[Show abstract][Hide abstract] ABSTRACT: Patients with inflammatory bowel disease may develop dysplasia in the cryptal epithelium, polypoid neoplasias, and nonpolypoid (flat) adenomas, lesions at risk to proceed to colorectal carcinoma. The onset of invasion in nonpolypoid adenomas may occur without changes in the shape or the size of the lesion. In experimental animals, some colonotropic carcinogens induce polypoid and nonpolypoid neoplasias and others induce polypoid neoplasias exclusively. Some of the biologic attributes of nonpolypoid adenomas in humans can be demonstrated in laboratory animals.
Gastrointestinal endoscopy clinics of North America. 07/2014; 24(3):455-468.
[Show abstract][Hide abstract] ABSTRACT: Gastric serrated adenoma is an apparently rare adenoma phenotype characterized by branched villi exhibiting lateral saw-tooth indentations lined with dysplastic cells. Out of the 21 gastric serrated adenomas now in record, including the case reported here, 76% (n=16) exhibited invasive carcinoma. In contrast, only 15% of the gastric tubular/villous (that is, non-serrated) adenomas reported in the literature revealed invasive growth. Although the cause for the virulent behaviour of gastric serrated adenomas remains elusive, it would appear that not only the degree of severity of the cellular dysplasia but also the serrated ornamental configurations might play a particular role in the unusual virulence of these adenomas.
Anticancer research 06/2014; 34(6):3007-3010. · 1.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Inflammatory bowel diseases (IBDs) are lifelong disorders predominantly present in developed countries. In their pathogenesis, an interaction between genetic and environmental factors is involved. This practice guide, prepared on behalf of the European Society of Pathology and the European Crohn's and Colitis Organisation, intends to provide a thorough basis for the histological evaluation of resection specimens and biopsy samples from patients with ulcerative colitis or Crohn's disease. Histopathologically, these diseases are characterised by the extent and the distribution of mucosal architectural abnormality, the cellularity of the lamina propria and the cell types present, but these features frequently overlap. If a definitive diagnosis is not possible, the term indeterminate colitis is used for resection specimens and the term inflammatory bowel disease unclassified for biopsies. Activity of disease is reflected by neutrophil granulocyte infiltration and epithelial damage. The evolution of the histological features that are useful for diagnosis is time- and disease-activity dependent: early disease and long-standing disease show different microscopic aspects. Likewise, the histopathology of childhood-onset IBD is distinctly different from adult-onset IBD. In the differential diagnosis of severe colitis refractory to immunosuppressive therapy, reactivation of latent cytomegalovirus (CMV) infection should be considered and CMV should be tested for in all patients. Finally, patients with longstanding IBD have an increased risk for the development of adenocarcinoma. Dysplasia is the universally used marker of an increased cancer risk, but inter-observer agreement is poor for the categories low-grade dysplasia and indefinite for dysplasia. A diagnosis of dysplasia should not be made by a single pathologist but needs to be confirmed by a pathologist with expertise in gastrointestinal pathology.
Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 02/2014; · 2.68 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To assess the frequency of advanced colorectal adenomas in consulting patients in Iceland.
The histological configuration of colorectal adenomas (CRA) found in 3603 patients was classified into tubular (TA), villous (VA) and serrated (SA) and the degree of neoplastic severity into low-grade dysplasia (LGD), high-grade dysplasia (HGD), carcinoma in situ (CIS), intramucosal carcinoma (IMC) and submucosal carcinoma (SMC). Advanced CRA were those showing HGD, CIS, IMC and/or SMCs. In patients with two or more adenomas, the adenoma with the highest degree of epithelial neoplasia was selected to record cases.
Between 2003 and 2006 a total of 19424 endoscopic examinations (13572 colonoscopies and 5852 sigmoidoscopies) were performed in Iceland (mean, 4856 endoscopies per year). At histology a mean of 759.3 CRA per year were found. Thus, CRA were found in 15.6% of the colorectal endoscopies performed per year. Out of the 3037 CRA studied, 67% were TA, 29% VA and the remaining 4% SA. LGD was present in 79%, HGD in 15%, CIS in 2.4%, IMC in 1.9% and SMC in 1.9%. Consequently, out of 3037 CRA investigated, 652 (21.5%) were advanced CRA; 71% of these showed HGD, 11% CIS, 9% IMC and 9% SMC. Two-thirds of the 652 advanced CRA were advanced VA, and more than three-quarters of 58 advanced CRA with SMC, were advanced VA.
Advanced VA displaying intraepithelial neoplasia (HGD and CIS) showed a propensity to evolve into invasive carcinoma. Accordingly, VA displaying HGD and CIS might be regarded as biological markers for predicting colorectal cancer risk. This is the first study in which the frequency of CRA and advanced CRA detected in consulting patients is reported on a nationwide basis.
[Show abstract][Hide abstract] ABSTRACT: The prevalence and role of human papillomavirus (HPV) in the aetiology of oesophageal squamous cell carcinoma is uncertain. Based on the presence of HPV in the oral cavity and its causal association with squamous cell carcinoma of the oropharynx, we hypothesised that HPV is more strongly associated with proximal than distal oesophageal squamous cell carcinoma.
A population-based study comparing HPV infection in relation to tumour site in patients diagnosed with oesophageal squamous cell carcinomas in the Stockholm County in 1999-2006. Multiplex polymerase chain reaction genotyping (PCR) with Luminex was conducted on pre-treatment endoscopic biopsies to identify type specify HPV. Carcinogenic activity of HPV was assessed by p16(INK4a) expression. Multivariable logistic regression was used to calculate odds ratios and 95% confidence intervals.
Among 204 patients, 20 (10%) had tumours harbouring HPV DNA, almost all (90%) of HPV high-risk type, mainly HPV16. Tumours containing HPV were not overrepresented in the upper compared to the middle or lower third of the oesophagus (odds ratio 0.6, 95% confidence interval 0.2-1.9). P16(INK4a) expression was similarly common (24% and 16%) in the HPV-positive and HPV-negative groups.
This study found a limited presence of HPV in oesophageal squamous cell carcinoma of uncertain oncogenic relevance and did not demonstrate that HPV was more strongly associated with proximal than distal tumours.
PLoS ONE 01/2012; 7(10):e46538. · 3.73 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The cellular DNA pattern in 66 colo-rectal adenocarcinomas was studied by means of flow-cytometric DNA analysis. The degree of ploidy and the proportion of cells in S-phase were related to the clinical stage according to Dukes' classification and to the histological differentiation. Multiple cell populations were found in about 60 per cent of the tumours but more frequently in advanced clinical stages. According to the DNA index the cell populations were bimodally distributed with one peak in the diploid-peridiploid region and one peak in the tri- to tetraploid region. In the second group there was a higher frequency of more advanced tumours as compared to the first. The proportion of cells in S-phase was higher in pure diploid tumour cell populations of all clinical stages as compared to normal mucosa but lower as compared to peridiploid and aneuploid cell populations with high DNA index. High as well as low S-phase values may occur in all clinical stages, but a significant higher mean value was found for Dukes' C compared to Dukes' B tumours. Distant metastases occur at all DNA indices and with various S-phase values. In conclusion, tumours of different clinical stages and histological differentiation may be subdivided according to DNA index, to the existence of single or multiple cell populations and to the proportion of cells in S-phase. The biological significance of this subdivision can only be evaluated by means of clinical follow-up.
[Show abstract][Hide abstract] ABSTRACT: To test the assumption that epithelioid granulomas found in colonoscopic biopsy specimens in patients with Crohn's colitis are markers of a different clinical behaviour.
Sections from colonoscopic biopsy specimens from 352 consecutive patients (119 children and 233 adults) were investigated.
A total of 1117 colonoscopies were performed: 293 in children (mean 2.46 per patient) and 824 in adults (mean 3.53 per patient) (p<0.05). Granulomas at initial colonoscopy were recorded in 67.2% (43/64) of children and 65.9% (27/41) of adults (p>0.6), and at subsequent colonoscopies in 53.8% (64/119) of children and 17.6% (41/233) of adults (p<0.05). Surgical intervention was required in 6.3% (4/64) of the children having previous granuloma, but also in 14.5% (8/55) of those without previous granuloma, the rate for operated adults being 26.8% (11/41) and 24.5% (47/192), respectively (p>0.6).
Granulomas in entry and/or in subsequent colonoscopic biopsy specimens in patients with Crohn's colitis did not predict the need for subsequent surgical intervention. The fact that the frequency of granulomas was significantly higher in children than in adults with Crohn's colitis (despite a higher mean number of colonoscopic biopsies in adults), and that granulomas were present in colonoscopic biopsy specimens but not in the subsequent surgical specimens from 50% of the paediatric and 36% of the adult patients strengthen the conviction that granulomas in Crohn's colitis might evolve or regress at different time intervals during the course of the disease. This behaviour would reflect a particular immunological reaction, an epiphenomenon from immature tissues-as in children-when challenged by the so far elusive aetiological agent responsible for Crohn's disease.
Journal of clinical pathology 12/2007; 60(11):1268-72. · 2.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In a population-based cohort study of all women aged over 50 years with breast cancer in the Swedish Cancer Register in 1961-2003, those diagnosed before 31 December 1987 were regarded as unexposed to tamoxifen, whereas those diagnosed after that date were considered potentially exposed. Crosslinkages within the Cancer Register and the Registers of Death and Emigration enabled follow-up. Standardised incidence ratios (SIRs) of oesophageal and gastric cancer represented relative risks. Among 138 885 cohort members contributing with 1 075 724 person-years of follow-up, we found a nonsignificantly increased risk of oesophageal adenocarcinoma during the potential tamoxifen exposure period (SIR 1.60, 95% confidence interval (CI) 0.83-3.08), but the risk estimates decreased with increasing latency interval. No association was observed during the unexposed period. No increased risk of cardia adenocarcinoma was identified in either period. The risk of non-cardia gastric adenocarcinoma was increased in the potential tamoxifen period (SIR 1.27, 1.03-1.57), and almost doubled (SIR 1.86, 95% CI 1.10-3.14) in the period of longest latency (10-14 years). The corresponding overall SIR was increased in the unexposed group also, but here SIR did not increase with longer latency intervals. An increased risk of tobacco-related tumours, that is, oesophageal squamous-cell carcinoma and lung cancer, was limited to the unexposed cohort, indicating that confounding by smoking might explain the increased SIR during the unexposed period. We concluded that there might be a link between tamoxifen and risk of non-cardia gastric adenocarcinoma.
British Journal of Cancer 08/2006; 95(1):118-22. · 5.08 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Patients with hyperplastic polyposis coli syndrome (HPCS) have a propensity to develop colorectal carcinoma (CRC).
Details were retrieved from the files of patients attending our hospital between 1988 and 2004 who fulfilled the World Health Organization criteria for HPCS.
Over a period of 16 years, 10 cases of HPCS were identified at our hospital (0.625 cases/year or one case every 1.6 years). A mean of 40.3 hyperplastic polyps per patient were found (range 6-159). Other colorectal lesions were found as follows: two patients each had one mixed polyp; there were 15 serrated adenomas in eight patients; and there were 30 tubular, tubulovillous, or villous adenomas in eight patients. Among the 10 patients with HPCS, seven developed a CRC. Of the four villous adenomas, three were associated with a CRC, but only one of the 15 serrated adenomas was associated with a CRC. The pathway of cancer evolution in HPCS patients remains unresolved.
Similarly to our results, a review of the literature indicates a high incidence of CRCs in HPCS patients. These patients are at a high risk of developing a CRC and should therefore receive regular colonoscopic surveillance.
[Show abstract][Hide abstract] ABSTRACT: Extensive intestinal metaplasia (EIM) has been reported in gastrectomies from patients dwelling in the Pacific and Atlantic basins.
To compare all the results in an attempt to explain the findings.Method: All sections from 3,421 gastrectomies were reviewed at various hospitals: 1946 in the Atlantic and 1475 in the Pacific basin. Sections with EIM showed IM encompassing one or more entire low power field (>or=5 mm in length/section) in one or more section.
In the Atlantic basin, EIM was present in 18.8% (153 of 814) of specimens with intestinal carcinoma (IC) and in 10.3% (65 of 630) of those with diffuse carcinoma (DC). In the Pacific basin, EIM was found in 62.9% (412 of 655) of gastrectomies with IC and in 33.3% (160 of 481) of those with DC. The numbers of specimens with EIM were significantly higher in the Pacific than in the Atlantic basin for both carcinoma phenotypes, particularly among elderly patients (>or=60 years).
The proportion of gastrectomies with EIM was higher among populations at a higher gastric cancer risk than in those with a lower cancer risk. EIM was mostly associated with IC rather than DC or with miscellaneous gastric diseases (841 control gastrectomies) in both basins. The proportion of gastrectomies with EIM was significantly higher in Vancouver than in New York and in Santiago de Chile than in Buenos Aires, even though these populations reside at approximately the same geographical latitude, but in different basins. Environmental factors seem to accelerate the evolution of EIM.
Journal of Clinical Pathology 12/2005; 58(12):1271-7. · 2.44 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Ciliated cells in gastrectomies from patients dwelling in the Pacific and Atlantic basins have been reported previously.
To compare all the results in an attempt to explain the findings.
Sections from 3406 gastrectomies were reviewed: 1966 and 1440 from the Atlantic and Pacific basins, respectively. Ciliated cells and intestinal metaplasia (IM) were recorded; IM was classified into focal or extensive IM. The total number of sections/gastrectomy was noted.
In the Atlantic basin, 5% of specimens had ciliated metaplasia (CM); it was more frequent in intestinal carcinoma (IC; 9%) than diffuse carcinoma (DC; 3%) or miscellaneous gastric diseases (MGD; 3%). In the Pacific basin, the frequency of specimens with CM was 29%: it was more frequent in IC (43%) than in DC (16%) or MGD (10%). The difference between the frequency of CM in specimens with IC or with DC/MGD in the Atlantic and the Pacific basins was significant (p < or = 0.05). The presence of CM was influenced by age and the extent of IM in both basins, but not by sex or the number of sections investigated.
CM-apparently an independent microscopic marker-was significantly higher in the Pacific than in the Atlantic basin. Environmental carcinogens involved in the evolution of IM and IC seem to be implicated in gastric ciliogenesis. Carcinogens that differ in nature and/or in strength in both basins might activate the latent natural genes encoding ciliated processes in gastric cells in patients subsequently developing gastric carcinoma, more notably of intestinal type.
Journal of Clinical Pathology 07/2005; 58(6):605-10. · 2.44 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: An association between mutations in a gene involved in bacterial recognition by monocytes, CARD15/NOD2 and Crohn disease (CD) has been reported in studies of adults and children. The aim of this study was to investigate the presence of CARD15 mutations in Swedish children with CD and analyze genotype-phenotype correlations.
Fifty-eight children (62% boys) with CD diagnosed between 2.8 and 16.9 years (median 10.9 years), were reviewed. Histopathology, retrospective data collection and mutational analyses for the three main mutations R702W, G908R and 1007fs were independently performed. First-degree relatives were also genotyped.
A CARD15 mutation was found in 8.6% (95% confidence interval, 2.9% to 19.0%), all of whom were heterozygotes, giving an overall allele frequency of 4.3% (95% confidence interval, 1.4-9.8). In 12%, all patients without mutations, a first-degree relative had CD. In four of five children, mutations were transferred from their healthy mothers. Granulomas at onset were found in 80% of patients with mutations and in 43% of those without (P = 0.17). No statistical association was found between mutation and phenotype regarding age at onset, anatomic location at onset or follow-up, severity of inflammation at onset, development of stenosis, perianal disease or extra intestinal manifestations.
The frequency of CARD15 mutation in this Swedish pediatric CD population is lower than reported in a mixed adult and pediatric population. The genotype-phenotype correlations were non-significant although a trend was found between the presence of mutations and granuloma formation. Healthy heterozygote mothers conveyed the mutation to their children with CD.
Journal of Pediatric Gastroenterology and Nutrition 05/2005; 40(4):456-60. · 2.20 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Fifteen years ago we detected gastric cells with glassy cytoplasm (GCs) in the human pyloric antrum. The frequency of these cells was subsequently investigated in sections from gastrectomies carried on in populations dwelling on the rim of the Atlantic and Pacific basins. In this work we compared the results obtained in these disparate geographic regions. We reviewed sections from 3203 gastrectomies (1942 in the Atlantic basin and 1261 in the Pacific basin). In the Atlantic basin 12/1942 (0.6%) of the gastrectomies had GCs, whereas in the Pacific basin 26/1261 (2.1%) of the gastrectomies had GCs. The difference was significant (p<0.05). The proportion of gastrectomies with GCs was higher in patients in Vancouver, Canada, than in New York, and higher in Santiago de Chile than in Buenos Aires, despite the fact that these populations reside at approximately the same geographic latitude. Previous studies with the same material indicated that both the extension of intestinal metaplasia and the frequency of ciliated metaplasia were significantly higher in the Pacific than in the Atlantic basin. Hence, the difference in the frequencies of GCs appears to be a new indication that dissimilar environmental exposures in the two basins might have influenced the histological make-up of the gastric mucosa.
Journal of Environmental Pathology Toxicology and Oncology 01/2005; 24(4):281-9. · 0.92 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A case of congenital bronchogenic cyst in the gastric mucosa is presented. The cyst was lined by pseudostratified epithelium and covered with ciliated cells. Congenital bronchogenic cysts should be differentiated from acquired gastric cysts lined with ciliated metaplastic cells that evolve as a result of environmental factors.
In vivo (Athens, Greece) 01/2005; 19(2):383-5. · 1.22 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Previous studies in human and in experimentally-induced colorectal carcinomas showed that the material retained in dilated glands at the growing tumour edge was directly released into the peritumoral extracellular matrix (ECM) through glandular faults called glandular pores. In this work, the characteristics of the glands at the growing edge in adenomas with submucosal invasion were investigated in 56 patients. Sections (stained with hematoxylin-eosin, and MNF 116) from 56 colonic adenomas with submucosal invasion were reviewed. Pore formation was defined as a glandular defect characterised by lack of a group of epithelial cells in the deeper portion of the glands. Numerous dilated submucosal glands with pores were found in 46 (82%) of the 56 neoplasias. Through those pores retained mucin, neutophils and/or necrotic material, containing proteolytic enzymes, were siphoned off into the surrounding tissues, causing disruption of the paratumoral ECM and facilitating host penetration by neoplastic cells. Glandular continuity seems to be restored by the proliferation of malignant cells from the tip of the free borders of the pores into the disrupted ECM. The sealing of the glandular flaws would permit the re-accumulation of intraglandular proteolytic material, a mechanism that would replicate a new wave of host invasion, thus ensuring a stepwise, but continual, tumour progression at the growing edge in untreated patients.
Anticancer research 01/2005; 25(3c):2503-7. · 1.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Colorectal adenomas from 1552 Italian patients were histologically classified into tubular (TAs), tubulo-villous (TVAs), villous (VAs), serrated (SAs) and microtubular (MTAs). The purpose was to compare the results to those in 3135 colorectal adenomas from Swedish patients. Of the 1552 adenomas, 827 (53%) were TAs, 352 (23%) TVAs, 196 (12%) VAs, 102 (7%), SAs and 14 (0.9%) MTAs. The remaining 61 (4%) were of combined phenotypes (COMBAs). The percentage of VA (considered as the most important dysplastic precursor of colorectal cancer) was higher in Florence than in Stockholm. Notably, the incidence of colorectal cancer in males was also higher in Florence (78.6/10(5)) than in Stockholm (57.2/10(5)). Notwithstanding, the highest rate of submucosal invasion (7%) was found among SAs. The diameter of the largest section was used to define the size of the largest adenoma in individual patients. Of the 1380 neoplasias measuring < or =12 mm, only 0.9% (n=13) had invasive carcinomas, but as many as 8.1% (n=14) of the 172 neoplasias measuring > or =13 mm. SAs and MTAs are special adenoma phenotypes with particular morphological and cell proliferative attributes at variance from those of TAs, VAs or TVAs. In the light of the present results, it is proposed that SAs and MTAs are included in future reports of colorectal adenomas in order to compare their frequency worldwide.
Anticancer research 01/2005; 25(2B):1353-9. · 1.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The global pattern of male predominance in gastric cancer incidence remains unexplained. We tested the hypothesis that estrogen prevents gastric cancer in a cohort of men heavily exposed to estrogen.
We conducted a nationwide cohort study of men with a diagnosis of prostate cancer recorded in the Swedish Cancer Register in 1961-2000. Because estrogen therapy was the treatment of choice for prostate cancer in Sweden between 1950 and 1980, cohort members diagnosed earlier than 1980 were considered exposed to estrogen. Standardized incidence ratios (SIR) estimated relative risk. Complete follow-up was achieved through cross-linkages within the cancer register and the Swedish nationwide registers of emigration and causes of death.
In 515,961 person-years of follow-up, we observed 304 gastric cancers as compared with 349 expected for the cohort members in the predefined "exposed" period 1961-1980, rendering a 13% decreased risk (SIR, 0.87; 95% confidence interval (95% CI), 0.78-0.98). Among patients with a latency of > or =15 years after a prostate cancer diagnosis in 1961-1980, SIR was 0.57 (95% CI, 0.30-0.97), suggesting a dose-response relation. Similarly, reduced risks were found for cardia cancer and noncardia gastric cancer. No decreased risk was found for the cohort members in 1981-2000, when estrogen treatment was less common (SIR, 0.99; 95% CI, 0.89-1.11).
Our study indicates a reduced risk of gastric cancer in a male cohort exposed to estrogen. These results support the hypothesis that estrogen may prevent gastric cancer, but additional studies are warranted.
[Show abstract][Hide abstract] ABSTRACT: A review of the literature indicated that only one case of serrated adenoma of the appendix has been recorded. The aim was to explore the possible occurrence of serrated adenomas of the appendix at the department of pathology, Karolinska Institute and University Hospital, Stockholm, Sweden.
Between January 1993 and December 2003, 38 non-carcinoid, non-neoplastic, or neoplastic polyps or tumours of the appendix were surgically removed at this hospital. All filed histological sections (haematoxylin and eosin stained) were reviewed.
Of the 38 lesions, four were hyperplastic polyps, 10 serrated adenomas, six villous adenomas, and the remaining eight mucinous adenocarcinomas without a remnant adenoma. Serrated adenomas accounted for six of the 11 adenomas without invasion, and four of the 15 adenomas with invasive carcinoma. At the time of surgical resection, four of the 10 serrated adenomas had evolved into invasive carcinomas, in addition to 11 of the 16 villous adenomas.
Serrated and villous adenomas of the appendix appear to be highly aggressive lesions, more aggressive than similar adenomas in the colon and rectum. Of the seven cases with a hyperplastic polyp, one concurred with a serrated adenoma, two with a serrated adenoma having an invasive carcinoma, and one with invasive carcinoma without a remnant adenomatous structure. At present, there is an increased awareness that some hyperplastic polyps of the colon and rectum may evolve into serrated adenomas. Whether this pathway is also valid for the appendix vermiformis should be investigated in a larger number of cases.
Journal of Clinical Pathology 10/2004; 57(9):946-9. · 2.44 Impact Factor