Clinical relevance of proliferation biomarkers and p53 expression in rectal mucosa and sporadic colonic adenomas: a prospective study

BACKGROUND/AIMS: Prospective study to evaluate 1) the pattern of proliferation biomarkers and p53 expression in rectal mucosa and adenomatous tissue, and 2) the clinical relevance of these biomarkers as predictors for adenoma recurrence. METHODOLOGY: 40 patients with sporadic adenomas underwent colonoscopic polypectomy and rectal biopsies. Assessment of proliferation biomarkers--Ornithine decarboxylase, PCNA and Ki-67--was done in adenomas and rectal mucosa, while p53 was performed in adenomas. After polypectomy, 34 adenoma patients were followed for 36 months to detect metachronous polyps. 20 controls underwent colonoscopy and rectal biopsies, with assessment of proliferation biomarkers. RESULTS: Mean values of ornithine decarboxylase, PCNA and Ki-67 in rectal mucosa from adenoma patients were not significantly different when compared with the control group. The expression of these biomarkers was significantly increased in adenomas versus rectal mucosa. Only 6 (15%) out of 40 adenomas were found to overexpress p53 protein. During follow-up, recurrent polyps were detected in 12 patients (relapsing group). Mean values of ornithine decarboxylase, detected at index colonoscopy, were not significantly higher in relapsing group versus non-relapsing group. Mean values of PCNA and Ki-67 detected in adenomas at index colonoscopy were significantly higher in relapsing group when compared with non-relapsing group. Adenoma recurrence was observed in all patients with p53 overexpression. CONCLUSIONS: Ornithine decarboxylase, PCNA and Ki-67 expression in rectal mucosa did not show clinical relevance. Yet, increased expression of PCNA or Ki-67 in adenomatous tissue may be a predictor of adenoma recurrence. Positive p53 might have the same predictive value.     

Total colonic dye-spray increases the detection of diminutive adenomas during routine colonoscopy: a randomized controlled trial

BACKGROUND: Small adenomas may be missed during colonoscopy, but chromoscopy has been reported to enhance detection. The aim of this randomized-controlled trial was to determine the effect of total colonic dye spray on adenoma detection during routine colonoscopy. METHODS: Consecutive outpatients undergoing routine colonoscopy were randomized to a dye-spray group (0.1% indigo carmine used to coat the entire colon during withdrawal from the cecum) or control group (no dye). RESULTS: Two hundred fifty-nine patients were randomized, 124 to the dye-spray and 135 to the control group; demographics, indication for colonoscopy, and quality of the preparation were similar between the groups. Extubation from the cecum took a median of 9:05 minutes (range: 2:48-24:44 min) in the dye-spray group versus 4:52 minutes (range: 1:42-15:21 min) in the control group (p < 0.0001). The proportion of patients with at least 1 adenoma and the total number of adenomas were not different between groups. However, in the dye-spray group significantly more diminutive adenomas (<5 mm) were detected proximal to the sigmoid colon (p = 0.026) and more patients were identified with 3 or more adenomas (p = 0.002). More non-neoplastic polyps were detected throughout the colon in the dye-spray group (p = 0.003). There were no complications. CONCLUSIONS: Dye-spray increases the detection of small adenomas in the proximal colon and patients with multiple adenomas, but long-term outcomes should be studied to determine the clinical value of these findings.     

Colonic Adenomas in Asymptomatic Women with a History of Breast Cancer

One hundred ninety-three asymptomatic women with a personal history of breast cancer underwent screening colonoscopy. One hundred sixty-eight women had breast cancer as their only potential risk factor for colonic neoplasia, and 25 had a family history of colorectal neoplasia in addition to their personal history of breast cancer. Among women with breast cancer, increasing age and body weight were each predictive of an increasing prevalence of colonic adenomas. The prevalence of colonic adenomas in women aged 50–75 yr whose only potential risk factor was breast cancer was 18%, and was identical to the prevalence of colonic adenomas in 186 asymptomatic average-risk control women aged 50-75 yr (odds ratio 1.0. 95% CI 0.54-1.87). We conclude that a personal history of breast cancer does not predict a higher prevalence of colonic adenomas.     

p53 protein accumulation and colonic adenoma recurrence

OBJECTIVES: The prognostic value of p53 protein accumulation in colonic adenomas is still controversial. The aim of the present study was to determine whether the evaluation of p53 protein accumulation in newly diagnosed colonic adenomas could predict the development of metachronous adenomas. DESIGN/METHODS: Fifty-five patients who underwent prior endoscopic polypectomy for colonic adenomas were colonoscopically re-evaluated at 24-38 months after index colonoscopy. In cases with more than one adenoma, the one with the greatest diameter and the most serious histology was taken into account. p53 protein expression was immunohistochemically examined using specific monoclonal antibody. RESULTS: p53 protein was detected in 41.8% of the 55 index adenomas. Recurrent adenomas were present in 21 patients (38.2%). Metachronous adenomas were present in 56.5% of patients with p53-positive index adenomas and in 25% of those with p53-negative index adenomas (odds ratio 3.90, P = 0.018). Among patients with 1 or 2 index adenomas, metachronous adenomas were found in 50% of those with p53-positive index adenomas and in 22.6% of those with p53-negative index adenomas (odds ratio 3.43, P= 0.042). Multivariate stepwise logistic regression analysis revealed that number of index adenomas per patient (1 or 2 versus > 2) and p53 expression (positive versus negative) in index adenomas contain independent prognostic information for adenoma recurrence (chi2 = 8.2, P= 0.004 and chi2 = 4.08, P = 0.04 respectively). Patients aged < 60 years developed recurrent adenomas relatively more frequently if they had a p53-positive index adenoma (P= 0.068). In the subgroup of patients aged < 60 years with 1 or 2 index adenomas, the recurrence of adenomas was more frequent in those with a p53-positive index adenoma but the difference did not reach statistical significance (P= 0.13). CONCLUSIONS: Our data suggest that p53 expression in index adenomas is associated with recurrent colonic adenomas.     

Colonoscopic follow-up of colorectal carcinoma

PURPOSE: The value of routine colonoscopy in the prevention or early detection of metachronous carcinoma of the colon and rectum remains unproven. This study attempts to clarify this issue. METHODS: An analysis of a personal series of 460 patients with primary colorectal carcinoma treated by the second author between 1972 and 1990 was reviewed. After various exclusions, there remained 231 patients who had been prospectively followed by colonoscopy with a mean follow-up period of 56 years. RESULTS: In 48 (21 percent) patients, there were synchronous adenomas present at the time of the initial resection for carcinoma and 35 (73 percent) of these patients subsequently developed metachronous adenomas, being recurrent in 22. Ninety-five (52 percent) of the 183 patients without synchronous adenomas eventually developed metachronous adenomas, so that overall 130 (56 percent) patients developed metachronous adenomas. Four patients developed a metachronous carcinoma that was either Dukes A or B, and all remain well at the time of final follow-up. These metachronous carcinomas were found after a mean interval of seven and three-quarter years. All four patients had synchronous adenomas and all developed metachronous adenomas on multiple occasions before the metachronous carcinoma was detected. Thus, a subset consisting of only 22 patients produced all four metachronous malignancies—a rate of 18 percent. CONCLUSION: It would appear that the presence of synchronous adenomas with the subsequent development of recurring metachronous adenomas is significant and warrants a more intensive follow-up program to ensure the early diagnosis and more likely cure of any metachronous carcinoma.Read at the Tripartite Colorectal Meeting, Sydney, Australia, October 17 to 20, 1993.     

Rectal aberrant crypt foci identified using high-magnification-chromoscopic colonoscopy: biomarkers for flat and depressed neoplasia

BACKGROUND: Aberrant crypt foci may represent preneoplastic lesions in the human colon. The prevalence of aberrant crypt foci detected using magnification chromoscopic colonoscopy is known to follow a stepwise progression from normal subjects to those with exophytic adenomas and colon cancer. No studies have addressed the prevalence of rectal aberrant crypt foci in patients with flat and depressed colonic lesions that cluster within the right hemi-colon and may undergo de novo neoplastic transformation. METHODS: All patients underwent total colonoscopy by a single endoscopist using the Olympus CF240Z magnifying colonoscope. Flat and depressed lesions were diagnosed using targeted indigo carmine chromoscopy. Prior to extubation, pan high-magnification-chromoscopy using indigo carmine was applied to the rectum and the distal 10 cm of mucosa examined using forward and retroflexed views. Aberrant crypt foci were defined as two or more crypts with dilated or slit-like openings that were raised above the adjacent mucosa. Using high-magnification chromoscopic colonoscopy we assessed the prevalence and dysplastic features of aberrant crypt foci in three groups: endoscopically "normal" subjects, patients with flat/depressed adenoma, and flat/depressed cancer. RESULTS: Two thousand five hundred and fifty-nine patients underwent colonoscopy of which 1,000 were eligible for inclusion. The median number of aberrant crypt foci per patient in the endoscopically normal, adenoma, and cancer group was 1 (range: 0-5), 9 (range: 0-22), and 38 (range: 14-64), respectively. The estimated relative risk of dysplastic aberrant crypt foci when comparing the flat adenoma group with the endoscopically "normal" group was 4.68 (95% CI: 2.23-9.91) with the relative risk for flat cancer versus endoscopically normal group being 21.8 (95% CI: 10.9-23.8). Patients with >5 flat adenomas had higher crypt foci densities than those with <5 adenomas (r=0.53; p<0.001). CONCLUSIONS: The number of aberrant crypt foci in normal patients, patients with flat adenoma, and flat cancer follow a stepwise incremental change as previously observed for exophytic adenomas and cancer. Detection of aberrant crypt foci in the rectum may be a useful biomarker for proximal colonic flat neoplasia and could be used at index flexible sigmoidoscopic screening to stratify risk of proximal colonic neoplasia. Patients with dysplastic aberrant crypt foci of high density should receive total colonoscopy.     

Patterns of metachronous adenoma after colorectal cancer surgery]

BACKGROUND/AIMS: After colorectal cancer surgery, colonoscopic surveillance should be done for prevention and early detection of secondary cancer. This study aimed to identify the group with high risk of developing colorectal adenoma after curative surgery of colorectal cancer. METHODS: We retrospectively investigated the medical records of the subjects of 130 patients who had been examined using colonoscopy before and after the curative surgery. RESULTS: The average age was 59.4 years. Synchronous adenomas were in 42 patients (32.3%). The occurrence rate was significantly high in men (38.8%) than women (22.0%). After the operation, the mean interval of examining colonoscopy was 11.6 months (3-24 months) and metachronous adenomas were detected in 26 patients (20.0%). The patients who have both metachronous and synchronous adenomas were observed in 13/42 (30.9%) and the patients of metachronous adenomas without synchronous adenomas were observed in 13/88 (14.8%). The occurrence rate of metachronous adenomas with synchronous adenomas was significantly high. The frequency of synchronous adenomas didn't increase with age. However, the frequency of metachronous adenomas increased with age: 0/9 (0%) under 40 years, 7/49 (14.3%) in 41-61 years and 19/72 (26.4%) over 61 years. The occurrence rate was higher in men (26.3%) than women (10.0%). CONCLUSIONS: The occurrence rate of metachronous adenomas after colorectal cancer surgery was higher in the patients with synchronous adenomas, male gender and old aged patients.     

Colorectal Cancer Location and Synchronous Adenomas

In this study, the relationship between the location of colorectal cancer and synchronous benign adenomas was assessed in 591 patients. Adenomas were found in 29.7% of all patients. Patients with cancer of the cecum, ascending colon, and hepatic flexure had the highest percentage of benign adenomas. Patients with right-sided cancer had adenomas in 47% of resected specimens, which percentage was significantly higher than that in the group of patients with left-sided cancer, who had adenomas in 22% of their specimens (p less than 0.001). Patients with cancer and synchronous adenomas were also older (70.2 vs 67.8, p less than 0.02) and more likely to be male (p less than 0.002) than patients with cancer and no adenomas. It is suggested that efforts be made to identify adenomas preoperatively in patients with colorectal cancer. In addition, since patients with cancer and associated adenomas are at increased risk of developing metachronous cancer, the group with right-sided cancer should be part of a particularly active surveillance program.     

Warm water irrigation for dealing with spasm during colonoscopy: simple,inexpensive, and effective

BACKGROUND: Colonic spasm can interfere with colonoscopy by hindering insertion of the colonoscope and by making polypectomy difficult, painful, and dangerous. Methods for dealing with colonic spasm include waiting for it to subside and administration of antispasmodic agents such as glucagon or hyoscyamine. Glucagon is expensive and hyoscyamine has side effects. This study evaluated an inexpensive technique, warm water irrigation, for overcoming colonic spasm during colonoscopy. METHODS: A prospective, randomized, controlled trial in a consecutive series of patients was conducted to compare warm water irrigation for relaxation of spasm with standard examination techniques. Patients in whom the sigmoid colon had been resected were excluded. In the test group, water from the hot water tap at approximately body temperature was instilled into the colon by means of the accessory channel of the colonoscope with a 30 mL syringe. Any irrigation, either for removal of stool or control of spasm, was performed with warm water in the test group and water at room temperature in the control group. After each colonoscopy, the level of pain experienced by the patient was recorded with a linear analog scale. RESULTS: Sixty-nine patients were randomized. The groups were similar with respect to gender distribution, age, and degree of spasm. There was no difference between groups for insertion time, total duration of colonoscopy, dose of midazolam administered, or frequency of severe spasm. Patients who had warm water irrigation had significantly less discomfort than control patients (median 2.0, interquartile range: 1-4 on a 10 point linear analog scale, vs. 4.0, interquartile range: 2-5). CONCLUSIONS: Although glucagon and hyoscyamine remain options for treatment of colonic spasm, the results of this study suggest that warm water is also effective. It has no side effects and costs practically nothing.     

Significance of a normal surveillance colonoscopy in patients with a history of adenomatous polyps

PURPOSE: The aim of this study was to determine the appropriate surveillance for patients with a history of adenomatous polyps whose last colonoscopic examination was normal. METHODS: This was a retrospective review of a database of 7,677 colonoscopies (1990 to 1996). In patients under colonoscopic surveillance, we reviewed cases of patients who had received three colonoscopies (an index (initial) colonoscopy positive for adenomas and 2 follow-up colonoscopies (interim and final)). The risk of adenomas and cancers at final follow-up colonoscopy was compared between patients having a normal interim colonoscopy and those with a positive interim colonoscopy. The risk at final colonoscopy was also stratified by time interval and the size and number of adenomas at the initial index colonoscopy. RESULTS: Two hundred four patients undergoing surveillance for adenomas met inclusion criteria. At index colonoscopy the median polyp size was 1 cm and median frequency was three polyps. At all follow-up colonoscopies, we detected 493 adenomas and one cancer (median follow-up, 55 months). At 36 months patients with a normal interim colonoscopy (n = 91) had significantly fewer polyps than patients with a positive interim colonoscopy (n = 113; 15 vs. 40 percent; P = 0.0001). By 40 months, adenomas were detected in more than 40 percent of patients in both groups. The risk after a normal interim colonoscopy was not affected by time interval or number or size of polyps. Adenomas found subsequent to a normal interim colonoscopy were dispersed throughout the colon in 28 patients and isolated to the rectosigmoid in 6 patients. CONCLUSIONS: In patients with a history of adenomas, a normal follow-up colonoscopy is associated with a statistically but not clinically significant reduction in the risk of subsequent colonic neoplasms. These patients require follow-up surveillance colonoscopy at a four-year to five-year interval.     

Detecting diminutive colorectal lesions at colonoscopy: a randomised controlled trial of pan-colonic versus targeted chromoscopy

BACKGROUND: Diminutive and flat colorectal lesions can be difficult to detect using conventional colonoscopic techniques. Previous data have suggested that pan-chromoscopy may improve detection rates. No randomised control trial has been performed examining detection rates of such lesions while controlling for extubation time and lavage effect. AIM: We conducted a randomised controlled trial of pan-colonic chromoscopic colonoscopy for the detection of diminutive and flat colorectal lesions while controlling for extubation time and lavage effect. METHODS: Consecutive patients attending for routine colonoscopy were randomised to either pan-chromoscopy using 0.5% indigo carmine (IC) or targeted chromoscopy (control group). A minimum diagnostic extubation time was set at eight minutes with controls undergoing a matched volume of saline wash. RESULTS: A total of 260 patients were randomised; 132 controls and 128 to pan-colonic chromoscopy. Extubation times did not differ significantly between the control (median 15 minutes (range 8-41)) and chromoscopy (median 17 minutes (range 8-39)) groups. The volume of IC used in the pan-chromoscopy group (median 68 ml (range 65-90)) and normal saline used in the control group (69 ml (range 60-93)) did not differ significantly. There was a statistically significant difference between the groups regarding the total number of adenomas detected (p<0.05) with significantly more diminutive (<4 mm) adenomas detected in the pan-chromoscopy group (p = 0.03). Pan-chromoscopy diagnosed more diminutive and flat lesions in the right colon compared with controls (p<0.05), with more patients with multiple adenomas (>3) detected using pan-chromoscopy (p<0.01). Hyperplastic lesions were more commonly detected in the pan-chromoscopy group compared with controls (p<0.001). More hyperplastic polyps were detected in the left colon (86% rectosigmoid) using chromoscopy compared with controls. CONCLUSION: Chromoscopy improves the total number of adenomas detected and enhances the detection of diminutive and flat lesions. Importantly, eight diminutive lesions had foci of high grade dysplasia. Chromoscopy may benefit patients, assuming a high risk of colorectal cancer, and help in risk stratification and planning follow up colonoscopy intervals.     

Metachronous colon tumors: risk factors and rationale for the surveillance colonoscopy after initial polypectomy

PURPOSE: We analyzed the possible risk factors for metachronous colon tumors after endoscopic resection of initial tumors. METHODS: Three hundred and twenty-one patients entered the surveillance study after colonoscopic resection of initial tumors between 1985 and 1999. Histology of initial tumors was adenoma in 214 patients and carcinoma in 107 patients. Solitary tumor was observed in 196 patients and multiple tumors in 125 at initial endoscopy. The median surveillance period was 39 (range, 12-112) months, and the median frequency of surveillance colonoscopy was three (range, 2-10) times. RESULTS: Metachronous neoplasms were identified in 114 of 321 surveillance cases (36%). In the 114 cases, the number of patients with metachronous adenoma was 103 (90%) and that of carcinoma was 11 (10%). Clinical characteristics at entry - including age, gender, multiplicity of polyp, histology of polyp, and site of polyp - were not different between patients with metachronous tumors and those without metachronous tumors. Kaplan-Meier analysis revealed that patients with a histology of carcinoma and those with multiple polyps at entry developed metachronous tumors significantly earlier than did patients with initial adenomas and initial solitary polyp, respectively ( P<0.001, P<0.001). However, other characteristics at entry did not produce significant differences in the rate of the development of metachronous tumors using Kaplan-Meier analysis. Proportional hazards model analysis revealed that histology of the initial tumor as carcinoma (relative risk, 1.690, 95% confidence interval, 1.118-2.555) and multiplicity (1.472, 1011-2.143) were significant risk factors for metachronous colon tumors. The 75%, 50%, and 25% metachronous tumor-free periods after initial polypectomy were 14, 21, and 39 months, respectively. CONCLUSIONS: These results may help optimizing surveillance strategies for metachronous colon tumors and raising the economic benefit of colonoscopy.     

Immunohistochemical Expression of PCNA and CD34 in Colorectal Adenomas and Carcinomas Using Specified Automated Cellular Image Analysis System: A Clinicopathologic Study

Background/Aim:

To evaluate the immunohistochemical expression of proliferating cell nuclear antigen (PCNA) and CD34 in colorectal adenomas and carcinomas, and to correlate this expression with different clinicopathologic parameters.

Materials and Methods:

The study was retrospectively designed. A total of 86 tissue samples, including 33 paraffin blocks from patients with colorectal adenomas, 33 paraffin blocks from patients with colorectal adenocarcinomas, and a control group of 20 samples of nontumerous colonic tissue, were included in the study. From each block, 3 sections of 5 ΅m thickness were taken, 1 section was stained with hematoxylin and eosin (H and E) and the other 2 sections were stained immunohistochemically for PCNA and CD34. Scoring of the immunohistochemical staining was performed using a specified automated cellular image analysis system (Digimizer).

Results:

PCNA expression was significantly increased in a sequence of normal mucosa–adenoma–carcinoma. It was significantly higher in adenomas ≥ 1 cm and those with severe dysplasia, and it showed a significant positive correlation with grade and lymph node involvement in colorectal carcinoma. CD34 showed significantly higher expression in carcinoma than adenoma and in adenoma than in the control group. CD34 expression showed a significant correlation with adenomas carrying severe dysplasia and large-sized adenomas (≥1cm). It was significantly correlated with tumor grade, lymphovascular invasion, and lymph node involvement in colorectal carcinoma.

Conclusion:

PCNA plays an important role in colorectal neoplastic progression and can be utilized as ancillary marker for the risk of malignant transformation in colorectal adenomas as it correlates with high grade dysplasia and size. Intratumoral quantification of the mean (A and N) of CD34 in colorectal carcinoma reflects the grade of tumors and can predict lymph node involvement and lymphovascular invasion, to make a useful additional prognostic factor.     

Two-Year Incidence of Colon Adenomas Developing after Tandem Colonoscopy

Objective: We attempted to determine an accurate frequency of new polyp growth in a cohort of veteran male patients who were initially cleared of polyps by tandem colonoscopy. Methods: Followup colonoscopy was performed 2 yr after tandem colonoscopy. A polyp was categorized as "new" if it was not located in a segment of the colon or rectum that had harbored a neoplastic polyp of the same histology at tandem colonoscopy, in contradistinction to lesions designated as "same-segment" polyps. Results: Fifty-eight of 90 patients who had tandem colonoscopy as a part of a previous study were available for follow-up colonoscopy for 2 yr. Ninety-one percent had a history of benign neoplastic polyps or cancer. Neoplastic polyps were documented in 52% (95% CI, 45–74%) of patients at followup, and 38% (95% CI, 26–52%) were found to have a total of 31 "new" lesions. All new lesions were tubular adenomas. The largest number of new polyps in an individual patient was four, and the largest new lesion was 20 mm in size with a flat, linear configuration. Most (25/31) new polyps were <5 mm, and the number of neoplastic polyps per patient at follow-up was less than at tandem colonoscopy. Conclusions: Approximately one-half of older, male patients with a history of neoplastic polyps will demonstrate neoplastic polyps at 2 yr. In at least one-third of patients, these appear to be new lesions. In some patients, de novo neoplastic polyps can grow to ≥1 cm within 2 yr.     

Adenomas of the large intestine after cholecystectomy

The frequency of adenomas of the large intestine in 331 cholecystectomised patients who underwent total colonoscopy was compared with that of a control group of patients with asymptomatic cholelithiasis who were matched for age and sex. Whereas no significant difference in the frequency of adenomas was found between two groups, a subgroup of patients aged 60-80 years with a postcholecystectomy interval of 10 years or greater exhibited a significantly (p less than 0.05) greater frequency of adenomas (38.5%) than matched patients with a postcholecystectomy interval of less than 10 years (21.8%) and matched controls with cholelithiasis (23.7%). This increase in the frequency of adenomas was primarily accounted for by an increase in the percentage of tubular adenomas (p less than 0.05) and corresponded to an increase in the frequency of cancer (p less than 0.05) of the large bowel.     

Birthplace is not a determinant of colorectal adenomas

AIM: To examine the impact of the patient’s birthplace on the prevalence of colonic polyps and histopathological subtypes.METHODS: This is a retrospective audit of the colonoscopy practice of one Gastroenterologist in a tertiary-referral hospital from 2008 to 2011. Data collected include demography, birthplace, language spoken, details of the colonoscopy including indications, completion rates, complications, results including prevalence and histopathology of polyps. Statistical methods used were binary logistic regression, χ² and Mann-Whitney U.RESULTS: A total of 623 patients (48% male, 67% aged over 50 years) were recruited and categorised according to birthplace: Australia/New Zealand 42%, European 20%, Asian 15%, Middle Eastern/African 11%, South American 9% and Pacific Islander 3%. The median age of the cohort was 56.3 years (range: 17-91 years), median body mass index 27.3 kg/m² (range: 16-51 kg/m²), 25% were smokers, 25% had hypercholesterolemia, 20% had diabetes mellitus 16% were on aspirin and 7% were on non-steroidal anti-inflammatory drugs. A total of 651 colonoscopies were performed for standard indications. The prevalence of polyps varied according to patient’s birthplace: Europe 45.1%, Australia and New Zealand 39.5%, Pacific Islands 33.3%, Asia 30.3%, Middle East and Africa 26.9% and South America 24.5% (P = 0.027, df = 6). However, multivariate analysis revealed that birthplace was not an independent predictor of developing polyps, including adenomas and advanced adenomas after correcting for age and male sex.CONCLUSION: Birthplace is not a predictor for developing colorectal neoplasia, including adenomas and advanced adenomas; hence, should not influence the recommendations for colorectal cancer screening.     

Does ursodeoxycholic acid change the proliferation of the colorectal mucosa?. A randomized, placebo-controlled study

BACKGROUND: In animal models ursodeoxycholic acid (UDCA) showed a chemoprotective effect against colon cancer. To explain this, a reduced proliferation of the colorectal mucosal proliferation was suggested. We, therefore, examined the influence of UDCA on the proliferation of normal colorectal mucosa in humans. METHODS: Following endoscopic polypectomy, 20 patients with colorectal adenomas were randomized to receive either UDCA (750 mg/day, n = 10, group A) or placebo (n = 10, group B) for 6 months in a double-blinded way. Colorectal biopsies were sampled before and at the end of the medication by total colonoscopy. Colorectal mucosal proliferation was measured by FACScan analysis of propidium iodine labeling. Serum was sampled, and serum bile acids were analyzed by gas chromatography. RESULTS: The proliferation rates at the end of the study were similar in both groups (median 15.4%; range 12.0-20.9 in group A; median 16.0%, 14.0-20.2 in group B, p = 0.41). Serum lithocholic acid levels at the end of the study were significantly higher in group A (1.3 micromol/l, 0.9-1.8) than in group B (0.7 micromol/l, 0-1.7, p < 0.02), whereas serum deoxycholic acid levels were similar in both groups. CONCLUSIONS: In this study, UDCA treatment for 6 months does not seem to induce changes in the proliferative behavior of the colorectal mucosa in patients with adenomas. It seems likely that a putative chemopreventive effect of UDCA in humans is not exerted by a reduction of the colorectal proliferation.     

The yield of colonoscopy in average-risk patients with non-specific colonic symptoms

OBJECTIVES: The need for full colonoscopies in average-risk patients with non-specific colonic symptoms is controversial. We aimed to evaluate: (1) the yield of full colonoscopy; (2) the prevalence of proximal neoplasia in these patients; (3) the yield if any of doing full colonoscopies to diagnose proximal lesions in patients in whom the distal colon was clear; (4) the significance of this yield with respect to age. DESIGN: This is a retrospective analysis to assess the value of open access colonoscopy. PATIENTS AND METHODS: All patients who underwent a colonoscopy in our Endoscopy Unit during January 1996 to December 1999 were assessed (n = 3357). RESULTS: We analysed 945 patients with average risk and non-specific colonic symptoms (significant risk factors excluded). The overall yield of adenomas was 5.8%. The yield of distal adenomas in patients > or= 50 years of age was 8.2% (37 out of 450) versus 0.2% in the 50 years group (one out of 495; = 0.0001). The proximal adenoma yield in > or= 50 year olds was 3.8% (17 out of 495) versus 0.2% in < 50 year olds (one out of 495) (P = 0.0001). CONCLUSIONS: In a cohort of average-risk patients with non-specific colonic symptoms attending an "open access" colonoscopy clinic, the yield for proximal adenomas is small in the < 50 years group. In patients aged < 50 years, distal colonic examination is all that is required, whereas a full colonoscopy may be justified in patients > or = 50 years old.     

Laser-induced Fluorescence Microscopy of Normal Colon and Dysplasia in Colonic Adenomas: Implications for Spectroscopic Diagnosis

Objectives : To determine what structures fluoresce and to what extent in normal colon and colonic adenomas to fully exploit laser-induced fluorescence spectroscopy as a tool for the diagnosis of dysplasia at endoscopy. Methods : Unstained frozen sections of normal colon and colonic adenomas were studied by fluorescence microscopy under 351–364-nm argon ion laser excitation. Tissue fluorescence was observed and compared to morphology in serial sections stained with hematoxylin and eosin (H&K), Movat pentachrome, mucicarmine, and oil red O. Results : In normal colon, fluorescence correlated morphologically with connective tissue fibers (principally collagen) in all layers of the bowel wall and with cytoplasmic granules within eosinophils present between the crypts in the lamina propria of the mucosa. Fluorescence of absorptive cells in normal crypts was very faint, and Goblet cells did not fluoresce. However, marked fluorescence was observed in the cytoplasm of dysplastic epithelial cells in the crypts of colonic adenomas. Fewer fluorescent connective tissue fibers were present in the lamina propria of colonic adenomas resulting in decreased fluorescence intensity as compared to that of normal colon. Fluorescent eosinophil granules were present in larger numbers in adenomas as compared with normal colon. Conclusion : Laser-induced fluorescence in normal colon and colonic adenomas correlates with morphology. Previous reported differences in laser-induced fluorescence emission spectra of normal colon and colonic adenomas obtained in vitro and in vivo may be due to differences in the cytoplasmic fluorescence between the dysplastic epithelium in colonic adenomas and normal colonic epithelium. Laser-induced fluorescence spectroscopy may be useful in studying other forms of epithelial dysplasia such as that which occurs in ulcerative colitis.     

Missed colonic adenomas in routine primary care endoscopy: a prospective tandem colonoscopy study

Colonoscopy is the gold standard in the diagnosis of colorectal neoplasia. Several lines of independent evidence, however, suggest that a significant number of small adenomas and also some advanced lesions are missed even by experienced endoscopists. With large-scale screening colonoscopy programmes installed, information on quality of colonoscopy in primary care is essential, but not available. Between July 2006 and December 2008, a total of 40 patients (23 men and 17 women, median age: 69 years) underwent a second colonoscopy within 42 days after the first endoscopy (median: 11 days), in all cases exclusively for clinical reasons. Index colonoscopy was performed by 14 endoscopists in 6 hospitals and 4 private practices. Data on all consecutive patients were collected prospectively. A total of 98 neoplastic lesions were identified in 34 patients at the index colonoscopy, an additional 53 adenomas were removed at the second colonoscopy, 33 of them smaller than 5 mm. 25 out of 53 missed adenomas were identified between the coecum and the right colonic flexure. 12 of the additional lesions were considered significant lesions (larger than 10 mm or tubulovillous adenoma), nine of these were located between the coecum and the right colonic flexure. In 24 patients repeat colonoscopy detected adenomas not described in the original report. In eight patients a total of 12 significant lesions were removed, nine of these were located between the coecum and the right colonic flexure. About one-third of adenomas were missed in 40 routine colonoscopies, most of them only small and therefore probably of little clinical significance. However, 12 significant lesions were missed in 8 patients. Adenomas in the right colon seem to be a particular problem.