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UEG Week 2013 highlights: putting endoscopy into perspective
Authors
Ioannis S. Papanikolaou1, Peter D. Siersema2
Institutions
1
Bibliography DOI http://dx.doi.org/ 10.1055/s-0033-1359089 Endoscopy 2013; 45: 1047– 1053 © Georg Thieme Verlag KG Stuttgart · New York ISSN 0013-726X
The 21st United European Gastroenterology (UEG) Week was held in Berlin in October 2013 and presented the opportunity for those interested in gastrointestinal endoscopy to learn of recent developments and research trends from all
over the world. This report highlights oral presentations of the most important and exciting topics in gastrointestinal endoscopy and reviews them in the context of current knowledge.
Esophageal disease
type distinct from eosinophilic esophagitis. The underlying mechanism is unknown. In a study from Spain [2], baseline and long-term eotaxin-3 levels and Th2 cytokine expression profiles were determined in patients with suspected eosinophilic esophagitis. Of the 47 patients included, 23 patients (46 %) had PPI-REE. No differences were observed between patients with PPI-REE and those with eosinophilic esophagitis in terms of demographics, symptoms, endoscopic findings, esophageal eosinophilia, and baseline molecular characteristics. PPI therapy significantly downregulated eotaxin-3 levels and Th2 cytokine expression profiles in PPI-REE patients in a similar way to that observed in patients with eosinophilic esophagitis after topical steroids. These results show that both PPI-REE and eosinophilic esophagitis are similar cytokine-mediated entities, and more research is needed to investigate whether PPI-REE is indeed distinct from eosinophilic esophagitis. Continuing efforts are being made to find alternative treatment modalities for steroids in eosinophilic esophagitis. CRTH2 (chemo-attractant receptor-homologous molecule expressed on Th2 cells) is a receptor expressed by Th2 cells and eosinophils that mediates chemotaxis and activation in response to prostaglandin D2. OC000459 is a selective CRTH2 antagonist that blocks the ability of prostaglandin D2 to recruit and activate Th2 cells and eosinophils, and may be able to suppress tissue inflammation associated with eosinophilic esophagitis. In a randomized trial [3], 26 patients with active, corticosteroid-dependent and/or -resistant eosinophilic esophagitis were treated either with 100 mg OC000459 (n = 14) or placebo (n = 12) twice daily for 8 weeks. The
!
Various case series presented during UEG Week 2013 were on the use of peroral endoscopic myotomy (POEM) for achalasia. The so-called classical treatments for achalasia include balloon dilation and botulinum toxin injection (BTI). In a randomized study from China [1], 45 patients were randomized in equal proportions to undergo POEM, BTI, or balloon dilation. Patients were compared 1 year after treatment with respect to symptom remission (Eckardt score ≤ 3). In addition, complications, lower esophageal sphincter (LES) pressure, and maximum esophageal width by barium swallow were evaluated. POEM was performed by incising the inner circular muscle, BTI by injecting 100 units (4 × 25 units in each quadrant) of botulinum toxin at the level of the LES, and balloon dilation by a single session of Rigiflex pneumatic 30mm balloon dilation to a maximum of 12 psi. Endoscopic treatments were successful in all 45 patients. Symptom remission rate at 1 year was 100 % in the POEM group, 5.4 % in the BTI group, and 64.3 % in the balloon dilation group. Complication rates were 20.0 %, 0 %, and 6.7 %, respectively. LES pressure and maximum width of esophagus were similar both before and 3 months after each of the three treatments. This study suggests that POEM may well be the preferred treatment in achalasia but further studies that include laparoscopic Heller myotomy are needed . This year only a few oral presentations reported on eosinophilic esophagitis, as no real new developments have emerged during the past year. Proton pump inhibitor-responsive esophageal eosinophilia (PPI-REE) is a recently described pheno-
Papanikolaou Ioannis S et al. UEG Week 2013 Highlights … Endoscopy 2013; 45: 1047–1053
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Corresponding author Ioannis S. Papanikolaou, MD Hepatogastroenterology Unit 2nd Department of Internal Medicine and Research Unit Attikon University General Hospital University of Athens Greece Fax: +30-210-5326422 [email protected]
Hepatogastroenterology Unit, 2nd Department of Internal Medicine and Research Unit, “Attikon” University General Hospital, University of Athens, Greece 2 Department of Gastroenterology and Hepatology, University Medical Center Utrecht, The Netherlands
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mean eosinophil number decreased from 114.7 to 74.2 eosinophils/high power field with OC000459, whereas placebo gave no reduction. The endoscopic appearance decreased from 6.3 to 5.5 with OC000459 and increased with placebo. In spite of these differences, the symptom score decreased equally in both the OC000459 group (from 16.5 to 8.8) and the placebo group (from 16.7 to 9.8). No serious adverse events occurred. This study shows that the CRTH2-antagonist OC000459 exerts a moderate anti-inflammatory effect in active eosinophilic esophagitis, but its clinical effect in terms of symptoms needs to be further established. The endoscopic detection of dysplasia in Barrett’s esophagus is challenging. Over the years, new endoscopic imaging modalities have been introduced but have not been well evaluated. In a study from the United Kingdom [4], the detection of dysplasia with autofluorescence imaging (AFI) + probe-based confocal laser endomicroscopy (pCLE) was compared with AFI + narrow band imaging with zoom (NBI) in 39 patients with different grades of Barrett’s esophagus. pCLE had a higher sensitivity for dysplasia than NBI but a lower specificity. In the per-patient analysis, pCLE correctly classified all but one dysplastic patient, leading to a higher diagnostic accuracy than NBI. pCLE analysis also required a shorter time than the Seattle protocol. It was concluded that AFI + pCLE allows accurate in vivo diagnosis of dysplasia in Barrett’s esophagus and may have the potential to enable clinicians to dispense with multiple random biopsies currently taken during endoscopic surveillance. In a study from Sweden [5], the yield of neoplasia of high definition magnification endoscopy (HDME, Fujinon EG-590ZW) with multiple band imaging (MBI) was compared with 4-quadrant biopsies using white light endoscopy (WLE; Olympus GIF-Q160) in a randomized crossover trial. Of 110 patients, 59 were randomized to HDME with MBI and 51 to WLE as the first investigating procedure. Four of 107 patients showed Barrett’s esophagus with high grade dysplasia (HGD), three in the HDME group and one in the WLE group. No difference regarding the yield of low grade dysplasia (LGD) was found. The number of biopsies taken during WLE was 3 times as high as during HDME + MBI (mean 11.7 vs. 3.8). This study shows that detection of neoplasia was at least equivalent with HDME + MBI despite fewer biopsies being taken. To date, the management of Barrett’s esophagus with confirmed LGD has been unclear but early ablation may be an interesting option. In a multicenter randomized trial, the Amsterdam group [6] randomly assigned 136 patients with LGD Barrett’s esophagus to RFA + surveillance or surveillance alone. A total of 68 patients underwent RFA every 2 – 3 months (maximum of five sessions) and subsequent endoscopic surveillance with four-quadrant/2cm biopsy, while 68 underwent only endoscopic surveillance. After review at 2 years, the data safety monitoring board recommended early termination of the study protocol due to superiority of RFA. Patients in the RFA group had fewer progressions to HGD/early adenocarcinoma (EAC) (1.5 % vs. 26.5 %) and less progression to EAC (1.5 % vs. 8.8 %) compared with controls. The single case of progression in the RFA group (EAC) achieved complete eradication of dysplasia and complete eradication of intestinal metaplasia after endoscopic resection. Of the 18 cases of progression in the control group (12 HGD, 6 EAC), 1 underwent esophagectomy (T1bN0M0) and 17 underwent endoscopic treatment or surveillance. Adverse events occurred in 13 RFA patients (19 %) and 4 controls (6 %, all those with progression who underwent therapy). The most common adverse event was stenosis: 12 % in
the RFA group (n = 8) and 3 % in the control group (n = 2). This is a milestone study as it shows that preventive RFA treatment in patients with LGD Barrett’s esophagus is able to reduce, if not eliminate, neoplastic progression in Barrett’s esophagus; however, long-term results are needed.
Endoscopic treatment !
Because neither en bloc resection nor assessment of the resection margin can be obtained with piecemeal endoscopic mucosal resection (EMR) for larger esophageal lesions, endoscopic submucosal dissection (ESD) seems a promising alternative and is now being increasingly used for these lesions. However, the technical difficulty of ESD has repeatedly been shown to be associated with a higher complication rate. During UEG Week 2013, several studies presented the results of ESD for esophageal lesions. In a study from China [7], 63 patients with an esophageal lesion ≥ 15 mm underwent piecemeal EMR and 198 patients underwent ESD. The local recurrence rate was higher in the piecemeal EMR group than in the ESD group (11.5 % vs. 3.7 %), although both groups obtained the same tumor-free rate of deep margins. Severe shortterm complications, including severe bleeding and perforation, were similar between the groups. Esophageal stricture occurred more frequently in the piecemeal EMR group (6.2 % vs. 23.0 %), probably due to the larger circumferential mucosal defect in this group. Local recurrence after ESD was related to tumor size, and procedure time, tumor size, and percentage of the circumferential mucosal defect were independent risk factors for postoperative stricture. ESD seems superior to piecemeal EMR for large superficial esophageal lesions but randomized studies, particularly in Western countries, are needed to evaluate whether the results on ESD can be repeated. An ongoing debate is whether ESD for early gastric cancer (EGC) can also be performed beyond the established criteria for ESD. In Japan, “expanded resection criteria” have been defined since the introduction of ESD [8] and using Gotoda’s data on the risk for lymph node metastasis in EGC [9]. In Western guidelines, endoscopic resection is performed for small, well differentiated lesions without submucosal invasion (“guideline criteria”). For lesions beyond these criteria, surgery is recommended. Only a few follow-up data are available from Europe after resection of expanded criteria lesions. In a study from Germany [10], ESD for EGC was performed in 114 cases, with 94 resections performed according to the expanded criteria (82.5 %). Expanded criteria known prior to resection were lesion diameter in 77 /94 lesions (81.9 %) and ulceration in 9 lesions (7.9 %). Expanded criteria after resection included a G3 histology in 16 lesions (17 %), submucosal infiltration in 16 (17 %), and an L1 histology in 5 (5 %), for which surgery was advised. For expanded criteria, the en bloc resection rate was 87.2 % (82 /94) and the R0 resection rate was 72.3 % (68 /94). There were six recurrences (five after piecemeal resection, one after en bloc resection). Therefore, in Europe, ESD in EGC fulfilling the expanded resection criteria also seems to be an adequate treatment for this subgroup; however, longer follow-up data are required. Postoperative bleeding is a major complication after ESD for EGC and it occurs in up to 11.3 % of cases [11]. Second-look endoscopy (SLE) on the day after ESD to evaluate bleeding is often performed but the effectiveness of SLE in prevention of post-ESD bleeding remains controversial. In a randomized study from Japan [11], 130 patients were assigned to SLE and 132 to a wait-and-see pol-
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icy. Post-ESD bleeding occurred in 7 /130 patients (5.5 %) in the SLE group and in 5 /126 patients (3.8 %) in the non-SLE group, meeting the predefined noninferiority criterion of 7 %. All bleeding cases and one case of postoperative perforation were successfully managed with conservative treatment without the need for blood transfusion or surgery. This study clearly shows that SLE after gastric ESD is not required because it contributes little or not at all to the prevention of post-ESD bleeding. Submucosal tunneling endoscopic resection (STER) has emerged as a new technique for resecting upper gastrointestinal subepithelial tumors (SETs). The advantages of STER over ESD are that the anatomic structure of the digestive tract is maintained, the risk of pleural/abdominal infection is reduced, and rapid wound healing is promoted. Endoscopic resection with STER performed through a submucosal tunnel to the lesion without interruption of the lesion is the goal of treatment. If gastric SETs connect tightly to the underlying muscularis propria or serosal layer, the lesion can be resected with these underlying layers. Frequently, pneumoperitoneum develops during and after the procedure, but this can be relieved with a 20-G needle. A single-center experience from China [12] reported complete resection of all 71 SETs using STER. Histology included 53 leiomyomas, 17 gastrointestinal stromal tumors, and 1 calcifying fibrous tumor. There were no complications reported. Another study from China [13] evaluated the STER method in submucosal tumors originating from the muscularis propria at the esophagogastric junction. The esophagogastric junction is a difficult location for endoscopic resection due to its narrow lumen and sharp angle. A total of 76 SETs originating from the muscularis propria were removed using STER. The mean diameter was 21.5 mm (range 6 – 35 mm) and the mean procedure time was 47 minutes (range 15 – 120 minutes). The en bloc resection rate was 100 % (76 /76). Histology included 61 leiomyomas, 10 gastrointestinal stromal tumors, 1 intramuscular lipoma, 1 granular cell tumor, and 1 schwannoma. No delayed hemorrhage or severe adverse events were reported. Over a period of 12 – 24 months, no local recurrence or distant metastasis was observed. These two studies show that STER is safe, effective, and provides accurate histologic evaluation for SETs in the deeper layers but also at the technically more challenging locations in the upper gastrointestinal tract.
Gastrointestinal bleeding !
Gastrointestinal bleeding and endoscopic hemostasis is a field of endoscopy that attracts a lot of attention because technical advances can be rapidly incorporated into routine clinical practice. At UEG Week 2013, there were fewer abstracts on gastrointestinal bleeding compared with last year’s meeting, continuing a trend that has been noted previously [14, 15]. However, some innovative hemostatic techniques that were introduced at previous meetings appear to be finding their way into everyday practice. For example, Hemospray (Cook Medical) is a new inorganic nanopowder with clotting abilities, which is sprayed onto a bleeding site via a 10-Fr catheter in order to treat bleeding peptic ulcers, uncontrollable diffuse or cancer-related bleeding [16, 17]. Limited initial experience was presented at last year’s meeting [18]. However, at this year’s meeting it appeared that the method is not only gradually being established as treatment for its initial indications [19] but is also broadening its therapeutic applications to include variceal bleeding [20]. A bicentric prospective pilot trial included nine patients with acute variceal bleeding; he-
mostasis was achieved with application of 21 g of Hemospray. No rebleeding occurred within 24 hours (although it was not stated what happened after the first day), nor was there any mortality within 15 days of follow-up. The same group reported similar encouraging results in two patients with acute bleeding from duodenal varices [21]. These preliminary reports are in line with other recently published cases [22, 23] and provide hope that the new spray will be used not only to control peptic ulcer or diffuse bleeds, but may also be an effective tool in treating portal hypertension-associated hemorrhage, which in many cases can be life threatening. The other “new” device that was presented as a hemostatic tool was the Over-The-Scope Clip (OTSC), which has been presented at previous UEG Weeks [15], mostly as a means of endoscopic closure for natural orifice transluminal endoscopic surgery [24, 25]. This year, a multicenter Italian study attempted to evaluate whether, by compressing large amounts of tissue, the OTSC could be superior to “standard” (i. e. through the scope) clips for hemostasis in 48 consecutive patients who underwent emergency endoscopy for nonvariceal gastrointestinal bleeds (40 upper, 8 lower). OTSC were placed after failure of conventional hemostatic therapy and repeat endoscopy was performed 2 – 4 days after the first procedure. Primary hemostasis was achieved in 46 /48 cases (96 %); 2 failures and 2 cases of rebleeding occurred (12 and 24 hours postprocedure, both of which were successfully treated with saline/adrenaline injection) [26]. These results endorse the use of the OTSC as an effective treatment for hemostasis when conventional modalities fail. However, issues such as training, availability, and costs should also be taken into account when deciding whether to use them in daily clinical practice.
Colonoscopy topics !
Screening and surveillance colonoscopy for colorectal cancer (CRC) is a field that incorporates essential topics of interest to endoscopists, including colonoscopy quality and training, innovative technologies, and management of detected polyps. It is therefore not surprising that colonoscopy is an important subject for major endoscopy societies [27, 28] and is an area highly represented at UEG Week. Interval cancers (i. e. cancers diagnosed shortly after complete colonoscopy), constitute a major concern for the endoscopist and a threat to CRC screening. The majority of such lesions seem to arise from incompletely removed lesions or ones that are missed during initial colonoscopy [29, 30]. This finding was also suggested by a study presented at UEG Week 2013, which attempted to assess the association between colonoscopy quality indicators and 17 interval cancers that were found in 13 048 symptomatic and high-risk individuals with previous normal colonoscopies in an academic center (mean time to cancer was 1.65 ± 1.32 years). With the exception of increasing age, a low polyp detection rate was the most important risk factor associated with interval cancer [31]. New sophisticated imaging techniques have been widely incorporated into colonoscopes in the hope of improving the detection of polyps, but until now do not seem to have resulted in a significant breakthrough [32, 33]. This year, however, some new technologies were presented that could have a positive impact on the detection of polyps, especially adenomas. The first new technology is full spectrum endoscopy (Fuse) colonoscopy (EndoChoice), which allows 330° viewing projected onto three viewing screens.
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Initial results showed the technique to be feasible, safe, and user friendly [34]. An international multicenter working group recruited 185 patients and evaluated its performance in two prospective randomized tandem studies. The first study found that the incremental adenomas detected by Fuse after standard colonoscopy were higher than when standard colonoscopy followed Fuse (71.4 vs. 8.2 % respectively); moreover, the adenoma miss rate for standard colonoscopy was higher than that of Fuse (41.7 vs. 7.6 %) [35]. The second study highlighted the fact that Fuse could help to improve protection against interval cancers by significantly impacting adenoma surveillance recommendations, as it shortened examination intervals in 60 % of cases in which Fuse detected adenomas that standard colonoscopy had missed, whereas standard colonoscopy had no impact on surveillance recommendations [36]. The other technological advancement aimed at improving polyp and adenoma detection rate is a novel balloon colonoscope (NaviAid G-EYE; Smart Medical Systems Ltd.) [37]. The idea of using an endoscope endowed with a balloon to examine the colon is not new, as balloon enteroscopes (double and single) have been used effectively for completion of colonoscopy in cases with incomplete conventional examinations [38]. The new device consists of a standard colonoscope with a permanently integrated balloon at its distal end. The aim of the balloon is to improve colon visibility. The scope is inserted with the balloon deflated until it reaches the cecum, at which point the balloon is inflated to a medium pressure and the balloon colonoscope is withdrawn, allowing the intestinal folds to be straightened. An interim analysis of the first 74 patients (out of 126 planned) was presented. Additional polyp detection rate was 115 % when balloon colonoscopy followed standard colonoscopy compared with only 4.5 % when standard colonoscopy followed balloon colonoscopy. These results support the use of the balloon colonoscope and the withdrawal technique to reduce the polyp miss rate of colonoscopy. What about the management of the polyps that are detected? Data presented by an Austrian team suggest that we are not always resecting polyps in the way we should and that polyps of 5 – 10 mm in size are often inadequately resected (i. e. using a biopsy forceps instead of a snare) [39]. Though small, treatment of these polyps should be performed according to guidelines, as interval carcinoma may develop at the site of an inadequate polypectomy.
Small-bowel enteroscopy !
The modalities used nowadays for the endoscopic examination of the small bowel are video capsule endoscopy (VCE) and pushand-pull enteroscopy (i. e. double- and single-balloon enteroscopy and enteroscopy with a spiral overtube or spiral enteroscopy) [40]. The push-and-pull techniques have some differences between them and, despite a lot of discussion regarding the superior modality [41, 42], they can all be used effectively in the everyday clinical management of small-bowel pathologies. However, the fact that these modalities have gradually evolved from “novel” to “routine” has created a trend towards fewer enteroscopyrelated oral presentations at recent UEG Week meetings [14, 15]. One of the few reports this year on new enteroscopes was on a prototype short single-balloon enteroscope designed for endoscopic retrograde cholangiopancreatography (ERCP) in patients with surgically altered anatomy. The device was characterized as “effective” (though not spectacularly superior) compared with
historical results of the performance of a standard enteroscope [43]. VCE was slightly better represented by oral presentations due to technical innovations or alterations that have been incorporated into the established VCE. Reports on VCE steering were presented at UEG Week 2010 [44] and since then there has been steady progression of this device including therapeutic attempts presented at the subsequent two meetings [14, 15]. It seems that the quest for steerable VCE that can even perform biopsies and/or therapy is well underway [45, 46]. In this context, a Japanese study group, which last year presented a capsule that could perform a complete gastrointestinal screen with its position being recognized by remote portable devices [47], presented a wireless internetlinked robotic capsule endoscope endowed with therapeutic tools and a biopsy device (iRoboCap) based on the “traditional” PillCam SB2 (Given Imaging). Real-time viewing was available (with some time lag), and the capsule was steered with a joystick in a phantom and a pig’s stomach [48]. Despite battery problems, the transmission lag, difficulties in overcoming sphincter contraction, and biopsy acquisition (50 % success), the iRoboCap could become an experimental platform for an alternative VCE. Another new capsule was also presented (“Capsovision”), which has four cameras to allow a 360° examination of the small-bowel lumen. In a French multicenter trial, 73 patients with obscure gastrointestinal bleeding were recruited to ingest Capsovision and PillCam SB2 in a randomized order and with a 1-hour interval between. Disappointingly there were 13 technical issues (11 with Capsovision, 2 with PillCam) allowing only 60 patients to be finally analyzed. Concordance was good (kappa value 0.63; 46.7 % diagnosis with Capsovision vs. 48.3 % with PillCam), and Capsovision detected more lesions (108 vs. 85; P = 0.001), but at a cost of a longer reading time (32.0 vs. 26.2 minutes; P = 0.002) [49]. A possible pitfall is that the device currently has no recording system and therefore the capsule must be retrieved and returned after its expulsion in order to download the film.
ERCP and pancreatobiliary topics !
ERCP and pancreatobiliary endoscopy maintained the importance they demonstrated at previous meetings [14, 15]. For example, biliary drainage and stenting remained “hot” issues. Benign biliary strictures can be treated with placement of one or multiple plastic stents (“multistenting”) or covered removable self-expandable metal stents (CRSEMS) in the bile duct [50]. However, as most data from published series regarding these approaches lack big patient numbers or long-term outcomes, further reports are still needed. In a prospective, multicenter randomized study from Finland, 60 patients with biliary strictures due to chronic pancreatitis have been recruited since 2008 [51]. At the initial ERCP, a single plastic stent was placed, followed by randomization at the next ERCP to either CRSEMS or three plastic stents (with three more plastic stents added 3 months later), followed by stent removal 6 months after randomization. Clinical follow-up was performed 6 and 24 months after stent removal. To the date of abstract submission, 59 % of the patients in the plastic stent group and 53 % in the CRSEMS group had finished their follow-up. Relief from the strictures was seen in both groups, with bilirubin and alkaline phosphatase levels falling to similar levels, diameter of the common bile duct above the stricture dropping from 12 and 13 mm, respectively, to 7 mm in both groups, and stricture recurrence of 6 % in both groups. Morbidity
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ductal papillary mucinous neoplasm (IPMNs) of the main pancreatic duct was 100 % and 73.3 %, respectively. When considering its value as a therapeutic tool, the system achieved complete clearance in 74.2 % of cases with bile duct stones, but in only 28.6 % of cases with lithiasis in the pancreatic duct. Outcome reports such as this are of high interest, as they show us the applicability of a method in the “real world” outside of the “protected” environment of studies.
Endoscopic ultrasonography !
The role of endoscopic ultrasonography (EUS) has more recently been widely recognized. The method is no longer considered to be a specialist technique for a small group of endoscopists but rather an important tool that can be used to tackle a plethora of diagnostic and therapeutic problems both within [58, 59] and outside of the gastrointestinal tract [60, 61]. The advent of EUSguided fine-needle aspiration (EUS – FNA) gave EUS a new boost, and resulted not only in an improvement in its diagnostic ability but also involvement in therapeutic maneuvers. Without it, EUS would probably still exist as a diagnostic tool with limited indications. An important recent advancement of therapeutic EUS is EUSguided biliary drainage, a rescue technique used in cases of failed (or impossible to perform) ERCP [62]. Among its existing variants, biliogastric anastomosis or hepaticogastrostomy has been frequently reported [63]. Outcomes from hepaticogastrostomy in 61 patients (65 attempted procedures) in a high-volume center in France were retrospectively analyzed [64]. The procedure was chosen following failure to perform ERCP overall or a failure to reach the papilla or to achieve left biliary drainage (33 %, 16 %, and 51 %, respectively). The technical success rate of hepaticogastrostomy was 94 % and stent migration occurred in 11 %. Morbidity was 33 % (including pneumoperitoneum [n = 5], bile leakage [n = 7], bleeding [n = 1], and sepsis [n = 1], all of which were effectively treated, apart from one death). Various stents were used, but partially covered metallic stents appeared to be associated with reduced morbidity. In addition to EUS-guided biliary drainage, drainage of peripancreatic fluid collections is also an established indication for EUS. As the effectiveness of this method was often limited by the small diameter of plastic stents that were typically used, large-diameter, fully covered, self-expanding metal stents with anchoring devices have been used and were reported at last year’s UEG Week with promising results [65]. These positive preliminary data were further confirmed this year in multicenter studies using more than one type of large-diameter metal stent [66, 67]. Another interesting EUS topic that attracted interest during UEG Week 2013 is the optimal diagnostic and therapeutic approach of pancreatic cystic lesions, including IPMNs [14, 15]. Classical tools in this include imaging [68] and EUS – FNA [69]. Results from a combination of both approaches (i. e. needle-based CLE) in the interpretation of pancreatic serous cystadenomas, were presented in a prospective multicenter study from France (20 patients) [70]. Classical EUS was initially performed, followed by EUS – FNA and advancement of the special AQ-Flex 19 miniprobe through the needle and real-time in vivo endomicroscopy of the cyst wall. Finally, intracystic fluid was analyzed. Based on a new nCLE criterion (i. e. the “superficial vascular network”), specificities and positive predictive values of 100 %, with good-to-excellent intra- and interobserver agreement were achieved. However, as nCLE is a
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and mortality were similar but migration occurred in three cases in the plastic stent group compared with one in the CRSEMS group. These results together with the easy placement of CRSEMS could make these stents the preferred treatment [51]. CRSEMS have been left even longer in the bile duct (up to 9 months) in an ongoing prospective study in six European tertiary centers. To the date of abstract submission, 36 patients had been enrolled (27 with previous endoscopic treatments). All CRSEMS were placed without complication either endoscopically or percutaneously (29 vs. 7), and the strictures resolved immediately in 35 patients (97 %). CRSEMS patency was 100 %, 80 %, and 66.4 % at 1, 6, and 9 months after placement. No migrations occurred and the CRSEMS was successfully removed in 15 cases (8 after completion of treatment). However, in seven cases the stent was retrieved earlier due to occlusion, cholangitis, choledocholithiasis, acute pancreatitis, or before planned pancreatic head resection, and stricture recurrence was observed (immediately and up to 1 month after stent removal) in 7 of 15 patients [52]. These results should be taken into consideration when deciding which strategy to follow in endotherapy of biliary strictures; further large outcome studies on this issue are required. Other routine ERCP-related topics reported this year included wire-guided cannulation of the bile duct as the method preferred by many endoscopists who perform ERCP. There are many commercially available guidewires, with different tips according to the shape of the papilla or the bile duct course and therefore choosing the optimal guidewire is an important issue. However, the need for low examination costs dictates the use of a single wire if possible when performing ERCP. A randomized trial from Japan including 225 patients compared guidewires with two different types of tips – angled or straight [53]. ERCP completion rate was 85.4 % (105 /123) in the angled vs. 73.5 % (75 /102) in the straight-tip group (P = 0.027), suggesting that angled guidewires could be considered as the first-choice wire for ERCP. Deep cannulation and complication rates were similar in both groups. Ultimately though, differences such as these might play a minor role, as endoscopists will have their preferences based on experience and the actual choice of ERCP accessories is usually a more complex issue (availability and costs play an important role). However, results from studies such as this one should be considered and are thus important. ERCP in altered gastrointestinal anatomy has been mentioned above [43]. Finally, peroral cholangioscopy has continued to attract attention at UEG Week following the advent of SpyGlass (Boston Scientific) [54], a single-operator instrument with improved handling that allows biopsies to be taken (Spybite) [54]. Following its initial use in imaging, the SpyGlass has recently advanced into the therapeutic arena not only of the bile duct [55] but also of the pancreatic duct [56]. In addition to intriguing reports from specialized centers, the clinical utility of this device in widespread application also remains interesting. In a prospective case series from 22 centers in Japan, outcomes were reported from 162 patients who underwent single-operator peroral cholangioscopy using the SpyGlass system for the diagnosis or therapy of pancreatobiliary lesions [57]. The system displayed impressive success rates, including 95.8 % for the visualization of target lesions and 76.2 % for the acquisition of adequate tissue for histology. The sensitivity and specificity were 88.1 % and 80.0 %, respectively, for SpyGlass in terms of visual impression of the bile duct and 65.1 % and 89.3 %, respectively, for biopsy sampling. The sensitivity of the system’s visual impression and directed biopsy to detect intra-
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new method, results from these first studies should be viewed with caution. In fact, limitations of nCLE in pancreatic masses were also reported this year [71]. Finally, other EUS “classics” included its role in the differential diagnosis of gastric SETs. Once again, the well known limitations of EUS – FNA [72] were confirmed, and the superiority of another approach, namely bloc biopsy using submucosal endoscopy to create a mucosal flap [73], was demonstrated [74]. However, in everyday life, such approaches are not always necessary and “plain” diagnostic EUS accompanied by simple criteria can suffice [75]. At the point when characterization of subepithelial lesions in the gastrointestinal tract is known and decisions need to be made on how aggressive treatment should be, the importance of clinical judgment should, once again, be highlighted. Competing interests: None
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UEG Week 2013 highlights: putting endoscopy into perspective
Authors
Ioannis S. Papanikolaou1, Peter D. Siersema2
Institutions
1
Bibliography DOI http://dx.doi.org/ 10.1055/s-0033-1359089 Endoscopy 2013; 45: 1047– 1053 © Georg Thieme Verlag KG Stuttgart · New York ISSN 0013-726X
The 21st United European Gastroenterology (UEG) Week was held in Berlin in October 2013 and presented the opportunity for those interested in gastrointestinal endoscopy to learn of recent developments and research trends from all
over the world. This report highlights oral presentations of the most important and exciting topics in gastrointestinal endoscopy and reviews them in the context of current knowledge.
Esophageal disease
type distinct from eosinophilic esophagitis. The underlying mechanism is unknown. In a study from Spain [2], baseline and long-term eotaxin-3 levels and Th2 cytokine expression profiles were determined in patients with suspected eosinophilic esophagitis. Of the 47 patients included, 23 patients (46 %) had PPI-REE. No differences were observed between patients with PPI-REE and those with eosinophilic esophagitis in terms of demographics, symptoms, endoscopic findings, esophageal eosinophilia, and baseline molecular characteristics. PPI therapy significantly downregulated eotaxin-3 levels and Th2 cytokine expression profiles in PPI-REE patients in a similar way to that observed in patients with eosinophilic esophagitis after topical steroids. These results show that both PPI-REE and eosinophilic esophagitis are similar cytokine-mediated entities, and more research is needed to investigate whether PPI-REE is indeed distinct from eosinophilic esophagitis. Continuing efforts are being made to find alternative treatment modalities for steroids in eosinophilic esophagitis. CRTH2 (chemo-attractant receptor-homologous molecule expressed on Th2 cells) is a receptor expressed by Th2 cells and eosinophils that mediates chemotaxis and activation in response to prostaglandin D2. OC000459 is a selective CRTH2 antagonist that blocks the ability of prostaglandin D2 to recruit and activate Th2 cells and eosinophils, and may be able to suppress tissue inflammation associated with eosinophilic esophagitis. In a randomized trial [3], 26 patients with active, corticosteroid-dependent and/or -resistant eosinophilic esophagitis were treated either with 100 mg OC000459 (n = 14) or placebo (n = 12) twice daily for 8 weeks. The
!
Various case series presented during UEG Week 2013 were on the use of peroral endoscopic myotomy (POEM) for achalasia. The so-called classical treatments for achalasia include balloon dilation and botulinum toxin injection (BTI). In a randomized study from China [1], 45 patients were randomized in equal proportions to undergo POEM, BTI, or balloon dilation. Patients were compared 1 year after treatment with respect to symptom remission (Eckardt score ≤ 3). In addition, complications, lower esophageal sphincter (LES) pressure, and maximum esophageal width by barium swallow were evaluated. POEM was performed by incising the inner circular muscle, BTI by injecting 100 units (4 × 25 units in each quadrant) of botulinum toxin at the level of the LES, and balloon dilation by a single session of Rigiflex pneumatic 30mm balloon dilation to a maximum of 12 psi. Endoscopic treatments were successful in all 45 patients. Symptom remission rate at 1 year was 100 % in the POEM group, 5.4 % in the BTI group, and 64.3 % in the balloon dilation group. Complication rates were 20.0 %, 0 %, and 6.7 %, respectively. LES pressure and maximum width of esophagus were similar both before and 3 months after each of the three treatments. This study suggests that POEM may well be the preferred treatment in achalasia but further studies that include laparoscopic Heller myotomy are needed . This year only a few oral presentations reported on eosinophilic esophagitis, as no real new developments have emerged during the past year. Proton pump inhibitor-responsive esophageal eosinophilia (PPI-REE) is a recently described pheno-
Papanikolaou Ioannis S et al. UEG Week 2013 Highlights … Endoscopy 2013; 45: 1047–1053
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Corresponding author Ioannis S. Papanikolaou, MD Hepatogastroenterology Unit 2nd Department of Internal Medicine and Research Unit Attikon University General Hospital University of Athens Greece Fax: +30-210-5326422 [email protected]
Hepatogastroenterology Unit, 2nd Department of Internal Medicine and Research Unit, “Attikon” University General Hospital, University of Athens, Greece 2 Department of Gastroenterology and Hepatology, University Medical Center Utrecht, The Netherlands
Review
mean eosinophil number decreased from 114.7 to 74.2 eosinophils/high power field with OC000459, whereas placebo gave no reduction. The endoscopic appearance decreased from 6.3 to 5.5 with OC000459 and increased with placebo. In spite of these differences, the symptom score decreased equally in both the OC000459 group (from 16.5 to 8.8) and the placebo group (from 16.7 to 9.8). No serious adverse events occurred. This study shows that the CRTH2-antagonist OC000459 exerts a moderate anti-inflammatory effect in active eosinophilic esophagitis, but its clinical effect in terms of symptoms needs to be further established. The endoscopic detection of dysplasia in Barrett’s esophagus is challenging. Over the years, new endoscopic imaging modalities have been introduced but have not been well evaluated. In a study from the United Kingdom [4], the detection of dysplasia with autofluorescence imaging (AFI) + probe-based confocal laser endomicroscopy (pCLE) was compared with AFI + narrow band imaging with zoom (NBI) in 39 patients with different grades of Barrett’s esophagus. pCLE had a higher sensitivity for dysplasia than NBI but a lower specificity. In the per-patient analysis, pCLE correctly classified all but one dysplastic patient, leading to a higher diagnostic accuracy than NBI. pCLE analysis also required a shorter time than the Seattle protocol. It was concluded that AFI + pCLE allows accurate in vivo diagnosis of dysplasia in Barrett’s esophagus and may have the potential to enable clinicians to dispense with multiple random biopsies currently taken during endoscopic surveillance. In a study from Sweden [5], the yield of neoplasia of high definition magnification endoscopy (HDME, Fujinon EG-590ZW) with multiple band imaging (MBI) was compared with 4-quadrant biopsies using white light endoscopy (WLE; Olympus GIF-Q160) in a randomized crossover trial. Of 110 patients, 59 were randomized to HDME with MBI and 51 to WLE as the first investigating procedure. Four of 107 patients showed Barrett’s esophagus with high grade dysplasia (HGD), three in the HDME group and one in the WLE group. No difference regarding the yield of low grade dysplasia (LGD) was found. The number of biopsies taken during WLE was 3 times as high as during HDME + MBI (mean 11.7 vs. 3.8). This study shows that detection of neoplasia was at least equivalent with HDME + MBI despite fewer biopsies being taken. To date, the management of Barrett’s esophagus with confirmed LGD has been unclear but early ablation may be an interesting option. In a multicenter randomized trial, the Amsterdam group [6] randomly assigned 136 patients with LGD Barrett’s esophagus to RFA + surveillance or surveillance alone. A total of 68 patients underwent RFA every 2 – 3 months (maximum of five sessions) and subsequent endoscopic surveillance with four-quadrant/2cm biopsy, while 68 underwent only endoscopic surveillance. After review at 2 years, the data safety monitoring board recommended early termination of the study protocol due to superiority of RFA. Patients in the RFA group had fewer progressions to HGD/early adenocarcinoma (EAC) (1.5 % vs. 26.5 %) and less progression to EAC (1.5 % vs. 8.8 %) compared with controls. The single case of progression in the RFA group (EAC) achieved complete eradication of dysplasia and complete eradication of intestinal metaplasia after endoscopic resection. Of the 18 cases of progression in the control group (12 HGD, 6 EAC), 1 underwent esophagectomy (T1bN0M0) and 17 underwent endoscopic treatment or surveillance. Adverse events occurred in 13 RFA patients (19 %) and 4 controls (6 %, all those with progression who underwent therapy). The most common adverse event was stenosis: 12 % in
the RFA group (n = 8) and 3 % in the control group (n = 2). This is a milestone study as it shows that preventive RFA treatment in patients with LGD Barrett’s esophagus is able to reduce, if not eliminate, neoplastic progression in Barrett’s esophagus; however, long-term results are needed.
Endoscopic treatment !
Because neither en bloc resection nor assessment of the resection margin can be obtained with piecemeal endoscopic mucosal resection (EMR) for larger esophageal lesions, endoscopic submucosal dissection (ESD) seems a promising alternative and is now being increasingly used for these lesions. However, the technical difficulty of ESD has repeatedly been shown to be associated with a higher complication rate. During UEG Week 2013, several studies presented the results of ESD for esophageal lesions. In a study from China [7], 63 patients with an esophageal lesion ≥ 15 mm underwent piecemeal EMR and 198 patients underwent ESD. The local recurrence rate was higher in the piecemeal EMR group than in the ESD group (11.5 % vs. 3.7 %), although both groups obtained the same tumor-free rate of deep margins. Severe shortterm complications, including severe bleeding and perforation, were similar between the groups. Esophageal stricture occurred more frequently in the piecemeal EMR group (6.2 % vs. 23.0 %), probably due to the larger circumferential mucosal defect in this group. Local recurrence after ESD was related to tumor size, and procedure time, tumor size, and percentage of the circumferential mucosal defect were independent risk factors for postoperative stricture. ESD seems superior to piecemeal EMR for large superficial esophageal lesions but randomized studies, particularly in Western countries, are needed to evaluate whether the results on ESD can be repeated. An ongoing debate is whether ESD for early gastric cancer (EGC) can also be performed beyond the established criteria for ESD. In Japan, “expanded resection criteria” have been defined since the introduction of ESD [8] and using Gotoda’s data on the risk for lymph node metastasis in EGC [9]. In Western guidelines, endoscopic resection is performed for small, well differentiated lesions without submucosal invasion (“guideline criteria”). For lesions beyond these criteria, surgery is recommended. Only a few follow-up data are available from Europe after resection of expanded criteria lesions. In a study from Germany [10], ESD for EGC was performed in 114 cases, with 94 resections performed according to the expanded criteria (82.5 %). Expanded criteria known prior to resection were lesion diameter in 77 /94 lesions (81.9 %) and ulceration in 9 lesions (7.9 %). Expanded criteria after resection included a G3 histology in 16 lesions (17 %), submucosal infiltration in 16 (17 %), and an L1 histology in 5 (5 %), for which surgery was advised. For expanded criteria, the en bloc resection rate was 87.2 % (82 /94) and the R0 resection rate was 72.3 % (68 /94). There were six recurrences (five after piecemeal resection, one after en bloc resection). Therefore, in Europe, ESD in EGC fulfilling the expanded resection criteria also seems to be an adequate treatment for this subgroup; however, longer follow-up data are required. Postoperative bleeding is a major complication after ESD for EGC and it occurs in up to 11.3 % of cases [11]. Second-look endoscopy (SLE) on the day after ESD to evaluate bleeding is often performed but the effectiveness of SLE in prevention of post-ESD bleeding remains controversial. In a randomized study from Japan [11], 130 patients were assigned to SLE and 132 to a wait-and-see pol-
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icy. Post-ESD bleeding occurred in 7 /130 patients (5.5 %) in the SLE group and in 5 /126 patients (3.8 %) in the non-SLE group, meeting the predefined noninferiority criterion of 7 %. All bleeding cases and one case of postoperative perforation were successfully managed with conservative treatment without the need for blood transfusion or surgery. This study clearly shows that SLE after gastric ESD is not required because it contributes little or not at all to the prevention of post-ESD bleeding. Submucosal tunneling endoscopic resection (STER) has emerged as a new technique for resecting upper gastrointestinal subepithelial tumors (SETs). The advantages of STER over ESD are that the anatomic structure of the digestive tract is maintained, the risk of pleural/abdominal infection is reduced, and rapid wound healing is promoted. Endoscopic resection with STER performed through a submucosal tunnel to the lesion without interruption of the lesion is the goal of treatment. If gastric SETs connect tightly to the underlying muscularis propria or serosal layer, the lesion can be resected with these underlying layers. Frequently, pneumoperitoneum develops during and after the procedure, but this can be relieved with a 20-G needle. A single-center experience from China [12] reported complete resection of all 71 SETs using STER. Histology included 53 leiomyomas, 17 gastrointestinal stromal tumors, and 1 calcifying fibrous tumor. There were no complications reported. Another study from China [13] evaluated the STER method in submucosal tumors originating from the muscularis propria at the esophagogastric junction. The esophagogastric junction is a difficult location for endoscopic resection due to its narrow lumen and sharp angle. A total of 76 SETs originating from the muscularis propria were removed using STER. The mean diameter was 21.5 mm (range 6 – 35 mm) and the mean procedure time was 47 minutes (range 15 – 120 minutes). The en bloc resection rate was 100 % (76 /76). Histology included 61 leiomyomas, 10 gastrointestinal stromal tumors, 1 intramuscular lipoma, 1 granular cell tumor, and 1 schwannoma. No delayed hemorrhage or severe adverse events were reported. Over a period of 12 – 24 months, no local recurrence or distant metastasis was observed. These two studies show that STER is safe, effective, and provides accurate histologic evaluation for SETs in the deeper layers but also at the technically more challenging locations in the upper gastrointestinal tract.
Gastrointestinal bleeding !
Gastrointestinal bleeding and endoscopic hemostasis is a field of endoscopy that attracts a lot of attention because technical advances can be rapidly incorporated into routine clinical practice. At UEG Week 2013, there were fewer abstracts on gastrointestinal bleeding compared with last year’s meeting, continuing a trend that has been noted previously [14, 15]. However, some innovative hemostatic techniques that were introduced at previous meetings appear to be finding their way into everyday practice. For example, Hemospray (Cook Medical) is a new inorganic nanopowder with clotting abilities, which is sprayed onto a bleeding site via a 10-Fr catheter in order to treat bleeding peptic ulcers, uncontrollable diffuse or cancer-related bleeding [16, 17]. Limited initial experience was presented at last year’s meeting [18]. However, at this year’s meeting it appeared that the method is not only gradually being established as treatment for its initial indications [19] but is also broadening its therapeutic applications to include variceal bleeding [20]. A bicentric prospective pilot trial included nine patients with acute variceal bleeding; he-
mostasis was achieved with application of 21 g of Hemospray. No rebleeding occurred within 24 hours (although it was not stated what happened after the first day), nor was there any mortality within 15 days of follow-up. The same group reported similar encouraging results in two patients with acute bleeding from duodenal varices [21]. These preliminary reports are in line with other recently published cases [22, 23] and provide hope that the new spray will be used not only to control peptic ulcer or diffuse bleeds, but may also be an effective tool in treating portal hypertension-associated hemorrhage, which in many cases can be life threatening. The other “new” device that was presented as a hemostatic tool was the Over-The-Scope Clip (OTSC), which has been presented at previous UEG Weeks [15], mostly as a means of endoscopic closure for natural orifice transluminal endoscopic surgery [24, 25]. This year, a multicenter Italian study attempted to evaluate whether, by compressing large amounts of tissue, the OTSC could be superior to “standard” (i. e. through the scope) clips for hemostasis in 48 consecutive patients who underwent emergency endoscopy for nonvariceal gastrointestinal bleeds (40 upper, 8 lower). OTSC were placed after failure of conventional hemostatic therapy and repeat endoscopy was performed 2 – 4 days after the first procedure. Primary hemostasis was achieved in 46 /48 cases (96 %); 2 failures and 2 cases of rebleeding occurred (12 and 24 hours postprocedure, both of which were successfully treated with saline/adrenaline injection) [26]. These results endorse the use of the OTSC as an effective treatment for hemostasis when conventional modalities fail. However, issues such as training, availability, and costs should also be taken into account when deciding whether to use them in daily clinical practice.
Colonoscopy topics !
Screening and surveillance colonoscopy for colorectal cancer (CRC) is a field that incorporates essential topics of interest to endoscopists, including colonoscopy quality and training, innovative technologies, and management of detected polyps. It is therefore not surprising that colonoscopy is an important subject for major endoscopy societies [27, 28] and is an area highly represented at UEG Week. Interval cancers (i. e. cancers diagnosed shortly after complete colonoscopy), constitute a major concern for the endoscopist and a threat to CRC screening. The majority of such lesions seem to arise from incompletely removed lesions or ones that are missed during initial colonoscopy [29, 30]. This finding was also suggested by a study presented at UEG Week 2013, which attempted to assess the association between colonoscopy quality indicators and 17 interval cancers that were found in 13 048 symptomatic and high-risk individuals with previous normal colonoscopies in an academic center (mean time to cancer was 1.65 ± 1.32 years). With the exception of increasing age, a low polyp detection rate was the most important risk factor associated with interval cancer [31]. New sophisticated imaging techniques have been widely incorporated into colonoscopes in the hope of improving the detection of polyps, but until now do not seem to have resulted in a significant breakthrough [32, 33]. This year, however, some new technologies were presented that could have a positive impact on the detection of polyps, especially adenomas. The first new technology is full spectrum endoscopy (Fuse) colonoscopy (EndoChoice), which allows 330° viewing projected onto three viewing screens.
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Initial results showed the technique to be feasible, safe, and user friendly [34]. An international multicenter working group recruited 185 patients and evaluated its performance in two prospective randomized tandem studies. The first study found that the incremental adenomas detected by Fuse after standard colonoscopy were higher than when standard colonoscopy followed Fuse (71.4 vs. 8.2 % respectively); moreover, the adenoma miss rate for standard colonoscopy was higher than that of Fuse (41.7 vs. 7.6 %) [35]. The second study highlighted the fact that Fuse could help to improve protection against interval cancers by significantly impacting adenoma surveillance recommendations, as it shortened examination intervals in 60 % of cases in which Fuse detected adenomas that standard colonoscopy had missed, whereas standard colonoscopy had no impact on surveillance recommendations [36]. The other technological advancement aimed at improving polyp and adenoma detection rate is a novel balloon colonoscope (NaviAid G-EYE; Smart Medical Systems Ltd.) [37]. The idea of using an endoscope endowed with a balloon to examine the colon is not new, as balloon enteroscopes (double and single) have been used effectively for completion of colonoscopy in cases with incomplete conventional examinations [38]. The new device consists of a standard colonoscope with a permanently integrated balloon at its distal end. The aim of the balloon is to improve colon visibility. The scope is inserted with the balloon deflated until it reaches the cecum, at which point the balloon is inflated to a medium pressure and the balloon colonoscope is withdrawn, allowing the intestinal folds to be straightened. An interim analysis of the first 74 patients (out of 126 planned) was presented. Additional polyp detection rate was 115 % when balloon colonoscopy followed standard colonoscopy compared with only 4.5 % when standard colonoscopy followed balloon colonoscopy. These results support the use of the balloon colonoscope and the withdrawal technique to reduce the polyp miss rate of colonoscopy. What about the management of the polyps that are detected? Data presented by an Austrian team suggest that we are not always resecting polyps in the way we should and that polyps of 5 – 10 mm in size are often inadequately resected (i. e. using a biopsy forceps instead of a snare) [39]. Though small, treatment of these polyps should be performed according to guidelines, as interval carcinoma may develop at the site of an inadequate polypectomy.
Small-bowel enteroscopy !
The modalities used nowadays for the endoscopic examination of the small bowel are video capsule endoscopy (VCE) and pushand-pull enteroscopy (i. e. double- and single-balloon enteroscopy and enteroscopy with a spiral overtube or spiral enteroscopy) [40]. The push-and-pull techniques have some differences between them and, despite a lot of discussion regarding the superior modality [41, 42], they can all be used effectively in the everyday clinical management of small-bowel pathologies. However, the fact that these modalities have gradually evolved from “novel” to “routine” has created a trend towards fewer enteroscopyrelated oral presentations at recent UEG Week meetings [14, 15]. One of the few reports this year on new enteroscopes was on a prototype short single-balloon enteroscope designed for endoscopic retrograde cholangiopancreatography (ERCP) in patients with surgically altered anatomy. The device was characterized as “effective” (though not spectacularly superior) compared with
historical results of the performance of a standard enteroscope [43]. VCE was slightly better represented by oral presentations due to technical innovations or alterations that have been incorporated into the established VCE. Reports on VCE steering were presented at UEG Week 2010 [44] and since then there has been steady progression of this device including therapeutic attempts presented at the subsequent two meetings [14, 15]. It seems that the quest for steerable VCE that can even perform biopsies and/or therapy is well underway [45, 46]. In this context, a Japanese study group, which last year presented a capsule that could perform a complete gastrointestinal screen with its position being recognized by remote portable devices [47], presented a wireless internetlinked robotic capsule endoscope endowed with therapeutic tools and a biopsy device (iRoboCap) based on the “traditional” PillCam SB2 (Given Imaging). Real-time viewing was available (with some time lag), and the capsule was steered with a joystick in a phantom and a pig’s stomach [48]. Despite battery problems, the transmission lag, difficulties in overcoming sphincter contraction, and biopsy acquisition (50 % success), the iRoboCap could become an experimental platform for an alternative VCE. Another new capsule was also presented (“Capsovision”), which has four cameras to allow a 360° examination of the small-bowel lumen. In a French multicenter trial, 73 patients with obscure gastrointestinal bleeding were recruited to ingest Capsovision and PillCam SB2 in a randomized order and with a 1-hour interval between. Disappointingly there were 13 technical issues (11 with Capsovision, 2 with PillCam) allowing only 60 patients to be finally analyzed. Concordance was good (kappa value 0.63; 46.7 % diagnosis with Capsovision vs. 48.3 % with PillCam), and Capsovision detected more lesions (108 vs. 85; P = 0.001), but at a cost of a longer reading time (32.0 vs. 26.2 minutes; P = 0.002) [49]. A possible pitfall is that the device currently has no recording system and therefore the capsule must be retrieved and returned after its expulsion in order to download the film.
ERCP and pancreatobiliary topics !
ERCP and pancreatobiliary endoscopy maintained the importance they demonstrated at previous meetings [14, 15]. For example, biliary drainage and stenting remained “hot” issues. Benign biliary strictures can be treated with placement of one or multiple plastic stents (“multistenting”) or covered removable self-expandable metal stents (CRSEMS) in the bile duct [50]. However, as most data from published series regarding these approaches lack big patient numbers or long-term outcomes, further reports are still needed. In a prospective, multicenter randomized study from Finland, 60 patients with biliary strictures due to chronic pancreatitis have been recruited since 2008 [51]. At the initial ERCP, a single plastic stent was placed, followed by randomization at the next ERCP to either CRSEMS or three plastic stents (with three more plastic stents added 3 months later), followed by stent removal 6 months after randomization. Clinical follow-up was performed 6 and 24 months after stent removal. To the date of abstract submission, 59 % of the patients in the plastic stent group and 53 % in the CRSEMS group had finished their follow-up. Relief from the strictures was seen in both groups, with bilirubin and alkaline phosphatase levels falling to similar levels, diameter of the common bile duct above the stricture dropping from 12 and 13 mm, respectively, to 7 mm in both groups, and stricture recurrence of 6 % in both groups. Morbidity
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ductal papillary mucinous neoplasm (IPMNs) of the main pancreatic duct was 100 % and 73.3 %, respectively. When considering its value as a therapeutic tool, the system achieved complete clearance in 74.2 % of cases with bile duct stones, but in only 28.6 % of cases with lithiasis in the pancreatic duct. Outcome reports such as this are of high interest, as they show us the applicability of a method in the “real world” outside of the “protected” environment of studies.
Endoscopic ultrasonography !
The role of endoscopic ultrasonography (EUS) has more recently been widely recognized. The method is no longer considered to be a specialist technique for a small group of endoscopists but rather an important tool that can be used to tackle a plethora of diagnostic and therapeutic problems both within [58, 59] and outside of the gastrointestinal tract [60, 61]. The advent of EUSguided fine-needle aspiration (EUS – FNA) gave EUS a new boost, and resulted not only in an improvement in its diagnostic ability but also involvement in therapeutic maneuvers. Without it, EUS would probably still exist as a diagnostic tool with limited indications. An important recent advancement of therapeutic EUS is EUSguided biliary drainage, a rescue technique used in cases of failed (or impossible to perform) ERCP [62]. Among its existing variants, biliogastric anastomosis or hepaticogastrostomy has been frequently reported [63]. Outcomes from hepaticogastrostomy in 61 patients (65 attempted procedures) in a high-volume center in France were retrospectively analyzed [64]. The procedure was chosen following failure to perform ERCP overall or a failure to reach the papilla or to achieve left biliary drainage (33 %, 16 %, and 51 %, respectively). The technical success rate of hepaticogastrostomy was 94 % and stent migration occurred in 11 %. Morbidity was 33 % (including pneumoperitoneum [n = 5], bile leakage [n = 7], bleeding [n = 1], and sepsis [n = 1], all of which were effectively treated, apart from one death). Various stents were used, but partially covered metallic stents appeared to be associated with reduced morbidity. In addition to EUS-guided biliary drainage, drainage of peripancreatic fluid collections is also an established indication for EUS. As the effectiveness of this method was often limited by the small diameter of plastic stents that were typically used, large-diameter, fully covered, self-expanding metal stents with anchoring devices have been used and were reported at last year’s UEG Week with promising results [65]. These positive preliminary data were further confirmed this year in multicenter studies using more than one type of large-diameter metal stent [66, 67]. Another interesting EUS topic that attracted interest during UEG Week 2013 is the optimal diagnostic and therapeutic approach of pancreatic cystic lesions, including IPMNs [14, 15]. Classical tools in this include imaging [68] and EUS – FNA [69]. Results from a combination of both approaches (i. e. needle-based CLE) in the interpretation of pancreatic serous cystadenomas, were presented in a prospective multicenter study from France (20 patients) [70]. Classical EUS was initially performed, followed by EUS – FNA and advancement of the special AQ-Flex 19 miniprobe through the needle and real-time in vivo endomicroscopy of the cyst wall. Finally, intracystic fluid was analyzed. Based on a new nCLE criterion (i. e. the “superficial vascular network”), specificities and positive predictive values of 100 %, with good-to-excellent intra- and interobserver agreement were achieved. However, as nCLE is a
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and mortality were similar but migration occurred in three cases in the plastic stent group compared with one in the CRSEMS group. These results together with the easy placement of CRSEMS could make these stents the preferred treatment [51]. CRSEMS have been left even longer in the bile duct (up to 9 months) in an ongoing prospective study in six European tertiary centers. To the date of abstract submission, 36 patients had been enrolled (27 with previous endoscopic treatments). All CRSEMS were placed without complication either endoscopically or percutaneously (29 vs. 7), and the strictures resolved immediately in 35 patients (97 %). CRSEMS patency was 100 %, 80 %, and 66.4 % at 1, 6, and 9 months after placement. No migrations occurred and the CRSEMS was successfully removed in 15 cases (8 after completion of treatment). However, in seven cases the stent was retrieved earlier due to occlusion, cholangitis, choledocholithiasis, acute pancreatitis, or before planned pancreatic head resection, and stricture recurrence was observed (immediately and up to 1 month after stent removal) in 7 of 15 patients [52]. These results should be taken into consideration when deciding which strategy to follow in endotherapy of biliary strictures; further large outcome studies on this issue are required. Other routine ERCP-related topics reported this year included wire-guided cannulation of the bile duct as the method preferred by many endoscopists who perform ERCP. There are many commercially available guidewires, with different tips according to the shape of the papilla or the bile duct course and therefore choosing the optimal guidewire is an important issue. However, the need for low examination costs dictates the use of a single wire if possible when performing ERCP. A randomized trial from Japan including 225 patients compared guidewires with two different types of tips – angled or straight [53]. ERCP completion rate was 85.4 % (105 /123) in the angled vs. 73.5 % (75 /102) in the straight-tip group (P = 0.027), suggesting that angled guidewires could be considered as the first-choice wire for ERCP. Deep cannulation and complication rates were similar in both groups. Ultimately though, differences such as these might play a minor role, as endoscopists will have their preferences based on experience and the actual choice of ERCP accessories is usually a more complex issue (availability and costs play an important role). However, results from studies such as this one should be considered and are thus important. ERCP in altered gastrointestinal anatomy has been mentioned above [43]. Finally, peroral cholangioscopy has continued to attract attention at UEG Week following the advent of SpyGlass (Boston Scientific) [54], a single-operator instrument with improved handling that allows biopsies to be taken (Spybite) [54]. Following its initial use in imaging, the SpyGlass has recently advanced into the therapeutic arena not only of the bile duct [55] but also of the pancreatic duct [56]. In addition to intriguing reports from specialized centers, the clinical utility of this device in widespread application also remains interesting. In a prospective case series from 22 centers in Japan, outcomes were reported from 162 patients who underwent single-operator peroral cholangioscopy using the SpyGlass system for the diagnosis or therapy of pancreatobiliary lesions [57]. The system displayed impressive success rates, including 95.8 % for the visualization of target lesions and 76.2 % for the acquisition of adequate tissue for histology. The sensitivity and specificity were 88.1 % and 80.0 %, respectively, for SpyGlass in terms of visual impression of the bile duct and 65.1 % and 89.3 %, respectively, for biopsy sampling. The sensitivity of the system’s visual impression and directed biopsy to detect intra-
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new method, results from these first studies should be viewed with caution. In fact, limitations of nCLE in pancreatic masses were also reported this year [71]. Finally, other EUS “classics” included its role in the differential diagnosis of gastric SETs. Once again, the well known limitations of EUS – FNA [72] were confirmed, and the superiority of another approach, namely bloc biopsy using submucosal endoscopy to create a mucosal flap [73], was demonstrated [74]. However, in everyday life, such approaches are not always necessary and “plain” diagnostic EUS accompanied by simple criteria can suffice [75]. At the point when characterization of subepithelial lesions in the gastrointestinal tract is known and decisions need to be made on how aggressive treatment should be, the importance of clinical judgment should, once again, be highlighted. Competing interests: None
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