Noriyuki Kuwabara

The liver in systemic lupus erythematosus: pathologic analysis of 52 cases and review of Japanese autopsy registry data

We present pathologic findings for 52 livers (51 autopsy specimens and one wedge biopsy specimen) from patients with systemic lupus erythematosus (SLE). Hepatic congestion was the most common disease (40 livers), followed by fatty liver (38), arteritis (11), cholestasis (nine), peliosis hepatis (six), chronic persistent hepatitis (six), nonspecific reactive hepatitis (five), cholangiolitis (four), nodular regenerative hyperplasia of the liver (three), and hemangioma (three). The data obtained here suggest that arteritis of the SLE liver is more common than has been recognized previously. One patient had hepatic infarction complications induced by arteritis. On the basis of the findings in the present study and a review of the literature, we suggest that hepatic infarction resulting from arteritis is rare in SLE. On the other hand, while occurrence of nodular regenerative hyperplasia of the liver in SLE patients has been considered to be rare, our findings suggest that it may be more common than has been recognized previously. Although congestion and cholestasis may be acute terminal illnesses, fatty change is considered to be specific to the SLE liver. Statistical analysis indicates that exposure to a large dosage of glucocorticoids is a significant factor in the etiology of severe fatty liver. In addition, our review of Japanese autopsy registry data for 1,468 patients with SLE indicates that the incidence of chronic liver diseases in SLE autopsy cases is as follows: chronic hepatitis, 2.4%; cirrhosis, 1.1%; and liver fibrosis, 0.8%.

Induction of Colorectal Tumors in Rats by Sulfated Polysaccharides

Some sulfated polysaccharides, such as d-CGN, APS, and DSS, have carcinogenicity to the rat colorectum. These materials first induced colitis, secondly squamous metaplasia, and finally tumors at the colorectum. Initially, colitis was located in the columnar epithelium of the rectum and extended proximally thereafter. Squamous metaplasia persisted in almost all experimental rats and progressed irreversibly. The tumors were adenoma, adenocarcinoma, squamous cell papilloma, and squamous cell carcinoma. Macrophages containing these materials were observed in the lamina propria mucosa and submucosa of the colorectum. There were differences in the molecular weight of the substances and their tumor incidences. However, with regard to their carcinogenicity, these sulfated polysaccharides were inferred to be similar to each other in their target organs and process of tumor development. Consequently, these sulfated polysaccharides may be one entity of carcinogenic sulfates.

The lung in polyarteritis nodosa: A pathologic study of 10 cases

Polyarteritis nodosa (PAN) is characterized by necrotizing arteritis of medium-sized and small arteries in various organs. Pulmonary artery involvement in PAN has been considered rare. Previously, it also has been thought that patients with PAN do not have interstitial pneumonitis and fibrosis. A detailed pathologic analysis of pulmonary diseases associated with PAN was made in 10 autopsy cases of PAN. Arteritis affecting bronchial arteries was present in seven patients (70%). The data obtained suggest that arteritis in the lung in patients with PAN is more common than has been recognized previously. Diffuse alveolar damage (DAD) involving all lobes bilaterally was present in five patients; it was acute in two patients and organizing in three. In the patients with organizing DAD the degree of fibrosis in the interstitium differed among the lobes, and the fibrosis was more severe in the lower lobe than in the other lobes. Two patients presented with interstitial fibrosis with honeycomb lung of the posterior and lateral basal segments of the lower lobes of both lungs; in one of these patients interstitial fibrosis was present in an area of organizing DAD. Five patients died of respiratory failure resulting from DAD. In conclusion, it is important to consider DAD and interstitial fibrosis as complications of PAN.

Gastric stump carcinosarcoma with rhabdomyosarcomatous differentiation

Gastric carclnosarcoma is an unusual tumor and its occurrence in the gastric stump Is extremely rare. A report is presented here of a unique case of gastric stump carcinosarcoma with rhabdomyosarcomatous differentiation In a 74‐year‐old man. The patient had undergone partial gastrectomy with gastrojejunostomy (Billroth II method) 30 years previously. The tumor had both adenocarcinoma and sarcoma components, and an immunohistochemlcal study suggested a focal transition between these components. The main sarcomatous components showed fibrosarcomatous features with a scattered distribution of rounded tumor cells, whose rhabdomyosarcomatous differentiation was lmmuno‐histochemlcaily determined. Ultrastructural examination supported the rhabdomyosarcomatous natures. Experience with the present tumor indicates that carclnosarcoma with rhabdomyosarcomatous differentiation can occur in the gastric stump and that this disease Is capable of aggressive behavior.

A study on carcinogenesis induced by degraded carrageenan arising from squamous metaplasia of the rat colorectum

We have undertaken studies on carcinogenesis arising from precancerous lesions, such as squamous metaplasia and ulcerative lesions of the rat colorectum, after termination of degraded carrageenan administration. Rates of tumor incidence in groups that were given a 10% diet of degraded carrageenan for 2, 6 and 9 months were 5 rats out of 39 (12.8%), 8 out of 42 (19.0%) and 17 out of 42 (40.5%), respectively. The colorectal squamous metaplasia persisted in all rats and progressed irreversibly. Degraded carrageenan was deposited not only in the colorectal propria mucosa, but also in the other reticuloendothelial organs. These results show that, even with short-term degraded carrageenan administration, degraded carrageenan is carcinogenic to the colorectum of the rat after a prolonged period.

Transplacentally induced anorectal malformations in rats.

Twenty-eight pregnant rats (Wistar-Imamichi) on the 11th gestation day were treated with a single intragastric administration of ethylenethiourea (ETU) of 100, 125, 150, and 200 mg/kg body weight, and received cesarean section on the 20th gestation day. No dam died following the ETU treatment. In these transplacentally treated rat fetuses, various types of externally visible malformations were frequently observed; absent or kinked short tail in 100% and spina bifida or myeloschisis in 48.6% to 86.8%. The incidences of these anomalies were significantly higher in males than females. The fetuses were fixed in Bouins solution and embedded in paraffin, and the step-serial section were sagittally prepared. Then they were stained with phosphotungstic acid hematoxylin for the light microscopic examination. In a preparation of just midsagittal section, malformations of rectum and anus were investigated. The results were as follows: (1) the most appropriate dose of ETU might be 125 mg/kg, body weight of dam, which was suggested by number of the fetuses, prenatal development of the fetuses and incidences of externally visible anomalies in the fetuses; (2) various types of anorectal anomalies, including rectourethral fistula, rectocloacal fistula, covered anus-complete, anoperineal fistula, and anal membrane stenosis, were induced; (3) the incidence of anorectal anomalies was significantly higher in males than females; (4) in every type of anorectal anomalies, inner circular layer of smooth muscle was hypertrophied at the rectum end, which seemed to be considered as the internal sphincter muscle; and (5) the external sphincter muscle complex was hypoplastic in the high deformity fetuses associated with sacrococcygeal anomaly.

Incidence of Paneth Cells in Minute Tubular Adenomas and Adenocarcinomas of the Large Bowel

This study attempted to demonstrate the incidence of Paneth cells within large bowel tubular adenoma and adenocarcinoma according to location and macroscopic appearance using minute tumors (up to 5 mm in size). We have shown that Paneth cells were sometimes seen in the early stage of the development of large bowel epithelial neoplasia. According to the macroscopic appearance (elevated or depressed type), in large bowel epithelial neoplasia, there was a statistical difference between the depressed type (32.5%, 14 of 40 cases) and the elevated type (16.6%, 24 of 145 cases) (Chi square analysis, p < 0.05) in the incidence of Paneth cells. Paneth cells were seen more frequently in adenocarcinoma (45.8%, 11 of 24 cases) than in tubular adenoma (16.8%, 27 of 161 cases), with a significant statistical difference (Chi square analysis, p < 0.01). According to location, in both tubular adenoma and adenocarcinoma, Paneth cells were more frequently observed in the proximal colon (tubular adenoma: p < 0.01, adenocarcinoma: p < 0.05, Chi square analysis). Acta Pathol Jpn 42: 579 584, 1992.

Experimental study of the pathogenesis of infantile obstructive cholangiopathy and its clinical evaluation

1,4-phenylenediisothiocyanate was given to five groups of rats of different developmental stages (97 in all), and the changes in the hepatobiliary system were compared histopathologically. Three groups of rats given the drug after birth showed dilatation of the extrahepatic bile ducts with inflammation. Two groups given the drug during the fetal period or added after birth showed stenotic or atretic extrahepatic bile ducts due to thickening and fibrosis of the wall. This experimental model suggests that differences in the pathologic features of infantile obstructive cholangiopathy (biliary atresia, neonatal hepatitis, and bile duct dilatation) may be the result of various developmental stages in the pathogenic process. After the experiment, 11 cases of correctable type biliary atresia were compared to 24 cases of noncorrectable type in various aspects. It is suggested that the correctable type may have suffered pathogenic process later in the developmental stages than noncorrectable type.

Carcinogenic activity of 2-(2-furyl)-3-(5-nitro-2-furyl)-acrylamide, a food additive, in mice and rats

The carcinogenicity of a food additive, 2-(2-furyl)-3-(5-nitro-2-furyl)acrylamide (AF-2), was studied in Wistar rats and CDF1 mice. The rats developed mammary tumors; the first appearing 9 months after the start of the experiment. In mice fed AF-2 diet, squamous cell carcinoma of the forestomach was observed in the 11th month. Some mice had metastases in the liver, spleen, lymph nodes and peritoneal cavity.

Paget sarcoma of the cervical vertebrae: An autopsy case report and review of the literature

A 69 year old Japanese woman was hospitalized for emergency treatment of sudden onset of tetraplegia and somnolence. The patient had a long history of occipital pain without definite diagnosis. After admission, the patient progressively developed generalized palsy including respiratory paralysis, and died of bronchopneumonia. Autopsy revealed osteosarcoma of the cervical vertebrae with the features of Pagets disease involving the skull and the cervical vertebrae. Paget sarcoma is rare in Japan, where Pagets disease of the bone is an uncommon condition. A review of the world literature failed to reveal any reports describing Paget sarcoma of the cervical vertebrae. The present report indicates that the development of Paget sarcoma in the upper cervical vertebrae may cause life‐threatening neurologic complications.