Uwe Will

Transluminal endoscopic necrosectomy after acute pancreatitis: a multicentre study with long-term follow-up (the GEPARD Study)

Background: As with endoscopic transmural drainage of peripancreatic fluid collections, the same transluminal access can be expanded to introduce an endoscope through the gastrointestinal wall into the retroperitoneum and remove infected pancreatic necroses under direct visual control. This study reports the first large series with long-term follow-up. Methods: Data for all patients undergoing transluminal endoscopic removal of (peri)pancreatic necroses between 1999 and 2005 in six different centres were collected retrospectively, and the patients were followed up prospectively until 2008. The initial patient and treatment outcome data were recorded, as were long-term results. Results: Ninety-three patients (63 men, 30 women; mean age 57 years) underwent a mean of six interventions starting at a mean of 43 days after an attack of severe acute pancreatitis. After establishment of transluminal access to the necrotic cavity and subsequent endoscopic necrosectomy, initial clinical success was obtained in 80% of the patients, with a 26% complication and a 7.5% mortality rate at 30 days. After a mean follow-up period of 43 months, 84% of the initially successfully treated patients had sustained clinical improvement, with 10% receiving further endoscopic and 4% receiving surgical treatment for recurrent cavities; 16% suffered recurrent pancreatitis. Conclusions: Direct transluminal endoscopic removal of pancreatic necroses is associated with good long-term maintenance of the high initial efficacy; complications can occur, with an associated mortality of around 7.5%. Further studies are necessary in order to optimise endotherapy and define its role in relation to surgery in the clinical management of such patients.

Accuracy of endoscopic ultrasound elastography used for differential diagnosis of focal pancreatic masses: a multicenter study.

BACKGROUND AND STUDY AIMS Endoscopic ultrasound (EUS) elastography represents a new imaging procedure that might characterize the differences of hardness and strain between diseased tissue and normal tissue. The aim of this study was to assess the efficiency of EUS elastography for the differentiation of focal masses in chronic pancreatitis and pancreatic cancer. PATIENTS AND METHODS The study group comprised 258 patients with focal pancreatic masses included prospectively at 13 participating centers. Qualitative analysis of the diagnoses made by two expert doctors using all recorded video clips was performed in order to test the interobserver variability. A post-processing software analysis was used to examine the EUS elastography videos by calculating average-hue histograms of individual elastography images. The quantitative information was used to calculate intra-observer variability and the accuracy of the method. RESULTS Qualitative analysis of the recorded videos revealed a kappa value of 0.72. Intra-observer variability analysis revealed that the single measure intraclass correlation ranged between 0.86 and 0.94. The average-hue histogram analysis of the data indicated a sensitivity of 93.4 %, a specificity of 66.0 %, a positive predictive value of 92.5 %, a negative predictive value of 68.9 %, and an overall accuracy of 85.4 %, based on a cut-off value of 175. Area under the receiver operating characteristic curve (AUROC) was 0.854 ( P < 0.0001) with a confidence interval of 0.804 - 0.894. CONCLUSION The value of quantitative analysis of EUS elastography recordings was proven by good reproducibility of the videos, as well as good parameters of the AUROC analysis. (Clinical Trials.gov identifier: CT00909103).

A novel lumen-apposing metal stent for endoscopic ultrasound-guided drainage of pancreatic fluid collections: a prospective cohort study

BACKGROUND AND STUDY AIMS A novel large-diameter, lumen-apposing, self-expanding metal stent with bilateral flanges was recently developed for endoscopic ultrasound (EUS)-guided transmural drainage of symptomatic pancreatic fluid collections (PFCs). The aim of this study was to evaluate the efficacy and safety of this stent in a large cohort. PATIENTS AND METHODS Patients with a PFC undergoing EUS-guided drainage with this novel stent were prospectively enrolled in this multicenter cohort study. RESULTS There were 61 patients: 46 patients (75 %) with walled-off necrosis (WON) and 15 (25 %) with a pancreatic pseudocyst. Stent placement was technically successful in 60 patients (98 %, 95 %CI 95 % - 100 %). Clinical success, defined as resolution of clinical symptoms in combination with a decrease in the PFC size to ≤ 2 cm on imaging, was achieved in 93 % of patients with a pancreatic pseudocyst (95 %CI 77 % - 100 %) and in 81 % of patients with WON (95 %CI 69 % - 94 %). Treatment failure occurred in nine patients (16 %, 95 %CI 6 % - 26 %), including four patients who required surgical intervention. Stent removal was performed in 82 % of patients after a median of 32 days (range 2 - 178) and was rated as easy in all but one patient. In 10 patients, endoscopic stent removal was not performed because of stent migration (n = 3), stent dislodgement during necrosectomy (n = 3), stent removal during surgery (n = 2), or refusal by the patient (n = 2). In total, five major complications were reported (9 %, 95 %CI 2 % - 16 %), including PFC infection (n = 4) and perforation (n = 1). CONCLUSION EUS-guided drainage using this novel stent is feasible and the clinical results obtained are promising with a low major complication rate.

Efficacy of an Artificial Neural Network–Based Approach to Endoscopic Ultrasound Elastography in Diagnosis of Focal Pancreatic Masses

BACKGROUND & AIMS By using strain assessment, real-time endoscopic ultrasound (EUS) elastography provides additional information about a lesions characteristics in the pancreas. We assessed the accuracy of real-time EUS elastography in focal pancreatic lesions using computer-aided diagnosis by artificial neural network analysis. METHODS We performed a prospective, blinded, multicentric study at of 258 patients (774 recordings from EUS elastography) who were diagnosed with chronic pancreatitis (n = 47) or pancreatic adenocarcinoma (n = 211) from 13 tertiary academic medical centers in Europe (the European EUS Elastography Multicentric Study Group). We used postprocessing software analysis to compute individual frames of elastography movies recorded by retrieving hue histogram data from a dynamic sequence of EUS elastography into a numeric matrix. The data then were analyzed in an extended neural network analysis, to automatically differentiate benign from malignant patterns. RESULTS The neural computing approach had 91.14% training accuracy (95% confidence interval [CI], 89.87%-92.42%) and 84.27% testing accuracy (95% CI, 83.09%-85.44%). These results were obtained using the 10-fold cross-validation technique. The statistical analysis of the classification process showed a sensitivity of 87.59%, a specificity of 82.94%, a positive predictive value of 96.25%, and a negative predictive value of 57.22%. Moreover, the corresponding area under the receiver operating characteristic curve was 0.94 (95% CI, 0.91%-0.97%), which was significantly higher than the values obtained by simple mean hue histogram analysis, for which the area under the receiver operating characteristic was 0.85. CONCLUSIONS Use of the artificial intelligence methodology via artificial neural networks supports the medical decision process, providing fast and accurate diagnoses.

Successful endoscopic treatment of an esophageal duplication cyst.

Duplication cysts of the gastrointestinal tract are rare, particularly in adults. Endoscopic minimally invasive treatment is still a challenging approach even in the endoscopically accessible sections of the gastrointestinal tract. In a 25-year-old patient suffering from dysphagia, an endoscopy and subsequent endosonography revealed a spherical duplication cyst in the lower third of the esophagus, which prompted us to puncture the cyst and subsequently to perform a fenestration (marsupialization; diameter 1 cm) in the anterior wall of the cyst, resulting in permanent drainage of the cystic fluid. Because of the recurrent complaints of the patient after 6 weeks, the anterior wall of the duplication cyst, the former esophageal wall, was partially resected, resulting in a permanent 4-cm opening including the cystic cavity into the esophageal lumen. Thereafter, there were no further complaints from the patient and the findings in the follow-up endoscopy were normal. A successful endoscopic intervention for this type of gastrointestinal duplication cyst is described for the first time. The minimally invasive resection of the anterior wall of the esophageal duplication cyst, simultaneously with the former regular wall at this segment of the esophagus, resulted in permanent inclusion of the cystic cavity into the esophageal lumen with no disadvantageous passage of fluid and food through the lower esophagus or changes in the former cystic epithelium. This method is considered to be feasible and a reasonable treatment alternative to the more invasive surgical approach.

Similar Efficacies of Endoscopic Ultrasound Gallbladder Drainage With a Lumen-Apposing Metal Stent Versus Percutaneous Transhepatic Gallbladder Drainage for Acute Cholecystitis

Background & Aims Acute cholecystitis in patients who are not candidates for surgery is often managed with percutaneous transhepatic gallbladder drainage (PT‐GBD). Endoscopic ultrasound‐guided gallbladder drainage (EUS‐GBD) with a lumen‐apposing metal stent (LAMS) is an effective alternative to PT‐GBD. We compared the technical success of EUS‐GBD versus PT‐GBD, and patient outcomes, numbers of adverse events (AEs), length of hospital stay, pain scores, and repeat interventions. Methods We performed a retrospective study to compare EUS‐GBD versus PT‐GBD at 7 centers (5 in the United States, 1 in Europe, and 1 in Asia), from 2013 through 2015, in management of acute cholecystitis in patients who are not candidates for surgery. A total of 90 patients (56 men) with acute cholecystitis (61 calculous, 29 acalculous) underwent EUS‐GBD (n = 45) or PT‐GBD (n = 45). Data were collected on technical success, clinical success (resolution of symptoms or laboratory and/or radiologic abnormalities within 3 days of intervention), and need for repeat intervention. Characteristics were compared using Student t tests for continuous variables and the chi‐square test, or the Fisher exact test, when appropriate, for categorical variables. Adverse events were graded according to American Society for Gastrointestinal Endoscopy definitions and compared using the Fisher exact test. Postprocedure pain scores were compared using the Mann‐Whitney U test. Results Baseline characteristics, type, and clinical severity of cholecystitis were comparable between groups. In the EUS‐GBD group, noncautery LAMS were used in 30 patients and cautery‐enhanced LAMS were used in 15. Technical success was achieved for 98% of patients in the EUS‐GBD and 100% of the patients in the PT‐GBD group (P = .88). Clinical success was achieved by 96% of patients in the EUS‐GBD group and 91% in the PT‐GBD group (P = .20). There was a nonsignificant trend toward fewer AEs in the EUS‐GBD group (5 patients; 11%) than in the PT‐GBD group (14 patients; 32%) (P = .065). There were no significant differences in the severity of the AEs: mild, 2 in the EUS‐GBD group versus 5 in the PT‐GBD group (P = .27); moderate, 4 versus 3 (P = .98); severe, 1 versus 3 (P = .62); or deaths, 1 versus 3 (P = .61). The mean postprocedure pain score was lower in the EUS‐GBD group than in the PT‐GBD group (2.5 vs 6.5; P < .05). The EUS‐GBD group had a shorter average length of stay in the hospital (3 days) than the PT‐GBD group (9 days) (P < .05) and fewer repeat interventions (11 vs 112) (P < .05). The average number of repeat interventions per patients was 0.2 ± 0.4 EUS‐GBD group versus 2.5 ± 2.8 in the PT‐GBD group (P < .05). Median follow‐up after drainage was comparable in EUS‐GBD group (215 days; range, 1–621 days) versus the PT‐GBD group (265 days; range, 1–1638 days). Conclusions EUS‐GBD has similar technical and clinical success compared with PT‐GBD and should be considered an alternative for patients who are not candidates for surgery. Patients who undergo EUS‐GBD seem to have shorter hospital stays, lower pain scores, and fewer repeated interventions, with a trend toward fewer AEs. A prospective, comparative study is needed to confirm these results.

Endoscopic papillectomy: Data of a prospective observational study

AIM To investigate the clinical value of endoscopic papillectomy indicated by feasibility and safety of the procedure in various diseases of the papilla in a representative number of patients in a setting of daily clinical and endoscopic practice and care by means of a systematic prospective observational study. METHODS Through a defined time period, all consecutive patients with tumor-like lesions of the papilla, who were considered for papillectomy, were enrolled in this systematic bicenter prospective observational study, and subdivided into 4 groups according to endoscopic and endoscopic ultrasonography (EUS) findings as well as histopathological diagnosis: adenoma; carcinoma/neuroendocrine tumor (NET)/lymphoma; papilla into which catheter can not be introduced; adenomyomatosis, respectively. Treatment results and outcome were characterized by R0 resection, complication, recurrence rates and tumor-free survival. RESULTS Over a 7-year period, 58 patients underwent endoscopic papillectomy. Main symptoms prompting to diagnostic measures were unclear abdominal pain in 50% and cholestasis with and without pain in 44%. Overall, 54/58 patients [inclusion rate, 93.1%; sex ratio, males/females = 25/29 (1:1.16); mean age, 65 (range, 22-88) years] were enrolled in the study. Prior to papillectomy, EUS was performed in 79.6% (n = 43/54). Group 1 (adenoma, n = 24/54; 44.4%): 91.6% (n = 22/24) with R0 resection; tumor-free survival after a mean of 18.5 mo, 86.4% (n = 19/22); recurrence, 13.6% (n = 3/22); minor complications, 12.5% (n = 3/24). Group 2 (carcinoma/NET/lymphoma, n = 18/54; 33.3%): 75.0% (n = 10/18) with R0 resection; tumor-free survival after a mean of 18.5 (range, 1-84) mo, 88.9% (n = 8/9); recurrence, 11.1% (n = 1/9). Group 3 (adenomyomatosis, n = 4/54; 7.4%). Group 4 (primarily no introducible catheter into the papilla, n = 8; 14.8%). The overall complication rate was 18.5% (n = 10/54; 1 subject with 2 complications): Bleeding, n = 3; pancreatitis, n = 7; perforation, n = 1 (intervention-related mortality, 0%). In summary, EUS is a sufficient diagnostic tool to preoperatively clarify diseases of the papilla including suspicious tumor stage in conjunction with postinterventional histopathological investigation of a specimen. Endoscopic papillectomy with curative intention is a feasible and safe approach to treat adenomas of the papilla. In high-risk patients with carcinoma of the papilla with no hints of deep infiltrating tumor growth, endoscopic papillectomy can be considered a reasonable treatment option with low risk and an approximately 80% probability of no recurrence if an R0 resection can be achieved. In patients with jaundice and in case the catheter can not be introduced into the papilla, papillectomy may help to get access to the bile duct. CONCLUSION Endoscopic papillectomy is a challenging interventional approach but a suitable patient- and local finding-adapted diagnostic and therapeutic tool with adequate risk-benefit ratio in experienced hands.

EUS-guided gallbladder drainage in patients with acute cholecystitis and high surgical risk using an electrocautery-enhanced lumen-apposing metal stent device

BACKGROUND AND AIMS In high-risk surgical patients, the treatment of choice of acute cholecystitis is percutaneous transhepatic gallbladder drainage (PTGBD). Recently, a novel endoscopic device containing a lumen-apposing metal stent with an electrocautery (ECE-LAMS) on the tip has been developed. METHODS High-risk surgical patients with acute cholecystitis who underwent EUS-guided gallbladder drainage (EUS-GBD) with the novel device were retrospectively retrieved from 7 tertiary care referral centers. Main endpoints were technical and clinical success rates, rate of procedural adverse events, and short- and long-term adverse events. RESULTS Seventy-five patients (mean age, 75 ± 11 years; 36 men) underwent EUS-GBD. The procedure was technically and clinically successful in 98.7% and 95.9% of cases, respectively. Three patients without resolution of cholecystitis died, and 2 patients had procedure-related adverse events: 1 perforation requiring surgery and 1 major bleeding resolved conservatively. The mean follow-up for the entire cohort was 201 ± 226 days. Seven patients (9.6%) died within the first 30 days; 50 patients (71.4%) were alive at the last date of follow-up. Short- and long-term adverse events occurred in 6 patients: 3 had recurrent cholecystitis, 2 had migration of the stent, and 1 developed Bouveret syndrome, all managed nonsurgically. Overall, 8 adverse events (10.7%) occurred in the entire cohort of patients. CONCLUSIONS The novel ECE-LAMS for high-risk surgical patients with acute cholecystitis is safe, with a high technical and clinical success rate. Future multicenter studies comparing EUS-GBD versus PTGBD are warranted to determine which procedure is safer and clinically more effective for patients with high surgical risk acute cholecystitis.

Use of Intestinal Ultrasound to Monitor Crohn’s Disease Activity

BACKGROUND & AIMS We performed a multicenter study to determine whether transabdominal bowel wall ultrasonography, a noninvasive procedure that does not require radiation, can be used to monitor progression of Crohn’s disease (CD). METHODS We performed a 12‐month prospective, noninterventional study at 47 sites in Germany, from December 2010 through September 2014. Our study included 234 adult patients with CD who experienced a flare, defined as Harvey‐Bradshaw index score of ≥7. All patients received treatment intensification, most with tumor necrosis factor antagonists. Ultrasound parameters and clinical data were assessed at baseline and then after 3, 6, and 12 months. The primary endpoint was the change in ultrasound parameters within 12 months of study enrollment. RESULTS All patients included had bowel wall alterations either within the terminal ileum and/or segments of the colon. After 3 and 12 months, ultrasonographic examination showed significant improvements of nearly all ultrasound parameters, including reductions in bowel wall thickening or stratification, decreased fibrofatty proliferation, and increased signals in color Doppler ultrasound (P < .01 for all parameters at months 3 and 12). Median Harvey‐Bradshaw index scores decreased from 10 at baseline to 2 after 12 months. Improvement in bowel wall thickness correlated with reduced levels of C‐reactive protein after 3 months (P ≤ .001). CONCLUSIONS In a multicenter prospective study, we found that ultrasonographic examination can be used to monitor disease activity in patients with active CD. Bowel ultrasonography seems to be an ideal follow‐up method to evaluate early transmural changes in disease activity, in response to medical treatment. German Clinical Trials Register: drks.de/DRKS00010805.

Endoscopic ultrasonography-guided drainage for patients with symptomatic obstruction and enlargement of the pancreatic duct.

AIM To evaluate the use of translumenal pancreatography with placement of endoscopic ultrasonography (EUS)-guided drainage of the pancreatic duct. METHODS This study enrolled all consecutive patients between June 2002 and April 2014 who underwent EUS-guided pancreatography and subsequent placement of a drain and had symptomatic retention of fluid in the pancreatic duct after one or more previous unsuccessful attempts at endoscopic retrograde cannulation of the pancreatic duct. In all, 94 patients underwent 111 interventions with one of three different approaches: (1) EUS-endoscopic retrograde drainage with a rendezvous technique; (2) EUS-guided drainage of the pancreatic duct; and (3) EUS-guided, internal, antegrade drainage of the pancreatic duct. RESULTS The mean duration of the interventions was 21 min (range, 15-69 min). Mean patient age was 54 years (range, 28-87 years); the M:F sex ratio was 60:34. The technical success rate was 100%, achieving puncture of the pancreatic duct including pancreatography in 94/94 patients. In patients requiring drainage, initial placement of a drain was successful in 47/83 patients (56.6%). Of these, 26 patients underwent transgastric/transbulbar positioning of a stent for retrograde drainage; plastic prostheses were used in 11 and metal stents in 12. A ring drain (antegrade internal drainage) was placed in three of these 26 patients because of anastomotic stenosis after a previous surgical intervention. The remaining 21 patients with successful drain placement had transpapillary drains using the rendezvous technique; the majority (n = 19) received plastic prostheses, and only two received metal stents (covered self-expanding metal stents). The median follow-up time in the 21 patients with transpapillary drainage was 28 mo (range, 1-79 mo), while that of the 26 patients with successful transgastric/transduodenal drainage was 9.5 mo (range, 1-82 mo). Clinical success, as indicated by reduced or absence of further pain after the EUS-guided intervention was achieved in 68/83 patients (81.9%), including several who improved without drainage, but with manipulation of the access route. CONCLUSION EUS-guided drainage of the pancreatic duct is a safe, feasible alternative to endoscopic retrograde drainage when the papilla cannot be reached endoscopically or catheterized.