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Clinical Case Conference

Clinical Case Conference. November 30 th , 2011 Allen Hwang, MD. HPI. 30 y/o M with h/o cystic fibrosis c/b multiple pneumonias, chronic sinusitis, pancreatic insufficiency, failure to thrive, chronic O2 requirement s/p bilateral lung transplant June, 2010 (CMV D-/R-). HPI.

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Clinical Case Conference

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  1. Clinical Case Conference November 30th, 2011 Allen Hwang, MD

  2. HPI • 30 y/o M with h/o cystic fibrosis c/b multiple pneumonias, chronic sinusitis, pancreatic insufficiency, failure to thrive, chronic O2 requirement s/p bilateral lung transplant June, 2010 (CMV D-/R-).

  3. HPI • Post-operative course relatively uneventful, extubated on POD #1. However, did develop: • prednisone induced glucose intolerance • gastric dysmotility and ileus requiring NGT decompression • self-limited atrial fibrillation • sinus tachycardia

  4. HPI • One month post-operatively, developed: • wound infection and PNA requiring admission and intravenous antibiotics • chronic MDR pseudomonas pneumonia • multiple courses of outpatient antibiotics • acute cellular rejection noted on serial bronchoscopies

  5. HPI • Patient endorsed some reflux-type symptoms. Given multiple episodes of rejection and chronic pneumonia, concern for GERD as underlying cause. Patient referred to GI for further evaluation.

  6. HPI • In clinic, the patient reported intermittent nausea, early satiety, and rare emesis containing undigested food. He has not gained any weight since his transplant surgery. Mild dyspepsia controlled with PPI. • Of note, he denies odynophagia, abdominal pain, dysphagia, hematemesis, diarrhea, or other changes in his bowel movements.

  7. PMH • As mentioned, CF c/b PNA, sinusitis, pancinsuff, s/p B lung transplant c/b Pseudomonal infection and rejection • Corticosteroid induced diabetes • Sinus tachycardia

  8. PMH • FH: non-contributory • SH: works in office • Tob: none • Alc: none • IVDU: none

  9. Medications • Alendronate • ASA • Atovaquone • Calcium/VitD • Ferrous sulfate • Magnesium oxide • Metoprolol • Mometasone • Omeprazole • Pancrelipase • Miralax • Prednisone • Tacrolimus • Valacyclovir Allergy to Zosyn, Bactrim

  10. Exam • BP 110/70 P 100 T 98.1 RR 18 • NAD • Trachea midline • Bibasilar rhonchi • RRR no m/r/g • soft, NT, ND, NABS, no succussion splash • Surgical scars present • Thin

  11. Labs • WBC 5.5, Hb 10.8, MCV 94.2, Plt 275 • Albumin 4.5, Total Protein 7.6 • TB 0.4, AST 17, ALT 15, AP 54 • Na 140, K 4.4, Cl 106, CO2 20, BUN 44, Cr 1.42 • PTT 36, INR 1.25

  12. Labs • Bronchoscopy/pathology • Lung, right middle and lower lobes, transbronchial biopsy: Fragments of alveolated lung parenchyma with minimal acute cellular rejection, OISHLT Grade A1

  13. Labs Many Pseudomonas aeruginosa, Mucoid Strain Source: Bronch Wash 11-301-03081 ORGANISM F Piperacillin-tazobactam R F Ceftazidime R F Cefepime R F Meropenem R F Amikacin R F Gentamicin R F Tobramycin R F Levofloxacin R

  14. What do you think? • What is causing his nausea, vomiting, and early satiety? • Do you believe that his GERD is contributing to his rejection and infections? • Are there studies that you would like to perform before deciding?

  15. Gastric emptying study • The residual activity within the stomach is 95% at one hour, 94% at two hours, 87% at 3 hours, and 80% at 4 hours.

  16. Barium swallow test • Normal swallowing function and normal esophageal motility • Patulous gastroesophageal junction with mild to moderate gastroesophageal reflux • Retained food debris in the stomach raising possibility of gastroparesis

  17. 24-hr pH probe

  18. 24-hr pH probe

  19. Esophageal manometry

  20. Esophageal manometry

  21. What to do next? • Given this newly acquired information, do you feel that this patient’s reflux is the cause of his rejection and pneumonias? • What do you believe is the next best course of action?

  22. GERD and acute lung rejection • 1,200 lung transplant in US annually • Significant improvement in 1 year survival since 1963: >80% • Five-year survival remains significantly lower compared to other solid organ transplants: Lung: 43% - 49% Kidney 66-78% Heart 64-74% Liver 55%-72%

  23. BronchiolitisObliterans Syndrome • Long term morbidity and mortality after lung transplantation are largely attributable to bronchiolitisobliterans syndrome (BOS), a form of chronic rejection • CMV • PNA • HLA mismatch • GERD?!!!!

  24. GERD and BOS • GERD has been proposed as a possible mechanism for this to happen (all theoretical): • Impaired cough reflex • Impaired mucociliary clearance (15% after transplant) • Esophageal and gastric dysmotility after transplant (limited data; no prospective study) • Vagal nerve injury • Ischemia • Scarring • Immunosuppressive drug

  25. Does GERD cause BOS?Observational studies • Case series from Western Ontario with 11 heart/lung transplant patients • 5 with BOS • All had chronic cough, delayed gastric emptying, esophageal dysmotility Lancet. 1990 Jul 28;336(8709):206-8.

  26. Does GERD cause BOS?Observational studies • Case report from Duke University • Lung transplant recipient developed acute decline in pulmonary function testing • Biopsy showed acute inflammation, no rejection • Further testing showed severe reflux • Underwent Nissen with full recovery Chest. 2000 Oct;118(4):1214-7.

  27. Does GERD cause BOS?Rat studies • WKY-to-F344 rat orthotopic lung transplant model used • Compared controls vs. 8 weekly gastric fluid aspirations • 6/9 allografts with aspiration demonstrated bronchioles with surrounding monocytic infiltrates, fibrosis and loss of normal lumen anatomy • None of the allografts without aspiration (n = 10) demonstrated these findings (p = 0.002) • Aspiration was associated with increased levels of IL-1 alpha, IL-1 beta, IL-6, IL-10, TNF-alpha and TGF-beta in BAL and of IL-1 alpha, IL-4 and GM-CSF in serum Am J Transplant. 2008 Aug;8(8):1614-21. Epub 2008 Jun 28.

  28. Does GERD cause BOS?Retrospective studies • At Harefield Hospital in Middlesex, UK, 59 pts with LTP underwent esophageal manometry • Compared BOS-free survival between abnormal refluxers (37) vs. control (HR 3.6, p=0.022) and abnormal acid control (16) vs. control (NS) J Heart Lung Transplant. 2009 Sep;28(9):870-5.

  29. Does GERD cause BOS?Retrospective studies • Institutional observational study from Emory • 60 LT subjects, 33 with GERD versus 27 without GERD. • Observed 51 episodes of rejection. • The rate of rejection was highest among patients with GERD: 8.49 versus 2.58, an incidence density ratio (IDR) of 3.29 (P = .00016) Transplant Proc. 2010 Sep;42(7):2702-6.

  30. Does antireflux surgery prevent BOS?Observational studies • Case series from Western Ontario with 11 heart/lung transplant patients • 5 with BOS • All had chronic cough, delayed gastric emptying, esophageal dysmotility • Three patients improved with antireflux precautions • One patient improved with pyloroplasty Lancet. 1990 Jul 28;336(8709):206-8.

  31. Does antireflux surgery prevent BOS? Retrospective studies • Duke University, 18/298 lung transplant patients with documented reflux • Performed 13 laparoscopic Nissenfundoplications, four laparoscopic Toupets, and one open Nissen • Two of the 18 patients reported recurrence of symptoms (11%), and two others reported minor GI complaints postoperatively (nausea, bloating). • There were no deaths from the antireflux surgery. • After fundoplication surgery, 12 of the 18 patients showed measured improvement in pulmonary function (67%). SurgEndosc. 2002 Dec;16(12):1674-8. Epub 2002 Jul 29.

  32. Does antireflux surgery prevent BOS? Retrospective studies • Duke University, retrospective cohort survival analysis in no reflux, reflux no surgery, reflux early surgery, reflux late surgery • Significantly reduced incidence of BOS Ann Thorac Surg. 2004 Oct;78(4):1142-51; discussion 1142-51.

  33. Does antireflux surgery prevent BOS? Retrospective studies • Duke University study of 222 patients that underwent LTP. • Divided into three groups: No GERD (pre/post XP pH normal), GERD no fundo, GERD with fundo Ann Thorac Surg. 2011 Aug;92(2):462-8; discussion; 468-9.

  34. Among GERD patient (no fundo): Ann Thorac Surg. 2011 Aug;92(2):462-8; discussion; 468-9.

  35. Between no GERD, GERD, and FUNDO groups: Ann Thorac Surg. 2011 Aug;92(2):462-8; discussion; 468-9.

  36. Does antireflux surgery prevent BOS? Retrospective studies • At University of Pittsburgh, study done on the effect of anti-reflux surgery on pre-TP and post-TP patients • Forty-three patients with ESLD and documented GERD (pre-LTx, 19; post-LTx, 24). Arch Surg. 2011 Sep;146(9):1041-7.

  37. How to perform Nissenfundoplication • Step 1: Open patient • Step 2: Do a Nissen • Step 3: Close patient • Step 4: Celebratory beer

  38. How to perform a Nissen • Laparoscopic fundoplication with or without pyloroplasty in patients with gastroesophageal reflux disease after lung transplantation: how I do it. Christopher S. Davis, et al. J GastrointestSurg.;14(9):1434-1441.

  39. Patient Course • Patient underwent Nissenfundiplication with pyloroplasty • Post-operatively, continues to have difficulty eating with peri-umbilical pain post-prandially, with early satiety • GES now normal • However, less frequent cough, and resolution of acute cellular rejection on subsequent BAL

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