World J Surg DOI 10.1007/s00268-014-2787-5
SURGICAL SYMPOSIUM CONTRIBUTION
Laparoscopic Heller Myotomy for Achalasia: Does the Age of the Patient Affect the Outcome? Sheraz R. Markar • Giovanni Zaninotto
Ó Socie´te´ Internationale de Chirurgie 2014
Abstract Esophageal achalasia is the most common primary motility disorder of the esophageal body and lower esophageal sphincter. The optimal management strategy for elderly patients with achalasia remains inconclusive, however elderly patients are still more likely to be recommended for endoscopic treatments rather than LHM, due to a perception of increased surgical risk in these patients. Advantages of surgical myotomy in the elderly over pneumatic dilation are: 1. the risk of mucosal perforation during surgery is better controlled than after endoscopic balloon dilatation and 2. the greater efficacy for the surgical approach where only one procedure is routinely required whereas pneumatic dilation often requires repeat treatment to achieve long-term relief of symptoms.
Introduction Esophageal achalasia is the most common primary motility disorder of the esophageal body and lower esophageal sphincter. Common symptoms associated with achalasia include chest pain, odynophagia, dysphagia, regurgitation, and weight loss. The progressive nature of these symptoms ensure the diagnosis of esophageal achalasia is challenging and often preceded by a 2- to 3-year delay after the onset of symptoms [1]. Findings that have been associated with the diagnosis include: myenteric inflammation with associated injury and loss of ganglion cells, along with fibrosis of myenteric nerves, reduced synthesis of nitric oxide and vasoactive intestinal polypeptide. The exact etiology of achalasia remains unknown, however it has been
S. R. Markar (&) G. Zaninotto Division of Surgery, Department of Surgery and Cancer, St Mary’s Hospital, Imperial College, 10th Floor QEQM Building, South Wharf Road, London W2 1NY, UK e-mail: [email protected] G. Zaninotto e-mail: [email protected]
hypothesized that autoimmune-mediated destruction of inhibitory neurons is a possible explanation. The incidence of achalasia varies from 0.3 to 1.63 per 100,000 people and increases with age to 17 per 100,000 people in those who are 80 years or older [2, 3]. Sonnenberg in an analysis of hospital admission for achalasia in USA found the highest peak of admission among patients aged 65–84 (=24,581 39 % of all admission for achalasia), two and half times higher than in younger patients aged 18–44 (16,030 16 % of all admission for achalasia) [4]. A recent study performed in the Veneto Region of northeast Italy identified an achalasia incidence of 4.8 new cases per 100,000 population a year among the elderly (\75 years old), 4 times higher than in the population \45 years old [5]. The reason for this age-related pattern in the incidence of achalasia is still not clear, but an agerelated increase in neuron degeneration and loss of neuron control have been suggested as possible contributors [4]. The Veneto study also showed that 60 % of [75-yearold patients with achalasia went untreated [5]. The reasons for this nihilist attitude to achalasia in the elderly remain unclear. The capacity of older patients to compensate for their swallowing difficulties by changes in their diet, eating
123
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soft or liquid foods, and/or a lower awareness of their esophageal symptoms may account for patients being less likely to ask for a treatment. On the other hand, a false perception of achalasia as a ‘‘benign’’ disease (failing to consider the effect of dysphagia on quality of life and the risk of ab ingestis pneumonia) and the perceived high risk of endoscopic or surgical treatments in elderly patients may make general practitioners less inclined to refer older achalasia patients to the specialist for treatment [6]. At present, two treatment options, pneumatic dilation and cardiomyotomy (either performed surgically or endoscopically) are offered with the intention to offer longlasting improvement of symptoms in patients with achalasia. Surgical cardiomyotomy (Heller myotomy) is now one hundred years old, the first report being dated in 1914. In the nineties, it has been revived through a minimal invasive approach (Laparoscopic Heller myotomy, LHM) and since then it has become the golden standard to measure the efficacy of treatments for achalasia. Apart from its efficacy in resolving dysphagia, LHM is a remarkably safe operation with minimal complications rate and in most cases it is performed with a postoperative hospital stay of 1–2 days. Clinical guidelines encourage surgical myotomy for patients under 45 years old (because of the poor outcome of balloon dilation for patients in this age group) and pneumatic dilatation for poor-risk patients, including all patients aged over 65 years old, but this choice is made on the unproven assumption that LHM has a higher surgical risk and/or worse outcome in older patients [7, 8]. The relative risk and effectiveness of LHM in younger and older patient age groups is yet to be documented. The present review is aimed at addressing the possible treatments of achalasia in elderly patients and at evaluating specific risk and outcome of LHM in this cohort of patients.
Alternative treatment to laparoscopic myotomy Pharmacological therapy Calcium channel Blockers and long-acting nitrates act as smooth muscle relaxants and have been shown to be effective in reducing LES pressure and providing temporary relief of dysphagia in a small proportion of patients. However their use is limited as they do not improve LES relaxation or peristalsis, and they have a short duration of action and typically provide incomplete symptom relief. Their role is limited to symptom relief in patients with very early achalasia or those that are felt to be at high risk including elderly patients or refuse more aggressive treatments [9]; in patients with severe
123
achalasia, pharmacological treatments have not been shown to be beneficial. Endoscopic therapy—botulinum toxin injection Elderly patients or those that are felt to be at high risk for more invasive procedures are considered for endoscopic Botox injection. Botulinum toxin is a neurotoxin that inhibits acetylcholine release at motor neuron presynaptic terminals and thereby promotes LES relaxation. It has a remarkable safety profile, but its effectiveness is shortlived. A Cochrane review of 4 randomized controlled trials suggested that when compared to pneumatic dilation, Botulinum toxin injection was less effective in the longterm control of symptoms arising from achalasia, with only 25.6 % having symptomatic remission at 1 year compared to 70.2 % in the Pneumatic Dilation group [10]. The same results were obtained in a RCT comparing Botox to LHM: at 2 year follow-up 85 % of achalasia patients undergoing LHM were symptoms-free, compared to 20 % of those having Botox injection (p \ 0.001) [11]. The action of Botox in eighty-nonagenarians has been specifically addressed by Bassotti et al. [12]: 78 and 54 % of their original group of 33 patients were free of symptoms at one and two years, respectively, showing that in this specific age-group of patients could be considered a feasible option. Endoscopic therapy – Pneumatic dilation Endoscopic pneumatic dilation is considered the most effective non-surgical treatment for the palliation of dysphagia associated with achalasia. Older patients are commonly referred for endoscopic pneumatic dilation due to the perception of an increased risk associated with surgery. A recent multicenter European RCT comparing surgical myotomy and pneumatic dilation demonstrated equivalent rates of success at two years follow-up [13]. However, the most severe complication following pneumatic dilation is esophageal perforation that is quoted to occur in 4–7 % of dilations (4 % of patients in the European RCT). Interestingly in this study, patients who suffered a perforation were older (61 years) than those who did not (46 years), (95 % CI 43–50, p = 0.003) suggesting that age could be a risk factor for dilatation. It must be also be considered that esophageal perforation may have a disastrous outcome in old patients. Laparoscopic Heller myotomy in elderly patients Recently, two large scale meta-analyses have demonstrated that LHM is superior to endoscopic balloon dilatation in terms of short- and long-term efficacy [14, 15]. The
A: 31 (10.1) B: 19 (8.4) C: 3 (7.5)
A: 274 (89.8) B: 207 (91.6) 37 (92.5)
A: 3 (3–4) B: 3 (3–4) C: 3 (3–6)
B: 2 (4.5) A: 6 (2) B: 8 (3.5) C: 3 (7.5)
B: 4 (9.1) A: 4 (1.3) B: 1 (0.4) C: 1 (2.5)
B: 17 (38.6) A: 169 (55.4) B: 123 (54.4) C: 21 (52.5)
A: 57
A: 118
B: 44
A: 305
B: 226
C: 40
A: [70
A: \60
B: C60
A: B45
B: 45–70
C: C70
Kilic [17]
Roll [28]
b
a
median Eckardt score
intraoperative complications
Salvador [18]
A: 54 (45.8)
A: 32 (56.1) A: 15 (12.7)
A: 11 (19.3) A: 4 (3.4)
3 (5.3)
4 (group not specified)
B: 50
3 (1–56)
4 (3–14)
B: 3.7 ± 0.6
A: 3.6 ± 0.8
Improved dysphagia score: 55 (97) Satisfaction score:
B: 7 to 1
A: 8 to 2
Eckardt score decreaseb:
B: 11 (25)
A: 25 (21.2)
4 (7)
–
A: 24
B:7 (63.6)
A:15 (71.4)
B: [ 40
–
A: \40
Gockel [27]
2 (group not specified)
B: 2 (18.2)a
B:11
A: 11 (22)
B: [70
–
A: 2 (9.5)a
A: 31 (73.8) (only 42 patients followed up)
B: 0 (0)
A: 0 (0)
Additional treatment (%)
A:21
A: 3 (1–26)
B: 3.9 (2–8)
A: 2.9 (1–7)
Symptomatic relief (%)
A: \70
A: 1 (1.9)
B: 0 (0)
A: 2 (2.7)
A: 2 (3.8)
B: 4 (23.5)
A: 10 (13.5)
LOS (days)
Ferulano [26]
A: 22 (43.1)
B: 13 (76.5)
A: 49 (65.5)
Mucosal injury (%)
A: 51
B: 17
B: C70
Complications (%)
A: C65
A: 75
A: \70
Bodnar [24]
Male proportion (%)
Craft [25]
Patient No
Age groups (years)
Author
Table 1 Published outcomes from Laparoscopic Heller myotomy (LHM in different age groups)
LHM can be used as first therapeutic approach in elderly patients
LHM can be performed safely in elderly patients Supports LHM as first line therapy in older patients with achalasia
LHM can be performed safely in patients [40 years
QOL improves irrespective of age
Advanced age does not affect outcomes of LHM
LHM can be performed safely in elderly patients
Conclusion
World J Surg
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optimal management strategy for elderly patients with achalasia remains inconclusive, however elderly patients are still more likely to be recommended for endoscopic treatments rather than LHM, due to a perception of increased surgical risk in these patients. Advances in perioperative care and the extensive use of minimally invasive surgery have brought some specialized centers to extend the indications for surgical myotomy in achalasia to include elderly patients with optimal results in terms of outcome and morbidity. The outcomes of surgical myotomy in older patients with achalasia are reported in Table 1. Advantages of surgical myotomy in the elderly over pneumatic dilation may be: 1. The risk of mucosal perforation during surgery is better controlled than after endoscopic balloon dilatation. A perforation after endoscopic pneumatic dilation in elderly patients may fail to be recognized and can represent a fatal event, whereas all the reported perforations that occurred after LHM were immediately repaired without further consequence. 2. The greater efficacy for the surgical approach where only one procedure is routinely required whereas pneumatic dilation often requires repeat treatment to achieve long-term relief of symptoms. One large population based study on achalasia treatment [16] and the above mentioned Veneto study [4] showed that the risk for re-treatment is 3 to 4 times greater after dilatation than after surgery. This entails multiple visits to the hospital with its associated logistic and economic burden and adverse impact on quality of life especially for elderly patients. The largest case series of LHM in patients 70 years or older comprises 57 patients and was published in 2007 by Kilic et al. [17]. LHM was performed safely with no perioperative mortality and a complication rate of 19.3 %, including only 3 (5.3 %) intraoperative perforations. Kilic et al. also demonstrated the efficacy of LHM in the elderly population with an improvement in mean dysphagia score from 3.38 to 1.36. During a mean follow-up period of 23.5 months, only four patients (7 %) required reoperation due to recurrence of dysphagia. Salvador et al. [18] recently compared the outcomes of LHM stratifying the patients according to their age: 571 patients were divided into three groups; group A (B45 years), group B (45–70), and group C (C70 years) [17]. No mortality was observed in any of the groups, with an overall complication of 1.1 %. However, only one complication was observed in group C which was bleeding from the edge of the myotomy. Fifty-three patients had a postoperative symptom score [8 and were considered as treatment failures. Age did not appear to be a factor that affected treatment failure as these were equally distributed among the groups; group A (10.1 %), group B (8.4 %), and
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group C (7.5 %); p = 0.80, with a tendency to a better result in the elderly, probably because of a lower incidence of type III achalasia in this group of patients. The authors concluded that, ‘‘LHM with Dor fundoplication can be used as the first therapeutic approach to achalasia even in elderly patients with an acceptable surgical risk.’’ LHM and division of the lower esophageal sphincter muscle fibres commonly results in postoperative gastroesophageal reflux. It is for this reason many surgeons perform an anti-reflux procedure as an anterior or posterior 270 degree fundal wrap. A recent meta-analysis has suggested that partial posterior fundoplication when combined with LHM may be associated with reduced re-intervention rates for postoperative dysphagia, while providing similar control of reflux when compared to anterior partial fundoplication [19]. Currently no study has been published comparing anterior and posterior fundoplication LHM specifically in elderly patients. However, given the benefits seen in the general population it may be assumed that the results of any such trial would be same as the previous published meta-analysis. Despite the published literature evaluating the influence of age upon LHM, suggests that age does not affect shortor long-term outcomes following LHM, and specifically elderly patients can undergo LHM safely with a similar complication profile to younger patients, the current practice patterns in most centers across the world is to offer elderly patients presenting with idiopathic achalasia primary endoscopic treatment. No randomized clinical trial has compared endoscopic and surgical treatments for esophageal achalasia in the elderly patients and this represents an area for future investigation. Future treatments; Per-Oral Endoscopic Myotomy (POEM) Per-Oral Endoscopic Myotomy (POEM) has been recently introduced as a ‘scarless’ (endoscopic) approach to myotomy. There has been significant variability in the technical approach employed in POEM surgery. The most commonly described technique is that of Inoue et al. [20], which involves endoscopic selective myotomy of the inner circular muscle layer within the submucosal layer. The attraction of this technique is the minimally invasive nature of the procedure, with no external scarring and less surgical stress, while ensuring the creation of a myotomy identical to that created by traditionally open or laparoscopic surgery. To date only a handful of small case series have been published that describe the use of POEM procedures in patients with achalasia [21–23]. These publications suggest POEM is an effective treatment for achalasia with a postoperative improvement in dysphagia scores, and a reduced LOS pressure. The potential negatives associated with
World J Surg
POEM are similar to those seen with LHM, including a risk of esophageal perforation that is very rare in published reports to date, but is likely to include a significant publication bias. POEM surgery does not allow for a concurrent anti-reflux procedure, and thus critics have suggested that POEM may result in a high incidence of long-term reflux disease. The small number of cases reported, and a lack of comparative data with LHM, mean that the relative merits, or otherwise, of POEM surgery are still to be clearly determined. POEM may be an ideal treatment in the elderly patient subgroup due to the effectiveness of the treatment combined with a less invasive approach than LHM, representing less operative risk. However, it is important to note that even though POEM is an endoscopic procedure it is performed under general anesthetic in most regions across the world. Furthermore, as suggested above POEM remains a therapeutic strategy that is in an experimental stage in most centers across the world. However, it remains an exciting concept and may revolutionize the treatment of achalasia as a whole and in subsets of patients including elderly patients. Conclusion Laparoscopic Heller myotomy can be performed safely in elderly patients and with similar symptomatic outcomes compared to younger patients. Future areas for assessment include direct comparison of endoscopic and surgical treatments for elderly patients with idiopathic esophageal achalasia. Per-oral endoscopic myotomy offers a promising treatment option, which may be seen to have specific applications and benefits in elderly patients with achalasia.
Conflict of interest Funding
None.
None.
References 1. Park W, Vaezi MF (2005) Etiology and pathogenesis of achalasia: the current understanding. Am J Gastroenterol 100:1404–1414 2. Birgisson S, Richter JE (2007) Achalasia in Iceland, 1952–2002: an epidemiologic study. Dig Dis Sci 52(8):1855–1860 3. Sadowski DC, Ackah F, Jiang B, Svenson LW (2010) Achalasia: incidence, prevalence and survival. A population-based study. Neurogastroenterol Motil 22(9):e256–e261 4. Sonnenberg A (2009) Hospitalization for achalasia in the United States 1997–2006. Dig Dis Sci 54:1680–1685 5. Gennaro N, Portale G, Gallo C, Riocchietto S, Caruso V et al (2011) Esophageal achalasia in the Veneto region: epidemiology and treatment. Epidemiology and treatment of achalasia. J Gastrointest Surg 15:423–428
6. Gockel I, Junginger T, Eckardt VF (2006) Long-term results of conventional myotomy in patients with achalasia: a prospective 20-year analysis. J Gastrointest Surg 10:1400–1410 7. Triadafidapulos G, Boeckstaens GE, Gullo R, Patti MG, Pandolfino JE et al (2012) The Kagoshima consensus on esophageal achalasia. Dis Esophagus 25:337–348 8. Boeckxstaens GE, Zaninotto G, Richter JE (2014) Achalasia. Lancet 383:83–93 9. Stefanidis D, Richardson W, Farrell TM, Kohn GP, Augenstein V, Fanelli RD (2012) SAGES guidelines for the surgical treatment of esophageal achalasia. Surg Endosc 26:296–311 10. Leyden JE, Moss AC, MacMathuna P (2006) Endoscopic pneumatic dilation versus botulinum toxin injection in the management of primary achalasia. Cochrane Database Sys Rev 4:CD005046 11. Zaninotto G, Annese V, Costantini M, Del Genio A et al (2004) Randomized control trial of Botox injection versus laparoscopic Heller myotomy for esophageal achalasia. Ann Surg 239:364–370 12. Bassotti G, D’Onofrio V, Battaglia E et al (2006) Treatment with botulinum toxin of octo-nonagerians with oesophageal achalasia: a two-year follow-up study. Aliment Pharmacol Ther 23:1615–1619 13. Boeckxstaens GE, Annese V, Bruley des Varammes S et al (2011) Pneumatic dilation versus laparoscopic Heller myotomy for idiopathic achalasia. N Engl J Med 364:1807–1816 14. Schoenberg MB, Marx S, Kersten JF et al (2013) Laparoscopic Heller myotomy versus endoscopic balloon dilatation for the treatment of achalasia: a network meta-analysis. Ann Surg 258:943–952 15. Yaghoobi M, Mayrand S, Martel M et al (2013) Laparoscopic Heller’s myotomy versus pneumatic dilation in the itreatment of idiopathic achalasia: a meta-analysis of randomized, controlled trials. Gastrointest Endosc 78:468–475 16. Lopushinski SR (2006) Urban DR Pneumatic dilatation and surgical myotomy for achalasia. JAMA 296:2227–2233 17. Kilic A, Schuchert MJ, Pennathur A et al (2008) Minimally invasive myotomy for achalasia in the elderly. Surg Endosc 22:862–865 18. Salvador R, Costantini M, Cavallin F et al (2014) Laparoscopic heller myotomy can be used as primary therapy for esophageal achalasia regardless of age. J Gastrointest Surg 18:106–112 19. Kurian AA, Bhayani N, Sharata A et al (2013) Patial anterior vs. partial posterior fundoplication following transabdominal esophagocardiomyotomy for achalasia of the esophagus. JAMA Surg 148:85–90 20. Inoue H, Tianle KM, Ikeda H et al (2011) Peroral endoscopic myotomy for esophageal achalasia: technique, indication and outcomes. Thorac Surg Clin 21:519–525 21. Inoue H, Minami H, Kobayashi Y et al (2010) Peroral endoscopic myotomy (POEM) for esophageal achalasia. Endoscopy 42:265–271 22. Von Renteln D, Inoue H, Minami H et al (2012) Peroral endoscopic myotomy for the treatment of achalasia: a prospective single center study. Am J Gastroenterol 107:411–417 23. Swanstrom LL, Rieder E, Dunst CM (2011) A stepwise approach and early clinical experience in peroral endoscopic myotomy for the treatment of achalasia and esophageal motility disorders. J Am Coll Surg 213:751–756 24. Bodnar AM, Schmidt HM, Markar SR, Low DE. Surgical myotomy should be considered as primary treatment in elderly patients with achalasia. Dis Esophagus 2014 25. Craft RO, Aguilar BE, Flahive C et al (2010) Outcomes of minimally invasive myotomy for the treatment of achalasia in the elderly. JSLS 4:342–347
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World J Surg 26. Ferulano GP, Dilillo S, D’Ambra M et al (2005) Oesophageal achalasia in elderly people: results of the laparoscopic Heller-Dor mytomy. Acta Biomed 76(Suppl 1):37–41 27. Gockel I, Gith A, Drescher D et al (2012) Minimally invasive surgery for achalasia in patients [40 years: more favorable than anticipated. Langenbecks Arch Surg 397:69–74
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28. Roll GR, Ma S, Gasper WJ et al (2010) Excellent outcomes of laparoscopic esophagomyotomy for achalasia in patients older than 60 years of age. Surg Endosc 24:2562–2566
SURGICAL SYMPOSIUM CONTRIBUTION
Laparoscopic Heller Myotomy for Achalasia: Does the Age of the Patient Affect the Outcome? Sheraz R. Markar • Giovanni Zaninotto
Ó Socie´te´ Internationale de Chirurgie 2014
Abstract Esophageal achalasia is the most common primary motility disorder of the esophageal body and lower esophageal sphincter. The optimal management strategy for elderly patients with achalasia remains inconclusive, however elderly patients are still more likely to be recommended for endoscopic treatments rather than LHM, due to a perception of increased surgical risk in these patients. Advantages of surgical myotomy in the elderly over pneumatic dilation are: 1. the risk of mucosal perforation during surgery is better controlled than after endoscopic balloon dilatation and 2. the greater efficacy for the surgical approach where only one procedure is routinely required whereas pneumatic dilation often requires repeat treatment to achieve long-term relief of symptoms.
Introduction Esophageal achalasia is the most common primary motility disorder of the esophageal body and lower esophageal sphincter. Common symptoms associated with achalasia include chest pain, odynophagia, dysphagia, regurgitation, and weight loss. The progressive nature of these symptoms ensure the diagnosis of esophageal achalasia is challenging and often preceded by a 2- to 3-year delay after the onset of symptoms [1]. Findings that have been associated with the diagnosis include: myenteric inflammation with associated injury and loss of ganglion cells, along with fibrosis of myenteric nerves, reduced synthesis of nitric oxide and vasoactive intestinal polypeptide. The exact etiology of achalasia remains unknown, however it has been
S. R. Markar (&) G. Zaninotto Division of Surgery, Department of Surgery and Cancer, St Mary’s Hospital, Imperial College, 10th Floor QEQM Building, South Wharf Road, London W2 1NY, UK e-mail: [email protected] G. Zaninotto e-mail: [email protected]
hypothesized that autoimmune-mediated destruction of inhibitory neurons is a possible explanation. The incidence of achalasia varies from 0.3 to 1.63 per 100,000 people and increases with age to 17 per 100,000 people in those who are 80 years or older [2, 3]. Sonnenberg in an analysis of hospital admission for achalasia in USA found the highest peak of admission among patients aged 65–84 (=24,581 39 % of all admission for achalasia), two and half times higher than in younger patients aged 18–44 (16,030 16 % of all admission for achalasia) [4]. A recent study performed in the Veneto Region of northeast Italy identified an achalasia incidence of 4.8 new cases per 100,000 population a year among the elderly (\75 years old), 4 times higher than in the population \45 years old [5]. The reason for this age-related pattern in the incidence of achalasia is still not clear, but an agerelated increase in neuron degeneration and loss of neuron control have been suggested as possible contributors [4]. The Veneto study also showed that 60 % of [75-yearold patients with achalasia went untreated [5]. The reasons for this nihilist attitude to achalasia in the elderly remain unclear. The capacity of older patients to compensate for their swallowing difficulties by changes in their diet, eating
123
World J Surg
soft or liquid foods, and/or a lower awareness of their esophageal symptoms may account for patients being less likely to ask for a treatment. On the other hand, a false perception of achalasia as a ‘‘benign’’ disease (failing to consider the effect of dysphagia on quality of life and the risk of ab ingestis pneumonia) and the perceived high risk of endoscopic or surgical treatments in elderly patients may make general practitioners less inclined to refer older achalasia patients to the specialist for treatment [6]. At present, two treatment options, pneumatic dilation and cardiomyotomy (either performed surgically or endoscopically) are offered with the intention to offer longlasting improvement of symptoms in patients with achalasia. Surgical cardiomyotomy (Heller myotomy) is now one hundred years old, the first report being dated in 1914. In the nineties, it has been revived through a minimal invasive approach (Laparoscopic Heller myotomy, LHM) and since then it has become the golden standard to measure the efficacy of treatments for achalasia. Apart from its efficacy in resolving dysphagia, LHM is a remarkably safe operation with minimal complications rate and in most cases it is performed with a postoperative hospital stay of 1–2 days. Clinical guidelines encourage surgical myotomy for patients under 45 years old (because of the poor outcome of balloon dilation for patients in this age group) and pneumatic dilatation for poor-risk patients, including all patients aged over 65 years old, but this choice is made on the unproven assumption that LHM has a higher surgical risk and/or worse outcome in older patients [7, 8]. The relative risk and effectiveness of LHM in younger and older patient age groups is yet to be documented. The present review is aimed at addressing the possible treatments of achalasia in elderly patients and at evaluating specific risk and outcome of LHM in this cohort of patients.
Alternative treatment to laparoscopic myotomy Pharmacological therapy Calcium channel Blockers and long-acting nitrates act as smooth muscle relaxants and have been shown to be effective in reducing LES pressure and providing temporary relief of dysphagia in a small proportion of patients. However their use is limited as they do not improve LES relaxation or peristalsis, and they have a short duration of action and typically provide incomplete symptom relief. Their role is limited to symptom relief in patients with very early achalasia or those that are felt to be at high risk including elderly patients or refuse more aggressive treatments [9]; in patients with severe
123
achalasia, pharmacological treatments have not been shown to be beneficial. Endoscopic therapy—botulinum toxin injection Elderly patients or those that are felt to be at high risk for more invasive procedures are considered for endoscopic Botox injection. Botulinum toxin is a neurotoxin that inhibits acetylcholine release at motor neuron presynaptic terminals and thereby promotes LES relaxation. It has a remarkable safety profile, but its effectiveness is shortlived. A Cochrane review of 4 randomized controlled trials suggested that when compared to pneumatic dilation, Botulinum toxin injection was less effective in the longterm control of symptoms arising from achalasia, with only 25.6 % having symptomatic remission at 1 year compared to 70.2 % in the Pneumatic Dilation group [10]. The same results were obtained in a RCT comparing Botox to LHM: at 2 year follow-up 85 % of achalasia patients undergoing LHM were symptoms-free, compared to 20 % of those having Botox injection (p \ 0.001) [11]. The action of Botox in eighty-nonagenarians has been specifically addressed by Bassotti et al. [12]: 78 and 54 % of their original group of 33 patients were free of symptoms at one and two years, respectively, showing that in this specific age-group of patients could be considered a feasible option. Endoscopic therapy – Pneumatic dilation Endoscopic pneumatic dilation is considered the most effective non-surgical treatment for the palliation of dysphagia associated with achalasia. Older patients are commonly referred for endoscopic pneumatic dilation due to the perception of an increased risk associated with surgery. A recent multicenter European RCT comparing surgical myotomy and pneumatic dilation demonstrated equivalent rates of success at two years follow-up [13]. However, the most severe complication following pneumatic dilation is esophageal perforation that is quoted to occur in 4–7 % of dilations (4 % of patients in the European RCT). Interestingly in this study, patients who suffered a perforation were older (61 years) than those who did not (46 years), (95 % CI 43–50, p = 0.003) suggesting that age could be a risk factor for dilatation. It must be also be considered that esophageal perforation may have a disastrous outcome in old patients. Laparoscopic Heller myotomy in elderly patients Recently, two large scale meta-analyses have demonstrated that LHM is superior to endoscopic balloon dilatation in terms of short- and long-term efficacy [14, 15]. The
A: 31 (10.1) B: 19 (8.4) C: 3 (7.5)
A: 274 (89.8) B: 207 (91.6) 37 (92.5)
A: 3 (3–4) B: 3 (3–4) C: 3 (3–6)
B: 2 (4.5) A: 6 (2) B: 8 (3.5) C: 3 (7.5)
B: 4 (9.1) A: 4 (1.3) B: 1 (0.4) C: 1 (2.5)
B: 17 (38.6) A: 169 (55.4) B: 123 (54.4) C: 21 (52.5)
A: 57
A: 118
B: 44
A: 305
B: 226
C: 40
A: [70
A: \60
B: C60
A: B45
B: 45–70
C: C70
Kilic [17]
Roll [28]
b
a
median Eckardt score
intraoperative complications
Salvador [18]
A: 54 (45.8)
A: 32 (56.1) A: 15 (12.7)
A: 11 (19.3) A: 4 (3.4)
3 (5.3)
4 (group not specified)
B: 50
3 (1–56)
4 (3–14)
B: 3.7 ± 0.6
A: 3.6 ± 0.8
Improved dysphagia score: 55 (97) Satisfaction score:
B: 7 to 1
A: 8 to 2
Eckardt score decreaseb:
B: 11 (25)
A: 25 (21.2)
4 (7)
–
A: 24
B:7 (63.6)
A:15 (71.4)
B: [ 40
–
A: \40
Gockel [27]
2 (group not specified)
B: 2 (18.2)a
B:11
A: 11 (22)
B: [70
–
A: 2 (9.5)a
A: 31 (73.8) (only 42 patients followed up)
B: 0 (0)
A: 0 (0)
Additional treatment (%)
A:21
A: 3 (1–26)
B: 3.9 (2–8)
A: 2.9 (1–7)
Symptomatic relief (%)
A: \70
A: 1 (1.9)
B: 0 (0)
A: 2 (2.7)
A: 2 (3.8)
B: 4 (23.5)
A: 10 (13.5)
LOS (days)
Ferulano [26]
A: 22 (43.1)
B: 13 (76.5)
A: 49 (65.5)
Mucosal injury (%)
A: 51
B: 17
B: C70
Complications (%)
A: C65
A: 75
A: \70
Bodnar [24]
Male proportion (%)
Craft [25]
Patient No
Age groups (years)
Author
Table 1 Published outcomes from Laparoscopic Heller myotomy (LHM in different age groups)
LHM can be used as first therapeutic approach in elderly patients
LHM can be performed safely in elderly patients Supports LHM as first line therapy in older patients with achalasia
LHM can be performed safely in patients [40 years
QOL improves irrespective of age
Advanced age does not affect outcomes of LHM
LHM can be performed safely in elderly patients
Conclusion
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optimal management strategy for elderly patients with achalasia remains inconclusive, however elderly patients are still more likely to be recommended for endoscopic treatments rather than LHM, due to a perception of increased surgical risk in these patients. Advances in perioperative care and the extensive use of minimally invasive surgery have brought some specialized centers to extend the indications for surgical myotomy in achalasia to include elderly patients with optimal results in terms of outcome and morbidity. The outcomes of surgical myotomy in older patients with achalasia are reported in Table 1. Advantages of surgical myotomy in the elderly over pneumatic dilation may be: 1. The risk of mucosal perforation during surgery is better controlled than after endoscopic balloon dilatation. A perforation after endoscopic pneumatic dilation in elderly patients may fail to be recognized and can represent a fatal event, whereas all the reported perforations that occurred after LHM were immediately repaired without further consequence. 2. The greater efficacy for the surgical approach where only one procedure is routinely required whereas pneumatic dilation often requires repeat treatment to achieve long-term relief of symptoms. One large population based study on achalasia treatment [16] and the above mentioned Veneto study [4] showed that the risk for re-treatment is 3 to 4 times greater after dilatation than after surgery. This entails multiple visits to the hospital with its associated logistic and economic burden and adverse impact on quality of life especially for elderly patients. The largest case series of LHM in patients 70 years or older comprises 57 patients and was published in 2007 by Kilic et al. [17]. LHM was performed safely with no perioperative mortality and a complication rate of 19.3 %, including only 3 (5.3 %) intraoperative perforations. Kilic et al. also demonstrated the efficacy of LHM in the elderly population with an improvement in mean dysphagia score from 3.38 to 1.36. During a mean follow-up period of 23.5 months, only four patients (7 %) required reoperation due to recurrence of dysphagia. Salvador et al. [18] recently compared the outcomes of LHM stratifying the patients according to their age: 571 patients were divided into three groups; group A (B45 years), group B (45–70), and group C (C70 years) [17]. No mortality was observed in any of the groups, with an overall complication of 1.1 %. However, only one complication was observed in group C which was bleeding from the edge of the myotomy. Fifty-three patients had a postoperative symptom score [8 and were considered as treatment failures. Age did not appear to be a factor that affected treatment failure as these were equally distributed among the groups; group A (10.1 %), group B (8.4 %), and
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group C (7.5 %); p = 0.80, with a tendency to a better result in the elderly, probably because of a lower incidence of type III achalasia in this group of patients. The authors concluded that, ‘‘LHM with Dor fundoplication can be used as the first therapeutic approach to achalasia even in elderly patients with an acceptable surgical risk.’’ LHM and division of the lower esophageal sphincter muscle fibres commonly results in postoperative gastroesophageal reflux. It is for this reason many surgeons perform an anti-reflux procedure as an anterior or posterior 270 degree fundal wrap. A recent meta-analysis has suggested that partial posterior fundoplication when combined with LHM may be associated with reduced re-intervention rates for postoperative dysphagia, while providing similar control of reflux when compared to anterior partial fundoplication [19]. Currently no study has been published comparing anterior and posterior fundoplication LHM specifically in elderly patients. However, given the benefits seen in the general population it may be assumed that the results of any such trial would be same as the previous published meta-analysis. Despite the published literature evaluating the influence of age upon LHM, suggests that age does not affect shortor long-term outcomes following LHM, and specifically elderly patients can undergo LHM safely with a similar complication profile to younger patients, the current practice patterns in most centers across the world is to offer elderly patients presenting with idiopathic achalasia primary endoscopic treatment. No randomized clinical trial has compared endoscopic and surgical treatments for esophageal achalasia in the elderly patients and this represents an area for future investigation. Future treatments; Per-Oral Endoscopic Myotomy (POEM) Per-Oral Endoscopic Myotomy (POEM) has been recently introduced as a ‘scarless’ (endoscopic) approach to myotomy. There has been significant variability in the technical approach employed in POEM surgery. The most commonly described technique is that of Inoue et al. [20], which involves endoscopic selective myotomy of the inner circular muscle layer within the submucosal layer. The attraction of this technique is the minimally invasive nature of the procedure, with no external scarring and less surgical stress, while ensuring the creation of a myotomy identical to that created by traditionally open or laparoscopic surgery. To date only a handful of small case series have been published that describe the use of POEM procedures in patients with achalasia [21–23]. These publications suggest POEM is an effective treatment for achalasia with a postoperative improvement in dysphagia scores, and a reduced LOS pressure. The potential negatives associated with
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POEM are similar to those seen with LHM, including a risk of esophageal perforation that is very rare in published reports to date, but is likely to include a significant publication bias. POEM surgery does not allow for a concurrent anti-reflux procedure, and thus critics have suggested that POEM may result in a high incidence of long-term reflux disease. The small number of cases reported, and a lack of comparative data with LHM, mean that the relative merits, or otherwise, of POEM surgery are still to be clearly determined. POEM may be an ideal treatment in the elderly patient subgroup due to the effectiveness of the treatment combined with a less invasive approach than LHM, representing less operative risk. However, it is important to note that even though POEM is an endoscopic procedure it is performed under general anesthetic in most regions across the world. Furthermore, as suggested above POEM remains a therapeutic strategy that is in an experimental stage in most centers across the world. However, it remains an exciting concept and may revolutionize the treatment of achalasia as a whole and in subsets of patients including elderly patients. Conclusion Laparoscopic Heller myotomy can be performed safely in elderly patients and with similar symptomatic outcomes compared to younger patients. Future areas for assessment include direct comparison of endoscopic and surgical treatments for elderly patients with idiopathic esophageal achalasia. Per-oral endoscopic myotomy offers a promising treatment option, which may be seen to have specific applications and benefits in elderly patients with achalasia.
Conflict of interest Funding
None.
None.
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