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M Robaszkiewicz

Publications and source records attributed to M Robaszkiewicz.

At least 37 records · Page 2Linked to original sources
PubMed1995

p53 protein accumulation in oesophageal squamous cell carcinomas and precancerous lesions.

AIMS: To investigate the immunohistochemical expression of p53 protein in oesophageal squamous cell carcinomas and in dysplastic areas of the oesophageal mucosa surrounding the tumours. METHODS: Biopsy samples were obtained from 20 patients with an oesophageal squamous cell carcinoma. Blocks of the tumours and of the surrounding mucosa were immunostained with the monoclonal antibody DO-7. RESULTS: Fourteen of the 20 carcinomas were positive for p53 (70%). The frequency of p53 overexpression increased with the differentiation of the tumour. Nine out of 13 dysplastic specimens were positive for p53 (69%): eight cases with severe dysplasia and one case with moderate dysplasia. No p53 immunostaining was detected in normal oesophageal epithelium. All p53 positive dysplastic specimens were taken from the mucosa adjacent to tumours that were also immunostained. In moderate dysplastic mucosa the p53 positive cells were located in the proliferative basal zone, whereas in severe dysplasia the immunostained cells increased in number and spread to upper cell layers of the epithelium. CONCLUSION: This study supports the hypothesis that TP53 gene is frequently involved in the development of oesophageal squamous cell carcinoma and that p53 protein accumulation is an early event in human oesophageal carcinogenesis.

Adult↗
PubMed1995

[Overexpression of protein p53 and Barrett esophagus. A frequent and early event in the course of carcinogenesis].

OBJECTIVES AND METHODS: In Barrett's oesophagus, the risk of malignancy is evaluated histologically with the presence of dysplasia. The abnormal expression of p53 protein could represent a useful new marker. The aim of this study was evaluate the abnormal expression of p53 protein in a series of 52 oesophagectomy specimens with Barrett's oesophagus, either non-dysplastic (n = 3), dysplastic (n = 8), or malignant (n = 41). The immunohistochemical study was made on deparaffinized sections with the monoclonal anti-p53 antibody DO7. RESULTS: The 3 non-dysplastic cases were p53 negative; 1 case of low-grade dysplasia in 5 was positive, as were the 3 cases of high grade dysplasia and 33 of 41 cancers (80%), including 13 superficial cancers in 14 (93%) and 20 invasive cancers in 27 (74%). A common feature was the presence of rare p53 positive crypts in low grade dysplastic areas and non-dysplastic specialized mucosa that surrounded high grade dysplasia and cancers. CONCLUSIONS: Our results confirm the high frequency of the abnormal expression of p53 protein in cancer developed in Barrett's oesophagus. This expression is a consequence of alterations of the TP53 gene, and has an important role in the carcinogenesis of Barrett's mucosa; it is likely to represent an early event. Prospective studies are needed to evaluate its interest in the surveillance of patients with Barrett's oesophagus.

Barrett Esophagus↗
PubMed1995

[Therapeutic management and survival of gastric adenocarcinoma in the province of Finistère between 1984 and 1989].

OBJECTIVES: The aim of this study was to analyze the evolution of treatment regimens and survival rates of stomach adenocarcinoma recorded in the Finistère cancer registry from 1984 to 1989. METHODS: In a population of 838,627 inhabitants, 1,280 patients with a gastric cancer were registered; 1,164 patients (693 males and 471 females) had an adenocarcinoma. Survival rates were estimated by the actuarial method, and compared using the logrank test and the Cox model. RESULTS: Surgical resection was the main treatment for 661 patients (57%). The frequency of curative resection increased from 25% between 1984 and 1986 to 35% after 1986. Among the other patients, 39 (3%) were treated by chemotherapy and/or radiotherapy, and 53 patients (4%) by endoscopy alone; 253 patients had only symptomatic treatment. The survival rates of all patients were 43% at 1 year and 20% at 5 years. The median survival was 9.2 +/- 0.6 months. In patients with cancer managed surgically, the factors associated with a better prognosis were young age, long duration of symptoms before diagnosis, ulcerated macroscopic aspect, limited tumour extension and curative surgical resection. In other patients, 2 factors were associated a with better prognosis: the absence of metastases and an endoscopic palliative treatment. CONCLUSIONS: Surgical resection is the main treatment of gastric adenocarcinoma. Although the frequency of surgery increased, the prognosis of gastric adenocarcinoma did not improve within this 6-year period.

Adenocarcinoma↗
PubMed1994

[Barrett esophagus. Current situation of the risk and surveillance policy].

Barrett's oesophagus is a condition in which a metaplastic columnar mucosa replaces the normal squamous epithelium of the lower oesophagus. Barrett's oesophagus develops as a complication of gastro-oesophageal reflux and predisposes to the development of oesophageal adenocarcinoma. Most adenocarcinomas arising in Barrett's mucosa are far advanced at the time of diagnosis, and prognosis is consequently poor. Regular endoscopic surveillance of patients with Barrett's oesophagus is recommended to detect the oesophageal malignancy in an early presymptomatic stage. The concept of screening is based on the notion that regular surveillance can reduce the mortality, but there is yet little evidence that this is the case in Barrett's oesophagus. Screening is generally carried out by regular endoscopy with multiple biopsies in an attempt to detect dysplasia. Unfortunately, dysplasia is not an ideal biomarker of malignant potential in Barrett's oesophagus. There is an interest in research into more sensitive and effective predictors of heightened risk for development of malignancy. DNA content flow cytometry and p53 protein expression might be useful in managing the cancer risk in Barrett's patients. However these new techniques need further evaluation before they can be applied to routine clinical investigation.

Adenocarcinoma↗
PubMed1994

[Flow cytometry and digestive pathologies].

Flow cytometry provides rapid evaluation of nuclear DNA content and cell cycle analysis. The major applications of flow cytometry in gastroenterology are the evaluation of DNA content and proliferative indices as prognostic indicators of gastrointestinal malignancies, and the screening of premalignant conditions of the digestive tract.

Digestive System Diseases↗
PubMed1994

Four-week treatment with omeprazole increases the metabolism of caffeine.

OBJECTIVES: It has been suggested that omeprazole is an inducer of the cytochrome P450 1A, both in vitro and in vivo. To evaluate whether omeprazole treatment might affect the activity of P450 1A2, we performed a study of caffeine metabolism, which is mainly via P450 1A. METHODS: Thirteen subjects (one healthy volunteer and 12 patients) who were treated with omeprazole, 20 mg each morning for 4 wk, and a control group of 13 healthy volunteers, participated in the study. A test of caffeine metabolism was performed before treatment, 28 days after beginning treatment and, whenever possible, 28 days after treatment. Blood samples were analyzed for theobromine, paraxanthine, and theophylline, by high performance liquid chromatography. RESULTS: P4501A2 activity was determined as the ratio of (paraxanthine + theobromine + theophylline)/(metabolites + caffeine) which represents the total caffeine N-oxidative demethylations; this ratio was expressed as a percentage. For patients, on day 0, the percentage of total metabolism was 34.3% +/- 8.3; on day 28, it was 42.7% +/- 10.8; the difference was statistically significant (p < 0.01). No intra-individual variation of P450 1A2 activity was observed in the control group. CONCLUSIONS: These results demonstrate that omeprazole increases the metabolism of caffeine, especially N-1 and N-3 demethylation pathways, after 28 days of treatment with omeprazole, and suggest that omeprazole, when used for this period, is an inducer of hepatic cytochrome P4501A2.

Caffeine↗
PubMed1993

TP53 gene mutation profile in esophageal squamous cell carcinomas.

Esophageal squamous cell carcinoma is a form of cancer occurring most commonly in males, particularly those living in some areas of Asia, Africa, and western Europe. In some of these tumors, a sequence alteration has been identified in the coding region of the TP53 gene which is known to inactivate the tumor suppressor function of its product. Using a GC clamp (i.e., a GC rich domain) denaturing gradient gel electrophoresis assay we have been able to identify sequence modifications in 27 of the 32 tumor samples analyzed (84%). Most of the mutations occur in exon 6, a region of the gene which has not previously been reported as being a hot spot for the mutations of other cancers. Twelve of the mutations reported here have not been described in other types of tumors and these consist mostly of frameshift or splice mutations. The distribution of mutations [transitions (45%), transversions (34%), and frameshift (21%)] suggests that the etiological contribution of genotoxic factors might be complex and might associate different exogenous and endogenous mutagen exposures.

Adult↗
PubMed1992

Endosonography can detect residual tumour infiltration after medical treatment of oesophageal cancer in the absence of endoscopic lesions.

Endoscopic ultrasound (endosonography) is useful in the preoperative staging of oesophageal tumours. It may also have a role in evaluation and surveillance of patients with inoperable carcinomas. Thirty four patients with inoperable oesophageal cancer were investigated by endosonography and computed tomography before medical treatment. In 10 patients receiving combined chemotherapy and radiotherapy, the endoscopic lesions resolved and biopsy specimens were negative. When endosonography suggested the persistence of tumour infiltration in these patients, a local recurrence or distant metastases appeared within a few months. In contrast, when no infiltration was detected, no tumoral recurrence or progression was observed within eight months. These results suggest that endosonography is better than endoscopic biopsy specimens and computed tomography in assessing the response of oesophageal carcinoma to non-surgical treatment.

Combined Modality Therapy↗
PubMed1992

[Primary colonic intussusception protruding from the anus in adults. Two cases].

The authors report two cases of colonic intussusception in the adult protruding from the anus--or colon-anal intussusception--, not due to a tumor. The first case was a chronic ileo-caeco-colique intussusception, the second case was an acute colo-rectal intussusception. Colo-anal intussusceptions are very rare: less than twenty cases have been described since 1925 in adults. The absence of a tumor origin in our cases represents a special feature, as only three other similar cases have been described. The surgical treatment in both cases was primary colonic resection without colostomy. The surgical treatment of the first case was subtotal colectomy with ileo-rectal anastomosis. The second case was primarily reduced by barium enema which allowed optimal secondary surgical resection of a prepared colon.

Adolescent↗
PubMed1992

[Demonstration of clonal heterogeneity in adenocarcinomas on Barrett's esophagus by flow cytometric study of cellular DNA content].

Flow cytometry was used to examine the spatial distribution of nuclear DNA content in Barrett's mucosa, in one patient with high grade dysplasia and in 6 patients with Barrett's adenocarcinoma. All tumors were aneuploid. Each adenocarcinoma but the most advanced seemed to arise from a single clone of aneuploid or near-tetraploid cells which was found in all biopsy specimens taken from the tumor. Multiple aneuploid populations of cells were seen in the larger tumors. Eight clones were individualized in the most advanced case of cancer. In all patients with carcinoma, the mucosa surrounding the tumor was aneuploid. Some areas were characterized by the same DNA index as in the tumor, others contained distinct aneuploid cell populations. The spatial distributions of aneuploid clones and dysplastic areas were not perfectly superimposed. These data suggest that neoplastic progression in Barrett's esophagus is associated with genomic instability preceding the development of malignancy. Clonal heterogeneity in Barrett's adenocarcinoma is more marked when compared to other tumors and suggests a majoration of genomic instability during tumor progression.

Adenocarcinoma↗
PubMed1992

[Primary colonic intussusception protruding from the anus in adults. Two cases].

The authors report two cases of colonic intussusception in the adult protruding from the anus--or colo-anal intussusception--, not due to a tumor. The first case was a chronic ileo-caeco-colique intussusception, the second case was an acute colo-rectal intussusception. Colo-anal intussusceptions are very rare: less than twenty cases have been described since 1925 in adults. The absence of a tumor origin in our cases represents a special feature, as only three other similar cases have been described. The surgical treatment in both cases was primary colonic resection without colostomy. The surgical treatment of the first case was subtotal colectomy with ileo-rectal anastomosis. The second case was primarily reduced by barium enema which allowed optimal secondary surgical resection of a prepared colon.

Acute Disease↗
PubMed1991

Flow-cytometric DNA content analysis of esophageal squamous cell carcinomas.

To better understand the mechanisms of esophageal carcinogenesis, abnormalities in DNA content of esophageal squamous cell carcinomas were studied. Cellular DNA content was determined by flow cytometric study of 70 endoscopic biopsy specimens obtained from 26 patients with esophageal squamous carcinoma. High-quality histograms were obtained for 23 patients. Twenty-one patients had at least one aneuploid population in their tumor. In 7 patients, multiple aneuploid peaks were detected. Specimens from 2 patients were diploid. The interpretation of the DNA histograms was difficult in 3 patients; an aneuploid population of cells was probable in 2 of them. A statistically significant relationship was found between the degree of differentiation and DNA content abnormalities in the regions of the tumors that could be evaluated by endoscopic biopsies: well-differentiated carcinomas had diploid or small aneuploid populations containing less than 15% of the cells, whereas DNA histograms of moderately or poorly differentiated carcinomas were characterized by large aneuploid peaks representing 25%-90% of the cells and a higher proliferative fraction. No relationship was found between the size or the stage of the tumor and the DNA content detected in endoscopic biopsy samples. The frequency and the multiplicity of abnormal clones in esophageal squamous carcinomas indicates that this cancer, like esophageal adenocarcinoma, develops an association with an acquired genomic instability that produces abnormal clones of cells, according to the multistep model of neoplastic progression.

Adult↗