Hidejiro Yokoo

Thorotrast-induced cancer in man

The case history is presented of a malignant tumor in man attributed to the injection of Thorotrast. 55 references. (C.H.)

Experimental Production of Mallory Bodies in Mice by Diet Containing 3,5-Diethoxycarbonyl-1,4-Dihydrocollidine

The first experimental production of Mallory bodies was reported by Denk et al. in 1975 in mice fed griseofulvin. We discovered a second chemical capable of producing Mallory bodies in the mouse liver in a manner similar to griseofulvin. Male Swiss albino mice were fed a powdered standard diet containing 2.5% of 3,5-diethoxycarbonyl-1,4-dihydrocollidine up to 95 days. The animals were killed at intervals and their livers were examined by light and electron microscopy. In general, the morphologic changes in the liver were similar to, but more marked than, those seen in griseofulvin-fed mice. Mallory bodies were first observed in the livers of mice killed at 40 days. In our previous experiment using griseofulvin, we first observed Mallory bodies in mice killed at 61 days. These observations suggest that 3,5-diethoxycarbonyl-1,4-dihydrocollidine may be more effective than griseofulvin in the production of Mallory bodies in mice.

Natural history and significance of esophageal squamous cell dysplasia

Balloon‐mesh cytologic screening for esophageal cancer done in 255 asymptomatic high‐risk United States veterans (age > 40 years, ethanol abuse for > 20 years, and cigarette smoking > 20 pack years} identified 37 patients with squamous cell dysplasia. Of the 37 patients with dysplasia, 28 were re‐evaluated prospectively at 6‐month intervals for up to 36 months by balloon‐mesh cytology, esophagoscopy with vital staining and biopsies, chest radiographs, oropharyngeal examination, and indirect laryngoscopy. During prospective follow‐up evaluation, cytology specimens were repetitively normal in 16 patients (57%), showed inflammatory changes in eight patients (29%), persisted as dysplasia in two patients (7%) (both had endoscopic and histologic evidence of esophagitis), and progressed to carcinoma in two patients (7%) (one esophageal, one laryngeal). Although histologic findings concurred with the resolution of dysplasia, biopsy specimens were characterized by a similar difficulty in distinguishing dysplasia from inflammation. Erroneous histologic diagnoses of carcinoma in situ were made in two patients with reflux esophagitis evident endoscopically and confirmed during the course of a 24‐36 month follow‐up period. The authors conclude that squamous cell dysplasia detected by balloon‐mesh cytology is seldom a precursor of esophageal cancer in the high‐risk U.S. population but, rather, is often related to esophagitis. Thus, balloon‐mesh cytology has limited use as a screening method for the early detection of esophageal cancer in the United States.

Kinetics of D–xylose absorption in patients with human immunodeficiency virus enteropathy

D‐Xylose absorption was studied in 12 patients with acquired immunodeficiency syndrome (AIDS) or advanced AIDS‐related complex who had had diarrhea for more than 8 weeks, averaged an 11% (range, 3% to 21%) body weight loss during the previous 6 months, and had had negative stool examinations for enteric pathogens. Patients were evaluated by duodenal aspiration and biopsy and received both 25 gm oral and 10 gm intravenous doses of D‐xylose. Kinetic analysis of D‐xylose absorption was characterized by an absorption rate constant (ka) and a rate constant (ko) reflecting nonabsorptive loss. Extent of D‐xylose absorption averaged 18.4% ± 9.3% (±SD) in the 12 patients (normal >60%). Percentage of weight loss during the previous 6 months was negatively correlated with ka (r = ‐0.69; p = 0.018) in the 11 patients in whom this parameter was reduced but was not correlated with either ko or extent of D‐xylose absorption. In these patients with human immunodeficiency virus enteropathy, ka was reduced out of proportion to the minor histologic changes present in the duodenal biopsy specimens.

Cytoskeletal alterations leading to Mallory body formation in livers of mice fed 3,5-diethoxycarbonyl-1,4-dihydrocollidine.

Cytoskeletal alterations of hepatocytes were studied in mice fed 3,5-diethoxycarbonyl-1,4-dihydrocollidine from the onset of the experiment to the time when Mallory bodies were induced, using immunofluorescent microscopy and a method which we devised in order to visualize the cytoskeletal framework of hepatocytes. The results showed that the cytoskeletal framework of the normal murine hepatocyte is composed of a network of uniformly distributed, interconnecting bundles of filaments. In the drug-fed mice, the cytoskeletal network of the hepatocytes became coarser and distorted. The Mallory body-containing hepatocytes were mostly devoid of cytoskeletal filaments, containing only a few thick bundles of filaments, which appeared partly smudgy and electron-dense. These results suggest that the formation of Mallory bodies in this animal model is associated with a marked derangement of the cytoskeletal framework, which appears to result from the progressive loss of normal filaments and the aggregation of abnormal ones.

Pyogenic granuloma in Barrett's esophagus mimicking esophageal carcinoma

A 31-year-old white man with a history of testicular carcinoma and lymphoma developed severe reflux esophagitis with stricture formation requiring repeated dilatation. Barretts esophagus was histologically confirmed. The Barretts mucosa was observed endoscopically and became polypoid, mimicking an esophageal carcinoma. The polyp was evaluated by endoscopic ultrasonography and ultrasonically guided aspiration cytology. It was managed by snare cautery removal, which showed a pyogenic granuloma.

Griseofulvin-induced cholestasis in Swiss albino mice.

Griseofulvin was fed to male Swiss albino mice, which were sacrificed at varying times after the initiation of the feeding. The following were compared with mice fed a control diet: hepatic histology, hepatic weight, plasma glycocholate, glycolithocholate, cholesterol, bilirubin, and alkaline phosphatase. Concurrent with the development of hepatic protoporphyria, a progressive cholestatic lesion was produced with marked bile canalicular dilatation and elevation of the plasma bile salts, alkaline phosphatase, and cholesterol without a rise in bilirubin. Adaptation to the cholestatic injury occurred in about 60 days despite continued griseofulvin feeding. This was evidenced by decreased values in the biochemical profile with concomitant improvement in the bile canalicular morphology. Following this event of adaptation, Mallory bodies began to appear in the livers, often in the periphery of the hepatic lobule. This model may be useful in studying mechanisms of cholestasis, Mallory body formation, and their relationship to altered microtubular systems in the hepatocyte.

Bile exclusion from the gut exacerbates acute pancreatitis caused by pancreatic duct obstruction in rats

Acute pancreatic duct obstruction causes hyperamylasemia and mild pancreatic inflammation. We hypothesized that bile exclusion from the gut, which stimulates pancreatic secretion, exacerbates acute pancreatitis caused by pancreatic duct obstruction. Rats were surgically prepared with gastric, duodenal, bile, and pancreatic fistula catheters and a jugular vein catheter. After a 4-day recovery, groups of rats (a) served as controls, (b) had complete pancreatic duct obstruction for 6 h, or (c) had bile excluded from the gut for 24 h and then, during the final 6 h, complete pancreatic duct obstruction. Plasma amylase was measured, and all rats were euthanized at the end of experiments. Each pancreas was excised and weighed, and portions were fixed in formalin and glutaraldehyde. In blind fashion, each pancreas was examined under light microscopy and assigned a pancreatitis score based on presence of edema and severity of acinar cell changes and inflammation. Acute pancreatic duct obstruction was associated with increased pancreas weight, hyperamylasemia, and elevated pancreatitis score; moderate acinar cell vacuoles, which were observed in the cytoplasm near the basolateral membrane, and loss of microvilli were noted with electron microscopy. Bile exclusion from the gut exacerbated the acute pancreatitis caused by pancreatic duct obstruction; acinar cell distortion and destruction, as well as marked inflammation, were seen microscopically. These observations suggest that the absence of intestinal bile contributes to the pathogenesis of acute pancreatitis associated with pancreatic duct obstruction.