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Biomedical subjects

J M Scheiman

Publications and source records attributed to J M Scheiman.

At least 37 records · Page 2Linked to original sources

Is upper gastrointestinal radiography a cost-effective alternative to a Helicobacter pylori "test and treat" strategy for patients with suspected peptic ulcer disease?

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.

Anti-Ulcer Agents↗

The clinical and economic impact of alternative staging strategies for adenocarcinoma 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.

Adenocarcinoma↗

Endoscopic ultrasound is highly accurate and directs management in patients with neuroendocrine tumors of the pancreas.

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.

Adenoma, Islet Cell↗

Clinical and economic effects of population-based Helicobacter pylori screening to prevent gastric cancer.

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.

Cost-Benefit Analysis↗

Helicobacter pylori and gastric cancer.

Infection with Helicobacter pylori is now recognized as the primary cause of peptic ulcers and their recurrence. Compelling evidence has also been found linking H. pylori infection to gastric cancer, the second most common cancer in the world. Given the high rate of patient morbidity and mortality associated with gastric cancer, any method by which one can reduce the occurrence of the disease or increase its early detection is desirable. The strong correlation with H. pylori infection and the current availability of easily administered tests for the detection of the pathogen argue for screening at least those individuals with a family history of gastric cancer or other risk factors. This article reviews the association between H. pylori and gastric cancer and the pathologic changes that the infection produces in the gastric mucosa, as well as the cost-effectiveness of universal testing and eradication of the infection in H. pylori-positive individuals to reduce gastric cancer.

Gastritis, Atrophic↗

EUS compared with CT, magnetic resonance imaging, and angiography and the influence of biliary stenting on staging accuracy of ampullary neoplasms.

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.

Adult↗

Cost effectiveness of EUS for preoperative localization of pancreatic endocrine tumors.

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.

Angiography↗

Cyclooxygenase-2 expression in gastric antral mucosa before and after eradication of Helicobacter pylori infection.

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.

Acute Disease↗

Giant peptic ulcer: a surgical or medical disease?

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.

Adult↗

Pure cut electrocautery current for sphincterotomy causes less post-procedure pancreatitis than blended current.

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.

Acute Disease↗

Identification of patients with resectable pancreatic cancer: at what stage are we?

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.

Diagnostic Imaging↗

Transforming growth factor-alpha (TGF-alpha) levels in human proximal gastrointestinal epithelium. Effect of mucosal injury and acid inhibition.

TGF-alpha inhibits gastric acid secretion and may play an important role in epithelial repair. We quantitated regional levels of TGF-alpha in the human proximal gastrointestinal tract and determined whether they are affected by acid suppression or aspirin-induced injury. Ten healthy volunteers were studied. After baseline endoscopy with biopsy, five randomly received no treatment, aspirin, omeprazole, or cimetidine for one week. Endoscopy was repeated and prior unhealed biopsy sites quantitated. TGF-alpha levels were measured by RIA. Five additional subjects then completed an extended protocol of three weeks duration. All subjects were free of H. pylori infection. TGF-alpha levels in the antrum, 34.76 +/- 5.54 pg TGF-alpha/micrograms DNA were threefold higher than in the gastric body and duodenum (11.03 +/- 2.60 and 10.41 +/- 1.64 respectively, P < 0.01). The number of unhealed sites in the aspirin group was significantly greater than in the control or acid inhibition groups; however, TGF-alpha levels were not different from-the surrounding mucosa. TGF-alpha increased in the controls after biopsy; the increase was significant in the body at week 2 only. Aspirin significantly increased TGF-alpha levels in the gastric body and duodenum after one week. The rise in antral TGF-alpha appeared delayed and blunted by the aspirin treatment compared to control. There was no relationship between the number of visible biopsy sites, degree of aspirin-induced injury, and the TGF-alpha level. Acid suppression was associated with a significant increase in TGF-alpha in the gastric body and antrum at one week. Immunochemical staining did not demonstrate differences in proliferation in any treatment group compared to controls. TGF-alpha levels vary by location in the proximal gastrointestinal tract, with significantly greater levels in the antrum. After biopsy, TGF-alpha levels increase; short-term aspirin and acid inhibitors modulate this effect. Aspirin significantly impaired the healing of endoscopic biopsies in the antrum; however, this was not associated with changes in TGF-alpha levels. TGF-alpha levels did not change in response to acid secretory state. Further studies of mucosal levels of TGF-alpha in response to aspirin-induced injury in humans appear warranted.

Adult↗

Aberrant expression of gland-type gastric mucin in the surface epithelium of Helicobacter pylori-infected patients.

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.

Adult↗

Reduction of non-steroidal anti-inflammatory drug induced gastric injury and leucocyte endothelial adhesion by octreotide.

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.

Animals↗