Systemic sclerosis (scleroderma) and other collagen diseases (mixed connective tissue disease, dermatomyositis, polymyositis, etc.) are connective tissue disorders (CTDs) that involve the esophagus resulting in esophageal hypomotility. Studies on the pathogenesis of gastroesophageal reflux disease (GERD) in patients with CTDs suggest that decreased esophageal clearance is a central pathophysiologic factor for the development of GERD (1,2). Shoenut et al. demonstrated higher amounts of acid refluxate in both the distal and proximal esophagus in those with aperistalsis than in those with intact peristalsis (3). Gyger et al. and Spechler et al. also showed that patients with CDTs are frequently found to have absent esophageal peristalsis and an incompetent lower esophageal sphincter (LES) (4,5). Therefore, GERD in these patients may be severe, leading to major complications such as Barrett’s metaplasia, erosive esophagitis, and strictures. Medical treatment for GERD in patients with CTDs is effective in most cases (6,7). However, some patients do not improve and symptoms worsen over time. In addition, pharmacological therapy does not stop the backflow of gastroesophageal contents into the esophagus and may not prevent aspiration, with consequent damage to the lungs from pepsin and bile acids (8-12). Hence, medical therapy should give way to surgical correction of reflux in selected cases: those refractory to PPIs and those who aspirate. Surgical correction of reflux in those with CTDs after lung transplantation is still matter of debate in the transplant community. Even if worsening of dysphagia after a laparoscopic fundoplication remains a concern in those with severely impaired esophageal clearance, laparoscopic antireflux surgery (LARS) should be considered as an effective treatment, as outcomes have been proven satisfactory in selected patients (13,14).
The diagnostic evaluation of GERD in patients with CTDs should include endoscopy, barium swallow, high-resolution impedance manometry (HRIM), and ambulatory pH monitoring.
Esophagogastroduodenoscopy could confirm the diagnosis of GERD or can identify other pathologies; in fact, it is usually the initial evaluation modality of patients with reflux symptoms. The presence of severe erosive esophagitis or Barrett’s esophagus can indirectly support the diagnosis of GERD and, in some cases it can be therapeutic (e.g., dilation of a peptic stricture) (15,16). Despite the long-term medical treatment of these patients, Marie et al. showed that the incidence of esophagitis and Barrett’s esophagus in patients with scleroderma was 32% and 7%, respectively (17).
The barium swallow has no diagnostic role, as the presence of reflux during the test does not correlate with the pH monitoring data (18). The diagnostic value of barium swallow in the evaluation of GERD is therefore limited to the identification of anatomical problems, like a hiatal hernia, the presence of a Schatzki ring, or an esophageal stricture. More recently, a modified barium swallow has been increasingly used to detect aspiration in those with worsening lung function.
HRIM has a central role in the evaluation of patients with CTDs. Typically, CTDs present with ineffective or absent esophageal motility and hypotensive LES (1,19). Roman et al. studied the esophageal peristalsis of 51 patients with scleroderma and the results showed that that 83% had hypotensive LES, 47% and 20% had absent or weak peristalsis, respectively (20). In particular, in the group of patients with Barrett’s esophagus or esophagitis, they all had absent peristalsis and a hypotensive LES. Conversely, Dantas et al. showed that only 6% of patients with systemic sclerosis had a deterioration of the esophageal motility, at a median follow-up of 40 months (21). Hence, esophageal peristalsis does not always worsen.
Ambulatory pH monitoring
Ambulatory pH monitoring is an essential test in all patients undergoing LARS, especially in the presence of extra-esophageal manifestations or in patients unresponsive to PPIs because it confirms the diagnosis of GERD, ruling out other potential pathologies causing the symptoms (22,23). Impedance measures the intra-esophageal contents and when combined with the pH probe, can detect acid and non-acid refluxate. Since PPIs increase gastric pH, the impedance pH monitoring help to detect reflux episodes while on PPIs, and might provide prognostic information in patients with CTDs and interstitial lung disease (ILD) (24). In a prospective study by Savarino et al., 40 patients with scleroderma underwent pulmonary high-resolution computed tomography (HRCT) and 24-hour impedance pH monitoring. The results showed that the refluxate (acid and non-acid) reached more often the proximal esophagus in patients with ILD compared to patients with normal lungs, and that the total number of reflux episodes correlated with the degree of pulmonary fibrosis (25). In addition, Fisichella et al., in retrospective study of 10 patients with severe scleroderma who underwent esophageal functional testing for lung transplant evaluation, found that severe reflux was a better predictor of survival than pulmonary function testing values (24).
Surgical indications and treatment
LARS is often indicated for patients with refractory GERD, for patients who opt out long-term medical treatment, or in those with side effects of PPIs or who aspirate. However, in patients with CTDs a fundoplication has been considered with suspicion because of the risk of worsening dysphagia in those with severely impaired esophageal peristalsis (6,26,27). For this reason, PPIs are considered the treatment of choice. Unfortunately, the pharmacological approach has downsides that must be taken into account. PPIs in patients with CTDs are not always able to heal esophagitis (26) and do not prevent nocturnal refluxate (27). Acid-reducing medications also only affect acid production and raise the pH of the gastric content, while reflux into the esophagus still occurs (28-30) thus potentially leading to aspiration and deterioration of the lung function with resultant pulmonary fibrosis (2,9,10,13,31). Furthermore, although esophageal manometry is often abnormal (32), the classical depiction of aperistalsis and hypotensive LES is not always present. Patti et al. (33) showed that in 20 patients with CTDs their LES pressure and esophageal motility were not different from the control group. Conversely, esophageal peristalsis was most often lacking in patients with end-stage lung disease secondary to CTDs. Based on these data, one may speculate that an early screening would increase the chance to detect GERD in patients with effective esophageal peristalsis, reducing the risk of postoperative dysphagia in case a fundoplication is performed.
Few authors have reported the outcomes of LARS in patients with CTDs. Poirier et al. and Kent et al. have shown that a fundoplication reduces reflux symptoms and improve esophageal acid exposure in the majority of cases. Postoperatively, the incidence of dysphagia was 71% in both studies; however, Poirier et al. reported that dysphagia was already present in 86% of patients before the operation, and that a postoperative radionuclide transit study showed no significant decrease in esophageal emptying. Similarly, Kent et al. showed the incidence of preoperative dysphagia was already high (61%), and that the average postoperative dysphagia score was 1.8, on a scale from 0 to 5 (34,35). In addition to the small number of patients, another limitation of these studies is that a total fundoplication was performed in all patients, even in those with absent peristalsis.
Conversely, Patti et al. demonstrated that a tailored approach for patients with CTDs was effective in improving reflux while it was associated to a low incidence of post-operative dysphagia. Only one patient out of ten presented with dysphagia, but it improved with two Savary dilatations. They performed a total fundoplication in all patients with normal esophageal motility and a partial 240º fundoplication in those with weak (distal esophageal amplitude ≤40 mmHg) or absent peristalsis (33). Similarly, Watson et al. performed LARS (4 total and 22 partial anterior fundoplication) in 26 patients with GERD (six had scleroderma, while the remaining 20 had no evidence of CTDs) in whom manometry showed complete aperistalsis. At a 5- to 12-year follow-up, good outcomes were recorded in 93% of patients (36). Many believe that these results can be attributed to a properly constructed fundoplication, tailored to the patient’s esophageal motility (37,38).
Scleroderma and other CTDs have long been considered a strict contraindication for lung transplantation. In addition, 50% to 80% of these patients have some form of esophageal dysfunction, leading to GERD (39). The incumbent risk of aspiration following transplantation is the main area of concern, as GERD-induced aspiration has been linked to the development of bronchiolitis obliterans syndrome (BOS), which has limited the transplant options for these patients. In support of these data, Fisichella et al. demonstrated that pH monitoring could predict survival status in patients with scleroderma awaiting lung transplantation, as the severity of reflux seemed to have a direct correlation with the survival rate (24). In the most recent updated guidelines for the selection of transplant candidates, the International Society for Heart and Lung Transplantation (ISHLT) stated that carefully selected candidates with scleroderma can undergo lung transplantation; however, in the “relative contraindication” section they state that “Other medical conditions…such as…gastroesophageal reflux, should be optimally treated before transplantation” (40). In addition, LARS has been shown to preserve lung function in these patients, before and after the transplant (41), reducing the risk of rejection (13,42). The available evidence seems to suggest that a pH monitoring must be performed early in these patients, as this test can identify those who will benefit from LARS, preventing GERD and its harmful effects on the allograft.
Finally, a laparoscopic Roux-en-Y gastric bypass (RYGB) has been recently proposed as an alternative to control GERD in patients with CTDs (35,43,44). In a series of patients with CTDs who underwent RYGB (35), Kent et al. showed better outcomes for dysphagia, bloating, diarrhea, and GERD score than in those who underwent a fundoplication. However, the authors performed a total fundoplication in all patients, including those with absent esophageal peristalsis.
The management of GERD in patients with CTDs is challenging. It is based on the evaluation of clinical features, objective evidence of reflux, manometric patterns, likelihood of aspiration, and lung function. Regardless of the medical treatment efficacy, these patients need to be screened early and a careful assessment of the esophageal motility is essential. In the setting of a significant esophageal dysfunction, the role of fundoplication has been controversial given the potential for dysphagia. However, the few data available support the thought that these patients should be evaluated for a tailored antireflux procedure. Although the literature on LARS and CTDs is scant and all series have a small number of patients and short follow-up, evidence seems to suggest that the success of the operation relies in the proper patient selection. Patients refractory to PPIs and those with suspected aspiration should be referred to LARS early enough before the progression of the disease precludes any meaningful surgical intervention.
Conflicts of Interest: The authors have no conflicts of interest to declare.
- Yarze JC, Varga J, Stampfl D, et al. Esophageal function in systemic sclerosis: a prospective evaluation of motility and acid reflux in 36 patients. Am J Gastroenterol 1993;88:870-6. [PubMed]
- Fisichella PM, Jalilvand A. The role of impaired esophageal and gastric motility in end-stage lung diseases and after lung transplantation. J Surg Res 2014;186:201-6. [Crossref] [PubMed]
- Shoenut JP, Yamashiro Y, Orr WC, et al. Effect of severe gastroesophageal reflux on sleep stage in patients with aperistaltic esophagus. Dig Dis Sci 1996;41:372-6. [Crossref] [PubMed]
- Gyger G, Baron M. Gastrointestinal manifestations of scleroderma: Recent progress in evaluation, pathogenesis, and management. Curr Rheumatol Rep 2012;14:22-9. [Crossref] [PubMed]
- Spechler SJ, Castell DO. Classification of oesophageal motility abnormalities. Gut 2001;49:145-51. [Crossref] [PubMed]
- Carlson DA, Hinchcliff M, Pandolfino JE. Advances in the evaluation and management of esophageal disease of systemic sclerosis. Curr Rheumatol Rep 2015;17:475. [Crossref] [PubMed]
- Savarino E, Furnari M, de Bortoli N, et al. Gastrointestinal involvement in systemic sclerosis. Presse Med 2014;43:e279-91. [Crossref] [PubMed]
- Fisichella PM, Davis CS, Lundberg PW, et al. The protective role of laparoscopic antireflux surgery against aspiration of pepsin after lung transplantation. Surgery 2011;150:598-606. [Crossref] [PubMed]
- Patti MG, Vela MF, Odell DD, et al. The Intersection of GERD, Aspiration, and Lung Transplantation. J Laparoendosc Adv Surg Tech A 2016;26:501-5. [Crossref] [PubMed]
- Reder NP, Davis CS, Kovacs EJ, et al. The diagnostic value of gastroesophageal reflux disease (GERD) symptoms and detection of pepsin and bile acids in bronchoalveolar lavage fluid and exhaled breath condensate for identifying lung transplantation patients with GERD-induced aspiration. Surg Endosc 2014;28:1794-800. [Crossref] [PubMed]
- Davis CS, Mendez BM, Flint DV, et al. Pepsin concentrations are elevated in the bronchoalveolar lavage fluid of patients with idiopathic pulmonary fibrosis after lung transplantation. J Surg Res 2013;185:e101-8. [Crossref] [PubMed]
- Allaix ME, Fisichella PM, Noth I, et al. The pulmonary side of reflux disease: from heartburn to lung fibrosis. J Gastrointest Surg 2013;17:1526-35. [Crossref] [PubMed]
- Lo WK, Goldberg HJ, Wee J, et al. Both Pre-Transplant and Early Post-Transplant Antireflux Surgery Prevent Development of Early Allograft Injury After Lung Transplantation. J Gastrointest Surg 2016;20:111-8; discussion 118. [Crossref] [PubMed]
- Fisichella PM, Davis CS, Lowery E, et al. Pulmonary immune changes early after laparoscopic antireflux surgery in lung transplant patients with gastroesophageal reflux disease. J Surg Res 2012;177:e65-73. [Crossref] [PubMed]
- Johnsson F, Joelsson B, Gudmundsson K, et al. Symptoms and endoscopic findings in the diagnosis of gastroesophageal reflux disease. Scand J Gastroenterol 1987;22:714-8. [Crossref] [PubMed]
- Katz PO, Gerson LB, Vela MF. Guidelines for the diagnosis and management of gastroesophageal reflux disease. Am J Gastroenterol 2013;108:308-28. [Crossref] [PubMed]
- Marie I, Ducrotte P, Denis P, et al. Oesophageal mucosal involvement in patients with systemic sclerosis receiving proton pump inhibitor therapy. Aliment Pharmacol Ther 2006;24:1593-601. [Crossref] [PubMed]
- Bello B, Zoccali M, Gullo R, et al. Gastroesophageal reflux disease and antireflux surgery-What is the proper preoperative work-up? J Gastrointest Surg 2013;17:14-20. [Crossref] [PubMed]
- Ebert EC. Esophageal disease in scleroderma. J Clin Gastroenterol 2006;40:769-75. [Crossref] [PubMed]
- Roman S, Hot A, Fabien N, et al. Esophageal dysmotility associated with systemic sclerosis: a high-resolution manometry study. Dis Esophagus 2011;24:299-304. [Crossref] [PubMed]
- Dantas RO, Meneghelli UG, Oliveira RB, et al. Esophageal dysfunction does not always worsen in systemic sclerosis. J Clin Gastroenterol 1993;17:281-5. [Crossref] [PubMed]
- Herbella FA, Andolfi C, Vigneswaran Y, et al. Importance of esophageal manometry and pH monitoring for the evaluation of otorhinolaryngologic (ENT) manifestations of GERD. A multicenter study. J Gastrointest Surg 2016;20:1673-8. [Crossref] [PubMed]
- Andolfi C, Bonavina L, Kavitt RT, et al. Importance of Esophageal Manometry and pH Monitoring in the Evaluation of Patients with Refractory Gastroesophageal Reflux Disease: A Multicenter Study. J Laparoendosc Adv Surg Tech A 2016;26:548-50. [Crossref] [PubMed]
- Fisichella PM, Reder NP, Gagermeier J, et al. Usefulness of pH monitoring in predicting the survival status of patients with scleroderma awaiting lung transplantation. J Surg Res 2014;189:232-7. [Crossref] [PubMed]
- Savarino E, Bazzica M, Zentilin P, et al. Gastroesophageal reflux and pulmonary fibrosis in scleroderma. A study using pH impedance monitoring. Am J Respir Crit Care Med 2009;179:408-13. [Crossref] [PubMed]
- Hendel L, Hage E, Hendel J, et al. Omeprazole in the long-term treatment of severe gastro-oesophageal reflux disease in patients with systemic sclerosis. Aliment Pharmacol Ther 1992;6:565-77. [Crossref] [PubMed]
- Janiak P, Thumshirn M, Menne D, et al. Clinical trial: the effect of adding ranitidine at night to twice daily omeprazole therapy on nocturnal acid breakthrough and acid reflux in patients with systemic sclerosis—a randomized controlled, cross-over trial. Aliment Pharmacol Ther 2007;26:1259-65. [Crossref] [PubMed]
- Tamhankar AP, Peters JH, Portale G, et al. Omeprazole does not reduce gastroesophageal reflux: new insights using multichannel intraluminal impedance technology. J Gastrointest Surg 2004;8:890-7; discussion 897-8. [Crossref] [PubMed]
- Mainie I, Tutuian R, Shay S, et al. Acid and non-acid reflux in patients with persistent symptoms despite acid suppressive therapy: a multicenter study using combined ambulatory impedance-pH monitoring. Gut 2006;55:1398-402. [Crossref] [PubMed]
- Mainie I, Tutuina R, Agrawal A, et al. Combined multichannel intraluminal impedance-pH monitoring to select patients with persistent gastro-esophageal reflux for laparoscopic Nissen fundoplication. Br J Surg 2006;93:1483-7. [Crossref] [PubMed]
- Allaix ME, Fisichella PM, Noth I, et al. Idiopathic pulmonary fibrosis and gastroesophageal reflux. Implications for treatment. J Gastrointest Surg 2014;18:100-4; discussion 104-5. [Crossref] [PubMed]
- Lahcene M, Oumnia N, Matougui N, et al. Esophageal involvement in scleroderma: Clinical, endoscopic, and manometric features. ISRN Rheumatol 2011;2011:325826.
- Patti MG, Gasper WJ, Fisichella PM, et al. Gastroesophageal reflux disease and connective tissue disorders: Pathophysiology and implications for treatment. J Gastrointest Surg 2008;12:1900-6. [Crossref] [PubMed]
- Poirier NC, Taillefer R, Topart P, et al. Antireflux operations in patients with scleroderma. Ann Thorac Surg 1994;58:66-72. [Crossref] [PubMed]
- Kent MS, Luketich JD, Irshad K, et al. Comparison of surgical approaches to recalcitrant gastroesophageal reflux disease in the patient with scleroderma. Ann Thorac Surg 2007;84:1710-5. [Crossref] [PubMed]
- Watson DI, Jamieson GG, Bessell JR, et al. Laparoscopic fundoplication in patients with an aperistaltic esophagus and gastroesophageal reflux. Dis Esophagus 2006;19:94-8. [Crossref] [PubMed]
- Heider TR, Behrns KE, Koruda MF, et al. Fundoplication improves disordered esophageal motility. J Gastrointest Surg 2003;7:159-63. [Crossref] [PubMed]
- Herbella FA, Tedesco P, Nipomnick I, et al. Effect of partial and total fundoplication on esophageal body motility. Surg Endosc 2007;21:285-8. [Crossref] [PubMed]
- Gasper WJ, Sweet MP, Golden JA, et al. Lung transplantation in patients with connective tissue disorders and esophageal dysmotility. Dis Esophagus 2008;21:650-5. [Crossref] [PubMed]
- Weill D, Benden C, Corris PA, et al. A consensus document for the selection of lung transplant candidates: 2014--an update from the Pulmonary Transplantation Council of the International Society for Heart and Lung Transplantation. J Heart Lung Transplant 2015;34:1-15. [Crossref] [PubMed]
- Hoppo T, Jarido V, Pennathur A, et al. Antireflux surgery preserves lung function in patients with gastroesophageal reflux disease and end-stage lung disease before and after lung transplantation. Arch Surg 2011;146:1041-7. [Crossref] [PubMed]
- Cantu E, Appel JZ, Hartwig MG, et al. J. Maxwell Chamberlain Memorial Paper. Early fundoplication prevents chronic allograft dysfunction in patients with gastroesophageal reflux disease. Ann Thorac Surg 2004;78:1142-51; discussion 1142-51. [Crossref] [PubMed]
- Makris KI, Lee T, Mittal SK. Roux-en-Y reconstruction for failed fundoplication. J Gastrointest Surg 2009;13:2226-32. [Crossref] [PubMed]
- Menezes MA, Herbella FA, Patti MG. Laparoscopic Antireflux Surgery in Patients with Connective Tissue Diseases. J Laparoendosc Adv Surg Tech A 2016;26:296-8. [Crossref] [PubMed]
Cite this article as: Andolfi C, Furno S, Orthopoulos G, Fisichella PM. Secrets for successful laparoscopic antireflux surgery: patients with collagen diseases. Ann Laparosc Endosc Surg 2017;2:44.