Euro-NOTES Status Paper: from the concept to clinical practice.

BACKGROUND: The concept of natural orifice transluminal endoscopic surgery (NOTES) consists of the reduction of access trauma by using a natural orifice access to the intra-abdominal cavity. This could possibly lead to less postoperative pain, quicker recovery from surgery, fewer postoperative complications, fewer wound infections, and fewer long-term problems such as hernias. The Euro-NOTES Foundation has organized yearly meetings to work on this concept to bring it safely into clinical practice. The aim of this Euro-NOTES status update is to assess the yearly scientific working group reports and provide an overview on the current clinical practice of NOTES procedures. METHODS: After the Euro-NOTES meeting 2011 in Frankfurt, Germany, an analysis was started regarding the most important topics of the European working groups. All prospectively documented information was gathered from Euro-NOTES and D-NOTES working groups from 2007 to 2011. The top five topics were analyzed. RESULTS: The statements of the working group activities demonstrate the growing information and changing insights. The most important selected topics were infection issue, peritoneal access, education and training, platforms and new technology, closure, suture, and anastomosis. The focus on research topics changed over time. The principle of hybrid access has overcome the technical and safety limitations of pure NOTES. Currently the following NOTES access routes are established for several indications: transvaginal access for cholecystectomy, appendectomy and colon resections; transesophageal access for myotomy; transgastric access for full-thickness small-tumor resections; and transanal/transcolonic access for rectal and colon resections. CONCLUSIONS: NOTES and hybrid NOTES techniques have emerged for all natural orifices and were introduced into clinical practice with a good safety record. There are different indications for different natural orifices. Each technique has been optimized for the purpose of finding a safe and realistic solution to perform the procedure according to the specific indication.

Standard diagnostic laparoscopy is superior to NOTES approaches: results of a blinded, randomized controlled porcine study.

BACKGROUND AND STUDY AIM: The use of transluminal endoscopic access via the stomach or colon for flexible diagnostic peritoneoscopy has been proposed, although the diagnostic value of the technique has not yet been fully clarified. In this animal trial, the two main natural orifice transluminal endoscopic surgery (NOTES) approaches - transgastric (TG) and transcolonic (TC) - were compared with standard transabdominal access using both rigid (TAR) and flexible instruments (TAF) for diagnostic laparoscopy. METHODS: A total of 48 peritoneoscopies were performed using two randomly assigned approaches in 24 anesthetized pigs. The ability of the examinations to detect 576 electrocautery markings simulating intraperitoneal metastases, to achieve complete organ visualization, and to simulate organ biopsies was analyzed. RESULTS: Sensitivities for the detection of lesions were 78.5 %, 59.7 %, 48.6 %, and 38.9 % for TAR, TAF, TC, and TG, respectively; standard laparoscopy was superior to all other approaches (P < 0.01). Among the NOTES approaches, TC was superior for examining the upper abdomen (P = 0.03). Complete organ visualization was better with the transabdominal approach (visual analogue scale TAR 7.15, TAF 6.71) than with the NOTES access routes (TC 5.07, TG 4.35); standard rigid laparoscopy was superior to both NOTES approaches (P < 0.01). Organ biopsy simulation was possible in 87 %, 85 %, 72 %, and 65 % of cases with TAR, TAF, TC, and TG, respectively. Standard rigid laparoscopy was again superior to both NOTES approaches (TAR vs. TC, P = 0.03; TAR vs. TG, P < 0.01). CONCLUSIONS: In this experimental trial, rigid standard laparoscopy provided better organ visualization, better lesion detection, and better biopsy capability than the transgastric and transcolonic NOTES approaches. In its current form, NOTES appears to be unsuitable for diagnostic laparoscopy.

Endoscopic vs. laparoscopic gastrojejunostomy for duodenal obstruction: a randomized study in a porcine model.

BACKGROUND AND STUDY AIMS: Open or laparoscopic gastrojejunostomy is an established treatment for malignant duodenal obstruction but may be associated with significant morbidity and mortality. The purpose of this study was to develop a model for an entirely endoscopic gastrojejunostomy to treat duodenal obstruction, and to compare this with the laparoscopic technique. METHODS: During the first part of the study the endoscopic technique was developed and tested in porcine nonsurvival and survival experiments (n=12). During the second part of the study (n=10), endoscopic gastrojejunostomy for duodenal occlusion was compared with laparoscopic gastrojejunostomy in a survival randomized controlled trial (RCT). For both groups duodenal occlusion was achieved by the laparoscopic approach. RESULTS: In the RCT, the median times for laparoscopic vs. endoscopic gastrojejunostomy were 70 minutes (interquartile range [IQR] 65-75) vs. 210 minutes (IQR 197-220; P=0.01). There was a trend toward increased anastomotic diameter at necropsy in the laparoscopic group (2 cm, IQR 2-3) compared to the endoscopic group (1.8 cm, IQR 1.6-1.8; P=0.06). One animal in the endoscopic group died secondarily to bowel ischemia from volvulus of the jejunal loop. One animal in the laparoscopic group was prematurely sacrificed due to extensive pulmonary congestion and edema. All anastomoses were intact and patent. CONCLUSIONS: Purely endoscopic gastrojejunostomy using the developed technique and devices is feasible and can result in adequate relief of duodenal obstruction. Endoscopic anastomoses tend to be smaller than laparoscopic anastomoses, with the procedures being more time-consuming and associated with higher complication rates.

Endoscopic mucosal resection using a grasp-and-snare technique.

BACKGROUND AND STUDY AIM: Endoscopic mucosal resection (EMR) is a minimally invasive method for en bloc removal of superficial gastrointestinal lesions. The aim of this study was to evaluate the feasibility of a novel grasp-and-snare EMR technique. METHODS: In 10 domestic pigs, gastric lesions of approximately 3 cm were marked using electrocautery. EMR was performed using a double-channel endoscope. A novel tissue anchor was used through one channel, and a monofilament snare through the other. After submucosal injection, a circumferential mucosal incision was created. The tissue-anchoring device was then advanced through the open snare and anchored into the submucosal layer. The tissue-anchoring device was partly retracted into the endoscope and the snare was positioned into the circular incision. The snare was subsequently closed and the specimen resected by applying high-frequency electrocautery. RESULTS: Mean time to perform EMR was 32.4 minutes (range 22-41 minutes, SD 6.3). EMR yielded specimens that ranged in area from 2.7 cm (minor axis) by 2.8 cm (major axis) to 4.0 cm by 4.2 cm (mean area 9.36 cm(2); range 5.94-13.19 cm(2); SD +/- 2.50). Complete en bloc resection including all electrocautery markings was achieved in 9/10 cases. In one case, resection was achieved in two steps. One gastric wall perforation occurred. No other adverse events were observed. CONCLUSIONS: Grasp-and-snare EMR is feasible in an animal model. The technique can be performed efficiently compared with standard methods. To avoid perforation, caution is needed to ensure that tissue anchor needles are placed within and not deeper than the submucosal layer prior to tissue retraction.

Effectivity of current sterility methods for transgastric NOTES procedures: results of a randomized porcine study.

BACKGROUND AND AIM: Natural-orifice transluminal endoscopic surgery (NOTES) is an emerging transluminal technique in which interventions are carried out by entering the abdominal cavity via a natural orifice such as the stomach. Infection is a potential risk of the procedure, and the potential pathogens are different from those encountered with skin incisions. Currently, available data regarding prophylactic anti-infective treatment are limited. We compared the effectiveness of topical antimicrobial lavage of mouth and stomach and proton pump inhibitor therapy with gastric cleansing with sterile saline solution in preventing NOTES-related contamination and infection. METHODS: A randomized survival swine study was performed. Eight pigs underwent preparation with intravenously administered proton pump inhibitors, mouth and gastric lavage (chlorhexidine), and gastric irrigation (diluted neomycin), plus single-shot intravenous antibiotics. Control group (n = 8) underwent gastric cleansing with sterile saline solution. Peritoneal biopsy, multiple smears, and dilutions for cultures were taken and incubated. The swine were sacrificed after 14 days. Bacterial load was expressed in colony-forming units (CFU). RESULTS: One pig died due to gallbladder perforation after 3 days, 2/15 swine presented minor clinical signs of infection in the 14-day follow-up (all 3 pigs were in the control group). Mean C-reactive protein levels were 5.7 +/- 2.4 g/dL (therapy group) and 12.2 +/- 3.8 g/dL (control) ( P = 0.17). Bacterial growth was seen in 1/8 swine (therapy group) and 6/8 swine (control group) ( P = 0.002). Bacterial load was 282 CFU/mL (therapy) vs. 3.2 x 10 (5) CFU/mL (control) ( P = 0.023) in the follow-up. CONCLUSION: The use of intravenous antibiotics in addition to topical antimicrobial lavage of mouth and stomach and treatment with proton pump inhibitors decreased the peritoneal bacterial load to almost zero and this was associated with a significantly lower peritoneal infection rate compared with saline-only lavage.

Randomized controlled trial comparing endoscopic clips and over-the-scope clips for closure of natural orifice transluminal endoscopic surgery gastrotomies.

BACKGROUND AND STUDY AIM: Secure and reliable endoscopic closure is of paramount importance before clinical introduction of transgastric natural orifice transluminal endoscopic surgery (NOTES). Gastrotomy closure in humans using standard endoclips has been reported. The aim of this study was to assess the safety of standard endoclip closure and to compare it to a new over-the-scope clip (OTSC) specifically designed for gastrotomy closure. MATERIAL AND METHODS: Gastric wall puncture and balloon dilation followed by peritoneoscopy was carried out in 20 female swine. After randomization, closure of the gastric incision was performed using a tissue approximation grasper and either endoclips or OTSCs. RESULTS: Mean (+/- SD) time for gastrotomy closure using endoclips was 31.5 +/- 24.2 minutes (range 8 - 88 minutes) compared with 8.5 +/- 9.1 minutes (range 2 - 31 minutes) using OTSC (P = 0.002). No intraoperative complications occurred. Laparoscopic leak tests with insufflation and saline immersion demonstrated three minor leaks and one major leak in the endoclip closures. No leaks were observed in the OTSC group. At necropsy, complete sealing of the gastrotomy sites was found in all OTSC closures. Small, localized perigastric abscesses were observed in two animals in the OTSC group and in three animals in the endoclip group. One animal in the endoclip group was sacrificed prematurely due to signs of sepsis and was found to have gross peritonitis secondary to a leak. At necropsy, evidence of peritonitis was identified in two other animals in the endoclip group. CONCLUSION: NOTES gastrotomy closure using standard endoclips, even with a tissue approximation grasper, is associated with an increased risk of leakage and intra-abdominal infection compared with OTSC. The significance of perigastric abscesses, which were seen in both groups, warrants further investigation.

Endoscopic closure of the natural orifice transluminal endoscopic surgery (NOTES) access site to the peritoneal cavity by means of transmural resorbable sutures: an animal survival study.

BACKGROUND AND STUDY AIMS: Endoscopic closure of the transgastric access site is still a critical area of active research and development into natural orifice transluminal surgery (NOTES). To date, no endoscopic technique has utilized resorbable transmural sutures for closure of the NOTES gastrostomy. MATERIAL AND METHODS: Endoscopic gastrostomy closure by means of resorbable sutures was performed in ten female domestic pigs in an animal survival study. Peritoneal cavity access was gained through the anterior gastric wall using the percutaneous endoscopic gastrostomy (PEG) technique and an 18-mm balloon dilator. NOTES exploration of the gallbladder and tubal ligation were performed prior to endoscopic gastrostomy closure. Necropsy was performed 3 weeks post procedure. RESULTS: Mean suturing time was 26 minutes (range 14 - 35 minutes). In total 90 % (9/10) of gastrostomy closures were performed by means of two transmural resorbable sutures. One gastrostomy was closed using a single resorbable suture. One case of gallbladder perforation occurred during peritoneoscopy and the pig was sacrificed due to subsequent peritonitis 2 days after the procedure. All other pigs (9/10) were found to be healthy 3 weeks after the NOTES procedure and were sacrificed as planned per protocol. Of all the 17 sutures that were applied in the remaining nine pigs, 16 (94 %) had been absorbed, releasing the pledgets intraluminally. During laparotomy no signs of injury to adjacent organs were found in any of these nine animals. In 8/10 pigs (80 %) the gastrostomy site did not burst with pressures exceeding 100 mmHg. Two suturing sites did burst at pressures of 57 and 62 mmHg, respectively. CONCLUSIONS: Endoscopic transmural suturing enables rapid and easy placement of leak-proof resorbable sutures and is suitable for closure of the NOTES transgastric access.

Endoscopic closure of large colonic perforations using an over-the-scope clip: a randomized controlled porcine study.

BACKGROUND AND STUDY AIMS: Perforation of the colon is considered to be one of the most serious complications of flexible endoscopy. The over-the-scope clip system (OTSC) has previously been shown to close small colonic perforations effectively. The aim of this randomized controlled porcine study was to compare acute closure strengths between the novel 11-mm over-the-scope-clip and surgical closure for large colonic perforations. MATERIAL AND METHODS: In 24 anesthetized domestic pigs, an 18-mm sigmoid perforation was created endoscopically using a needle knife and dilating balloon. The animals were randomly assigned to undergo either open surgical repair (n = 12) or endoscopic closure using the OTSC system (n = 12). Pressurized leak tests were performed during necropsy. RESULTS: Mean time to perform the incision in the sigmoid colon and obtain peritoneal access was 5.5 minutes (range 3-12; SD +/- 2.5). Mean time for endoscopic closure was 6.8 minutes (range 3-14; SD +/- 3). At necropsy, all OTSC and surgical closures demonstrated complete sealing of colotomy sites. In one case peritoneum and in a second case adjacent small intestine were found incorporated into the OTSC closure. No other complications occurred. Pressurized leak tests revealed a mean burst pressure of 62.8 mmHg (range 18-112; SD 35.7) for OTSC closures and 67.4 mmHg (range 30-90; SD 19) for sutured closure. No significant differences in burst pressures were noted between the OTSC closures and surgical repair. CONCLUSION: Closure of acute perforations using the OTSC system is comparable to surgical closure in a nonsurvival porcine model.

Endoscopic full-thickness plication for the treatment of gastroesophageal reflux disease using multiple Plicator implants: 12-month multicenter study results.

BACKGROUND: The full-thickness Plicator (Ethicon Endosurgery, Sommerville, NJ, USA) was developed for endoscopic treatment of gastroesophageal reflux disease (GERD). The goal is to restructure the antireflux barrier by delivering transmural pledgeted sutures through the gastric cardia. To date, studies using this device have involved the placement of a single suture to create the plication. The purpose of this study was to evaluate the 12-month safety and efficacy of this procedure using multiple implants to restructure the gastroesophageal (GE) junction. METHODS: A multicenter, prospective, open-label trial was conducted at four tertiary centers. Eligibility criteria included symptomatic GERD [GERD Health-Related Quality-of-Life (GERD-HRQL) questionnaire, off of medication], and pathologic reflux (abnormal 24-h pH) requiring daily proton pump inhibitor therapy. Patients with Barrett's epithelium, esophageal dysmotility, hiatal hernia > 3 cm, and esophagitis (grade III or greater) were excluded. All patients underwent endoscopic full-thickness plication with linear placement of at least two transmural pledgeted sutures in the anterior gastric cardia. RESULTS: Forty-one patients were treated. Twelve months post treatment, 74% of patients demonstrated improvement in GERD-HRQL scores by > or = 50%, with mean decrease of 17.6 points compared with baseline (7.8 vs. 25.4, p < 0.001). Using an intention-to-treat model, 63% of patients had symptomatic improvements of > or = 50%, with mean GERD-HRQL decrease of 15.0 (11.0 vs. 26.0, p < 0.001). The need for daily proton pump inhibitor (PPI) therapy was eliminated in 69% of patients at 12 months on a per-protocol basis, and 59% on an intention-to-treat basis. Adverse events included postprocedure abdominal pain (44%), shoulder pain (24%), and chest pain (17%). No long-term adverse events occurred. CONCLUSIONS: Endoscopic full-thickness plication using multiple Plicator implants can be used safely and effectively to improve GERD symptoms and reduce medication use.

Endoscopic full-thickness plication (Plicator) with two serially placed implants improves esophagitis and reduces PPI use and esophageal acid exposure.

BACKGROUND AND STUDY AIMS: Recently, several endoluminal procedures for the treatment of gastroesophageal reflux disease (GERD) have been introduced. Most of these techniques have been abandoned because they lack long-term efficacy or have serious side effects. In a recently published prospective randomized, sham-controlled trial, the Plicator was shown to be effective at controlling reflux symptoms and esophageal acid exposure. In all previous studies, only a single implant was used. The aim of the present pilot study was to determine the safety and efficacy of two serially placed Plicator implants. PATIENTS AND METHODS: Thirty-seven patients requiring maintenance therapy with proton pump inhibitors (PPIs) were enrolled in this single-center pilot study. All patients received two Plicator implants. Exclusion criteria were hiatus hernia larger than 3 cm, grade IV esophagitis, Barrett's esophagus, and esophageal motility disorders. The primary study end point was at least 50 % improvement in the GERD Health-Related Quality of Life (HRQL) score. Secondary end points included GERD medication use, esophageal acid exposure, esophagitis grade, and heartburn/regurgitation scores. RESULTS: Thirty-seven patients underwent endoscopic full-thickness plication using two serially placed Plicator implants. At 6 months after treatment, the proportion of patients achieving at least 50 % improvement in GERD-HRQL score was 68 %. Complete cessation of PPI treatment was achieved in 59 % of patients. In pH studies conducted at 6 months (n = 29), median percentage of time for which pH was below 4 decreased by 36 %, with 28 % of patients experiencing pH normalization. There were no serious adverse events requiring intervention. CONCLUSIONS: Endoscopic full-thickness plication using two serially placed Plicator implants was both safe and effective in reducing esophagitis, GERD symptoms, medication use, and esophageal acid exposure.

[A 42 year old patient with bilateral loss of sight and hypertension. Gemcitabine-associated thrombotic microangiopathy (TMA)]. / 42-jähriger Patient mit bilateralem Visusverlust und hypertensiver Entgleisung. Gemcitabin-assoziierte thrombotische Microangiopathie (TMA).

We report a case of a 42 year old male patient with a history of adrenocortical carcinoma, who was admitted with bilateral loss of sight and hypertension. Laboratory tests and further clinical evaluation showed hemolytic anemia, thrombocytopenia and acute renal failure. This was consistent with thrombotic microangiopathy / hemolytic uremic syndrome (HUS) due to gemcitabine therapy. The patient was successfully treated with prednisolon and antihypertensive drugs. Visus was completely restored, plasmapheresis was not needed. Clinicians should be aware of HUS as a rare complication of gemcitabine therapy.