Endoscopic ultrasound of the colon for the differentiation of Crohn's disease and ulcerative colitis in comparison with healthy controls.

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.

Prospective evaluation of malignant cell seeding after percutaneous endoscopic gastrostomy in patients with oropharyngeal/esophageal cancers.

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.

Endoscopic ultrasound-guided fine needle aspiration training: evaluation of a new porcine lymphadenopathy model for in vivo hands-on teaching and training, and review of the literature.

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.

Endoscopic transesophageal vs. thoracoscopic removal of mediastinal lymph nodes: a prospective randomized trial in a long term animal survival model.

BACKGROUND AND STUDY AIMS: In cases where biopsies remain inconclusive, removal of mediastinal lymph nodes for further analysis requires surgical means. Natural orifice transluminal endoscopic surgery (NOTES) procedures allow incision/closure of the gut wall, which might enable endoscopic excision of pre-marked nodes. The aims of the current study were to investigate the feasibility, safety, and reproducibility of lymph node generation in an animal model to enable endoscopic ultrasound-guided (EUS) lymph node removal (ELR) using transesophageal NOTES access/closure and to compare this procedure with thoracoscopic lymph node removal (TLR) in a randomized long term survival animal study. PATIENTS AND METHODS: Lymph node creation using graphite injection was performed in 12 pigs. After randomization into ELR and TLR groups, lymph nodes were marked with newly developed anchors under EUS guidance and removed using either ELR or TLR. ELR included incision of the esophageal wall and closure after lymph node removal. The main outcome measures were success in lymph node generation, technical success of lymph node removal, complications, and comparability of ELR and TLR. RESULTS: Generation of lymph nodes proved successful in all animals in 46/48 sites injected (96 %). Anchors were placed through the selected nodes in a mean of 9.4 minutes. TLR and ELR were successful in all cases. One bleeding occurred during esophageal incision in ELR, which was stopped endoscopically. After lymph node removal, endoscopic suturing of the incision took a mean of 18 minutes. Procedure time was longer for ELR than TLR (mean 48 vs. 42 minutes). All animals survived the procedures. Autopsy after 4 weeks showed two thoracic wall abscesses in the TLR group and none in the ELR group.  Microscopic analysis revealed well healed esophageal scars. CONCLUSION: ELR proved to be feasible in this limited sample size and complications were not observed more frequently in this group than in the TLR group.

Granulomatous mediastinal adenopathy: can endoscopic ultrasound-guided fine-needle aspiration differentiate between tuberculosis and sarcoidosis?

BACKGROUND AND STUDY AIMS: Mediastinal lymphadenopathy may indicate diseases such as tuberculosis or sarcoidosis, and it is often difficult to establish a diagnosis when standard medical work-up is inconclusive. In this study we investigated the diagnostic yield of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) in the differentiation between tuberculosis and sarcoidosis. PATIENTS AND METHODS: In this prospective study, 72 consecutive patients with mediastinal lymphadenopathy, negative endoscopic investigations including bronchoscopic procedures, and no radiological evidence of lung cancer or other malignancies on computed tomography were enrolled. EUS-FNA and subsequent cytology, microscopy for acid-fast bacilli, and culture were performed. At least 12 months' follow-up including further investigations was included to exclude tuberculosis. RESULTS: Adequate samples were obtained from 71/72 patients (36 male; mean age 50.2 years). No complications occurred. The final diagnosis included 30 cases of sarcoidosis, 28 of tuberculosis, four malignancies, one abscess, and nine benign lymphadenopathies. The size of lymph nodes on EUS varied from 0.5 cm to 4.2 cm. Tuberculosis nodes were significantly smaller than those in sarcoidosis. Unrelated nodes were significantly smaller than in either tuberculosis or sarcoidosis. The sensitivity, specificity, and positive and negative predictive values of EUS - FNA for tuberculosis were 86 %, 100 %, 100 %, and 91 %, respectively; those for sarcoidosis were 100 %, 93 %, 91 %, and 100 %, respectively. For culture of tuberculosis, they were 71 %, 100 %, 100 %, and 84 %, respectively. EUS - FNA led to a definite diagnosis in 64/72 cases (89 %) that had not been previously diagnosed by routine methods. CONCLUSION: EUS - FNA offers a high diagnostic yield for the differential diagnosis of tuberculosis and sarcoidosis that have not been diagnosed by conventional methods.

Drainage of esophageal leakage using endoscopic vacuum therapy: a prospective pilot study.

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.

Use of a NOTES closure device for full-thickness suturing of a postoperative anastomotic esophageal leakage.

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.

[Transesophageal/transgastric access for NOTES]. / NOTES über den transösophagealen/transgastrischen Zugang.

The new surgical concept of "natural orifice transluminal endoscopic surgery" (NOTES) breaks with the old dogma that gastrointestinal flexible endoscopy should be performed exclusively within the gastrointestinal lumen. It guides flexible endoscopy into the peritoneal cavity and to date any access to this was and is a feared complication. NOTES offers a new potential alternative to open surgery as well as laparoscopic surgery. Technical challenges of this new technique include the need for the development of new tools and devices. This is most important for the access to and closure of incisions to the peritoneal and thoracic cavities. The successful incision and closure is a prerequisite for the development of acceptable indications for this new method. In this overview the access and closure techniques currently used as well as some of those which are being considered will be described. Furthermore, possible indications for NOTES will be evaluated and discussed.

Randomized comparative long-term survival study of endoscopic and thoracoscopic esophageal wall repair after NOTES mediastinoscopy in healthy and compromised animals.

BACKGROUND AND STUDY AIMS: Natural orifice transluminal endoscopic surgery (NOTES) has not yet been widely adopted because of lack of suitable equipment and fear of possible serious complications, especially in the mediastinum. We compared endoscopic with thoracoscopic esophageal wall repair after full-thickness esophageal wall incision (FTEI) and NOTES mediastinoscopy in healthy versus compromised animals. METHODS: After FTEI for mediastinoscopy, 24 pigs (12 healthy, 12 compromised) were randomly allocated to endoscopic or thoracoscopic repair (each arm of each group, n = 6). They were kept alive for 3 months after endoscopic closure with prototype T-anchor suturing or thoracoscopic repair. RESULTS: FTEI and mediastinoscopy were uneventful in all as was the initial repair of the incision (mean repair times: thoracoscopic 65 +/- 3.2 minutes, endoscopic 52 +/- 5.1 minutes; P < 0.0005). Post procedure, all 12 healthy pigs thrived with no complications or deaths. Two compromised animals died during the preparation period, and had to be replaced. In the compromised group, during endoscopic repair, 2 / 6 pigs suffered from gastric reflux into esophagus and mediastinum; the repair was completed and the pigs kept alive; one subsequently died of mediastinitis, and in the other, autopsy showed a gastric abscess in the lower mediastinum. Regarding the compromised thoracoscopic subgroup, one animal died from mediastinitis and all had abscesses at or near the incision sites. CONCLUSION: Transesophageal mediastinoscopy could be performed equally well as the transthoracic procedure, both in healthy and compromised animals. However, on follow-up, the compromised animals had worse outcomes, with more complications and two deaths (17 %), one in each arm.

The feasibility of wireless capsule endoscopy in detecting small intestinal pathology in children under the age of 8 years: a multicentre European study.

OBJECTIVE: To systematically evaluate the feasibility and methodology to carry out wireless capsule endoscopy (WCE) in children <8 years to define small intestinal pathology. DESIGN: Prospective European multicentre study with negative prior investigation. PATIENTS AND INTERVENTIONS: 83 children aged 1.5-7.9 years were recruited. Initially, all were offered "swallowing" (Group 1) for capsule introduction. If this failed endoscopic placement (Group 2) was used and the Roth net, Advance or custom-made introducers were compared. OUTCOME MEASURES: Primary endpoint: to determine pathology; secondary endpoint: comparison of capsule introduction methods. RESULTS: Capsule introduction: 20 (24%) children aged 4.0-7.9 years (mean, 6.9 years; 14 male) comprising Group 1 were older (p<0.025) than 63 (76%) aged 1.5-7.9 years (mean, 5.25 years; 30 male) forming Group 2. COMPLICATIONS: Roth net mucosal trauma in 50%; no others occurred. The available recording apparatus was inappropriate for those <3 years. INDICATIONS: gastrointestinal bleeding: n = 30 (16 positive findings: four ulcerative jejunitis, four polyps, two angiodysplasia, two blue rubber blebs, two Meckel's diverticula, one anastomotic ulcer, one reduplication); suspected Crohn's disease: n = 20 (11 had Crohn's disease); abdominal pain: n = 12 (six positive findings: three Crohn's disease, two lymphonodular hyperplasia, one blue rubber bleb); protein loss: n = 9 (four lymphangectasia); malabsorption: n = 12 (seven positive findings: six enteropathy, one ascaris). No abnormalities overall: 45%. CONCLUSION: WCE is feasible and safe down to the age of 1.5 years. 20 children >4 years swallowed the capsule. The Advance introducer proved superior for endoscopic placement. The pathologies encountered showed age specificity and, unlike in adolescents, obscure gastrointestinal bleeding was the commonest indication.

Beyond NOTES: randomized controlled study of different methods of flexible endoscopic hemostasis of artificially induced hemorrhage, via NOTES access to the peritoneal cavity.

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.

Comparative study of NOTES alone vs. EUS-guided NOTES procedures.

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.

Natural orifice transluminal endoscopic surgery (NOTES) in the mediastinum: long-term survival animal experiments in transesophageal access, including minor surgical procedures.

BACKGROUND AND STUDY AIMS: Natural orifice transluminal endoscopic surgery (NOTES) within the peritoneal cavity is rapidly evolving, using transgastric, transcolonic, or transvaginal access. There is little experience with transesophageal NOTES access to the mediastinum. This prospective long-term animal survival study was performed to explore the feasibility and safety of transesophageal intrathoracic procedures including minor surgery. MATERIAL AND METHODS: Nine pigs were used for acute (n = 2) and up to 6-week survival studies (n = 7), followed by autopsy and histological investigation. The esophageal incision site was chosen using EUS; this was followed by endoscopic mediastinoscopy and therapeutic procedures such as mediastinal lymph node removal, saline injection into myocardium, and pericardial fenestration. The wall was closed using a suturing system or endoscopic clips. RESULTS: No acute complications were recorded with respect to mediastinal structures, pericardium, cardiac rhythm, or circulatory parameters. Removal of small mediastinal lymph nodes (n = 2) was feasible, but proved to be difficult. Other procedures, specifically at the heart were all successfully performed. Endoscopy after 4 - 6 weeks showed a well-healed esophageal incision. Autopsy with histology revealed no signs of mediastinitis, infection, bleeding, or pericarditis. The esophageal scar was found to be well healed in all cases, but with a muscular gap where clip closure had been used. CONCLUSIONS: Transmural esophageal incision and endoscopic partial mediastinoscopy including therapeutic procedures on the heart or mediastinum proved feasible in long-term survival animal studies. Clip closure of the defect was effective, but did not close the esophageal muscle layer. Other means such as endoscopic suturing appear to be preferable.

Which parameters might predict complications after natural orifice endoluminal surgery (NOTES)? Results from a randomized comparison with open surgical access in pigs.

BACKGROUND AND STUDY AIMS: Natural orifice transluminal endoscopic surgery (NOTES) is currently developed and assessed mainly in pig experiments. The vast majority of studies show a good outcome in short-term follow-up. The current study aims at comparing various parameters of postinterventional assessment and surveillance in relation to clinical behavior and autopsy results to find suitable control parameters and also to assess the pig as suitable model for NOTES compared with open surgery. METHODS: Within the framework of a randomized prospective study of 20 pigs with iatrogenic colonic perforation comparing endoscopic with open surgical closure, clinical examination, including observation of behavior, food intake, and body temperature, was carried out daily. Laboratory parameters (white blood cells [WBC], granulocytes) were measured in 14 animals. Weight was measured preoperatively and on days 2 and 7 postoperatively. Results were matched with complications found during/after 2 weeks' survival. Pre-autopsy sterile cultures were taken from the peritoneal cavities to determine possible bacterial contamination. RESULTS: Three animals from the surgical group were sacrificed on days 4, 8, and 12 because they became severely ill, with autopsy revealing intussusception from adhesions, peritoneal abscess, and peritonitis, in one pig each; another animal had culture positive for ESCHERICHIA COLI. Three minor complications (2 cough, 1 continuing fever with adhesions to the bladder found on autopsy) occurred in the endoscopic group without compromised recovery. WBC were measured in 14 animals, and found to be elevated (8 - 36 x 10 (9)/l) in six on day 2 including the two animals with severe complications. Between pre- and post-procedure, WBC increased about twofold in the uneventful cases but fourfold in the two animals with severe complications. Cultures from the abdominal cavity before autopsy were negative in all but one animal. CONCLUSION: Animal behavior was a reliable indicator of severe complications. Fever, body weight, and the results of in vitro cultures of the peritoneal fluid did not indicate complications. WBC proved not to be specific but showed a larger increase in pigs with severe complications.

The new scopes--broadening the colonoscopy marketplace.

Colonoscopy has been established as a screening tool for colorectal cancer and precursors in some countries. Efforts to improve instrument performance as well as patient comfort, safety and compliance have led to modifications of existing endoscopes as well as to the development of new scopes with different working mechanisms, including the colon capsule. While the former have not substantially changed performance, the true value of new scopes - partially single use and/or self propelling - can not be fully assessed, since they are either still under development and/or tested only in animals and in small groups of patients or volunteers. The colon capsule holds promise but has a too complicated preparatory regimen and too low a sensitivity at the moment. Future developments and further studies will show which of these techniques may complement or even replace traditional screening colonoscopy.