DNA flow-cytometric analysis in colorectal cancer: A comparison of metastasizing and non-metastasizing tumours

The most common cause of death in patients with colorectal cancer is metastatic liver disease. In order to identify patients at a high risk of developing hepatic secondaries from colorectal cancers, DNA content was measured in metastasizing colorectal primaries (Group I, n= 32) as well as in their subsequently resected liver secondaries and in sections of non-metastasizing colorectal cancers (Group II, n= 25). A modified interpretation system involving both a DNA index and percentage of cycling cells (those in S and G2 + M phases) was developed. DNA content was measured in paraffin-embedded sections by flow cytometry using internal controls (human peripheral blood mononuclear cells) and non-malignant tissue controls (19 patients with diverticular disease). In Group I there were significantly more tumours with both abnormal ploidy (aneuploid or abnormal tetraploid peak) and > 15% cycling cells compared with Group II (Chi-squared; P= 0.034). The combination of abnormal ploidy and > 15% cycling cells was superior to Dukes’ classification for identifying metastasizing tumours (Logistic Regression; P= 0.047). However, it was not possible to discriminate between the two groups using either DNA ploidy or the percentage of cycling cells alone. The metastasizing colorectal cancers exhibited similar DNA ploidy characteristics and had a similar percentage of cycling cells compared with their liver metastases. These results suggest that tumour DNA ploidy plus the percentage of cycling cells may predict the development of liver metastases and thus survival in patients with colorectal cancer.     

Assessment of enamel hypoplasia in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED)

The features of enamel hypoplasia in a small group of patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) are described. Using a recently developed method, the authors evaluated quantitatively the amount of defect in each tooth by measuring the width of the hypoplastic lesions and dividing the value by the crown height. They then assessed the degree of damage in each tooth type (from central incisors to second premolars) and patient. Canines were the most severely affected among maxillary and mandibular teeth, but all tooth types were involved. Analysing both the differences between patients and their age at the beginning of the defect, the authors observe that hypoparathyroidism is not responsible for the onset of enamel hypoplasia in APECED, although it may contribute to the damage.     

Pre- and postoperative nutritional care in liver transplantation in children

Orthotopic liver transplantation (OLT) is now a definitive treatment option for most cases of endstage liver disease (ESLD) in children. Efforts now focus on active supportive treatment to maintain, if not improve, the patient's clinical status before OLT and to ensure normal patterns of growth and development after OLT. Malnutrition adversely affects the outcome of OLT and is probably the single area in pre-operative management where the largest potential improvement can be made. Our studies indicate significant abnormalities of protein energy metabolism and body composition in children referred for OLT. We have shown that the use of enteral formulae, enriched with branched-chain amino acids, have significant advantages. Other adjunctive therapy, such as growth hormone, is the subject of current investigation. Following transplantation, catch-up weight and growth does occur with the advent of normal liver functioning, but patients at continuing risk for undernutrition, such as those with rejection and/or chronic infection, need to be targeted for specific nutritional therapy.     

Disposition of the neuroleptic zuclopenthixol cosegregates with the polymorphic hydroxylation of debrisoquine in humans

The pharmacokinetics of a single oral dose of the neuroleptic drug zuclopenthixol (10 or 6 mg) was studied in 6 extensive and 6 poor metabolizers of debrisoquine. The peak plasma concentrations of zuclopenthixol did not differ between the phenotypes, whereas the plasma elimination half-life was significantly longer in poor than in extensive metabolizers (29.9 +/- 6.6 vs 17.6 +/- 6.9 h). Accordingly, the total oral plasma clearance was lower in poor than in extensive metabolizers (0.78 +/- 0.27 vs 2.12 +/- 0.65 1/h/kg). Ten of the volunteers had previously participated in a similar study in which the kinetics of perphenazine, another neuroleptic drug, were studied in poor and in extensive metabolizers of debrisoquine. There was a significant correlation between the oral clearance of perphenazine and that of zuclopenthixol among these 10 subjects. The study indicates that the disposition of zuclopenthixol, as well as that of perphenazine, is related to the genetically determined capacity to hydroxylate debrisoquine. The significance of this polymorphism for the clinical use of neuroleptics is discussed.     

Establishment and Characterization of Cell Lines from Human Adenovirus Type 12-induced Murine Tumors Producing Endogenous Virus Particles

Two cell lines designated IC KMS and D KMS were established from human adenovirus type 12 induced tumors of C3Hf/OK mouse. The cell lines retained the characteristics of the original tumor i.e., production of numerous C type and intracisternal A-type particles, integration of Adl2 El region DNA and amplification of the myc gene family. Chromosomal analysis revealed chromosome aberrations in both IC KMS and D KMS cells. The modal chromosome number of IC KMS cells was 54 and that of D-KMS cells was 48. Metacentric chromosomes and mini-chromosomes were found. Trisomy of chromosome 3, 7 and 12 was seen frequently in D KMS cells. Although DNA aneuploidy was revealed by flow cytometry, the DNA indices of these cells showed no relation to the copy number of integrated Adl2 DNA. These cells have been propagated by serial culture during the past 17 months. Production of endogenous virus particles is a unique characteristic of IC KMS and D KMS cells. These cell lines would be useful materials for examining the contribution of Adl2 carcinogenesis to activation of endogenous virus particles, and also the correlation between Adl2 carcinogenesis and cancer related genes. Acta Pathol Jpn 42: 242-248, 1992.     

HEREDITARY HEMORRHAGIC TELANGIECTASIA WITH MALIGNANT LYMPHOMA An Autopsy Case

A 60-year-old Japanese woman was diagnosed at autopsy as having had hereditary hemorrhagic telangiectasia (HHT) associated with systemic hemangiomas. In her repoduction period, premenstrual epistaxis frequently occurred. At the age of 60, the patient died of malignant lymphoma. At autopsy, multiple telangiectatic spots were noted on the face, limbs and trunk. The paraaortic lymph nodes, which were enlarged and irregularly conglomerated, were histologically diagnosed as malignant lymphoma of the diffuse large cell type. Submucosal telangiectatic lesions were found in the gastrointestinal system from the oral cavity to the rectum. Cavernous hemangiomas were present in various visceral organs including the liver, spleen, small and large intestines, rectum, appendix, uterus, and jejunal and colonic mesenteries. There was an arteriovenous fistula in the left lung. Examination of her family pedigree showed that the patient had an autosomal dominant trait of inheritance. The pathogenesis of the systemic visceral hemangiomas observed in this patient was considered to be similar to that of hamartoma.