Endoscopic full-thickness resection of subepithelial tumors with the use of resorbable sutures (with video)

Endoscopic full-thickness resection of subepithelial tumors with the use of resorbable sutures (with video)

CASE STUDIES Endoscopic full-thickness resection of subepithelial tumors with the use of resorbable sutures (with video) Bastian Walz, MD, Daniel von...

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CASE STUDIES

Endoscopic full-thickness resection of subepithelial tumors with the use of resorbable sutures (with video) Bastian Walz, MD, Daniel von Renteln, MD, Arthur Schmidt, MD, Karel Caca, MD Ludwigsburg, Germany

GI stromal tumors (GISTs) are the most common mesenchymal tumors of the GI tract, containing cellular spindle cell, epithelioid, or occasionally pleomorphic mesenchymal tumors that express c-KIT (CD117) protein. Approximately two-thirds of all diagnosed GISTs are located in the stomach. GISTs are often small, indolent tumors but can transform to sarcomas, and some tumors may cause abdominal pain or obscure/overt bleeding. Studies with prolonged follow-up have shown an existing risk for malignant behavior according to tumor size and mitotic activity.1-9 Surgery is considered the mainstay of therapy for resectable, nonmetastatic GISTs ⬎2 cm in size. Even small, mitotically inactive tumors, labeled as benign, can occasionally metastasize.5,10-16 Different case series and studies have evaluated the feasibility of EMR and endoscopic submucosal dissection (ESD) for the removal of such tumors from the muscularis propria. ESD enables en bloc resection of such lesions, regardless of their size and shape.12-14 ESD of neoplastic masses in deeper gastric wall layers is technically demanding and associated with a high rate of complications, such as bleeding or perforation.13,17-20 Although a minimally invasive, endoscopic treatment approach for GIST resection is desirable, the oncologic standard requires a complete tumor resection (R0 resection). Lymphadenectomy is not obligatory because lymph node metastases are exceptionally rare. So far, endoscopic full-thickness resection of GISTs ⬎2 cm in size was performed only with laparo-

Abbreviations: GIST, GI stromal tumor; ePTFE, expanded polytetrafluoroethylene; ESD, endoscopic submucosal dissection; IV, intravenous. DISCLOSURE: K. Caca received research support from NDO Surgical, Inc in 2007 and 2008. No other financial relationships relevant to this publication were disclosed. Copyright © 2011 by the American Society for Gastrointestinal Endoscopy 0016-5107/$36.00 doi:10.1016/j.gie.2011.01.052 Received October 26, 2010. Accepted January 24, 2011. Current affiliations: Department of Gastroenterology, Hepatology and Oncology, Klinikum Ludwigsburg, Ludwigsburg, Germany. Reprint requests: Karel Caca, MD, Klinikum Ludwigsburg, Department of Gastroenterology, Hepatology and Oncology, Teaching Hospital of Heidelberg University, Posilipostr. 4, 71640 Ludwigsburg, Germany.

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scopic assistance.21 Therefore, successful endoluminal R0 full-thickness resection and suturing might represent an optimal minimally invasive treatment approach. The Plicator (NDO Surgical, Inc, Mansfield, Mass), with nonresorbable polypropylene sutures and expanded polytetrafluoroethylene (ePTFE) bolsters, was initialy developed for treatment of GERD but recently was reported to be a suitable instrument to restore or prevent gastric wall defects after resections or natural orifice transluminal endoscopic surgery procedures.22,23 Follow-up endoscopy showed durable plications and sutures, which partly caused small mucosal irritiations. Yet there are no viable techniques that use resorbable sutures to perform endoscopic full-thickness resections of subepithelial gastric tumors.

PATIENTS AND METHODS From July 2008 until October 2010, 4 patients received endoscopic full-thickness resections done with resorbable transmural suturing below the supposed GIST. The patients were two women (ages 44 and 68 years) and two men (ages 48 and 73 years). Written informed consent was obtained by all patients before the interventions. The clinical study was approved by the local institutional review board. Each patient was prepared and sedated with our facility’s standard protocol (continuous intravenous [IV] propofol and midazolam sedation). Prophylactic antibiotics (ceftriaxone 2 g IV for 3 days) were also administered. No intubation was necessary in any of the patients; only oxygen was administered through a nasal probe. Blood pressure, electrocardiogram, and oxygen saturation were constantly monitored during the procedure. After an initial gastroscopy to locate and diagnose the subepithelial tumor, including the mucosal lifting sign above the tumor, a Savary guidewire was placed on withdrawal of the gastroscope. The Plicator was then introduced over the guidewire into the stomach, and a low-profile (5.8 mm) videogastroscope was passed through the Plicator to enable direct endoscopic visualization during the procedure. We used a standard Plicator endoscopic sewing device with modified ePTFE pledgets and resorbable, pretied 4-mm sutures (50% shorter than standard) to create a stitching line below the subepithelial tumor. The Plicator arms were www.giejournal.org

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Resection of subepithelial tumors

Figure 1. A, Gastric GI stromal tumor (case 1) with closed Plicator (NDO Surgical, Inc, Mansfield, Mass) arms after tissue retraction. B, Deployed sutures underneath resection site after resection by means of standard polypectomy snare. C, Full-thickness resected tissue. D, Endoscopic result after 4 weeks.

subsequently opened, and the central endoscopic tissue retractor was positioned at the lower border of the tumor and advanced into the tissue underneath the tumor. The tissue retractor was then drawn back to gather tissue between the open arms of the Plicator. The arms were firmly closed, and a pledgeted suture was deployed, which applied a suture underneath the tumors by creating a serosato-serosa tissue apposition. These sutures ensured GI wall patency during endoscopic resection of the GIST. A standard electrocautery polypectomy snare was used to resect the GIST above the stitching line. Afterward, full-thickness resected tissue was preserved for histopathologic analysis (Fig. 1). The Plicator and the gastroscope were removed, and the gastroscope was reinserted to evaluate the resulting suture and GI-wall patency. EUS was used before and after the procedure to evaluate the tumor (size, localization, and perfusion), the morphology of the local lymph nodes, and the endoscopic sutures. Follow-up endoscopy was performed on the next day and at 1, 2, and 4 weeks after the procedure. Primary outcome measurements were clinical procedural success and procedure-related adverse events. www.giejournal.org

Case 1 The first patient was a 44-year-old woman. EUS confirmed a subepithelial circumscribed tumor with low echogenicity measuring 26 ⫻ 17 mm, located in the anterior wall of the gastric body. Local lymph nodes were dimensioned for normal. Two resorbable sutures were applied via Plicator arms on opposite sides of the large tumor to isolate and lift the suspect subepithelial tissue. A standard electrocautery polypectomy snare in Endocut (Erbe, Tuebingen, Germany) mode was used to resect the GIST above the stitching line. Another, third suture was placed on the cranial boarder of the lesion to assure the resection area. Follow-up controls showed rapidly increasing healing with GI-wall patency and complete resorption of the sutures within 2 weeks with excretion of the nonabsorbable pledgets, whereas just a plane, thin scar remained after 4 weeks (Fig. 1). The histopathologic analysis showed complete full-thickness R0 GIST resection. The tumor was found to be 35 mm in size and located within the submucosal layer. Oral food administration was started on the second day after resection and was well tolerated. The patient was discharged from the hospital after 7 days. Volume 73, No. 6 : 2011 GASTROINTESTINAL ENDOSCOPY 1289

Resection of subepithelial tumors

Case 2 The second patient was a 68-year-old woman referred to our institution because of a suspected gastric submucosal tumor causing intermittent epigastric pain. An EUS showed a 20-mm, large tumor in the posterior wall of the gastric antrum, without any suspicious perigastric lymph nodes. After application of two resorbable sutures underneath the tumor, it was resected via polypectomy snare (Video 1, available online at www.giejournal.org). Bioptical and endosonographic controls indicated no sign of a recurrence and rapid healing. Final pathologic analysis revealed complete full-thickness resection of a glomangioma arising from the muscularis propria. The patient was discharged from the hospital after 6 days.

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clips, coagulation probe, or hot biopsy forceps), used for hemorrhage after standard polypectomy in the stomach. Serosa-to-serosa apposition below the tumor supported GI wall patency. Histopathologic examination showed complete R0 resection in all cases. Endoscopic follow-up showed complete resorption of the sutures within 2 weeks, with excretion of the nonabsorbable ePTFE pledgets. Two weeks later, gastric wall integrity was completely re-established, and a plane scar remained. The application of absorbable sutures helped reduce the tension in the plicated tissue. Maximum hospital stay was 1 week, and re-establishment of increasing enteral feeding was well tolerated 2 days after resection.

DISCUSSION Case 3 The third patient was a 73-year-old man with a 30-mm, subepithelial gastral tumor located in the anterior wall of the gastric body and was referred to us because of suspected intestinal bleeding and loss of weight. EUS criteria suggested a GIST. The tumor was diathermically resected after application of two resorbable transmural sutures by using the Plicator device, then a dual-channel endoscope with over-the-scope clip system anchor and polypectomy snare. Arterial bleeding was successfully stopped by using two Resolution Clips (Boston Scientific, Natick, Mass), one EZ Clip (Olympus, Hamburg, Germany), and injection of diluted adrenalin. Pathohistologic analysis showed a GIST arising from the muscularis mucosa. Follow-up revealed no noticeable problems, and the patient was discharged from the hospital after 4 days.

Case 4 The fourth patient was a 48-year-old man with a 16mm, large tumor located near the lesser curvature of the gastric body. The tumor was an incidental finding of GI endoscopy. Having resected the tumor after full-thickness suturing with two resorbable sutures, we stopped some bleeding by using 3 Resolution Clips and 2 EZ Clips. Histopathology and immunohistochemical staining confirmed a GIST located within the muscularis mucosa. Endoscopic and EUS controls indicated no sign of recurrence and showed a plane scar. The patient was discharged from the hospital after 5 days.

RESULTS The average procedure time was 35 minutes. The mean time for endoscopic full-thickness suturing with the use of resorbable sutures was 10 minutes. EUS during the procedure confirmed tumor lifting and an adequate safety margin before resection. Endoscopic resections were performed without major adverse events, and the resected specimens contained serosa, which documented fullthickness resection. Several episodes of bleeding were easily stopped by using established procedures (hemo1290 GASTROINTESTINAL ENDOSCOPY Volume 73, No. 6 : 2011

As part of the search for alternative solutions to laparoscopic surgical procedures for the treatment of GISTs and other subepithelial tumors in the stomach, this technique using resorbable endoscopic full-thickness sutures allowed for safe and complete R0 resections. The sequence of ensuring gastric wall tightness and lifting the tumor before resection by using Plicator sutures prevents (stretched) perforations because they are more common in EMR/ESD procedures of larger GISTs.24-27 The so-far applied nonresorbable polypropylene Plicator sutures created durable plications with retained ePTFE pledgets. The nonresorbable sutures compromised the endoscopic view at follow-up investigations, and these sutures could cause chronic irritations and small mucosal erosions.27 However, the use of resorbable sutures led to a slow but complete relief of tension in the plicated tissue, with the result that just a plane scar remained after 4 weeks. Frequent bleeding during/after resection can be completely controlled endoscopically by using common procedures like hemoclips and hot biopsy forceps. GISTs are the most commonly identified subepithelial tumors in the upper GI tract and frequently arise from the interstitial cells of Cajal in the muscularis propria. Even small GISTs (⬍3 cm) can have malignant behavior.28 One of our patients had a glomus tumor, which is usually benign but has potential for malignant degeneration and also originates from modified vascular smooth muscle cells in the muscularis propria.29,30 The risk of endoscopic resections is thereby directly related to the original layer of the tumor within the gastric wall. Including full-thickness suturing as discribed previously, many subepithelial masses arising from the muscularis propria become amenable to endoscopic resections and do not require laparoscopic stand-by.13 In the debate as to whether the potential morbidity and mortality associated with surgical resection of small GISTs are acceptable, we show an alternative solution that can partly finalize the controversy for removing small, submucosal lesions. In comparison with EMR or ESD, including usage of insulated-tip knife resection, the Plicator-assisted suturing primarily prevents www.giejournal.org

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gastric wall defects.31 Recently reported endoscopic band ligation for treatment of submucosal tumors arising from the muscularis propria mostly treated smaller lesions (1-2 cm), and a complete histologic evaluation of the lesions was not possible because the tumor was excreted through the GI tract via natural processes.32 Further development should be focused on wider availability and modified smaller Plicator devices that enable better patient comfort and easier handling. In addition, more experienced operators might lead to shorter hospital stays.

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