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Confocal Laser Endomicroscopy Guided Endoscopic Myotomy
GASTROENTEROLOGY IN MOTION Ralf Kiesslich and Thomas D. Wang, Section Editors
Confocal Laser Endomicroscopy Guided Endoscopic Myotomy Helmut Neumann,1 Michael Vieth,2 Bernard Dallemagne,4 Jacques Marescaux,4 Haru Inoue,3 and Silvana Perretta4 1
Department of Medicine I, University Hospital Erlangen, Erlangen; 2Institute of Pathology, Klinikum Bayreuth, Bayreuth, Germany; 3Digestive Disease Center, Showa University Toyosu Hospital, Japan; and 4Strasbourg Institute of Image-Guided Surgery (IHU Strasbourg), University of Strasbourg, France
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A
chalasia is a primary esophageal motor disorder characterized by degenerative changes of the myenteric plexus.1 Until recently, laparoscopic Heller myotomy, represented the most successful treatment option.2 Most recently, peroral endoscopic myotomy (POEM) was introduced as a novel, minimally invasive treatment option for patients with achalasia.3–5 Nevertheless, adequate length of the myotomy, either performed surgically or endoscopically, still remains unknown and is guided by an approximation extrapolated by clinical, manometric and radiological findings. Adequate clearance of the esophagus, the main objective of the operation, is sometimes difficult to achieve as about 25% of patients complain of residual dysphagia or gastroesophageal reflux symptoms when myotomy alone is employed.6 In addition, ultrastructural examinations of the myenteric plexus were only performed on esophagectomy specimens and biopsies taken at Heller myotomy. Recent data has shown that myenteric neurons could selectively be visualized by using confocal laser endomicroscopy (CLE), an endoscopic imaging technique allowing obtainment of optical biopsies at 1000-fold magnification during ongoing endoscopy after application of appropriate fluorescence agents.7 Fluorescence agents yet used to visualize myenteric neurons include acriflavine hydrochloride and a specific fluorescent neuronal molecular probe. Although the potential of CLE to visualize the myenteric neuronal network has been shown in these initial studies, none of the fluorescent stains used are approved for their use in humans.8,9 In contrast, intravenously injected fluoresceine sodium is widely used as the contrast stain for CLE in humans. Here, we present the potential of fluoresceine-guided CLE to visualize the myenteric neuronal network during POEM procedures.
Technologies, Paris, France) was used. CLE is based on tissue illumination with a lower power laser. The handheld pCLE probe is advanced through the working channel of a standard endoscope and gently applied to the esophageal tissue. In order to obtain real-time videos, confocal images are streamed at a frame rate of 12 frames per second. In our study, the GastroFlex UHD (Mauna Kea Technologies, Paris, France) probe was used. Technical features of the probe include a lateral resolution of 1 mm, a field of view of 240 mm and an imaging plane depth of 55–65 mm.
Video Description With the pig supine under general anesthesia a single channel endoscope (Storz, Tuttlingen, Germany) is advanced in the esophagus and the gastroesophageal junction (GEJ) is carefully inspected to determine adequate landmarks for the myotomy. The site for mucosotomy in the midesophagus is selected to be 15 cm from the GEJ. A submucosal lift is achieved at the 12 o’clock position, by submucosal injection of 10 mL saline with 1% methylene blue. A triangle-tip (TT) endoscopic cautery knife (Triangle Tip Knife; Olympus, Tokyo, Japan) is used to make a 1.5cm–2 cm longitudinal mucosal incision at the site of the submucosal bleb. The endoscope is subsequently inserted into the newly created submucosal space and a submucosal tunnel is created to the GEJ and 2 cm beyond onto the lesser curve using a combination of blunt dissection, CO2 insufflation, and electrocautery. Then, the pCLE-probe is advanced through the working channel of the endoscope and gently applied onto the newly created muscular pit within the submucosal space (Figure 1). Afterwards, 7 mL of 10% fluoresceine sodium (Alcon Pharma, Freiburg, Germany) are administered intravenously. In vivo CLE is performed using blue laser light (488 nm) for fluorophore excitation and returning light is detected from 205nm to 585 nm. Optical sections are collected with 12 frames per second, a lateral resolution of 1.4 mm, an optical sectioning of 10 mm and a 240 mm field of view. Image interpretation is performed in real time. The clear distal cap (Olympus) attached to the endoscope facilitated the stabilization of the probe for subsequent highmagnification imaging. Confocal imaging reveals muscle
Description of Technology For the purpose of this study, the probe-based confocal laser endomicroscopy system (pCLE; Cellvizio, Mauna Kea
© 2014 by the AGA Institute 0016-5085/$36.00 http://dx.doi.org/10.1053/j.gastro.2014.04.044
Gastroenterology 2014;147:31–32
GASTROENTEROLOGY IN MOTION B
CLE provides optical biopsies at 1000-fold magnification.
B
Fluoresceine-guided CLE allows visualization of myenteric neurons in real time in POEM procedures.
B
Confocal imaging may serve as a helpful clinical tool to improve the determination of the adequate length of myotomy in patients with achalasia.
Supplementary Material Note: To access the supplementary material accompanying this article, visit the online version of Gastroenterology at www.gastrojournal.org, and at http://dx.doi.org/10.1053/ j.gastro.2014.04.044. Figure 1. The pCLE-probe is advanced through the working channel of the endoscope and gently applied onto the newly created muscular pit within the submucosal space.
fibers as reticular, light grey fibers while microvessels appear as white (fluorescein-filled) structures containing red blood cells appearing as small dark spots flowing through the blood vessels. In contrast, the myenteric plexus is identified as dark bands existing in the muscle layer of the esophagus (Figure 2; Video). After the procedure, the pig is euthanized, after biopsies were taken at studied sites and fixed in 10% formalin for subsequent histopathological analysis. Biopsies are showing findings consistent with the endomicroscopic findings. Additionally, post hoc assessment of confocal images is completed with an expert gastrointestinal pathologist.
References 1.
2. 3.
4.
5.
6.
Take Home Message B
Adequate length of the myotomy in patients with achalasia still remains unknown.
7.
8.
9.
Francis DL, Katzka DA. Achalasia: update on the disease and its treatment. Gastroenterology 2010;139: 369–374. Boeckxstaens GE, Zaninotto G, Richter JE. Achalasia. Lancet 2014;383:83–93. Inoue H, Minami H, Kobayashi Y, et al. Peroral endoscopic myotomy (POEM) for esophageal achalasia. Endoscopy 2010;42:265–271. Von Renteln D, Fuchs KH, Fockens P, et al. Peroral endoscopic myotomy for the treatment of achalasia: an international prospective multicenter study. Gastroenterology 2013;145:309–311. Perretta S, Dallemagne B, Marescaux J. STEPS to POEM: introduction of a new technique at the IRCAD. Surg Innov 2012;19:216–220. Bombeck CT, Nyhus LM, Donahue PE. How far should the myotomy extent on the stomach? In: Giuli R, McCallum RW, Skinner DB, eds. Primary Motility Disorders of the Esophagus 450 questions, 450 answers. Paris: John Libbey Eurotext, 1991. Neumann H, Kiesslich R, Wallace MB, et al. Confocal laser endomicroscopy: technical advances and clinical applications. Gastroenterology 2010;139:388–392. Sumiyama K, Kiesslich R, Ohya TR, et al. In vivo imaging of enteric neuronal networks in humans using confocal laser endomicroscopy. Gastroenterology 2012;143: 1152–1153. Ohya TR, Sumiyama K, Takahashi-Fujigasaki J, et al. In vivo histologic imaging of the muscularis propria and myenteric neurons with probe-based confocal laser endomicroscopy in porcine models (with videos). Gastrointest Endosc 2012;75:405–410.
Reprint requests Address requests for reprints to: Helmut Neumann, MD, PhD, Department of Medicine I, University of Erlangen-Nuremberg, Ulmenweg 18 91054, Erlangen, Germany. e-mail: [email protected]; fax: þ49 9131 85-35209.
Figure 2. The myenteric plexus (arrows) is identified as dark bands existing in the muscle layer of the esophagus.
32
Conflicts of interest The authors disclose no conflicts.
Confocal Laser Endomicroscopy Guided Endoscopic Myotomy Helmut Neumann,1 Michael Vieth,2 Bernard Dallemagne,4 Jacques Marescaux,4 Haru Inoue,3 and Silvana Perretta4 1
Department of Medicine I, University Hospital Erlangen, Erlangen; 2Institute of Pathology, Klinikum Bayreuth, Bayreuth, Germany; 3Digestive Disease Center, Showa University Toyosu Hospital, Japan; and 4Strasbourg Institute of Image-Guided Surgery (IHU Strasbourg), University of Strasbourg, France
Scan the quick response (QR) code to the left with your mobile device to watch this article’s video abstract and others. Don’t have a QR code reader? Get one by searching ‘QR Scanner’ in your mobile device’s app store.
A
chalasia is a primary esophageal motor disorder characterized by degenerative changes of the myenteric plexus.1 Until recently, laparoscopic Heller myotomy, represented the most successful treatment option.2 Most recently, peroral endoscopic myotomy (POEM) was introduced as a novel, minimally invasive treatment option for patients with achalasia.3–5 Nevertheless, adequate length of the myotomy, either performed surgically or endoscopically, still remains unknown and is guided by an approximation extrapolated by clinical, manometric and radiological findings. Adequate clearance of the esophagus, the main objective of the operation, is sometimes difficult to achieve as about 25% of patients complain of residual dysphagia or gastroesophageal reflux symptoms when myotomy alone is employed.6 In addition, ultrastructural examinations of the myenteric plexus were only performed on esophagectomy specimens and biopsies taken at Heller myotomy. Recent data has shown that myenteric neurons could selectively be visualized by using confocal laser endomicroscopy (CLE), an endoscopic imaging technique allowing obtainment of optical biopsies at 1000-fold magnification during ongoing endoscopy after application of appropriate fluorescence agents.7 Fluorescence agents yet used to visualize myenteric neurons include acriflavine hydrochloride and a specific fluorescent neuronal molecular probe. Although the potential of CLE to visualize the myenteric neuronal network has been shown in these initial studies, none of the fluorescent stains used are approved for their use in humans.8,9 In contrast, intravenously injected fluoresceine sodium is widely used as the contrast stain for CLE in humans. Here, we present the potential of fluoresceine-guided CLE to visualize the myenteric neuronal network during POEM procedures.
Technologies, Paris, France) was used. CLE is based on tissue illumination with a lower power laser. The handheld pCLE probe is advanced through the working channel of a standard endoscope and gently applied to the esophageal tissue. In order to obtain real-time videos, confocal images are streamed at a frame rate of 12 frames per second. In our study, the GastroFlex UHD (Mauna Kea Technologies, Paris, France) probe was used. Technical features of the probe include a lateral resolution of 1 mm, a field of view of 240 mm and an imaging plane depth of 55–65 mm.
Video Description With the pig supine under general anesthesia a single channel endoscope (Storz, Tuttlingen, Germany) is advanced in the esophagus and the gastroesophageal junction (GEJ) is carefully inspected to determine adequate landmarks for the myotomy. The site for mucosotomy in the midesophagus is selected to be 15 cm from the GEJ. A submucosal lift is achieved at the 12 o’clock position, by submucosal injection of 10 mL saline with 1% methylene blue. A triangle-tip (TT) endoscopic cautery knife (Triangle Tip Knife; Olympus, Tokyo, Japan) is used to make a 1.5cm–2 cm longitudinal mucosal incision at the site of the submucosal bleb. The endoscope is subsequently inserted into the newly created submucosal space and a submucosal tunnel is created to the GEJ and 2 cm beyond onto the lesser curve using a combination of blunt dissection, CO2 insufflation, and electrocautery. Then, the pCLE-probe is advanced through the working channel of the endoscope and gently applied onto the newly created muscular pit within the submucosal space (Figure 1). Afterwards, 7 mL of 10% fluoresceine sodium (Alcon Pharma, Freiburg, Germany) are administered intravenously. In vivo CLE is performed using blue laser light (488 nm) for fluorophore excitation and returning light is detected from 205nm to 585 nm. Optical sections are collected with 12 frames per second, a lateral resolution of 1.4 mm, an optical sectioning of 10 mm and a 240 mm field of view. Image interpretation is performed in real time. The clear distal cap (Olympus) attached to the endoscope facilitated the stabilization of the probe for subsequent highmagnification imaging. Confocal imaging reveals muscle
Description of Technology For the purpose of this study, the probe-based confocal laser endomicroscopy system (pCLE; Cellvizio, Mauna Kea
© 2014 by the AGA Institute 0016-5085/$36.00 http://dx.doi.org/10.1053/j.gastro.2014.04.044
Gastroenterology 2014;147:31–32
GASTROENTEROLOGY IN MOTION B
CLE provides optical biopsies at 1000-fold magnification.
B
Fluoresceine-guided CLE allows visualization of myenteric neurons in real time in POEM procedures.
B
Confocal imaging may serve as a helpful clinical tool to improve the determination of the adequate length of myotomy in patients with achalasia.
Supplementary Material Note: To access the supplementary material accompanying this article, visit the online version of Gastroenterology at www.gastrojournal.org, and at http://dx.doi.org/10.1053/ j.gastro.2014.04.044. Figure 1. The pCLE-probe is advanced through the working channel of the endoscope and gently applied onto the newly created muscular pit within the submucosal space.
fibers as reticular, light grey fibers while microvessels appear as white (fluorescein-filled) structures containing red blood cells appearing as small dark spots flowing through the blood vessels. In contrast, the myenteric plexus is identified as dark bands existing in the muscle layer of the esophagus (Figure 2; Video). After the procedure, the pig is euthanized, after biopsies were taken at studied sites and fixed in 10% formalin for subsequent histopathological analysis. Biopsies are showing findings consistent with the endomicroscopic findings. Additionally, post hoc assessment of confocal images is completed with an expert gastrointestinal pathologist.
References 1.
2. 3.
4.
5.
6.
Take Home Message B
Adequate length of the myotomy in patients with achalasia still remains unknown.
7.
8.
9.
Francis DL, Katzka DA. Achalasia: update on the disease and its treatment. Gastroenterology 2010;139: 369–374. Boeckxstaens GE, Zaninotto G, Richter JE. Achalasia. Lancet 2014;383:83–93. Inoue H, Minami H, Kobayashi Y, et al. Peroral endoscopic myotomy (POEM) for esophageal achalasia. Endoscopy 2010;42:265–271. Von Renteln D, Fuchs KH, Fockens P, et al. Peroral endoscopic myotomy for the treatment of achalasia: an international prospective multicenter study. Gastroenterology 2013;145:309–311. Perretta S, Dallemagne B, Marescaux J. STEPS to POEM: introduction of a new technique at the IRCAD. Surg Innov 2012;19:216–220. Bombeck CT, Nyhus LM, Donahue PE. How far should the myotomy extent on the stomach? In: Giuli R, McCallum RW, Skinner DB, eds. Primary Motility Disorders of the Esophagus 450 questions, 450 answers. Paris: John Libbey Eurotext, 1991. Neumann H, Kiesslich R, Wallace MB, et al. Confocal laser endomicroscopy: technical advances and clinical applications. Gastroenterology 2010;139:388–392. Sumiyama K, Kiesslich R, Ohya TR, et al. In vivo imaging of enteric neuronal networks in humans using confocal laser endomicroscopy. Gastroenterology 2012;143: 1152–1153. Ohya TR, Sumiyama K, Takahashi-Fujigasaki J, et al. In vivo histologic imaging of the muscularis propria and myenteric neurons with probe-based confocal laser endomicroscopy in porcine models (with videos). Gastrointest Endosc 2012;75:405–410.
Reprint requests Address requests for reprints to: Helmut Neumann, MD, PhD, Department of Medicine I, University of Erlangen-Nuremberg, Ulmenweg 18 91054, Erlangen, Germany. e-mail: [email protected]; fax: þ49 9131 85-35209.
Figure 2. The myenteric plexus (arrows) is identified as dark bands existing in the muscle layer of the esophagus.
32
Conflicts of interest The authors disclose no conflicts.