Commentary on "Prognostic effect of carcinoma in situ in muscle-invasive urothelial carcinoma patients receiving neoadjuvant chemotherapy."

BACKGROUND: Carcinoma in situ (CIS) is a poor prognostic finding in urothelial carcinoma. However, its significance in muscle-invasive urothelial carcinoma (MIUC) treated with neoadjuvant chemotherapy (NAC) is uncertain. We assessed the effect of CIS found in pretreatment transurethral resection of bladder tumor (TURBT) biopsies on the pathologic and clinical outcomes. MATERIALS AND METHODS: Subjects with MIUC treated with NAC before cystectomy were identified. The pathologic complete response (pCR) rates stratified by TURBT CIS status were compared. The secondary analyses included tumor response, progression-free survival (PFS), overall survival (OS), and an exploratory post hoc analysis of patients with pathologic CIS only (pTisN0) at cystectomy. RESULTS: A total of 137 patients with MIUC were identified. TURBT CIS was noted in 30.7% of the patients. The absence of TURBT CIS was associated with a significantly increased pCR rate (23.2% vs. 9.5%; odds ratio = 4.08; 95% CI: 1.19-13.98; P = 0.025). Stage pTisN0 disease was observed in 19.0% of the TURBT CIS patients. TURBT CIS status did not significantly affect the PFS or OS outcomes. Post hoc analysis of the pTisN0 patients revealed prolonged median PFS (104.5 vs. 139.9 months; P = 0.055) and OS (104.5 vs. 152.3 months; P = 0.091) outcomes similar to those for the pCR patients. CONCLUSION: The absence of CIS on pretreatment TURBT in patients with MIUC undergoing NAC was associated with increased pCR rates, with no observed differences in PFS or OS. Isolated CIS at cystectomy was frequently observed, with lengthy PFS and OS durations similar to those for pCR patients. Further studies aimed at understanding the biology and clinical effect of CIS in MIUC are warranted.

Clinical stage B non-seminomatous germ cell testis cancer: the Indiana University experience (1965-1989) using routine primary retroperitoneal lymph node dissection.

Between 1965 and 1989, 1180 patients at Indiana University, U.S.A., underwent retroperitoneal lymph node dissection (RPLND) for non-seminomatous germ cell (NSGC) testis cancer of whom 638 cases had primary RPLND. A subset of 174 cases were considered clinical stage B (or II) before surgery (retroperitoneal nodal metastases by clinical staging). Surgery revealed that 23% (n = 41) had pathological stage A disease (no cancerous nodes). This error rate in clinical staging has decreased somewhat with improved techniques, but remains approximately 20% over the last decade. The relapse rate in pathological stage A (n = 41) was 5% (n = 2), both of whom were cured by chemotherapy. The relapse rate in pathological stage B without postoperative adjuvant treatment (n = 54) was 35% (n = 19); 2 patients died. This indicates that 65% of pathological stage B cases were cured by RPLND alone. From 1979 to 1989, the 140 pathological stage B cases participated in a randomised prospective trial of post-RPLND adjuvant chemotherapy versus no postoperative treatment. Forty two per cent (n = 59) received postoperative platinum-based therapy (two cycles), and there has been no relapse after RPLND for stage B disease. While advances in chemotherapy for NSGC testis cancer have led to its application by several study groups to clinical stage B (or II) testis cancer (with surgery reserved only for those in partial remission), the equivalent cure rate with RPLND surgery with chemotherapy rescue reserved for those who relapse appears to have both cost and risk-benefit advantages.

Local synthesis of amyloid fibril precursor in AL amyloidosis of the urinary tract.

An amyloid tumor localized to the urethra was resected and shown by immunohistochemistry to contain fibril deposits that stained with antisera specific for lambda VI immunoglobulin light chain. The amino acid sequence of the fibril protein was homologous to lambda VI Positive staining of subepithelial plasma cells with lambda VI specific monoclonal antibody was consistent with the hypothesis that the fibril precursor light chain protein is synthesized and processed locally to give this type of localized amyloidosis.

An alternative surgical technique for the management of afferent limb structure in Kock pouch continent urinary diversion.

Stenosis of the afferent limb has recently been recognized as a rare cause of upper urinary tract obstruction in patients with a Kock pouch continent urinary diversion. Usually, it can be managed by endoscopic balloon dilation but occasionally open surgical reconstruction is required. We describe an alternative simpler surgical technique that was used in a patient who presented with anuria due to afferent limb stenosis 13 years after the construction of a Kock pouch continent urinary diversion.

Early urethral catheter removal following radical prostatectomy: a pilot study.

OBJECTIVES: Postoperative urethral catheter drainage after radical prostatectomy is bothersome to patients. A pilot study was initiated to determine if urethral catheter removal prior to hospital discharge is feasible. METHODS: Thirty-three consecutive men undergoing radical retropubic prostatectomy were prospectively studied and followed for a minimum of 6 months (mean, 8.5). Postoperative cystography was utilized to direct early catheter removal. RESULTS: Of 33 patients, 27 (82%) underwent successful catheter removal at a mean of 4.2 postoperative days. No patient experienced urinary retention, urinoma development, pelvic abscess, or anastomotic stricture. Urinary continence is excellent (no pads required) in 70% and good (stress incontinence requiring 1 to 2 pads/24 hours) in 18% of patients at last follow-up. CONCLUSIONS: Following radical prostatectomy, early catheter removal prior to hospital discharge is feasible. Early results suggest no deleterious consequences. Prospective monitoring of more patients is needed to determine if this practice is widely applicable.

Urethral catheter removal prior to hospital discharge following radical prostatectomy.

OBJECTIVES: To investigate the feasibility of early catheter removal following radical prostatectomy. METHODS: Fifty-eight consecutive patients underwent radical prostatectomy, with intent of early catheter removal. Catheter removal was based on postoperative cystograms performed on postoperative day (POD) 3 or 4. Charts were retrospectively reviewed and patients were contacted by phone and specifically questioned regarding continence and bladder control. RESULTS: Fifty-one patients (87.9%) had a cystogram performed on POD 3 or 4. In 43 patients (74.1%), the catheter was successfully removed prior to hospital discharge. Eight patients experienced either early or late complications (excluding incontinence); these included 3 patients with a superficial wound infection, 2 patients with hematuria requiring reinsertion of a urethral catheter, 1 patient with a spontaneous pneumothorax, 1 patient who developed a deep vein thrombosis and lymphocele, and 1 patient with a bladder neck contracture. Urinary continence was reported as excellent to good in 86% of the patients at a mean follow-up of 17.4 months. Three patients (5%) underwent placement of an artificial urinary sphincter. CONCLUSIONS: Catheter removal prior to hospital discharge after radical prostatectomy is feasible without any increase in morbidity.

Genital Fournier's gangrene: experience with 38 patients.

OBJECTIVES: Fournier's gangrene (FG) is an extensive fulminant infection of the genitals, perineum, or the abdominal wall. We report our experience with the management of this difficult infectious disease. METHODS: Thirty-eight patients were admitted with the diagnosis of FG between May 1993 and May 1995. All patients were treated with broad-spectrum triple antimicrobial therapy, broad debridement, exhaustive cleaning, and application of unprocessed honey dressings. Patients then underwent split-thickness skin grafts or delayed closure as needed. RESULTS: Patient ages ranged between 33 and 86 years (mean, 54) with a mean hospital stay of 17 days (range, 1 to 45). Sixty-six percent of the patients were diabetic, 16% had previous orchiepididymitis, and 5% had scrotal and urethral trauma. All the patients underwent surgical debridement and application of unprocessed honey to the wound. Cystostomy was performed in 60% of the patients and 21% underwent orchiectomy of the affected side. Free skin grafts were applied to 6 patients (16%) and the remaining wounds, once clean, were approximated. One patient died as a result of severe metabolic acidosis and sepsis. CONCLUSIONS: The management of this infectious entity should be aggressive. Patients with FG need extensive debridement and cystostomy or colostomy when necessary. Broad-spectrum triple antimicrobial regimen and aggressive debridement are mandatory. Topical application of unprocessed honey is beneficial to the healing process. A minority of patients require split-thickness skin grafts on denuded areas.

Amebiasis of the penis.

Penile amebiasis is rarely a recognized entity because the penis is not the usual site of presentation for amebiasis. Homosexual men have a higher risk of acquiring the lesion. Amebic ulcers resemble cutaneous lesions arising from squamous cell carcinoma, chancroid, primary syphilis, granuloma inguinale, and many other causes. An amebic ulcer should be suspected in a patient with balanoposthitis that resists antibiotic therapy. Biopsy is fundamental to isolate the trophozoites to confirm the diagnosis. Metronidazole and hydrochloric emetine are still the treatment of choice. This diagnosis should especially be considered in cases of lesions detected in patients who practice anogenital sex or who are immunocompromised.

Transverse colon-gastric tube composite reservoir.

We describe our technique for a new form of continent urinary diversion. This reservoir includes a detubularized segment of transverse colon to provide low pressure urine storage, tunneled ureteral reimplants to prevent reflux, and a tubularized gastric segment used as a continent catheterizable efferent limb. This technique provides a new option for continent diversion in a variety of patients.

Cystography after radical retropubic prostatectomy: clinical implications of abnormal findings.

OBJECTIVES: In many institutions, cystography is obtained routinely after radical retropubic prostatectomy to assess the integrity of the vesicourethral anastomosis before the removal of the catheter. This study presents the Indiana experience with cystograms performed following radical retropubic prostatectomy. METHODS: The experience with 260 cystograms performed in 245 consecutive patients following radical retropubic prostatectomy was reviewed retrospectively, with a special reference to the clinical implications of abnormal findings. RESULTS: After a standard catheterization period of 14 to 21 days (mean, 19.2), 94.3% of the catheters were removed safely without adverse clinical consequences. The presence of a minimal contained contrast extravasation did not affect outcome after the removal of the catheter. The overall incidence of clinically significant extravasation was found to be 5.7% and was further reduced to 2.4% if extravasation was not suggested clinically in the postoperative course. CONCLUSIONS: Based on the current literature, significant extravasation is a common finding during the first 5 to 8 postoperative days. Therefore, management strategies advocating early urethral catheter removal should include routine cystographic studies. Otherwise, cystographic confirmation of anastomotic integrity before the removal of the catheter following 14 to 21 days of catheterization is not indicated in the routine postradical prostatectomy patient.

Ectopic ureters and ureteroceles in adults.

Ectopic ureters and ureteroceles are typically diagnosed in childhood and rarely present in adults. Nevertheless, ureteral ectopia should be included in the differential diagnosis of older patients who present with urinary tract infections or urinary incontinence. Detection is often delayed because of inadequate evaluation and heightened awareness is necessary on the part of treating physicians. Earlier detection and proper diagnosis serves to minimize morbidity and, in some cases, may maximize the possibility of renal preservation. Case reports serve to highlight the spectrum of these uncommon but clinically important anomalies.

High-intensity focused ultrasound in the treatment of prostatic tissue.

OBJECTIVE: Beginning in 1987, high-intensity focused ultrasound was investigated in the canine model to determine the feasibility of destroying prostate tissue. After demonstrating the ability to ablate prostate tissue reliably in a canine model, a 15-patient pilot clinical study was undertaken at Indiana University in the fall of 1992. This pilot study was undertaken to assess the safety in the human clinical situation, as well as to give some early efficacy results. METHODS: The early canine feasibility studies were conducted via a suprapubic extracorporeal approach using two separate transducers, one for imaging and the other for therapy. Subsequent to this, a transrectal probe, which had the dual capability of both imaging and therapy, was developed and used to treat canine prostates in a formal, "good laboratory practice" study to determine the safety of this technology prior to beginning treatment of human benign prostatic hypertrophy. RESULTS: The formal canine studies demonstrated that prostatic tissue could be reliably ablated in the therapy zone. The dosimetry and duty cycle required to ablate canine prostatic tissue effectively was also determined in this study. The study also demonstrated that the prostatic tissue could be ablated without injury to the intervening rectal tissue or periprostatic tissue. The human pilot study has also demonstrated safety of high-intensity focused ultrasound, as well as early efficacy. CONCLUSIONS: These early clinical results are encouraging, but assessment of efficacy will require a randomized study comparing high-intensity focused ultrasound to sham and to transurethral prostatectomy. This multicenter trial is currently planned.

Mohs' micrographic surgery and distal urethrectomy with immediate urethral reconstruction for glanular carcinoma in situ with significant urethral extension.

OBJECTIVES: To report the use of conservative extirpative surgical techniques to manage glanular carcinoma in situ with significant urethral extension. METHODS: Over a 5-year period, 2 patients with carcinoma in situ of the glans with significant distal urethral involvement, who refused penectomy, were managed with combined treatment modalities using Mohs' micrographic surgery and distal urethrectomy with immediate urethral reconstruction. RESULTS: At follow-up of 5 years and of 12 months, there has been no evidence of meatal or proximal urethral recurrence. CONCLUSIONS: Mohs' micrographic surgical excision and distal urethrectomy with immediate urethral reconstruction offers an acceptable alternative to partial penectomy in patients with perimeatal carcinoma in situ who fail conservative treatment or refuse penectomy.

Use of magnetic resonance imaging to determine surgical approach to renal cell carcinoma with vena caval extension.

Extension of renal cell carcinoma into the vena cava is found in 4 to 10 percent of patients. One key to successful surgical management is defining the superior extent of the thrombus. Currently, this is accomplished by using inferior venacavography. The limitations of this imaging technique include difficulty in defining the superior extent of the thrombus and determining the presence of hepatic vein involvement. We report our experience using magnetic resonance imaging (MRI) in 9 patients to stage the thrombus and to determine the operative approach. We believe that MRI supplants other imaging techniques for staging tumor thrombi in renal cell carcinoma.

Testicular ultrasonography after chemotherapy for germ cell neoplasm: significance of highly hyperechoic lesions.

The sonographic appearance of the testis after administration of chemotherapy for metastatic germ cell neoplasm is not well known. Fifty-six patients (60 testes) who were previously treated with chemotherapy for metastatic germ cell neoplasm (originally diagnosed by removal of the contralateral testis or by biopsy of metastatic disease) underwent sonography followed by orchiectomy. The sonographic characteristics found to predict viable intratesticular tumor were: lesion size larger than 5 mm, fewer echoes than adjacent parenchyma (hypoechoic), inhomogeneous echo texture, poor margin definition, cystic areas, or highly hyperechoic foci within a hypoechoic lesion. Fibrosis was predicted by finding single or multiple small, highly hyperechoic lesions. These results suggest the potential for predicting the pathologic diagnosis in some patients after receiving chemotherapy for germ cell neoplasm.

Postchemotherapy retroperitoneal lymph node dissection is effective therapy in selected patients with elevated tumor markers after primary chemotherapy alone.

OBJECTIVES: Elevated tumor markers after primary chemotherapy for metastatic testis cancer are usually an indication of persistent cancer. Subsequent treatment has usually been salvage chemotherapy. This article examines the possibility that selected patients can achieve long-term disease-free survival with surgery alone. METHODS: Using a computerized data base of 627 postinduction chemotherapy retroperitoneal lymph node dissections (PC-RPLND), 23 patients with elevated tumor markers who have undergone PC-RPLND after induction chemotherapy alone were identified. Of the 23 patients, 15 were considered candidates for salvage chemotherapy, but instead underwent salvage surgery. Case histories were reviewed to establish selection criteria for PC-RPLND. RESULTS: Eight patients originally presented as clinical Stage C, 6 as clinical Stage B-3, and 1 as clinical Stage B-2. All patients initially received cisplatin combination chemotherapy. Twelve patients had an elevated alpha-fetoprotein level and 3 patients had an elevated beta human chorionic gonadotropin level prior to PC-RPLND. Seven patients had rising markers at the time of PC-RPLND. Seven patients had teratoma only in their resected specimen and all have no evidence of disease (NED) at a median of 35 months. Two patients had necrosis only in their RPLND specimen and both are NED at 10 and 42 months. Six patients had cancer in their resected specimen and 2 are NED, 1 is alive with disease, and 3 are dead of disease. Five of the 6 patients with cancer in their resected specimen were the only patients who received postoperative chemotherapy. CONCLUSIONS: Some patients with modest elevations of tumor markers after induction chemotherapy may only have teratoma or necrosis in the postchemotherapy resected specimen. These patients (n = 9) remain continuously NED. Patients who undergo salvage surgery and have cancer in the resected specimen do less well, but selected patients can be cured with this modality and thus avoid the morbidity of salvage chemotherapy.

The Indiana pouch continent urinary reservoir.

The right colon reservoir using a stapled plicated ileal efferent limb (Indiana continent urinary reservoir) has been demonstrated to be a reproducible durable form of continent diversion. The overall day and nocturnal continence rate of 94% compares favorably with all other forms of continent cutaneous diversion. Carefully following the technique of stapling and plicating the ileal efferent limb and ileocecal valve as described in this article nearly ensures adequate competence of the outlet valve. In the rare case in which incontinence occurs, it is almost always on the basis of high-pressure unit contractions of the reservoir. On occasion, patients who develop incontinence are observed to have high pressures within the reservoir despite complete detubularization of the right colon segment. When this problem is encountered it can be corrected successfully by adding an ileal patch augmentation to the previously detubularized reservoir. The issue of ureteral implantation in continent urinary diversions is as yet unsettled. Many authors have not used ureteral tenial tunnels and have reported a reflux rate of < 13%. Furthermore, these patients have not developed any long-term sequelae of their reflux. Although favorable results have been obtained without creating tunneled tenial reimplantation, we believe that continent cutaneous reservoirs are almost always colonized with bacteria, and an antireflux mechanism may offer protection against subsequent pyelonephritis. Closure of the reservoir traditionally has been conducted by hand at our institution; however, the development of smaller absorbable gastrointestinal anastomosis stapling devices offers the theoretic advantage of shortening the operative time. We anxiously await follow-up, including larger patient numbers and longer term follow-up of the absorbable staple technique. The use of continent cutaneous urinary diversion clearly has decreased as bladder replacement has become a more viable procedure over the past decade. Despite this, the urologic reconstructive surgeon must maintain the ability to perform continent cutaneous diversion in patients who are unwilling to accept the potential for nocturnal incontinence observed in all forms of bladder replacement as well as the patients who have ineffective sphincter mechanism or who need a urethrectomy due to their primary disease.

Complications of retroperitoneal lymph node dissection.

In summary, the complications of retroperitoneal lymph node dissection for low-stage testis cancer appear to be minimal, especially with the advent of nerve sparing techniques. However, the approximate 30 per cent of patients who require primary chemotherapy and do not attain a complete remission are candiates for postchemotherapy retroperitoneal lymphadenectomy, and these patients are subject to a higher risk of intraoperative and postoperative complications. Maintaining awareness of these potential complications may aid in preventing morbidity in this group of patients.

Alternative techniques for a continent urinary reservoir.

A modification of the Gilchrist procedure is used to create a continent urinary reservoir that provides reliable continence and antireflux mechanisms. The tubular form of the cecum is altered by a patch or reconfiguration to prevent bolus contractions of the reservoir. The procedure offers a choice of locations of the reservoir and stoma in most patients. Each step of the procedure uses techniques already familiar to urologists.

Ultrasound and microbubbles: their generation, detection and potential utilization in tissue and organ therapy--experimental.

Ultrasound-induced cavitation in tissue and organs has been well recognized and documented. Generally, this phenomenon has been seen as something to be avoided except in cases such as lithotripsy, where its production is considered an essential part of the treatment process or as a desirable contrast media in some areas of visualization enhancement. This article covers three areas in which the phenomenon has been observed, and shows how the effect can or may be therapeutically beneficial. Studies in the pig show that implanted human gallstones and the gallbladder itself can be eliminated in a nonsurgical procedure using ultrasound-induced cavitation in the gallbladder. In the dog brain, relatively stable cavitation-induced microbubbles have been transported through the vascular system to regions outside a focal seeding site. These bubbles produce ablation of tissue volumes at a remote site when irradiated with appropriate ultrasound. The cavitation phenomenon has been observed in the dog and human prostate. In the human prostate, microbubbles transported from ultrasound-induced focal seeding sites can be readily visualized with ultrasound and may be potentially useful under controlled conditions in tissue debulking for the treatment of benign prostatic hyperplasia (BPH). A similar microbubble transport has not been seen in the dog prostate under similar ultrasound treatment parameters. The ability to detect cavitation-induced microbubbles, follow their transportation through the vascular system and excite them at the appropriate time and place provides interesting possibilities for therapy. Of course, the entire microbubble process can be avoided by working below the cavitation threshold, thereby using only the absorption of ultrasound in tissue to produce focal thermal lesions. The term microbubble is used here in the context of those bubbles which can be transported in the vascular system down to vessels diameters below the 100-microns range. This is the vessel size in the vascular field into which microbubbles are transported and can be both visualized as well as disrupted with ultrasound.