Renato Santucci

Morphologic and cytoproliferative patterns of duodenal mucosa in two patients after long-term total parenteral nutrition: changes with oral refeeding and relation to intestinal resection.

The morphologic and cytoproliferative patterns of the duodenal mucosa of two adult patients, one of whom had a short bowel, were evaluated after more than 2 months of postoperative total parenteral nutrition and 2 and 12 months after the resumption of oral alimentation. Morphometric analysis was performed on routinely processed duodenal biopsies. Cell proliferation was evaluated by means of in vitro bromodeoxyuridine uptake. The results were compared with those obtained in five healthy controls. After parenteral nutrition, patients showed significantly lower villus height and crypt depth than those of controls and a normal bromodeoxyuridine labeling index. After 2 months of refeeding, villus and crypt returned to normal, and the labeling index was increased. After 12 months of oral refeeding, labeling index, villus height, and crypt depth were similar to those of controls. The patient with the short bowel showed a number of cells per unit length of villus and crypt significantly greater than those of the controls and of the patient who underwent shorter intestinal resection. In human duodenal mucosa, (1) hypoplasia develops after long-term total parenteral nutrition; (2) mucosal recovery occurs through an increased cell proliferation after oral refeeding; and (3) extensive small bowel resection determines the development of relative hyperplasia.

Rectal cell proliferation and colorectal cancer risk level in patients with nonfamilial adenomatous polyps of the large bowel

The authors evaluated cell kinetics of apparently normal rectal mucosa in the following subjects: 25 with single small adenoma (smaller than 10 mm) of the large bowel, 12 with multiple small adenomas, 28 with a single large adenoma (larger than 10 mm), 22 bearing multiple adenomas among which at least one was larger than 10 mm, 32 with cancer of the large intestine, and 32 controls without colorectal diseases. The study was performed by means of incubation of biopsy specimens with tritiated thymidine and autoradiography. The labeling index was similar in all of the groups. However, patients with one or more large adenomas showed a shift of the proliferative compartment toward the top of the crypts similar to that observed in patients with cancer. This abnormal proliferative pattern was not noticed in patients with one or more small adenomas and was not related to the number of adenomas of each subject. The presence of defects of cell growth in the normal rectal mucosa of patients with large adenomas may indicate that subjects with this abnormality are at high risk of adenoma growth and progression to cancer. 68:2451‐2454, 1991.

Cancer surveillance in ulcerative colitis: critical analysis of long-term prospective programme

BACKGROUND Patients with longstanding ulcerative colitis are at increased risk of colorectal cancer. In the literature, no agreement has yet been reached regarding prevention strategies. Our report sums up a prospective study started in 1980. METHODS A total of 65 patients affected by ulcerative colitis for more than seven years were admitted to a regular colonoscopic and biopsy follow-up programme. RESULTS Some 20 years after the beginning of the study, 23 (35.3%) patients have been operated upon, 2 patients have died but not from cancer 29 (44.66%) patients have abandoned the programme. Only 11 (16.9%) patients have remained under colonoscopic surveillance. CONCLUSION These results cast some doubts on the significance of such a programme and on its long-term feasibility.

Effect of sex and age on rectal cell renewal in humans

We evaluated the influence of age and sex on rectal cell proliferation of 69 hospital controls and 66 patients with colorectal adenomas, by means of incubation of rectal biopsies with tritiated thymidine and autoradiography. In particular, we evaluated the labeling frequency in the upper 40% of rectal crypts (0 h), actually considered as a reliable kinetic marker of colon cancer risk. A direct correlation between 0h and age was found in control subjects (P less than 0.02) but not in adenomas patients (P = NS). Moreover, control subjects over 65 years of age showed a shift of the proliferative compartment similar to that observed in the adenomas group. After adjusting for the age, we did not observe any significant effect of the sex of patients or controls on their cell kinetics parameters. Our results are in agreement with those previously reported on smaller series and with epidemiological studies which indicate a high risk for developing colorectal neoplasia in the elderly subjects.

Abnormal rectal cell proliferation and p52p35 protein expression in patients with ulcerative colitis

We evaluated the presence of cell proliferation and antigenic abnormalities in rectal biopsies from 37 patients affected by ulcerative colitis and 15 controls. The study was carried out by thymidine labeling and immunochemistry, using antibodies against specific cytoskeletal-associated proteins (p52, p35, alpha-actinin). Among ulcerative colitis patients, 24 had an immunofluorescence pattern similar to that of controls, while 13 showed an abnormal distribution of one or more proteins (p52 alone or p52 and either p35 or alpha-actinin) within the rectal crypts. Patients showed a shift of the proliferative compartment towards the top of the rectal crypts compared with controls. This finding was more evident in patients with p52 or p35 abnormalities. Proliferative and antigenic defects were not related either to age or the duration of colitis. These phenotypic changes might be a biomarker of increased risk of colon cancer in ulcerative colitis.

Correlation between bromodeoxyuridine labelling and ornithine decarboxylase levels in normal rectal mucosa of patients with colorectal adenoma

We studied rectal cell proliferation by means of bromodeoxyuridine labelling and ornithine decarboxylase activity assay in 16 patients with colorectal adenoma. In each patient, three rectal biopsy specimens taken from normal-appearing mucosa were incubated with bromodeoxyuridine (BrdU), fixed in ethanol and stained with avidin-biotin peroxidase complex using a monoclonal antibody against BrdU. In addition, two biopsies were homogenized and incubated with [1-14C]-ornithine for ornithine decarboxylase (ODC) assay. A direct, significant correlation was found between BrdU-labelling index and ODC levels in the mucosa (r = 0.6511, P less than 0.01). We conclude that BrdU labelling and ODC activity assay give comparable results in the analysis of cell proliferation rate of rectal mucosa. These methods are useful to investigate rectal cell proliferation pattern of patients with increased risk of colorectal cancer.