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Whole-genome and whole-exome sequencing of individual patients allow the study of rare and potentially causative genetic variation. In this study, we sequenced DNA of a trio comprising a boy with very-early-onset inflammatory bowel disease (veoIBD) and his unaffected parents. We identified a rare, X-linked missense variant in the NAPDH oxidase NOX1 gene (c.C721T, p.R241C) in heterozygous state in the mother and in hemizygous state in the patient. We discovered that, in addition, the patient was homozygous for a common missense variant in the CYBA gene (c.T214C, p.Y72H). CYBA encodes the p22phox protein, a cofactor for NOX1. Functional assays revealed reduced cellular ROS generation and antibacterial capacity of NOX1 and p22phox variants in intestinal epithelial cells. Moreover, the identified NADPH oxidase complex variants affected NOD2-mediated immune responses, and p22phox was identified as a novel NOD2 interactor. In conclusion, we detected missense variants in a veoIBD patient that disrupt the host response to bacterial challenges and reduce protective innate immune signaling via NOD2. We assume that the patient's individual genetic makeup favored disturbed intestinal mucosal barrier function.

Background & Aims Confocal laser endomicroscopy (CLE) is a technique that permits real-time detection and quantification of changes in intestinal tissues and cells, including increases in intraepithelial lymphocytes and fluid extravasation through epithelial leaks. Using CLE analysis of patients with irritable bowel syndrome (IBS), we found that more than half have responses to specific food components. Exclusion of the defined food led to long-term symptom relief. We used the results of CLE to detect reactions to food in a larger patient population and analyzed duodenal biopsy samples and fluid from patients to investigate mechanisms of these reactions. Methods In a prospective study, 155 patients with IBS received 4 challenges with each of 4 common food components via the endoscope, followed by CLE, at a tertiary medical center. Classical food allergies were excluded by negative results from immunoglobulin E serology analysis and skin tests for common food antigens. Duodenal biopsy samples and fluid were collected 2 weeks before and immediately after CLE and were analyzed by histology, immunohistochemistry, reverse transcription polymerase chain reaction, and immunoblots. Results from patients who had a response to food during CLE (CLE+) were compared with results from patients who did not have a reaction during CLE (CLE–) or healthy individuals (controls). Results Of the 108 patients who completed the study, 76 were CLE+ (70%), and 46 of these (61%) reacted to wheat. CLE+ patients had a 4-fold increase in prevalence of atopic disorders compared with controls (P = .001). Numbers of intraepithelial lymphocytes were significantly higher in duodenal biopsy samples from CLE+ vs CLE– patients or controls (P = .001). Expression of claudin-2 increased from crypt to villus tip (P Conclusions In a CLE analysis of patients with IBS, we found that more than 50% of patients could have nonclassical food allergy, with immediate disruption of the intestinal barrier upon exposure to food antigens. Duodenal tissues from patients with responses to food components during CLE had immediate increases in expression of claudin-2 and decreases in occludin. CLE+ patients also had increased eosinophil degranulation, indicating an atypical food allergy characterized by eosinophil activation.

Summary Background Diagnosis of inflammatory bowel disease (IBD) is based on clinical presentation, colonoscopy and histology. Differentiation of Crohn's disease (CD) and ulcerative colitis (UC) can be difficult in some patients. Endoscopic ultrasound (EUS) provides high resolution images of the gastrointestinal wall (GI) and may be an alternative to differentiate CD/UC. Aim EUS of the GI layers in patients with IBD and healthy controls (HC) for the differential diagnosis of UC/CD in a prospective, blinded study. Methods Consecutive patients with CD, UC or HC underwent EUS in the mid sigmoid colon with a forward-viewing radial echoendoscope. Mucosal, submucosal, total wall thickness (TWT) and locoregional lymphnodes (LN) were assessed by EUS in a blinded fashion. TWT was correlated with macroscopic IBD scores and histological inflammation scores. Results Total wall thickness of 61 HC was 1.71 ± 0.02 mm, and 3.51 ± 0.15 mm in n = 52 with active IBD. In patients with active UC significant thickening of the mucosa was observed but nearly normal submucosa and m.propria. In active CD significant thickening of the submucosal layer was seen with nearly normal mucosa and m.propria [MucosaUC = 2.08 ± 0.11 mm, MucosaCD = 1.32 ± 0.17 mm (P = 0.0001); SubmucosaUC = 1.01 ± 0.08 mm, SubmucosaCD = 2.01 ± 0.22 mm (P = 0.0001)]. In 73.7% of patients with active CD, but in none with UC, paracolonic lymph nodes were detected. When mucosal-submucosal and TWT and LNs were combined, the sensitivity was 92.3% for the differentiation of active UC/CD. There was a strong correlation of TWT with histological inflammation scores (UC: r = 0.43; CD: r = 0.69). Conclusions Increased total wall thickness has a high positive predictive value for active IBD. EUS can differentiate active UC from CD and quantify the level of colonic inflammation.

Background and study aims: Radiofrequency ablation (RFA) is an accepted method of tissue destruction for solid organ tumors. Endoscopic ultrasound (EUS)-guided RFA has been used for lesions in the pancreas and liver, but there is limited experience of lymph node ablation using EUS-guided RFA. The aim of this study was to determine feasibility and safety of prototype EUS-guided RFA of mediastinal lymph nodes. Methods: This was an endoscopic experimental feasibility study in a porcine model. After EUS-guided puncture of targeted lymph nodes, the stylet of a 19-G needle was replaced by a prototype RFA probe. RFA was performed by ERBE generator (bipolar settings: 10 watts, effect 2, 2 minutes). The animals were euthanized, and the targeted lymph nodes were identified and removed for histology and measurement of the effect achieved. Results: A total of 18 mediastinal lymph nodes were ablated (mean size 20.8 ± 6.6 mm in the long axis). The average length of exposed probe was 10.0 ± 3.0 mm. The mean length and diameter of necrosis was 9.8 ± 3.6 mm and 5.5 ± 1.6 mm, respectively. Linear regression comparing needle length with necrosis diameter revealed a coefficient gradient of r = 0.92 ( P = 0.0001). With EUS-RFA a mean of 17.6 ± 10.3 % (range 8.0 % – 53.2 %) of the respective lymph node area was ablated. No complications (i. e. hemodynamic instability, local bleeding, tissue damage) occurred during the procedure. Technical problems included stripping of the probe by the EUS needle and bending of the tip of the probe. Conclusions: EUS-RFA of lymph nodes was performed safely and successfully using a prototype EUS-compatible probe. This method may have the potential for future use in patient care.

Background and study aims: Insertion of a percutaneous endoscopic gastrostomy (PEG) is standard care for many patients with oropharyngeal (ENT) and esophageal malignancies in order to ensure enteral feeding. The current pull-through insertion technique involves direct contact with the tumor and case reports have demonstrated the presence of metastases at insertion sites. The aim of the current study was to prospectively evaluate the risk of malignant cell seeding and the development of abdominal wall metastases after PEG placement. Patients and methods: A total of 50 consecutive patients with ENT/esophageal tumors were included. After PEG placement (40 pull-through technique, 10 direct insertion), brush cytology was taken from the PEG tubing and the transcutaneous incision site. A second cytological assessment was performed after a follow-up period of 3 – 6 months. Results: In total, 26 patients with ENT cancer, 13 with esophageal cancer, and one with esophageal infiltration of lung cancer underwent pull-through PEG placement with no immediate complications. Cytology following brushing of tubing and incision sites demonstrated malignant cells in 9 /40 cases (22.5 %). Correlation analyses revealed a higher rate of malignant seeding in older patients and in those with higher tumor stages. At follow-up, cytology was undertaken in 32 /40 patients who had undergone pull-through PEG placement. Malignant cells were present in three on cytology, resulting in a metastatic seeding rate of 9.4 %. Conclusion: This study showed that malignant cells were present in 22.5 % of patients immediately after pull-through PEG placement; local metastases were verified at follow-up in 9.4 %, all of which were from esophageal squamous cell carcinoma. This risk is particularly high in the older age group and in patients with higher tumor stages. Therefore, pull-through PEG placement should be avoided in these patients and direct access PEG favored instead.

Background: Many GI motility disorders are associated with underlying GI neuromuscular pathology, which requires full-thickness biopsies (FTB) for histopathologic diagnosis. Currently, none of the endoscopy-based attempts to obtain FTB specimens have proven suitable for routine use. This study evaluated a novel endoscopic prototype device (ED) for this purpose.Objective: To determine (1) the ability of the ED to obtain suitable FTB specimens, (2) associated complications, (3) feasibility of reliable defect closure, and (4) ability to evaluate intramural neuromuscular components. Design: Preclinical proof-of-concept study in 30 pigs.Setting: Animal laboratory. Intervention: Gastric FTB specimens were obtained with a circular cutter and anchor. The defect was closed by over-the-scope clips/T-tags. The resection site was inspected via laparoscopy. After 2 to 4 weeks, necropsy was carried out to evaluate late complications. Main Outcome Measurements: Feasibility, safety, and closure rate of the procedure. FTB specimens were assessed by histology/immunohistochemistry to visualize enteric neuromusculature. Results: A total of 29 of 30 procedures were successfully performed; one hemorrhage required endoscopic treatment. A total of 29 of 30 FTB specimens (mean diameter 9.1 mm) were retrieved in 7.1 0.4 minutes (range 3.0-12.5 minutes), displaying optimal tissue quality. Defect closure took 10.8 0.9 minutes (range 7.2-32 minutes). Laparoscopy did not reveal damage to adjacent organs. Necropsy showed well-healed scars at the resection site and no complications, peritonitis, or abscess formation. Histology showed smooth muscle layers and submucosal and myenteric ganglia. Limitations: Survival animal pilotstudy, no patients. Conclusion: The novel ED enabled safe harvesting of well-preserved FTB specimens. Defect closure proved to be reliable. All neuromuscular structures relevant for histopathologic evaluation of GI neuromuscular pathology were demonstrated. Further studies are needed to verify the efficacy of this prototype device in the entire gut and in humans.

Phosphorylated alpha-synuclein (p-α-syn) containing Lewy bodies (LBs) and Lewy neurites (LNs) are neuropathological hallmarks of Parkinson’s disease (PD) in the central nervous system (CNS). Since they have been also demonstrated in the enteric nervous system (ENS) of PD patients, the aim of the study was to analyze enteric p-α-syn positive aggregates and intestinal gene expression. Submucosal rectal biopsies were obtained from patients with PD and controls and processed for dual-label-immunohistochemistry for p-α-syn and PGP 9.5. p-α-syn positive aggregates in nerve fibers and neuronal somata were subjected to a morphometric analysis. mRNA expression of α-syn and dopaminergic, serotonergic, VIP (vaso intestinal peptide) ergic, cholinergic, muscarinergic neurotransmitter systems were investigated using qPCR. Frequency of p-α-syn positive nerve fibers was comparable between PD and controls. Although neuronal p-α-syn positive aggregates were detectable in both groups, total number and area of p-α-syn positive aggregates were increased in PD patients as was the number of small and large sized aggregates. Increased expression of dopamine receptor D1, VIP and serotonin receptor 3A was observed in PD patients, while serotonin receptor 4 and muscarinic receptor 3 (M3R) were downregulated. M3R expression correlated negative with the number of small sized p-α-syn positive aggregates. The findings strengthen the hypothesis that the CNS pathology of increased p-α-syn in PD also applies to the ENS, if elaborated morphometry is applied and give further insights in altered intestinal gene expression in PD. Although the mere presence of p-α-syn positive aggregates in the ENS should not be regarded as a criterion for PD diagnosis, elaborated morphometric analysis of p-α-syn positive aggregates in gastrointestinal biopsies could serve as a suitable tool for in-vivo diagnosis of PD. Electronic supplementary material The online version of this article (doi:10.1186/s40478-016-0408-2) contains supplementary material, which is available to authorized users.

Background and study aims: Adequate training is required to achieve successful endoscopic ultrasound (EUS)-guided fine-needle aspiration (EUS – FNA). Of the variety of training models currently available, none offers verisimilitude to the tactile feel of puncturing a human lymph node. The aim of the current study was to evaluate a new porcine lymph node model for EUS – FNA training and to evaluate its impact on trainees’ performance in patients compared with the literature of other models available. Methods: Two trainees each performed EUS – FNA of 96 lymph nodes in 18 animals with induced lymphadenopathy (mean 1.6 cm [range 0.9 – 3.5 cm]). Accuracy, speed, adequacy of sampling, and trainees’ performance pre- and post-training were measured. Using a questionnaire, data were gathered regarding the effect of training and comfort level in patients. Results were compared with those in the literature. Results: Trainees progressed from hands-on assistance to occasional verbal guidance toward the end of animal training. There was good correlation between puncture time and number of EUS – FNA procedures performed in all but the subcarinal location (r = – 0.17). Comparison of trainee performance in patients before and after training showed a reduction in puncture time (P = 0.0014). Questionnaire analysis revealed increased confidence in echoendoscope- and needle-handling. Comparison with other published models supports these results. Conclusion: Results from the literature and the current study showed that animal training improves trainee performance, confidence, and procedural comfort when returning to patient examinations. The new model produces a realistic response that is similar to EUS – FNA in patients; this experience provides a benefit to endoscopists in terms of improved performance in patients and could be considered for use in accreditation. Due to the small numbers of trainees, larger experiences are needed to confirm training efficacy.

Findings have shown endoscopic necrosectomy to be beneficial for patients with symptomatic pancreatic necrosis accessible for an endoscopic approach. The available studies show that endoscopic necrosectomy requires a multitude of subsequent procedures including repeat irrigation for removal of the necrotic material. This study aimed to investigate the need for additional irrigation in patients with necrotizing pancreatitis treated by endoscopic necrosectomy. The study enrolled 35 consecutive patients (27 men) with a median age of 59 years who had pancreatic necrosis treated with endoscopic necrosectomy. Endoscopic ultrasound–guided internal drainage and consecutive endoscopic necrosectomy was combined with interval multistenting of the cavity. Neither endoscopic nor external irrigation was part of the procedure. An average of 6.2 endoscopy sessions per patient were needed for access, necrosectomy, and stent management. The in-hospital mortality rate was 6% (2/35), including one procedure-related death resulting from postinterventional aspiration. The immediate morbidity rate was 9% (3/35). It was possible to achieve clinical remission for all the surviving patients with no additional surgery needed for management of the necroses. The median follow-up period was 23 months. Neither endoscopic nor external flushing is needed for successful endoscopic treatment of symptomatic necroses. Even without irrigation, the outcome for patients treated with endoscopic necrosectomy is comparable to that described in the published data.

BACKGROUND AND STUDY AIMS: Major leakage from an esophageal anastomosis is a life-threatening surgical complication. Endoscopically guided endoluminal vacuum therapy using polyurethane sponges is a new method for treating such leakage. PATIENTS AND METHODS: Between June 2007 and June 2009, five patients (mean age 68 years) who developed anastomotic leakage after esophageal surgery were prospectively evaluated. After endoscopic diagnosis of a major leakage, polyurethane sponges were endoscopically positioned in the wound cavity of the anastomosis. Continuous suction was applied via drainage tubes fixed to the sponges. Initially sponges were endoscopically changed three times per week. RESULTS: In all five patients treatment was successful. Median time to reduce levels of inflammation markers by 50 % was 10 days for white blood cell (WBC) count and 7 days for C-reactive protein (CRP). The smallest initial wound cavity size was 42 cm 3 and the largest was 157 cm 3 . The median duration of drainage was 28 days, with a median of 9 sponge changes and a median time to total cavity closure of 42 days. Two patients needed anastomotic dilation by Savary-Miller bougienage due to stenosis found on further follow-up. One of these patients died of acute severe hemorrhage from an aortoanastomotic fistula after the dilation procedure. CONCLUSIONS: Endoscopically assisted vacuum therapy is a well-tolerated and effective therapeutic option for treatment of major esophageal leaks after surgery. Additional surgery was avoided in all cases. However, the occurrence of a delayed aortoesophageal fistula calls for careful further investigation of this new technique.

Leakages at surgical anastomoses in the gastrointestinal tract represent a challenging clinical problem. Standard therapy entails conservative or surgical revision of the anastomotic area with high morbidity and mortality up to 30 %. None of the previous endoscopic approaches, which include stenting, endoscopic clip closure, and fibrin glue injection, are sufficiently established for routine clinical use. We report a case of a 68-year-old woman with a postoperative leakage and abscess at the esophagojejunostomy. The defect was closed with two anchor-lock sutures. The patient was able to resume oral food intake 5 days later and made a full recovery with endoscopically documented mucosal healing at the site of the anastomosis. In summary, endoscopic suturing may be a promising approach for the treatment of postoperative leaks that warrants further, controlled investigation.

Background The first experiences with endoscopic closure of esophageal perforations in animal survival studies encouraged us to extend these procedures to full-thickness resections of pieces of the esophageal wall (FTEW). Objective To learn the feasibility, safety, and long-term effects of FTEW removal and defect closure. Design Feasibility animal study. Setting Approved animal facility. Interventions Twelve pigs were used for 3-month survival studies, autopsy, and histologic examination. Resection of a 2-cm piece of wall was performed with needle-knife and forceps/snare. Closure was performed by using prototype endoscopic suturing. Main Outcome Measurements Feasibility and complication assessment of this new endoscopic method. Results There were no complications relating to incision, resection, or closure. All pigs recovered quickly. In 2 animals a larger piece of wall causing a larger defect was removed, resulting in much air penetrating into the mediastinum, causing difficult ventilation. This was resolved with thoracic drain. In 3 of 12 animals a toxic substance slipped into the mediastinum, resulting in an abscess in 1 pig and misfire of an anchor as a result of obscured vision. This caused temporary illness of the animal but not death. Autopsy and histologic study confirmed no mediastinitis and well-healed scars in all but one. Limitation Animal study. Conclusion FTEW has proven to be feasible. Long-term survival demonstrated no mediastinitis and only 1 abscess after contamination of the mediastinum. These first experiences encourage further animal studies because the prospect of endoscopic full-thickness removal of esophageal lesions in patients might be very advantageous.

Background and study aim Significant hemorrhage is a likely complication during natural orifice transluminal endoscopic surgery (NOTES) procedures. We tested three different prototype devices (involving endoscopic suturing, monopolar forceps, and forced argon plasma coagulation [FAPC]) for treatment of acute bleeding in a survival animal model. Method Using transgastric access (TGA) or transvaginal access (TVA), the endoscope was introduced into the peritoneal cavity and the first side-branch of the gastroepiploic artery (1aGE) was cut before the different hemostatic methods were applied. Results Sutures could not be placed quickly enough before vision was inhibited. With monopolar forceps via TGA, the time to control bleeding was 10 - 140 s (mean 58 +/- 41 s) and with TVA it was 25 - 115 s (mean 57 +/- 26 s) (P = 0.54). It was not possible to stop the bleeding in 4/6 animals with TGA access and in 3/6 with TVA, and FAPC was needed to entirely stop it, taking a further 10 - 280 s (TGA mean 126 +/- 90 s, 34 - 242 s; TVA mean 152 +/- 61 s; P = 0.42). Using FAPC with TGA took 4 - 72 s (mean 28 +/- 20 s) to stop the bleeding, and 16 - 41 s (mean 24 +/- 9.4 s) with TVA ( P = 0.64). As the FAPC technique was relatively so much better, additional treatment of bleeding from the main gastroepiploic artery (aGe) was added in four cases for each method of access; this was successful but took significantly longer, with TGA at 10 - 260 s and with TVA at 30 - 172 s (means 98 +/- 82, 117 +/- 54 s, respectively; not significant). Conclusion Regarding the three methods tested, the new prototype FAPC device allowed hemostasis of notable bleeding from a major vessel even more quickly than forceps coagulation of a bleeding side branch. More studies are needed to further explore this potentially very valuable tool.

BACKGROUND AND STUDY AIMS: Natural-orifice transluminal endoscopic surgery (NOTES) is in the developmental stage for various indications, but several obstacles remain to be overcome before NOTES procedures can come into routine clinical use. Of these obstacles, (1) transluminal injury due to exclusive use of endoluminal endoscopy to create the incision and (2) lack of orientation might be prevented by employing endoscopic ultrasound guidance. In this comparative study we assessed the role of endoscopic ultrasound guidance in various NOTES procedures. METHODS: Three transesophageal (mediastinoscopy/thoracoscopy) or transgastric procedures (gastrojejunostomy, adrenal gland removal) were performed in pigs using NOTES alone or with endoscopic ultrasound guidance (EUS). In NOTES alone the study end point was three major complications, at which point EUS guidance was added for the same procedures up to the same number of cases. The primary outcome was the rate of major complications; secondary outcome parameters were all complications and technical success. RESULTS: Forty-six pigs were included. Three major complications occurred in the first 24 NOTES-alone procedures: these were bleeding and organ injury, all during mediastinoscopy/thoracoscopy procedures. Adrenal gland removal failed in all procedures in which it was attempted, while gastrojejunostomy (n = 6) was performed successfully and without complications. In the next 22 animals EUS guidance enabled safe mediastinal access (n = 10) and adrenal gland removal (n = 6). For gastrojejunostomy, EUS guidance offered no additional benefit. CONCLUSIONS: EUS guidance appears to be helpful in gaining access or identifying structures in anatomically difficult areas in NOTES procedures.

Background Endoscopic closure of inadvertent or intentional colon perforations might be valuable if comparable to surgical closure. Objective The aim of this study was to compare endoscopic closure of a 4-cm colon perforation in a porcine model with surgical closure in a multicenter study. Setting University hospitals in the United States and Europe. Design and Interventions After creating a 4-cm linear colon perforation, the animals were randomized to either endoscopic or surgical closure. The total procedure time from the beginning of perforation to the completion of procedure was measured. The animals were euthanized after 2 weeks to evaluate healing, unless there was a complication. Results Fifty-four animals were randomized to either surgical or endoscopic closure of colon perforation. Eight animals developed complications, and 7 of these were euthanized before 2 weeks. Twenty-three animals in each group survived for 2 weeks. Surgical closure of the perforation was successful in all animals in that group, and endoscopic closure was successful in 25 of the 27 animals. The median procedure time was shorter in the surgery group compared to the endoscopy group (35 vs 44 minutes, P = .016). Peritonitis, local adhesions, and leak test results were comparable in both groups. Distant adhesions were less frequent in the endoscopic closure group (26.1% vs 56.5%, P = .03). Five of the 186 T-tags (2.7%) were noted in the adjacent viscera. Limitation This porcine study does not mimic clean colon perforation in humans; it mimics dirty colon perforation in humans. Conclusions Endoscopic closure of a 4-cm colon perforation was comparable to surgery, and this technique can be potentially used for closure of intentional or inadvertent colon perforations.

Objective: Endoluminal gastroplication (EG) is emerging as a minimally invasive procedure for the treatment of gastroesophageal reflux disease (GERD). The aim of this study is to evaluate the medium-term outcomes after EG in a pediatric patient population. Patients and Methods: Seventeen children with a median age of 12.4 years (range 6.1-15.9 years) with GERD underwent EG using a flexible endoscopic sewing device (EndoCinch) over a period of 3 years. Three plications were placed in the gastric tissue below the lower esophageal sphincter. Drug dose requirement, pH measurements, symptom severity and frequency, and validated Quality of Life in Reflux and Dyspepsia (QOLRAD) scores were compared before EG and 1 and 3 years after EG. Statistical analysis was performed using a Wilcoxon rank-sum test and P < 0.05 was the threshold for significance. Results: All patients showed an immediate posttreatment improvement in symptom severity, symptom frequency, and quality of life scores. Completed 1- and 3-year data were obtained from 16 patients. Four cases (25%) required a repeat procedure as a result of recurrence of symptoms after 2 to 24 months. Fourteen patients (88%) at 1 year and 9 patients (56%) at 3 years remained without a need for any antireflux medication. A sustained improvement in heartburn (P = 0.004), regurgitation (P = 0.017), and vomiting (P = 0.018) was seen at 3 years. The total QOLRAD score (maximum of 175) improved from a median of 87 (range 69-142) to 156 (range 111 -175) at 1 year (P

Background Pyloroplasty with myotomy and sutured closure is a surgical treatment for gastric outlet obstruction. It has not been previously performed at flexible endoscopy. Objective To develop and test a method for performing a sutured pyloroplasty at flexible endoscopy. Design A Heinicke-Miculicz pyloroplasty was performed, forming a linear myotomy through the pylorus from the gastric side into the duodenal bulb. This was subsequently sutured transversely to increase the opening. The operation was performed in 3 nonsurvival studies in pigs. The safety and the efficacy was then studied in 7 animals followed for up to 4 weeks after the procedure. Setting The studies were performed in experimental surgical units in Gothenburg, Sweden, and London, UK. Interventions A linear needle-knife incision was made through the pylorus; full-thickness sutures, by using a new T-tag and polypropylene thread suturing system through a flexible gastroscope, were placed to close the incision transversely. In 2 pigs, the prepyloric bulge was excised before the pyloroplasty. Results Pyloroplasty was readily accomplished at flexible endoscopy in the 3 nonsurvival studies. Six of 7 pigs that survived in this study for periods of 7 to 28 days, recovered well, without complications. One pig (with bulge removal) developed gastric retention. The pyloric opening was increased; it was then easy to enter the duodenum at follow-up endoscopy. Limitations This method has yet to be studied clinically. Conclusions Pyloroplasty with full–thickness pyloromyotomy and transverse closure of a linear myotomy was accomplished by using a simple flexible endosurgical technique to test a new flexible suturing system.

Technical advances in linear echoendoscopes with larger accessory channels opened up the possibility for development of new devices and procedures. If looking further into the future, one could envisage an evolution of these technologies to exciting newer dimensions in the form of EUS-guided minimally invasive surgery. EUS-guidance may also play a role in the new field of natural orifice transgastric endoscopic surgery serving as a guide for the transgastric assessment of organs within the peritoneal cavity without the need for direct access. This article provides an overview on some of the possible near and far future EUS-guided interventions that have the potential to evolve into routine procedures.

Interventional endoscopies entail a risk of infection secondary to perforation of the luminal wall. Thereby, bacteria may be introduced into the sterile environment of the peritoneal cavity (PC). Limited data are available regarding the efficacy of prophylactic anti-infective treatments. The aim of the study was to examine the efficacy/safety of anti-infective means in the prevention of infection by interventional endoscopies in a randomized controlled animal trial. Forty pigs were randomized to: 1: control; 2: oral lavage; 3: gastric lavage; 4: oral/gastric lavage; 5: i.m. antibiotics. Lavage was performed with Octenisept prior to the operation. After gastric wall perforation, peritoneoscopy was performed. Before the procedure, after closure and prior to autopsy, intraabdominal lavage for bacterial culture was taken using mini-laparoscopy. At autopsy, macroscopic appearance of the PC was scored. Lavage fluids were grown to identify/quantify bacterial load. Concentration of intraperitoneal bacteria at autopsy was defined as main outcome parameter. No major complications occurred in any of the procedures. Bacterial load of the PC at autopsy was significantly reduced with antibiotics compared to all other groups, whereas it did not differ between the lavage groups and control. Macroscopic scoring of the PC showed significant lower rate of intraabdominal abscesses in the antibiotic group compared to the lavage groups and control (p

Guidewires and catheters exert less force on the gut wall than an endoscope.To develop a guidewire-assisted device for colonoscopy.A light-weight flexible catheter illuminated with light-emitting diodes was designed to carry an ultraslim high-resolution videoendoscope of 3 mm. Tip bend stiffness was 5 times less than a colonoscope. Hinged guidewires were passed, folded, through the accessory channel. A loop could be rapidly formed to explore the lumen.The catheter followed curves of excised pig colon and exerted significantly less force on the colon wall than a colonoscope (mean 1.6 +/- 0.23 N vs 3.0 +/- 0.37 N, P.05; bend-radius, 80 mm). Survival studies in pigs showed that the guidewire loop could be advanced under visual control and the Cath-Cam could be advanced by using much less force than the colonoscope.A catheter-based colonoscope with a miniature video imager reduced the force required for successful colonoscopy in pigs.

Background Endoscopic full-thickness resection (EFTR) at flexible endoscopy might allow less-invasive removal of more deeply penetrating cancers that have not spread to the serosal surface and more complete histologic examination of the excised tissue. Objective A method for closure of full-thickness defects in the stomach wall would be valuable for other endosurgical applications. Setting A method that uses an end cap and band-ligation without prior injection of saline solution to perform EFTR gave good results and was safe in pig studies. There is a size limitation of cancers that can be resected en bloc when using this method. The depth of resection was also variable. Design and Interventions EFTR was achieved by circumferential cutting with a sphincterotome and a snare. A prototype bidirectional cutter was tested. Sutured closure was accomplished by using a sheathed needle, a metal tag, and a thread at the tip, passed through a 2.8-mm accessory channel. Knot-tying devices secured the sutured defect. Main Outcome Measurements EFTR was studied in nonsurvival (n = 4) and survival (n = 8) experiments in pigs. Results Full-thickness specimens were resected from the gastric wall (100%, 12/12), and the defects were closed by using sewing and knot-tying devices (100%, 12/12). Limitations A healing ulcer at the suturing site was evident at follow-up endoscopy in the survival experiments. Bleeding, which was stopped by suturing, occurred in 1 pig (8.3%, 1/12). All pigs survived these experiments without complications (100%, 8/8). Conclusions Circumferential EFTR was feasible and appeared safe in survival experiments. This method might allow larger and deeper resection of tumors in the gastric wall.

Background and study aims Conventional colonoscopy as the gold standard for large-bowel diagnostics and therapy may fail in 5 %-20 % of cases, depending on the experience of the examiner. Colonoscopy is regarded as difficult and painful by many patients. In an attempt to overcome the limitations of conventional colonoscopes, a guide wire-directed, thin, flexible diagnostic colonoscope, the CathCam was developed. In this prospective pilot study, we report its use in patients in whom conventional colonoscopy had failed. Patients and methods 49 patients with a previous or current failure of complete colonoscopy were invited to participate in a trial using the new CathCam system, and 14 (nine men; mean age 59 years) accepted. The CathCam is an 11-mm diameter disposable, multilumen catheter, with visualization by a 3-mm camera with six light-emitting diodes. In the first five patients, the CathCam was inserted over a newly developed 0.024-inch, hinged, lumen-seeking guide wire. Subsequently, a modified combined approach was used: a conventional colonoscope was introduced into the sigmoid or left colon, then the guide wire was advanced as far as possible, followed by CathCam insertion over it. Caecal intubation rate, insertion times and patient discomfort were recorded; patients received low-dose midazolam sedation (2-5 mg). Results One patient was excluded during colonoscopy. The caecum could be eventually reached in 12 of 13 patients; in the remaining patient a significant sigmoid stricture could be passed, but further advancement appeared too risky. The mean caecal intubation time was 24 minutes (range 3-105 min). Only two patients experienced pain and discomfort during the procedure (one immediate assessment and one case reported at later telephone interview). No complications occurred, and previously undiagnosed important findings were obtained in 9 cases. Conclusions A combined approach, consisting of guide wire insertion via a partially introduced colonoscope followed by CathCam or colonoscope insertion into the caecum was successful in over 90 % of patients with previous failure of complete colonoscopy. Further improvements may make this system suitable for use as a standard diagnostic colonoscope, either as a single unit (CathCam plus guide wire) or using the guide wire alone with a standard colonoscope in difficult cases.

Background EUS-guided fine needle aspiration (EUS-FNA) is a reliable tool for tissue diagnosis of unexplained mediastinal or perigastric lymphadenopathy but may be ineffective in sampling a small malignant focus in it or removing an entire node. Objective To develop a new EUS-guided endoscopic-transgastric method to approach (sentinel) lymph nodes, including node marking and lymphadenectomy. Design Experimental study. Setting Animal experiments at an approved university college. Subjects Six pigs had a linear-array EUS examination 1 week after a transgastric procedure. All had reactive perigastric lymph nodes. Interventions Selected nodes were punctured with a 19-gauge EUS needle. A metal anchor with thread, loaded onto the needle, was placed across the lymph nodes to pull the node toward the stomach. After gastric-wall dissection with a needle knife at the point of emergence of the thread, the nodes were removed by pulling on the thread and the anchor. The gastric incision was closed with an endoscopic suturing system. Main Outcome and Measurements Proof of the feasibility to endoscopically remove paragastric lymph nodes by an EUS-guided transgastric approach. Results In all pigs, lymph-node marking with an anchor and thread was possible. Traction exerted on these nodes showed that they could be pulled against the gastric wall for subsequent removal. In 2 of 6 examinations, the entire sequence of the procedure, node tagging, gastric-wall incision, lymphadenectomy, and wall closure was performed. No serious complication occurred. Limitations Animal study throughout, small numbers, no humans to date. Conclusions Transgastric lymphadenectomy with EUS for node selection and capturing seems feasible.

Endoluminal operations for reflux are currently limited by the inability to visualise and manipulate structures outside the wall of the gut. This may be possible using endoscopic ultrasound (EUS). The aim of this study was to define EUS-anatomy of structures outside the gut which influence reflux; to place stitches in the median arcuate ligament (MAL); to perform posterior gastropexy (Hill procedure) and test the feasibility of crural repair under EUS control in pigs. In survival experiments in 14 pigs, using linear array echo-endoscopes the MAL and part of the right crus were identified and punctured with a needle, which served as a carrier for a tag and thread. These were anchored into the muscle. An endoscopic sewing device was used allowing stitches to be placed through a 2.8 mm accessory channel to any predetermined depth. New methods allowed knot-tying and thread-cutting through the 2.8 mm channel of the echo-endoscope. Stitches were placed through the gastric wall into the MAL and one just beyond the wall of the lower esophageal sphincter (LES). They were tied together and locked against the gastric wall. Preoperative manometry showed a median LES pressure of 11 mm/Hg and 21 mm/Hg after stitch placement (p = 0.0028). The length of the LES increased from median 2.8 cm pre-procedure to 3.5 cm post-procedure. At post mortem, the force to pull the tags out of the MAL was 2.8 kg median. This study shows that transgastric gastro-esophageal reflux surgery using stitching under EUS control can significantly increase the lower oesophageal sphincter pressure in pigs.

Background Some early gastric cancers might be advantageously staged and treated by full-thickness resection if secure methods for closing the defect were available. The aim of this study was to test the feasibility of full-thickness gastric resection. Methods Full-thickness gastric resections were performed by using a ligating device without submucosal injection in survival studies in pigs (n = 8). The defects were closed by using new methods for suturing, locking, and cutting thread through a 2.8-mm accessory channel. Stitches (n = 2-4) were placed close to the target area before resection. Observations Full-thickness resections (n = 8) were performed. The pigs survived without incident for 21 to 28 days. Healing of the suture site was evident at follow-up endoscopy. Suture sites were water tight. The pull-out force with stitches by using this new sewing method was significantly higher than with endoscopic clips (20.3 N ± 0.94 vs. 2.2 N ± 0.42, p Conclusions Endoscopic full-thickness resection with sutured defect closure was feasible and appeared safe in these survival experiments.

Whipple's disease is a chronic multisystem disorder caused by infection with the rod-shaped bacterium, Tropheryma whippelii. We report the case of a 65-year-old woman with intestinal Whipple's disease that had been refractory to monotherapy with a number of antibiotics over a 2-year period. The patient then presented with watery diarrhoea, cachexia (body mass index 18 kg/m (2)) and chronic anaemia (haemoglobin 7.6 g/dl). Wireless capsule endoscopy showed that the disease affected the entire small intestine. Focal occult areas of bleeding were observed in different parts of the jejunum. The capsule's transit time through the small intestine was 2 hours 43 minutes. Capsule endoscopy allows novel insights into the pathophysiology of Whipple's disease.

Background Endoluminal operations for gastroesophageal reflux currently are limited by the inability to visualize and manipulate structures outside the wall of the gut. This may be possible by using EUS. The aims of this study were the following: to define the EUS anatomy of structures outside the gut that influence reflux, to place stitches in the median arcuate ligament, to perform posterior gastropexy, and to test the feasibility of crural repair under EUS control in pigs. Methods In survival experiments in 22 pigs, by using a linear-array echoendoscope, the median arcuate ligament and part of the right crus were identified and punctured with a needle, which served as a carrier for a tag and thread. These were anchored into the muscle. An endoscopic sewing device was used, allowing stitches to be placed through a 2.8-mm accessory channel to any predetermined depth. New methods allowed knot tying and thread cutting through the 2.8-mm channel of the echoendoscope. Results Stitches were placed through the gastric wall into the median arcuate ligament, and one stitch was placed just beyond the wall of the lower esophageal sphincter. The stitches were tied together and locked against the gastric wall. Median lower esophageal sphincter pressure, determined manometrically, was 11 mm Hg before surgery and 21 mm Hg after stitch placement ( p =0.0002). The length of the lower esophageal sphincter increased from a median of 2.8 cm before the procedure to 3.5 cm after the procedure. At the postmortem, the median force required to pull the tags out of the median arcuate ligament was 2.8 kg. Conclusions This study demonstrates that transgastric gastroesophageal reflux surgery, by using stitching under EUS control, can significantly increase lower esophageal sphincter pressure in pigs.

The detection of mediastinal lymph node metastases in patients with lung cancer is most important. These nodes may be used for tissue diagnosis of the malignancy, if sampling techniques of the primary have failed. Their presence implies a stage III disease and may exclude a patient from surgery. CT is the standard imaging, but is relatively poor at staging the mediastinum (overall sensitivity: 50-70%), and is especially unreliable for lesions1 cm. PET is a new physiological imaging technique, which seems to be superior to CT (sensitivity: 67-100%). Transesophageal EUS delivers high resolution imaging, offers the advantage of simultaneous tissue sampling (EUS-FNA sensitivity: 84-94%), but is limited to the posterior mediastinum. This review compares the diagnostic value of CT, PET and EUS as well as the different tissue sampling methods for mediastinal metastases with EUS-FNA. The technique of EUS and FNA is described, and a special interest is taken to stress out the different areas of the mediastinum accessible for each of the tissue sampling methods as well as the pros and cons for its use. Advantages and disadvantages of EUS-FNA are shown and the new efforts described to improve the outcome of EUS-FNA by adding molecular methods for the detection of micrometastases.

Background: The development of wireless capsule endoscopy allows painless imaging of the small intestine. Its clinical use is not yet defined. The aim of this study was to compare the clinical efficacy and technical performance of capsule endoscopy and push enteroscopy in a series of 50 patients with colonoscopy and gastroscopy negative gastrointestinal bleeding. Methods: A wireless capsule endoscope was used containing a CMOS colour video imager, transmitter, and batteries. Approximately 50 000 transmitted images are received by eight abdominal aerials and stored on a portable solid state recorder, which is carried on a belt. Push enteroscopy was performed using a 240 cm Olympus video enteroscope. Results: Studies in 14 healthy volunteers gave information on normal anatomical appearances and preparation. In 50 patients with gastrointestinal bleeding and negative colonoscopy and gastroscopy, push enteroscopy was compared with capsule endoscopy. A bleeding source was discovered in the small intestine in 34 of 50 patients (68%). These included angiodysplasia (16), focal fresh bleeding (eight), apthous ulceration suggestive of Crohn’s disease (three), tumour (two), Meckel’s diverticulum (two), ileal ulcer (one), jejunitis (one), and ulcer due to intussusception (one). One additional intestinal diagnosis was made by enteroscopy. The yield of push enteroscopy in evaluating obscure bleeding was 32% (16/50). The capsule identified significantly more small intestinal bleeding sources than push enteroscopy (p

Objectives Needle biopsy of splenic lesions using computed tomography (CT) or ultrasound (US) is difficult if the size of the lesion is small. It may be dangerous if the lesion is adjacent to the splenic hilum or located peripherally. We used endoscopic ultrasound–guided fine needle aspiration (EUS-FNA) to elucidate the tissue diagnosis of splenic abnormalities. Methods EUS-FNA was performed in 12 patients when US- or CT-guided biopsy was inconclusive (n = 5), was not attempted because of small tumor size (0.9–1.4 cm; n = 4), or was considered dangerous (n = 3). A linear echo-endoscope and 22-gauge needles were used for cytology and bacteriology. Results The age of the patients was 19–68 yr (median 32 yr). Seven patients were male and five female. The size of the lesions was 0.8–4.2 cm (median 1.4 cm). Cytology was inadequate in one patient. Bacteriology was positive for Staphylococcus aureus and Serratia in one patient each, and cultures were positive for Mycobacterium tuberculosis in two patients. A positive diagnosis was made in 10 of 12 patients (83%). Final diagnoses were tuberculosis in two patients, Hodgkin’s disease in two, sarcoidosis in two, abscesses in two, metastatic colon cancer in one, and infarction in one. Suspected recurrence of non-Hodgkin’s lymphoma was not confirmed in one case. One patient experienced pain after puncture, but no hematoma was demonstrated on subsequent US examination. Conclusions EUS-FNA cytodiagnosis in patients with unknown splenic lesions seems feasible, even in very small foci, when CT- or US-guided biopsy fails. Additional material for bacteriology may show benign treatable diseases such as abscesses or tuberculosis.

Purpose: A prospective comparison of three imaging techniques: thoracic CT, positron emission tomography (PET), and endoscopic ultrasonography (EUS) with fine needle aspiration (FNA), each performed under routine conditions, for the detection of metastatic lymph nodes metastases in patients with lung cancer considered for operative resection. Patients and methods: Following bronchoscopic evaluation, CT, PET, and EUS were performed to evaluate potential mediastinal involvement in 33 consecutive patients with bronchoscopic biopsy/cytology proven (n = 25) or radiologically suspected (n = 8) lung cancer prior to surgery. Surgical histology was used as “gold standard” to confirm the diagnosis of the primary tumor and the mediastinal status in all patients. Histology proved non-small cell lung cancer in 30 patients, neuroendocrine tumor in 1 patient, and benign disease in 2 patients. Results: The mean age of the study group was 61.5 years (range, 41 to 80 years; 23 male patients). CT, PET, and EUS detected mediastinal lymph nodes (size, 0.4 to 1.6 cm) in 15, 14, and 27 patients (21 of which were suspected to be malignant on EUS), respectively. With respect to the correct prediction of mediastinal lymph node stage, the sensitivities of CT, PET, and EUS were 57%, 73%, and 94%. Specificities were 74%, 83%, and 71%. Accuracies were 67%, 79%, and 82%. Results of PET could be improved when combined with CT (sensitivity, 81%; specificity, 94%; accuracy, 88%). The specificity of EUS (71%) was improved to 100% by FNA cytology (EUS-guided FNA), which gave a tissue diagnosis including tumor type, without complications. Conclusions: No single imaging method alone was conclusive in evaluating potential mediastinal involvement in apparently operable lung cancer and routine clinical conditions. A tissue diagnosis is extremely helpful. Because FNA can be performed at the same time as EUS, this combination emerged as the most useful technique in the evaluation of even very small mediastinal metastases of lung cancer. CT seems necessary additionally to evaluate the pretracheal region as well as the rest of the thorax, and PET may be valuable to detect distant metastases.

The development of wireless capsule endoscopy offers the potential to examine the whole small intestine, with its 5-meter length, and has the advantage of being painless. Using a miniature CMOS camera and a short focal length lens, images are obtained, as the optical window of the capsule sweeps past the gut wall, without requiring air inflation of the gut lumen. The capsule endoscope is propelled by peristalsis through the gastrointestinal tract. The video images are transmitted using radiotelemetry to an array of aerials attached to the body which allows image capture. The images are stored on a small portable recorder carried on a belt and subsequently downloaded for analysis. The system allows more than 7 h of continuous recording of images of the gastrointestinal tract. The patients are free to continue their daily routine during the examination. The capsule endoscope has performed well in trials in patients with difficult gastrointestinal bleeding and in comparative studies with push enteroscopy. It has received both a CE mark and FDA approval for use in patients. It has been used to date in about 4,000 patients. The current clinical data are reviewed.

Background and aims Aggregation of alpha-synuclein (a-syn) has been implicated in the development of neurodegenerative diseases including its spread from the enteric nervous system (ENS) to the brain. Physiologically, a-syn is located at the presynapse and might be involved in regulating of neurotransmission. Therefore, the aim of the study was to characterize the physiological ontogenetic and locoregional expression pattern of a-syn in the ENS and its association with the synaptic vesicle apparatus. Material and methods Ontogenetic mRNA expression of a-syn and synaptophysin was determined in the rat intestine. Myenteric plexus cultures treated with glial cell line-derived neurotrophic factor (GDNF) were assessed for mRNA expression of a-syn, co-localization of a-syn with the pan-neuronal marker PGP 9.5 and the synaptic vesicle marker synaptophysin and studied by scanning electron microscopy (SEM). Human colonic specimens were subjected to co-localization studies of a-syn with synaptophysin. Results a-syn and synaptophysin intestinal gene expression levels were highest during early postnatal life and also detectable at adult age. a-syn was co-localized with PGP 9.5 and synaptophysin in myenteric plexus cultures and up-regulated after GDNF treatment. SEM confirmed the presence of neuronal varicosities to which a-syn was associated. Consistently, a-syn and synaptophysin showed partial co-localization in the human ENS. Conclusions The ontogenetic and cellular expression pattern as well as the regulation by GNDF give evidence that a-syn is physiologically associated to the synaptic vesicle apparatus. The data suggest that a-syn is involved in the regulation of synaptic plasticity in the ENS during early postnatal life and adult age.

Resectional surgery offers a curative intent and a survival benefit for patients with hilar cholangiocarcinoma, but is associated with high morbidity. Since morphological imaging cannot solve differential diagnosis preoperatively, in order to exclude patients inappropriate to this aggressive surgery, we evaluated the impact of functional imaging using fluorodeoxyglucose positron emission tomography (FDG PET) in the detection of cholangiocarcinoma and its usefulness in the differentiation from benign Klatskin tumour-mimicking lesions. Fifteen consecutive patients aged 47-78 years underwent standardized whole-body FDG PET with attenuation correction before potentially curative surgery using a conventional full-ring PET scanner with an axial field-of-view of 16.2 cm. FDG PET was evaluated visually and semiquantitatively using tumour-to-background ratios (T/B) ratios. All lesions were evaluated histopathologically. FDG PET presumed to be indicative for carcinoma was positive in 12 of 15 patients, true positive in 10 (T/B ratio, 3.2+/-1.9) and false positive in two of them (T/B ratios, 2.1 and 2.8) with Klatskin tumour-mimicking lesions. While all true positive PET results were seen in the tubular type of cholangiocarcinoma with a high amount of tumour cells and only low production of mucus, a false negative FDG PET in three patients was observed in mucinous adenocarcinoma. Additionally, FDG PET detected locoregional lymph nodes in two patients and distant metastases in a further three patients. Due to false positive results FDG PET does not allow the differentiation of benign from malignant lesions, and FDG PET should be avoided in patients with mucinous cholangiocarcinoma. However, FDG PET may have significant influence on the treatment strategy in as much as 20% of the patients, since it may detect distant metastases.

Background and Study Aims: The results of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) in focal pancreatic lesions are less impressive than those in the mediastinum. The aim of this prospectively randomized study was to compare two commercially available needle assemblies with regard to handling and cytopathological yield. Patients and Methods: A total of 30 patients (19 men, 11 women; mean age 61) with focal pancreatic lesions underwent EUS-FNA with each of the two needles (GIP, Wilson-Cook). The sequence was randomized for the examiner and blinded for the cytologist. Three patients had to be excluded because of the impossibility of sample assignment or patient follow-up. EUS-FNA was performed using the standard technique with linear echo endoscopes. Results: None of the characteristics evaluated by the examiner differed significantly between either of the needles. Inadequate results were obtained in 11 % using the GIP needle, but in none with the Wilson-Cook needle. GIP needle cytology revealed malignancy in 11 patients (sensitivity, specificity, and accuracy were 55%, 100%, and 65 %, respectively, including inadequate results). The aspirates obtained with the Wilson-Cook needle identified malignancy in 16 patients (sensitivity, specificity, and accuracy were 85 %, 100 %, and 89 %, respectively). Conclusions: No statistically significant differences were detected in the handling of either of the two needle assemblies. No complications were reported using the GIP needles. However, in four procedures breakages of the outer Teflon sheath of the Wilson-Cook needle occurred, and in another four cases re-insertion of the stylet was impossible. Nevertheless, cytopathologic results were significantly better with the Wilson-Cook needle.

Study objectives: Small-cell lung cancer (SCLC) has an unfavorable prognosis, especially when the disease is extensive at presentation. Accurate staging procedures are therefore needed for treatment planning. Positron emission tomography (PET) is a modern noninvasive imaging technique, the value of which for the staging of SCLC was investigated in the present study. Setting: University hospital. Patients: Thirty-one patients with suspected lung cancer were investigated for staging purposes using chest radiography, CT of the thorax and abdomen, abdominal ultrasound, and bone scanning. Twenty-five patients also received PET examinations during the staging procedures. Five of these patients were found to have SCLC, while two patients had mixed lesion types. Further analysis of the latter group was carried out. Results: PET detected the primary tumor in all patients, and lymph nodes in five patients. All lymph nodes were proved to be malignant by endoscopic ultrasonography-guided fine-needle aspiration. Only one patient had distant metastases, which were detected by both CT and PET. Conclusions: PET appears be a suitable imaging method in SCLC. A potential role for the technique as a standard staging procedure will need to be tested by investigating a larger number of patients in a prospective study. (CHEST 2001; 119:950 ‐954)

Background: Improved methods of tissue diagnosis for obstruction at the hilum of the liver (porta hepatis) have contributed substantially to the preoperative diagnosis of cholangiocarcinoma. Endoscopic brushing during endoscopic retrograde cholangiopancreatography (ERCP), with sensitivity of 20% to 100%, is the preferred technique for obtaining accurate pathologic results. Extensive hepatic resection with curative intent as well as modern approaches to palliative treatment are based on definitive diagnosis. This is a study involving endosonography-guided, fine-needle aspiration (EUS-FNA) for cytodiagnosis of potentially operable hilar cholangiocarcinoma when brush cytology was negative or unavailable. Methods: Ten consecutive patients (7 men, 3 women; age 47 to 78 years, median 59 years) with bile duct strictures at the hepatic hilum, diagnosed by CT and/or ERCP, underwent EUS-FNA using linear echoendoscopes and 22-gauge needles. Results: Adequate material was obtained in nine patients. Cytology revealed cholangiocarcinoma in seven and hepatocellular carcinoma in one. One benign inflammatory lesion identified on cytology proved to be a false-negative finding by frozen section. Metastatic locoregional hilar lymph nodes were detected in two patients, and in one patient the celiac and para-aortic lymph nodes were aspirated to obtain tissue proof of distant metastasis. There were no complications. Conclusions: When standard methods of tissue diagnosis are inconclusive, EUS-guided FNA may have a potential role in the diagnosis of primary cholangiocarcinoma of the hepatic hilum. As a new, minimally invasive approach, it proved to be technically feasible without significant risks.