Early growth response-1 gene: potential radiation response gene marker in prostate cancer.

This study was undertaken to determine whether the transcription factor EGR-1 expression: (1) in the primary tumor, correlates with radiation response in terms of complete local tumor control with no evidence of disease or recurrence and no evidence of metastasis; (2) in the postirradiated biopsies correlates with residual tumor; and (3) correlates with the expression of Egr-1 target genes such as TP53, pRB, and Bax. The authors analyzed: (1) 25 pretreated surgically resected paraffin-embedded primary adenocarcinomas of the prostate for the presence of EGR-1 expression and mutation, and correlated this with clinical endpoints such as serum prostate-specific antigen levels and current clinical status; (2) 27 postirradiated biopsies of prostate for the presence of EGR-1 expression, and correlated these findings to the residual tumor status; and (3) 12 prospective prostate tumor specimens for EGR-1 expression and its target genes. EGR-1 expression was determined by immunohistochemistry and mutations were screened in two regions of the Egr-1 gene (trinucleotide AGC repeats in transactivation domain [TD] and poly A tract in 3'UTR) by polymerase chain reaction-single strand conformational polymorphism analysis. Of 25 patients, 18 patients showed expression of EGR-1. EGR-1 overexpression correlated with treatment failure. No correlation with EGR-1 overexpression and its target genes was found, which may indirectly suggest that overexpressed EGR-1 may lack transactivation function. In summary, EGR-1 overexpression in the mutant form may provide an indication of clinical failure (local recurrence or metastasis).

Bladder cancer clinical guidelines panel summary report on the management of nonmuscle invasive bladder cancer (stages Ta, T1 and TIS). The American Urological Association.

PURPOSE: The American Urological Association convened the Bladder Cancer Clinical Guidelines Panel to analyze the literature regarding available methods of treating nonmuscle invasive bladder cancer, and to make practice policy recommendations based primarily on treatment outcomes data. MATERIALS AND METHODS: The panel searched the MEDLINE database for all articles related to nonmuscle invasive bladder cancer published from 1966 to January 1998. Outcomes data were extracted from articles accepted after panel review and meta-analyzed to produce comparative probability estimates for alternative treatments. RESULTS: All of the intravesical agents (thiotepa, bacillus Calmette-Guerin, mitomycin C and doxorubicin) when used as adjuvant therapy after transurethral resection resulted in a lower probability of recurrence compared to resection alone. However, there is no evidence that intravesical therapy affects long-term progression. CONCLUSIONS: For patients with no prior intravesical therapy adjuvant intravesical chemotherapy or immunotherapy is a treatment option after endoscopic removal of low grade Ta bladder cancers. Intravesical instillation of bacillus Calmette-Guerin or mitomycin C is recommended for carcinoma in situ, and after endoscopic removal of T1 and high grade Ta tumors.

Combined post-chemotherapy retroperitoneal lymph node dissection and resection of chest tumor under the same anesthetic is appropriate based on morbidity and tumor pathology.

PURPOSE: We determine if post-chemotherapy resection of residual retroperitoneal and chest tumor under the same anesthetic is reasonable based on tumor pathology and morbidity, and if the finding of necrosis in the abdomen allows observation of chest tumor. MATERIALS AND METHODS: We retrospectively reviewed 143 post-chemotherapy patients who underwent resection of residual retroperitoneal and chest disease under the same anesthetic. RESULTS: Retroperitoneal pathology was generally predictive of chest pathology. Concordance existed in 77.5% of patients with necrosis, 70% with teratoma and 69% with cancer of the abdomen. However, the correlation was much stronger (86%) in predicting necrosis/fibrosis if cases were categorized as uncomplicated by Indiana University criteria. Although the morbidity of the combined approach is higher than that of standard post-chemotherapy retroperitoneal lymph node dissection, it was acceptable. CONCLUSIONS: The morbidity of post-chemotherapy retroperitoneal lymph node dissection and resection of chest disease under the same anesthetic is acceptable. Retroperitoneal pathology generally predicts chest pathology but this correlation is much stronger if the case is uncomplicated based on our criteria. In an uncomplicated case the discovery of necrosis of the abdomen allows observation of chest tumor.

En bloc nephrectomy in patients undergoing post-chemotherapy retroperitoneal lymph node dissection for nonseminomatous testis cancer: indications, implications and outcomes.

PURPOSE: We review the indications for nephrectomy at post-chemotherapy retroperitoneal lymph node dissection, identify patients at risk for nephrectomy and assess the impact of nephrectomy on outcome. MATERIALS AND METHODS: Using a computerized data base and chart review we retrospectively reviewed the records of 848 patients who underwent retroperitoneal lymph node dissection after chemotherapy. RESULTS: En bloc nephrectomy was performed at retroperitoneal lymph node dissection after chemotherapy in 162 of the 848 patients (19%). The indications for nephrectomy included contiguous involvement of perirenal structures in 73% of the cases, renal vein thrombosis in 6%, a poorly functioning or nonfunctioning renal unit in 5% and a combination of these conditions in 16%. Pathological studies of the hilum revealed cancer in 20% of the cases, teratoma in 49% and fibrosis in 31%. Patients requiring nephrectomy had significantly more advanced disease and larger disease volume at presentation and after chemotherapy. There were no significant differences in perioperative morbidity or mortality compared with patients who did not undergo nephrectomy. Only 3 patients required perioperative dialysis and none required long-term renal support. CONCLUSIONS: These findings support en bloc nephrectomy at post-chemotherapy retroperitoneal lymph node dissection in select patients with large volume perihilar retroperitoneal disease.

Continent cutaneous urinary diversion.

Using the case history of a 57-year-old woman with a G3 T1 bladder cancer as a reference point, general considerations on tumor biology and therapeutic choices are reviewed. Options for urinary tract diversion or reconstruction are presented. This author recommends radial cystectomy for this patient with continent cutaneous urinary diversion, the Indiana pouch. Important technical points of the surgical procedure are emphasized.

[The Indian pouch as an orthotopic reservoir]. / L'indiana pouch come reservoir ortotopico.

Patients undergoing this procedure should be strongly motivated and should have normal or near-normal bowel function. A reservoir is made using an 18-20 cm segment of terminal ileum, caecum and ascending colon. The ureters are implanted along the taenia of the ascending colon. The result is a neo-bladder that is close to the ideal ellipsoid shape. The stapling technique used decreases operating time and the detubularisation maintains low pressure in the neo-bladder. Although the operation has so far been performed on only 10 patients results have been very favourable and it has proved to be a useful alternative form of diversion.

[The Indiana pouch continent cutaneous urinary diversion]. / Derivazione urinaria cutanea continente indiana pouch.

Initially, the procedure was simply an ileo-caecal segment, as it was thought that peristalsis of the terminal ileum and the ileo-caecal valve accounted for continence. The Rowland group made some modifications, using 8-10 cm of terminal ileum and 30 cm of caecum and ascending ileum. By constructing an efferent limb using staples, a highly reliable continence mechanism is created. The absorbable staples reduce the operating time by about 1 hour and make the been operated on using these staples, and no problems with stones or infections have been encountered, with only 2 patients reporting fragments of staples in their urine.

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.

Nerve sparing post-chemotherapy retroperitoneal lymph node dissection for advanced testicular cancer.

PURPOSE: Nerve sparing techniques are used routinely during retroperitoneal lymph node dissection in patients with low stage testis cancer in an attempt to preserve postoperative ejaculation. Preservation of ejaculation without an increased retroperitoneal recurrence rate in such patients prompted us to reevaluate the role of nerve sparing techniques in select patients undergoing post-chemotherapy retroperitoneal lymph node dissection. MATERIALS AND METHODS: Of 472 patients who underwent post-chemotherapy retroperitoneal lymph node dissection between March 1988 and January 1995, 93 (19.7%) underwent a nerve sparing procedure. Two patients died of disseminated cancer within 6 months after post-chemotherapy retroperitoneal lymph node dissection. In 10 patients the ejaculatory status could not be established from the clinical notes and the patient was lost to followup. The remaining 81 patients form the basis of this report. Disease status, complications and ejaculatory status were evaluated. Mean followup was 35.5 months. RESULTS: Of the patients 76.5% reported normal ejaculation after post-chemotherapy retroperitoneal lymph node dissection. Testis cancer recurred after nerve sparing surgery in 6 patients but no tumor was retroperitoneal. Ten pregnancies have been reported to date with uneventful term deliveries in 7. CONCLUSIONS: Select patients are candidates for nerve sparing post-chemotherapy retroperitoneal lymph node dissection. Although indications for nerve sparing techniques in the post-chemotherapy population have expanded, the local recurrence rate has not increased. Nerve sparing post-chemotherapy retroperitoneal lymph node dissection can preserve the inherent fertility potential of the patient without increasing retroperitoneal relapse rates.

Post-chemotherapy resection of nonseminomatous germ cell testicular tumors metastatic to the mediastinum.

PURPOSE: We determined if the behavior of germ cell tumors metastatic to the mediastinum is different from that of primary mediastinal germ cell tumors, a group known to have distinct clinical features. MATERIALS AND METHODS: A search of the computerized data base for germ cell tumors metastatic to the mediastinum at our university revealed 80 patients, 65 of whom underwent concomitant retroperitoneal lymph node dissection at mediastinal surgery. RESULTS: Of the patients 60 (75%) are free of disease, 14 (18%) died of cancer and 6 (8%) are living with disease. Mediastinal pathology included teratoma in 65% of the patients, cancer in 26% and fibrosis in 9%. Of the 65 patients who underwent retroperitoneal lymph node dissection 75% had teratoma, 15% had fibrosis and 10% had cancer. Mediastinal relapses after dissection were rare (4 of 80 patients). CONCLUSIONS: Germ cell tumors metastatic to the mediastinum appear to behave similarly to those metastatic to the retroperitoneum. Primary mediastinal germ cell tumors have an entirely different clinical course. Teratoma is the predominant pathological type of post-chemotherapy germ cell cancer metastatic to the mediastinum.

The impact of pre-donated autologous blood and intra-operative isovolaemic haemodilution on the outcome of transfusion in patients undergoing radical retropubic prostatectomy.

OBJECTIVE: To assess the impact of pre-donated autologous blood and intra-operative isovolaemic haemodilution on the outcome of transfusions in patients undergoing radical retropubic prostatectomy. PATIENTS AND METHODS: The charts and transfusion records of 192 consecutive patients undergoing radical retropubic prostatectomy were reviewed retrospectively. RESULTS: Of 192 patients, 14% required homologous transfusions, the rate of which varied significantly depending upon blood availability (autologous, haemodilution or homologous) (P < 0.001): 66% of patients with only autologous blood available were transfused a mean of 1.96 units (range 1-6) of blood, of which 87% received autologous alone. 12% both autologous and homologous and 1% homologous blood only. Of the pre-donated autologous units, 44% were wasted. CONCLUSIONS: Both the pre-donation of autologous blood and intra-operative isovolaemic haemodilution lower the risk of homologous blood transfusion. It is recommended that patients pre-donate 2 units of autologous blood and undergo intra-operative isovolaemic haemodilution before radical prostatectomy.

Malignant testicular neoplasms in immunosuppressed patients.

PURPOSE: Testicular cancers were studied in patients on immunosuppression. MATERIALS AND METHODS: A retrospective analysis was done of testicular cancer in patients on immunosuppression reported on between 1975 and 1995. RESULTS: The management schemes adopted in the immunosuppressed population followed the generally accepted management concepts. No patient with low stage (A to B1) disease died of testis cancer. Only 4 of 66 patients (6.1%) with the acquired immunodeficiency syndrome died of testis cancer compared to 5 of 20 (25%) after transplantation, implying significantly higher cause specific mortality in post-transplant patients (Fisher's exact test, p < 0.01). The incidence of adverse effect of therapy did not differ from the expected incidence in other patients. CONCLUSIONS: Patients on immunosuppression with testicular neoplasms should be treated in the standard fashion as indicated by tumor histology and stage of disease, since most will tolerate therapy and benefit from the standard treatment protocols.

Delayed orchiectomy after chemotherapy for metastatic nonseminomatous germ cell tumors.

PURPOSE: We reviewed current experience at our university with delayed orchiectomy after chemotherapy in patients with metastatic nonseminomatous germ cell tumors. MATERIALS AND METHODS: We retrospectively analyzed the records of 160 patients with metastatic germ cell cancer who were given systemic chemotherapy, and subsequently underwent orchiectomy and retroperitoneal lymph node dissection. RESULTS: Analysis of 160 testicular specimens revealed necrosis or scar in 70 (43.7%), pure teratoma in 50 (31.2%) and persistent germ cell cancer in 40 (25%). Corresponding incidences of histopathological findings in the post-chemotherapy retroperitoneal lymph node dissection specimens were significantly different, correlating with less than half of the cases (chi-square, p = 0.002). CONCLUSIONS: Our study confirms the need for delayed orchiectomy after systemic chemotherapy even when there seems to be a partial or complete clinical response at other sites.

Present experience with the Indiana pouch.

The Indiana pouch was developed as a modification of the Glichrist procedure in 1984. The need for full detubularization of the reservoir was recognized early and was achieved by an ileal patch on the cecal reservoir or by an antimesenteric incision of the cecal segment with folding and transverse closure, the efferent limb and continence mechanism were modified to promote ease of catheterization and improved continence. These modifications gave markedly better results with lower reoperation rates. A group of 81 patients with a minimum of 2 years of follow-up are reported herein. The most recent modification uses absorbable GIA and TA55 staples to detubularize and close the reservoir. This stapling technique has been employed in 20 patients and has resulted in decreased operating times without any significant increase in complications. In its current form, the Indiana pouch meets all the criteria for a satisfactory continent cutaneous reservoir and has a favorable reoperation rate as compared with other pouches.