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Esophageal cell proliferation in gastroesophageal reflux disease: Clinical-morphological data before and after pantoprazole

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World Journal of Gastroenterology 2009年第8期15卷 936-941页

作者： carlo calabrese Davide Treré Giuseppina Liguori Veronica Gabusi Manuela Vici Giovanna Cenacchi Massimo Derenzini Giulio Di Febo Department of Clinical Medicine University of Bologna Bologna 40138 Italy Department of Experimental Pathology Clinical Pathology University of Bologna Bologna 40138 Italy Clinical Department of Radiologic and Histopathologic Sciences University of Bologna Bologna 40138 Italy

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 pHmonitoring, 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 asignificant 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.

关键词：胃食管反流病癌细胞增殖形态数据胃食管反流性疾病糜烂性食管炎治疗前后透射电子显微镜超微结构

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Cell proliferation of esophageal squamous epithelium in erosive and non-erosive reflux disease

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World Journal of Gastroenterology 2011年第40期17卷 4496-4502页

作者： carlo calabrese Lorenzo Montanaro Giuseppina Liguori Elisa Brighenti Mauela Vici Paolo Gionchetti Fernando Rizzello Massimo Campieri Massimo Derenzini Davide Trerè Department of Clinical Medicine University of Bologna 40138 Bologna Italy Department of Experimental Pathology University of Bologna 40138 Bologna Italy Clinical Department Radiological and Histocytopathological Sciences University of Bologna 40138 Bologna Italy

AIM:To elucidate cell proliferation in erosive reflux disease (ERD) and non-erosive reflux disease (NERD), we evaluated markers in squamous epithelial cells. METHODS: Thirty-four consecutive patients with gas-troesophageal-reflux-disease-related symptoms (21 NERD and 13 ERD) were evaluated for the enrolment into the study. All patients underwent 24-h pH monitoring, standard endoscopy, and biopsy for histological evaluation. The expression of cyclins D and A was evaluated by real-time reverse transcription polymerase chain reaction (RT-PCR) from isolated epithelial cells. In all samples, analysis of the isolated cell population revealed the presence of epithelial cells only. RESULTS:Real-time RT-PCR showed that, in patients with ERD, the relative expression of cyclin D1 mRNA in esophageal epithelium was strongly decreased in comparison with NERD patients. The mean value of relative expression of cyclin D1 mRNA in NERD patients was 3.44 ± 1.9, whereas in ERD patients, it was 1.32 ± 0.87 (P = 0.011). Real-time RT-PCR showed that, in patients with ERD, relative expression of cyclin A mRNA in esophageal epithelium was decreased in comparison with that in NERD patients (2.31 ± 2.87 vs 0.66 ± 1.11). The mean bromodeoxyuridine labeling index in the NERD patients was 5.42% ± 1.68%, whereas in ERD patients, it was 4.3% ± 1.59%. CONCLUSION:We confirmed reduced epithelial pro- liferation in ERD compared with NERD patients, and that individuals who develop ERD are characterized by weaker epithelial cell proliferation.

关键词：上皮细胞细胞增殖食管糜烂细胞周期蛋白D1 反流逆转录聚合酶链反应 PCR技术

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Role of conventional therapies in the era of biological treatment in Crohn’s disease

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World Journal of Gastroenterology 2011年第14期17卷 1797-1806页

作者： Paolo Gionchetti carlo calabrese Rosy Tambasco Ramona Brugnera Giulia Straforini Giuseppina Liguori Giulia Spuri Fornarini Donatella Riso Massimo Campieri Fernando Rizzello Department of Clinical Medicine University of Bologna40138 BolognaItaly

Outstanding progress regarding the pathophysiology of Crohn's disease (CD) has led to the development of innovative therapeutic concepts. Numerous controlled trials have been performed in CD. This review concentrates on the results of randomized,placebo-controlled trials,and meta-analyses when available,that provide the highest degree of evidence. Current guidelines on the management of CD recommend a step-up approach to treatment involving the addition of more powerful therapies as the severity of disease and refractoriness to therapy increase. The advent of biological drugs has opened new therapeutic horizons for treating CD,modifying the treatment goals. However,the large majority of patients with CD will be managed through conventional therapy,even if they are a prelude to biological therapy.

关键词：生物治疗疗法传统对照试验病理生理学生物药物 CD 耐火度

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Effect of omeprazole on symptoms and ultrastructural esophageal damage in acid bile reflux

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World Journal of Gastroenterology 2005年第12期11卷 1876-1880页

作者： carlo calabrese Anna Fabbri Mauro Bortolotti Giovanna Cenacchi Scialpi carlo Desiree Zahlane Mario Miglioli Giulio Di Febo Dipartimento di Medicina Interna e Gastroenterologia

AIM: To value whether omeprazole could induce the healing of DIS and regression of symptoms in patients with DGER.METHODS: 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.RESULTS: 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 esophagus,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%, P＜0.01)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.CONCLUSION: 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.

关键词：食道损伤胆汁逆流奥美拉唑药物治疗

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Antibiotics and probiotics in treatment of inflammatory bowel disease

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World Journal of Gastroenterology 2006年第21期12卷 3306-3313页

作者： Paolo Gionchetti Fernando Rizzello Karen M Lammers Claudia Morselli Lucia Sollazzi Samuel Davies Rosy Tambasco carlo calabrese Massimo Campieri Departmentof Internal Medicine and Gastroenterology University of Bologna BolognaItaly

许多试验性、临床的观察建议肠的微植物群在煽动性的肠疾病(IBD ) 的致病起一个潜在的作用。用抗菌素或职业人员生命学的钠内容的操作代表一种潜在地有效的治疗学的选择。可得到的研究不在 ulcerative (UC ) 支持抗菌素的使用。抗菌素... 详细信息

许多试验性、临床的观察建议肠的微植物群在煽动性的肠疾病(IBD ) 的致病起一个潜在的作用。用抗菌素或职业人员生命学的钠内容的操作代表一种潜在地有效的治疗学的选择。可得到的研究不在 ulcerative (UC ) 支持抗菌素的使用。抗菌素在对待是有效的腐败 Crohn 的疾病(CD ) 的复杂并发症但是他们主要治疗是更争论的使用，尽管这条途径经常并且成功地在临床的实践被采用。有证据关於生命的治疗可以是的那个职业人员在预防和处理有效对中等 UC 温和。相反，成功的学习数据的缺乏目前预防在 CD 的处理的专业版生命学的普遍使用。抗菌素和职业人员生命学看起来在 pouchitis 的处理和预防起一个有益的作用，进一步的审判被保证充分确定他们的临床的功效。

关键词：抗生素肠炎治疗临床

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Eviendep~ reduces number and size of duodenal polyps in familial adenomatous polyposis patients with ileal pouchanal anastomosis

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World Journal of Gastroenterology 2013年第34期19卷 5671-5677页

作者： carlo calabrese Chiara Praticò Andrea Calafiore Maurizio Coscia Lorenzo Gentilini Gilberto Poggioli Paolo Gionchetti Massimo Campieri Fernando Rizzello Dipartimento di Scienze Mediche e Chirurgiche (DIMEC) University of Bologna

AIM:To evaluate if 3 mo oral supplementation with Eviendep was able to reduce the number of duodenal polyps in familial adenomatous polyposis(FAP)patients with ileal pouch-anal anastomosis(IPAA).METHODS:Eleven FAP patients with IPAA and duodenal polyps were enrolled.They underwent upper gastrointestinal(GI)endoscopy at the baseline and after 3 mo of treatment.Each patient received 5 mg Eviendep twice a day,at breakfast and dinner time,for3 mo.Two endoscopists evaluated in a blinded manner the number and size of duodenal polyps.Upper GI endoscopies with biopsies were performed at the baseline(T0)with the assessment of the Spigelman score.Polyps>10 mm were removed during endoscopy and at the end of the procedure a new Spigelman score was determined(T1).The procedure was repeated 3 mo after the baseline(T2).Four photograms were examined for each patient,at T1 and T2.The examined area was divided into 3 segments:duodenal bulb,second and third portion duodenum.Biopsy specimens were taken from all polyps>10 mm and from all suspicious ones,defined by the presence of a central depression,irregular surface,or irregular vascular pattern.Histology was classified according to the updated Vienna criteria.RESULTS:At baseline the mean number of duodenal detected polyps was 27.7 and mean sizes were 15.8mm;the mean Spigelman score was 7.1.After polypectomy the mean number of duodenal detected polyps was 25.7 and mean sizes were 7.6 mm;the mean Spigelman score was 6.4.After 3 mo of Eviendep bid,all patients showed a reduction of number and size of duodenal polyps.The mean number of duodenal polyps was 8(P=0.021)and mean size was 4.4 mm;the mean Spigelman score was 6.6.Interrater agreement was measured.Lesions>1 cm found a very good degree of concordance(kappa 0.851)and a good concordance was as well encountered for smaller lesions(kappa 0.641).CONCLUSION:Our study demonstrated that shortterm(90 d)supplementation with Eviendep in FAP patients with IPAA and with recurrent adenomas in the duodenal mucosa,resulted effective in reducin

关键词： Familial adenomatous polyposis Ileal pouch-anal anastomosis Duodenal polyps Eviendep

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Asthma and gastroesophageal reflux disease: Effect of long-term pantoprazole therapy

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World Journal of Gastroenterology 2005年第48期11卷 7657-7660页

作者： calabrese carlo Fabbri Anna Areni Alessandra Scialpi carlo Zahlane Desiree Di Febo Giulio Department of Internal Medicine and Gastroenterology

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 μm 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 32-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 FEV1 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 FEV1. Four patients reported a significant improvement of symptoms and their FEV1 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.

关键词：哮喘胃食管逆流治疗病理机制

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