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P Slezak

Publications and source records attributed to P Slezak.

At least 19 recordsLinked to original sources
PubMed2001

Genetic pathways in the evolution of morphologically distinct colorectal neoplasms.

Colorectal adenomas can be morphologically classified as exophytic or flat. Polypoid cancers and cancers arising de novo (ie., without any adenomatous component) might be the results of genetic progression from exophytic and flat adenomas, respectively. In this study, we examined 94 morphologically distinct neoplastic specimens for mutations in K-RAS and analyzed 10 microsatellite loci tightly linked to the tumor suppressor genes APC, p53, DCC/SMAD4, hMSH2, and hMLH1. K-RAS mutations were significantly associated with exophytic adenomas [11 of 21 (52%)] compared to flat adenomas [2 of 13(15%), P < 0.03] and polypoid cancers [17 of 25 (68%)] compared to cancers arising de novo [7 of 25 (28%), P < 0.01]. Two polypoid cancer cases demonstrated three and four different K-RAS mutations, respectively, suggesting multiple areas of clonal expansion. Cancers arising de novo were significantly associated with loss of heterozygosity (LOH) at chromosome 3p compared to pol ypoid cancers [6 of 18(33%) versus 1 of 20(5%), P < 0.03], whereas the prevalence of LOH at chromosomes 2p, 5q, 17p, and 18q and microsatellite instability were not different between the groups. For all cancers, LOH at chromosomes 17p and 18q occurred in 47 and 51%, respectively. However, LOH at 17p and 18q occurred in 0 and 16% of benign lesions, respectively, suggesting their role in malignant transformation. There was no difference in LOH at chromosomes 17p and 18q between exophytic and flat lesions. These findings suggest that (a) mutant K-RAS is associated with the exophytic growth of colonic neoplasms, and that (b) some colorectal cancers arising de novo lose chromosome 3p during their evolution, which is not seen in polypoid cancers. Half of all cancers lose chromosomes 17p and 18q at or near the malignant transition of benign lesions as reported previously, irrespective of morphology. There may be more than one genetic avenue for colorectal cancer formation, and this correlates with the morphological characteristics.

Adenoma↗
PubMed2001

Aberrant expression of G1-phase cell cycle regulators in flat and exophytic adenomas of the human colon.

BACKGROUND & AIMS: The G1/S-phase controlling mechanism known as the RB pathway is commonly deregulated in human malignancies. Here, the abundance and localization of key components of the retinoblastoma (RB) pathway were determined in exophytic and flat colorectal adenomas. METHODS: Samples of normal colonic mucosa (n = 41) and flat (n = 45) and exophytic (n = 26) adenomas were examined immunohistochemically using antibodies to cyclins D1, D2, D3, cyclin-dependent kinase (CDK) 4, retinoblastoma protein (pRB), and the CDK inhibitors p16INK4a, p18INK4c, and p19INK4d. RESULTS: In normal colonic epithelium, cyclin D2 was undetectable; expression of cyclin D1, CDK4, and pRB correlated with proliferation; and p16, p18, p19, and cyclin D3 were most abundant in quiescent, differentiated cells. Adenomas showed elevated expression of cyclin D1 and pRB, frequent induction of cyclin D2, and absence of p16. No obvious abnormalities were found for p18, p19, or cyclin D3. Overexpressed cyclin D2 was more common among exophytic and pRB among flat adenomas, respectively. Elevated cyclin D1, D2, and CDK4 correlated with enhanced dysplasia. CONCLUSIONS: Aberrant expression of cyclins D1, D2, CDK4, p16, and pRB occur in significant subsets of exophytic and flat adenomas, particularly among cases with high-grade dysplasia. Such defects of the RB pathway may perturb cell-cycle control and thereby contribute an early step in colorectal tumorigenesis.

Adenoma↗
PubMed2001

Dynamic 99Tcm-HIDA SPET: non-invasive measuring of intrahepatic bile flow. Description of the method and a study in primary sclerosing cholangitis.

In this study dynamic 99Tcm-HIDA single photon emission tomography (SPET) was performed in patients with primary sclerosing cholangitis and normal test subjects. The method offers the possibility of functional analysis of individual liver segments. After injection of 120 MBq of 99Tcm-HIDA, 12 consecutive SPET examinations were performed at 6-min intervals. The segmental borders of liver segments as seen on computed tomography or magnetic resonance examinations were superimposed on the scintigraphic images allowing placement of regions of interest (ROIs) in specific liver segments. Sampling from the same ROIs in consecutive SPET images enabled creation of time-activity curves for individual liver segments. A range of normal values was created by quantitative analysis of normal volunteer studies. Results of the studies in patients correlated well with cholangiographic extent of disease, liver function tests and histological stage. The technique may have particular value in diseases that affect the liver in a nonhomogenous or segmental fashion. Giving an indication of bile clearance from individual liver segments, it can quantify the functional importance of radiologically detected strictures. Percutaneous liver biopsy can be directed to the worst affected parts of the liver, making biopsy more representative. Sequential studies may allow monitoring of disease progression, aiding in selection and timing of therapeutic procedures.

Adult↗
PubMed2000

Somatic mutations of the APC, KRAS, and TP53 genes in nonpolypoid colorectal adenomas.

Colorectal adenomas are macroscopically visible morphological changes of the mucosa that can develop focal carcinoma in the absence of surgical intervention. The successive molecular changes proposed to occur at different stages in the adenoma-carcinoma sequence were primarily based on DNA studies of exophytic, polypoid-type adenomas. Not all colorectal lesions, however, display an exophytic phenotype and a presumed distinct colorectal neoplasm, the nonpolypoid adenoma, was subsequently described as a precursor of colorectal cancer. The low incidence of KRAS mutations in nonpolypoid colorectal adenomas reported previously suggested a different genetic basis for the transformation process in these lesions. We have pursued the identification of genetic changes in benign sporadic nonpolypoid colorectal adenomas in a selected Swedish patient group with no family history of colorectal cancer. Mutation screening of the adenomatous polyposis coli (APC), KRAS, and TP53 genes was conducted using the protein truncation test, heteroduplex-single-strand conformation polymorphism analysis, and denaturing gradient gel electrophoresis on PCR-amplified fragments. Fourteen mutations in the APC gene were characterized in 10/20 samples. Mutations in the KRAS and TP53 genes were identified in 3/57 and 4/51 adenomas, respectively. The mutation frequencies and distribution of mutations in APC correlate with published data on exophytic adenomas. The low mutation frequency of the TP53 gene is consistent with the benign nature of the research material. KRAS activation (an early event in polypoid colorectal adenomas) apparently does not play a significant role in nonpolypoid adenoma development but may result in the development of a polypoid configuration. Genes Chromosomes Cancer 27:202-208, 2000.

Adenoma↗
PubMed1999

Multiple APC mutations in sporadic flat colorectal adenomas.

Adenomas are established pre-malignant lesions in colorectal carcinogenesis. To date the adenoma-carcinoma sequence for the development of colorectal carcinoma (CRC) has been based largely on molecular data of exophytic, polypoid-type adenomas. Subsequently, a different type of adenoma has been identified: the flat adenoma, so called for its flat, non-exophytic appearance, making it less likely to be detected during conventional endoscopy. However, due to technological advances in endoscopic methods, flat-type adenomas can now frequently be detected and are no longer considered rare colorectal lesions. The phenotype of flat colorectal adenomas differs macroscopically and histologically from exophytic adenomas. Flat colorectal adenomas, as a rule, are tubular structures often revealing high-grade dysplasia, irrespective of the size or villous component. Flat adenomas have also been recognised as pre-cancerous lesions in gastric cancer. Unlike the wealth of clinical and molecular information available for polypoid (exophytic) adenomas, molecular profiles of flat-type lesions have not yet been characterised systematically and the full clinical significance hereto realised. Previous molecular investigation of the K-ras gene in flat colorectal adenomas suggests a distinct pathway in their development. In this study, mutation analysis of the adenomatous polyposis coli (APC) gene using the protein truncation test (PTT) in 20 flat colorectal adenomas in a selected group of 16 patients without hereditary predisposition to colorectal cancer, revealed double truncations of the APC gene in four adenomas. In one of these adenomas a third mutation was detected by DNA sequence analysis.

Adenoma↗
PubMed1999

Clinical spectral characterisation of colonic mucosal lesions using autofluorescence and delta aminolevulinic acid sensitisation.

BACKGROUND AND AIMS: Laser induced fluorescence (LIF) from colonic mucosa was measured in vivo with and without delta aminolevulinic acid (ALA) in an attempt to differentiate between neoplasia and non-neoplasia in real time during colonoscopy. METHODS: Spectra from 32 adenomas, 68 normal sites, and 14 hyperplastic polyps in 41 patients were obtained with a point monitoring system. Twenty one of the patients had been given a low dose of ALA as a photosensitiser before the examination. Light of 337, 405, or 436 nm wavelength was used as excitation. Stepwise multivariate linear regression analysis was performed. RESULTS: With 337 nm excitation, 100% sensitivity and 96% specificity was obtained between normal mucosa and adenomas. Seventy seven per cent of the hyperplastic polyps were classified as non-neoplastic. When exciting with 405 and 436 nm, the possibility of distinguishing different types of tissue was considerably better in the ALA patients than in the non-ALA patients. CONCLUSIONS: The in vivo point measurements imply that a good discrimination between normal tissue and adenomatous polyps can be obtained using the LIF technique. Excitation at 337 nm and at 405 nm or 436 nm using ALA gives good results. LIF also shows potential for distinguishing adenomatous from hyperplastic polyps. The number of detection wavelengths could be reduced if chosen properly.

Adenoma↗
PubMed1998

Somatically acquired genetic alterations in flat colorectal neoplasias.

Somatically acquired mutations in several genes have been reported as playing an important role during colorectal tumorigenesis. Two alternative groups of carcinomas, termed LOH+ and RER+, have been defined on the basis of their genetic anomalies, a biallelic inactivation of the APC or the TGF-betaRII genes, occurring as an alternative, in LOH+ or RER+ tumors. It is a generally accepted hypothesis that most of colorectal cancers (CRC) develop from a pre-existing adenomatous polyp. Such benign lesions are usually exophytic polyps, a small proportion of adenomas having been described as flat lesions. The latter histological category has thus been proposed to bear specific genetic alterations. In order to examine this hypothesis, we have characterized a series of 44 flat colorectal neoplasias for their RER status and for somatic APC, KRAS and TGF-betaRII genes mutations. Flat colorectal neoplasias were found to be of the RER+ subtype in 22% of cases, all of them exhibiting a TGF-betaRII mutation. A mutation of the APC and KRAS genes has been found in 42% and 4% of tumors, respectively, none of these tumors being of the RER+ subtype. With the exception of a low KRAS mutation rate, flat adenomas appear to follow tumorigenesis pathways very similar to those identified in exophytic adenomas and carcinomas.

Adenoma↗
PubMed1997

Small colorectal serrated adenomas: endoscopic findings.

BACKGROUND AND STUDY AIMS: Serrated adenomas are a distinct form of colorectal neoplasia. Several reports have indicated that serrated adenomas may give rise to invasive adenocarcinoma. The present study describes the endoscopic findings in 54 colorectal serrated adenomas detected in 35 patients. PATIENTS AND METHODS: Thirty-five of 1225 patients (2.9%) who underwent colonoscopy during 1993 in the gastrointestinal endoscopy section at Karolinska Hospital (22 men, 13 women; mean age 68 years, range 49-84 years) were found to have a total of 182 polyps, including 118 adenomas and 64 hyperplastic polyps at histopathology. Fifty-four of the 118 adenomas (46%) were of the serrated type. In two of the 35 patients, two large exophytic colorectal adenocarcinomas were also present. RESULTS: Twenty-nine of the serrated adenomas (53.5%) were flat, 23 were sessile (42.5%), and two were pedunculated (4%). The mean sizes of the flat and sessile lesions were 3.5 mm (range 2-10 mm) and 5.9 mm (range 2-20 mm), respectively. The endoscopic appearance of serrated adenomas of 5 mm or less (n = 39, 72%) was similar to that of hyperplastic polyps. Forty-two (78%) of the lesions were located in the sigmoid and rectum. Fifty-one lesions showed low-grade dysplasia (including one with microinvasive carcinoma), and the remaining three had high-grade dysplasia. CONCLUSIONS: The study suggests that small polyps with a hyperplastic appearance should not be regarded as innocuous, since they may represent serrated adenomas carrying a malignant potential.

Adenoma↗
PubMed1996

Small, flat colorectal neoplasias in long-standing ulcerative colitis detected by high-resolution electronic video endoscopy.

BACKGROUND: High-resolution video endoscopy complemented with chromoscopy allows for more detailed visualization of the colonic mucosal surface. METHODS: Using high-resolution video endoscopy and chromoscopy, we investigated 85 patients with extensive ulcerative colitis with a disease duration of at least 10 years who were taking part in a cancer surveillance program. RESULTS: In 38 of the 85 patients, 104 polyps were detected at endoscopy. Seventy-seven (74%) of the 104 polyps were endoscopically flat, 21 (20%) were sessile, 3 (3%) were pedunculated, and 3 (3%) had no recorded morphology. Twenty-three (22%) polyps were neoplastic (15 flat, 5 sessile, 2 pedunculated, 1 not recorded). Low-grade dysplasia was found in 21 of the 23 neoplastic polyps and high-grade dysplasia in the remaining 2 (1 flat tubular adenoma and 1 sessile villous adenoma with invasive growth). Flat polyps were small, with a diameter of 5 mm or less in 73% (n = 56) of cases. At histology flat polyps revealed either flat adenomas (n = 11; 14.3%), tubular or villous structures with dysplastic cells at the lower part of the crypts (n = 4; 5.2%), flat hyperplastic polyps (n = 26; 34%), inflammatory mucosa (n = 5; 6.5%), or mucosa in remission (n = 31; 40%). CONCLUSION: The use of high-resolution video endoscopy complemented with chromoscopy in ulcerative colitis enables the detection of flat neoplastic polyps. The existence of those hitherto undetected neoplasms in ulcerative colitis and their possible role in the histogenesis of colorectal cancer in ulcerative colitis deserve further investigation.

Adenoma↗
PubMed1995

Flat neoplastic lesions of the colon and rectum detected by high-resolution video endoscopy and chromoscopy.

Because small flat colorectal neoplastic lesions (i.e., flat adenomas and flat adenocarcinomas) may be as translucent as the surrounding mucosa, they can remain undetected at conventional endoscopy. By combining high-resolution video endoscopy and chromoscopy, we detected 109 colorectal flat neoplastic lesions in 55 of 232 patients studied. Forty-three (78%) of the 55 patients with flat neoplastic lesions were over 60 years of age. No flat neoplastic lesions were seen in patients under 40 years of age. Flat neoplastic lesions were more frequent in men (35%) than in women (15%). Seventy-seven (71%) of the 109 flat neoplastic lesions measured 0.5 cm or less, 23 (21%) between 0.6 and 1.0 cm, and 9 (8%) more than 1.0 cm. Low-grade dysplasia and high-grade dysplasia were found in 94 (86%) and 13 (12%) of the flat neoplastic lesions, respectively. Adenocarcinoma was diagnosed in 3 (3%) flat lesions: 1 (1%) carcinoma originating in a flat adenoma and 2 (2%) adenocarcinomas without recognizable adenomatous elements. No adenocarcinomas were seen in lesions measuring 1.0 cm or less. Fourteen flat neoplastic lesions had a central depression at endoscopy. Flat neoplastic lesions with central depression more frequently showed high-grade dysplasia (43%) than did flat neoplastic lesions without central depression (7%). Central depression in flat neoplastic lesions should be considered a possible endoscopic marker for severe dysplasia. Our results suggest that flat neoplastic lesions occur more frequently than previously reported in Scandinavia. Flat adenomas may play an important role in the histogenesis of colorectal cancer.

Adenocarcinoma↗
PubMed1995

Quantitative endoscopic classification of esophagitis by means of computerized image processing. Part 1: Theoretical background.

The potential sources of error for quantitative mapping of pathological areas in tubular organs are investigated mathematically and discussed. The first of the main errors stems from a predominance of red in the illuminating light reflected and re-reflected from the side wall of the tubular organ as compared with the white illuminating light coming directly from the light source in the endoscope. A mathematical model for this has been constructed to define an allowed interval of observation distance. The second error is due to geometrical projection, and results from the fact that more distant parts of the inside of a tube subtends a smaller solid angle than closer parts.

Esophagitis↗
PubMed1995

[Upper gastrointestinal bleeding--diagnosis and treatment guidelines].

Upper gastrointestinal bleeding is often an emergency condition requiring immediate treatment. With the introduction of acute endoscopy, the efficacy of diagnosis and treatment in such cases has been greatly improved. General guidelines for the treatment of upper gastrointestinal bleeding are given in the article.

Aged↗
PubMed1994

The costs of colonoscopy in patients with ulcerative pan-colitis in Sweden.

The costs of colonoscopy examinations at a hospital in Sweden were calculated in ten consecutive patients with ulcerative pan-colitis. Since colonoscopy in such patients is incomplete if not followed by microscopic study of the state of the colon mucosa, the costs of both the endoscopic and histological examinations were calculated together. The costs of the material used (disposable items, recycled items and durable items) and the wages for personnel involved (endoscopists, pathologists, nurses, laboratory technicians, secretaries and clerks) were calculated for each colonoscopic and histological examination. The mean cost per complete examination was US$223, which is moderate despite the high personnel costs in Sweden. Since the biopsy material obtained in an endoscopic examination is of value not only for conventional histological study but also for DNA analysis, periodic colonoscopy is still to be recommended in patients with long-standing ulcerative pan-colitis until new methods of cancer detection and prevention become available.

Adult↗
PubMed1994

The significance of mucosal staining for the endoscopic diagnosis of chronic esophagitis as assessed in biopsy findings.

A total of 115 patients with clinical signs of esophagitis were examined by endoscopy and mucosal biopsy combined with Lugol solution. Overall, 175 mucosal areas (105 stained and 70 unstained) were subjected to histopathological examination. The correlation between the staining properties of the esophageal mucosa and the histopathological diagnosis resulted in a diagnostic sensitivity of 51.9%, a specificity of 70.2%, a positive predictive value of 60.0% and a negative predictive value of 62.9% for Lugol combined endoscopy. Lugol combined endoscopy did not appear to result in any improvement in the diagnosis or staging of reflux esophagitis in our study.

Adult↗
PubMed1994

Duodenitis--distinguishing features in a retrospective endoscopic and histological study.

Routine films of 596 upper GI endoscopies with the diagnosis of duodenitis were reviewed and a classification was made into granular (G), multi-polypoid (MP), reddened (R) and erosive (E) types. Two hundred and thirty-four histological specimens from 117 of the patients, as well as 100 specimens from 50 controls, were analyzed for villous obliteration, Brunner's gland dilatation and mucus depletion, erosion, mucosal hemorrhage and edema, atypia of the surface epithelium and gastric surface epithelial metaplasia. Inflammatory cell counts for polymorphonuclear and mononuclear cells in the epithelium, in the lamina propria together with a histological score was also made. On the basis of this study and a review of classifications of duodenitis in the literature, it is concluded that some endoscopical features like erosions and redness may represent more acute phases of duodenitis, mucosal elevations representing more hyperplastic changes and that the endoscopic classification into G, MP, R and E types seem relevant to use in clinical practice.

Biopsy↗
PubMed1993

Gastric intestinal metaplasia eleven years after randomized selective proximal vagotomy for peptic ulcer.

The presence of intestinal metaplasia (IM) 11 years after selective proximal vagotomy (SPV), selective proximal vagotomy with pyloroplasty (SPV + PP) and selective vagotomy with pyloroplasty (SV + PP) was investigated in 38 consecutive patients. IM was significantly more frequent in SPV than in SV + PP, SPV + PP or in unoperated controls of matching ages. IM occurred more frequently both at an older age (> or = 60 years) in SPV and in a larger number of gastric areas than in the other group of patients. Reports in the literature indicate that vagotomy may increase the risk of gastric carcinoma and that IM may antedate malignant transformation. It would thus appear that patients previously operated with SPV (without pyloroplasty) having IM, should be the group of patients to be enrolled in endoscopical surveillance programs for detection of possible cancer development.

Adult↗
PubMed1992

Comparison between double-contrast barium enema and colonoscopy to investigate lower gastrointestinal bleeding.

A retrospective study was performed to compare the diagnostic accuracy of high-quality double-contrast barium enema (DCBE) against gold standard colonoscopy in 288 patients with suspected lower gastrointestinal bleeding who went through both examinations. Colonoscopy detected the potential cause of bleeding in 99 patients (100%); in order of frequency: polyps greater than or equal to 1 cm (N = 47; 48%), carcinoma (N = 21; 21%), inflammatory bowel disease (IBD) (N = 15; 15%), solitary ulcers (N = 6; 6%), other types of colitis (N = 5; 5%), angiodysplasia (N = 3; 3%), and stenosis (N = 2; 2%). DCBE diagnosed 88 cases (89%) and missed 11 consisting of IBD (N = 4), angiodysplasia (N = 3), solitary ulcers (N = 3), and polyps (N = 1). The overall sensitivity and specificity of DCBE was 0.89 and 0.97, respectively. The sensitivity for carcinoma, polyps, and IBD was 1.00, 0.98, and 0.73, respectively. We conclude that DCBE is very effective to diagnose carcinoma and polyps greater than or equal to 1 cm, the most frequent causes of bleeding, but less effective to diagnose IBD and other nonfrequent causes. If a high-quality DCBE does not reveal the cause of bleeding, the contribution of a following colonoscopy will be to diagnose causes of bleeding other than carcinoma and polyps less than 1 cm and to offer therapeutic possibilities.

Adolescent↗