In vitro MRS and HPLC studies on human renal cell carcinomas.

Samples from ten patients with renal cell carcinomas (RCC) were examined by 1H MRS and high performance liquid chromatography (HPLC) measurements. Twenty samples, ten from the tumor and ten from the surrounding healthy renal region were obtained. MRS yielded information on renal osmolytes which can be considered markers of physiological kidney function. The marked decrease of these osmolytes is a hallmark of cancer. Moreover, HPLC measurements disclosed the amino acid pattern of both healthy and neoplastic tissues. The Glu and Ea content had statistical significance. GSH was present in tumor tissues only.

A new regimen of cisplatin, epirubicin and methotrexate (PEM-3) as primary chemotherapy for locally advanced bladder cancer.

In this phase II study, 41 patients with locally advanced urothelial bladder cancer (T2-4, N0, M0) were treated with primary chemotherapy (cisplatin, epirubicin, methotrexate: PEM-3). All the patients were assessable for response and toxicity. Clinical monitoring was performed with computerized tomography and cystoscopy. Nineteen clinical complete remissions (46%) and 10 partial remissions (24.5%) were obtained (CR + PR, 70.5%; 95% confidence interval, 57%-85%). Ten patients were considered to have clinically stable disease (24.5%), and 2 patients progressed (5%). Surgery after chemotherapy was performed in 22 cases: in 6 patients (27%) a pathologic complete response was achieved. The pathologic stage was lower than the initial clinical stage in 13 patients (59%). After a median follow-up of 3 years (range, 1-4), the median time to progression was 104 weeks. At this writing, 20 patients, 12 of which were submitted to surgery and 8 were not operated, are disease-free. The 3-year survival rate is 52%. No one had to interrupt the treatment because of toxicity. In conclusion, the PEM-3 regimen is a very active and well-tolerated regimen in locally advanced bladder cancer.

[Orthotopic neobladder in women]. / La neovescica ortotopica nella donna.

In women undergoing radical cystectomy for bladder cancer, orthotopic bladder reconstruction is now a viable alternative to urinary diversion: preservation of the external urethral sphincter by sectioning the urethra 0.5-1 cm distally to the bladder neck allows maintenance of urinary continence without compromising cancer control. 12 cases of bladder reconstruction in women operated on from 1986 to 1995 are presented here. A personal technique for the creation of an ileal neobladder is described: the use of staplers for detubularization of the ileum significantly reduces the operating time ("simplified ileal bladder"). Other important points of technique are as follows: 1. Careful preparation of the bladder neck and proximal urethra, staying above the pubo-urethral ligaments that must be preserved as the distal landmark of dissection; 2. "Nerve-sparing" isolation of the posterolateral wall of the bladder from the vagina; 3. Careful positioning of the pouch in the true pelvis, in order to avoid posterior prolapse of the neobladder. So far, results of bladder reconstruction in this series of patients are encouraging, both from a functional and oncological standpoint.

Color Doppler ultrasonographic scanning in prostatitis: clinical correlation.

Color Doppler and endorectal ultrasonography were performed in 25 patients with acute prostatic syndromes (APS; 13 acute and 12 chronic recurrent forms). In addition, 7 patients with asymptomatic chronic prostatitis, 13 men with prostatic carcinoma and 6 healthy young volunteers were studied. In the 25 APS, a marked increase in color was observed in the cervicourethral site and/or around the ejaculatory ducts and close to the seminal vesicles. The observed pattern is probably explained by vessel dilatation due to acute inflammation. The color increase in these 25 patients was greater than in the 6 normal prostates and 8/9 prostate carcinomas. Moreover, we observed that color intensity matched the severity of symptoms in APS.

Chemotherapy with cisplatin, epirubicin, methotrexate in the treatment of locally advanced or metastatic transitional cell cancer of the bladder (TCC).

Forty patients with advanced transitional cell cancer (TCC) of the bladder were treated with cisplatin, epirubicin, methotrexate (PEM, every 3-4 weeks). If creatinine clearance was reduced to 40 ml/min, the usual full doses of cisplatin and methotrexate, 50 mg/m2, were proportionally reduced. 23 patients had full-dose (FD) therapy, 17 had reduced dose (RD) (40-20 mg/m2). Two patients achieved complete response and 17 partial response. The overall response rate was 19/40 (47.5%), 11/23 (48%) for FD and 8/17 (47%) for RD (p = 1.000). 17/40 pts (42.5%) had no-change and 4/40 (10%) had disease progression. The median duration of CR and PR was 32 weeks, range 4-82 (22 weeks, range 12-52 for FD; 32 weeks, range 4-82 for RD, cisplatin p = .7362). The main side effect was vomiting (35/40 pts, 87.5%, 20/23 = 87% for FD, 15/17 = 90% for RD, p = 1.000). Leukopenia was observed in 12 patients (30%, nadir 3,240 range 900-3,800, 6/23 = 26% for FD, 6/17 = 35% for RD, p = .7285), alopecia in 18 patients (45%, 15/23 = 65% for FD, 3/17 = 18% for RD, p = .004). The results of this study show that a dose escalation to 50 mg/m2 for cisplatin, epirubicin and methotrexate in the PEM regimen results in an increase in overall response (OR) (19/40 = 47.5%) with respect to a historical control using the same drugs at doses of 40 mg/m2 (12/35 = 34%). In patients with normal renal function the escalated dose was tolerated without a corresponding increase in toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

The prognostic significance of DNA ploidy pattern in transitional cell cancer of the renal pelvis and ureter: continuing follow-up.

Among 190 patients operated on for transitional cell cancer of the renal pelvis and/or ureter from 1976 to 1990, 95 had their tumor studied by flow cytometry. Of these, the prognostic significance of the DNA ploidy pattern with respect to the standard pathologic features was assessed in a retrospective analysis, where survival information were updated to October 1991 and the mean follow-up of patients exceeded 5.5 years (longest follow-up: 15.5 years). Five and ten-year survival probabilities for the whole group were, respectively, 65.5 and 51%. Patients with a diploid tumor had significantly better survival rates than patients with tetraploid/aneuploid cancer (p less than 0.00001). The impact of the DNA ploidy on survival was confirmed by a multivariate analysis of prognostic factors, where only tumor grade (p less than 0.0001), tumor stage (p less than 0.0001), number of neoplastic foci (p = 0.022) and nuclear DNA pattern (p less than 0.068) had a significant influence on survival. In the group of patients with low-stage (pTa-pT1) and low-grade (G1-G2) transitional cell cancer of the upper urinary tract, the DNA analysis was unable to identify any subset of patients at higher risk for disease progression.

Transitional cell carcinoma of the upper urinary tract: evaluation of prognostic factors by histopathology and flow cytometric analysis.

Prognostic factors in transitional cell carcinoma of the upper urinary tract were assessed with histopathological examination and flow cytometric analysis in a series of 127 patients operated upon between 1976 and 1988. In particular, we evaluated the usefulness of flow cytometry to identify patients who require adjuvant treatment among those with low grade and low stage disease (51% in this series). A multivariate analysis was done on 92 cases, considering patient age and sex, stage, grade and number of lesions (unifocal versus multifocal), site (renal pelvis versus ureter), presence of vesical tumors, recurrences along the urinary tract or in the bladder, type of operation and nuclear deoxyribonucleic acid (DNA) ploidy (diploid versus tetraploid/aneuploid tumors). Only the stage (p = 0.001), grade (p = 0.001) and, to a lesser extent, the DNA pattern (p = 0.031), as well as the number of lesions (p = 0.061) were determinant for prognosis. In regard to the subgroup of 41 patients with grade 2 or less, stage P1 or less tumors, no significant difference in survival was demonstrated between diploid and nondiploid tumor patients. However, 7 of 10 patients from the latter group are still under observation. Therefore, our conclusions may have to be modified in the future.

Oncocytoma and low-grade oncocytic carcinoma of the kidney.

Oncocytoma is a term generally used to describe a neoplasm of the renal parenchyma consisting of well-differentiated cells with prominently eosinophilic granular cytoplasm. We report our experience with such tumors and with 4 cases of granular cell carcinoma (grade 2). We present the histopathology, surgical staging studies, treatment, and clinical outcome. Of the 10 patients, 7 are alive without evidence of tumor at a mean follow-up of 5 years from the initial treatment. Three patients have died, 2 from nontumor-related causes while the cause of death of the third patient is uncertain, possibly due to the tumor. Although well-differentiated oncocytic renal tumors are usually considered as uncommon when the diagnosis is made, nonaggressive behavior is expected. However, careful radiographic and pathologic examination is required to avoid the pitfall of overlooking a higher-grade, more lethal neoplasm which may be mixed with the well-differentiated oncocytic neoplasm and form a minority component. A wide resection, which in most cases is nephrectomy, is apparently curative and assures that complete pathological examination of the specimen can be accomplished. In more than 90% of the cases, the tumor is solitary and unilateral. Cases in which there are multiple tumors are often bilateral, and this finding may create diagnostic confusion.

[Papillary nephrocarcinoma: radiographic and echographic aspects]. / Nefrocarcinoma papillifero. Aspetti radiografici ed ecografici.

Between 1976 and 1987, 395 patients with kidney tumors were studied with radiological techniques and sonography. In 37 cases (9.4%) histopathology diagnosed pure papillary renal cell carcinoma. Analyzing the radiographic patterns of these neoplasms, the authors observed constantly diminished vascularity (100%), frequent calcifications (35.1%) and necrotic areas (51.3%). Such X-ray features are not specific: nevertheless, their coexistence is strongly suggestive of papillary renal cell cancer. No consistent US pattern was found; however, necrotic areas were easily demonstrated in most cases. It must be stressed how patients with papillary carcinoma experienced a longer postoperative survival; it has not yet been established whether such favorable behavior is due to low biological aggressiveness or to earlier diagnosis.

Spontaneous circadian fluctuations of prostate specific antigen and prostatic acid phosphatase serum activities in patients with prostatic cancer.

Spontaneous circadian variations of prostate specific antigen (PSA) and prostatic acid phosphatase (PAP), determined simultaneously by radioimmunoassay (RIA), were investigated by multiple sampling, over a 24-hour period, in 32 patients with prostatic cancer. In 29/32 patients (91%), the coefficient of variation of 24-hour values, for either marker, was greater than that of the RIA method at the same range of values; stage D patients showed the greatest spontaneous variability. Fluctuations around the mean of 24-hour values ranged from -65% to +85% for PAP, from -72% to +190% for PSA, occurring random and independently for each marker. Variability was about 20% greater for PSA than for PAP. The existence of spontaneous fluctuations should be considered in multiple marker evaluation of prostatic cancer patients.