Achalasia: Pre-operative tests, post-operative symptoms and surgical outcomes

2014/2015 Raul Miguel de Freitas Lima Neto Achalasia: Pre-operative tests, post-operative symptoms and surgical outcomes março, 2015 Mestrado Integrado em Medicina Área: Cirurgia Geral Tipologia: Dissertação Trabalho efetuado sob a Orientação de: Professor Doutor José Adelino Lobarinhas Barbosa Trabalho organizado de acordo com as normas da revista: Surgery Today março, 2015 Raul Miguel de Freitas Lima Neto Achalasia: Pre-operative tests, post-operative symptoms and surgical outcomes Dedicatória Dedico esta tese aos meus pais, à Isabel Sousa, aos meus avós e a todos os familiares e amigos que me apoiaram de qualquer forma ao longo deste percurso na FMUP, em todo e qualquer momento. Sozinho seria uma tarefa muito mais difícil. Um profundo agradecimento a todos eles. 1 Title: Achalasia: Pre-operative tests, post-operative symptoms and surgical outcomes Authors: Name: Raul Miguel de Freitas Lima Neto Affiliation : Faculdade de Medicina da Universidade do Porto Address : Alameda Prof. Hernâni Monteiro, 4200 - 319 Porto, PORTUGAL E-mail: [email protected] Telephone number:+351 919190022 Fax: N/a Name: José Adelino Lobarinhas Barbosa Affiliation: Departamento de Cirurgia Geral, Centro Hospitalar de São João Address: Alameda Prof. Hernâni Monteiro, 4200 - 319 Porto, PORTUGAL E-mail: [email protected] Telephone number: +351 913805368 Fax: N/a Article Type: Original Article (Clinical original) Key Words: Achalasia; Manometry; Outcomes; Morbidity; Heller-myotomy 2 ABSTRACT Purpose: The main goal of this study was to search for predictors, of post-operative dysphagia and heartburn, need for medical treatment during follow-up and the occurrence on intra and post-operative morbidity in patients with achalasia. Methods: The records of the patients who underwent myotomy for achalasia from 2005 to 2014 were reviewed (n=46). Data regarding pre-operative and post-operative manometry and pH-metry was compiled, along with patients’ symptoms and characteristics.. Results: Our sample was composed by 25 female patients and 21 male patients. No parameter of the conventional manometry was associated with post-operative dysphagia, heartburn or medical treatment. Pre-operative heartburn and regurgitation were associated with less post-operative dysphagia (p<0.01 and p=0,034, respectively); Pre-operative dilatations were associated with post-operative morbidity (p=0.035) but not with intra-operatory morbidity (p=0.898). Relapse of achalasia was associated with greater usage of PPI during follow-up (p= 0.028). Conclusions: Heller myotomy is an effective treatment option for Achalasia. Dilatations should be used carefully since they can lead to an increase in post—operative morbidity. Patients with relapse of achalasia are more likely to need medical treatment after re-intervention while patients with pre-operative regurgitation and heartburn have less post-operative dysphagia. 3 INTRODUCTION Achalasia is a disorder of oesophageal motility characterized by impaired relaxation of the lower oesophageal sphincter (LES), frequently associated with an increase in the pressure of LES and an absence of peristalsis of the oesophageal body [1]. Complete lower esophageal sphincter (LES) relaxation occurs in approximately 15–30% of patients with achalasia and is not a characteristic of early achalasia [2]. It’s annual incidence is about 1 case per 100000 habitants and the prevalence is around 10 in 10000 [3]. There is no sexual and racial prevalence and, while it is a disease that can appear at any age, there are two peaks of incidence: between 20-40 years old and between 70-80 years old [3, 4]. The main symptom is dysphagia, usually progressive for solids and liquids, although it can also present itself as paradoxal dysphagia. Other common presentation symptoms include thoracic pain, regurgitation, heartburn and weight loss [1, 5]. As of now, the pathogenesis of this disease is unknown, [6] although it is hypothesized that it results from the loss of the ganglionic cells of the myenteric plexus of the esophagus [1]. Other current train of thought deals with a possible viral etiology [7, 8]. Achalasia has been associated with, at various degrees of risk, squamous cell carcinoma. However, there are no recommendations for screening for cancer in patients with Achalasia [3, 9]. Diagnosing Achalasia requires a high index of clinical suspicion. The current gold-standard is the oesophageal manometry [6]. A complete workup usually includes oesophageal manometry, upper gastrointestinal endoscopy and a barium esophagogram [3]. The cardinal feature of this disease is the impaired relaxation of the LES in response to swallowing. Other abnormalities include an increase in the LES pressure and absence of peristalsis in the oesophageal body [10]. Currently, there are two forms of manometry, conventional and the more recent high-resolution manometry (HRM). Conventional manometry has some disadvantages in comparison to HRM manometry, since it is unable to account for the intrabolus pressure, the crural diaphragm relaxation, radial asymmetry of the gastroesophageal junction (GEJ) and deglutive oesophageal shortening [11]. As for the upper gastrointestinal endoscopy, it’s important to exclude a serious differential diagnosis, the Pseudo-Achalasia [6]. Barium esophagogram can also help in the diagnosis, identifying the so called “Bird’s Beak [3, 6]. The advancements brought by HRM allowed the classification of Achalasia into 3 different subtypes, a classification known as the Chicago Classification of Motility Disorders [12]. Type I 4 represents classic achalasia, associated with low intra-oesophageal pressure and minimum levels of oesophageal contractility; Type II is characterized by panoesophageal pressure elevations and an absence of peristalsis [1]; Type III is usually called “spastic achalasia” [5, 10, 13]. HRM proved to be an important evolution in terms of diagnosis and classification of Achalasia [14, 15]. The available treatments are used for symptom relief. Currently, no curative interventions exist [1]. Regarding pharmaceutic interventions, the most common drugs used are calcium channel blockers, but they are ineffective [4, 16]. The other treatment options are injection of botulin toxin, pneumatic dilatation and surgery. Regarding botulin toxin injection, it’s ineffective in the long term, with its’ effects reverting in a period between 6 and 9 months after the intervention [5]. It is currently reserved for elderly patients and high surgical risk patients [4]. Pneumatic dilatation and surgical myotomy are more useful treatment options. Pneumatic dilatation is performed by insufflating a balloon in the distal oesophagus, causing the forced distension of the muscular fibers of the LES. Usually a balloon of 30 mm is used due to a lower perforation rate [17]. It’s possible to achieve similar long-term results to surgery with pneumatic dilatation if multiple dilatations are used. It seems to be a more effective treatment in patients over 40 years old [16, 18]. It is also the most cost effective procedure [4] and has a lower risk of gastroesophageal reflux disease [17]. Surgery is the gold-standard treatment and the most frequently used surgical procedure is Heller’s myotomy, performed laparoscopically (section of the muscular fibers of the LES). The laparoscopic approach results in shorter hospitalization times [19]. To prevent gastroesophageal reflux a partial fundoplicature must also be performed in conjunction with the myotomy [3, 16]. There seems to be no difference between the two different partial fundoplicatures, Dor or Toupet [20]. For the myotomy, most surgeons will perform a section of 6-8 cm of the LES fibres in the oesophagus and prolong it 1-2 cm into the stomach [21]. Surgery has great success rate in the long term [22], even though it is not completely free of complications and does not warrant the absence of relapse. Choosing between pneumatic dilatation or surgery has been a topic of recent discussion. A recent European RCT could not determine which approach was better, finding no statistical difference between them [17]. The symptom which shows greater improvement with surgery is regurgitation, in contrast with heartburn [20]. In general, post-surgical complications are scarce, with one studying relating incidence of complications in less than 4% of patients [23]. The most frequent adverse effect of the surgical intervention is gastroesophageal reflux. Another complication is the perforation of the oesophagus, 11 DISCUSSION Achalasia has no curative treatment. All available treatments are palliative and have the main purpose of assuring the passage of liquids and solids through the gastroesophageal junction, therefore alleviating the symptomatology, preventing food stasis in the oesophagus and ultimately allowing the patient to eat. Furthermore, our knowledge of the disease, in pathophysiological terms, is still suboptimal. This leads to difficulty in identifying predictors of favourable outcomes for all treatments, including surgery. There have been previous reports regarding predictors of surgical success. One study reported that patients with a higher pre-operative score of dysphagia had better surgical outcomes [23], while other reported that a duration of symptoms longer than 10 years predicted more post-operative dysphagia [29]. This was also supported by Krishnamohan P et al., whose study also found that a sigmoid oesophagus shape in pre-operative tests was also a predictor of surgical success [30]. In this study we provide a complete report of the patients’ complaints, both pre-operatively and postoperatively. The most commons symptoms before surgery, besides dysphagia, were heartburn and regurgitation. Heartburn remained the most common symptom even after surgery (34.8%). This is probably due to the fact that pre-operative and post-operative heartburn have different pathophysiological origins. This rate of heartburn is similar to other reports in the literature [31]. Despite this, only 17.4% of patients had had acid pathological reflux detected in the pH-metry post-operatively. This is in accordance to previous literature results [32] and can be explained by the low correlation between a patient complaining of heartburn and reflux and the demonstration of said reflux in the pH-metry. One of our main goals was to try and find which pre-operative characteristics could predict better outcomes after the surgery, namely less dysphagia, less reflux, less intra-operative and post-operative complications and a lower usage of PPI medication. Regarding post-operative dysphagia, we found two associations. First, patients which had pre-operative regurgitation had less post-operative dysphagia when compared with patients who did not have preoperative regurgitation (13.3% vs 45.2%, respectively, p=0.034). Interestingly, patients with preoperative regurgitation were older, at the time of diagnosis, than patients without regurgitation (56.53 vs 43.90; p= 0.024). This was the only symptom which showed an association with age. It is a well-known fact that older patients, particularly over 60, have better outcomes after surgery, including less postoperative dysphagia [33]. As such, we think that this predictor effect of regurgitation of a better outcome was due to the fact that, in our sample, patients who complained of said symptom were older. Secondly, 12 another interesting finding was that patients who had pre-operative complaints of heartburn were less likely to have dysphagia post-operatively (p<0.01). As in the case of regurgitation, patients who experienced pre-operative heartburn were older than patients who didn’t (51.04 years old vs 44.10 years old), even though it was not statistically significant (p=0.254). It’s possible that the explanation for this association is the same that we propose for the regurgitation and dysphagia association, and that our sample simply did not have the statistical power to demonstrate it. The type of diagnosis, the type of surgical approach, the number of co-morbidities did not prove to be predictors of post-operative dysphagia. Although women had more dysphagia post-operatively (40% vs 37.5%) there was no significance (p=0.538). Contrary to what has been reported about the patient’s age as a predictor of surgical outcomes [31], no association was found in our sample, even though patients who had post-operative dysphagia also had a higher age at diagnosis (50.94 vs 46.47 years old; p= 0.334). In terms of heartburn, we did not find any factors that could predict a higher incidence of this symptom post-operatively. This seems to be the case with other similar studies [29]. 39.1% of our patients started proton-pump inhibitor medication during follow-up. Although we could not find any predictors for postop heartburn, we did discover that the diagnosis can predict the need for PPI medication. Patients who had relapse of Achalasia were more likely to need PPI treatment (83.3% of patients with relapse needed PPI vs only 32.5% of patients with primary Achalasia; p= 0.028). No similar reports were found in the literature. A possible explanation may result from the fact that patients who relapse must endure a second myotomy, which further weakens the physiological anti-reflux mechanism, predisposing to more severe heartburn and a greater need for medication. LHM plus Dor fundoplicature proved to be an excellent treatment option for Achalasia. Our rate of postoperative dysphagia rounded 21.8%, which is in accordance to the rates reported in the literature [4]. After the surgery there was a significant decrease in LES basal pressure (26.76 vs 6.41; p<0.01), as well as LES Residual pressure (13.10 vs 2,70, p<0.01). LES relaxation increased after the surgery (from 55.54% to 67,54%) even though this was not a statistically significant increase ( p=0.134). Other studies have showed a non-significant increase as well [32]. As for the pre-operative manometric parameters, we did not find any association between these characteristics and post-operative dysphagia, need for medical treatment and post-operative heartburn (Table 4). 13 We also evaluated intra-operative and post-operative morbidity. Our rate of complications, 13% and 7%, respectively, is within the normal range reported in previous works [23, 30, 31]. When trying to assert possible predictors of morbidity, we found no factors that could predict intraoperative morbidity. However, we did find an association between pre-operative pneumatic dilatations and post-operative morbidity (p=0.035). Dilatations are one of the most effective treatments available for Achalasia [4]. Nonetheless, one must take into account that previous dilatations can make the surgical technique more challenging and can perhaps lead to more complications for patients. Multiple reports in the literature have associated the existence of previous treatments and poorer surgical outcomes, this effect being greater with botulin toxin injection [5, 34, 35]. Smith et al. state that, in patients with previous dilatations, the submucosal dissection plane is obliterated [36]. Nevertheless, other articles found no association between pre-operative dilatations and surgical outcomes [29, 31]. Taking this information into consideration, we think that pneumatic dilatations should be used carefully and that there should be a strict decision-making process on which patient does dilatation before surgery. One recent development that might help in this decision is the Chicago Classification, since it has been shown that patients with type II achalasia as defined by this classification respond better to any form of treatment and this subtype is a predictor of therapeutical success [10]. On the other hand, type I and type III of the Chicago Classification tend to predict a poorer outcome [5]. The limitations of this study are the retrospective approach and the small sample size. Due to our sample size, a risk for a Type II error exists. Another limitation was the lack of complete data regarding the manometric reports of all patients. In conclusion, our study reinforces the efficacy of LHM as the current gold-standard of treatment for Achalasia while introducing the notion that there should be an extra care in terms of reflux for patients with relapse of the disease. It also shows that pneumatic dilatations, while curiously a safe option in terms of intra-operative morbidity, can lead to a higher incidence of post-operative morbidity and, as such, should be used with great care. It is our opinion that prospective studies with long follow-up are needed to uncover new predictors of surgery success or failure, specially taking into account the differences between subtypes of Achalasia elucidated by the new Chicago Classification. 14 REFERENCES 1. Tolone S, Limongelli P, Del Genio G, Brusciano L, Russo A, Cipriano L, et al. Recent trends in endoscopic management of achalasia. World journal of gastrointestinal endoscopy. 2014;6(9):407-14. 2. Felix VN, DeVault K, Penagini R, Elvevi A, Swanstrom L, Wassenaar E, et al. Causes and treatments of achalasia, and primary disorders of the esophageal body. Annals of the New York Academy of Sciences. 2013;1300:236-49. 3. Katada N, Sakuramoto S, Yamashita K, Shibata T, Moriya H, Kikuchi S, et al. Recent trends in the management of achalasia. Annals of thoracic and cardiovascular surgery : official journal of the Association of Thoracic and Cardiovascular Surgeons of Asia. 2012;18(5):420-8. 4. 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Um agradecimento também para a auxiliar Sara Taveiras, pelo auxílio na procura de informação nos relatórios dos doentes. 17 ANNEXES 18 ANNEX ITables Symptom Pre-Operative Period Post-Operative Period Absolute Frequency Relative Frequency Absolute Frequency Relative Frequency Nausea 1 2,2% 5 10,9% Vomit 4 8,7% 5 10,9% Bloating/Fullness 2 4,3% 5 10.9% Regurgitation 15 32,6% 6 13% Heartburn 26 56,5% 16 34,8% Chest Pain 8 17,4% 1 2,2% Nocturnal Cough 3 6,5% 1 2,2% Aspiration 1 2,2% 0 0 Sialorrhea 1 2,2% 1 2,2% Halitosis 2 4,3% 1 2,2% Weight Loss 9 19,6% 0 0 Eructation 2 4,3% 1 2,2% Table 1: Patients’s symptons, pre-operative and post-operative 19 Pre-operative symptoms/Patient data N (%) Post-op Dysphagia Post-Op Heartburn Post-Op PPI Treatment Chest Pain 8 (17.4%) p=1 p=1 p=1 Regurgitation 15 (32.6%) p=0,878 p=0,034 p=0,503 Weight loss 9 (19.6%) p=1 p=0,7 p=1 Nocturnal cough 3 (6.5%) p=0,542 p=1 p=0,270 Heartburn 26 (56.5%) p=0,433 p<001 p=0,805 Diagnosis (Primary or Relapse) p=0,405 p=0,405 p=0,028 Primary Achalasia 40 (87%) Relapse 6 (13%) Surgical approach p=1 p=0,602 p=0,284 Laparoscopic 41 (89.1%) Laparotomy 5 (10.9%) Intra-Operative Morbidity 6 (13%) p=0,405 p=0,649 p=1 Table 2: Associations between patient data and post-operative dysphagia, heartburn and PPI treatment 20 Patient Data Mean Intra-Operative Morbidity (p value) Post-Operative Morbidity (p value) Age 48.02 0.794 0.575 Number of dilatations 0.61 0.898 0.035 Number of surgeries 0.33 0.778 0,781 Number of comorbidities 1.11 0.997 0,281 Table 3: Predictors of intra-operative and post-operative morbidity consecutive numbering of the main text. 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