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We investigated the anti-angiogenic effects of the water extract of HangAmDan (WEHAD), which is a crude extract of nine Korean medicinal substances of animal and plant origin. In human umbilical vein endothelial cells, WEHAD significantly inhibited bFGF-induced proliferation, adhesion, migration, and capillary tube formation. We used an antibody array to perform an analysis of signaling proteins, which showed up-regulated expression of various proteins including RAD51, RAD52, and p73, and down-regulated expression of pFAK. Blood vessel formation in a chick chorioallantoic membrane (CAM) treated with WEHAD was markedly reduced in length compared with a PBS-treated control group. These results suggest that inhibition of angiogenesis by WEHAD may be the mechanism of action for the anti-cancer effects of HAD.

Pharmacological agents that are safe and can sensitize the lung cancer are urgently required. We investigated whether Atractylenolide III (ATL-III), the major component of Atractylodes rhizome can induce apoptosis of the lung carcinoma cells. ATL-III inhibited cell growth, increased lactate dehydrogenase release and modulated cell cycle on human lung carcinoma A549 cells. ALT-III induced the activation of caspase-3 and caspase-9 and cleavage of poly-(ADP)-ribose polymerase. ATL-III induced the release of cytochrome c, upregulation of bax expression, and translocation of apoptosis-inducing factor. In addition, ATL-III inhibited the proliferation and capillary tube formation of human umbilical vein endothelial cells. These data indicate that ATL-III is a potential candidate for treatment of human lung carcinoma.

Background & Aims Outcomes of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) evaluation vary with technique, needles, and methods of specimen evaluation. We performed a direct comparison of diagnostic yields of EUS-FNA samples collected using different gauge needles (22- vs 25-gauge), with or without suction. Methods We performed a randomized controlled study of 352 patients with suspected pancreatic masses, referred for EUS-FNA at a tertiary referral center. Patients were randomly assigned to 22-gauge needles with or without suction or 25-gauge needles with or without suction. Specimens were evaluated offsite by cell block and rapid onsite cytologic evaluation (ROSE). Final diagnoses were made based on histologic analyses or 12-month follow-up evaluations. The primary outcome was diagnostic adequacy of cell blocks. Secondary outcomes were operating characteristics of ROSE and EUS-FNA, number of passes required for accurate onsite diagnosis, and amount of blood in specimens. Results The final diagnoses were malignancy (81.5% of patients) and benign disease (17.0% of patients); 1.4% of patients were lost during follow up. Cell block, ROSE, and EUS-FNA led to diagnostic accuracies of 71.9%, 95.5%, and 96.6%, respectively. A 22-gauge needle with suction was associated with more passes for adequate onsite diagnosis (P = .003) and specimens contained more blood (P = .01). Diagnostic accuracy of specimens collected by transduodenal EUS-FNA was lower with 22-gauge needles with suction compared to other techniques (P = .004). Conclusion In a randomized trial of patients undergoing EUS-FNA for pancreatic masses, samples collected with 22-gauge vs 25-gauge needles performed equally well for offsite specimen evaluation. Use of suction appears to increase number of passes needed and specimen bloodiness. Specimen collection techniques should be individualized based on method of evaluation. ClinicalTrials.gov no: NCT02424838 .

The inhibitory effects of the water extract of HangAmDan-B(WEHAD-B), which is a crude extract of eight Korean medicinal animals and plants on bFGF-induced neovascularization were investigated. WEHAD-B significantly prevented bFGF-induced HUVE cell proliferation, adhesion, migration, and capillary-like tubular network formation. Half-maximal inhibition of proliferation on the endothelial cells by WEHAD-B was observed at a concentration of approximately 250 μg/mL. Our antibody microarray-based ProteoChip data showed that WEHAD-B increased the expression of STAT1 and Rb2, which are involved in cell growth, apoptosis, and controlling the cell cycle in bFGF-induced HUVECs. These results indicate that the inhibition of bFGF-induced angiogenesis by WEHAD-B may be due to upregulation of cell signaling proteins, STAT1 and Rb2. The blood vessel formation in a chick chorioallantoic membrane (CAM) treated with WEHAD-B was markedly reduced in length compared with a PBS-treated control group. Taken together, these data suggest that antibody-arrayed ProteoChip technology may be an useful tool for determining molecular mechanism of natural products in biological samples.

As an extension of our previous studies on the mitochondrial citrate synthase of Aspergillus nidulans and cloning of its coding gene (citA), we analyzed differential expression of citA in response to the progress of development and change of carbon source. The cDNA consisted of 1,700 nucleotides and was predicted to encode a 474-amino acid protein. By comparing the cDNA sequence with the corresponding genomic sequence, we confirmed that citA gene contains 7 introns and that its transcription starts at position -26 (26-nucleotide upstream from the initiation codon). Four putative CreA binding motifs and three putative stress-response elements (STREs) were found within the 1.45-kb citA promoter region. The mode of citA expression was examined by both Northern blot and confocal microscopy using green fluorescent protein (sGFP) as a vital reporter. During vegetative growth and asexual development, the expression of citA was ubiquitous throughout the whole fungal body including mycelia and conidiophores. During sexual development, the expression of citA was quite strong in cleistothecial shells, but significantly weak in the content of cleistothecia including ascospores. Acetate showed a strong inductive effect on citA expression, which is subjected to carbon catabolite repression (CCR) caused by glucose. The recombinant fusion protein CitA(40)::sGFP (sGFP containing the 40-amino acid N-terminal segment of CitA) was localized into mitochondria, which supports that a mitochondrial targeting signal is included within the 40-amino acid N-terminal segment of CitA.

Background and aim Endoscopic ultrasound (EUS) is considered the most sensitive modality for local staging of esophageal cancer (ECA) and current guidelines recommend EUS in all patients with non-metastatic disease. Our aim was to identify a subset of patients with stenotic, non-metastatic ECA who will not benefit from staging EUS. Methods This multicenter study evaluated consecutive patients with newly diagnosed non-metastatic ECA referred for local staging by EUS. All patients had endoscopic evaluation of malignant strictures with 9.8/9.9-mm diagnostic gastroscope prior to EUS. Main outcome measure was to evaluate the relationship between degree of malignant stenosis and tumor staging by EUS. Results Of 100 patients (median age, 65 years; male 81%), gastroscope could not be advanced past the stricture in 46, all of whom (100%) had locally advanced disease at EUS: T3N0/N+ in 39 and T4N0/N+ in seven. Echoendoscope could not traverse the stricture in any of these patients. Gastroscope could be advanced through the stricture in 54 patients in whom EUS staging was T1N0 in five, T2N0/N+ in eight and T3N0/N+ in 41; echoendoscope could not pass through the stricture in 24 of these 54 (44.4%) patients, all of whom had T3N0/N+ disease. On logistic regression analysis, inability to pass a gastroscope through the stricture was significantly associated with advanced (T3/4) tumor stage (OR = 28.7, 95% CI = 1.64-501.2; P = 0.021). Conclusion Routine EUS examination may not be required in all patients with ECA as the inability to advance a diagnostic gastroscope past a malignant stricture correlates 100% with locally advanced disease on EUS.

Background and study aims: To overcome the limitations associated with cytology, a uniquely designed needle (ProCore) was introduced in an effort to obtain a core of tissue under endoscopic ultrasound (EUS) guidance. However, studies comparing the sample quality between ProCore and standard-design fine-needle aspiration (FNA) needles have yielded varying results. A systematic review and meta-analysis was therefore conducted to compare the performance of the ProCore and standard FNA needles when performing EUS-guided tissue acquisition. Patients and methods: MEDLINE and EMBASE were searched to identify all published manuscripts that compared the ProCore needle with standard FNA needles. Noncomparative and technical feasibility studies were excluded. The main outcome measures were diagnostic adequacy, diagnostic accuracy, acquisition of histological core tissue, and mean number of passes required to achieve a diagnosis when sampling solid lesions. Results: Nine studies (total 576 patients) met the inclusion criteria. There was no significant difference in diagnostic adequacy (75.2 % vs. 89.0 %, odds ratio [OR] 0.39, P = 0.23), diagnostic accuracy (85.8 % vs. 86.2 %, OR 0.88, P = 0.53) or rate of histological core specimen acquisition (77.7 % vs. 76.5 %, OR 0.94, P = 0.85) between the ProCore and standard FNA needles, respectively. The mean number of passes required for diagnosis, however, was significantly lower when using the ProCore needle (standardized mean difference – 1.2, P Conclusions: Current data do not demonstrate a significant difference between the ProCore and standard FNA needles for sample adequacy, diagnostic accuracy or acquisition of a core specimen. However, the ProCore needle establishes the diagnosis with fewer passes.

An asymptomatic 72-year-old woman underwent EUS-guided FNA of an incidental side-branch intraductal papillary mucinous neoplasm (SB-IPMN) in the head of the pancreas at an outside facility. Forty-eight hours after the procedure, she presented to our institution with severe epigastric pain, fever, jaundice, leukocytosis, and elevated lipase consistent with acute pancreatitis. CT of the abdomen andpelvis with contrast medium showed multiple peripancreatic fluid collections (PFC) around the pancreatic head. EUS showed a large PFC in the head region compressing the distal common bile duct (Fig. 1) and a pancreatic duct leak in the neck region. Because the PFC was causing obstructive jaundice, it was aspirated, revealing hemorrhagic fluid. ERCP was then performed to evaluate the pancreatic duct. A leak from a side branch in the head region was demonstrated on pancreatogram, which was bridged with a 4F 10-cm stent (Video 1, available online at www.giejournal.org). The patient also underwent jejunal feeding for 4 weeks through a nasojejunal tube, with resultant clinical improvement and resolution of the PFC on follow-up CT at 30 days. The risk of acute pancreatitis after EUS-FNA of pancreatic lesions is highest with SB-IPMN at 8%. Despite the lack of data, the use of indomethacin before EUS-FNA for pancreatitis prophylaxis can be considered in high-risk patients.

Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is an indispensable tool for tissue acquisition. The National Comprehensive Cancer Network has incorporated EUS-FNA cytology in its diagnostic algorithm for pancreatic cancer 1. EUS-FNA is a multi-step procedure involving not only best practices in technique but also in specimen collection and processing; thus, rapid on-site evaluation (ROSE), needle selection, and sampling technique determine the outcomes of EUS-FNA diagnosis of pancreatic cancer. The availability of on-site cytopathology services increases diagnostic accuracy and decreases the number of suboptimal specimens such that the non-diagnostic rate has been reported to be as low as 1 % for FNAs with ROSE, whereas it is 20 % without ROSE 2 3. However, ROSE is not available at many centers because of the time needed, cost, and inadequate financial reimbursement. Hence, most centers depend on off-site laboratory interpretation of FNA specimens. In this issue of the journal, Schneider and colleagues from Germany report on 63 patients who underwent EUS-FNA of pancreatic lesions in two phases: In phase I, the in-house pathology laboratory evaluated the FNA aspirates, and in phase II, a specialized outside cytology laboratory evaluated them 4. The diagnostic sensitivity in phase II improved to 91.4 % from 38.5 % found in phase I, which emphasizes the importance of specialized diagnostic services in evaluating FNA specimens. In a retrospective study of 876 EUS-FNA specimens obtained from a tertiary referral center, the overall cumulative sum charts for both the non-diagnostic error rate and diagnostic error rate showed a short learning period and improved to an acceptable level at case numbers 121 and 97, respectively 5. These findings suggest that like the practice of EUS-FNA where diagnosis improves with the endosonographer’s experience 6, the accuracy of specimen interpretation improves with the cytopathologist’s experience. Therefore, high-volume centers practicing EUS-FNA must implement ROSE or the services of an off-site cytopathology laboratory to obtain the best diagnostic outcomes. In addition to specimen interpretation as performed by cytopathologists, the endosonographers must be familiar with the techniques for handling and processing tissues to optimize specimens sent for off-site evaluation. Assigning one person to handle the aspirated materials establishes a protocol for consistent sample preparation and minimizes artifacts resulting from improper tissue handling and collection. Although most endosonographers do not routinely practice in-room cytomorphological analysis, it has been shown that microscopic evaluation of smears by endosonographers without access to ROSE improves diagnostic accuracy 7. In a recent study, we showed that a short, intensive EUS cytopathology course for endosonographers provided effective training in cytopathological interpretation 8. In our opinion, consideration must be given to incorporating basic cytopathology during an EUS fellowship to improve the endosonographer’s performance of FNA procedures. There are several technical issues that are critical to improving the results of EUS-FNA of pancreatic lesions. These include needle selection, FNA technique, use of suction or stylet, and the number of passes. Most masses in the pancreas originate in the head region and require transduodenal sampling. This mandates the need for a flexible, thin caliber needle that can easily exit the biopsy channel of the echoendoscope; that is, a needle with an angled tip used during sampling of head and uncinate masses. Limited evidence suggests that a 25G needle is suitable for sampling pancreatic masses. A recent meta-analysis compared the 22G and 25G needles for EUS-FNA of pancreatic masses and found that use of the 25G needle yielded a higher diagnostic sensitivity than the 22G needle 9. However, if the endosonographer must rely on only the cell block for off-site diagnosis, the 25G needle may not be optimal. In a recent randomized trial, we demonstrated that the 25G needle yielded a diagnostic cell block in only 80.5 % of patients irrespective of the number of FNA passes performed 10. Therefore, in most centers in Europe and Asia, where ROSE is not available, the 22G needle is used in conjunction with suction for better tissue procurement. There has been growing interest in the use of core biopsy needles for histological tissue procurement when sampling pancreatic masses. However, in a recent meta-analysis, it was evident that the performance of the ProCore biopsy needle was not superior to the performance of the standard FNA needle either for cytological or histological assessment 11. Although many techniques have been suggested for tissue procurement, our recommendation is to keep the procedure simple! We recommend fanning the needle when sampling a mass. This ensures not only the procurement of good quality tissue that is representative of the lesion (minimizing sampling error) but also allows diagnosis with fewer passes 12. In addition, we do not recommend the routine use of suction during EUS-FNA because it increases the amount of blood in the specimen. Suction may be used when sampling a mass in the setting of chronic pancreatitis when tissue yield can be minimal, and there is a growing body of evidence that suction may augment the performance of the 25G needle. In a randomized trial comparing high negative pressure suction (50 mL negative pressure) with normal negative pressure suction (10 mL negative pressure) for EUS-FNA of pancreatic masses using the 25G needle, a higher proportion of diagnostically adequate samples were obtained using high negative pressure suction (90.0 % vs 72.2 %, P = 0.003) 13. We do not recommend the routine use of a stylet during EUS-FNA because it prolongs the procedure, increases the amount of blood in the specimen, and does not improve the accuracy of the diagnosis. Finally, when sampling pancreatic masses, one reaches a point of “diminishing returns” after seven passes 14. The most common reason for non-diagnostic interpretation is inadequate sampling and, hence, a sufficient number of passes must be performed to yield an adequate sample. Therefore, our recommendations to endosonographers for superior outcomes during EUS-FNA of the pancreas include: 1) use of a 25G needle, 2) use of a 19/22G needle if the diagnosis is to be established only by cell block or when ROSE is not available, 3) use of the fanning technique, 4) avoidance of the routine use of suction and stylet, 5) procuring an adequate quantity of the specimen, 6) learning to self-assess for diagnostic adequacy of FNA specimens if ROSE is not available, and 7) hiring the services of an expert cytopathologist who can provide off-site interpretations. EUS-FNA is an art — just keep it simple! Abbreviations EUS endoscopic ultrasound FNA fine needle aspiration ROSE rapid on-site evaluation

Despite advances in cross-sectional imaging and a deeper understanding of the genetic and epigenetic factors associated with acute pancreatitis (AP), up to 20 % of cases remain idiopathic. Of these, many patients are at risk of having multiple episodes and progressing to chronic pancreatitis. Classically, AP is idiopathic when no etiology is identified after a negative history, physical, basic laboratories, and cross-sectional imaging. Improvements in less invasive pancreatic imaging, an evolving understanding of autoimmune pancreatitis, and better genetic tests have impacted the threshold after which endoscopic retrograde cholangiopancreatography (ERCP) should be utilized in the diagnostic work up of unexplained AP. Furthermore, the role of ERCP as a therapeutic modality remains unclear. In this chapter, we will discuss the diagnostic yield and therapeutic impact of ERCP in the management of idiopathic AP and sphincter of Oddi dysfunction (SOD).

Background and Aim Metal stents are being used more frequently for transmural endoscopic drainage of pancreatic fluid collections (PFC) despite lack of data. The present systematic review was conducted to compare the rates of treatment success, adverse events and recurrence between patients undergoing metal versus plastic stent placement for endoscopic transmural drainage of PFC. Methods MEDLINE and EMBASE were searched to identify all published manuscripts that evaluated metal stents for endoscopic transmural drainage of PFC. All published studies from the same period involving plastic stent placement for PFC drainage that included >50 patients were also identified. Main outcome measures were to compare the rates of treatment success, adverse events and recurrence between the metal and plastic stent cohorts. Results Seventeen studies (881 patients) met inclusion criteria. There was no difference in overall treatment success between patients treated with plastic and metal stents (81% [95% CI, 77–84%] vs 82% [95% CI, 74–88%]) for both pseudocysts (85% [95% CI, 81–89%] vs 83% [95% CI, 74–89%]) and walled-off necrosis (70% [95% CI, 62–76%] vs 78% [95% CI, 50–93%]). Also, there was no difference in the rates of adverse events (16% [95% CI, 14–39%] vs 23% [95% CI, 16–33%]) or recurrence (10% [95% CI, 8–13%] vs 9% [95% CI, 4–19%]) between plastic and metal stents. Conclusions Current evidence does not support routine placement of metal stents for transmural drainage of PFC. Randomized trials are needed to justify the use of metal stents for PFC drainage.

Background The aim of the study was to compare the outcomes of patients with pancreatic or peripancreatic walled-off necrosis by endoscopy using the conventional approach versus an algorithmic approach based on the collection size, location and stepwise response to intervention. Methods This was an observational before–after study of consecutive patients managed over two time intervals. In the initial period (2004–2009) symptomatic patients with walled-off necrosis underwent conventional single transmural drainage with placement of two stents and a nasocystic catheter, followed by direct endoscopic necrosectomy, if required. In the later period (2010–2013) an algorithmic approach was adopted based on size and extent of the walled-off necrosis and stepwise response to intervention. The main outcome was treatment success, defined as a reduction in walled-off necrosis size to 2 cm or less on CT after 8 weeks. Results Forty-seven patients were treated in the first interval and 53 in the second. There was no difference in patient demographics, clinical or walled-off necrosis characteristics and laboratory parameters between the groups, apart from a higher proportion of women and Caucasians in the later period. The treatment success rate was higher for the algorithmic approach compared with conventional treatment (91 versus 60 per cent respectively; P < 0·001). On multivariable logistic regression, management based on the algorithm was the only predictor of treatment success (odds ratio 6·51, 95 per cent c.i. 2·19 to 19·37; P = 0·001). Conclusion An algorithmic approach to pancreatic and peripancreatic walled-off necrosis, based on the collection size, location and stepwise response to intervention, resulted in an improved rate of treatment success compared with conventional endoscopic management.

To compare the interpretation of probe-based confocal laser endomicroscopy (pCLE) findings between endoscopists and gastrointestinal (GI)-pathologists.All pCLE procedures were undertaken and the endoscopist rendered assessment. The same pCLE videos were then viewed offline by an expert GI pathologist. Histopathology was considered the gold standard for definitive diagnosis. The sensitivity, specificity and accuracy for diagnosis of dysplastic/ neoplastic GI lesions and interobserver agreement between endoscopists and experienced gastrointestinal pathologist for pCLE findings were analyzed.Of the 66 included patients, 40 (60.6%) had lesions in the esophagus, 7 (10.6%) in the stomach, 15 (22.7%) in the biliary tract, 3 (4.5%) in the ampulla and 1 (1.5%) in the colon. The overall sensitivity, specificity and accuracy for diagnosing dysplastic/neoplastic lesions using pCLE were higher for endoscopists than pathologist at 87.0% vs 69.6%, 80.0% vs 40.0% and 84.8% vs 60.6% (P = 0.0003), respectively. Area under the ROC curve (AUC) was greater for endoscopists than the pathologist (0.83 vs 0.55, P = 0.0001). Overall agreement between endoscopists and pathologist was moderate for all GI lesions (K = 0.43; 95%CI: 0.26-0.61), luminal lesions (K = 0.40; 95%CI: 0.20-0.60) and those of dysplastic/neoplastic pathology (K = 0.55; 95%CI: 0.37-0.72), the agreement was poor for benign (K = 0.13; 95%CI: -0.097-0.36) and pancreaticobiliary lesions (K = 0.19; 95%CI: -0.26-0.63).There is a wide discrepancy in the interpretation of pCLE findings between endoscopists and pathologist, particularly for benign and malignant pancreaticobiliary lesions. Further studies are needed to identify the cause of this poor agreement.

Transmural stents are placed at endoscopy to drain pancreatic fluid collections. This study evaluated the relationship between stent placement and treatment outcomes in patients undergoing endoscopic transmural drainage of uncomplicated pancreatic pseudocysts. This is a retrospective study of all patients who underwent endoscopic drainage of uncomplicated pancreatic pseudocysts over a 10-year period. After dilating the transmural tracts in the range of 8–15 mm, single or multiple, 7 or 10Fr double-pigtail plastic stents were deployed. The main outcome measure was to evaluate the relationship between stent characteristics and the number of endoscopic interventions required to achieve resolution of the pancreatic pseudocyst (treatment success). Of 122 patients, 45 (36.9 %) had 10Fr stents of which 30 patients (66.7 %) had more than one stent; the remaining 77 (63.1 %) patients had 7Fr stents of which 56 (72.7 %) had more than one stent. The overall treatment success was 94.3 %. Treatment was successful in 102 patients (83.6 %) with one intervention; 13 patients (10.7 %) required re-intervention for successful drainage and 7 patients (5.7 %) failed endoscopic treatment. There was no significant difference in the number of interventions required for treatment success between patients with 7 or 10Fr stents (one intervention required in 87.7 vs. 90.5 %, respectively; p = 0.766) and between patients with 1 or >1 stent (one intervention required in 88.9 vs. 88.6 %, respectively; p = 0.999). On multiple logistic regression analysis, the stent size (OR 1.54; 95 % CI 0.23–10.4) and number (OR 1.15; 95 % CI 0.25–5.25) were not associated with the number of interventions required for treatment success when adjusted for pseudocyst size, location, drainage modality, the presence or absence of pancreatic duct stent and luminal compression. There appears to be no relationship between the number of interventions required for treatment success and stent characteristics in patients undergoing endoscopic transmural drainage of uncomplicated pancreatic pseudocysts.

Background Despite an increasing number of procedures being performed, there is no consensus on an optimal approach to EUS-guided FNA (EUS-FNA) or interventions. Objective Validate an algorithmic approach to EUS-FNA/interventions with the objective of improving technical outcomes and resource use. Design Prospective study. Setting Tertiary-care referral center. Patients Consecutive patients undergoing EUS-FNA and/or interventions. Intervention Phase I was a retrospective analysis of EUS-FNA/interventions performed in 548 patients. The 19-gauge needle was used for interventions, and the 22- or 25–gauge needle was used interchangeably for performing FNAs. At phase I, the technical failure rate was 11.5%. Based on these observations, an algorithm was proposed by which all transduodenal FNAs were performed by using a 25-gauge needle and other FNAs with a 22-gauge needle. All transduodenal interventions were performed with a Flexible 19-gauge needle and others with a standard 19-gauge needle. This algorithm was tested prospectively in phase II on 500 patients. Main Outcome Measurements Compare technical failure, diagnostic adequacy, procedural complications, and average needle costs between both phases. Results The technical failure rate was significantly less in phase II compared with that of phase I (1.6% vs 11.5%; P P P = .001). Although there was no difference in diagnostic adequacy (97.1% vs 98.4%; P = .191) or complications (0.4% vs 0.2%; P = 1.0) between phases I and II, the average cost per case was significantly less in phase II ($199.59 vs $188.30; P = .008). Limitations Single-center study. Conclusion An algorithmic approach to EUS-FNA/interventions yielded better technical outcomes and cost savings without compromising diagnostic adequacy.

Background and Aims Although EUS-guided celiac plexus neurolysis (EUS-CPN) is performed frequently for palliation of pain in pancreatic cancer, response to treatment is variable. Although intraprocedural increases in heart rate during alcohol injection are observed frequently, their significance and relationship to treatment outcome are unknown. The objective of this study was to examine whether a correlation exists between an increase in heart rate and treatment outcomes in patients undergoing EUS-CPN for pain relief in pancreatic cancer. Methods This is a prospective observational study of patients with abdominal pain caused by inoperable pancreatic cancer who underwent EUS-CPN. Heart rate change was defined as an increase of ≥15 beats per minute (bpm) for ≥30 seconds during alcohol injection. Main outcome measures were to compare pain, quality of life, opioid use, and survival between heart rate change and no-change groups. Results Heart rate change was observed in 25 of 51 patients (49.0%) who underwent EUS-CPN over a 12-month period. Although the heart rate change cohort had significantly better adjusted scores for pain (60 vs 73; P = .042) and components of quality of life such as nausea and/or vomiting (65 vs 81; P = .004), financial difficulties (41 vs 57; P = .02), weight loss (45 vs 65; P = .007), and satisfaction with body image (52 vs 62; P = .035), there was no significant difference in postprocedural opioid use or survival between groups. Conclusions Because patients with an increase in intraprocedural heart rate experienced significant improvement in pain and quality of life components, this observation must be further explored in order to improve the technique and outcomes of EUS-CPN.

Management of Hemorrhagic Walled-Off Necrosis Using the Multiple Transluminal Gateway Technique

Transrectal endoscopic ultrasound (EUS)-guided pelvic abscess drainage has been reported, but data on transcolonic drainage are scant.To compare outcomes in patients undergoing transcolonic and transrectal drainage of abdominopelvic abscesses.Retrospective study of all patients who underwent EUS-guided drainage of abdominopelvic abscesses over a 7-year period. Abscesses were drained by a standard single-step EUS-guided technique with deployment of double-pigtail stents ± catheters. Technical success was defined as successful placement of stents or drainage catheters within the abscess cavity. Treatment success was defined as resolution of abscess on follow-up computed tomography at 2 weeks with symptom improvement.Of 38 patients, 11 underwent transcolonic and 27 transrectal drainages. There was no difference in patient demographics, laboratory values, and median abscess size (65 vs 70 mm, P = 0.85) between the two cohorts. Etiology of abscess was postsurgical in 65.7%, diverticulitis in 13.1%, perforated viscus in 10.5%, and other causes in 10.5%. There was no difference in rates of technical success (100% in each cohort), treatment success (70% vs 96.3%, P = 0.052), or complications (none). Three patients in the transcolonic and one in the transrectal cohort underwent surgery for failed endoscopic drainage (27.3% vs 3.7%, P = 0.06). When evaluated by etiology, treatment success for diverticular abscess was significantly lower compared with others (25% vs 97%, P = 0.002). At a median follow-up of 1228.5 days (interquartile range = 131-1660), all patients with treatment success were doing well with no recurrence.Except for patients with diverticular etiology, treatment of abdominopelvic abscess under EUS guidance is highly effective and safe for both routes.

Gastrointestinal bleeding in individuals with Turner syndrome is relatively rare and there have been only a handful of reported cases in the literature. Here, we present two patients with Turner syndrome who were evaluated for obscure gastrointestinal bleeding. Our first patient presented with iron deficiency anemia and the work-up for a possible gastrointestinal bleed was pertinent only for polyps and a non-bleeding vein in the colon seen on colonoscopy. Our second patient had a history of unexplained recurrent melena and iron deficiency anemia, with previously normal esophagogastroduodenoscopies, colonoscopies and a Meckel's diverticulum scan. Both patients were subsequently diagnosed with gastrointestinal vascular malformations via capsule endoscopy.

Background To overcome limitations of cytology, biopsy needles have been developed to procure histologic samples during EUS. Objective To compare 22-gauge (G) FNA and 22G biopsy needles (FNB) for EUS-guided sampling of solid pancreatic masses. Design Randomized trial. Setting Tertiary-care medical center. Patients This study involved 56 patients with solid pancreatic masses. Intervention Sampling of pancreatic masses by using 22G FNA or 22G FNB devices. Main Outcome Measurements Compare the median number of passes required to establish the diagnosis, diagnostic sufficiency, technical performance, complication rates, procurement of the histologic core, and quality of the histologic specimen. Results A total of 28 patients were randomized to the FNA group and 28 to the FNB group. There was no significant difference in median number of passes required to establish the diagnosis (1 [interquartile range 1-2.5] vs 1 [interquartile range 1-1]; P = .21), rates of diagnostic sufficiency (100% vs 89.3%; P = .24), technical failure (0 vs 3.6%; P = 1.0), or complications (3.6% for both) between FNA and FNB needles, respectively. Patients in whom diagnosis was established in passes 1, 2, and 3 were 64.3% versus 67.9%, 10.7% versus 17.9%, and 25% versus 3.6%, respectively, for FNA and FNB cohorts. There was no significant difference in procurement of the histologic core (100% vs 83.3%; P = .26) or the presence of diagnostic histologic specimens (66.7% vs 80%; P = .66) between FNA and FNB cohorts, respectively. Limitations Only pancreatic masses were evaluated. Conclusion Diagnostic sufficiency, technical performance, and safety profiles of FNA and FNB needles are comparable. There was no significant difference in yield or quality of the histologic core between the 2 needle types. (Clinical trial registration number: NCT01394159.)

Although endoscopic retrograde cholangiopancreatography (ERCP) is a well-established technique for both the diagnosis and treatment of biliary and pancreatic disorders in adults, indications for some pediatric applications, such as idiopathic and recurrent pancreatitis, remain contentious. This NewsViews article discusses a recent study that evaluated the technical outcomes and safety of 231 ERCPs in children.

Integrin alpha5beta1 immobilized on a ProteoChip was used to screen new antagonistic peptides from multiple hexapeptide sub-libraries of the positional scanning synthetic peptide combinatorial library (PS-SPCL). The integrin alpha5beta1-Fibronectin interaction was demonstrated on the chip. A novel peptide ligand, A5-1 (VILVLF), with high affinity to integrin alpha5beta1 was identified from the hexapeptide libraries with this chip-based screening method on the basis of a competitive inhibition assay. A5-1 inhibits the integrin-fibronectin interaction in a dose-dependent manner (IC(50); 1.56+/-0.28 microM. In addition, it inhibits human umbilical vein endothelial cell proliferation, migration, adhesion, tubular network formation, and bFGF-induced neovascularization in a chick chorioallantoic membrane. These results suggest that A5-1 will be a potent inhibitor of neovascularization.

Integrins consist of transmembrane glycoproteins noncovalently associated to form alphabeta heterodimers. Various alpha/beta associations determine binding specieficities for cell surface molecules of the immunoglobulin superfamily as well as for extracellular matrix components. Through their cytoplasmic domains, integrins are responsible for the transmission of signals between the intracellular and the extracellular environment. We immobilized an integrin alpha5beta1 microarray on a ProteoChip to screen Korean medicinal plant extracts for binding activity. The microarray preserved the integrin alpha5beta1-fibronectin interaction, and was suppressed by the synthetic RGD peptide. We identified ten extracts with high integrin affinity using a high-throughput, competitive inhibition assay. We also demonstrate the biological function of these extracts in HUVECs.