Can endoscopic ultrasound distinguish between mediastinal benign lymph nodes and those involved by sarcoidosis, lymphoma, or metastasis?

BACKGROUND: Lymph nodes (LNs) echofeatures on endoscopic ultrasound (EUS) and concurrent fine needle aspiration (FNA) are alternatives to highly invasive approaches for etiologic diagnosis of mediastinal lymphadenopathy (MLAD). AIMS: To evaluate the efficacy of LNs echofeatures and FNA via EUS to distinguish benign LNs from LNs involved by sarcoidosis, lymphoma, and metastasis in non-lung cancer patients. METHODS: A retrospective review of patients who underwent EUS-FNA for MLAD was performed. Echofeatures of LNs including echogenicity, margins, shape, and LN size were recorded. Final diagnosis was made based on surgical sampling or clinical diagnosis with long-term follow-up. Only patients diagnosed as benign MLAD, sarcoidosis, lymphoma, and metastasis included. Diagnostic value of echofeatures and FNA was evaluated. RESULTS: Included were 162 patients with final diagnosis of benign (68), sarcoidosis (33), lymphoma (20), and metastasis (41). The median LN along axis in the benign group [20.5 mm (6-76)] was significantly shorter than in the metastasis [28 mm (9-82)] and sarcoidosis [27 mm (17-50)] groups (p < 0.05). The median LN short axis in the benign group [11 mm (2-50)] was significantly shorter than in the metastasis [17 mm (5-44)] and lymphoma [16 mm (7-47)] groups (p < 0.05). No other echofeatures showed a discriminant value among the groups. When performing FNA, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of EUS-FNA were 73.7, 100, 100, 72.2, and 84.4 %, respectively. CONCLUSION: Although benign MLAD tend to be smaller than other etiologies, echofeatures of LNs are not reliable etiologic diagnostic approach to MLAD. Therefore, FNA is suggested when feasible. However, due to relatively low sensitivity, LNs with benign FNA results should be subjected to further work-up if they are clinically suspicious.

Trainee participation is associated with increased small adenoma detection.

BACKGROUND: Previous studies examining the effect of fellow participation on adenoma detection rate in colonoscopy have yielded conflicting results, and factors such as adenoma size and location have not been rigorously evaluated. OBJECTIVE: To examine whether fellow participation during screening, surveillance, or diagnostic colonoscopy affects overall, size-specific, or location-specific adenoma or polyp detection rate. METHODS: This was a retrospective study of 2430 colonoscopies performed in our ambulatory surgical center between September 2006 and December 2007, comparing adenoma and polyp detection rates of colonoscopies performed by fellows with supervising staff endoscopists (n = 318) with colonoscopies performed by staff endoscopists without fellow participation (n = 2112). Study participants included patients who underwent screening, surveillance, or diagnostic colonoscopies in our GI suite. Logistic regression analysis was used to evaluate the association of fellow participation with adenoma and polyp detection. RESULTS: There was evidence of a higher rate of small (<5 mm) adenoma detection in colonoscopies with a fellow present (25% vs 17%, P = .001). This remained significant after multiple-testing adjustment (P ≤ .003 considered significant). Findings were similar, although not significant for small polyps (36% vs 29%, P = .007). There was a trend toward increased adenoma detection in colonoscopies with a fellow present compared with those without (30% vs 26%, P = .11). Multivariable adjustment for potentially confounding variables did not alter these associations. LIMITATIONS: The study had a retrospective design, and information regarding bowel preparation was not available for 37% of patients. CONCLUSION: Fellow involvement was associated with increased detection rates of small adenomas, providing evidence that the presence of a fellow during colonoscopy plays a role in enhancing the effectiveness of the examination.

The learning curve of in vivo probe-based confocal laser endomicroscopy for prediction of colorectal neoplasia.

BACKGROUND: Probe-based confocal laser endomicroscopy (pCLE) is an emerging tool for in vivo imaging of the GI tract that requires the endoscopist to interpret microscopic images. The learning curve for interpretation of pCLE images is unknown. OBJECTIVE: To examine the learning curve of correctly identifying benign and neoplastic colorectal lesions by using pCLE and to evaluate the learning curve of obtaining high-quality images. DESIGN: Prospective, double-blind review of pCLE images of 76 colorectal lesions by using corresponding polypectomies as the reference standard. A training set of 20 images with known histology was first reviewed to standardize image interpretation, followed by blinded review of 76 unknown images. SETTING: Eleven endoscopists from 3 different endoscopy centers evaluated the images obtained by 1 endoscopist using the high-definition confocal probe. PATIENTS: Patients undergoing screening and surveillance colonoscopies. INTERVENTION: Intravenous fluorescein pCLE imaging of colorectal lesions followed by polypectomies. MAIN OUTCOME MEASUREMENTS: Accuracy of image interpretation with constructing learning curve for pCLE image interpretation and acquisition. RESULTS: Of the 76 colorectal lesions, 51 (67%) were neoplastic and 25 (33%) were benign, based on histopathology. Accuracy for the overall group was 63% for lesions 1 to 20, 64% for lesions 21 to 40, 79% for lesions 41 to 60, and 86% for lesions 61 to 76. The ability to obtain high-quality images was stable over the 76 cases. LIMITATIONS: Small sample size and use of offline video sequences. CONCLUSIONS: Accurate interpretation of pCLE images for predicting neoplastic lesions can be learned rapidly by a wide range of GI specialists. Furthermore, the ability to acquire high-quality pCLE images is also quickly learned.

High-definition colonoscopy detects colorectal polyps at a higher rate than standard white-light colonoscopy.

BACKGROUND & AIMS: Adenoma detection rates might be improved through use of high-definition colonoscopy, which can detect subtle mucosal changes. We investigated whether the use of high-definition white-light (HDWL) colonoscopy resulted in a higher rate of adenoma detection than standard-definition white-light (SDWL) colonoscopy in a clinical practice setting. METHODS: This retrospective study included 2430 patients who underwent colonoscopies from September 2006 to December 2007; 1226 received SDWL colonoscopy and 1204 received HDWL colonoscopy. We analyzed data from consecutive screening, surveillance, and diagnostic colonoscopies, comparing adenoma and overall polyp detection between procedures. Potentially confounding variables were controlled using multivariable logistic regression analysis. RESULTS: The adenoma detection rate was higher among patients who underwent HDWL compared with SDWL colonoscopies (28.8% vs 24.3%; P = .012), as was the polyp detection rate (42.2% vs 37.8%; P = .026). These findings remained after adjustments for potentially confounding variables (P = .018 and .022, respectively). CONCLUSIONS: In a general clinical practice setting, HDWL colonoscopy resulted in a higher adenoma detection rate compared with SDWL colonoscopy. The use of SDWL colonoscopy could reduce the number of missed adenomas and the subsequent risk for colorectal cancer.

Endosonographic features predictive of malignancy in mediastinal lymph nodes in patients with lung cancer.

BACKGROUND: EUS is useful in determining mediastinal lymph node (LN) metastases in patients undergoing staging for lung cancer. However, FNA of LNs is often performed only if suspicious features are present. The utility of individual LN features in predicting malignant cytology remains unclear. OBJECTIVE: To evaluate the utility of EUS-determined LN features for predicting malignant cytology. DESIGN: Prospective observational study. SETTING: Two U.S. tertiary-care centers. PATIENTS: This study involved 425 patients with primary lung cancer who underwent EUS. INTERVENTION: All mediastinal LNs were described according to size, shape, echogenicity, and margin characteristics. FNA was performed on LNs with any features suggestive of malignancy. EUS-guided FNA cytology was classified as benign or abnormal (suspicious/malignant). The utility of LN features in predicting malignant cytology was determined and further analyzed by logistic regression, and a predictive model was established. MAIN OUTCOME MEASUREMENTS: Accuracy of individual LN features for predicting malignancy. RESULTS: EUS detected 836 LNs in 425 patients, and FNA was obtained in 698 patients. On multivariable analysis, only round shape, a short axis of >8.3 mm, and sharp margins were predictive of malignant cytology. According to the predictive model, the calculated probability of having malignancy is less than 4% (95% confidence interval [CI], 0.022-0.064) when none of the LN features are present and 63% (95% CI, 51%-72.2%) when all features were seen. LIMITATIONS: No surgical histology as the criterion standard. CONCLUSION: Among patients with lung cancer, EUS features of round shape, sharp margins, and short axis of >8.3 mm are significant predictors of malignancy. The probability of malignancy is low when none of the features are present.

Pilot study on light dosimetry variables for photodynamic therapy of Barrett's esophagus with high-grade dysplasia.

PURPOSE: Photodynamic therapy (PDT) is used to treat Barrett's esophagus with high-grade dysplasia and mucosal carcinoma. Outcomes are variable with some patients having persistent disease, whereas others develop strictures. The aims of this study were (a) to compare porfimer sodium tissue uptake, light dose, and esophageal thickness with clinical outcomes and (b) to determine the selectivity of porfimer sodium uptake in diseased and normal epithelium. EXPERIMENTAL DESIGN: Forty-eight hours after porfimer sodium infusion, patients underwent mucosal biopsy for quantification of the porfimer sodium. Laser light was delivered at 48 hours and again 24 or 48 hours later. Porfimer sodium was extracted from the biopsy samples and quantified using fluorescence spectroscopy. The enhanced photodynamic dose was determined as [porfimer sodium content * light dose/esophageal thickness]. PDT efficacy was determined 6 to 8 weeks later based on persistence or complete ablation of dysplasia or carcinoma. RESULTS: Mean porfimer sodium content of 6.2 mg/kg (range, 2.6-11.2 mg/kg) and mean total light dose of 278 J/cm (range, 225-360 J/cm) resulted in a complete treatment. Mean porfimer sodium tissue content of 3.9 mg/kg (range, 2.1-8.1 mg/kg) and mean total light dose of 268 J/cm (range, 250-350 J/cm) resulted in an incomplete treatment. The total esophageal thickness (range, 1.7-6.0 mm) and enhanced photodynamic dose were correlated with treatment outcome. CONCLUSIONS: Esophageal thickness is the strongest predictor of treatment outcome. The porfimer sodium content of Barrett's and normal tissue is not significantly different. "Photodynamic dose" for esophageal PDT should incorporate the esophageal thickness.

CXC-chemokine/CXCR2 biological axis promotes angiogenesis in vitro and in vivo in pancreatic cancer.

Angiogenesis is essential for tumor growth and metastasis. Although ELR(+)-CXC-chemokines and their corresponding receptor, CXC-receptor 2 (CXCR2), are known mediators of angiogenesis, little is known about their role in pancreatic cancer (PaCa). The aim of our study was to determine the role of ELR(+)-CXC-chemokine/CXCR2 biological axis in promoting PaCa angiogenesis. We prospectively collected secretin-stimulated exocrine pancreatic secretions (SSEPS) from normal individuals (NP) and PaCa patients. We showed that summed concentrations of ELR(+)-CXC-chemokines in SSEPS from PaCa patients were significantly higher than in those from NP (p = 0.002). We measured ELR(+)-CXC-chemokine levels in supernatants from multiple PaCa cell lines and confirmed that BxPC-3, Colo-357 and Panc-28 had significantly higher expression compared with an immortalized human pancreatic ductal epithelial (HPDE) cell line. After confirming lack of autocrine effects of ELR(+)-CXC-chemokines on PaCa cells (due to absence of CXCR2 expression), we investigated paracrine effects of these chemokines on human umbilical vein endothelial cells (HUVEC). Both recombinant ELR(+)-CXC-chemokines and co-culturing with BxPC-3 significantly enhanced proliferation, invasion, and tube formation of HUVEC (p < 0.05). These biological effects were significantly inhibited by treatment with a neutralizing antibody against CXCR2 (anti-CXCR2 Ab) (p < 0.05). Finally, anti-CXCR2 Ab significantly reduced tumor volume (p < 0.05), Ki-67 proliferation index (p = 0.043) and Factor VIII(+) microvessel density (p = 0.004) in an orthotopic nude mouse PaCa model. Our results show that ELR(+)-CXC-chemokines promote PaCa tumor-associated angiogenesis through CXCR2, suggesting that CXCR2 is an anti-angiogenic target in PaCa.

The natural history of upper gastrointestinal subepithelial tumors: a multicenter endoscopic ultrasound survey.

GOALS: To evaluate the natural course of <3-cm upper gastrointestinal subepithelial tumors by endoscopic ultrasound (EUS) and to determine the appropriate timing for EUS follow-up. BACKGROUND: Subepithelial tumors (SETs) can range from benign lesions to tumors with malignant behavior or potential to become malignant such as gastrointestinal stromal tumors (GISTs). EUS is considered a valuable tool for their evaluation as it estimates the exact size and layer of origin, and also additional morphologic features that can suggest the diagnosis. For high surgical risk patients and when no worrisome EUS features are seen, EUS surveillance of subepithelial tumors is often used. METHODS: Fifty-one patients (mean age, 61.2+/-11.8 y; median, 63 y) with asymptomatic <3-cm SETs of second and fourth echolayer were followed for a mean period of 29.7 months (range, 3 to 84; median, 23 mo) in 3 tertiary care institutions. Evaluation included location, echolayer, tumor diameter, internal echo pattern, and outer margin of lesions by EUS. EUS was performed by using miniprobes, radial and linear echoendoscopes. RESULTS: Follow-up revealed increase in size and/or change in echogenic features in 7/51 (13.7%) patients. Surgical follow-up was available for 3 of 7 of these patients. Two of the fourth layer SETs, which had both increase in size and change in echogenicity were found to be GISTs (+c-kit). CONCLUSIONS: The majority of <3-cm SETs does not change during a median of 23 months. The change in echogenicity and increase in size may indicate a GIST.

Changes in efficiency and resource utilization after increasing experience with double balloon enteroscopy.

AIM: To investigate changes in efficiency and resource utilization as a single endoscopist's experience increased with each subsequent 100 double balloon enteroscopy (DBE) procedures. METHODS: We reviewed consecutive DBE procedures performed by a single endoscopist at our center over 4 years. DBE was employed when the clinician deemed the procedure was needed for disease management. The approach (oral, anal or both) was chosen based on suspected location of the target lesion. All DBE was performed in a standard endoscopy room with a portable fluoroscopy unit. Fluoroscopy was used to aid in shortening the small intestine and reducing bowel loops. For oral DBE, measurements were taken from the incisors. For anal DBE, measurements were taken from the anal verge. Enteroscopy continued until the target lesion was reached, until the entire small intestine was examined, or until no further progress was deemed possible. The length of small intestine examined (cm), procedure duration (min), and fluoroscopy time (s) were analyzed for sequential groups of 100 DBE. Sub-groups of diagnostic and therapeutic procedures were analyzed using multivariable linear regression. RESULTS: 802 consecutive DBE procedures were analyzed. For oral DBE, median [interquartile range (IQR)] length of small bowel examined was 230.8 cm (range: 210-248 cm) and for anal DBE was 143.5 cm (range: 100-180 cm). No significant increase in length examined was noted for either the oral or anal approach with advancing position in series. In terms of duration of procedure, the median (IQR) for oral DBE was 86 min (range: 71-105 min) and for anal DBE was 81.3 min (range: 67-105 min). When comparing by the position in series, there was a significant (P value < 0.001) decrease in procedure duration for both upper and lower procedures with increasing experience. Median (IQR) time of exposure to fluoroscopy for oral DBE was 190 s (114-275) compared to anal DBE which was 196.4 s (312-128). This represented a significant (P value < 0.001) decrease in the amount of fluoroscopy used with increasing position in series. For both oral and anal DBE, fluoroscopy time was reduced by greater than 50% over the course of 802 total procedures performed. Sub-group analysis was conducted on therapeutic and diagnostic groups. Out of 802 procedures, a total of 434 were considered therapeutic. Argon plasma coagulation was by far the most common therapeutic intervention performed. There was no evidence of a difference in length examined or fluoroscopy exposure among oral DBE for diagnostic and therapeutic procedures, P = 0.91 and P = 0.32 respectively. The median (IQR) for length was 235 cm (range: 178-280 cm) for diagnostic vs 230 cm (range: 180-275 cm) for therapeutic procedures; additionally, fluoroscopy time median (IQR) was 180 s (range: 110-295 s) and 162 s (range: 102-263 s) for no intervention and intervention. However, there was a significant difference in procedure duration among oral DBE (P < 0.001). The median (IQR) was 80 min (range: 60-97 min) and 94 min (range: 77-110 min) for diagnostic and therapeutic interventions respectively. CONCLUSION: For a single endoscopist, increased DBE experience with number of performed procedures is associated with increased efficiency and decreased resource utilization.

A case of mesenteric ischemia secondary to Fibromuscular Dysplasia (FMD) with a positive outcome after intervention.

Fibromuscular dysplasia (FMD) is a non-inflammatory, non-atherosclerotic angiopathy, which commonly affects the renal and internal carotid arteries. Although rare, FMD has the potential of involving the mesenteric vasculature. Due its low incidence and relatively little knowledge concerning its risk factors and etiology, actual diagnosis of FMD involving the mesenteric vessels requires a very high degree of suspicion. Upon review of the few reported cases of FMD causing mesenteric ischemia, it is clear that therapeutic interventions are rarely discussed and that positive outcomes are even more uncommon. Herein, we present the case of a 47 year-old female with mesenteric ischemia secondary to FMD, which was diagnosed and treated originally with angioplasty, then repeat angioplasty with stent placement, and finally with a bypass graft. Ultimately, the patient had a positive outcome, including eight month follow-up.

Glycemic control after total pancreatectomy for intraductal papillary mucinous neoplasm: an exploratory study.

Background. Glycemic control following total pancreatectomy (TP) has been thought to be difficult to manage. Diffuse intraductal papillary mucinous neoplasm (IPMN) is a potentially curable precursor to pancreatic adenocarcinoma, best treated by TP. Objective. Compare glycemic control in patients undergoing TP for IPMN to patients with type 1 diabetes mellitus (DM). Design/Setting. Retrospective cohort. Outcome Measure. Hemoglobin A1C(HbA1C) at 6, 12, 18, and 24 months after TP. In the control group, baseline was defined as 6 months prior to the first HbA1c measure. Results. Mean HgbA1C at each point of interest was similar between TP and type I DM patients (6 months (7.5% versus 7.7%, P = 0.52), 12 months (7.3% versus 8.0%, P = 0.081), 18 months (7.7% and 7.6%, P = 0.64), and at 24 months (7.3% versus 7.8%, P = 0.10)). Seven TP patients (50%) experienced a hypoglycemic event compared to 65 type 1 DM patients (65%, P = 0.38). Limitations. Small number of TP patients, retrospective design, lack of long-termfollowup. Conclusion. This suggests that glycemic control following TP for IPMNcan be well managed, similar to type 1 DM patients. Fear of DM following TP for IPMN should not preclude surgery when TP is indicated.

Lung cancer staging by combined endobronchial ultrasound (EBUS) and endoscopic ultrasound (EUS): The gastroenterologist's perspective.

This review deals with the combined approach of endoscopic ultrasound and endobronchial ultrasound for lung cancer staging. The review provides an overview for the gastroenterologist who performs endosonography with regard to the current evidence supporting the use of endoscopic ultrasound and endobronchial ultrasound in clinical practice.

Patient outcomes after total pancreatectomy: a single centre contemporary experience.

INTRODUCTION: Total pancreatectomy (TP) is associated with significant metabolic abnormalities leading to considerable morbidity. With the availability of modern pancreatic enzyme formulations and improvements in control of diabetes mellitus, the metabolic drawbacks of TP have diminished. As indications for TP have expanded, we examine our results in patients undergoing TP. MATERIALS AND METHODS: Retrospective study of 47 patients undergoing TP from January 2002 to January 2008 was performed. Patient data and clinical outcomes were collected and entered into a database. Disease-free survival and overall survival were estimated using the Kaplan-Meier method. RESULTS: Fifteen males and 32 females with a median age of 70 years underwent TP for non-invasive intraductal papillary mucinous neoplasms (IPMN) (21), pancreatic adenocarcinoma (20), other neoplasm (3), chronic pancreatitis (2) and trauma (1). Median hospital stay and intensive care stay were 11 days and 1 day, respectively. Thirty-day major morbidity and mortality was 19% and 2%, respectively. With a median follow-up length of 23 months, 33 patients were alive at last follow-up. Estimated overall survival at 1, 2 and 3 years for the entire cohort was 80%, 72% and 65%, and for those with pancreatic adenocarcinoma was 63%, 43% and 34%, respectively. Median weight loss at 3, 6 and 12 months after surgery was 6.8 kg, 8.5 kg and 8.8 kg, respectively. Median HbA1c values at 6, 12 and 24 months after surgery were 7.3, 7.5 and 7.7, respectively. Over one-half of the patients required re-hospitalization within 12 months post-operatively. CONCLUSION: TP results in significant metabolic derangements and exocrine insufficiency, diabetic control and weight maintenance remain a challenge and readmission rates are high. Survival in those with malignant disease remains poor. However, the mortality appears to be decreasing and the morbidities associated with TP appear acceptable compared with the benefits of resection in selected patients.

Endoscopic mucosal ablation for the treatment of gastric antral vascular ectasia with the HALO90 system: a pilot study.

BACKGROUND: Gastric antral vascular ectasia (GAVE) often results in GI bleeding and chronic anemia. Treatment options are limited and include medical, endoscopic, and surgical therapies. OBJECTIVE: To assess the utility of endoscopic mucosal ablative therapy by using the HALO(90) system for patients with GAVE and recurrent bleeding. DESIGN: Prospective open-label case series. SETTING: Tertiary referral center. PATIENTS: Six consecutive patients with GAVE, bleeding, and blood transfusion dependence. MAIN OUTCOME MEASUREMENTS: Comparison of preablation and postablation Hb levels and transfusion requirements. To assess the number of ablation sessions needed to stabilize the Hb level and eliminate the need for blood transfusion. RESULTS: Six patients, (4 men, mean age 58 years, range 47-65 years) underwent endoscopic mucosal ablation of antral lesions (mean procedure time 29 minutes; mean treatments 1.7, range 1-3). The mean Hb level improved from 8.6 to 10.2 g/dl (mean 2 months after the last ablation). Five of 6 patients are no longer dependent on blood transfusions to maintain a stable Hb level. LIMITATIONS: This is a pilot study, with a small number of patients at a single center, with limited patient follow-up. CONCLUSIONS: This study suggests that endoscopic mucosal ablation by using the HALO(90) system is a promising treatment option for chronic bleeding related to GAVE.

West Nile Virus infection with hearing loss.

Since the New York outbreak in 1999, West Nile Virus (WNV) has spread across the United States and North America. The spectrum of disease may range from asymptomatic to debilitating neuroinvasive. We present a case of a woman with myasthenia gravis on immunosuppressive therapy who developed WNV meningoencephalitis presenting as flaccid paralysis and severe bilateral hearing loss. To our knowledge this is the first reported case of WNV-associated hearing loss, and the first reported in a patient with previously diagnosed myasthenia gravis. Of epidemiologic interest was that her mother, 81 years old and in previous good health, developed a WNV infection shortly before the patient's infection.