Clinical Radiology 70 (2015) 898e908
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Pictorial Review
Extravascular complications following abdominal organ transplantation G. Low a, b, *, J.L. Jaremko a, D.J. Lomas b a b
Department of Radiology & Diagnostic Imaging, University of Alberta Hospital, Edmonton, Alberta, Canada Department of Radiology, Addenbrooke’s Hospital, Cambridge University Hospitals NHS Trust, England, UK
article in formation Article history: Received 15 December 2014 Received in revised form 3 March 2015 Accepted 9 April 2015
A variety of transplants have been performed in the abdomen including liver, kidney, pancreas and islet, bowel, and multivisceral transplants. Imaging plays an important role in graft surveillance particularly to exclude post-transplant complications. When complications occur, therapeutic image-guided interventions are invaluable as these may be graft-saving and even life-saving. Vascular complications following transplantation have been extensively reported in recent reviews. The focus of this review is to discuss post-transplant complications that are primarily extravascular in location. This includes biliary, urological, intestinal, malignancy, infections, and miscellaneous complications. Familiarity with the imaging appearances of these complications is helpful for radiologists as accurate diagnosis and expedient treatment has an impact on graft and patient survival. Ó 2015 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
Introduction Transplantation is the most effective treatment for endstage organ dysfunction. Grafts used in the abdomen include liver, kidney, pancreas and islet, bowel, and multivisceral transplants. Imaging has a limited role in detecting graft rejection. Its main function is for detecting complications other than rejection, which may present with similar clinical and laboratory findings. When complications occur, therapeutic image-guided interventions may be graftsaving and even life-saving. Vascular complications following abdominal transplantation have been extensively reviewed in several recent reports.1e5 The focus of this
* Guarantor and correspondent: G. Low, Department of Radiology & Diagnostic Imaging, University of Alberta Hospital, 2A2.41 WMC, 8440-112 Street, Edmonton, Alberta, T6G 2B7, Canada. Tel.: þ1 780 407 6907; fax: þ1 780 407 3853. E-mail address: [email protected] (G. Low).
review is to discuss complications following abdominal transplantation that are primarily extravascular in location.
Biliary complications Biliary-related issues are the second most common complication (10e34% incidence) in liver transplant recipients after rejection.6e10 The risk is highest for livingdonor and split transplants, which utilise complex and small-calibre biliary anastomoses. A study of 1792 liver transplant recipients found that the incidence of biliary complications was 38% at 1 month, 28% at 3 months, 15% at 6 months, and 8% after 12 months.11 These complications included biliary strictures (43%), leaks (27%), obstruction (14%), and ampullary dysfunction (17%).11 Magnetic resonance cholangiopancreatography (MRCP) is the imaging test of choice with 95% sensitivity for post-transplant biliary complications.7,10,12 MRCP is often combined with a multiphasic contrast-enhanced magnetic resonance imaging (CEMRI) examination to provide a comprehensive
http://dx.doi.org/10.1016/j.crad.2015.04.001 0009-9260/Ó 2015 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
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evaluation of the liver transplant. The adoption of modern bolus-tracking techniques, state-of-the-art ultrafast pulse sequences, and sophisticated parallel imaging methods allow the acquisition of high spatial and temporal resolution MRI images on a consistent basis. Cholangitis may be recognised as focal or generalised periductal enhancement (most appreciable on the portal phase) with or without ductal wall thickening. A high-quality MR angiogram can be produced to rule out hepatic artery thrombosis or stenosis. These images are displayed on the MRI workstation using multiplanar, volume-rendered or maximum intensity projection formats for optimal image analysis and can help to road map vascular interventions. Testament to the diagnostic capabilities of MRI, nowadays invasive procedures such as endoscopic retrograde cholangiopancreatography (ERCP) and percutaneous transhepatic cholangiography (PTC) are generally reserved for therapeutic manoeuvres. Contrast-enhanced (CE) MRI cholangiography utilising biliary excretory contrast agents, such as gadoxetic acid disodium (Bayer Healthcare, Leverkusen, Germany), is an alternative to MRCP, which can improve biliary visualisation and is particularly useful for the detection of bile leaks.7 Compared with standard gadolinium agents, gadoxetic acid has a dual contrast property, which expands its clinical applicability. Early on, it behaves as an extracellular agent providing dynamic morphologic evaluation of the graft parenchyma and relevant arterial and venous anastomoses. During the hepatospecific phase, at 20 minutes or later, the liver shows contrast medium uptake (due to organic anion transporting polypeptides [OATPs] on the cell membranes of hepatocytes) followed by biliary excretion of the gadoxetic acid. This combines high-quality anatomical imaging with a functional hepatobiliary assessment. Hepatobiliary technetium-99m iminodiacetic acid (HIDA) scintigraphy can also provide a functional biliary assessment, but is limited by poor anatomical resolution. Both techniques can be used to evaluate the presence of a bile leak, but gadoxetic acid enhanced MRI is superior to HIDA in pinpointing the exact site of the leak. MRI also has the advantage over HIDA of being an ionising radiation-free examination.
Biliary leaks Bile leaks are an early complication (>70% occur within the first postoperative month), which predispose to biliary peritonitis and biloma formation (Figs 1e2).8 Typical leak sites include the biliary anastomosis, T-tube insertion site, cystic duct stump, and the cut surface of the liver.9,13 Bile leaks can be due to direct mechanical injury, such as excessive periductal dissection, tension on the biliary anastomosis, or electrocautery trauma.6 As, unlike the remainder of the liver, vascular supply to biliary structures is entirely arterial and can be fragile, anastomotic leaks are frequently due to hepatic artery thrombosis (HAT).14,15 Greif et al.11 reported a similar incidence of leaks and a higher incidence of strictures with biliaryeenteric reconstructions compared to duct-to-duct reconstructions, whereas Stratta et al.16 found an equivalent incidence of leaks and strictures for either reconstruction. Biliary necrosis is a severe
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complication of HAT that may affect the bile ducts diffusely and predisposes to the development of bile leaks, biliary strictures, and abscesses (Fig 3).
Biliary obstruction Biliary obstruction may be due to luminal (e.g., sludge, stones, haemobilia), mural (e.g., strictures, sphincter of Oddi dysfunction), or extraluminal (e.g., cystic duct mucocoele) aetiologies.7,9 Predisposing factors for the development of biliary sludge and calculi include biliary stasis (e.g., strictures or gallbladder conduits), supersaturation of bile (e.g., altered biliary composition due to use of cyclosporine, depletion of bile salts due to T-tube drainage), biliary epithelial damage (e.g., ischaemia), and foreign bodies (e.g., T-tubes, stents). Sludge, stones, and haemobilia appear as intraductal filling defects on imaging (Fig 4). Stones may be differentiated on ultrasound, as these are typically associated with posterior acoustic shadowing. Biliary necrosis leads to epithelial sloughing, luminal debris, and bile duct calibre irregularities. Rarely, the intraductal debris may form a cast of the biliary tree leading to biliary cast syndrome (Fig 5). This is particularly associated with prolonged graft ischaemic time and most recently with non-heartbeating donors. Haemobilia should be considered when intraductal filling detects develop acutely following liver biopsy or percutaneous intervention.
Biliary strictures Biliary strictures (typically occurring within the first postoperative year) may be classified as anastomotic or non-anastomotic (Figs 3a, 6).8,13 Anastomotic strictures are generally secondary to inadequate surgical technique leading to local ischaemia and fibrotic anastomotic narrowing.13 Focal calibre reduction at the ductal anastomosis with upstream biliary dilatation may be visualised on imaging. However, a stricture may occur without appreciable upstream biliary dilatation.8,17 Non-anastomotic strictures are most commonly a consequence of HAT (in 50%) or highgrade hepatic artery thrombosis.13,18 Another important cause of non-anastomotic strictures is ischaemic cholangiopathy (IC), a wide-spectrum pathological entity (aetiological factors include ischaemicereperfusion injury, ABO blood group incompatibility, rejection, and cytomegalovirus [CMV] infection) characterised by multifocal biliary strictures in the liver transplant, in the absence of HAT or stenosis.19 IC was initially described by Sanchez-Urdazpal et al.20 and Li et al.21 from the Mayo Clinic and the University of Nebraska, respectively. Recipients of liver grafts from non-heart-beating donors have increased susceptibility to IC due to prolonged ischaemic times leading to ischaemicereperfusion injury.22 Most cases of IC occur within the first 6 months of transplantation.19 On imaging, IC typically manifests as diffuse and multifocal strictures of the intrahepatic and extrahepatic bile ducts (intrahepatic only or extrahepatic only involvement is uncommon).19,23,24 The middle third of the common duct is reported to be most often involved followed by the hilar confluence.19
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Figure 1 Bile leak in a patient 8 days after transplantation with a cut-down liver graft (segments 2 and 3 removed). (a) A non-contrast fatsuppressed axial T1-weighted sequence demonstrates a small collection and probable haematoma adjacent to the cut edge of the graft (arrow). (b) Forty-five minutes following administration of gadoxetic acid, the bile ducts are clearly delineated and leakage of contrast medium into the lateral edge of the haematoma is visualised (arrow).
Cholangiographic abnormalities secondary to HAT or IC may appear indistinguishable on imaging. Non-anastomotic strictures may also be due to recurrence of PSC; this occurs in 20%, with a mean interval of 350 days following transplantation (Fig 7).9,25 Endoluminal balloon dilatation and stenting is the first-line treatment for anastomotic strictures.13 Non-anastomotic ischaemic-type strictures generally require surgery (e.g., conversion to a biliaryeenteric anastomosis or retransplantation).13 Rarely, surgical devascularisation/denervation of the ampulla of Vater may cause functional biliary obstruction due to sphincter of Oddi dysfunction. Imaging shows ductal dilatation down to the level of the ampulla. A mucocoele of the cystic duct remnant is a rare complication that may cause compression on the common duct. Biliary stasis from obstruction predisposes to
ascending cholangitis. This may manifest as ductal wall thickening and periductal enhancement.
Urological complications Acute renal allograft dysfunction is most commonly due to acute tubular necrosis (ATN), acute rejection, or drug toxicity.26 ATN is related to cold ischaemiaereperfusion injury and has a higher incidence in cadaveric compared to living-donor renal transplants.27,28 It occurs early in the postoperative course, and most cases show spontaneous recovery within 2e3 weeks.27,28 Acute rejection (found in 40% of cases) is a cell-mediated process and typically occurs between 1e3 weeks following transplantation.27 Nephrotoxicity is a side-effect of immunosuppressive drugs, such
Figure 2 Infected biloma in the right lobe of a living-donor liver transplant in a 31-year-old woman. (a) An axial CT image shows a right perihepatic collection (asterisks) which contains fluid and gas. Associated right basal pleural effusion. (b) A corresponding coronal image from a hepatobiliary technetium-99m iminodiacetic acid (HIDA) examination shows a bile leak (asterisks) from the cut surface of the liver that drains into a percutaneous catheter.
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Figure 3 Bilomas and multifocal non-anastomotic biliary strictures secondary to hepatic artery thrombosis in a 62-year-old male liver transplant recipient. (a) A coronal maximum intensity projection image from a magnetic resonance cholangiography examination shows two intrahepatic collections (arrow) that communicate with the biliary tree (bilomas) and multifocal strictures of the intrahepatic bile ducts and common bile duct. (b) Axial and sagittal grey-scale ultrasound images show a lentiform-shaped collection in the right hepatic lobe. This collection has thick irregular walls, echogenic internal debris, and anechoic fluid contents that give rise to posterior acoustic enhancement.
as cyclosporine and tacrolimus.27 ATN, acute rejection, and drug toxicity may share similar clinical, laboratory, and imaging findings, so biopsy is often necessary to achieve the definitive diagnosis.27,28 Patients typically present with oliguria and rising serum creatinine levels. Sonographic findings include allograft enlargement, poor corticomedullary differentiation, altered parenchymal echogenicity, renal sinus effacement, and urothelial thickening. Spectral Doppler ultrasound may show an elevated resistive index (RI) (>0.8) with or without reversed or absent
Figure 4 Anastomotic stricture and intraductal calculi in a 61-yearold woman with a right lobe liver transplant performed with a biliaryeenteric anastomosis. A coronal image from a magnetic resonance cholangiography examination demonstrates a high-grade stricture at the biliary-enteric anastomosis (arrow) associated with intrahepatic biliary dilatation. Filling defects (asterisks) in the proximal intrahepatic bile duct represents intraductal calculi.
diastolic arterial flow.27e29 Chronic rejection may occur as early as 3 months following transplantation and is associated with allograft atrophy and increased parenchymal echogenicity.27 A chronic non-functioning renal allograft may show dense calcifications.
Figure 5 Biliary cast syndrome in a liver transplant patient with a duct-to-duct anastomosis. A coronal image from a percutaneous transhepatic cholangiogram examination shows cast-like filling defects (arrows) in the intra- and extrahepatic bile ducts with associated ductal dilatation.
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Figure 6 Anastomotic biliary stricture in a 51-year-old female liver transplant recipient. A high-grade stricture (arrow) at the duct-to-duct anastomosis is shown on corresponding coronal images from a magnetic resonance cholangiography examination (a) and an endoscopic retrograde cholangiography examination (b).
Urological complications affect 4e8% of renal transplants with 75% of complications occurring within the first month.26,30 Urinary leaks and strictures typically involve the distal ureter or the ureterovesical anastomosis.26,29 These may be due to vascular insufficiency or technical problems with the surgical procedure.30,31 The transplant ureter is liable to ischaemia as it is supplied solely by the renal allograft.31 Urinary leaks predispose to urinomas and urinary ascites. A urinary leak can be detected on excretory phase contrast-enhanced computed tomography (CECT)/ CEMRI or radioisotope scintigraphy (Fig 8). Treatment options include ureteric stenting or surgery. Urinomas generally develop within the first 2 weeks following transplantation and may be associated with pain, swelling, and wound discharge. Lymphocoeles, typically occurring
Figure 7 Biopsy confirmed recurrent primary sclerosing cholangitis (PSC) in a 21-year-old male liver transplant recipient. A coronal maximum intensity projection image from a magnetic resonance cholangiography examination shows ductal changes consistent with the histological diagnosis. The right and left intrahepatic bile ducts demonstrate calibre irregularity and areas of stricturing (arrows).
1e2 months after surgery, are the most common post-renal transplant collection (15% incidence) and are caused by disrupted lymphatic channels (Fig 9).28,29,32 Large lymphocoeles may cause hydronephrosis (from urinary tract compression) and ipsilateral lower-limb oedema (from external iliac vein compression). Aspiration is not an adequate treatment as recurrence is high (80e90%).31 Treatment options include sclerotherapy, laparoscopic fenestration, or open surgery.33 Ureteric strictures are a common cause of urinary obstruction.30 Abrupt narrowing at the stricture site with upstream hydronephrosis and hydro-ureter is the typical imaging finding (Fig 10). Ureteroplasty and stent placement is the first-line treatment for ureteric strictures with surgery reserved for failed cases. Other causes of urinary obstruction include ureteral kinking, peri-graft fibrosis,
Figure 8 A 67-year-old female renal transplant recipient with a urinary leak. A coronal image of a technetium-99m mercaptoacetyltriglycine (MAG 3) examination shows a high-grade intraperitoneal urine leak (arrow) from the lower pole of the transplant.
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Figure 9 A surgically confirmed lymphocoele in a 63-year-old female renal transplant recipient. A coronal CT image shows a large lobulated perirenal lymphocoele (arrow) surrounding the renal transplant and extending cephalad into the right side of the upper abdomen. This lymphocoele recurred following catheter drainage and required surgery for definitive treatment.
blood clots, calculi, and extrinsic compression from a peritransplant collection (Figs 11e12).31 Obstruction leading to urinary stasis predisposes to urinary tract infections. Renal transplants are at increased risk for developing urinary calculi and approximately 1e2% develop a clinically significant calculus.34 These patients do not experience typical renal colic because the transplanted kidney is denervated. Vesico-ureteric reflux is a late complication occurring in one-third to half of all renal transplant recipients (Fig 13).26 Pancreas transplantation utilising the systemicebladder drainage technique exposes the bladder and urethra to exocrine pancreatic secretions. This is associated with an increased risk of urological complications, such as haematuria, urinary tract infections, chemical cystitis, urethritis, urethral stricture, and urethral perforation.35e37
Intestinal complications Intestinal complications of organ transplantation include bowel perforation or obstruction, intestinal bleeding, bowel-related infections, bowel ischaemia, and graftversus-host disease. The procedures that are most susceptible include intestinal or pancreas transplants, which involve either a duodenoenterostomy or duodenocystostomy, and liver transplants that involve a hepaticojejunostomy.18,37e40 Most bowel perforations/leaks typically occur at the enteric anastomosis and are secondary to staple-line dehiscence. Perforation secondary to ulcerations may occur anywhere within the gastrointestinal tract. CECT performed with positive oral contrast medium can
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Figure 10 A 65-year-old female renal transplant recipient with a ureteric stenosis. A coronal image from a nephrostogram examination shows a long high-grade stenosis (arrow) of the distal ureter.
confirm the presence of perforation by demonstrating pneumoperitoneum and oral contrast medium extravasation. Radiological signs that can be used to localise the perforation site include focal bowel wall thickening, a focal bowel wall defect, and bubbles of extraluminal gas in close proximity to the bowel wall. Causes of bowel obstruction include anastomotic strictures, adhesions, hernias (internal hernias, incisional hernias, stoma-related hernias, diaphragmatic hernias), and volvulus (Fig 14). On CECT, the site of obstruction is demarcated by a transition point between the dilated bowel proximally and collapsed bowel distally. Intestinal bleeding may be related to a suture line or may be secondary to mucosal inflammation and ulceration. Opportunistic intestinal infections (e.g., cytomegalovirus (CMV) enteritis, Clostridium difficile, etc.) typically present clinically with diarrhoea. Imaging findings include bowel wall thickening, peri-intestinal fat stranding, free fluid, and adenopathy. Rarely, transplants may be complicated by graft-versus-host disease with the highest incidence for intestinal transplants (5e6%) due to the large quantity of immune-related tissue in the intestines.39 Graft-versushost disease in the intestines has non-specific imaging findings, such as bowel-wall thickening, mucosal hyperenhancement, mesenteric adenopathy, and mesenteric hypervascularity.39
Neoplasms Solid-organ transplant recipients have a two-to fourfold increased risk of developing de novo malignancies when
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Figure 11 Biopsy-induced haematoma in the collecting system of a 60-year-old female renal transplant recipient. (a) A sagittal ultrasound image shows echogenic material (arrow) in the dilated collecting system representing acute haematoma. (b) A corresponding coronal image from a nephrostogram examination demonstrates the haematoma as a large filling defect (arrow) in the pelvicalyceal system. Passage of contrast medium into the bladder confirms that the haematoma is not causing complete urinary tract obstruction.
compared to the general population.41 Immunosuppression and oncogenic viruses are implicated as the major causative factors.41 The incidence of neoplasms is related to the intensity and duration of the immunosuppression. Furthermore, immunosuppression predisposes to infections by oncogenic viruses that are critical in the development of certain malignancies. These include EpsteineBarr virus (EBV; linked to post-transplant lymphoproliferative disorder), human herpes virus 8 (linked to Kaposi’s sarcoma), and human papilloma virus (linked to non-melanoma skin cancers and squamous cell cancers of the cervix, perineum, penis, and oropharynx).41 Post-transplant lymphoproliferative disorder (PTLD) is a generic term that refers to a variety of disorders ranging from abnormal lymphoid hyperplasia to frankly malignant lymphomas (predominantly B-cell).9,42 Most cases are
related to EBV infection. PTLD is the second most common post-transplant malignancy after skin cancer and affects approximately 10% of adults after solid-organ transplantation.43 Children have a higher risk of PTLD as they are more likely to be EBV-seronegative and develop PTLD as a consequence of primary EBV infection following transplantation.43 PTLD typically occurs within the first year of transplantation with an incidence of 224/100,000.44 The incidence of PTLD varies for different organ transplants according to the degree of immunosuppression required for these procedures.43 In the abdomen, the highest prevalence is recorded for multivisceral transplants (13e33% of cases), followed by intestine (7e11%), pancreas (6%), liver (2.2%), and kidney (1%) transplants.40,42,45 PTLD most commonly affects the abdomen with 80% of cases being extranodal and 20% nodal.42 The gastrointestinal tract (particularly the
Figure 12 A 62-year-old female renal transplant recipient with haematuria. (a) A coronal CT image shows a 1.8 cm calculus (arrow) in the transplant renal pelvis. (b) Corresponding coronal image from a nephrostogram examination shows that the calculus is causing complete obstruction of the collecting system.
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Figure 13 Vesico-ureteric reflux in a 23-year-old male renal transplant recipient. A coronal image from a cystogram examination shows gross contrast medium reflux into a dilated transplant collecting system. In addition, the bladder has a trabeculated outline.
distal jejunum and ileum) and the liver are the most common extranodal structures involved (Fig 15).42 Multifocal disease, diffuse hepatic infiltration, or a porta hepatis mass are manifestations of PTLD in the liver.9,42 The transplant allograft may be affected by PTLD to varying frequencies, as high as 70e75% in renal transplant recipients, with renal and peri-renal involvement, and in 10% of pancreas transplant recipients.33,46,47 Renal transplant recipients are at increased risk of renal cell carcinoma (RCC) due to the higher incidence in this population for acquired renal cystic disease associated with dialysis. Approximately 50% of chronic dialysis patients develop acquired renal cystic disease, and 9% develop tumours.48 RCC involves the native kidney in 90% of cases and the renal allograft in 10% (Fig 16).29,30 Patients with preoperative liver neoplasms (e.g., hepatocellular carcinoma, cholangiocarcinoma, metastases) may develop posttransplant recurrence with the incidence related to the preoperative tumour stage. Recurrent hepatocellular carcinoma has a 10e18% incidence and develops at a median time interval of 14e25 months following liver transplantation.49,50
Infections Immunosuppression increases the susceptibility to infections in the post-transplant period. Intestinal transplant
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Figure 14 A right diaphragmatic hernia containing bowel loops in a 12-year-old male recipient of a left lobe liver transplant. A coronal CECT image shows herniation of dilated small bowel loops (arrow) into the right hemithorax across an inadvertent surgically induced diaphragmatic defect. An ipsilateral pleural effusion is also noted.
recipients are more susceptible to infections than recipients of other forms of abdominal organ transplantation.51 This is related to the greater immunosuppression required for intestinal transplantation as well as the high native microbial load in the intestinal allograft. Standard postoperative infections predominate within the first month following transplantation.51,52 These are generally caused by bacterial pathogens, particularly Gram-negative bacilli. A variety of factors may be implicated including problems with the surgical anastomosis (e.g., leaks, strictures, obstruction, etc.), biliary necrosis, superinfection of peri-graft collections, indwelling catheters, and use of broad spectrum antibiotics (predisposing to C. difficile). Immunosuppression exerts its maximum pharmacological effects between 1e6 months post-transplant so opportunistic infections are more common during this period.52 The usual suspects include viruses such as CMV, EBV, adenovirus, and fungi, such as Pneumocystis carinii, Candida spp., and Aspergillus spp. Reactivation of hepatitis B or C may adversely affect the transplanted liver (Fig 17). The surgical procedure itself may predispose to infections. Patients with liver transplants that employ a biliaryeenteric anastomosis are at increased risk of ascending cholangitis due to reflux of intestinal contents and microbes into the bile ducts. Patients with pancreas transplants that employ systemic bladder drainage are at increased risk for urine infections due to alkalisation of the urine by exocrine pancreatic secretions. The likelihood of infections declines after the sixth post-transplant month as
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Figure 15 PTLD involving the renal transplant, liver, porta hepatis, and small bowel in a 60-year-old woman. A coronal intravenous and oral CECT image shows multi-organ PTLD manifesting as multifocal renal transplant (curved arrow), liver (stars), and portal hepatis (asterisks) hypodensities and irregular bowel wall thickening and aneurysmal dilatation (straight arrow) of a focal segment of ileum.
this coincides with the tapering of immunosuppression in patients with good allograft function.52 Special mention is made of hepatic abscesses, which occur in 1e3% of liver transplant recipients.53 The most important risk factor for this in the early post-transplant period is biliary ischaemia from hepatic artery thrombosis or stenosis. This leads to biliary necrosis, bilomas, and secondary infection culminating in abscess development. Hepatic abscesses due to biliary ischaemia can be multiple and recurrent. Another important cause of hepatic abscesses is biliary obstruction leading to bile stasis and cholangitis. On CECT/CEMRI, a hepatic abscess is generally visualised as a fluid focus with a thin hyperenhancing wall. Gas (if present) within the fluid focus is a pathognomonic finding for an abscess due to the presence of gas-forming organisms. The regional liver tissue surrounding the abscess may show hypervascularity and heterogeneity due to hyperaemia and inflammation. On ultrasound, echogenic debris is typically seen within the abscess cavity, while internal gas may be appreciated as dirty shadowing. In many institutions, radiologists play a first-line role in the treatment of abscesses by performing minimally invasive percutaneous drain placement under ultrasound or CT guidance.
Miscellaneous Right adrenal gland haemorrhage is a rare complication of liver transplantation. It may be due to venous
Figure 16 A surgically confirmed RCC involving the native left kidney in a 60-year-old male renal transplant recipient. A coronal T1weighted maximum intensity projection CEMRI image shows an exophytic, solid, enhancing mass (arrow) in the left kidney, which represents an RCC. The renal transplant (star) is noted in the right lower quadrant.
engorgement of the adrenal from adrenal vein ligation (during surgical dissection of the inferior vena cava) or may be secondary to a pre-existing coagulopathy. MRI is the test of choice given its high specificity for characterising haemorrhage. In islet transplantation, a benign peri-portal granular pattern of hepatic steatosis may occur as a result of insulin secretion by functioning islets in the liver.54 Islet transplantation also predisposes to the development of
Figure 17 Multifocal splenic abscesses in a 60-year-old man with biopsy-confirmed recurrent hepatitis C virus (HCV) in the liver transplant. A coronal CECT image shows several ill-defined splenic hypodensities (stars) that represent abscesses. Although the liver biopsy confirmed HCV recurrence, the liver appeared grossly unremarkable on imaging.
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Figure 18 A haemorrhagic ovarian cyst in a 32-year-old female islet transplant recipient on sirolimus immunosuppression. A sagittal fatsuppressed T1-weighted MRI image shows a high signal intensity cystic lesion (arrow) consistent with a large haemorrhagic ovarian cyst.
large ovarian cysts (median size of 6 cm) in 70% of premenopausal women due to sirolimus immunosuppression, which inhibits cyst rupture (Fig 18).54
Conclusion Extravascular complications following abdominal transplantation include biliary, urological, intestinal, neoplasms, infection, and miscellaneous issues. Clinical and laboratory information is often non-specific and sometimes unhelpful in the post-transplant period; hence, the need for imaging to accurately detect post-transplant complications. Furthermore, therapeutic image-guided interventions can often be graft-saving and life-saving. Radiologists need to be familiar with the imaging appearances of these extravascular complications as accurate diagnosis and prompt treatment has an impact on graft and patient survival.
References 1. Low G, Crockett AM, Leung K, et al. Imaging of vascular complications and their consequences following transplantation in the abdomen. RadioGraphics 2013;33:633e52. 2. Granata A, Floccari F, Lentini P, et al. Vascular complications following kidney transplant: the role of color-Doppler imaging. G Ital Nefrol 2012;29(Suppl. 57):S99e105. 3. Norton PT, DeAngelis GA, Ogur T, et al. Noninvasive vascular imaging in abdominal solid organ transplantation. AJR Am J Roentgenol 2013;201:W544e53. 4. Khaja MS, Matsumoto AH, Saad WE. Vascular complications of transplantation. Part 2: pancreatic transplants. Cardiovasc Interv Radiol 2014. 5. Khaja MS, Matsumoto AH, Saad WE. Complications of transplantation. Part 1: renal transplants. Cardiovasc Interv Radiol 2014;37:1137e48. 6. Thuluvath PJ, Pfau PR, Kimmey MB, et al. Biliary complications after liver transplantation: the role of endoscopy. Endoscopy 2005;37:857e63.
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7. Girometti R, Cereser L, Bazzocchi M, et al. Magnetic resonance cholangiography in the assessment and management of biliary complications after OLT. World J Radiol 2014;6:424e36. 8. Meng XC, Huang WS, Xie PY, et al. Role of multi-detector computed tomography for biliary complications after liver transplantation. World J Gastroenterol 2014;20:11856e64. 9. Itri JN, Heller MT, Tublin ME. Hepatic transplantation: postoperative complications. Abdomin Imaging 2013;38:1300e33. 10. Dani G, Sun MR, Bennett AE. Imaging of liver transplant and its complications. Semin Ultrasound CT MRI 2013;34:365e77. 11. Greif F, Bronsther OL, Van Thiel DH, et al. The incidence, timing, and management of biliary tract complications after orthotopic liver transplantation. Ann Surg 1994;219:40e5. 12. Valls C, Alba E, Cruz M, et al. Biliary complications after liver transplantation: diagnosis with MR cholangiopancreatography. AJR Am J Roentgenol 2005;184:812e20. 13. Karimian N, Westerkamp AC, Porte RJ. Biliary complications after orthotopic liver transplantation. Curr Opin Organ Transplant 2014;19:209e16. 14. Northover JM, Terblanche J. A new look at the arterial supply of the bile duct in man and its surgical implications. Br J Surg 1979;66:379e84. 15. Gunji H, Cho A, Tohma T, et al. The blood supply of the hilar bile duct and its relationship to the communicating arcade located between the right and left hepatic arteries. Am J Surg 2006;192:276e80. 16. Stratta RJ, Wood RP, Langnas AN, et al. Diagnosis and treatment of biliary tract complications after orthotopic liver transplantation. Surgery 1989;106:675e83. discussion 83e4. 17. St Peter S, Rodriquez-Davalos MI, Rodriguez-Luna HM, et al. Significance of proximal biliary dilatation in patients with anastomotic strictures after liver transplantation. Dig Dis Sci 2004;49:1207e11. 18. Pascher A, Neuhaus P. Bile duct complications after liver transplantation. Transpl Int 2005;18:627e42. 19. Mourad MM, Algarni A, Liossis C, et al. Aetiology and risk factors of ischaemic cholangiopathy after liver transplantation. World J Gastroenterol 2014;20:6159e69. 20. Sanchez-Urdazpal L, Gores GJ, Ward EM, et al. Ischemic-type biliary complications after orthotopic liver transplantation. Hepatology 1992;16:49e53. 21. Li S, Stratta RJ, Langnas AN, et al. Diffuse biliary tract injury after orthotopic liver transplantation. Am J Surg 1992;164:536e40. 22. Chan EY, Olson LC, Kisthard JA, et al. Ischemic cholangiopathy following liver transplantation from donation after cardiac death donors. Liver Transplant 2008;14:604e10. 23. Fisher A, Miller CH. Ischemic-type biliary strictures in liver allografts: the Achilles heel revisited? Hepatology 1995;21:589e91. 24. Guichelaar MM, Benson JT, Malinchoc M, et al. Risk factors for and clinical course of non-anastomotic biliary strictures after liver transplantation. Am J Transplant 2003;3:885e90. 25. Gow PJ, Chapman RW. Liver transplantation for primary sclerosing cholangitis. Liver 2000;20:97e103. 26. Nixon JN, Biyyam DR, Stanescu L, et al. Imaging of pediatric renal transplants and their complications: a pictorial review. RadioGraphics 2013;33:1227e51. 27. Langer JEJL. Sonographic evaluation of the renal transplant. Ultrasound Clin 2007;2:73e88. 28. Brown ED, Chen MY, Wolfman NT, et al. Complications of renal transplantation: evaluation with US and radionuclide imaging. RadioGraphics 2000;20:607e22. 29. Weber TM, Lockhart ME. Renal transplant complications. Abdominal Imaging 2013;38:1144e54. 30. Akbar SA, Jafri SZ, Amendola MA, et al. Complications of renal transplantation. RadioGraphics 2005;25:1335e56. 31. Kobayashi K, Censullo ML, Rossman LL, et al. Interventional radiologic management of renal transplant dysfunction: indications, limitations, and technical considerations. RadioGraphics 2007;27:1109e30. 32. Sebastia C, Quiroga S, Boye R, et al. Helical CT in renal transplantation: normal findings and early and late complications. RadioGraphics 2001;21:1103e17. 33. Lucewicz A, Wong G, Lam VW, et al. Management of primary symptomatic lymphocele after kidney transplantation: a systematic review. Transplantation 2011;92:663e73.
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34. Kim H, Cheigh JS, Ham HW. Urinary stones following renal transplantation. Korean J Intern Med 2001;16:118e22. 35. Torigian DA, Banner MP, Ramchandani P. Imaging urologic complications of pancreas transplantation with bladder drainage. Clin Imaging 2000;24:132e8. 36. Boggi U, Amorese G, Marchetti P. Surgical techniques for pancreas transplantation. Curr Opin Organ Transplant 2010;15:102e11. 37. Dillman JR, Elsayes KM, Bude RO, et al. Imaging of pancreas transplants: postoperative findings with clinical correlation. J Comput Assist Tomogr 2009;33:609e17. 38. Phillips GS, Bhargava P, Stanescu L, et al. Pediatric intestinal transplantation: normal radiographic appearance and complications. Pediatr Radiol 2011;41:1028e39. 39. Sandrasegaran K, Lall C, Ramaswamy R, et al. Intestinal and multivisceral transplantation. Abdomin Imaging 2011;36:382e9. 40. Vandermeer FQ, Manning MA, Frazier AA, et al. Imaging of whole-organ pancreas transplants. RadioGraphics 2012;32:411e35. 41. Engels EA, Pfeiffer RM, Fraumeni Jr JF, et al. Spectrum of cancer risk among US solid organ transplant recipients. JAMA 2011;306:1891e901. 42. Borhani AA, Hosseinzadeh K, Almusa O, et al. Imaging of posttransplantation lymphoproliferative disorder after solid organ transplantation. RadioGraphics 2009;29:981e1000. discussion -2. 43. LaCasce AS. Post-transplant lymphoproliferative disorders. Oncologist 2006;11:674e80. 44. Opelz G, Dohler B. Lymphomas after solid organ transplantation: a collaborative transplant study report. Am J Transplant 2004;4:222e30.
45. Cockfield SM. Identifying the patient at risk for post-transplant lymphoproliferative disorder. Transplant Infect Dis 2001;3:70e8. 46. Kew 2nd CE, Lopez-Ben R, Smith JK, et al. Postransplant lymphoproliferative disorder localized near the allograft in renal transplantation. Transplantation 2000;69:809e14. 47. Lopez-Ben R, Smith JK, Kew 2nd CE, et al. Focal posttransplantation lymphoproliferative disorder at the renal allograft hilum. AJR Am J Roentgenol 2000;175:1417e22. 48. Bretan Jr PN, Busch MP, Hricak H, et al. Chronic renal failure: a significant risk factor in the development of acquired renal cysts and renal cell carcinoma. Case reports and review of the literature. Cancer 1986;57:1871e9. 49. Sharma P, Welch K, Hussain H, et al. Incidence and risk factors of hepatocellular carcinoma recurrence after liver transplantation in the MELD era. Dig Dis Sci 2012;57:806e12. 50. Nissen NN, Menon V, Bresee C, et al. Recurrent hepatocellular carcinoma after liver transplant: identifying the high-risk patient. HPB (Oxford) 2011;13:626e32. 51. Fryer JP. Intestinal transplantation: current status. Gastroenterol Clin N Am 2007;36. 145e59, vii. 52. Fishman JA. Infection in solid-organ transplant recipients. N Engl J Med 2007;357:2601e14. 53. Camacho JC, Coursey-Moreno C, Telleria JC, et al. Nonvascular post-liver transplantation complications: from US screening to cross-sectional and interventional imaging. RadioGraphics 2015;35:87e104. 54. Low G, Hussein N, Owen RJ, et al. Role of imaging in clinical islet transplantation. RadioGraphics 2010;30:353e66.
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Pictorial Review
Extravascular complications following abdominal organ transplantation G. Low a, b, *, J.L. Jaremko a, D.J. Lomas b a b
Department of Radiology & Diagnostic Imaging, University of Alberta Hospital, Edmonton, Alberta, Canada Department of Radiology, Addenbrooke’s Hospital, Cambridge University Hospitals NHS Trust, England, UK
article in formation Article history: Received 15 December 2014 Received in revised form 3 March 2015 Accepted 9 April 2015
A variety of transplants have been performed in the abdomen including liver, kidney, pancreas and islet, bowel, and multivisceral transplants. Imaging plays an important role in graft surveillance particularly to exclude post-transplant complications. When complications occur, therapeutic image-guided interventions are invaluable as these may be graft-saving and even life-saving. Vascular complications following transplantation have been extensively reported in recent reviews. The focus of this review is to discuss post-transplant complications that are primarily extravascular in location. This includes biliary, urological, intestinal, malignancy, infections, and miscellaneous complications. Familiarity with the imaging appearances of these complications is helpful for radiologists as accurate diagnosis and expedient treatment has an impact on graft and patient survival. Ó 2015 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
Introduction Transplantation is the most effective treatment for endstage organ dysfunction. Grafts used in the abdomen include liver, kidney, pancreas and islet, bowel, and multivisceral transplants. Imaging has a limited role in detecting graft rejection. Its main function is for detecting complications other than rejection, which may present with similar clinical and laboratory findings. When complications occur, therapeutic image-guided interventions may be graftsaving and even life-saving. Vascular complications following abdominal transplantation have been extensively reviewed in several recent reports.1e5 The focus of this
* Guarantor and correspondent: G. Low, Department of Radiology & Diagnostic Imaging, University of Alberta Hospital, 2A2.41 WMC, 8440-112 Street, Edmonton, Alberta, T6G 2B7, Canada. Tel.: þ1 780 407 6907; fax: þ1 780 407 3853. E-mail address: [email protected] (G. Low).
review is to discuss complications following abdominal transplantation that are primarily extravascular in location.
Biliary complications Biliary-related issues are the second most common complication (10e34% incidence) in liver transplant recipients after rejection.6e10 The risk is highest for livingdonor and split transplants, which utilise complex and small-calibre biliary anastomoses. A study of 1792 liver transplant recipients found that the incidence of biliary complications was 38% at 1 month, 28% at 3 months, 15% at 6 months, and 8% after 12 months.11 These complications included biliary strictures (43%), leaks (27%), obstruction (14%), and ampullary dysfunction (17%).11 Magnetic resonance cholangiopancreatography (MRCP) is the imaging test of choice with 95% sensitivity for post-transplant biliary complications.7,10,12 MRCP is often combined with a multiphasic contrast-enhanced magnetic resonance imaging (CEMRI) examination to provide a comprehensive
http://dx.doi.org/10.1016/j.crad.2015.04.001 0009-9260/Ó 2015 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
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evaluation of the liver transplant. The adoption of modern bolus-tracking techniques, state-of-the-art ultrafast pulse sequences, and sophisticated parallel imaging methods allow the acquisition of high spatial and temporal resolution MRI images on a consistent basis. Cholangitis may be recognised as focal or generalised periductal enhancement (most appreciable on the portal phase) with or without ductal wall thickening. A high-quality MR angiogram can be produced to rule out hepatic artery thrombosis or stenosis. These images are displayed on the MRI workstation using multiplanar, volume-rendered or maximum intensity projection formats for optimal image analysis and can help to road map vascular interventions. Testament to the diagnostic capabilities of MRI, nowadays invasive procedures such as endoscopic retrograde cholangiopancreatography (ERCP) and percutaneous transhepatic cholangiography (PTC) are generally reserved for therapeutic manoeuvres. Contrast-enhanced (CE) MRI cholangiography utilising biliary excretory contrast agents, such as gadoxetic acid disodium (Bayer Healthcare, Leverkusen, Germany), is an alternative to MRCP, which can improve biliary visualisation and is particularly useful for the detection of bile leaks.7 Compared with standard gadolinium agents, gadoxetic acid has a dual contrast property, which expands its clinical applicability. Early on, it behaves as an extracellular agent providing dynamic morphologic evaluation of the graft parenchyma and relevant arterial and venous anastomoses. During the hepatospecific phase, at 20 minutes or later, the liver shows contrast medium uptake (due to organic anion transporting polypeptides [OATPs] on the cell membranes of hepatocytes) followed by biliary excretion of the gadoxetic acid. This combines high-quality anatomical imaging with a functional hepatobiliary assessment. Hepatobiliary technetium-99m iminodiacetic acid (HIDA) scintigraphy can also provide a functional biliary assessment, but is limited by poor anatomical resolution. Both techniques can be used to evaluate the presence of a bile leak, but gadoxetic acid enhanced MRI is superior to HIDA in pinpointing the exact site of the leak. MRI also has the advantage over HIDA of being an ionising radiation-free examination.
Biliary leaks Bile leaks are an early complication (>70% occur within the first postoperative month), which predispose to biliary peritonitis and biloma formation (Figs 1e2).8 Typical leak sites include the biliary anastomosis, T-tube insertion site, cystic duct stump, and the cut surface of the liver.9,13 Bile leaks can be due to direct mechanical injury, such as excessive periductal dissection, tension on the biliary anastomosis, or electrocautery trauma.6 As, unlike the remainder of the liver, vascular supply to biliary structures is entirely arterial and can be fragile, anastomotic leaks are frequently due to hepatic artery thrombosis (HAT).14,15 Greif et al.11 reported a similar incidence of leaks and a higher incidence of strictures with biliaryeenteric reconstructions compared to duct-to-duct reconstructions, whereas Stratta et al.16 found an equivalent incidence of leaks and strictures for either reconstruction. Biliary necrosis is a severe
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complication of HAT that may affect the bile ducts diffusely and predisposes to the development of bile leaks, biliary strictures, and abscesses (Fig 3).
Biliary obstruction Biliary obstruction may be due to luminal (e.g., sludge, stones, haemobilia), mural (e.g., strictures, sphincter of Oddi dysfunction), or extraluminal (e.g., cystic duct mucocoele) aetiologies.7,9 Predisposing factors for the development of biliary sludge and calculi include biliary stasis (e.g., strictures or gallbladder conduits), supersaturation of bile (e.g., altered biliary composition due to use of cyclosporine, depletion of bile salts due to T-tube drainage), biliary epithelial damage (e.g., ischaemia), and foreign bodies (e.g., T-tubes, stents). Sludge, stones, and haemobilia appear as intraductal filling defects on imaging (Fig 4). Stones may be differentiated on ultrasound, as these are typically associated with posterior acoustic shadowing. Biliary necrosis leads to epithelial sloughing, luminal debris, and bile duct calibre irregularities. Rarely, the intraductal debris may form a cast of the biliary tree leading to biliary cast syndrome (Fig 5). This is particularly associated with prolonged graft ischaemic time and most recently with non-heartbeating donors. Haemobilia should be considered when intraductal filling detects develop acutely following liver biopsy or percutaneous intervention.
Biliary strictures Biliary strictures (typically occurring within the first postoperative year) may be classified as anastomotic or non-anastomotic (Figs 3a, 6).8,13 Anastomotic strictures are generally secondary to inadequate surgical technique leading to local ischaemia and fibrotic anastomotic narrowing.13 Focal calibre reduction at the ductal anastomosis with upstream biliary dilatation may be visualised on imaging. However, a stricture may occur without appreciable upstream biliary dilatation.8,17 Non-anastomotic strictures are most commonly a consequence of HAT (in 50%) or highgrade hepatic artery thrombosis.13,18 Another important cause of non-anastomotic strictures is ischaemic cholangiopathy (IC), a wide-spectrum pathological entity (aetiological factors include ischaemicereperfusion injury, ABO blood group incompatibility, rejection, and cytomegalovirus [CMV] infection) characterised by multifocal biliary strictures in the liver transplant, in the absence of HAT or stenosis.19 IC was initially described by Sanchez-Urdazpal et al.20 and Li et al.21 from the Mayo Clinic and the University of Nebraska, respectively. Recipients of liver grafts from non-heart-beating donors have increased susceptibility to IC due to prolonged ischaemic times leading to ischaemicereperfusion injury.22 Most cases of IC occur within the first 6 months of transplantation.19 On imaging, IC typically manifests as diffuse and multifocal strictures of the intrahepatic and extrahepatic bile ducts (intrahepatic only or extrahepatic only involvement is uncommon).19,23,24 The middle third of the common duct is reported to be most often involved followed by the hilar confluence.19
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Figure 1 Bile leak in a patient 8 days after transplantation with a cut-down liver graft (segments 2 and 3 removed). (a) A non-contrast fatsuppressed axial T1-weighted sequence demonstrates a small collection and probable haematoma adjacent to the cut edge of the graft (arrow). (b) Forty-five minutes following administration of gadoxetic acid, the bile ducts are clearly delineated and leakage of contrast medium into the lateral edge of the haematoma is visualised (arrow).
Cholangiographic abnormalities secondary to HAT or IC may appear indistinguishable on imaging. Non-anastomotic strictures may also be due to recurrence of PSC; this occurs in 20%, with a mean interval of 350 days following transplantation (Fig 7).9,25 Endoluminal balloon dilatation and stenting is the first-line treatment for anastomotic strictures.13 Non-anastomotic ischaemic-type strictures generally require surgery (e.g., conversion to a biliaryeenteric anastomosis or retransplantation).13 Rarely, surgical devascularisation/denervation of the ampulla of Vater may cause functional biliary obstruction due to sphincter of Oddi dysfunction. Imaging shows ductal dilatation down to the level of the ampulla. A mucocoele of the cystic duct remnant is a rare complication that may cause compression on the common duct. Biliary stasis from obstruction predisposes to
ascending cholangitis. This may manifest as ductal wall thickening and periductal enhancement.
Urological complications Acute renal allograft dysfunction is most commonly due to acute tubular necrosis (ATN), acute rejection, or drug toxicity.26 ATN is related to cold ischaemiaereperfusion injury and has a higher incidence in cadaveric compared to living-donor renal transplants.27,28 It occurs early in the postoperative course, and most cases show spontaneous recovery within 2e3 weeks.27,28 Acute rejection (found in 40% of cases) is a cell-mediated process and typically occurs between 1e3 weeks following transplantation.27 Nephrotoxicity is a side-effect of immunosuppressive drugs, such
Figure 2 Infected biloma in the right lobe of a living-donor liver transplant in a 31-year-old woman. (a) An axial CT image shows a right perihepatic collection (asterisks) which contains fluid and gas. Associated right basal pleural effusion. (b) A corresponding coronal image from a hepatobiliary technetium-99m iminodiacetic acid (HIDA) examination shows a bile leak (asterisks) from the cut surface of the liver that drains into a percutaneous catheter.
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Figure 3 Bilomas and multifocal non-anastomotic biliary strictures secondary to hepatic artery thrombosis in a 62-year-old male liver transplant recipient. (a) A coronal maximum intensity projection image from a magnetic resonance cholangiography examination shows two intrahepatic collections (arrow) that communicate with the biliary tree (bilomas) and multifocal strictures of the intrahepatic bile ducts and common bile duct. (b) Axial and sagittal grey-scale ultrasound images show a lentiform-shaped collection in the right hepatic lobe. This collection has thick irregular walls, echogenic internal debris, and anechoic fluid contents that give rise to posterior acoustic enhancement.
as cyclosporine and tacrolimus.27 ATN, acute rejection, and drug toxicity may share similar clinical, laboratory, and imaging findings, so biopsy is often necessary to achieve the definitive diagnosis.27,28 Patients typically present with oliguria and rising serum creatinine levels. Sonographic findings include allograft enlargement, poor corticomedullary differentiation, altered parenchymal echogenicity, renal sinus effacement, and urothelial thickening. Spectral Doppler ultrasound may show an elevated resistive index (RI) (>0.8) with or without reversed or absent
Figure 4 Anastomotic stricture and intraductal calculi in a 61-yearold woman with a right lobe liver transplant performed with a biliaryeenteric anastomosis. A coronal image from a magnetic resonance cholangiography examination demonstrates a high-grade stricture at the biliary-enteric anastomosis (arrow) associated with intrahepatic biliary dilatation. Filling defects (asterisks) in the proximal intrahepatic bile duct represents intraductal calculi.
diastolic arterial flow.27e29 Chronic rejection may occur as early as 3 months following transplantation and is associated with allograft atrophy and increased parenchymal echogenicity.27 A chronic non-functioning renal allograft may show dense calcifications.
Figure 5 Biliary cast syndrome in a liver transplant patient with a duct-to-duct anastomosis. A coronal image from a percutaneous transhepatic cholangiogram examination shows cast-like filling defects (arrows) in the intra- and extrahepatic bile ducts with associated ductal dilatation.
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Figure 6 Anastomotic biliary stricture in a 51-year-old female liver transplant recipient. A high-grade stricture (arrow) at the duct-to-duct anastomosis is shown on corresponding coronal images from a magnetic resonance cholangiography examination (a) and an endoscopic retrograde cholangiography examination (b).
Urological complications affect 4e8% of renal transplants with 75% of complications occurring within the first month.26,30 Urinary leaks and strictures typically involve the distal ureter or the ureterovesical anastomosis.26,29 These may be due to vascular insufficiency or technical problems with the surgical procedure.30,31 The transplant ureter is liable to ischaemia as it is supplied solely by the renal allograft.31 Urinary leaks predispose to urinomas and urinary ascites. A urinary leak can be detected on excretory phase contrast-enhanced computed tomography (CECT)/ CEMRI or radioisotope scintigraphy (Fig 8). Treatment options include ureteric stenting or surgery. Urinomas generally develop within the first 2 weeks following transplantation and may be associated with pain, swelling, and wound discharge. Lymphocoeles, typically occurring
Figure 7 Biopsy confirmed recurrent primary sclerosing cholangitis (PSC) in a 21-year-old male liver transplant recipient. A coronal maximum intensity projection image from a magnetic resonance cholangiography examination shows ductal changes consistent with the histological diagnosis. The right and left intrahepatic bile ducts demonstrate calibre irregularity and areas of stricturing (arrows).
1e2 months after surgery, are the most common post-renal transplant collection (15% incidence) and are caused by disrupted lymphatic channels (Fig 9).28,29,32 Large lymphocoeles may cause hydronephrosis (from urinary tract compression) and ipsilateral lower-limb oedema (from external iliac vein compression). Aspiration is not an adequate treatment as recurrence is high (80e90%).31 Treatment options include sclerotherapy, laparoscopic fenestration, or open surgery.33 Ureteric strictures are a common cause of urinary obstruction.30 Abrupt narrowing at the stricture site with upstream hydronephrosis and hydro-ureter is the typical imaging finding (Fig 10). Ureteroplasty and stent placement is the first-line treatment for ureteric strictures with surgery reserved for failed cases. Other causes of urinary obstruction include ureteral kinking, peri-graft fibrosis,
Figure 8 A 67-year-old female renal transplant recipient with a urinary leak. A coronal image of a technetium-99m mercaptoacetyltriglycine (MAG 3) examination shows a high-grade intraperitoneal urine leak (arrow) from the lower pole of the transplant.
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Figure 9 A surgically confirmed lymphocoele in a 63-year-old female renal transplant recipient. A coronal CT image shows a large lobulated perirenal lymphocoele (arrow) surrounding the renal transplant and extending cephalad into the right side of the upper abdomen. This lymphocoele recurred following catheter drainage and required surgery for definitive treatment.
blood clots, calculi, and extrinsic compression from a peritransplant collection (Figs 11e12).31 Obstruction leading to urinary stasis predisposes to urinary tract infections. Renal transplants are at increased risk for developing urinary calculi and approximately 1e2% develop a clinically significant calculus.34 These patients do not experience typical renal colic because the transplanted kidney is denervated. Vesico-ureteric reflux is a late complication occurring in one-third to half of all renal transplant recipients (Fig 13).26 Pancreas transplantation utilising the systemicebladder drainage technique exposes the bladder and urethra to exocrine pancreatic secretions. This is associated with an increased risk of urological complications, such as haematuria, urinary tract infections, chemical cystitis, urethritis, urethral stricture, and urethral perforation.35e37
Intestinal complications Intestinal complications of organ transplantation include bowel perforation or obstruction, intestinal bleeding, bowel-related infections, bowel ischaemia, and graftversus-host disease. The procedures that are most susceptible include intestinal or pancreas transplants, which involve either a duodenoenterostomy or duodenocystostomy, and liver transplants that involve a hepaticojejunostomy.18,37e40 Most bowel perforations/leaks typically occur at the enteric anastomosis and are secondary to staple-line dehiscence. Perforation secondary to ulcerations may occur anywhere within the gastrointestinal tract. CECT performed with positive oral contrast medium can
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Figure 10 A 65-year-old female renal transplant recipient with a ureteric stenosis. A coronal image from a nephrostogram examination shows a long high-grade stenosis (arrow) of the distal ureter.
confirm the presence of perforation by demonstrating pneumoperitoneum and oral contrast medium extravasation. Radiological signs that can be used to localise the perforation site include focal bowel wall thickening, a focal bowel wall defect, and bubbles of extraluminal gas in close proximity to the bowel wall. Causes of bowel obstruction include anastomotic strictures, adhesions, hernias (internal hernias, incisional hernias, stoma-related hernias, diaphragmatic hernias), and volvulus (Fig 14). On CECT, the site of obstruction is demarcated by a transition point between the dilated bowel proximally and collapsed bowel distally. Intestinal bleeding may be related to a suture line or may be secondary to mucosal inflammation and ulceration. Opportunistic intestinal infections (e.g., cytomegalovirus (CMV) enteritis, Clostridium difficile, etc.) typically present clinically with diarrhoea. Imaging findings include bowel wall thickening, peri-intestinal fat stranding, free fluid, and adenopathy. Rarely, transplants may be complicated by graft-versus-host disease with the highest incidence for intestinal transplants (5e6%) due to the large quantity of immune-related tissue in the intestines.39 Graft-versushost disease in the intestines has non-specific imaging findings, such as bowel-wall thickening, mucosal hyperenhancement, mesenteric adenopathy, and mesenteric hypervascularity.39
Neoplasms Solid-organ transplant recipients have a two-to fourfold increased risk of developing de novo malignancies when
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Figure 11 Biopsy-induced haematoma in the collecting system of a 60-year-old female renal transplant recipient. (a) A sagittal ultrasound image shows echogenic material (arrow) in the dilated collecting system representing acute haematoma. (b) A corresponding coronal image from a nephrostogram examination demonstrates the haematoma as a large filling defect (arrow) in the pelvicalyceal system. Passage of contrast medium into the bladder confirms that the haematoma is not causing complete urinary tract obstruction.
compared to the general population.41 Immunosuppression and oncogenic viruses are implicated as the major causative factors.41 The incidence of neoplasms is related to the intensity and duration of the immunosuppression. Furthermore, immunosuppression predisposes to infections by oncogenic viruses that are critical in the development of certain malignancies. These include EpsteineBarr virus (EBV; linked to post-transplant lymphoproliferative disorder), human herpes virus 8 (linked to Kaposi’s sarcoma), and human papilloma virus (linked to non-melanoma skin cancers and squamous cell cancers of the cervix, perineum, penis, and oropharynx).41 Post-transplant lymphoproliferative disorder (PTLD) is a generic term that refers to a variety of disorders ranging from abnormal lymphoid hyperplasia to frankly malignant lymphomas (predominantly B-cell).9,42 Most cases are
related to EBV infection. PTLD is the second most common post-transplant malignancy after skin cancer and affects approximately 10% of adults after solid-organ transplantation.43 Children have a higher risk of PTLD as they are more likely to be EBV-seronegative and develop PTLD as a consequence of primary EBV infection following transplantation.43 PTLD typically occurs within the first year of transplantation with an incidence of 224/100,000.44 The incidence of PTLD varies for different organ transplants according to the degree of immunosuppression required for these procedures.43 In the abdomen, the highest prevalence is recorded for multivisceral transplants (13e33% of cases), followed by intestine (7e11%), pancreas (6%), liver (2.2%), and kidney (1%) transplants.40,42,45 PTLD most commonly affects the abdomen with 80% of cases being extranodal and 20% nodal.42 The gastrointestinal tract (particularly the
Figure 12 A 62-year-old female renal transplant recipient with haematuria. (a) A coronal CT image shows a 1.8 cm calculus (arrow) in the transplant renal pelvis. (b) Corresponding coronal image from a nephrostogram examination shows that the calculus is causing complete obstruction of the collecting system.
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Figure 13 Vesico-ureteric reflux in a 23-year-old male renal transplant recipient. A coronal image from a cystogram examination shows gross contrast medium reflux into a dilated transplant collecting system. In addition, the bladder has a trabeculated outline.
distal jejunum and ileum) and the liver are the most common extranodal structures involved (Fig 15).42 Multifocal disease, diffuse hepatic infiltration, or a porta hepatis mass are manifestations of PTLD in the liver.9,42 The transplant allograft may be affected by PTLD to varying frequencies, as high as 70e75% in renal transplant recipients, with renal and peri-renal involvement, and in 10% of pancreas transplant recipients.33,46,47 Renal transplant recipients are at increased risk of renal cell carcinoma (RCC) due to the higher incidence in this population for acquired renal cystic disease associated with dialysis. Approximately 50% of chronic dialysis patients develop acquired renal cystic disease, and 9% develop tumours.48 RCC involves the native kidney in 90% of cases and the renal allograft in 10% (Fig 16).29,30 Patients with preoperative liver neoplasms (e.g., hepatocellular carcinoma, cholangiocarcinoma, metastases) may develop posttransplant recurrence with the incidence related to the preoperative tumour stage. Recurrent hepatocellular carcinoma has a 10e18% incidence and develops at a median time interval of 14e25 months following liver transplantation.49,50
Infections Immunosuppression increases the susceptibility to infections in the post-transplant period. Intestinal transplant
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Figure 14 A right diaphragmatic hernia containing bowel loops in a 12-year-old male recipient of a left lobe liver transplant. A coronal CECT image shows herniation of dilated small bowel loops (arrow) into the right hemithorax across an inadvertent surgically induced diaphragmatic defect. An ipsilateral pleural effusion is also noted.
recipients are more susceptible to infections than recipients of other forms of abdominal organ transplantation.51 This is related to the greater immunosuppression required for intestinal transplantation as well as the high native microbial load in the intestinal allograft. Standard postoperative infections predominate within the first month following transplantation.51,52 These are generally caused by bacterial pathogens, particularly Gram-negative bacilli. A variety of factors may be implicated including problems with the surgical anastomosis (e.g., leaks, strictures, obstruction, etc.), biliary necrosis, superinfection of peri-graft collections, indwelling catheters, and use of broad spectrum antibiotics (predisposing to C. difficile). Immunosuppression exerts its maximum pharmacological effects between 1e6 months post-transplant so opportunistic infections are more common during this period.52 The usual suspects include viruses such as CMV, EBV, adenovirus, and fungi, such as Pneumocystis carinii, Candida spp., and Aspergillus spp. Reactivation of hepatitis B or C may adversely affect the transplanted liver (Fig 17). The surgical procedure itself may predispose to infections. Patients with liver transplants that employ a biliaryeenteric anastomosis are at increased risk of ascending cholangitis due to reflux of intestinal contents and microbes into the bile ducts. Patients with pancreas transplants that employ systemic bladder drainage are at increased risk for urine infections due to alkalisation of the urine by exocrine pancreatic secretions. The likelihood of infections declines after the sixth post-transplant month as
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Figure 15 PTLD involving the renal transplant, liver, porta hepatis, and small bowel in a 60-year-old woman. A coronal intravenous and oral CECT image shows multi-organ PTLD manifesting as multifocal renal transplant (curved arrow), liver (stars), and portal hepatis (asterisks) hypodensities and irregular bowel wall thickening and aneurysmal dilatation (straight arrow) of a focal segment of ileum.
this coincides with the tapering of immunosuppression in patients with good allograft function.52 Special mention is made of hepatic abscesses, which occur in 1e3% of liver transplant recipients.53 The most important risk factor for this in the early post-transplant period is biliary ischaemia from hepatic artery thrombosis or stenosis. This leads to biliary necrosis, bilomas, and secondary infection culminating in abscess development. Hepatic abscesses due to biliary ischaemia can be multiple and recurrent. Another important cause of hepatic abscesses is biliary obstruction leading to bile stasis and cholangitis. On CECT/CEMRI, a hepatic abscess is generally visualised as a fluid focus with a thin hyperenhancing wall. Gas (if present) within the fluid focus is a pathognomonic finding for an abscess due to the presence of gas-forming organisms. The regional liver tissue surrounding the abscess may show hypervascularity and heterogeneity due to hyperaemia and inflammation. On ultrasound, echogenic debris is typically seen within the abscess cavity, while internal gas may be appreciated as dirty shadowing. In many institutions, radiologists play a first-line role in the treatment of abscesses by performing minimally invasive percutaneous drain placement under ultrasound or CT guidance.
Miscellaneous Right adrenal gland haemorrhage is a rare complication of liver transplantation. It may be due to venous
Figure 16 A surgically confirmed RCC involving the native left kidney in a 60-year-old male renal transplant recipient. A coronal T1weighted maximum intensity projection CEMRI image shows an exophytic, solid, enhancing mass (arrow) in the left kidney, which represents an RCC. The renal transplant (star) is noted in the right lower quadrant.
engorgement of the adrenal from adrenal vein ligation (during surgical dissection of the inferior vena cava) or may be secondary to a pre-existing coagulopathy. MRI is the test of choice given its high specificity for characterising haemorrhage. In islet transplantation, a benign peri-portal granular pattern of hepatic steatosis may occur as a result of insulin secretion by functioning islets in the liver.54 Islet transplantation also predisposes to the development of
Figure 17 Multifocal splenic abscesses in a 60-year-old man with biopsy-confirmed recurrent hepatitis C virus (HCV) in the liver transplant. A coronal CECT image shows several ill-defined splenic hypodensities (stars) that represent abscesses. Although the liver biopsy confirmed HCV recurrence, the liver appeared grossly unremarkable on imaging.
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Figure 18 A haemorrhagic ovarian cyst in a 32-year-old female islet transplant recipient on sirolimus immunosuppression. A sagittal fatsuppressed T1-weighted MRI image shows a high signal intensity cystic lesion (arrow) consistent with a large haemorrhagic ovarian cyst.
large ovarian cysts (median size of 6 cm) in 70% of premenopausal women due to sirolimus immunosuppression, which inhibits cyst rupture (Fig 18).54
Conclusion Extravascular complications following abdominal transplantation include biliary, urological, intestinal, neoplasms, infection, and miscellaneous issues. Clinical and laboratory information is often non-specific and sometimes unhelpful in the post-transplant period; hence, the need for imaging to accurately detect post-transplant complications. Furthermore, therapeutic image-guided interventions can often be graft-saving and life-saving. Radiologists need to be familiar with the imaging appearances of these extravascular complications as accurate diagnosis and prompt treatment has an impact on graft and patient survival.
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