Successful Airway Management in a Patient with Severe Proximal Achalasia Requires Interdisciplinary Cooperation Benjamin G. Ekstrom, MD,* Sarah Dance, MD,* Donald E. Low, MD, FACS,† and R. Eliot Fagley, MD* We report a case of a patient undergoing esophagectomy for end-stage achalasia, a rare condition associated with potentially catastrophic ventilatory and circulatory complications. The complexity of the case necessitated preoperative planning with the surgical specialist, development of a novel algorithm for airway management, and careful implementation of our plan. Isolation of the lungs from the esophagus presented unique challenges due to not only the anatomic derangements that are the hallmark of this disease process but also an unusual anatomic finding seen in this patient. (A&A Case Reports. 2014;3:153–5.)
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egaesophagus from end-stage achalasia is a rare condition that is challenging in its surgical management and may be equally challenging in its anesthetic management. Previously reported complications of achalasia include airway obstruction,1–8 malnutrition,9 left atrial obstruction,10,11 respiratory failure and arrest,4,8 acute and chronic aspiration,11,12 dyspnea,13 pneumonia,13,14 and lethal cardiac arrhythmias.15,16 The challenges to the anesthesiologist arise in accomplishing a safe induction, securing the airway, and appropriately timing extubation. Important anesthetic and surgical goals include rapid tracheal intubation,1 catheter or endoscopic aspiration of esophageal contents,2,6,17 careful evaluation of fitness for tracheal extubation,8 and definitive treatment of achalasia.18 Palliative tracheal stenting for airway obstruction may be a consideration for nonsurgical candidates refractory to medical therapy.7 We present a patient with severe end-stage achalasia and our algorithm for anesthetic induction and airway management. We report 2 novel complications of severe achalasia and megaesophagus that have not been previously reported. In addition, we identify several key factors that allow safe and effective management of this challenging problem. Finally, we discuss the generalizability of our strategies to other patients with achalasia. The patient gave permission for the authors to publish this case report.
CASE DESCRIPTION
A 69-year-old, 64-kg, 170-cm female with end-stage achalasia with megaesophagus and secondary tracheal obstruction, atrial fibrillation, and emphysema presented for perioperative planning before a right thoracotomy and esophagectomy with From the *Department of Anesthesiology, Virginia Mason Medical Center, Seattle, Washington; and †Department of General, Thoracic, and Vascular Surgery, Virginia Mason Medical Center, Seattle, Washington. Accepted for publication May 21, 2014.
Funding: Supported by the Department of Anesthesiology of Virginia Mason Medical Center. The authors declare no conflicts of interest. Address correspondence to Benjamin G. Ekstrom, MD, Department of Anesthesiology, Virginia Mason Medical Center, 1100 Ninth Ave., Seattle, WA 98101. Address e-mail to [email protected]. Copyright © 2014 International Anesthesia Research Society DOI: 10.1213/XAA.0000000000000094
salivary fistula creation. She had suffered multiple complications of achalasia since her diagnosis 13 years prior, including chronic reflux, aspiration, and dysphagia. Conservative management had included numerous esophagogastroduodenoscopies with bougie dilations and botulinum toxin injections of the lower esophageal sphincter. Four months prior, she had an episode of complete esophageal obstruction at mealtime resulting in acute airway obstruction and aspiration pneumonia requiring tracheal intubation, and nearly 4 weeks in the intensive care unit. She suffered prolonged respiratory failure which, in combination with esophageal mass effect on the trachea, resulted in subglottic stenosis necessitating tracheostomy. She also had paroxysmal episodes of severe bradycardia when placed supine. Having excluded cardiac causes, stimulation of the vagus nerve by the esophageal mass with reflex bradycardia was the presumptive diagnosis. Thereafter, the patient was maintained upright or sitting as much as possible. Per the surgeon’s recommendation, a jejunostomy tube was placed for nutritional support and, in preparation for surgery, she was transferred to a rehabilitation facility for further care until her nutritional status improved. She subsequently presented to our thoracic surgery clinic for surgical evaluation and anesthesiology consultation. Her preoperative otolaryngology examination suggested tracheomalacia and confirmed tracheal stenosis while preoperative computed tomography (CT) scan of the chest and neck showed subglottic narrowing and profoundly dilated proximal esophagus that produced visible tracheal compression (Fig. 1, CT images). The surgeon requested a double-lumen tube (DLT) for single lung ventilation but was amenable to a bronchial blocker if DLT placement could not be achieved. The airway plan is shown in Figure 2. On the day of surgery and after insertion of a thoracic epidural catheter at T5-T6, oxygen administration was accomplished using her in situ cuffless tracheostomy appliance and a high-flow tracheal mask with the patient in the seated position. Anesthesia was induced with lidocaine 1 mg/kg, propofol 2 mg/kg, and glycopyrrolate 0.2 mg. Upon loss of consciousness, her uncuffed tracheostomy tube was removed from the mature tracheostomy site, easily exchanged for a 7.0 cuffed endotracheal tube. Neuromuscular blockade followed with cisatracurium 0.15 mg/kg, and as her lungs were ventilated with sevoflurane, her back was slowly lowered to 45 degrees without cardiac dysrhythmia. Esophagoscopy resulted in
December 1, 2014 • Volume 3 • Number 11 cases-anesthesia-analgesia.org 153
Figure 1. Representative computed tomography images for our patient. A, Axial image at the level of the superior sternum. B, Annotated axial image. Green is dilated esophagus, red is airway/trachea, and blue is lung parenchyma. C, Midline sagittal image of the head and neck. D, Annotated sagittal image. Color key is same as (B).
Figure 2. Airway management plan for end-stage achalasia in our patient. Bold arrows represent the ideal course of action, which occurred with our patient. Dotted arrows include courses of action which could be considered but are not part of our algorithm.
suctioning >800 mL of thick secretions and air after which she was gradually positioned supine without complication. Before DLT placement, the oropharynx was suctioned and direct laryngoscopy revealed a grade 1 view of the larynx.
154 cases-anesthesia-analgesia.org
The tracheal tube was removed, and the tracheostomy stoma was occluded by a second operator with a red rubber catheter inserted into the trachea to maintain lumenal patency. A well-lubricated 37 French left-sided DLT was introduced to
A & A case reports
the glottic opening under direct laryngoscopy and advanced until the tracheal balloon was through the cords, at which point the red rubber catheter was removed. To minimize the possibility of creating tracheoesophageal fistula or posterior tracheal rupture, the curvature of the DLT was intentionally directed anteriorly, away from the esophagus, and the DLT was digitally palpated through the stoma and guided into the trachea to prevent exiting or “hanging up” on the tracheostomy. The tracheal cuff was inflated and proper position confirmed with fiberoptic bronchoscopy. After successfully securing the airway, an additional peripheral IV catheter and arterial catheter were placed. Surgery proceeded without incident and included esophagectomy with the creation of an esophagostomy spit fistula over the right clavicle. A gastrostomy tube was placed distally for feeding. A pertinent operative finding was adherence of the esophagus to the upper thoracic trachea. The patient remained hemodynamically stable throughout the operation. The trachea was extubated at the end of the procedure, and her cuffless tracheostomy tube was replaced. Postoperatively, she had no respiratory complications, her pain was well controlled with the thoracic epidural, and her esophagostomy was shown to be functional with barium swallow studies. She was discharged to home on postoperative day 3. By postoperative day 5, her tracheostomy tube had been removed without subsequent respiratory distress. Her otolaryngologist’s evaluation confirmed the stoma had closed and did not necessitate tracheostomy tube replacement due to lack of respiratory symptoms. At follow up 1 month postoperatively, she had recovered well, experienced no complications, and was able to lie flat, which had been impossible preoperatively. She returned approximately 4 months after the initial surgery for reanastomosis.
DISCUSSION
In this case report, we describe the successful anesthetic management of end-stage achalasia, also known as megaesophagus, with secondary tracheal obstruction. This case highlights the importance of excellent preoperative communication and planning between anesthesiologists and surgeons. The airway algorithm for this patient was reviewed in detail with all members of the anesthesia, surgical, and nursing teams, which likely contributed to a successful DLT placement. We report 2 novel complications of achalasia: reversible tracheal compression by the profoundly dilated proximal esophagus and positional bradycardia. Subglottic stenosis, which has been reported in achalasia, may have resulted from prolonged tracheal intubation in our patient. Severe achalasia contributed a second component of tracheal obstruction, which improved with esophagectomy to the point that she was no longer dependent on a tracheal tube for lumenal patency. Preoperative cross-sectional imaging is essential to fully evaluate the tracheal, pharyngeal, and esophageal anatomy for anesthetic management in patients with achalasia. Our patient’s preoperative CT scan revealing posterior tracheal wall compression by the profoundly dilated proximal esophagus guided our management to minimize trauma to this region. We emphasize early isolation of the respiratory tree from the esophagus and decompression of the esophagus. Evacuation of esophageal contents to reduce aspiration risk is a necessary step in airway management for patients with
achalasia and can be accomplished before induction of anesthesia with a carefully placed nasogastric tube, understanding that a nasogastric tube will be inadequate for removal of particulate material. Otherwise, awake tracheal intubation for elective procedures or early tracheal intubation in emergent circumstances (e.g., severe hypoxia or ongoing aspiration) should be considered. The surgical approach for esophagectomy may require lung isolation, but the risks of DLT placement compared to single-lumen tracheal tube placement in this clinical condition have not been described. Tewari and Gupta9 argue that the additional time needed to place a DLT may increase the risk of aspiration. In our case, tracheostomy facilitated isolation of the tracheobronchial tree before endoscopic aspiration of esophageal contents. Endoscopy to facilitate tracheal intubation is a novel technique for the patient at high risk for aspiration. In conclusion, interdisciplinary communication and collaboration along with a preplanned scheme for airway management allowed safe and effective anesthesia care for a patient with an unusual constellation of problems associated with end-stage achalasia. E REFERENCES 1. Hay H. Rapidly developing airway obstruction resulting from achalasia of the oesophagus. Eur J Anaesthesiol 2000;17:398–400 2. Arcos E, Medina C, Mearin F, Larish J, Guarner L, Malagelada JR. Achalasia presenting as acute airway obstruction. Dig Dis Sci 2000;45:2079–83 3. Wagh MS, Matloff DS, Carr-Locke DL. Life-threatening acute airway obstruction in achalasia. MedGenMed 2004;6:12 4. Bruijns SR, Hicks A. Achalasia: an unusual cause of airway obstruction. Emerg Med J 2009;26:148 5. Becker DJ, Castell DO. Acute airway obstruction in achalasia. Possible role of defective belch reflex. Gastroenterology 1989;97:1323–6 6. Dominguez F, Hernandez-Ranz F, Boixeda D, Valdazo P. Acute upper-airway obstruction in achalasia of the esophagus. Am J Gastroenterol 1987;82:362–4 7. Berrisford RG, Oo A, Walshaw MJ, Drakeley MJ. Tracheal obstruction in achalasia: a role for airway stenting? Ann Thorac Surg 1998;66:939–41 8. Galan G, Faure F, Tinturier F, Ossart M. [Respiratory failure caused by megaesophagus and tracheomalacia]. Ann Fr Anesth Reanim 1999;18:987–90 9. Tewari P, Gupta D. Megaesophagus: a challenge for anesthesiologists. Ann Card Anaesth 2013;16:61–2 10. Shillcutt SK, Roberts EK. Achalasia-induced left atrial compression diagnosed by transesophageal echocardiography. Anesth Analg 2011;113:476–8 11. Schalinski S, Guddat SS, Tsokos M, Byard RW. Megaesophagus and possible mechanisms of sudden death. J Forensic Sci 2009;54:216–9 12. Feo CV, Caramori G, Conti V, Calia N, Guzzinati I, Ravenna F, Pasquini C, De Troia A, Liboni A, Papi A. Esophageal achalasia with recurrent aspiration pneumoniae treated by laparoscopic Heller myotomy. Am Surg 2012;78:E168–70 13. Sinan H, Tatum RP, Soares RV, Martin AV, Pellegrini CA, Oelschlager BK. Prevalence of respiratory symptoms in patients with achalasia. Dis Esophagus 2011;24:224–8 14. Akritidis N, Gousis C, Dimos G, Paparounas K. Fever, cough, and bilateral lung infiltrates. Achalasia associated with aspiration pneumonia. Chest 2003;123:608–12 15. Sperry K. Achalasia, the Valsalva maneuver, and sudden death: a case report. J Forensic Sci 1994;39:547–51 16. Rösch W, Bachmann K, Ottenjann R. [Asystolic heart arrest in achalasia]. Dtsch Med Wochenschr 1969;94:2191–4 17. Ajani S, Shah NB, Vlahakis NE. Achalasia: a diagnosis that’s hard to swallow. Am J Respir Crit Care Med 2012;185:893 18. Richter JE. Update on the management of achalasia: balloons, surgery and drugs. Expert Rev Gastroenterol Hepatol 2008;2:435–45
December 1, 2014 • Volume 3 • Number 11 cases-anesthesia-analgesia.org 155
M
egaesophagus from end-stage achalasia is a rare condition that is challenging in its surgical management and may be equally challenging in its anesthetic management. Previously reported complications of achalasia include airway obstruction,1–8 malnutrition,9 left atrial obstruction,10,11 respiratory failure and arrest,4,8 acute and chronic aspiration,11,12 dyspnea,13 pneumonia,13,14 and lethal cardiac arrhythmias.15,16 The challenges to the anesthesiologist arise in accomplishing a safe induction, securing the airway, and appropriately timing extubation. Important anesthetic and surgical goals include rapid tracheal intubation,1 catheter or endoscopic aspiration of esophageal contents,2,6,17 careful evaluation of fitness for tracheal extubation,8 and definitive treatment of achalasia.18 Palliative tracheal stenting for airway obstruction may be a consideration for nonsurgical candidates refractory to medical therapy.7 We present a patient with severe end-stage achalasia and our algorithm for anesthetic induction and airway management. We report 2 novel complications of severe achalasia and megaesophagus that have not been previously reported. In addition, we identify several key factors that allow safe and effective management of this challenging problem. Finally, we discuss the generalizability of our strategies to other patients with achalasia. The patient gave permission for the authors to publish this case report.
CASE DESCRIPTION
A 69-year-old, 64-kg, 170-cm female with end-stage achalasia with megaesophagus and secondary tracheal obstruction, atrial fibrillation, and emphysema presented for perioperative planning before a right thoracotomy and esophagectomy with From the *Department of Anesthesiology, Virginia Mason Medical Center, Seattle, Washington; and †Department of General, Thoracic, and Vascular Surgery, Virginia Mason Medical Center, Seattle, Washington. Accepted for publication May 21, 2014.
Funding: Supported by the Department of Anesthesiology of Virginia Mason Medical Center. The authors declare no conflicts of interest. Address correspondence to Benjamin G. Ekstrom, MD, Department of Anesthesiology, Virginia Mason Medical Center, 1100 Ninth Ave., Seattle, WA 98101. Address e-mail to [email protected]. Copyright © 2014 International Anesthesia Research Society DOI: 10.1213/XAA.0000000000000094
salivary fistula creation. She had suffered multiple complications of achalasia since her diagnosis 13 years prior, including chronic reflux, aspiration, and dysphagia. Conservative management had included numerous esophagogastroduodenoscopies with bougie dilations and botulinum toxin injections of the lower esophageal sphincter. Four months prior, she had an episode of complete esophageal obstruction at mealtime resulting in acute airway obstruction and aspiration pneumonia requiring tracheal intubation, and nearly 4 weeks in the intensive care unit. She suffered prolonged respiratory failure which, in combination with esophageal mass effect on the trachea, resulted in subglottic stenosis necessitating tracheostomy. She also had paroxysmal episodes of severe bradycardia when placed supine. Having excluded cardiac causes, stimulation of the vagus nerve by the esophageal mass with reflex bradycardia was the presumptive diagnosis. Thereafter, the patient was maintained upright or sitting as much as possible. Per the surgeon’s recommendation, a jejunostomy tube was placed for nutritional support and, in preparation for surgery, she was transferred to a rehabilitation facility for further care until her nutritional status improved. She subsequently presented to our thoracic surgery clinic for surgical evaluation and anesthesiology consultation. Her preoperative otolaryngology examination suggested tracheomalacia and confirmed tracheal stenosis while preoperative computed tomography (CT) scan of the chest and neck showed subglottic narrowing and profoundly dilated proximal esophagus that produced visible tracheal compression (Fig. 1, CT images). The surgeon requested a double-lumen tube (DLT) for single lung ventilation but was amenable to a bronchial blocker if DLT placement could not be achieved. The airway plan is shown in Figure 2. On the day of surgery and after insertion of a thoracic epidural catheter at T5-T6, oxygen administration was accomplished using her in situ cuffless tracheostomy appliance and a high-flow tracheal mask with the patient in the seated position. Anesthesia was induced with lidocaine 1 mg/kg, propofol 2 mg/kg, and glycopyrrolate 0.2 mg. Upon loss of consciousness, her uncuffed tracheostomy tube was removed from the mature tracheostomy site, easily exchanged for a 7.0 cuffed endotracheal tube. Neuromuscular blockade followed with cisatracurium 0.15 mg/kg, and as her lungs were ventilated with sevoflurane, her back was slowly lowered to 45 degrees without cardiac dysrhythmia. Esophagoscopy resulted in
December 1, 2014 • Volume 3 • Number 11 cases-anesthesia-analgesia.org 153
Figure 1. Representative computed tomography images for our patient. A, Axial image at the level of the superior sternum. B, Annotated axial image. Green is dilated esophagus, red is airway/trachea, and blue is lung parenchyma. C, Midline sagittal image of the head and neck. D, Annotated sagittal image. Color key is same as (B).
Figure 2. Airway management plan for end-stage achalasia in our patient. Bold arrows represent the ideal course of action, which occurred with our patient. Dotted arrows include courses of action which could be considered but are not part of our algorithm.
suctioning >800 mL of thick secretions and air after which she was gradually positioned supine without complication. Before DLT placement, the oropharynx was suctioned and direct laryngoscopy revealed a grade 1 view of the larynx.
154 cases-anesthesia-analgesia.org
The tracheal tube was removed, and the tracheostomy stoma was occluded by a second operator with a red rubber catheter inserted into the trachea to maintain lumenal patency. A well-lubricated 37 French left-sided DLT was introduced to
A & A case reports
the glottic opening under direct laryngoscopy and advanced until the tracheal balloon was through the cords, at which point the red rubber catheter was removed. To minimize the possibility of creating tracheoesophageal fistula or posterior tracheal rupture, the curvature of the DLT was intentionally directed anteriorly, away from the esophagus, and the DLT was digitally palpated through the stoma and guided into the trachea to prevent exiting or “hanging up” on the tracheostomy. The tracheal cuff was inflated and proper position confirmed with fiberoptic bronchoscopy. After successfully securing the airway, an additional peripheral IV catheter and arterial catheter were placed. Surgery proceeded without incident and included esophagectomy with the creation of an esophagostomy spit fistula over the right clavicle. A gastrostomy tube was placed distally for feeding. A pertinent operative finding was adherence of the esophagus to the upper thoracic trachea. The patient remained hemodynamically stable throughout the operation. The trachea was extubated at the end of the procedure, and her cuffless tracheostomy tube was replaced. Postoperatively, she had no respiratory complications, her pain was well controlled with the thoracic epidural, and her esophagostomy was shown to be functional with barium swallow studies. She was discharged to home on postoperative day 3. By postoperative day 5, her tracheostomy tube had been removed without subsequent respiratory distress. Her otolaryngologist’s evaluation confirmed the stoma had closed and did not necessitate tracheostomy tube replacement due to lack of respiratory symptoms. At follow up 1 month postoperatively, she had recovered well, experienced no complications, and was able to lie flat, which had been impossible preoperatively. She returned approximately 4 months after the initial surgery for reanastomosis.
DISCUSSION
In this case report, we describe the successful anesthetic management of end-stage achalasia, also known as megaesophagus, with secondary tracheal obstruction. This case highlights the importance of excellent preoperative communication and planning between anesthesiologists and surgeons. The airway algorithm for this patient was reviewed in detail with all members of the anesthesia, surgical, and nursing teams, which likely contributed to a successful DLT placement. We report 2 novel complications of achalasia: reversible tracheal compression by the profoundly dilated proximal esophagus and positional bradycardia. Subglottic stenosis, which has been reported in achalasia, may have resulted from prolonged tracheal intubation in our patient. Severe achalasia contributed a second component of tracheal obstruction, which improved with esophagectomy to the point that she was no longer dependent on a tracheal tube for lumenal patency. Preoperative cross-sectional imaging is essential to fully evaluate the tracheal, pharyngeal, and esophageal anatomy for anesthetic management in patients with achalasia. Our patient’s preoperative CT scan revealing posterior tracheal wall compression by the profoundly dilated proximal esophagus guided our management to minimize trauma to this region. We emphasize early isolation of the respiratory tree from the esophagus and decompression of the esophagus. Evacuation of esophageal contents to reduce aspiration risk is a necessary step in airway management for patients with
achalasia and can be accomplished before induction of anesthesia with a carefully placed nasogastric tube, understanding that a nasogastric tube will be inadequate for removal of particulate material. Otherwise, awake tracheal intubation for elective procedures or early tracheal intubation in emergent circumstances (e.g., severe hypoxia or ongoing aspiration) should be considered. The surgical approach for esophagectomy may require lung isolation, but the risks of DLT placement compared to single-lumen tracheal tube placement in this clinical condition have not been described. Tewari and Gupta9 argue that the additional time needed to place a DLT may increase the risk of aspiration. In our case, tracheostomy facilitated isolation of the tracheobronchial tree before endoscopic aspiration of esophageal contents. Endoscopy to facilitate tracheal intubation is a novel technique for the patient at high risk for aspiration. In conclusion, interdisciplinary communication and collaboration along with a preplanned scheme for airway management allowed safe and effective anesthesia care for a patient with an unusual constellation of problems associated with end-stage achalasia. E REFERENCES 1. Hay H. Rapidly developing airway obstruction resulting from achalasia of the oesophagus. Eur J Anaesthesiol 2000;17:398–400 2. Arcos E, Medina C, Mearin F, Larish J, Guarner L, Malagelada JR. Achalasia presenting as acute airway obstruction. Dig Dis Sci 2000;45:2079–83 3. Wagh MS, Matloff DS, Carr-Locke DL. Life-threatening acute airway obstruction in achalasia. MedGenMed 2004;6:12 4. Bruijns SR, Hicks A. Achalasia: an unusual cause of airway obstruction. Emerg Med J 2009;26:148 5. Becker DJ, Castell DO. Acute airway obstruction in achalasia. Possible role of defective belch reflex. Gastroenterology 1989;97:1323–6 6. Dominguez F, Hernandez-Ranz F, Boixeda D, Valdazo P. Acute upper-airway obstruction in achalasia of the esophagus. Am J Gastroenterol 1987;82:362–4 7. Berrisford RG, Oo A, Walshaw MJ, Drakeley MJ. Tracheal obstruction in achalasia: a role for airway stenting? Ann Thorac Surg 1998;66:939–41 8. Galan G, Faure F, Tinturier F, Ossart M. [Respiratory failure caused by megaesophagus and tracheomalacia]. Ann Fr Anesth Reanim 1999;18:987–90 9. Tewari P, Gupta D. Megaesophagus: a challenge for anesthesiologists. Ann Card Anaesth 2013;16:61–2 10. Shillcutt SK, Roberts EK. Achalasia-induced left atrial compression diagnosed by transesophageal echocardiography. Anesth Analg 2011;113:476–8 11. Schalinski S, Guddat SS, Tsokos M, Byard RW. Megaesophagus and possible mechanisms of sudden death. J Forensic Sci 2009;54:216–9 12. Feo CV, Caramori G, Conti V, Calia N, Guzzinati I, Ravenna F, Pasquini C, De Troia A, Liboni A, Papi A. Esophageal achalasia with recurrent aspiration pneumoniae treated by laparoscopic Heller myotomy. Am Surg 2012;78:E168–70 13. Sinan H, Tatum RP, Soares RV, Martin AV, Pellegrini CA, Oelschlager BK. Prevalence of respiratory symptoms in patients with achalasia. Dis Esophagus 2011;24:224–8 14. Akritidis N, Gousis C, Dimos G, Paparounas K. Fever, cough, and bilateral lung infiltrates. Achalasia associated with aspiration pneumonia. Chest 2003;123:608–12 15. Sperry K. Achalasia, the Valsalva maneuver, and sudden death: a case report. J Forensic Sci 1994;39:547–51 16. Rösch W, Bachmann K, Ottenjann R. [Asystolic heart arrest in achalasia]. Dtsch Med Wochenschr 1969;94:2191–4 17. Ajani S, Shah NB, Vlahakis NE. Achalasia: a diagnosis that’s hard to swallow. Am J Respir Crit Care Med 2012;185:893 18. Richter JE. Update on the management of achalasia: balloons, surgery and drugs. Expert Rev Gastroenterol Hepatol 2008;2:435–45
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