Prophylactic Antireflux Surgery in Lung Transplantation


Patient population (P)

Intervention (I)

Comparison (C)

Outcome (O)

Lung transplant recipients

Fundoplication

No fundoplication

Symptomatology, lung function, survival, operative mortality

Lung transplant patients who Received Fundoplication

Timing of fundoplication

Early vs. late intervention

Symptomatology, lung function, survival





Review of the Literature


There are three pertinent questions that we have chosen to explore. The first is whether antireflux surgery has a beneficial effect on GERD and aspiration, an effect on the development of BOS, or an effect on overall outcomes including survival. The second is whether antireflux surgery is safe in the lung transplant population. The third questions the proper timing of antireflux surgery in transplant patients. We will review the literature examining the strengths of studies, and determining areas for further exploration. We will later discuss appropriate recommendations based on the current literature.


Effect of Antireflux Surgery on GERD, the Development of BOS, and Outcomes


Unfortunately, there are no prospective, randomized controlled trials examining the effect of antireflux surgery on GERD and aspiration in lung transplant patients. Lung transplant patients differ from the traditional patient population due to differing mechanisms underlying the reflux, likely related to the procedure itself, and therefore data from the general population cannot necessarily be extrapolated to lung transplant patients [1517,23]. Furthermore, trials investigating GERD often rely on surrogate measures of aspiration such as pH data. D’Ovidio et al. demonstrated that only 72 % of patients with bile acid detected upon bronchoalveolar lavage (BAL), which is more likely indicative of gastro-duodenal aspiration, had abnormal pH findings [11]. Studies have also demonstrated that it is likely not the acidity of the reflux but other gastro-duodenal contents which contribute to the adverse effects following lung transplantation [19]. Despite the absence of randomized controlled trial data in this patient population, there have been numerous retrospective and prospective observational and non-randomized controlled studies examining antireflux surgery after lung transplantation which will be described here. The quality of evidence associated with each study as determined based on the GRADE criteria can be found in Table 31.2.


Table 31.2
Studies investigating the effect of fundoplication on lung transplant patients evaluated in our review including study characteristics and the overall quality of evidence based on the GRADE criteria












































































Study

Patients

Study type

Outcome recorded

Quality of evidence

Cantu et al. [21]

381 total, 201 with GERD, 76 had fundoplication

Retrospective, controlled study

Freedom from BOS, acute rejection, survival

Low

Hartwig et al. [24]

297 total, 222 with GERD, 157 had fundoplication

Prospective, non-randomized controlled study

PFTs

Low

Neujahr et al. [9]

21 total, 8 had fundoplication

Non-randomized controlled prospective study

Frequency of CD8 cells from BAL expressing granzyme B and PFTs

Low

Lau et al. [20]

18 total

Retrospective, non-controlled study

PFTs

Low

Robertson et al. [22]

16 total

Prospective, non-controlled study

PFTs, and RSI and GIQLI questionnaires

Low

Abbassi-Ghadi et al. [25]

40 total

Retrospective, non-controlled study

PFTs

Low

Davis et al. [26]

43 total

Retrospective, non-controlled study

PFTs, survival

Low

Fisichella et al. [27]

8 total

Prospective non-controlled study

Leukocyte differential and inflammatory mediators in BAL and PFTs

Low

Burton et al. [28]

21 total

Prospective, non-controlled study

Questionnaire on symptomatology, PFTs

Low

Hoppo et al. [29]

43 total, 19 pre-transplant and 24 post-transplant

Prospective, non-controlled study

PFTs, pneumonia, acute rejection

Low


GERD gastroesophageal reflux disease, BOS bronchiolitis obliterans syndrome, PFTs pulmonary function tests, BAL bronchioalveolar lavage, RSI Reflux Symptom Index, GIQLI Gastro-Intestinal Quality of Life Index

Cantu et al. reported on a total of 381 lung transplant patients, 201 of whom had documented reflux. Of those with reflux, 76 had a fundoplication while 125 did not. They further delineated those who received surgery into two groups, one who underwent early fundoplication (range 0–87 days) and one who underwent late fundoplication (range 106–2,999 days). They measured freedom from BOS, rates of acute rejection, and overall survival among patients. They discovered that recipients undergoing early fundoplication had significantly increased freedom from BOS than patients with no documented GERD, patients with GERD who did not receive fundoplication, and patients who received delayed fundoplication. With regards to acute rejection, they found no significant differences among the four groups. With regards to survival, the early surgery group had significantly increased survival at 1 and 3 years than any other group [21]. An interesting finding in this study was that patients with no documented reflux fared worse than those following early fundoplication. It can be hypothesized that this may be secondary to reflux and micro-aspiration that was not discovered via evaluative studies, raising the question how should patients be chosen for fundoplication following transplant?

Another study was performed by Hartwig et al. who analyzed 297 patients from a prospective database who underwent pH probe evaluation either before or immediately following lung transplantation. Two hundred twenty-two of these patients had an abnormal pH study, 157 of whom underwent fundoplication within 1 year of transplant. They evaluated pulmonary function tests (PFTs) and found that patients who had documented GERD but no fundoplication had significantly decreased FEV1 measurements when compared to the no-GERD and GERD with fundoplication groups. Those latter two groups had similar measurements [24].

Neujahr et al. analyzed eight patients following lung transplant who underwent gastric fundoplication, and compared them with 13 patients who were determined to have GERD but did not undergo fundoplication. GERD was diagnosed by a DeMeester score greater than or equal to 14. Patients were evaluated by BAL including flow cytometry assessing for CD8+ effector cells, and PFTs. They found a significant decrease in the frequency of CD8 cells expressing granzyme B, a cytotoxic intracellular protein, between patients before and after gastric fundoplication. Furthermore, patients who did not undergo fundoplication had increased numbers of CD8 cells expressing granzyme B. Despite these findings, the study did not find any significant difference in pulmonary function between the two groups [9].

In a retrospective review of PFTs in 18 patients who had undergone an antireflux procedure following lung transplant, Lau et al. found an improvement in 67 % of the subjects’ FEV1 following the procedure [20]. A prospective review by Robertson et al. examined 16 patients who underwent laparoscopic Nissen fundoplication following lung transplant, evaluating pre and post-operative PFTs along with Reflux Symptom Index (RSI) and Gastro-Intestinal Quality of Life Index (GIQLI) questionnaires. They discovered a significant improvement in symptoms based on the questionnaires, but no improvement in lung function [22].

Abbassi-Ghadi et al. performed a retrospective study of lung transplant patients who underwent anti-reflux surgery at their institution. They evaluated pre and post-operative PFTs. They discovered that among 40 patients, only those with a positive pre-operative impedance and declining FEV1 had a significant PFT improvement post procedure [25].

Davis et al. performed a retrospective review of 43 patients who underwent an antireflux procedure following lung transplant. They evaluated patients with PFTs and studied overall survival. A significant improvement was seen in the fundoplication group with regards to FEV1. Furthermore, 26 patients in the fundoplication group met the criteria for BOS prior to the procedure, whereas only 13 met the criteria post-procedure. With regards to survival, the fundoplication group had a significantly improved survival compared to the overall series [26].

Fisichella et al. performed a prospective study on eight transplant patients with known GERD. They evaluated for leukocyte differential and inflammatory mediators from BAL samples pre and post-fundoplication, and also examined PFTs. They found a significant decrease in the percentage of neutrophils and lymphocytes following the procedure as well as significant decreases in interferon-gamma and interferon-1beta. They hypothesized that this may be indicative of a protective effect against the development of BOS. Despite this, they found no significant differences in PFTs [27].

A review of a prospectively maintained database of 21 patients who underwent fundoplication following lung transplant was performed by Burton et al. They evaluated symptomatology, lung function, and type of fundoplication. They found 76 % of patients had an improvement in symptoms following fundoplication. However, they found no significant improvements in lung function. Only two were performed within 6 months of transplant. With regards to type of fundoplication, 16 patients had a Toupet while five had a Nissen. When looking at patient satisfaction, dysphagia, or gas bloating, there was no significant differences between the two [28].

Lastly, Hoppo et al. performed an analysis of a prospectively compiled database containing 43 patients with end stage lung disease and GERD, including both pre and post-transplant patients (24 were post-transplant). All 43 underwent antireflux procedures. They evaluated changes in PFTs along with episodes of pneumonia and acute rejection. They found significant improvements in the FEV1 of both groups, as well as a significant reduction in pneumonia and acute rejection in the post-transplant group [29].

None of the studies presented here evaluated the efficacy of fundoplication with respect to decreasing the incidence or the severity of gastro-duodenal reflux and aspiration. This is particularly important in that failed or slipped fundoplication procedures are frequently associated with worsened reflux and aspiration. To date, there have been no randomized controlled trials evaluating the effect of antireflux surgery on GERD and aspiration, BOS, or survival in patients following lung transplant, significantly affecting the availability of high grade evidence. There have been numerous small prospective and retrospective studies at individual institutions, however based on the GRADE criteria, these are all ranked as low with regards to quality of evidence. Therefore, further higher grade research is still necessary in order to reach definitive conclusions with regards to these questions.


Safety of Antireflux Surgery in the Post-lung Transplant Population


Antireflux surgery has been found to be an effective and safe tool for the management of GERD in the general population [30,31]. However, lung transplant recipients have underlying issues that raise concern when contemplating even the simplest procedures. This is secondary to their immune suppression and lung physiology, which could cause an increased rate of infection or sepsis and possible ventilation issues during and following surgery [32,33]. We have therefore reviewed the current literature to investigate the safety of this procedure in lung transplant patients. As before, the GRADE criteria was used to evaluate each study presented in this section for quality of evidence. The evaluation of any study not described in Table 31.2 was compiled in Table 31.3.


Table 31.3
Studies investigating the safety of fundoplication in lung transplant patients evaluated in our review including study characteristics and the overall quality of evidence based on the GRADE criteria (does not include studies already presented in Table 31.1)
























Study

Patients

Study type

Outcome used

Quality of evidence

Gasper et al. [34]

35 total (20 post-transplant)

Retrospective non-controlled study

30-day mortality

Low

Fisichella et al. [23]

Only gold members can continue reading. Log In or Register to continue

Dec 30, 2016 | Posted by in CARDIOLOGY | Comments Off on Prophylactic Antireflux Surgery in Lung Transplantation
Premium Wordpress Themes by UFO Themes