C A Rubio

Karolinska University Hospital, Tukholma, Stockholm, Sweden

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Publications (227)671.05 Total impact

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    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
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    ABSTRACT: The histologic examination of endoscopic biopsies or resection specimens remains a key step in the work-up of affected inflammatory bowel disease (IBD) patients and can be used for diagnosis and differential diagnosis, particularly in the differentiation of UC from CD and other non-IBD related colitides. The introduction of new treatment strategies in inflammatory bowel disease (IBD) interfering with the patients' immune system may result in mucosal healing, making the pathologists aware of the impact of treatment upon diagnostic features. The European Crohn's and Colitis Organisation (ECCO) and the European Society of Pathology (ESP) jointly elaborated a consensus to establish standards for histopathology diagnosis in IBD. The consensus endeavors to address: (i) procedures required for a proper diagnosis, (ii) features which can be used for the analysis of endoscopic biopsies, (iii) features which can be used for the analysis of surgical samples, (iv) criteria for diagnosis and differential diagnosis, and (v) special situations including those inherent to therapy. Questions that were addressed include: how many features should be present for a firm diagnosis? What is the role of histology in patient management, including search for dysplasia? Which features if any, can be used for assessment of disease activity? The statements and general recommendations of this consensus are based on the highest level of evidence available, but significant gaps remain in certain areas. © 2013 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved
    Journal of Crohn s and Colitis 01/2013; · 3.39 Impact Factor
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    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.
    Colorectal Disease 06/2012; 14(9):e595-602. · 2.08 Impact Factor
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    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
  • Acta Pathologica Microbiologica Scandinavica Series A :pathology. 01/2009;
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    C A Rubio, A Orrego, G Nesi, Y Finkel
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    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
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    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
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    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.
    Endoscopy 04/2006; 38(3):266-70. · 5.74 Impact Factor
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    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
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    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
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    C A Rubio, A Orrego, R Willén
    Journal of Clinical Pathology 04/2005; 58(3):335. · 2.44 Impact Factor
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    C A Rubio, A Orrego, R Willén
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    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
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    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
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    C A Rubio, G Nesi, L Messerini, G Zampi
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    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
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    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.
    Cancer Epidemiology Biomarkers &amp Prevention 12/2004; 13(12):2203-7. · 4.56 Impact Factor
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    C A Rubio, R Befrits
    Journal of Clinical Pathology 09/2004; 57(8):894-5. · 2.44 Impact Factor
  • C A Rubio, R Befrits
    Gastroenterology 06/2004; 126(5):1494; author reply 1494-5. · 12.82 Impact Factor
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    J Shetye, C A Rubio
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    ABSTRACT: Following weekly s.c. injections of the colonotropic carcinogen 1,2-dimethylhydrazine (DMH), we investigated the occurrence of flat and protruding neoplasias in the colon of rats at various time intervals. Forty-seven DMH-treated rats were sacrificed at the 13th, 15th, 19th, 21st and 22nd weeks. A total of 88 tumors evolved in 35 of the 47 DMH-treated rats. The number of neoplasias/animal was 0.3 at week 13, 1.2 at week 15, 2.0 at week 19, 2.5 at week 21 and 4.0 at week 22. In the right colon, although the percent of flat adenomas was lower than of protruding adenomas, the percent of flat carcinomas was significantly higher than of protruding carcinomas, indicating that flat adenomas progress more rapidly to invasive carcinoma than protruding adenomas in the right colon. The opposite was recorded in the left colon where the percent of protruding adenomas was lower than of flat adenomas, but the percent of protruding carcinomas was higher than of flat carcinomas. During the last experimental week as many as 63% of the protruding carcinomas occurred but only 25% of the flat carcinomas. These experimental results seem to substantiate previous observations in humans suggesting that, in the colonic mucosa, flat and protruding adenomas follow different pathways of neoplastic transformation.
    In vivo (Athens, Greece) 01/2004; 18(2):197-202. · 1.22 Impact Factor
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    ABSTRACT: To assess the extent of gastric intestinal metaplasia (IM) in gastrectomy specimens in populations of the Pacific basin having different incidence of gastric carcinoma. One thousand three hundred and nine-two gastrectomies were investigated: 1088 had a gastric carcinoma and 304 miscellaneous gastric diseases. Twenty-one thousand three hundred and fourteen histological sections were reviewed under low-power (4X). IM was either spotty (SIM) or extended (EIM= encompassing one or more entire low-power fields/section). Widespread IM (WIM) was regarded as EIM if present in > or =5 histological sections. The percent of gastrectomies harboring a carcinoma increased significantly with increasing age more notably in those with diffuse carcinomas (DC) than in those with intestinal carcinomas (IC). The percent of gastrectomies with EIM was significantly higher in specimens with IC than with DC, particularly among elderly patients, and in specimens from countries with a high cancer incidence. The percent of gastrectomies with WIM was higher in specimens having IC than in those having DC. Migration per se did not influence the frequency of specimens with EIM in elderly Japanese patients: Japanese migrants to Hawaii had a similarly high frequency of EIM as those dwelling in Japan. Japanese patients with a gastric carcinoma showed atypical mitoses in areas with EIM far from the tumor, suggesting that cellular mutation(s) play a role in the evolution of EIM towards gastric dysplasia and carcinoma in that ethnic group. The drawback of gastric biopsies in assessing the extent of gastric intestinal metaplasia and, thereby, estimating possible cancer risk in long-term studies has been stressed.
    Anticancer research 01/2004; 24(5B):3185-92. · 1.71 Impact Factor
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    ABSTRACT: Colorectal adenomas are recognised as precursors of colorectal carcinomas. The significance of hyperplastic (metaplastic) colorectal polyps is unknown. The relationship between hyperplastic polyps and adenomas, and the prevalence and incidence of these lesions were evaluated in individuals predisposed to familial colorectal cancer. A total of 299 individuals participating in our surveillance programme during 1990-2000 were retrospectively evaluated. Subjects were classified into three groups: hereditary non-polyposis syndrome (HNPCC) (n=108), hereditary colorectal cancer (HCRC) (n=127), and individuals with empirical risk estimates-two close relatives (TCR) (n=64). Findings from 780 colonoscopies were evaluated regarding prevalence and incidence of hyperplastic polyps and adenomas. Correlations between hyperplastic polyps and adenomas were calculated by Pearson correlation. In total, 292 hyperplastic polyps and 186 adenomas were observed in 98 and 90 individuals, respectively. A positive correlation was found between the numbers of hyperplastic polyps and adenomas (r=0.40; p<0.001). Correlations between adenomas and hyperplastic polyps were similar in the three groups. The risk of detecting new hyperplastic polyps (odds ratio 5.41) or adenomas (OR 2.56) increased significantly when there was a positive finding at first colonoscopy. Hyperplastic polyps as well as adenomas may identify individuals with a high risk of colorectal cancer. This information is important when these individuals are selected and included in tailored surveillance programmes.
    Gut 08/2003; 52(8):1140-7. · 10.73 Impact Factor

Publication Stats

2k Citations
671.05 Total Impact Points


  • 1983–2013
    • Karolinska University Hospital
      • • Department of Surgery
      • • Department of Clinical Genetics
      Tukholma, Stockholm, Sweden
  • 1980–2012
    • Karolinska Institutet
      • • Department of Oncology-Pathology
      • • Institutionen för molekylär medicin och kirurgi
      • • Gastrointestinal and Liver Pathology Research Laboratory
      • • Institutionen för medicin, Huddinge
      Solna, Stockholm, Sweden
  • 2005
    • Stockholm University
      Tukholma, Stockholm, Sweden
  • 2000–2005
    • University of Florence
      • Dipartimento di Scienze Biomediche, Sperimentali e Cliniche
      Florence, Tuscany, Italy
  • 1999–2000
    • Lund University
      • • Department of Oncology
      • • Department of Physics
      Lund, Skane, Sweden
  • 1994
    • University of Auckland
      • Department of Medicine
      Auckland, Auckland, New Zealand
  • 1983–1993
    • National Cancer Center
      • Endoscopy Division
      Edo, Tōkyō, Japan
  • 1989–1990
    • Chinese Academy of Medical Sciences
      Peping, Beijing, China
  • 1988
    • Cancer Institute and Hospital, Chinese Academy of Medical Sciences
      Peping, Beijing, China