Pharmacokinetics of propranolol and atenolol in patients after partial gastric resection: a comparative study.

OBJECTIVE: Partial gastric resection alters the anatomy and secretory activity of the gastrointestinal tract. It might be expected that the consequences of such changes should affect the pharmacokinetics, especially concerning the absorption of orally administered drugs. Propranolol and atenolol, as representatives of lipophilic and hydrophilic beta-adrenoreceptor antagonists, have been studied in order to define their pharmacokinetic characteristics in patients after partial gastrectomy. METHODS: The study was carried out in 29 patients after gastric resection with Billroth I (B1) anastomosis and in 18 healthy volunteers as controls. Pharmacokinetics of propranolol and atenolol was investigated after a single oral dose of 80 mg and 100 mg, respectively, following a cross-over schedule. Blood samples were collected ten times during the 24 h after the drug administration. Pharmacokinetic parameters of propranolol and atenolol were calculated using a one-compartment open model with first-order absorption. RESULTS: The average blood plasma concentrations of propranolol in gastrectomised patients were lower than those in controls, reaching significance between 1.5 h and 6.0 h of the observation period. Pharmacokinetic parameters of propranolol were different in subjects submitted to surgery compared with healthy persons. We observed a significant decrease in the area under the concentration-time curve (32%) and the peak plasma concentration (20%), and an increase in half-life (25%). Mean plasma concentrations and pharmacokinetic parameters of atenolol in patients following partial gastric resection were not significantly different from those in the controls. No relationship between time interval following partial gastrectomy and pharmacokinetic parameters of the investigated drugs was noted. CONCLUSION: Partial gastrectomy with B1 anastomosis affects the pharmacokinetics of propranolol (lipophilic drug) but not atenolol (hydrophilic drug).

Electrochemical therapy in palliative treatment of malignant dysphagia: a pilot study.

BACKGROUND/AIMS: Electrochemical therapy (ECT), a method based on the application of a low-level direct current, was employed in this study to relieve severe dysphagia. In addition, we aimed to assess the efficacy, safety and requirements for follow-up re-interventions. METHODOLOGY: Sixteen patients with inoperable and circumferential malignant stenosis of the esophagus were palliated by ECT at presentation and then repeatedly whenever tumor growth and dysphagia recurred. The electrode was inserted and placed at the level of stenosis under fluoroscopic guidance, and an electric quantity of 300-560 coulombs (5-6.5 V; 60-90 mA) was given. When total luminal occlusion was found, prior balloon dilatation enabled insertion of the electrode. Patients with squamous cell carcinoma also received external beam radiotherapy of 20-30 Gy in 10 daily fractions. Dysphagia was graded on a scale of O to 4 (O = normal; 4 = complete dysphagia), and follow-up esophagograms were obtained for response evaluation. RESULTS: The severity of dysphagia decreased by 1-4 (median: 2) grades with an improvement in 6 patients with totally obstructing lesions. Dysphagia recurred in all but 1 patient after a median interval of 10 weeks, but was easily treated with repeat ECT sessions. However, 2 patients became unresponsive to ECT after 7 and 3 months of therapy, respectively. There were no ECT-related complications. CONCLUSIONS: In conclusion, this pilot study suggests that electrochemical therapy may provide safe and effective palliation of narrowing and circumferential esophageal carcinoma. It requires repeat interventions and dilatation expertise is necessary for insertion of the electrode through the totally obstructing lesion.

[Complications after esophageal resection due to cancer]. / Powiklania po resekcji przelyku z powodu raka.

The aim of the study was to evaluate complications searching for ways of decreasing their incidence. 225 patients with the diagnosis of thoracic esophageal cancer had been treated in the Department of General and Transplantation Surgery, Medicala Academy, Szczecin, within the period of 1984-1995, esophageal resection was done in 90 of them and 75 were submitted to the analysis. The majority of patients i.e. 65 of them had esophagogastric anastomosis performed within the thorax while in 10 patients the anastomosis was accomplished in the neck. Complications concerning cardiovascular and respiratory system wound healing, anastomotic leakage and gastric blood supply have been analysed. Cardiovascular and respiratory complications occurred in 24 and 66 per cent of patients with mortality rate of 28.6 and 12 per cent, respectively. Wound healing disturbances were found in 3.7 per cent of patients. Anastomotic fistulas and necrosis of the stomach were observed in 4 and 5.3 per cent of patients with mortality rate of 75 and 100 per cent, respectively. A statistically significant correlation between the incidence of cardiovascular complications and disease stage was found. Only in patients operated on in I and II disease stage can we expect the serious complications to be less frequent.