Sclerotherapy versus sclerotherapy and propranolol in the prevention of rebleeding from oesophageal varices: a randomised study.

BACKGROUND: This trial was carried out to assess the value of propranolol in the prevention of recurrent variceal bleeding when combined with longterm endoscopic sclerotherapy. PATIENTS AND METHODS: Two hundred patients (161 male, 39 female, age range 20-68 years) with portal hypertension resulting mainly from schistosomal periportal fibrosis or posthepatitic cirrhosis presenting with their first episode of haematemesis or melena, or both were included. This was confirmed endoscopically to result from ruptured oesophageal varices. After initial control of bleeding, patients were randomised into two groups: group 1 treated with endoscopic sclerotherapy alone and group 2 treated with sclerotherapy plus propranolol. They were followed up for two years. RESULTS: Group (2) had a lower rebleeding rate (14.3% v 38.6% in group 1), lower variceal recurrence after obliteration (17% v 34% in group 1), longer period between variceal obliteration and recurrence (36 weeks v 21 weeks in group 1); but no change in mortality (12% in both groups). CONCLUSIONS: Patients treated with sclerotherapy should be given propranolol for longterm management.

The combined use of radiation therapy and lonidamine in the treatment of brain metastases.

Lonidamine is an indazole carboxylic acid that has been shown to be synergistic with radiotherapy (RT) in tissue culture and animal models. Clinical experience has shown that lonidamine is well-tolerated, and appears to potentiate the activity of conventional chemotherapy in the treatment of brain metastases. A prospective randomized trial was undertaken to evaluate the use of lonidamine in combination with RT in the treatment of brain metastases. All patients received 3000 cGy of whole brain radiotherapy (WBRT). Fifty eight patients were enrolled; 31 received lonidamine plus WBRT and 27 received WBRT alone. There was no significant difference in response rate or survival between the treatment groups. Lonidamine blood levels were measured in 30 of the 31 patients who received the drug, and were therapeutic (greater than or equal to 15 micrograms/ml) in 50%. Survival and response rate were unaffected by the presence or absence of a therapeutic lonidamine level. The most common side-effects of lonidamine were myalgia, testicular pain, anorexia, and ototoxicity; however, only 2 patients had to discontinue the drug because of intolerable myalgias. No serious organ toxicity or myelosuppression was observed.

Primary hepatocellular carcinoma: clinical, ultrasonic, and pathological patterns and correlations.

Twenty-seven patients with tissue diagnosis of hepatocellular carcinoma were reviewed retrospectively in an attempt to do a correlative study between clinical echographic patterns and the pathologic grading. The mean of the anterior hepatic linear projection (AHLP) was 33 cm; the surface was smooth in 26% and irregular in 30% and a single mass was detected in 44% of cases. Ultrasonically, three patterns were detected: 1) solitary mass in 66.6% of cases: hyperechogenicity in 22.2%, hypoechogenicity in 27.8%, and compound echogenicity in 50% of cases; 2) multiple masses in 25.9% of cases: hyperechogenicity in 71.4% and compound echogenicity in 28.6%; and 3) diffuse distortion of hepatic architecture with areas of heterogenous echopattern in 7.4% of cases. Pathological grading was carried out according to the generally accepted criteria, grades I in 29.6%, II in 33.3%, and III in 37.1% of cases. No correlation could be detected between the AHLP, patient age, sex, duration of complaint, or incidence of distant metastases and the pathologic grading. Also, there was no correlation between the duration of complaint and the AHLP. However, a significant relation was detected between the character of the hepatic surface and the pathologic grading; a smooth liver was associated with lower pathologic grading compared to either the surface with a single mass or to the irregular surface. On the other hand, no significant relation could be detected between lobar affection, ultrasonic pattern, or echogenicity and the pathologic grading.

Phase I and clinical pharmacologic evaluation of Lonidamine in patients with advanced cancer.

Lonidamine was studied in 31 patients with different types of advanced cancer. With one exception, patients were pretreated. Lonidamine was given at 6 dosage levels from 180 to 520 mg/m2 for at least 28 days. No toxicity on hematopoietic function was observed. Side effects consisted mostly in musculoskeletal discomfort, testicular pain in males and a reversible ototoxicity. In 2 patients conjunctivitis and photophobia occurred. Plasma Lonidamine levels were measured in 14 patients. Peak concentrations were observed from 1 to 2 h after administration and ranged from 3 to 35 micrograms/ml. Objective antitumoral effects were observed in only 2 patients with mycosis fungoides; a 3rd patient with mycosis fungoides was considered to have stable disease.