EUS and EUS-Guided Interventions Alter Clinical Management in Children With Digestive Diseases.

OBJECTIVES: Endoscopic ultrasound (EUS) ± fine needle aspiration (FNA) is a useful tool to evaluate gastrointestinal tract disorders in adults because of its established feasibility and safety. Its role in children has not been well established and continues to evolve. Our objective was to evaluate the utility and impact on clinical management of EUS and EUS-guided interventions in the pediatric population at our institution. METHODS: Retrospective, single-center study including 43 patients undergoing EUS and EUS-FNA between August 2005 and January 2012. RESULTS: Fifty-one EUS procedures were performed in 43 patients, 30 girls, median age 14.5 (range 4-18). The most common indications were suspected biliary obstruction in 11 of 51 (22%), pancreatic cysts in 10 of 51 (20%), acute or recurrent pancreatitis in 9 of 51 (18%), and abdominal pain in 8 of 51 (16%). The most common findings of EUS included normal 11 of 51 (22%), pancreas cyst 6 of 51 (12%), pancreatic pseudocyst 5 of 51 (10%), biliary system sludge or stones 9 of 51 (18%), and acute and chronic pancreatitis 5 of 51 (10%). EUS-FNA was performed in 13 cases: 7 solid masses or nodes, 4 pancreatic pseudocyst, 1 pancreatic cyst, and 1 celiac plexus block. FNA cyst drainage was successful in resolving all 4 pancreatic pseudocysts. EUS prompted a surgical procedure in 13 cases (25%), ERCP in 5 cases (10%), and repeat EUS in 5 cases (10%). EUS led to a new diagnosis in 34 of 43 (79%) patients and prompted further intervention in 24 of 51 (47%) procedures. CONCLUSIONS: In this large cohort study, we found that EUS and EUS-guided interventions assist in diagnosing and altering clinical management in pediatric patients and should be considered in cases with vexing pancreaticobiliary disorders.

The yield of EUS-FNA in undiagnosed upper abdominal adenopathy is very high.

PURPOSE: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) allows sampling of abdominal adenopathy easily and safely from locations that were previously deemed too risky and inaccessible. The efficacy of EUS-FNA in a large cohort of patients with abdominal adenopathy has not been previously described in the literature. METHODS: We conducted a large retrospective study at a tertiary referral center. Two hundred twenty-five consecutive patients undergoing EUS-FNA for only abdominal adenopathy between 2004 through August 2009 were included in our study. Patient demographics, indications, EUS findings, and final cytologic diagnoses were recorded. RESULTS: A total of 230 lymph nodes were biopsied in 225 patients. Common locations of nodes included peripancreatic (19%), porta hepatis (18%), and celiac axis (18%). Adequate specimens were obtained in 200/230 nodes (87%) and the most common diagnoses based on cytology were: benign/reactive (50%), adenocarcinoma (20%), lymphoma (8%). The sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy were 71%, 99%, 99%, 78%, and 85%, respectively, for EUS-FNA. Based on EUS imaging alone, malignant nodes were more likely to be larger in diameter (17 mm versus 26 mm, p < 0.001), have a round shape (p = 0.002), well-defined borders (p = 0.04), and hypoechic echotexture (p < 0.001). CONCLUSIONS: EUS-FNA allows for excellent tissue acquisition in abdominal lymphadenopathy. Our study supports the use of traditional EUS imaging criteria to identify suspected malignant adenopathy. The results from our large cohort of patients show that EUS-FNA should be considered as a first-line diagnostic modality for ascertaining the etiology of abdominal lymphadenopathy.

Which patients with dilated common bile and/or pancreatic ducts have positive findings on EUS?

BACKGROUND: Patients with dilated common bile duct (CBD) (>7mm) and/or pancreatic duct (PD) on abdominal imaging are often referred for endoscopic ultrasound (EUS). In many cases, the EUS shows no obvious etiology for the dilated ducts. OBJECTIVE: Find clinical factors that may predict which patients are more likely to have positive findings on EUS to explain the etiologies for the dilated ducts. DESIGN: Retrospective database analysis. SETTING: Tertiary-care university hospital. PATIENTS: Patients referred for EUS for dilated CBD and/or PD from January 2004 to February 2010 were included in this study. Only patients without an obvious etiology for the dilated ducts on abdominal imaging were included. INTERVENTIONS: An EUS was performed by using either a radial echoendoscope or a linear endoscope to evaluate the common bile duct and/or the pancreatic duct. When appropriate fine needle aspiration of the mass or cyst was performed. MAIN OUTCOME MEASUREMENTS: The characteristics of patients who had positive findings on EUS to explain the etiology of their dilated PD and/or CBD. RESULTS: A total of 140 patients were included in the study with a mean age of 64 years, 51 (36%) male and 115 (82%) white. The majority of our patients had a presenting symptom of abdominal pain 105 (75%). 49 (36%) had elevated AST or ALT, 25 (8%) had an elevated bilirubin and 13 (23%) had an elevated lipase. EUS findings explained the dilated ducts in 54 (39%) of our patients, most common diagnoses included: CBD stone in 11 (8%), non-calcific chronic pancreatitis in 9 (6%), pancreatic mass in 8 (6%), IPMN in 7 (5%). On bivarate analysis patients who were older (p = 0.006), male (p = 0.001), had elevated LFTs (p = <0.001), had elevated lipase (p = 0.021) or had dilated CBD and PD (p = 0.007) were more likely to have an etiology for their dilated duct(s) discovered on EUS. LIMITATIONS: A retrospective study with a small number of patients. CONCLUSION: Older patients, males and those patients presenting with concurrent elevations in the AST/ALT and/or lipase were more likely to have an underlying etiology discovered on EUS. Furthermore, EUS may detect an undiagnosed pancreatic malignancy in patients presenting with unexplained duct dilation.

Intra-operative MRI-assisted spinal localization.

BACKGROUND: Level localization in the thoracic spine can be problematic. We describe a new method that can be used in difficult cases, e.g., ones where lesions are mid-thoracic, small, or only visible on MRI. METHODS: Intra-operatively, a midline incision was made and the thoracic spinous processes were exposed. A length of contrast-filled tubing was wound around the processes and the incision was temporarily closed and the patient was transferred to the radiology department for MRI under general anesthetic. Upon return to theatre, the cross sections of contrast-filled tubing and the lesion itself were visible on the MRI scan, allowing localization of the level. FINDINGS: This method was accurate and minimized the extent of bone removal required for access. CONCLUSIONS: This technique, while not appropriate in every case, is repeatable, and does not require specialized equipment or training. It is an extremely accurate method of localization for difficult cases.

A role for nucleoprotein Zap3 in the reduction of telomerase activity during embryonic stem cell differentiation.

Telomerase, the enzyme which maintains the ends of linear chromosomes in eukaryotic cells is found in murine embryonic stem cells; however, its activity is downregulated during in vitro differentiation. Previous work has indicated that this is due to the transcriptional downregulation of murine reverse transcriptase unit (mTert) of telomerase. To investigate the factors that cause the transcriptional repression of mTert we defined a 300 bp region which is essential for its transcription and performed site directed mutagenesis and electrophoretic mobility shift assays. This analysis indicated that Sp1, Sp3 and c-Myc bind to the GC-boxes and E-boxes, respectively, within the promoter and help activate the transcription of mTert gene. We also identified a novel binding sequence, found repeated within the mTert core region, which when mutated caused increased mTert expression. Yeast one hybrid screening combined with electrophoretic mobility shift assays indicated that the nuclear protein Zap3 binds to this site and its overexpression leads to the downregulation of mTert during differentiation. This suggests that regulation of mTert transcription is a complex process which depends on a quantitative balance between transcription factors that cause activation or repression of this gene. Overexpression of Zap3 in murine embryonic stem cells results in reduction in telomerase activity and telomere length as well as reduced proliferative capacity and limited ability to contribute to the development of haematopoietic cells upon differentiation.

Derivation of human embryonic stem cells from day-8 blastocysts recovered after three-step in vitro culture.

Human embryonic stem cells (hESCs) have been derived from the inner cell mass (ICM) of day 5-7 blastocysts and hold great promise for research into human developmental biology and the development of cell therapies for the treatment of human diseases. We report here that our novel three-step culture conditions successfully support the development of day-8 human blastocysts, which possess significantly (p <.01) more ICM cells than day-6 blastocysts. Plating of ICMs isolated from day-8 blastocysts resulted in the formation of a colony with hESC morphology from which a new hESC line (hES-NCL1) was derived. Our stem cell line is characterized by the expression of specific cell surface and gene markers: GTCM-2, TG343, TRA1-60, SSEA-4, alkaline phosphatase, OCT-4, NANOG, and REX-1. Cytogenetic analysis of the hESCs revealed that hES-NCL1 line has a normal female (46, XX) karyotype. The pluripotency of the cell line was confirmed by the formation of teratomas after injection into severely combined immunodeficient mice and spontaneous differentiation under in vitro conditions.