Klaus J. Lewin

Cryopreserved microencapsulated hepatocytes--transplantation studies in Gunn rats.

Hepatocyte transplantation has been shown to provide significant metabolic support in several animal models of liver diseases. However, for it to be a viable alternative for supplementation of liver function in disease, large quantities of isolated hepatocytes would be necessary. At the present time there are no inexpensive routine methods for cryopreservation of hepatocytes. Existing procedures are cumbersome and require expensive programmable freezers. Hepatocyte cultures are sensitive and easily damaged in handling. By utilizing techniques of microencapsulation and cryopreservation we have attempted to overcome these problems. We have developed a simple, convenient, and inexpensive technique for the long-term storage of hepatocytes. Biological activity of the nonfrozen isolated encapsulated hepatocytes (IEH) and cryopreserved IEH (cIEH) was assessed both in tissue culture and by transplantation in Gunn rats. Significant urea and protein syntheses were detectable during the 10-day culture period even in the 30-day cIEH. Additionally, transplanted IEH and cIEH significantly reduced hyperbilirubinemia in Gunn rats for up to 30 days posttransplantation. Control (empty) microcapsules did not lower serum bilirubin levels. Thus we conclude: (1) cryopreservation of IEH is a convenient and cost-effective method for preserving and storing hepatocytes; (2) cryopreserved IEH function as well as nonfrozen IEH both in vitro and in vivo; (3) microencapsulation may protect hepatocytes from the adverse effects of cryopreservation.

Malacoplakia. An electron-microscopic study: demonstration of bacilliform organisms in malacoplakic macrophages.

A case of malacoplakia of the bladder and intestinal tract is reported in which bacilliform organisms are demonstrated within the malacoplakic macrophages by light and electron microscopy. On electron microscopy, two types of cytoplasmic inclusions are found, those corresponding to the periodic acid Schiff-positive granules which are phagolysosomes, and the Michaelis-Gutmann bodies. Bacteria, probably coliforms, in various stages of degradation, are found within phagocytic vacuoles and phagolysosomes, sometimes in close apposition to phospholipid membranes. The Michaelis-Gutmann bodies develop within the phagolysosomes. It is postulated that the following sequence of events occurs in the pathogenesis of Michaelis-Gutmann bodies. Bacteria are phagocytosed by the malacoplakic macrophages, incorporated into phagolysosomes, and killed, but are incompletely digested. They persist as dense amorphous aggregates and phospholipid membranes which later become encrusted with calcium phosphate crystals to form the laminated Michaelis-Gutmann bodies. Why the macrophages respond in this unusual fashion to a common infectious organism is not clear. It may be due to an immunological abnormality affecting intracellular digestion. Other factors, such as infection with an unusual strain of coliform or intrinsically abnormal macrophages, are discussed. The world literature of intestinal malacoplakia is reviewed and the aggressive nature of intestinal involvement is stressed.

Recommendations for the Reporting of Resected Esophageal CarcinomasAssociation of Directors of Anatomic and Surgical Pathology

The Association of Directors of Anatomic and Surgical Pathology has named several committees to develop recommendations about the content of the surgical pathology report for common malignant tumors. A committee of individuals with special interest and expertise writes the recommendations, and they are reviewed and approved by the council of the Association of Directors of Anatomic and Surgical Pathology and subsequently by the entire membership. The recommendations have been divided into 4 major areas: (1) items that provide an informative gross description; (2) additional diagnostic features that are recommended to be included in every report if possible; (3) optional features that may be included in the final report; and (4) a checklist. The purpose of these recommendations is to provide an informative report for the clinician. The recommendations are intended as suggestions, and adherence to them is completely voluntary. In special clinical circumstances, the recommendations may not be applicable. The recommendations are intended as an educational resource rather than a mandate.

Is colonoscopy needed for the nonadvanced adenoma found on sigmoidoscopy

BACKGROUND & AIMS The need for colonoscopy when small tubular adenomas with low-grade dysplasia are found on sigmoidoscopy is uncertain. The aim of this study was to examine the prevalence and characteristics of proximal adenomas in patients with distal adenomas. METHODS We studied 981 subjects with distal adenomas found on the index colonoscopy before randomization in the Polyp Prevention Trial. RESULTS Four hundred sixty patients (46.9%) had >/=1 distal adenoma that was pathologically advanced (villous component, high-grade dysplasia, or >/=1 cm); 21.5% (211 of 981) had any proximal adenoma; and 4.3% (42 of 981) (95% confidence interval [CI], 3.0-5.5) had an advanced proximal adenoma. A greater percentage of patients with an advanced distal adenoma (5.9%) (95% CI, 3.7-8.0) had an advanced proximal adenoma compared with those with a nonadvanced distal adenoma (2.9%) (95% CI, 1.4-4.3) (OR, 2.1; 95% CI, 1.1-4.3; P = 0.03). Not performing a colonoscopy in patients with a nonadvanced distal adenoma would have missed 36% (15 of 42) of the advanced proximal adenomas. CONCLUSIONS Patients with an advanced distal adenoma are twice as likely to have an advanced proximal adenoma as patients with a nonadvanced distal adenoma. However, eschewing a colonoscopy in patients with a nonadvanced distal adenoma would result in not detecting a sizeable percentage of the prevalent advanced proximal adenomas. These data support performance of a colonoscopy in patients with a nonadvanced distal adenoma. Confirmation of these results in asymptomatic subjects undergoing screening sigmoidoscopy is advisable.