The community pharmacy model for colorectal cancer screening: Policy insights from a national programme.

BACKGROUND: In Italy, a recent national project has expanded local collaboration between colorectal (CRC) screening programmes and pharmacies to the national level. OBJECTIVE: The objective of this study is to provide an overview of the existing agreements between regional authorities and pharmacy owners in Italy regarding CRC screening programmes, to make internationally available the most qualifying elements of the collaboration. METHODS: We analyzed the agreements, in force on 01/08/2021, arranged between the Regions and their respective pharmacy owners, describing the process phases addressed such as the faecal occult blood test pathway and supplementary activities provided by the pharmacies together with the CRC screening kit delivery. RESULTS: Agreements were received from 18 Regions (86% of the total). The amount of money paid for each kit varies a lot, with a range from 0 to 18 EUR. The number of process phases covered by the agreements ranged from a maximum of 16 (out of 18) to a minimum of 0. The processes most frequently covered were the supply/delivery of kits and education/awareness of CRC screening (68.8%). Less covered processes were warehouse management and awareness of other healthcare initiatives (12.5%), and delivery of preparation for intestinal cleansing (6.3%). CONCLUSIONS: Arrangements between pharmacies and CRC screening programmes in Italy vary widely and lack a unified model. Collaboration quality standards should be set at the national/international level.

hr-HPV testing in the follow-up of women with cytological abnormalities and negative colposcopy.

BACKGROUND: The follow-up after abnormal Pap smear and negative colposcopy is not clearly defined. This study aimed at investigating the role of hr-HPV testing in the management of abnormal Pap test and negative colposcopy for Cervical Intraepithelial Neoplasia grade 2 or worse (CIN2+). methods: The study enrolled 1029 women with abnormal screening cytology (years 2006-2010) and negative colposcopy for CIN2+, which subsequently performed a hr-HPV test. Incident CIN2+ lesions were identified through linkage with cancer registry, hospital discharge records, neoplastic pathology reports and the archive of screening programme (2006-2011). RESULTS: During the follow-up, the cohort developed 133 CIN2+ lesions; only one among hr-HPV-negative women. The probability of developing CIN2+ on follow-up time was 0.44% (95% confidence interval (CI) 0.1-3.1) and 41.8% (95% CI 31.8-53.5) for hr-HPV-negative women and hr-HPV-positive women, respectively. A woman with a positive hr-HPV test had about 105 times higher probability of developing a CIN2+ lesion than a woman with a negative hr-HPV test (hazard ratio (HR)=104.5, 95% CI 14.5-755.1), adjusted for index Pap test result, age and cervix squamocolumnar junction visualisation. CONCLUSION: Our results confirm that hr-HPV testing is able to select the real group of women at risk of developing CIN2+ lesions in the follow-up of abnormal cytology and first negative colposcopy.

Quality indicators in breast cancer care.

To define a set of quality indicators that should be routinely measured and evaluated to confirm that the clinical outcome reaches the requested standards, Eusoma has organised a workshop during which twenty four experts from different disciplines have reviewed the international literature and selected the main process and outcome indicators available for quality assurance of breast cancer care. A review of the literature for evidence-based recommendations have been performed by the steering committee. The experts have identified the quality indicators also taking into account the usability and feasibility. For each of them it has been reported: definition, minimum and target standard, motivation for selection and level of evidence (graded according to AHRO). In overall 17 main quality indicators have been identified, respectively, 7 on diagnosis, 4 on surgery and loco-regional treatment, 2 on systemic treatment and 4 on staging, counselling, follow-up and rehabilitation. Breast Units in Europe are invited to comply with these indicators and monitor them during their periodic audit meetings.

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.

Sensitivity of latex agglutination faecal occult blood test in the Florence District population-based colorectal cancer screening programme.

We evaluated the sensitivity for colorectal cancer (CRC) of the latex agglutination test (LAT), an immunochemical test routinely used in the Florence District screening programme since 2000. Sensitivity was calculated by the proportional interval cancer incidence method in a population of 27,503 consecutive subjects screened in 2000-2002, interval cancers being identified by linkage to the Tuscany Cancer Registry files. Sensitivity was calculated overall and by gender, age, time since last negative LAT, CRC site, and rank of screening. Overall 1- and 2-year sensitivity estimates were 80.7 and 71.5%, respectively, suggesting that faecal occult blood testing screening sensitivity may be suboptimal due to testing or programme quality problems. Increasing screening sensitivity might be achieved if the detection rate of advanced adenomas could be increased without unacceptable loss in specificity.

Association of FOBT-assessed faecal Hb content with colonic lesions detected in the Florence screening programme.

We assessed the correlation between quantitative results of immunological faecal occult blood testing (I-FOBT) and colonic lesions (191 colorectal cancers, 890 adenomas) detected at colonoscopy in 2597 FOBT+ (cutoff 100 ng ml(-1) Hb) subjects. At univariate analysis, a higher average faecal Hb content was significantly associated with male gender (P=0.003), age (P=0.02), and colonoscopy findings (P=0.000). Among adenomas, higher faecal Hb content was significantly associated with size (P=0.0000), presence of severe dysplasia (P=0.0001), presence of villous component (P=0.0002), and location in the left colon (P=0.003). At multivariate analysis adjusting for potential confounders, age (P=0.03), size (P=0.0000), and location in the left colon (P=0.0005) were confirmed as having an independent association with higher faecal Hb content. Immunological FOBT is confirmed to be a specific screening test to detect cancer and adenoma, with a low positivity rate (3.7%) and a high positive predictive value (41.5%). Faecal Hb content is significantly higher for those lesions (cancer and high-risk adenomas) screening is aimed at detecting.

The role of arbitration of discordant reports at double reading of screening mammograms.

OBJECTIVE: To asses the effectiveness of arbitration of discordant double readings in mammography screening. DESIGN: A retrospective study of 1217 consecutive arbitrations. SETTING: A subset of discordant double readings from the Florence screening programme underwent arbitration by a third reader. RESULTS: Positive arbitration of 1217 discordant double readings prompted assessment in 476 cases (39.2%), detecting 30 cancers (6.3%). Of 741 negative arbitrations (60.8%), 311 have been followed up thus far, and two cancers (0.64%) occurred in the site previously suspected at one of the two independent readings. Arbitration had a sensitivity of 86.3% and a negative predictive value of 99.3%. Arbitration reduced the overall referral rates from 3.82% to 2.59% (relative decrease 32.1%). Due to false-negative arbitration, cancers detected per 1000 women screened would decrease from 4.58 to 4.50 (relative decrease 1.7%). For every cancer missed due to false-negative arbitration, 151 unnecessary recalls and 21,248 euro would have been saved, whereas the saved cost per screened woman due to arbitration was 1.72 euro. DISCUSSION: Arbitration of discordant double reading would substantially reduce referral rates with a limited reduction in cancer detection rate, and may be recommended as a routine procedure. Greater benefit from arbitration might be expected in the presence of high referral rates at independent double reading, a common scenario in a newly implemented service screening.

Second reading of screening mammograms increases cancer detection and recall rates. Results in the Florence screening programme.

OBJECTIVE: To assess double reading effectiveness in mammography screening. DESIGN: Retrospective study of 177,631 consecutive mammograms double read during 1998-2003. SETTING: The Florence screening programme, involving 11 trained radiologists. Abnormalities reported by at least one reader prompted assessment. RESULTS: The referral rate was 2.89% for the first reader, 3.15% for the second reader, and 3.59% for either reader. Of 713 total cancers detected, 43 were suspected only by the second reader (6.4% relative, 0.024% increase in absolute detection rate) and had a lower stage compared to the first reader (pTis-pT1b = 65.7 versus 52.0%): 41 were reviewed and classified (error type) as "minimal sign" in six, and "screening error" in 35 cases, or as BI-RADS 3 in one, 4a in 20, 4b in 13, and 4c in three cases. The second reading cost was 2.70 per woman examined, or 11,168 per additional cancer detected (versus 11,585 at a single reading). DISCUSSION: Second reading is effective in detecting a limited number of additional cancer cases. Tumour stage (one-third over 1 cm in diameter) and review findings (high rate of "screening errors" and BI-RADS R4b-c categories) suggest that second reading detects small "difficult cases" as well as larger cancers missed due to fatigue or loss of attention. Second reading reduces screening specificity to a minor extent, and since cancer detection at second reading seems cost-effective the procedure is recommendable in routine practice.

Comparison of early performance indicators for screening projects within the European Breast Cancer Network: 1989-2000.

In 1989 the European Breast Cancer Network (EBCN) was established by the first pilot projects for breast cancer screening, co-funded by the Europe Against Cancer programme. We report early performance indicators for these EBCN projects while taking into account their organizational setting. Out of 17 projects in the network, 10 projects from six European countries contributed aggregated data on number of invitations, screening examinations, and breast cancers detected over the period 1989-2000. Results were summarized separately for projects in centralized versus decentralized health care environments. The European Guidelines for quality assurance in mammography screening provided reference values for the performance indicators. The most prominent finding in this study was the higher participation rate in centralized versus decentralized projects (average participation in 1998: 74 versus 33%; P<0.001), whereas the invitation system and screening policy in these projects were similar. Detection rates and characteristics of cancers detected at initial and subsequent screening examinations showed no significant differences between centralized and decentralized projects. Even though early performance indicators for centralized versus decentralized projects were similar, the impact of breast screening on mortality from this disease at the population level will differ since the decentralized projects reach only part of the target population.

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.

Colorectal cancer screening by fecal occult blood testing: results of a population-based experience.

AIMS AND BACKGROUND: The study evaluated the results of an experimental screening protocol for colorectal cancer by fecal occult blood testing in a municipality of the Province of Florence. METHODS: A total of 15,235 subjects aged 50-70 years were invited to perform a 1-day immunochemical fecal occult blood testing without any dietary restrictions. All eligible subjects were sent a personal invitation letter, followed by a postal reminder to non-responders. Subjects with a negative stool test were advised to repeat screening after 2 years. Subjects with a positive screening test were invited to undergo full colonoscopy or a combination of left colonoscopy and a double contrast barium enema. RESULTS: A total of 6,418 subjects performed the screening test, with an overall compliance of 42.1%. A total of 268 compliers had positive test results. The positivity rate was 4.2%. Detection rate for cancer and for adenomas was 5.1% and 11.6%, respectively. The positive predictive value was 14.3% for cancer and 32.5% for adenoma. A higher compliance was recorded in subjects born in the province of Florence or living in the centre of the town, in married subjects, and in women. The best results in compliance were associated with the direct distribution of fecal occult blood testing kits by general practitioners to their outpatients. CONCLUSIONS: The study provides useful information about the efficiency and feasibility of a screening program for colorectal cancer using fecal occult blood testing. Compliance results confirm the importance of GP involvement in oncological screening.

Do patients with rectosigmoid adenomas 5 mm or less in diameter need total colonoscopy?

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.

Substance P and vasoactive intestinal polypeptide but not calcitonin gene-related peptide concentrations are reduced in patients with moderate and severe ulcerative colitis.

BACKGROUND AND AIMS: Ulcerative colitis is a chronic inflammatory condition characterized by an altered intestinal immunoinflammatory response. Since increasing evidence indicates that neuropeptides play a key role in the regulation of gastrointestinal immune function, the aims of this study were: a) to determine tissue and plasma levels of Vasoactive Intestinal Polypeptide, Substance P, and Calcitonin Gene-Related Peptide in patients with ulcerative colitis, and b) to ascertain whether a relationship exists between tissue concentrations of neuropeptides and the histological grading of mucosal inflammation. METHODS: A total of 29 patients with active and 39 with inactive ulcerative colitis, and 16 control subjects took part in the study. Biopsy specimens of colonic mucosa and blood samples were obtained from each subject, and neuropeptide concentrations were measured by sensitive and specific radioimmunoassays. RESULTS: Both Vasoactive Intestinal Polypeptide and Substance P concentrations were found to be significantly reduced in endoscopic biopsy specimens of patients with ulcerative colitis compared to controls (p < 0.01 and p = 0.05, respectively), and the reduction appeared to be related to the degree of mucosal inflammation; in contrast, Calcitonin Gene-Related Peptide tissue levels were unchanged. In addition, there was no significant difference in the neuropeptide plasma levels between ulcerative colitis patients and control subjects. CONCLUSIONS: Taken together, our results suggest that the reduction of Vasoactive Intestinal Polypeptide and Substance P is probably a secondary phenomenon, correlated with the degree of mucosal inflammation; whatever the mechanism, the decreased availability of these neuropeptides in the local microenvironment may play an important role in the pathogenesis of ulcerative colitis, by affecting many components of the normal immune response. Moreover, based on our data, the measurement of neuropeptide plasma concentrations does not appear to be a useful tool to monitor disease activity.

Distal hyperplastic polyps do not predict proximal adenomas: results from a multicentric study of colorectal adenomas.

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.

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.

Effect of octreotide on neuroenolase levels in patients with small cell lung cancer.

AIMS AND BACKGROUND: The somatostatin analog octreotide has an antiproliferative effect on small cell lung cancer lines in vitro and in experimental xenograft transplantation systems in vivo. Thus it is worth investigating octreotide activity in the clinical setting. METHODS: We studied the effect of octreotide (200 micrograms three times a day subcutaneously for seven days) on serum levels of the tumor marker neuroenolase in 13 patients with small cell lung cancer. RESULTS: A decrease in neuroenolase levels was observed at day 7 during octreotide treatment, with a mean +/- SD of 32.6 +/- 42.0 ng/ml compared to basal values of 44.4 +/- 57.7 ng/ml and to washout values of 50.3 +/- 65.7 ng/ml (P < 0.03). CONCLUSIONS: Our results indicate that octreotide is effective in reducing neuroenolase levels in small cell lung cancer patients. These data suggest a possible role for octreotide in the treatment of this kind of tumor.

Concurrent carboplatin (CBDCA), vindesine (VDS) and radiotherapy in stage III non small cell lung cancer (NSCLC).

AIMS: Aim of the study was to test, in a cooperative and prospective trial, the effectiveness and feasibility of a chemoradio-therapy program in stage III non small cell lung cancer (NSCLC). METHODS: The schedule consisted in carboplatin (CBDCA) 150 mg/m2/iv on days 1, 3, 5 and vindesine VDS 2.5 mg/m2/iv on days 1, 8, 15, 22 every 4 weeks for 2 cycles followed by radiotherapy 60 Gy with CBDCA 50 mg/m2 weekly as radioenhancer. The same schedule was proposed as neoadjuvant treatment in 10/47 patients (stage III A) and as exclusive treatment in 37/47 (stage III B) admitted patients. RESULTS: In the neoadjuvant subgroup partial remission was obtained in 5/10 patients, and 3 of them underwent surgery with consequent CR. In the stage III B subgroup, 2 complete remissions were obtained (survival 14 and 9+ months). Toxicity was mild. CONCLUSIONS: Our results confirm the feasibility of the schedule in stage III NSCLC.

Capsaicin-induced release of neurokinin A from muscle and mucosa of gastric corpus: correlation with capsaicin-evoked release of calcitonin gene-related peptide.

It has been proposed that capsaicin-sensitive nerves might participate in a gastric defence mechanism, possibly via a local release of sensory neuropeptides. In this study, it was examined whether capsaicin might induce the release of neurokinin A (NKA), substance P (SP) and calcitonin gene-related peptide (CGRP) from different regions of rat stomach. Firstly, the tissue content of NKA-, SP- and CGRP-like immunoreactivity (LI) was measured in the fundus, in the corpus, in the muscle layer and in the mucosa of corpus of control rats and rats pre-treated with systemic capsaicin, s.c. (50 mg/kg as newborn). A large depletion (about 80%) of CGRP-LI following capsaicin treatment was observed in all regions examined, while no difference was observed for NKA-LI and SP-LI. NKA-LI, SP-LI and CGRP-LI release induced by capsaicin was measured in different regions of the rat stomach. Both in the gastric fundus and in the corpus, capsaicin (10 microM) produced a remarkable release of of CGRP-LI and NKA-LI, but not of SP-LI. A second administration of the drug had no longer effect, indicating desensitization. In the gastric corpus, the capsaicin-induced NKA-LI and CGRP-LI release was larger from the muscle layer than from the mucosa. The present findings provide neurochemical evidence that both NKA-LI and CGRP-LI are released from different regions of the rat stomach and both peptides should therefore be taken into account when considering the efferent function of capsaicin-sensitive primary afferents at gastric level.

Ruthenium red selectively antagonizes capsaicin-induced release of vasoactive intestinal polypeptide (VIP) from the human colon.

Ruthenium red (RR) is an inorganic dye that has shown to block the actions of capsaicin on primary sensory neurons in different animal models. The aim of this study was to assess whether RR is able to antagonize the release of vasoactive intestinal polypeptide (VIP) evoked by capsaicin in the human colon. Samples of descending colon were collected from patients undergoing colectomy for carcinoma of the colon. Tissue slices from the muscle of human colon were exposed to either 10 microM capsaicin or an isotonic high K+ medium (KCl 80 mM), in the absence or presence of 10 microM RR. Either capsaicin or high K+ produced a prompt release of VIP. RR (10 microM) completely antagonized the capsaicin-induced release of VIP from muscle of human colon. This effect was elective, since VIP release evoked by high K+ was unaffected by the presence of RR. These findings indicate that RR acts as a selective antagonist of capsaicin in human tissue and that the mechanism underlying peptide release by capsaicin is preserved across species. Multiple mechanisms leading to VIP release exist in the human colon.

Decrease of duodenal calcitonin gene-related peptide- and substance P-like immunoreactivity in rat duodenal ulcers.

We have investigated the endogenous levels of duodenal calcitonin gene-related peptide- (CGRP) and Substance P- (SP) like immunoreactivity (li) following the induction of duodenal ulcers in rats. Using three duodenal ulcerogens, namely cysteamine, dulcerozine or mepirizole given in a single oral dose, a decrease of duodenal CGRP-li and SP-li was observed. Time-relationship studies of this phenomenon show that CGRP-li and SP-li were decreased concomitantly to the formation of gastroduodenal ulcers after the administration of cysteamine (900 mg/kg p.o.). Pretreatment with the selective sensory neurotoxin capsaicin induced CGRP-li decrease in the duodenum, which was not further decreased by an ulcerogenic dose of cysteamine, indicating that cysteamine induced a release of CGRP-li of capsaicin-sensitive origin. Otherwise duodenal SP-li was not sensitive to capsaicin pretreatment and its duodenal content decreased by cysteamine originates from an intrinsic source. Our observations indicate that CGRP and SP may play an important local role in duodenal ulcerogenesis.