Ağustos 2012

Elmas KASAP (1) , Müjdat ZEYBEL (1) , Elif Tu¤ba TUNCEL 1 , Selim SERTER (2) , Semin AYHAN (3) , Hakan YÜCEYAR (1)

Departments of (1) Gastroenterology, (2) Radiology and (3) Pathology, Celal Bayar University, Faculty of Medicine, Manisa

Giriş ve Amaç:Akut pankreatit?li olgularda akut pankreatite bağlı çeşitli üst gastrointestinal mukoza lezyonları görülebildiği ve akut pankreatitle ilişkili olduğu belirtilsede, bu ilişkinin patogenezi ve klinik önemi tam olarak araştırılmamış ve ortaya çıkarılmamıştır. Bu çalışmamızın amacı kliniğimizde akut biliyer pankreatit tanısı ile yatan olgularda üst gastrointestinal mukozal lezyonları saptamak ve bu lezyonlarda Helikobakter pilori prevalansını retrospektif olarak belirlemektir. Gereç ve Yöntem: Çalışmaya retrospektif ola-rak 94 akut biliyer pankreatitli ve toplam 179 safra taşı birlikteliği olan ve olmayan dispeptik olgu kontrol grubu olarak şdahil edilmiştir. Çalışmaya dahil edilen tüm vakalardan antrum ve korpustan hem Helikobakter pilori hemde mukozanın histolojik yapısını belirlemek için ikişer adet biyopsi alın-mıştı.Bulgular: Akut biliyer pankreatitli olguların %71?inde üst gastrointes-tinal mukozal lezyon saptandı. Özofajit ve peptik ülser akut biliyer pankre-atitli olgularda kontrol grubuna göre anlamlı olarak yüksek çıktı (p<0.05). Pankreatitli olgularda saptanan mide ülserli olgularda helikobakter pilori kontrol grubuna göre daha düşük saptanmıştır (p<0.05). Sonuç:Akut biliyer pankreatitli olgularda gastrointestinal mukozal lezyonlar sık görülsede mide ülseri olanda helikobakter pilori ilişkisi peptik ülserde düşük düzeydedir.

Biliyer pankreatit, peptik ülser, Helikobakter pilori

Acute pancreatitis is an inflammatory disease of the pancreas and one of the leading gastrointestinal causes of hospitalizati-on in the Western world (1). The majority of cases are caused by gallstone disease and alcohol abuse. Importantly, inciden-ce is increasing in line with heavier alcohol consumption worldwide; survival rates are not improving with the advan-ces in diagnosis and treatment (2). Acute pancreatitis can lead to a clinical spectrum ranging from mild local manifestations to severe systemic complicati-ons. Local complications, such as gastritis, duodenitis, splenic vein thrombosis, and colonic necrosis, along with external compression of the common bile duct have been described in the course of pancreatitis (3). Previous studies have shown that mucosal lesions in the upper gastrointestinal tract comp-licate more than 50% of cases of acute pancreatitis (4-6). He-licobacter pylori (H. pylori) has been implicated as the major causative agent in cases of chronic gastritis and peptic ulcera-tion worldwide, but its role in upper gastrointestinal mucosal lesions associated with acute pancreatitis is not known (7,8). Therefore, the aims of this study were to retrospectively in-vestigate the characteristics of upper gastrointestinal mucosal lesions associated with acute gallstone pancreatitis and the re-lation with H. pyloriinfection

In this study, we evaluated the prevalence of upper gastroin-testinal mucosal lesions and their characteristics in acute bili-ary pancreatitis. The clinical significance of these lesions was also investigated retrospectively. We found a significant asso-ciation between upper gastrointestinal mucosal abnormalities and acute biliary pancreatitis, with 71% of patients having these abnormalities. Previous studies have also shown that more than half of the patients with acute pancreatitis were complicated with upper gastrointestinal mucosal lesions (4,5). Our study population with acute biliary pancreatitis was predominantly female (67%). Amongst the global popu-lation, there is a higher prevalence of gallstone disease in wo-men. It can therefore be seen that the risk of development of acute pancreatitis is greater in females, especially in the low alcohol-consuming population. Upper gastrointestinal endoscopies revealed that esophagitis was significantly more common in the acute biliary pancreati-tis group than the dyspepsia group. Most patients with acute pancreatitis develop some level of nausea and vomiting, which may partially explain why we observed more esopha-geal lesions in patients with pancreatitis. It is also well known that the nasogastric tubes themselves may lead to mucosal le-sions in the esophagus and/or stomach. Peptic ulcer has also been found to be associated with pancreatitis. Duodenal ulcer is the prevailing endoscopic finding in patients with alcoholic chronic pancreatitis and acute pancreatitis (13); similarly, we encountered a duodenal ulcer in five patients of the study po-pulation. In addition, we also observed a high incidence of antral ulcers in the biliary pancreatitis group, which has not been observed previously (6). There was no association between the presence of upper gas-trointestinal mucosal lesions and the severity of pancreatitis according to the two severity scores, which shows consistency with the previous studies (4,5). However, a recent study by Lee and colleagues (6) reported the clinical association of peptic ulcers with APACHE scores in acute pancreatitis pati-ents. This can be explained by application of endoscopy at different time points of the disease course. We usually per-form upper gastrointestinal endoscopy during the first two days of abdominal pain rather than just before beginning oral feeding. In our study, none of the patients suffered complica-tions such as bleeding. This can be explained by either a rela-tively small research population or routine prophylaxis with H2 receptor blockers and proton pump inhibitors. By histological examination, the prevalence of H. pyloriinfec-tion was found as 64% and 55% in the pancreatitis and con-trol groups, respectively. Khan et al. (14) reported a 20% in-cidence of H. pyloriin alcohol-induced acute pancreatitis, which was similar to the control groups. Manes et al. (15) fo-und that the prevalence of H. pyloriinfection in patients with chronic pancreatitis was similar to that of patients with alco-holic liver cirrhosis and healthy subjects. Our results indica-ted a higher H. pyloripositivity in all subgroups, correlating with the higher prevalence of H. pyloriin Turkey. H. pylori infection is strongly associated with peptic ulceration of the duodenum and stomach. In our study, almost all peptic ul-cers in the dyspepsia group were associated with H. pyloriin-fection, probably due to the exclusion of non-steroidal anti-inflammatory drug users. However, H. pyloriprevalence was significantly lower in patients with peptic ulcers and pancre-atitis and similar to the non-ulcer dyspeptic population. Whether the lower incidence of H. pyloriinfection in this pa-tient group can be partly explained with stress ulcer, the pat-hogenesis remains unclear. The pathogenesis of these lesions is not completely understood, but gastric acid secretion, mu-cosal ischemia and reflux of upper gastrointestinal contents into the stomach may have a role in this process, similar to stress ulcers (16-18). Regarding the ulcer localization and H. pyloristatus of the patients, these lesions should be defined as pancreatitis-associated peptic ulcers rather than stress-as-sociated mucosal damage. In conclusion, esophagitis and antral and duodenal ulcers are common endoscopic findings in acute biliary pancreatitis, alt-hough they are not correlated with the severity of pancreati-tis. H. pyloriis less strongly associated with upper gastroin-testinal mucosal lesions in acute biliary pancreatitis.

The study was conducted as a single-center, retrospective, co-hort study. The patient records of the Gastroenterology De-partment, Celal Bayar University Hospital, Manisa, Turkey, from 2006 to 2010 were reviewed. Acute pancreatitis was di-agnosed by the presence of two of the following three factors: typical upper abdominal pain, hyperamylasemia and/or hyperlipasemia of more than three times the upper limit of normal, as well as typical radiologic findings of pancreatitis during abdominal ultrasonography and/or computed tomog-raphy (CT). Acute biliary pancreatitis was diagnosed as visu-alization of a common bile duct stone by ultrasonography, CT or magnetic resonance cholangiopancreatography. Patients who had undergone upper gastrointestinal endoscopy during their hospitalization were included in the study. We routinely recommend upper gastrointestinal endoscopy to all hospitali-zed patients with the initial diagnosis of acute pancreatitis in order to rule out any other cause of abdominal pain or hyper-lipasemia, unless this is contraindicated. Patients were exclu-ded if they had a history of acid suppression therapy, antibio-tic or non-steroidal anti-inflammatory drug treatment during the previous four weeks or any known peptic ulcer disease, chronic pancreatitis or pancreatitis from another etiology. Data collected from the case notes were as follows: age, gen-der, comorbid risk factors and other possible etiologic factors such as alcohol consumption, and serum calcium and trigl-yceride levels. All patients with the initial diagnosis of acute pancreatitis underwent an abdominal CT to evaluate the se-verity of the acute pancreatitis, and were graded from A to E according to the scoring system established by Balthazar et al. (9). Ranson?s criteria on admission were measured and recor-ded (10). Suspected and documented upper gastrointestinal bleeding was also searched from the patient files. Our control group included patients with functional dyspep-sia according to the Rome II criteria (11). They were divided into two subgroups according to the presence or absence of gallstones on ultrasound, as Group 1 and Group 2, respecti-vely. Patients who had been receiving acid suppressive the-rapy or antibiotics and those who had a history of acute pan-creatitis and cholangitis were excluded. All groups of patients underwent endoscopy, and esophageal findings were assessed using the Los Angeles classification (12). Two biopsy specimens were taken from the antrum and gastric body for histological examination and detection of H. pylori.Biopsy specimens were fixed in formalin, embedded in paraffin, and stained with a modified toluidine blue for detec-tion ofH. pylori. The study was carried out with the approval of the Institutio-nal Review Board of Celal Bayar University Medical Center, Manisa, Turkey. The study protocol conformed to the ethical guidelines of the Declaration of Helsinki. Data were compa-red by χ 2 (SPSS 11.5 for Windows; SPSS Inc., Chicago, IL) or Fisher exact tests, as appropriate. Statistical significance was considered to be p<0.05

One hundred and six patients with acute pancreatitis who had undergone upper gastrointestinal endoscopy during the-ir hospitalization were identified. Twelve patients were exclu-ded from the study (etiologic factors other than gallstone di-sease). The baseline characteristics of patients were similar in the acute biliary pancreatitis group and control groups (Tab-le 1). Sixty-three patients were female and 31 were male. The mean age was 48.1±18 years (range: 21-87). One hundred and seventy-nine patients were identified as controls. Of tho-se, 84 patients (Group 1) had gallstones and 95 patients (Gro-up 2) did not. The mean ages for control Groups 1 and 2 we-re 51.3±18 and 50.2±18 years, respectively. Both control gro-ups showed female predominance (73% and 61%). Firstly, the correlation between acute biliary pancreatitis and gastrointestinal mucosal lesions was investigated. Seventy-one percent (n=66) of patients with acute gallstone pancreati-tis were found to have abnormal findings during upper gas-trointestinal endoscopy, including esophagitis, gastritis and peptic ulcer, and the rates were significantly higher when compared to both control groups. The incidence of esophagi-tis was significantly higher in patients with acute biliary pan-creatitis than the control groups (p<0.05). There was a signi-ficant rise in the incidence of gastric and duodenal ulcer in the pancreatitis group (p<0.01) compared to controls. The anatomic localization of gastrointestinal mucosal lesions is il-lustrated in Table 2. No patient was reported to have upper gastrointestinal bleeding. There was no significant difference in the CT grading and Ranson?s scoring between patients with normal endoscopic findings and gastrointestinal mucosal lesi-ons (Table 3). The histological analysis of biopsy samples from the gastric antrum and corpus revealed no difference in the prevalence of H. pyloriinfection between groups. However, patients with pancreatitis who had peptic ulceration at endoscopy showed significantly lower H. pyloripositivity than controls. The H. pyloriprevalence in patients with gastrointestinal mucosal le-sions is summarized in Table 4

In this study, we evaluated the prevalence of upper gastroin-testinal mucosal lesions and their characteristics in acute bili-ary pancreatitis. The clinical significance of these lesions was also investigated retrospectively. We found a significant asso-ciation between upper gastrointestinal mucosal abnormalities and acute biliary pancreatitis, with 71% of patients having these abnormalities. Previous studies have also shown that more than half of the patients with acute pancreatitis were complicated with upper gastrointestinal mucosal lesions (4,5). Our study population with acute biliary pancreatitis was predominantly female (67%). Amongst the global popu-lation, there is a higher prevalence of gallstone disease in wo-men. It can therefore be seen that the risk of development of acute pancreatitis is greater in females, especially in the low alcohol-consuming population. Upper gastrointestinal endoscopies revealed that esophagitis was significantly more common in the acute biliary pancreati-tis group than the dyspepsia group. Most patients with acute pancreatitis develop some level of nausea and vomiting, which may partially explain why we observed more esopha-geal lesions in patients with pancreatitis. It is also well known that the nasogastric tubes themselves may lead to mucosal le-sions in the esophagus and/or stomach. Peptic ulcer has also been found to be associated with pancreatitis. Duodenal ulcer is the prevailing endoscopic finding in patients with alcoholic chronic pancreatitis and acute pancreatitis (13); similarly, we encountered a duodenal ulcer in five patients of the study po-pulation. In addition, we also observed a high incidence of antral ulcers in the biliary pancreatitis group, which has not been observed previously (6). There was no association between the presence of upper gas-trointestinal mucosal lesions and the severity of pancreatitis according to the two severity scores, which shows consistency with the previous studies (4,5). However, a recent study by Lee and colleagues (6) reported the clinical association of peptic ulcers with APACHE scores in acute pancreatitis pati-ents. This can be explained by application of endoscopy at different time points of the disease course. We usually per-form upper gastrointestinal endoscopy during the first two days of abdominal pain rather than just before beginning oral feeding. In our study, none of the patients suffered complica-tions such as bleeding. This can be explained by either a rela-tively small research population or routine prophylaxis with H2 receptor blockers and proton pump inhibitors. By histological examination, the prevalence of H. pyloriinfec-tion was found as 64% and 55% in the pancreatitis and con-trol groups, respectively. Khan et al. (14) reported a 20% in-cidence of H. pyloriin alcohol-induced acute pancreatitis, which was similar to the control groups. Manes et al. (15) fo-und that the prevalence of H. pyloriinfection in patients with chronic pancreatitis was similar to that of patients with alco-holic liver cirrhosis and healthy subjects. Our results indica-ted a higher H. pyloripositivity in all subgroups, correlating with the higher prevalence of H. pyloriin Turkey. H. pylori infection is strongly associated with peptic ulceration of the duodenum and stomach. In our study, almost all peptic ul-cers in the dyspepsia group were associated with H. pyloriin-fection, probably due to the exclusion of non-steroidal anti-inflammatory drug users. However, H. pyloriprevalence was significantly lower in patients with peptic ulcers and pancre-atitis and similar to the non-ulcer dyspeptic population. Whether the lower incidence of H. pyloriinfection in this pa-tient group can be partly explained with stress ulcer, the pat-hogenesis remains unclear. The pathogenesis of these lesions is not completely understood, but gastric acid secretion, mu-cosal ischemia and reflux of upper gastrointestinal contents into the stomach may have a role in this process, similar to stress ulcers (16-18). Regarding the ulcer localization and H. pyloristatus of the patients, these lesions should be defined as pancreatitis-associated peptic ulcers rather than stress-as-sociated mucosal damage. In conclusion, esophagitis and antral and duodenal ulcers are common endoscopic findings in acute biliary pancreatitis, alt-hough they are not correlated with the severity of pancreati-tis. H. pyloriis less strongly associated with upper gastroin-testinal mucosal lesions in acute biliary pancreatitis.

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