Infectious disorders of the upper gastrointestinal tract (excluding Helicobacter pylori)

The upper gastrointestinal (GI) tract, including the oesophagus, stomach and small intestine, is subject to a vast array of pathogens. While some may be a reflection of disseminated infection, others produce disease specific to the upper GI tract. This review focuses on the most common infectious disorders of the upper GI tract that may be encountered by the general surgical pathologist, including viral, bacterial, fungal and parasitic organisms. Clinical and diagnostic histological features are discussed, as well as useful ancillary diagnostic techniques.     

Infectious disorders of the upper gastrointestinal tract (excluding Helicobacter pylori)

The upper gastrointestinal (GI) tract, including the oesophagus, stomach and small intestine, is host to numerous microorganisms. Some reflect gastrointestinal involvement by systemic disease, but others are primary digestive disorders that first present at GI sites. This review focuses on the most common infectious disorders of the upper GI tract encountered in general surgical pathology practice, including viral, bacterial, fungal and parasitic organisms. Clinical and histological features are discussed, as well as useful ancillary diagnostic techniques.     

Cytotoxin production by Campylobacter pylori strains isolated from patients with peptic ulcers and from patients with chronic gastritis only.

A total of 66.6% of Campylobacter pylori strains isolated from patients with peptic ulcers produced a cytotoxin active against mammalian cells in vitro, versus 30.1% of strains isolated from patients with chronic gastritis of various degrees of severity only. This difference was statistically significant and suggests that the toxic substance could be involved in the development of peptic ulcers.     

Campylobacter pylori in the upper gastrointestinal tract of patients with HIV-1 infection.

Fifty one patients with human immuno-deficiency virus (HIV-1) infection who had been consecutively endoscoped for upper gastrointestinal symptoms were biopsied (stomach or duodenum, or both) and compared with 59 age and sex matched controls for the presence of Campylobacter pylori. In 28 (47%) of the control group but in only seven (14%) of the HIV seropositive patients were C pylori seen on histological examination (p less than 0.001, odds ratio 5.6, 95% confidence interval 2.2-14.5). Sixteen patients who were HIV antibody positive had other index diseases for the diagnosis of AIDS in the biopsy material and, when these were excluded, comparison with the control group still showed a significant difference; p less than 0.01, odds ratio 3.6, 95%, confidence interval 1.4-9.6. In this series, therefore, C pylori were far less common in HIV antibody positive patients than in controls. Among the HIV positive patients, a higher proportion of C pylori negative cases had AIDS but this trend was not significant. The findings of this study indicate that whatever abnormalities of cell mediated mucosal immunoregulation are caused by HIV infection, they do not seem to be important in the response to infection by C pylori.     

Infectious diseases of the upper gastrointestinal tract

A broad spectrum of pathogens produce gastrointestinal disease. The ongoing spread of human immunodeficiency virus/acquired immune deficiency syndrome, the increased use of immunosuppressive therapy and the persistence of overcrowding and suboptimal sanitation in underdeveloped areas facilitate both disease transmission from environmental and foodborne sources and person‐to‐person transmission. Clinicians increasingly rely on endoscopic biopsy sample interpretation to diagnose gastrointestinal infections. Thus, pathologists must be aware of diagnostic features of a variety of microbial pathogens. Detection with molecular techniques also allows for correlation between infectious agents and their histopathological features, which has expanded our knowledge of the inflammatory changes produced by infectious agents. This review covers infectious disorders of the upper gastrointestinal tract encountered in surgical pathology. Clinical, endoscopic and pathological features are presented. The review emphasises morphological features of viruses, bacteria, fungi and parasites that may be found in tissue samples, and the inflammatory patterns that they produce. Differential diagnoses and useful ancillary techniques are discussed.     

Binding of the Helicobacter pylori Vacuolating Cytotoxin to Target Cells

The vacuolating cytotoxin of Helicobacter pylori, VacA, enters the cytoplasm of target cells and causes vacuolar degeneration by interfering with late stages of endocytosis. By using indirect immunofluorescence and flow cytometry, we have demonstrated that VacA binds to specific high-affinity cell surface receptors and that this interaction is necessary for cell intoxication.     

Preventing recurrent upper gastrointestinal bleeding in patients with Helicobacter pylori infection who are taking low-dose aspirin or naproxen

BACKGROUND: Many patients who have had upper gastrointestinal bleeding continue to take low-dose aspirin for cardiovascular prophylaxis or other non-steroidal antiinflammatory drugs (NSAIDs) for musculoskeletal pain. It is uncertain whether infection with Helicobacter pylori is a risk factor for bleeding in such patients. METHODS: We studied patients with a history of upper gastrointestinal bleeding who were infected with H. pylori and who were taking low-dose aspirin or other NSAIDs. We evaluated whether eradication of the infection or omeprazole treatment was more effective in preventing recurrent bleeding. We recruited patients who presented with upper gastrointestinal bleeding that was confirmed by endoscopy. Their ulcers were healed by daily treatment with 20 mg of omeprazole for eight weeks or longer. Then, those who had been taking aspirin were given 80 mg of aspirin daily, and those who had been taking other NSAIDs were given 500 mg of naproxen twice daily for six months. The patients in each group were then randomly assigned separately to receive 20 mg of omeprazole daily for six months or one week of eradication therapy, consisting of 120 mg of bismuth subcitrate, 500 mg of tetracycline, and 400 mg of metronidazole, all given four times daily, followed by placebo for six months. RESULTS: We enrolled 400 patients (250 of whom were taking aspirin and 150 of whom were taking other NSAIDs). Among those taking aspirin, the probability of recurrent bleeding during the six-month period was 1.9 percent for patients who received eradication therapy and 0.9 percent for patients who received omeprazole (absolute difference, 1.0 percent; 95 percent confidence interval for the difference, -1.9 to 3.9 percent). Among users of other NSAIDs, the probability of recurrent bleeding was 18.8 percent for patients receiving eradication therapy and 4.4 percent for those treated with omeprazole (absolute difference, 14.4 percent; 95 percent confidence interval for the difference, 4.4 to 24.4 percent; P=0.005). CONCLUSIONS: Among patients with H. pylori infection and a history of upper gastrointestinal bleeding who are taking low-dose aspirin, the eradication of H. pylori is equivalent to treatment with omeprazole in preventing recurrent bleeding. Omeprazole is superior to the eradication of H. pylori in preventing recurrent bleeding in patients who are taking other NSAIDs.     

Role of Helicobacter pylori in pathogenesis of upper respiratory system diseases

Helicobacter pylori (H. pylori) is one of the frequently encountered micro-organisms in the aerodigestive tract. Although infections caused by H. pylori are this common, the exact mode of transmission has not been fully understood yet. Oral-oral, fecal-oral and gastrointestinal-oral routes are the possible modes of transmission. This infection is usually acquired in childhood and may persist for the whole life of the patient. However, about 80% of the infected humans are asymptomatic. Human stomach was considered to be the only reservoir of H. pylori until bacteria were discovered in human dental plaque, in oral lesions, in saliva, in tonsil and adenoid tissue. It is suggested that H. pylori enters the nasopharyngeal cavity by gastroesophageal reflux and colonize in the dental plaques, adenoid tissues and tonsils. From these localizations, the bacteria ascend to the middle ear and to the paranasal sinuses directly or by the reflux again and may trigger some diseases, including otitis, sinusitis, phyrangitis, laryngitis and glossitis. But still, the exact mechanism remains unclear.     

Helicobacter pylori in gastroduodenal diseases

OBJECTIVE: To determine the prevalence and disease association of Helicobacter pylori (H. pylori) in dyspeptic patients in southwest Nigeria. Setting: Obafemi Awolowo University Teaching Hospitals Complex, Ile-lfe, Nigeria. METHODS: Consecutive dyspeptic patients for upper gastrointestinal endoscopy from January 1996 to March 1997 were investigated for H. pylori in gastric biopsy by histopathology and culture. Patients without gastroduodenal ulcerations or neoplastic lesions constituted the nonulcer dyspeptic (NUD) group. RESULTS: 138 (92 males, 46 females) patients aged 4.5-85 years [mean (7) = 45+/-SD 17.8 years] who had upper gastrointestinal endoscopy were analyzed for presence of H. pylori. Eighty-three had histopathology alone, while 55 others had both histology and culture. Endoscopic diagnosis included duodenal ulcer (DU) (n=35, 23%); gastric ulcer (n=4, 3%); gastric cancer (n=14, 9%); NUD, including gastritis (n=49, 32%); duodenitis (n=47, 31%); and normal (n=16, 11%). Overall, H. pylori was positive in 107 of 138 (77.5%) patients. There was a significant association of H. pylori with DU and NUD (p<0.000). Three-quarters of cases of normal endoscopy harbored H. pylori. The finding of 80% and 85% H. pylori in gastritis and duodenitis, respectively, was of interest. CONCLUSIONS: These findings suggest that DU and NUD were the main clinical expressions of H. pylori infection in southwest Nigerian dyspeptic patients similar to what is found in developed nations. Of note is the high incidence of H. pylori in endoscopically normal patients.     

Medication-induced upper gastrointestinal tract injury

Medication-induced upper gastrointestinal (GI) tract injuries are probably fairly common, yet these injuries are rarely documented in pathology reports. Since these injuries often manifest as non-specific histological changes, making a definitive diagnosis of medication-induced injury can be challenging. Three types of evidence can assist in the establishment of a diagnosis: specific histological patterns, the presence of medication fragments in tissue, and clinical data. Histological patterns may reflect specific tissue responses to medication effects or medication toxicity. Morphological clues of medication use such as pill fragments and crystal deposition may be visible within the tissue itself. Clinical data, including medication history, endoscopic findings, and predisposing conditions can alert the pathologist to situations where medication-induced injury should merit a high ranking on the differential diagnosis list. Except for rare cases where characteristic histological changes can be diagnostic, clinical correlation is essential when diagnosing medication-induced injuries. In this review, key features of the most commonly encountered medication-induced upper GI tract injuries are briefly discussed, and a practical guide to assist the practicing pathologist in the recognition and diagnosis of these injuries is provided.     

Urease production by Helicobacter (Campylobacter) pylori

Urease activity of 50 Helicobacter pylori (H. pylori) strains was assessed employing a photometric assay. Urea hydrolysis reached a maximum in the late log-phase and during the plateau phase of bacterial growth. The reaction time of H. pylori urease was significantly shorter than that of other urease producing bacteria (P. mirabilis, P. vulgaris, K. pneumoniae, K. oxytoca). Increasing the reaction temperature hardly led to an acceleration of the quick urea hydrolysis of H. pylori, in contrast to the situation with P. mirabilis. Acetohydroxamic acid showed a dose-dependent non-competitive suppression of urease production, whereas 9 antibiotics in subinhibitory concentrations did not influence urease production of H. pylori.     

Helicobacter heilmannii gastritis: association with acid peptic diseases and comparison with Helicobacter pylori gastritis.

We analyzed 2 antral and 1 corpus full-thickness random endoscopic gastric mucosal samples obtained from 946 patients with duodenal ulcers (6077 biopsies) and from 281 patients with nonsteroidal anti-inflammatory drug-associated gastric ulcers (1794 biopsies). We stained tissue sections with hematoxylin and eosin and Warthin-Starry silver stain and immunostained them with polyclonal antibodies against Helicobacter pylori. Hematoxylin- and eosin-stained sections from 6 patients with Helicobacter heilmannii (18 biopsies) and 23 randomly selected patients with H. pylori (68 biopsies) were evaluated and semiquantitated for the presence of acute inflammation, chronic inflammation, glandular atrophy, intestinal metaplasia, H. pylori, H. heilmannii, lymphoid follicles, or vasodilatation. Additional specimens were obtained for H. pylori culture, a CLO test, and serologic examination. H. heilmannii was detected in 6 (0.49%) of 1227 patients (14 [0.18%] of 7871 biopsies). Of these, 4 (0.42%) of 946 were patients with duodenal ulcers (9 [0.15%] of 6077 biopsies), and 2 (0.71%) of 281 were patients with nonsteroidal anti-inflammatory drug-associated gastric ulcers (5 [0.28%] of 1794 biopsies). We found H. heilmannii with hematoxylin and eosin stain, Warthin-Starry stain, and immunoperoxidase stain for H. pylori. Culture for H. pylori was negative in the four patients with duodenal ulcers. The CLO and serologic tests were positive in three of five and five of five patients, respectively. Our results indicate that H. heilmannii, like H. pylori, is associated with peptic ulcer disease (both active and inactive gastritis) and that it preferentially colonizes the gastric antrum. The severity of the H. heilmannii-associated gastritis is less intense and lymphoid aggregates are less common than in H. pylori-associated gastritis. Morphologic detection seems to be the method of choice for detecting H. heilmanni. Immunoperoxidase stain specific for H. pylori also stains H. heilmannii, indicating cross-reacting antigenic epitopes between H. heilmannii and H. pylori.     

Adherence of Helicobacter pylori to primary human gastrointestinal cells.

Helicobacter pylori adheres only to gastric cells in vivo. However, the organism adheres to a wide variety of nongastric cells in vitro. In this study, we have used flow cytometry to assess the adherence of H. pylori to primary epithelial cells isolated from gastric, duodenal, and colonic biopsy specimens by collagenase digestion. After incubation of bacteria and cells together and subsequent staining with a two-stage fluorescein isothiocyanate-labelled H. pylori antibody method, cells with adherent bacteria could be easily distinguished from cells without bacteria. Binding to Kato III cells (a gastric adenocarcinoma cell line) was saturable when bacteria and cells were mixed at a ratio of 250:1. Adherence to cells isolated from gastric biopsy specimens was significantly better than adherence to cells isolated from duodenal or colonic biopsy specimens. Almost 70% of gastric cells had bacteria bound, in contrast to 30% of duodenal cells and 32% of colonic cells (P < 0.0001). There was no correlation between expression of hemagglutinins by the bacteria and ability to bind to either Kato III cells or primary epithelial cells isolated from gastric biopsy specimens. In view of the strict tropism that the organism exhibits in vivo for gastric cells, the results of this study indicate that primary cells are ideal for assessing the factors that might play a role in the pathogenesis of disease caused by the organism.     

Simple and Accurate PCR-Based System for Typing Vacuolating Cytotoxin Alleles of Helicobacter pylori

Alleles of the vacuolating cytotoxin gene (vacA) of Helicobacter pylori vary between strains, particularly in the region encoding the signal sequence (which may be type s1 or s2) and the midregion (which may be type m1 or m2). Using a PCR-based typing system developed in the United States, we showed that 36 strains from Asia and South America were all vacA signal sequence type s1; 3 were midregion type m1 and 11 were m2, but 22 could not be typed for the vacA midregion. All strains possessed cagA (cytotoxin-associated gene A), another virulence marker. vacA nucleotide sequence analysis showed that midregion typing failure was due to base substitutions at the primer annealing sites. Using the new sequence data, we developed two new PCR-based vacA midregion typing systems, both of which correctly typed 41 U.S. strains previously typed by the old system and successfully typed all 36 of the non-U.S. strains. All previously untypeable strains were vacA m1, other than one m1/m2 hybrid. In summary, we describe and validate a simple PCR-based system for typing vacuolating cytotoxin (vacA) alleles of H. pylori and show that this system correctly identifies the signal and midregion types of vacA in 77 strains from Asia and North and South America.     

Helicobacter pylori and associated gastroduodenal diseases. Review article

Helicobacter pylori is a microaerophilic, Gram-negative, spiral rod, the role of which in different gastric diseases has been investigated worldwide since the beginning of the 1980s. H. pylori has been shown to be the causative agent in active chronic gastritis, and it is regularly found in patients endoscopied for duodenal ulcer. The bacterium is also frequently isolated from persons with gastric ulcer, gastric carcinoma and non-ulcer dyspepsia. Apart from cultivation of the bacterium, other diagnostic procedures include various staining methods and urease tests of gastric biopsy samples. The application of non-invasive diagnostic methods, serology and urea breath tests, is rapidly increasing. H. pylori is susceptible to several antimicrobials in vitro, but eradication of the bacterium from the gastric mucosa is not always achieved. The best results until now have been obtained with the combined use of bismuth salts and two antibiotics. In active chronic gastritis and duodenal ulcer patients, eradication of the bacteria has resulted in healing of the disease with permanent decrease of circulating antibodies and negative urease tests. H. pylori has been found worldwide and the infection shows an age-dependent increase. Man, apparently, is the reservoir of the bacterium, but the exact mechanisms of interhuman transmission are still not defined.     

TNF基因多态性与胃十二指肠疾病幽门螺杆菌感染的相关性研究

目的：研究我国湖北汉族人群肿瘤坏死因子（Tumor Necrosis Factor,TNF）基因多态性与胃十二指肠疾病及幽门螺杆菌（Helicobacter Pylori,Hp）感染的关系,探讨宿主遗传因素对Hp感染在胃十二指肠疾病尤其是非贲门胃癌的作用.方法：采用病例对照研究和PCR-RFLP方法,检测210例胃十二指肠疾病患者（包括73例慢性胃炎、78例十二指肠溃疡及59例非贲门胃癌患者）和264例正常对照者的TNF-α 308、LT-α Nco Ⅰ、AspH Ⅰ双等位基因型分布.Hp感染检测血清Hp Ab-IgG.结果：胃十二指肠疾病患者的Hp阳性率90.5%,显著高于正常对照组62.1%（P＜0.000 1,Odds ratio=5.793,95%CI：3.431～9.780）.LT-α Nco Ⅰ A/G基因型在Hp阳性非贲门胃癌患者（64.0%）高于Hp阳性的正常对照组（46.0%）,差异有显著性意义（P=0.029 7,OR=2.026,95%CI：1.080～3.803）,该基因型与其他胃十二指肠疾病无相关性.TNF-α 308、LT-α AspH Ⅰ与Hp感染及胃十二指肠疾病亦无相关性.结论：LT-α Nco Ⅰ A/G基因型与中国湖北汉族人群非贲门胃癌Hp阳性相关.