T. Schärfe

Extracorporeal shock wave lithotripsy of urinary calculi: experience in treatment of 3,278 patients using the Siemens Lithostar and Lithostar Plus.

Between March 1986 and June 1989, 3,278 patients with upper urinary tract calculi were treated at our medical center with the Lithostar lithotriptor. The stones were located in the calices in 41.9% of the cases, renal pelvis in 25.7% and ureter in 32.4%. Perirenal hematoma was noted in 0.5% of the patients but this resolved spontaneously within a few days. Auxiliary procedures were performed in 37.3% of the cases, including Double-J stent and ureteral catheter in 26.8%, ureterorenoscopy in 2.1%, percutaneous nephrostomy in 1.6%, Zeiss loop in 4.3% and percutaneous nephrolithotripsy in 3.5%. Of the treatments 83.1% were performed without general or regional anesthesia. Followup after 3 months showed a 63.8% rate free of stone. The Lithostar upgraded with the overhead lithotripsy module is called Lithostar Plus. A total of 25 patients with upper urinary stones underwent treatment with the overhead module. Initial experience revealed fragmentation of stones after the first session in 20 patients, while a second session was necessary in 5. Analgesic sedation was used in 4 patients in whom a Double-J stent was inserted.

Tumor-specific monoclonal antibodies for renal cell carcinoma.

Monoclonal antibodies, tumor-specific for renal cell carcinoma (RCC), were produced in Balb/C mice, hyperimmunized with tumor cell suspensions from a histological grade II tumor. Boosting with lectin-immobilized tumor-antigen rendered high yields of specific antibody-producing hybrids. Hybridoma supernatants were screened for specificity using a solid-phase enzyme-linked immunoassay. Testing in parallel for reactivity with tumor tissue and corresponding autologous normal kidney material, only those hybrids producing antibodies exclusively reactive with RCC were propagated, resulting in 4 stable, highly productive subclones. Using the immunoperoxidase staining technique, tissue sections from 97 different RCC specimens and corresponding normal kidneys were evaluated for reactivity with the monoclonal antibodies. Over 90% of RCC were strongly positive, whereas normal kidney tissue did not react. Other normal human organ sections, including pancreas, liver, lung, stomach, small intestine, spleen, lymph node, arteries, veins, skeletal muscle, heart, skin and fetal tissues were negative for tumor-associated antigens. Mucous substances and Panets granular cells in colon mucosa showed nonspecific binding suppressible by addition of normal human serum. Adenocarcinoma of the stomach, colon, pancreas or breast did not demonstrate cross-reactivity with the antibodies to RCC. These monoclonal antibodies apparently recognize a tumor-associated antigen possibly specific for RCC. They could prove to be potent tools in the search for specific tumor markers applicable in the early diagnosis of the disease and immunotargeting cancer therapy.

Immunotherapy of Metastasizing Renal Cell Carcinoma

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

Active immunotherapy of stage IV renal cell cancer using autologous tumor cells

SummaryA total of 53 patients with stage IV renal cell carcinoma were treated by vaccination with autologous tumor cells in Candida-antigen after palliative tumor nephrectomy. Follow-up has been up to 9 years. Complete remission within 48 months after nephrectomy was observed in 3 patients, while 6 showed partial remission and 18 are stable with disease. Of 26 patients with rapid progression, 17 died within 1 year after operation. The best response was seen in metastases to the liver and lung. CNS-lesions or bone metastases do not appear to respond to this treatment. We conclude that this mode of therapy is beneficiary to a certain group of patients and should be offered, as no severe side effects have been observed so far. Whether new perspectives of adoptive immunotherapy using tumor-specific monoclonal antibodies or recombinant interferons will prove effective remains to be seen.

Local excision of urothelial cancer of the upper urinary tract

In 9 of 93 patients (9.7%) with urothelial cancer of the upper tract (7 renal pelvis tumors, 3 ureteral tumors), conservative surgery was employed using a free peritoneal autotransplant for replacement of the renal pelvis in 5 kidneys. Absolute indications for conservative surgery were solitary kidneys/nonfunctioning contralateral kidneys in 4 patients and bilateral tumors in 1 patient. Local recurrences developed 1-3 years after operation in 4 of 6 kidneys (3 patients), 3 of which had grade-2 and grade-3 primary lesions. All patients were treated successfully by repeated local excision. In the presence of a normal contralateral kidney, local tumor excision was done electively in 4 patients (3 low-grade/low-stage lesions, 1 high-risk patient), none of these patients developed recurrences. Two patients died without evidence of tumor recurrence, 7 patients are free of tumor at an average follow-up of 23 months (range 5-65 months). Local excision of urothelial cancer should be considered not only for solitary kidneys, bilateral tumors and cases with renal failure, but also for low-stage/low-grade localized tumors, leaving the patient better prepared for later treatment of a possible recurrence due to the well recognized chance of a multiplicity of tumors in time and space.

Slightly Radiopaque Uric Acid Calculi: Impact upon Therapeutic Considerations?

Ten patients with slightly radiopaque urinary calculi were treated by percutaneous litholapaxy or even open surgery. The stone analysis revealed uric acid as the main stone composite suggesting that these patients should have been treated by oral litholysis alone alkalinizing the urine and decreasing uric acid levels with allopurinol. CT density measurements proved that concrements with HE less than 600 can be successfully dissolved by oral medication alone. Twenty-four patients were subsequently treated by oral citrate alkalinizing the spontaneous urine to pH 6.8-7.2 dissolving even large staghorns within 6-8 weeks. CT density measurements have become a routine diagnostic procedure when poorly radiopaque calculi are found on the standard plain film. The patient can thus be spared invasive treatment which is unnecessary in most cases.

Karyotype analysis and marker chromosomes of renal cell carcinoma.

Karyotyping was performed in 46 human renal cell carcinomas of various histological grades. Controls included chromosome analysis of normal renal parenchymal cells from the same patients. Various numerical chromosome aberrations were found as well as marker chromosomes. They are specific of the individual tumor but no single marker was identified occurring in all tumors tested. Only trisomy 3 was found in different tumors (31%), suggesting a more general character of this aberration. Histological dedifferentiation and large tumor size correlate with focusing of the karyotype towards distinct chromosomal modes indicative of distinct tumor cell subclones within these tumors. Their rapid growth, reflecting biological aggressiveness, is most probably responsible for the patients poor prognosis.

Tumor-Specific Antigen for Human Renal Cell Carcinoma: Ultrastructural Localization of the Antigen Using 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 cells 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.

Extracorporeal Perfusion of the Tumor Bearing Human Kidney Using Tumor-Specific Monoclonal Antibodies: A Therapeutic Model

The use of monoclonal antibodies for tumor specific in vitro diagnosis is well established. With the possibility of producing tumor specific monoclonal antibodies, not only the in vitro application but also the in vivo use for tumor imaging is of great interest (Bander 1984; Mitchell and Oettgen 1982; Moon et al. 1983; Ritz et al. 1981). Methodology for radiolabelling of immunoglobulines is a well established and simple biochemical procedure thus making these antibodies ideal for immuno-szintigraphy (Greenwood et al. 1963; Hunter and Greenwood 1962; Mach et al. 1981; Scheinberg et al. 1982; Solter et al. 1982). Using alpha- or beta-emitting isotopes the therapeutic use of antibodies as tumor-targetted vehicles is feasible. With advances in biochemical conjugation procedures the coupling of cytotoxic drugs or cell toxines is now possible making the tumor specific antibody an ideal carrier for tumor specific application of drugs (Herlyn et al. 1980; Herlyn and Koprowski 1981; Houston and Nowinski 1981; Jansen et al. 1981; Krolik et al. 1983). Unfortunately presently only murine monoclonal antibodies are being produced which may cause problems in vivo being an alien proteine. A number of suggestions were made as how to circumvent the allergic complications possible after application of animal proteins (Baldwin et al. 1985; Craso and Griffin 1981; Gilliand et al. 1980). For the evaluation of our antibodies as possible carriers for radionuclides or cytotoxic drugs to the kidney tumor we developed an extracorporeal therapy model using the tumor bearing vital kidney.

Immunoperoxidase staining of fine-needle aspiration biopsies of renal cell carcinoma using tumor-specific monoclonal antibody.

In 30 nephrectomy specimens, fine needle aspiration biopsies (FNAB) were performed both in the tumor and in the macroscopically normal part of the kidney: 18 were well differentiated renal cell carcinoma (RCC), 6 were moderately differentiated RCC, 4 were poorly differentiated RCC, and 2 were oncocytomas. FNAB was also performed in a bone metastasis of RCC. FNAB materials were stained using the immunoperoxidase method with RCC-specific monoclonal antibody and were compared with the staining of frozen sections. In all cases where tumor-antigen expression could be demonstrated in the frozen sections, a FNAB had already proven positive. There were only 2 false-negative cases where sufficient cellular material could not be obtained due to extensive tumor necrosis. There was no false-positive case. Oncocytomas showed no expression of antigen. The use of immunoperoxidase staining of FNAB with tumor-specific monoclonal antibody is discussed.