Etsuji Nakano

Interleukin-6 Activity in Urine and Serum in Patients with Bladder Carcinoma

To investigate the correlation between interleukin-6 and urothelial neoplasms, interleukin-6 activities in blood and urine samples of patients with bladder carcinoma were measured with a proliferation assay using an interleukin-6 dependent murine hybridoma clone, MH60.BSF2. A total of 43 patients and 15 normal volunteers were entered into this study. All of the patients were examined preoperatively and 26 were reexamined more than 6 days postoperatively to eliminate the effect of surgical injury on interleukin-6 secretion. The interleukin-6 titers in urine and serum increased in accordance with the progression of the tumor stage, and tumor removal induced a remarkable decrease in the titer of urinary interleukin-6. Although the interleukin-6-producing site has not been elucidated yet, our study suggests that interleukin-6 activity in bladder carcinoma patients may reflect the immunoreaction against the tumor in local urothelium.

Late recurrence of renal cell carcinoma after nephrectomy.

Late recurrence of renal cell carcinoma is unusual. Of 43 patients who underwent curative nephrectomy more than 10 years before, 2 cases (4.7%) had late recurrence. The 2 cases, both female patients, had late recurrence 12 and 19 years from the date of nephrectomy. The clinical aspects of late recurrence are discussed briefly.

Incidentally diagnosed renal cell carcinoma.

We analyzed the incidence, sex and age distribution, diagnostic methods and survival rate of incidentally detected renal cell carcinomas (RCCs) and compared these factors with those of symptomatic RCCs. Of 141 patients with RCC treated between 1980 and 1989, 44 cases (31.4%) were incidentally detected. Thirty-one of these 44 cases were diagnosed by abdominal ultrasonography. The age of the incidental cases was significantly higher than that of the symptomatic ones (p = 0.045), particularly in male patients (p = 0.049). The tumor size in incidental cases was smaller and tumor stage earlier (p less than 0.0001). Moreover, the grade of malignancy was significantly lower, and clear cell type tumors were more frequently detected in the incidental cases. No difference was observed between the survival rates of incidental and symptomatic cases with stage 1 or 2 tumors. Of the incidental cases with stage 1 or 2, however, no patient with a tumor 3 cm or less in diameter has died. In conclusion, abdominal ultrasonography is a useful tool to detect RCC at an early stage, and patients with a relatively small tumor tend to have a good prognosis.

Hormone Receptor in Renal Cell Carcinoma and Correlation With Clinical Response to Endocrine Therapy

Analyses of hormone receptors in cytosols from 41 renal cell carcinoma specimens were performed by the dextran-coated charcoal technique, using estradiol, synthetic progestin R5020 and synthetic androgen R1881. Binding data were calculated according to the method of Scatchard. Of 41 renal cell carcinomas estradiol receptor was detected in 11, R5020 receptor in 11 and R1881 receptor in 13. No significant correlation between histopathological findings and hormone receptors was observed. Patients were classified into those positive and negative for receptors. The clinical response of endocrine therapy for 17 with advanced residual or metastatic lesions after nephrectomy was studied in regard to the survival rates. Although there was no complete or partial regression in tumor size, the survival rate of patients with 1 or more receptors was significantly higher than that of patients negative for receptors (p less than 0.01). In conclusion, hormonal manipulation in patients with renal cell carcinoma cannot induce an antitumor effect but seems to increase survival in patients with receptors.

Clinical Manifestations of Calcium Oxalate Monohydrate and Dihydrate Urolithiasis

We studied retrospectively 155 patients with calcium oxalate urolithiasis. The patients were divided into 3 groups: 1) those with calcium oxalate monohydrate, 2) those with calcium oxalate dihydrate and 3) those with mixed calcium oxalate monohydrate and dihydrate. Various differences were noted between patients with calcium oxalate monohydrate and those with calcium oxalate dihydrate, with respect to stone characteristics, spontaneous passage of stones, stone recurrence and multiple occurrence. Most important, we noted that patients with calcium oxalate dihydrate had more stone recurrences than patients with calcium oxalate monohydrate.

Solitary late recurrence of renal cell carcinoma.

Solitary late recurrence is an unpredictable behavior pattern of renal cell carcinoma. We describe a patient with recurrence at the cranial bone 10 years after surgical management and another with recurrence at the sacral bone 13 years after treatment with radiotherapy and alpha-interferon. Both patients have been followed satisfactorily for 9 months. Unpredictable behavior of renal cell carcinoma makes lifelong followup of patients necessary. If a solitary recurrence is detected operative management definitely should be considered depending on the site of recurrence.

Spontaneous regression of pulmonary metastases after nephrectomy for renal cell carcinoma

A case of spontaneous regression of pulmonary metastases from renal cell carcinoma after nephrectomy is presented. In a 57-year-old Japanese male who had already had pulmonary metastases at the time of nephrectomy, the metastatic lesions disappeared without adjuvant therapy 8 years after nephrectomy. He is still surviving without recurrence or any signs indicative of new metastasis at the present. The clinical aspects of this interesting phenomenon are discussed briefly.

Enhancement of interleukin-2-induced lymphokine-activated killer activity by interleukin 7 against autologous human renal cell carcinoma.

Adjuvant immunotherapy with interferons and/or interleukin 2 (IL-2) is widely used for advanced kidney cancer. However, the results are not satisfactory so far. The purpose of this study is to evaluate the inducible activity of lymphokine-activated killer (LAK) cells against autologous human renal cell carcinoma. The effect of interleukin 7 (IL-7) on IL-2-induced LAK activity was assessed by the autologous assay system which we have established. Peripheral blood lymphocytes from patients with renal cell carcinoma were stimulated with IL-2 and/or IL-7, and tested for antitumor activity against autologous renal cell carcinoma. In all 10 cases tested, IL-7 alone induced LAK activity. Moreover, IL-2-induced LAK activity was augmented by the concomitant addition of IL-7. Flow cytometry revealed an increase in IL-2-receptor-positive lymphocytes following incubation with IL-7. These results suggest that combination therapy using IL-2 and IL-7 may be a useful treatment for patients with advanced renal cell carcinoma.

Renal Arteriovenous Fistula Associated with a Huge Renal Vein Dilatation

We report a case of an aneurysmal type of renal arteriovenous fistula with a huge spherically dilated renal vein. Although the findings on routine computerized tomography made us strongly suspect renal cell carcinoma associated with a hilar lymph node metastasis, we were able to diagnose the arteriovenous fistula by means of a dynamic computerized tomography scan. On the basis of the roentgenographic findings, partial nephrectomy was performed successfully.

Lysis of autologous tumor cells by peripheral blood lymphocytes treated with interleukin 2 in patients with renal cell carcinoma.

Peripheral blood lymphocytes derived from patients with renal cell carcinoma were stimulated with interleukin 2 and tested in a 4-hour 51chromium-release cytotoxicity assay against autologous cultured tumor and myeloid K562 cells. Of 23 patients autologous tumor lysis of more than 0 per cent was observed in 20 (range 5.3 to 82.8 per cent) and more than 10 per cent lysis was noted in 16. Since no significant correlation between the degree of cytotoxicity and the pathological findings of tumor stage, grade, cell type or lymphocyte infiltration in the tumor was found, it was impossible to predict from the pathological findings which tumor could be lysed by peripheral blood lymphocytes treated with interleukin 2. Comparison of natural killer cell activity against K562 of freshly prepared peripheral blood lymphocytes to that of interleukin 2-treated lymphocytes revealed significant augmentation from 23.6 +/- 9.7 to 65.2 +/- 29.1 per cent. From the kinetics study the lysis of autologous tumor cells was detectable on day 2 of interleukin 2 exposure and the peak activity was observed on day 5. A similar trend was noted in regard to K562 cell lysis. Measurements of peripheral blood lymphocyte subsets with monoclonal antibodies and argon ion laser flow cytometry resulted in a significant decrease of cells positive for OKT 4 (helper/inducer) and a significant increase of cells positive for OKT 8 (suppressor/cytotoxic) and Leu 7 (natural killer) by interleukin 2 treatment. A cold target cell inhibition test was performed in 2 patients with unlabeled autologous tumor and K562 cells as cold inhibitors. In 1 patient unlabeled K562 completely inhibited the tumor lysis but in 1 complete inhibition by autologous tumor and incomplete blockade by K562 were found. From this observation we concluded that peripheral blood lymphocytes treated with interleukin 2 lysed not only autologous tumor cells but also K562. Our results demonstrate that adoptive immunotherapy with peripheral blood lymphocytes activated by interleukin 2 in patients with renal cell carcinoma could be appropriate as a therapeutic procedure.