Carlos A. Rubio

The Vienna classification of gastrointestinal epithelial neoplasia

BACKGROUND Use of the conventional Western and Japanese classification systems of gastrointestinal epithelial neoplasia results in large differences among pathologists in the diagnosis of oesophageal, gastric, and colorectal neoplastic lesions. AIM To develop common worldwide terminology for gastrointestinal epithelial neoplasia. METHODS Thirty one pathologists from 12 countries reviewed 35 gastric, 20 colorectal, and 21 oesophageal biopsy and resection specimens. The extent of diagnostic agreement between those with Western and Japanese viewpoints was assessed by kappa statistics. The pathologists met in Vienna to discuss the results and to develop a new consensus terminology. RESULTS The large differences between the conventional Western and Japanese diagnoses were confirmed (percentage of specimens for which there was agreement and kappa values: 37% and 0.16 for gastric; 45% and 0.27 for colorectal; and 14% and 0.01 for oesophageal lesions). There was much better agreement among pathologists (71% and 0.55 for gastric; 65% and 0.47 for colorectal; and 62% and 0.31 for oesophageal lesions) when the original assessments of the specimens were regrouped into the categories of the proposed Vienna classification of gastrointestinal epithelial neoplasia: (1) negative for neoplasia/dysplasia, (2) indefinite for neoplasia/dysplasia, (3) non-invasive low grade neoplasia (low grade adenoma/dysplasia), (4) non-invasive high grade neoplasia (high grade adenoma/dysplasia, non-invasive carcinoma and suspicion of invasive carcinoma), and (5) invasive neoplasia (intramucosal carcinoma, submucosal carcinoma or beyond). CONCLUSION The differences between Western and Japanese pathologists in the diagnostic classification of gastrointestinal epithelial neoplastic lesions can be resolved largely by adopting the proposed terminology, which is based on cytological and architectural severity and invasion status.

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.

SCENIC International Consensus Statement on Surveillance and Management of Dysplasia in Inflammatory Bowel Disease

Patients with ulcerative colitis or Crohn’s colitis have an increased risk of colorectal cancer (CRC). Most cases are believed to arise from dysplasia, and surveillance colonoscopy therefore is recommended to detect dysplasia. Detection of dysplasia traditionally has relied on both examination of the mucosa with targeted biopsies of visible lesions and extensive random biopsies to identify invisible dysplasia. Current U.S. guidelines recommend obtaining at least 32 random biopsy specimens from all segments of the colon as the foundation of endoscopic surveillance. However, much of the evidence that provides a basis for these recommendations is from older literature, when most dysplasia was diagnosed on random biopsies of colon mucosa. With the advent of video endoscopy and newer endoscopic technologies, investigators now report that most dysplasia discovered in patients with inflammatory bowel disease (IBD) is visible. Such a paradigm shift may have important implications for the surveillance and management of dysplasia. The evolving evidence regarding newer endoscopic methods to detect dysplasia has resulted in variation among guideline recommendations from organizations around the world. We therefore sought to develop unifying consensus recommendations addressing 2 issues: (1) How should surveillance colonoscopy for detection of dysplasia be performed? (2) How should dysplasia identified at colonoscopy be managed?

INVESTIGATION ON TUMOUR SPREAD IN CONNECTION WITH ASPIRATION BIOPSY

(1971). Investigation on Tumour Spread in Connection with Aspiration Biopsy. Acta Radiologica: Therapy, Physics, Biology: Vol. 10, No. 4, pp. 385-398.

Low-grade dysplasia in extensive, long-standing inflammatory bowel disease: a follow-up study.

AbstractPURPOSE: Extensive, long-standing inflammatory bowel disease is associated with an increased risk of developing colorectal carcinoma. Low-grade dysplasia has been used as a marker for malignant transformation and by some as an indication for prophylactic colectomy. The aim of the present study was to follow up all inflammatory bowel disease patients with extensive, long-standing colitis who had low-grade dysplasia in flat colonic mucosa. METHODS: All patients with low-grade dysplasia in flat mucosa found at screening or at surveillance colonoscopy with at least one follow-up colonoscopy or with colectomy were included. RESULTS: Sixty patients (40 males; mean age at diagnosis, 24 ± 12 (range, 3–59) years) were found and followed up for a mean of 10 ± 6 (range, 1–22) years. Mean time from onset of disease to discovery of low-grade dysplasia was 17 ± 11 (range, 1–55) years. Low-grade dysplasia was present in more than 1 biopsy in 37 (62 percent) of 60 patients at the index colonoscopy. Low-grade dysplasia was again detected in 1.8 (1–6) subsequent colonoscopies in 44 (73 percent) of 60 patients. High-grade dysplasia was found in 2 of 11 patients with dysplasia-associated lesion or mass at follow-up. Thirteen patients were subjected to colectomy (7 for dysplasia, 6 for therapy failure). Dysplasia was confirmed in five of these patients. CONCLUSION: Although low-grade dysplasia occurred at several colonic levels and at repeated colonoscopies in 73 percent of the patients, no progression to high-grade dysplasia was found during 10 years of follow-up, except in 2 cases with dysplasia-associated lesion or mass. Colectomy in cases with single or repeated low-grade dysplasia in flat mucosa does not appear to be justified.

Adenoma prevalence and cancer risk in familial non-polyposis colorectal cancer

Background and aims: Polypectomy in the colon has been shown to prevent colorectal cancer in both the general population and in familial colorectal cancer. Individuals with a family history of colorectal cancer have an increased risk of the disease. Over a period of 10 years, 304 subjects at risk were included in ongoing surveillance with regular colonoscopies. To compile the medical findings and experience generated during this period, a retrospective cross sectional study was performed. Subjects: Subjects were classified into three family groups: families with hereditary non-polyposis colorectal cancer (HNPCC); families with hereditary colorectal cancer (HCC, non-Lynch syndrome); and a third group of families with only empirical risk estimates based on a family history of two close relatives (TCR) with colorectal cancer. Methods: The risk population was studied with regard to age at onset, prevalence, number, cancer risk, size, dysplasia, and distribution of adenomas. A comparison was made within the family groups and with a reference group representing the general population. Results: In total, 195 adenomas and six cancers were detected among 85 individuals. The relative risk of having an adenoma in the whole risk population compared with the general population was 2.6. Subjects from TCR families had most adenomas and HNPCC subjects had the least. A shift from proximal adenomas to distal carcinomas in families with HCC and TCR suggested a higher cancer risk in distal adenomas in these syndromes. HNPCC families showed a younger age at onset and adenomas with a higher degree of dysplasia. In HNPCC, there was a similar localisation of adenomas and carcinomas, suggesting a high risk of cancer in all adenomas. Conclusions: There was clear overrepresentation of adenomas in all three family types compared with the reference population. In HNPCC, we found earlier onset of adenomas and faster progression to cancer. Families with HCC, and even more so TCR subjects, had a later onset and lower risk of cancer from proximal adenomas. Based on these results, surveillance protocols in Sweden have been revised.

SCENIC international consensus statement on surveillance and management of dysplasia in inflammatory bowel disease.

Section of Digestive Diseases, Yale School of Medicine, New Haven, Connecticut; Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut; Veterans Affairs Palo Alto Healthcare System and Stanford University School of Medicine (affiliate), Palo Alto, California; Division of Gastroenterology, McGill University, Montreal, Quebec, Canada; University of California at San Francisco, Veterans Affairs Medical Center, San Francisco, California; University of Leeds, Leeds, United Kingdom

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.

Genomic and genetic alterations influence the progression of gastric cancer

Gastric cancer is one of the leading causes of cancer-related deaths worldwide, although the incidence has gradually decreased in many Western countries. Two main gastric cancer histotypes, intestinal and diffuse, are recognised. Although most of the described genetic alterations have been observed in both types, different genetic pathways have been hypothesized. Genetic and epigenetic events, including 1q loss of heterozygosity (LOH), microsatellite instability and hypermethylation, have mostly been reported in intestinal-type gastric carcinoma and its precursor lesions, whereas 17p LOH, mutation or loss of E-cadherin are more often implicated in the development of diffuse-type gastric cancer. In this review, we summarize the sometimes contradictory findings regarding those markers which influence the progression of gastric adenocarcinoma.

Microsatellite Instability and hMLH1 and hMSH2 expression analysis in familial and sporadic colorectal cancer.

Immunohistochemical expression analysis of mismatch repair gene products has been suggested for the prediction of hereditary nonpolyposis colorectal cancer (HNPCC) carrier status in cancer families and the selection of microsatellite instability (MSI)-positive tumors in sporadic colorectal cancer. In this study, we aimed to evaluate hMSH2 and hMLH1 immunohistochemistry in familial and sporadic colorectal cancer. We found that immunohistochemistry allowed us to identify patients with germline mutations in hMSH2 and many cases with germline mutations in hMLH1. However, some missense and truncating mutations may be missed. In addition, hMLH1 promoter methylation, commonly occurring in familial and sporadic MSI-positive colorectal cancer, can complicate the interpretation of immunohistochemical expression analyses. Our results suggest that immunohistochemistry cannot replace testing for MSI to predict HNPCC carrier status or identify MSI-positive sporadic colorectal cancer.