Helicobacter pylori-Negative Duodenal Ulcer YAWERM. NENSEY,M.D., TIMOTHYT. SCHUBERT,M.D., SANTED. BOLOGNA,M.D., CHAN K. MA, M.D., Detroit, Michigan





batter pylon’ (HP) is present in more than 90% of duodenal ulcers (DUs). To investigate the pathophysiology in those patients with DU who are HP-negative compared with those who are HP-positive, we interviewed consecutive patients prior to endoscopy regarding factors often associated with ulcer disease. At esophagogastroduodenogcopy, antral biopsy specimens were obtained for urease test, culture, and Warthin Starry staining for HP in all patients with DU who did not have active bleeding. REsuLTs: Compared with HP-positive patients who had DU, HP-negative patienta with DU were more likely to be aspirin users and less likely to have had prior ulcers. HP-positive patients with DU had more severe antral inflammation than HP-negative patients. Whites were more likely to be HP-negative than blacks. HPnegative patients with DU most commonly presented with bleeding, whereas HP-positive patients with DU presented with pain. coNCLUSIONs: Our fmdings suggest a different mechanism for DUs in patients who are HP-positive versus those who are HP-negative, and this difference might have a bearing on treatment. The absence of HP should lead to a more thorough search for nonsteroidal anti-kflammatory drug/aspirin use, Zollinger-Ellison syndrome, and other potential causes of DUs.

From the Division of Gastroenterology (YMN, TTS, SDB) and the Department of Pathology (CKM), Henry Ford Hospital, Detroit, Michigan. This study was reported in part as an abstract published in Gastroenterology(l990; 98: A96). and was presented as a poster at the Digestive Disease Week American Gastroenterological Association meeting, May 15, 1990. Requests for reprints should be addressed to Timothy T. Schubert, M.D., Gastroenterology K7, Henry Ford Hospital, 2799 West Grand Boulevard, Detroit, Michigan 48202. Manuscript submitted September 24, 1990, and accepted in revised form February 19, 1991.

number of risk factors have beenidentified in A the past that are associatedwith the development of duodenalulcer (DU). Theseinclude gender, smoking, alcoholuse,useof aspirin and nonaspirin nonsteroidal anti-inflammatory drugs (NSAIDs), and presenceof prior ulcer. Overthe last few years, He2icobacterpylori (HP), previously called Campylobacter pylori, hasbeen implicated asa causeof gastritis and DU. Our goal wasto re-evaluatepreviouslyidentified ulcer risk factorsand to assesstheir relative importance in patients with DU who were HP-positive compared with those who were HPnegative. PATIENTSAND METHODS Patients evaluatedwerereferredto us for endoscopy betweenNovember 1988 and May 1990.The patients were referred primarily from the internal medicineserviceand the emergencyroom.A majority of these were health maintenanceorganization patients, with an evenmix of blue- and white-collar workers. A minority belongedto the upper class, and about 10%were medically indigent (uninsured or Medicaid). Prior to endoscopy,everypatient was askeda seriesof questionsregardingthe risk factors for ulcers(alcoholuse,smoking,aspirin use,NSAID use,prednisoneandulcer history) and useof antibiotics, bismuth-containing compounds,antacids,Hz blockers, sucralfate, and chemotherapy.Excluded were those with coagulopathy,acute bleeding, or inability to give a history. After the endoscopicdiagnosiswas determined, forceps biopsy specimensof the antrum were obtained for the following: (1) culture (placedin Stuart’s transport media), (2) ureasetesting, and (3) histology (placedin formalin). The endoscopewas cleanedin glutaraldehyde,and the biopsy forceps were gas-sterilizedbefore use in each patient. Specimenswereprocessedthrough a tissuegrinder and streaked on two chocolate plates, one of which was placed in a Bio-Bag (Marion Scientific, Kansas City, Missouri) and the other in a GasPak Jar (BBL, Hunt Valley, Maryland). After 2 to 6 days of incubation at 37”C, a positive culture had translucent colonies,wasurease-,catalase-,and oxidase-positive,and had a characteristicGram stain. After fixation in formalin, gastric antral tissue was stained with Warthin Starry silver stain (WS). A July

1991 The American


of Medicine









Characteristicsof Patients with DU H;PJg


p Value Age(meanf SD) Blacks(35) y$s (12) Histotyof ulcers Smoking Alcohol ASA NSAID ASA/NSAID

50.6 f 17.2 83% 50% 83% 29/40 (73%) 12/38 (32%) 14/40 (35%) 4/40 (10%) lo/40 (25%) 13/40 (33%)

59.5 + 8.4 17% 50% 75% 4/12 (33%) 4/12 (33%) 4/12 (33%) 7/12 (58%) 3/12 (25%) 9/12 (75%)


0.05 0::1 Iis 0.0003 o.Ndjo9

single pathologist (CKM) identified the characteristic organism on the surface of the mucosal cells using a 40X objective lens. A specimen was determined positive if the characteristic organism was seen and negative if no organism was seen (after searching at least two different tissue cuts). Antral urease was measured using a gel urease test (CLOteat, Trimed, Overland Park, Kansas). The medium was refrigerated until the day used and then warmed to room temperature before inoculation with tissue. Positivity was determined by a magenta or orange color change within 24 hours. A patient was deemed HP-positive if any one of the three tests (culture, urease, WS) was positive. The presence or absence of gastritis was evaluated on hematoxylin and eosin-stained sections. Following the Sydney convention, “normal” biopsy specimens were those with no acute inflammatory cells and no or only occasional chronic (mononuclear) cells. The interpretation was “chronic gastritis” if there was an excess of mononuclear cells but no polymorphonuclear cells. When polymorphonuclear cells were seen, the interpretation was “chronic active gastritis.” Statistical Analysis StatView 512+ (Brainpower, Inc., Agoura Hills, California) statistical software package was used. Analysis of variance was used to compare the patient ages between the two groups. Chi-square analysis was performed to compare categorical variables (gender, smoking status,-prior ulcer, NSAID use), with p

Helicobacter pylori-negative duodenal ulcer.

PURPOSE PATIENTS AND METHODS: Helicobacter pylori (HP) is present in more than 90% of duodenal ulcers (DUs). To investigate the pathophysiology in tho...
444KB Sizes 0 Downloads 0 Views