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Biomedical subjects

Gregory Zuccaro

Publications and source records attributed to Gregory Zuccaro.

At least 19 recordsLinked to original sources

The efficiency of endoscopic pancreatic function testing is optimized using duodenal aspirates at 30 and 45 minutes after intravenous secretin.

OBJECTIVES: The endoscopic secretin test (ePFT) takes an hour to perform, limiting its practicality for routine use. We sought to determine which timed endoscopic collections best predict the peak bicarbonate concentration from full hour-long test. METHODS: A cross-sectional study was performed of all ePFTs performed at our institution from 2000 to 2004. We compared 7 theoretical shortened tests [4-single collections (15, 30, 45, or 60 minutes after secretin) and 3-dual collections (15/30, 30/45, 45/60 minutes after secretin)] to the full test and to each other using multivariate linear and Deming regression models. RESULTS: The bicarbonate results of 240 ePFTs were analyzed. The dual 30/45-minute collection was the optimal method based on the closest agreement with the full test (94%). Deming regression reveals the 30/45 estimate to be the best combination from an analytic perspective, owing to its lack of significant proportional bias and minimal constant bias (5.1 mEq/L) as compared to the reference test. Use of the 30/45 method with the adjusted cutpoint 75 mEq/L produces very good specificity (93%) for ruling in exocrine insufficiency. CONCLUSIONS: A dual timed aspiration at 30 and 45 minutes can be used to screen for pancreatic exocrine insufficiency in patients with abdominal pain, simplifying the use of the ePFT in clinical practice.

Abdominal Pain↗

A randomized crossover study of secretin-stimulated endoscopic and dreiling tube pancreatic function test methods in healthy subjects.

OBJECTIVES: We have developed an endoscopic method of secretin endoscopic pancreatic function testing (ePFT) to simplify duodenal fluid collection. Validation of the ePFT requires a direct comparison to the traditional PFT using a Dreiling tube (DT). Our aim was to compare bicarbonate concentrations [HCO3-] obtained by the ePFT and DT methods in healthy subjects (HS). METHODS: HS were randomized to either DT or ePFT, then crossed over to the other test after a minimum 1-wk washout. An age/weight-based sedation bolus was used for each test. DT protocol: Endoscopic placement of a DT was confirmed by fluoroscopy. After a baseline 15-min collection and administration of IV synthetic secretin, fluid was continuously collected in 15-min aliquots for an hour. ePFT protocol: Endoscopy was performed using a 6-mm endoscope. After gastric aspiration and discard and IV secretin, duodenal aspirates were obtained every 15-min for an hour. Fluid specimens were auto-analyzed for [HCO3-]. RESULTS: Twelve HS were enrolled (6F, mean age 37 yr). The difference in [HCO3-] between the two methods was not significant at the 0-, 30-, 45-, or 60-min collections. An excellent correlation in peak [HCO3-] was observed (R2 = 0.84, p < 0.001). Using a peak [HCO3-] cutpoint 80 mEq/L, there was 100% agreement between the methods; using cutpoint 90 mEq/L, there was 83% agreement. CONCLUSIONS: The accuracy of the ePFT is similar to DT: There were minimal differences in [HCO3-] at each of the timed collections and at peak. There is an excellent correlation in peak [HCO3-] and high level of diagnostic agreement between the tests.

Adult↗

Endoscopic ultrasound classification of esophageal cancer after chemotherapy or chemoradiotherapy.

Because of its ability to provide high resolution images of the esophageal wall and surrounding structures, Endoscopic Ultrasound (EUS) is thought to be well suited for prediction of T classification (depth of tumor invasion) and N classification (lymph node status) in patients with newly diagnosed esophageal cancer. EUS is also frequently used for interim classification after neoadjuvant therapy (chemotherapy or chemoradiotherapy). This editorial will focus on the potential goals of EUS in interim classification, its performance in this setting, and the relevance of interim staging.

Antineoplastic Combined Chemotherapy Protocols↗

Sedation for endoscopic procedures: not as simple as it seems.

The Bispectral Index (BIS) is a processed electroencephalogram, which has been evaluated as an automated monitoring technique for patients receiving sedation for endoscopic procedures. BIS monitoring has not been shown to be of significant clinical benefit, but the need for an objective quantitative measure of the depth of sedation in patients undergoing endoscopy remains.

Procedural Sedation↗

Natural history of indeterminate pancreatic cysts.

BACKGROUND: The optimal treatment for incidental asymptomatic pancreatic cysts is not known. The purpose of this study was to determine whether nonmucinous cysts by cyst-aspiration analysis can be observed safely. METHODS: A prospective protocol was initiated in September of 1999 for all suspected cystic neoplasms. Asymptomatic patients with negative cyst aspirates (no extracellular mucin, and concentration of carcinoembryonic antigen in the cyst fluid <200 ng/mL) were followed-up clinically and radiographically. RESULTS: Through December 2004, 221 patients have been evaluated, and 80 (36%) initially were operated. There were 141 (64%) patients with indeterminate cysts, 98 have been followed-up for more than 12 months. Compared with resected patients, observed patients were older (62 vs 56 y, P < .006), and had smaller cysts (2.4 vs 4.0, P = .001). At a mean follow-up period of 24 months, 4 patients (4%) were resected. The indication, time to resection, and pathology were as follows: 2 patients for symptoms (abdominal pain and obstructive jaundice) at 24 and 72 months, respectively: mucinous and serous cystadenomas; 1 patient for an increase in size (6.6 to 7.8 cm) at 18 months: lymphoepithelial cyst; and 1 patient for abdominal pain and increase in size (2.0 to 3.7 cm) at 41 months: pseudocyst. The only patient resected for a mucinous neoplasm had a cyst fluid carcinoembryonic antigen level of 896 ng/mL. In the remaining observed patients, 20 (23%) showed a decrease in cyst size, and 16 (19%) showed an increase in size (mean diameter change, 21%). CONCLUSIONS: Initial follow-up evaluation indicates that asymptomatic patients without evidence of a mucinous neoplasm by cyst aspiration can be followed clinically and with interval imaging.

Carcinoembryonic Antigen↗

Propofol versus traditional sedative agents for gastrointestinal endoscopy: a meta-analysis.

BACKGROUND & AIMS: Even though propofol has better recovery profile than traditional agents, its use is limited because of the perception of increased complication rates. Because an adequately powered trial comparing risk of propofol with traditional agents is lacking, we performed a meta-analysis of the current literature. METHODS: We searched Medline (1966-October 2004), EMBASE (1980-October 2004), and Cochrane controlled trials registry. The following 4 cardiopulmonary complications were assessed: hypoxia, hypotension, arrhythmias, and apnea. Procedures were divided into 3 groups: esophagogastroduodenoscopy group, colonoscopy group, and endoscopic retrograde cholangiopancreatography/endoscopic ultrasonography group. Pooled odds ratios for complications were calculated for all the procedures combined and then separately for the 3 groups. Random effects models were used for 2-proportion comparisons. RESULTS: Of the 90 citations identified, 12 original studies qualified for this meta-analysis and included 1161 patients. Of these, 634 received propofol, and 527 received midazolam, meperidine, and/or fentanyl. Most of the included studies were randomized trials of moderate quality and nonsignificant heterogeneity (Cochran Q = 4.81, P = .90). Compared with traditional sedative agents, the pooled odds ratio with the use of propofol for developing hypoxia or hypotension for all the procedures combined was 0.74 (95% confidence interval [CI], 0.44-1.24); for EGD, 0.85 (95% CI, 0.33-2.17); for colonoscopy, 0.4 (95% CI, 0.2-0.79); and for ERCP/EUS, 1.07 (95% CI, 0.38-3.01). CONCLUSIONS: Propofol sedation during colonoscopy appears to have lower odds of cardiopulmonary complications compared with traditional agents, but for other procedures, the risk of complications is similar.

Apnea↗

Deep sedation occurs frequently during elective endoscopy with meperidine and midazolam.

BACKGROUND AND AIMS: Although moderate (conscious) sedation is intended during elective gastrointestinal endoscopy, unintended levels of deep sedation occur. The aims of this study were to prospectively evaluate the incidence and risk factors of deep sedation during elective endoscopy with meperidine and midazolam intended to maintain a level of moderate sedation. METHODS: Eighty American Society of Anesthesiology class 1-2, outpatients presenting for elective esophagogastroduodenoscopy (EGD), colonoscopy, endoscopic retrograde cholangiopancreatography (ERCP), and endoscopic ultrasonography (EUS) were offered enrollment. Intravenous meperidine and midazolam were administered according to a standardized protocol. Hemodynamic parameters and levels of sedation were assessed and recorded by a single observer at 3-min intervals. The Modified Observer's Assessment of Alertness/Sedation (MOAA/S) scale (ranging 1-5) is a subjective sedation assessment scale used to assess sedation levels. Occurrence of deep sedation, defined by MOAA/S 1-2, was recorded. Univariable and multivariable analyses were used to assess predictors of deep sedation. RESULTS: Deep sedation occurred in 54/80 (68%) patients for a total of 204/785 (26%) of total sedation assessments. The percentage of deep sedation episodes of all sedation-level observations by procedure was 26% for EGD, 11% for colonoscopy, 35% for ERCP, and 29% for EUS. Deep sedation occurred at least once in 60% of EGD, 45% of colonoscopy, 85% of ERCP, and 80% of EUS. Multivariable analysis showed that only ERCP and EUS were independent risk factors of deep sedation. CONCLUSIONS: Deep sedation occurs frequently during elective endoscopy with meperidine and midazolam used with the intent of moderate sedation. ERCP and EUS are risk factors for the occurrence of deep sedation, independent of sedation dose or length of procedure.

Aged↗

Endoscopic ultrasound errors in esophageal cancer.

BACKGROUND: Previous assessments of endoscopic ultrasound (EUS) classification of esophageal cancer are dominated by symptomatic patients with advanced stage disease. Fewer data exist on EUS errors in a cohort balanced between early and advanced disease. PURPOSE: Assess EUS errors in classification of esophageal cancer in a more balanced cohort, and identify clinical and tumor characteristics associated with EUS errors. METHODS: A total of 266 patients underwent EUS and esophagectomy without preoperative chemoradiotherapy. Pathologic classification of disease extent: 108 (41%) tumors were confined to the esophageal wall (pTis-pT2, pN0, pM0); 158 (59%) were advanced beyond (pT3-pT4, pN1, or pM1). Logistic regression analysis was performed to identify correlates of error in T classification and disease extent using 10 clinical and tumor characteristics (gender, age, dysphagia, weight loss, tumor length, location, traversability, morphology, histopathologic type, and histologic grade). RESULTS: EUS erroneously predicted pathologic T (pT) in 119 patients (45%). When T classification was dichotomized into tumors whose depth of invasion was not beyond the muscularis propria (pTis-pT2) and those beyond (pT3-pT4), errors occurred in 42 patients (16%). EUS erroneously predicted N classification in 67 patients (25%), and was insensitive to the presence of distant metastases. EUS misclassified disease extent in 40 patients (15%). Logistic regression analysis indicated that weight loss and tumor length were the only clinical and tumor characteristics correlated with EUS errors; more weight loss was associated with decreased odds of misclassification, while the odds of misclassification were four to six times greater for intermediate length tumors than for shorter tumors. CONCLUSIONS: EUS errors, particularly in predicting pT, are more frequent than previously reported. Weight loss and tumor length are the only clinical and tumor characteristics correlated with EUS errors.

Diagnostic Errors↗

The effect of moderate sedation on exocrine pancreas function in normal healthy subjects: a prospective, randomized, cross-over trial using the synthetic porcine secretin stimulated Endoscopic Pancreatic Function Test (ePFT).

BACKGROUND: We have developed a purely endoscopic collection method for the assessment of pancreatic secretory function (ePFT). The pancreatic secretory effects of sedation medications utilized during endoscopic procedures are not completely known. AIMS: To study the effect of moderate sedation on the exocrine pancreas gland in a prospective, randomized trial. METHODS: Healthy volunteers were randomized by computers to one of two treatments (A-no sedation, B-sedation) in period 1 and crossed-over to the other treatment in period 2 with a minimal washout interval of 7 days. Sedation dosage was standardized for each patient based on age, gender and weight from a previously published dosing nomogram. Synthetic porcine secretin (ChiRhoClin, Inc., Burtonsville, Maryland) was used as the pancreatic stimulant. Duodenal fluid samples were aspirated via the endoscope every 5 min for 1 h and sent on ice to our hospital laboratory for the measurement of pancreatic secretory electrolyte concentrations by autoanalyzer. RESULTS: A total of 17 healthy volunteers were enrolled. Sixteen subjects (8 males and 8 females) completed the randomized prospective trial. Median intravenous meperidine and midazolam sedation dose was 62.5 mg and 2.5 mg, respectively. Maximum pancreatic juice flow occurred during the early phase of secretion and maximum bicarbonate concentration occurred during the late phase of secretion. Analysis of the electrolyte composition of the endoscopically collected duodenal drainage fluid revealed a constant cation concentration for both sodium and potassium over the 1 h collection period. The anions, chloride and bicarbonate, exhibited a reciprocal relationship identical to that seen in traditional gastroduodenal tube collection studies. There was no statistical difference observed between the sedation and no sedation groups. The estimated total bicarbonate output (area under curve, AUC) for the sedated and non-sedated groups were 5,017 meq + 724 (range 3,663-6,173) and 5,364 meq +/- 583 (range 4,323-6563) respectively (p= 0.0656). The mean peak bicarbonate concentrations for sedated (n = 8) versus non-sedated (n = 8) groups were 103 +/- 11 meq/L (range 78-125) and 106 +/- 11 meq/L (range 87-138), respectively (p= 0.1346). There was excellent correlation of peak bicarbonate concentrations when sedation and no sedation groups were compared (r= 0.744, p < 0.05; Spearman rank correlation). There were no episodes of pancreatitis. CONCLUSIONS: (a) Moderate sedation used for upper endoscopy does not effect the clinical diagnostic parameters (peak bicarbonate concentration or total bicarbonate output) utilized to diagnose pancreatic insufficiency. (b) Analysis of duodenal drainage fluid collected endoscopically after synthetic secretin stimulation produces an identical pancreatic secretory curve described with traditional gastroduodenal tube collection methods.

Adult↗

Optical coherence tomography in the gastrointestinal tract.

Conventional gastrointestinal endoscopic instruments have provided ready access to the mucosal surface of the esophagus, stomach,small intestinal, colon, bile duct, and pancreatic duct. The evolution of endoscopic ultrasonography has provided an additional dimension to the clinical application of modern endoscopy and imaging technology.

Endoscopy, Gastrointestinal↗

Electrolyte composition of endoscopically collected duodenal drainage fluid after synthetic porcine secretin stimulation in healthy subjects.

BACKGROUND: Traditional pancreatic function tests are sensitive for the diagnosis of pancreatic exocrine insufficiency but are cumbersome and difficult to perform. A sedationless endoscopic pancreatic function test that has the potential for wide clinical application was developed by us, but data on the results of this method in healthy subjects are lacking. This study analyzed endoscopically collected duodenal fluid from healthy subjects after synthetic porcine secretin stimulation. METHODS: Healthy subjects underwent the sedationless endoscopic pancreatic function test. After secretin stimulation, duodenal aspirates were obtained every 5 minutes for 1 hour. The collected fluid was analyzed for electrolyte concentrations. RESULTS: Sixteen healthy subjects (8 women, 8 men; median age 34.5 years) underwent the endoscopic pancreatic function test. The concentrations of the sodium ([Na+]) and potassium ([K+]) cations remained constant, similar to normal concentrations in plasma (median [Na+], 155 mEq/L; median [K+], 4.3 mEq/L). The concentrations of the bicarbonate ([HCO 3 - ]) and chloride anions increased and decreased, respectively, in an inverse and reciprocal manner, similar to the previously characterized "secretory curve." The median peak [HCO 3 - ] was 108 mEq/L IQR: 99-110). By the 20-minute collection, the [HCO 3 - ] was greater than 80 mEq/L for 94% (15/16) of subjects, the historic cut point for [HCO 3 - ] in studies based on traditional methods of pancreatic function testing. CONCLUSIONS: Endoscopic collection of pancreatic fluid reproduces the anion-cation secretory curve described by prior studies of pancreatic secretory physiology based on traditional collection methods.

Adult↗

Ex vivo histology-correlated optical coherence tomography in the detection of transmural inflammation in Crohn's disease.

BACKGROUND AND AIMS: Distinguishing Crohn's disease (CD) from ulcerative colitis (UC) can be difficult. Transmural inflammation, a key feature of CD, cannot be assessed by conventional colonoscopy with biopsy. Optical coherence tomography (OCT) provides high-resolution, cross-sectional images of the gut wall and might become a new diagnostic tool. The aims of this study were to perform histology-correlated OCT on surgical specimens of CD and UC and to determine its diagnostic accuracy. METHODS: Colectomy specimens from patients with a preoperative diagnosis of CD (N = 24) or UC (N = 24) were studied with OCT in the operating room. OCT and histopathology were assessed blindly, and diagnostic accuracy of OCT was assessed. RESULTS: Eight preoperatively identified UC patients (33%) with transmural inflammation on postoperative histology were diagnosed with CD, and all 8 had a disrupted layered structure on OCT, a characteristic feature of transmural disease. Sixteen UC patients (67%) had superficial inflammation on histology; of them, 13 (81%) had an intact layered structure on OCT. All 24 preoperative CD patients had transmural inflammation on histology, and 23 (96%) had a disrupted layered structure on OCT. Of 585 histology-OCT image sets from the 48 patients, 152 sets (26%) had transmural inflammation on histology. The sensitivity and specificity for OCT to detect transmural disease were 86% and 91%, respectively. CONCLUSIONS: Transmural inflammation, as characterized by disruption of the layered structure of colon wall on OCT, is an accurate marker for the diagnosis of CD. Ex vivo OCT predicted transmural inflammation on postoperative histopathology.

Adult↗

In vivo colonoscopic optical coherence tomography for transmural inflammation in inflammatory bowel disease.

BACKGROUND & AIMS: Transmural inflammation, a distinguishing feature of Crohn's disease (CD), cannot be assessed by conventional colonoscopy with mucosal biopsy. Our previous ex vivo study of histology-correlated optical coherence tomography (OCT) imaging on colectomy specimens of CD and ulcerative colitis (UC) showed that disruption of the layered structure of colon wall on OCT is an accurate marker for transmural inflammation of CD. We performed an in vivo colonoscopic OCT in patients with a clinical diagnosis of CD or UC using the previously established, histology-correlated OCT imaging criterion. METHODS: OCT was performed in 40 patients with CD (309 images) and 30 patients with UC (292 images). Corresponding endoscopic features of mucosal inflammation were documented. Two gastroenterologists blinded to endoscopic and clinical data scored the OCT images independently to assess the feature of disrupted layered structure. RESULTS: Thirty-six CD patients (90.0%) had disrupted layered structure, whereas 5 UC patients (16.7%) had disrupted layered structure (P < .001). Using the clinical diagnosis of CD or UC as the gold standard, the disrupted layered structure on OCT indicative of transmural inflammation had a diagnostic sensitivity and specificity of 90.0% (95% CI: 78.0%, 96.5%) and 83.3% (95% CI: 67.3%, 93.3%) for CD, respectively. The kappa coefficient in the interpretation of OCT images was 0.80 (95% CI: 0.75, 0.86, P < .001). CONCLUSIONS: In vivo colonoscopic OCT is feasible and accurate to detect disrupted layered structure of the colon wall indicative of transmural inflammation, providing a valuable tool to distinguish CD from UC.

Adult↗

Analysis of pancreatic elastase-1 concentrations in duodenal aspirates from healthy subjects and patients with chronic pancreatitis.

Fecal pancreatic elastase 1 (PE-1) has been advocated as a noninvasive marker of pancreatic function and allows detection of moderate and severe exocrine insufficiency. Few studies have evaluated the utility of measuring PE-1 in duodenal fluid for the diagnosis of pancreatic insufficiency. Our purpose was (1) to determine the feasibility of measuring PE-1 concentrations in duodenal aspirates obtained through our endoscopic pancreatic function test (ePFT) in healthy subjects and patients with chronic pancreatitis (CP) and (2) to determine correlations between duodenal PE-1 concentrations and bicarbonate and lipase concentrations in duodenal fluid. Healthy subjects (HS) and CP patients underwent an ePFT with CCK or secretin. CP was defined as endoscopic retrograde pancreatography (ERP) Cambridge class III-IV, endoscopic ultrasound (EUS) score >5, or presence of pancreatic calcifications on CT scan. Duodenal fluid PE-1, lipase, and bicarbonate concentrations were measured in each study group. Duodenal lipase and bicarbonate concentrations were measured using an autoanalyzer (Roche Diagnostics, Indianapolis, IN). PE-1 was measured using an ELISA (Genova Diagnostics, Asheville, NC). Ten HS and 10 CP patients were studied. In the CCK test the median peak lipase for HS and CP was 1605 and 113 IU/L, respectively (P < 0.008). In the secretin test the median peak bicarbonate for HS and CP was 102 and 40 mEq/L, respectively (p < 0.008). Median PE-1 concentrations for HS and CP were 317 and 63 microg/ml, respectively, after CCK stimulation (p = 0.046) and 87 and 17 microg/ml, respectively, after secretin stimulation (p = 0.033). Statistically significant correlations were found between [PE-1] and peak [lipase] (r = 0.83, P < 0.001), as well as [PE-1] and peak [HCO3(3)-] (r = 0.65, P = 0.037). Conclusions are as follows: (1) PE-1 concentrations can be measured from duodenal fluid obtained by endoscopic aspiration. (2) Duodenal fluid PE-1 concentrations are decreased in CP compared to HS. (3) Duodenal fluid [PE-1] has an excellent correlation with [lipase] and therefore is a marker of acinar cell function. (4) Secretin-stimulated endoscopic function testing with measurement of bicarbonate and PE-1 may provide a simultaneous assessment of both ductal cell and acinar cell function.

Adult↗

Pathogenesis of chronic pancreatitis: an evidence-based review of past theories and recent developments.

In the past several decades, four prominent theories of chronic pancreatitis pathogenesis have emerged: the toxic-metabolic theory, the oxidative stress hypothesis, the stone and duct obstruction theory, and the necrosis-fibrosis hypothesis. Although these traditional theories are formulated based on compelling scientific observations, substantial contradictory data also exist for each. Furthermore, the basic premises of some of these theories are directly contradictory. Because of the recent scientific progress in the underlying genetic, cellular, and molecular pathophysiology, there have been substantial advances in the understanding of chronic pancreatitis pathogenesis. This paper will provide an evidence-based review and critique of the traditional pathogenic theories, followed by a discussion of the new advances in pancreatic fibrogenesis. Moreover, we will discuss plausible pathogenic sequences applied to each of the known etiologies.

Animals↗