Diagnostic use of endoscopic full-thickness wall resection (eFTR)-a novel minimally invasive technique for colonic tissue sampling in patients with severe gastrointestinal motility disorders.

BACKGROUND: Complex gastrointestinal (GI) motility disorders such as chronic intestinal pseudo-obstruction (CIPO) or Hirschsprung's disease (HD) are challenging to diagnose and treat appropriately. Thorough assessment of patient history, radiographic exams, endoscopy, and motility measurements aid in diagnostic workup, yet underlying histology is the cornerstone to enable a more distinct diagnosis of neuromuscular GI disorders. Traditionally, surgical procedures have been performed to obtain specimen suitable for accurate histologic analysis. METHODS: We performed endoscopic full-thickness resection (eFTR) using a full-thickness-resection device (FTRD) under moderate propofol sedation in four patients with suspected severe neuromuscular gut disorders including CIPO. KEY RESULTS: The mean age of the four patients was 43 y (range 19-56 y). Technical and histological success providing large colonic full-thickness tissue samples of excellent quality was achieved in all four patients (success rate 100%). The mean procedure time was 12 min (range 5-20 min). The mean diameter of the resected specimen was 21 mm (range 20-22 mm). No adverse events connected to the procedure itself occurred. Histology ranged from aganglionosis such as Hirschsprung's disease (HD) to hypoganglionosis and eosinophilic leiomyositis combined with lymphocytic ganglionitis in a third patient. Histology was unspecific in one patient. CONCLUSION AND INFERENCES: EFTR allows safe and minimal invasive harvesting of ample full-thickness tissue samples for accurate histological analysis in patients with suspicion of neuromuscular gut disorders.

Safe and successful resection of difficult GI lesions using a novel single-step full-thickness resection device (FTRD®).

BACKGROUND AND STUDY AIMS: Classic endoscopic resection techniques (EMR and ESD) are limited to mucosal lesions. In the case of deeper growth into the gut wall and anatomic sites prone to perforation, the novel full-thickness resection device (FTRD®) opens a new dimension of possibilities for endoscopic resection. PATIENTS AND METHODS: Sixty patients underwent endoscopic full-thickness resection (eFTR) at our institution. Safety, learning curve, R0 resection rate, and clinical outcome were studied. RESULTS: In 97% (58/60) of the interventions, the FTRD®-mounted endoscope reached the previously marked lesion and eFTR was performed (technical success). Full-thickness resection was achieved in 88% of the cases, with an R0 resection on histological examination in 79%. The clinical success rate based on follow-up histology was even higher (88%). Adverse events occurred in 7%. Appendicitis of the residual cecal appendix after eFTR of an adenoma arising in the appendix led to the only post-eFTR surgery (1/58, 2%). Minor bleeding at the eFTR site (2/58, 3%) and an eFTR performed accidently without proper prior deployment of the OTSC® (1/58, 2%) were successfully treated endoscopically. There was no secondary perforation or eFTR-associated mortality. CONCLUSIONS: After specific training, eFTR is a feasible, safe, and promising all-in-one endoscopic resection technique. Our data show that eFTR allows complete resection of lesions affecting layers of the gut wall beneath the mucosa with a low risk of adverse events. However, our preliminary results need to be confirmed in larger, controlled studies.

[Pharyngoesophageal diverticulum]. / Pharyngoösophageale Divertikel.

Over the last 20-30 years, treatment of pharyngoesophageal diverticula was subject to a number of fundamental changes. Considering the classical open transcervical approaches, the necessity for myotomy of the upper esophageal sphincter with the goal of interrupting the pathogenesis of the disease has become a standard component of the operation. On the other hand, with the growing popularity of rigid and flexible endoscopic techniques, pharyngoesophageal diverticula are increasingly being treated by gastroenterologists and otorhinolaryngologists, often with the argument of a technically easier and less invasive procedure; however, it remains unclear whether this shift towards endoscopic techniques truly translates into better outcome quality. This aim of this CME article is to summarize the available scientific evidence on the complex pathophysiology, diagnostics and treatment of pharyngoesophageal diverticula and to provide the reader with an updated guide to best clinical practice for diagnostics and treatment.

Establishment of Over-The-Scope-Clips (OTSC®) in daily endoscopic routine.

BACKGROUND: Alongside the evolution of interventional endoscopy, the need for a more sophisticated closure tool tailored to the treatment of new challenging indications has been increasing rapidly. METHODS: We here present our collected data on 262 Over-The-Scope-Clip (OTSC®) placements in a total of 233 interventions at our institution. Follow-up was focused on clinically lasting success with regards to different indications. RESULTS: Immediate success of OTSC® treatment was observed in 87.1% of all sessions (203/233). The success rates per indication were as follows: spontaneous bleeding 84.8% (28/33); iatrogenic bleeding 100% (20/20); acute perforation 90.3% (65/72); prophylaxis for perforation 100% (24/24); anastomotic leakage 61.1% (11/18); fistulae 80.7% (46/57); diameter reduction of the gastrojejunal anastomosis 100% (6/6); and stent fixation 100% (3/3). At 30-day follow-up, the overall success rate was 67.4% (157/233). The success rates per indication were as follows: spontaneous bleeding 69.7% (23/33); iatrogenic bleeding 90% (18/20); acute perforation 86.1% (62/72); prophylaxis for perforation 100% (24/24); anastomotic leakage 33.3% (6/18); fistulae 29.8% (17/57), diameter reduction of the gastrojejunal anastomosis 83.3% (5/6); and stent fixation 66% (2/3). CONCLUSIONS: Our cohort confirms previous data on the clinical usefulness of the OTSC® in daily routine practice.

18FDG-PET-CT improves specificity of preoperative lymph-node staging in patients with intestinal but not diffuse-type esophagogastric adenocarcinoma.

INTRODUCTION: The accuracy of preoperative lymph-node staging in patients with adenocarcinoma of the esophagogastric junction (AEG) or gastric cancer (GC) is low. The aim of this study was to assess the accuracy of [18F]fluorodeoxyglucose positron emission tomography/computed tomography (PET-CT) for lymph-node staging in patients with AEG or GC, with or without neoadjuvant treatment. PATIENTS AND METHODS: 221 consecutive patients with GC (n = 88) or AEG (n = 133) were evaluated. Initial staging included endoscopic ultrasound (EUS), multidetector spiral CT (MDCT) and PET-CT. PET-CT was performed for restaging in patients after neoadjuvant treatment (n = 94). Systematic lymphadenectomy was routinely performed with histopathological assessment of individual mediastinal and abdominal lymph-node stations. Preoperative staging from EUS, MDCT, and PET-CT was correlated with histopathological results. RESULTS: PET-CT showed a high specificity (91%) and positive predictive value (89%) for the preoperative detection of lymph-node metastases. In comparison, EUS was more sensitive (73% versus 50%, P < 0.01) but less specific (60%, P < 0.01). In patients with intestinal/mixed-type tumors, PET-CT improved the detection of extra-regional lymph-node metastases (P = 0.01) and distant metastases (P = 0.01) compared to CT alone. In contrast, lymph-node assessment by PET/CT after neoadjuvant treatment (32%, P < 0.01) and in diffuse-type cancers (24%, P < 0.01) is futile because of low sensitivities. CONCLUSION: PET-CT does not improve the overall accuracy of N staging, but does improve specificity compared to EUS and MDCT in AEG and GC. We do not recommend routine PET-CT for the initial staging in patients with diffuse-type cancer or for restaging of lymph nodes after neoadjuvant treatment.

Epigenetic silencing of monoallelically methylated miRNA loci in precancerous colorectal lesions.

Epigenetic silencing of protein-encoding genes is common in early-stage colorectal tumorigenesis. Less is known about the methylation-mediated silencing of genes encoding microRNAs (miRNAs), which are also important epigenetic modulators of gene expression. Using quantitative PCR, we identified 56 miRNAs that were expressed in normal colorectal mucosa and in HT29 colorectal cancer cells treated with demethylating agents but not in untreated HT29 cells, suggesting that they probably undergo methylation-induced silencing during colorectal tumorigenesis. One of these, miR-195, had recently been reported to be underexpressed in colorectal cancers and to exert tumor-suppressor effects in colorectal cancer cells. We identified the transcription start site (TSS) for primary miRNA (pri-miR)-497/195, the primary precursor that yields miR-195 and another candidate on our list, miR-497, and a single CpG island upstream to the TSS, which controls expression of both miRNAs. Combined bisulfite restriction analysis and bisulfite genomic sequencing studies revealed monoallelic methylation of this island in normal colorectal mucosa (50/50 samples) and full methylation in most colorectal adenomas (38/50; 76%). The hypermethylated precancerous lesions displayed significantly downregulated expression of both miRNAs. Similar methylation patterns were observed at two known imprinted genes, MEG3 and GNAS-AS1, which encode several of the 56 miRNAs on our list. Imprinting at these loci was lost in over half the adenomas (62% at MEG3 and 52% at GNAS-AS1). Copy-number alterations at MEG3, GNAS-AS1 and pri-miR-497/195, which are frequent in colorectal cancers, were less common in adenomas and confined to tumors displaying differential methylation at the involved locus. Our data show that somatically acquired, epigenetic changes at monoallelically methylated regions encoding miRNAs are relatively frequent in sporadic colorectal adenomas and might contribute to the onset and progression of these tumors.

[Gastro-highlights 2012]. / Gastro-Highlights 2012.

The annual Gastro Highlights training event, held at the university Hospital Zurich last autumn, also celebrated the 60th birthday of prof.Dr.med. Michael Fried, who initiated this widely recognized event 17 years ago. Featured at the symposium was a round up of the most important new discoveries in the field of gastroenterology and hepatology to be published during the course of the previous year or represented at the Digestive Disease Week (DDW). To mark the birthday of Prf. Dr. med. Michael Fried, two international experts made a special report on the key developments in the gastroenterology to emerge over the past decades.

Complex anastomotic leaks following esophageal resections: the new stent over sponge (SOS) approach.

A new approach for the treatment of complicated anastomotic leaks following esophageal resections by combining vacuum-assisted therapy with covered self-expanding stents is reported. This is not an approach for a simple leak but a rescue maneuver for complex uncontained leaks. It is known that anastomotic leakages particularly situated in the chest can be successfully treated with endoscopically placed self-expanding stents with/without additional drainage. If this approach fails, reoperation with substantial morbidity is frequently necessary. Two complicated anastomotic leakages refractory to stenting alone were successfully treated with the combination of an endo-sponge-assisted device covered by a self-expanding metallic stent. If stent therapy fails or the perianastomotic abscess cavity is large and complex to drain from outside, the endoscopic two-modality approach can be considered.

Colorectal polypectomy during insertion and withdrawal or only during withdrawal? A randomized controlled trial.

BACKGROUND AND STUDY AIMS: Removal of colorectal polyps is routinely performed during withdrawal of the endoscope. However, polyps detected during insertion of the colonoscope may be missed at withdrawal. We aimed to evaluate whether polypectomy during both insertion and withdrawal increases polyp detection and removal rates compared with polypectomy at withdrawal only, and to assess the duration of both approaches. PATIENTS AND METHODS: Patients were included into the study when the first polyp was detected, and randomized into two groups; in group A, polyps ≤ 10 mm in diameter were removed during insertion and withdrawal of the colonoscope, while in group B, these polyps were removed at withdrawal only. Main outcome measures were duration of colonoscopy, number of polyps detected during insertion but not recovered during withdrawal, technical ease, patient discomfort, and complications. RESULTS: 150 patients were randomized to group A and 151 to group B. Mean (± standard deviation [SD]) duration of colonoscopy did not differ between the groups (30.8 ± 15.6 min [A] vs. 28.5 ± 13.8 min [B], P = 0.176). In group A 387 polyps (mean 2.58 per colonoscopy) were detected and removed compared with 389 polyps detected (mean 2.58 per colonoscopy) in group B of which 376 were removed (13 polyps were missed, mean size [SD] 3.2 [1.3] mm; 7.3 % of patients). Patient tolerance was similar in the two groups. CONCLUSIONS: Removal of polyps ≤ 10 mm during withdrawal only is associated with a considerable polyp miss rate. We therefore recommend that these polyps are removed during both insertion and withdrawal.

Successful treatment of anastomotic jejunal varices with N-butyl-2-cyanoacrylate (Histoacryl): single-center experience.

Obscure gastrointestinal bleeding can lead to extensive diagnostic work-up, as well as repeated episodes of hospitalizations with significant morbidity. Patients with a previous small-bowel anastomosis seem to be prone to varices at this site, even in the absence of portal hypertension. We report here five cases with varices of this type. All the anastomoses in these patients were reached using overtube-assisted single- or double-balloon enteroscopy. The bleeding varices were treated by injecting N-butyl-2-cyanoacrylate (Histoacryl). Bleeding was stopped in all five patients without any adverse events, requiring one session in four patients and a second session in one patient.

[Highlights in gastroenterology 2011]. / Gastro-Highlights 2011. Zusammenfassung der Referate anlässlich des gastroenterologischen Symposiums am Universitätsspital Zürich vom 10. September 2011 unter der Leitung von Professor Michael Fried.

«Gastro-Highlights¼, an annual symposium dedicated to continuing education, took place at the University Hospital Zürich for the sixteenth time this autumn. In this well-attended event, major new findings in the fields of gastroenterology and hepatology that were published in the past year or recently presented at the «Digestive Disease Week (DDW)¼ were summarized for practising gastroenterologists and internists.

[New options for helicobacter pylori antibiotic treatment]. / Neue Möglichkeiten der Helicobacter-pylori-Behandlung mit Antibiotika.

Helicobacter plays a central role in the pathogenesis of several gastric diseases and its eradication has a therapeutic or prophylactic effect in many clinical situations. However, treatment of Helicobacter infection can be challenging and the frequently recommended clarithromycin based triple therapy fails in more than 20% of patients. Reasons for treatment failure include antibiotic resistances and bacterial persistence in an acidic stomach, for instance due to rapid metabolization of the proton pump inhibitor by the host. Therapeutic efficiency can be improved by a therapy tailored for an individual patient and the respective pathogen. In an alternative approach the antibiotic therapy can be intensified leading to a sequential or concomitant therapy. These and other strategies tested only in single studies can achieve eradication in 90 % and up to over 95 % of patients, respectively, and should be used more often in clinical practice.

"Sparing the surgeon": clinical experience with over-the-scope clips for gastrointestinal perforation.

With increasingly advanced therapeutic endoscopic procedures and more complex gastrointestinal surgery, endoscopists are more often confronted with perforations, fistulas, and anastomotic leakages for which nonsurgical closure is desired. The over-the-scope clip (OTSC) is a novel endoscopic tool for consideration in such situations. We treated seven patients (age range 35 - 83 years; five men, two women), three with colonic perforation, one with perforation of the stomach, and three with anastomotic leakage after gastrointestinal surgery. Follow-up was at least 74 days. Eight OTSCs were deployed. In all but one patient closure of the perforation was demonstrated. Further surgery was avoided in four of the seven patients. The OTSC is a system that is easy to handle and safe. It seems to be ideally suited to use for a relatively small (iatrogenic) perforation, where a single clip can be released with carbon dioxide insufflation. Anastomosis leakage and larger dehiscence can also be treated to avoid further surgery, but the utility in this situation needs to be defined in the future.

[Highlights in gastroenterology 2010]. / Gastro-Highlights 2010.

This summer saw the fifteenth edition of «Gastro-Highlights¼, a well-attended symposium dedicated to continuing education that takes place each year at the University Hospital in Zurich. Major new findings in the fields of gastroenterology and hepatology that were achieved in the past year and were recently presented at the «Digestive Disease Week (DDW)¼ were summarized here for practising gastroenterologists and internists.

Value of combined 6-[18F]fluorodihydroxyphenylalanine PET/CT for imaging of neuroendocrine tumours.

BACKGROUND: Accurate knowledge of tumour presence and location is essential to treat neuroendocrine tumours (NETs). Standard imaging has been hampered by low sensitivity and lack of spatial resolution. This study assessed prospectively the diagnostic value and impact of combined 6-[18F]fluorodihydroxyphenylalanine positron emission tomography-computed tomography (18F-DOPA-PET/CT) in the management of NET. METHODS: 18F-DOPA-PET/CT findings in 61 patients with suspected NET were compared with a composite reference standard including somatostatin receptor scintigraphy (SRS), magnetic resonance imaging, computed tomography, histological examination and clinical follow-up. The impact on clinical management was estimated by calculating the proportion of patients whose treatment changed as a result of 18F-DOPA-PET/CT findings. RESULTS: 18F-DOPA-PET/CT correctly identified 32 of 36 patients with NET. The sensitivity and specificity of 18F-DOPA-PET/CT for the detection of NET were 91 and 96 per cent respectively. Sensitivity using SRS was significantly lower (59 per cent), whereas the specificity was similar (86 per cent). In 16 (26 per cent) of the 61 patients the management was altered as a result of new findings on 18F-DOPA-PET/CT. CONCLUSION: 18F-DOPA-PET/CT yields a high sensitivity and specificity in the detection of NET. The clinical impact was highly relevant as changes in therapy were observed in more than a quarter of the patients.