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Background: Azithromycin is an acid-stable macrolide that achieves remarkably high concentrations in gastric tissue, persisting above the MIC90 for Helicobacter pylori over a period of 5-days, after a single 500 mg oral dose. Aim: To evaluate and compare the efficacy, safety, and tolerability of two eradicating regimens of pantoprazole, azithromycin and tinidazole. Methods: A total of 100 consecutive symptomatic H. pylori-positive patients received pantoprazole 40 mg b.d. for 1 week, and were randomly assigned to either azithromycin 500 mg o.m. and tinidazole 500 mg b.d. during the first 3 days (early group, n = 50) or during the last 3 days of therapy with pantoprazole (late group, n = 50). H. pylori status was assessed by histology and rapid urease test at entry and by histology and 13C-urea breath test 1 month after the end of the therapy. Results: Ninety-nine patients completed the study. H. pylori was eradicated in 86% of patients in the early group (intention-to-treat 86%) and in 88% of patients in the late group (intention-to-treat 88%). Conclusions: This short triple therapy is effective for H. pylori eradication. The compliance was excellent and side-effects negligible. Moreover, the pantoprazole pretreatment did not modify the efficacy of the therapy.

Cell proliferation kinetics of 30 patients affected by extensive ulcerative colitis in remission have been studied with autoradiography of rectal biopsies incubated with tritiated thymidine. The results have been compared with those of 20 control subjects without evidence of colonic diseases, and of 16 patients with multiple nonfamilial colonic adenomas. The labeling index was similar in the three groups (P = NS). On the contrary, the labeling frequency (SEM) in the upper 40% of the crypt (phi h value) was 0.04 +/- 0.01 in controls, 0.16 +/- 0.02 in ulcerative colitis, and 0.10 +/- 0.01 in adenoma patients (P less than 0.001 ulcerative colitis versus controls, P less than 0.01 adenomas versus controls, P = NS ulcerative colitis versus adenomas). The distribution of phi h values in ulcerative colitis showed a bimodal trend with 22 patients having mean phi h values similar to adenoma patients (0.10 +/- 0.01) and 8 with higher values (0.30 +/- 0.02). No relationship was found between phi h values and duration of colitis, age of patients, or age at onset of symptoms. These data show that cell kinetics studies can detect patients at particularly high risk of colon cancer, and that additional factors should determine colon cancer risk level in ulcerative colitis.

AIM: To define the prevalence of gastroesophageal reflux disease (GERD) in mild persistent asthma and to value the effect of pantoprazole therapy on asthmatic symptoms. METHODS: Seven of thirty-four asthmatic patients without GERD served as the non-GERD control group. Twenty-seven of thirty-four asthmatic patients had GERD (7/27 also had erosive esophagitis, sixteen of them presented GERD symptoms. An upper gastrointestinal endoscopy was performed in all the subjects to obtain five biopsy specimens from the lower 5 cm of the esophagus. Patients were considered to have GERD when they had a dilation of intercellular space (DIS) >0.74 mum at transmission electron microscopy. Patients with GERD were treated with pantoprazole, 80 mg/day. Forced expiratory volume in one second (FEV1) was performed at entry and after 6 mo of treatment. Asthmatic symptoms were recorded. The required frequency of inhaling rapid acting beta2-agonists was self-recorded in the patients' diaries. RESULTS: Seven symptomatic patients presented erosive esophagitis. Among the 18 asymptomatic patients, 11 presented DIS, while all symptomatic patients showed ultrastructural esophageal damage. Seven asymptomatic patients did not present DIS. At entry the mean of FEV(1) was 1.91 L in symptomatic GERD patients and 1.88 L in asymptomatic GERD patients. After the treatment, 25 patients had a complete recovery of DIS and reflux symptoms. Twenty-three patients presented a regression of asthmatic symptoms with normalization of FEV(1). Four patients reported a significant improvement of symptoms and their FEV(1) was over 80%. CONCLUSION: GERD is a highly prevalent condition in asthma patients. Treatment with pantoprazole (80 mg/day) determines their improvement and complete regression.

Objective. To examine consecutive patients with Whipple’s disease (WD) for the full clinical spectrum of spondyloarthritis. Methods. Nine consecutive patients, 8 men, 1 woman, with WD were clinically evaluated and examined for clinical and radiological manifestations of spondyloarthritis by 2 rheumatologists with special interest in spondyloarthritis. The mean age of the patients at the time of study and at the time of their initial diagnosis of WD by duodenal biopsy was 62.4 years (range 42–71) and 54.4 years (range 40–62), respectively. Each patient had an anteroposterior radiographic view of the pelvis and also had HLA typing for class I and II alleles. Pelvis radiographs were read blindly for evidence of sacroiliitis. Results. All but one patient had rheumatologic manifestations related to WD. The mean interval between the onset of these symptoms and the diagnosis of WD was 6.1 years (range 1–15). One had recurrent polyarthritis, 1 recurrent oligoarthritis, 3 recurrent monoarthritis, 2 recurrent synovitis with pitting edema of the dorsum of hands and/or feet, and 1 isolated De Quervain’s tenosynovitis. Of the 5 patients with arthritis, 3 also had episodes of swelling with pitting edema over the dorsum of hands and/or feet together with flexor digit tenosynovitis, 2 also had olecranon bursitis, and 1 tibial tenosynovitis. No patient had clinical or radiological manifestations of spondyloarthritis. None had the HLAB27. Conclusion. In Italian Caucasian patients with WD there was no association with spondyloarthritis and HLA-B27.

Background: Helicobacter pylori induces histologic inflammation of mucosa variably correlated to different macroscopic features. Recent studies highlight that the presence of Helicobacter pylori could be assessed on the basis of the macroscopic pattern only, in particular nodularity. The present prospective study has correlated this and other endoscopic features, defined by Sydney classification of gastritis, both to Helicobacter pylori presence and histological patterns. Results: Out of 532 patients, 364 were evaluable. The prevalence of Helicobacter pylori was 51.1% with a different distribution between the endoscopic features. Nodularity showed the highest positive predictive value in detecting the Helicobacter pylori presence (69.9%). The histological findings were: normal 26.9%, non atrophic gastritis 55.2%, atrophic gastritis 17.9%. There was a significant difference between abnormal endoscopic features in detecting the histologic gastritis, with endoscopic atrophy and nodularity showing the highest positive predictive value which reaches 96.7% and 91.8%, respectively. Helicobacter pylori infection and histologic gastritis were also present in 30.9% and 41.8%, respectively, of endoscopically normal subjects. Multivariate analysis has strictly correlated age with all abnormal endoscopic features, metaplasia with endoscopic atrophy, and chronic inflammation (gastritis) with nodularity. Conclusions: The single endoscopic features are poorly correlated with histologic changes and Helicobacter pylori status. Biopsies are mandatory in all cases. The causes of the different macroscopic findings are not yet fully understood.

During the last decade the number of cases of abdominal tuberculosis diagnosed in Western countries has dramatically increased. There are many reasons, including the appearance of AIDS and the increased morbidity of people across the world due to the westward migration of many people coming from areas with a high incidence of tuberculosis. Oesophageal involvement is rare in tuberculosis, occurring mainly as an extension of the disease from the adjacent tuberculous lymph nodes. Fifty-eight cases of oesophageal tuberculosis have so far been reported. We describe a patient affected by oesophageal tuberculosis mimicking secondary oesophageal involvement of mediastinal malignancy.

To evaluate the effect of weight loss induced by dietetic treatment, with or without an intragastric balloon, on gastric emptying of obese subjects.20 morbidly obese subjects (21-54 years, 45.3-58.0 kg/m2) and 20 healthy controls (21-56 years, 20.3-24.8 kg/m2).Parallel study of a 4 month, low calorie dietetic treatment with or without a 500 ml intragastric balloon.In basal conditions, obese subjects had accelerated gastric emptying as compared to healthy controls. At the end of the dietetic treatment period, a significant decrease of body weight was obtained. Patients also showed a slowing of gastric emptying. Both the weight loss and the slowing of gastric emptying occurred irrespective of the presence or absence of the intragastric balloon.The present findings are compatible with the hypothesis that gastric emptying, food intake and body weight are integrated parameters in subjects with morbid obesity.

It has been suggested that colon cancer risk in ulcerative colitis (UC) is correlated to a reduced bioavailability of folate. We studied the effects of folate supplementation on the pattern of rectal cell proliferation in patients affected by long-standing UC. In the rectal mucosa of these patients, an expansion of proliferating cells to the crypt surface is found frequently. This abnormality is considered an intermediate biomarker in chemoprevention trials. Twenty-four patients (13 males; age, 26-70 years; UC duration, 7-34 years) with UC in remission for 1 month at least were assigned randomly to one of the following treatments: (a) folinic acid (15 mg/day) or (b) placebo. Cell proliferation was analyzed through immunohistochemistry on sections of rectal biopsies incubated for 1 hour in a culture medium containing bromodeoxyuridine. Fragments were taken at admission to the study and after 3 months of treatment. As compared to the baseline values, after 3 months of therapy in patients treated with folinic acid, a significant reduction of the frequency of occurrence of labeled cells in the upper 40% of the crypts (phi h value) was observed (0.1836 +/- 0.0278 versus 0.1023 +/- 0.0255; P0.01). On the contrary, no significant proliferative changes were observed in the placebo group. These results suggest that folate supplementation contributes to regulating rectal cell proliferation in patients with long-standing UC. These findings may be significant for chemoprevention of colon cancer in these patients.

Background: Collagenous colitis (CC) and lymphocytic colitis (LC) are chronic inflammatory diseases of the colon with a benign and sometimes relapsing course. Frequency among patients with chronic diarrhea and normal looking colonoscopy is around 10–15%. To date, treatment of CC and LC is not well defined. Data about these conditions are mostly derived from retrospective studies. The aim of the present study was to evaluate the response to treatment and the clinical course of CC and LC in a large group of patients prospectively diagnosed. Methods and Results: A total of 819 patients underwent a colonoscopy because of chronic watery diarrhea and among them we found 41 patients with LC and 23 with CC. These patients were later randomized and assigned to treatment with mesalazine or mesalazine + cholestyramine for 6 months. Fifty-four patients (84.37%) had resolved diarrhea in less than 2 weeks. After 6 months a colonoscopy with biopsies was repeated. Clinical and histological remission was achieved in 85.36% of patients with LC and in 91.3% with CC, with a better result in patients with CC treated with mesalazine + cholestyramine. During a mean period of 44.9 months, 13% of patients relapsed; four with LC and three with CC. They were retreated for another 6 months. At the end of this period one patient with CC was still symptomatic and persistence of CC was confirmed at histology. Conclusions: Treatment with mesalazine seems to be an effective therapeutic option for LC to date, while mesalazine + cholestyramine seems to be more useful in the treatment of CC.

Precancerous duodenal lesions in patients with familial adenomatous polyposis can be detected with duodenoscopy and treatment may prevent the development of cancer. We proposed to determine the frequency, natural history, cumulative risk, and risk factors of the precancerous duodenal lesions in a series of patients diagnosed in northern Italy. METHODS: A prospective, endoscopic, follow-up protocol was performed in 50 patients examined by gastroduodenoscopy at two years of interval or less. The presence and severity of precancerous lesions of the duodenal mucosa were evaluated by Spigelman score. Twenty-five patients (50 percent) had proctocolectomy and ileoanal anastomosis, 15 (30 percent) had colectomy and ileorectal anastomosis, and 5 (10 percent) had proctocolectomy and definitive ileostomy from 0 to 3 years before the admission to the surveillance program. All patients showed more than a thousand adenomas in the colorectal mucosa. No patients with attenuated polyposis were found. RESULTS: At the first endoscopy, duodenal adenomas could be detected in 19 of 50 patients (38 percent), whereas at the end of the follow-up, 43 (86 percent) had duodenal lesions. The final mean Spigelman score increased during the follow-up period (P < 0.001 respect to baseline values). No duodenal cancer could be detected. Eleven patients had or developed severe precancerous duodenal lesions (Stage IV) treated with endoscopic or surgical resection. The istribution of patients with Stage IV according to the surgery of the colon was: 2 of 25 treated with ileoanal anastomosis and 8 of 15 with ileorectal anastomosis (P = 0.0024, Fisher_s exact test). CONCLUSIONS: Patients with familial adenomatous polyposis are at risk of significant neoplasia. The natural history of precancerous lesions might be related to surgical treatment of colorectal neoplasms.

BACKGROUND Many bacteria carry the urease enzyme in different human ecosystems, but Helicobacter pylori is AND AIM: the only known bacterium showing urease activity in gastric ecosystems. For this reason, the rapid urease test (RUT) on gastric biopsies and urea breath test (C-UBT) are used to detect H. pylori infection.The aim of this study was to evaluate the presence of urease-positive bacteria other than H. pylori in gastric juice and mucosa in hypochlorhydric subjects. METHODS: Twenty-five hypochlorhydric and 10 normochlorhydric patients were analyzed for the presence of H. pylori and bacterial overgrowth both in gastric juice and on the mucosa. During upper gastrointestinal endoscopy at 8.00 a.m. gastric juice samples and biopsy specimens were taken from the antrum and corpus. All samples were analyzed using standard microbiological procedures like aerobic/anaerobic growth, gram-staining, gas chromatography, API test, 96-clone method, and selective medium to search for specific bacteria. In addition, all strains isolated were screened for urease activity using the CP-test. Urease positive strains were tested for the capacity to survive in an acid environment with or without urea (10 mM/L), at pH 7, 4, 3, and 2, respectively, at different times (0, 20, 30, and 60 min). RESULTS: Six hypochlorhydric patients had 10 strains of urease-positive non-H. pylori bacteria among which Staphylococcus capitis urealiticum showed the strongest urease activity. CONCLUSIONS: Hypochlorhydric patients present many urease-positive bacteria other than H. pylori. The strong urease activity may be responsible for false positive results at RUT or UBT test in patients with suspected H. pylori infection.

Diarrhea is the most common gastrointestinal symptom of AIDS, affecting 50–90% of patients with a very low CD4 lymphocyte count (1). Together with malabsorption and weight loss, it identifies the so-called wasting syndrome frequently reported during HIV infection (2). The origin of these symptoms is still uncertain since failure to identify an enteric pathogen occurs in as many as 30–40% of all cases. AIDS enteropathy has, thus, been defined as chronic, well-established diarrhea, lasting longer than 1 month, for which no infectious cause can be determined after a complete evaluation including electron microscopy of the small bowel, in patients with documented advanced HIV infection (3–6). The nosologic concept of an HIV enteropathy is supported by the detection of HIV proteins and nucleic acids in various cell types of the gut, such as epithelial cells, but also lymphocytes and macrophages. Although HIV itself does not seem to directly infect enterocytes, it may have an indirect effect via cytokines released from infected lymphoid cells, leading to villous atrophy and crypt atrophy, or, on the contrary, to hyperplasia, and possibly resulting in malabsorption, diarrhea, and weight loss (1, 3, 7).

To value whether omeprazole could induce the healing of DIS and regression of symptoms in patients with DGER.We enrolled 15 symptomatic patients with a pathological esophageal 24-h pH-metry and bilimetry. Patients underwent endoscopy and biopsies were taken from the distal esophagus. Specimens were analyzed at histology and transmission electron microscopy (TEM). Patients were treated with omeprazole 40 mg/d for 3 mo and then endoscopy with biopsies was repeated. Patients with persistent heartburn and/or with an incomplete recovery of DIS were treated for 3 more months and endoscopy with biopsies was performed.Nine patients had a non-erosive reflux disease at endoscopy (NERD) while 6 had erosive esophagitis (ERD). At histology, of the 6 patients with erosive esophagitis, 5 had mild esophagitis and 1 moderate esophagitis. No patients with NERD showed histological signs of esophagitis. After 3 mo of therapy, 13/15 patients (86.7%, P0.01) showed a complete recovery of DIS and disappearance of heartburn. Of the 2 patients treated for 3 more months, complete recovery of DIS and heartburn were achieved in one.Three or 6 mo of omeprazole therapy led to a complete regression of the ultrastructural esophageal damage in 86.7% and in 93% of patients with DGER, NERD and ERD respectively. The ultrastructural recovery of the epithelium was accompanied by regression of heartburn in all cases.

BACKGROUND: Dilation of intercellular spaces (DIS) of human esophageal epithelium, evident at transmission electron microscopy (TEM), is an early marker of damage caused by gastroesophageal reflux, but its reversibility after therapy has not been investigated. AIM: To evaluate whether omeprazole can induce the healing of DIS. METHODS: Thirty-eight symptomatic patients, 22 with nonerosive reflux disease (NERD) and 16 with erosive esophagitis (EE), classified on the basis of 24-h pH monitoring, were enrolled. During upper gastrointestinal endoscopy, six biopsies from apparently normal mucosa were taken within the lower 5 cm of the esophagus for histological and TEM analysis. One hundred computer measurements were taken on TEM photomicrographs of the specimens in each patient. After 3 months of omeprazole 40 mg/die a further endoscopy with biopsies was performed. In patients with persistent heartburn and/or incomplete ultrastructural recovery of esophageal epithelium, a new endoscopy was performed after 3 more months of treatment. RESULTS: After 3 months of therapy, 35 patients (92.1%) showed a complete recovery of DIS and resolution of heartburn. Three patients required 3 more months of therapy because of an incomplete recovery of the epithelium correlated with sporadic heartburn. Healing of the mucosa was achieved in two patients, whereas one had an incomplete recovery of DIS with persistent heartburn. CONCLUSIONS: Three and six months of omeprazole therapy led to a complete recovery of DIS in 92.1% and 97.4% of cases, respectively. No significant differences of DIS between NERD and EE were noted. Complete recovery of DIS was accompanied by regression of heartburn in all cases.

atients affected by familial adenomatous polyposis (FAP) are at risk of developing duodenal neoplasia. Our objective was to detect early abnormalities of the epithelial cell proliferation and ultrastructure of apparently normal duodenal mucosa of FAP patients. Biopsy specimens were taken from the duodenal mucosa. Cell proliferation was studied by immunohistochemistry with proliferating cell nuclear antigen (PCNA), and ultrastructure, by transmission electron microscopy. We found that the PCNA labeling index for duodenal mucosa of patients with FAP was higher in comparison to the case of hospital controls without cancer risk (P = 0.019). Moreover, ultrastructural changes related to an impairment of cell adhesion function were found in all biopies of FAP patients but not in the duodenal mucosa of the controls. We conclude that alterations of cell proliferation kinetics and epithelial adherens junction structures were phenotypic characteristics of histologically normal duodenal mucosa of FAP patients. These abnormalities may be considered as intermediate biomarkers of neoplasia and potential surrogate endpoints in chemoprevention studies. © 2004 Elsevier Inc. All rights reserved

Background: The dilation of oesophageal intercellular spaces, clearly apparent in transmission electron microscopy images, is a marker of cellular damage induced by acid. Aim: To analyse the presence of dilated intercellular spaces and to quantify the scores in controls and in patients with gastro-oesophageal reflux disease or duodenal gastro-oesophageal reflux accompanied by erosive or non-erosive reflux disease. Methods: Thirty-eight symptomatic patients with gastro-oesophageal reflux disease or duodenal gastro-oesophageal reflux and 12 asymptomatic controls, classified on the basis of pH-metry and bilimetry, underwent endoscopy. Six tissue biopsies were taken from the normal mucosa for light microscopy and transmission electron microscopy evaluation. Dilated intercellular spaces were measured on photomicrographs of the specimens (at least 100 transects were measured for each patient). Results: Twenty-two patients with gastro-oesophageal reflux disease had normal macroscopic mucosa but, at histology, five patients with erosive gastro-oesophageal reflux disease had mild oesophagitis and one had moderate oesophagitis. Seven patients with duodenal gastro-oesophageal reflux had normal mucosa, whilst three with erosive duodenal gastro-oesophageal reflux had mild oesophagitis at histology. At transmission electron microscopy, all controls had dilated intercellular spaces of less than 1.69 μm. Each symptomatic patient had a mean dilated intercellular space value and a mean value of the maximum dilated intercellular space at least three or more times greater than that in controls (P < 0.001). No statistical differences were observed between erosive and non-erosive oesophagitis. Conclusions: The dilated intercellular space is an extremely sensitive marker of damage in gastro-oesophageal reflux disease, duodenal gastro-oesophageal reflux and non-erosive reflux disease, and serves as the most appropriate marker of damage evaluation in non-erosive reflux disease reported to date. A mean dilated intercellular space of 0.74 μm provides a cut-off score for damage. No quantitative or qualitative differences in dilated intercellular space scores were found between pure and mixed acid reflux.

Gastro-oesophageal reflux is an almost universal daily occurrence, but only a small percentage of the population develops gastro-oesophageal reflux disease (GORD) and, among them, a small number develop erosive oesophagitis (ERD) or one of its complications.1,2 It is well accepted that the pathophysiology of GORD is related to failure of antireflux mechanisms but several phenomena are not fully explained on the basis of this sequence.3 There is no apparent relation between damage and the amount and quality of refluxate.4 It is not known why the same amount of refluxate determines GORD in one patient and not in another.2 It is also unclear whether there is a relation between these unexplained questions and the possible influence of proliferative responses of epithelial proliferating cells to damage. Hence we evaluated cell proliferation of the oesophageal epithelium using Ki67 immunostaining in normal subjects and in patients with GORD, with or without erosions. Patients gave written informed consent to participate in the study which was approved by the ethics committee. The design was blinded for epithelial cell kinetic evaluation. Thirty five subjects were enrolled: nine were healthy voluntary controls with normal pH testing and normal endoscopic, histological, and ultrastructural patterns. Twenty six patients were affected by GORD, defined as frequent heartburn for at least a year, and abnormal 24 hour pH, histological, and ultrastructural parameters. Of these 26 patients, 13 had a normal appearing oesophageal mucosa at endoscopy (NERD) while 13 had ERD. All subjects underwent gastroscopy; six biopsies were obtained within the lower 5 cm of the oesophagus from areas of macroscopically intact oesophageal mucosa. The presence of oesophagitis was graded according to the Los Angeles classification.5 pH parameters were not statistically different between NERD and ERD. At transmission electron microscopy (TEM), all patients with GORD, with or without erosions, showed ultrastructural signs of damage, defined by the presence of dilation of intercellular spaces (>0.74 µm).6 No significant differences were observed between the two groups. For assessment of the proliferative activity of epithelial cells, we used the immunohistochemical approach based on the Ki67 marker of cell proliferation which provides an accurate estimate of the cell growth fraction.7 Ki67-labelling index (LI) ranged from 8.9% to 74.4% among all patients (mean (SD) 33.5 (19.7)%; median 27.8%). Mean Ki67-LI values for the three groups of patients (normal, NERD, and ERD) were 62.2%, 29.8%, and 17.2%, respectively, and the difference among the groups was significant (p

Rectal treatment with enemas, foams, and suppositories is the most efficient method of delivering an adequate quantity of locally active drugs to the distal colon. In a pilot study carried out by colonoscopy in four patients, it was observed that 4 g 5-ASA in 20 ml foam spread up or beyond the splenic flexure and more extensively than 2 g 5-ASA in 10 ml foam. Therefore we have undertaken a study in order to compare by scintigraphy the colonic distribution of 4 g 5-ASA foam versus 4 g 5-ASA in 100 ml liquid enemas in 10 patients with ulcerative colitis using a crossover randomized design. Both preparations were labeled with 100 MBq [99mTc] sulfur colloid before administration. Anterior scans were taken at intervals for 4 hr. Activity, expressed as a percentage of total radioactivity, was measured in the rectum, sigmoid, descending, transverse, and ascending colon. Six patients had the same extent of spread with the two formulations; in three patients with foam and in one patient with enema a greater spread was observed. the foam reached the upper limit of disease in all cases, while enema failed in two cases. The maximum spread with foam was observed within 30 min in nine of 10 patients compared with seven of 10 after enema. Compared to enema, foam distributes more uniformly and seems to persist longer in the descending and sigmoid colon. The 5-ASA colonic foam shows some more favorable characteristics than enema for the local treatment of left-sided ulcerative colitis. © 1992 Plenum Publishing Corporation.

AIM: To evaluate esophageal mucosal defense mechanisms at an epithelial level to establish if pantoprazole treatment can induce ultrastructural healing and improvement in the proliferation activity of the esophageal epithelium in gastroesophageal reflux disease (GERD). METHODS: This was a single-blinded study for pH-monitoring, and histological, ultrastructural and MIB1 immunostaining evaluation. Fifty eight patients with GERD were enrolled and underwent 24 h pH-monitoring and endoscopy. Patients were treated for 12 and 24 mo with pantoprazole. Esophageal specimens were taken for histological and ultrastructural evaluation, before and after the treatment. RESULTS: With transmission electron microscopy, all patients with GERD showed ultrastructural signs of damage with dilation of intercellular spaces (DIS). After 3 mo of therapy the mean DIS values showed a significant reduction and the mean MIB1-LI values of GERD showed an increase in cell proliferation. A further 3 mo of therapy significantly increased cell proliferation only in the erosive esophagitis (ERD) group. CONCLUSION: Three months of pantoprazole therapy induced ultrastructural healing of mucosal damage in 89% and 93% of ERD and non-erosion patients, respectively. Moreover, long-term pantoprazole treatment may be helpful in increasing the capability for esophageal cell proliferation in GERD, particularly in ERD patients.