Combined hyperfractionated radiotherapy and protracted infusion chemotherapy in bladder cancer for organ preservation.

PURPOSE: To test an innovative schedule of concurrent protracted intravenous infusion (PVI) of cisplatin (CDDP) and 5-fluorouracil (5-FU) and hyperfractionated radiotherapy (HFRT) with organ-sparing intent in bladder cancer. PATIENTS AND METHODS: Fifty-two patients (pts) were selected to receive an aggressive TURB followed by 2 MCV cycles, and HFRT with concomitant CDDP and 5-FU PVI (33 pts) or HFRT and concomitant CDDP and 5-FU PVI (20 pts). The 5-FU and CDDP doses ranged from 180 to 220 mg/sm/day and from 4 to 6 mg/sm/day, respectively. Radiotherapy was delivered as three 100 cGy fraction per day or two 150 cGy fraction per day to a total dose of 50 Gy to the pelvis and a 20 Gy boost to the bladder. RESULTS: Grade III toxicity in pts who received or not MCV was: rectal tenesmus 12/33 and 0/20, dysuria 6/33 and 4/20, leukopenia 3/33 and 0/20, thrombocytopenia 7/33 and 1/20 pts, respectively. A Grade IV toxicity was observed in 2 pts. Of the 28 evaluable patients treated with MCV, CR were observed in 23 (82%) and PR in 5 cases. Of the 18 evaluable patients treated without MCV, CR were observed in 18 cases (100%). Actually, 65% and 14% of the CR pts treated with or without HCV are alive and free of tumor. CONCLUSIONS: This bladder-sparing treatment shows an acceptable acute and late toxicity, similar to that observed with radiotherapy alone. The high CRs and bladder preservation rates observed deserve further clinical evaluation.

Radiotherapy with or without androgen deprivation in the treatment of localized adenocarcinoma of the prostate.

This study analyzes the results of disease relapse and survival in two series of patients treated between 1974 and 1991 with definitive irradiation, with or without early androgen deprivation, for carcinoma of the prostate localized to the pelvis. All 264 patients were irradiated to the prostate and pelvic lymph nodes with a dose of 50 to 54 Gy in 25 to 27 fractions, followed by a 16- to 20-Gy boost in 8 to 10 fractions to the prostate and periprostatic region. Ninety percent of patients received a total dose to the prostate (pelvis + boost) of 70 Gy. Ninety-nine of the 264 patients underwent early androgen deprivation. The endocrine manipulation program was initiated 0 to 9 months before the beginning of the radiotherapy course and was continued for 2 or more years or until disease progression. All patients who relapsed after radiotherapy alone received late hormonal manipulation. After a median follow-up of 100 months, no difference in the incidence of local and distant failure rate and cancer-specific mortality was detected between the two treatment groups. The local and distant failure rates were, respectively, 19% and 40% in patients who had undergone radiotherapy and early androgen deprivation and 20% and 36% in patients who received radiotherapy alone. Cancer mortality was similar, with 35% and 30% of deaths in the former and latter group, respectively. Death for intercurrent disease, however, was significantly more frequent (p = 0.03) in patients treated with radiotherapy and hormones (19%) than in those who received radiotherapy alone (8%). Actuarial analysis of both metastasis-free and disease-free survival detected no difference between the two treatment groups, with 10-year rates of 53.3% and 42.5%, respectively, in the radiation-alone group and 45.5% and 47%, respectively, in the radiation-plus-androgen deprivation group. A statistically significant difference (p = 0.03) in overall survival in favor of patients treated with radiotherapy alone was noted, with a 10-year rate of 47%, compared with 26% observed in the radiotherapy-plus-androgen deprivation group. In conclusion, results of our study confirm numerous reports based on retrospective analyses that failed to show any benefit of hormonal management adjuvant to a definitive irradiation. The disappointing finding was the significantly better overall survival in patients who underwent radiotherapy alone.

Combined treatment of invasive bladder carcinoma with transurethral resection, induction chemotherapy, and radical radiotherapy plus concomitant protracted infusion of cisplatin and 5-fluorouracil: a phase I study.

BACKGROUND: The aim of this study was to define the maximum tolerated doses (MTDs) of cisplatin (CDDP) and 5-fluorouracil (5-FU) administered as protracted intravenous infusion (PVI) during hyperfractionated radiotherapy (HFRT) administered with organ-sparing intent to patients with infiltrating transitional cell carcinoma of the bladder (TCCB). METHODS: Twenty-five patients with T2-T4aNXM0 TCCB were enrolled in this study. After a complete transurethral resection, bladder mapping, and two cycles of induction chemotherapy, patients were submitted to HFRT and CDDP + 5-FU as concomitant PVI at escalating dose levels until MTDs were reached. Treatment efficacy was also evaluated, in terms of complete response (CR) rates and cystectomy free, disease free, and overall survival. RESULTS: Combined treatment was well tolerated. The recommended doses for Phase II studies of PVI chemotherapy and radiotherapy for patients with invasive bladder carcinoma are CDDP 5 mg/m2/day and 5-FU 220 mg/m2/day. Twenty-four patients were evaluable for response: 21 (87.5%) had CR and 3 PR. After a median follow-up of 31 months (range, 11-49 months), 18 of 21 patients with CRs (86%) were alive: 15 (71.4%) had tumor free bladder, of whom 3 had superficial recurrence successfully treated with endovesical therapy and 1 had distant metastases. Three patients were submitted to cystectomy, one for superficial recurrence and hematuria and two for invasive bladder recurrence. CONCLUSIONS: This study defines the MTDs of CDDP and 5-FU concomitantly administered with hyperfractionated radiotherapy. The low toxicity observed and the high CRs and bladder preservation rates deserve further study.

[Study of prostatic carcinoma with ultrasonography and magnetic resonance with "dedicated" surface coil]. / Studio del carcinoma prostatico mediante ecografia e Risonanza Magnetica con bobina di superficie dedicata.

We investigated the role of an experimental surface coil for low field (0.2 T) MRI of prostatic gland carcinoma; the study was performed comparing MRI with US findings and with bioptic and pathologic results. To this purpose, 16 patients with prostatic cancer suspected at US and demonstrated with US-guided biopsy, were examined with low intensity field (0.2 T) MRI performed with a dedicated saddle-shaped coil and a body coil. This experimental surface coil with perineal application is used to study the prostatic gland with low field MR equipment where no transrectal probe is available. We analyzed the results of this study and found that, in all patients but one, the neoplastic lesions exhibited low signal intensity on T2-weighted images, while the normal gland was hyperintense. Six patients underwent radical prostatectomy and diagnostic imaging findings were correlated with pathologic findings obtained with whole mount specimens and serial histologic slides. The number of tumor foci, their site and size, and stromal reaction were studied on T2-weighted images; the typical low signal intensity was absent in one of 16 patients, in which case the microscopic exam of pathologic specimens showed extensive tumor spread with infiltration of perineural lymphatic vessels, with neither nodular patterns nor stromal reactions. The correlation between MR findings and the whole mount specimens (n = 6) demonstrated MR underestimation of tumor spread. In our opinion, this technique is useful for the detection and characterization of prostatic lesions, in spite of the presence of isointense lesions and the risk of underestimating the disease, especially to the prostatic capsule. To conclude, the dedicated surface coil can improve the diagnostic accuracy of low field MRI.

[Role of computerized tomography in bladder carcinoma treated with simultaneous combined radiotherapy and chemotherapy]. / Ruolo della Tomografia Computerizzata nel carcinoma vescicale sottoposto a radio e chemioterapia contemporanee associate.

We report on the pneumocystography-CT follow-up of locally aggressive bladder carcinoma patients treated with combined and simultaneous irradiation and chemotherapy. Particular attention was paid to assess residual thickening of the wall involved by the tumor, which is the most critical parameter to discriminate a persistent from a resolved condition. We examined 16 patients (mean age: 66.5 years) with histologically locally advanced urinary bladder cancer staged T2-T3. All patients underwent the first CT exam of the bladder with the pneumocystography technique before therapy, for disease staging, another exam after chemotherapy and a third one after simultaneous irradiation and chemotherapy. The endoluminal mass completely regressed in all cases, with normal endoscopic findings. In 9 of 16 cases, the bladder wall was thickened in the tumor site, with normal mucosal surface. The histology of bioptic specimens obtained during cystoscopy showed a high frequency of phlogistic reactions from foreign bodies, corresponding to the bladder wall thickening seen on CT images. We conclude that, in extensive neoplastic bladder wall involvement, therapy-induced histologic regressive phenomena can cause a granulomatous reaction in the bladder wall, thus thickening it, which is the most frequent sign in these cases but that, in our experience, was never associated with tumor invasion. This should be always considered in the CT studies performed after this kind of combined treatment.

Purification and properties of Oryza sativa Cu-Zn superoxide dismutase.

Superoxide dismutase has been purified to homogeneity from Oryza sativa germinated seeds growth in the dark. The purified enzyme contained two electrophoretically distinct bands on continuous gel electrophoresis or analytical gel electrofocusing. SDS-PAGE showed a single band of an M(r) 15000 while gel chromatography on Sephadex G 100 showed a single peak of an M(r) 32000. It contained two Cu and two Zn ions. The spectra of ultraviolet and visible regions were similar to those of Cu-Zn mammalian and plant superoxide dismutases. The activation energy was estimated at 16 Kcal mol-1.

Fractionation and characterization of two forms of peroxidase from Oryza sativa.

Peroxidase (E.C. 1.11.1.7., hydrogen donor oxidoreductase) is widely distributed and has been isolated from many higher plants (1). The wide distribution of the enzyme suggests that it could be of great biological importance. However the role that it plays in metabolism is not clear due to the large number of reactions it catalyzes and the considerable number of isozymic species (2). In tomato plants, Evans and Aldridge (3) separated out six isoperoxidases and in a later paper Evans reported 12 isoperoxidases from tomato shoots (4). A homogeneous tomato fruit peroxidase isozyme was obtained by Jen et al. (5) using hydrophobic chromatography. Isozymes were not detected in Euphorbia characias peroxidase (6), in Ipomoea batatas peroxidase (7) and in Hordeum vulgare peroxidase (8). The simultaneous presence of Cu (II) amine oxidase and peroxidase in cell walls suggests that the peroxide generated on oxidation of the amines could be utilized by the peroxidase (6,8,9). In the graminea Oryza sativa, widely distributed, an FAD amine oxidase is present that oxidizes diamines (10). In this plant we also found two isoperoxidases called perox I and II. Only perox I was purified to homogeneity and its enzymatic, physical and chemical properties have been studied.

[An expert system for the staging and therapy of carcinoma of the bladder]. / Sistema esperto per la stadiazione e la terapia del carcinoma della vescica.

Expert systems are application tools based on logic and containing a wide knowledge in a specific field; their aim is the simulation of an expert's behavior in reasoning and making decisions inherent a small cultural domain. Applications in medicine and radiology are numerous and constantly increasing. The possibility of their use in the application of diagnostic and staging protocols seems particularly interesting. The development and commercial availability of expert systems programming tools (called shells) make it certainly easier to develop consultations systems, even to non-experienced users. The purpose of this research is the definition and description of the stages encountered during the development of an expert system for diagnosis, staging and treatment of bladder cancer using self-developed shell, designed for radiological use, called Experto. The steps of knowledge collection, definition of diagnostic and therapeutic protocols and system development are described. The consultation system assessed the correct TNM stage of the 27 examined cases.

Radiological changes and circulating immune complexes in patients with urinary schistosomiasis.

The degree of infection and the urographic picture was correlated to the presence and level of circulating immune complexes (CICs) in 69 patients affected by urinary schistosomiasis. Patients were divided into 2 groups: those eliminating less and those eliminating more than 25 eggs/10 ml of urine. Radiological changes in the urinary tract were present in 67% of patients, the most frequent finding being single or multiple filling defects in the bladder. CICs were present in 39 patients. A positive correlation was found between the presence and level of CICs and the output of Schistosoma haematobium eggs, as well as between the presence of CIC and single or multiple filling defects of the bladder. Our findings indicated that CICs were present in patients with urinary schistosomiasis, but the different incidence in patients with a large egg output and radiological filling defects suggests a possible pathogenic role only in the earlier phase of the infection.

Tissue levels of ofloxacin in the urogenital system.

The authors evaluated the tissue levels of ofloxacin in 63 patients with urogenital diseases, in comparison to the minimum inhibitory concentrations 80% (MIC80) of some strains. The drug was administered in a single dose (300 mg) about 3 hours before surgery. After washing carefully, the tissue-levels were measured by using the HPLC method. In the normal renal parenchyma of 8 patients, the mean value was 22.10 micrograms/g of tissue; 19.23 micrograms/g in 13 patients with deranged excretory pathways; 10.62 micrograms/g in 25 patients with benign prostatic hypertrophy; 10.90 micrograms/g in 14 deferent duct patients. These results indicate that the drug is promptly distributed in various tissues of the urinary-genital apparatus at high concentrations.

[Hemitrigonectomy: a personal technic]. / L'emitrigonectomia: tecnica personale.

The Authors show an operation of urological surgery, unusual in relation to the rather limited indications. The operation of hemitrigonectomy, although it is framed in the chapter of the partial resections of bladder, does not get an exact identity in literature; yet, it is peculiar for both technical problems and some basic expedients sheltering surgeons from various complications. Hemitrigonectomy, performed by the Authors in six cases in the last 3 years, supplied excellent anatomic and functional results, and was burdened by no relevant complications.

Ureterocystoneostomy in urinary tuberculosis: a personal technique.

A personal surgical technique in the treatment of the tuberculous stenosis of the juxtavesical and intramural ureter, is described. 62 patients suffering from tuberculosis of the urinary tract underwent surgical treatment. 42 of these cases presented with ureteral stenosis: 14 were submitted to ureterocystoneostomy (UCNS) according to a personal technique. The results confirmed the initial hypotheses.