Curative radiotherapy following chemotherapy for invasive bladder carcinoma (a preliminary report)

Twenty-five patients with invasive transitional cell carcinoma of the bladder (Stage T2, T3, T4) received combined modality therapy using four cycles of methotrexate, vinblastine, adriamycin, and cisplatin (MVAC) chemotherapy followed by surgery or radiation therapy (RT). Sixteen patients had complete (N = 8) or partial (N = 8) response to MVAC. Curative RT was delivered to 11 responders with T2 or T3 disease and to 2 patients with T4 disease. All 11 with T2 and T3 disease are currently alive, 7 with normal bladder function. The two with T4 disease are dead of disease. Three patients required salvage cystectomy for local recurrence and one patient had cystectomy for bladder stones. Follow-up ranged from 11 to 50 months with a median of 31 months. No late chemo-radiotherapy treatment-related complications to the intestines or in bladder function (other than one bladder stone formation) occurred. These preliminary results are encouraging and warrant further evaluation of this innovative approach in treating invasive carcinoma of the bladder. T2 and T3 patients with a complete or partial response to MVAC may be excellent candidates for a bladder-sparing treatment.     

The syndrome of inappropriate antidiuretic hormone secretion associated with induction chemotherapy for squamous cell carcinoma of the head and neck

Two patients with squamous cell carcinoma of the head and neck are reported in whom the syndrome of inappropriate antidiuretic hormone (SIADH) secretion occurred transiently during the rapid cytolytic phase of tumor destruction after chemotherapy with cis-platinum diamminedichloride and bleomycin. Immunoperoxidase staining for ADH of the original biopsy specimens from both patients was negative. Possible mechanisms for and the implications of the production of SIADH in this setting are discussed.     

Is pelvic irradiation necessary in stage III1A Hodgkin's disease?

Eighteen patients with pathologic Stage (PS) III1A Hodgkin's disease were treated with mantle and para-aortic field radiation therapy alone between 1973 and 1988. The median follow-up time is 84 months (range 20-174 months). The 5-year survival and relapse-free survival rates are 76 and 82%. Six patients had extensive splenic involvement or bulky mediastinal adenopathy, and three have relapsed and are dead of disease. Of the other 12 patients, only one has had recurrence of disease and died. Patients with PS III1A Hodgkin's disease are good candidates for mantle and para-aortic radiation therapy only, provided that they do not have extensive splenic involvement or large mediastinal adenopathy.     

Intravenous digital subtraction renal angiography: use in screening for renovascular hypertension

Intravenous digital subtraction renal angiography (DSRA) has been compared with conventional angiography only in small, selected series of hypertensive patients. The authors prospectively examined with intravenous DSRA 94 patients at increased risk for renovascular hypertension and compared these studies with conventional angiography. A stenosis of at least one main renal artery was identified with intravenous DSRA in 22 patients and confirmed in 20 patients. No significant stenoses were seen with conventional angiography in any of the 64 patients in whom lesions were not seen with intravenous DSRA. Since inadequate DSRA studies were considered positive for renal artery stenosis, the sensitivity of intravenous DSRA was 100% (25 of 25); specificity, 93% (64 of 69); positive predictive value, 83% (25 of 30); and negative predictive value, 100% (64 of 64). The authors conclude that intravenous DSRA is a sensitive test for identifying stenosis of the main renal arteries and is appropriate to use as a screening test among patients at increased risk for renovascular hypertension.     

Indacrinone (MK-196) - a specific inhibitor of the voltage-dependent CI- permeability in toad skin

The effect of indacrinone (MK-196) on Cl^- transport through toad (Bufo bufo) skin epithelium was studied by the voltage clamping technique. At the transepithelial potential, V = 50 mV (serosal bath grounded) the unidirectional fluxes, governed by a Cl^- self-exchange diffusion pathway, were not affected by 1 mM racemic MK-196 in the outer bath. Likewise at V = 0 mV, the unidirectional fluxes as well as the active (net) inward flux of Cl^- were unaffected by MK-196. Voltage clamping the epithelium in the physiological range of potentials activated a Cl^- specific passive conductance that saturated for V ±– 90 mV. The influx and efflux of Cl^- through this pathway were inhibited by MK-196, and the (passive) Cl^- current was inhibited in a dose-dependent way for [MK-196] ± 50 μM with about 70% inhibition for [MK-196] = I mM. The maximum Cl^- conductance was decreased without shifting the position along the V-axis of the inverted S-shaped conductance–voltage relationship. The time constants for the voltage-stimulated Cl^- conductance activation were not affected by MK-196 (50 μM ± [MK-196] ± 1 mM). The (+) and (–) isomers and racemic MK-196 affected the voltage-dependent Cl^- conductance in similar ways. It is concluded that MK-196 has the properties of a Cl^- channel blocker which is specific for the voltage-dependent Cl^- permeability of the epithelium. The time course for development of inhibition exhibited a fast (min) and a slow (h) component. The fast component may reflect a direct interaction of MK-196 with an extracellular site of the Cl^- channel, whereas the slow one may reflect impairment of a metabolic pathway regulating the Cl^- permeability, or an interaction of MK-196 with a cytoplasmic site of the anion permeation pathway.     

Increased tumor necrosis factor alpha mRNA after cellular exposure to ionizing radiation.

We report that tumor necrosis factor alpha (TNF-alpha) mRNA is increased after treatment with x-rays in certain human sarcoma cells. An increase in TNF-alpha mRNA is accompanied by the increased production of TNF-alpha protein. TNF-alpha enhances radiation lethality in both TNF-alpha-producing and -nonproducing tumor cells. These data suggest that, in addition to the direct cytotoxic effects of x-rays, production of TNF-alpha may add to radiation lethality through autocrine and paracrine mechanisms. Combinations of TNF-alpha and therapeutic radiation may be useful in clinical cancer therapy.