Quantitative breath testing does not predict the presence of peptic ulcer disease.
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Publications and source records attributed to D C Metz.
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BACKGROUND: Gastroesophageal reflux disease occasionally presents with laryngeal symptoms. Such patients are often referred for a gastroenterology evaluation. This study was designed to determine whether an empiric trial of high-dose omeprazole therapy could reliably identify patients with reflux laryngitis and thus obviate the need for a gastroenterology workup. METHODS: Patients were evaluated with a history, physical examination, esophageal manometry, upper endoscopy, and 24-hour pH-metry for determination of the presence of absence of underlying gastroesophageal reflux disease and then received an empiric trial of oral omeprazole therapy (20 mg twice daily for 1 month). A positive omeprazole test result was defined as resolution of all laryngeal symptoms on completion of the empiric trial of therapy. RESULTS: Two patients were classified as having no reflux, and eight were classified as having reflux. Omeprazole test results were positive in six patients. Five of six had reflux, but one patient had no evidence for reflux. Omeprazole test results were negative in four patients. Three of four had reflux, and one did not. Despite the absence of antisecretory therapy, laryngeal symptoms did not recur in either patient without reflux during follow-up. Laryngeal symptoms were managed in two of the three patients with reflux who had negative omeprazole test results and who were using inhalers in combination with histamine H2 receptor antagonist therapy for their reflux disease. One patient with reflux who had a negative omeprazole test result responded to higher doses of omeprazole, and the five patients with reflux who had positive omeprazole test results all responded to continuation of omeprazole. CONCLUSIONS: The omeprazole test may be useful in confirming the suspicion of reflux laryngitis in patients suspected of having this disease after an otolaryngology evaluation. However, there is a potential for false-positive and false-negative test results. A gastroenterology evaluation may aid in the identification of false-positive test results by documenting the absence of reflux in certain responders.
Endoscopic evaluation of the presence or absence of gastritis is often performed in lieu of biopsy and histologic diagnosis. The purpose of our study was to assess the value of endoscopic examination as a diagnostic test for gastritis. Two endoscopists prospectively assessed the antrum of 73 patients undergoing upper gastrointestinal endoscopy and graded, on a scale of 0-4 (0 = completely absent, 4 = definitely present), the likelihood of gastritis. The following features were also assessed at the time of endoscopy: erythema, nodularity, erosion, edema, and friability. Two concomitant antral biopsies (3 cm from the pylorus on the greater curvature of the stomach) were performed regardless of the endoscopic impression. The histologic findings were graded independently on a scale of 0-3 by two pathologists who were not aware of the endoscopic findings. The following histologic features were graded: acute inflammation, chronic inflammation, lymphoid aggregates, intestinal metaplasia, and quantity of Helicobacter pylori organisms. Receiver operator characteristic analysis, a method derived from signal detection theory, assesses the trade-off of sensitivity and specificity over all cutoff points of a test and is considered the best method by which to compare tests and determine the diagnostic utility of a given test. Receiver operator characteristic analysis gave an area of 0.65 +/- 0.01 SE for endoscopy as a test for gastritis (0.5 = chance, 1 = perfect) as defined by the histologic presence of inflammation. Additionally, endoscopy as a test for the presence of histologically proven Helicobacter pylori gave an area of 0.55 +/- 0.01 SE. All endoscopically graded features treated as separate tests for gastritis and/or H. pylori gave areas of approximately 0.44-0.61, indicative of a poor test. While H. pylori was always associated with at least some degree of inflammation, linear regression analysis revealed no correlation among any of the histologic features or of any histologic feature with any endoscopic feature. We conclude that a tissue diagnosis is essential for the proper diagnosis of gastritis.
To determine whether the urease-based CLOtest or low-dose 14C urea breath test can predict severity of gastritis or the presence of peptic ulcers, we studied 84 patients presenting for upper endoscopy. Antral biopsies were obtained for histologic analysis and CLOtesting, and urea breath testing was performed. The time to a positive CLOtest and the breath test peak values were correlated with endoscopic findings, severity of gastritis, and bacterial burden. Twenty-four patients had positive urea breath test results (22 with positive CLOtests). Patients with positive breath test results were more likely to have duodenal ulcers, higher grades of gastritis, and increased bacterial burden (p < 0.01 for all comparisons). Correlation between the time to a positive CLOtest or peak breath test values and gastritis severity or bacterial burden was poor (p > 0.05 for all comparisons). In patients with positive tests, no difference was observed between the time to a positive CLOtest or peak breath test value in patients with or without peptic ulcers (p < 0.2 for all comparisons). The low-dose 14C urea breath test and the CLOtest are both accurate for Helicobacter pylori diagnosis. However, neither test predicts the severity of the gastritis, the degree of bacterial burden, or the presence of peptic ulcers.
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Numerous detection methods for Helicobacter Pylori (H. pylori) have been developed with varying degrees of purported diagnostic utility. We have developed a rapid nonradioactive in situ hybridization (ISH) method for H. pylori detection in paraffin-embedded tissue and assessed its relative diagnostic performance by receiver operator characteristics (ROC) in comparison to the thiazine stain and CLOtest. Forty-five patients undergoing endoscopy had antral biopsies and concomitant CLOtest performed. ISH for H. pylori was done using a 22-base, biotin-labeled oligonucleotide probe complementary to a portion of H. pylori 16s rRNA with the following sequence: 5'-GGACATAGGCTGATCTTAGC-3'. ISH using this probe was specific for H. pylori with no crossreactivity with other bacterial or fungal organisms. Receiver operator characteristic analysis was used to assess the diagnostic performance of ISH and thiazine techniques. ISH and thiazine stains were done on serial sections, reviewed independently, and scored on a graded scale from 1-5 based upon the degree of assurance of H. pylori presence. Diagnostic performance was assessed in "expert" and "nonexpert" pathologist groups with the CLOtest serving as the invariant test for relative test comparison. The ISH test performed slightly better (ROC area 0.9) than the thiazine (ROC area 0.8) in the nonexpert population, but equally well in the "expert" group (ROC area 0.95, 0.95). ISH followed by routine hematoxylin and eosin staining showed detailed mucosal histology with a dramatic visualization of H. pylori along the surface of the foveolar cells with no evidence of lamina propria invasion. In summary, ISH for H. pylori is an excellent test that is specific, easily read, and allows concomitant detailed histologic mucosal examination.
BACKGROUND: Most patients with esophageal carcinoma present with locally advanced disease and a poor prognosis. Surgery or radiation provides palliation for locally advanced esophageal carcinoma. The role of neoadjuvant therapy remains to be defined. We administered neoadjuvant chemotherapy consisting of 5-fluorouracil (5-FU), leucovorin, interferon-alpha, and cisplatin to 11 patients with locally advanced disease. METHODS: Eleven patients with squamous cell or adenocarcinoma of the esophagus were treated peroperatively with two to three cycles of combination chemotherapy. Nine patients underwent resection with curative intent. RESULTS: Six patients received three cycles of chemotherapy, and five received two. Dose reduction was necessary for two patients. One patient achieved a pathologic complete response, histologically confirmed. Of the eleven patients, two did not undergo surgery because of progressive disease during chemotherapy. Seven of the 9 patients relapsed after surgery and 2 have been disease free for 27 months. CONCLUSIONS: The combination 5-FU leucovorin, interferon-alpha-2a, and cisplatin administered in a neoadjuvant setting resulted in a median survival of 11.8 months with a median time to relapse of 7 months.
Helicobacter pylori is a common cause of gastritis. No single test is 100% accurate for H. pylori diagnosis. In order to determine whether the presence of typical histological features of H. pylori gastritis may yield diagnostic information, we compared antral histology by H & E stain to the presence of organisms as detected on Thiazine stain of antral specimens, CLOtest, urea breath test and anti-H. pylori serology in 50 consecutive patients. Patients were diagnosed as having active H. pylori infection if at least two of these tests were positive. Patients with only one test positive (N = 5) were considered indeterminate for H. pylori and were excluded, resulting in 19 patients (42%) being classified as H. pylori positive. All slides were reviewed by a single blinded expert gastrointestinal pathologist and graded 0 (none) to 3 (severe) for the presence of acute (polymorphonuclear cells) or chronic (lymphocytes, monocytes, plasma cells) inflammation, lymphoid aggregates, and intestinal metaplasia. Active infection was associated with the presence of both acute and chronic inflammation (P < 0.0001) but not lymphoid aggregates (P = 0.09) or intestinal metaplasia (P = 0.10). The best positive predictors of infection were the presence of any acute inflammation (PPV = 86%) and the combination of any acute and chronic inflammation (PPV = 92%). The best negative predictor was absence of chronic inflammation (NPV = 100%). The presence of moderate to severe (grade 2 or 3) acute or chronic inflammation were each 100% predictive of infection. Moderate to severe chronic inflammation had both 100% sensitivity and specificity for active H. pylori infection, while moderate to severe acute inflammation was only 26% sensitive but 100% specific. The presence of any acute, or the combination of acute and chronic gastritis, is predictive of active H. pylori infection. Moreover, the predictive value correlates closely with the severity of the inflammation. The absence of chronic inflammatory cells rules out active H. pylori infection. These findings support the use of H & E histology-determined features in conjunction with other tests to diagnose H. pylori infection.
We reviewed the discharge records of all diabetic ketoacidosis hospitalizations over 30 months for the presence of clinically significant upper gastrointestinal hemorrhage. Of 284 hospitalizations in 193 patients, hemorrhage occurred in 26 hospitalizations (9%) in 25 patients (13%). None required invasive therapy to achieve hemostasis, and there were no bleeding recurrences and no deaths due to bleeding. Endoscopy in eight revealed esophagitis in all (five had erosions or ulcerations), one Mallory-Weiss tear, five with gastritis (mild in four), four with duodenitis (one erosive), one duodenal ulcer, and no gastric ulcers. Hemorrhage patients had a longer diabetes duration (14.85 vs 9.16 years, P < 0.02), and more nephropathy (40% vs 11%, P < 0.001), retinopathy (28% vs 12%, P < 0.03) and gastroparesis (36% vs 10%, P < 0.002) than those without hemorrhage. Ulcer medication (42% vs 23%, P < 0.03) or anticoagulant (12% vs 1%, P < 0.005) but not nonsteroidal antiinflammatory drug usage (12% vs 12%) was higher in the hemorrhage group. Admission glucose (P < 0.02), BUN (P < 0.04), and creatinine (P < 0.02) levels were higher in hemorrhage patients, but arterial pH, serum ketones, hemoglobin, platelet count, and coagulation values were not. Hemorrhage patients required more blood transfusions (27% vs 10%, P < 0.003) and intensive care unit admissions (69% vs 43%, P < 0.009). Total (15% vs 3%, P < 0.003) and intensive care unit mortality (22% vs 6%, P < 0.026) were higher in the hemorrhage group. We conclude that upper gastrointestinal hemorrhage complicates 9% of diabetic ketoacidosis hospitalizations. Blood transfusion may be required, but the bleeding is self-limited and not severe. The most common lesion is erosive esophagitis. Hemorrhage correlates with glucose level, admission to the intensive care unit, duration of diabetes, the presence of diabetic complications, and portends a high non-bleeding-related mortality.
The current gold standard for diagnosing H. pylori gastritis requires antral biopsy for urease test (eg, CLOtest) and/or history. We compared this gold standard to a new low-dose capsule-based 1 microCi [4C]urea breath test (UBT) and a rapid serum test for anti-H. pylori antibodies (FlexSure HP) in 50 consecutive patients undergoing upper endoscopy. Antral biopsies within 3 cm of the pylorus were used for CLOtest and were stained with H&E and thiazine. Slides were reviewed by a single, blinded pathologist (Review) and compared to the pathology department report (Report). A true positive was defined as a positive CLOtest or Review. The prevalence of H. pylori infection by each test was: CLOtest 32%, Review 36%, gold standard 42%, UBT 38%, FlexSure HP 44%, Report 44%. UBT had sensitivity = 90%, specificity = 96%, positive predictive value = 95%, and negative predictive value = 93% and accurately determined H. pylori status in a subgroup of 10 patients who had completed treatment. The one false positive breath test occurred in a patient with 2+ chronic inflammation on biopsy and a positive antibody test. There were two false negative breath tests. Each had both negative CLOtests and negative antibody tests. FlexSure HP had sensitivity = 74%, specificity = 89%, positive predictive value = 88%, and negative predictive value = 77% in patients not previously treated, but had a high false-positive rate in the 10 patients after treatment. Pathology department Report and blinded pathologist Review had only 84% agreement, kappa = 0.67. Both CLOtest and UBT agreed better with Review (86%, 87%, kappa = 0.68, 0.73, respectively) than Report (78%, 77%, kappa = 0.53, 0.53, respectively) suggesting that Review is more accurate than Report. When biopsy is done, we recommend that a CLOtest be performed followed by histological examination if the CLOtest is negative to ensure adequate sensitivity. However, interpretation of histological slides has significant interobserver variability even in experienced hands and may be inaccurate at times. FlexSure HP has good PPV but inadequate sensitivity to rule out active infection and is not useful in patients after treatment. UBT is an excellent noninvasive test that should be considered in cases where EGD is otherwise not indicated.
This article provides the primary care clinician with a general diagnostic and therapeutic approach to the adult patient with diarrhea. Basic pathophysiologic mechanisms are described. Important causes and clinical features of each type of diarrhea are highlighted. A step-by-step diagnostic evaluation is suggested, and an overview of treatment options is presented.
We report a case of a patient who developed gastroparesis after laparoscopic Nissen fundoplication. The development of postoperative gastroparesis after either an open or laparoscopic Nissen fundoplication is uncommon but may result in significant morbidity. With greater numbers of laparoscopic fundoplications being performed, the complication of gastroparesis may be noted more frequently.
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The present report describes two patients with fasting hypergastrinemia, gastric acid hypersecretion, and Helicobacter pylori gastritis. Provocative testing for Zollinger-Ellison syndrome was negative and imaging studies did not demonstrate an intra-abdominal mass. Following eradication of the Helicobacter pylori infection, the fasting hypergastrinemia resolved in both patients and in one patient the gastric acid hypersecretion also resolved. The implications of this case on the differential diagnosis of Zollinger-Ellison syndrome are discussed.
An antibiotic combination that includes a proton pump inhibitor such as omeprazole and an antibiotic such as clarithromycin is likely to become the new standard regimen for treatment of Helicobacter pylori gastritis because this combination is extremely effective and very well tolerated. The current report highlights a potentially significant pharmakokinetic drug interaction between clarithromycin and carbamazepine in two patients with long-standing epilepsy who were given such therapy for Helicobacter pylori gastritis. In both cases, clarithromycin therapy was temporally related to an increase in serum carbamazepine levels, which returned to the therapeutic range following cessation of clarithromycin therapy. The potential implications of this newly recognized drug interaction are discussed.
BACKGROUND/AIMS: It is unclear whether tumor location, size, or the presence of multiple endocrine neoplasia type 1 (MEN-1) alters metastatic rate and survival in patients with pancreatic endocrine tumors. The purpose of this study was to determine the prognostic factors of survival and metastatic rate in patients with Zollinger-Ellison syndrome (ZES). METHODS: Data were analyzed from 185 consecutive patients with ZES who were followed up prospectively. RESULTS: Liver metastases were present in 24% of patients and correlated with the size of the primary tumor. Duodenal tumors were smaller than pancreatic tumors. Liver metastases occurred more often (P < 0.00001) with pancreatic than duodenal tumors, whereas the metastatic rate to lymph nodes was not different. Survival of patients with liver but not lymph node metastases was shortened. In patients with sporadic ZES, liver metastases were more common during the initial evaluation and survival was decreased compared with patients with MEN-1; however, during follow-up, an equal percentage of patients with and without MEN-1 developed liver metastases. CONCLUSIONS: Survival was primarily determined by the presence of liver metastases. The frequency of liver metastases depends on the size and location of the primary tumor and on the presence of MEN-1 at the initial presentation. Metastases to the lymph nodes do not depend on these factors. A benign and malignant form of ZES exists.
Manifestations of esophageal disease are present in up to 60% of patients with Zollinger-Ellison syndrome (ZES), although esophageal function has been studied in only a few patients and the prevalence of Barrett's mucosa is unknown in these patients. It is unclear whether the high prevalence of esophageal disease is related to gastric acid hypersecretion alone or to abnormalities of esophageal motility or lower esophageal sphincter (LES) function in addition. To address these issues in the present study esophageal function was evaluated prospectively in 92 consecutive patients with ZES (66 with active disease, 26 disease-free after curative resection) seen during a 1-year period after controlling acid hypersecretion. In the patients with active disease the mean basal acid output (BAO) was 33 +/- 3.0 mEq/h, the maximal acid output (MAO) was 56 +/- 4.0 mEg/h, fasting serum gastrin was 8,736 +/- 4,813 pg/ml and duration of disease prior to study was 12.5 +/- 2.0 years. At the time of manometry, gastric acid secretion was controlled in all patients and no patient had evidence of gastroesophageal reflux disease at upper gastrointestinal endoscopy. Esophageal manometry revealed normal motility in 85% of patients. Eleven percent had low LES pressures, and only 1% of patients had an elevated LES pressure. The frequency of Barrett's mucosa (3%) was similar to that found in the general population but much less than that reported in patients with idiopathic GERD. No correlation was noted between LES pressures or manometric abnormalities and the fasting serum gastrin, BAO, MAO or the presence or absence of multiple endocrine neoplasia type I or previous vagotomy. Esophageal manometric results and LES pressure were similar in disease-free patients and those with active ZES. In conclusion, these results suggest that hypergastrinemia or other disease-specific abnormalities are not contributing to the high incidence of esophageal disease in patients with ZES because esophageal function in patients with ZES is similar to normals. Specifically, motility disorders in patients with ZES occur in similar frequency to normals, and LES pressure is normal in most patients. Despite the high levels of acid secretion and prominence of symptoms, the occurrence of Barrett's mucosa was uncommon (3%) raising the possibility of additional protective mechanisms in patients with ZES.
In contrast to the acute leukemias, chronic lymphocytic leukemia (CLL) is a hematological malignancy with a generally good prognosis. Gastrointestinal (GI) involvement with CLL is unusual, and GI complications generally occur after malignant transformation to diffuse large cell lymphoma (Richter's syndrome). We present a case of CLL directly infiltrating the gastro-esophageal junction resulting in upper GI hemorrhage. This is only the second such case in the literature. We emphasize the consideration of direct leukemic infiltration in addition to Richter's syndrome in the differential diagnosis of GI bleeding in patients with CLL. Whereas the prognosis of Richter's syndrome is poor, CLL involvement of the GI tract may respond to treatment with chemo- or radiotherapy.