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

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Presentation on theme: "Clinical Case Conference November 30 th, 2011 Allen Hwang, MD."— Presentation transcript:

1 Clinical Case Conference November 30 th, 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, panc insuff, 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 Wash11-301-03081ORGANISM FPiperacillin-tazobactamR FCeftazidime R FCefepime R FMeropenem R FAmikacin R FGentamicin R FTobramycin R FLevofloxacin 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


19 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 Bronchiolitis Obliterans Syndrome Long term morbidity and mortality after lung transplantation are largely attributable to bronchiolitis obliterans 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 Nissen fundoplications, 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%). Surg Endosc. 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 Nissen fundoplication 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 Gastrointest Surg.;14(9):1434-1441.

39 Patient Course Patient underwent Nissen fundiplication 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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