p53-expression and chromosome 17-copy number in colorectal adenomas

To get better insight into the role of numerical chromosome 17-aberrations and functional loss of the tumor suppressor gene TP53 during the early steps of colorectal carcinogenesis we analyzed paraffin-embedded tumor tissue from 58 colorectal adenomas with different histological features for p53-expression by immunohistology (IH; moAb DO1), #17-copy number by interphase-cytogenetics [nonradioactive in situ-hybridization (NISH) with a centromer-specific DNA-probe (D17Z1)], and DNA-ploidy by flow cytometry (FCM) with special emphasis on histopathological correlation. Seven adenomas (12%) showed nuclear p53-immunoreactivity. p53-expression was correlated with villous/tubulo-villous growth pattern (p=0.005) and grade of atypia (p=0.003) or dysplasia (p=0.0018). #17-aneusomy was present in 31% of the cases (29% deletions, 2% gains). In the FCM-analysis, 33% of the adenomas were DNA-non-diploid. p53-immunoreactivity correlated statistically significantly with FCM-non-diploidy (p=0.004) suggesting a role for the TP53-gene in the aneuploidization process. #17-deletions were associated to p53-immunoreactivity (p=0.046) but no correlation was found between FCM-ploidy and #17-copy number. As for loss of a tumor suppressor gene both alleles have to be affected, our data suggest a multistep process of TP53-inactivation. Whether the subgroup of adenomas with p53-expression might progress faster into invasive carcinoma than p53-negative cases remains to be tested.     

Beta-oxidation of 1-[14C]-17-[131I]-iodoheptadecanoic acid following intracoronary injection in humans results in similar release of both tracers

Radioiodine labelled 17-iodo-heptadecanoic acid (IHA) is used for non-invasive study of myocardial metabolism in coronary heart disease and cardiomyopathy. Yet in the interpretation of in vivo myocardial tracer kinetics, it is controversial whether the intracellular degradation of IHA or the removal of iodide across cellular membranes is the rate-limiting step in iodide release from the myocardium. In five patients undergoing coronary sinus catheterization, a mixture of about 40 kBq of [¹²³I] NaI was injected into the left coronary artery. During the following 15-min period, frequent blood samples were taken from the aorta and the coronary sinus. In the aqueous phase of the venous blood, ¹⁴CO₂ and inorganic ¹³¹I appeared nearly in parallel, with a peak time of 4–5 min. Moreover, as shown by the AV difference, there was no significant back diffusion of IHA and no significant non-specific deiodination detectable over the period of observation. There was myocardial retention of inorganic iodide (¹²³I) injected into the left coronary artery. The data strongly support the premise that lipid turnover through -oxidation is the rate-limiting step in the externally measured release of iodide after IHA injection, provided that recirculating inorganic radioactive iodide is corrected for. In addition, 15 volunteers were studied using [¹¹C]palmitic acid and [¹²³I]IHA using PET and dynamic planar camera scintigraphy with iodide correction. There was no significant difference between the mean values of the elimination half-times, and also no significant correlation between half-times of both fatty acids for single individuals.     

Expired air carbon monoxide and serum thiocyanate as objective measures of cigarette exposure.

Expired air carbon monoxide (CO) and serum thiocyanate (SCN) were used to asses exposure to cigarettes in 139 middle-aged men. Subjects who reported smoking cigarettes generally had CO levels exceeding 8ppm and SCN levels exceeding 100umol/L; non-smokers had lower levels. For both tests the mean concentration among men smoking more than one pack daily was three times that of non-smokers. The is a high correlation between the two tests (r=.571 for smokers), an association that was largely independent of the smaller correlations between either test and reported smoking frequency (r=.476 for CO; r=.479 for SCN). The ability to distinguish between individuals who reported "typical" smoking habits and non-smokers was best when the CO and SCN analyses were used together to take advantage of their separate sources of variance; it was 99 per cent when the two tests were mutually concordant (91 per cent of cases). The CO and SCN measurements allowed 16 individuals who reported light smoking habits to be categorized into high and low presumptive tobacco exposure groups. The two tests are inexpensive and suitable for use in epidemiologic and health care delivery programs.     

Primary non-Hodgkin's lymphoma of the spinal cord

STUDY DESIGN: Case report. OBJECTIVE: To report a rare case of primary lymphoma of the spinal cord and to discuss therapeutic options. SUMMARY OF BACKGROUND DATA: Only few cases of primary spinal cord lymphomas are reported. Prognosis is often poor, and therapy is not yet established.METHODS: A primary lymphoplasmacytoid lymphoma of the thoracic cord in a 75-year-old woman was treated with focal radiotherapy (30 Gy) and three cycles of chemotherapy consisting of procarbazine, lomustine, and vincristine. RESULTS: Complete tumor response and partial recovery of neurologic symptoms were achieved. The patient was in complete remission at last follow-up (11 months after diagnosis). CONCLUSIONS: Primary spinal cord lymphomas should be considered in the differential diagnosis of spinal cord tumors, especially in older patients. Combination therapy with radiotherapy and chemotherapy may be superior to radiotherapy alone in these tumors. Rapid initiation of treatment is essential to achieve recovery of neurologic function.     

First experience with gamma probe guided sentinel lymph node surgery in penile cancer

Because of the curative approach, the detection of lymph node metastases in squamous cell carcinoma (SCC) of the penis is of significant clinical relevance. Sentinel lymph node (SLN) identification by means of lymphangiography has been proven to be insufficiently safe. However, the high morbidity of inguinal lymphadenectomy and the considerable individual variability regarding the location of lymph node metastases justify the necessity of a technique that enables the identification of SLNs. Since 1998, SLNs have been intraoperatively identified and selectively dissected, after peritumoral injection of technetium-99m nanocolloid and using lymphoscintigraphy, in three patients (one with malignant melanoma and two with SCC). At least one SLN could be detected in each patient. The maximum surgical time was 30 min. There were no severe complications. Lymph node metastases did not occur in any patient. Upon a mean follow-up of 10 months, all patients are currently free of tumor. Owing to the long-term results of sentinel lymphadenectomy in malignant melanoma of other locations and our preliminary results with respect to penile carcinoma, we consider the current method appropriate as the only primary operation for lymph node staging in early stages and, in combination with modified inguinal lymphadenectomy, in locally advanced stages. Received: 24 November 1999 / Accepted: 21 April 2000     

Melanoma. Results with "sentinel node" sampling

Since June 1995 we have practised a gamma probe guided sentinel lymphadenectomy (SLNE) in 274 patients after injecting a colloidal 99 m-Tc labelled solution around the tumor. By this technique the detection and excision of the SLN succeeded in 99.3% of all cases. We found micrometastases in about 53.1% of patients with pT3 and pT4 melanomas. The specimen of the radical lymph node dissection contained in 30% further metastases. A regional recurrence after SLNE occurred only in one case, a SLN-negative patient.     

Survival and developmental disability in infants with birth weights of 501 to 800 grams, born between 1979 and 1994

OBJECTIVE: Because the survival rate has increased for extremely low birth weight neonates, many have raised the concern that the rate of developmental disability among survivors will also increase. To address this concern, we analyzed changes over time in survival and major neurosensory impairment in a sample of extremely low birth weight infants born between July 1, 1979, and June 30, 1994. METHODS: The study sample included 513 infants with birth weights of 501 to 800 g who were cared for in either of the two neonatal intensive care units that serve a 17-county region in northwest North Carolina and who were born to mothers residing in that region. At 1 year of age (corrected for gestation), survivors were examined by a pediatrician and were tested using the Bayley Scales of Infant Development. Major neurosensory impairment was defined as cerebral palsy, a Bayley Mental Developmental Index <68, or blindness. A total of 209/216 (97%) of survivors were examined at 1 year of age. Epoch of birth was defined as follows: epoch 1, July 1, 1979 to June 30, 1984; epoch 2, July 1, 1984 to June 30, 1989; and epoch 3, July 1, 1989 to June 30, 1994. RESULTS: Survival rates for epochs 1, 2, and 3 were, respectively, 24/120 (20%), 63/175 (36%), and 129/218 (59%). In contrast, the proportions with a major neurosensory impairment did not increase over time; rates for successive epochs were 6/24 (25%), 17/61 (28%), and 26/124 (21%). Rates of cerebral palsy were 3/24 (13%), 12/61 (20%), and 9/124 (7%); rates of delayed mental development were 4/24 (17%), 12/61 (20%), and 17/124 (14%); and rates of blindness were 2/24 (8%), 0/62, and 5/124 (4%), respectively. CONCLUSIONS: This analysis suggests that the increasing survival of extremely low birth weight neonates since the late 1970s has not resulted in an increased rate of major developmental problems identifiable at 1 year of age.     

Aberrant crypt focus promotion and glucose intolerance: correlation in the rat across diets differing in fat, n-3 fatty acids and energy

McKeown-Eyssen (Cancer Epidemiol. Biomarkers Prevent., 3, 687-695, 1994) and Giovannucci (Cancer Causes Control, 6, 164-179, 1995), noting the striking similarity in lifestyle risk factors for colorectal cancer and insulin resistance, proposed that the hyperinsulinemia, glycemia and hypertriglyceridemia associated with insulin resistance promotes colon cancer. To compare the effect of diet on colon cancer promotion and insulin resistance in the F344 rat, we assessed the effect of fat, n-3 fatty acids and energy in pairwise comparisons on average size of aberrant crypt foci (ACF) and on glucose intolerance in the same animals in a single experiment. Diets high in fat and energy increased and diets with increased n-3 fatty acids and calorie restriction decreased both ACF growth and glucose intolerance compared with control diets. The measures of promotion of colon cancer and insulin resistance were strongly correlated (n = 98, r = 0.67, P < 0.001). In addition, both were highly correlated with daily energy intake (r = 0.62 and 0.66) and were also correlated with basal (post-prandial) insulin, glucose and triglycerides (r = 0.31-0.53, P < 0.01). We concluded that ACF growth and glucose intolerance are correlated for a wide range of diets and that increased circulating energy (glucose and triglycerides) may lead to both colon cancer promotion and insulin resistance.