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Biomedical subjects

M B Wallace

Publications and source records attributed to M B Wallace.

At least 37 records · Page 2Linked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

CT or EUS for the initial staging of esophageal cancer? A cost minimization analysis.

BACKGROUND: Patients with advanced (T4 and/or M1) esophageal cancer are offered palliative therapy. Computed tomography (CT) is sensitive for distant metastases but is less sensitive than endosonography for T4 disease and celiac lymphadenopathy. The aim of this study was to determine whether initial CT or endosonography costs less to diagnose advanced esophageal cancer. METHODS: A decision model compared the costs of the 2 strategies. Sensitivity analysis and threshold analysis were used to identify the most important determinants of the overall cost of identifying advanced disease. RESULTS: Initial CT is the least costly strategy if the probability of finding advanced disease by initial CT is greater than 20%, if the probability of finding advanced disease by initial endoscopic ultrasound (EUS) is less than 30%, or if the cost of EUS is greater than 3.5 times the cost of CT. However, in our referral center population, endosonography found advanced disease more frequently than CT (44% vs. 13%; p < 0.0001) and the least costly strategy was initial endosonography (expected cost $804 vs. $844). CONCLUSION: CT remains as the initial staging test of choice in most clinical settings. However, in referral centers, initial EUS may be reasonable, but individualized model inputs must be obtained before reliable conclusions can be drawn.

Adult↗

Remote clinical assessment of gastrointestinal endoscopy (tele-endoscopy): an initial experience.

BACKGROUND: Gastrointestinal (GI) endoscopy is an effective tool to screen for cancers of the digestive tract. However, access to endoscopy is limited in many parts of South Carolina. This trial is a part of a prospective multi-part study for remote cancer screening in coastal South Carolina. This pilot study was to evaluate the quality of tele-endoscopy for cancer screening. METHODS: 10 patients scheduled for endoscopic procedures were observed simultaneously by the endoscopist and a remote observer connected over a 512 kbps ISDN line. Findings by both were compared for concordance on malignant or premalignant lesions. RESULTS: The image quality was adequate to support remote diagnosis of GI cancer and abnormal lesions by an experienced observer. However, assessment of the esophagogastric junction for Barrett's esophagus was equivocal. CONCLUSIONS: Overall, our tele-endoscopy setup shows great promise for remote supervision or observation of endoscopic procedures done by nurse endoscopists. Tele-endoscopy is both adequate and feasible for diagnosis of most gastrointestinal lesions. Subtle lesions still may be missed in our current setup. However, improvements are being made in our setup to address the problem with resolution prior to further evaluation.

Endoscopes, Gastrointestinal↗

Screening for colorectal cancer with flexible sigmoidoscopy by nonphysician endoscopists.

PURPOSE: Screening with sigmoidoscopy reduces the risk of death from colorectal cancer. Only 30% of eligible patients have undergone sigmoidoscopy, in part because of a limited supply of endoscopists. We evaluated the performance and safety of screening sigmoidoscopic examinations by trained nonphysician endoscopists in comparison with board-certified gastroenterologists. SUBJECTS AND METHODS: Asymptomatic patients 50 years or older without evidence of fecal occult blood and no personal history or family history of a first-degree relative with colorectal cancer under age 55 years were offered sigmoidoscopy. All examinations were performed either by a gastroenterologist or a trained nonphysician endoscopist at a staff model health maintenance organization. Outcomes included the depth of examination, number and histology of polyps, and complications. RESULTS: Nonphysicians performed 2,323 sigmoidoscopic examinations, and physicians performed 1,378 examinations. The mean (+/-SD) depth of sigmoidoscopy examinations performed by nonphysicians was 52 +/- 10 cm compared with 55 +/- 9 cm (P <0.001) in physicians. Nonphysicians detected neoplastic polyps in a greater proportion of patients (7.8%) than physicians (5.8%), but this difference was not significant after adjusting for differences in the age, sex, and family history of the patients (P = 0.35). No major complications occurred. The cost per examination, including the nonphysician training cost, was lower for nonphysicians ($186 per examination) than for physicians ($283 per examination). CONCLUSIONS: Appropriately trained nonphysicians may be capable of performing safe and effective screening for colorectal cancer with flexible sigmoidoscopy. An increased use of nonphysicians to perform sigmoidoscopy may increase the availability and reduce the cost of the procedure.

Aged↗

Effects of dehydroepiandrosterone vs androstenedione supplementation in men.

PURPOSE: The purpose of this study was to compare the effects of short-term (12 wk) supplementation with androstenedione versus dehydroepiandrosterone (DHEA) on body composition, strength, and related hormones in middle-aged men. METHODS: A randomized, placebo-controlled, double-blind design was used to study 40 healthy, trained (>1 yr weight training) male subjects (mean +/- SD: age 48.1 +/- 3.9 yr; weight 79.8 +/- 9.8 kg). Subjects were randomly assigned to one of three groups: placebo (P), DHEA (D), or androstenedione (A). Supplements (50 mg capsules) were ingested two times daily for 12 wk. All testing, including venous blood samples, body composition, and performance, was conducted at three time points: presupplementation (1 d), at 6 wk, and postsupplementation (12 wk). RESULTS: Despite a small increase in lean body mass (0.8 +/- 0.4 and 0.5 +/- 0.3 kg) and mean strength (6.8 +/- 2.7 and 5.7 +/- 2.4 kg) in both D and A groups respectively, these changes were not significantly different from P. In D, there was a significantly greater increase in DHEA-S levels than in P (P < 0.05). There were no adverse side effects demonstrated during D or A supplementation including significant changes in PSA, liver function, or lipid levels (P < 0.05). CONCLUSIONS: The results of this study suggest that supplementation with 100 mg x d(-1) of either androstenedione or DHEA does not independently elicit a statistically significant increase in lean body mass, strength, or testosterone levels in healthy adult men over a 12-wk period.

Adult↗