Late invasive recurrence despite long-term surveillance for superficial bladder cancer

Superficial transitional cell carcinoma of the bladder is associated with a 15 to 70% recurrence rate within 2 years. Most recurrences are superficial. A recurrence after 2 disease-free years is unusual. A review of the tumor registry revealed 124 patients followed for superficial disease at the Veterans Administration Center in Baltimore. Of the patients 20 were identified with either stage Ta (7) or stage T1 (13) papillary transitional cell carcinoma who had completed at least 5 years of surveillance without tumor recurrence. Invasive transitional cell carcinoma of the bladder requiring cystectomy developed in 7 of these 20 patients after remaining tumor-free for 5 years (stage Ta in 4 and stage T1 in 3). All 7 patients had organ-confined disease and were alive with no evidence of disease at 18 months to 5 years after cystectomy. These results demonstrate that superficial, low grade transitional cell carcinoma of the bladder can become muscle invasive despite careful surveillance and a long dormant period. In our series yearly cystoscopy and urine cytology identified tumor recurrence before metastases developed, suggesting that long-term surveillance is required in patients with superficial bladder cancer.     

Stromelysin 3 is overexpressed in human pancreatic carcinoma and regulated by retinoic acid in pancreatic carcinoma cell lines

OBJECTIVE: To develop a simple prognostic index for anticipating more precisely the early clinical course of primary superficial bladder cancer. PATIENTS AND METHODS: The prognostic value of patient and tumour characteristics was examined in 333 patients with primary Ta or T1 bladder cancer who participated in a multicentre prospective study already completed. Primary tumour multiplicity, a diameter of > 3 cm, stage T1, and grade 2 or 3 were independent predictors of earlier recurrence in a multivariate analysis. A simplified prognostic index consisted of the number of adverse tumour characteristics (ATCs) initially present. RESULTS: After a median follow-up of 35.3 months, the 60 patients free of ATCs (19%) had a recurrence-free probability at 12 and 24 months of 86% and 69%, respectively, and none experienced progression. Recurrence outcomes deteriorated consistently as the number of ATCs increased among the other three groups. In patients with 3-4 ATCs, the 12- and 24-month recurrence-free probability was as low as 30% and 19%, and recurrence and tumour rates were about 2.6 times higher than in patients free of ATCs; 7% of these patients experienced progression within 35 months of follow-up. CONCLUSION: A prognostic index based on the number of ATCs (primary tumour multiplicity, diameter > 3 cm, stage T1, and grade 2 or 3) is a strong indicator of the clinical course of superficial bladder cancer within 3 years of the first endoscopic resection. This proposal is suggested for discussion and for validation in future studies but if confirmed, this simple prognostic index may greatly help to identify indicators for adjuvant intravesical therapy and to determine the optimal periodicity of control cystoscopy regimens.     

Clinical vs haemodynamic response to drugs in portal hypertension

OBJECTIVE: Intercellular adhesion molecule-1 (ICAM-1) is known to play a role in immunity against bladder cancer and can be detected in the supernatants of cultured bladder cancer cells that constitutively express ICAM-1. This study was performed to examine the relevance of the ICAM-1 urine test in patients with bladder cancer. METHODS: A total of 53 patients with bladder carcinoma, 35 with history of bladder cancer, and 30 normal control subjects were included in this analysis. Urinary ICAM-1 (ulCAM-1) levels were measured by immunoassay and corrected for hydration status. RESULTS: Levels of ulCAM-1 were significantly elevated in patients with bladder cancer or those at tumor-free status compared with normal control subjects (P=0.001). However, there was no apparent difference between the two groups of urothelial disorders (P >0.1). ulCAM-1 did not correlate with clinicopathologic variables of bladder cancer or patient outcome (P >0.1). Six patients at tumor-free status had multiple ulCAM-1 determinations during the study period. Three of these 6 patients had elevated ulCAM-1 levels and proved to have recurrent tumors; 3 of the 6 had stable ulCAM-1 levels and were still free of disease. CONCLUSIONS: Our results suggest that urinary excretion of ICAM-1 is elevated in the early stage of bladder carcinogenesis, but is independent of biologic properties of bladder cancer. Serial monitoring of ulCAM-1 may be helpful in selecting patients who are at risk of tumor recurrence.     

Active specific immunotherapy for stage II and stage III human colon cancer: a randomised trial

BACKGROUND: Colon cancer is curable by surgery, but cure rate depends on the extent of disease. We investigated whether adjuvant active specific immunotherapy (ASI) with an autologous tumour cell-BCG vaccine with surgical resection was more beneficial than resection alone in stage II and III colon cancer. METHODS: In a prospective randomised trial, 254 patients with colon cancer were randomly assigned postoperative ASI or no adjuvant treatment. ASI was three weekly vaccinations starting 4 weeks after surgery, with a booster vaccination at 6 months with 10(7) irradiated autologous tumour cells. The first vaccinations contained 10(7) BCG organisms. We followed up patients for time to recurrence, and recurrence-free and overall survival. Analysis was by intention to treat. FINDINGS: The 5.3 year median follow-up (range 8 months to 8 years 11 months) showed 44% (95% CI 7-66) risk reduction for recurrence in the recurrence-free period in all patients receiving ASI (p=0.023). Overall, there were 40 recurrences in the control group and 25 in the ASI group. Analysis by stage showed no significant benefit of ASI in stage III disease. The major impact of ASI was seen in patients with stage II disease, with a significantly longer recurrence-free period (p=0.011) and 61% (18-81) risk reduction for recurrences. Recurrence-free survival was significantly longer with ASI (42% risk reduction for recurrence or death [0-68], p=0.032) and there was a trend towards improved overall survival. INTERPRETATION: ASI gave significant clinical benefit in surgically resected patients with stage II colon cancer. ASI has minimal adverse reactions and should be considered in the management of stage II colon cancer.     

Prognostic factors for loco-regional control and outcome of re-irradiation for patients with poorly-differentiated squamous cell carcinoma of the nasopharynx

Retrospective analysis was performed to evaluate the prognostic factors for loco-regional control and the results of re-irradiation for 28 patients with recurrent, poorly-differentiated squamous cell carcinoma (PDSCC) of the nasopharynx. Twenty-four of them received re-irradiation. Local, local plus regional and regional recurrences were observed in 19, five and four patients, respectively. Except for three patients, all had Stage IV disease at the initial diagnosis. The only parameters influencing loco-regional recurrence were T and N stage categories. The median latent period from initial treatment to recurrence was 18.5 (range, 2-100) months. There was no difference in latent period by first recurrence site, although recurrent tumors confined to the nasopharynx or those only regionally developed had a longer latent period. Only four patients developed secondary distant bone metastases with a median latency of three months from loco-regional relapse. The patients with local recurrent tumors confined to the nasopharynx, and those with regional recurrences only, could be salvaged by re-irradiation, with five-year survival rates of 44 and 100%, respectively. Five of 28 patients (18%) developed severe chronic radiation sequelae: cerebrospinal complications in four patients, bilateral neck fibrosis in one. We conclude that recurrent PDSCC of the nasopharynx can be controlled by re-irradiation with some success. Radiation therapy techniques must, however, be carefully planned in order to avoid the severe late post re-irradiation sequelae. For patients with advanced non-curable local recurrences, palliative care should be recommended instead of agressive re-irradiation.     

Conservative therapy for stage T1b, grade 3 transitional cell carcinoma of the bladder

OBJECTIVES: To retrospectively evaluate the usefulness of transurethral resection of bladder tumor (TURBT) and intravesical instillation for pT1bG3 transitional cell carcinoma of the urinary bladder. METHODS: Between May 1984 and May 1997, 45 patients with pT1bG3 transitional cell carcinoma of the urinary bladder underwent TURBT and intravesical instillation with bacillus Calmette-Guerin (BCG) or other anticancer agents. Random biopsy was carried out in 37 patients. The recurrence-free survival rate was determined by tumor size, number of tumors, lymphovascular invasion, and drugs used for intravesical instillation. The median follow-up period was 63 months (range 4 to 145) after the initial TURBT. RESULTS: Of 37 patients who underwent random biopsy, concomitant carcinoma in situ was detected in 18 patients (48.6%). The incidence of concomitant CIS was significantly higher in patients with multiple tumors (P = 0.029). Vesical recurrence was noted in 16 patients (35.6%). The overall 1-, 3-, and 5-year recurrence-free survival rates were 88.5%, 66.7%, and 66.7%, respectively. Progression (muscular invasion) occurred in only 2 patients (4.4%). Total cystectomy was performed in 4 patients, including the 2 patients with progressive disease, and 2 patients with recurrent CIS that resisted BCG therapy. None of the patients died of bladder cancer. CONCLUSIONS: Our results suggest that aggressive attempts at initial or subsequent TURBT combined with BCG therapy achieved good control of pT1bG3 transitional cell carcinoma of the urinary bladder.     

Expectant treatment of superficial bladder tumors: preliminary results]

A group of patients presenting with superficial bladder tumors (Ta-T1, G1-G3) was entered in a surveillance program following TUR. A standard univariative analysis was used to study tumor and patient prognostic factors to recurrence and progression. To define further the importance of each variable, a multivariative analysis was performed. Regardless of stage, grade and sex, patients with multiple tumors and/or size > or = 2 cm were particularly exposed to frequent recurrences. Early recurrences (before month 9) were associated with high recurrence rates. Considering the results of topical chemotherapy and toxicity of BCG immunotherapy, surveillance could be and option for superficial bladder tumors, reserving adjuvant therapy for large, multiple or early recurrence.     

Copper(II) as an efficient scavenger of singlet molecular oxygen

A retrospective study of DNA flow cytometry (FCM) in paraffin-embedded tissues of urinary bladder transitional cell carcinoma (TCC) was performed on 239 biopsy samples taken from 81 patients in the period from 1984 to 1994. 210 (87%) were analysable. Of these samples 21 patients had multiple biopsies taken from large tumours and/or bladder mucosa showing an endoscopically normal appearance. DNA-FCM results have been evaluated comparing ploidy and histopathological grade, clinical stage and different clinical status, i.e., first diagnosis, recurrence and patients who died from bladder cancer. Our results indicate that 'diploid' FCM correlated with a better prognosis, whilst DNA aneuploid correlated with malignancy and a poorer prognosis. There was a trend to an increasing incidence of DNA aneuploidy as the grade of the tumour rose and the proportion of biopsies with aneuploidy was significantly higher in malignant tissue samples, recurrences and in biopsies from patients who died from TCC than in other groups. In 12 patients from whom several biopsies were obtained, samples from recurrences had significantly higher DNA aneuploidy than those from the first diagnosis.     

Effects of oral glucose on intermediary metabolism in continuous ambulatory peritoneal dialysis patients versus healthy subjects

AIM OF THE STUDY: Retrospective analysis of result of radical cystectomy at Cochin Hospital. PATIENTS AND METHODS: We report the results of a 106 patients series treated by radical cystectomy for bladder carcinoma after a 5-year period follow-up. RESULTS: The extent of the tumour invasion according to pathological analysis was: pT1 or less: 26%, pT2 and pT3a: 33%, pT3b and over: 41%. Morbidity rate was 19% with a 7.5% reintervention rate. Long term complication rate was 31%, concerning essentially ureteral stenosis. A local recurrence or distant metastasis occurred in 35% of patients. Local recurrence rate was 10.7%. Cancer specific survival rates were 88%, 81% and 42% for pT1, pT2-pT3a, and pT3b patients respectively. CONCLUSION: The present results confirm that radical cystectomy is the most effective curative treatment for invasive bladder carcinoma.     

Patterns of recurrence of intussusception in children: a 17-year review

PURPOSE: Patterns of recurrence of intussusception (INT) were reviewed to determine whether changes in management have affected the rate and patterns of recurrence as well as long-term outcome in children with multiple (i. e., 2 or more) recurrences. MATERIALS AND METHODS: Review was done of 763 children with 876 intussusceptions, including (1) recurrence rate, (2) patterns of recurrence (number of and interval between recurrences), (3) reducibility, (4) pathologic lead points (PLP), (5) operative findings and (6) long-term follow-up in those with multiple recurrences. RESULTS: Above features (1)-(6) were the same in those managed with barium enema (1979-1985) and those managed with air enema (1985-1996). Overall recurrence rate was 9 %; 11 % with barium enema and 8 % with air enema. Sixty-nine patients had 113 recurrences: 47/69 (68 %) and 1 recurrence and 22/69 (32 %) had multiple recurrences. Multiple recurrences presented as isolated episodes or in clusters up to 8 years. Reducibility was 100 % for initial INT and 95 % for recurrent episodes; there were no perforations. Surgery, in 4 with irreducible recurrence, revealed no PLP. PLP were present in 5 (8 %): 2 (4 %) with 1 recurrence and 3 (14 %) with multiple recurrences. No pattern of recurrence was predictive for PLP. Long-term follow-up (up to 15 years) available in 11 with multiple recurrences revealed a favourable outcome. CONCLUSIONS: Rates and patterns of recurrence did not change with altered management. Because of the high reduction rate of recurrences, lack of perforation and favourable long-term follow-up, we recommend radiological reduction for recurrent INT. Multiple recurrences are not a contraindication. A careful search for PLP is mandatory. Surgery should be reserved for irreducible recurrences or for demonstrated PLP.     

Disease-free survival and recurrence after resection of colorectal carcinoma

Recurrence data from a series of 1,315 colorectal cancer patients managed by one surgeon with potentially curative resection are presented. Complete follow-up information was available on 1,287 (98%) patients. At the time of the last recurrences, 164 and 232 months for rectal and colonic tumours respectively, the long-time recurrence rate was significantly (P = 0.001) higher for rectal tumours (42%) than for colonic (33%). Although local recurrences tended to be more common in rectal than in colonic tumours (18% compared to 15%), only those in contiguity with the operative area were significantly (P less than 0.005) more common in rectal tumours. Systemic recurrences were also significantly (P less than 0.025) commoner for rectal tumours. The greater recurrence rates in rectal tumours were associated with significantly (P less than 0.001) higher incidence of stage C tumours shorter recurrence-free survival in rectal stage C tumours (P = 0.001) and higher incidence of pulmonary metastases (P less than 0.001).     

The prevalence of verbal communication disability in patients with Parkinson''s disease

BACKGROUND: We evaluated and compared the efficacy and safety of sertraline and fluvoxamine in a randomized, double-blind, parallel-group study during a follow-up of 24 months. METHOD: Sixty-four patients with recurrent, unipolar depression (DSM-IV criteria) who had at least one depressive episode during the 18 months preceding the index episode were accepted into the trial. Patients were randomly assigned to one of the two long-term treatment groups and evaluated monthly by trained psychiatrists, blinded to treatment option, on the basis of the Hamilton Rating Scale for Depression. RESULTS: All patients completed the 24-month follow-up period. Sertraline and fluvoxamine showed an equal efficacy in preventing new recurrences. In fact, there was no significant difference in survival rates between the two medication groups: 7 sertraline-treated patients (21.9%) and 6 fluvoxamine-treated patients (18.7%) had a single new recurrence (z = 0.14; p = .88). Moreover, recurrence observed during maintenance therapies was less severe and/or of shorter duration than index episodes. CONCLUSION: Long-term treatment with sertraline or fluvoxamine has been shown to be effective for prevention of highly recurrent unipolar depression. The high tolerability of these compounds, together with their prophylactic effectiveness, has an important role in improving the quality of life of these patients.     

Transoral laser surgery of supraglottic cancer: follow-up of 141 patients

OBJECTIVE: To determine the role of transoral laser resection of supraglottic carcinomas. DESIGN: Retrospective unicenter study of the oncologic results of transoral carbon dioxide laser microsurgery for supraglottic carcinomas performed between February 1979 and December 1993. Median follow-up was 37 months. SETTING: University hospital academic tertiary referral center. PATIENTS: We reviewed the medical records of 141 patients (a consecutive sample of 131 men and 10 women; mean age, 60 years) with histologically proven supraglottic carcinomas undergoing transoral laser surgery, possibly in combination with neck dissection or radiotherapy. Stage distribution of patients was as follows: stage I, 23.4%; stage II, 25.5%; stage III, 16.3%; and stage IV, 34.8% (according to the Union Internationale Contre le Cancer staging system). MAIN OUTCOME MEASURES: Recurrence-free survival rates and local and regional recurrence rates. RESULTS: Five-year recurrence-free survival rates were as follows: the whole case load, 65.7%; stage I, 85.0%; stage II, 62.6%; stage III, 74.2%; and stage IV, 45.3%, according to the Union Internationale Contre le Cancer staging system. The local and regional recurrence rates were 16.3% and 9.9%, respectively. CONCLUSIONS: The oncologic results of transoral carbon dioxide laser surgery are satisfying if clean surgical margins (R0 resection) can be reached. In patients in whom tumor-free margins are not achieved (R1 and R2 resection) and transoral revision is not possible, transcervical procedures (partial or total laryngectomy) should be performed. The indication for transoral supraglottic laryngectomy in T3 lesions should be considered with restraint.     

"Big Smoke" has big risks: daily cigar use causes cancer, heart disease

BACKGROUND: To study the behaviour of recurrent benign parotid tumours, recurrence characteristics and problems faced with the removal of these lesions. METHODS: We reviewed the charts of the work of a single surgeon between 1971 and 1996. RESULTS: There were 24 patients (13 women, 11 men) with a mean age of 44 years at re-operation. Mean follow-up period was 10 years (range 1-22 years). There were 21 recurrent pleomorphic adenomas, two monomorphic adenomas and one patient with recurrent oncocytoma. Nine patients had solitary recurrence with a mean size of 14 mm, 15 patients had multiple recurrences with a mean size of 8 mm. There was malignant transformation of a previously benign lump in one patient. Three patients presented with a second or third recurrence. Overall facial nerve paralysis was 53% (38% temporary and 15% permanent). Frey's syndrome occurred in four patients (17%). CONCLUSIONS: Recurrent benign parotid tumours are uncommon if superficial parotidectomy (SP) is the performed initially; recurrence rates are between 0-4%. The recurrences are usually slow growing and require lengthy follow-up. Pre-operative diagnosis of a lump in the region of previous excision is useful in treatment planning. Malignant transformation in previous benign lump should be considered and fine needle aspiration biopsy may help in diagnosis. Facial nerve injury is more likely if the tumour is deep, in multiple sites or involves extensive scar tissue. Radiotherapy is controversial, it should be considered if there has been tumour spillage following re-operation.     

Results of renal transplantation in patients with Schistosoma infection

PURPOSE: We evaluated the results of renal transplantation in patients infected with Schistosoma haematobium, as well as the risks of urological complications and post-transplant reinfection. MATERIALS AND METHODS: The outcome of 20 kidney transplants was retrospectively studied. Based on our experience and review of the literature, our clinical practice to prevent urological complications consisted of antischistosomal chemotherapy given at the pre-transplant evaluation, with endovesical ureteroneocystostomy preferred in case of bladder calcifications. A Foley catheter was maintained for 10 days. A transurethral bladder neck incision was performed before removal of the Foley catheter when bladder neck sclerosis was present. RESULTS: The 1 and 2-year patient survival rate was 93%, and 1 and 2-year graft survival rates were 88 and 81%, respectively, which were not different from those of a cohort of 167 patients without schistosomal infection. Surgical complications included 2 postoperative hemorrhages, 2 urinary leaks and 1 nonschistosomal related ureteral stricture. Post-transplant schistosomal infection never occurred when antischistosomal chemotherapy was given at the pre-transplant evaluation. CONCLUSIONS: Patients with schistosomal infection are suitable recipients for kidney transplantation, although they are at risk for urological complications. Unlike other infectious diseases, such as tuberculosis, the risk of recurrence due to reactivation of chronically hosted pathogens seems to be low or absent in patients who received antischistosomal chemotherapy at the pre-transplant evaluation. Long-term urological followup is recommended, including urethrocystoscopy, because of the theoretically increased risk for bladder malignancy.     

The fate of patients with locally advanced bladder cancer treated conservatively with neoadjuvant chemotherapy, extensive transurethral resection and radiotherapy: 10-year experience

PURPOSE: We assess the results of bladder preservation for infiltrating bladder cancer. The potential for neoadjuvant chemotherapy followed by extensive transurethral resection and radiotherapy was evaluated in 40 patients with T2-T4a G2-G3 bladder carcinoma. MATERIALS AND METHODS: From 1983 to 1995, 40 patients with bladder cancer underwent bladder sparing treatment, consisting of neoadjuvant chemotherapy, extensive transurethral resection and radiotherapy. Most patients had T3G3 cancer. A deep transurethral resection biopsy was performed before and after chemotherapy, and an extensive transurethral resection was repeated at the end of radiotherapy. Of the patients 30 received cisplatin and methotrexate and 10 also received vinblastine. Total dose of radiotherapy was 60 to 65 Gy. Recurrent superficial tumors were treated transurethrally. Radical cystectomy was considered for persistent or recurrent invasive disease. RESULTS: Complete response occurred in 19 patients (47.5%) after chemotherapy, and in 8 patients after transurethral resection and radiotherapy (67.5%). Within 10 years 8 responding patients (30%) had local recurrences and 3 underwent cystectomy. Of the patients 14 (35%) are alive, including 13 with no evidence of disease (mean survival 65 months), 5 died of unrelated disease and 21 (52.5%) died of distant metastases (mean survival 28 months). Of the 21 patients 14 had residual tumor after radiotherapy, 3 presented with distant metastases after vesical infiltrating recurrence and 4 had distant metastases in the absence of locoregional recurrence. In 22 patients (55%) the bladder was salvaged. Patients with complete response to chemotherapy had a low risk for recurrent infiltrating tumors and metastases. CONCLUSIONS: Complete tumor control was maintained at 5 years in more than 50% of the patients treated conservatively. Bladder salvage is feasible in select patients.     

Salivary duct carcinoma: a report of nine cases

We studied loco-regional recurrence during follow-up (median observation time 8 years) in 1,153 patients, who underwent modified mastectomy and were randomly assigned to one of the following postoperative treatments; Premenopausal patients: radiotherapy, cyclophosphamide, or both; Post-menopausal patients: radiotherapy, tamoxifen, or both. Recurrence occurred in a total of 419 patients, 123 of whom had loco-regional recurrence with or without distant metastasis. The loco-regional recurrence rate was 7% in the irradiated subgroups and 17% in the non-irradiated subgroups, the corresponding cure rates being 43% and 58%. Complete remission of all local recurrence was obtained after the first treatment in 67% of the cases, and was persistent in 67% of them (44% overall). Complete remission was obtained in all patients with local recurrence who received local treatment only, and was persistent in 65%. Of local recurrences treated with a combination of surgery, radiotherapy and hormone therapy, complete response was obtained in 94% of the patients, and was persistent in 94% of them (88% overall). Complete remission of all regional recurrence was obtained after the first treatment in 58% of the patients and was persistent in 67% of them (39% overall). Postoperative radiotherapy reduced not only the total number of loco-regional recurrences but also the number of uncontrolled loco-regional recurrences. Aggressive local treatment would appear to yield both satisfactory initial control and, when combined with the hormone therapy, a high rate of persistent loco-regional control.     

Single-dose versus multiple instillations of epirubicin as prophylaxis for recurrence after transurethral resection of pTa and pT1 transitional-cell bladder tumours: a prospective, randomized controlled study

OBJECTIVE: To compare single-dose and multiple instillations of epirubicin in the chemoprophylaxis of superficial bladder tumours. PATIENTS AND METHODS: In a prospective randomized and controlled study, 168 evaluable patients were assigned to three groups after transurethral resection of bladder tumour (TURBT) and histological confirmation of its superficial nature (pTa and pT1). The groups were comparable for tumour stage, grade and other tumour characteristics. In group 1, patients received a single dose of 50 mg epirubicin in 50 mL normal saline immediately after TURBT; group 2 received 50 mg epirubicin in 50 mL normal saline 1-2 weeks after TURBT and the instillations were repeated for 8 weeks and thereafter monthly to complete one year of treatment: group 3 (control group) received no adjuvant therapy after TURBT. The patients were assessed by cysto-urethroscopy, urine cytology and DNA flow cytometry 8 weeks after resection and then every 3 months during the first 2 years and 6 monthly thereafter during the next 2 years. Intravenous urography was performed annually and when otherwise indicated. RESULTS: The recurrence rate was significantly lower in the patients treated with epirubicin than in the control group (24, 25 and 52%, respectively; P < 0.001). In those receiving epirubicin, the rates of recurrence were statistically comparable (P = 0.9). Patients who had a large tumour burden showed slightly lower recurrence rates with single-dose epirubicin than with delayed maintenance therapy but the difference was statistically insignificant. Patients with a history of bladder tumours before treatment had lower recurrence rates with maintenance treatment than with a single dose (34.6 and 22.6% in groups 1 and 2, respectively); again this difference was statistically insignificant. Patients with grade 3 tumours showed a marginal difference in favour of maintenance therapy. The rates of progression amongst the three groups were 5.5, 3.4 and 9.3%, respectively, with no significant differences. The overall toxicity rates were comparable in the two treated groups (22 and 25%). CONCLUSION: With the possible exception of grade 3 tumours, single-dose immediate epirubicin is as effective as delayed maintenance therapy, with the advantage of being more cost-effective.     

Expression of bcl-2 and bcl-X in bladder cancer

PURPOSE: TP53 and RB1 gene mutations in bladder transitional cell carcinoma (TCC) are correlated with grade, stage, recurrence, and survival and may correlate with tumor cell apoptotic potential. Overexpression of the bcl-2 and bcl-X anti-apoptotic genes has been correlated with poor prognosis and chemotherapy resistance in other systems. Similar studies have not been performed in TCC. We thus sought to determine expression of bcl-2 and bcl-X in TCC and correlate these with stage, survival and abnormal pRb or p53 expression. MATERIALS AND METHODS: Forty-two TCC samples (19 Ta and 23 locally advanced tumors) and normal urothelial controls were examined. Immunohistochemistry for p53, pRb, bcl-2 and bcl-X was performed on an automated system using indirect streptavidin biotin/horseradish peroxidase staining. Western immunoblot analysis was performed on bladder cancer cell lines to further characterize bcl-X expression. Recurrence-free and disease-specific survival were retrospectively determined. Kaplan-Meier survival curves were compared using the log rank test, and correlation of abnormal staining with stage and p53 or pRb status was determined using Fisher's exact test. RESULTS: Bcl-2 was expressed in less than 1% of normal urothelial cells, but moderate expression of bcl-x was found in all normal urothelial samples. Only 7.0% of TCC samples (1/19 Ta and 2/23 locally advanced tumors) demonstrated bcl-2 overexpression. Bcl-X overexpression was observed in 45.2% of TCC (8/19 Ta and 11/23 locally advanced tumors). Western blot analysis also revealed that both the long (29 kDa) anti-apoptotic form and short (19 kDa) pro-apoptotic form were overexpressed in bladder cancer cell lines and normal human urothelial cells. Bcl-X overexpression was weakly correlated with normal p53 expression (p = 0.06). There were no correlations of bcl-2 and bcl-X overexpression with abnormal p53, pRb, or tumor stage. There were no differences in recurrence-free or overall survival in patients with abnormal bcl-X staining. CONCLUSIONS: Bcl-2 overexpression is rare in TCC. Bcl-X overexpression is common, likely reflecting its expression pattern in normal urothelium, but is not correlated with stage or abnormal p53 or pRb staining. Within the power limitations of this small study, bcl-X overexpression is not correlated with recurrence or survival.     

Metabolism of quinine in children with global malnutrition

OBJECTIVE: To evaluate the frequency, predictive parameters and prognosis of urethral recurrence after cystoprostatectomy for urothelial bladder cancer. MATERIAL AND METHODS: From 1989 to 1994, 8 of a series of 185 patients (4.3%) treated by cystoprostatectomy for bladder carcinoma between 1988 and 1993 developed urethral recurrence revealed by urethral bleeding, with a follow-up of 6 to 36 months (m = 16). RESULTS: The initial bladder tumour was localized in 3 cases and multifocal in 5 cases. The posterior urethra was not involved in 5 cases, but presented lesions of CIS in 1 case and neoplastic infiltration also involving the prostate in 2 cases. These recurrences were treated by urethrectomy, as first-line treatment in 7 cases and after failure of endoscopic treatment in 1 case. A balanic recurrence required distal penectomy following insufficient urethral resection. The course was very rapidly unfavourable for 3 patients with generalized cancer and an intercurrent disease was fatal in 1 other case. With a follow-up of 12 to 44 months (m = 26), 4 patients are alive with no obvious signs of disease progression. CONCLUSION: The indications for prophylactic urethrectomy can be reserved to patients with positive urethral resection margins, provided all other cases are submitted to strict surveillance. In the context of a replacement bladder, it is essential to exclude neoplastic involvement of the posterior urethra or prostate, especially in patients previously treated by intravesical instillations.