十二指肠球部微小黏膜隆起的临床分析

目的探讨十二指肠球部直径≤0.5cm黏膜隆起性病变的内镜特征、病理及其与临床的关系。 方法回顾性分析解放军总医院海南分院消化科2012年8月至2018年3月期间25例十二指肠球部微小黏膜隆起性病变的内镜表现特点及病理。 结果25例患者内镜表现为单个或多个广基息肉状隆起,10例患者于十二指肠球部黏膜隆起行活检病理检查,其中,十二指肠球慢性炎3例,十二指肠球慢性炎伴腺体增生2例,十二指肠球胃黏膜异位5例。 结论十二指肠球部黏膜直径≤0.5 cm的广基息肉状隆起多为慢性炎症所致的良性增生性病变及胃黏膜异位。     

Mucosal cell proliferation in duodenal ulcer and duodenitis.

Mucosal cell proliferation in the first part of the duodenum was studied in 24 patients using a tissue culture technique in which endoscopic biopsies were subjected to autoradiography after exposure to tritiated thymidine. Eight patients had a normal duodenum, eight had duodenal ulcer, and eight had symptomatic chronic non-specific duodenitis. The mean crypt labelling index (LI) in normal duodenum was 8.8 0.4% (SEM). Increased labelling indices of 15.6 +/- 1.7% were found near the edge of duodenal ulcers and 17.8 1.8% in duodenitis. Treatment with cimetidine reduced both the severity of duodenitis and the mean crypt LI. The LI of histologically normal duodenal mucosa distal to ulcer of duodenitis was similar to that of the control subjects' mucosa. The increased mucosal cell proliferation seen in severe duodenitis, either alone or associated with duodenal ulceration, suggested that erosions and ulcers arose when the crypts passed into 'high output failure' and were unable to compensate for further epithelial cell loss. There was no evidence in out study for a generalised failure of mucosal cell proliferation in duodenal ulcer or duodenitis.     

Duodenal epithelial thymidine uptake in patients with duodenal ulcer or endoscopic duodenitis

To evaluate the relationship between duodenal ulcer disease and duodenitis, duodenal epithelial cell renewal was measured in mucosal biopsies by the incorporation of [³H]thymidine. When 14 patients with duodenal ulcer were compared to 13 control subjects or 7 with endoscopic duodenitis alone, the crypt size was the same in all groups. Similar to other inflammatory processes of the gastrointestinal tract, patients with endoscopic duodenitis showed increased proliferative indices including a greater number of cells incorporating [³H]thymidine. In contrast, the proliferative indices from the duodenal mucosa of patients with duodenal ulcers did not differ from a control group. In a group of 6 patients with both endoscopic duodenitis and duodenal ulcer, the [³H]thymidine incorporation was intermediate between control subjects or patients with duodenal ulcer alone and those with endoscopic duodenitis alone. When subjects were divided according to the histologic appearance of the duodenal mucosa, those having chronic duodenitis demonstrated enhanced [³H]thymidine incorporation in comparison to a control group or patients with chronic active duodenitis (polymorphonuclear leukocytes present). Although there are many possible explanations of these findings, one may speculate that duodenal ulceration does not stimulate duodenal epithelial proliferation. This project was supported by the Yale Digestive Cancer Research Fund. Dr. Gorelick was supported by a Research Fellowship Award from the National Foundation for Ileitis and Colitis during a portion of this study and is currently a recipient of a Clinical Investigator Award (KO8-AM-00659) from the National Institute of Arthritis, Metabolism and Digestive Diseases.     

Nodular duodenitis in chronic maintenance hemodialysis patients

A retrospective study of 138 cases of chronic hemodialysis between 1977 and 1982 were reviewed for endoscopic, radiographic, and histologic characteristics of duodenitis. Forty patients underwent upper gastrointestinal barium x-rays; 13 were found to have multiple duodenal bulb nodules and three of these patients had very prominent duodenal bulb folds. There were 42 patients on whom upper panendoscopy was performed, and multiple duodenal nodules were seen in 15 patients and thickened folds in three patients. There were five patients in whom nodules were seen only on endoscopy. The size of the nodules varied between 3 and 8 mm in diameter and mucosal folds between 4 and 8 mm. Duodenal mucosal hyperplasia with chronic inflammatory cell infiltrate was found on biopsy of the nodules in 12 cases, while three cases with nodules revealed blunted villous structure with chronic inflammatory cells.     

结节型十二指肠炎的内镜表现及其临床病理学特征

目的 探讨结节型十二指肠炎内镜下表现与其组织学特征的关系及其发病机制。方法 观察内镜下136例结节型十二指肠炎的表现，对其活检标本均行H-E染色，观察病理改变，Giemsa染色及快速尿素酶试验诊断幽门螺杆菌感染，十二指肠黏膜兼作AB／PAS染色，观察十二指肠胃上皮化生。结果 136例结节型十二指肠炎内镜下表现为直径0．2～1．0cm大小不等的结节，伴有不同程度的充血、水肿，其中伴糜烂21例，出血点及（或）瘀斑30例。检出率占同期15820例内镜检查的0．9％，十二指肠炎的3．8％。病理诊断为十二指肠炎107例，其中慢性十二指肠炎53例，表现为间质内可见慢性炎性细胞浸润，肠绒毛缩短或萎缩、变平．肠腺不同程度减少；活动性十二指肠炎54例，除慢性炎性细胞外，黏膜层及固有层内还有不同程度的中性粒细胞浸润，伴Brunner腺增生51例，胃型上皮化生59例。136例中检出胃黏膜异位增生7例以及血吸虫虫卵所致的炎性病变4例，107例结节型十二指肠炎中，幽门螺杆阳性（Hp^＋）者为45．8％（49／107）。其中，53例慢性十二指肠炎患者中HP^＋者为32．1％（17／53），54例活动性十二指肠炎中Hp^＋检出率为59．3％（32／54），后者的Hp^＋检出率显著高于前者（P〈0．01）。结论 结节型十二指肠炎是一类特殊的非特异性十二指肠炎，内镜下表现与组织学改变存在不一致性。其发生可能与Hp感染及胃上皮化生、Brunner腺增生有关。     

Duodenal bulb plasma cells in duodenitis and duodenal ulceration

Using an immunoperoxidase technique IgA, IgM, IgE and IgG plasma cells were studied in endoscopic duodenal bulb biopsies taken from 14 controls, 25 patients with grade 1 duodenitis (Whitehead classification), 12 patients with grade 2 duodenitis and three with grade 3 duodenitis. The control counts were compared with those in the jejunum and rectum. In addition cell counts were compared in 16 pairs of patients, with and without duodenal ulcer, exactly matched for grade of duodenitis. The control counts were not significantly different from counts in jejunum or rectum except for IgG which were higher in the jejunum (p = 0.03). IgA plasma cell counts were significantly increased in both grade 1 and grade 2 duodenitis compared with controls (p less than 0.05 and p less than 0.01). There was no significant difference for the other plasma cells. All plasma cell counts were decreased in the small group of grade 3 duodenitis compared with the other groups. There was no significant difference between counts in duodenitis whether or not there was associated duodenal ulceration. The isolated IgA plasma cell response of the duodenal bulb mucosa in duodenitis is very different from that of the jejunal mucosa in coeliac disease, and the rectal mucosa in inflammatory bowel disease and bacterial colitis and probably represents the basic response to any mucosal damage.     

GNAS-mutated carcinoma arising from gastric foveolar metaplasia in the duodenum after 9 years of observation

This case involved an 80-year-old man. Screening with esophagogastroduodenoscopy (EGD) in 2004 revealed Brunner’s gland hyperplasia (BGH), 5 mm in size, in the duodenal bulb. The size of the lesion increased and its shape has changed since then, as detected in subsequent EGDs. The lesion had increased in size to 15 mm with a depression and biopsy specimens revealed an adenocarcinoma. The patient underwent endoscopic mucosal resection. Histopathological assessments indicated an adenocarcinoma arising from gastric foveolar metaplasia (GFM) adjacent to BGH. BGH stained positive for MUC6, and GFM and the adenocarcinoma stained positive for MUC5AC. Mutations of the GNAS gene were not detected in the GFM biopsied in 2007. On the other hand, common GNAS mutations (R201H) were detected in GFM and the adenocarcinoma in the endoscopically resected specimen in 2013. Moreover, mutant allele frequencies were higher in the carcinoma than in GFM. The patient remains disease-free for 4 years after endoscopic treatment. This case report further supports the notion that GFM may be a precursor lesion in the process of GNAS-mutated, gastric-type duodenal carcinogenesis.     

Quantitative histological study of mucosal inflammatory cell densities in endoscopic duodenal biopsy specimens from dyspeptic patients using computer linked image analysis.

Inflammatory cell counting in endoscopic biopsy sections was carried out on duodenal mucosal samples from defined sites in patients with duodenal ulcer, duodenitis but no ulcer, non-ulcer dyspepsia, and asymptomatic controls using computer linked image analysis. The variables measured included polymorphonuclear and mononuclear cells per mm of superficial epithelium and per mm2 lamina propria. Duodenal ulcer crater margin and mucosal biopsy specimens from endoscopically inflamed mucosa in the group with duodenitis but no ulcer showed significantly higher inflammatory cell counts than endoscopically normal non-ulcer dyspepsia and control mucosa. Biopsy specimens from non-ulcer dyspepsia patients showed significantly higher lamina propria polymorphs than control group mucosa. Endoscopically normal duodenal ulcer and duodenitis but no ulcer mucosa also showed significantly higher acute and chronic inflammatory cell counts than controls. The prevalence of Helicobacter pylori in duodenal biopsy specimens was low (0-22%) and unrelated to local inflammatory response. Despite histological appearances, duodenal biopsy specimens from non-ulcer dyspepsia patients showed significantly higher inflammatory cell infiltration than control specimens, suggesting that at least some represent part of a spectrum of subclinical peptic disease.     

Duodenitis: a reliable radiologic diagnosis?

The authors performed a retrospective study of 50 patients with endoscopically diagnosed duodenitis who had undergone double-contrast upper gastrointestinal (GI) examinations. Duodenitis was diagnosed on the original radiographic reports in six of 37 patients (16%) with mild-to-moderate duodenitis, five of 13 patients (38%) with severe duodenitis, and 11 of 50 patients (22%) with all grades of duodenitis on endoscopy. Subsequent analysis of the films revealed one or more radiologic signs of duodenitis (including folds more than 4 mm in thickness, mucosal nodularity, bulbar deformity, and erosions) in 18 of 37 patients (49%) with mild-to-moderate duodenitis, eight of 13 patients (62%) with severe duodenitis, and 26 of 50 patients (52%) with all grades of duodenitis on endoscopy. In a separate part of the study, the authors identified another 20 patients with radiographically diagnosed duodenitis who had undergone endoscopic examinations. Nine of those 20 patients (45%) had duodenitis on endoscopy. Subsequent analysis of the films revealed one or more signs of duodenitis in 17 patients from this group. Nine of the latter patients (53%) had duodenitis on endoscopy. Using established radiologic criteria for duodenitis, our rate of false-positive and false-negative radiologic diagnoses still was about 50%. Thus, the double-contrast upper GI examination is a relatively unreliable technique for diagnosing duodenitis.     

Pain provocation test in peptic duodenitis

Controversy exists as to whether or not duodenitis alone can cause peptic ulcer symptoms. A modified provocation perfusion test has been performed in 10 symptomatic patients with duodenitis confirmed by endoscopy and histology. The test was conducted without the patient being aware of whether 0.1 N hydrocholoric acid, normal saline, or 8.5% sodium bicarbonate was being perfused directly on the area of duodenitis through the endoscopic irrigation cannula at a fixed rate of 10 ml/min for 10 min. The test was also performed in eight patients with dyspepsia alone and in five patients with chronic duodenal ulceration. Intraduodenal infusion of acid reproduced the epigastric pain in all patients with peptic duodenitis and duodenal ulcer patients, including the feeling of nausea in several which was partially relieved by bicarbonate infusion. In patients with dyspepsia but no peptic duodenitis, the symptoms were not reproduced. It would appear that "peptic duodenitis" can cause symptoms and that this "pain provocation test" may prove useful in its diagnosis.     

Duodenal erosions,a common and distinctive feature of portal hypertensive duodenopathy

OBJECTIVE: The aim of the present study was to assess the presence of duodenal erosion and its clinical characteristics on endoscopy in patients with portal hypertension who had undergone endoscopic injection sclerotherapy and/or endoscopic variceal ligation for esophagogastric varices. METHODS: The subjects were 440 patients with portal hypertension, 450 with chronic hepatitis as a related control group, and 450 who underwent upper endoscopic examination as part of their routine physical examination as the controls. The underlying hepatic disease, hepatic function, and endoscopic findings of duodenal erosion among the patients with portal hypertension were studied. RESULTS: Duodenal erosion was found in 68 patients with portal hypertension (68 of 440, 15.5%), four patients with chronic hepatitis (four of 450, 0.9%), and two controls (two of 450, 0.4%). The incidence of duodenal erosion among the patients with portal hypertension was significantly higher than that in the other two groups (p < 0.01, p < 0.01, respectively). The lesions commonly observed in duodenitis are speckle erosions mainly located in the duodenal bulb. However, the most frequently seen form of duodenal erosion among the patients with portal hypertension extended from the superior portion to the descending portion, and tended to show a circular alignment along the Kerckring's folds. The patients with portal hypertension with reduced hepatic reserve capacity had more severe duodenal erosion. Endoscopic ultrasonography revealed thickening of the duodenal wall and proliferation of vascular structures within and around the wall. The histological findings of the duodenal erosion included edema and vascular dilation in the mucosal and submucosal layers. CONCLUSIONS: The location of duodenal erosion in patients with portal hypertension differs from that in patients with ordinary duodenitis. Duodenal erosion in patients with portal hypertension is considered to be one of the lesions of portal hypertensive duodenopathy.     

The results of caustic ingestions

BACKGROUND/AIMS: The ingestion of caustic substances is a common condition, which may result in serious injuries of the upper gastrointestinal system. The purpose of this study is to assess the outcomes of patients who had a history of the ingestion of caustic substances. METHODOLOGY: Between January 1995 and May 2002, 53 patients with clinical and/or endoscopic signs of caustic agents injury admitted to the Emergency Surgery Service of University of Istanbul, Istanbul Medical School, were retrospectively evaluated. RESULTS: The group consisted of 29 females and 24 males with a mean age of 33 years (range 15 to 77). Caustic ingestion was accidental in 31 (59%) and suicidal in 22 (41%). Twenty-five (47%) patients had history of acid ingestions, 21 (40%) alkaline and 7 (12%) unknown agents. The findings of upper gastrointestinal tract endoscopy in 37 patients were as follows: i) fourteen patients had Grade I esophagitis, ii) fourteen patients had Grade II esophagitis; four with gastric mucosal burn, three with gastric and duodenal mucosal burn, five with pharyngeal mucosal burns, iii) two patients had gastric and duodenal mucosal burns, iv) four patients had gastric mucosal burn, vi) three patients had esophageal, gastric and duodenal mucosal burn. Eight patients (15%) with signs of acute abdomen underwent urgent surgery (six of these cases were acid ingestions and seven were suicidal ingestions); four of these patients with esophageal necrosis and gastric perforation, two with esophageal, gastric, duodenal and jejunal necrosis, one with local necrosis in the gastric fundus, and one had normal findings at laparotomy. The mean follow-up period was 11.6 months (range 1 to 42 months). During the follow-up one patient presented with pyloric stenosis, which required surgery. The mortality rate was 11%. CONCLUSIONS: Suicidal caustic ingestion and acid ingestion seem to cause more severe injuries. Early admission to the hospital with clinical and endoscopic evaluation and early surgery when required may reduce morbidity and mortality.     

The endoscopic diagnosis of duodenal ulcer disease. A randomized clinical trial of bias and of interobserver variation

In a randomized design we examined whether endoscopists are biased by knowledge of the radiologic diagnosis of duodenal ulcer and deformity of the duodenal bulb when recording the corresponding endoscopic diagnoses. A total of 156 patients had a barium meal and were subsequently randomized into 2 groups. In 74 of the cases the 2 endoscopists knew the result of the X-ray examination when doing the endoscopy; in 82 of the cases they did not. One endoscopist was significantly biased by his knowledge of the radiologic diagnosis of deformity of the duodenal bulb. Neither of the endoscopists was biased by his knowledge of the radiologic diagnosis of duodenal ulcer. In addition, the interobserver variation between the two endoscopists with regard to the endoscopic diagnoses of duodenal ulcer, deformity of the duodenal bulb, and duodenitis was examined. The interobserver variation was expressed by the overall agreement and by the kappa statistics, which adjusts the overall agreement for expected chance agreement. For duodenal ulcer, deformity of the duodenal bulb, and duodenitis, the overall agreements and kappa values were 0.91, 0.78, and 0.75, and 0.54, 0.42, and 0.33, respectively.     

内镜治疗十二指肠非壶腹性黏膜病变的回顾性分析

分析内镜下切除治疗十二指肠非壶腹性黏膜病变的疗效。收集2016年1月—2019年6月于3所医院行内镜下切除治疗的58例十二指肠非壶腹性黏膜病变患者的内镜及病理资料进行回顾性分析。58例患者中,病变位于十二指肠球部27例(46.6%),十二指肠降部(包括球降交界)31例(53.4%);行内镜黏膜切除术治疗者46例(79....     

Nodular duodenitis

This prospective study evaluated the radiographic, endoscopic, histologic, and clinical characteristics of nodular duodenitis found in 17 of 50 (34%) patients with end-stage renal disease. By comparison, nodular duodenitis was noted in only 23 of 557 (4%) consecutive endoscopies in a general medical population. Endoscopic nodular duodenitis consisted of two or more nodules, 2.5-7.0 mm in diameter, with apical erythema, with or without tip erosions. Eight patients had nodules in the bulb only, eight had diffuse duodenal nodules, and a single patient had nodules only in the second portion of the duodenum. Single-contrast barium x-rays were sensitive in detecting the nodules only when they were 5 mm or greater in diameter. Some degree of inflammatory infiltrate was found in 14 of 17 (82%) of the patients with nodular duodenitis; 10 of 17 had a moderate to severe histologic grade compared to 3 of 18 (P = 0.015) patients with a normal endoscopic appearance to the duodenum. Several patients with endoscopic nodular duodenitis, in whom biopsies were taken both of the nodule and surrounding mucosa, were found to have a focal histologic lesion which consisted of villous blunting and thickening due to fibrosis and a chronic inflammatory infiltrate or lymphoid aggregate in the stroma. A higher incidence of peptic ulcers occurred in the nodular duodenitis group (3 of 17) compared to the remainder of the group (0 of 33) during a mean follow-up of 38 months (P = 0.03). Resolution of the nodules occurred in six patients following successful renal transplant (four patients) and following vagotomy and pyloroplasty (two patients).(ABSTRACT TRUNCATED AT 250 WORDS)     

Duodenitis.

Many questions regarding duodenitis remain unanswered. However, the evidence suggests that duodenitis is a clinical entity which can give rise to dyspepsia and, on rare occasions, gastrointestinal haemorrhage. Conventional and double contrast radiology has only a small part to play in the diagnosis of duodenitis but is important in helping to exclude other lesions such as duodenal ulcer. Provided care is taken during the fibre-optic visualization of the duodenal bulb, the endoscopic appearances of moderately severe duodenitis correlate well with the histological changes seen. A diagnosis of apparent duodenitis should be confirmed by the histological criteria described. Treatment at present is similar to that of peptic ulcer, with the withdrawal of any predisposing and precipitating factors such as aspirin, alcohol and smoking. Antacids may relieve the symptoms. It is not yet known what effect these measures may have on the duodenitis as opposed to the symptoms of dyspepsia. The H2-receptor antagonist, cimetidine, should be effective in treating duodenitis but double blind clinical and endoscopic studies are required to confirm this. The place of surgery is as yet undefined. With the data at present available, it appears that duodenitis is part of the pathophysiological spectrum of the duodenal ulcer diathesis rather than a separate disease. It may represent both the production and healing phases of duodenal ulceration. In some patients the duodenal mucosa may proceed from normal to duodenitis and then to normal again without the development of frank duodenal ulceration (Figure 4). Prospective studies are required which should include a long-term clinical follow-up of a large number of patients with duodenitis accurately and specifically diagnosed by endoscopy and histopathology.     

Cimetidine tablets or suspension for the prevention of gastrointestinal mucosal lesions caused by non-steroidal, anti-inflammatory drugs

We compared the protection offered by cimetidine 400 mg b.i.d. as tablets or suspension vs. placebo, in Naproxen-induced gastrointestinal damage in 17 healthy males. Upper endoscopy was performed before and after each drug period, with separate evaluation of duodenal mucosa distal to the duodenal bulb. 51Cr-EDTA absorption tests were done to assess distal mucosal integrity, and symptoms were registered. All regimens caused a significant increase in mucosal damage (p less than 0.01). Cimetidine tablets gave a significantly lower damage score than placebo for gastritis/duodenitis and hemorrhagic lesions in the stomach/duodenal bulb, and for the sum of scores in both scoring regions (p = 0.02). Cimetidine suspension was not significantly different from placebo for any of the endoscopic parameters. The 51Cr-EDTA absorption was significantly increased after all drug periods. However, there was no difference between the three drug combinations. Symptoms reported were mild and equal in the three groups. Cimetidine tablets offered protection against Naproxen-induced mucosal damage, primarily in the stomach and duodenal bulb, but lacked any effect on permeability changes. Cimetidine suspension was not significantly different from placebo in any respect.     

The clinical relevance of endoscopic and histologic inflammation of gastroduodenal mucosa in dyspepsia of unknown origin

Two hundred and ten patients were defined as having dyspepsia of unknown origin. At endoscopy 11% had body gastritis, 46% antral gastritis, and 19% bulbitis (two thirds combined with antral gastritis). Histologically, 22% had chronic corpus gastritis (79% superficial, 21% atrophic), which was combined with chronic antral gastritis in 84%, 33% had chronic antral gastritis (82% superficial, 18% atrophic); and 14% had duodenitis, which was combined with antral gastritis in 65%. Polymorphonuclear leukocytes were found in specimens from the body mucosa in 6%, from the antral mucosa in 13%, and from the duodenal cap in 4%. The endoscopic findings correlated significantly with the histologic findings in the duodenal bulb (kappa = 0.33) but not in the stomach. The frequency of endoscopic antral gastritis and the frequency of histologic chronic body and antral gastritis increased with age. Endoscopic bulbitis and histologic duodenitis and gastric metaplasia were commoner in men than in women. Peak acid output was higher in patients with than in those without endoscopic bulbitis and higher in smokers than in non-smokers when the significant sex differences in peak acid output were taken into account. Gastric metaplasia of the bulb was predominantly correlated to higher peak acid output and to some extent also to sex and smoking. Episodic pain was correlated to histologic duodenitis. Other dyspeptic symptoms and the intragastric bile acid concentration were not associated with any endoscopic or histologic findings. Of the 210 patients, 172 were reexamined after a double-blind 6-week treatment period with cimetidine, antacid, or placebo. The symptomatic outcome of these treatments was not associated with any significant change in endoscopic or histologic findings.     

Duodenal mucosal architecture in non-specific and ulcer-associated duodenitis.

This study was done to determine the severity and extent of abnormalities of duodenal mucosal architecture in non-specific (non-ulcerative) and ulcer-associated duodenitis. The effect of successful treatment with cimetidine on these changes has also been assessed. A method of microdissection and measurement of villus height, crypt depth, and mitotic figure count per crypt was applied to endoscopic biopsies from the duodenum. Five groups of patients were studied: untreated ulcer-associated duodenitis, untreated non-specific duodenitis, healed ulcer-associated and non-specific duodenitis after cimetidine treatment, and controls. Significant reduction in villus height, increase in crypt length, and increase in mitotic figure count per crypt were all found in both ulcer-associated and severe non-specific duodenitis as compared with controls. These changes were localised to visually inflamed areas and regressed after healing of these lesions with cimetidine. This is the first quantitative comparison of the architectural features between diseased states in the duodenum and control in the same study. Identical morphological changes in the form of crypt hyperplasia and villus atrophy were demonstrated in areas of non-specific and ulcer-associated duodenitis. No evidence could be found from this study that non-specific duodenitis constitutes a different disease from ulcer-associated duodenitis.     

Pirenzepine in erosive duodenitis. A controlled clinical trial versus ranitidine

Fifty-five outpatients with chronic duodenal erosions and no previous ulcer history were treated, in a double-blind fashion, with either pirenzepine (50 mg twice daily) or ranitidine (150 mg twice daily) for 6 weeks. The drugs were equally effective in inducing symptomatic relief. At endoscopic control, 70.4% of subjects in the pirenzepine group and 39.3% of ranitidine-treated patients showed complete healing (p less than 0.05). The results suggest that acid secretion is not an important factor in the pathogenesis of erosive duodenitis and that other mechanisms (such as impaired mucosal blood flow) must be considered.