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Postoperative imaging of living donor liver transplantation complications
The Egyptian Journal of Radiology and Nuclear Medicine xxx (xxxx) xxx–xxx
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Original Article
Postoperative imaging of living donor liver transplantation complications ⁎
Mary Y. Tadros , Amir L. Louka Radiology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt
A R T I C LE I N FO
A B S T R A C T
Keywords: Living donor liver transplantation (LDLT) Endoscopic retrograde cholangiopancreatography (ERCP) percutaneous cholangiography (PTC) Hepatic artery thrombosis (HAT)
Background: There is no doubt that the role of Different diagnostic imaging is well established in the evaluation of patients who are being evaluated for potential liver transplantation but it plays a huge role in the success of transplanted liver operations. Technical advances in imaging equipment and techniques allow more accurate assessment of postoperative living donor transplantation complications. Objective: To assess the role and importance of different radiological imaging modalities in evaluating and diagnosing recipient complications after living donor liver transplantation. Materials and methods: 50 patients who underwent living donor liver transplantation (LDLT) were followed for at least 6 months and submitted for routine investigation including laboratory tests and imaging. The biliary complications were diagnosed with ultrasound (US) but MRCP was more diagnostic over ultrasound in case of location of strictures. Endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous cholangiography (PTC) was used for therapeutic reasons. Stenting was tried in cases of biliary leakage. Doppler US was used in cases of graft rejection. CTA was used in cases whose HA (hepatic artery) couldn’t be detected by Doppler. Conventional angiography was used as a therapeutic tool for restoration of HA patency. This study was held between November 2014 until December 2016. Results: Over 50 patients who underwent living donor liver transplantation. The morbidity rate was 66% (33 patients), where 17 patients passed an uncomplicated course, Biliary tract complications occurred in 13 patients (26%). Vascular complications were found in 8 patients (16%), one had portal vein thrombus and another patient had hepatic artery stenosis and underwent stent. Mild pleural effusion was seen in 30 patients (60%). Moderate to marked pleural effusion was seen in 13 patients (26%), Ascites was considered significant in case of moderate to marked or that persist after two weeks. Six patients complained significant collections, two of them improved by single tapping, whereas two patients required pig tail drainage (7 to14 days). The incidence of rejection was 24% in our study (12 patients) 75% of rejection (nine patients) occurred during the first two months postoperative. One case showed multiple hypodense hepatic focal lesions and the diagnosis was made by histopathology (biopsy) and was lymphoma. Conclusion: The different radiological modalities are a cornerstone in the success of the liver transplantation operation together with curious postoperative follow up are the key for diagnosis of most of the complications including vascular, biliary and collections and even rejection cases.
1. Introduction Liver cell failure is the major indication of liver transplantation, which is developed either due to severe acute or chronic liver insult and in cases which no other therapy is beneficial [1]. Other indications include metabolic, neoplastic causes or chronic liver disease due to several causes [2]. Liver transplantation for hepatic malignancies has become a welldocumented and proven treatment modality for these patients [3].
However, early unsatisfactory results emphasized that only a highlyselected patient population would benefit from transplantation. < 10% of all liver transplants performed are for hepatocellular cancer (HCC). There is no controversy that hepatoblastoma is an appropriate indication in pediatric patients with unresectable tumors. Also, liver transplantation for HCC in the adult population yields good results for patients whose tumor masses do not exceed Milan criteria (The criteria for eligibility for transplantation were the presence of a tumor 5 cm or less in diameter in patients with single focal lesion and no more than three
Peer review under responsibility of The Egyptian Society of Radiology and Nuclear Medicine. ⁎ Corresponding author. E-mail address: [email protected] (M.Y. Tadros). https://doi.org/10.1016/j.ejrnm.2017.10.009 Received 13 July 2017; Accepted 21 October 2017 0378-603X/ copyright 2018 The Egyptian Society of Radiology and Nuclear Medicine. Production and hosting by Elsevier. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/BY-NC-ND/4.0/).
Please cite this article as: Tadros, M.Y., The Egyptian Journal of Radiology and Nuclear Medicine (2018), https://doi.org/10.1016/j.ejrnm.2017.10.009
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2. Materials & methods
Table 1 Contraindication of liver transplantation [4]. Absolute contraindications
Relative contraindications
HIV Extrahepatic malignancy. Uncontrolled infection. Advanced cardiopulmonary disease. Active drug or alcohol abuse.
Advanced age. HBs Ag positivity. HIV positivity without clinical AIDS Massive portal vein thrombosis. Extensive biliary surgery. Psychological/ compliance problems.
2.1. Subjects This study was done from November 2014 until December 2016, where 50 patients underwent living donor liver transplantation at university hospitals. Each patient was followed for at least 6 months. The patients include 44 males and 6 females with mean age of 48 years. All patients were admitted to ICU in the postoperative period where a routine full laboratory and radiological assessment were done. The laboratory assessment included full liver function tests, kidney functions, complete blood picture, C reactive protein (CRP), immunosuppressant level and bilirubin level in drains. The routine radiological assessment included ultrasound and duplex assessment as well as a chest X ray. The chest X ray was done once daily, but the ultrasound and duplex were done twice daily in the first week then once daily during the rest of the hospital stay. CT angiography (CTA) was used in patients with suspected vascular problems, improper visualization of the hepatic artery or patients with abnormal laboratory results that were not caused by known problem. In cases of HA occlusion CTA was performed for confirmation followed by immediate interventional angiography for confirmation and possible therapeutic options. CTA was also done in patients with thrombosed hepatic vein to confirm the duplex results. Increased serum bilirubin and increased bilirubin in drains were the indications for T tube cholangiogram or ERCP, when the biliary leak was confirmed biliary stenting was done to control the bile leak. Other cases of increased serum bilirubin without significant dilated intrahepatic biliary radicles by ultrasound were submitted to MRCP to diagnose possible anastomotic strictures and other biliary complications. Oral consent was taken from the patients in accord with the ethics committee of the institution.
nodules, each 3 cm or less in diameter in patients with multiple tumors). Epithelioid hemangioendothelioma is also an appropriate indication for liver transplantation. Metastatic liver disease is not an indication for liver transplantation, except for cases in which the primary source is a neuroendocrine tumor, for which liver transplantation can result in long-term survival and even cures in several patients [3]. There are many relative and absolute contraindications for liver transplantation (Table 1) [4]. Types of liver transplantation: Knowledge of the types of transplantation procedures and the postoperative imaging appearance of the anatomy of the transplanted liver graft is essential for radiologists [5]. 1. Whole cadaveric liver transplantation (Whole cadaveric liver harvested from donors who have died from causes not affecting hepatic function. 2. Segmental (split) adult cadaveric organ graft. 3. Segmental (split) left lobe living related adult organ graft (segments II and III or segments II, III, and IV). 4. Right lobe graft of the living donor liver transplantation [6]. Living donor liver transplantation has two major advantages over cadaveric transplantation. First, a living donor has completely normal liver function with hemodynamic stability, and second, graft preservation time can be reduced to less than a few hours. However, although these conditions may provide a well preserved viable graft, the disadvantage of LDLT is that graft volume is smaller than that of a cadaveric whole-liver graft. Post-transplantation complications are categorized into vascular that includes hepatic artery thrombosis and portal vein thrombosis or stenosis, biliary complications such as biliary obstruction or stricture, and parenchymal complications as rejection or infection or malignancy recurrence and other less occurrence complications (Table 2) [7]. The aim of this study was to emphasis on the role and importance of different diagnostic imaging modalities in the evaluation of recipient complications after living donor liver transplantation.
2.2. Methods 2.2.1. Ultrasound and duplex assessment The ultrasound and duplex assessment was done by GE LOGIC 5 machine using the curved 3.5–5 MHz probe with color and spectral facilities. The liver was assessed for size and abnormal echogenicity such as area of infarctions or congestions, also the presence of dilated biliary system to exclude biliary strictures, biloma or any collection which mentioned by site and estimated volume. The portal vein and its branches were examined by B-mode and color mode, and then spectral assessment was done for velocity and pulsatility of the flow, which was measured at the pre-and post-anastomotic sites as well as within the branches of the portal vein. The hepatic artery was tested for patency using the color, then pulsed waves at the hilum and at intrahepatic segment to ensure patency after the post anastomotic site, the pulsed wave measured mainly the resistive index (RI) and peak systolic velocity (PSV). The hepatic veins were evaluated 3 cm from the anastomotic site for patency and wave character. Limitations were encountered in cases of patient obesity, dressing covering the large incisions and rapid respiratory movements of the patients.
Table 2 The classification of postsurgical complications of liver transplantation (7). Liver transplantation complications
Vascular
Biliary
Parenchymal
Other
artery thrombosis, • Hepatic stenosis and pseudo aneurysm. vein stenosis or thrombosis. • Portal Hepatic vein stenosis or • IVC, thrombosis. obstruction. • Biliary stricture. • Biliary formation. • Stones leak and biloma. • Bile • Rejection. (recurrent malignancy • Malignancy and Lymphoproliferative disorders). abscess. • Infection, hepatitis and cirrhosis. • Recurrent hemorrhage. • Postoperative adrenal hemorrhage. • Right • Bowel perforation.
2.2.2. Technique of triphasic CT and CT angiography Seventeen patients were examined by CT either for abnormal ultrasound Doppler findings or abnormal clinical and laboratory results. CT scans were done with a dual 64 channel multi-detector row CT scanner (Siemens Definition Dual Source). The renal function tests were revised at first to assure safety of using contrast materials. Fasting was not needed in urgent assessment of the patency of the hepatic artery. The pre-contrast series is taken first by using a 10-mm thickness, with slice pitch of 5, gantry rotation = 0.6 s, table speed = 15 mm 2
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3. Results
/rotation. Tube voltage = 120 kV, tube current 270–300 Ma. The timing of injection was determined by bolus tracking technique in a computer automated scanner technology, where the region of interest was just above the celiac axis with a threshold of contrast concentration at 120 HU. Post-contrast series were obtained following injection of non-ionic contrast (Ultravist 300 or 370 mg) using an automatic pump (Vistron, USA) with average volume of about 120 ml injected at a flow rate = 4–5 ml/s. Multislice CT performed by using a 2.5 mm thickness and a slice pitch of 6. Arterial phase started ∼18–20 s post-injection. The portal phase was started ∼40 s post-injection, Then the 3rd phase (delayed phase) started after a delay of 10 s from the end of the 2nd phase. Sections were reconstructed at 2.5 mm. The whole examination took about 68 s. Post processing for all images was done on a workstation. All phases of the study were assessed using maximum intensity projections (MIP) with volume rendering techniques and zooming on areas of abnormal findings. The 1st phase of contrast injection was used to delineate the arterial axis, especially the hepatic artery and its branches with coronal reconstruction images. The portal phase was used to visualize the portal venous system, including the splenic, superior mesenteric and main portal vein, anastomotic site and its intra hepatic branches. The last phase was used to visualize the hepatic veins, anastomotic site and the IVC.
Forty-six patients had HCV related cirrhosis (92%) with three of them had co-infection by HBV and HCV. Two patients had cryptogenic cirrhosis, one case had veno-occlusive disease related cirrhosis (Budd Chiari syndrome), and one case was Wilson disease. Four patients had hepatocellular carcinoma on top of their cirrhotic liver with enhancing lesions during the arterial phase of contrast studies. Ninety-six percent of cases were suffering from end stage liver disease with 80% had ascites before the operation. 3.1. Post-operative complications The morbidity rate was 66% (33 patients), where 17 patients passed uncomplicated course, considering that mild ascites and mild pleural effusion are acceptable early post-operative findings. Also, collections were considered as complication if they persisted or had a progressive course. 3.1.1. Biliary complications Biliary tract complications were seen in 13 patients (26%). Nine of them had biliary stricture after variable periods of the transplantation while the other four had biliary leakage. The patients of the biliary strictures, underwent biliary stenting through ERCP and three of them needed combined PTC and ERCP (Rendezvous technique) (Figs. 1 and 2). Two patients with bile leak finally died due to sepsis (re-exploration was done for both cases). One case had large biloma that was drained (Fig. 3). The last one was controlled after biliary stent. In our study ultrasound was as effective as MRCP in the diagnosis of biliary dilatation and both detected dilatation in four patients. Two patients that underwent MRCP due to suspected biliary obstruction with negative ultrasound results revealed no intrahepatic biliary dilatation where one of them showed mild anastomotic biliary stricture. All patients of the biliary leakage started about 10 days after the operation while 61.5% of biliary stricture formation came late after 6 months. The frequency of occurrence of both biliary leak and strictures is listed in (Table 3) and the date of onset of biliary strictures is listed in (Table 4).
2.2.3. Technique of magnetic resonance cholangiography Twelve patients with suspected biliary complications underwent MR imaging (MRI) at 1.5-T MR system (Intera Achieva; Philips Medical Systems). The MRI examinations were done after fasting for at least 6 h. Biliary tree was assessed by one of two protocols of MRCP. we started by, 2D breath-hold single-slice rapid acquisition with relaxation enhancement (RARE) was acquired by with repetition time in milliseconds/echo time in ms, 9817/920; flip angle, 90°; slice thickness, 40 mm; field of view, 35 × 35 cm2; acquisition time, 9.8 s for each slice number of signal averages, 1; matrix, 308 × 256; echo train length, 256; and coronal 15-degree oblique coronal orientation resulting in 9 slices. Then, respiratory-triggered 3-dimensional (3D) TSE using a respiratory belt was acquired with repetition time/echo time, 2500/740; flip angle, 90°; matrix, 256 × 512; echo train length, 100; slice thickness, 1 mm; field of view, 30 × 35 cm2; number of signal averages, 1; SENSE factor, 2; acquisition time, 2–5 m depending on respiratory frequency.
3.1.2. Vascular complications Vascular complications were found in 8 patients (16%), one had portal vein thrombus and another patient had hepatic artery stenosis and underwent stent. Five patients diagnosed as hepatic artery occlusion (2 of them underwent re-exploration and interventional angiography with thrombolytic treatment was used in two, that was successful in one of them, the second patient re-thrombosis occurred in the following 24 h). One patient had thrombosis of the middle hepatic vein stent. All cases with HA thrombosis occurred in the first 5 days’ post transplantation and 4 of them seen in the first 24 h (Fig. 4). CTA was done in 10 patients in whom arteries were difficult to be found by the Doppler examination where the artery was patent in five of them, likely due to spasticity or attenuated course of the artery. In general CT scan was done in 17 cases for different reasons and the following table (Table 5) shows the results of CTA and duplex study in detecting patency of the hepatic artery. The table shows that all cases with normal Doppler study were patent by CTA. However, patients with undetectable Doppler signals in HA were related to arterial thrombosis, attenuated flow, spasm or technical difficulties, as declared by CTA. The ultrasound had a sensitivity of 83.3% and 97.5% negative predictive value. One case was reported as attenuated very small artery in CTA and angiography was done which confirmed its patency. No disagreement between Duplex and CTA studies as regard the portal or hepatic vein patency. One case was portal vein thrombosis and another case with MHV stent thrombosis and were confirmed by CT.
2.2.4. T Tube cholangiogram Six patients underwent T tube cholangiogram (Seimens Axiom Iconos R200) spot images were obtained in antero-posterior and oblique views after injection of 15–20 ml Ultravist in biliary tube under screen monitoring. 2.2.5. Percutaneous trans hepatic cholangiogram After reviewing patients’ bleeding profile and infusion of plasma if necessary the PTC using chiba needle was used in five patients underwent PTC under guidance of (Toshiba Infinix software version V3.52∗R005 and Siemens Axiom Artis). 2.2.6. Statistical analysis Data were statistically described in terms of mean ± standard deviation ( ± SD), median and range, or frequencies (number of cases) and percentages. Comparison between the study groups was done using Student t test for independent samples. For comparing categorical data, we used Chi square (χ2) test. McNemar test used within group comparison while the agreement was done using kappa statistics. p values < 0.05 were considered statistically significant. All statistical calculations were done by SPSS (Statistical Package for the Social Science; SPSS Inc., Chicago, IL, USA) version 15 for Microsoft Windows. 3
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Fig. 1. A 56 years old male patient underwent transplantation for HCV related cirrhosis complicated by HCC. (A) Ultrasound image showed dilated intrahepatic biliary radicles (double barrel sign, black arrow). (B) coronal MRCP T2WI showed anastomotic biliary stricture (arrow). (C and D) PTC and PTD images showed anastomotic biliary stricture with subsequent wire and catheter bypassing its site. Biliary stent was inserted by using rendezvous technique.
Fig. 2. A 17 years old female with Wilson disease related liver cell failure. She underwent left lobe living donor liver transplantation with choledocho-jujenostomy was done for the biliary anastomosis. (A and B) ultrasound images showed significantly dilated IHBRs within the left lobe graft. (C) PTC (percutaneous trans hepatic cholangiography) showed marked biliary dilatation within the transplanted left lobe graft. (D) Subsequent external biliary drainage was done with insertion of catheter through the anastomotic stricture followed by dilatation of the stricture.
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Fig. 3. A 54 years’ male, underwent right lobe living donor liver transplantation due to HCV related cirrhosis. A, B and C. A axial CT scan show hypodense collection with minimal adjacent dilatation of the biliary radicles (arrow). B and C; coronal T2 MRI weighted images showed large biloma (arrow) with dilated intrahepatic biliary radicles (thin arrow) due to compression by the biloma. Table 3 Biliary complications frequency. Biliary complication
No. of patients
Frequency of total patients
Stricture Leak Total
9 4 13
18% 8% 26%
Table 5 Comparison between Duplex examination and CTA in detection of hepatic artery (significant < 0.05). HA by CT angiography
Hepatic Detected artery by Undetected Duplex Total Chi-square test P-value
Table 4 Biliary stricture occurrence onset. Biliary stricture date
No. of cases
Percentage
Early (1st three months) Late (after 6 months) Total
5 8 13
38.5% 61.5% 100%
Total
Patent
Occluded
Attenuated
7 (63.64%) 4 (36.36%)
0 (0.0%) 5 (100%)
0 (0.0%) 1 (100.0%)
7 (41.2%) 10 (58.8%)
11 6.491 0.038
5
1
17 (100.0%)
patients complained significant collections, two of them improved by single tapping, whereas two patients required pig tail drainage (7 to14 days). Two collections were hematomas, one of the patients died and the other hematoma was controlled after re-exploration (Fig. 5).
3.1.3. Pleural effusion The pleural effusion considered significant if respiratory distress happened that necessitating thoracocentesis. Mild pleural effusion was seen in 30 patients (60%). Moderate to marked pleural effusion was in 13 patients (26%), of which 4 cases underwent thoracocentesis. The other 9 patients improved with conservative treatment and good progress of the graft function.
3.1.6. Graft rejection Rejection was diagnosed by biopsy as well as by clinical improvement on anti-rejection drugs dose modification. The incidence of rejection was 24% in our study (12 patients). (Table 6). In this study 18% of rejection (nine patients) occurred during the first two months postoperative while the rest 4 cases occurred between 2 and 6 months (Table 7).
3.1.4. Ascites Ascites was considered significant in case of marked ascites or if it persistent after two weeks. Six cases were diagnosed as considerable ascites, three of them underwent drainage while the other three improved conservatively.
3.1.6.1. Doppler findings in rejection. The portal vein velocity was fluctuating in the post-operative period, but it was significantly changed with rejection and the mean velocity decreased to 16.67 cm/ s with 2.84 SD compared to 26.29 cm/s with 4.93 SD in patients who did not suffer from rejection. Portal flow is usually monophasic and non-pulsatile. The pulsatility was correlated with rejection. Among the twelve patients diagnosed with rejection, six cases showed pulsatile flow (50%), however, four cases were reported to have pulsatile portal flow of those patients
3.1.5. Abdominal collection It was recorded significant when it persisted or had progressive course amount considering fever and increased total leucocystic count as an indication for drainage. The encysted collections were seen sub hepatic and epigastric in locations (at the hepatic cut surface). Six
Fig. 4. A 52 years old male patient with HCV related liver cirrhosis. Six hours after right lobe living donor liver transplantation. a, b and c. Multiple axial CT cuts of the liver showing occluded hepatic artery after its origin from the celiac trunk (open arrows), also extensive graft inhomogeneity or different densities are noted (black arrows).
a)
c)
b) 5
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Fig. 5. A 56 years old male underwent right lobe living donor liver transplantation due to HCV related cirrhosis. A and B ultrasound images showed collecting hematoma at the cut surface of the graft.
without rejection (Table 8). The hepatic arterial resistance couldn’t be correlated to the cases of rejection as there was no difference between the hepatic artery resistivity in cases with and without rejection.
Table 6 Shows the incidence of rejection. Rejection
No. of patients
Percent
Yes No Total
12 38 50
24% 76% 100.0
3.1.6.2. Post transplantation lympho-proliferative disorders. One case showed multiple hypodense hepatic focal lesions and the diagnosis was done by histopathology (biopsy) and was lymphoma (Fig. 6).
Table 7 Shows distribution of rejection cases according to the time of onset.
3.2. Mortality
Rejection time of onset
No. of cases
Percent
In the 1st two months From to 2 to 6 months No rejection Total
9 3 38 50
18% 6% 76% 100%
The overall mortality rate was 22% (11 patients). Three cases were hepatic artery occlusion, two due to primary graft dysfunction and four cases due to sepsis. One case had an internal hemorrhage and the last was related to non-proper management of biliary stricture. Two of the cases that died due to sepsis were related to biliary complications (two cases were biliary leak with re-exploration) and the other two died due to septicemia and uncontrolled chest infection). Mortality occurred after 6 months, so it was beyond study time limit.
Table 8 Illustrates the difference of the portal velocity in cases of rejection as compared to the rest of the patients. The P value was < 0.001 (significant relations) and Shows the incidence of portal vein pulsatility in correlation with rejection, P value is = 0.003 (significant < 0.05). Rejection
No Yes Total
Portal velocity cm/s
4. Discussion Liver transplantation is lifesaving treatment for patient with liver cell failure. Improvement of preoperative selection, surgical techniques, immunosuppressive therapy, postoperative care and follow up has resulted in increased patient graft survival after the transplantation [8]. The indications for liver transplantation are multiple and in our study 46 cases (92%) were due to HCV related cirrhosis. In contrast to our study in which HCV related cirrhosis represent 30–50% of indications for liver transplantation in other countries [9]. Despite the improvement in the liver transplantation surgical techniques and post-operative management, there are still significant and
Portal vein pulsatility
Number of cases
Mean
Std. Deviation
Yes
No
38 12 50
26.29 16.67 23.98
4.93 2.84 6.12
4 (10.5%) 6 (50%)
34 (89.5%) 6 (50%)
Fig. 6. A 56 years old male patient underwent right lobe living donor liver transplantation due to HCV related liver cirrhosis. A and B axial CT scan showed variable sized hypodense hepatic focal lesions. A-showed the largest focal lesion in segment 8. B showed smaller hepatic focal lesions (arrow heads) with celiac lymph node (black arrow).
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Fig. 7. Imaging algorithm for evaluation of recipient complications.
serious complication as the incidence of sepsis after second exploration for biliary leakage was 100%. This doesn’t agree with a study by Londono et al. who reported that surgical intervention for biliary leakage after liver transplantation is rare and 85–100% of leakage are controlled without surgery [14]. Pleural effusion was detected in 46 cases (92%) but considered as a complication in 13 only (26%), however, pleural effusion did not lead to long term morbidity or death. In our study, four cases (8%) required drainage and this is considered relatively higher than other research done by Shandalakis where pleural effusion required drainage in 3% of patients [15]. The graft rejection incidence in our study, was 24% (12 cases), however, no graft loss or mortality seen. Ashok J et al., proved also that graft loss from acute or chronic rejection has emerged as a rarity [16]. Our results showed that the graft rejection is associated with lower velocities of the portal vein as well as increased incidence of pulsatility. Usually the portal vein velocities are high in the early postoperative days due to reduction of hepatic resistance, then it starts to be lower to normal level. The flow is usually monophasic hepatopedal flow with respiratory waveness. When histological changes of rejection occur the increased hepatic resistance results in a decrease in portal blood velocity (PBV) and change of the portal flow into pulsatile form [17]. In our study, 60% of cases with pulsatile flow were diagnosed as variable degree of rejection. Also, the mean velocities for cases with rejection was 12.89 ± 3.6 cm/s, while PBV in cases with no rejection showed mean velocity of 21.85 ± 4.1. In a Doppler finding study in acute rejection by So et al., 47 patients with biopsy proved rejection and 47 control group without rejection, found that pulsatile venous flow was seen more in cases with rejection than in cases without rejection with estimated P value of 0.001 which was significant and that was compatible to our study [18]. The hepatic artery resistive index (RI) did not change in cases of rejection. Hiroyuki et al., explained that by that rejection increased mainly the portal venous resistance and not affecting the hepatic arterial resistance which may be even decreased as a compensatory buffer mechanism [19]. The vascular complications in this research were seen in 16% of
life threatening complications that can lead to graft failure and increased patient morbidity and mortality. Imaging is very important in the early diagnosis and management of these complications. [10]. The Doppler ultrasonography is the initial imaging modality for evaluation of liver parenchyma, biliary tree and hepatic vasculature abnormalities. When an ultrasound result was indeterminate or there is persistent clinical suspicion of an abnormality, computed tomography (CT) is often performed. The major indications for CT are confirmation of patency of hepatic vascular, also assessment for hemorrhage, biliary leak and abscess. In cases of suspected biliary leak or stricture, the Ttube cholangiography and MRCP are the best noninvasive imaging tools. (Some recommend ERCP for evaluation of the biliary system but it is an invasive technique) [7]. In our study, ultrasound and duplex were done twice daily in the first week (ICU period), then once daily in the ward during the rest of the hospital stay period. CT, T tube cholangiogram and MRCP were used when needed. Invasive procedures like DSA, PTC and ERCP were done mainly for therapeutic purpose. In our study, the biliary complications were the most common complications that were seen in 13 patients (26%). Biliary stricture was found in 9 cases (18%), which considered responsible the cause of long term morbidity as about 60% of the cases occurred after six months. These results are comparable to a study in which 230 patients were evaluated for postoperative biliary tract complications and its risk factors. The overall biliary complication rate was 20.7%. The biliary leak was 7.6% and the biliary stricture 16.2%. The biliary leak occurred early and biliary strictures developed lately [11]. Zeopf et al. [12] reported a higher incidence of biliary complications as the incidence of biliary stricture was 34%, which may be due to longer follow up and routine use for MRCP. In our study, ultrasound was as effective as MRCP in the diagnosis of biliary dilatation. In one case, the MRCP diagnosed anastomotic biliary stricture without significant dilatation of the intrahepatic biliary radicles. Boraschi et al. reported a sensitivity of 93%, specificity of 92%, a positive predictive value of 86% and a negative predictive value of 96% for MRCP in detecting post-LTX biliary complications [13]. Biliary leak (which occurred by in 4 cases) in our study, was a 7
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References
cases. The most common vascular complications were hepatic artery thrombosis (HAT) which occurred 5 times (10% of cases) with three of them suffered graft loss (27% of mortality cases were due to HAT in our study). The cases of the HAT were diagnosed first by absence flow and Doppler signal that was confirmed by CTA. The DSA with thrombolytic therapy was effective in two patients but re-thrombosis occurred in one of them. All cases of hepatic artery thrombosis occurred in the early postoperative days. Hepatic artery stent was placed in one case with anastomotic hepatic artery stenosis. This is comparable to other researches Sanjeev et al. who found that vascular complications occurred in 25% of the cases with HAT was 11% and portal vein stenosis was 5.5% [20]. We had one patient with partial portal vein thrombosis with rejection and did not lead to mortality. Also, the patient with occluded MHV stent showed no affection on the hepatic graft, except for the area of hepatic congestion noted. CT angiography is a non-invasive method of detecting suspected hepatic arterial complications after liver transplantation. The excellent spatial resolution and fast scan times afforded with the multislice scanner allow CT angiography to depict smaller arteries, not only for patency but also for luminal stenosis. CT angiography has many advantages over other imaging modalities. Compared with conventional angiography, CT angiography is non-invasive and cheaper than conventional angiography. Compared to duplex examination, CT angiography is not as dependent on performer experience or body habitus of the patient [21] These facts have led some investigators to suggest that multislice CT angiography is more accurate than Doppler sonography in the detection of vascular complications [21]. In our study, the mortality rate was 22% and the sepsis was the leading cause for the graft failure (4 cases), followed by hepatic artery thrombosis (3 cases), biliary complications (3 cases) and primary graft dysfunction (2 cases). Two cases that died from sepsis were related to biliary complications two of them had leakage and reconstruction of the biliary anastomosis was reattempted. At the end, we suggest that the following imaging algorithm (Fig. 7) is sufficient to follow up patients as we believe it is ideal to pick up the complication with high sensitivity and accordingly expected reduction in graft failure and recipient mortality.
[1] Abt PL, Kelz R, Desai NM, et al. A Survival among pediatric liver transplant recipients: impact of segmental grafts. Liver Transpl 2004;10:1287–93. [2] Strong RW. Liver transplantation current status and future prospects. JR Coll: Surg. Edinb 2001; 46-1-8. [3] Hertl M, Cosimi AB. Liver transplantation for malignancy. Oncologist 2005;10(4):269–81. [4] Min Xu, Clavien PA. Liver transplantation. Transplantation Surgery; 2001. p. 181–183. [5] Almousa O, Michael PF. Liver Transplantation 2006; 12(2): 84–193. [6] Lee WK, Chang Silvia D, Duddalwar Vinay A, Jules MC, Warren P, Wing-Fai EL, et al. Imaging assessment of congenital and acquired abnormalities of the portal venous system. Radiographic 2011; 31. doi:http://dx.doi.org/10.1148/rg. 314105104. [7] Singh Ajay K, Arun CN, Verma Hetal A, et al. Postoperative imaging in liver transplantation: what radiologists should know. Radiographics 2010; 30: 339–351. [8] Busuttil RW, Lake JR. Role of tacrolimus in the evolution of liver transplantation. Transplantation 2004;77:S44–S51. [9] Nadalin S, Bockhorn M, Malagó M, Valentin G, Frilling A, Broelsch CE. Living donor liver transplantation, HPB (Oxford). 2006; 8(1): 10–21, doi:http://dx.doi.org/10. 1080/13651820500465626. [10] Hussain Hero K, Nghiem Hanh Vu. Imaging of hepatic transplantation. Clin Liver Disease 2002; 6(1). [11] Ye Ben Q, Chi LL, Chung ML, et al. Risk factors for biliary complications after liver transplantation. Arch Surg 2004;139:1101–5. [12] Zoepf T, Maldonado-Lopez EJ, Hilgard P, et al. Diagnosis of biliary stricture after liver transplantation: which is the best tool? World J Gastroenterol 2005;21:2945–8. [13] Boraschi P, Donati F, Gigoni R, et al. Ischemic-type biliary lesions in liver transplant recipients: evaluation with magnetic resonance cholangiography. Transplant Proc 2004;36:2744–7. [14] Londono MC, Balderramo D, Cardenas A. Management of biliary complications after orthotopic liver transplantation: the role of endoscopy. World J Gastroenterol 2008; 14(4): 493–7 [Jan 28]. [15] Shandalakis JE. Extrahepatic biliary tract anatomy. In: By John ES, Panajiotis NS, Lee JS, editors. Surgical anatomy and technique, 2nd edition, WB Saunder; 2000. p. 573–581. [16] Ashok J, Jorge R, Randeeb K, et al. Long-term survival after liver transplantation in 4,000 consecutive patients at a single center. Ann Surg 2000 Oct;232(4):490–500. [17] Hadengue A, Lebrec D, Moreau R, et al. Persistence of systemic and splanchnic hyperkinetic circulation in liver transplant patients. Hepatology 1993;17:175–8. [18] So Jung L, Kyoung WK, Jin HK, et al. Doppler sonography of patients with and without acute cellular rejection after right-lobe living donor liver transplantation. J Ultrasound Med 2011;31(5):6845–51. [19] Hiroyuki Sugimoto, Tetsuya Kiushi, Akimasa Nakao. Department of transplantation surgery. Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Japan, 2007; 35(6). [20] Sanjeev K, James H, Oliver III, David GB, Michael P. Detection of vascular complications after liver transplantations after liver transplantation early experiences with multislice CT angiography with volume rendering, AJT 2000; 175(6): 1735–9. [21] Katyal S, Oliver JH, Buck DG, Federle MP. Detection of vascular complications after liver transplantation: early experience in multislice CT angiography with volume rendering. AJR 2000;175:1735–9.
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Contents lists available at ScienceDirect
The Egyptian Journal of Radiology and Nuclear Medicine journal homepage: www.elsevier.com/locate/ejrnm
Original Article
Postoperative imaging of living donor liver transplantation complications ⁎
Mary Y. Tadros , Amir L. Louka Radiology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt
A R T I C LE I N FO
A B S T R A C T
Keywords: Living donor liver transplantation (LDLT) Endoscopic retrograde cholangiopancreatography (ERCP) percutaneous cholangiography (PTC) Hepatic artery thrombosis (HAT)
Background: There is no doubt that the role of Different diagnostic imaging is well established in the evaluation of patients who are being evaluated for potential liver transplantation but it plays a huge role in the success of transplanted liver operations. Technical advances in imaging equipment and techniques allow more accurate assessment of postoperative living donor transplantation complications. Objective: To assess the role and importance of different radiological imaging modalities in evaluating and diagnosing recipient complications after living donor liver transplantation. Materials and methods: 50 patients who underwent living donor liver transplantation (LDLT) were followed for at least 6 months and submitted for routine investigation including laboratory tests and imaging. The biliary complications were diagnosed with ultrasound (US) but MRCP was more diagnostic over ultrasound in case of location of strictures. Endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous cholangiography (PTC) was used for therapeutic reasons. Stenting was tried in cases of biliary leakage. Doppler US was used in cases of graft rejection. CTA was used in cases whose HA (hepatic artery) couldn’t be detected by Doppler. Conventional angiography was used as a therapeutic tool for restoration of HA patency. This study was held between November 2014 until December 2016. Results: Over 50 patients who underwent living donor liver transplantation. The morbidity rate was 66% (33 patients), where 17 patients passed an uncomplicated course, Biliary tract complications occurred in 13 patients (26%). Vascular complications were found in 8 patients (16%), one had portal vein thrombus and another patient had hepatic artery stenosis and underwent stent. Mild pleural effusion was seen in 30 patients (60%). Moderate to marked pleural effusion was seen in 13 patients (26%), Ascites was considered significant in case of moderate to marked or that persist after two weeks. Six patients complained significant collections, two of them improved by single tapping, whereas two patients required pig tail drainage (7 to14 days). The incidence of rejection was 24% in our study (12 patients) 75% of rejection (nine patients) occurred during the first two months postoperative. One case showed multiple hypodense hepatic focal lesions and the diagnosis was made by histopathology (biopsy) and was lymphoma. Conclusion: The different radiological modalities are a cornerstone in the success of the liver transplantation operation together with curious postoperative follow up are the key for diagnosis of most of the complications including vascular, biliary and collections and even rejection cases.
1. Introduction Liver cell failure is the major indication of liver transplantation, which is developed either due to severe acute or chronic liver insult and in cases which no other therapy is beneficial [1]. Other indications include metabolic, neoplastic causes or chronic liver disease due to several causes [2]. Liver transplantation for hepatic malignancies has become a welldocumented and proven treatment modality for these patients [3].
However, early unsatisfactory results emphasized that only a highlyselected patient population would benefit from transplantation. < 10% of all liver transplants performed are for hepatocellular cancer (HCC). There is no controversy that hepatoblastoma is an appropriate indication in pediatric patients with unresectable tumors. Also, liver transplantation for HCC in the adult population yields good results for patients whose tumor masses do not exceed Milan criteria (The criteria for eligibility for transplantation were the presence of a tumor 5 cm or less in diameter in patients with single focal lesion and no more than three
Peer review under responsibility of The Egyptian Society of Radiology and Nuclear Medicine. ⁎ Corresponding author. E-mail address: [email protected] (M.Y. Tadros). https://doi.org/10.1016/j.ejrnm.2017.10.009 Received 13 July 2017; Accepted 21 October 2017 0378-603X/ copyright 2018 The Egyptian Society of Radiology and Nuclear Medicine. Production and hosting by Elsevier. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/BY-NC-ND/4.0/).
Please cite this article as: Tadros, M.Y., The Egyptian Journal of Radiology and Nuclear Medicine (2018), https://doi.org/10.1016/j.ejrnm.2017.10.009
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2. Materials & methods
Table 1 Contraindication of liver transplantation [4]. Absolute contraindications
Relative contraindications
HIV Extrahepatic malignancy. Uncontrolled infection. Advanced cardiopulmonary disease. Active drug or alcohol abuse.
Advanced age. HBs Ag positivity. HIV positivity without clinical AIDS Massive portal vein thrombosis. Extensive biliary surgery. Psychological/ compliance problems.
2.1. Subjects This study was done from November 2014 until December 2016, where 50 patients underwent living donor liver transplantation at university hospitals. Each patient was followed for at least 6 months. The patients include 44 males and 6 females with mean age of 48 years. All patients were admitted to ICU in the postoperative period where a routine full laboratory and radiological assessment were done. The laboratory assessment included full liver function tests, kidney functions, complete blood picture, C reactive protein (CRP), immunosuppressant level and bilirubin level in drains. The routine radiological assessment included ultrasound and duplex assessment as well as a chest X ray. The chest X ray was done once daily, but the ultrasound and duplex were done twice daily in the first week then once daily during the rest of the hospital stay. CT angiography (CTA) was used in patients with suspected vascular problems, improper visualization of the hepatic artery or patients with abnormal laboratory results that were not caused by known problem. In cases of HA occlusion CTA was performed for confirmation followed by immediate interventional angiography for confirmation and possible therapeutic options. CTA was also done in patients with thrombosed hepatic vein to confirm the duplex results. Increased serum bilirubin and increased bilirubin in drains were the indications for T tube cholangiogram or ERCP, when the biliary leak was confirmed biliary stenting was done to control the bile leak. Other cases of increased serum bilirubin without significant dilated intrahepatic biliary radicles by ultrasound were submitted to MRCP to diagnose possible anastomotic strictures and other biliary complications. Oral consent was taken from the patients in accord with the ethics committee of the institution.
nodules, each 3 cm or less in diameter in patients with multiple tumors). Epithelioid hemangioendothelioma is also an appropriate indication for liver transplantation. Metastatic liver disease is not an indication for liver transplantation, except for cases in which the primary source is a neuroendocrine tumor, for which liver transplantation can result in long-term survival and even cures in several patients [3]. There are many relative and absolute contraindications for liver transplantation (Table 1) [4]. Types of liver transplantation: Knowledge of the types of transplantation procedures and the postoperative imaging appearance of the anatomy of the transplanted liver graft is essential for radiologists [5]. 1. Whole cadaveric liver transplantation (Whole cadaveric liver harvested from donors who have died from causes not affecting hepatic function. 2. Segmental (split) adult cadaveric organ graft. 3. Segmental (split) left lobe living related adult organ graft (segments II and III or segments II, III, and IV). 4. Right lobe graft of the living donor liver transplantation [6]. Living donor liver transplantation has two major advantages over cadaveric transplantation. First, a living donor has completely normal liver function with hemodynamic stability, and second, graft preservation time can be reduced to less than a few hours. However, although these conditions may provide a well preserved viable graft, the disadvantage of LDLT is that graft volume is smaller than that of a cadaveric whole-liver graft. Post-transplantation complications are categorized into vascular that includes hepatic artery thrombosis and portal vein thrombosis or stenosis, biliary complications such as biliary obstruction or stricture, and parenchymal complications as rejection or infection or malignancy recurrence and other less occurrence complications (Table 2) [7]. The aim of this study was to emphasis on the role and importance of different diagnostic imaging modalities in the evaluation of recipient complications after living donor liver transplantation.
2.2. Methods 2.2.1. Ultrasound and duplex assessment The ultrasound and duplex assessment was done by GE LOGIC 5 machine using the curved 3.5–5 MHz probe with color and spectral facilities. The liver was assessed for size and abnormal echogenicity such as area of infarctions or congestions, also the presence of dilated biliary system to exclude biliary strictures, biloma or any collection which mentioned by site and estimated volume. The portal vein and its branches were examined by B-mode and color mode, and then spectral assessment was done for velocity and pulsatility of the flow, which was measured at the pre-and post-anastomotic sites as well as within the branches of the portal vein. The hepatic artery was tested for patency using the color, then pulsed waves at the hilum and at intrahepatic segment to ensure patency after the post anastomotic site, the pulsed wave measured mainly the resistive index (RI) and peak systolic velocity (PSV). The hepatic veins were evaluated 3 cm from the anastomotic site for patency and wave character. Limitations were encountered in cases of patient obesity, dressing covering the large incisions and rapid respiratory movements of the patients.
Table 2 The classification of postsurgical complications of liver transplantation (7). Liver transplantation complications
Vascular
Biliary
Parenchymal
Other
artery thrombosis, • Hepatic stenosis and pseudo aneurysm. vein stenosis or thrombosis. • Portal Hepatic vein stenosis or • IVC, thrombosis. obstruction. • Biliary stricture. • Biliary formation. • Stones leak and biloma. • Bile • Rejection. (recurrent malignancy • Malignancy and Lymphoproliferative disorders). abscess. • Infection, hepatitis and cirrhosis. • Recurrent hemorrhage. • Postoperative adrenal hemorrhage. • Right • Bowel perforation.
2.2.2. Technique of triphasic CT and CT angiography Seventeen patients were examined by CT either for abnormal ultrasound Doppler findings or abnormal clinical and laboratory results. CT scans were done with a dual 64 channel multi-detector row CT scanner (Siemens Definition Dual Source). The renal function tests were revised at first to assure safety of using contrast materials. Fasting was not needed in urgent assessment of the patency of the hepatic artery. The pre-contrast series is taken first by using a 10-mm thickness, with slice pitch of 5, gantry rotation = 0.6 s, table speed = 15 mm 2
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3. Results
/rotation. Tube voltage = 120 kV, tube current 270–300 Ma. The timing of injection was determined by bolus tracking technique in a computer automated scanner technology, where the region of interest was just above the celiac axis with a threshold of contrast concentration at 120 HU. Post-contrast series were obtained following injection of non-ionic contrast (Ultravist 300 or 370 mg) using an automatic pump (Vistron, USA) with average volume of about 120 ml injected at a flow rate = 4–5 ml/s. Multislice CT performed by using a 2.5 mm thickness and a slice pitch of 6. Arterial phase started ∼18–20 s post-injection. The portal phase was started ∼40 s post-injection, Then the 3rd phase (delayed phase) started after a delay of 10 s from the end of the 2nd phase. Sections were reconstructed at 2.5 mm. The whole examination took about 68 s. Post processing for all images was done on a workstation. All phases of the study were assessed using maximum intensity projections (MIP) with volume rendering techniques and zooming on areas of abnormal findings. The 1st phase of contrast injection was used to delineate the arterial axis, especially the hepatic artery and its branches with coronal reconstruction images. The portal phase was used to visualize the portal venous system, including the splenic, superior mesenteric and main portal vein, anastomotic site and its intra hepatic branches. The last phase was used to visualize the hepatic veins, anastomotic site and the IVC.
Forty-six patients had HCV related cirrhosis (92%) with three of them had co-infection by HBV and HCV. Two patients had cryptogenic cirrhosis, one case had veno-occlusive disease related cirrhosis (Budd Chiari syndrome), and one case was Wilson disease. Four patients had hepatocellular carcinoma on top of their cirrhotic liver with enhancing lesions during the arterial phase of contrast studies. Ninety-six percent of cases were suffering from end stage liver disease with 80% had ascites before the operation. 3.1. Post-operative complications The morbidity rate was 66% (33 patients), where 17 patients passed uncomplicated course, considering that mild ascites and mild pleural effusion are acceptable early post-operative findings. Also, collections were considered as complication if they persisted or had a progressive course. 3.1.1. Biliary complications Biliary tract complications were seen in 13 patients (26%). Nine of them had biliary stricture after variable periods of the transplantation while the other four had biliary leakage. The patients of the biliary strictures, underwent biliary stenting through ERCP and three of them needed combined PTC and ERCP (Rendezvous technique) (Figs. 1 and 2). Two patients with bile leak finally died due to sepsis (re-exploration was done for both cases). One case had large biloma that was drained (Fig. 3). The last one was controlled after biliary stent. In our study ultrasound was as effective as MRCP in the diagnosis of biliary dilatation and both detected dilatation in four patients. Two patients that underwent MRCP due to suspected biliary obstruction with negative ultrasound results revealed no intrahepatic biliary dilatation where one of them showed mild anastomotic biliary stricture. All patients of the biliary leakage started about 10 days after the operation while 61.5% of biliary stricture formation came late after 6 months. The frequency of occurrence of both biliary leak and strictures is listed in (Table 3) and the date of onset of biliary strictures is listed in (Table 4).
2.2.3. Technique of magnetic resonance cholangiography Twelve patients with suspected biliary complications underwent MR imaging (MRI) at 1.5-T MR system (Intera Achieva; Philips Medical Systems). The MRI examinations were done after fasting for at least 6 h. Biliary tree was assessed by one of two protocols of MRCP. we started by, 2D breath-hold single-slice rapid acquisition with relaxation enhancement (RARE) was acquired by with repetition time in milliseconds/echo time in ms, 9817/920; flip angle, 90°; slice thickness, 40 mm; field of view, 35 × 35 cm2; acquisition time, 9.8 s for each slice number of signal averages, 1; matrix, 308 × 256; echo train length, 256; and coronal 15-degree oblique coronal orientation resulting in 9 slices. Then, respiratory-triggered 3-dimensional (3D) TSE using a respiratory belt was acquired with repetition time/echo time, 2500/740; flip angle, 90°; matrix, 256 × 512; echo train length, 100; slice thickness, 1 mm; field of view, 30 × 35 cm2; number of signal averages, 1; SENSE factor, 2; acquisition time, 2–5 m depending on respiratory frequency.
3.1.2. Vascular complications Vascular complications were found in 8 patients (16%), one had portal vein thrombus and another patient had hepatic artery stenosis and underwent stent. Five patients diagnosed as hepatic artery occlusion (2 of them underwent re-exploration and interventional angiography with thrombolytic treatment was used in two, that was successful in one of them, the second patient re-thrombosis occurred in the following 24 h). One patient had thrombosis of the middle hepatic vein stent. All cases with HA thrombosis occurred in the first 5 days’ post transplantation and 4 of them seen in the first 24 h (Fig. 4). CTA was done in 10 patients in whom arteries were difficult to be found by the Doppler examination where the artery was patent in five of them, likely due to spasticity or attenuated course of the artery. In general CT scan was done in 17 cases for different reasons and the following table (Table 5) shows the results of CTA and duplex study in detecting patency of the hepatic artery. The table shows that all cases with normal Doppler study were patent by CTA. However, patients with undetectable Doppler signals in HA were related to arterial thrombosis, attenuated flow, spasm or technical difficulties, as declared by CTA. The ultrasound had a sensitivity of 83.3% and 97.5% negative predictive value. One case was reported as attenuated very small artery in CTA and angiography was done which confirmed its patency. No disagreement between Duplex and CTA studies as regard the portal or hepatic vein patency. One case was portal vein thrombosis and another case with MHV stent thrombosis and were confirmed by CT.
2.2.4. T Tube cholangiogram Six patients underwent T tube cholangiogram (Seimens Axiom Iconos R200) spot images were obtained in antero-posterior and oblique views after injection of 15–20 ml Ultravist in biliary tube under screen monitoring. 2.2.5. Percutaneous trans hepatic cholangiogram After reviewing patients’ bleeding profile and infusion of plasma if necessary the PTC using chiba needle was used in five patients underwent PTC under guidance of (Toshiba Infinix software version V3.52∗R005 and Siemens Axiom Artis). 2.2.6. Statistical analysis Data were statistically described in terms of mean ± standard deviation ( ± SD), median and range, or frequencies (number of cases) and percentages. Comparison between the study groups was done using Student t test for independent samples. For comparing categorical data, we used Chi square (χ2) test. McNemar test used within group comparison while the agreement was done using kappa statistics. p values < 0.05 were considered statistically significant. All statistical calculations were done by SPSS (Statistical Package for the Social Science; SPSS Inc., Chicago, IL, USA) version 15 for Microsoft Windows. 3
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Fig. 1. A 56 years old male patient underwent transplantation for HCV related cirrhosis complicated by HCC. (A) Ultrasound image showed dilated intrahepatic biliary radicles (double barrel sign, black arrow). (B) coronal MRCP T2WI showed anastomotic biliary stricture (arrow). (C and D) PTC and PTD images showed anastomotic biliary stricture with subsequent wire and catheter bypassing its site. Biliary stent was inserted by using rendezvous technique.
Fig. 2. A 17 years old female with Wilson disease related liver cell failure. She underwent left lobe living donor liver transplantation with choledocho-jujenostomy was done for the biliary anastomosis. (A and B) ultrasound images showed significantly dilated IHBRs within the left lobe graft. (C) PTC (percutaneous trans hepatic cholangiography) showed marked biliary dilatation within the transplanted left lobe graft. (D) Subsequent external biliary drainage was done with insertion of catheter through the anastomotic stricture followed by dilatation of the stricture.
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Fig. 3. A 54 years’ male, underwent right lobe living donor liver transplantation due to HCV related cirrhosis. A, B and C. A axial CT scan show hypodense collection with minimal adjacent dilatation of the biliary radicles (arrow). B and C; coronal T2 MRI weighted images showed large biloma (arrow) with dilated intrahepatic biliary radicles (thin arrow) due to compression by the biloma. Table 3 Biliary complications frequency. Biliary complication
No. of patients
Frequency of total patients
Stricture Leak Total
9 4 13
18% 8% 26%
Table 5 Comparison between Duplex examination and CTA in detection of hepatic artery (significant < 0.05). HA by CT angiography
Hepatic Detected artery by Undetected Duplex Total Chi-square test P-value
Table 4 Biliary stricture occurrence onset. Biliary stricture date
No. of cases
Percentage
Early (1st three months) Late (after 6 months) Total
5 8 13
38.5% 61.5% 100%
Total
Patent
Occluded
Attenuated
7 (63.64%) 4 (36.36%)
0 (0.0%) 5 (100%)
0 (0.0%) 1 (100.0%)
7 (41.2%) 10 (58.8%)
11 6.491 0.038
5
1
17 (100.0%)
patients complained significant collections, two of them improved by single tapping, whereas two patients required pig tail drainage (7 to14 days). Two collections were hematomas, one of the patients died and the other hematoma was controlled after re-exploration (Fig. 5).
3.1.3. Pleural effusion The pleural effusion considered significant if respiratory distress happened that necessitating thoracocentesis. Mild pleural effusion was seen in 30 patients (60%). Moderate to marked pleural effusion was in 13 patients (26%), of which 4 cases underwent thoracocentesis. The other 9 patients improved with conservative treatment and good progress of the graft function.
3.1.6. Graft rejection Rejection was diagnosed by biopsy as well as by clinical improvement on anti-rejection drugs dose modification. The incidence of rejection was 24% in our study (12 patients). (Table 6). In this study 18% of rejection (nine patients) occurred during the first two months postoperative while the rest 4 cases occurred between 2 and 6 months (Table 7).
3.1.4. Ascites Ascites was considered significant in case of marked ascites or if it persistent after two weeks. Six cases were diagnosed as considerable ascites, three of them underwent drainage while the other three improved conservatively.
3.1.6.1. Doppler findings in rejection. The portal vein velocity was fluctuating in the post-operative period, but it was significantly changed with rejection and the mean velocity decreased to 16.67 cm/ s with 2.84 SD compared to 26.29 cm/s with 4.93 SD in patients who did not suffer from rejection. Portal flow is usually monophasic and non-pulsatile. The pulsatility was correlated with rejection. Among the twelve patients diagnosed with rejection, six cases showed pulsatile flow (50%), however, four cases were reported to have pulsatile portal flow of those patients
3.1.5. Abdominal collection It was recorded significant when it persisted or had progressive course amount considering fever and increased total leucocystic count as an indication for drainage. The encysted collections were seen sub hepatic and epigastric in locations (at the hepatic cut surface). Six
Fig. 4. A 52 years old male patient with HCV related liver cirrhosis. Six hours after right lobe living donor liver transplantation. a, b and c. Multiple axial CT cuts of the liver showing occluded hepatic artery after its origin from the celiac trunk (open arrows), also extensive graft inhomogeneity or different densities are noted (black arrows).
a)
c)
b) 5
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Fig. 5. A 56 years old male underwent right lobe living donor liver transplantation due to HCV related cirrhosis. A and B ultrasound images showed collecting hematoma at the cut surface of the graft.
without rejection (Table 8). The hepatic arterial resistance couldn’t be correlated to the cases of rejection as there was no difference between the hepatic artery resistivity in cases with and without rejection.
Table 6 Shows the incidence of rejection. Rejection
No. of patients
Percent
Yes No Total
12 38 50
24% 76% 100.0
3.1.6.2. Post transplantation lympho-proliferative disorders. One case showed multiple hypodense hepatic focal lesions and the diagnosis was done by histopathology (biopsy) and was lymphoma (Fig. 6).
Table 7 Shows distribution of rejection cases according to the time of onset.
3.2. Mortality
Rejection time of onset
No. of cases
Percent
In the 1st two months From to 2 to 6 months No rejection Total
9 3 38 50
18% 6% 76% 100%
The overall mortality rate was 22% (11 patients). Three cases were hepatic artery occlusion, two due to primary graft dysfunction and four cases due to sepsis. One case had an internal hemorrhage and the last was related to non-proper management of biliary stricture. Two of the cases that died due to sepsis were related to biliary complications (two cases were biliary leak with re-exploration) and the other two died due to septicemia and uncontrolled chest infection). Mortality occurred after 6 months, so it was beyond study time limit.
Table 8 Illustrates the difference of the portal velocity in cases of rejection as compared to the rest of the patients. The P value was < 0.001 (significant relations) and Shows the incidence of portal vein pulsatility in correlation with rejection, P value is = 0.003 (significant < 0.05). Rejection
No Yes Total
Portal velocity cm/s
4. Discussion Liver transplantation is lifesaving treatment for patient with liver cell failure. Improvement of preoperative selection, surgical techniques, immunosuppressive therapy, postoperative care and follow up has resulted in increased patient graft survival after the transplantation [8]. The indications for liver transplantation are multiple and in our study 46 cases (92%) were due to HCV related cirrhosis. In contrast to our study in which HCV related cirrhosis represent 30–50% of indications for liver transplantation in other countries [9]. Despite the improvement in the liver transplantation surgical techniques and post-operative management, there are still significant and
Portal vein pulsatility
Number of cases
Mean
Std. Deviation
Yes
No
38 12 50
26.29 16.67 23.98
4.93 2.84 6.12
4 (10.5%) 6 (50%)
34 (89.5%) 6 (50%)
Fig. 6. A 56 years old male patient underwent right lobe living donor liver transplantation due to HCV related liver cirrhosis. A and B axial CT scan showed variable sized hypodense hepatic focal lesions. A-showed the largest focal lesion in segment 8. B showed smaller hepatic focal lesions (arrow heads) with celiac lymph node (black arrow).
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Fig. 7. Imaging algorithm for evaluation of recipient complications.
serious complication as the incidence of sepsis after second exploration for biliary leakage was 100%. This doesn’t agree with a study by Londono et al. who reported that surgical intervention for biliary leakage after liver transplantation is rare and 85–100% of leakage are controlled without surgery [14]. Pleural effusion was detected in 46 cases (92%) but considered as a complication in 13 only (26%), however, pleural effusion did not lead to long term morbidity or death. In our study, four cases (8%) required drainage and this is considered relatively higher than other research done by Shandalakis where pleural effusion required drainage in 3% of patients [15]. The graft rejection incidence in our study, was 24% (12 cases), however, no graft loss or mortality seen. Ashok J et al., proved also that graft loss from acute or chronic rejection has emerged as a rarity [16]. Our results showed that the graft rejection is associated with lower velocities of the portal vein as well as increased incidence of pulsatility. Usually the portal vein velocities are high in the early postoperative days due to reduction of hepatic resistance, then it starts to be lower to normal level. The flow is usually monophasic hepatopedal flow with respiratory waveness. When histological changes of rejection occur the increased hepatic resistance results in a decrease in portal blood velocity (PBV) and change of the portal flow into pulsatile form [17]. In our study, 60% of cases with pulsatile flow were diagnosed as variable degree of rejection. Also, the mean velocities for cases with rejection was 12.89 ± 3.6 cm/s, while PBV in cases with no rejection showed mean velocity of 21.85 ± 4.1. In a Doppler finding study in acute rejection by So et al., 47 patients with biopsy proved rejection and 47 control group without rejection, found that pulsatile venous flow was seen more in cases with rejection than in cases without rejection with estimated P value of 0.001 which was significant and that was compatible to our study [18]. The hepatic artery resistive index (RI) did not change in cases of rejection. Hiroyuki et al., explained that by that rejection increased mainly the portal venous resistance and not affecting the hepatic arterial resistance which may be even decreased as a compensatory buffer mechanism [19]. The vascular complications in this research were seen in 16% of
life threatening complications that can lead to graft failure and increased patient morbidity and mortality. Imaging is very important in the early diagnosis and management of these complications. [10]. The Doppler ultrasonography is the initial imaging modality for evaluation of liver parenchyma, biliary tree and hepatic vasculature abnormalities. When an ultrasound result was indeterminate or there is persistent clinical suspicion of an abnormality, computed tomography (CT) is often performed. The major indications for CT are confirmation of patency of hepatic vascular, also assessment for hemorrhage, biliary leak and abscess. In cases of suspected biliary leak or stricture, the Ttube cholangiography and MRCP are the best noninvasive imaging tools. (Some recommend ERCP for evaluation of the biliary system but it is an invasive technique) [7]. In our study, ultrasound and duplex were done twice daily in the first week (ICU period), then once daily in the ward during the rest of the hospital stay period. CT, T tube cholangiogram and MRCP were used when needed. Invasive procedures like DSA, PTC and ERCP were done mainly for therapeutic purpose. In our study, the biliary complications were the most common complications that were seen in 13 patients (26%). Biliary stricture was found in 9 cases (18%), which considered responsible the cause of long term morbidity as about 60% of the cases occurred after six months. These results are comparable to a study in which 230 patients were evaluated for postoperative biliary tract complications and its risk factors. The overall biliary complication rate was 20.7%. The biliary leak was 7.6% and the biliary stricture 16.2%. The biliary leak occurred early and biliary strictures developed lately [11]. Zeopf et al. [12] reported a higher incidence of biliary complications as the incidence of biliary stricture was 34%, which may be due to longer follow up and routine use for MRCP. In our study, ultrasound was as effective as MRCP in the diagnosis of biliary dilatation. In one case, the MRCP diagnosed anastomotic biliary stricture without significant dilatation of the intrahepatic biliary radicles. Boraschi et al. reported a sensitivity of 93%, specificity of 92%, a positive predictive value of 86% and a negative predictive value of 96% for MRCP in detecting post-LTX biliary complications [13]. Biliary leak (which occurred by in 4 cases) in our study, was a 7
The Egyptian Journal of Radiology and Nuclear Medicine xxx (xxxx) xxx–xxx
M.Y. Tadros, A.L. Louka
References
cases. The most common vascular complications were hepatic artery thrombosis (HAT) which occurred 5 times (10% of cases) with three of them suffered graft loss (27% of mortality cases were due to HAT in our study). The cases of the HAT were diagnosed first by absence flow and Doppler signal that was confirmed by CTA. The DSA with thrombolytic therapy was effective in two patients but re-thrombosis occurred in one of them. All cases of hepatic artery thrombosis occurred in the early postoperative days. Hepatic artery stent was placed in one case with anastomotic hepatic artery stenosis. This is comparable to other researches Sanjeev et al. who found that vascular complications occurred in 25% of the cases with HAT was 11% and portal vein stenosis was 5.5% [20]. We had one patient with partial portal vein thrombosis with rejection and did not lead to mortality. Also, the patient with occluded MHV stent showed no affection on the hepatic graft, except for the area of hepatic congestion noted. CT angiography is a non-invasive method of detecting suspected hepatic arterial complications after liver transplantation. The excellent spatial resolution and fast scan times afforded with the multislice scanner allow CT angiography to depict smaller arteries, not only for patency but also for luminal stenosis. CT angiography has many advantages over other imaging modalities. Compared with conventional angiography, CT angiography is non-invasive and cheaper than conventional angiography. Compared to duplex examination, CT angiography is not as dependent on performer experience or body habitus of the patient [21] These facts have led some investigators to suggest that multislice CT angiography is more accurate than Doppler sonography in the detection of vascular complications [21]. In our study, the mortality rate was 22% and the sepsis was the leading cause for the graft failure (4 cases), followed by hepatic artery thrombosis (3 cases), biliary complications (3 cases) and primary graft dysfunction (2 cases). Two cases that died from sepsis were related to biliary complications two of them had leakage and reconstruction of the biliary anastomosis was reattempted. At the end, we suggest that the following imaging algorithm (Fig. 7) is sufficient to follow up patients as we believe it is ideal to pick up the complication with high sensitivity and accordingly expected reduction in graft failure and recipient mortality.
[1] Abt PL, Kelz R, Desai NM, et al. A Survival among pediatric liver transplant recipients: impact of segmental grafts. Liver Transpl 2004;10:1287–93. [2] Strong RW. Liver transplantation current status and future prospects. JR Coll: Surg. Edinb 2001; 46-1-8. [3] Hertl M, Cosimi AB. Liver transplantation for malignancy. Oncologist 2005;10(4):269–81. [4] Min Xu, Clavien PA. Liver transplantation. Transplantation Surgery; 2001. p. 181–183. [5] Almousa O, Michael PF. Liver Transplantation 2006; 12(2): 84–193. [6] Lee WK, Chang Silvia D, Duddalwar Vinay A, Jules MC, Warren P, Wing-Fai EL, et al. Imaging assessment of congenital and acquired abnormalities of the portal venous system. Radiographic 2011; 31. doi:http://dx.doi.org/10.1148/rg. 314105104. [7] Singh Ajay K, Arun CN, Verma Hetal A, et al. Postoperative imaging in liver transplantation: what radiologists should know. Radiographics 2010; 30: 339–351. [8] Busuttil RW, Lake JR. Role of tacrolimus in the evolution of liver transplantation. Transplantation 2004;77:S44–S51. [9] Nadalin S, Bockhorn M, Malagó M, Valentin G, Frilling A, Broelsch CE. Living donor liver transplantation, HPB (Oxford). 2006; 8(1): 10–21, doi:http://dx.doi.org/10. 1080/13651820500465626. [10] Hussain Hero K, Nghiem Hanh Vu. Imaging of hepatic transplantation. Clin Liver Disease 2002; 6(1). [11] Ye Ben Q, Chi LL, Chung ML, et al. Risk factors for biliary complications after liver transplantation. Arch Surg 2004;139:1101–5. [12] Zoepf T, Maldonado-Lopez EJ, Hilgard P, et al. Diagnosis of biliary stricture after liver transplantation: which is the best tool? World J Gastroenterol 2005;21:2945–8. [13] Boraschi P, Donati F, Gigoni R, et al. Ischemic-type biliary lesions in liver transplant recipients: evaluation with magnetic resonance cholangiography. Transplant Proc 2004;36:2744–7. [14] Londono MC, Balderramo D, Cardenas A. Management of biliary complications after orthotopic liver transplantation: the role of endoscopy. World J Gastroenterol 2008; 14(4): 493–7 [Jan 28]. [15] Shandalakis JE. Extrahepatic biliary tract anatomy. In: By John ES, Panajiotis NS, Lee JS, editors. Surgical anatomy and technique, 2nd edition, WB Saunder; 2000. p. 573–581. [16] Ashok J, Jorge R, Randeeb K, et al. Long-term survival after liver transplantation in 4,000 consecutive patients at a single center. Ann Surg 2000 Oct;232(4):490–500. [17] Hadengue A, Lebrec D, Moreau R, et al. Persistence of systemic and splanchnic hyperkinetic circulation in liver transplant patients. Hepatology 1993;17:175–8. [18] So Jung L, Kyoung WK, Jin HK, et al. Doppler sonography of patients with and without acute cellular rejection after right-lobe living donor liver transplantation. J Ultrasound Med 2011;31(5):6845–51. [19] Hiroyuki Sugimoto, Tetsuya Kiushi, Akimasa Nakao. Department of transplantation surgery. Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Japan, 2007; 35(6). [20] Sanjeev K, James H, Oliver III, David GB, Michael P. Detection of vascular complications after liver transplantations after liver transplantation early experiences with multislice CT angiography with volume rendering, AJT 2000; 175(6): 1735–9. [21] Katyal S, Oliver JH, Buck DG, Federle MP. Detection of vascular complications after liver transplantation: early experience in multislice CT angiography with volume rendering. AJR 2000;175:1735–9.
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