Management of invasive squamous cell carcinoma of the bulbomembranous male urethra with co-ordinated chemo-radiotherapy and genital preservation.

OBJECTIVE: To determine the success of chemo-radiotherapy for squamous cell carcinoma (SCC) of the bulbar male urethra, an uncommon but aggressive cancer usually treated by radical deforming surgery. PATIENTS AND METHODS: Two men, aged 42 and 49 years, with locally advanced SCC of the proximal deep urethra were treated with a modified Nigro chemo-radiation protocol. The initial treatment was by suprapublic cystotomy urinary diversion followed by 45 Gy in 25 fractions over 5 weeks to the penis, perineum and regional lymphatics. Chemotherapy consisted of a single intravenous dose of mitomycin C (10 mg/m2) and an intravenous infusion of 5-fluorouracil (1 g/m2/day) for 96 h starting on the first day of radiation therapy and repeated 28 days later. RESULTS: Follow-up evaluation with urethral biopsies, retrograde urethrography, computed tomography of the pelvis and cysto-urethroscopy under anaesthesia showed no residual tumour in either patient but the development of a proximal urethral stricture at 1.5 and 4 years, respectively. CONCLUSION: This report presents the first evidence of a successful reduction of tumour stage with the local eradication of invasive SCC and penile preservation with no recurrence of the tumour or the need to excise the urethra.

Flutamide-associated liver toxicity during treatment with total androgen suppression and radiation therapy for prostate cancer.

PURPOSE: To examine the frequency and severity of toxicity associated with flutamide inpatients treated with total androgen suppression before and during pelvic radiation therapy (RT) for prostate cancer. MATERIALS AND METHODS: Sixty-five patients with T2b-T4 prostate cancer received flutamide and goserelin acetate for 4 months, with RT beginning at the 3rd month. Treatment records including liver function test (LFT) results at baseline and during treatment were reviewed and toxicities noted. RESULTS: In 30 (46%) of 65 patients, flutamide was discontinued prematurely. Primary reasons included elevation in LFT levels (n=14); gastro-intestinal toxicity (n=9); decreased hemoglobin level (n=2); patient refusal (n=2); and arthralgia, rash, and malaise (n=1 each). Hepatotoxicity generally was manifest as asymptomatic transaminase level elevation. Grade 3-4 hepatotoxicity was noted in four of 65 patients. Mean aspartase aminotransferase increased from 23 (baseline) to 67 U/L (during flutamide treatment) (P<.02); mean alanine aminotransferase level increased from 26 (baseline) to 94 U/L (during flutamide treatment) (P<.005). CONCLUSION: Flutamide toxicity was common. LFTs should be monitored during flutamide therapy. The role of flutamide in this treatment regimen may need to be reevaluated.

Intraluminal low-dose rate brachytherapy for malignant endobronchial obstruction.

From October 1985 through October 1989, 87 patients underwent 105 intraluminal brachytherapy treatments for endobronchial or endotracheal malignant tumors. Low-dose rate iridium-192 seeds were used. Of the 60 patients treated for primary lung carcinoma, 52 patients (87%) had previously received full-course external beam radiotherapy to the tumor sites. Ten patients were treated for symptomatic metastatic disease, and one patient had extension of tumor into the trachea from carcinoma of the cervical esophagus. Clinical or bronchoscopic improvement was noted in 42 patients (59%). No significant difference in the response rate was observed between various types of tumor. Patients who were treated with a radiation dose larger than 2500 cGy at a 2 cm radius had a significantly greater response rate (77%) than patients treated with a dose less than 2500 cGy (38%) (p = 0.001). A trend toward better results was apparent in patients who had undergone Nd:YAG laser bronchoscopy in the 2 weeks before brachytherapy. The treatments were well tolerated, and the incidence of serious complications was low and acceptable.

Prognostic indicators of laparotomy findings in clinical stage I-II supradiaphragmatic Hodgkin's disease.

Between July 1968 and July 1986, 915 patients with clinical stage (CS) I and II Hodgkin's disease limited to sites above the diaphragm underwent laparotomy and splenectomy at Stanford University. Fifteen percent were CS I, of whom 76% had cervical/supraclavicular disease, 13% axillary disease, and 9% mediastinal presentations. CS I patients were more likely to be male, were significantly older, and were significantly less likely to have nodular sclerosis (NS) histology than CS II patients. Twenty percent of CS I patients and 30% of CS II patients were pathologically upstaged. No CS I patients were upstaged to pathological stage (PS) IV. Univariate and multivariate analyses of presenting clinical characteristics were performed to predict staging laparotomy findings. CS I women, CS I patients with mediastinal-only disease, and CS I men with either lymphocyte predominance or interfollicular histologies were at low risk for having disease below the diaphragm (5%) or requiring chemotherapy (0%). CS II women who were less than 27 years old and had only two or three sites of disease were also at low risk for upstaging (9%) or requiring chemotherapy (2%). Mixed cellularity histology and male gender were associated with increased risk for subdiaphragmatic disease and require laparotomy; the presence of systemic symptoms was not correlated with laparotomy findings. These results confirm the importance of performing staging laparotomy for the majority of patients who present with supradiaphragmatic Hodgkin's disease if treatment programs are based on the presence and extent of subdiaphragmatic disease. Selected subgroups are at low risk for subdiaphragmatic disease and might be spared laparotomy if they are treated with mantle, paraaortic, and splenic irradiation.

Subdiaphragmatic Hodgkin's disease: laparotomy and treatment results in 49 patients.

The clinical records of 1,616 patients with previously untreated Hodgkin's disease were reviewed. Forty-nine of these patients (3%) presented with disease limited to sites below the diaphragm and underwent laparotomy as part of their staging evaluation. The clinical and histological characteristics of this group of patients with subdiaphragmatic Hodgkin's disease are compared with those who presented with supradiaphragmatic disease. Splenectomy in 47 patients revealed splenic involvement in 16 (39%), and bulky splenic involvement (more than five gross nodules) in ten (24%). The final pathological stage (PS) distribution was PS I = 8, PS II = 37, PS IV = 4. No clinical stage (CS) IA patients and only two of 20 patients with negative paraaortic nodes on lymphogram had splenic involvement in contrast to eight of nine CS IIB patients. Freedom from relapse and survival were similar to patients with equivalent stage supradiaphragmatic disease. Splenic involvement and bulky splenic involvement were associated with a significantly decreased survival. Twelve out of 44 PS IA to IIB patients relapsed. In eight of these 12 patients, relapse was limited to sites above the diaphragm and another two patients relapsed both above and below the diaphragm. Patients who received total lymphoid irradiation were less likely to relapse above the diaphragm than patients who received no supradiaphragmatic irradiation. We recommend that CS IA and IIA patients with subdiaphragmatic disease undergo staging laparotomy and receive supradiaphragmatic irradiation as part of their treatment. Laparotomy may not be necessary for CS IIB patients who are at high risk for splenic disease if chemotherapy is planned as part of their treatment program.

Secondary Haemophilus influenzae type b in day-care facilities. Risk factors and prevention.

The risk factors for acquisition of secondary day-care-associated Haemophilus influenzae type b disease were evaluated in a cohort of children in Seattle-King County, Washington; Atlanta; and the state of Oklahoma. During the study period, 129 primary cases were identified in children less than 5 years old who attended day-care facilities. In ten instances (8%), a secondary case occurred between one and 60 days after a primary case in the same classroom. Risk of secondary disease in classroom contacts was strongly age related: 2.4% in children 0 to 11 months old, 1.2% in children 12 to 23 months old, and 0.0% in children 24 to 59 months old. Controlling for age, children attending day-care more hours per week were more likely to transmit or acquire secondary disease. Risk of secondary disease for children in other classrooms at a center where a case had occurred was not significantly greater than risk of primary disease. Administration of rifampin to classroom contacts of a child with invasive H influenzae was effective in preventing secondary cases (95% confidence interval for rifampin efficacy, 47% to 100%). For children 0 to 23 months old not treated with rifampin, risk of secondary disease was 2.7% (95% confidence interval, 1.1% to 4.3%), a risk approaching that reported in household contacts.