Debate on colorectal cancer screening by faecal occult blood.
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Biomedical subjects
Publications and source records attributed to G Castiglione.
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OBJECTIVES: Screening by faecal occult blood testing (FOBT) is effective in decreasing mortality and incidence of colorectal cancer (CRC). Immunochemical tests have proved to be more cost effective than guaiac FOBTs. The latex agglutination test (LAT) has the advantage of being a fully automated, quantitative test. The aim of this study is to interpret the overall experience with LAT according to different positivity thresholds. SETTING: A population based screening programme is currently running involving subjects aged 50-70, invited every 2 years to have an FOBT. LAT is the standard screening test and has a positivity threshold for further diagnostic tests of 100 ng haemoglobin/ml of sample solution. METHODS: Positivity rates, detection rates for CRC high risk adenomas, and positive predictive values for CRC, high risk adenomas, and low risk adenomas were calculated for several positivity thresholds. RESULTS: 19,132 attendances at screening were recorded (11,774 at first screening, 7358 at subsequent screenings). Progressively increasing the positivity threshold from 100 to 200 ng/ml showed (a) a decrease in positivity rate; (b) a decrease in detection rates for CRC or high risk adenomas; (c) an increase in positive predictive values for cancer; (d) an increase in positive predictive value for high risk adenomas. CONCLUSIONS: Increasing the positivity threshold of the LAT reduces recall rate and improves positive predictive value for cancer or high risk adenomas but substantially decreases the detection rate of CRC and high risk adenomas. For this reason increasing the positivity cut off for LATs is not advisable. On the other hand decreasing the positivity threshold would increase recall rate and sensitivity of screening. Careful evaluation of sensitivity of the quantitative results of the LAT for interval cancers is needed to definitively assess the optimal positivity threshold for LATs in population based screening programmes.
The fecal occult blood test (FOBT) has demonstrated its efficacy in reducing mortality from colorectal cancer (CRC). The guaiac-based FOBT has been criticized for its low sensitivity. In this study, two different assays for FOBT (guaiac or an immunochemical test based on reversed passive hemagglutination [RPHA]) were tested for comparison within a population-based screening program for colorectal cancer in the province of Florence (Italy). The proportional incidence method was used to calculate sensitivity for both FOBTs, according to rank of screening (first or repeat), age at entry (two groups of 50 to 59 and 60 to 70 years old) and lesion site (colon or rectum). When comparing FOBTs, the sensitivity multivariate Poisson regression was used to adjust for other variables. The sensitivity after the first 2 years was 50% (95% confidence interval [CI] 34% to 63%) for the guaiac test versus 82% (95% CI 67% to 92%) for RPHA. At multivariate analysis the risk of developing an interval cancer after a guaiac test is almost 3 times that after RPHA (rate ratio = 2.64; 95% CI 1.3 to 5.4). Our study confirms that RPHA is more sensitive than the guaiac test. The assumption that FOBT screening for CRC has to be based on a guaiac test should be reconsidered, and RPHA should be recommended as the standard FOBT for screening purposes.
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OBJECTIVE: To compare two immunochemical faecal occult blood tests based on reversed passive haemagglutination (RPHA) or latex agglutination (Hdia) in a population based screening setting. METHOD: Hdia was interpreted according to three positivity thresholds: 100, 150, or 200 ng of haemoglobin/mg of specimen solution. A total of 5844 subjects were recruited into the study, from 17432 invited subjects aged 50-70. RESULTS: Positivity rates were 3.3% for RPHA, Hdia100 3.5%, Hdia150 2.5%, Hdia200 2.0%. Among subjects complying with the diagnostic work up, colorectal cancer (CRC) was detected in 19 subjects (17 RPHA positive, 16 Hdia100 positive, 15 Hdia150 positive, 14 Hdia200 positive) and high risk adenoma/s in 41 subjects (28 RPHA positive, 32 Hdia100 positive, 29 Hdia150 positive, 25 Hdia200 positive). The prevalence of screen positive CRC in the population was for RPHA 2.9 per thousand, Hdia100 2.7 per thousand, Hdia150 2.6 per thousand, Hdia200 2.4 per thousand. The prevalence of screen positive high risk adenomas in the population was for RPHA 4.8 per thousand, Hdia100 5.5 per thousand, Hdia150 5.0 per thousand, Hdia200 4.3 per thousand. CONCLUSION: Hdia100 was as sensitive as RPHA for cancer and high risk adenomas. As Hdia is less technically complex than RPHA, it is a valid alternative to the latter, provided that full automation of the development procedure is available. Increasing the positivity threshold of Hdia up to 150 or 200 ng of haemoglobin/mg of specimen solution is not advisable as the increase in specificity is too small to justify the corresponding decrease in the detection of screen positive cancers in the population.
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BACKGROUND: The need for colonoscopy in the care of patients with rectosigmoid adenoma 5 mm or less in diameter is still debatable. METHODS: We estimated the prevalence of proximal adenomas among 3052 consecutive subjects undergoing total colonoscopy. Rectosigmoid adenoma was classified as diminutive (5 mm), small (6 to 10 mm), or large (>/=11 mm). Advanced proximal adenoma was 10 mm in diameter or larger, or with a villous component, severe dysplasia, or infiltrating adenocarcinoma. RESULTS: Proximal adenoma was found in 212 of 2483 patients (8.5%, 95% CI [7.5, 9.7]) without distal neoplastic polyps, 49 of 214 (22.9%, 95% CI [17.6, 29.2]) with diminutive, 44 of 174 (25.3%, 95% CI [19.1, 32.5] with small, and 70 of 181 (38.7%, 95% CI [31.6, 46.2]) with large distal adenoma. Advanced proximal adenoma was found in 49 (2.0%, 95% CI [1.5, 2.6]), 8 (3.7%, 95% CI [1.7, 7.5]), 17 (9.8%, 95% CI [6.0, 15.4]), and 29 patients (16.0%, 95% [11.2, 22.4]), respectively. In patients with distal adenoma risk for proximal lesions increased with increasing age, size, and number of distal adenomas (p = 0.01). Size of distal adenoma was the strongest predictor of the presence of proximal advanced adenoma (multivariate analyses). CONCLUSIONS: In a clinical setting, the decision to perform colonoscopy should take into account proximal lesions of clinical interest, life expectancy, costs, and risks associated with the procedure. When detection of advanced proximal adenoma is the goal, presence of distal diminutive adenoma alone might not be an indication for total colonoscopy.
Dermatofibrosarcoma protuberans is an uncommon slow-growing cutaneous neoplasm. Surgical excision is an effective therapeutic approach although a significant number of local recurrences has been documented in the literature. In the present paper the Authors report 3 cases of dermatofibrosarcoma protuberans. All cases have been surgically treated with a wide local excision extended up to 3 cm from the tumor borders. No local recurrence has been reported. The Authors conclude that the surgical technique employed could reduce the local recurrence rate of dermatofibrosarcoma protuberans.
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The Authors, on the base of three cases of intracystic papillary carcinoma of the breast, discuss about the diagnostic means and the modalities of treatment of such rare cancer. They stress the value of cytology by fine needle aspiration, which gives more detailed informations than mammography or ultrasonography. As far as the treatment concerns, the Authors, according to the data of the literature, suggest for this tumor, still at an "in situ" stage, a conservative surgical treatment such as a quadrantectomy or tumorectomy plus lymphadenectomy followed both by radiotherapy. Finally, they remark that the intracystic papillary carcinoma of the breast, mainly arising in old women (7th, 8th decade), was found within their series (two out of three) in young women in the 5th decade of life.
The authors report their experience with 850 consecutive laparoscopic cholecystectomies performed from May 1990 to July 1997. In this series, despite a sporadic use of intraoperative cholangiography (IOC), there were no lesions of main biliary tract and there was only a biliary leaking cystic duct resolved with conservative treatment. The authors are satisfied with selective use of endoscopic cholangiography and sphincterotomy for the management of choledocholithiasis, and conclude that the use of IOC is not so essential to avoid iatrogenic lesions of main biliary tract, that could be avoid by applying a meticulous operative technique.
The authors surgically treated 281 consecutive women with breast cancer by breast conservation techniques (45.2%) or by mastectomy (38.8%), during a four-year period. Forty-five of these 281 patients (16%) were treated in the same period of time by mastectomy and immediate reconstruction (IR) of the breast. IR of the breast was performed by inserting a submuscular tissue expander at the same time of mastectomy (first stage of reconstruction). A second operation allowed the replacement of the expander with a prosthesis (second stage of reconstruction) and the simultaneous symmetrization of the contralateral breast (not always performed, however). In some cases nipple-areola complex was eventually reconstructed with a delayed surgical procedure (third stage of reconstruction). In the present paper the authors analyze the results and outline the advantages of IR. This easy and safe technique slightly increased the average operative time of a mastectomy, did not interfere with routine oncological follow-up, did definitely reduce patient's psychological trauma following mastectomy. The authors conclude that IR of the breast undoubtedly plays a major role in the so called "onco-plastic"" surgical management of breast cancer.
The aim of our case-control study was to estimate the effect on mortality from colorectal cancer (CRC) of a population-based screening with a faecal occult blood test started in 1982 in a rural area of the district of Florence. We examined the relationship between mortality and the interval since the most recent screening. The cases in the study were 206 individuals who had died from CRC after the age of 41 years. Five controls were selected randomly from the list of individuals alive at the time of diagnosis of the corresponding case and were matched by sex, age and place and length of residence. After adjustment for potentially confounding factors, the odds ratio (OR) for death from CRC for screened persons vs. those not screened was 0.60 [95% confidence interval (CI), 0.4-0.9]. The OR was lowest in the first 3 years after the most recent test (OR = 0.54; 95% CI, 0.3-0.9) and increased towards unity subsequently. Our results suggest that screening for CRC by biennial faecal occult blood testing can reduce mortality from the disease.
BACKGROUND: The association between distal hyperplastic polyps and proximal adenomas is still a matter of debate. We investigated this association while taking into account patient characteristics. METHODS: After exclusion of patients with inflammatory bowel diseases, familial adenomatous polyposis, or any cancer, 3088 eligible consecutive subjects aged 18 to 69 years underwent total colonoscopy in four gastroenterology units. The odds ratios (OR) of having proximal adenomas according to patient characteristics (age, sex, medical center, year of endoscopy, reasons for referral, and distal findings) were estimated in univariate and multivariate analyses. RESULTS: Patients with distal polyps of any type showed an adjusted OR of 2.5 (95% CI [1.9, 3.1] p < .001) of having proximal adenomas as compared with those without distal polyps. When distal adenomas and distal hyperplastic polyps were included in the multivariate model as independent factors, the presence of adenomas significantly increased the risk of proximal adenomas (OR = 2.8: 95% CI [2.2, 3.6] p < .001), whereas the presence of hyperplastic polyps did not (OR = 1.1: 95% CI [0.8, 1.5] p = .64). No association with number, size, or location of distal hyperplastic polyps was seen. CONCLUSIONS: Our data show that the presence of hyperplastic polyps should not be the sole indication for total colonoscopy because they are not associated with proximal adenomas when adjusting for patient characteristics and presence of distal adenomas.
OBJECTIVE: To compare the costs of colorectal cancer (CRC) screening by two faecal occult blood tests (FOBT)-namely, Hemoccult (guaiac based) and reversed passive haemagglutination (RPHA) tests. RPHA was interpreted according to two positivity thresholds (+ or +/-). METHODS: Attenders performed both tests. Subjects with a positive FOBT test were invited to have a complete exploration of the colon. The total costs for every 10,000 screened subjects and costs for each unit of result (screened subject, or patient with adenoma/s or cancer detected) were calculated for both tests. RESULTS: 8353 subjects were enrolled. A total of 2109 repeated screening after two years. RPHA(+ and +/-) showed the highest and RPHA(+) the lowest positivity rate at first screening. The Hemoccult positivity rate was highest at repeat screening. Total costs of screening by RPHA(+ and +/-) were highest as this method had the highest recall rate. Screening by RPHA(+) was the least costly. Costs for each screened subject were highest for RPHA(+ and +/-) and lowest for RPHA(+). Costs for each cancer detected were lowest for RPHA(+) and highest for Hemoccult or RPHA(+ and +/-) in subjects aged > 49 or < 50, respectively. Costs for subjects with detected adenoma/s of > 9 mm were lowest for RPHA(+ and +/-) and highest for Hemoccult. At repeat screening total costs of RPHA(+ and +/-) were lower than at first screening, whereas for each subject with cancer or adenoma/s costs were increased. CONCLUSIONS: Our data confirm that screening by RPHA is more cost effective than by Hemoccult.
We developed a procedure for the endoscopic visualization in humans of aberrant crypt foci (ACF), preneoplastic lesions of the colon mucosa, and we determined the frequency of ACF in resected sections of human colon. For the endoscopy we studied 12 consenting adults (6 controls and 6 colon cancer cases) by dyeing colon mucosa with 0.5% methylene blue and searching ACF with a magnifying endoscope. ACF of varying dimensions were visualized in all subjects. We also studied colon surgical specimens from patients with colon cancer or diverticulitis. After staining the mucosa with 2% methylene blue, we found approximately the same density of ACF in the colon mucosa of the patients with colon cancer as in that of patients with diverticulitis (ACF/cm2 were 0.124 +/- 0.143 [N = 14] and 0.108 +/- 0.210 [N = 4], respectively [mean +/- SD]). In conclusion, the visualization of ACF with methylene blue in humans does not identify groups at low and high risk of colon cancer.
Two faecal occult blood tests (FOBTs), Hemoccult II (guaiac based) and Hemeselect (immunochemical) were compared in a population screening for colorectal cancer on 24 282 subjects aged 40-70. Hemeselect was interpreted according to a lower (+ and +/-) and a higher (+) positivity threshold. A total of 8008 compliers were enrolled in the study. Positivity rates: Hemoccult = 6.0%, Hemeselect (+ and +/) = 8.2%, Hemeselect (+) = 3.1%. Among FOBT-positive subject complying with the diagnostic work-up, 22 had colorectal cancer (17 Hemeselect-positive (+), four Hemeselect-borderline (+/-), 15 Hemoccult-positive) and 166 subjects had adenomas (62 Hemeselect(+), 56 Hemeselect-borderline (+/-), 79 Hemoccult-positive) were detected. The positive predictive values (PPVs) for cancer were as follows: Hemoccult = 3.7%, Hemeselect (+ and +/-) = 3.8%, Hemeselect (+) = 8.4%. The PPVs for adenoma(s) were: Hemoccult = 19.7%, Hemeselect (+ and +/-) = 21.4%, Hemeselect (+) = 30.5%. The specificity for cancer was: Hemoccult = 94.1%, Hemeselect (+ +/-) = 92%, Hemeselect (+) = 97.1%. Ratios between detection rates of each test and expected incidence of colorectal cancer suggest that Hemoccult anticipates cancer diagnosis by approximately 2 years on average whereas the mean diagnostic anticipation of Hemeselect ranges between 2.5 and 3.2 years. Hemeselect is superior to Hemoccult as it is at least as effective but more efficient and acceptable than guaiac testing. Further evaluation of Hemeselect cost-effectiveness and sensitivity is needed in order to assess the optimal threshold of positivity and screening frequency.
This study aimed to evaluate survival in 2,339 colorectal cancer patients diagnosed in 1985-87 in the province of Florence, where the Tuscany Tumour Registry is active. The effect of sex, site (colon, rectum), sub-site, disease diffusion (localized, regional, distant, unspecified), year of diagnosis, place of residence (municipalities involved in the screening programme, Florence, others) and source of diagnosis (Center for the Study and Prevention of Cancer-CSPO, others) were evaluated. Five-year observed and relative survivals were 37.9 and 48.1% respectively. Five-year prognosis was worse in men, in older age groups, in advanced stages and in patients not diagnosed at the CSPO. No differences were shown in residents of municipalities involved in the screening programme. Relative 5-year survival in Florence was among the highest in Europe for cancers of both the colon and the rectum. Sex, age, disease diffusion and source of diagnosis showed an independent prognostic effect. The effect of screening was not evident, probably due to the low compliance during the period under study and to the use of a low sensitivity test.