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Biomedical subjects

M B Wallace

Publications and source records attributed to M B Wallace.

At least 19 recordsLinked to original sources
PubMed2001

Predictors of survival for esophageal cancer patients with and without celiac axis lymphadenopathy: impact of staging endosonography.

BACKGROUND: Esophageal cancer patients with M1a disease are reported to have poor survival. We hypothesized that patients with celiac lymph node metastases (CLN) identified by endoscopic ultrasonography (EUS) would predict a cohort with significantly worse survival postoperatively. Accurate preoperative identification of this group will facilitate future adjuvant studies. METHODS: During the study period, 211 patients with esophageal cancer underwent EUS staging. Patients with evaluable celiac axis (n = 182) were included in this study. Survival of patients with and without CLNs was compared and the factors affecting overall survival were assessed. A subgroup analysis based on CLN status was performed in the subgroup of patients who underwent surgical procedures. RESULTS: Follow-up data was available in 91.2% (166 of 182) of the patients. As staged by EUS, T1, T2, T3, and T4 tumors accounted for 9.3%, 11.5%, 56%, and 21% of the cases, respectively. At least one CLN was imaged by EUS in 40% (72 of 182). The 5-year survival in patients with CLNs detected by EUS was 13% (95% confidence interval, 5% to 21%) compared with 30% (95% confidence interval, 21% to 40%) in patients with no CLNs detected by EUS (p = 0.007). In the subgroup of patients who underwent surgical procedures (n = 68), patients with CLN involvement had worse survival compared with those who did not have malignant involvement of CLNs at the time of their operation (median survival 39.8 versus 13.8 months, p = 0.0008). In a Cox proportional model, adjusting for race and the type of therapy, patients with CLN involvement or advanced EUS American Joint Committee on Cancer stage were more likely to have worse survival (p < 0.05) CONCLUSIONS: EUS base line findings correlate with long term survival in patients with esophageal cancer. Patients with M1a disease as identified by EUS had a significantly worse postoperative survival when compared with non-M1a patients. This cohort of patients will be ideal for the study of induction therapy since the effect of down staging can be assessed before operation.

Adenocarcinoma↗
PubMed2001

Endoscopic ultrasound-guided fine needle aspiration for staging patients with carcinoma of the lung.

BACKGROUND: Endoscopic ultrasound (EUS)-guided fine needle aspiration is a safe, cost-effective procedure that can confirm the presence of mediastinal lymph node metastases and mediastinal tumor invasion. We studied the accuracy of EUS in a large population of lung cancer patients with and without enlarged mediastinal lymph nodes on computed tomographic (CT) scan. METHODS: From 1996 to 2000 all patients referred to our institution with lung tumors and no proven distant metastases were considered for EUS and surgical staging. Patients had endoscopic ultrasound with fine needle aspiration of abnormal appearing mediastinal lymph nodes and evaluation for mediastinal invasion of tumor (stage III or IV disease). Patients without confirmed stage III or IV disease had surgical staging. RESULTS: Two hundred seventy-seven patients met the inclusion criteria, including 121 who had EUS. Endoscopic ultrasound and fine needle aspiration detected stage III or IV disease in 85 of 121 (70%). Among patients with enlarged lymph nodes on CT, 75 of 97 (77%) had stage III or IV disease detected by EUS. Among a small cohort of patients without enlarged mediastinal lymph nodes on CT, 10 of 24 (42%) had stage III or IV disease detected by EUS. For mediastinal lymph nodes only, the sensitivity of endoscopic ultrasound and CT was 87%. The specificity of EUS (100%) was superior to that of CT (32%) (p < 0.001). CONCLUSIONS: Endoscopic ultrasound with fine needle aspiration identified and histologically confirmed mediastinal disease in more than two thirds of patients with carcinoma of the lung who have abnormal mediastinal CT scans. Although mediastinal disease was more likely in patients with an abnormal mediastinal CT, EUS also detected mediastinal disease in more than one third of patients with a normal mediastinal CT and deserves further study. Endoscopic ultrasound should be considered a first line method of presurgical evaluation of patients with tumors of the lung.

Adult↗
PubMed2001

The reliability of EUS for the diagnosis of chronic pancreatitis: interobserver agreement among experienced endosonographers.

BACKGROUND: Endoscopic ultrasound (EUS) is a minimally invasive, low risk method of diagnosis for chronic pancreatitis (CP). The degree to which endosonographers agree on the features and diagnosis of CP is unknown. For EUS to be considered an accurate test for CP, there must be good interobserver agreement. METHODS: Forty-five pancreatic EUS examinations were videotaped by 3 experienced endosonographers. Examinations from 33 patients with suspected CP based on typical symptoms, as well as 12 control patients without suspected CP, were included. Eleven experienced endosonographers ("experts") who were blinded to clinical information independently evaluated all videotaped examinations for the presence of CP and the following 9 validated features of CP: echogenic foci, strands, lobularity, cysts, stones, duct dilatation, duct irregularity, hyperechoic duct margins, and visible side branches. The experts also ranked (most to least) which features they believed to be the most indicative of CP. Interobserver agreement was expressed as the kappa (kappa) statistic. RESULTS: There was moderately good overall agreement for the final diagnosis of CP (kappa = 0.45). Agreement was good for individual features of duct dilatation (kappa = 0.6) and lobularity (kappa = 0.51) but poor for the other 7 features (kappa < 0.4). The expert panel had consensus or near consensus agreement (greater than 90%) on 206 of 450 (46%) individual EUS features including 22 of 45 diagnoses of CP. Agreement on the final diagnosis of CP was moderately good for those trained in third tier fellowships (kappa = 0.42 +/- 0.03) and those with more than 1100 lifetime pancreatic EUS examinations (kappa = 0.46 +/- 0.05). The presence of stones was regarded as the most predictive feature of CP by all endosonographers, followed by visible side branches, cysts, lobularity, irregular main pancreatic duct, hyperechoic foci, hyperechoic strands, main pancreatic duct dilatation, and main duct hyperechoic margins. The most common diagnostic criterion for the diagnosis of CP was the total number of features (median 4 or greater, range 3 or greater to 5 or greater). CONCLUSIONS: EUS is a reliable method for the diagnosis of chronic pancreatitis with good interobserver agreement among experienced endosonographers. Agreement on the EUS diagnosis of chronic pancreatitis is comparable to other commonly used endoscopic procedures such as bleeding ulcer stigmata and computed tomography of the brain for stroke localization and better than the physical diagnosis of heart sounds.

Chronic Disease↗
PubMed2001

Fluorescence, reflectance, and light-scattering spectroscopy for evaluating dysplasia in patients with Barrett's esophagus.

BACKGROUND & AIMS: The aim of this study was to assess the potential of 3 spectroscopic techniques (fluorescence, reflectance, and light-scattering spectroscopy) individually and in combination, for evaluating low- and high-grade dysplasia in patients with Barrett's esophagus (BE). METHODS: Fluorescence spectra at 11 excitation wavelengths and a reflectance spectrum were acquired in approximately 1 second from each site before biopsy using an optical fiber probe. The measured fluorescence spectra were combined with the reflectance spectra to extract the intrinsic tissue fluorescence. The reflectance spectra provided morphologic information about the bulk tissue, whereas light-scattering spectroscopy was used to determine cell nuclear crowding and enlargement in Barrett's epithelium. RESULTS: Significant differences were observed between dysplastic and nondysplastic BE in terms of intrinsic fluorescence, bulk scattering properties, and levels of epithelial cell nuclear crowding and enlargement. The combination of all 3 techniques resulted in superior sensitivity and specificity for separating high-grade from non-high-grade and dysplastic from nondysplastic epithelium. CONCLUSIONS: Intrinsic fluorescence, reflectance, and light-scattering spectroscopies provide complementary information about biochemical and morphologic changes that occur during the development of dysplasia. The combination of these techniques (Tri-Modal Spectroscopy) can serve as an excellent tool for the evaluation of dysplasia in BE.

Barrett Esophagus↗
PubMed2001

An assessment of the potential value of endoscopic ultrasound as a cost-minimizing tool in dyspeptic patients with persistent symptoms.

STUDY AIMS: To quantify resource utilization in dyspeptic patients with persistent symptoms and to determine whether using both the endoscopic and ultrasound capabilities of endoscopic ultrasound could reduce costs. METHODS: Consecutive patients with persistent dyspepsia, after a minimum 1-month trial of acid suppression, underwent endoscopic ultrasound (EUS) and upper endoscopy using the GF-UM20 echo endoscope. Assuming EUS could replace imaging tests which had been requested in addition to upper endoscopy, the hypothetical costs of the EUS-based and upper endoscopy-based strategies were compared. RESULTS: 116 patients with persistent dyspepsia underwent EUS, of whom 64.6 % had > or = 2 imaging procedures, most commonly computed tomography (CT) (70.6 %) and abdominal ultrasound (64.7 %). The number of tests did not correlate strongly with any demographic variables. The fiberoptic echo endoscope provided an adequate endoscopic and ultrasound examination but was damaged by retroflexion. Direct hospital costs were lowest for the EUS-based strategy. Total avoidable cost for 116 patients was $ 4137 to $ 14 121 (or $ 36 to $ 122 per patient), depending on whether upper endoscopy was performed in the non-EUS strategies. CONCLUSIONS: Patients with persistent dyspepsia may undergo multiple abdominal imaging procedures. Clinical variables do not predict the need for additional testing. An EUS-based strategy may reduce overall costs if it prevents additional testing.

Cost-Benefit Analysis↗
PubMed2001

Randomized controlled trial of EUS-guided fine needle aspiration techniques for the detection of malignant lymphadenopathy.

BACKGROUND: EUS-guided fine needle aspiration (EUS-FNA) is a highly accurate method of detecting malignant lymphadenopathy. The optimal methods for performing EUS-FNA to maximize sensitivity and to minimize the number of needle passes necessary are unknown. This is a report of the results of a prospective randomized controlled trial to determine the effect of suction, the site of FNA (edge or center of lymph node), and the method of preparation of cytologic specimens on accuracy, number of needle passes needed, and specimen quality. METHODS: Consecutive patients with lymphadenopathy detected by EUS underwent FNA. Each lymph node was sampled with or without suction and from the edge or center in a 2 x 2 factorial design. The samples were expressed onto slides for cytology, and the residual material in the needle was analyzed by the cytospin-cellblock technique. Each aspirate was individually characterized for a diagnosis of malignancy, cellularity, and bloodiness. RESULTS: Forty-three patients with a total of 46 lymph nodes were evaluated. The final lymph node diagnosis was benign in 22 (48%), "suspicious for malignancy" in 6 (13%), and malignant in 18 (39%). The use of suction was associated with an increase in the cellularity of the specimen, but did not improve the likelihood of obtaining a correct diagnosis (OR 1.52: 95% CI [0.81, 2.85]). Samples obtained with suction were of worse quality because of excessive bloodiness (OR 4.7: 95% CI [1.99, 11.24]). Aspiration from the edge of the lymph node (compared with the center) did not increase the likelihood of a correct diagnosis (OR 1.16: 95% CI [0.42, 3.21]). For 78% of malignant lymph nodes, the correct diagnosis was obtained on the first needle pass and for 100% by the third pass. Cytospin-cellblock methods did not add any additional diagnostic information compared with direct smear cytology. CONCLUSIONS: The traditional method of applying suction during EUS-FNA does not improve diagnostic accuracy and worsens specimen bloodiness compared with FNA without suction. The site of FNA within the lymph node does not affect accuracy. When EUS-FNA is necessary, our recommendation is up to 3 FNAs without suction from the most convenient and safe location within abnormal-appearing lymph nodes.

Biopsy, Needle↗
PubMed2001

The utility of EUS and EUS-guided fine needle aspiration in detecting celiac lymph node metastasis in patients with esophageal cancer: a single-center experience.

BACKGROUND: The aims of this study were to determine the utility of EUS and EUS-guided fine needle aspiration (EUS-FNA) in the detection and confirmation of celiac lymph node metastasis in patients with esophageal cancer and to define EUS features predictive of celiac lymph node metastasis in these patients. METHODS: The records of 211 patients with esophageal cancer who underwent EUS staging were reviewed. The operating characteristics of EUS were determined in patients where either surgery, EUS-FNA of a celiac lymph node, or both were performed (n = 102). The association between selected variables and the presence of celiac lymph node metastasis was evaluated by univariate and multivariable analyses. RESULTS: EUS in 48 patients provided a true-positive diagnosis of celiac lymph node involvement, a false-positive and false-negative result, respectively, in 6 and 14 patients, and a true-negative diagnosis in 34 patients. The sensitivity of EUS in detecting celiac lymph node was 77% (95% CI [67, 88]), specificity 85% (95% CI [74, 96]), negative predictive value 71% (95% CI [58, 84]), and the positive predictive value 89% (95% CI [81, 97]). EUS-FNA was performed in 94% (51/54) of patients with celiac lymph nodes. The accuracy of EUS-FNA in detecting malignant celiac lymph nodes was 98% (95% CI [90, 100]). Advanced T-stage, the need for dilation, detection of peritumoral lymph nodes, and black race were associated with celiac lymph node involvement. In multivariable analysis, advanced T-stage was the strongest predictor of celiac lymph node involvement. CONCLUSION: EUS and EUS-FNA are highly accurate in detecting and confirming celiac lymph nodes metastasis. Depth of tumor invasion as assessed by EUS is a strong predictor of celiac lymph node metastasis in patients with esophageal cancer.

Adenocarcinoma↗
PubMed2001

Endoscopic ultrasound in the evaluation and treatment of chronic pancreatitis.

Endoscopic ultrasound (EUS) was developed in the 1970s specifically for the purpose of improved imaging of the pancreas. The close proximity of the pancreas to the gastric and duodenal lumen allows EUS to obtain high-resolution images, unobstructed by overlying bowel gas. EUS has fewer complications than endoscopic retrograde cholangiopancreatography (ERCP) and can detect features of chronic pancreatitis (CP) in the pancreatic parenchyma and duct that are not visible to any other imaging modality. Because of this high sensitivity, questions have arisen whether EUS is oversensitive, especially to ''early" CP. Without a definitive gold standard against which to measure EUS (or ERCP and function testing), it is currently not possible to know the true accuracy of these modalities for early CP. There is now an extensive body of literature suggesting that these early changes detected by EUS correlate with histologic changes of CP, and may predict response to pancreatic therapy. EUS is uniquely suited to performing endoscopic cyst drainage for pancreatic pseudocysts and for controlling the pain of CP by EUS-directed celiac plexus block. For endoscopic cystenterostomy, EUS allows the endoscopist to localize the cyst, determine if the cyst is drainable, and guide a needle and stent into the cyst in a single step. Several major questions remain. Can EUS features of CP guide other forms of therapy for CP such as enzyme replacement, sphincter of Oddi therapy, and stent therapy? Can the detection of early CP by EUS, and subsequent therapy, delay or prevent the onset of more severe CP? Can EUS detect early forms for dysplasia and malignancy in patients who are at high risk for pancreatic carcinoma? Do changes of "early" CP detected by EUS progress to more classic changes (calicification) over time?

Adult↗
PubMed2001

Age and alarm symptoms do not predict endoscopic findings among patients with dyspepsia: a multicentre database study.

INTRODUCTION: Symptoms of dyspepsia are common but most patients do not have major upper gastrointestinal pathology. Endoscopy is recommended for dyspeptic patients over the age of 45, or those with certain "alarm" symptoms. We have evaluated the effectiveness of age and "alarm" symptoms for predicting major endoscopic findings in six practising endoscopy centres. METHODS: Clinical variables of consecutive patients with dyspepsia symptoms undergoing upper endoscopy examinations were recorded using a common endoscopy database. Patients who had no previous upper endoscopy or barium radiography were included. Stepwise multivariate logistic regression was used to identify predictors of endoscopic findings. The accuracy of these for predicting endoscopic findings was evaluated with receiver operating characteristic analysis. The sensitivity and specificity of age thresholds from 30 to 70 years were evaluated. RESULTS: Major pathology (tumour, ulcer, or stricture) was found at endoscopy in 787/3815 (21%) patients with dyspepsia. Age, male sex, bleeding, and anaemia were found to be significant but weak independent predictors of endoscopic findings. A multivariate prediction rule based on these factors had poor predictive accuracy (c statistic=0.62). Using a simplified prediction rule of age > or =45 years or the presence of any "alarm" symptom, sensitivity was 87% and specificity was 26%. Increasing or decreasing the age cut off did not significantly improve the predictive accuracy. CONCLUSIONS: Age and the presence of "alarm" symptoms are not effective predictors of endoscopic findings among patients with dyspepsia. Better clinical prediction strategies are needed to identify patients with significant upper gastrointestinal pathology.

Adult↗
PubMed2000

Substituted benzamide inhibitors of human rhinovirus 3C protease: structure-based design, synthesis, and biological evaluation.

A series of nonpeptide benzamide-containing inhibitors of human rhinovirus (HRV) 3C protease was identified using structure-based design. The design, synthesis, and biological evaluation of these inhibitors are reported. A Michael acceptor was combined with a benzamide core mimicking the P1 recognition element of the natural 3CP substrate. alpha,beta-Unsaturated cinnamate esters irreversibly inhibited the 3CP and displayed antiviral activity (EC(50) 0.60 microM, HRV-16 infected H1-HeLa cells). On the basis of cocrystal structure information, a library of substituted benzamide derivatives was prepared using parallel synthesis on solid support. A 1.9 A cocrystal structure of a benzamide inhibitor in complex with the 3CP revealed a binding mode similar to that initially modeled wherein covalent attachment of the nucleophilic cysteine residue is observed. Unsaturated ketones displayed potent reversible inhibition but were inactive in the cellular antiviral assay and were found to react with nucleophilic thiols such as DTT.

3C Viral Proteases↗
PubMed2000

Imaging of esophageal tumors with a water-filled condom and a catheter US probe.

BACKGROUND: High-frequency catheter ultrasound (C-EUS) probes provide high resolution images of the gastrointestinal tract. Their use in the esophagus is limited by the requirement for a water-filled lumen for good acoustical coupling. We have developed a system using a condom that provides a continuous column of water for high resolution C-EUS imaging of the esophagus. METHODS: Nine patients underwent condom C-EUS for evaluation of esophageal mucosal and submucosal tumors. A standard latex condom was attached to a 2-channel endoscope and filled with water after esophageal intubation. A 20 MHz C-EUS probe placed within the water-filled condom was used to characterize all lesions. RESULTS: The condom C-EUS system provided a 360 degree, high resolution image throughout the length of the esophagus without air artifact and without the risk of aspiration associated with filling the esophageal lumen with water. Complete imaging of the tumor was obtained in all cases, and no additional C-EUS procedures were required. The condom C-EUS was subjectively rated superior overall in comparison to standard C-EUS by 4 independent endosonographers. CONCLUSIONS: Condom C-EUS is a new method of high resolution imaging of the esophagus. This method provides a contained column of water within the esophagus that improves image quality and ease of use and may reduce the risk of aspiration.

Adenocarcinoma↗
PubMed2000

Dilation of malignant esophageal stenosis to allow EUS guided fine-needle aspiration: safety and effect on patient management.

BACKGROUND: Endoscopic ultrasonography (EUS) with fine-needle aspiration identifies patients with esophageal cancer who are unlikely to be cured by surgery. In approximately 30% of patients the staging procedure cannot be completed without dilation of an obstructing tumor. METHODS: All EUS examinations for esophageal cancer requiring dilation from July 1995 to December 1998 were included. Yield was defined as newly diagnosed metastatic (celiac lymph nodes) or locally invasive disease that could not have been detected without dilation. RESULTS: EUS was performed in 132 patients. Forty-two (32%) required 44 dilations. No complications occurred. Of the 42 patients with obstruction, 18 (43%) had celiac adenopathy of which 7 had malignant cells confirmed histologically, 3 had benign adenopathy, and 8 did not undergo fine-needle aspiration due to T4 stage disease (5) or intervening vessels (3). Two patients were upstaged after successful dilation from T2 N1 Mx to T4 N1 Mx and from T3 Nx Mx to T3 N1 M1. Overall, dilation allowed detection of advanced disease in 8 of 42 (19%) patients. Dilation to 11 to 12.8 mm was insufficient (36% success rate) to complete EUS compared with dilation to 14 to 16 mm (87%, p < 0.01). CONCLUSION: Dilation of obstructing esophageal tumors allows identification of a large number of patients with advanced stage malignancy. Dilation to 14 to 16 mm is sufficient for complete staging in almost all patients.

Aged↗
PubMed2000

Endoscopic detection of dysplasia in patients with Barrett's esophagus using light-scattering spectroscopy.

BACKGROUND & AIMS: We conducted a study to assess the potential of light-scattering spectroscopy (LSS), which can measure epithelial nuclear enlargement and crowding, for in situ detection of dysplasia in patients with Barrett's esophagus. METHODS: Consecutive patients with suspected Barrett's esophagus underwent endoscopy and systematic biopsy. Before biopsy, each site was sampled by LSS using a fiberoptic probe. Diffusely reflected white light was spectrally analyzed to obtain the size distribution of cell nuclei in the mucosal layer, from which the percentage of enlarged nuclei and the degree of crowding were determined. Dysplasia was assigned if more than 30% of the nuclei exceeded 10 microm and the histologic findings compared with those of 4 pathologists blinded to the light-scattering assessment. The data were then retrospectively analyzed to further explore the diagnostic potential of LSS. RESULTS: Seventy-six sites from 13 patients were sampled. All abnormal sites and a random sample of nondysplastic sites were reviewed by the pathologists. The average diagnoses were 4 sites from 4 different patients as high-grade dysplasia (HGD), 8 sites from 5 different patients as low-grade dysplasia (LGD), 12 as indefinite for dysplasia, and 52 as nondysplastic Barrett's. The sensitivity and specificity of LSS for detecting dysplasia (either LGD or HGD) were 90% and 90%, respectively, with all HGD and 87% of LGD sites correctly classified. Decision algorithms using both nuclear enlargement and crowding further improved diagnostic accuracy, and accurately classified samples into the 4 histologic categories. CONCLUSIONS: LSS can reliably detect LGD and HGD in patients with Barrett's esophagus.

Aged↗
PubMed2000

EUS to detect evidence of pancreatic disease in patients with persistent or nonspecific dyspepsia.

BACKGROUND: Mild chronic pancreatitis is difficult to diagnose and the diagnosis is therefore not sought routinely in patients with dyspepsia. The aim of our study was to compare the prevalence of endosonographic pancreatic abnormalities in patients with dyspepsia and control subjects. METHODS: The number of endosonographic abnormalities was compared prospectively in patients with dyspepsia and control patients. Patients in whom there was any suspicion of pancreatic disease were analyzed separately. RESULTS: Between November 1998 and January 1999, 156 patients with dyspepsia were compared with 27 control patients. The groups were similar except that control patients were significantly older and more likely to be men. The mean number of endosonographic abnormalities was higher in dyspeptic patients than in control patients (mean number of abnormalities 3.3: 95% CI [2.9, 3.6] vs. 1.9: 95% CI [0.3, 1.7]). The strongest independent predictors of severe endosonographic abnormalities (defined as 5 or more abnormalities) were the presence of suspected pancreatic disease (odds ratio 7.29: 95% CI [2.03, 26. 14]) and dyspepsia (odds ratio 7.21: 95% CI [1.99, 26.26]). In the dyspepsia group, no clinical variables were significant predictors of severe abnormalities. However, most patients had nonspecific-type dyspepsia or persistent symptoms after therapeutic trials of acid suppression. CONCLUSIONS: Dyspepsia may be an atypical presentation of pancreatic disease in patients with persistent or nonspecific symptoms. Endosonography may be useful to screen for pancreatic disease in patients with persistent dyspepsia.

Adult↗