P. Marco Fisichella, Nathaniel J. Soper, Carlos A. Pellegrini and Marco G. Patti (eds.)Surgical Management of Benign Esophageal Disorders2014The ”Chicago Approach”10.1007/978-1-4471-5484-6_9
© Springer-Verlag London 2014
9. Minimally Invasive Treatment of GERD: Special Situations
(1)
Department of Surgery, Stritch School of Medicine, Loyola University Medical Center, 2160 South 1st Avenue, Maywood, IL 60153, USA
Abstract
Research progress over the past few decades has helped us understand the association between gastroesophageal reflux disease (GERD), various pulmonary diseases, and obesity. Even though the pathophysiology and mechanisms behind the association have yet to be fully elucidated, treatment for GERD in these special populations has dramatically changed over this period. While lifestyle and dietary changes remain important for the management of GERD, the results can be highly variable since they depend mostly on the compliance of the patients. Pharmacologic agents such as proton pump inhibitors (PPIs) and histamine-2 receptor antagonists are effective in reducing gastric acid and thereby improving symptoms secondary to acidic reflux; however, they do not prevent nonacidic reflux episodes and chronic microaspiration, which may contribute to poorly controlled asthma, progression to end-stage lung disease, and bronchiolitis obliterans syndrome (BOS) in lung transplant recipients. Therefore, surgical intervention may be necessary in selected patients. Today, with the advancement of laparoscopic techniques since their introduction in the 1990s, morbidity and mortality of anti-reflux and bariatric procedures have progressively improved, making them the treatment of choice for GERD in this special patient population.
Keywords
Laryngopharyngeal reflux (LPR)MicroaspirationBronchiolitis obliterans syndrome (BOS)Bariatric proceduresAsthmaIntroduction
Gastroesophageal reflux disease (GERD) is present in 10–20 % of the general population in the United States, and classic or “typical” reflux symptoms include heartburn and regurgitation. However, over the past few decades, increasing evidence has shown a strong association between GERD and various pulmonary disorders. Whether acid reflux predisposes patients to some of these pulmonary disorders or vice versa is still unclear, the diagnosis and treatment for these patients have posed an immense challenge for clinicians, since many of these patients do not present with the classic reflux symptoms or may be entirely asymptomatic and response to therapy is often variable. Lastly, as obesity is becoming an epidemic in the United States, the incidence of GERD may also be on the rise since obesity is a known contributing factor to the development of acid reflux disease. The goal of surgical intervention in this subset of patient addresses both the issues of obesity and reflux symptoms. In this chapter, the association between GERD, asthma, laryngopharyngeal reflux, (LPR) end-stage lung disease, and obesity will be discussed, as well as their challenges on diagnosis and treatment.
Asthma
Prevalence and Pathophysiology
The association between asthma and GERD has been well documented for years. It has been reported that GERD on pH monitoring is present in up to 80 % of patients with asthma [1]. A more recent systematic review looking at the prevalence of the two diseases showed that 59 % of patients with asthma also have a diagnosis of GERD compared with only 38 % of controls. Patients with asthma are also 1.8 times more likely to develop GERD compared to those without asthma. In addition, the prevalence of asthma in patients with GERD is 1.2 times higher than controls [2]. Even though the association seems clear, its pathophysiologic mechanism is not completely understood. One hypothesis suggests that aspiration of esophageal acid into upper airway leads to bronchospasm and increases airway reactivity through a vagal reflex [3]. On the other hand, bronchoconstriction in asthmatics can also trigger reflux symptoms. Further, lung hyperinflation in asthma may cause an increase in the pressure gradient between the abdomen and chest, which may lead to the herniation of the lower esophageal sphincter (LES) into the chest. As a result, the pressure of the LES is decreased and acid is refluxed into the esophagus [4]. These findings have since shaped the notion that surgical treatment of GERD in patients with asthma may improve symptoms and outcomes of both diseases.
Symptoms and Diagnosis
Although the association between the GERD and asthma diseases has been well established, GERD can be difficult to diagnose in asthmatic patients. About 40 % of patients with asthma do not present with typical reflux symptoms, such as regurgitation or heartburn, but have positive pH monitoring and are referred to as having “silent GERD” [5]. These patients often fail standard therapy for asthma control and may complain of frequent episodes of nocturnal respiratory symptoms. Inflammation of the esophageal mucosa from GERD can also cause chronic cough and bronchospasm through neurogenic mechanisms [6]. Diagnosing GERD in this patient population can often be challenging and is primarily a diagnosis of exclusion. A detailed clinical history should be obtained with focus on the “atypical” reflux symptoms, including substernal chest pain, dysphagia, hoarseness, or worsening of asthma symptoms when recumbent. A 24-h pH monitoring is commonly used to evaluate for acid reflux in proximal and distal esophagus. However, in patients with poorly controlled asthma, a positive pH test is not associated with increased asthma symptoms, worse outcome, decreased lung function, or increased airway hyperresponsiveness, if no typical reflux symptoms are present [7]. In addition, the result of a positive pH monitoring does not predict response to acid suppression treatment; therefore, the routine use of pH monitoring for poorly controlled asthmatics remains controversial [8].
A diagnostic modality for GERD that has been gaining widespread popularity since its introduction in 1991 is the multichannel intraluminal impedance test. It allows for measurements of acidic and nonacidic events, which some suggest may be the cause for poorly controlled asthma in some patients despite PPI therapy. The probe contains multiple impedance sensors and a pH sensor and is placed with its most distal impedance sensor within 2 cm of the lower esophageal sphincter (LES). When a more distal impedance sensor detects substance in the esophagus before the proximal sensors, it denotes a reflux episode. A nonacidic reflux event can be distinguished from an acidic episode when the impedance sensors are activated, but not the pH sensor. Another advantage of this technique is that the sensors can detect the characteristics of the esophageal refluxate, such as gas, liquid, or a mixture of both. One study suggests that the presence of gas in the refluxate may be associated with worse perception of symptoms by the patients [9]. Weakly acidic or nonacidic reflux episodes are also associated with chronic cough in some studies [10, 11]. In children with persistent respiratory symptoms, pH-impedance testing has been shown to be more useful in detecting nonacid reflux events that are often associated with respiratory symptoms than pH monitoring alone [12], making it a more preferred option in diagnosing GERD in asthmatic patients especially when they are refractory to medical therapy.
Treatment
Currently, the recommendations for conservative treatment of GERD are lifestyle modifications and initiation of medical therapy. Compared to histamine-2 receptor blockers, PPIs are superior in improving reflux symptoms and healing esophagitis [13]. However, in patients with moderate to severe asthma and symptoms of GERD, treatment with PPIs fails to improve asthma symptoms and pulmonary function, although patients usually report better quality of life and reduction in asthma exacerbation [14, 15]. In a randomized controlled trial studying the efficacy of PPIs in poorly controlled asthmatics with mild or no reflux symptoms, no benefit was shown with twice daily esomeprazole compared to placebo [5]. The results of these studies may support the notion that nonacidic gastric content can also exacerbate asthma. When comparing medical treatment with surgical intervention, multiple studies have shown that anti-reflux surgery is comparable, if not more effective, in improving asthma symptoms in patients with GERD. In a randomized study by Sontag et al., 62 patients were assigned to receiving Nissen fundoplication, ranitidine three times daily, or antacid as needed. The patients were followed for up to 19 years, and outcomes such as pulmonary medication requirement, asthma symptom score, overall clinical status, peak expiratory flow, and pulmonary function were collected. By 2 years, 74.9 % of patients in the surgical group had significant improvement in overall asthma status compared to 9.1 % of the medical group and 4.2 % of the control group. However, there was no significant difference in medication requirement, pulmonary function, or peak expiratory flow in the three treatment groups [16]. In a more recent study evaluating the effect of laparoscopic Nissen fundoplication in the pediatric population with steroid-dependent asthma, 89 % of patients reported significant improvement in overall symptoms, 90 % had reduction in nocturnal asthma, and 78 % of patients were weaned off oral steroids postoperatively [17]. Therefore, for patients with proven GERD and difficult to control asthma, anti-reflux surgery may provide symptomatic relief even if it may not improve pulmonary function or overall survival.
Laryngopharyngeal Reflux
Prevalence and Pathophysiology
Laryngopharyngeal reflux (LPR) is defined as the retrograde flow of gastric content up to the level of the upper esophageal sphincter. About 24 % of patients with GERD are also diagnosed with LPR [18]. LPR is associated with chronic laryngitis and difficult-to-treat sore throat in up to 60 % of patients [19]. Unlike patients with the “typical” GERD symptoms, only a small percentage of those diagnosed with LPR have evidence of esophagitis on endoscopy [20]. The reason for this finding is still poorly understood, but studies have shown that the presence of pepsin, in addition to a low pH, from gastric content, leads to tissue injury and altered epithelial repair that is not readily seen in the esophagus [21]. Therefore, as few as three proximal reflux episodes per week can lead to LPR compared with up to 50 episodes for GERD [22]. While the relationship between GERD and esophageal adenocarcinoma is well established, the association between LPR and laryngeal squamous cell carcinoma remains unproven. However, recent evidence suggests that pepsin promotes epithelial proliferation in larynx and pharynx, which may imply a role in the development of laryngeal cancer [23]. As a result of these studies, early diagnosis of LPR may be important in preventing progression to malignancy.
Symptoms and Diagnosis
Since most patients with LPR often do not have the finding of esophagitis on EGD, they may not complain of the typical GERD symptoms. More commonly, they may report hoarseness (95 %), globus pharyngeus (95 %), persistent cough (97 %), and throat clearing (98 %) [24]. A scoring system developed by Belafsky et al. can be used to aid with diagnosis and to assess treatment response. The Reflux Symptom Index uses a scale of 0–5 to grade the following symptoms: hoarseness or voice problem, throat clearing, excess throat mucus or postnasal drip, difficulty swallowing, coughing after eating or lying down, breathing difficulties or choking spells, persistent cough, sensation of something sticking or a lump in the throat, and heartburn, chest pain, indigestion, or regurgitation [25]. A score of 13 and above is considered abnormal and further diagnostic modalities are warranted.
Once LPR is suspected, laryngoscopy should be performed. Laryngeal inflammation is a nonspecific finding, but posterior laryngitis, with thickening, erythema, and edema concentrated in the posterior larynx, is a common finding in those with LPR. Contact granuloma is highly suggestive of LPR, as it is present in 65–74 % of patients with GERD on pH monitoring [26]. Another common finding at laryngoscopy is pseudosulcus, where diffuse infraglottic edema causes linear indentation to the medial edges of the vocal cords that resembles sulcus vocalis [27]. Other less specific findings include subglottic edema, diffuse laryngeal edema, ventricular obliteration, and posterior commissure hypertrophy. Although these findings are all suggestive of LPR, to confirm the diagnosis of reflux, pharyngeal pH monitoring and an ambulatory multichannel intraluminal impedance study are most commonly performed. LPR is diagnosed when total acid exposure time, defined as percentage of time when the sensor detects pH levels less than four during a 24-h monitoring, is more than 1 % [28]. However, some studies found the false-positive rate of pharyngeal pH monitoring ranging from 7 to 17 % [29, 30], and a positive test result does not necessarily correlate with response to PPI therapy [31]. More recently, impedance testing has been recommended in patients who are refractory to medical treatment since it offers more clinical information including nonacidic reflux episodes that may contribute to the development of LPR [32]. Lately, the Restech Dx-pH probe, introduced to improve the diagnosis of LPR, allows measurements of pH in a nonliquid environment, such as the pharynx, and may be able to detect reflux in areas not otherwise evident during conventional pH monitoring or impedance testing. One prospective study reported a sensitivity of 69 % and a specificity of 100 % with this diagnostic modality [33], although larger randomized studies are still needed to compare its efficacy with more traditional techniques.
Finally, although some clinicians may initiate a 3-month trial of high-dose PPIs to confirm the diagnosis of LPR before any invasive testing, it should be noted that the response to medical treatment can be variable and similar to that achieved in the asthmatic population with GERD. For these reasons, there is controversy today regarding the efficacy of PPIs in the treatment of LPR [19].
Treatment
Like those diagnosed with GERD, patients with LPR are counseled on dietary changes, as well as behavioral modifications, such as weight loss, decreased alcohol intake, and smoking cessation. One randomized controlled trial showed that lifestyle changes for 2 months, with or without PPIs, significantly improved symptoms of LPR [34]. Despite controversy about the efficacy of PPIs, the current recommendation in a suspected case of LPR is to initiate a high dose of PPIs twice daily for 3 months. However, symptoms may take up to 6 months to resolve in some patients. Therefore, unlike GERD, LPR should be treated more aggressively and consequently may require a more prolonged course of treatment [35, 36]. For patients with GERD who are refractory to conservative therapy, laparoscopic anti-reflux surgery is generally recommended. Pharyngeal reflux is reduced from 7.9 to 1.6 episodes per 24 h and esophageal acid exposure is reduced from 7.5 to 2.1 % after surgical intervention in a study by Oelschlager et al. [37]. A recent systematic review of literature that evaluated the effectiveness of laparoscopic fundoplication on the treatment of LPR showed an improvement of symptoms after surgery across the board [38]. However, because of the variability of the studies in terms of preoperative assessment, evaluation of outcomes, and inclusion criteria, clear recommendations could not be made. Nevertheless, for patients with LPR unresponsive to acid suppression treatment, laparoscopic fundoplication may successfully treat laryngeal symptoms secondary to GERD in those with positive pH monitoring.
End-Stage Lung Diseases Before and After Lung Transplantation
Since the first lung transplantation performed by Dr. James Hardy in 1963, over 32,000 transplants have since been performed [39]. From 1995 to 2009, over one third of the transplantations were for chronic obstructive pulmonary disease (COPD). Idiopathic pulmonary fibrosis (IPF) is the second leading cause of transplant with 22 %, cystic fibrosis (CF) accounts for 16 %, and α1-antitrypsin deficiency (AATD) emphysema composes 7 % of the procedures. Other indications include idiopathic pulmonary arterial hypertension, sarcoidosis, bronchiectasis, congenital heart disease, connective tissue disease, cancer, and obliterative bronchiolitis [39].
Emerging studies over the past decade have shed light on the association between some of these end-stage lung diseases, most notably IPF, and GERD. An early study by Mokhlesi et al. evaluated the prevalence of GERD in patients with COPD based on symptoms alone and found that a higher percentage of patients with mild to severe COPD have one or more reflux symptoms compared to those without COPD or asthma [40]. A more recent study utilized esophageal pH monitoring to confirm reflux events in patients with advanced COPD. The results of this study showed an overall prevalence of GERD of 57 % compared to that of 10–20 % in the general population and that only one third of these patients complained of symptoms of GERD [41]. The reasons for this increased prevalence are not entirely understood. However, some suggest that hyperinflation, chronic cough, and bronchospasm may increase the intra-abdominal pressure and reduce the tone of the LES by altering its relationship with the diaphragm. Some medications for the symptomatic treatment of COPD, such as beta-agonists, anticholinergics, and theophylline, have also been postulated to increase GERD by reducing the LES pressure, but studies evaluating the association between GERD and these medications have not been conclusive [42, 43].
Similarly, there is an increased prevalence of GERD in patients with IPF with Raghu et al. reporting it as high as 87 % [44]. A study by Sweet et al. also confirmed these findings and showed a 67 % prevalence of GERD in IPF patients [45]. IPF carries a high mortality rate with median survival between 3 and 5 years from diagnosis [46]. The traditional understanding of the pathogenesis of IPF has been chronic interstitial inflammation leading to fibrosis. Until recently, focus on the treatment of IPF has been on immune modulators and anti-inflammatory agents to halt the progression of disease; however, results have not been very promising, and mortality rate has not improved over the years, which has prompted a change in direction in identifying the pathophysiologic mechanisms of this disease. With increasing evidence of a strong association between GERD and IPF, many now hypothesize that chronic microaspiration may be the etiological factor in the development of pulmonary fibrosis [47]. Although the causal relationship remains unclear, examination of surgical lung biopsies of some patients with chronic hypersensitivity pneumonitis caused by aspiration also has shown the usual interstitial pneumonia pattern typical of IPF [48]. In addition, esophageal dysmotility has been proposed as a contributing factor to microaspiration leading to lung fibrosis. Patti et al. evaluated patients with end-stage IPF awaiting lung transplantation for GERD with esophageal manometry and pH monitoring. The authors found that reflux episodes were associated with a hypotensive LES and abnormal esophageal peristalsis in those with positive pH monitoring [49]. An additional finding that supports the microaspiration hypothesis is the positive effect of anti-reflux surgery on exercise capacity and oxygen requirement in IPF patients awaiting lung transplantation [50]. The use of anti-reflux medications has also been found to be an independent predictor of longer survival time and lowers the radiologic fibrosis score in patients with IPF [51]. New insight into the pathogenesis of idiopathic pulmonary fibrosis has thus led to the focus of targeting the underlying cause of the aspiration with the hope of improving mortality and quality of life.
In contrast to IPF, the pathogenesis of cystic fibrosis has been well established. Like other indications for lung transplantation, there is also a higher prevalence of GERD in the CF population. Mendez et al. from Loyola reported the prevalence of reflux disease in CF patients after transplantation to be as high as 90 % compared to lung transplant patients with other pulmonary disorders. Interestingly, these patients are also more prone to proximal reflux, which has a profound implication for the treatment of GERD in this population to prevent chronic allograft rejection [52]. In addition, patients with CF are six to eight times more likely than controls to experience GERD symptoms [53]. A recent study by Blondeau et al. utilized impedance pH monitoring to evaluate the prevalence of reflux in 24 children with CF and found 67 % of them have increased esophageal acid exposure. One third of the patients also tested positive for bile acid in their saliva, which may increase their risk for aspiration [54]. However, the mechanism of association between GERD and CF is still under debate and several theories have been proposed. Some contributing factors include increased frequency of transient LES relaxations, prolonged gastric emptying, reduced pulmonary function from chronic obstruction of the airways, chronic cough and wheezing with increased intra-abdominal pressure, high-fat diet, and alpha-adrenergic medications [53, 55]. Microaspiration from reflux may also contribute to poor control of CF and progression to end-stage lung disease necessitating lung transplantation. Therefore, the treatment of GERD is again crucial in the overall management of patients with end-stage CF.
Bronchiolitis Obliterans Syndrome
Chronic allograft rejection, also known as bronchiolitis obliterans syndrome (BOS), contributes to the lower survival rate of lung transplant patients compared to recipients of other solid organs. It usually develops 6 months to 2 years after transplant and affects 50–60 % of patients 5 years after transplantation. BOS is also responsible for about 30 % of deaths after 3 years of transplantation [56–58]. The disease is defined as a decreased of forced expiratory volume in 1 s (FEV1) from the best postoperative value without any other cause, such as infection or anastomotic strictures. Pathologically, BOS is characterized by progressive fibrosis of small airways, sclerosis, intimal thickening, and damage to pulmonary vasculature [57, 58]. Since GERD is highly associated with other pulmonary disorders, chronic aspiration secondary to reflux has also been suggested as a contributing factor to the development of BOS after transplant, and the prevalence of GERD in posttransplant patients is as high as 75 % [57]. A study from Duke found an increased incidence of GERD after transplant compared to before, as well as an increased acid exposure time from 5.6 to 9.3 % in the upright position and 5.1 to 11.4 % in the supine position [59]. Reasons for the increase in prevalence have been attributed to injury to the vagus nerve, which leads to delayed gastric emptying and dysmotility of the esophagus, or to the side effects of immunosuppression drugs. In fact, a study by Davis et al. found that 36 % of posttransplant patients diagnosed with GERD also had esophageal dysmotility compared to only 6 % of patients without GERD. Another study from Loyola has also shown that the prevalence of delayed gastric emptying and Barrett’s esophagus was reported at 36 and 12 %, respectively [60]. As the association between GERD and BOS becomes more evident, these findings support a more aggressive approach in the diagnosis and treatment of reflux disease for end-stage lung disease patients before or after lung transplantation.
Diagnosis and Treatment
Current consensus recommends that all patients should undergo ambulatory pH monitoring to diagnose GERD, as many patients with GERD may be asymptomatic. However, since weakly acidic or nonacidic reflux episodes have also been postulated as exacerbating factors for progression of BOS, the use of multichannel intraluminal impedance study has been increasingly employed for detecting reflux events [61]. Nonetheless, even though both pH monitoring and impedance can confirm the presence of reflux, they do not offer information on aspiration. As a result, some studies have measured the levels of biomarkers, such as pepsin or bile acids, in bronchoalveolar lavage (BAL) fluid to detect aspiration. In a study by Stovold et al., elevated levels of pepsin were found in BAL fluid of stable posttransplant patients, those with acute rejection, and those with BOS. Interestingly, recipients with acute rejection had the highest pepsin levels, which suggest that aspiration may play a role in non-alloimmune injury to graft [62]. Similarly, increased bile acid levels in BAL fluid were also found in 50 % of transplant patients. Of these patients, 70 % were diagnosed with BOS compared with 31 % of recipients without, which proposes that bile acids may be more specific compared to pepsin in the association with BOS. The study also found that PPI therapy had no impact on the levels of pepsin or bile acids in the BAL fluid [63].
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
