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Biomedical subjects

T Lerut

Publications and source records attributed to T Lerut.

At least 73 records · Page 4Linked to original sources
PubMed1996

Enrichment of tumor cells for cell kinetic analysis in human tumor biopsies using cytokeratin gating.

PURPOSE: To determine the feasibility of using cytokeratin antibodies to distinguish normal and malignant cells in human tumors using flow cytometry. The goal was ultimately to increase the accuracy of cell kinetic measurements on human tumor biopsies. MATERIAL AND METHODS: A panel of four antibodies was screened on a series of 48 tumors from two centres; 22 head and neck tumors (Amsterdam) and 26 esophagus carcinomas (Leuven). First, screening was carried out by immunohistochemistry on frozen sections to test intensity of staining and the fraction of cytokeratin-positive tumor cells. The antibody showing the most positive staining was then used for flow cytometry on the same tumor. RESULTS: The two broadest spectrum antibodies (AE1/AE3, E3/C4) showed overall the best results with immunohistochemical staining, being positive in over 95% of tumors. Good cell suspensions for DNA flow cytometry could be made from frozen material by a mechanical method, whereas enzymatic methods with trypsin or collagenase were judged failures in almost all cases. From fresh material, both collagenase and trypsin produced good suspensions for flow cytometry, although the fraction of tumor cells, judged by proportion aneuploid cells, was markedly higher for trypsin. Using the best cytokeratin antibody for each tumor, two parameter flow cytometry was done (cytokeratin versus DNA content). Enrichment of tumor cells was then tested by measuring the fraction of aneuploid cells (the presumed malignant population) of cytokeratin-positive cells versus all cells. An enrichment factor ranging between 0 (no enrichment) and 1 (perfect enrichment, tumor cells only) was then calculated. The average enrichment was 0.60 for head and neck tumors and 0.59 for esophagus tumors. CONCLUSIONS: We conclude that this method can substantially enrich the proportion of tumor cells in biopsies from carcinomas. Application of this method could significantly enhance accuracy of tumor cell kinetic measurements.

Aneuploidy↗
PubMed1996

Oesophageal carcinoma--past and present studies.

Surgery is a crucial part of therapy of oesophageal cancer. The many trials which are described focus on variations in surgical technique. A trend is found that results are better with more extensive procedures. Local control evidently is improved, but an effect on survival is not yet sufficiently shown. Combinations of neoadjuvant radiotherapy and/or chemotherapy with surgery are effective by downstaging offering seemingly better survival in responding patients. Interpretation of trial data, however, is difficult because of the relatively small numbers in individual studies; the differences of the used treatment modalities make an overview approach less reasonable. Great attention should be given in the future trial work to better standardization (interpretation of definitions). Directives for optimal staging should be described in all study protocols.

Clinical Trials as Topic↗
PubMed1996

Surgery for non-small cell lung cancer with unsuspected metastasis to ipsilateral mediastinal or subcarinal nodes (N2 disease).

OBJECTIVE: Although the results after surgery for N2 disease are disappointing, there seems to be a subgroup of patients which may benefit from primary resection. These patients have clinically unrecognized N2 involvement that is discovered only at the time of thoracotomy (unsuspected or unforeseen N2 disease). It was the aim of this retrospective study to analyze the survival after resection for unforeseen N2 disease and to evaluate different prognostic factors. We were interested to see whether our strategy of rigorous staging of the mediastinum with mediastinoscopy or anterior mediastinotomy had an effect on the resectability rate and survival of unsuspected N2 disease. METHODS: Between 1985 and 1990, 859 patients with potentially operable non-small cell lung cancer were referred to our surgical department. Despite rigorous preoperative staging with computed tomography scan and cervical mediastinoscopy and/or anterior mediastinotomy, 103 patients (14.5%) had unsuspected N2 disease at thoracotomy. The tumor could be completely resected in 90 patients (87.5%). RESULTS: The 5-year survival after complete resection was 22%. Histology of the tumor, number of involved levels and extent of nodal disease had no effect on survival. CONCLUSION: We conclude that resection is justified in patients with unforeseen N2 disease. Rigorous staging of the mediastinum by cervical mediastinoscopy or anterior mediastinotomy results in a high resectability rate and avoids unnecessary thoracotomies. Mediastinoscopy plays a central role in the staging of patients with carcinoma of the lung.

Actuarial Analysis↗
PubMed1996

Esophagocoloplasty for congenital, benign and malignant diseases. Surgical and long-term functional results.

OBJECTIVE: Aim of this report is to evaluate the results of 100 consecutive esophagocoloplasties performed for congenital, benign and malignant diseases. METHODS: From 1982 until 1993 one hundred consecutive esophagocoloplasties were performed. Fifty eight for benign diseases: 22 congenital atresias (group A), 36 acquired benign lesions (group B), and 42 for malignancy (group C). As 72% of the patients had undergone previous gastric or esophageal surgery, coloplasty had to be performed in 48 patients by necessity. In 85 patients the colon graft was vascularized by the ascending branch of left colic artery and in 95 the reconstruction was fashioned in isoperistaltic way. RESULTS: Fifty one complications occurred in 42 patients resulting in a hospital mortality of 8%. However, for all benign diseases (group A + B) mortality rate was 0, being 19% in malignancy (group C). Morbidity was significantly higher in group A + C as compared to group B (p < 0.0009). Anastomotic leak was the most frequent complication occurring in 13 patients however healing spontaneously in 11 patients (84.6%). Early revisional surgery was performed in 11 patients. Functional results were evaluated according to a new grading system, including the four main symptoms (dysphagia, pain, regurgitations, diarrhoea) and weight status, the latter for adult patients. Fifty one patients from group A and B were followed for at least one year and evaluated. The were divided in two groups: 25 pediatrics (0.18 years). Anastomotic stenosis occurred in 19 patients but resolved after one or more dilatations in 16 at final follow-up. Dysphagia decreased from 43.1% 3 months postoperatively to 17.6% at last follow-up (p < 0.01). In adult patients there was a strong correlation between dysphagia and weight loss (p < 0.02). This correlation was not found in children. No differences were detectable when comparing preoperative mean weight of adult patients with mean weight of adult patients with mean weight at last follow-up. Of all 51 patients, 82.3% had an excellent (grade 1) or very good (grade 2) result at final evaluation versus 49% at 3 months follow-up (p < 0.0001). Only one patient had an unsatisfactory final result. CONCLUSIONS: Esophagocoloplasty is a valuable and for some patients an essential technique in reconstruction of esophageal continuity. Mortality can be kept very low, especially in benign diseases, guaranteeing satisfactory results in the majority of patients, despite an initial substantial perioperative morbidity.

Adolescent↗
PubMed1996

Endoscopic In Utero Tracheal Plugging in the Fetal Lamb to Treat Congenital Diaphragmatic Hernia

A case control surgical trial was performed in 13 time-dated pregnant ewes to evaluate the feasibility and pulmonary effects of intratracheal obstruction by an endoscopically positioned balloon. Fifteen fetuses were subjected to tracheoscopic balloon obstruction for progressively longer periods (range 2-18 days). In case of multiple pregnancies, 10 other fetuses were used as negative controls. A 1.2-mm miniscope with a double-lumen sheath and a detachable balloon were used. Feasibility of the technique was assessed in all animals based on operating time, intraoperative complications, and tracheal obstruction. Pulmonary effects were assessed by lung-to-body weight ratio (LBWR) and morphometric terminal brachial density (MTBD). In 14 animals the trachea was successfully obstructed until delivery. Tracheoscopic manipulation time ranged from 3 to 14 minutes. One intraoperative death occurred, but the contralateral control fetus also died during the procedure. When obstruction lasted for more than 7 days, the mean LBWR was 0.060 &plusmn; 0.01 (range 0.051-0.075) and in controls 0.031 &plusmn; 0.01 (range 0.017-0.039, p <0.0005). The MTBD was 0.65 &plusmn; 0.59, compared with 1.30 &plusmn; 0.80 for controls. Using a simple and fast technique of fetoscopic tracheoscopy, the trachea can be obstructed, leading to pulmonary hyperplasia, which is of potential value when treating congenital diaphragmatic hernia.

Journal Article↗
PubMed1995

Pulmonary neuroepithelial bodies in neonatal and adult dogs: histochemistry, ultrastructure, and effects of unilateral hilar lung denervation.

In neonatal dogs, neuroepithelial bodies (NEB) are located in the distal lung. They consist of closely packed and granulated epithelial cells showing a positive immune reaction to serotonin and carrying well-developed apical microvilli. They make close contact with capillaries and form morphologically afferent synaptic junctions with intracorpuscular nerve endings. Since most nerve endings degenerate after hilar lung denervation, they are carried by extrinsic, most likely vagal, sensory nerve fibers. We conclude that pulmonary NEB probably are receptor organs, sampling the inspired air and secreting bioactive substances. These might have a local vaso- or bronchoactive regulatory effect, or could be carried to other body parts via the blood vessels. In addition, NEB might induce integrative reflexes via the central nervous system. The NEB intracorpuscular nerve endings also show spontaneous degeneration. This, in addition to the scarcity of NEB in the distal lungs of adult dogs, strongly suggests that the pulmonary NEB are particularly important during the perinatal period of life.

Aging↗
PubMed1994

Surgical treatment of Barrett's carcinoma. Correlations between morphologic findings and prognosis.

Barrett's carcinoma occurred in 66 of 331 patients with adenocarcinomas of the esophagus or gastroesophageal junction. Only 32 (46%) of these patients had a history of gastroesophageal reflux. A history of alcohol and tobacco abuse was absent in 50% and 47.5%, respectively. The mean length of Barrett's metaplasia was 7.37 cm. Operability was 98.5% and resectability 95.5%. No postoperative or hospital deaths occurred. Pathologic staging was as follows: stage 0 and I, 38.3%; stage II, 20.6%; stage III, 22.2%; and stage IV, 19%. Overall survivals were 80.5% at 1 year, 62.7% at 2 years, and 58.2% at 5 years. Five-year survival for patients with stage I disease was 100%; for stage II, 87.5%; for stage III, 22.2%; and for stage IV, 0%. Thirty-four (51.5%) patients were under surveillance for a related or unrelated condition before diagnosis of their carcinoma; only nine (26.5%) had diseased lymph nodes. In 32 the diagnosis was made at their first medical contact, and 78% of them had diseased lymph nodes. Five-year survival without nodal metastasis was 85.3% and significantly better than for patients with metastasis, 38.3% (p = 0.0033). Of the 66 patients, 19 (28.7%) had a biopsy-proved history of Barrett's metaplasia before malignancy developed. Mean time interval between diagnosis of metaplasia and degeneration was 3.8 years (89.5% > 1 year). Over the surveillance period, the length of metaplastic Barrett's esophagus remained unchanged in all patients. Barrett's ulceration was present from the beginning in 14 patients, and three patients never had an ulcer. Intestinal metaplasia was seen in 18 patients. Resected specimens revealed severe dysplasia in 16 patients. Of the 19 patients, 73.7% had stage I disease. Our data suggest that close endoscopic monitoring and systematic biopsies of the smallest irregularities in the metaplastic mucosa may result in early detection of carcinoma. In this respect, patients with an ulcer within a zone of intestinal metaplasia seem to be at risk. Early detection increases substantially the chances for cure by diminishing the risks of lymph node involvement. Resection remains the treatment of choice in Barrett's adenocarcinoma including high-grade dysplasia, because mortality can be kept low with excellent to very good functional results in the majority of the patients provided the intervention is performed by experienced teams.

Adenocarcinoma↗
PubMed1994

A model for fetal surgery through intrauterine endoscopy.

Video-endoscopic technology may offer new hope for the future of fetal surgery. Ten time-dated pregnant ewes (95 to 105 days; term, 145 days) were used to develop a model of fetal surgery through intrauterine endoscopy. Special 5-mm ports were designed with short, flexible, balloon-tipped shafts. The cannulas were inserted through purse-stringed hysterostomies. Amnioinfusion of warmed physiological fluid (Hartmann) was used as the work medium. Fetal heart rate and oxygen saturation (pulse oximetry), temperature, and amniotic pressure were monitored continuously through endoscopically placed sensors. Surgical procedures included subcutaneous dissection of the abdominal wall and ligation of the urethra in the male fetus (n = 7), ligation of the urachus within the umbilical cord (n = 8), and endoscopy of the fetal esophagus and trachea (n = 6). Bloodless surgery was achieved with a novel coagulation device that allows bipolar cutting and coagulation in an electrolyte-rich fluid medium. The mean fetal operative time was 147 minutes (range, 130 to 195). The intraamniotic temperature was maintained between 38.0 +/- 0.9 degrees C and 41.7 +/- 1.7 degrees C throughout the procedure. Oxygen saturation ranged from 51 +/- 20% to 72 +/- 14%, and fetal heart rate from 120 to 140 beats per minute. In conclusion, intrauterine endoscopy in a fluid medium allows fully monitored surgical procedures, lasting more than 2 hours, to be performed on the fetal lamb.

Animals↗
PubMed1994

In vivo cell kinetic measurements in human oesophageal cancer: what can be learned from multiple biopsies?

The importance of intratumour variability of cell kinetics was studied in 60 patients with cancer of the oesophagus. Five biopsies per tumour were taken. The labelling index, S-phase duration and potential doubling time (Tpot) were measured using flow cytometry. The mean Tpot value was 5.56 +/- 4.43 days (+/- 1S.D.) for adenocarcinomas and 4.40 +/- 2.45 days (+/- 1S.D.) for squamous cell carcinomas. These values were statistically significantly different. Although intratumour variation in Tpot measurements occurred, the intertumour variability was more important (P < 0.00001). This feature permits classification of tumours into slow and fast proliferating groups, leaving an intermediate group of tumours that could not be unequivocally categorised. The relative distribution of tumours into these three categories depends on the intratumour and intertumour variability of Tpot, and on the cut-off values used. Increasing the number of biopsies from one to five reduces the number of non-classifiable tumours.

Adenocarcinoma↗
PubMed1994

Fetoscopy-guided fetal endoscopy in a sheep model.

Video-endoscopic surgical treatment of the fetus may, in the future, become an alternative to open fetal operation. Six 95-day-old fetal lambs were examined through intrauterine endoscopy using amnioinfusion and specially designed balloon-tipped cannulas. The fetuses were monitored endoscopically for oxygen saturation, heart rate and temperature throughout the procedure. With a rigid 5 millimeter telescope and a flexible 3 millimeter endoscope, the respiratory and upper gastrointestinal tracts could be examined. No mucosal or other trauma was noted upon completion of the endoscopy; all lambs survived the procedure. While the applications of fetal endosurgery are likely to be similar to those of open fetal operation, fetal endoscopy (looking in the fetus) is a new entity for which clinical relevance (rather than mere feasibility) remains to be demonstrated. This technique, however, could become a valuable research tool to study fetal gastrointestinal and pulmonary physiologic factors in situ.

Animals↗
PubMed1993

[Functioning of the tube stomach following esophagus resection for carcinoma].

A retrospective study was made of the functional results of the tube stomach created in 80 patients after oesophageal resection because of carcinoma to restore the continuity. The study concerned patients who had survived the operation for longer than 18 months without indications of tumour recurrence or metastases and of whom clinical and endoscopical data of 3 months and one year after the operation were available. The functional results of the tube stomach may be regarded as good because one year postoperatively 86% of the patients were classified as excellent or very good according to the modified Visick classification. Dumping (18%), a sensation of fullness (26%) and diarrhoea (28%) were frequent complaints, occurring mostly soon after the operation. After one year these complaints are almost completely gone. Three months postoperatively, 19% of the patients had a stenosis of the anastomosis that required one or more dilatations. Reflux oesophagitis is the major late complication, leading to late stricture of the anastomosis. Reflux oesophagitis was encountered in 43% of the patients with an intrathoracic anastomosis and in only 6% of those with a cervical anastomosis; the difference is statistically significant. After one year, a stenosis due to reflux was encountered in four of the 30 patients (13%) with an intrathoracic anastomosis and in only one of the 50 patients (2%) with a cervical anastomosis. These results show that from the functional point of view, as well, the stomach is a good substitution organ after oesophageal resection, provided the anastomosis is created in the neck.

Adult↗
PubMed1993

Adenine nucleotide degradation in ischemic rabbit lung tissue.

The aim of the study was to determine the pathways and site of adenosine triphosphate (ATP) catabolism during lung ischemia, which thus far are largely unknown. For this purpose we used the isolated rabbit lung. Rabbit lungs were flushed in situ with a modified Krebs-Henseleit solution (60 ml/kg), the deflated heart lung blocks were isolated, immersed in saline solution, and stored at 37 degrees C. In group I (normothermic ischemia; n = 6) tissue content of ATP decreased progressively from 9.42 +/- 0.58 mumol/g dry wt to 3.42 +/- 0.24 mumol/g dry wt after 30 min of ischemia and further to 0.51 mumol/g dry weight after 4 h. Hypoxanthine was the major catabolite (92% of the nucleoside and purine base fraction at 4 h ischemia). Adenosine did not accumulate (preischemic 0.08 +/- 0.02 mumol/g dry weight vs. 0.13 +/- 0.01 mumol/g dry weight; P > 0.05). AMP accumulated, but also inosine monophosphate (IMP), which was undetectable before ischemia, increased significantly during ischemia. To determine the breakdown pathway of AMP, 400 microM of the adenosine deaminase inhibitor EHNA was added to the flush solution in group II (n = 6). During ischemia, ATP breakdown was unaltered but adenosine became the major catabolite (2.8 times the concentration of hypoxanthine at 4 h ischemia). By pretreatment of the rabbits with the nucleoside transport inhibitor R 75231 (group III; n = 6) no effect was observed on the concentrations during ischemia of inosine and hypoxanthine and only a minor increase of adenosine was found. Cytochemical localization of nucleoside phosphorylase revealed activity predominantly in the endothelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenine Nucleotides↗
PubMed1993

[Familial occurrence of esophageal atresia].

Two siblings with esophageal atresia are reported, and literature data as to familial occurrence and heredity have been reviewed. Until now, only statistical data can be given: the recurrence risk for sibs after one affected child is around 0.5-2% and after two affected children around 20%. The risk for the children of a parent affected by congenital esophageal atresia is estimated at around 3-4%. This is compatible with the recurrence risk of a multifactorial condition in first degree relatives. However, two patients have been described in which the possibility of autosomal dominant transmission has been raised.

Chromosome Aberrations↗
PubMed1992

Factors influencing local relapse and survival and results of salvage treatment after breast-conserving therapy in operable breast cancer: EORTC trial 10801, breast conservation compared with mastectomy in TNM stage I and II breast cancer.

A (modified) radical mastectomy (RM) was compared with breast-conserving therapy (BCT) in stage I and stage II breast cancer patients. Treatment of the study arm comprised lumpectomy, axillary clearance and radiotherapy to the breast (50 Gy in 5 weeks external irradiation and a boost with iridium implant of 25 Gy). 902 patients were included. There were 734 TNM stage II patients. Patients with microscopically incomplete excision of the tumour were not excluded. After a median follow-up of 6 years, overall survival and local recurrence rates do not differ significantly between the two study arms. Actuarial survival at 8 years was 73% after RM and 71% after BCT; actuarial local recurrence at 8 years was 9% and 15%, respectively. In the mastectomy group tumour size did not affect local relapse, but after BCT the incidence of local recurrences was higher for tumours of 2-5 cm (16%) than for smaller tumours (7%) (at 8 years, P = 0.08). Results of salvage treatment for local recurrence so far were similar in both the BCT and the mastectomy group.

Aging↗
PubMed1992

Early and late functional results in patients with intrathoracic gastric replacement after oesophagectomy for carcinoma.

The function of the gastric substitute after oesophagectomy for carcinoma was studied retrospectively in 80 patients. At 3 months and 1 year postoperatively, a clinical and endoscopical examination was performed. A modified Visick grading of the results was used for scoring the final result. At 3 months 90% of the patients lost weight, compared with their preoperative status. At 1 year postoperatively, however, only 10% of the patients noted a further weight loss. One-fourth of the patients suffered 3 months postprandial fullness and diarrhoea, while 18% had dumping symptoms. These symptoms are mostly temporarily and disappear almost completely at 1 year. Three months postoperatively, 27% of patients had dysphagia, and 15% had heartburn and/or regurgitation. At 1 year, heartburn and/or regurgitation were increasingly reported (up to 21%), while less dysphagia was noted (15%). Early stricture requiring one or more dilatations was present in 18.7% of the patients. Five patients developed a late anastomotic stricture; 4 were located at the level of the intrathoracic anastomosis and were associated with severe oesophagitis. At 1 year there was a statistically significant difference between patients with cervical anastomosis and those with intrathoracic anastomosis when comparing reflux symptoms (4% vs. 50%; p = 0.0001) and oesophagitis (8% vs. 53%; p = 0.001). In all, 86% of patients had an excellent or very good late functional result, but only 6% of patients who underwent cervical anastomosis have a Visick score 3 or 4 vs. 23% after intrathoracic anastomosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗