J. N. Kulkarni

Long-term results of orthotopic neobladder reconstruction after radical cystectomy

To assess, in a retrospective study, the long‐term results of neobladder reconstruction after radical cystectomy, as this is the standard of care for muscle‐invasive bladder cancer.

Interstitial brachytherapy in carcinoma of the penis

AimKeeping in line with the increasing emphasis on organ preservation, we at the Tata Memorial Hospital have evaluated the role of Ir-192 interstitial implant as regards local control, functional and cosmetic outcome in early as well as locally recurrent carcinoma of the distal penis.Patients and MethodsFrom October 1988 to December 1996, 23 patients with histopathologically proven cancer of the penis were treated with radical radiation therapy using Ir-192 temporary interstitial implant. Our patients were in the age group of 20 to 60 years. The primary lesions were T1 in 7, T2 in 7 and recurrent in 9 patients. Only 7 patients had palpable groin nodes at presentation, all of which were pathologically negative. The median dose of implant was 50 Gy (range 40 to 60 Gy), using the LDR afterloading system and the Paris system of implant rules for dosimetry. Follow-up ranged from 4 to 117 months (median 24 months).ResultsAt last follow-up 18 of the 23 patients remained locally controlled with implant alone. Three patients failed only locally, 2 locoregionally and 1 only at the groin. Of the 5 patients who failed locally, 4 were successfully salvaged with partial penectomy and remained controlled when last seen. Local control with implant alone at 8 years was 70% by life table analysis. The patients had excellent functional and cosmetic outcome. We did not record any case of skin or softtissue necrosis. Only 2 patients developed meatal stenosis, both of which were treated endoscopically.ConclusionOur results lead us to interpret that interstitial brachytherapy with Ir-192 offers excellent local control rates with preservation of organ and function. Penectomy can be reserved as a means for effective salvage.ZusammenfassungZielDas Prinzip des Organerhalts gewinnt in der Onkologie zunehmend an Bedeutung. Ziel dieser Untersuchung war es, die Rolle der interstitiellen Brachytherapie mit Ir-192 zur Behandlung des frühen und rezidivierten Peniskarzinoms zu evaluieren. Endpunkte waren die lokale Tumorkontrolle sowie funktioneile und kosmetische Resultate.Patienten und MethodenInsgesamt 23 Patienten mit einem histologisch gesicherten Peniskarzinom wurden zwischen 1988 und 1996 durch ein interstitielles Ir-192-Implantat behandelt. Die T-Kategorien (UICC 1979) waren wie folgt verteilt: Tl sieben Patienten, T2 sieben Patienten; einen Rezidivtumor hatten neun Patienten. Nur sieben Paienten wiesen vor Therapiebeginn tastbar vergrö\erte Leistenlymphknoten auf, die ausnahmslos zytologisch nicht befallen waren. Die Brachytherapie wurde mit einer medianen Dosis von 50 Gy (Spanne 40 bis 60 Gy) unter Verwendung eines Low-dose-rate-Afterloading-Systems ausgeführt. Die Dosiskalkulation und Implantation erfolgten analog zum Paris-System. Die Nachbeobachtungszeit lag zwischen vier und 117 Monaten (Median 24 Monate).Ergebnisse18 der 23 Patienten blieben in lokaler Tumorkontrolle. Drei Patienten erlitten ein lokales, zwei ein lokoregionÄres und ein Patient ein Leistenrezidiv. Vier der fünf Patienten mit Lokalrezidiv konnten durch eine Teilamputation saniert werden. Die lokale Tumorkontrolle (Kaplan-Meier) betrug 70% nach acht Jahren. Nur zwei Patienten erlitten eine Meatusstenose, die endoskopisch therapiert wurde. Die übrigen Patienten hatten ein exzellentes funktionelles Resultat.Schlu\folgerungDie interstitielle Brachytherapie im Low-dose-rate-Verfahren erbringt für das Peniskarzinom gute lokale Tumorkontrollraten bei Erhalt des Organs. Eine Amputation ist als Salvage-Prozedur immer noch effektiv.

Recurrence and progression in stage T1G3 bladder tumour with intravesical bacille Calmette-Guérin (Danish 1331 strain)

Objective  To report recurrence and progression rates in patients with T1G3 superficial bladder carcinoma treated with intravesical bacille Calmette‐Guérin (BCG, Danish 1331 strain) after complete transurethral resection.

Proliferating cell nuclear antigen and epidermal growth factor receptor (EGFr) status in renal cell carcinoma patients with polysomy of chromosome 7.

We investigated 40 cases of renal cell carcinoma (RCC) to study the polysomy 7 status in papillary and clear-cell types (nonpapillary RCC) and relationship with clinical, pathological, and biological features such as grade, stage, tumor proliferation rate (PCNA expression) and epidermal growth factor receptor (EGFr) expression and thereby to understand the prognostic significance of polysomy 7 and EGFr expression. In a prospective study, chromosome 7 copy number was analyzed in tumor cells by using fluorescence in situ hybridization (FISH) with an alpha-satellite DNA probe for chromosome 7. Both proliferating cell nuclear antigen (PCNA) and EGFr expression were examined in paraffin sections by immunostaining. The relationship between clinicopathological and clinicobiological parameters was evaluated by appropriate statistical methods. Polysomy 7 was present in 100% of papillary and 56.2% of clear-cell types RCC. In clear-cell RCC, in comparison with polysomy 7-dominant (D) category (20-50% polysomy-7 cells), polysomy 7-major (M) category (>50% polysomy 7 cells) was associated with higher tumor grade (P = 0.05). Polysomy 7 was also correlated with stage of the disease (P = 0.006). The PCNA index ranged between 12.8-89.6% and was comparatively high in high-grade tumors (P = 0.001). The PCNA index was also correlated with polysomy 7 (P = 0.002), and the association was stronger in tumors with polysomy M versus polysomy D category (P = 0.02). The EGFr expression did not correlate with either grade, stage, PCNA, or polysomy 7. The correlation of polysomy 7 with less favorable prognostic factors such as higher tumor grade, stage, and higher proliferative index in the present study indicates that polysomy 7 might be used as a prognostic predictor in clear-cell RCC. Evaluation of clinical end points will confirm the prognostic potential of the genetic marker polysomy 7 in our study.

Intravesical bacillus Calmette-Guerin for superficial bladder cancer: experience with Danish 1331 strain.

A total of 95 patients with stage Ta/T1 superficial bladder cancer was eligible for intravesical bacillus Calmette-Guerin (BCG) immunoprophylaxis according to the standard high risk criteria for tumor recurrence and progression. Of these patients 50 agreed to undergo treatment while the remaining 45 refused any intravesical therapy and served as concurrent nonrandomized controls. The patient and tumor characteristics in the 2 groups of patients were identical. All patients underwent complete transurethral resection of the bladder tumor. Therapy consisted of 120 mg. weekly instillations of BCG (Danish 1331 strain) for 6 weeks. Among the 50 patients 33 received BCG initially while 17 received it after failure of intravesical chemotherapy. Responses were evaluated according to standard criteria. Recurrence was noted in 24 patients (48%) in the BCG group compared to 38 (84.4%) in the control group. The recurrence rates per year and per 100 patient-months were significantly reduced in the BCG arm compared to the control arm. The mean interval to first recurrence and the mean recurrence interval were significantly increased in the BCG arm compared to the control arm. The relative risk of recurrence in the BCG group was 0.62 versus 1.63 in the control group. Subgroup analysis showed significant benefit of BCG for patients with single as well as multiple, stages Ta and T1, and grades II and III tumors. Comparison with pretreatment controls in the BCG group revealed a significant reduction in the recurrence rate in those patients after treatment with BCG, which was not seen in the control group. The benefit of BCG was seen in those who received BCG initially as well as in those who received it after failure of intravesical chemotherapy. Multivariate analysis of prognostic factors showed that this benefit in the BCG group was related only to the treatment, while other prognostic parameters, such as tumor stage, grade, number and so forth were not independent prognostic variables. The rate of progression to muscle invasion was not significantly different in the 2 treatment groups. The relapse-free survival in the BCG group was 35.4% at 60 months compared to 11.2% in the control group (p < 0.001). The side effects of BCG therapy were mild, brief and easily controlled with conservative measures.

Is bladder conservation feasible? An Indian experience.

With the introduction of chemotherapy in the treatment of muscle invasive bladder cancers, endeavors at improving disease-free survival/overall survival are ongoing. As high objective response rates were seen with MVAC/CMV regimens (M-methotrexate, V-vinblastine, A-adriamycin, C-cisplatin) organ conservation is being attempted. A phase II protocol was designed using MVAC as the initial therapy. Based on the response to two cycles all patients were evaluated and where possible the bladder was preserved. Twenty-nine patients completed the protocol and had a median follow-up of 24 months. Complete response (CR) was noted in 7/29 (24.1%) of patients, while 11/29 (38%) had partial response (PR) and 11/29 (38%) showed no response (NR). Bladder conservation was possible in 15/29 (51.7%) patients initially with the use of radiation therapy after the initial chemotherapy. Ten of these patients are presently alive with their bladders intact. Three patients died of distant disease, two with normal bladders and one with local relapse. Two of the other patients required salvage cystectomy and are alive and disease-free. All complete responders 7/7 (100%) and 5/11 (45%) partial responders could have their bladders conserved. Three of 11 partial responders who refused radiotherapy and 11/11 non-responders underwent radical cystectomy after initial chemotherapy. Subset analysis indicates that low stage and grade tumours had the highest likelihood of bladder preservation, and there was no difference in overall survival in the groups according to response criteria. As our study consists of a small number of selected patients, it would be improper to draw firm conclusions. However, it seems that initial chemotherapy selects out a subset of patients with a good prognosis and the chance for bladder conservation.