Clinical Imaging 37 (2013) 617–623

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Clinical Imaging

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Pictorial essay

Postoperative imaging after lung transplantation☆

Patricia Diez Martinez a, Mini Pakkal b, Julie Prenovault a, Marie-Claude Chevrier a, Jean Chalaoui a,Andrei Gorgos a, Pasquale Ferraro c, Charles Poirier d, Carl Chartrand-Lefebvre a,e,⁎a Radiology, University of Montreal Medical Centerb Radiology, Glenfield hospital, Leicester University Hospitals NHS Trustc Thoracic Surgery, University of Montreal Medical Centerd Pulmonary Medicine, University of Montreal Medical Centere Research Center of the University of Montreal Medical Center

☆ Submitted to Clinical Imaging.⁎ Corresponding author. Radiology Department, Un

Center (CHUM), Hôtel-Dieu Hospital, 3840, Montréal (Q+1 514 890 8150; fax: +1 514 412 7193.

E-mail address: chartrandlef@videotron.ca (C. Chartr

0899-7071/$ – see front matter © 2013 Elsevier Inc. Alhttp://dx.doi.org/10.1016/j.clinimag.2013.02.008

a b s t r a c t

a r t i c l e i n f o

Article history:Received 27 January 2013Accepted 21 February 2013

Keywords:Lung transplantationPostoperative complicationsChestLungTransplantation

Lung transplantation (LT) is an established procedure for chronic end-stage lung diseases. Complicationsare frequent and diverse and are the consequence of the complex surgical technique, the severity of theinitial pathology, and the deep state of posttransplantation immunosuppression. Complications followingLT include primary graft dysfunction, rejection (hyperacute, acute, and chronic), infections, posttrans-plantation lymphoproliferative disease, pleural and airway complications, native lung complications, andrecurrence of primary disease. An understanding of these complications, their temporal evolution, andthe role of radiology and other diagnostic methods in their diagnosis and management will help reducethe morbidity and mortality associated with LT.

iversity of Montreal Medicaluébec), Canada H2W 1T8. Tel.:

and-Lefebvre).

l rights reserved.

© 2013 Elsevier Inc. All rights reserved.

1. Introduction

This pictorial review covers the spectrum of postoperativeimaging of lung transplantation (LT) based on our experience ofan LT program established since 1994. LT is now an establishedprocedure for end-stage lung disease; the most frequent indicationsare emphysema, idiopathic pulmonary fibrosis, and cystic fibrosis(Fig. 1). A detailed knowledge of immediate and late complications,both surgical and medical, is essential for earlier detection andtreatment. Complications are frequent and diverse and are due tothe complex surgical technique, the severity and chronicity of theinitial pathology, as well as the immunosuppressive therapyrequired after transplantation.

The most important complications following LT include primarygraft dysfunction (PGD), rejection (hyperacute, acute, and chronic),infections, posttransplantation lymphoproliferative disease, compli-cations involving the pleura and airways, complications of the nativelung, and recurrence of primary disease.

1.1. Primary graft dysfunction

PGD is the recommended term by the International Society ofHeart and Lung Transplantation [1]. It is also known asreimplantation or reperfusion edema and primary graft failure.PGD incidence varies from 11% [1] to nearly 100% [2]. Because ofan increased capillary permeability and alveolar damage caused byan ischemic vascular injury to the transplanted lung, an interstitialand alveolar edema of the allograft occurs when reperfusion isinitiated. It appears within the first 48–72 h and resolves within 3weeks [2]. PGD is a diagnosis of exclusion. The most frequentradiological manifestation is air space disease occurring in thelower and middle lung zones, which may progress to total lungopacification (Fig. 2).

1.2. Hyperacute rejection

Hyperacute rejection is a rapidly fulminating syndromeoccurring within hours following the completion of the vascularanastomoses. It is extremely infrequent, with only few casesreported [3]. It probably results from the interaction ofpreformed recipient antibodies directed against major donorallograft antigens. Chest radiograph (CXR) shows diffuse consol-idation of the entire transplanted lung. Only one suspected case

Fig. 1. Patients pre-LT. (A) LAM. Thirty-five-year-old woman with a proved LAM onnoncontrast chest CT. Presence of multiple cysts and recurring pneumothorax; (B)Severe centrilobular lung emphysema. Noncontrast chest CT showing numerous zonesof widespread centrilobular emphysema; (C) Cystic fibrosis. Twenty-five-year-old manwith bilateral bronchiectasis and bronchial thickening on noncontrast chest CT.

Fig. 2. PGD. (A) anteroposterior CXR of a patient with unilateral right LT showing totalopacification of the right lung due to PGD; (B) Noncontrast chest CT of a patient withPGD with bilateral LT. The diagnosis of PGD was made in the absence of volumeoverload, infection, or rejection. Note the bibasilar distribution of ground-glassopacities (grey arrow) and also the fluid in the right oblique fissure (white arrow).

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of hyperacute rejection was encountered in our center. The lungallograft became grossly edematous intraoperatively, and thepatient died within hours.

1.3. Acute rejection

The time frame for acute rejection extends from within the firstweek [4] through the first year after LT [5] but most often occurswithin the first 3 to 6 months. Risk factors are still not wellunderstood. However, acute rejection is a known risk factor for thedevelopment of bronchiolitis obliterans syndrome (BOS). Histolog-ically, acute rejection consists of perivascular or bronchiolarmononuclear inflammation. Transbronchial lung biopsy is thegold standard for the diagnosis. The radiological findings are notspecific (Fig. 3). CXR can be normal in low-grade acute rejection.In high-grade acute rejection, there are usually ground-glassopacities (localized or widespread). Absence of ground-glassopacities makes severe acute rejection unlikely [6].

Fig. 3. Acute lung rejection. (A) posteroanterior CXR of a patient with Grade 1 rejectionshowing nonspecific finding of a small left-sided pleural effusion 15 days posttransplant; (B) Histology of acute rejection showing lymphocytic infiltration (arrows)in a perivascular distribution.

Fig. 4. Chronic lung rejection. (A) Patient with bilateral bronchiectasis giving rise to a“signet ring appearance” (white arrow), on inspiratory noncontrast chest CT; (B) Airtrapping (white arrow) on expiratory noncontrast chest CT, in another patient; smalbilateral bronchiectasis are also seen; (C) Histology showing peribronchial fibroticprocess (black arrow).

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1.4. Chronic rejection

Chronic rejection is the main factor limiting long-term survivalafter LT. It affects 45% of patients who survive 5 years or moreand is responsible for 57% of the deaths occurring after the firstyear from LT. Chronic rejection usually begins 6 months after LT[6]. Among proven risk factors are prior episodes of acute rejectionand cytomegalovirus (CMV) infection. BOS is classically defined asa manifestation of chronic lung allograft dysfunction (CLAD). Atpathology, it presents as eosinophilic hyaline fibrosis in therespiratory bronchiole walls, with luminal occlusion [7], leadingto airway distortion and scarring.

In the current nomenclature, chronic rejection is classified aspresent or absent [7]. However, because of the patchy distributionof CLAD, transbronchial lung biopsies often provide inadequatetissue samples. Recent investigators [5,8] proposed changes in theclassification of chronic rejection as there are other manifestationsinvolved. Knoop & Estenne [5] have identified four differentpathologic entities: neutrophilic reversible allograft airways dys-function, upper lobe fibrosis, exudative follicular bronchiolitis, andlarge airway stenosis/malacia. Sato et al. differentiates BOS fromrestrictive allograft syndrome (RAS) [8]. RAS presents restrictive

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functional changes, extensive interstitial and pleural fibrosis, incontrast to BOS, which has relatively intact peripheral lung tissue.RAS also has an adverse effect on patient survival [8]. BOSfrequently shows air trapping on expiration computed tomography(CT). On follow-up, CT can show central or peripheral bronchiec-tasis, bronchial wall thickening, mosaic pattern on inspiration,interlobular septal thickening, and peribronchovascular infiltrates

Fig. 5. Lung infections. (A) Noncontrast chest CT of a patient who underwent bilateralLT for cystic fibrosis. It shows ground-glass opacity in the right middle lobe (blackarrow) due to pseudomonas infection; (B) Noncontrast chest CT in a patient withbilateral LT. Cavitating mass in the left lower lobe with adjacent consolidation due toaspergillosis (white arrow). There is also an ill-defined nodule in the right middle lobe(black arrow) also probably due to aspergillosis.

Fig. 6. PTLD. (A) Noncontrast chest CT of a patient with PTLD showingwell-defined lungnodules (white arrow) and a small left-sided pleural effusion (black arrow); (B)Noncontrast chest CT of another patient with PTLD showing bilateral foci ofconsolidation and ground glass (white arrow).

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[5] (Fig. 4). Sensitivity of CT for diagnosis of chronic rejection ishowever still limited [5].

1.5. Infections

The incidence of infections after LT is 34–59% [9], morefrequent than in other organ transplant patients. Bacterial andfungal infections are the most frequent in the first month after LT.Viral infections are more common in the second and thirdpostoperative months. Unfortunately, no specific radiographic orCT findings can allow an accurate distinction between bacterial,viral, and fungal etiologic agents [9]. Patients with pulmonaryinfections after LT may have normal findings at CXR. CT can showground-glass opacities, tree-in-bud pattern, consolidation, nodules,septal thickening, pleural effusions, and bronchiectasis [9,10](Fig. 5).

Bacterial infection, especially due to gram-negative bacteria,can show consolidation (94%), ground-glass opacity (81%),nodules (44%), tree-in-bud appearance, and pleural effusions(75%) [9]. Mycobacterium abscessus is the most frequent atypical

bacteria, while reactivation of pulmonary tuberculosis has beenreported in 2% [10]. Nocardiosis can present a nodular orconsolidative pattern.

Fungal infections, most often due to Aspergillus and Candidaalbicans [6,9], are associated with a high mortality rate and occur2 to 9 weeks after transplantation [9]. CMV infection is the mostcommon viral pathogen following LT and is also the second mostfrequent cause of pneumonia, after bacterial infection. It occurs 1–6 months post-LT. Pneumocystis jirovecii is uncommon nowadays,thanks to the universal prophylaxis.

1.6. Posttransplant lymphoproliferative disease (PTLD)

PTLD refers to a spectrum of diseases in transplanted patientsranging from abnormal lymphoid hyperplasia to true neoplasia, with aprevalence of 2 to 10%within 1 year of LT [11]. Mortality remains high,ranging from 40 to 90% [11]. Deep immunosuppression, a greaterquantity of lymphoid tissue in the pulmonary allograft [11], and ahistory of viral infection (especially Epstein–Barr) are risk factors forPTLD. At imaging, single or multiple nodules or masses, predomi-nantly basal and peripheral [6], are the most frequent manifestation

Fig. 7. Pleural complications. (A) Noncontrast chest CT. Pneumothorax communicatingacross the midline in a patient with bilateral LT (white arrow); (B) Noncontrast chestCT. Left-sided extrapleural hematoma (long white arrow). The position of the chesttube is useful to demarcate the pleural space, note a small pleural effusion (short whitearrow). A small area of extrapleural fat is seen (black arrow) between the extrapleuralhematoma and the pleural effusion. Those subtle signs on noncontrast-enhanced CT areimportant to recognize the extrapleural hematoma. Pleural adhesions were encoun-tered at the time of the transplant surgery for cystic fibrosis. This extrapleuralhematoma occurred most probably due to disruption of extrapleural blood vessels atthe time of the surgery.

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(Fig. 6). The presence of enlarged lymph nodes varies widely in series,from 10 to 78% [11].

1.7. Pleural complications

Pleural complications after LT can be divided into pleuraleffusion, empyema, and pneumothorax. They are often bilateralowing to the fact that the pleural space frequently becomes aunique interconnected space in bilateral LT [4] (Fig. 7).

Pleural effusion occurs in the early postoperative period [4,12]and usually resolves within 2 weeks. It tends to be hemorrhagic,becoming less hemorrhagic and more serous after 7 days [13].Long-term pleural changes (59%) include pleural thickening (48%),calcifications (4%), and effusion (3%). The frequency of empyemavaries between 3% and 8% in various series [13]. It occurs usually6 weeks after LT and is more common after bilateral LT [13].Fungal pathogens, particularly C. albicans, are the most frequentpathogens. Empyema is associated with poor survival requiring anaggressive therapeutic approach [13]. Pneumothorax is a common

complication and usually resolves with drain placement. Atransient air leak is seen in 10% of patients and resolves within1–2 weeks. A persisting pneumothorax beyond 1 week cansuggest bronchial dehiscence or ruptured bulla.

1.8. Airway anastomotic complications

Airway anastomotic complications include bronchial dehiscence,bronchial stenosis, bronchomalacia, as well as bronchovascular,bronchopleural, and bronchomediastinal fistula. Globally, theincidence of airway complications is 15% [14]. The principal riskfactors are donor bronchi ischemia [14], postoperative infection,acute rejection, prolonged mechanical ventilation, and mismatch inthe sizes of donor and recipient bronchi.

Bronchial anastomotic dehiscence typically occurs 2–4 weeksafter LT. With CT, bronchial anastomotic dehiscence can be directlydemonstrated as a site of bronchial wall discontinuity [15], withextraluminal mediastinal air adjacent to the bronchus [15].Persistent pneumothorax, pneumomediastinum, or posterior aircollection are indirect CT signs of bronchial anastomotic dehis-cence [6,15] (Fig. 8).

Bronchial stenosis and bronchomalacia are long-term complica-tions typically occurring 2 to 9 months after LT [6]. Bronchial stenosisis the most frequent complication of large airways and occurs at thesite of the anastomosis, or distally.

1.9. Vascular complications

Vascular anastomotic complications are uncommon [4] andinclude pulmonary artery and vein stenosis. Pulmonary embolismand pulmonary infarction have been reported to be as high as 27% and40%, respectively. The risk of infarction could be related to theinsufficient bronchial arterial supply in the early postoperative periodand thus to fewer available collaterals.

1.10. Complications of the native lung

In patients receiving a single LT, complications are 14–15% morefrequent and are attributable to infection, malignancy (related to thepatients' underlying risk factors, as well as immunosuppressivetherapy), pneumothorax, bronchopleural fistulas, and pulmonaryembolism [16] (Fig. 9).

1.11. Recurrence of primary disease

Recurrence of primary disease has an incidence of approxi-mately 1% and has been described to occur months to yearsfollowing LT [16]. Sarcoidosis is the most common condition torecur; other frequent recurring conditions are Langerhans cellhistiocytosis (Fig. 10) and lymphangioleiomyomatosis (LAM) [16].

2. Conclusion

Postoperative imaging and its interpretation in patients with LTis a challenging task. Complications following LT are diverse andcan be serious. The radiologist's contribution to the multidisci-plinary team approach involves an understanding and earlyrecognition of these complications, as well as of their temporalevolution, for the most appropriate postoperative management ofthese vulnerable patients.

Fig. 8. Anastomotic airway complications. (A) PA CXR in a patient who had undergone bilateral LT showing an abnormal mediastinal air collection below the left hilum (whitearrow); (B) Corresponding noncontrast chest CT of the same patient showing dehiscence of the left main bronchus anastomosis and a large air collection anteriorly (white arrow);(C) Later noncontrast chest CT in the same patient. It shows an incomplete regression of the left main bronchus anastomosis dehiscence and persistent air collection (white arrow).The patient developed superadded Aspergillus infection presenting with bilateral ill-defined centrilobular opacities (black arrow); (D) This patient subsequently underwent surgicalrepair with placement of a stent in the left main bronchus (white arrow).

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Fig. 9. Complications of native lung. Noncontrast chest CT, showing a hyperinflatedemphysematous left native lung, with compression of the right transplanted lung, aswell as an adenocarcinoma in the left native lung (white arrow).

Fig. 10. Recurrence of primary disease. (A) Pulmonary Langerhans cell histiocytosis(PLCH) before LT; (B) PLCH recurrence 3 years after bilateral LT.

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