Endoscopic gastrojejunostomy with survival in a porcine model

NEW METHODS

Endoscopic gastrojejunostomy with survival in a porcine model Sergey V. Kantsevoy, MD, PhD, Sanjay B. Jagannath, MD, Hideaki Niiyama, MD, Sydney S. C. Chung, MD, Peter B. Cotton, MD, Christopher J. Gostout, MD, Robert H. Hawes, MD, Pankaj J. Pasricha, MD, Carolyn A. Magee, MS, Cheryl A. Vaughn, RN, BSN, David Barlow, PhD, Hideki Shimonaka, BS, Anthony N. Kalloo, MD Baltimore, Maryland, USA

Background: We have previously reported the feasibility and the safety of an endoscopic transgastric approach to the peritoneal cavity in a porcine model. We now report successful performance of endoscopic gastrojejunostomy with survival. Methods: All procedures were performed on 50-kg pigs, with the pigs under general anesthesia, in aseptic conditions with sterilized endoscopes and accessories. The stomach was irrigated with antibiotic solution, and a gastric incision was performed with a needle-knife and a sphincterotome. A standard upper endoscope was advanced through a sterile overtube into the peritoneal cavity. A loop of jejunum was identified, was retracted into the stomach, and was secured with sutures while using a prototype endoscopic suturing device. An incision was made into the jejunal loop with a needle-knife, and the filet-opened ends of the jejunal wall were secured to the gastric wall with a second line of sutures, completing the gastrojejunostomy. Observations: Two pigs survived for 2 weeks. Endoscopy and a radiographic contrast study performed after gastrojejunostomy revealed a patent anastomosis with normal-appearing gastric and jejunal mucosa. Postmortem examination demonstrated a well-healed anastomosis without infection or adhesions. Conclusions: The endoscopic transgastric approach to create a gastrojejunostomy is technically feasible and can be performed, with survival, in a porcine model.

Many unresectable primary (gastric, duodenal, pancreatic) or metastatic (colorectal, renal, etc.) malignancies can cause gastric outlet and duodenal obstruction.1-3 Open surgery for palliation of this obstruction is associated with high morbidity and mortality.4-7 Although the laparoscopic approach is less traumatic than open surgery, the laparoscopic creation of a gastrojejunostomy is technically difficult, requires extensive surgical and laparoscopic skills, and is associated with numerous complications, primarily anastomotic stricture (3.1%8.8%) and leak (1.2%-3.0%).8-14 The aims of this study were to determine the technical feasibility and the success of creating an endoscopically performed gastrojejunal anastomosis in a porcine model.

Copyright ª 2005 by the American Society for Gastrointestinal Endoscopy 0016-5107/$30.00 PII: S0016-5107(05)01565-8

Review Board. We performed transgastric gastrojejunostomy in two 50-kg pigs (Sus scrofus domesticus). All the pigs were fed daily with 6 cans of Ensure (16 oz; Abbott Laboratories, North Chicago, Ill) 2 days before endoscopy and then were fasted overnight. All endoscopes and accessories were prepared with high-level disinfection (Cidex OPA; Ethicon, Inc, Irvine, Calif), followed by gas sterilization with ethylene oxide. The procedures were performed under aseptic conditions. All procedures were performed with the pigs under 1.5% to 2% isoflurane general anesthesia with 7.0-mm endotracheal intubation (Mallinckrodt Co, C. D. Juarez, Chih, Mexico). Preanesthesia medication consisted of an intramuscular injection of 100 mg/mL Telazol (tiletamine HCl C zolazepam HCl; Lederle Parenterals, Inc, Carolina, Puerto Rico) reconstituted with 100 mg/mL ketamine HCl and 100 mg/mL xylazine at a total dose of approximately 0.05 cc/kg. Intramuscular injection of 600,000 units of penicillin G benzathine C penicillin G procaine based antibiotic and 1 g intravenous (IV) cefazolin was administered before endoscopy. An IV was placed in the marginal ear vein, and 1 g thiopental sodium was injected at a dose of 6.6 to 8.8 mg/kg IV.

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PATIENTS AND METHODS The study was approved by the Johns Hopkins University School of Medicine Animal Care Institutional

Endoscopic gastrojejunostomy with survival in porcine model

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Capsule Summary What is already known on this topic d

Peroral endoscopic transgastric abdominal surgery is being very actively investigated in both animals and humans, aiming at replacing laparoscopic surgery.

What this study adds to our knowledge d

Figure 1. A, Schematic drawing of gastric-wall incision with needle knife; note the endoscope inside the sterile overtube. B, Endoscopic view of the gastric-wall incision with the needle-knife.

In a pilot animal study, endoscopic transgastric gastrojejunostomy was technically feasible.

long incision with a pull-type sphincterotome (210Q-0720; Olympus) with identical settings. The endoscope was advanced into the peritoneal cavity. A random small-bowel loop was grasped with endoscopic forceps (FG-47L-1; Olympus) (Fig. 2A and B), was pulled into the stomach, and was fixed with a holding suture inside the stomach and then connected to the gastric wall by using a prototype endoscopic suturing device (Eagle Claw; Olympus) (Fig. 3A and B). Then, a 15-mm-long incision was made on the antimesenteric surface of the small-bowel loop by using the needle-knife (KD-10Q-1.A; Olympus) with a combination of 20 J pure cautery and 30 J pure-cut (Fig. 4A and B). By using the same prototype endoscopic suturing device, a second line of sutures was created, which connected the open ends of the intestinal-wall incision to the gastric wall to complete the gastrojejunostomy (Fig. 5A and B). The pigs were given a second IV dose of broadspectrum antibiotics after the procedure, and they recovered from general anesthesia. Oral feeding was started within the following 24 hours. The patency of the anastomosis was studied with repeated endoscopy and radiographic contrast (60% Hypaque contrast; Amersham Health Inc, Princeton, NJ) studies 1 week after the procedure. All the pigs were euthanized 1 week later, and a postmortem examination was performed.

RESULTS Subsequently, a sterile overtube (Olympus Optical Co Ltd, Tokyo, Japan) was advanced into the pig’s stomach with standard upper endoscope (GIF-160; Olympus) inside the overtube. The stomach was irrigated with 1000 mL of an antibiotic solution (40 mg neomycin and 2 HTU/mL polymyxin B sulfates in 1000 mL normal saline solution). An endoscopic needle knife (KD-10Q-1.A; Olympus) was used to create an initial 2-mm incision in the anterior wall of the stomach with a combination of 20 J pure cautery and 30 J pure-cut (Valleylab SSE2L; Boulder, Colo) (Fig. 1A and B). This opening was enlarged by a 20-mm-

Endoscopic transgastric gastrojejunostomy with survival was successfully performed in 2 pigs by using endoscopes and endoscopic accessories. The gastric-wall incision was easily done with the combination of the needle knife and a pull-type sphincterotome. There was no bleeding associated with creating an incision. The gastric incision site was chosen on the border of anterior gastric wall and the greater curve at the junction of body and the antrum of the stomach. In both pigs, there were no complications because of the gastric-wall incision and transgastric access to the peritoneal cavity. The endoscope was directed into the

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Endoscopic gastrojejunostomy with survival in porcine model

Figure 3. A, Schematic drawing of small-bowel loop fixed inside the gastric incision with the first line of stitches. B, Endoscopic view of smallbowel loop is sutured to the gastric wall (large arrows at gastric wall and small bowel; small arrows that show the holding suture). Figure 2. A, Schematic drawing of small-bowel loop grasped by endoscopic forceps inside the peritoneal cavity. B, Endoscopic view of small-bowel loop grasped by endoscopic forceps inside the peritoneal cavity.

peritoneal cavity, and insufflation of air lifted the anterior abdominal wall that provided an excellent view of the internal organs and easy access to the small bowel. The small-bowel loop was easily grasped with an atraumatic endoscopic forceps and was pulled to the stomach by withdrawing the endoscope from the peritoneal cavity. As a first suture line, 2 to 3 full-thickness

stitches were placed with the prototype endoscopic suturing device to fix the small bowel loop inside the gastric-wall incision (Fig. 3A and B). We observed only minor bleeding from the incision of the antimesenteric surface of the intestinal loop, which was easily controlled with endoscopic electrocautery. The second line of sutures (between the open ends of the intestinal wall and the gastric wall) was created with 2 to 4 stitches. The total time to complete the anastomosis ranged from 90 to 120 minutes. Both pigs tolerated a regular diet within 24 hours after the procedure; they ate heartily and thrived over the next

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Endoscopic gastrojejunostomy with survival in porcine model

Figure 4. A, Schematic drawing of small-bowel-loop incision on the antimesenteric surface with needle-knife. B, Endoscopic view of smallbowel incision with the needle-knife.

Kantsevoy et al

Figure 5. A, The open ends of the intestinal incision are sutured to the gastric wall, with a second line of stitches completing the gastrojejunostomy. B, Endoscopic view of completed gastrojejunal anastomosis.

DISCUSSION

14 days. The repeated endoscopy and radiograph contrast study 1 week after creation of the gastrojejunostomy revealed patent anastomosis with healthy-appearing mucosa (Fig. 6). The endoscope was easily advanced into both afferent and efferent loops of the small bowel. Contrast radiologic studies with Hypaque demonstrated patency of the anastomosis without extravasation (Fig. 7). The postmortem examination 2 weeks after creation of the gastrojejunostomy revealed the gastrojejunal anastomosis located on the border of anterior abdominal wall and the greater curve of the stomach and normalappearing small and large bowel, and the stomach (Fig. 8). There were no signs of infection or adhesions in the peritoneal cavity.

Gastric outlet obstruction frequently is caused by advanced malignancies, mostly gastric and pancreatic cancer.1-3 As many as 50% of patients with advanced gastric cancer are unsuitable for surgery,2 and, of the 28,000 patients diagnosed with pancreatic cancer in the United States annually, approximately 80% will have advanced disease not amenable to surgical resection.15,16 Of all patients with pancreatic cancer, 3% to 19% will develop gastric outlet obstruction and will require palliative surgical or laparoscopic procedures.17,18 Surgical gastrojejunostomy is associated with appreciable morbidity and mortality rates up to 40% and 15%,

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Figure 6. Endoscopic view 1 week after creation of gastrojejunostomy.

respectively.3,4,19-22 Laparoscopic interventions were introduced into the clinical practice in an attempt to reduce invasiveness of surgical procedures and to decrease morbidity, mortality, and length of hospital stay.3,12,23-25 Unfortunately, laparoscopic creation of a gastrojejunal anastomosis is technically difficult, requires advanced laparoscopic skills, and decreases but does not eliminate the risk of postoperative complications (anastomotic leakage and strictures, wound infection, etc.).9-14 Endoscopic stent placement of a gastric outlet or a duodenal obstruction has definitive short-term advantages over the surgical and laparoscopic gastrojejunostomy (shorter length of stay, earlier oral intake, lower complication rate), although recurrent obstruction because of stent occlusion, malignant overgrowth, or migration are common, which leads to a decrease in medium- to long-term patency of the endoprostheses.1,3,26-29 Our experiments demonstrate that another potential option may exist to palliate malignant gastric outlet or duodenal obstruction by the creation of a gastrojejunal anastomosis. This can be done successfully by using only endoscopes and endoscopic accessories. We previously reported successful use of the endoscopic transgastric approach for access into the peritoneal cavity in a porcine model.30 Our current series of experiments expand on the application of the transgastric approach by the successful creation of a functional gastrojejunal anastomosis. Two weeks of follow-up did not reveal any complications: the anastomosis was patent, and both pigs started to eat within 24 hours of creation of the gastrojejunostomy. All pigs ate heartily, were active, and thrived. Postmortem examination demonstrated normal small and large bowel, stomach, and anastomosis. There was no infection or adhesion inside the peritoneal cavity. Our experiments demonstrated safety and feasibility of transgastric endoscopic gastrojejunostomy, with survival, in a porcine model. Potential advantages of this procedure in comparison with surgical or laparoscopic gastroenteric anastomosis include minimal invasiveness, no need for an www.mosby.com/gie

Figure 7. Hypaque contrast radiograph 1 week after creation of gastrojejunostomy: afferent loop of small bowel is filled with the contrast. Endoscope is in the efferent loop of small intestine. There is no leakage of contrast into the peritoneal cavity.

Figure 8. Postmortem examination 2 weeks after creation of gastrojejunostomy: normal stomach, small bowel, and anastomosis.

anterior abdominal wall and skin incisions, thereby eliminating the risk of skin wound infection and postoperative hernias. For these reasons, transgastric endoscopic gastrojejunal anastomosis may not only be a valuable therapeutic procedure to palliate gastric outlet or duodenal obstruction but may potentially be used in patients with obesity to create transgastric endoscopic GI bypass. DISCLOSURE The authors would like to acknowledge the support of the Apollo Group and Olympus Optical Co, Ltd, Tokyo, Japan, for their assistance in this project. REFERENCES 1. Alam TA, Baines M, Parker MC. The management of gastric outlet obstruction secondary to inoperable cancer. Surg Endosc 2003;17: 320-3.

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2. Cogliandolo A, Scarmozzino G, Pidoto RR, Pollicino A, Florio MA. Laparoscopic palliative gastrojejunostomy for advanced recurrent gastric cancer after Billroth I resection. J Laparoendosc Adv Surg Tech A 2004;14:43-6. 3. Mittal A, Windsor J, Woodfield J, Casey P, Lane M. Matched study of three methods for palliation of malignant pyloroduodenal obstruction. Br J Surg 2004;91:205-9. 4. Bakkevold KE, Kambestad B. Morbidity and mortality after radical and palliative pancreatic cancer surgery. Risk factors influencing the short-term results. Ann Surg 1993;217:356-68. 5. Reed DN Jr, Cacchione RN, Allen JW, Arlauskas V, Casey J, Larson GM, et al. Laparoscopic choledochojejunostomy and gastrojejunostomy in a porcine model. Surg Endosc 2003;17:86-8. 6. DeMaria EJ, Schweitzer MA, Kellum JM, Meador J, Wolfe L, Sugerman HJ. Hand-assisted laparoscopic gastric bypass does not improve outcome and increases costs when compared to open gastric bypass for the surgical treatment of obesity. Surg Endosc 2002;16:1452-5. 7. McCormick JT, Papasavas PK, Caushaj PF, Gagne DJ. Laparoscopic revision of failed open bariatric procedures. Surg Endosc 2003;17: 413-5. 8. Higa KD, Boone KB, Ho T. Complications of the laparoscopic Roux-en-Y gastric bypass: 1,040 patients: what have we learned? Obes Surg 2000; 10:509-13. 9. Hamad MA, Mentges B, Buess G. Laparoscopic sutured anastomosis of the bowel. Surg Endosc 2003;17:1840-4. 10. Sundbom M, Gustavsson S. Randomized clinical trial of hand-assisted laparoscopic versus open Roux-en-Y gastric bypass for the treatment of morbid obesity. Br J Surg 2004;91:418-23. 11. Nguyen NT, Stevens CM, Wolfe BM. Incidence and outcome of anastomotic stricture after laparoscopic gastric bypass. J Gastrointest Surg 2003;7:997-1003; discussion 1003. 12. Papasavas PK, Caushaj PF, McCormick JT, Quinlin RF, Hayetian FD, Maurer J, et al. Laparoscopic management of complications following laparoscopic Roux-en-Y gastric bypass for morbid obesity. Surg Endosc 2003;17:610-4. 13. Ahmad J, Martin J, Ikramuddin S, Schauer P, Slivka A. Endoscopic balloon dilation of gastroenteric anastomotic stricture after laparoscopic gastric bypass. Endoscopy 2003;35:725-8. 14. DeMaria EJ, Sugerman HJ, Kellum JM, Meador JG, Wolfe LG. Results of 281 consecutive total laparoscopic Roux-en-Y gastric bypasses to treat morbid obesity. Ann Surg 2002;235:640-5; discussion 645-7. 15. Rosewicz S, Wiedenmann B. Pancreatic carcinoma. Lancet 1997;349: 485-9. 16. Gentileschi P, Kini S, Gagner M. Palliative laparoscopic hepatico- and gastrojejunostomy for advanced pancreatic cancer. JSLS 2002;6:331-8. 17. Espat NJ, Brennan MF, Conlon KC. Patients with laparoscopically staged unresectable pancreatic adenocarcinoma do not require subsequent surgical biliary or gastric bypass. J Am Coll Surg 1999; 188:649-55; discussion 655-7. 18. Lillemoe KD, Cameron JL, Hardacre JM, Sohn TA, Sauter PK, Coleman J, et al. Is prophylactic gastrojejunostomy indicated for unresectable periampullary cancer? A prospective randomized trial. Ann Surg 1999; 230:322-8; discussion 328-30.

19. Lawrence W Jr, Mc NG. The effectiveness of surgery for palliation of incurable gastric cancer. Cancer 1958;11:28-32. 20. Bozzetti F, Bonfanti G, Audisio RA, Doci R, Dossena G, Gennari L, et al. Prognosis of patients after palliative surgical procedures for carcinoma of the stomach. Surg Gynecol Obstet 1987;164:151-4. 21. Watanapa P, Williamson RC. Surgical palliation for pancreatic cancer: developments during the past two decades. Br J Surg 1992; 79:8-20. 22. Smith AC, Dowsett JF, Russell RC, Hatfield AR, Cotton PB. Randomised trial of endoscopic stenting versus surgical bypass in malignant low bileduct obstruction. Lancet 1994;344:1655-60. 23. Gal I, Szivos J, Balint A, Hejjel L, Gyory I, Nagy B. Laparoscopic gastric surgery. Early experiences. Acta Chir Hung 1999;38:163-5. 24. Dresel A, Kuhn JA, Westmoreland MV, Talaasen LJ, McCarty TM. Establishing a laparoscopic gastric bypass program. Am J Surg 2002; 184:617-20. 25. Gonzalez R, Lin E, Venkatesh KR, Bowers SP, Smith CD. Gastrojejunostomy during laparoscopic gastric bypass: analysis of 3 techniques. Arch Surg 2003;138:181-4. 26. Bethge N, Breitkreutz C, Vakil N. Metal stents for the palliation of inoperable upper gastrointestinal stenoses. Am J Gastroenterol 1998; 93:643-5. 27. Feretis C, Benakis P, Dimopoulos C, Manouras A, Tsimbloulis B, Apostolidis N. Duodenal obstruction caused by pancreatic head carcinoma: palliation with self-expandable endoprostheses. Gastrointest Endosc 1997;46:161-5. 28. Nevitt AW, Vida F, Kozarek RA, Traverso LW, Raltz SL. Expandable metallic prostheses for malignant obstructions of gastric outlet and proximal small bowel. Gastrointest Endosc 1998;47:271-6. 29. Topazian M, Ring E, Grendell J. Palliation of obstructing gastric cancer with steel mesh, self-expanding endoprostheses. Gastrointest Endosc 1992;38:58-60. 30. Kalloo AN, Kantsevoy SV, Singh VK, Magee CA, Vaughn CA, Hill SL. Flexible transgastric peritoneoscopy: a novel approach to diagnostic and therapeutic interventions in the peritoneal cavity. Gastrointest Endosc 2004;60:114-7.

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Received October 6, 2004. Accepted March 16, 2005. Current affiliations: Division of Gastroenterology, Johns Hopkins Hospital, Baltimore, Maryland; The Mayo Clinic College of Medicine, Division of Gastroenterology, Rochester, Minnesota; The Medical University of South Carolina, Division of Gastroenterology, Charleston, South Carolina; The University of Texas at Galveston, Division of Gastroenterology, Galveston, Texas; The University of Papua New Guinea, Department of Surgery, Papua, New Guinea; Olympus Optical, Tokyo, Japan; Kyushu University, Department of Surgery, Fukuoka, Japan. This work was presented in part at Digestive Disease Week, May 19-23, 2002, San Francisco, California (Gastrointest Endosc 2002;55:AB96). Reprint requests: Anthony N. Kalloo, MD, Division of Gastroenterology, Johns Hopkins Hospital 1830 E. Monument Street, Room 419 Baltimore, MD 21205.