CT colonography before colonoscopy in subjects with positive faecal occult blood test. Preliminary experience.

PURPOSE: We report a preliminary evaluation of the performance of computed tomography colonography (CTC) systematically obtained before optical colonoscopy (OC) in subjects with positive faecal occult blood test (FOBT) within a population-based screening programme for colorectal cancer (CRC). MATERIALS AND METHODS: Seventy-nine subjects with positive FOBT from a regional screening programme were invited to perform same day CTC and OC. CTC was performed with standard bowel preparation. OC with segmental unblinding was the reference standard. A per-patient per-adenoma analysis was performed. RESULTS: Forty-nine of 79 subjects (62%) with positive FOBT adhered to the study and completed both examinations. Twenty-two (44.9%) of the 49 had a cancer or an adenoma ≥6 mm. Per-patient sensitivity, specificity, negative predictive value and positive predictive value for cancer or adenoma ≥6 mm were 95.5% (95%CI:77.2%-99.9%), 51.9% (95%CI:32.0%-71.3%), 93.3% (95%CI:68.1%-99.8%) and 61.8% (95%CI:43.6%-77.8%). CONCLUSIONS: In the setting of a FOBT-based screening programme for CRC, CTC showed a high sensitivity, but relatively low specificity and positive predictive value, for cancer and adenoma ≥6 mm. Probably performing CTC without faecal tagging as second line test after a positive FOBT is not a cost-effective strategy.

Immunochemical faecal occult blood test: number of samples and positivity cutoff. What is the best strategy for colorectal cancer screening?

Immunochemical faecal occult blood tests have shown a greater sensitivity than guaiac test in colorectal cancer screening, but optimal number of samples and cutoff have still to be defined. The aim of this multicentric study was to evaluate the performance of immunochemical-based screening strategies according to different positivity thresholds (80, 100, 120 ng ml(-1)) and single vs double sampling (one, at least one, or both positive samples) using 1-day sample with cutoff at 100 ng ml(-1) as the reference strategy. A total of 20 596 subjects aged 50-69 years were enrolled from Italian population-based screening programmes. Positivity rate was 4.5% for reference strategy and 8.0 and 2.0% for the most sensitive and the most specific strategy, respectively. Cancer detection rate of reference strategy was 2.8 per thousand, and ranged between 2.1 and 3.4 per thousand in other strategies; reference strategy detected 15.6 per thousand advanced adenomas (range=10.0-22.5 per thousand). The number needed to scope to find a cancer or an advanced adenoma was lower than 2 (1.5-1.7) for the most specific strategies, whereas it was 2.4-2.7, according to different thresholds, for the most sensitive ones. Different strategies seem to have a greater impact on adenomas rather than on cancer detection rate. The study provides information when deciding screening protocols and to adapt them to local resources.

Gastric cancer after positive screening faecal occult blood testing and negative assessment.

BACKGROUND: Gastric cancer may be suspected with otherwise unexplained positive faecal occult blood testing. AIMS: To assess the frequency of gastric cancer following positive faecal occult blood testing and negative colonoscopy. SUBJECTS: Age 40-74 cohort at first screening (1985-2001) with (a) faecal occult blood testing- (83,489), (b) faecal occult blood testing +/colonoscopy+ (2025), or faecal occult blood testing+/colonoscopy- (3555). METHODS: Gastric cancer incidence in faecal occult blood testing subsets, compared with expected standardized incidence rates. RESULTS: Gastric cancer risk was increased (standardized incidence rate=146.7; 95% confidence interval: 105.8-203.4) in faecal occult blood testing+/colonoscopy- subjects. A four-fold excess incidence occurred during first year (observed cases=10, standardized incidence rate=408.3; 95% confidence interval: 219.7-758.8), irrespective of faecal occult blood testing type (guaiac, immunological). No excess risk occurred in faecal occult blood testing- (observed cases=53, standardized incidence rate=91.2; 95% confidence interval: 84.1-98.8) or in faecal occult blood testing+/colonoscopy+ subjects (observed cases=2, standardized incidence rate=101.9; 95% confidence interval: 25.5-407.4). Assuming a 100% 3-year study sensitivity for gastric cancer, faecal occult blood testing positive predictive value would be 0.4% (40-74 years) or 0.7% (> or =60 years) in faecal occult blood testing+/colonoscopy- subjects. CONCLUSIONS: Data suggest an association of faecal occult blood testing+/colonoscopy- and excess gastric cancer incidence in the following year. Due to low faecal occult blood testing+ positive predictive value, routine upper digestive tract endoscopy in these subjects is questionable.

Nipple sparing subcutaneous mastectomy: sixty-six months follow-up.

AIM: Validation of oncological and reconstructive efficacy of nipple sparing subcutaneous mastectomy. METHODS: We enrolled 50 patients on behalf of Humanitas Centro Catanese di Oncologia fulfilling appropriate reconstructive and oncological criteria to undergo nipple sparing subcutaneous mastectomy. We preferably selected women with medium size-small breast affected by early stage breast cancer peripherally located with intra-operative negative frozen section of the major ducts. RESULTS: fourty-six patients were alive after a mean follow-up of 5.5 years. We observed a single case of local recurrence in the nipple successfully treated with local excision. Five patients presented metastatic disease. One is currently alive, 4 died because of progressive disease. CONCLUSIONS: Our study supports other findings regarding safety and efficacy of nipple sparing subcutaneous mastectomy for selected patients.

Evaluation of diagnostic accuracy of screening by fecal occult blood testing (FOBT). Comparison of FOB Gold and OC Sensor assays in a consecutive prospective screening series.

We evaluated a new immunological fecal occult blood testing assay (FOB Gold, Sentinel = SENT) compared to the assay currently employed in the Florence screening program (OC-Hemodia, Eiken = OC). A total of 4,133 subjects were screened with both tests and underwent colonoscopy if positive (100 ng/mL Hb cutoff) to either test: 190 (4.59%) were positive (OC =140 (3.4%); SENT = 131 (3.2%)). The relative sensitivity for 7 cancers was 100% with OC and 67.9% with SENT, and for 48 high-risk adenomas (HRAs) it was 77.0% with OC and 66.6% with SENT. The positive predictive value (PPV) for cancer+HRA was 31.4% for OC and 28.2% for SENT and the specificity was 97.7 for both. The differences were not statistically significant. Adding SENT to OC increased the positivity rate by 32% and the cancer+HRA detection rate by 25%, and decreased the PPV by 10%. Both tests were performed on the same tubes in 1,601 cases, and in 18 of 47 cases they differed on different tubes but not on the same tube, suggesting inhomogeneous Hb content or varying fecal matrix influence in different samples. SENT has practical advantages for screening [corrected] (fully automated, high output, requires no dedicated instrument), a comparable specificity and a lower sensitivity, though the latter difference may be partially ascribed to differences in sampling and not to the assay itself [corrected] Because of the statistical insignificance of the differences, further studies are needed for confirmation.

Enhancement of osteoinduction by vitamin D metabolites in rachitic host rats.

Diaphyseal bone from normal Sprague-Dawley rats was delipidated in chloroform-methanol and demineralized in 0.6 N HCl at 4 degrees C. The bones were then implanted for 7-28 days into rats made rachitic by a low-phosphate, vitamin D-deficient diet (VDP-) for 3 weeks. Bones from VDP- and normal rats were also implanted into normal hosts. When normal rats were used as the host environment, a consistent sequence of cartilage induction and bone formation was observed. Demineralized rachitic bone (RB) implanted into normal host rats resulted in cartilage and bone induction similar to that seen for normal bone (NB) implants. Transmission electron microscopy of RB in normal hosts revealed morphologically normal chondrocytes and cartilage matrix with normal mineralization. In contrast, implantation of NB in VDP- hosts resulted in delayed chondrogenesis and lack of calcification. Furthermore, similar results were observed when RB was implanted into VDP- hosts. Treatment of VDP- hosts with either 1 alpha-hydroxyvitamin D3 or 24,25-dihydroxyvitamin D3 did not accelerate the sequential appearance of precartilage or cartilage. However, 24,25-(OH)2D3 administered alone or in combination with 1 alpha-OHD3 significantly increased the amount of calcified cartilage observed at 2 weeks postimplantation compared to implants from either untreated VDP-hosts or those treated only with 1 alpha-OHD3. New bone formation was observed at 4 weeks postimplantation in all vitamin D-treated groups as determined by von Kossa staining or direct electron microscope examination. There was no apparent difference in the quantitative or qualitative bone formed within the various vitamin D-treated groups. Serum calcium and phosphorus levels were lower and alkaline phosphatase levels were higher in VDP- hosts compared with normal animals or those treated with vitamin D metabolites. The results of this study show a reduction in the capacity of progenitor cells in VDP- rat hosts to respond to osteoinductive factor(s). This impaired response appears to be corrected by vitamin D metabolites.

Effects of vitamin D metabolites on healing of low phosphate, vitamin D-deficient induced rickets in rats.

A model of low-phosphate, vitamin D-deficient rachitic rats was used to compare the effects of 1 alpha(OH)D3, 1,25(OH)2D3, and 24,25(OH)2D3 on cartilage and bone. The rats were maintained for 3 weeks on a high-calcium, low-phosphate, vitamin D-deficient diet, during which period they developed severe rickets. The rachitic rats were injected for 2 or 3 consecutive days with a physiologic dose of either metabolite. Other littermates were given a single dose of 50,000 IU of cholecalciferol in combination with a normal diet. Samples of cartilage fluid (Cfl) and of blood were removed prior to sacrifice for biochemical studies of some parameters of calcification. These parameters were correlated with the results of light and electron microscopic studies of the growth plate cartilage and bone. Treatment with 1 alpha (OH)D3 or with 1,25(OH)2D3, in spite of increasing Ca and P levels in the Cfl, induced only partial healing of the rickets. In contrast, 24,25(OH)2D3 or vitamin D with a normal diet resulted in complete morphologic and biochemical healing of the rickets. Transmission electron microscopic (TEM) studies have shown partial mineralization of the wide hypertrophic zone of the growth plate following treatment with 1 alpha(OH)D3 or with 1,25(OH)2D3. Mineralization was more complete with 24,25(OH)2D3 treatment. The results of this study emphasize the importance of 24,25(OH)2D3 for normal endochondral bone formation and mineralization.

Oral beclometasone dipropionate in the treatment of active ulcerative colitis: a double-blind placebo-controlled study.

AIM: To evaluate efficacy and safety of oral beclometasone dipropionate (BDP) when added to 5-ASA in the treatment of patients with active ulcerative colitis. METHODS: In a 4-week, placebo-controlled, double-blind study, patients with extensive or left-sided mild to moderate active ulcerative colitis were randomized to receive oral 5-ASA (3.2 g/day) plus BDP (5 mg/day) or placebo. Clinical, endoscopic and histologic features, and haematochemical parameters were recorded at baseline and at the end of the study. RESULTS: One hundred and nineteen patients were enrolled and randomly treated with BDP plus 5-ASA (n = 58) or placebo plus 5-ASA (n = 61). Both treatment groups showed a statistically significant decrease of disease activity index (DAI) and histology score at the end of treatment (P = 0.001, each). DAI score was lower in the BDP group than in the placebo group (P = 0.014), with more patients in clinical remission in the BDP group (58.6% vs. 34.4%, P = 0.008). Serum cortisol levels significantly decreased in BDP group vs. baseline (P = 0.002), but without signs of pituitary-adrenal function depletion. A low incidence of adverse events was observed in both groups. CONCLUSIONS: Oral BDP in combination with oral 5-ASA is significantly more effective than 5-ASA alone in the treatment of patients with extensive or left-sided active ulcerative colitis.

Beclomethasone dipropionate enemas versus prednisolone sodium phosphate enemas in the treatment of distal ulcerative colitis.

AIM: To compare beclomethasone dipropionate 3 mg/60 mL enema (BDP) and prednisolone sodium phosphate 30 mg/60 mL enema (PP) once daily in patients with active distal ulcerative colitis. METHODS: One hundred and fifty-seven patients were enrolled in a multicentre, 4-week, randomized, double-blind trial. Patients were assessed at baseline, 2 and 4 weeks. RESULTS: Both treatment groups showed statistically significant improvement of clinical activity after 2 and 4 weeks. Endoscopy and biopsy showed a reduction in the activity score at the end of the treatment period in both groups. No statistically significant difference was observed between the two treatment groups. After 4 weeks, 29% of patients in the BDP group and 25% in the PP group were considered to be in clinical remission; an improvement was observed in 40% of patients on BDP and in 47% on PP. Mean morning plasma cortisol levels showed a slight but significant reduction in the PP group, while the ACTH test showed that neither drug interfered with the hypothalamic-pituitary-adrenal (HPA) axis function. No significant changes were observed in the laboratory tests. Finally, there was a low incidence of adverse events in both groups. CONCLUSIONS: It is concluded that, in the topical treatment of active distal ulcerative colitis, BDP 3 mg enemas are as efficacious as PP 30 mg enemas, without interference with the HPA axis.

Oral beclometasone dipropionate in the treatment of extensive and left-sided active ulcerative colitis: a multicentre randomised study.

AIM: To explore the efficacy and safety of the topically acting steroid beclometasone dipropionate (BDP) in an oral controlled release formulation in the treatment of extensive or left-sided ulcerative colitis. METHODS: In a multicentre, randomised, parallel-group, single-blind study, patients with active mild to moderate ulcerative colitis were randomised to a 4-week treatment with BDP 5 mg/day o.d. vs. 5-ASA 0.8 g t.d.s. The primary efficacy variable was the decrease of Disease Activity Index (DAI) (clinical symptoms and endoscopic appearance of mucosa). Safety was evaluated by monitoring adverse events, vital signs, haematochemical parameters and adrenal function. RESULTS: One hundred and seventy-seven patients were enrolled and randomly treated with BDP (n = 90) or 5-ASA (n = 87). Mean DAI score decreased in both treatments groups (P < 0.0001 vs. baseline for both groups). Clinical remission was achieved in 63.0% of patients in the BDP group vs. 62.5% in the 5-ASA group. A significant DAI score improvement (P < 0.05) in favour of BDP was observed in patients with extensive disease. Both treatments were well tolerated. Mean plasma cortisol levels were significantly reduced vs. baseline in BDP recipients, but without signs of pituitary-adrenal function depletion. CONCLUSION: Oral BDP gave an overall treatment result in patients with active ulcerative colitis without signs of systemic side-effects.

Colorectal cancer survival--population-based rates in the province of Florence.

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.

Comparative analysis of results of guaiac and immunochemical tests for faecal occult blood in colorectal cancer screening in two oncological institutions.

The performances of three faecal occult blood tests, rehydrated Hemoccult (HOR), Hemoccult sensa (HOS) and Hemeselect (HSEL) on 3 days were compared in 1,725 subjects consecutively recruited in two oncological institutions in Milan and Florence. Significant differences between the results were evident as far as HOR positivity rates (7.5% vs 4.0%, respectively) and specificity (94.3% vs 97.5%, respectively) are concerned. Overall positivity rates of HOR, HOS and HSEL were 5.9%, 5.4% and 12%, respectively; significant differences were evident between HSEL and each of the two guaiac tests. Cancer was detected in eight subjects, adenoma/s in 47. Specificity estimates were 95.8%, 90.2% and 90.5% for HOR, HOS and HSEL, respectively; significant differences were evident between HSEL and the other two tests. No significant difference between tests was evident for sensitivity or positive predictive values for cancer or adenomas. In the CSPO (Florence) population (1,223 subjects; five with cancer, 16 with adenoma/s) the performances of 1-day HSEL testing were determined on the basis of the first faecal sample only and compared with 3-day HOR, HOS and HSEL testing. The positivity rates of 1-day HSEL, 3-day HOR, HOS and HSEL testing were 7.0%, 5.0%, 5.5% and 12.9%, respectively. Only 3-day HSEL positivity rate was significantly higher than 1-day HSEL. One-day HSEL specificity (94.9%) was significantly higher than 3-day HSEL (90.0%), whereas no significant difference was seen between 1-day HSEL, HOR (96.5%), and HOS (96.1%) specificity. No significant difference between tests is evident in the CSPO population as far as positive predictive values and sensitivity for cancer and adenomas are concerned.(ABSTRACT TRUNCATED AT 250 WORDS)

Colorectal cancer screening programme by faecal occult blood test in Tuscany: first round results.

Screening with faecal occult blood test (FOBT) has been shown to be effective in reducing mortality from colorectal cancer. Tuscany was the first region in Italy in which a screening programme for colorectal cancer by FOBT was initiated region-wide. The aim of the paper was to describe organizational aspects, a quality control model and the results of this experience. From June 2000 to December 2001, 192583 subjects aged 50-70 were invited to undergo a 1-day immunochemical test without any dietary restriction. A total of 78505 subjects (41%) performed the screening test, of whom 4537 responders had a positive test result (5.8%). Among them, 1122 refused any form of assessment or underwent a colonoscopy outside the screening referral centres, with an overall assessment compliance of 75.3%. Malignancies were found in 193 patients and at least a high-risk adenomatous polyp in 692 patients. In about a quarter of the positive subjects who underwent assessment, cancer or high-risk adenoma was detected. In conclusion, data from this experience supported the feasibility of biennial colorectal screening programme by FOBT, particularly regarding invitation compliance and positivity rate. Further efforts are necessary to implement screening extension and to improve data collection.

Transplacental effects of vitamin A on fetal bones in mice--follow-up studies on postnatal recovery.

Pregnant mice were injected with pharmacological doses of vitamin A during days 11-19 of gestation with the purpose of studying the long bones of offspring up to the age of 1 week. Tibiae were collected for routine light microscopic examination and tranmission electron microscopic examination. In addition, biochemical studies were conducted to determine the calcium, phosphorus, and magnesium content as well as the hydroxyproline and protein content of the bones. Treatment with vitamin A resulted in reduced weight and length of the long bones, as well as the presence of excessive calcification throughout the hypertrophic zone of the cartilaginous epiphyses. Matrix vesicles, many of them containing hydroxyapatite crystals, were observed and found to be distributed within the cartilaginous epiphyses in a similar pattern as in untreated control mice offspring, but mineral crystals were also observed unassociated with the matrix vesicles. The calcium, phosphate, magnesium, and hydroxyproline content was reduced in the vitamin A offspring. However, the percentage of these minerals expressed per dry weight bone was higher than in controls, verifying the morphological findings that although vitamin A inhibits bone growth, it enhances calcification in the growth plate.

Feasibility study of colorectal cancer screening by immunochemical faecal occult blood testing: results in a northern Italian community.

AIM: Screening by means of faecal occult blood testing (FOBT) has proved to be effective in reducing colorectal cancer incidence and mortality. We performed a pilot screening for colorectal cancer by latex immunological FOBT in two municipalities of the region Valle d'Aosta, Italy, focusing on problems and obtaining indications for the feasibility and extension of the screening programme on a regional basis. METHODS: A total of 2961 subjects aged 50-74 years were invited by mail to perform a one-day immunochemical FOBT without any dietary restrictions and with a positive threshold put at 100 ng/ml. Patients with positive tests were then invited to undergo colonoscopy and double-contrast barium enema if colonoscopy was incomplete. RESULTS: A total of 1631 subjects performed the screening test with an overall compliance of 55.1%. Seventy-two subjects had a positive FOBT. Detection rates for cancer and adenomas were 1.8 per thousand and 16.6 per thousand, respectively. Positive predictive values (PPVs) for cancer and adenomas were 4.5% and 40.3%, respectively. CONCLUSIONS: Screening had an adequate attendance rate and the majority of the indicators were satisfactory. The use of a one-day quantitative latex FOBT with no dietary restrictions, automation of the analytical procedure, and a positive threshold of 100 ng/ml has shown that a programme based on this test is feasible in both organizational and attendance terms. On the basis of this experience, the extension of the screening on a regional basis is suggested.

Screening for colorectal cancer by faecal occult blood test: comparison of immunochemical tests.

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.

Cost analysis in a population based screening programme for colorectal cancer: comparison of immunochemical and guaiac faecal occult blood testing.

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.

Basic variables at different positivity thresholds of a quantitative immunochemical test for faecal occult blood.

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.

Selection criteria in colorectal cancer screening.

The authors report the results of a risk questionnaire (RQ) used in a population-based screening program for colorectal cancer. The positive predictive value (PPV) for cancer or adenoma was evaluated for the Hemoccult test (HO) and for all RQ items (symptoms, personal and familial risk) in 8,114 cases, by univariate and multivariate analysis. A significant correlation with the presence of cancer or adenoma was observed for HO-positive tests, whereas a significant correlation was absent for most RQ variables. The use of an RQ in screening practice is disregarded since it does not improve the rate of cancer detection. Moreover, the increase in the detection rate of HO-negative adenomas does not justify the high rate (0.18) of screening responders selected for endoscopic diagnostic workup, a figure which influences negatively the overall compliance to screening.

Hemoccult sensitivity estimate in a screening program for colorectal cancer in the Province of Florence.

The sensitivity of Hemoccult testing (HO) in a population-based screening for colorectal cancer was evaluated. HO sensitivity estimates were calculated as the ratio of screen-detected HO-positives to total screen or interval-detected cancers. Sensitivity was estimated according to 1, 2, and 3-year rescreening intervals. Corresponding estimates are 69.4%, 61.8% and 57.7%, respectively. No significant correlation was observed between HO sensitivity and other variables, such as calendar period, tumor stage or site, or patient age or sex. HO sensitivity as estimated in the present experience is consistent with other reports of population-based screenings. Screening every year would achieve too limited an increase in sensitivity, compared to biennal screening, to be worth the difficulties of doubling organizational efforts and costs.