Primary Chemotherapy in the Treatment of Children With Bladder-Prostate Tumors in the Intergroup Rhabdomyosarcoma Study (IRS-II)

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ONCOLOGY AND CHEMOTHERAPY

lower and upper incisions. The catheter is pushed gently from the lower to the upper incision to locate it in the tunnel. A puncture is made over the subclavian vein and a guide wire is passed into the superior vena cava. Then, the needle is removed and the catheter is passed over the wire and lodged in the superior vena cava. X-ray studies with or without fluoroscopy will confirm the position of the catheter. The procedure is simple and reliable, and gives an easy access to the vein under local anesthesia. N. J. 6 figures, 3 references

The Quality of Life in Patients With Cancer. A Survey at One Treatment Center D. L. COOKFAIR, w. LANE AND J. PICKREN, Departments of Cancer Control and Epidemiology, and Pathology, and the Computer Center, Roswell Park Memorial Institute, New York State Department of Health, Buffalo, New York

C. METTLIN,

N. Y. State J. Med., 83: 187-193 (Feb.) 1983 A number of hospitals maintain tumor registries, tumor cell type, tumor stages and followup for cancer patients. However, there are little quantitative data on the quality of life. Also, there is a lack of information concerning permanent disability, employability and social performance of these patients. The authors have collected such data on 1,902 cancer patients seen at the Roswell Park Memorial Institute during the last decade. Various cancers and treatments are reviewed. Treatment by surgery only was associated with lowest levels of impairment and nursing care needs, and highest employability of any treatment type. N. J. 1 figure, 8 tables, 8 references

Macrophage-Mediated Tumor Cytotoxicity: Role of Macrophage Surface Sialic Acid

D. J. CAMERON, Department of Surgery, Medical University of South Carolina, Charleston, South Carolina J. Surg. Oncol., 22: 77-80 (Feb.) 1983 Human macrophages obtained from peripheral blood monocytes, when incubated with lipopolysaccharide, acquired enhanced cytotoxicity for human tumor cells. The author has investigated the effects of neuraminidase on cytotoxicity of the macrophage in normal volunteers and patients with breast cancer. Human peripheral blood mononuclear cells obtained from breast cancer patients as well as normal volunteers were isolated on Ficoll-Hypaque gradients. Cell surface sialic acid levels were compared for macrophages obtained from normal volunteers and breast cancer patients. Although there was no difference between the quantity of sialic acid found on the monocytes of these 2 groups, approximately 60 per cent more cell surface sialic acid was found on the macrophages from patients with breast cancer than from normal volunteers. High levels of sialic acid have been found in the serum of cancer patients. It is postulated that the high serum levels of sialic acid may interfere with the immune response in these cancer patients. To determine whether cell surface sialic acid had any effect on macrophage-mediated cytotoxicity, macrophages were pre-treated with neuraminidase before co-cultivation with tumor cells. After neuraminidase treatment of macrophages from normal volunteers their ability to kill tumor cells is lost. However, in samples obtained from patients with breast cancer no

difference was determined in the ability of untreated and treated macrophages to kill tumor cells. Further experiments are needed to ascertain the exact role of cell surface sialic acid in macrophage-mediated cytotoxicity. N. J. 3 tables, 13 references

Suppressor Cells and Increased Primary Tumor Growth Rate Induced by Thiopental E. J. LOVETT, III, J. VARANI AND J. LUNDY, Department of Surgery, University of Connecticut Health Center, Farmington, Connecticut J. Surg. Oncol., 22: 26-32 (Jan.) 1983 As early as 1965 reports have indicated that anesthetic agents could influence the growth of tumors. Sodium pentobarbital was shown to increase the tumor induction rate in rodents. The development of spontaneous and chemically induced liver tumors in C3H mice was enhanced by phenobarbital. More recently, Pollard has shown that barbiturates can modify the rate and extent of spontaneous metastasizing prostate tumors in rats. The authors have shown that thiopental can increase the number of artificial pulmonary metastases in a syngeneic murine fibrosarcoma. This study was designed to determine if thiopental influences the rate of growth of primary tumors and if an underlying immunologic mechanism was at least partly responsible for increased tumor growth. A single dose of thiopental (3 to 42 mg./kg.) sufficient to achieve anesthesia increased the growth rate of 3-methylcholanthrene-induced syngeneic murine fibrosarcoma in C57Bl/6 mice. While no alterations in in vitro growth kinetics of tumor cells cultured with thiopental could explain these data, significant alterations in cell-mediated immunity were observed. Spleen cells from C57Bl/6 mice treated with thiopental were impaired in their ability to respond in a mixed leukocyte culture to BALB/c stimulator cells. Spleen cells from thiopentaltreated mice suppressed the ability of cells from untreated animals to respond in a third-party mixed leukocyte culture. The degree of suppression was directly proportional to the number of cells from thiopental-treated mice in the third party. When these cells were added to a mixed leukocyte culture at various times during the culture interval suppression of the early phases of the mixed leukocyte culture was seen. Removal of plastic adherent cells from the third party resulted in loss of suppression but treatment of third-party cells with anti-thy 1.2 serum or irradiation did not prevent suppression. Transfer of spleen cells from thiopental-treated mice enhances growth of the B-16 melanoma. Suppressor cell activity may be 1 mechanism by which thiopental promotes tumor growth. W. W K. 5 figures, 2 tables, 19 references

Primary Chemotherapy in the Treatment of Children With Bladder-Prostate Tumors in the Intergroup Rhabdomyosarcoma Study (IRS-II) D. M. HAYS, R. B. RANEY, JR., w. LAWRENCE, JR., M. TEFFT, E. H. SOULE, W. M. CRIST, M. FOULKES AND H. M. MAURER, The Intergroup Rhabdomyosarcoma Study Committee, Richmond, Virginia J. Ped. Surg., 17: 812-820 (Dec.) 1982 The purpose of this study was to limit radical surgery, spe-

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TRAUMA

cifically pelvic exenteration, and radiotherapy when possible in the treatment of nondisseminated rhabdomyosarcoma of the bladder or prostate. In > 75 per cent of the children the diagnosis was made during the first 4 years of life. Of the 24 boys and 5 girls studied 27 had ~3 of the following symptoms or signs: 1) urinary frequency or urgency, 2) lower abdominal discomfort, 3) hematuria, 4) palpable abdominopelvic mass, 5) fever and 6) constipation. Diagnosis was made by biopsy at cystoscopy in 13 children, combined cystoscopy and perineal (needle) biopsy in 3 and perineal biopsy in 8. Biopsy was done at laparotomy in 4 patients and at cystoscopy in 1. Therapy included a primary chemotherapy regimen consisting of vincristine, actinomycin D and cyclophosphamide (pulse V AC) with or without local radiotherapy. During the initial 20 weeks of chemotherapy 9 children achieved a clinical complete response: 3 are free of disease and have functional bladders (2 after partial cystectomy), 4 subsequently suffered a relapse or biopsy remained positive but presently are free of disease following radiotherapy and anterior exenteration, and 2 have died of recurrent disease. Twelve patients had a clinical partial response at <20 weeks and 2 at <40 weeks: 7 are free of disease with intact bladders following chemotherapy-radiotherapy, 1 is free of disease following partial cystectomy, 4 have been treated by exenteration following failure to achieve complete response and are free of disease, 1 died and 1 has progressive disease. Six patients had an inadequate response to chemotherapy. Anterior exenteration was done in 3 patients and 2 have survived. Overall, of these 29 patients 11 are free of disease with functional bladders, 10 are free of disease following anterior exenteration, and 8 are dead or death of tumor is anticipated. The function of retained bladders (11 patients) has been satisfactory. These results can be summarized as follows: 1) the rate of bladder salvage (38 per cent) was appreciable, although not as high as some studies, 2) the mortality (27 per cent) was higher than in similar patients treated by different regimens but not significantly so, 3) anterior pelvic exenteration is an effective salvage procedure in almost all patients in whom the tumor shows an initial response to chemotherapy, even when used late in the course, and 4) partial cystectomy resulted in survival with functioning bladders in 3 patients. H. M. S. 4 tables, 10 references

Editorial comment. Rhabdomyosarcoma is another of the childhood malignancies that often is dramatically responsive to chemotherapy. This finding has led to the attempt described in this study to treat local (groups 1 and 2) disease by chemotherapy alone, using surgery for biopsy only or "lumpectomy" when residual tumors have become small and are in an accessible location. These early results are impressive but suggest that radiotherapy usually will be needed also. If this is the case earlier radiotherapy may increase bladder salvage and also survivorship. It also seems clear that cystoprostatectomy should be done early if the tumor fails to disappear with radiation and chemotherapy. In 4 ofmy own patients treated primarily with chemotherapy and early radiation 3 children became free of disease in <4 months and did not suffer relapse. One bladder eventually was lost to intractable hemorrhagic cystitis owing to cyclophosphamide. The fourth patient had residual disease but the family refused anterior exenteration. Cyclic vincristine-actinomycin D and cyclophosphamide were continued, and the tumor disappeared gradually during the next year. This patient is well 2½ years off therapy. Radiation therapy remains an important adjunct in treatment if the bladder is to be retained. L. R. K.

DISEASES OF BLOOD VESSELS, HYPERTENSION AND RENOVASCULAR SURGERY Thiazides III. Evidence of Dose Proportionality of Hydrochlorothiazide 25, 50 and 100 Mg Tablets

V. P. SHAH, J. J. LEE, V. K. PRASAD, J. P. HUNT AND B. E. CABANA, Division of Biopharmaceutics/Biopharmaceutics Laboratory, National Center for Drugs and Biologics, Food and Drug Administration, Washington, D. C. Res. Comm. Chem. Path. Pharm., 39: 39-48 (Jan.) 1983 Hydrochlorothiazide is a widely prescribed thiazide diuretic used to treat hypertension, congestive heart failure and edematous conditions. The drug currently is marketed as 25, 50 and 100 mg. tablets, and the daily recommended dose varies between 50 and 100 mg. 1 or 2 times daily. Despite the availability of 3 dosage strengths a dose proportionality for hydrochlorothiazide among 25, 50 and 100 mg. tablets has not been demonstrated clearly. Studies with a similar drug, chlorothiazide, suggested that dose proportional absorption or excretion does not exist between the commercially available 250 and 500 mg. tablets. On an average, 50 mg. chlorothiazide were absorbed and recovered in 48 hours after administration of the 250 or 500 mg. dose. Whether this nondose proportionality phenomenon extends to commercially available hydrochlorothiazide tablets was studied. A pilot bioavailability study was done in which 2 subjects were administered a dose of 25, 50 or 100 mg. commercially available hydrochlorothiazide tablets. Plasma and urine samples were analyzed. A maximum plasma concentration of 50 to 285 ng./ml. was reached in 1 to 2 hours and plasma levels decreased rapidly, with a half life of about 2 to 4 hours during the first 12-hour interval. A plot of the amount of hydrochlorothiazide eliminated as a function of dose administered shows a good linear relationship, suggesting that according to this limited study a dose proportional urinary excretion exists at the 3 dose levels studied. H. D. P. 2 figures, 1 table, 15 references

TRAUMA Blunt Renal Trauma. Analysis of 417 Patients D. BERGQVIST, L. GRENABO, H. HEDELIN, B. LINDBLAD AND T. MATZSCH, Department of Surgery, Karnsjukhuset, Skoude, Sweden

Eur. Urol., 9: 1-5 (Jan.) 1983 The records of 417 patients hospitalized because of blunt renal trauma during a 29-year interval were analyzed. Approximately half of the patients were between 10 and 29 years old and 83 per cent were male patients. Traffic accidents accounted for 51 per cent of the injuries. Of the patients 332 had minor injuries (mild hematuria with delayed, diminished or normal function on urography and stable vital signs), 20 had major injuries (severe hematuria, nonvisualization of the kidney or unstable vital signs) and 65 had intermediate injuries. There were 292 associated injuries recorded in the series. Treatment was conservative in 82 per cent of the patients, while 73 underwent surgical exploration. Of the latter patients 37 required renal exploration: 19 had an intermediate renal injury and 18 had severe renal trauma, with nephrectomy being