Elastic scattering spectroscopy for the diagnosis of colonic lesions: initial results of a novel optical biopsy technique

BACKGROUND: Biopsy and polypectomy frequently are performed for lesions that carry a low risk of malignant transformation in the colon. Elastic scattering spectroscopy (ESS) is a novel optical biopsy technique that can distinguish, almost instantaneously, between normal and abnormal tissue in vivo, without the need to remove tissue. We assessed the diagnostic potential of ESS in the colon to differentiate normal colonic mucosa, chronic colitis, hyperplastic polyps, adenomatous polyps (with dysplasia), and adenocarcinoma. METHODS: ESS spectra were obtained from 138 sites in 45 patients at colonoscopy. They were then compared with conventional biopsy specimens taken from the same site, including normal colonic mucosa, hyperplastic polyps, adenomatous polyps, chronic colitis, and colon cancer. Spectral analysis was carried out with a validated computerized model that used principal component analysis followed by linear discriminant analysis. Cross validation was carried out by using 60% of the data as a "training set" and the remaining 40% of the data as a "test set." RESULTS: A total of 483 spectra were analyzed (290 normal, 19 hyperplastic, 69 adenomatous polyps, 74 chronic colitis, and 31 colorectal cancer). The sensitivity and the specificity of differentiating adenomas from hyperplastic polyps was 84% and 84%, respectively; for cancer from adenomatous polyps, 80% and 75%, respectively; for colitis from normal tissue, 77% and 82%, respectively; and for dysplastic mucosa (from polyps) from colitis, 85% and 88%, respectively. CONCLUSIONS: ESS holds promise for differentiating colonic lesions with good accuracy and, therefore, is a potentially useful tool to make an instantaneous diagnosis during colonoscopy. It could prove a valuable aid for targeting biopsies in dysplasia surveillance in inflammatory bowel disease and for deciding which small polyps should be removed.     

Differences in laser-induced autofluorescence between adenomatous and hyperplastic polyps and normal colonic mucosa by confocal microscopy

Laser-induced autofluorescence has been used to discriminate normal from adenomatous colonic mucosa. However, few studies to date have studied the origin of colonic autofluorescence. Using confocal microscopy (excitation wavelength 488 nm), we have shown that autofluorescence at this wavelength is present predominantly in the lamina propria of normal mucosa but in the epithelium in adenomatous and hyperplastic polyps. The intensity ratio of epithelial cell to lamina propria fluorescence was significantly lower (P<0.0001) in normal mucosa (0.52±0.01) compared with either adenomatous (1.6±0.2) or hyperplastic polyps (1.7±0.15). However, the ratios were not significantly different between hyperplastic and adenomatous polyps. Thus, confocal microscopy enables the detection of the sites of autofluorescence within colonic mucosa and the quantitation of differences in fluorescence between different tissue types.     

Histogenesis of human colorectal adenomas and hyperplastic polyps: the role of cell proliferation and crypt fission.

BACKGROUND: The histogenesis of human colorectal hyperplastic polyps and colorectal adenomas is poorly understood even now. METHOD: Human colorectal adenomas, hyperplastic polyps, and normal colorectal mucosae (patients with familial adenomatous polyposis and hereditary non-polyposis colorectal carcinoma were excluded) were obtained during colonoscopy and microdissected into individual crypts. Morphology, cell proliferation characteristics, and fission indices of crypts isolated from these lesions were then studied. RESULTS: Crypts isolated from colorectal adenomas and colorectal hyperplastic polyps were significantly larger (p<0.001) than crypts from normal colorectal mucosae. Crypt fission was an uncommon event in normal colonic mucosae but common in crypts isolated from adenomas and hyperplastic polyps (p<0.001). Analysis of the distribution of mitoses suggested an upward expansion of the proliferation compartment in adenomas to the surface of the crypt with no reversal of proliferating cell distribution, as has previously been described. CONCLUSIONS: Sporadic human colorectal adenomas and hyperplastic polyps grow by the process of crypt fission. Expansion of the proliferative compartment was demonstrated in crypts from adenomas, consistent with deregulation of cell cycle control.     

Differential activation of ornithine decarboxylase and tyrosine kinase in the rectal mucosa of patients with hyperplastic and adenomatous polyps

Hyperplastic polyps are considered to be benign colonic lesions with almost no potential for malignant transformation. Recent reports have shown an increased association of hyperplastic polyps with adenomatous polyps and have advocated a full colonoscopy in patients who harbor hyperplastic polyps. Hyperproliferative mucosa is known to be associated with adenomatous polyps, but its relationship to hyperplastic polyps is unknown. In the present pilot study, it is determined whether a change in mucosal proliferative patterns is observed in patients who harbor only hyperplastic polyps or a history of hyperplastic polyps relative to those who harbor both hyperplastic polyps and adenomatous polyps by measuring ornithine decarboxylase and tyrosine kinase activity in macroscopically normal rectal mucosa. Fifteen patients had either adenomatous polyps proximally or harbored adenomatous polyps and hyperplastic polyps. Seven patients had hyperplastic polyps and 15 patients had a prior history of hyperplastic polyps with no polyps found during the current examination. The ornithine decarboxylase activity of the rectal mucosa with proximal adenomatous polyps or both polyp types was significantly higher than that of hyperplastic polyps, the history of hyperplastic polyps, or controls, and values for hyperplastic polyps and the history of hyperplastic polyps were similar to controls. On the other hand, tyrosine kinase activity in the rectal mucosa of patients with both or either polyp type was elevated without any significant difference between hyperplastic and adenomatous polyps. Thus, it is concluded that although increased ornithine decarboxylase activity in rectal mucosa suggests the presence of adenomatous polyps or a combination of adenomatous with hyperplastic polyps, increased tyrosine kinase activity suggests the presence of any type of polyp.     

Criteria for the diagnosis of dysplasia by endoscopic optical coherence tomography

BACKGROUND: Endoscopic optical coherence tomography provides images of the GI mucosa and submucosa in microscopic detail. It is unknown whether endoscopic optical coherence tomography can reliably detect dysplasia. Colon polyps were used as a model to determine whether dysplasia in GI tissue has characteristic optical coherence tomography imaging features. METHODS: Endoscopic optical coherence tomography images of colon polyps and normal colon tissue were obtained at colonoscopy. In real time, endoscopists compared tissue organization and light scattering for polyps and normal mucosa with endoscopic optical coherence tomography. Imaged polyps were removed and evaluated histopathologically. Organization and light scattering, as assessed by endoscopic optical coherence tomography at colonoscopy, were compared for adenomas versus hyperplastic polyps. A computer program also quantified and compared the degree of light scattering for hyperplastic polyps and adenomas. RESULTS: A total of 44 polyps were imaged in 24 patients (30 adenomas, 14 hyperplastic polyps). Endoscopic optical coherence tomography images of adenomas had significantly less structure (p = 0.0005) and scattered light to a lesser degree than hyperplastic polyps (p = 0.0007). Hyperplastic polyps were significantly closer in organization (p = 0.0003) and light scattering (p = 0.0006) to normal mucosa as compared with adenomas. By digital image analysis, the light-scattering property of hyperplastic polyps was closer to normal mucosa compared with adenomas (14.86 vs. 45.81; p = 0.0001). CONCLUSIONS: Real-time endoscopic optical coherence tomography imaging differentiated adenomas, hyperplastic polyps, and normal colon tissue. By using the colon adenoma as a model, the endoscopic optical coherence tomography characteristics of dysplasia are loss of tissue organization and reduced light scattering.     

Laser-induced fluorescence spectroscopy of human colonic mucosa. Detection of adenomatous transformation

To evaluate the potential of laser-induced fluorescence spectroscopy for the detection of premalignant lesions of the gastrointestinal tract, the hypothesis that adenomatous transformation of colonic mucosa results in an alteration of laser-induced fluorescence that enables its differentiation from normal or hyperplastic tissue was tested. A fiberoptic catheter coupled to a helium-cadmium laser (325 nm) and an optical multichannel analyzer were used to obtain fluorescence spectra (350-600 nm) from 35 normal colonic specimens and 35 resected adenomatous polyps. A score based on six wavelengths was derived by stepwise multivariate linear regression analysis of the spectra. The mean score (+/- SEM) was + 0.86 +/- 0.06 for normal mucosa and -0.86 +/- 0.06 for adenomatous polyps (P less than 0.001). Spectra from an additional 34 normal specimens, 16 adenomatous polyps, and 16 hyperplastic polyps were prospectively classified with accuracies of 100%, 100%, and 94%, respectively. The mean score for hyperplastic polyps was significantly different from adenomatous (P less than 0.001) but not from normal tissue. Thus, quantitative analysis of fluorescence spectra enables the detection of adenomatous transformation in colonic mucosa.     

Mutations in c-K-ras 2 gene codon 12 during colorectal tumorigenesis in familial adenomatous polyposis.

Colorectal carcinomas may be induced from adenomas, or they may occur de novo. To clarify the histogenesis of colorectal carcinomas, point mutations in codon 12 of the c-K-ras 2 gene in neoplasias of familial adenomatous polyposis patients were examined. Nineteen colorectal advanced carcinomas, 135 adenomatous polyps, 9 hyperplastic polyps, and 27 normal colonic mucosae were obtained from 48 patients. In 27 normal mucosae and 9 hyperplastic polyps, a mutation in the K-ras gene was not detected. Mutations were detected as follows: 0 of 24 in adenomas with mild atypia, 10 of 77 in adenomas with moderate atypia, and 24 of 34 in adenomas with severe atypia. The incidence of mutations in c-K-ras 2 codon 12 is correlated with the degree of atypia of adenomas. However, only 5 such mutations were detected in 19 advanced carcinomas, indicating that the mutation frequency in advanced carcinomas is much lower than that in adenomas with severe atypia. If a mutation of c-K-ras 2 gene is an important component in the formation of adenocarcinoma, these results did not confirm the successive development from adenomas with severe atypia to advanced carcinomas as the main route for colorectal carcinogenesis in familial adenomatous polyposis patients.     

Gastric and duodenal polyps in familial polyposis coli.

Endoscopy with multiple biopsies of the upper gastrointestinal tract was repeated yearly over a two to six year period in nine patients with familial polyposis coli from three families. Adenomatous polyps, one to 20 in number and 2-8 mm in size, were detected in the antrum and the first and second duodenal portions in seven patients, while hyperplastic polyps were detected in four patients in the gastric body. In two patients adenomatous tubules were observed in the biopsies of endoscopically normal mucosa from the same area where adenomatous polyps later developed. Lymphoid polyps were detected in the antrum in three cases. Double contrast radiology correlated poorly with endoscopy in the gastric body; it allowed detection of polyps in the third duodenal portion in two more patients. These results confirm that the incidence of adenomas in the upper gastrointestinal tract in familial polyposis coli may be higher than previously suspected.     

Small colorectal polyps

The histology of small (≤0.5 cm.) colorectal polyps removed during total colonoscopy in 303 patients was reviewed to determine their clinical significance. There were 178 male patients and 125 females, with a median age of 64 years (range, 26 to 97 years). A total of 766 polyps were treated, 60 percent being adenomatous and 22 percent hyperplastic. Hyperplastic polyps were more common in the rectum (71 percent) while adenomas were more common in the colon (63 percent). Hyperplastic polyps in the colon were associated with adenomas in 75 percent of cases and hyperplastic rectal polyps were associated with proximal adenomas in 63 percent. There were six mixed hyperplastic/adenomatous polyps. Of the 458 adenomas, 449 were tubular, eight were tubulovillous, and one was villous. Moderate dysplasia was noted in 23 (5 percent) and severe dysplasia in four (0.9 percent). There were associated large adenomas in 84 patients. Small colonic polyps are usually adenomatous and should be destroyed. Biopsy may be important if no other neoplasm has been identified. Small rectal polyps are usually hyperplastic but may be associated with proximal adenomas. Because of the uncertain significance of hyperplastic polyps they should also be treated, and are a relative indication for total colonoscopy. Read at the meeting of the American Society of Colon and Rectal Surgeons, Washington, D.C., April 5 to 10, 1987.     

Diagnostic value of high-resolution micro-endoscopy for the classification of colon polyps

AIM: To study a new imaging equipment, highresolution micro-endoscopy(HRME), in the diagnosis and pathological classification of colon polyps.METHODS: We selected 114 specimens of colon polyps, 30 of which were colon polyps with known pathological types and 84 that were prospective polyp specimens; 10 normal colon mucosa specimens served as controls. We obtained images of 30 colon polyp specimens with known pathological types using HRME and analyzed the characteristics of these images to develop HRME diagnostic criteria for different pathological types of colon polyps. Based on these criteria, we performed a prospective study of 84 colon polyp specimens using HRME and compared the results with those of the pathological examination to evaluate the diagnostic value of HRME in the pathological classification of different types of colon polyps. RESULTS: In the 30 cases of known pathological type of colon polyp samples, there were 21 cases of adenomatous polyps, which comprised nine cases of tubular adenoma, seven cases of villous adenoma and five cases of mixed adenomas. The nine cases of non-adenomatous polyps included four cases of inflammatory polyps and five cases of hyperplastic polyps five. Ten cases of normal colonic mucosa were confirmed pathologically. In a prospective study of 84 cases using HRME, 23 cases were diagnosed as inflammatory polyps, 11 cases as hyperplastic polyps, 18 cases as tubular adenoma, eight cases as villous adenoma and 24 cases as mixed adenomas. After pathological examination, 24 cases were diagnosed as inflammatory polyps, 11 cases as hyperplastic polyps, 19 cases as tubular adenoma, eight cases as villous adenoma and 22 cases as mixed adenomas. Compared with the pathological examinations, the sensitivities, specificities, accuracies, and positive and negative predictive values of HRME in diagnosing inflammatory polyps(87.5%, 96.7%, 94.0%, 91.3% and 95.1%), hyperplastic polyps(72.7%, 95.9%, 92.9%, 72.7% and 95.9%), tubular adenomas(73.7%, 93.8%, 89.3%, 77.8% and 92.4%), villous adenomas(75.0%, 97.4%, 95.2%, 75.0% and 97.4%), and mixed adenomas(75.0%, 93.3%, 88.1%, 81.8% and 90.3%) were relatively high.CONCLUSION: HRME has a relatively high diagnostic value in the pathological classification of colon polyps. Thus, it may be an alternative to confocal microendoscopy in lower-resource or community-based settings.     

Hyperplastic polyps seen at sigmoidoscopy are markers for additional adenomas seen at colonoscopy

Asymptomatic individuals undergoing screening flexible sigmoidoscopy were prospectively studied. Polyps were found in 185 subjects. The endoscopist recorded an opinion on the polyps' histology based on endoscopic appearance. No polyps were removed at sigmoidoscopy. All subjects with rectosigmoid polyps then underwent colonoscopy and polypectomy. Of them, 99 subjects (54%) had at least one rectosigmoid adenoma, 69 (37%) had only hyperplastic polyps, and 17 (9%) had other findings. The endoscopists' opinion of the histopathology of polyps at sigmoidoscopy was correct for 61% of the lesions. Of subjects with adenomatous rectosigmoid polyps, 29% had additional adenomas at more proximal sites. Proximal adenomas were found in 28% of patients with hyperplastic rectosigmoid polyps. Patients with rectosigmoid hyperplastic polyps had the same risk for additional proximal adenomas as patients with rectosigmoid adenomatous polyps.     

Tissue CA-19.9 content in colorectal adenomas and its value in the assessment of dysplasia.

BACKGROUND: occasionally, the risk of malignant transformation may be difficult to establish in adenomatous polyps due to the fact that they contain areas with variable grades of dysplasia. A measurement of tissue tumor markers may be useful to recognize these adenomas. OBJECTIVES: the aims of this study were: to established firstly the relationship between carbohydrate antigen 19.9 (CA-19.9) content in the colorectal mucosa and the characteristics of polyps, and secondly, the diagnostic value of the formers measurement. PATIENTS AND METHODS: tissue CA-19.9 concentration was measured in 155 colorectal samples obtained from 145 patients (21 normal mucosa; 113 adenomatous polyps; 21 adenocarcinoma). Cytosol CA-19.9 content was determined by enzyme-linked immunoadsorbant assay, and the measurement of this protein was achieved by quantitative assay. Tissue samples were also processed for histological examination. RESULTS: we demonstrated that CA-19.9 levels in adenomatous polyps and adenocarcinomas were significantly higher than in the normal mucosa. These levels varied significantly according to polyp size, histological type, and grade of dysplasia. CA-19.9 contents were higher in polyps with a high risk of malignant transformation than in those with a low risk of severe dysplasia. The cut-off value 214 U/mg of protein properly differentiated both types of risk. The area under the receiver operating characteristic (ROC) curves showed that cytosol CA-19.9 levels allow classifying polyps according to their histological features. CONCLUSIONS: we concluded that the measurement of CA-19.9 content in adenomatous polyps may be useful to classify these tumors and confirm the feasibility to separate adenomas into two groups: low and high risk of malignant change.     

Gastrointestinal tissue diagnosis by laser-induced fluorescence spectroscopy at endoscopy

An endoscope-compatible, optical fiber system has been developed which can be used to obtain laser-induced fluorescence spectra of mucosal abnormalities during endoscopy in real time. The results of our previous in vitro studies have suggested that laser-induced fluorescence tissue spectra are sufficiently unique that they can be used to accurately diagnose mucosal abnormalities in some systems. To test this hypothesis in vivo, laser-induced fluorescence spectra were obtained during colonoscopy from 31 colonic adenomas, 4 hyperplastic polyps, and 32 examples of normal mucosa in 20 patients. The resulting spectra could be used to correctly differentiate adenomas from normal colonic mucosa and hyperplastic polyps in 97% of the specimens studied with the resulting sensitivity, specificity, and positive predictive value of 100%, 97%, and 94%, respectively. These results, although preliminary in nature, suggest that laser-induced fluorescence spectra can be used in the recognition and differential diagnosis of mucosal abnormalities at endoscopy.     

Fluorescence diagnostics of Helicobacter pylori-infected human gastric mucosa: establishing technique and validity

OBJECTIVE: Bacterial factors, including strain type, anatomic distribution and density, and host responses are important determinants in the pathogenesis of erosive and neoplastic changes linked to gastric Helicobacter pylori (H. pylori) infection. The purpose of this study was to investigate the potential use of photodiagnostics in mapping H. pylori infection. The relationship between fluorescence in individual gastric pits of H. pylori(+) and H. pylori(-) subjects versus that in larger field views of the gastric mucosa and the use of fluorescence to determine H. pylori status in different gastric areas were studied. MATERIAL AND METHODS: Antrum, corpus and fundus biopsies from 8 H. pylori(+) and 4 H. pylori(-) subjects taken during two gastroscopies were used for autofluorescence (535 nm excitation) and aminolevulinic acid (ALA)-induced protoporphyrin IX fluorescence (405 nm excitation) determinations. RESULTS: In the antrum, corpus and fundus a close correlation between individual pit and full-field image (FFI) fluorescence was demonstrated for H. pylori status (R>0.85; R>0.75; R>0.80) and both excitation wavelengths (R>0.89; R>0.85; R>0.95), respectively. In the antrum, FFI in H. pylori(+) subjects exceeded that in H. pylori(-) subjects using 405 nm but not 535 nm excitation regardless of ALA treatment (pcorpus>antrum for both H. pylori(+) and H. pylori(-) subjects regardless of ALA treatment (p=0.03). CONCLUSIONS: Fluorescence-based identification of areas of H. pylori-infected gastric mucosa using 405 nm excitation combined with ALA treatment is feasible and, using a ratio of 535 nm:405 nm-excited fluorescence, it is possible to distinguish H. pylori status and the different areas of the stomach even without ALA.     

Aberrant P-cadherin expression is an early event in hyperplastic and dysplastic transformation in the colon

BACKGROUND: Colorectal adenomatous and, probably, hyperplastic polyp development requires epithelial remodelling and stratification, with loss of E-cadherin expression implicated in adenoma formation. We have shown that P-cadherin, normally expressed in stratified epithelia and placenta, is aberrantly expressed in disturbed epithelial architecture associated with colitis. AIMS: (i) To investigate the role of P-cadherin in colonic polyp formation. (ii) To ascertain whether expression of P-cadherin is independent of or correlated with expression of its associated proteins--E-cadherin, beta-catenin, and gamma-catenin. (iii) To determine if P-cadherin is functional regarding catenin binding in polyps. METHODS: Expression and localisation of cadherins (E- and P-) and their associated catenins (beta- and gamma-) were determined in aberrant crypt foci (ACF), in polyps with hyperplastic morphology (hyperplastic polyps and serrated adenomas), and in adenomatous polyps by immunohistochemistry, western blotting, and mRNA in situ hybridisation. Assessment of cadherin-catenin binding was evaluated by co-immunoprecipitation. Adenomatous polyposis coli (APC) mutation was assessed in adenomatous polyps. RESULTS: P-cadherin was expressed from ACF through to hyperplastic and adenomatous polyps. Alterations in E-cadherin and catenin expression occurred later, with variant patterns in (i) ACF, (ii) hyperplastic polyps and serrated adenomas, and (iii) adenomatous polyps. P-cadherin present in adenomas was functional with regard to catenin binding, and its expression was independent of APC mutational status. CONCLUSIONS: P-cadherin is aberrantly expressed from the earliest morphologically identifiable stage of colonocyte transformation, prior to changes in E-cadherin, catenin, and APC expression/mutation. P-cadherin expression alone does not predict tissue morphology, and such expression is independent of that of associated cadherins and catenins.     

Immunohistochemical study of epithelial cell proliferation in hyperplastic polyps, adenomas, and adenocarcinomas of the large bowel

A monoclonal antibody to bromodeoxyuridine was used in tissue specimens previously incubated with bromodeoxyuridine to show S-phase cells by immunohistochemical technique. Biopsy specimens of normal mucosa (n = 10), hyperplastic polyps (n = 10), adenomas with low-grade dysplasia (n = 20), adenomas with high-grade dysplasia (n = 10), and invasive adenocarcinomas (n = 10) of the large bowel were studied. Labeling index and cell proliferative patterns were analyzed. No statistically significant difference was found in labeling index between normal mucosa and hyperplastic polyps or between adenomas with high-grade dysplasia and adenocarcinomas. The labeling index was significantly lower in normal mucosa and in hyperplastic polyps than in adenomas and adenocarcinomas (p less than 0.001). The difference in labeling index between adenomas with high-grade dysplasia and low-grade dysplasia was also statistically significant (0.01 less than p less than 0.05). In normal mucosa and in hyperplastic polyps the proliferative zone was confined to the lower two-thirds of the crypt; no kinetic activity was found in the upper portions of the crypt or in surface epithelium. In adenomas the labeled cells were either present in the upper third or scattered along the whole axis of the crypt and in the surface epithelium. Labeling patterns in invasive carcinomas were similar to those observed in adenomas with high-grade dysplasia. The difference in proliferative patterns between hyperplastic polyps and adenomas supports a different significance of the two polypoid lesions in the histogenesis of large bowel cancer; our results confirm the subsequent steps of the adenoma-carcinoma sequence. Immunohistochemical labeling patterns observed with monoclonal antibody to bromodeoxyuridine in polypoid and cancer lesions of the large bowel are similar to those described by autoradiographic studies.     

SFRP2 methylation in fecal DNA—a marker for colorectal polyps

Introduction DNA methylation of secreted frizzled-related proteins (SFRPs) can be detected in colorectal cancer (CRC) tissue, in tissue of adenomas, and in aberrant crypt foci, whereas in normal colorectal mucosa tissue, SFRP genes are unmethylated. Recently, our study group was able to demonstrate SFRP2 methylation as the most sensitive single DNA-based marker in stool for identification of CRC. The purpose of this study was to clarify whether SFRP2 methylation in fecal DNA can be found in stool of individuals with hyperplastic and adenomatous colorectal polyps. Materials and methods Patients who were diagnosed with colorectal polyps or showed negative colonoscopy were included in this study. DNA from stool samples was isolated. SFRP2 methylation was assessed by means of MethyLight. Results Stool samples from 68 individuals were checked for DNA content; 23% of the samples (6 of 26) from healthy controls, 46% of the samples (6 of 13) from patients with hyperplastic polyps, and 45% of the samples (13 of 29) from patients with adenomas were positive for human DNA. SFRP2 methylation in stool samples was found in none of the healthy controls, in 33% (2 of 6) patients with hyperplastic polyps, and in 46% (6 of 13) patients with adenomas. Statistical analysis revealed that the frequency of SFRP2 methylation increased significantly (P = 0.028) from healthy controls to patients with hyperplastic polyps and to patients with adenomas. Conclusions In the current study, we report for the first time that SFRP2 methylation in fecal DNA increases significantly from healthy controls to patients with hyperplastic polyps and to patients with adenomas. SFRP2 methylation may serve as a marker for molecular stool-based adenoma and CRC screening.     

Enzyme patterns and flow cytometric DNA measurements in colorectal hyperplastic polyps and tubular adenomas less than five millimeters

Glucose-6-phosphate dehydrogenase (G6PD) activity, lactate dehydrogenase (LD) activity, and cytometric flow measurement of nuclear size and cell cycle distributions were registered in biopsy specimens from adenomas and hyperplastic polyps less than 5 mm. The G6PD and LD activities in adenomas, 36.8 +/- 4 U/g protein and 1580 +/- 163 U/g, respectively, were significantly higher than in hyperplastic polyps, 17.9 +/- 2.6 U/g and 1080 +/- 107 U/g, or in normal mucosa, 14.7 +/- 0.8 U/g and 1174 +/- 56 U/g, respectively. G6PD activity was significantly higher in adenomas with moderate (44 +/- 5.8 U/g) than in those with mild (32 +/- 5.9 U/g) dysplasia, in contrast to LD. No difference in enzyme activity was observed between hyperplastic polyps and normal mucosa. The growth of adenomas and hyperplastic polyps was not significantly different during the 2 years of follow-up study before biopsy specimens were taken. Increased nuclear size, unrelated to grade of dysplasia, was registered in 12 of 20 adenomas, in 1 of 10 hyperplastic polyps, and in 2 of 42 specimens from normal mucosa. Adenomas and normal mucosa from individuals with adenomas showed a significantly increased number of cells in S-phase. The values were 10.2 +/- 3% and 8.8 +/- 4%, respectively. Normal control value was 6.8 +/- 2.2%. An increased number of cells in G2-phase was observed only in adenomas (6.9 +/- 2.7% compared with 4.9 +/- 1% in controls). None of the adenomas showed aneuploidy.(ABSTRACT TRUNCATED AT 250 WORDS)     

High-resolution chromoendoscopy for classifying colonic polyps: a multicenter study

BACKGROUND: Chromoendoscopy may reliably separate adenomatous from nonadenomatous polyps. The aim of this multicenter trial was to determine the accuracy of high-resolution chromoendoscopy for the determination of colonic polyp histology. METHODS: This multicenter trial included 4 academic centers and a primary care practice. In 299 patients referred for routine colonoscopy or sigmoidoscopy, 520 polyps 10 mm in size were sprayed with indigo carmine dye. Using a high-resolution endoscope, the endoscopist predicted the histology of each polyp based on its surface characteristics. Hyperplastic polyps had a "pitted" surface pattern of orderly arranged "dots" that resembled surrounding normal mucosa. Adenomatous polyps had at least one surface "groove" or "sulcus." Each polyp was subsequently resected for histopathologic evaluation. RESULTS: The resected polyps were comprised by 193 adenomas (37%), 225 hyperplastic polyps (43%), and 102 "other" types (20%). Forty polyps (7.7%) could not be classified by high resolution chromoendoscopy with indigo carmine dye. For the remaining polyps, the sensitivity, specificity, and negative predictive value of indigo carmine dye staining for adenomatous polyps were, respectively, 82%, 82%, and 88%. The results were consistent among the academic centers and the primary care practice. CONCLUSIONS: High-resolution chromoendoscopy with indigo carmine dye demonstrates morphologic detail of diminutive colorectal polyps that can reliably be used to separate adenomatous from nonadenomatous polyps.     

Background mucosal changes of primary advanced large intestinal cancer in patients without familial polyposis coli

In 337 cases of primary advanced large intestinal cancer in patients without familial polyposis coli, the risk factor for cancer was discussed chiefly from the background mucosa surrounding and apart from the cancers. The following findings were obtained: (1) in the mucosa surrounding cancers, adenoma was seen in 23 cases (6.8 per cent), adenomatous changes of the basal cells in 211 cases (62.6 per cent), and hyperplastic glands in 167 cases (49.6 per cent), (2) in the mucosa at least 10 mm from the cancers, adenoma, adenomatous changes of the basal cells, and hyperplastic glands were seen in 42 cases (12.5 per cent), 129 cases (38.3 per cent), and 40 cases (11.9 per cent), respectively. Therefore, it is suggested that microscopic adenoma and adenomatous changes of the basal cells might be a sign of premalignancy in patients without familial polyposis coli.