Andrew G.N. Robertson

Lung Transplantation, Gastroesophageal Reflux, and Fundoplication

Lung transplantation is an accepted treatment strategy for end-stage lung disease; however, bronchiolitis obliterans syndrome is a major cause of morbidity and mortality. This review explores the role of gastroesophageal reflux disease in bronchiolitis obliterans syndrome and the evidence suggesting the benefits of anti-reflux surgery in improving lung function and survival. There is a high prevalence of gastroesophageal reflux in patients post lung transplantation. This may be due to a high preoperative incidence, vagal damage and immunosuppression. Reflux in these patients is associated with a worse outcome, which may be due to micro-aspiration. Anti-reflux surgery is safe in selected lung transplant recipients; however there has been one report of a postoperative mortality. Evidence is conflicting but may suggest a benefit for patients undergoing anti-reflux surgery in terms of lung function and survival; there are no controlled studies. The precise indications, timing, and choice of fundoplication are yet to be defined, and further studies are required.

Aspiration and allograft injury secondary to gastroesophageal reflux occur in the immediate post-lung transplantation period (prospective clinical trial)

Objectives:To provide novel pilot data to quantify reflux, aspiration, and allograft injury immediately post–lung transplantation. Background:Asymptomatic reflux/aspiration, associated with allograft dysfunction, occurs in lung transplant recipients. Early fundoplication has been advocated. Indications for surgery include elevated biomarkers of aspiration (bile salts) in bronchoalveolar lavage fluid (BALF). Measurements have been mostly documented after the immediate posttransplant period. We report the first prospective study of reflux/aspiration immediately posttransplantation to date. Methods:Lung transplant recipients were recruited over 12 months. At 1 month posttransplantation, patients completed a Reflux Symptom Index questionnaire and underwent objective assessment for reflux (manometry and pH/impedance). Testing was performed on maintenance proton pump inhibitor. BALF was assessed for pepsin, bile salts, interleukin-8 and neutrophils. Results:Eighteen lung transplant recipients, median age of 46 years (range: 22–59 years), were recruited. Eight of 18 patients had abnormal esophageal peristalsis. Five of 17 patients were positive on Reflux Symptom Index questionnaire. Twelve of 17 patients had reflux. Three patients exclusively had weakly acid reflux. Median acid exposure was 4.8% (range: 1%–79.9%) and median esophageal volume exposure was 1.6% (range: 0.7–5.5). There was a median of 72 reflux events (range: 27–147) per 24 hours. A correlation existed between Reflux Symptom Index score and proximal reflux (r = 0.533, P = 0.006). Pepsin was detected in 11 of 15 BALF samples signifying aspiration (median: 18 ng/mL; range: 0–43). Bile salts were undetectable, using spectrophotometry and rarely detectable using dual mass spectrometry (2/15) (levels 0.2 and 1.2 &mgr;mol/L). Lavage interleukin-8 and neutrophil levels were elevated. A correlation existed between proximal reflux events and neutrophilia (r = 0.52, P = 0.03). Conclusions:Lung transplant recipients should be routinely assessed for reflux/aspiration within the first month posttransplant. Reflux/aspiration can be present early postoperatively. Pepsin was detected suggesting aspiration. Bile salts were rarely detected. Proximal reflux events correlated with neutrophilia, linked to allograft dysfunction and mortality. These results support the need for early assessment of reflux/aspiration, which may inform fundoplication.

Bile acid aspiration in people with cystic fibrosis before and after lung transplantation

Cystic fibrosis (CF) is a genetic condition that is caused by abnormalities in the CF transmembrane conductance regulator (CFTR) gene. People with CF experience life-long morbidity and premature mortality, the vast majority of which is associated with lung disease. Bile acids are detectable in the lower airway in advanced CF lung disease and persist after lung transplantation http://ow.ly/RTvNW

A Call for Standardization of Antireflux Surgery in the Lung Transplantation Population

Long-term survival post lung transplant is reduced significantly by Bronchiolitis Obliterans Syndrome. It is suggested that extra-esophageal reflux disease is a risk factor for Bronchiolitis Obliterans Syndrome and that antireflux surgery may be beneficial. However, practice between centers varies greatly. We suggest a need for improved evidence and standardization.

Are the enzymatic methods currently being used to measure bronchoalveolar lavage bile salt levels fit for purpose

BACKGROUND Microaspiration after gastroesophageal reflux has been implicated in the chronic loss of allograft function in lung transplant patients. Bronchoalveolar lavage fluid (BALF) assessment for pepsin and bile salts is a common method to document reflux and aspiration. Clinically used methods for bile salt analysis include tandem mass spectrometry and diagnostic enzymatic kits designed to measure bile salts in serum. In clinical research, the enzymatic kits have been commonly used for BALF assays in lung transplant recipients, with reports of detection limits of 0.2 μmol/liter, and the levels used to inform clinical decisions. This study assessed the sensitivity of detection by 2 enzymatic assay kits compared with tandem mass spectrometry. METHODS These 2 kits were used to measure (1) the absorbance changes for 0 to 50 μmol/liter bile salts, (2) levels in gastric juice (10-10,010 μmol/liter), and (3) bile salt levels of 40 BALF samples that were also measured using tandem mass spectrometry (0.01-1.19 μmol/liter). Measurements of pH/impedance were done in 14 of 15 patients. RESULTS Neither kit had detection limits as low as claimed in previous BALF studies. The kits could be made more sensitive with a longer incubation time, (5 μmol/liter). All patients had detectable lavage bile acids using mass spectroscopy, 71% had pathologic distal gastroesophageal reflux, and 43% had pathologic proximal reflux. CONCLUSIONS The enzymatic kits are not sensitive enough for use in situations where bile salt levels are much below 5 μmol/liter, which is the case in BALF. In addition, reports in the literature of levels significantly below 5 μmol/liter need reassessing. Tandem mass spectrometry with a lower limit of detection of 0.01 μmol/liter should be the method of choice.

Barrett's Adenocarcinoma 52 Years After Subtotal Esophagectomy for Pediatric Peptic Stricture

Barretts esophagus results from the long-term effects of both acid and bile reflux. After subtotal esophagectomy and reconstruction with a gastric tube, many patients experience profound reflux. Development of Barretts epithelium in the esophageal remnant has been reported. Here we report the case of a man who was diagnosed with adenocarcinoma in his esophageal remnant on a background of Barretts change 52 years after undergoing one of the first esophageal resections for benign disease as a child.

Randomized clinical trial of laparoscopic total (Nissen) versus posterior partial (Toupet) fundoplication for gastro-oesophageal reflux disease based on preoperative oesophageal manometry (Br J Surg 2008; 95: 57–63)

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Prophylactic Antireflux Surgery in Lung Transplantation

Longterm survival of lung allograft recipients is lower than for other solid organ transplants, due to chronic allograft dysfunction manifested as Bronchiolitis Obliterans Syndrome(BOS).1,2 Chronic micro-aspiration, secondary to gastro-esophageal reflux, may contribute to BOS and up to 75% of patients have Gastro-esophageal reflux disease (GERD) following lung transplantation.3–10 This chapter looks at the evidence base supporting prophylactic antireflux surgery in lung transplant recipients.

Stage-for-stage comparison of definitive chemoradiotherapy, surgery alone and neoadjuvant chemotherapy for oesophageal carcinoma (Br J Surg 2009; 96: 1300-1307).

Sir I read with interest the article by Neudecker and colleagues, which described a prospective randomized trial comparing laparoscopic and open surgery for colorectal cancer. The authors concluded that laparoscopic colorectal cancer surgery was associated with increased operating time but did not decrease morbidity even in a moderate-risk population. Besides the series supporting this conclusion, I still found some large series with pros and cons1 – 4. Nevertheless, I have several questions regarding this manuscript. In Table 4, it is noted that 13 patients (5·2 per cent) receiving a laparoscopic approach developed small bowel obstruction and seven (2·8 per cent) were treated surgically. Reviewing the other series1 – 4, I found that this problem was seldom mentioned. However, causes of this relatively rare complication were not discussed. Surgeons might gain from this to avoid the same complication. The authors mentioned that a body mass index of more than 26 kg/m2 increased the risk of general morbidity by 2·5-fold, but the opposite result was recorded in Table 8. Finally, the authors concluded that laparoscopic colorectal cancer surgery did not decrease morbidity even in a moderate-risk population. However their criteria for designating ‘moderate risk’ were not clearly defined. They did not analyse the morbidities of laparoscopic and open approaches based on individual American Society of Anesthesiologists grades. Hence, this conclusion seemed a little debatable. C.-C. Chiu Department of General Surgery, Chi Mei Medical Centre, Tainan County, Taiwan (e-mail: chiuchongchi@yahoo.com.tw) DOI: 10.1002/bjs.7064

Risk factors for lung disease progression in children with cystic fibrosis

We read with interest the recent paper by van Horck et al. [1], which studied 545 children followed for 5 years with longitudinal data from the Dutch Cystic Fibrosis registry. Data from 2009 to 2014 showed that proton pump inhibitor (PPI) use was associated with annual decline of % predicted forced expiratory volume in 1 s and future pulmonary exacerbation rates. In a discussion of potential mechanisms, the authors considered that bacteria are normally killed by acid conditions in the stomach but that gastric pH is raised following PPI use. It was therefore hypothesised that with extra-oesophageal reflux, surviving pathogens could reach the upper airway and be aspirated. We call for studies of widespread use of proton pump inhibitor therapy in people with cystic fibrosis and chronic lung disease; these should evaluate patient benefit and potential iatrogenic effects, including dysregulation of aerodigestive homeostasis http://ow.ly/ym6H30lxxZu