Prognostic parameters in renal cell carcinoma--a new approach.

The prognostic potential of the parameters TNM staging, Robson staging, grading, cell type, growth pattern, and patient age was investigated for 431 patients with operated renal cell carcinoma (RCC). In the individual analyses, staging and grading attained the best results, whereby Robson staging proved to be superior to TNM staging by comparison. Morphological parameters had a more modest effect on the prognosis, but this should not be underestimated. A scale of points based on a comparative biometric evaluation of the various parameters was devised. From this scale, three significantly distinct prognostic groups evolved with a correct prognosis of over 80% on the average for an individual case. In comparison with other proposals for assessing prognosis for RCCs, the suggested scale of points had the greatest prognostic potential.

Tumor volume, CT scan, lymphography, sonography, intravenous pyelography, and tumor markers in testis tumors.

Correlation of tumor volume to tumor stage in 134 patients with nonseminomatous testicular tumors, which were classified according to the TNM system, revealed similar tumor load for N0 and N1 patients. CT scans (n = 92), lymphangiography (n = 47), intravenous pyelography (IVP) (n = 134), sonography (n = 118) and serial tumor markers (n = 82) were evaluated for sensitivity, specificity and accuracy, both separately and in different combinations. The best individual results were obtained by lymphangiography (sensitivity 0.77, specificity 0.73, accuracy 0.75) and CT scan (sensitivity 0.52, specificity 0.91, accuracy 0.70). In combination CT scan and lymphangiography were the most valuable diagnostic tools (accuracy 0.79) with high sensitivity (0.88) and specificity (0.77). For patients with negative CT scans, subsequent lymphangiography is recommended for accurate staging, as seems mandatory in stage 1 patients entering surveillance programs.

[Classification, histogenesis, and prognosis of renal cell carcinoma and renal oncocytoma]. / Systematik, Histogenese und Prognose der Nierenzellkarzinome und des renalen Onkozytoms.

Typing of renal cell tumours according to cytomorphological criteria results in different basic cell types, i.e. the clear cell type, the chromophilic cell type, the chromophobic cell type, the oncocytic cell type and the cell type of Duct-Bellini-Carcinoma. Each basic cell type exhibits a typical spectrum of cytological variability including eosinophilic (granular) variants. Antigenic properties of the proximal tubule can mainly be detected in clear cell and chromophilic renal cell carcinomas, whereas antigenic properties of the connecting tubule and collecting duct can be found especially in the chromophobic renal cell carcinoma and oncocytoma as far as in Duct-Bellini-Carcinoma. These different phenotypes of epithelial renal cell tumours are possibly due to various histogenetic pathways. Prognostic factors in renal cell carcinoma include staging, grading and to a less extent cytological and histological parameters which are summarized in a new prognostic score. From this score, three significantly distinct prognostic groups evolved with a correct prognosis of over 80% on the average for an individual case, which suggests a great prognostic potential.

Immunotherapy of metastasizing renal cell carcinoma. Results of a multicentered trial.

119 patients with stage-IV renal cell carcinoma were treated using immunotherapy with autologous tumor vaccine. The immunization was carried out at monthly intervals, the patients were restaged every 3 months using X-ray, ultrasound scanning or computed tomography as well as bone scintigraphy in the follow-up. The patients' follow-up periods run from 6 to 66 months averaging in 38.5 months. 6 complete remissions, 4 partial responses and 29 stable diseases were seen, whereas 54 patients had progressive disease. Patients with a T1 primary tumor all survived the follow-up period irrespective of whether lymph node metastases (n = 2), venous invasion (n = 12) or distant metastases (n = 6) were present at the time of operation. Follow-up periods run from 12 to 48 months (averaging 23 months). Patients with T2 tumors showed survival up to 50 months postoperatively, of these only 3 died. Follow-up averages 30 months. The 3 patients died within the first year after operation. Patients with very large primary tumors showed the poor prognosis normally expected. 23 of these 40 patients died after a mean follow-up of 15 months. These results may indicate that immunotherapy can slow down tumor progression and induce objective responses. Those patients with small primary lesions apparently benefit from the treatment even though metastases are present at the time of diagnosis.

Effect of lectins on KK-47 bladder cancer cell line.

The effect of three lectins, Ricinus communis agglutinin (RCA II), concanavalin agglutinin (ConA), and wheat germ agglutinin (WGA), on KK-47 bladder cancer cell line was studied, RCA II showed effective inhibition of H3-uridine and H3-thymidine uptake by KK-47. ConA showed a stimulatory effect in all three concentrations used. WGA also showed stimulatory effect, but it was less pronounced than ConA.

100 cases of Mainz pouch: continuing experience and evolution.

The surgical technique for creation of the Mainz pouch uses 10 to 15 cm. of cecum and ascending colon and 2 ileal loops of the same length for construction of a urinary reservoir. Initial applications of the Mainz pouch were for bladder augmentation after subtotal cystectomy and for continent urinary diversion. Current indications have been extended to complete bladder substitution after radical cystoprostatectomy with anastomosis of the pouch to the membranous urethra. For cosmetic reasons the umbilicus is used as a stomal site for continent urinary diversion, and the technique of intussuscepting the continence nipple has been modified accordingly. A total of 100 patients underwent a Mainz pouch procedure since 1983: 34 for bladder augmentation, 15 for total bladder substitution after cystoprostatectomy and 51 for continent urinary diversion. In the bladder augmentation group 1 patient underwent conversion to a continent stoma, 1 has urge and frequency, and the remaining 32 are completely dry day and night. These patients empty the bladder at normal intervals spontaneously except for 3 who rely on intermittent catheterization. In the bladder substitution group 1 patient has grade 1 stress incontinence and the remainder are completely dry during the day. However, at night 4 patients have leakage and they use a condom urinal. In the urinary diversion group all but 2 patients are completely dry and are on intermittent catheterization. The main problem of the initial series was prolapse of the continence nipple, which has been solved by staple fixation of the nipple to the bowel wall and to the ileocecal valve.

In vitro chemosensitivity testing of renal cell cancer. Short-term culture technique.

In an attempt to solve the problem of chemosensitivity testing of renal cell carcinoma in vitro, a modified short-term culture technique was developed. The kinetic study of hypernephroma cells and normal renal cells showed that the uptake of H3-uridine and H3-thymidine is at its maximum after eighty hours. The effect of doxorubicin, cisplatinum, vinblastine, and mitomycin C in different concentrations was tested. Tumors generally showed more resistance than sensitivity. Some tumors showed sensitivity to one or more drugs, but no one drug was persistently effective in all tumors. Our short-term culture technique solved the discrepancy between cell kinetics and test duration found in the Volm test and the problem of nongrowth in the clonogenic assay.

[Importance of early cystectomy for the prognosis of cancer of bladder]. / Importance d'une cystectomie précoce pour le pronostic du cancer de la vessie.

Between 1967 and 1985, 246 cystectomies were performed for the treatment of urothelial carcinoma of the bladder. Surgery-related mortality, initially 15%, was equal to 0% in 1985. Preoperative radiation therapy was not given. Despite strictly comparable T and N stages, prognosis was markedly better in patients who had undergone cystectomy as soon as the diagnosis of invasive cancer of the bladder was established than in patients who had undergone cystectomy after one or more recurrences of invasive carcinoma of the bladder and after transurethral resection. Twenty-six patients, undergoing cystectomy because of recurrence after curative radiation therapy, were the group with the worst 5--years survival--less than 10%. These results allow us to conclude that for the prognosis of carcinoma after total cystectomy, it is of the utmost importance to differentiate between an initially invasive tumor and a recurrence of an invasive carcinoma after transurethral resection. If performed immediately after infiltration has been demonstrated, cystectomy may greatly contribute to improving the long-term prognosis. As soon as the tumor extends to the lamina propria (pT1), one can no longer expect transurethral electroresection to suffice as reliable curative treatment of carcinoma of the bladder. As for the argument that the procedure is mutilating, one can counter with the increasing success in the last few years, of urinary derivation with continence, including bladder replacement or even total cystoprostatectomy, which does not result in impotence.

Tumor-specific antigen for human renal cell carcinoma. Ultrastructural localization of the antigen by immunoelectron microscopy.

Hybridoma technology enabled the production of tumor-specific monoclonal antibodies reactive exclusively with human renal cell carcinoma. Intracellular localization of the antigen was undertaken in order to gain understanding of its possible physiological role in cellular metabolism and to investigate its future clinical applicability for immunoscintigraphy in tumor localization. For immunoelectron microscopy a special paraformaldehyde-periodate fixation process (PLP fixation) had to be employed, in order to preserve the cell's ultrastructure without destruction of the antibody-binding epitope. The antigen was found to be strictly intracytoplasmic in close correlation to the glycogen particles characteristic for human renal cell carcinoma. These findings suggest that this antigen may be involved in the pathological glycogen synthesis, explaining the specific staining pattern of these monoclonal antibodies.

Endocrine and clinical evaluation of 107 patients with advanced prostatic carcinoma under long-term pernasal buserelin or intramuscular decapeptyl depot treatment.

Three major assumptions emerged from these clinical and endocrine long-term studies. First, buserelin, given pernasally in the conventional doses, and Decapeptyl microcapsules administered intramuscularly in 5-week intervals are equally effective in terms of their long-term castration effect in previously untreated patients with prostatic carcinoma. However, Decapeptyl causes complete LH and subsequent testosterone down-regulation 1 week earlier than buserelin. Furthermore, this treatment is more convenient, and the compliance is better. Both LHRH analogues are equally well tolerated. Second, in groups of prostate cancer patients with far advanced disease treated with palliative intention, only true subjective or objective remission should be considered a positive treatment response. Third, our results comparing PAP and PSA as the two most useful tumor markers with the corresponding testosterone levels suggest a close correlation.

Bladder carcinogenesis in portacaval shunt rats.

The induction of transitional cell bladder tumors following portacaval shunt (PCA) in rats was investigated. Thirty-five (29 males; 6 females) out of 86 animals developed a carcinoma. The highest incidence of tumors (73%) was seen in control animals without a PCA but with implantation of a bladder stone. PCA rats had an induction rate of 34% and a spontaneous bladder tumor was seen in 2/13 sham-operated controls. All rats with a bladder tumor also had urolithiasis; 34 rats had bladder stones in 1 rat had kidney stones. The induction rate in males was 29/52, 55.7% compared to 6/34, 17.6% in females. All tumors were transitional cell carcinomas and were graded G0-GIII [1(G0); 24 (GI); 1 (GI-II); 9 (GII)] accompanied in 20 cases by squamous cell metaplasia. Chronic irritation by stones and infection are the most likely causes of tumor development; however, other mechanisms such as excretion of carcinogens or tumor promoters cannot be completely excluded. The sex difference in stone formation - and tumor induction - are subject to further investigations.

Radical cystectomy--often too late?

From 1967 to 1985, 246 cystectomies for treatment of transitional cell carcinoma of the urinary bladder were performed. Perioperative mortality decreased from 15% in the early years to 0% in 1985. Preoperative radiotherapy was not given. Patients who underwent cystectomy immediately following the diagnosis of invasive bladder carcinoma had a significantly better prognosis than those having cystectomy after recurrence of a transurethrally resected invasive carcinoma in spite of identical G and T criteria. A total of 26 patients who were cystectomized because of tumor recurrence after definitive radiotherapy (salvage cystectomy) represented the group with the worst prognosis: they had a 5-year survival rate of less than 10%. It is concluded from these results that recurrence of an infiltrating bladder tumor is an indication of poor prognosis. Early cystectomy after diagnosis of tumor infiltration can improve survival rates. Transurethral resection without adjuvant therapy cannot be regarded as reliable curative treatment of bladder cancer infiltrating the lamina propria (pT1). Modern surgical techniques of continent urinary diversion or total bladder replacement combined with sparing of the pelvic nerves (and thus preservation of potency) reinforce our view that radical cystoprostatectomy need no longer be regarded as mutilating surgery.