Urodele limb and tail regeneration in early biological thought: an essay on scientific controversy and social change

Some features of digestive cancers encourage screening programs, even though no such program has been shown so far effective in reducing mortality rates. The visual inspection of the oral cavity and pharynx, with the addition of flexible endoscopy and, possibly, blue-toluidine staining, can be easily performed by specialists and dentists. The strong association with smoking habits and alcohol consumption favours the organization of screening programs but primary prevention maintains the highest priority. For cancer of the colon-rectum two different screening approaches are under close scrutiny: fecal occult blood testing, on an yearly basis, and once-in-a-life sigmoidoscopy at 55-60 years of age. Only one of five ongoing randomized prospective studies on occult blood testing has reported, so far, a significant reduction, around 33%, of mortality from colorectal cancer, with, however, a large burden of sigmoidoscopies.     

Colocare self-test versus Hemoccult II Sensa for fecal occult blood testing

OBJECTIVES: To compare the efficacy of ColoCARE Self-Test pads against Hemooccult II SENSA, a traditional guaiac-based card test, in the screening for colorectal neoplasia. METHODS: Prospective crossover analysis of 102 high-risk patients for screening of colorectal neoplasia with fecal occult blood testing, using ColoCARE Self-Test pads and Hemoccult II SENSA cards. RESULTS: Sixty-eight of the 102 patients (67%) had colorectal lesions diagnosed at colonoscopy. Of this group, 55 patients (81%) had either a polyp or cancer diagnosed at colonoscopy, with 13 of these 55 patients having polyps > or = 1 cm. ColoCARE detected 21% of all lesions, compared with 72% for Hemoccult II SENSA. ColoCARE detected only 16% of cases involving either a cancer or a polyp, and 24% of cases involving either a cancer or polyp > or = 1 cm in size. This compares with 75% and 95%, respectively, for Hemoccult II SENSA. Significantly more patients preferred ColoCARE (84%) to Hemoccult II SENSA (5%) (p < 0.00001), and patients found it easier to use ColoCARE (p < 0.01). However, 33% of patients did not feel comfortable interpreting the ColoCARE results, and 29% found it difficult to interpret the color change. CONCLUSION: These results indicate that patients may prefer the simplicity and convenience of ColoCARE; however, the test is not sensitive for the detection of colorectal neoplasia. Furthermore, patients do not feel comfortable interpreting ColoCARE results and prefer to have fecal occult blood testing interpreted by medical personnel.     

Detection of protein p53 in the stool of patients with colorectal cancer

BACKGROUND AND AIMS: Mutations of TP53, a tumor suppressor gene, are found in 60% to 70% of colorectal cancers. These mutations usually induce an overexpression caused by modification of the p53 protein conformation. The aim of this study was to investigate whether stool specimens of patients with colorectal cancer contain increased amounts of p53 protein. METHODS: p53 protein was measured using a sandwich enzyme immunoassay in the stool specimens of 52 patients: 25 with colorectal cancer, 4 with colorectal adenomas and 23 apparently free of gastrointestinal disease. Results were expressed as pg/mg of total protein. The presence of fecal occult-blood was searched using Hemoccult II and Hemolex (an immunochemical assay for human hemoglobin). RESULTS: Median concentrations of stool p53 protein were 16.6 pg/mg (range: 0-591 pg/mg) in patients with colorectal cancers, 39.1 pg/mg (range: 5-72 pg/mg) in patients with adenomas and 5.9 pg/mg (range: 0-65 pg/mg) in control subjects. Resection of colorectal cancers caused a marked decrease of stool p53 protein concentrations. When the cut-off value for stool p53 protein was set at 60 pg/mg of fecal protein (concentrations over the 95th percentile), the positivity of the assay was independent of tumor size and Astler-Coller stage, but weakly associated with rectal location of cancer. The sensitivity of stool p53 protein for colorectal cancer was 44%, and the specificity was 96%. In contrast, the sensitivity of Hemoccult II and Hemolex tests was 48% and 44%, whereas their specificity was 91% and 96%, respectively. CONCLUSION: The detection of p53 protein is achievable in stool, but this assay is not more efficient than fecal occult blood tests for detection of colorectal cancer.     

Detection of decay-accelerating factor in stool specimens of patients with colorectal cancer

BACKGROUND & AIMS: Colorectal cancers have an increased expression of decay-accelerating factor (DAF). The aim of this study was to determine whether stool specimens of patients with colorectal cancer contain increased amounts of DAF. METHODS: DAF was measured using an immunoassay in the stool specimens of 40 persons with colorectal cancer, 18 with colorectal adenomatous polyps, 13 with upper gastrointestinal cancer, and 41 without gastrointestinal disease. RESULTS: Stool DAF concentrations in patients with colorectal cancer (0-9.8 ng/g stool; median, 1.6 ng/g) were significantly higher than those in patients with adenoma (0-6.4 ng/g; median, 0 ng/g) (P < 0.05), patients with upper gastrointestinal cancer (0-3.1 ng/g; median, 0 ng/g) (P < 0.05), and subjects without gastrointestinal disease (0-3.4 ng/g; median, 0 ng/g) (P < 0.01). Resection of colorectal cancers caused a marked decrease in stool DAF concentrations. The stool DAF test was positive in a substantial portion of patients with colorectal cancer whose tumors were small ( < 2 cm), at an early TNM stage, or unassociated with fecal occult blood positivity. The sensitivity of the test for colorectal cancer was 55%, and the specificity was 85%. CONCLUSIONS: The measurement of stood DAF deserves evaluation as a test for detection of colorectal cancer.     

Five-year follow-up of asymptomatic patients with negative fecal occult blood test results in whom clinically significant colorectal pathology was detected

OBJECTIVES: To determine from a 5-yr longitudinal study (a) rate of compliance with follow-up, (b) number of new clinically significant colorectal lesions discovered by sigmoidoscopy or colonoscopy at later examination, (c) number and causes of deaths, and (d) rate of diagnosis of new cancers among 36 asymptomatic patients with negative fecal occult blood tests in whom clinically significant colorectal lesions were found initially by 60-cm flexible sigmoidoscope. METHODS: For the 36 patients, medical records were reviewed throughout the 5-yr study period. These records included pathology reports, results from 60-cm sigmoidoscopy and colonoscopy examinations, and notations from visits to health facilities for reasons other than colorectal examinations. RESULTS: Seventy-one clinically significant lesions were removed during the 5-yr period; 58 were discovered by sigmoidoscopy and 13 by colonoscopy. Also, during the 5-yr period, noncolorectal cancer was diagnosed in six patients, and two patients died of cardiac disease. CONCLUSIONS: Patients who have clinically significant colorectal pathology found by 60-cm sigmoidoscope have a high prevalence of lesions beyond the view of this instrument. Therefore, colonoscopy should be performed when sigmoidoscopy shows clinically significant pathology. Because subsequent examinations show a high incidence of new lesions, rescreening is indicated.     

Screening for colorectal cancer

Second only to lung cancer in mortality, colon cancer is amenable to cure if detected early. Because fecal occult blood testing and flexible sigmoidoscopy are effective individually but have limitations, both are now recommended for screening. However, after successful polyp removal, surveillance colonoscopy does not need to be performed as often as previously thought.     

Evaluation of various screening and surveillance methods in colorectal carcinoma

Colorectal cancer is a common disease which is almost wholly preventable by early removal of adenomatous polyps. Screening should be offered to all persons without risk factors from the age of 50. Selection of the appropriate screening programme should take into account personal preference, local expertise and insurance coverage. Endoscopic screening and surveillance investigations should be strongly encouraged in all persons wit risk factors such as (1) previous treatment of colorectal adenomatous polyps or cancers, (2) ulcerative colitis, (3) patients with hereditary colorectal cancer syndromes and (4) first degree relatives of patients with colorectal cancer. The following four strategies are available for candidates > 50 years without risk factors: (1) faecal occult blood testing (annually), (2) flexible sigmoidoscopy (every 5 years), (3) a combination of both (1 + 2) strategies and (4) coloscopy (every 10 years). Coloscopy should be performed after a positive test result in strategy programs 1-3. Results from prospective randomized trials are available only for faecal occult blood testing, showing an approximately 15% reduction of mortality in the screening group. The potential for reduction of colorectal cancer mortality has been estimated at 30-70% and 60-90% for flexible sigmoidoscopy and coloscopy respectively. However, no results from prospective randomized trials are presently available. Cost-effectiveness analysis has not shown relevant differences between the four different screening strategies.     

Flat cancers do develop in the polyp-free large intestine

PURPOSE AND BACKGROUND: Qualitative and quantitative analysis of many flat early cancers that have been discovered during the last decade led us to recognize that a flat route of cancer development de novo is as important a route as the polypoid one. We aim to prove through a longitudinal study that these flat early cancers indeed develop in flat mucosa and not in an adenomatous polyp. METHODS: From January 1, 1990, to July 31, 1994, 554 patients underwent at least two colonoscopies. These patients consisted of 364 males, and average age was 59 years. We searched for flat early cancers developing in polyp-free colorectal mucosa on or after a second colonoscopy. Polyp-free mucosa here means an intestinal segment proved to possess no adenomatous polyp during the preceding colonoscopies, irrespective of the presence of polyps elsewhere. RESULTS: Four flat early cancers were found developing in polyp-free colonic mucosa in four patients. Average age of the patients was 67 years. Locations of the cancers were the transverse (3) and descending colons (1). The shapes were all depressed, and average size of the lesions was 11 mm. Two lesions were endoscopically resected, and two by surgery. CONCLUSION: These four depressed cancers developing in polyp-free mucosa show that flat early colorectal cancers do arise de novo and not from an adenomatous polyp having collapsed on itself.     

Reduction in risk of mortality from colorectal cancer by fecal occult blood screening with immunochemical hemagglutination test. A case-control study

Fecal occult blood testing by immunochemical hemagglutination has been shown to be superior to the Hemoccult test, both in sensitivity and in specificity. The test has been widely used as a tool for population screening in Japan, but there has been no study to evaluate the efficacy of screening using this test. A case-control study to evaluate the screening was conducted in study areas where no previous and no other concomitant colorectal cancer screening had been performed. Case series in the study were 193 cases who died of colorectal cancer. Three controls were selected randomly from the list of individuals who were alive at the time of diagnosis of the corresponding case and had been living in the same area as the case, matched by gender and by age. Odds ratios (OR) of dying of colorectal cancer for those screened within 1, 2 and 3 years of case diagnosis vs. those not screened were 0.40 [95% confidence interval (CI) 0.17-0.92], 0.41 (95% CI 0.20-0.82), and 0.48 (95% CI 0.25-0.92), respectively. OR increased towards 1.0 as the duration during which screening histories were compared was extended, and showed similar tendencies when analyzed by number of years since the most recent screening history. These results suggest that colorectal cancer screening by the immunochemical fecal occult blood test would reduce mortality from colorectal cancer.     

The outcomes utility index: will outcomes data tell us what we want to know?

BACKGROUND: Screening for occult blood by means of guaiac tests has an unsatisfactory sensitivity for the detection of colorectal neoplasms. To increase sensitivity and specificity the immunological determination of human hemoglobin and albumin in feces has been developed. The validity of analyzing only two samples from one bowel movement of either test is not known. METHODS: An immunological determination of human fecal hemoglobin and albumin using luminescence immunoassays (LIA) was performed in 739 patients with gastrointestinal complaints before scheduled colonoscopy. Each patient collected two 1 ml samples from one stool. There were no dietary restrictions. RESULTS: The sensitivity for detecting colorectal carcinomas was 95.3% (95% confidence interval 84.2-99.4%) with hemoglobin and 67.4% (95% confidence interval 51.2-80.9%) with albumin. The sensitivity for detecting large adenomatous polyps was 62.9% (95% confidence interval 50.5-74.1%) with hemoglobin and 32.9% (95% confidence interval 22.1-45.1%) with albumin. The specificity was 97% for hemoglobin, 96% for albumin and 94% for the combined test. CONCLUSIONS: The immunological determination of fecal hemoglobin is superior to albumin and has a better sensitivity for the detection of colorectal neoplasms than that reported for guaiac tests, even if two samples from one bowel movement are examined. The immunological determination of fecal hemoglobin should therefore be evaluated for use in colorectal cancer screening.     

Colorectal cancer: future population screening for early colorectal cancer

Colorectal cancer (CRC) is one of the most frequent cancers in Western countries. The identification of individuals at risk and the early diagnosis of CRC are of critical importance since a large proportion can be prevented or cured by surgical removal before metastasis has occurred. With increasing understanding of the genetic basis of hereditary and sporadic (non-hereditary) CRC, it becomes feasible to detect genetic alterations by molecular techniques. Familial adenomatous polyposis (FAP), hereditary nonpolyposis colorectal cancer (HNPCC), as well as early stages of spontaneous CRC, can be diagnosed by molecular characterisation of the adenomatous polyposis coli (APC) gene, the RAS oncogene and other genes in DNA from peripheral blood, stool or intestinal biopsies. With a better understanding of the genetic events leading to malignant transformation, molecular population screening should allow us to identify individuals at risk as well as patients with an early and potentially curable CRC. At present, careful patient and family history, physical examination and testing for occult blood as well as colonoscopy are still the key elements for clinical patient management. Molecular diagnosis will hopefully soon complement these analyses and should result in a reduction of morbidity and mortality from CRC.     

Lactate dehydrogenase isoenzymes in patients with HELLP syndrome

OBJECTIVES: A comparative study was carried out to clarify the clinicopathological features of colorectal cancer diagnosed after a false negative result on the immunochemical faecal occult blood test. METHODS: 236 patients with colorectal cancer were studied: 48 patients with negative results and 188 patients with positive results with the faecal occult blood test. The two groups were compared according to their age and sex and by the site, size, macroscopic type, Dukes's classification, and histological type of their cancer lesions. Additionally, the above factors were investigated prospectively and compared in 40 cases of colorectal cancer cases diagnosed as false negative and in matched cases diagnosed as true positive in cancer screening by the immunochemical faecal occult blood test. RESULTS: In both the hospital based case-control study and the screening programme based nested case-control study the prevalence of rectal cancers was higher in the false negative group than in the true positive group (P = 0.02, P = 0.03), but there were no differences between the two groups for any other factors. CONCLUSION: These results suggest that the immunochemical faecal occult blood test is unsuitable for the diagnosis of rectal cancer.     

Screening for colorectal cancer by immunochemical fecal occult blood testing

Screening for colorectal cancer using the conventional Hemoccult test has been shown to reduce mortality associated with cancer by 33% through a randomized controlled trial. However, the magnitude of effectiveness is small in terms of cost-effectiveness. The recently developed immunochemical fecal occult blood test (IFOBT) provides a potential replacement for the Hemoccult test as a screening test, due to its superior performance characteristics such as higher sensitivity shown in preliminary studies and the fact that it does not require any dietary restriction. The IFOBT method is reviewed, especially in relation to its specificity. In known colorectal cancer subjects, IFOBTs have shown both higher sensitivity and specificity than the Hemoccult test. Similarly, IFOBT has demonstrated a higher sensitivity than Hemoccult for colorectal cancer in an asymptomatic population. A nationwide screening program in Japan has demonstrated the feasibility of this approach for large population screening. However, the positivity rate varied according to the conditions at each screening facility. Therefore, technical factors that influence the positivity rate of IFOBTs in the screening program are discussed. Case-control studies have strongly suggested that screening using IFOBT would reduce mortality from colorectal cancer by 60% or more. Several observational studies have provided support for this estimate. The feasibility and effectiveness of population-based screening by IFOBT are discussed.     

Allergic granulomatous angiitis in a patient with positive reactions on serological tests for parasite antigens

PURPOSE: Colorectal cancer screening has become prevalent. To discuss the efficacy of screening, we studied the characteristic of asymptomatic colorectal cancer detected by screening. METHODS: This is a retrospective review of patients with colorectal cancer treated at our institution. During the past 20 years, 96 of 1,046 cases of colorectal cancer were asymptomatic and detected by screening. Sixty-one of these cases were detected in the recent five years. The initial screening procedures were fecal occult blood test in 51 cases, sigmoidoscopy or colonoscopy in 18, barium enema in 9, and other tests in 18. RESULTS: Thirteen lesions (14 percent) were smaller than 1.0 cm and 32 (33 percent) were 1-2 cm in size. There were 34 Tis, 21 T1, and 8 T2 tumors. Of the 55 Tis or T1 lesions, 14 showed nonpolypoid growth (5 flat-elevated, 7 flat-elevated with depression, 1 flat, 1 depressed), and 12 of these were detected on endoscopy. Thirty-four cases were TNM Stage 0, 25 were Stage I, 16 were Stage II, 12 were Stage III, and 9 were Stage IV. Sixty-one percent of those detected by screening were in either Stage 0 or Stage I compared with 16 percent in the symptomatic group. Cumulative five-year disease-free survival rates were 100 percent for both Stage 0 and Stage I, 94 percent for Stage II, and 52 percent for Stage III. Overall cumulative five-year survival rate was 87 percent for those detected by screening, compared with 57 percent in symptomatic patients. CONCLUSIONS: Asymptomatic cancers detected by screening were at a less advanced stage. In particular, many nonpolypoid early cancers were detected by endoscopic screening.     

A systematic review of the effects of screening for colorectal cancer using the faecal occult blood test, hemoccult

OBJECTIVE: To review effectiveness of screening for colorectal cancer with faecal occult blood test, Hemoccult, and to consider benefits and harms of screening. DESIGN: Systematic review of trials of Hemoccult screening, with meta-analysis of results from the randomised controlled trials. SUBJECTS: Four randomised controlled trials and two non-randomised trials of about 330 000 and 113 000 people respectively aged >=40 years in five countries. MAIN OUTCOME MEASURES: Meta-analysis of effects of screening on mortality from colorectal cancer. RESULTS: Quality of trial design was generally high, and screening resulted in a favourable shift in the stage distribution of colorectal cancers in the screening groups. Meta-analysis of mortality results from the four randomised controlled trials showed that those allocated to screening had a reduction in mortality from colorectal cancer of 16% (relative risk 0.84 (95% confidence interval 0.77 to 0.93)). When adjusted for attendance for screening, this reduction was 23% (relative risk 0.77 (0.57 to 0.89)) for people actually screened. If a biennial Hemoccult screening programme were offered to 10 000 people and about two thirds attended for at least one Hemoccult test, 8.5 (3.6 to 13.5) deaths from colorectal cancer would be prevented over a period of 10 years. CONCLUSION: Although benefits of screening are likely to outweigh harms for populations at high risk of colorectal cancer, more information is needed about the harmful effects of screening, the community's responses to screening, and costs of screening for different healthcare systems before widespread screening can be recommended.     

Is routine screening for colorectal cancer justifiable? These gastroenterologists say YES!

While methods of screening for colorectal cancer undoubtedly will be refined and new techniques developed, there is ample evidence to support use of the currently employed protocol: annual fecal occult blood testing and periodic flexible sigmoidoscopy. Aggressive attempts to educate physicians and patients on the importance of such screening are needed. Primary care physicians can play an important role in ensuring patient compliance and reducing the incidence of this serious public health problem.     

Immunologic detection of fecal occult blood from upper digestive tract diseases

BACKGROUND/AIMS: This study was conducted to evaluate the accuracy of the immunochemical occult blood test for upper digestive tract diseases. METHODOLOGY: The test was performed on 226 subjects, including 124 upper digestive tract diseases (12 ulcerative esophagitis cases, 10 esophageal cancer cases, 33 gastric ulcer cases, 33 gastric cancer cases, and 36 duodenal ulcer cases), 34 colorectal cancer cases, and 68 healthy subjects, after which, the accuracy of this test was evaluated. RESULTS: The test was positive 23 in upper digestive tract diseases (2 in ulcerative esophagitis, 2 in esophageal cancer, 5 in gastric ulcer, 8 in gastric cancer, 6 in duodenal ulcer), 31 in colorectal cancer, and 3 in healthy subjects, respectively. Thus, the sensitivity was 19% for upper digestive tract diseases (16.7% for ulcerative esophagitis, 20% for esophageal cancer, 15% for gastric ulcer, 24% for gastric cancer, 20% for duodenal ulcer) and 91% for colorectal cancer, and the specificity was 96%. Significant difference was noted in the sensitivity between upper digestive tract diseases and colorectal cancers (p0.001), whereas there was no difference among 5 upper digestive tract diseases. CONCLUSIONS: These results indicate that the immunochemical occult blood is inadequate as means for detection of upper digestive tract diseases, and that an examination of upper digestive tract is unnecessary in cases where the immunochemical occult blood test is positive, but there is no evidence of diseases in colon and rectum.     

Diagnosing colorectal carcinoma: clinical and molecular approaches

In summary, the ability to decrease the mortality of colorectal carcinoma is increasingly within the grasp of clinicians. With accurate family and personal history, it is possible to estimate the risk of colorectal cancer and initiate FOBT and colonoscopy where appropriate. In the future, germline and even somatic genetic testing will further increase our ability to diagnose cancers before they become widely invasive. As molecular biology unravels the cause of what currently appears to be the majority of sporadic cancers, it may be possible to characterize more colorectal cancers that are caused by novel, as yet not recognized mutator genes. Unfortunately, a set of patients is likely to exist who remain to be diagnosed by symptoms caused by advanced cancer. The goal for the clinician is to decrease this subset to as small a group as possible.