell line LNCaP. Using a radioligand binding assay, we found that androgen-binding activity was reduced 30-40% in cells treated with 10(-5) M RA plus 6 nM dihydrotestosterone (DHT), as compared to cells with the androgen alone. Moreover, the reduction of the androgen receptor (AR) was not accompanied by alteration of the ligand-binding affinity. Concomitant changes in the function of AR were manifested by a dramatic reduction in AR-mediated transcription activity in a transfection experiment. Androgen-induced levels of both prostate-specific antigen (PSA) and human glandular kallikrein-1 (hKLK2) mRNAs were significantly repressed by RA in a dose- and time-dependent manner. Consistent with this finding, androgen induction of PSA glycoprotein was also repressed by RA, with maximal inhibition occurring at 10(-5) M. These data suggest that the suppression of proliferation and function of prostatic cells by RA may be via modulatory effects on the AR.

Preoperative androgen deprivation therapy: artificial lowering of serum prostate specific antigen without downstaging the tumor.

We studied 22 patients with clinical stage B2 (T2c) or C (T3) prostate cancer who underwent androgen deprivation therapy before radical prostatectomy as part of a downstaging protocol (group 1). The concentration of serum prostate specific antigen (PSA) was determined before and at the conclusion of androgen deprivation therapy, just before the operation. For each group 1 patient a match patient who had not received preoperative endocrine therapy (group 2) was chosen. The age of the group 2 patients was similar to that of the group 1 patients. The clinical stage of disease and pretreatment tumor grade in group 2 were identical to the stage and grade in group 1, and the serum PSA value in group 2 was similar to that of group 1 before initiation of androgen deprivation therapy. In group 1 the median serum PSA concentration was 14.8 ng./ml. (range 3.1 to 99) before endocrine therapy and 0.2 ng./ml. (range 0.1 to 3.4) after hormonal treatment. Group 2 had a median level of 13.3 ng./ml. (range 3.4 to 100). The median decrease in the serum PSA concentration for group 1 as a result of androgen deprivation therapy was 98.5%. The radical prostatectomy specimens from these 2 groups of similar patients had no difference with regard to maximal tumor dimension, pathological stage and deoxyribonucleic acid ploidy status. These findings indicate that serum PSA becomes an unreliable indicator of disease status after initiating preoperative androgen deprivation therapy and that preoperative androgen deprivation therapy has little or no benefit for decreasing the extent of tumor or pathological stage. The concept of downstaging is misleading and must be examined in a randomized clinical trial.

Extrarenal Wilms' tumor: results of the National Wilms' Tumor Study.

Extrarenal Wilms' tumor is extremely rare and occurs predominantly in children. Eight cases of extrarenal Wilms' tumor were reported to the National Wilms' Tumor Study from 1980 to 1986. Patients were followed in the study and not randomized to a particular treatment protocol. Seven patients had a favorable histology. One tumor located in the sacrococcygeal region showed immature teratoma with nephroblastic tissue. The embryogenesis of extrarenal Wilms' tumor is controversial; however, tumor containing teratomatous elements most likely represents a different embryologic origin and, therefore, should be classified separately. All eight patients were treated with operative excision and chemotherapy. Seven of the eight patients were disease-free with a mean follow-up of 34.3 months. It can be inferred from this small group of patients that the prognosis is comparable to intrarenal Wilms' tumor in the National Wilms' Tumor Study.

Wilms' tumor: a new cause for urinary extravasation.

We report a case of Wilms' tumor associated with urinary extravasation due to tumor invasion through the renal pelvis and anterior renal capsule. Extravasation of urine exposed to tumor may lead to upstaging of the tumor and the requirement for more intensive therapy.

Tumor-promoting phorbol ester down-regulates the androgen induction of prostate-specific antigen in a human prostatic adenocarcinoma cell line.

Prostate-specific antigen (PSA) is the most sensitive marker available for monitoring the progression of prostate cancer and response to therapy. In a previous study, we demonstrated tissue-specific expression of PSA glycoprotein and mRNA and its regulation through the androgen receptor. In this study, we examine the effects of protein kinase A (PKA) and protein kinase C (PKC) on the androgen regulation of PSA in a human adenocarcinoma cell line, LNCaP. Northern blot analysis demonstrated that forskolin, an activator of PKA, had no effect on the androgen regulation of PSA. However, the phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate (TPA), a direct activator of PKC, showed a time- and dose-dependent repression of the androgen regulation of PSA glycoprotein and mRNA. The biologically inactive phorbol ester, 4 alpha-phorbol-12,13-didecanoate, had no effect. Staurosporine, a PKC inhibitor, blocked the TPA-mediated repression of the androgenic stimulation of PSA glycoprotein. In addition, the calcium ionophore, A23187, was able to simulate the actions of TPA, presumably through activation of PKC via calcium mobilization. In summary, the androgenic regulation of PSA protein and mRNA is repressed by tumor-promoting phorbol esters through the PKC pathway. This indicates that the effects of TPA may be secondary to repressed gene transcription or altered mRNA stability. In addition, this study emphasizes that the androgenic regulation of PSA is complex and may involve other extracellular transduction signals.

Tissue-specific and hormonal regulation of human prostate-specific glandular kallikrein.

Kallikreins are involved in the posttranslational processing of a number of specific polypeptide precursors. Previously, human glandular kallikrein (hGK-1) mRNA has been identified in the prostate; however, the hGK-1 protein has not been identified and characterized. Therefore, its physiologic function in the prostate is not known. In this study, we have isolated a full-length hGK-1 cDNA from a human adenocarcinoma cell line, LNCaP. In vitro translation experiments demonstrated that the molecular size of the hGK-1 protein generated from this cDNA is similar to that of prostate-specific antigen (PSA), a protein which is produced exclusively in the prostate. In situ hybridization with a hGK-1-specific oligonucleotide probe (77 bases), which can differentiate hGK-1 mRNA from PSA mRNA, demonstrated the hGK-1 mRNA to be located in the prostate epithelium. The hGK-1 mRNA was colocalized with PSA mRNA in prostatic epithelia. Moreover, in situ hybridization studies revealed that the level of hGK-1 mRNA in human benign prostatic hyperplasia tissues is approximately half that of PSA mRNA. Furthermore, we have demonstrated that hGK-1 mRNA is under androgenic regulation in LNCaP cells. Time course analysis revealed that hGK-1 mRNA levels increased significantly at 5 h of mibolerone treatment and reached maximal levels by 9 h. In addition, hGK-1 mRNA levels were increased by dihydrotestosterone, but not by dexamethasone or diethylstilbestrol treatments. Flutamide, a nonmetabolized anti-androgen, repressed the androgenic effects. These studies suggest that expression of hGK-1 mRNA is regulated by androgen via the androgen receptor.

Hormonal regulation of prostate-specific antigen (PSA) glycoprotein in the human prostatic adenocarcinoma cell line, LNCaP.

Prostate-specific antigen (PSA) has emerged as the most useful marker for management of patients with prostate cancer. The regulation of this glycoprotein in vivo has important clinical implications. Indirect evidence indicates that the PSA glycoprotein might be regulated by androgens, and previous studies in this laboratory have demonstrated that PSA mRNA is upregulated by androgens. The current work reports a detailed study of PSA glycoprotein expression as influenced by steroid hormones in a human prostatic adenocarcinoma cell line, LNCaP. First, we have examined the steroid binding specificity of the androgen receptor in this cell line. In comparison with wild-type rat androgen receptor in prostate, the receptor in LNCaP cells has altered affinity for a number of steroids or analogs such as progesterone (R5020), antiprogesterone (RU486), two antiandrogens (cyperoterone acetate and hydroxyflutamide), and an androgen metabolite (epitestosterone). However, its affinity for androgens (mibolerone, dihydrotestosterone, and testosterone) is not changed. The receptor does not bind to the synthetic glucocorticoids (triaminolone acetonide and dexamethasone) nor to a synthetic estrogen DES (diethylstilbestrol). The change of the steroid binding specificity of the receptor is correlated with a single mutation (A----G at nucleotide #876 relative to the initiation codon) of the steroid binding domain of the receptor. The mutation and alteration of steroid-binding specificity of the androgen receptor is also correlated with PSA glycoprotein expression affected by different ligands tested. We have demonstrated that the PSA glycoprotein is upregulated by androgens and is affected by neither epidermal growth factor nor basic fibroblast growth factor. Moreover, PSA glycoprotein could be induced by R5020, estradiol, and epitestosterone; but neither glucocorticoids nor DES had any effect on PSA induction. Interestingly, although the antiandrogen, cyperotone acetate, had the ability to induce PSA, both RU486 and hydroxyflutamide could block androgen and progesterone induction of PSA glycoprotein. Therefore, we conclude that the PSA glycoprotein expression is influenced predominantly by androgens via its receptor, and the mutation of the receptor can affect the expression of this cellular gene by the steroids other than androgens.

Squamous cell carcinoma of the scrotum: long-term followup of 14 patients.

Squamous cell carcinoma of the scrotum was diagnosed in 14 patients from 1945 to 1990. Patient age at diagnosis ranged from 40 to 73 years, with the mean age of 62 years. The most common presentation was a solitary skin lesion but inguinal adenopathy was noted in 5 patients (36%). The mean delay to diagnosis for all patients was 22 months, with a range of 2 months to 10 years. Predisposing factors included psoriasis treated with coal tar or arsenic, human papillomavirus infection and multiple cutaneous epitheliomas. The primary lesion was treated by local or wide local excision in all 14 patients. In addition, 4 patients underwent inguinal lymphadenectomy and 3 underwent radiotherapy to the pelvic and inguinal lymph nodes. Mean followup for all patients was 6 years. However, 11 patients were disease-free with a mean followup of 7 years. Improved prognosis was noted in patients with locally confined disease or carcinoma in situ only. There was no correlation between grade of tumor and survival. All patients with stages A1 and B disease treated with wide local excision and/or inguinal lymphadenectomy have done well on followup. Radiotherapy does not appear to impact on survival for patients with high stage disease.

Renal pelvic explosion during conservative management of upper tract urothelial cancer.

Ureteroscopic fulguration of a renal pelvic papillary transitional cell carcinoma is a relatively new and limited procedure. We present a case of intrarenal explosion during ureteroscopic fulguration.

Hormonal regulation of prostate-specific antigen messenger RNA in human prostatic adenocarcinoma cell line LNCaP.

Prostate-specific antigen (PSA) is a member of the kallikrein gene family and is expressed exclusively in human prostatic epithelial cells. PSA protein has been an important biological marker for prostate cancers. Until now, very little was known about the regulation of PSA expression in prostatic cells. In this study, we have developed a specific oligonucleotide probe which recognizes PSA but not the human glandular kallikrein. This is crucial because both PSA and human glandular kallikrein are expressed in the prostate at relatively high levels and have high nucleotide sequence homology (greater than 82%). Utilizing a S-labeled PSA-specific probe, PSA mRNA was localized within the glandular epithelium of the prostate. Northern blot analysis detected a single 1.6-kilobase transcript in LNCaP cells, a cell line derived from a human prostate adenocarcinoma metastasis. Therefore, LNCaP cells were used to study the androgenic effects on PSA mRNA expression. A time course study demonstrated that PSA mRNA was induced by mibolerone (a nonmetabolizable synthetic androgen) and reached maximal levels after 9 h. The induction of PSA mRNA required as little as 0.3 nM mibolerone. In addition to mibolerone, PSA mRNA could be induced by the natural androgen, dihydrotestosterone, but not by the synthetic glucocorticoid, dexamethasone, or the synthetic estrogen, diethylstilbestrol. Moreover, in the presence of dihydrotestosterone, PSA mRNA was depressed by hydroxyflutamide (an antiandrogen). These results suggest strongly that the androgenic effects on PSA mRNA in LNCaP cells may be via the function of the androgen receptor.

Endoscopic laser arytenoidectomy for the treatment of bilateral vocal cord paralysis.

Most patients with bilateral vocal cord paralysis have a fairly satisfactory voice, but their airway is usually compromised. The management of such patients presents a challenge to the otolaryngologist-head and neck surgeon. Numerous surgical procedures have been developed in an attempt to improve the patients's airway insufficiency without leaving him with a breathy, weak voice. Arytenoidectomy is currently the most reliable method of treating patients with bilateral vocal cord paralysis. Although both endoscopic and external approaches have been described for performing an arytenoidectomy, the endoscopic technique is more desirable since it requires no incision and theoretically allows for the immediate assessment of airway size. The addition of the CO2 laser to the surgical armamentarium offers certain refinements to the technique of endoscopic arytenoidectomy. Eleven patients with bilateral vocal cord paralysis of the larynx have been treated by endoscopic laser arytenoidectomy by the authors utilizing a technique developed by the two senior authors and subsequently taught to over 200 participants of the CO2 laser workshops sponsored by the Department of Otolaryngology-Head and Neck Surgery at Northwestern University Medical School; 10 of the 11 patients have been successfully decannulated. The technique and problems of this operation will be discussed.