Original Article
Botulinum toxin for prevention of delayed gastric emptying after esophagectomy
Asian Cardiovascular & Thoracic Annals 21(6) 689–692 ß The Author(s) 2012 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0218492312468438 aan.sagepub.com
Reza Bagheri1, Seyed Hossein Fattahi2, Seyed Ziaollah Haghi1, Kamran Aryana3, Ali Aryanniya2, Saeed Akhlaghi4, Fateme Naghavi Riyabi2 and Shima Sheibani5
Abstract Background: Esophageal cancer is among the most common gastrointestinal cancers for which the main treatment is surgery. This study was undertaken to analyze the results of Botox injection in preventing gastric stasis in these patients. Patients and methods: 60 patients with esophageal cancer in the middle and lower third parts were included in our study between 2010 and 2011, and were randomly divided into two groups. In group A, 30 patients underwent pyloroplasty, and in group B, injection of botulinum toxin into the pyloric sphincter muscle was used in 30 patients. Results: The mean age of these patients was 61 10.7 years and the male/female ratio was 33:27. Isotope scans 3 weeks after surgery showed that 5 patients in group A and 3 in group B had delayed gastric emptying; there was no significant difference between the 2 groups, and the success rate of Botox injection was 90%. Conclusion: Considering the fact that there was no significant difference between pyloroplasty and Botox injection on gastric emptying after surgery, and given the need to use less-aggressive techniques and facilitate greater use of endoscopic methods, botulinum toxin injection may be used instead of pyloroplasty as a simple, effective, and complicationfree method to prevent delayed gastric emptying.
Keywords Botulinum toxins, Esophageal neoplasms, Esophagectomy, Gastric emptying, Pylorus
Introduction Esophageal cancer is among the most common gastrointestinal cancers. The first choice of treatment is surgery in which a total or partial esophagectomy is performed along with anastomosis in the cervical or thoracic areas. Today, stomach and colon are the most widely used substitutes for esophagus, each having its own set of advantages and disadvantages.1,2 At present, stomach is the first choice after esophagectomy, being used in benign and malignant cases even when the patient is expected to have a long and normal life.2 In this procedure, the stomach is released based on the right gastroepiploic artery, and inserted into the thorax.1–3 Problems associated with stomach replacement include a stomach emptying disorder followed by vagotomy and practical clogging of the pylorus.4 To prevent complications resulting from severing of the vagus nerve and provide sufficient drainage, the patient has to undergo pyloroplasty, pyloromyotomy,
and bougienage. Different drainage techniques may be used to counter this problem, but pyloroplasty may 1
Cardiothoracic Surgery and Transplant Research Center, Emam Reza Hospital, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran 2 Endoscopic & Minimally Invasive Surgery Research Center, Ghaem Hospital, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran 3 Nuclear Medicine Research Center, Mashhad University of Medical Sciences, Mashhad, Iran 4 Department of Research, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran 5 Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran Corresponding author: Seyed Ziaollah Haghi, Cardiothoracic Surgery and Transplant Research Center, Emam Reza Hospital, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. Email: [email protected]
Downloaded from aan.sagepub.com at SUNY HEALTH SCIENCE CENTER on March 26, 2015
690
Asian Cardiovascular & Thoracic Annals 21(6)
result in the leakage of digestive contents and related complications.1,2 Botox injection has so far been used in the treatment of achalasia and diabetic gastroparesis.5,6 In terms of mechanism, botulinum toxin is known as an agent that blocks presynaptic neuromuscular receptors, capable of creating muscular weakness within moments of its intramuscular injection.6 Studies have shown that injection of Botox helps patients suffering from postsurgical pyloric clogging.6 Botox injection is also used as an alternative method for the treatment of gastric emptying disorder.7–9 Given the obvious preference for esophageal resection with minimally invasive combined surgeries, the use of thoracoscopy for esophagectomy and laparoscopy for preparation of the gastric conduit has been proposed.2 In this study, we compared the effects of Botox injection and pyloroplasty in preventing delayed gastric emptying after esophagectomy.
Patients and methods This study included 60 patients suffering from thoracic or gastric esophageal cancer who underwent esophagectomy at Ghaem and Omid Hospitals of Mashhad in 2010 and 2011. The patients were fully informed about the surgery and possible side effects, and their consent was obtained for the surgery. The study was in fact a clinical experiment with random allocation. Inclusion criteria included: patients with esophageal cancer in the middle and lower third parts, who underwent surgery in which stomach was used as a replacement; gastric emptying scan 3 weeks after surgery; and the patient’s voluntary participation. Exclusion criteria included: the finding during surgery that stomach was not a good substitute; patients dying at surgery due to medical or surgical complications; ischemia or gastric necrosis in replacement stomachs, resulting in the stomachs being removed; diabetic patients; those not volunteering for the study; and history of neoadjuvant therapy. Patients qualifying by the above criteria were randomly sampled, and 60 were chosen form the statistical population. They were randomly divided into even and odd groups, and treated by surgery. In group A, the stomach was prepared, the esophagus was removed, pyloroplasty and stomach replacement surgery were undertaken, followed by esophageal-to-stomach anastomosis at the neck. In group B, the stomach was prepared and the esophagus was removed, Botox was injected (200 units of toxin diluted in 5 mL of 0.9% saline solution) with a 21 G needle at the upper and lower sections of the pyloric muscle in a transmural manner. In both groups, the same methods and techniques for stomach preparation, esophagus replacement, and esophagus-to-stomach anastomosis were used.
Seven days after surgery, all patients were examined with barium to evaluate gastric emptying and to check for any sort of pyloric leakage. Delayed gastric emptying was determined by radiologists who performed the barium swallow tests under fluoroscopy. Any neck leakage was also reported as a finding of the study. All patients were examined by isotope scanning techniques for any type of gastric emptying disorder 3 weeks after surgery. For this technique, the patients had nil by mouth the night before the scan. They were prohibited from taking prokinetic agents such as metoclopramide or erythromycin. The scan was carried out with 100 g of egg albumin labeled with colloid solution, 2 pieces of extra-baked bread, and 120 mL of water. Patients were studied in terms of age, clinical symptoms, pathology, tumor position, surgical techniques, hospital side effects, mortality rate, and gastric emptying (1 and 3 weeks after surgery). The data obtained were entered into SPSS version 1.5 (SPSS, Inc., Chicago, IL, USA) and analyzed by the chi-square method.
Results Of the patients considered for the study, 5 were excluded due to intraoperative stomach ischemia in 1, past history of stomach surgery in 2, and death due to surgery in 2. The mean age of the 60 participants was 61 10.7 years, ranging from 41 years to 89 years; 33 (55%) were male and 27 (45%) were female. Statistical analyses demonstrated no significant difference in terms of sex, tumor position, and pathology in the 2 groups (Table 1). Each group had one death: due to pulmonary insufficiency 7 days after surgery in group A, and due to myocardial infarction 4 weeks after surgery in group B. Results of barium studies 7 days after surgery showed that group A had 21 cases of normal gastric emptying and 9 cases of delayed emptying, while group B had 24 cases of normal emptying and 6 cases of delayed emptying. The chi-square test results indicated no significant difference between the 2 groups in terms of gastric emptying at that time (Table 2). The isotope scans 3 weeks after surgery in the 59 survivors showed that group A had 23 cases of normal emptying and 7 cases of delayed emptying, while group B had 26 cases of normal emptying and 3 cases of delayed emptying. Results of the chi-square test showed no significant difference between the 2 groups in terms of gastric emptying at that time (Table 3). Among the patients with proven gastric dysfunction and stasis, 2 developed aspiration pneumonia. They were successfully treated medically. Of the 30 patients treated by Botox injection, 90% had normal gastric emptying after surgery; in the other 10%, there was symptomatic delayed gastric emptying in some patients who were treated without
Downloaded from aan.sagepub.com at SUNY HEALTH SCIENCE CENTER on March 26, 2015
Bagheri et al.
691 Table 1. Characteristics of 60 patients undergoing esophagectomy. Variable Sex Male Female Tumor position Middle third Inferior third Tumor pathology Squamous cell carcinoma Adenocarcinoma
Botox
Pyloromyotomy
19 (63.3%) 11 (36.7%)
14 (46.6%) 16 (53.4%)
20 (66.7%) 10 (33.3%)
18 (60%) 18 (40%)
30 (100%) 0
24 (80%) 6 (20%)
p value 0.196
0.637
0.021
Table 2. Barium study in 60 patients 7 days after esophagectomy. Findings
Botox
Pyloromyotomy
p value
Normal emptying Delayed emptying Total
24 (80%) 6 (20%) 30 (100%)
21 (70%) 9 (30%) 30 (100%)
0.446
Table 3. Gastric discharge by isotope scan 3 weeks after surgery in 59 patients. Findings
Botox
Pyloromyotomy
p value
Normal discharge Delayed discharge Total
27 (93%) 3 (7%) 30 (100%)
23 (76%) 6 (24%) 29 (100%)
0.355
further surgery (with conservation management). Of the 30 patients who underwent pylorotomy, 76% had normal gastric emptying after surgery. There were no Botox-related side effects.
Discussion Pyloric function disorder and improper gastric emptying results in diet resistance, feelings of fullness and fatigue, breathlessness, vomiting, aspiration, and eventually pneumonia, which may at times require interventions such as dilatation, pyloric stent fixation, or even a second surgery. Another problem is the risk of gastric acid reflux and its aspiration, which is mostly observed in cervical anastomoses rather than thoracic anastomoses, and increases with pyloric function disorder.1,10 On the other hand, drainage with methods such as
pyloroplasty may cause other complications such as dumping syndrome, esophagitis caused by biliary reflux, leakage at the pyloroplasty site, abdominal trauma, sepsis, and even mortality, with different results in various studies.1,2 Valanovich11 compared the drainage advantages (e.g., faster gastric discharge) and disadvantages (side effects), and concluded that compared to leaving the pylorus intact, the different methods of drainage not only had no advantage but also incurred many complications. Another study by Fok and colleagues12 compared drainage and no drainage, and reported better gastric emptying time in patients undergoing drainage. The most important clinical symptoms of gastric emptying delay are associated with stasis and pulmonary side effects, particularly aspiration. In a recent study by Hagen and Peyre,13 each gastric drainage operation was reported to reduce gastric stasis symptoms and improve quality of life, which translated into a higher chance of returning to normal life in a shorter time. Independent studies by Johansson and colleagues14 and Kobayashi and colleagues15 showed that patients who had undergone pyloric drainage surgery had fewer symptoms of gastric fullness, nausea, and vomiting. The better diet tolerance also resulted in better weight gain. Given the remarkable gastric emptying delay and its side effects in the group excluded from pyloric interventions, they recommended performing the drainage operation. In addition, the meta-analysis by Urschel and colleagues16 showed that pyloric drainage reduced gastric outlet obstruction and early post-surgical symptoms, but had few effects on other early or late results. Pyloroplasty is believed to be associated with fewer risks but may result in involuntary rupture of tissues. If treated, this may result in leakage in 2% of cases. It may even go unnoticed during the operation and later result in complications such as sepsis, abdominal abscess, and even mortality.1,4 In view of the better
Downloaded from aan.sagepub.com at SUNY HEALTH SCIENCE CENTER on March 26, 2015
692
Asian Cardiovascular & Thoracic Annals 21(6)
performance of patients undergoing pyloric drainage, efforts have been focused on creating techniques with minimum complications and maximum effectiveness. Botox injection at the pyloric site has been proposed to solve this problem, and its effectiveness and safety have been verified by numerous studies.7,8 Botulinum toxin injection in the lower esophageal sphincter for achalasia proved effective in reducing short-term achalasia symptoms in patients unable to tolerate surgery.5 Gastric motility deficiency following esophagectomy, and the potential destructive effects of pyloroplasty in the long-term functioning of the stomach, have resulted in more use of botulinum toxin. The other advantage of this approach is that the botulinum toxin maintains sufficient perioperative gastric emptying and seldom has long-term side effects such as dumping and biliary reflux.17 Considering the fact that there was no significant difference between pyloroplasty and Botox injection on gastric emptying after surgery to replace the esophagus with stomach, and given the need to use lessaggressive techniques and facilitate more use of endoscopic methods, botulinum toxin injection may be used instead of pyloroplasty as a simple, effective, and complication-free method to prevent gastric emptying delay. Acknowledgement This paper is the result of a thesis by Ali Aryanniya which was supported by the Deputy of Research, Mashhad University of Medical Sciences. The authors wish to thank the Vice Chancellor for Education and the research committee of the university for their support.
Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
Conflicts of interest statement None declared.
References 1. Orringer MB. Transhiatal esophagectomy. In: Patterson GA, Pearson FG, Cooper JD, Deslauriers J, Rice TW, Luketich JD, Leurt AEM (eds) Pearson’s thoracic and esophageal surgery, 13th edn. Philadelphia: Churchill Livingstone, 2008, pp. 551–589. 2. Orringer MB. Transhiatal esophagectomy. In: Shields TW, LoCicero J, Reed CE, Fines RH (eds) General Thoracic Surgery, 7th edn. Philadelphia: Lippincott Williams & Wilkins, 2009, pp. 1771–2002.
3. Dempsey DT. Stomach. In: Brunicardi F, Anderson D, Billiar T, Dunn D, Hunter J, Matthews J (eds) Schwartz’s Principles of Surgery, 8th edn. New York: McGraw Hill, 2005, pp. 960–975. 4. Zwischenberger JB, Savage C and Bhutani MS. Esophagus. In: Townsend Jr CM, Beauchamp RD, Evers BM, Mattox KL (eds) Sabiston Textbook of Surgery, 17th edn. Philadelphia: Elsevier, 2004, pp. 1129–1137. 5. Pasricha PJ, Rai R, Ravich WJ, Hendrix TR and Kalloo AN. Botulinum toxin for achalasia: long-term outcome and predictors of response. Gastroenterology 1996; 110: 1410–1415. 6. Bai Y, Xu MJ, Yang X, et al. A systematic review on intrapyloric botulinum toxin injection for gastroparesis. Digestion 2010; 81: 27–34. 7. Martin JT, Federico JA, McKelvey AA, Kent MS and Fabian T. Prevention of delayed gastric emptying after esophagectomy: a single center’s experience with botulinum toxin. Ann Thorac Surg 2009; 87: 1708–1713. 8. Kent MS, Pennathur A, Fabian T, et al. A pilot study of botulinum toxin injection for the treatment of delayed gastric emptying following esophagectomy. Surg Endosc 2007; 21: 754–757. 9. Tsui JK. Botulinum toxin as a therapeutic agent. Pharmacol Ther 1996; 72: 13–24. 10. Johansson J, Johnsson F, Groshen S and Walther B. Pharyngeal reflux gastric pull-up esophagectomy with neck and chest anastomosis. J Thorac Cardiovasc Surg 1999; 118: 1078–1083. 11. Valanovich V. Esophagogastrectomy without pyloroplasty. Dis Esophagus 2003; 16: 243–245. 12. Fok M, Cheng SW and Wong J. Pyloroplasty versus no drainage in gastric replacement of the esophagus. Am J Surg 1991; 162: 447–452. 13. Hagen JA and Peyre CG. Gastric emptying procedures after esophagectomy. In: Furgusun MK (ed.) Difficult decisions in thoracic surgery. London: Springer-Verlag, 2007, pp. 250–257. 14. Johansson J, Sloth M, Bajc M and Walther B. Radioisotope evaluation of the esophageal remnant and the gastric conduit after gastric pull-up esophagectomy. Surgery 1999; 125: 297–303. 15. Kobayashi A, Ide H, Eguchi R, Nakamura T, Hayashi K and Hanyu F. The efficacy of pyloroplasty affecting to oral-intake quality of life using reconstruction with gastric tube post esophagectomy. Nippon Kyobu Geka Gakkai Zasshi 1996; 44: 770–778. 16. Urschel JD, Blewett CJ, Young JE, Miller JD and Bennett WF. Pyloric drainage (pyloroplasty) or no drainage in gastric reconstruction after esophagectomy: a meta- analysis of randomized controlled trials. Dig Surg 2002; 19: 160–164. 17. Lanuti M, de Delva PE, Wright CD, et al. Postesophagectomy gastric outlet obstruction: role of pyloroplasty and management with endoscopic pyloric dilatation. Eur J Cardiothorac Surg 2007; 31: 149–153.
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Botulinum toxin for prevention of delayed gastric emptying after esophagectomy
Asian Cardiovascular & Thoracic Annals 21(6) 689–692 ß The Author(s) 2012 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0218492312468438 aan.sagepub.com
Reza Bagheri1, Seyed Hossein Fattahi2, Seyed Ziaollah Haghi1, Kamran Aryana3, Ali Aryanniya2, Saeed Akhlaghi4, Fateme Naghavi Riyabi2 and Shima Sheibani5
Abstract Background: Esophageal cancer is among the most common gastrointestinal cancers for which the main treatment is surgery. This study was undertaken to analyze the results of Botox injection in preventing gastric stasis in these patients. Patients and methods: 60 patients with esophageal cancer in the middle and lower third parts were included in our study between 2010 and 2011, and were randomly divided into two groups. In group A, 30 patients underwent pyloroplasty, and in group B, injection of botulinum toxin into the pyloric sphincter muscle was used in 30 patients. Results: The mean age of these patients was 61 10.7 years and the male/female ratio was 33:27. Isotope scans 3 weeks after surgery showed that 5 patients in group A and 3 in group B had delayed gastric emptying; there was no significant difference between the 2 groups, and the success rate of Botox injection was 90%. Conclusion: Considering the fact that there was no significant difference between pyloroplasty and Botox injection on gastric emptying after surgery, and given the need to use less-aggressive techniques and facilitate greater use of endoscopic methods, botulinum toxin injection may be used instead of pyloroplasty as a simple, effective, and complicationfree method to prevent delayed gastric emptying.
Keywords Botulinum toxins, Esophageal neoplasms, Esophagectomy, Gastric emptying, Pylorus
Introduction Esophageal cancer is among the most common gastrointestinal cancers. The first choice of treatment is surgery in which a total or partial esophagectomy is performed along with anastomosis in the cervical or thoracic areas. Today, stomach and colon are the most widely used substitutes for esophagus, each having its own set of advantages and disadvantages.1,2 At present, stomach is the first choice after esophagectomy, being used in benign and malignant cases even when the patient is expected to have a long and normal life.2 In this procedure, the stomach is released based on the right gastroepiploic artery, and inserted into the thorax.1–3 Problems associated with stomach replacement include a stomach emptying disorder followed by vagotomy and practical clogging of the pylorus.4 To prevent complications resulting from severing of the vagus nerve and provide sufficient drainage, the patient has to undergo pyloroplasty, pyloromyotomy,
and bougienage. Different drainage techniques may be used to counter this problem, but pyloroplasty may 1
Cardiothoracic Surgery and Transplant Research Center, Emam Reza Hospital, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran 2 Endoscopic & Minimally Invasive Surgery Research Center, Ghaem Hospital, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran 3 Nuclear Medicine Research Center, Mashhad University of Medical Sciences, Mashhad, Iran 4 Department of Research, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran 5 Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran Corresponding author: Seyed Ziaollah Haghi, Cardiothoracic Surgery and Transplant Research Center, Emam Reza Hospital, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. Email: [email protected]
Downloaded from aan.sagepub.com at SUNY HEALTH SCIENCE CENTER on March 26, 2015
690
Asian Cardiovascular & Thoracic Annals 21(6)
result in the leakage of digestive contents and related complications.1,2 Botox injection has so far been used in the treatment of achalasia and diabetic gastroparesis.5,6 In terms of mechanism, botulinum toxin is known as an agent that blocks presynaptic neuromuscular receptors, capable of creating muscular weakness within moments of its intramuscular injection.6 Studies have shown that injection of Botox helps patients suffering from postsurgical pyloric clogging.6 Botox injection is also used as an alternative method for the treatment of gastric emptying disorder.7–9 Given the obvious preference for esophageal resection with minimally invasive combined surgeries, the use of thoracoscopy for esophagectomy and laparoscopy for preparation of the gastric conduit has been proposed.2 In this study, we compared the effects of Botox injection and pyloroplasty in preventing delayed gastric emptying after esophagectomy.
Patients and methods This study included 60 patients suffering from thoracic or gastric esophageal cancer who underwent esophagectomy at Ghaem and Omid Hospitals of Mashhad in 2010 and 2011. The patients were fully informed about the surgery and possible side effects, and their consent was obtained for the surgery. The study was in fact a clinical experiment with random allocation. Inclusion criteria included: patients with esophageal cancer in the middle and lower third parts, who underwent surgery in which stomach was used as a replacement; gastric emptying scan 3 weeks after surgery; and the patient’s voluntary participation. Exclusion criteria included: the finding during surgery that stomach was not a good substitute; patients dying at surgery due to medical or surgical complications; ischemia or gastric necrosis in replacement stomachs, resulting in the stomachs being removed; diabetic patients; those not volunteering for the study; and history of neoadjuvant therapy. Patients qualifying by the above criteria were randomly sampled, and 60 were chosen form the statistical population. They were randomly divided into even and odd groups, and treated by surgery. In group A, the stomach was prepared, the esophagus was removed, pyloroplasty and stomach replacement surgery were undertaken, followed by esophageal-to-stomach anastomosis at the neck. In group B, the stomach was prepared and the esophagus was removed, Botox was injected (200 units of toxin diluted in 5 mL of 0.9% saline solution) with a 21 G needle at the upper and lower sections of the pyloric muscle in a transmural manner. In both groups, the same methods and techniques for stomach preparation, esophagus replacement, and esophagus-to-stomach anastomosis were used.
Seven days after surgery, all patients were examined with barium to evaluate gastric emptying and to check for any sort of pyloric leakage. Delayed gastric emptying was determined by radiologists who performed the barium swallow tests under fluoroscopy. Any neck leakage was also reported as a finding of the study. All patients were examined by isotope scanning techniques for any type of gastric emptying disorder 3 weeks after surgery. For this technique, the patients had nil by mouth the night before the scan. They were prohibited from taking prokinetic agents such as metoclopramide or erythromycin. The scan was carried out with 100 g of egg albumin labeled with colloid solution, 2 pieces of extra-baked bread, and 120 mL of water. Patients were studied in terms of age, clinical symptoms, pathology, tumor position, surgical techniques, hospital side effects, mortality rate, and gastric emptying (1 and 3 weeks after surgery). The data obtained were entered into SPSS version 1.5 (SPSS, Inc., Chicago, IL, USA) and analyzed by the chi-square method.
Results Of the patients considered for the study, 5 were excluded due to intraoperative stomach ischemia in 1, past history of stomach surgery in 2, and death due to surgery in 2. The mean age of the 60 participants was 61 10.7 years, ranging from 41 years to 89 years; 33 (55%) were male and 27 (45%) were female. Statistical analyses demonstrated no significant difference in terms of sex, tumor position, and pathology in the 2 groups (Table 1). Each group had one death: due to pulmonary insufficiency 7 days after surgery in group A, and due to myocardial infarction 4 weeks after surgery in group B. Results of barium studies 7 days after surgery showed that group A had 21 cases of normal gastric emptying and 9 cases of delayed emptying, while group B had 24 cases of normal emptying and 6 cases of delayed emptying. The chi-square test results indicated no significant difference between the 2 groups in terms of gastric emptying at that time (Table 2). The isotope scans 3 weeks after surgery in the 59 survivors showed that group A had 23 cases of normal emptying and 7 cases of delayed emptying, while group B had 26 cases of normal emptying and 3 cases of delayed emptying. Results of the chi-square test showed no significant difference between the 2 groups in terms of gastric emptying at that time (Table 3). Among the patients with proven gastric dysfunction and stasis, 2 developed aspiration pneumonia. They were successfully treated medically. Of the 30 patients treated by Botox injection, 90% had normal gastric emptying after surgery; in the other 10%, there was symptomatic delayed gastric emptying in some patients who were treated without
Downloaded from aan.sagepub.com at SUNY HEALTH SCIENCE CENTER on March 26, 2015
Bagheri et al.
691 Table 1. Characteristics of 60 patients undergoing esophagectomy. Variable Sex Male Female Tumor position Middle third Inferior third Tumor pathology Squamous cell carcinoma Adenocarcinoma
Botox
Pyloromyotomy
19 (63.3%) 11 (36.7%)
14 (46.6%) 16 (53.4%)
20 (66.7%) 10 (33.3%)
18 (60%) 18 (40%)
30 (100%) 0
24 (80%) 6 (20%)
p value 0.196
0.637
0.021
Table 2. Barium study in 60 patients 7 days after esophagectomy. Findings
Botox
Pyloromyotomy
p value
Normal emptying Delayed emptying Total
24 (80%) 6 (20%) 30 (100%)
21 (70%) 9 (30%) 30 (100%)
0.446
Table 3. Gastric discharge by isotope scan 3 weeks after surgery in 59 patients. Findings
Botox
Pyloromyotomy
p value
Normal discharge Delayed discharge Total
27 (93%) 3 (7%) 30 (100%)
23 (76%) 6 (24%) 29 (100%)
0.355
further surgery (with conservation management). Of the 30 patients who underwent pylorotomy, 76% had normal gastric emptying after surgery. There were no Botox-related side effects.
Discussion Pyloric function disorder and improper gastric emptying results in diet resistance, feelings of fullness and fatigue, breathlessness, vomiting, aspiration, and eventually pneumonia, which may at times require interventions such as dilatation, pyloric stent fixation, or even a second surgery. Another problem is the risk of gastric acid reflux and its aspiration, which is mostly observed in cervical anastomoses rather than thoracic anastomoses, and increases with pyloric function disorder.1,10 On the other hand, drainage with methods such as
pyloroplasty may cause other complications such as dumping syndrome, esophagitis caused by biliary reflux, leakage at the pyloroplasty site, abdominal trauma, sepsis, and even mortality, with different results in various studies.1,2 Valanovich11 compared the drainage advantages (e.g., faster gastric discharge) and disadvantages (side effects), and concluded that compared to leaving the pylorus intact, the different methods of drainage not only had no advantage but also incurred many complications. Another study by Fok and colleagues12 compared drainage and no drainage, and reported better gastric emptying time in patients undergoing drainage. The most important clinical symptoms of gastric emptying delay are associated with stasis and pulmonary side effects, particularly aspiration. In a recent study by Hagen and Peyre,13 each gastric drainage operation was reported to reduce gastric stasis symptoms and improve quality of life, which translated into a higher chance of returning to normal life in a shorter time. Independent studies by Johansson and colleagues14 and Kobayashi and colleagues15 showed that patients who had undergone pyloric drainage surgery had fewer symptoms of gastric fullness, nausea, and vomiting. The better diet tolerance also resulted in better weight gain. Given the remarkable gastric emptying delay and its side effects in the group excluded from pyloric interventions, they recommended performing the drainage operation. In addition, the meta-analysis by Urschel and colleagues16 showed that pyloric drainage reduced gastric outlet obstruction and early post-surgical symptoms, but had few effects on other early or late results. Pyloroplasty is believed to be associated with fewer risks but may result in involuntary rupture of tissues. If treated, this may result in leakage in 2% of cases. It may even go unnoticed during the operation and later result in complications such as sepsis, abdominal abscess, and even mortality.1,4 In view of the better
Downloaded from aan.sagepub.com at SUNY HEALTH SCIENCE CENTER on March 26, 2015
692
Asian Cardiovascular & Thoracic Annals 21(6)
performance of patients undergoing pyloric drainage, efforts have been focused on creating techniques with minimum complications and maximum effectiveness. Botox injection at the pyloric site has been proposed to solve this problem, and its effectiveness and safety have been verified by numerous studies.7,8 Botulinum toxin injection in the lower esophageal sphincter for achalasia proved effective in reducing short-term achalasia symptoms in patients unable to tolerate surgery.5 Gastric motility deficiency following esophagectomy, and the potential destructive effects of pyloroplasty in the long-term functioning of the stomach, have resulted in more use of botulinum toxin. The other advantage of this approach is that the botulinum toxin maintains sufficient perioperative gastric emptying and seldom has long-term side effects such as dumping and biliary reflux.17 Considering the fact that there was no significant difference between pyloroplasty and Botox injection on gastric emptying after surgery to replace the esophagus with stomach, and given the need to use lessaggressive techniques and facilitate more use of endoscopic methods, botulinum toxin injection may be used instead of pyloroplasty as a simple, effective, and complication-free method to prevent gastric emptying delay. Acknowledgement This paper is the result of a thesis by Ali Aryanniya which was supported by the Deputy of Research, Mashhad University of Medical Sciences. The authors wish to thank the Vice Chancellor for Education and the research committee of the university for their support.
Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
Conflicts of interest statement None declared.
References 1. Orringer MB. Transhiatal esophagectomy. In: Patterson GA, Pearson FG, Cooper JD, Deslauriers J, Rice TW, Luketich JD, Leurt AEM (eds) Pearson’s thoracic and esophageal surgery, 13th edn. Philadelphia: Churchill Livingstone, 2008, pp. 551–589. 2. Orringer MB. Transhiatal esophagectomy. In: Shields TW, LoCicero J, Reed CE, Fines RH (eds) General Thoracic Surgery, 7th edn. Philadelphia: Lippincott Williams & Wilkins, 2009, pp. 1771–2002.
3. Dempsey DT. Stomach. In: Brunicardi F, Anderson D, Billiar T, Dunn D, Hunter J, Matthews J (eds) Schwartz’s Principles of Surgery, 8th edn. New York: McGraw Hill, 2005, pp. 960–975. 4. Zwischenberger JB, Savage C and Bhutani MS. Esophagus. In: Townsend Jr CM, Beauchamp RD, Evers BM, Mattox KL (eds) Sabiston Textbook of Surgery, 17th edn. Philadelphia: Elsevier, 2004, pp. 1129–1137. 5. Pasricha PJ, Rai R, Ravich WJ, Hendrix TR and Kalloo AN. Botulinum toxin for achalasia: long-term outcome and predictors of response. Gastroenterology 1996; 110: 1410–1415. 6. Bai Y, Xu MJ, Yang X, et al. A systematic review on intrapyloric botulinum toxin injection for gastroparesis. Digestion 2010; 81: 27–34. 7. Martin JT, Federico JA, McKelvey AA, Kent MS and Fabian T. Prevention of delayed gastric emptying after esophagectomy: a single center’s experience with botulinum toxin. Ann Thorac Surg 2009; 87: 1708–1713. 8. Kent MS, Pennathur A, Fabian T, et al. A pilot study of botulinum toxin injection for the treatment of delayed gastric emptying following esophagectomy. Surg Endosc 2007; 21: 754–757. 9. Tsui JK. Botulinum toxin as a therapeutic agent. Pharmacol Ther 1996; 72: 13–24. 10. Johansson J, Johnsson F, Groshen S and Walther B. Pharyngeal reflux gastric pull-up esophagectomy with neck and chest anastomosis. J Thorac Cardiovasc Surg 1999; 118: 1078–1083. 11. Valanovich V. Esophagogastrectomy without pyloroplasty. Dis Esophagus 2003; 16: 243–245. 12. Fok M, Cheng SW and Wong J. Pyloroplasty versus no drainage in gastric replacement of the esophagus. Am J Surg 1991; 162: 447–452. 13. Hagen JA and Peyre CG. Gastric emptying procedures after esophagectomy. In: Furgusun MK (ed.) Difficult decisions in thoracic surgery. London: Springer-Verlag, 2007, pp. 250–257. 14. Johansson J, Sloth M, Bajc M and Walther B. Radioisotope evaluation of the esophageal remnant and the gastric conduit after gastric pull-up esophagectomy. Surgery 1999; 125: 297–303. 15. Kobayashi A, Ide H, Eguchi R, Nakamura T, Hayashi K and Hanyu F. The efficacy of pyloroplasty affecting to oral-intake quality of life using reconstruction with gastric tube post esophagectomy. Nippon Kyobu Geka Gakkai Zasshi 1996; 44: 770–778. 16. Urschel JD, Blewett CJ, Young JE, Miller JD and Bennett WF. Pyloric drainage (pyloroplasty) or no drainage in gastric reconstruction after esophagectomy: a meta- analysis of randomized controlled trials. Dig Surg 2002; 19: 160–164. 17. Lanuti M, de Delva PE, Wright CD, et al. Postesophagectomy gastric outlet obstruction: role of pyloroplasty and management with endoscopic pyloric dilatation. Eur J Cardiothorac Surg 2007; 31: 149–153.
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