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Objectives: Nonsteroidal anti-inflammatory drug (NSAID)-induced gastrointestinal (GI) toxicity remains the most frequent adverse drug event in the United States. The objective of this review is to update clinicians in recent advances in basic and clinical investigation regarding the pathogenesis and management of NSAID gastropathy., Methods: Based upon an extensive review of the published literature and abstracts of key work within the past decade, the framework for new approaches to the prevention and treatment of NSAID-associated ulceration is summarized., Results: The pathophysiology of NSAID-induced injury to the GI tract is multifaceted and includes both prostaglandin-dependent and independent components. The pharmaceutical industry has capitalized on the identification of two different isoforms of cyclooxygenase, enabling the development of specific inhibitors of one isoform that minimizes prostaglandin-dependent mechanisms that contribute to NSAID-induced injury. Clinical trials support the efficacy and reduced toxicity of these agents. Because acid exacerbates the injury initiated by NSAIDs, potent acid suppressive therapy, typically with proton pump inhibitors, is another common approach to the treatment of NSAID-related dyspepsia as well as NSAID-induced ulcer disease., Conclusions: Recent improvements in the understanding of NSAID-induced damage and new drug development have provided the opportunity for effective anti-inflammatory therapy with reduced GI toxicity. This illustrates the importance of identifying patients at risk for potential complications and the appropriate use of strategies to prevent and treat NSAID-induced complications.

Background: Pre-medication with droperidol has been used to improve sedation during endoscopy, especially in patients with a history of alcohol or narcotic abuse. We studied whether routine use of droperidol pre-endoscopic retrograde cholangiopancreatography (ERCP) could improve patient and physician satisfaction with sedation., Methods: Sixty-seven patients undergoing routine ERCP were enrolled in this double-blind placebo-controlled study. Patients were given either parenteral normal saline solution or 5 mg of droperidol 15 minutes before the procedure. After the ERCP, several parameters of procedural sedation were scored on an ordinal scale by the endoscopist, the endoscopy nurse, and the recovered patient. In addition, a follow-up telephone call was made to the patient after 24 hours., Results: The mean procedural room time was similar in the two groups. Nearly 25% less meperidine and diazepam was used in the droperidol-treated patients, making the overall medication cost similar in both groups. The mean recovery room time was 113 minutes for the placebo group and 106 minutes for the droperidol group. Droperidol premedication significantly decreased post-procedure nausea and vomiting, reduced gagging at intubation, and decreased retching during the procedure. Droperidol also improved physician (p = 0.001), nurse (p = 0.001), and patient (p = 0.0001) impressions of overall sedation and decreased the need for physical restraint during the procedure. Droperidol significantly increased the number of patients with no memory of the procedure., Conclusion: Droperidol improved overall patient, physician, and nurse satisfaction with sedation during ERCP. It also reduced post-ERCP nausea and vomiting without increasing recovery time or medication cost. Droperidol is recommended for routine pre-ERCP sedation. (Gastrointest Endosc 2000;52:362-6).

Unlabelled: Preoperative localization of pancreatic neuroendocrine tumors with traditional imaging fails in 40-60% of patients. Endoscopic ultrasound (EUS) is highly sensitive in the detection of these tumors. Previous reports included relatively few patients or required the collaboration of multiple centers. We report the results of EUS evaluation of 82 patients with pancreatic neuroendocrine tumors., Methods: We prospectively used EUS early in the diagnostic evaluation of patients with biochemical or clinical evidence of neuroendocrine tumors. Patients had surgical confirmation of tumor localization or clinical follow-up of >1 yr., Results: Eighty-two patients underwent 91 examinations (cases). Thirty patients had multiple endocrine neoplasia syndrome type 1. One hundred pancreatic tumors were visualized by EUS in 54 different patients. The remaining 28 patients had no pancreatic tumor or an extrapancreatic tumor. Surgical/pathological confirmation was obtained in 75 patients. The mean tumor diameter was 1.51 cm and 71% of the tumors were < or =2.0 cm in diameter. Of the 54 explorations with surgical confirmation of a pancreatic tumor, EUS correctly localized the tumor in 50 patients (93%). Twenty-nine insulinomas, 18 gastrinomas, as well as one glucagonoma, one carcinoid tumor, and one somatostatinoma were localized. The most common site for tumor localization was the pancreatic head (46 patients). Most tumors were hypoechoic, homogenous, and had distinct margins. EUS of the pancreas was correctly negative in 20 of 21 patients (specificity, 95%). EUS was more accurate than angiography with or without stimulation testing (secretin for gastrinoma, calcium for insulinoma), transcutaneous ultrasound, and CT in those patients undergoing further imaging procedures. EUS was not reliable in localizing extrapancreatic tumors., Conclusions: In this series, the largest single center experience reported to date, EUS had an overall sensitivity and accuracy of 93% for pancreatic neuroendocrine tumors. Our results support the use of EUS as a primary diagnostic modality in the evaluation and management of patients with neuroendocrine tumors of the pancreas.

Objective: Several innovative imaging modalities, including endoscopic ultrasound, have increased the number of available preoperative staging methods in patients with adenocarcinoma of the pancreas. Our goal was to estimate the clinical outcomes and cost-effectiveness of alternative staging strategies for pancreatic adenocarcinoma., Methods: Decision analysis was used to simulate alternative staging strategies. Cost inputs were based on Medicare reimbursements; clinical inputs were obtained from the available literature. Model endpoints of interest were cost per curative resection and appropriateness of treatment allocation based on pathological stage., Results: Endoscopic ultrasound followed by laparoscopy yielded the lowest cost per curative resection ($37,600) and minimized the number of unnecessary surgical explorations (5.4 per 100 patients staged). Requiring angiographic confirmation when endoscopic ultrasound demonstrated an unresectable tumor yielded an intermediate cost-effectiveness ratio and virtually eliminated the risk of overstaging. Laparoscopy alone maximized the resection rate, but each additional resection would cost approximately $2 million relative to a strategy employing both endoscopic ultrasound and angiography., Conclusions: Staging strategies incorporating endoscopic ultrasound may improve treatment allocation and are cost-effective relative to angiography-based strategies. A staging protocol that does not incorporate an imaging modality to detect vascular invasion dramatically increases the cost per additional curative resection compared with more comprehensive staging protocols.

Objective: Current clinical consensus supports an initial Helicobacter pylori (HP) "test and treat" approach when compared to immediate endoscopy for patients with suspected peptic ulcer disease. Alternative diagnostic approaches that incorporate upper GI radiography (UGI) have not been previously evaluated. We sought to determine the cost effectiveness of UGI compared to a HP test and treat strategy, incorporating recent data addressing the reduced prevalence of HP, lower cost of diagnostic interventions, and reduced attribution of PUD to HP., Methods: Using decision analysis, three diagnostic and treatment strategies were evaluated: 1) Test and Treat--initial HP serology, treat patients who test positive with HP eradication and antiulcer therapy; 2) Initial UGI series--treat all patients with documented ulcer disease with HP eradication and antiulcer therapy; and 3) Initial UGI series, HP serology if ulcer present--treat ulcer and HP based on diagnostic test results., Results: The estimated cost per ulcer cured for each strategy were as follows: test and treat, $3,025; initial UGI, $3,690; and UGI with serology, $3,790. The estimated cost per patient treatment were: test and treat, $498; initial UGI, $610; and UGI with serology, $620. When UGI reimbursement was decreased to less than $50, the UGI strategies yielded a lower cost per patient treated than the test and treat strategy., Conclusion: At the current level of reimbursement, UGI should not be considered a cost-effective alternative to the HP test and treat strategy for the initial evaluation of patients with suspected peptic ulcer disease.

Chronic ingestion of NSAIDs increases the risk for gastrointestinal complications, which range from dyspepsia to gastrointestinal bleeding, obstruction, and perforation. Among patients using NSAIDs, 0.1 to 2.0% per year suffer serious gastrointestinal complications. Patients who require analgesic therapy should be carefully assessed for the lowest possible dosage and shortest duration of NSAID use and for the potential of treatment with a non-NSAID pain reliever. These patients should also be assessed for factors that increase their risk of gastrointestinal complications, including increased age, concomitant anticoagulant or corticosteroid use, and past history of NSAID-associated gastrointestinal complications. The exact association between Helicobacter pylori infection and NSAID-related ulcer disease is unclear, and the routine testing and treatment of all NSAID using patients for H. pylori infection is not recommended at this time. NSAID-using patients who suffer from dyspepsia should have NSAIDs discontinued, the dosage changed, or be changed to a different class of NSAID. If NSAIDs cannot be discontinued, then an antisecretory agent should be initiated. Misoprostol prevents NSAID-associated gastrointestinal complications. Proton pump inhibitors are the most effective at healing NSAID-associated ulcers among patients who cannot discontinue NSAID therapy.

Background: Medical management of giant peptic ulcers has traditionally been associated with significant morbidity and mortality rates, dictating the need for surgical intervention., Methods: To determine if recent advances in therapy has reduced the number of patients who require surgical procedures, we reviewed the medical records of all patients with peptic ulcers of 2 cm or more at our institution from January 1991 to August 1996., Results: We identified 75 patients with giant ulcers who were followed for a mean duration of 36 months. Sixty-three patients (84%) were managed without operation with a good outcome, documented by healing on repeat esophagogastroduodenoscopy and/or resolution of symptoms. Medical management included treatment of Helicobacter pylori infection, stopping nonsteroidal anti-inflammatory drugs, and potent acid suppression. Endoscopic intervention to control bleeding was successful in 7 patients (9%), and 2 patients (3%) were treated successfully with angiographic embolization. Only 12 patients (16%) required surgical intervention: 6 as the result of bleeding, 2 as the result of perforation, 1 as the result of obstruction, and 3 with intractable disease., Conclusions: In this series of patients with giant peptic ulcers, most patients (84%) were managed without surgical treatment. Our data suggest that improvements in medical therapy have obviated the need for eventual surgical intervention in most patients with giant ulcers.

Background: Computerized tomography (CT), magnetic resonance imaging (MRI), and transabdominal ultrasound frequently fail to detect ampullary lesions. Endoscopic ultrasound (EUS) is a sensitive modality for detecting and staging ampullary tumors. Accurate staging may be affected by biliary stenting, which is frequently performed in these patients with obstructive jaundice. The present study assessed the accuracy of ampullary tumor staging with multiple imaging modalities in patients with and those without endobiliary stents., Methods: Fifty consecutive patients with ampullary neoplasms from two endosonography centers were preoperatively staged by EUS plus CT (37 patients), MRI (13 patients), or angiography (10 patients) over a 3(1/2) year period. Twenty-five of the 50 patients had a transpapillary endobiliary stent present at the time of endosonographic examination. Accuracy of EUS, CT, MRI, and angiography was assessed with the TNM classification system and compared with surgical-pathologic staging. The influence of an endobiliary stent present at the time of EUS on staging accuracy of EUS was also evaluated., Results: EUS was more accurate than CT and MRI in the overall assessment of the T stage of ampullary neoplasms (EUS 78%, CT 24%, MRI 46%). No significant difference in N stage accuracy was noted between the three imaging modalities (EUS 68%, CT 59%, MRI 77%). EUS T stage accuracy was reduced from 84% to 72% in the presence of a transpapillary endobiliary stent. This was most prominent in the understaging of T2/T3 carcinomas., Conclusions: EUS is superior to CT and MRI in assessing T stage but not N stage of ampullary lesions. The presence of an endobiliary stent at EUS may result in underestimating the need for a Whipple resection because of tumor understaging.

Objective: Helicobacter pylori (H. pylori) causes chronic gastritis. The inducible prostaglandin synthetase cyclooxygenase 2 (COX-2) plays an important role in inflammatory conditions. We hypothesized that H. pylori-associated chronic gastritis would express COX-2 protein. Our aim was to evaluate the effect of eradication of H. pylori infection on COX-2 expression in the antral mucosa of patients before and after antibiotic therapy., Methods: Tissues were obtained from patients with non-ulcer dyspepia undergoing H. pylori eradication. Ten patients with proven H. pylori infection and subsequent successful eradication were studied. Three biopsies of antral mucosa were evaluated before and after H. pylori eradication. The amount of acute and chronic inflammation was quantitated. Immunohistochemical staining for COX-2 was expressed as a percentage of the total number of cells and correlated with the degree of chronic inflammation., Results: Specific immunostaining for COX-2 was observed in antral mucosa of patients infected with H. pylori. Patchy cytoplasmic staining was seen in surface epithelial cells and strong cytoplasmic staining for COX-2 was seen in parietal cells. Spotty cytoplasmic staining for COX-2 was also seen in lamina propria plasma cells, as well as there being macrophages present in the germinal centers of lymphoid aggregates. COX-2 expression could be detected both before and after eradication of H. pylori. The mean percentage of cells staining for COX-2 was significantly higher in H. pylori-infected mucosa, compared with mucosa after successful H. pylori eradication (33.4% +/- 5.4 vs 18.9% +/- 3.3, p = 0.038). COX-2 immunostaining correlated best with the chronic inflammation score (r2 = 0.78, p < 0.001). There was a strong correlation for those subjects who were H. pylori infected, as well as for those who had successful H. pylori eradication., Conclusions: H. pylori associated acute and chronic antral inflammation was associated with immunohistochemical detection of COX-2 protein in epithelial cells, in addition to associated mononuclear cells and parietal cells. Expression was reduced, but not eliminated, in the epithelium after successful eradication of H. pylori. Despite the reduction in COX-2 expression after H. pylori eradication, expression of COX-2 in epithelial cells remained and strongly correlated with the extent of the chronic inflammatory cell infiltrate. The clinical implications of H. pylori-associated induction of COX-2 expression for patients on selective COX-2 inhibitors, in addition to the role of COX-2 in gastric carcinogenesis, deserve further study.

Background: Helicobacter pylori infection has been identified as a risk factor for certain types of gastric cancer. However, the extent to which H. pylori eradication decreases the risk of gastric cancer is unknown, raising the question of whether population-based H. pylori screening should be undertaken., Objective: To compare clinical and economic effects of H. pylori screening, with and without confirmatory testing, with no screening to prevent gastric cancer., Design: Decision analysis incorporating a Markov simulation., Patients: Simulated cohorts of men and women with varying risk of gastric cancer., Intervention: Three strategies were evaluated: (1) no screening; (2) H. pylori serologic testing, treat those positive for H. pylori, no follow-up testing; and (3) H. pylori serologic testing, treat those positive for H. pylori, followed by a test to confirm H. pylori eradication, retreat those who test positive. In the principal analysis, the risk of gastric cancer after H. pylori eradication was assumed to be similar to that for those without H. pylori infection. Scenarios with less optimistic assumptions regarding risk reduction of cancer were evaluated., Main Outcome Measures: Gastric cancer rates, discounted cost per life-year saved., Results: If H. pylori eradication reduced the risk of cancer to that of people never infected, both H. pylori intervention strategies reduced gastric cancer rates so that each yielded at least 12 additional life-years per 1000 40-year-old white men screened when compared with no screening. Helicobacter pylori serologic testing without posttreatment confirmatory testing resulted in the lowest cost per additional life-year saved (S6264). The cost-effectiveness of the H. pylori screening strategies varied substantially as the level of risk reduction of cancer was varied, but remained cost-effective even at moderate rates (<30%) of excess risk reduction of cancer in all cohorts evaluated., Conclusions: Population-based H. pylori screening has the potential to produce important health benefits at a reasonable cost at moderate rates of excess risk reduction of cancer. Controlled studies are necessary to confirm and quantify the impact of H. pylori eradication on the risk of gastric cancer.

Background: Endoscopic ultrasonography (EUS) is highly accurate in the localization of small pancreatic tumors. We determined the cost effectiveness of EUS used early in the preoperative evaluation of pancreatic endocrine tumors., Methods: In a study with a case-control design, 36 patients (19 men, 17 women) who underwent preoperative EUS were matched retrospectively with 36 patients who underwent surgical exploration immediately before the introduction of EUS. The number, cost, and effectiveness of preoperative localization studies, days of hospitalization, and surgical and anesthesia times were assessed., Results: The EUS group had reduced charges for preoperative localization studies: $2620 versus $4846 per patient (p < 0.05), largely because of reductions in the number of diagnostic angiograms and venous sampling procedures performed. Surgical and total anesthesia times were decreased, as were the number of preoperative admissions for angiographic procedures. The cost-effectiveness ratio for the EUS group was $3144 per tumor localized compared with $5628 per tumor localized for the group treated before EUS became available (p < 0.05)., Conclusion: EUS is highly accurate in the localization of pancreatic neuroendocrine tumors and is cost effective when used early in the preoperative localization strategy. EUS decreased the need for additional invasive tests and avoided unnecessary morbidity and resource consumption. EUS should play a primary role in preoperative localization of pancreatic neuroendocrine tumors.

Background: We report a clinical trial which evaluated the effectiveness of triple therapy containing low- and high-dose azithromycin to treat Helicobacter pylori infection., Methods: From March 1997 to March 1998, patients infected with H. pylori were assigned to receive either: Treatment 1: ranitidine bismuth citrate (RBC) (400 mg b.d.) and amoxycillin (1 g b.d.) for 10 days with azithromycin 500 mg o.m. for 3 days: or Treatment 2: RBC and amoxycillin for 10 days with azithromycin 1 g o.m. for 3 days. H. pylori eradication was established by a urea breath test at least 4 weeks after therapy. Side-effects and compliance were assessed using a diary., Results: Sixty-eight patients were enrolled. Fifty-seven per cent of patients were treated for active peptic ulcer disease or a history of peptic ulcer disease. Treatment 1 cured H. pylori in 44% and 44% by per protocol and intention-to-treat analysis, respectively. The corresponding eradication rates for Treatment 2 were 79% and 75%. Two patients taking Treatment 2 dropped out of the study because of side-effects., Conclusions: With RBC and amoxycillin for 10 days, azithromycin at a dose of 1 g/day for 3 days was significantly better at curing H. pylori infection than azithromycin 500 mg/day for 3 days.

In a prospective evaluation of 58 consecutive patients referred for operation of a suspected pancreatic or peri-ampullary cancer, the accuracy of ultrafast magnetic resonance imaging (UMRI) in predicting the resectability of pancreatic tumors compared with alternative staging interventions was assessed. The staging methods included: 1) transcutaneous ultrasound (US) with color Doppler, 2) UMRI, including echoplanar sequences and breath-hold gadolinium-enhanced dual-phase three-dimensional magnetic resonance angiography (MRA), 3) rapid bolus dual-phase helical computed tomography (CT), 4) angiography of celiac and mesenteric arterial systems, including portal venous phase, and 5) endoscopic cholangiopancreatography (performed in jaundiced patients). Patients were evaluated for extrapancreatic tumor spread, presence of hepatic metastases, lymph node involvement, and vascular involvement--each a sign of unresectability. After an investigator blinded to the results of the other imaging studies assessed resectability, patients were then divided into three categories: 1) probably resectable, 2) probably unresectable, and 3) certainly inoperable. Final diagnosis was obtained by laparotomy (47 of 58 pts), or by histopathological examination of fine needle aspiration specimens in patients deemed inoperable. The 58 suspected tumors were localized to the pancreatic head in 35 (60%), body in 11 (19%), and tail in one (2%). Nine (16%) ampullary tumors and two (3%) distal common bile duct tumors made up the remainder. For those 52 patients for whom histology was obtained, 44 were malignant and eight benign. Accuracy for assessing extrapancreatic tumor extension was highest with UMRI (95.7%) followed by US (85.1%), and CT (74.4%). UMRI provided the best means for detecting liver metastases with an accuracy of 93.5% compared with 87.2% for each of US and CT. UMRI, US, and CT had a reduced capacity for detecting lymph node involvement (80.4%, 76.6%, and 69.2%, respectively). In assessing vascular invasion, UMRI had an accuracy of 89.1%, US 83.0%, CT 79.5%, and angiography 68.8%. The findings suggest that UMRI is equal to or superior to other staging methods with regards to sensitivity, specificity, and overall accuracy. Since UMRI has the potential to reduce patient time, money, and discomfort, this study concludes that this staging technique should replace alternative methods as it provides an "all-in-one" diagnostic modality.

Endoscopic ultrasonography (EUS) is currently being used to evaluate and stage pancreaticobiliary malignancies and neuroendocrine tumors, and to perform aspiration for cytologic diagnosis. There are currently two different commercially available EUS systems for clinical use. One system uses a mechanical radial sector scanner oriented in a plane perpendicular to the long axis of the endoscope, and the other uses an electronic convex scanner that is oriented in the long axis of the endoscope. The vast majority of the current literature reports experience using the radial scanning device in the evaluation of pancreaticobiliary abnormalities. We prospectively evaluated the linear probe as the sole instrument for EUS in 26 patients with suspected pancreatic disease. The results of the endoscopic ultrasound examination were compared with the results of surgery or long-term clinical follow-up. The sensitivity and specificity of linear array EUS for benign pancreatic disease were 93.8% and 88.2%, respectively. The sensitivity and specificity for malignant disease of the pancreas were 80.0% and 88.9%, respectively. The linear array echoendoscope, employed as the only instrument for evaluation of the pancreas, is accurate in the evaluation of pancreatic disease. The addition of EUS-guided pancreatic biopsy would be anticipated to improve the sensitivity of the linear array instrument for detecting malignancy.

Background: Complications after endoscopic biliary sphincterotomy occur in 8% to 10% of patients when studied prospectively. It is not known whether the type of electrocautery current affects this rate. Theoretically, less edema of the ampulla after a pure cutting current sphincterotomy could decrease the risk of pancreatitis although the risk of postsphincterotomy hemorrhage might be greater., Methods: One hundred seventy patients undergoing sphincterotomy were prospectively randomized to either a blended or pure cut current on the Valleylab electrosurgical unit. The settings were a blended three current at a power setting of 30 watts/sec for both the cut and coagulation currents or a pure cut current at a power setting of 30 watts/sec. The individual determining whether a complication occurred was blinded to the type of current used, and all patients were hospitalized for 24 hours post-procedure. Pancreatitis was defined as mild if fewer than 5 days, moderate if 5 to 14 days, and severe if more than 14 days of hospitalization were required., Results: Indications for sphincterotomy were choledocholithiasis in 111 patients, sphincter of Oddi dysfunction in 36 patients, stent placement in 15 patients, and miscellaneous in 8 patients. There were a total of 16 complications in 170 patients (9%); 4 (5%) were in the pure cut current group of 86 patients (one episode of bleeding that required transfusion of 4 U and three episodes of mild pancreatitis), and 12 (14%) were in the blended current group of 84 patients (7 mild, 2 moderate, and 1 severe pancreatitis; 1 case of cholangitis; and one episode of bleeding that required transfusion of 2 U). There were significantly fewer complications in the pure cut group (p < 0.05 by chi-square)., Conclusion: The use of pure cut current is associated with a lower incidence of pancreatitis, the most common ERCP complication, than with blended current sphincterotomy. An insufficient number of patients were studied to comment on the relative risk of hemorrhage. However, because the complication of hemorrhage is much less common than pancreatitis, pure cut current is safer overall.

Background & Aims: Helicobacter pylori is found within the gastric mucous gel layer and in association with the epithelial surface. The aim of this study was to determine the effect of H. pylori infection on mucin gene expression (MUC6, MUC5, and MUC1) in the gastric epithelium., Methods: Gastric biopsy specimens were examined by immunohistochemistry and in situ hybridization for mucin gene expression., Results: MUC6 was limited to mucous glands of H. pylori-negative patients, but 72% of H. pylori-positive patients also expressed MUC6 in surface mucous cells. In contrast, MUC5 mucin was found in significantly fewer surface mucous cells of H. pylori-positive specimens. Carbohydrates recognized by Lewis (Le) X and paradoxical concanavalin A (con A) staining were aberrantly expressed in the surface mucous cells of 16 of 27 and 17 of 23 H. pylori-positive tissues, respectively. Surface Le(b) was present in 26 of 27 H. pylori-positive and 19 of 30 H. pylori-negative tissues. Eradication of H. pylori resulted in reversal of surface MUC5 and MUC6 expression toward normal patterns. Purified gastric mucins of H. pylori-positive patients bound more anti-MUC6 and anti-Le(b) than mucins from H. pylori-negative patients., Conclusions: The type of mucin that is normally limited to mucous glands is aberrantly expressed in surface mucous cells of H. pylori-positive patients, whereas less of the surface epithelium expresses normal surface-type gastric mucin.

Few patients with pancreatic cancer have resectable disease at the time of diagnosis, and a variety of nonsurgical techniques are available to provide effective palliation of jaundice and pain. Accurate preoperative staging is essential to identify patients with unresectable disease, thereby minimizing unnecessary surgery. Currently used diagnostic tests include contrast-enhanced computerized tomography (CT), visceral angiography, endoscopic ultrasound, and laparoscopy, but their utility remains controversial. To evaluate the accuracy of these various diagnostic tests, 30 consecutive patients with histologically proven pancreatic or ampullary adenocarcinoma treated between 1992 and 1996 were evaluated. All 30 patients had contrast-enhanced CT and laparoscopy, 22 patients (73%) had visceral angiography, and 16 patients (53%) had endoscopic ultrasound. Individual and combined predictive values of resectability and unresectability as well as the sensitivities and specificities were determined for all diagnostic tests and compared with intraoperative findings. When CT, visceral angiography, and laparoscopy were combined, the predictive values of resectability and unresectability were 75 and 90 per cent, respectively, with a sensitivity of 75 per cent and a specificity of 90 per cent. Therefore, the combined use of selected diagnostic tests proved more effective than any single diagnostic test for accurately staging patients with pancreatic head and ampullary cancers and should be considered to minimize unnecessary surgery.

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) induce gastric ulcers., Aims: To assess whether the somatostatin analogue octreotide prevents NSAID induced mucosal gastrointestinal damage in both animals and humans. The effect of octreotide on neutrophil adhesion to the endothelium was also evaluated., Methods: Male Sprague-Dawley rats were pretreated either with saline (0.3 ml subcutaneously) or octreotide (0.001-1 ng/kg subcutaneously). After 30 minutes gastric ulcers were induced by the intragastric application of NSAIDs (20 mg/kg indomethacin, 200 mg/kg aspirin, 200 mg/kg ibuprofen, or 50 mg/kg diclofenac). Four hours later the rats were killed and gastric mucosal lesions were assessed by computed planimetry. To determine whether octreotide could prevent indomethacin induced injury in humans, 20 healthy volunteers were evaluated in a double blind, placebo controlled study., Results: Octreotide prevented NSAID induced gastric mucosal lesions (p < 0.05). The dose response curve was U shaped and the most effective dose was 0.1 ng/kg. Leucocyte adherence in submucosal venules of the stomach was evaluated by in vivo microscopy. Octreotide (0.1 ng/kg subcutaneously) prevented indomethacin (20 mg/kg intragastric) induced leucocyte adherence in gastric submucosal venules (p < 0.05). Healthy human volunteers received 50 mg indomethacin orally thrice a day concomitantly with either an identical placebo or 0.01 microgram, 0.1 microgram, or 1 microgram octreotide subcutaneously thrice a day for three days. Injury was assessed by endoscopy. There was a negative correlation between the octreotide dose and injury score (p < 0.03 for gastric injury, p < 0.001 for duodenal injury)., Conclusions: Octreotide protects the stomach from NSAID induced gastric injury, probably via its ability to reduce NSAID induced neutrophilic adhesion to the microvasculature. Octreotide also ameliorated indomethacin induced gastric and duodenal injury in humans.

Objectives: To determine the effect of lansoprazole and high dose ranitidine on the accuracy of the 14C-urea breath test (UBT). Using intragastric pH recordings, we correlated the effect of these agents on the UBT with their potency of gastric acid suppression., Methods: Patients with active Helicobacter pylori infection underwent a baseline UBT before receiving 14 days of lansoprazole (30 mg/day) or ranitidine (300 mg b.i.d.). During therapy, patients were asked to undergo 24-h intragastric pH monitoring. Repeat breath testing was performed 1 day after completion of the study drugs. If the UBT was equivocal or negative (14CO2 excretion was < 200 dpm), further UBTs were completed until the 14CO2 excretion was > 200 dpm., Results: Thirteen patients received lansoprazole. Eight of thirteen patients developed a negative or equivocal UBT. All patients had 14CO2 excretion > 200 dpm 5 days after the cessation of lansoprazole. Eleven patients received ranitidine. Ranitidine led to equivocal or false negative UBTs in 2 of 11 cases. This effect resolved within 5 days of stopping ranitidine. Intragastric pH recordings revealed that the patients who experienced the most profound gastric acid suppression were those that developed equivocal or false negative UBTs., Conclusions: Lansoprazole significantly affected the accuracy of the UBT, causing equivocal or false negative results in 61%. High dose ranitidine affected the breath test in only 18%. The ability of these drugs to suppress gastric acid secretion predicted those patients who developed equivocal or false-negative UBTs. The effect on the accuracy of the UBT resolved within 5 days of drug cessation.

Gastrointestinal toxicity caused by nonsteroidal anti-inflammatory drugs (NSAIDs) is the most frequent drug side effect in the United States. NSAIDs are implicated in the development of complicated peptic ulcer disease and injury to the small bowel and colon. NSAIDs interfere with prostaglandin-mediated epithelial defense mechanisms and also cause direct epithelial toxicity. Current and future approaches to the prevention and management of NSAID injury are reviewed.

Objectives: We investigated omeprazole's effect on 14C-urea breath testing. We also determined the duration of omeprazole's effect on the breath test. Finally, we studied whether effects on breath testing were dose dependent., Methods: Fifty-seven employees and outpatients were screened for Helicobactor infection. Those positive for serology, CLO, or histology were asked to undergo baseline breath testing. Those with a positive breath test took omeprazole 20 mg/day for 14 days followed by repeat breath testing, 1, 3, and 5 days after therapy. Subjects with persistently positive breath tests despite omeprazole 20 mg/day were asked to take omeprazole 20 mg b.i.d. for 14 days. Repeat breath tests were performed as above., Results: Thirteen of 57 had HP infection. Ten of 13 underwent a baseline breath test. Eight of 10 with baseline breath test experienced a significant decrease in expired 14CO2 after omeprazole 20 mg/day. Five of 13 with active HP infection developed a negative breath test after omeprazole. All subjects had a positive breath test within 5 days of stopping omeprazole 20 mg/day. Five of eight with persistently positive breath tests despite omeprazole 20 mg/day took omeprazole 40 mg/day. Four of five developed a significant decrease in 14CO2 excretion after omeprazole. All subjects had a positive breath test within 5 days of stopping omeprazole 40 mg/day., Conclusions: Recent treatment with omeprazole 20 mg/day led to a false-negative breath tests in 38.5%. This effect appeared to be dose dependent and lasted up to 5 days after cessation of omeprazole.

Background/aims: It remains controversial whether Helicobacter pylori infection causes symptoms in non-ulcer dyspepsia. One hundred non-ulcer dyspepsia patients were screened for H. pylori infection between November 1989 and February 1994. Forty patients entered a trial where both infected and uninfected patients were treated with H. pylori therapy, with the uninfected group serving as controls., Methods: Non-ulcer dyspepsia was defined as unexplained epigastric discomfort lasting for at least 4 wk. From November 1989 until February 1992, all patients, regardless of H. pylori status, were treated with bismuth subsalicylate tablets (524 mg q.i.d.) for 4 wk and metronidazole (250 mg q.i.d.) for the first 2 of the 4 wk. From March 1992 until February 1994, only infected patients were treated in an attempt to obtain equal numbers in each group. H. pylori infection was diagnosed histologically at the index endoscopy and 1 month after completion of therapy. Symptoms were scored on a 0-5 scale for both frequency and severity., Results: Of 100 patients screened, 33 were infected with H. pylori (mean age, 42; 10 men, 23 women), and 67 were uninfected (mean age, 38; 16 men, 51 women). Thirty-six uninfected patients were not offered treatment during the latter part of the trial. Of the remaining 31 uninfected patients, 10 dropped out; of the 33 infected patients, 14 dropped out. Twenty-one uninfected patients and 19 H. pylori-infected patients completed treatment; in 13 of 19 patients (68%), H. pylori was eradicated. Symptoms improved in eight of 13 (61%) H. pylori-eradicated patients and in four of six (66%) H. pylori-persistent patients, compared with 14 of 21 (66%) uninfected patients. Long-term follow-up (mean, 34 months) showed similar symptom outcome in the two treatment groups., Conclusions: Thirty-three percent of our non-ulcer dyspepsia patients were infected with H. pylori, a number similar to the percentage of infected age-matched controls in the U.S. Treatment with bismuth subsalicylate and metronidazole resulted in symptomatic improvement in 61-66% of non-ulcer dyspepsia patients regardless of initial or post-treatment H. pylori status. Long-term symptom follow-up in both the control and infected groups gave similar results. H. pylori infection is not related to the symptoms of non-ulcer dyspepsia.

Background/aims: Acid and fat in the duodenum inhibit gastric acid secretion and increase plasma secretin. The role of prostaglandins and secretin in the inhibition of gastric acid secretion by duodenal infusion of hydrochloric acid and fat in healthy human volunteers was studied., Methods: Gastric acid secretion was submaximally stimulated with intravenous pentagastrin followed by duodenal infusion of 0.1N hydrochloric acid, oleic acid, or intravenous secretin. To inhibit endogenous prostaglandins, the protocol was then repeated after indomethacin treatment., Results: Duodenal fat infusion inhibited acid secretion 80% +/- 5% and was unaffected by indomethacin treatment. Intraduodenal acidification inhibited acid secretion by 43% +/- 8% and was reduced by indomethacin treatment to 15% +/- 4% (P < 0.01). Similarly, intravenous secretin inhibited acid secretion by 34% +/- 3%, which was decreased to 13% +/- 6% by indomethacin treatment (P < 0.01). The increase in plasma secretin levels after intraduodenal hydrochloric acid treatment was significantly greater than that observed with intravenous secretin or introduodenal oleic acid treatment; all were within the physiological range. Acid in the duodenum releases secretin, which inhibits gastric acid secretion at least in part via prostaglandins. In contrast, fat in the duodenum strongly inhibits gastric acid secretion via a nonprostaglandin pathway., Conclusions: Secretin is the predominant mediator for the inhibition of human gastric acid secretion induced by the presence of acid, but not fat, in the duodenum.

Background: We have previously found selective venous sampling to be the most sensitive method to localize otherwise occult functioning endocrine tumors. However, recently we have used endoscopic ultrasonography (EUS) as the initial and in some cases the only localization study in the preoperative evaluation of proven insulinomas and of selected cases of gastrinoma., Methods: All patients referred between April 1993 and April 1994 with a subsequently confirmed diagnosis of organic hyperinsulinism or Zollinger-Ellison syndrome (ZES) underwent EUS. Ten patients with insulinomas and six with gastrinomas were studied. Only one patient with ZES had multiple endocrine neoplasia type I. Patients with negative EUS findings had additional localization procedures including angiography and arterial stimulation tests. All but one patient underwent surgical exploration., Results: Solitary insulinomas were found in all 10 patients. EUS correctly identified and localized the insulinoma in seven (70%) of 10 patients but failed to identify two pedunculated insulinomas that were easily found at exploration. Because of an incomplete examination, a single insulinoma was not detected within the parenchyma. The EUS examination correctly excluded the pancreatic gastrinomas in five patients. The sixth patient, who had multiple endocrine neoplasia type I, had two 0.5 cm tumors in the head., Conclusions: EUS is a sensitive and cost-effective technique for localization of insulinomas and may be the only study needed. In patients with ZES a negative pancreatic result suggests the likelihood of a duodenal or other extrapancreatic tumor.

Nonsteroidal anti-inflammatory drugs (NSAIDs) initiate gastroduodenal ulceration and promote complications such as bleeding and perforation. Age greater than 60 years, a prior history of ulcer disease, and concomitant corticosteroid use are important risk factors for ulcer development. NSAIDs interfere with mucosal defense via direct toxic effects in addition to cyclooxygenase inhibition and subsequent depletion of endogenous prostaglandins. While all NSAIDs are ulcerogenic, drugs which avoid topical injury and do not inhibit mucosal prostaglandins appear to have lesser risk of toxicity. Although NSAID injury requires luminal acid, prophylactic use of H2 receptor antagonists has been disappointing, preventing duodenal injury only. Greater acid suppression with proton pump inhibition appears promising. Prostaglandins are effective for prevention of NSAID-induced gastroduodenal injury, but are not well tolerated. Recent evidence suggests NSAID ulcers heal rapidly with proton pump inhibitors compared to H2 receptor antagonists in those patients who require continued NSAID therapy.

Aspirin and nonsteroidal antiinflammatory drugs (NSAIDs) damage the gastroduodenal epithelium by two mechanisms: direct toxic effects and effects related to the depletion of endogenous prostaglandins. The prostaglandin-depleted mucosa has increased susceptibility to luminal aggressive factors, yet the role of acid in the pathogenesis of the NSAID ulcer is controversial. In humans, standard doses of H2-receptor antagonists prevent only duodenal injury and provide no protection for the gastric mucosa. It is not known whether more potent suppression of acid can prevent NSAID damage. Twenty healthy volunteers were randomized to a double-blind, placebo-controlled, crossover study to determine if omeprazole, 40 mg/day prevents gastroduodenal injury due to two weeks of aspirin administration (650 mg four times a day). The severity of mucosal injury was quantitated by endoscopy and stratified by a scale from 0 (normal) to 4 (ulcer). Fourteen of the 20 subjects had less gastric injury during cotherapy with omeprazole. All six with no difference received aspirin plus omeprazole in the first treatment period. Omeprazole significantly decreased aspirin-induced gastric mucosal injury (P < 0.001, Wilcoxon signed-rank test). Omeprazole protected 85% of subjects from extensive gastric erosions (often associated with evidence of intraluminal bleeding) or ulceration, whereas 70% of the subjects developed aspirin-induced grades 3 and 4 gastric injury on placebo (P < 0.01 by chi 2). No subject taking omeprazole developed duodenal injury of any grade, while 50% taking placebo developed erosions and 15% had ulcer (P < 0.001). Medication side effects were mild in the majority of subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Sarcoidosis is a granulomatous disease of unknown origin with a variable clinical presentation. The presenting complaint is usually referable to the lung. We describe an unusual presentation of sarcoidosis in a young black man who received medical attention for evaluation of pancytopenia, giant splenomegaly, and marked, refractory hypercalcemia. After extensive evaluation, including exploratory laparotomy, he was found to have sarcoidosis, with extensive involvement of his spleen, liver, and abdominal lymph nodes. Pulmonary involvement was notably absent, with no suggestive findings radiographically on gallium citrate Ga 67 scanning or on bronchoscopy with transbronchial biopsy. This patient underwent splenectomy and, following removal of the massive splenic granuloma burden, the hypercalcemia resolved completely with no other therapy.

Key components of the mucous gel include the glycoprotein mucin and surface-active phospholipids. In the present study, mucin production and release of the surface-active phospholipid phosphatidylcholine (PC) into the medium were measured with an isolated canine mucous cell culture system. Stimulation of glycoprotein synthesis in response to 10(-4) mol/L histamine (160% +/- 9% of control, P < 0.01), 10(-6) mol/L gastrin (129% +/- 7%, P < 0.01), and 10(-6) mol/L carbamylcholine (129% +/- 7%, P < 0.01) was observed by metabolic labeling, whereas prostaglandin E2 (PGE2) had no effect. The effect of histamine was blocked by the H2 receptor antagonist cimetidine but not the H1 receptor antagonist diphenhydramine (P < 0.01). Activators of adenylate cyclase and cyclic adenosine monophosphate analogs significantly stimulated mucin synthesis (P < 0.05). A 7.8% +/- 1.7% increase in mucin above basal levels after 24 hours was observed with a solid-phase immunoassay in control wells, whereas histamine, gastrin, and carbamylcholine increased total mucin by 14% +/- 0.7%, 17% +/- 4.3%, and 20.4% +/- 4%, respectively (all P < 0.01), and PGE2 had no significant effect. PC release was stimulated by the administration of histamine, carbamylcholine, gastrin (108%-110% of control, P < or = 0.05), and PGE2 (120% of control, P < 0.01). The acid secretagogues histamine, gastrin, and carbamylcholine stimulated mucin synthesis and PC release. PGE2 has no direct role in the synthesis of canine gastric mucin but stimulates release of surface-active phospholipids. The mechanisms responsible for acid secretion provide for the coordinated production of the primary layer of defense against the injurious effects of low pH.

The mucous gel maintains a neutral microclimate at the epithelial cell surface, which may play a role in both the prevention of gastroduodenal injury and the provision of an environment essential for epithelial restitution and regeneration after injury. Enhancement of the components of the mucous barrier by sucralfate may explain its therapeutic efficacy for upper gastrointestinal tract protection, repair, and healing. We studied the effect of sucralfate and its major soluble component, sucrose octasulfate (SOS), on the synthesis and release of gastric mucin and surface active phospholipid, utilizing an isolated canine gastric mucous cells in culture. We correlated these results with the effect of the agents on mucin synthesis and secretion utilizing explants of canine fundus in vitro. Sucralfate and SOS significantly stimulated phospholipid secretion by isolated canine mucous cells in culture (123% and 112% of control, respectively). Indomethacin pretreatment significantly inhibited the effect of sucralfate, but not SOS, on the stimulation of phospholipid release. Administration of either sucralfate or SOS to the isolated canine mucous cells had no effect upon mucin synthesis or secretion using a sensitive immunoassay. Sucralfate and SOS did not stimulate mucin release in the canine explants; sucralfate significantly stimulated the synthesis of mucin, but only to 108% of that observed in untreated explants. No increase in PGE2 release was observed after sucralfate or SOS exposure to the isolated canine mucous cells. Our results suggest sucralfate affects the mucous barrier largely in a qualitative manner. No increase in mucin secretion or major effect on synthesis was noted, although a significant increase in surface active phospholipid release was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Cytochrome P450 enzymes are capable of converting procarcinogens into either active mutagens or inactive metabolites. Because the distribution of these enzymes may be important for tissue susceptibility to procarcinogens, the expression and induction of CYP1A genes in the human alimentary tract were investigated. Endoscopic biopsy specimens were obtained from buccal mucosa, esophagus, gastric body, antrum, duodenum, and colon of 6 healthy volunteers before and 1 week after taking 20 mg of omeprazole daily. Tissue specimens were analyzed for the presence of CYP1A1 and 1A2 transcripts using hybridization methods and the polymerase chain reaction. P450-dependent enzymatic activity was assessed by deethylation of ethoxyresorufin. CYP1A1 messenger RNA (mRNA) and ethoxyresorufin activity were present constitutively in the duodenum of each volunteer. Omeprazole (20 mg/day for 1 week) induced CYP1A1 mRNA and enzymatic activity in 5 of 6 volunteers. The one individual who did not initially respond had a marked increase in both mRNA and enzymatic activity after receiving 60 mg of omeprazole daily for 1 week. After treatment with omeprazole, two individuals had low levels of CYP1A1 mRNA in several other alimentary tissues as well as low levels of CYP1A2 mRNA in the duodenum. The expression and induction by a pharmaceutical agent of CYP1A genes may have implications for intestinal metabolism of ingested xenobiotics including procarcinogens.

We studied the mechanism of cholinergic stimulation of mucin synthesis in canine antral explants, including the role of PGE2 as an intermediate messenger. Isolated antral mucosa was incubated with 10(-5) M carbachol (Cb), 10(-5) M indomethacin (IND), 10(-5) M pirenzepine (PZ), 10(-5) M Cb + 10(-5) M PZ, 10(-5) M Cb + 10(-5) M IND, and 10(-5) M IND + PGE2 (10(-8), 10(-7) and 10(-6) M) in the presence or absence of [3H]glucosamine. After 24 hr, total glycoprotein synthesis was quantitated by Sepharose-4B chromatography and by 10% TCA/1% PTA precipitation with lipid extraction. PGE2 released into the media was measured by radioimmunoassay (RIA). Cb significantly increased total glycoprotein synthesis and produced a significant increase in PGE2 release. The increase in glycoprotein synthesis and the release of PGE2 was blocked by the addition of muscarinic antagonist PZ. The addition of IND significantly inhibited glycoprotein synthesis and almost entirely suppressed PGE2 secretion. IND also inhibited the effect of Cb on glycoprotein synthesis and PGE2 release. Moreover, PGE2 (10(-6) and 10(-7) M) significantly increased the glycoprotein synthesis in the canine stomach. This suggests the coordinate participation of PGE2-releasing cell population in modulation of glycoprotein synthesis in gastric mucosa.

Nonsteroidal antiinflammatory drugs (NSAIDs) initiate gastroduodenal ulceration and promote complications such as bleeding and perforation by interfering with the ability of the proximal gastrointestinal tract to maintain its defensive capabilities. Mucosal defense is composed of three critical components: preepithelial, epithelial, and postepithelial. Preepithelial defense is composed of the mucous gel containing mucin, bicarbonate, and surface-active phospholipids. The epithelial component includes the surface cells, their apical tight junctions, and membrane transporters. Postepithelial defense is maintained by mucosal blood flow, which is essential for both defense and repair. NSAIDs interfere with each component of mucosal defense via direct toxic effects along with cyclooxygenase inhibition and depletion of endogenous prostaglandins. Although NSAID injury is dependent on luminal acid, attempts to prevent NSAID injury by acid suppression using H2-receptor antagonists in humans have had limited success, whereas complete inhibition of acid secretion with proton pump inhibition may have promise. Prostaglandins appear most effective for prevention of NSAID injury, sucralfate appears ineffective, and bismuth compounds have not been studied extensively. Recent evidence suggests that NSAID ulcers heal quickly with proton pump inhibitors compared with H2-receptor antagonists in patients who continue NSAID therapy.

Lipids, particularly surface-active phospholipids, have been proposed to provide an important protective barrier in the gastric mucosa. The predominant surface-active phospholipid in the pulmonary surfactant complex is dipalmitoylphosphatidylcholine. To determine whether the gastric epithelium synthesizes and secretes this phospholipid, primary cultures of canine gastric mucous cells isolated by counterflow elutriation were studied. During the 24-hour period of culture, the gastric mucous cells incorporated 3H-choline into phosphatidylcholine, with dipalmitoylphosphatidylcholine representing 13.8% +/- 0.6% of the phosphatidylcholine synthesized. When mucous cell preparations with greater chief cell contamination were studied, they incorporated significantly less precursor into dipalmitoylphosphatidylcholine. Administration of prostaglandin E2, a cytoprotective agent, to the cultured mucous cells for 1 hour led to a significant increase in phosphatidylcholine release, reaching a maximum of 120.4% +/- 4.2% (P less than 0.001) at 10(-6) mol/L. No significant stimulation of phospholipid release by prostaglandin E2 was seen in the fractions containing a greater proportion of chief cells. To further establish the relationship between mucin and phospholipid secretion, two gastric cancer cell lines, Hs746T and KATO III, were studied. Using immunocytochemical and biochemical techniques, mucin synthesis and secretion were confirmed by these cell lines. The Hs746T cells were significantly more active in the secretion of both mucin and phospholipid than the KATO III cells. The Hs746T line secreted 5.7-fold more mucin and 7.3-fold more phospholipid than KATO III cells during a 24-hour period of culture. The association between mucin and phospholipids in an aqueous solution was also studied. Purified mucin in the concentration of 0.5-2 mg/mL of glycoprotein led to a significant dose-dependent increase in phospholipid solubility, suggesting the formation of a glycoprotein-phospholipid complex. The current studies indicate that the gastric mucous cell is the source of surfactant phospholipids as well as mucin. The synthesis and release of mucin and phospholipid are functions of the mucous cell that play a critical role in the primary defense of gastric epithelium.

Animal models have identified multiple mechanisms of aspirin toxicity. Aspirin inhibits cyclooxygenase in the gastroduodenal mucosa leading to a decrease in endogenous prostaglandins. Prostaglandin mediated mucus and bicarbonate secretion, epithelial hydrophobicity, blood flow, and cellular proliferation are all decreased. Salicylates may cause direct cellular toxicity via inhibition of energy metabolism and membrane transport properties. Salicylate preparations have been designed to decrease gastroduodenal absorption. Endoscopic studies in humans have confirmed that buffering of aspirin does not ameliorate damage, but enteric coating does. Salicylsalicylic acid (salsalate) is an effective antirheumatic drug that bypasses gastric absorption and also avoids cyclooxygenase inhibition. In a randomized, single-blind, endoscopic comparison of salsalate versus enteric-coated aspirin, significantly less gastroduodenal damage was observed in volunteers after salsalate administration compared to enteric-coated aspirin. An endoscopic study in rheumatoid arthritics also confirmed the ability of salsalate to spare gastroduodenal mucosa when compared to naproxen administration. Salsalate may cause less gastroduodenal damage than enteric-coated aspirin based on the results of animal models and endoscopic studies in humans.

We report two additional cases of colonic xanthomatosis associated with persistent rectal symptoms. Disordered colonic motility in the areas of lipid infiltration was documented in one patient. We conclude these lesions may have a pathophysiologic role in the alteration of intestinal motility which appears to be the cause of our patients' symptoms.

A 29-year-old woman with a history of a maxillary plasmacytoma treated with radiation therapy presented with painless jaundice. A computed tomography (CT) scan revealed biliary dilatation and diffuse pancreatic enlargement suggestive of pancreatitis. Percutaneous transhepatic cholangiography demonstrated encasement of the distal common bile duct by an extrinsic mass. At exploratory laparotomy, a large mass replacing the entire pancreas was found. Pathologic examination confirmed plasmacytoma. This report presents a unique case of extramedullary plasmacytoma involving the pancreas early in a patient's clinical course. The CT appearance was similar to that of acute pancreatitis.

The gastroduodenal mucosal damage caused by aspirin and nonsteroidal antiinflammatory drugs is a common clinical problem. We compared two medications designed to diminish mucosal damage: enteric-coated aspirin and salicylsalicylic acid (salsalate). Ten healthy volunteers were randomized to receive either 1.5 g salsalate twice a day or 650 mg enteric-coated aspirin four times a day for six days and were then crossed over to the other drug after a one-week medication-free period. Endoscopic inspection of gastroduodenal mucosa was performed at entry and again after six days of drug therapy for each medicine. Mean serum salicylate concentrations taken before the morning drug dose were 11.2 mg/dl for enteric-coated aspirin and 18.1 mg/dl for salsalate. Only one of 10 subjects receiving salsalate developed mild (grade 1) mucosal damage while six of 10 receiving enteric-coated aspirin developed moderate to severe damage (grade 2-3) (P = 0.01). Symptoms were mild in both groups. We conclude that salsalate causes less gastroduodenal mucosal damage than enteric-coated aspirin.