LONG‐TERM FOLLOW UP OF PATIENTS WITH SMALL GASTROINTESTINAL STROMAL TUMORS IN THE STOMACH USING ENDOSCOPIC ULTRASONOGRAPHY‐GUIDED FINE‐NEEDLE ASPIRATION BIOPSY

Background: Gastrointestinal stromal tumors (GIST) are one of the most common mesenchymal tumors of the gastrointestinal tract. GIST are defined by positive immunohistochemical staining for KIT or CD34 and thus are generally diagnosed after surgery. Because small GIST are rarely diagnosed before surgery, the clinical course of these small tumors is not clear. The aim of the present study was to follow changes in size and configuration of small GIST that were pathologically confirmed using endoscopic ultrasonography‐guided fine‐needle aspiration biopsy (EUS‐FNAB). Methods: Between July 1997 and December 2003, 16 tumors in 16 patients (10 men and 6 women) with an immunohistochemical diagnosis of GIST were regularly followed in our hospital. The median patient age when EUS‐FNAB was performed was 62 years (range 26–82 years) and the median follow‐up period was 4.9 years (range 0.5–9.6 years). Results: Fourteen tumors showed no remarkable changes in size and shape during follow up compared with the initial diagnosis. Two tumors enlarged: one tumor approximately doubled its diameter in 8 years and the other tumor increased from 1.8 cm at diagnosis to up to 10 cm after only 2 years. Doubling time of the latter tumor was calculated as 3.1 months. Conclusions: We conclude that EUS‐FNAB might be a good modality for final diagnosis of GIST without surgery, and that GIST without rapid growth on follow up can be endoscopically followed.     

Biological activity of partially purified digitalis-like substance and Na-K-ATPase inhibitor in rats

In order to study the biological activity of endogenous digitalis-like substance (DLS) and Na-K-ATPase inhibitor (ATPI), human urine was partially purified and administered to rats, and its effects on the urinary volume, urinary Na excretion and blood pressure (BP) were determined. In addition, the effect on myocardial Na-K-ATPase activity was also measured. After the extraction of 40L of urine with a reversed phase cartridge column (S-fraction), 20 ml of chloroform was added and extraction was repeated. The chloroform layer was applied to an open silica gel column, and at a fraction with ethylacetate: methanol (60: 40, T-1 fraction), DLS and ATPI were eluted at the highest concentration. The water layer was treated with charcoal (D-1 fraction). The acute administration of K-1, T-1 fraction to rats in vivo caused significant rises in urinary volume, urinary Na excretion and BP. In chronic administration of K-1 fraction, urinary Na excretion was significantly elevated and myocardial Na-K-ATPase activity was also significantly suppressed. These results suggest that DLS and ATPI cause increase in the urinary volume and urinary Na excretion and also possess a hypertensive action; and moreover, these substance may affect the heart like cardiotonic steroids and regulate BP by increasing cardiac contractility.     

Effects of gallamine on the contractile response of the stomach in cats

Stimulation of the vagal trunk in cats anesthetized with pentobarbital sodium produced a contractile response of the stomach during stimulation (initial contraction). Pretreatment with either hexamethonium (0.3 to 30 mg/kg, i.v.) or gallamine (1 to 100 mg/kg, i.v.) dose-dependently produced a delayed contraction, following the initial contraction after stimulation. After the administration of either hexamethonium or gallamine produced a maximum delayed contraction, then an additional dose of gallamine or hexamethonium was administered. The subsequent treatment further augmented the delayed contraction. The results indicate that gallamine induced the delayed contraction by a mechanism different from hexamethonium.     

Tl-201 myocardial images in a patient with dialated cardiomyopathy, who finally received heart transplantation

The patient responded to treatment at the first onset of heart failure but gradually became irresponsive to treatment, experiencing fatigue and malaise as the chief complaints and suffering from gradually progressive decrease in exercise capacity and body weight. Dose of DOA gradually increased to maintain well clinical state of the patient. Unusual for heart failure, he had bradycardia as the basal rhythm without showing a tendency for tachycardia. Cardiac catheterization revealed pulmonary hypertension and low cardiac output, however, left ventricular ejection fraction was 37%. There were no notable changes in ultrasonic cardiogram or CTR through the clinical course. Tl-201 myocardial images and pulmonary perfusion images showed gradual worsening corresponding to progressive worsening of clinical state. From these findings, the patient was determined as a candidate for heart transplantation.     

Dysphagia aortica

Three patients with dysphagia caused by compression of the distal esophagus by a tortuous nonaneurysmal atherosclerotic aorta are described. All three patients were elderly women; systemic hypertension and cardiomegaly were present in two patients. Barium studies of the esophagus showed displacement and compression of the distal esophagus by the thoracic aorta. Debilitating dysphagia was treated surgically in one patient. The other two patients had milder symptoms and were managed conservatively. Esophageal manometry in these three patients showed superimposed pulsations and elevated intraluminal pressure just proximal to the lower esophageal sphincter. To evaluate the significance of these manometric findings and their correlation with clinical symptoms, we reviewed manometric tracings in 47 normal subjects. Ten of these subjects had an elevation of baseline intraluminal esophageal pressure as a result of superimposed vascular pulsations. We conclude that (1) compression of the distal esophagus by a tortuous atherosclerotic aorta in the appropriate setting can lead to clinically significant dysphagia and (2) a manometric finding of vascular compression of the esophagus does not necessarily correlate symptomatic dysphagia.     

Frequent premature ventricular contractions induced by itraconazole.

Itraconazole is widely used to treat onychomycosis because of its significant therapeutic effects. An otherwise healthy 30-year-old man treated with itraconazole developed frequent premature ventricular contractions (PVC). He presented with a dry cough and palpitation. The results of 12-lead electrocardiography (ECG) were essentially normal, but Holter ECG revealed 17,484 (18%) uniform PVC, including 4 short runs among 96,930 beats/day. Another Holter ECG after withdrawing itraconazole revealed 1,032 premature atrial contractions but no PVC. The corrected QT interval was 0.39 s without itraconazole, 0.41 s with itraconazole, and 0.43 s when multiple PVC were documented. Itraconazole inhibits the fungal cytochrome P450 that is involved in fungal cell membrane formation, interrupts human cytochrome P450A4 in the liver and causes adverse interactions with various drugs such as antiarrythmics, but its cardiac side-effects are obscure. Both patients and physicians should be aware that itraconazole can cause PVC as a side-effect.