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Biomedical subjects

G Castiglione

Publications and source records attributed to G Castiglione.

At least 37 records · Page 2Linked to original sources

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.

Adult↗

Aberrant crypt foci in human colon carcinogenesis.

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.

Adult↗

Immunochemical vs guaiac faecal occult blood tests in a population-based screening programme for colorectal 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.

Adult↗

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.

Adult↗

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)

Adenoma↗

Effect of rehydration on guaiac-based faecal occult blood testing in colorectal cancer screening.

Screening for colorectal cancer by means of unhydrated Hemoccult (HO) is in progress in the Province of Florence since 1982. In 1990 rehydrated HO was introduced in the town of Empoli. Five adjacent municipalities where screening had started in 1987 were selected for comparison. In both areas subjects aged 40-70 were invited by mail to undergo the screening protocol. HO-positive subjects were invited to undergo either pancolonoscopy or a combination of left colonoscopy and double contrast barium enema. HO-negative subjects were invited to repeat screening 2 years later. The positivity rate of HO was significantly higher (P < 0.001) for rehydrated (5%) as compared to unhydrated (3.1%) HO. The positive predictive values for cancer (unhydrated: 5.8%; rehydrated: 8.9%) and for adenomas (unhydrated: 26.7%; rehydrated: 25.5%) did not significantly differ. The detection rates of rehydrated HO were significantly higher as compared to unhydrated HO both for cancer (0.37% vs 0.15%; P < 0.05) and adenomas (1.06% vs 0.72%; P < 0.05%). In the present experience rehydration doesn't produce any decrease in the positive predictive value for cancer or adenomas and the increase in the positivity rate appears quite acceptable when considering the significant increase in the detection rates of cancer and adenomas. We conclude that rehydrated HO should be introduced as the standard test for screening in order to increase sensitivity for colorectal cancer and adenomas.

Adenoma↗

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.

24,25-Dihydroxyvitamin D 3↗

Guaiac and immunochemical tests for faecal occult blood in colorectal cancer screening.

Seven hundred and eighty-six subjects spontaneously referring to our Center performed two guaiac (Rehydrated Hemoccult II (R.HO), and Hemoccult Sensa (HO S.)), and two immunochemical (OC Hemodia (Hdia) and Hemeselect (Hsel)) faecal occult blood tests on three consecutive faecal determinations. The positivity rates of 3 day R.HO, HO S., Hdia, and Hsel were 4.8%, 5.6%, 8.4% and 11.2% respectively. One hundred and thirty-five of the 150 subjects with at least one positive test completed the diagnostic work-up. Cancer was detected in three subjects and adenomas in 15. Three-day specificity estimates of R.HO, HO S., Hdia and Hsel in the overall series were 96.1%, 96.0%, 93.8% and 91.2% respectively, the differences between guaiac and immunochemical tests being significant. Corresponding values of specificity as determined on the first faecal sample only in the overall series were 98.1%, 98.3%, 96.1% and 94.9% respectively. No significant difference in specificity is evident when 3-day guaiac tests are compared to 1-day immunochemical ones. Three-day immunochemical testing is not recommended for screening purposes due to its very low specificity. Nevertheless, 1-day immunochemical testing is almost as specific as 3-day guaiac testing. A preliminary estimate of colonic neoplasms detection rates shows no difference as well. The benefit of 1-day testing on screening acceptability is evident, but the impact on sensitivity should be evaluated in a screening situation with a proper study design and a larger sample size.

Carcinoma↗

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.

Adult↗

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.

Adult↗

The double contrast barium enema in the identification of proximal colonic adenomas and carcinomas beyond the limits of fiberoptic sigmoidoscopy.

Eight hundred and twenty patients were examined by fiberoptic sigmoidoscopy (SIG) and double contrast barium enema (DCBE) to detect colonic cancers or adenomas. Cancer or adenoma in the bowel tract proximal to the upper limit of SIG insertion was detected in 4 patients and in 12 on DCBE. The DCBE detection rate of proximal colonic lesions varied according to the hemoccult (HO) outcome. This was 1.16% for cancer and 2.03% for adenoma in HO+ patients and null for cancer and 1.23% for adenoma in HO- patients. The detection rate of proximal adenomas was higher in patients who presented adenomas on endoscopy in the distal bowel (SIG+), 2.46% as compared to 0.48% in SIG- patients, independent of the HO reports. Routine DCBE is practically useless in HO-SIG- patients and questionable in HO-SIG+ patients since improvement of the detection rate is null for cancer and moderate for adenoma. It is recommended for HO+ patients because it increases the colonic cancer detection rate (10.5% in this study).

Adenoma↗

EHDP-induced rachitic syndrome in rats is not reversed by vitamin D metabolites.

To examine whether either of the two known active vitamin D metabolites 1,25(OH)2D3 or 24,25(OH)2D3 could reverse the mineralization defect induced by 1-hydroxyethylidene-1,1-bis phosphonate (EHDP), a model of EHDP-induced rickets was used. Rats at the age of 31 days were injected for 10 consecutive days with EHDP (10 mg/kg). Other littermates were treated with a combination of EHDP and either 1,25(OH)2D3 or 24,25(OH)2D3 or were treated following 10 days of EHDP, with either of the vitamin D metabolites for an additional 72 hr. 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 microscope studies of growth plate cartilage and bone. EHDP-treated rats revealed signs of typical rickets, manifested by widened growth plates and impaired bone mineralization. Transmission electron microscope (TEM) examination revealed matrix vesicles distributed throughout the growth plate; however, there appeared to be an arrest of the spread of the crystals at the provisional zone of calcification. Treatment with either 1,25(OH)2D3 or 24,25(OH)2D3 failed to reverse the rachitic condition of the animals. Serum calcium blood levels were elevated in the 1,25(OH)2D3 and EHDP-treated group. 1,25(OH)2D3 and 24,25(OH)2/D3 further increased the already elevated serum alkaline phosphatase levels observed in EHDP rats, although the increase observed with 1,25(OH)2D3 was not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

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.

Animals↗

Billroth I versus Billroth II partial gastrectomy in the treatment of gastric ulcer.

Short- and long-term results of B-I and B-II reconstructions were compared in order to assess which anastomosis is to be recommended after partial gastrectomy for gastric ulcer. All the patients (287) electively operated for gastric ulcer 10-20 years ago were considered for the study. Operative mortality did not significantly differ, while duration of post-operative time before discharge and post-operative morbidity were significantly lower after B-I. Long-term percentage probability of survival was higher after B-I than after B-II (87.0 and 63.7 after 19 years, respectively), while quality of life was similar in the two groups. In the 64 subjects (26 B-I and 38 B-II) who underwent the study protocol, fasting bile reflux appeared more abundant and bile acid concentration greater after B-II than after B-I. While bacteria and nitrite concentrations did not differ in the two groups, bile acid pattern differed in a greater deoxycholic acid percentage concentration in the B-II group. In spite of an increased deoxycholic acid concentration and therefore a probably more lithogenic bile, gallstones were shown in 23.11% and 39.41% of the B-I and the B-II subjects, respectively, without significant differences. In conclusion, when partial gastrectomy is indicated for gastric ulcer, B-I reconstruction seems preferable to B-II because of its lower post-operative mobility, less evident entero-gastric reflux and histological consequences, less evident bile acid pattern changes from normal, and an apparently longer life-expectancy after discharge.

Adult↗

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.

24,25-Dihydroxyvitamin D 3↗