John Gásdal Karstensen

Endoscopic ultrasound-guided fine needle aspiration: From the past to the future

Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is a technique which allows the study of cells obtained through aspiration in different locations near the gastrointestinal tract. EUS-FNA is used to acquire tissue from mucosal/submucosal tumors, as well as peri-intestinal structures including lymph nodes, pancreas, adrenal gland, gallbladder, bile duct, liver, kidney, lung, etc. The pancreas and lymph nodes are still the most common organs targeted in EUS-FNA. The overall accuracy of EUS is superior to computed tomography scan and magnetic resonance imaging for detecting pancreatic lesions. In most cases it is possible to avoid unnecessary surgical interventions in advanced pancreatic cancer, and EUS is considered the preferred method for loco-regional staging of pancreatic cancer. FNA improved the sensitivity and specificity compared to EUS imaging alone in detection of malignant lymph nodes. The negative predictive value of EUS-FNA is relatively low. The presence of a cytopathologist during EUS-FNA improves the diagnostic yield, decreasing unsatisfactory samples or need for additional passes, and consequently the procedural time. The size of the needle is another factor that could modify the diagnostic accuracy of EUS-FNA. Even though the EUS-FNA technique started in early nineteens, there are many remarkable progresses culminating nowadays with the discovery and performance of needle-based confocal laser endomicroscopy. Last, but not least, identification and quantification of potential molecular markers for pancreatic cancer on cellular samples obtained by EUS-FNA could be a promising approach for the diagnosis of solid pancreatic masses.

Serial intralesional injections of infliximab in small bowel Crohn’s strictures are feasible and might lower inflammation

Background Crohn’s disease can cause strictures throughout the gastrointestinal tract. Endoscopic balloon dilatation is a well-established treatment, but recurrence is seen in up to three out of four cases. Infliximab is playing an increasingly important role in the modern systemic treatment of severe Crohn’s disease. Combining the anti-inflammatory effects of infliximab with the proven effect of endoscopic balloon dilatation could possibly improve outcome. In small studies, intralesional injections in perianal fistulas have been effective and endoscopic injection therapy in colonic strictures is feasible. Objective We wanted to assess whether serial intralesional injection of infliximab in small bowel strictures is feasible and reduces local inflammation. Methods We included six patients with Crohn’s disease and inflammatory small bowel strictures. They were treated with endoscopic serial balloon dilatation. Subsequent to each dilatation, 40 mg infliximab was injected submucosally. A modified simplified endoscopic score for Crohn’s disease was used for the involved area before the initial treatment and at the final follow-up after six months. Complications and development of symptoms were registered. Results Balloon dilatation and serial injection of infliximab were accomplished in five out of six patients. One patient completed the serial balloon dilatations and follow-up but received only one infliximab injection. The modified simplified endoscopic score for Crohn’s disease decreased in all patients. There were no adverse events registered and all patients described themselves as feeling well. Conclusions Combining balloon dilatation of strictures with serial intralesional injection of infliximab in Crohn’s disease of the small bowel is feasible and seems successful in reducing inflammation.

Confocal laser endomicroscopy: a novel method for prediction of relapse in Crohn's disease.

BACKGROUND AND STUDY AIMS Confocal laser endomicroscopy (CLE) has been shown to predict relapse in ulcerative colitis in remission, but little is currently known about its role in Crohns disease. The aim of this study was to identify reproducible CLE features in patients with Crohns disease and to examine whether these are risk factors for relapse. PATIENTS AND METHODS This was a single-center prospective feasibility study of CLE imaging in patients with Crohns disease. CLE imaging was performed in the terminal ileum and four colorectal sites, and was correlated with histopathology and macroscopic appearance. Clinical relapse, defined as the need for treatment escalation or surgical intervention, was recorded during follow-up. RESULTS The study included 50 patients: 39 with Crohns disease (20 in remission), and 11 controls. Ileal fluorescein leakage and microerosions were significantly more frequent in patients with endoscopically active Crohns disease compared with patients with inactive Crohns disease and controls (P = 0.005 and (P = 0.006, respectively). The same applied to colorectal fluorescein leakage and vascular alterations ((P = 0.043 and (P = 0.034, respectively). During a 12-month follow-up period, ileal fluorescein leakage and microerosions were significant risk factors for relapse in the subgroup of patients in remission (log rank (P = 0.009 and (P = 0.007, respectively) as well as in the entire group of patients with Crohns disease (log rank (P = 0.006 and (P = 0.01, respectively). Inter- and intraobserver reproducibility was almost perfect (κ > 0.80) or substantial (κ > 0.60) for the majority of CLE parameters. CONCLUSIONS CLE can identify reproducible microscopic changes in the terminal ileum that are risk factors for relapse in patients with otherwise inactive Crohns disease. TRIAL REGISTRATION ClinicalTrials.gov (NCT01738529).

Confocal Laser Endomicroscopy in Inflammatory Bowel Disease--A Systematic Review.

BACKGROUND AND AIMS Confocal laser endomicroscopy is an endoscopic method that provides in vivo real-time imaging of the mucosa at a cellular level, elucidating mucosal changes that are undetectable by white light endoscopy. This paper systematically reviews current indications and perspectives of confocal laser endomicroscopy for inflammatory bowel disease. METHODS Available literature was searched systematically for studies applying confocal laser endomicroscopy in Crohns disease or ulcerative colitis. Relevant literature was reviewed and only studies reporting original clinical data were included. Next, eligible studies were analysed with respect to several parameters, such as technique and clinical aim and definitions of outcomes. RESULTS Confocal laser endomicroscopy has been used for a wide range of purposes in inflammatory bowel disease, covering assessment of inflammatory severity, prediction of therapeutic response and relapse and adenoma surveillance in patients with ulcerative colitis. Methods for measurement of the histological changes ranged from subjective grading to objective quantification analysed by computer-aided models. The studies derived their conclusions from assessment of histological features such as colonic crypts, epithelial gaps and epithelial leakiness to fluorescein. CONCLUSIONS Confocal laser endomicroscopy remains an experimental but emerging tool for assessment of inflammatory bowel disease. It is the only method that enables in vivo functional assessment of intestinal barrier function. There is great heterogeneity in the literature and no single approach has been validated and reproduced to the level of general acceptance.

Molecular confocal laser endomicroscopy: a novel technique for in vivo cellular characterization of gastrointestinal lesions.

While flexible endoscopy is essential for macroscopic evaluation, confocal laser endomicroscopy (CLE) has recently emerged as an endoscopic method enabling visualization at a cellular level. Two systems are currently available, one based on miniprobes that can be inserted via a conventional endoscope or via a needle guided by endoscopic ultrasound. The second system has a confocal microscope integrated into the distal part of an endoscope. By adding molecular probes like fluorescein conjugated antibodies or fluorescent peptides to this procedure (either topically or systemically administered during on-going endoscopy), a novel world of molecular evaluation opens up. The method of molecular CLE could potentially be used for estimating the expression of important receptors in carcinomas, subsequently resulting in immediate individualization of treatment regimens, but also for improving the diagnostic accuracy of endoscopic procedures by identifying otherwise invisible mucosal lesions. Furthermore, studies have shown that fluorescein labelled drugs can be used to estimate the affinity of the drug to a target organ, which probably can be correlated to the efficacy of the drug. However, several of the studies in this research field have been conducted in animal facilities or in vitro, while only a limited number of trials have actually been carried out in vivo. Therefore, safety issues still needs further evaluations. This review will present an overview of the implications and pitfalls, as well as future challenges of molecular CLE in gastrointestinal diseases.

Endoscopic ultrasound-guided needle-based confocal laser endomicroscopy: a pilot study for use in focal pancreatic masses.

Copyright emerged in recent years as a novel method that enables in vivo microscopic analysis during ongoing endoscopy. Recently, CLE has gone beyond the superficial luminal indications with the development of a newmicroprobe (nCLE) (Cellvizio;Mauna Kea Technology, Paris, France). The aim of the present case series was to study the feasibility of EUS-guided nCLE and to correlate the findings with microscopy.

Endoscopic ultrasound guided needle-based confocal laser endomicroscopy in solid pancreatic masses – a prospective validation study

Background and study aims  Endoscopic ultrasound fine-needle aspiration (EUS-FNA) is a keystone in diagnosing and staging of pancreatic masses. Recently, a microfiber that can pass through a 19-gauge needle has been introduced for confocal laser endomicroscopy (nCLE). The aims of this study were to evaluate the diagnostic value and the reproducibility of nCLE criteria for solid malignant lesions. Patients and methods  This prospective dual-center study included patients with pancreatic masses suspicious of malignancy referred for EUS-FNA. Endomicroscopic imaging was performed under EUS-guidance until organ-specific structures were obtained. Afterwards, standard cytology was obtained and patients were followed for up to 12 months. All nCLE parameters included in former studies were correlated with the final diagnosis (dark lobular structures/normal acinar cells, dark cell aggregates > 40 µm, dilated irregular vessels with fluorescein leakage, fine white fibrous bands, small black cell movements, pseudoglandular structures). Finally, three CLE novices and three CLE experts assessed the unedited movies from all patients. Results  Twenty-eight patients were enrolled in the study. A final diagnosis was obtained in 24 patients (86 %). One patient (3 %) died before a diagnosis was obtained, while 3 were lost to follow-up (11 %). In 18/24 patients (74 %) the diagnosis was malignant. The mean sensitivity, specificity, and accuracy for the nCLE parameters ranged from 19 – 93 %, 0 – 56 %, 26 – 69 %, respectively. The inter-observer values ranged from κ = 0.20 – 0.41 for novices and κ = –0.02 – 0.38 for experts. Conclusions  The diagnostic value of nCLE in solid pancreatic masses is questionable and the inter-observer agreement for both novices and CLE experts appears limited.

Biodegradable stents for the treatment of bowel strictures in Crohn's disease: technical results and challenges

Background and study aims: In patients with Crohn’s disease, the idea of biodegradable stents for treatment of bowel strictures with limited effect of endoscopic balloon dilation is tempting and initial results have been promising. The aim of this study was to evaluate the technical and clinical success of biodegradable stents for treatment of inflamed Crohn’s strictures refractory to endoscopic balloon dilatation. Patients and methods: Consecutive patients treated with biodegradable stents due to Crohn’s disease and inflamed bowel strictures refractory to endoscopic balloon dilatation were included. Technical and clinical success were evaluated. Results: Six patients were included in the study. Technical success was obtained in five patients (83 %). Clinical success was limited to one patient (20 %); failure was observed due to mucosal overgrowth (n = 2), stent migration (n = 1), and stent collapse (n = 1). Conclusions: In Crohn’s disease, it is technically feasible to treat bowel strictures with biodegradable stents. However, we have stopped using biodegradable stents due to lack of clinical success and side effects such as mucosal overgrowth and stent collapse.

Partnership with African Countries: European Society of Gastrointestinal Endoscopy (ESGE) – Position Statement

Recommendations A new objective for the European Society of Gastrointestinal Endoscopy (ESGE) is to develop long-term partnerships with African countries. For this, an International Affairs Working Group (IAWG) was formed. In conjunction with the World Endoscopy Organization (WEO), ESGE conducted a survey of gastrointestinal (GI) endoscopy in Africa. Survey results showed that many African countries have few GI endoscopy centers with adequate resources. Barriers to the development of endoscopy services include a shortage of endoscopists who have undergone advanced endoscopy training, and a lack of equipment and basic infrastructure. Diseases related to infectious etiology are more prevalent than neoplastic diseases in Africa. Any development of endoscopy services needs to consider the local prevalence of diseases for which GI endoscopy is required, as well as the availability of resources. The IAWG will initiate a cascade approach to identify and adapt ESGE guidelines for local use. The guidelines will consider the level of resources available for each intervention, as well as cost, infrastructure, and training, and will be approved by consensus of local experts who are representative of different African areas. Suitable centers in African countries will be identified, and in future will be developed into WEO/ESGE training centers, to provide local training in both basic and advanced endoscopy according to the needs of the area.

Diagnosis of intraductal papillary mucinous neoplasm using endoscopic ultrasound guided microbiopsies: A case report

Pancreatic cysts are increasingly diagnosed due to expanding use of cross-sectional imaging, but current diagnostic modalities have limited diagnostic accuracy. Recently, a novel through-the-needle microbiopsy forceps has become available, offering the possibility of obtaining cyst-wall biopsies. We present a case of 41-year-old male with chronic pancreatitis and a 2-cm pancreatic cyst, initially considered a pseudocyst. Subsequently, endoscopic ultrasound guided microbiopsies were successfully obtained, which surprisingly revealed an intraductal papillary mucinous neoplasm of mixed subtype with low grade dysplasia. In conclusion, obtaining biopsies from the wall of the pancreatic cystic lesions with this novel instrument is feasible and, as demonstrated in this case, can possibly alter the clinical outcome. Microbiopsies offered enough cellular material, allowing supplemental gene mutation analysis, which combined with other modalities could lead to a more individual approach when treating pancreatic cysts. However, prospective studies are warranted before routine clinical implementation.