Edgar Jaramillo

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.

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.

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‐βRII 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‐βRII genes mutations. Flat colorectal neoplasias were found to be of the RER+ subtype in 22% of cases, all of them exhibiting a TGF‐βRII 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. Int. J. Cancer 77:366–369, 1998.

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≥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≥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 < 1 cm and to offer therapeutic possibilities.

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.

Endoscopic detection and complete removal of a micro-invasive carcinoma present in a flat colonic adenoma☆☆☆★★★♢

lous adenoma of the duodenal papilla presenting as necrotizing pancreatitis in a patient with Gardners syndrome. Gastroenterology 1987;92:532-5. 18. Reynolds R, Lloyd DA, Sweeney JP, Stamm B, Slinger RP. Villous adenoma of the duodenum presenting as acute pancreatitis. J Clin Gastroenterol 1982;4:533-6. 19. White SH, Nazarian NA, McEwen Smith A, Balfour TW. Periampullary adenoma causing pancreatitis. Br Med J 1981;283: 527. 20. Clarke DN, Norman IN, Smith JAR, Brunt PW. Pancreatitis and duodenal obstruction due to periampullary carcinoma associated with familial polyposis coli. Postgrad Med J 1978;54: 418-20.

Non-Polypoid Adenomas of the Colon Are Associated with Subjacent Lymphoid Nodules: An Experimental Study in Rats

BACKGROUND Subjacent lymphoid nodules (SLNs) have been found in 38% of non-polypoid colonic adenomas in humans. In the present work the presence of SLNs in experimentally induced colonic adenomas was investigated in rats. METHODS 1,2-Dimethylhydrazine was injected subcutaneously in 290 Sprague-Dawley rats for 27 weeks. RESULTS An SLN was present in 28.6% of the 84 adenomas, in 8.4% of the 119 adenocarcinomas, and in 9.7% of the 31 small carcinomas without remnant adenomatous tissue. An SLN was found in 35.6% of the 59 non-polypoid neoplasias but only in 9.1% of the 175 polypoid (that is, exophytic) neoplasias. When only adenomas were considered, SLNs were present in 50.0% of the 34 non-polypoid adenomas but only in 14.0% of the 50 polypoid adenomas. CONCLUSIONS Non-polypoid colonic adenomas evolve preferentially from the minimal fraction of the colonic mucosa that overlays the few existing lymphoid nodules in rats.

Microscopie à balayage électronique vidéo-endoscopique : une nouvelle méthode d’étude de la surface de l’épithélium du tractus digestif inférieur

RésuméAu cours de l’endoscopie conventionnelle, la surface épithéliale de la muqueuse colique est difficilement examinable et devient quasi transparente, ce qui permet la visualisation d’une sous-muqueuse richement vascularisée. Des études endoscopiques antérieures avaient montré que l’examen détaillé de la muqueuse intestinale nécessite des méthodes de coloration vitale combinées à l’usage d’endoscopes à optique grossissante. Le but du présent travail est d’étudier la muqueuse du tractus digestif inférieur grâce à un système de microscopie à balayage électronique vidéo-endoscopique, utilisé en immersion. Dans de telles conditions, les villosités de l’intestin grêle s’observent sous forme de projections digitiformes. La surface épithéliale de la muqueuse rectocolique apparaît irrégulière et composée d’une trame constituée de sillons inter-connectés délimitant des territoires correspondant à desareae colonicae. La constante amélioration du pouvoir de résolution des images obtenues par vidéo-coloscopie électronique devrait contribuer à une étude endoscopique plus détaillée des muqueuses du tractus gastrointestinal.SummaryDuring conventional endoscopy the epithelial surface of the colonic mucosa is hardly seen and becomes almost translucent permitting the visualization of the rich vascularized submucosa. Previous endoscopic studies have shown that to demonstrate the detailed surface of the intestinal mucosa it is necessary to use dye spraying methods combined with high-magnification endoscopy. The aim of this work was to study the mucosa of the lower gastrointestinal tract with a high resolution electronic video colonoscope when observed through water. By using this method the intestinal villi were seen as finger-like projections. The epithelial surface of the colorectal mucosa appeared rugged and composed of a network of interconnecting furrows delimiting territories corresponding to theareae colonicae. With the permanent improvement in the image resolution of the electronic video colonoscopes it is to expect that this technique will be of value for the endoscopic study of the gastrointestinal tract.

SUBTLE VILLOUS CHANGES DETECTED AT ENDOSCOPY IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE

Dysplastic areas in flat mucosa in patients with inflammatory bowel disease (IBD) are difficult to detect at endoscopic examination. We describe the endoscopic and clinicopathological characteristics of colorectal mucosa with subtle villous changes (SVC) detected by endoscopy and chromoscopy in patients with IBD. The present study consists of 18 IBD patients. The age at onset of the disease, duration and extent of disease, endoscopic features, and clinical follow up were noted. Of the 18 patients, 12 had ulcerative colitis and six had Crohns colitis. The mean duration from onset of disease to the detection of SVC was 25.4 years (range 4–50 years). All patients had extensive colitis. All SVC areas were present in colorectal segments having absent vascular pattern and decrease or loss of normal folds. Mucosal redness was frequently observed. Following indigo carmine dye spraying the SVC were characterized by a subtle villous surface resembling small intestinal mucosa. Biopsies taken from SVC areas showed dysplasia in nine of the 18 patients (50.0%): LGD in seven and HGD in two. SVC can be identified with endoscopy and chromoscopy. The endoscopic identification of SVC areas may increase the accuracy in detecting epithelial dysplasia in biopsies from patients with IBD.

Colonoscopy findings in high-risk individuals compared to an average-risk control population

Abstract Background and aims: There is clear evidence of reduced morbidity and mortality from regular colonoscopy programs in patients with Lynch syndrome (LS). Today, also individuals with empirically increased risks of colorectal cancer (CRC) are offered colonoscopic surveillance. The aim was to compare the findings at the first screening colonoscopy in LS carriers, and individuals with an increased risk of bowel cancer due to family history of CRC with a control population. Methods: Altogether 1397 individuals with an increased risk for CRC were divided in four risk groups: one with LS carriers and three groups with individuals with different family history of CRC. The findings were compared between the different risk groups and a control group consisting of 745 individuals from a control population who took part in a population-based colonoscopy study. Results: In LS, 30% of the individuals had adenomas and 10% advanced adenomas. The corresponding figures in the other risk groups were 14–24% and 4–7%, compared with 10% and 3% in the control group. The relative risk of having adenomas and advanced adenomas was, compared to controls, significantly higher for all risk groups except the group with the lowest risk. Age was a strong predictor for adenomas and advanced adenomas in both risk individuals and controls. Conclusions: Individuals with a family history of CRC have a high prevalence and cumulative risk of adenomas and advanced adenomas, and screening is motivated also in this risk group.