Towards texture accurate slice interpolation of medical images using PixelMiner.

Quantitative image analysis models are used for medical imaging tasks such as registration, classification, object detection, and segmentation. For these models to be capable of making accurate predictions, they need valid and precise information. We propose PixelMiner, a convolution-based deep-learning model for interpolating computed tomography (CT) imaging slices. PixelMiner was designed to produce texture-accurate slice interpolations by trading off pixel accuracy for texture accuracy. PixelMiner was trained on a dataset of 7829 CT scans and validated using an external dataset. We demonstrated the model's effectiveness by using the structural similarity index (SSIM), peak signal to noise ratio (PSNR), and the root mean squared error (RMSE) of extracted texture features. Additionally, we developed and used a new metric, the mean squared mapped feature error (MSMFE). The performance of PixelMiner was compared to four other interpolation methods: (tri-)linear, (tri-)cubic, windowed sinc (WS), and nearest neighbor (NN). PixelMiner produced texture with a significantly lowest average texture error compared to all other methods with a normalized root mean squared error (NRMSE) of 0.11 (p < .01), and the significantly highest reproducibility with a concordance correlation coefficient (CCC) ≥ 0.85 (p < .01). PixelMiner was not only shown to better preserve features but was also validated using an ablation study by removing auto-regression from the model and was shown to improve segmentations on interpolated slices.

Exploring imaging features of molecular subtypes of large cell neuroendocrine carcinoma (LCNEC).

OBJECTIVES: Radiological characteristics and radiomics signatures can aid in differentiation between small cell lung carcinoma (SCLC) and non-small cell lung carcinoma (NSCLC). We investigated whether molecular subtypes of large cell neuroendocrine carcinoma (LCNEC), i.e. SCLC-like (with pRb loss) vs. NSCLC-like (with pRb expression), can be distinguished by imaging based on (1) imaging interpretation, (2) semantic features, and/or (3) a radiomics signature, designed to differentiate between SCLC and NSCLC. MATERIALS AND METHODS: Pulmonary oncologists and chest radiologists assessed chest CT-scans of 44 LCNEC patients for 'small cell-like' or 'non-small cell-like' appearance. The radiologists also scored semantic features of 50 LCNEC scans. Finally, a radiomics signature was trained on a dataset containing 48 SCLC and 76 NSCLC scans and validated on an external set of 58 SCLC and 40 NSCLC scans. This signature was applied on scans of 28 SCLC-like and 8 NSCLC-like LCNEC patients. RESULTS: Pulmonary oncologists and radiologists were unable to differentiate between molecular subtypes of LCNEC and no significant differences in semantic features were found. The area under the receiver operating characteristics curve of the radiomics signature in the validation set (SCLC vs. NSCLC) was 0.84 (95% confidence interval (CI) 0.77-0.92) and 0.58 (95% CI 0.29-0.86) in the LCNEC dataset (SCLC-like vs. NSCLC-like). CONCLUSION: LCNEC appears to have radiological characteristics of both SCLC and NSCLC, irrespective of pRb loss, compatible with the SCLC-like subtype. Imaging interpretation, semantic features and our radiomics signature designed to differentiate between SCLC and NSCLC were unable to separate molecular LCNEC subtypes, which underscores that LCNEC is a unique disease.

Clinical risk factors of colorectal cancer in patients with serrated polyposis syndrome: a multicentre cohort analysis.

OBJECTIVE: Serrated polyposis syndrome (SPS) is accompanied by an increased risk of colorectal cancer (CRC). Patients fulfilling the clinical criteria, as defined by the WHO, have a wide variation in CRC risk. We aimed to assess risk factors for CRC in a large cohort of patients with SPS and to evaluate the risk of CRC during surveillance. DESIGN: In this retrospective cohort analysis, all patients with SPS from seven centres in the Netherlands and two in the UK were enrolled. WHO criteria were used to diagnose SPS. Patients who only fulfilled WHO criterion-2, with IBD and/or a known hereditary CRC syndrome were excluded. RESULTS: In total, 434 patients with SPS were included for analysis; 127 (29.3%) were diagnosed with CRC. In a per-patient analysis ≥1 serrated polyp (SP) with dysplasia (OR 2.07; 95% CI 1.28 to 3.33), ≥1 advanced adenoma (OR 2.30; 95% CI 1.47 to 3.67) and the fulfilment of both WHO criteria 1 and 3 (OR 1.60; 95% CI 1.04 to 2.51) were associated with CRC, while a history of smoking was inversely associated with CRC (OR 0.36; 95% CI 0.23 to 0.56). Overall, 260 patients underwent surveillance after clearing of all relevant lesions, during which two patients were diagnosed with CRC, corresponding to 1.9 events/1000 person-years surveillance (95% CI 0.3 to 6.4). CONCLUSION: The presence of SPs containing dysplasia, advanced adenomas and/or combined WHO criteria 1 and 3 phenotype is associated with CRC in patients with SPS. Patients with a history of smoking show a lower risk of CRC, possibly due to a different pathogenesis of disease. The risk of developing CRC during surveillance is lower than previously reported in literature, which may reflect a more mature multicentre cohort with less selection bias.

Is early Weight Bearing Allowed in Surgically Treated Talar Neck Fractures?

INTRODUCTION: Non-or partial weight bearing is frequently the standard treatment after peri-articular lower extremity fractures. Displaced talar neck fractures are severe injuries compromising vascularity of the corpus and consequently are at risk for non-union and avascular necrosis, the main reason to restrict weight bearing for up to three months according to most literature. CASE PRESENTATION: We report a case of a 31-year old male with a high impact car accident. His pelvic ring and Hawkins II talar fracture were treated by open reduction and internal fixation. Rehabilitation was based on permissive weight bearing following wound healing. His fractures healed uneventfully and he was able to run freely, without any discomfort within 8 weeks. Radiological evaluation of the talus showed complete bone healing without signs of avascular necrosis. At one year follow-up, the patient is free of the symptoms. CONCLUSION: We might consider changing the restricted or non-weight bearing protocol in surgically treated talar neck fractures at our centre and allow early weight bearing, based on body awareness and the creation of a safe environment during the rehabilitation phase.

Definition and taxonomy of interval colorectal cancers: a proposal for standardising nomenclature.

OBJECTIVE: Interval colorectal cancers (interval CRCs), that is, cancers occurring after a negative screening test or examination, are an important indicator of the quality and effectiveness of CRC screening and surveillance. In order to compare incidence rates of interval CRCs across screening programmes, a standardised definition is required. Our goal was to develop an internationally applicable definition and taxonomy for reporting on interval CRCs. DESIGN: Using a modified Delphi process to achieve consensus, the Expert Working Group on interval CRC of the Colorectal Cancer Screening Committee of the World Endoscopy Organization developed a nomenclature for defining and characterising interval CRCs. RESULTS: We define an interval CRC as a "colorectal cancer diagnosed after a screening or surveillance exam in which no cancer is detected, and before the date of the next recommended exam". Guidelines and principles for describing and reporting on interval CRCs are provided, and clinical scenarios to demonstrate the practical application of the nomenclature are presented. CONCLUSIONS: The Working Group on interval CRC of the World Endoscopy Organization endorses adoption of this standardised nomenclature. A standardised nomenclature will facilitate benchmarking and comparison of interval CRC rates across programmes and regions.

Quality colonoscopy and risk of interval cancer in Lynch syndrome.

PURPOSE: Despite colonoscopic surveillance, Lynch syndrome patients develop colorectal cancer (CRC). Identification of modifiable factors has the potential to improve outcome of surveillance. The aims of this study were to determine (1) characteristics of patients with CRC, (2) endoscopic and histological features of these cancers, and (3) quality of the previous colonoscopy. METHODS: Approximately 2,200 medical reports from proven and obligate mutation carriers identified at the Dutch Lynch Syndrome Registry and two large hospitals were retrospectively analyzed for the presence of an interval cancer defined as CRC diagnosed within 24 months of previous colonoscopy. RESULTS: Thirty-one interval cancers were detected in 29 patients (median age of 52 [range 35-73]), after a median time of 17 months. All were MLH1 or MSH2 mutation carriers, and 39 % had a previous CRC. In patients without previous surgery for CRC, 84 % was proximally located. Of all interval cancers, 77 % were at local stage (T1-3N0Mx). In three patients (9 %) with an incomplete previous colonoscopy, CRC was located in the unexamined colon. In six of the nine patients with an adenoma during previous colonoscopy, the cancer was detected in the same colonic segment as the previously removed adenoma. CONCLUSIONS: Interval cancers were detected in MLH1 and MSH2 mutation carriers, especially in those with a history of previous CRC and between 40 and 60 years. Interval cancer could be related to incompleteness of previous endoscopy and possibly residual adenomatous tissue. Further reduction of the interval cancer risk may be achieved by optimizing endoscopy quality and individualization of surveillance guidelines.

Nonpolypoid colorectal neoplasms: a challenge in endoscopic surveillance of patients with Lynch syndrome.

BACKGROUND AND STUDY AIMS: Patients with Lynch syndrome may develop colorectal cancer (CRC), despite intensive colonoscopic surveillance. Nonpolypoid colorectal neoplasms might be a major contributor to the occurrence of these cancers. The aim of this case - control study was to compare the endoscopic appearance of colorectal neoplasms between patients with Lynch syndrome and control individuals at average risk for CRC. PATIENTS AND METHODS: The endoscopists at the Maastricht University Medical Center were first given training to ensure familiarity with the appearance and classification of nonpolypoid lesions. Patients with Lynch syndrome and patients at average risk for CRC who underwent elective colonoscopy at the Center were prospectively included. Nonpolypoid lesions were defined as lesions with a height of less than half the diameter, and advanced histology was defined as the presence of high grade dysplasia or early cancer. RESULTS: A total of 59 patients with Lynch syndrome (mean age 48.7 years, 47.5 % men) and 590 matched controls (mean age 50.2 years, 47.5 % men) were included. In patients with Lynch syndrome, adenomas were significantly more likely to be nonpolypoid than they were in controls: 43.3 % vs. 16.9 % (OR 3.60, 95 %CI 1.90 - 6.83; P < 0.001). This was particularly true for proximal adenomas: 58.1 % vs. 16.3 % (OR 6.93, 95 %CI 2.92 - 16.40; P < 0.001). Adenomas containing advanced histology were more often nonpolypoid in patients with Lynch syndrome than in controls (4/5, 80.0 % vs. 5/17, 29.4 %; P = 0.19). Serrated polyps were also more often nonpolypoid in patients with Lynch syndrome than in controls: 49.2 % vs. 20.4 % (OR 3.57, 95 %CI 1.91 - 6.68; P < 0.001). CONCLUSIONS: In patients with Lynch syndrome, colorectal neoplasms are more likely to have a nonpolypoid shape than those from average risk patients, especially in the proximal colon. These findings suggest that proficiency in recognition and endoscopic resection of nonpolypoid colorectal lesions are needed to ensure colonoscopic prevention against CRC in this high risk population.

Endoscopic red flags for the detection of high-risk serrated polyps: an observational study.

BACKGROUND AND STUDY AIMS: In routine practice, colonoscopy may fail to prevent colorectal cancer (CRC), especially in the proximal colon. A better endoscopic recognition of serrated polyps is important, as this pathway may explain some of the post-colonoscopy cancers. In this study, the endoscopic characteristics of serrated polyps were examined. PATIENT AND METHODS: This was a cross-sectional, single-center study of all consecutive patients referred for elective colonoscopy during 1 year. The endoscopists were familiarized with the detection and treatment of nonpolypoid colorectal lesions. Serrated polyps were classified into high risk serrated polyps, defined as dysplastic or large (≥ 6 mm) proximal nondysplastic serrated polyps, and low risk serrated polyps including the remaining nondysplastic serrated polyps. Advanced colorectal neoplasms were defined as multiple (at least three),≥ 10 mm in size, high grade dysplastic adenomas or CRC. RESULTS: A total of 2309 patients were included (46.1 % men, mean age 58.4 years), of whom 2.5 % (57) had at least one high risk serrated polyp and 13.9 % (322) had at least one advanced neoplasm. Overall, serrated polyps were more often nonpolypoid than adenomas (16.2 % vs. 11.1 %; P = 0.002). In total, 65 high risk serrated polyps were found, of which 43.1 % (28) displayed a nonpolypoid endoscopic appearance. Patients with advanced neoplasms were more likely to have synchronous high risk serrated polyps than patients without advanced neoplasms: OR 3.66 (95 % CI 2.03 - 6.61, P < 0.001). CONCLUSIONS: High risk serrated polyps are frequently nonpolypoid and are associated with synchronous advanced colorectal neoplasms. Advanced colorectal neoplasms may therefore be considered red flags for the presence of high risk serrated polyps. Detection, diagnosis, and treatment of high risk serrated lesions may be important targets to improve the quality of colonoscopic cancer prevention.

Ratio between serum IL-8 and pepsinogen A/C: a marker for atrophic body gastritis.

BACKGROUND AND AIMS: Elevated serum gastrin and a low pepsinogen A/C ratio are well-recognized markers for atrophic body gastritis (ABG). We have shown that the presence of body atrophy is also associated with elevated serum pro-inflammatory cytokines. This study tested the hypothesis that serum cytokines provide additional information to gastrin and pepsinogens in screening for ABG. METHODS: Two hundred and twenty-six consecutive patients were investigated on referral for upper gastrointestinal endoscopy: 150 were patients with gastro-oesophageal reflux disease, receiving acid inhibitory medication either with proton pump inhibitors (n = 113) or with histamine2-receptor antagonists (n = 37), and 76 were nontreated controls, who had normal endoscopic findings. Gastric mucosal biopsies were sampled for histological examination (Sydney classification). Serum samples were analyzed for gastrin, chromogranin A (CgA), and pepsinogens A and C by RIA, and for the interleukins (IL)-1beta, IL-6, and IL-8 by ELISA. RESULTS: Subjects with ABG had significantly higher serum gastrin (P < 0.01) and serum CgA (P < 0.01) levels and significantly lower pepsinogen A/C ratios (P < 0.001) than those without ABG. Additionally, serum IL-1beta, IL-6 and, especially, IL-8 levels were significantly higher in the subjects with than in those without ABG (P < 0.0001, for all cytokines). To optimize the detection of body atrophy we defined the ABG index: the ratio between the simultaneously measured IL-8 and pepsinogen A/C. The area under the ROC curve for the ABG index was significantly greater than that for serum gastrin and for serum pepsinogen A/C alone (0.91 +/- 0.029 vs. 0.72 +/- 0.042, and vs. 0.83 +/- 0.031, P = 0.018 and P = 0.049). Using the ABG index at a cut-off value of 1.8 pg mL-1, 91% of the cases were classified correctly. CONCLUSIONS: The ratio between serum IL-8 and pepsinogen A/C accurately predicts the presence of ABG. We therefore propose the ABG index as a noninvasive screening test for ABG in population-based studies.

Screening for colorectal cancer: medical and economic aspects.

BACKGROUND: Colorectal cancer (CRC) is the second commonest cause of cancer death in the Western world. In The Netherlands, CRC causes about 4400 deaths per year, and its diagnosis and treatment make up for a large share of health-care costs. METHODS: Review and discussioN. RESULTS: Experts in the field presently assume that screening for CRC and its precursor lesions, colorectal adenomas (CRAs), could prevent death from colorectal neoplasia by more than 80%. Additionally, there is increasing acknowledgement that CRC screening programmes can save lives at a cost similar to, or even less than, the generally accepted breast cancer or cervical cancer screening programmes. Nonetheless, while neighbouring countries have taken vigorous measures to fight CRC, the Dutch are still hesitating in this matter. This is partly due to some yet unanswered questions concerning the acceptability of screening for CRC in the general population, the starting age and the frequency of screening, the type of screening tests to be used, and the programme organization. In this commentary, general epidemiological and pathogenetic aspects of CRC are addressed. In addition, some frequently asked questions (FAQ) and (very subjective) answers about screening for CRC are offered, as potential substrate for further in-depth discussions. CONCLUSION: The emerging message for the community is that an effective national screening programme is urgently required to reduce the substantial morbidity and mortality from this disease.

Serum chromogranin A as a screening test for gastric enterochromaffin-like cell hyperplasia during acid-suppressive therapy.

BACKGROUND: Serum chromogranin A (CgA), a marker of neuroendocrine neoplasia, increases during profound gastric acid inhibition, possibly reflecting the trophic effect of gastrin on the enterochromaffin-like (ECL) cells. AIMS: This study investigated the clinical value of serum CgA as a screening test for gastric fundic enterochromaffin-like (ECL) cell hyperplasia during acid-suppressive therapy. METHOD: A consecutive series of 230 dyspeptic patients referred for upper gastrointestinal endoscopy was investigated in a cross-sectional design. They were 154 patients on continuous medium-term (6 weeks to one year) or long-term (longer than one year) acid inhibition with either proton pump inhibitors (PPIs, n = 117) or histamine2-receptor antagonists (H2RAs, n = 37) for gastro-oesophageal reflux disease, and 76 nontreated subjects, with normal endoscopic findings (control group). Fasting blood samples were analysed for gastrin and CgA. Gastric biopsy specimens (oxyntic mucosa) were examined for histological evaluation of gastritis (Sydney classification) and of ECL cell hyperplasia (Solcia classification). RESULTS: Serum CgA levels correlated positively with serum gastrin, following a quadratic function (r = 0.78, P < 0.0001). Elevated serum CgA values during long-term acid inhibition correlated with the presence and severity of fundic ECL cell hyperplasia. Multivariate analysis identified hypergastrinaemia (P < 0.0001), duration of acid inhibition (P < 0.0001), H. pylori infection (P = 0.008), ECL cell hyperplasia (P = 0.012), and body gland atrophy (P = 0.043) as independent predictors of elevated serum CgA. In subjects on long-term acid inhibition (n = 123), serum CgA was equally sensitive but more specific than serum gastrin for the detection of ECL cell hyperplasia (sensitivity, 91.3% for both; specificity, 73% vs. 43%, P < 0.0001). CONCLUSIONS: During long-term gastric acid inhibition, serum CgA levels reflect the presence and severity of fundic ECL cell hyperplasia. Serum CgA is therefore a useful screening test for gastric ECL cell proliferative changes within this context.

Double gastric infection with Helicobacter pylori and non-Helicobacter pylori bacteria during acid-suppressive therapy: increase of pro-inflammatory cytokines and development of atrophic gastritis.

BACKGROUND: Long-term acid suppression may accelerate the development of atrophic gastritis in Helicobacter pylori-positive subjects. The pathogenetic mechanism remains unclear. AIM: To test the hypothesis that gastric double infection with H. pylori and non-H. pylori bacterial species-during acid suppression-may result in an enhanced inflammatory response, contributing to the development of atrophic gastritis. PATIENTS AND METHODS: A consecutive series of patients with gastro-oesophageal reflux disease undergoing treatment with proton pump inhibitors (n=113) or histamine2-receptor antagonists (H2-RAs) (n=37), and 76 non-treated dyspeptic controls were investigated. Gastric mucosal H. pylori and non-H. pylori bacteria, histological gastritis, H. pylori serology, and circulating interleukin (IL)-1beta, IL-6, and IL-8 were examined. RESULTS: Patients on acid suppression with either proton pump inhibitors or H2-RAs had a similar prevalence of H. pylori infection to the controls, but a higher prevalence of non-H. pylori bacteria (61% and 60% vs. 29%, P < 0.0001 and P < 0.002). Both the presence of H. pylori and non-H. pylori bacteria were independent risk factors of atrophic gastritis (antrum: relative risks (RRs), 10.1 and 5.07; corpus: RRs, 11.74 and 6.38). A simultaneous presence of H. pylori and non-H. pylori bacteria was associated with a markedly increased risk of atrophic gastritis (antrum: RR, 20.25; corpus: RR, 20.38), compatible with a synergistic effect. Furthermore, the simultaneous presence of both types of bacteria was associated with higher cytokine levels than in patients without any type of bacteria. This increase was also greater than in patients with H. pylori infection alone (P < 0.001, for both IL-1beta and IL-8). SUMMARY AND CONCLUSIONS: H. pylori-positive patients on long-term acid inhibition displayed three features: non-H. pylori bacterial growth; increased cytokine levels; and a higher risk of atrophic gastritis. We suggest that double infection with H. pylori and non-H. pylori bacteria is a major factor in the development of atrophic gastritis during gastric acid inhibition.

Non-Helicobacter pylori bacterial flora during acid-suppressive therapy: differential findings in gastric juice and gastric mucosa.

BACKGROUND: Intragastric growth of non-Helicobacter pylori bacteria commonly occurs during acid-suppressive therapy. The long-term clinical consequences are still unclear. AIM: To investigate the luminal and mucosal bacterial growth during gastric acid inhibition, in relation to the type and duration of acid-inhibitory treatment, as well as to concomitant H. pylori infection. METHODS: A total of 145 patients on continuous acid inhibition with either proton pump inhibitors (n=109) or histamine2-receptor antagonists (H(2)RAs, n=36) for gastro-oesophageal reflux disease, and 75 dyspeptic patients without acid inhibition (control group) were included. At endoscopy, fasting gastric juice was obtained for pH measurement and bacteriological culture. Gastric biopsy specimens were examined for detection of H. pylori (immunohistochemistry) and of non-H. pylori bacteria (modified Giemsa stain-positive and immunohistochemistry-negative at the same location). RESULTS: Non-H. pylori flora was detected in the gastric juice of 92 (41.8%) patients and in the gastric mucosa of 109 (49.6%) patients. In gastric juice, prevalence rate for non-H. pylori bacteria was higher in patients taking proton pump inhibitors than controls and those taking H(2)RAs (58.7% vs. 22.6% and vs. 30.6%, P < 0.0001 and P < 0.003, respectively), but did not differ statistically between H(2)RAs and controls. In gastric mucosa, prevalence rates for non-H. pylori bacteria were higher in patients taking proton pump inhibitors and H(2)RAs than in the controls (antrum: 46.9% and 48.6% vs. 25%, P < 0.05 for both; corpus: 52.2% and 56.8% vs. 23.7%, P < 0.001 for both), but did not differ between proton pump inhibitors and H(2)RAs. Both luminal and mucosal growth of non-H. pylori bacteria were significantly greater in H. pylori-positive than -negative patients taking proton pump inhibitors (P < 0.05 for both). Luminal growth of non-H. pylori flora increased with the intragastric pH level, whilst mucosal bacterial growth increased with the duration of acid inhibition. CONCLUSIONS: Non-H. pylori flora not only contaminates the gastric juice but also colonizes the gastric mucosa of a large proportion of patients treated long-term with acid inhibition. The relationship between H. pylori and non-H. pylori bacteria in the pathogenesis of atrophic gastritis and gastric cancer needs further elucidation.

Changes in gastric mucosa and luminal environment during acid-suppressive therapy: a review in depth.

Acid-suppressive therapy and subsequent changes in gastric mucosa and luminal environment rank highly amongst the investigated issues in gastroenterology over the past two to three decades. Herewith, we present an overview of these intragastric changes, particularly during long-term administration of acid-suppresive medication and concurrent infection with Helicobacter pylori. Current evidence indicates that: i) Long-term acid suppression facilitates the development of fundic ECL cell hyperplasia, especially in the presence of Helicobacter pylori. No neoplastic changes directly attributable to acid suppression have so far been demonstrated in humans. ii) Acid-suppressive therapy increases the risk of enteric infections. iii) Acid-suppressive therapy does not alter fat and mineral bioavailability, but may decrease the absorption of protein-bound vitamin B12. iv) Acid suppression invariably results in intragastric overgrowth of non-Helicobacter pylori bacterial species. The concurrent infection with Helicobacter pylori may promote this bacterial overgrowth and the intragastric formation of N-nitrosamines. v) Acid-suppressive therapy alters the natural course of Helicobacter pylori gastritis, transforming the antral-predominant pattern into a body-predominant pattern, which in turn may progress to body gland atrophy. The pathophysiology of this phenomenon is currently under investigation. vi) In view of the potential adverse effects of acid suppression in the presence of Helicobacter pylori, the screen-and-treat strategy is advocated for Helicobacter pylori in subjects considered for long-term treatment.

Serum gastrin and chromogranin A during medium- and long-term acid suppressive therapy: a case-control study.

BACKGROUND: Serum chromogranin A (CgA) is regarded as a reliable marker of neuroendocrine proliferation. We previously described increased serum CgA levels during short-term profound gastric acid inhibition. AIM: To investigate serum gastrin and CgA levels in dyspeptic patients during continuous medium- (6 weeks to 1 year), or long-term (1-8 years) gastric acid suppressive therapy. PATIENTS AND METHODS: 114 consecutive dyspeptic patients referred for upper gastrointestinal endoscopy were enrolled in a cross-sectional, case-control study [62 patients on continuous antisecretory therapy, either with proton pump inhibitors (n = 47) or H2-receptor antagonists (H2RA) (n = 15) for gastro-oesophageal reflux disease with or without Barrett's oesophagus or functional dyspepsia, and 52 age- and sex-matched patients without medical acid inhibition and with normal endoscopic findings (control group)]. Omeprazole doses ranged from 20 mg to 80 mg daily and ranitidine from 150 mg to 450 mg daily. Fasting serum CgA and serum gastrin levels were measured by radioimmunoassay (reference values: serum CgA < 4.0 nmol/L; serum gastrin < 85 ng/L). RESULTS: Fasting serum CgA levels positively correlated with serum gastrin in the entire study population (r = 0. 55, P = 0.0001). Median serum CgA values were higher in patients treated with a proton pump inhibitor than H2RA [2.8 (2.0-5.9) nmol/L vs. 2 (1.9-2.3) nmol/L, P < 0.002] and controls [2.8 (2.0-5.9) nmol/L vs. 1.8 (1.5-2.2) nmol/L, P < 0.0001) and did not differ between patients treated with H2RA or controls. Serum gastrin and CgA levels in patients on proton pump inhibitor therapy positively correlated with the degree and duration of acid inhibition. Patients on long-term proton pump inhibitor therapy had significantly higher fasting serum gastrin and CgA than those on medium-term proton pump inhibitor therapy [127 (73-217) ng/L vs. 49 (29-78) ng/L, P < 0.0001 and 4.8 (2.8-8) ng/L vs. 2.1 (1.9-2.6) ng/L, P < 0.001]. No such relation was found in patients on medium- vs. long-term H2RA. Overall, patients with positive Helicobacter pylori serology had higher serum gastrin and CgA levels than those with negative H. pylori serology [51 (27-119) ng/L vs. 27 (14-79) ng/L, P = 0.01, 2.4 (1.9-3.4) nmol/L vs. 2.0 (1.7-2.5) nmol/L, P = 0.05]. CONCLUSIONS: During long-term continuous proton pump inhibitor treatment, serum gastrin and CgA levels are significantly elevated compared to H2RA treatment and nontreated dyspeptic controls. H. pylori infection seems to affect gastric ECL cell secretory function. Increased serum CgA values during long-term profound gastric acid inhibition could reflect either gastric enterochromaffin-like cell hyperfunction or proliferative changes.