1991, The British Journal of Radiology, 64, 983-989
VOLUME 64 NUMBER 767
NOVEMBER 1991
The British Journal of Radiology Cholangiography in liver transplantation: a comparison of two types of biliary reconstruction By P. Holland, FRCR, E. Morris, FRCR and \ J . Buckels, FRCS Departments of Radiology and 'Surgery, Queen Elizabeth Hospital, Birmingham {Received February 1991 and in revised form June 1991) Keywords: Liver transplantation, Cholangiography, Biliary complications Abstract. Orthotopic liver transplantation has been performed in Birmingham since 1982. Two types of biliary reconstruction have been used, the choledocho-choledochostomy and the choledocho-cholecysto-choledochostomy (gallbladder (GB) conduit). A retrospective study was undertaken to compare the biliary tract complications encountered at cholangiography in these two groups to assess which reconstruction is safest. In the gallbladder (GB) conduit reconstruction, the incidence of biliary leakage (20.4%) and stricture formation (14.4%), the two most serious complications, was higher than in end-to-end duct anastomosis (11% and 10%, respectively), though these differences did not reach statistical significance. This supports evidence from other centres that the choledocho-choledochostomy is the procedure of choice to minimize biliary complications. Biliary debris (14.2%) presented additional problems and was strongly associated with biliary strictures. T-tube related problems were least troublesome. The close relationship between hepatic artery occlusion and biliary complications, particularly leakage, noted in other studies is also emphasized.
Orthotopic liver transplantation is now performed in many centres around the world, but controversy remains as to the best method of biliary reconstruction. Comparisons can be made between centres that employ different reconstructions, but each centre usually prefers the use of one type only for the majority of its patients. In Birmingham, over 350 transplantations have been performed and two principal types of biliary reconstruction have been used, the choledocho-cholecysto-choledochostomy (the GB conduit) and the choledochocholedochostomy (end-to-end donor to recipient bile duct anastomosis). All operations were performed by the same team in the same hospital, and in this study we compared the complications encountered during cholangiography in the two types of biliary reconstruction.
was used to splint the biliary anastomosis. Between 1982 and 1987, a choledocho-cholecysto-choledochostomy (GB conduit) was the preferred method of reconstruction. From 1987, a choledocho-choledochostomy (endto-end donor to recipient bile duct anastomosis) was used whenever possible. In those patients in whom neither of these methods were suitable, a choledochocholecysto-jejunostomy or choledocho-jejunostomy using a Roux loop was performed. In our centre the standard post-operative management includes a routine T-tube cholangiogram at Day 5, repeated at 3 months, just before T-tube removal.
Patients and methods
The cholangiograms of the first 300 consecutive orthotopic liver transplantations performed at the QueerT Elizabeth Hospital, Birmingham, between 1982 and 1989 were reviewed retrospectively. In total, 258 patients were transplanted (165 female, 93 male) and of these 34 received two transplants (18 female, 16 male) and four patients received three transplants (all female). The age range was 6 months to 67 years. The indications for liver transplantation are given in Table I. Two principal methods of biliary reconstruction were used, both incorporating a latex rubber T-tube, which
Primary biliary cirrhosis Acute and chronic hepatitis Malignant tumours Biliary atresia Cryptogenic cirrhosis Alcoholic cirrhosis Drug-induced hepatic failure Hepatic necrosis Neonatal hepatitis Budd Chiari (acute and chronic) a-1 antitrypsin deficiency Sclerosing cholangitis Heart-lung-liver transplants for cystic fibrosis
Address correspondence to Dr P. Holland, Consultant Radiologist, X-ray Department, Alexandra Hospital, Woodrow Drive, Redditch B98 7UB.
There were single cases of erythroprotoporphyria, haemachromatosis, Wilson's disease, tyrosinaemia and a benign liver tumour.
Vol. 64, No. 767
Table I. Indications for transplantation in the 258 patients studied 92 51 23 19 17 2 2 5 2 8 12 19 3
983
P. Holland, E. Morris and J. Buckets
Figure 2. GB conduit demonstrating duct disruption, multiple leaks and biliary debris.
Figure 1. Choledocho-choledochostomy with an anastomotic leak (arrow).
Additional cholangiography was performed as and when necessary in those patients whose clinical, biochemical or radiological findings suggested a possible underlying biliary complication. The T-tube was flushed twice daily with 10 ml of normal saline while in situ, a task the patients were taught to do themsleves. This was done to reduce the amount of biliary debris that might accumulate. All cholangiographic investigations were covered with an appropriate antibiotic chosen on the basis of recent sensitivities to organisms cultured from the T-tube. During cholangiography, every effort was 984
made tofillthe biliary system using gravity in preference to forceful injection so as to reduce the incidence of septicaemic episodes (Pitt et al, 1980). Included in the review were all T-tube cholangiograms, endoscopic retrograde cholangiograms (ERC) and percutaneous transhepatic cholangiograms performed. Features noted were biliary leaks, biliary strictures with or without obstruction, debris, stones, duct irregularity, duct disruption and tube related problems. Small leaks were defined as those that had resolved on subsequent cholangiography with minimal or no treatment. Large leaks (Figs 1 & 2) were associated with extrabiliary collections and required surgical intervention and often biliary reconstruction. Strictures (Figs 3 & 4) were defined as a significant change in calibre of the bile ducts with evidence of obstruction at cholangiography. They were divided into anastomotic and nonanastomotic groups and the relationship of the T-tube limbs to the structure was noted. Not all strictures were The British Journal of Radiology, November 1991
Biliary complications in liver transplantation
Figure 3. Choledocho-choledochostomy with an anastomotic stricture and obstruction.
associated with significant obstruction following T-tube removal. The clinical notes of any patient with a complication demonstrated at cholangiography were reviewed and details of their clinical course were noted. In particular, we looked for any evidence of hepatic artery complications, episodes of rejection or other abnormalities that may be related to the biliary complication. Results
Of the 258 patients (300 transplantations) reviewed, 41 were excluded because they had had a Roux-en-Y anastomosis (19 for biliary atresia, 17 for sclerosing cholangitis and five for other reasons). This left a group of 217 patients (252 transplantations). Of these, 62 patients (69 transplants) had no cholangiographic investigations available for review and so were also Vol. 64, No. 767
Figure 4. GB conduit with distal and proximal anastomotic strictures, and obstruction. There are bilary leaks along the T-tube tract and from the proximal anastomosis (arrow).
excluded. This left a study group of 155 patients, who had 183 transplantations. 83 transplantations used a gallbladder conduit anastomosis and 100 had an end-toend duct-to-duct anastomosis. The cholangiograms of 114 transplantations were considered normal and, to our knowledge, this group have not subsequently developed a biliary complication. Therefore, 69 transplants had evidence of a biliary complication. The incidence of these expressed as a percentage of the study group of 183 transplantations is shown in Table II. Of the 28 large leaks, 64% were associated with peribiliary or intraabdominal collections that were identified at cholangiography either using ultrasound or a 985
P. Holland, E. Morris and J. Buckets
Table II. Biliary complications encountered at cholangiography in 155 patients (183 transplants) studied. The figures are expressed as a percentage of the 183 transplantations Complications Actual number
(%)
Small leaks T-tube Anastomotic Total
11 5 16
(6.0) (2.8) (8.8)
Large leaks T-tube Anastomotic Non-anastomotic Multiple Total
7 9 — 12 28
(3.9) (4.9) (6.6) (15.4)
Strictures Anastomotic Non-anastomotic Multiple Total
15 4 3 22
(8.3) (2.2) (1.6) (12.1)
CT scan. In many of these patients, percutaneous drainage was established before definitive surgical repair was performed. No isolated non-anastomotic leaks were identified, but in those cases where multiple leaks were observed, the disruption of the biliary system was such that the actual sites of leakage were difficult to determine, though some were undoubtedly non-anastomotic. Biliary strictures occurred in 22 transplants (12.1%). Most were anastomotic, with four of the 22 at nonanastomotic sites and three of the 22 being multiple
strictures. In nine of the 22 transplants (41%) there was significant obstruction of the biliary tract requiring biliary intervention or surgical reconstruction. In the remainder, the strictures were not associated with obstruction following T-tube removal, as confirmed by endoscopic retrograde cholangiography, biochemical monitoring or DISIDA isotope scanning. Biliary calculi were identified in six patients and all were associated with a more distal stricture. The results were then analysed in terms of the type of biliary reconstruction used. Group I contained 83 transplants and consisted of those patients who had had a choledocho-cholecysto-choledochostomy (GB conduit). The 100 transplants in Group II had a choledochocholedochostomy (end-to-end anastomosis). The comparative results are shown in Table III. Of note are the higher incidences of the clinically significant large leaks and of the strictures in Group I. However, chi-squared analysis of these results showed that these differences did not reach statistical significance at the p = 0.05 level (p was between 0.05 and 0.1). Of the non-anastomotic strictures, those in Group I were both closely related to the position of the T-tube tip. Of those in Group II, no such relationship was noted in one, whilst the other occurred at the site of T-tube insertion. In Group I 50% of strictures were associated with obstruction after T-tube removal, compared with only 30% in Group II. Overall, debris or inspissated bile was identified in 26 (14.2%) transplants (Fig. 5), of which 15 were in Group I and 11 were in Group II. In 20 (77%) of these patients there was co-existing biliary leakage, stricture formation or both. Four transplants had tube related problems, namely tube migration (3) and a kinked tube (1). The latter
Table III. Comparison of biliary complications in the choledocho-cholecysto-choledochostomy and choledocho-choledochostomy groups. Figures expressed as a percentage of the transplants in each group Group I
Group II
Choledocho-cholecysto-choledochostomy (GB)
Choledocho-choledochostomy
Small leaks T-tube Anastomotic Total
(6.0) (1.2) (7.2)
4 10
(6.0) (4.0) (10.0)
Large leaks T-tube Anastomotic Non-anastomotic Multiple Total
5 5
(6.0) (6.0)
2 3
(2.0) (3.0)
7 17
(8.4) (20.4)
6 11
(6.0) (11.0)
Strictures Anastomotic Non-anastomotic Multiple Total
2 2 12
(9.6) (2.4) (2.4) (14.4)
7 2 1 10
(7.0) (2.0) (1.0) (10.0)
986
The British Journal of Radiology, November 1991
Biliary complications in liver transplantation Table IV. Biliary complications in which possible aetiological factors can be identified in 22 patients Complication
Aetiology Rejection Arterial complications
Leak
Stricture
Debris
10 9
6 1
2 1
In seven of these patients more than one possible cause was identified. In 25 patients no cause was found.
Figure 5. GB conduit with biliary debris within the conduit itself.
caused obstruction within the biliary tract until it was removed. In none of these patients was there a biliary problem after the T-tube was removed. In those patients with biliary debris, a leak, or a stricture, a possible relationship between the complication and episodes of rejection, or an hepatic artery complication was sought by reviewing the patients subsequent clinical course. This group comprised of 47 patients (27 in Group I, 20 in Group II). In 25 cases no such cause for the post-operative complication could be identified. The results of the remaining 22 patients are shown in Table IV. Overall, 11 out of 22 biliary complications were associated with acute rejection episodes, as indicated by liver biopsy and response to increased immunosuppression. Seven out of the 22 were associated with hepatic artery complications (occlusion, stenosis or aneurysm). In four patients, both rejection and arterial complications were found. No definite relationship between strictures and chronic rejection was noted. Discussion
Since the first human liver transplantation in 1963 (Starzl et al, 1963) the life expectancy of patients has Vol. 64, No. 767
improved, mainly as a result of better patient selection, refined organ procurement and preservation, meticulous surgical grafting techniques, the introduction of cyclosporin and improved post-operative management (Dominguez et al, 1986). This has resulted in substantial improvement in results from all centres. Despite this, biliary tract complications remain a major cause of post-transplantation morbidity. Ultrasound is useful in detecting biliary obstruction, though its reliability in excluding other biliary complications is poor (Zemel et al, 1988). Biliary scintigraphy provides an excellent means of differentiating obstruction from other causes of cholestasis (Lecklitner et al, 1986; Lee et al, 1986; Loken et al, 1986), but may also be unreliable at identifying leakage. Therefore, direct visualization of the biliary tract using tube cholangiography, percutaneous cholangiography or ERC remains the most accurate means of diagnosing a biliary tract problem (Zajko et al, 1985). Many techniques for biliary reconstruction have been used and debate still exists as to the most appropriate procedure. Choledocho-choledochostomy is popular and reported complication rates, usually expressed in terms of significant biliary leaks and strictures, vary from 17% to 48% (Iwatsuki et al, 1983; Neuhaus et al, 1984; Krom et al, 1985; Lerut et al, 1987). Overall, 21% of the transplants in our choledocho-choledochostomy series developed a complication using these criteria, comparing favourably with other results. The gallbladder conduit was considered an important development in the early years of liver transplantation when biliary leakage was a major cause of morbidity and mortality. Despite this, the choledochocholecysto-choledochostomy (GB conduit) has been little used in most centres other than our own and the Cambridge/King's College Hospital programme (Evans et al, 1990). The Cambridge/King's group identified biliary complications in 76 out of 148 (41%) of a series of transplants where a post-operative problem was suspected and cholangiography consequently performed. The commonest abnormality was biliary stricture formation (63%), with bile leakage present in only 18%. Halff et al (1989) similarly noted a high incidence of complication with the GB conduit (50%), though this reconstruction was used in only 10 of over 2000 transplantations. In this study, we demonstrated significant 987
P. Holland, E. Morris and J. Buckels
leaks and strictures in 35% of the GB conduit group. We believe that in our centre, the almost unique situation of having two large groups of alternative biliary reconstructions performed by the same team allowed us to compare reliably the two procedures. We accept that the retrospective, non-randomized nature of the study, together with improvements in transplantation technique over the 8 year study period, may make interpretation of findings related to the earlier gallbladder conduit group more difficult. Allowing for this, and although the differences between complication rates in the choledocho-choledochostomy and GB conduit groups did not reach statistical significance, we feel that the choledocho-choledochostomy should be the procedure of choice whenever possible. Biliary leakage in the immunosuppressed patient is a serious complication (Rolles, 1987) and in our experience was the most frequent in both types of reconstruction. Many of the small leaks, and a number of unsuspected large leaks, were discovered at routine cholangiography. To what extent early diagnosis altered morbidity is not known, but frequent cholangiographic review or speedy surgical intervention probably prevented more serious sequelae developing. No appreciable differences were seen regarding the site of leakage between the two types of reconstruction. No solitary non-anastomotic leak was identified, though several were seen in the 13 cases of multiple biliary leaks (or duct disruption). Of these cases, six were associated with hepatic artery occlusion and four with allograft rejection, emphasizing the close association of biliary abnormalities with vascular complications (Zajko et al, 1987). Ultrasound as a screen for biliary leakage is unreliable, despite the fact that most leaks are associated with peribiliary or intrahepatic collections (Zemel et al, 1988). Although the rate of stricture formation was higher in the GB conduit reconstruction, our experience did not reflect the findings of Evans et al (1990), who demonstrated strictures in 63% of their cases, over half of which were non-anastomotic in site. They identified a number of strictures that appeared to be related to the position of the T-tube limbs; we could identify only two cases (both GB conduits) in which this association was possible. We did, however, note that a large number (56.5%) of strictures identified at cholangiography did not demonstrate evidence of biliary obstruction following T-tube removal, underlining the role that the T-tube plays in obstruction whilst in situ. In addition, numerous cases were seen of biliary debris or inspissated bile complicating and adding to the obstruction of the biliary tree at the stricture level. The high coexistence of biliary debris with stricture formation suggests a mechanical aetiological factor (Starzl et al, 1977), though bile composition changes said to occur in posttransplant patients may play a part (Waldram et al, 1975). There is also evidence that the two complications may have a common ischaemic aetiology (McMaster et al, 1978). In several patients without a stricture, inspissated bile proved to be a problem after T-tube removal 988
and, for these, endoscopic papillotomy and balloon catheter removal of the debris was very successful. The relationship that exists between biliary complications, vascular complications and episodes of rejection is still not clear. Certainly hepatic artery occlusion is associated with both biliary leakage and stricture formation (Zajko et al, 1987), and may also be related to acute rejection (White et al, 1987), though which occursfirstis not certain. Doppler ultrasound as a screening examination of the hepatic vessels is sensitive and accurate (Segel et al, 1986; Flint et al, 1988) and provides a means of selecting patients who require arteriography. Likewise, cholangiographic changes may provide evidence supporting the need for angiography (Zajko et al, 1987) or liver biopsy (Bauman et al, 1989) in the evaluation of hepatic dysfunction after transplantation. Of the 47 patients in this study with a serious biliary complication, 26 had a possible aetiological cause identified, the strongest association being between leakage and both rejection and hepatic artery occlusion. In conclusion, when comparing complications identified at cholangiography in two principal types of biliary reconstruction used during liver transplantation within the same centre, it seems that the choledocho-choledochostomy should be the procedure of choice. Acknowledgments We would like to thank the clerical staff in the X-ray department and on the liver transplant unit of the Queen Elizabeth Hospital for their invaluable help. We are grateful to Mr P. McMaster for allowing us to use the films and data of the liver unit patients. References BAUMAN, J., CAMPBELL, W. L., DEMETRIS, A. J. & ZAJKO,
A. B., 1989. Intrahepatic cholangiographic abnormalities in liver transplants: correlation with biopsy evidence of rejection and other disorders. American Journal of Roentgenology, 152, 275-279. DOMINGUEZ,
R.,
CUERVAS-MONS,
V.,
VAN THIEL,
D. H.,
LECKY, J. W. & STARZL, T. E., 1986. Radiographic features
of liver allograft rejection. Gastrointestinal Radiology, 11, 326-329. EVANS, R. A., RABY, N. D., O'GRADY, J. G. O., KARANI, H. B., NUNNERLEY, H. B., CALNE, R. Y. & WILLIAMS, R.,
1990. Biliary complications following orthotopic liver transplantation. Clinical Radiology, 41, 190-194. FLINT, E. W., SUMKIN, J. H., ZAJKO, A. B. & BOWEN, A. D.,
1988. Duplex sonography of hepatic artery thrombosis after liver transplantation. American Journal of Roentgenology, 151, 481^83. HALFF, G., TODO, S., HALL, R. & STARZL, T. E., 1989. Late
complications with GB conduit biliary reconstruction after liver transplantation. Transplantation, 48, 537-539. IWATSUKI, S., SHAW, B. W. & STARZL, T. E., 1983. Bilary tract
complications in liver transplantation under cyclosporinsteroid therapy. Transplant Proceedings, 15, 1288-1291. KROM, R. A. F., KINGMA, L. M., HAAGSMA, E. B., WESENHAGEN, H., SLOOFT, M. J. H. & GIPS, C. H., 1985.
Choledochocholedochostomy; a relatively safe procedure in orthotopic liver transplantation. Surgery, 97, 552-556. LERUT, J., GORDON, R. D., IWATSUKI, S., ESQUIVEL, C. O., TODO, S., TZAKIS, A. & STARZL, T. E., 1987. Biliary tract
The British Journal of Radiology, November 1991
Biliary complications in liver transplantation complications in human orthotopic liver transplantation. Transplantation, 43, 47-51. LECKLITNER,
M. L., AUSTIN,
A. R.,
BENEDETTO,
A. R.
&
GROWCOCK, G. W., 1986. Positive predictive value of cholescintigraphy in common bile duct obstruction. Journal of Nuclear Medicine, 27, 1403-1406. LEE, A. W., RAM, U. D., SHIH, W. J. & MURPHY, K., 1986.
Technetium-99m BIDA biliary scintigraphy in the evaluation of the jaundiced patient. Journal of Nuclear Medicine, 27, 1407-1412. LOKEN, M. K., FISCHER, N. L., BOURDREAU, R. J. & NAJARIAN,
J. S., 1986. Scintigraphic evaluation of liver transplant function. Journal of Nuclear Medicine, 27, 451-459. MCMASTER, P., HERBERTSON, B., CUSICK, C , CALNE, R. Y. &
Homotransplantation of the liver in humans. Gynaecology and Obstetrics, 117, 659-676.
Surgery,
STARZL, T. E., PUTNAM, C. W., HANSBROUGH, J. F., PORTER,
K. A. & REID, H. A. S., 1977. Biliary complications after liver transplantation: with special reference to the biliary cast syndrome and techniques of secondary duct repair. Surgery, 81, 212-221. WALDRAM, R., WILLIAMS, R. & CALNE, R. Y.,
1975. Bile
composition and bile cast formation after transplantation of the liver in man. Transplantation, 19, 382-387. WHITE, R. M., ZAJKO, A. B., DEMETRIS, A. J., BRON, K. M.,
DEKKER, A. & STARZL, T. E., 1987. Liver
transplant
liver
rejection: angiographic findings in 35 patients. American Journal of Roentgenology, 148, 1095-1098.
RINGE, B., LANCHART, W. &
ZAJKO, A. B., CAMPBELL, W. L., BRON, K. M., LECKY, J. W., IWATSUKI, S., SHAW, B. W. & STARZL, T. E., 1985.
WILLIAMS, R., 1978. Biliary sludge following transplantation in man. Transplantation, 25, 56-62. NEUHAUS, P., BROLSCH, C ,
STARZL, T. E., MARCHIORO, T. L., VON KAULLA, K. N., HERMANN, G., BRITTAIN, R. S. & WADDELL, W. R., 1963.
PICHLMAYR, R., 1984. Results of biliary reconstruction after liver transplantation. Transplantation Proceedings, 16, 1225-1227. PITT, H. A., POSTIER, R.G. & CAMOERON, J. L., 1980. Post
Cholangiography and interventional biliary radiology in adult liver transplantation. American Journal of Roentgenology, 144, 127-133.
operative T-tube cholangiography. Is antibiotic coverage necessary? Annals of Surgery, 191, 30-34. ROLLES, K., 1987. Biliary tract complications. In Liver Transplantation, ed. by R. Calne, (Grune and Stratton, London), pp. 473-483.
ZAJKO, A. B., CAMPBELL, W. L., LOGSDON, G. A., BRON, K. M., TZAKIS, A., ESQUIVEL, C. O. & STARZL, T. E., 1987.
SEGEL, M. C , ZAJKO, A. B., BOWEN, A. D., BRON, K. M., SKOLNICK, M. L., PENKROT, R. J. & STARZL, T. E., 1986.
ZEMEL, G., ZAJKO, A. B., SKOLNICK, M. L., BRON, K. M. &
Hepatic artery thrombosis after liver transplantation: radiological evaluation. American Journal of Roentgenology, 146, 137-141.
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Cholangiographic findings in hepatic artery occlusion after liver transplantation. American Journal of Roentgenology, 149, 485-489. CAMPBELL, W. L., 1988. The role of sonography and transhepatic cholangiography in the diagnosis of biliary complications after liver transplantation. American Journal of Roentgenology, 151, 943-946.
989
VOLUME 64 NUMBER 767
NOVEMBER 1991
The British Journal of Radiology Cholangiography in liver transplantation: a comparison of two types of biliary reconstruction By P. Holland, FRCR, E. Morris, FRCR and \ J . Buckels, FRCS Departments of Radiology and 'Surgery, Queen Elizabeth Hospital, Birmingham {Received February 1991 and in revised form June 1991) Keywords: Liver transplantation, Cholangiography, Biliary complications Abstract. Orthotopic liver transplantation has been performed in Birmingham since 1982. Two types of biliary reconstruction have been used, the choledocho-choledochostomy and the choledocho-cholecysto-choledochostomy (gallbladder (GB) conduit). A retrospective study was undertaken to compare the biliary tract complications encountered at cholangiography in these two groups to assess which reconstruction is safest. In the gallbladder (GB) conduit reconstruction, the incidence of biliary leakage (20.4%) and stricture formation (14.4%), the two most serious complications, was higher than in end-to-end duct anastomosis (11% and 10%, respectively), though these differences did not reach statistical significance. This supports evidence from other centres that the choledocho-choledochostomy is the procedure of choice to minimize biliary complications. Biliary debris (14.2%) presented additional problems and was strongly associated with biliary strictures. T-tube related problems were least troublesome. The close relationship between hepatic artery occlusion and biliary complications, particularly leakage, noted in other studies is also emphasized.
Orthotopic liver transplantation is now performed in many centres around the world, but controversy remains as to the best method of biliary reconstruction. Comparisons can be made between centres that employ different reconstructions, but each centre usually prefers the use of one type only for the majority of its patients. In Birmingham, over 350 transplantations have been performed and two principal types of biliary reconstruction have been used, the choledocho-cholecysto-choledochostomy (the GB conduit) and the choledochocholedochostomy (end-to-end donor to recipient bile duct anastomosis). All operations were performed by the same team in the same hospital, and in this study we compared the complications encountered during cholangiography in the two types of biliary reconstruction.
was used to splint the biliary anastomosis. Between 1982 and 1987, a choledocho-cholecysto-choledochostomy (GB conduit) was the preferred method of reconstruction. From 1987, a choledocho-choledochostomy (endto-end donor to recipient bile duct anastomosis) was used whenever possible. In those patients in whom neither of these methods were suitable, a choledochocholecysto-jejunostomy or choledocho-jejunostomy using a Roux loop was performed. In our centre the standard post-operative management includes a routine T-tube cholangiogram at Day 5, repeated at 3 months, just before T-tube removal.
Patients and methods
The cholangiograms of the first 300 consecutive orthotopic liver transplantations performed at the QueerT Elizabeth Hospital, Birmingham, between 1982 and 1989 were reviewed retrospectively. In total, 258 patients were transplanted (165 female, 93 male) and of these 34 received two transplants (18 female, 16 male) and four patients received three transplants (all female). The age range was 6 months to 67 years. The indications for liver transplantation are given in Table I. Two principal methods of biliary reconstruction were used, both incorporating a latex rubber T-tube, which
Primary biliary cirrhosis Acute and chronic hepatitis Malignant tumours Biliary atresia Cryptogenic cirrhosis Alcoholic cirrhosis Drug-induced hepatic failure Hepatic necrosis Neonatal hepatitis Budd Chiari (acute and chronic) a-1 antitrypsin deficiency Sclerosing cholangitis Heart-lung-liver transplants for cystic fibrosis
Address correspondence to Dr P. Holland, Consultant Radiologist, X-ray Department, Alexandra Hospital, Woodrow Drive, Redditch B98 7UB.
There were single cases of erythroprotoporphyria, haemachromatosis, Wilson's disease, tyrosinaemia and a benign liver tumour.
Vol. 64, No. 767
Table I. Indications for transplantation in the 258 patients studied 92 51 23 19 17 2 2 5 2 8 12 19 3
983
P. Holland, E. Morris and J. Buckets
Figure 2. GB conduit demonstrating duct disruption, multiple leaks and biliary debris.
Figure 1. Choledocho-choledochostomy with an anastomotic leak (arrow).
Additional cholangiography was performed as and when necessary in those patients whose clinical, biochemical or radiological findings suggested a possible underlying biliary complication. The T-tube was flushed twice daily with 10 ml of normal saline while in situ, a task the patients were taught to do themsleves. This was done to reduce the amount of biliary debris that might accumulate. All cholangiographic investigations were covered with an appropriate antibiotic chosen on the basis of recent sensitivities to organisms cultured from the T-tube. During cholangiography, every effort was 984
made tofillthe biliary system using gravity in preference to forceful injection so as to reduce the incidence of septicaemic episodes (Pitt et al, 1980). Included in the review were all T-tube cholangiograms, endoscopic retrograde cholangiograms (ERC) and percutaneous transhepatic cholangiograms performed. Features noted were biliary leaks, biliary strictures with or without obstruction, debris, stones, duct irregularity, duct disruption and tube related problems. Small leaks were defined as those that had resolved on subsequent cholangiography with minimal or no treatment. Large leaks (Figs 1 & 2) were associated with extrabiliary collections and required surgical intervention and often biliary reconstruction. Strictures (Figs 3 & 4) were defined as a significant change in calibre of the bile ducts with evidence of obstruction at cholangiography. They were divided into anastomotic and nonanastomotic groups and the relationship of the T-tube limbs to the structure was noted. Not all strictures were The British Journal of Radiology, November 1991
Biliary complications in liver transplantation
Figure 3. Choledocho-choledochostomy with an anastomotic stricture and obstruction.
associated with significant obstruction following T-tube removal. The clinical notes of any patient with a complication demonstrated at cholangiography were reviewed and details of their clinical course were noted. In particular, we looked for any evidence of hepatic artery complications, episodes of rejection or other abnormalities that may be related to the biliary complication. Results
Of the 258 patients (300 transplantations) reviewed, 41 were excluded because they had had a Roux-en-Y anastomosis (19 for biliary atresia, 17 for sclerosing cholangitis and five for other reasons). This left a group of 217 patients (252 transplantations). Of these, 62 patients (69 transplants) had no cholangiographic investigations available for review and so were also Vol. 64, No. 767
Figure 4. GB conduit with distal and proximal anastomotic strictures, and obstruction. There are bilary leaks along the T-tube tract and from the proximal anastomosis (arrow).
excluded. This left a study group of 155 patients, who had 183 transplantations. 83 transplantations used a gallbladder conduit anastomosis and 100 had an end-toend duct-to-duct anastomosis. The cholangiograms of 114 transplantations were considered normal and, to our knowledge, this group have not subsequently developed a biliary complication. Therefore, 69 transplants had evidence of a biliary complication. The incidence of these expressed as a percentage of the study group of 183 transplantations is shown in Table II. Of the 28 large leaks, 64% were associated with peribiliary or intraabdominal collections that were identified at cholangiography either using ultrasound or a 985
P. Holland, E. Morris and J. Buckets
Table II. Biliary complications encountered at cholangiography in 155 patients (183 transplants) studied. The figures are expressed as a percentage of the 183 transplantations Complications Actual number
(%)
Small leaks T-tube Anastomotic Total
11 5 16
(6.0) (2.8) (8.8)
Large leaks T-tube Anastomotic Non-anastomotic Multiple Total
7 9 — 12 28
(3.9) (4.9) (6.6) (15.4)
Strictures Anastomotic Non-anastomotic Multiple Total
15 4 3 22
(8.3) (2.2) (1.6) (12.1)
CT scan. In many of these patients, percutaneous drainage was established before definitive surgical repair was performed. No isolated non-anastomotic leaks were identified, but in those cases where multiple leaks were observed, the disruption of the biliary system was such that the actual sites of leakage were difficult to determine, though some were undoubtedly non-anastomotic. Biliary strictures occurred in 22 transplants (12.1%). Most were anastomotic, with four of the 22 at nonanastomotic sites and three of the 22 being multiple
strictures. In nine of the 22 transplants (41%) there was significant obstruction of the biliary tract requiring biliary intervention or surgical reconstruction. In the remainder, the strictures were not associated with obstruction following T-tube removal, as confirmed by endoscopic retrograde cholangiography, biochemical monitoring or DISIDA isotope scanning. Biliary calculi were identified in six patients and all were associated with a more distal stricture. The results were then analysed in terms of the type of biliary reconstruction used. Group I contained 83 transplants and consisted of those patients who had had a choledocho-cholecysto-choledochostomy (GB conduit). The 100 transplants in Group II had a choledochocholedochostomy (end-to-end anastomosis). The comparative results are shown in Table III. Of note are the higher incidences of the clinically significant large leaks and of the strictures in Group I. However, chi-squared analysis of these results showed that these differences did not reach statistical significance at the p = 0.05 level (p was between 0.05 and 0.1). Of the non-anastomotic strictures, those in Group I were both closely related to the position of the T-tube tip. Of those in Group II, no such relationship was noted in one, whilst the other occurred at the site of T-tube insertion. In Group I 50% of strictures were associated with obstruction after T-tube removal, compared with only 30% in Group II. Overall, debris or inspissated bile was identified in 26 (14.2%) transplants (Fig. 5), of which 15 were in Group I and 11 were in Group II. In 20 (77%) of these patients there was co-existing biliary leakage, stricture formation or both. Four transplants had tube related problems, namely tube migration (3) and a kinked tube (1). The latter
Table III. Comparison of biliary complications in the choledocho-cholecysto-choledochostomy and choledocho-choledochostomy groups. Figures expressed as a percentage of the transplants in each group Group I
Group II
Choledocho-cholecysto-choledochostomy (GB)
Choledocho-choledochostomy
Small leaks T-tube Anastomotic Total
(6.0) (1.2) (7.2)
4 10
(6.0) (4.0) (10.0)
Large leaks T-tube Anastomotic Non-anastomotic Multiple Total
5 5
(6.0) (6.0)
2 3
(2.0) (3.0)
7 17
(8.4) (20.4)
6 11
(6.0) (11.0)
Strictures Anastomotic Non-anastomotic Multiple Total
2 2 12
(9.6) (2.4) (2.4) (14.4)
7 2 1 10
(7.0) (2.0) (1.0) (10.0)
986
The British Journal of Radiology, November 1991
Biliary complications in liver transplantation Table IV. Biliary complications in which possible aetiological factors can be identified in 22 patients Complication
Aetiology Rejection Arterial complications
Leak
Stricture
Debris
10 9
6 1
2 1
In seven of these patients more than one possible cause was identified. In 25 patients no cause was found.
Figure 5. GB conduit with biliary debris within the conduit itself.
caused obstruction within the biliary tract until it was removed. In none of these patients was there a biliary problem after the T-tube was removed. In those patients with biliary debris, a leak, or a stricture, a possible relationship between the complication and episodes of rejection, or an hepatic artery complication was sought by reviewing the patients subsequent clinical course. This group comprised of 47 patients (27 in Group I, 20 in Group II). In 25 cases no such cause for the post-operative complication could be identified. The results of the remaining 22 patients are shown in Table IV. Overall, 11 out of 22 biliary complications were associated with acute rejection episodes, as indicated by liver biopsy and response to increased immunosuppression. Seven out of the 22 were associated with hepatic artery complications (occlusion, stenosis or aneurysm). In four patients, both rejection and arterial complications were found. No definite relationship between strictures and chronic rejection was noted. Discussion
Since the first human liver transplantation in 1963 (Starzl et al, 1963) the life expectancy of patients has Vol. 64, No. 767
improved, mainly as a result of better patient selection, refined organ procurement and preservation, meticulous surgical grafting techniques, the introduction of cyclosporin and improved post-operative management (Dominguez et al, 1986). This has resulted in substantial improvement in results from all centres. Despite this, biliary tract complications remain a major cause of post-transplantation morbidity. Ultrasound is useful in detecting biliary obstruction, though its reliability in excluding other biliary complications is poor (Zemel et al, 1988). Biliary scintigraphy provides an excellent means of differentiating obstruction from other causes of cholestasis (Lecklitner et al, 1986; Lee et al, 1986; Loken et al, 1986), but may also be unreliable at identifying leakage. Therefore, direct visualization of the biliary tract using tube cholangiography, percutaneous cholangiography or ERC remains the most accurate means of diagnosing a biliary tract problem (Zajko et al, 1985). Many techniques for biliary reconstruction have been used and debate still exists as to the most appropriate procedure. Choledocho-choledochostomy is popular and reported complication rates, usually expressed in terms of significant biliary leaks and strictures, vary from 17% to 48% (Iwatsuki et al, 1983; Neuhaus et al, 1984; Krom et al, 1985; Lerut et al, 1987). Overall, 21% of the transplants in our choledocho-choledochostomy series developed a complication using these criteria, comparing favourably with other results. The gallbladder conduit was considered an important development in the early years of liver transplantation when biliary leakage was a major cause of morbidity and mortality. Despite this, the choledochocholecysto-choledochostomy (GB conduit) has been little used in most centres other than our own and the Cambridge/King's College Hospital programme (Evans et al, 1990). The Cambridge/King's group identified biliary complications in 76 out of 148 (41%) of a series of transplants where a post-operative problem was suspected and cholangiography consequently performed. The commonest abnormality was biliary stricture formation (63%), with bile leakage present in only 18%. Halff et al (1989) similarly noted a high incidence of complication with the GB conduit (50%), though this reconstruction was used in only 10 of over 2000 transplantations. In this study, we demonstrated significant 987
P. Holland, E. Morris and J. Buckels
leaks and strictures in 35% of the GB conduit group. We believe that in our centre, the almost unique situation of having two large groups of alternative biliary reconstructions performed by the same team allowed us to compare reliably the two procedures. We accept that the retrospective, non-randomized nature of the study, together with improvements in transplantation technique over the 8 year study period, may make interpretation of findings related to the earlier gallbladder conduit group more difficult. Allowing for this, and although the differences between complication rates in the choledocho-choledochostomy and GB conduit groups did not reach statistical significance, we feel that the choledocho-choledochostomy should be the procedure of choice whenever possible. Biliary leakage in the immunosuppressed patient is a serious complication (Rolles, 1987) and in our experience was the most frequent in both types of reconstruction. Many of the small leaks, and a number of unsuspected large leaks, were discovered at routine cholangiography. To what extent early diagnosis altered morbidity is not known, but frequent cholangiographic review or speedy surgical intervention probably prevented more serious sequelae developing. No appreciable differences were seen regarding the site of leakage between the two types of reconstruction. No solitary non-anastomotic leak was identified, though several were seen in the 13 cases of multiple biliary leaks (or duct disruption). Of these cases, six were associated with hepatic artery occlusion and four with allograft rejection, emphasizing the close association of biliary abnormalities with vascular complications (Zajko et al, 1987). Ultrasound as a screen for biliary leakage is unreliable, despite the fact that most leaks are associated with peribiliary or intrahepatic collections (Zemel et al, 1988). Although the rate of stricture formation was higher in the GB conduit reconstruction, our experience did not reflect the findings of Evans et al (1990), who demonstrated strictures in 63% of their cases, over half of which were non-anastomotic in site. They identified a number of strictures that appeared to be related to the position of the T-tube limbs; we could identify only two cases (both GB conduits) in which this association was possible. We did, however, note that a large number (56.5%) of strictures identified at cholangiography did not demonstrate evidence of biliary obstruction following T-tube removal, underlining the role that the T-tube plays in obstruction whilst in situ. In addition, numerous cases were seen of biliary debris or inspissated bile complicating and adding to the obstruction of the biliary tree at the stricture level. The high coexistence of biliary debris with stricture formation suggests a mechanical aetiological factor (Starzl et al, 1977), though bile composition changes said to occur in posttransplant patients may play a part (Waldram et al, 1975). There is also evidence that the two complications may have a common ischaemic aetiology (McMaster et al, 1978). In several patients without a stricture, inspissated bile proved to be a problem after T-tube removal 988
and, for these, endoscopic papillotomy and balloon catheter removal of the debris was very successful. The relationship that exists between biliary complications, vascular complications and episodes of rejection is still not clear. Certainly hepatic artery occlusion is associated with both biliary leakage and stricture formation (Zajko et al, 1987), and may also be related to acute rejection (White et al, 1987), though which occursfirstis not certain. Doppler ultrasound as a screening examination of the hepatic vessels is sensitive and accurate (Segel et al, 1986; Flint et al, 1988) and provides a means of selecting patients who require arteriography. Likewise, cholangiographic changes may provide evidence supporting the need for angiography (Zajko et al, 1987) or liver biopsy (Bauman et al, 1989) in the evaluation of hepatic dysfunction after transplantation. Of the 47 patients in this study with a serious biliary complication, 26 had a possible aetiological cause identified, the strongest association being between leakage and both rejection and hepatic artery occlusion. In conclusion, when comparing complications identified at cholangiography in two principal types of biliary reconstruction used during liver transplantation within the same centre, it seems that the choledocho-choledochostomy should be the procedure of choice. Acknowledgments We would like to thank the clerical staff in the X-ray department and on the liver transplant unit of the Queen Elizabeth Hospital for their invaluable help. We are grateful to Mr P. McMaster for allowing us to use the films and data of the liver unit patients. References BAUMAN, J., CAMPBELL, W. L., DEMETRIS, A. J. & ZAJKO,
A. B., 1989. Intrahepatic cholangiographic abnormalities in liver transplants: correlation with biopsy evidence of rejection and other disorders. American Journal of Roentgenology, 152, 275-279. DOMINGUEZ,
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LECKY, J. W. & STARZL, T. E., 1986. Radiographic features
of liver allograft rejection. Gastrointestinal Radiology, 11, 326-329. EVANS, R. A., RABY, N. D., O'GRADY, J. G. O., KARANI, H. B., NUNNERLEY, H. B., CALNE, R. Y. & WILLIAMS, R.,
1990. Biliary complications following orthotopic liver transplantation. Clinical Radiology, 41, 190-194. FLINT, E. W., SUMKIN, J. H., ZAJKO, A. B. & BOWEN, A. D.,
1988. Duplex sonography of hepatic artery thrombosis after liver transplantation. American Journal of Roentgenology, 151, 481^83. HALFF, G., TODO, S., HALL, R. & STARZL, T. E., 1989. Late
complications with GB conduit biliary reconstruction after liver transplantation. Transplantation, 48, 537-539. IWATSUKI, S., SHAW, B. W. & STARZL, T. E., 1983. Bilary tract
complications in liver transplantation under cyclosporinsteroid therapy. Transplant Proceedings, 15, 1288-1291. KROM, R. A. F., KINGMA, L. M., HAAGSMA, E. B., WESENHAGEN, H., SLOOFT, M. J. H. & GIPS, C. H., 1985.
Choledochocholedochostomy; a relatively safe procedure in orthotopic liver transplantation. Surgery, 97, 552-556. LERUT, J., GORDON, R. D., IWATSUKI, S., ESQUIVEL, C. O., TODO, S., TZAKIS, A. & STARZL, T. E., 1987. Biliary tract
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M. L., AUSTIN,
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GROWCOCK, G. W., 1986. Positive predictive value of cholescintigraphy in common bile duct obstruction. Journal of Nuclear Medicine, 27, 1403-1406. LEE, A. W., RAM, U. D., SHIH, W. J. & MURPHY, K., 1986.
Technetium-99m BIDA biliary scintigraphy in the evaluation of the jaundiced patient. Journal of Nuclear Medicine, 27, 1407-1412. LOKEN, M. K., FISCHER, N. L., BOURDREAU, R. J. & NAJARIAN,
J. S., 1986. Scintigraphic evaluation of liver transplant function. Journal of Nuclear Medicine, 27, 451-459. MCMASTER, P., HERBERTSON, B., CUSICK, C , CALNE, R. Y. &
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STARZL, T. E., PUTNAM, C. W., HANSBROUGH, J. F., PORTER,
K. A. & REID, H. A. S., 1977. Biliary complications after liver transplantation: with special reference to the biliary cast syndrome and techniques of secondary duct repair. Surgery, 81, 212-221. WALDRAM, R., WILLIAMS, R. & CALNE, R. Y.,
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composition and bile cast formation after transplantation of the liver in man. Transplantation, 19, 382-387. WHITE, R. M., ZAJKO, A. B., DEMETRIS, A. J., BRON, K. M.,
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WILLIAMS, R., 1978. Biliary sludge following transplantation in man. Transplantation, 25, 56-62. NEUHAUS, P., BROLSCH, C ,
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PICHLMAYR, R., 1984. Results of biliary reconstruction after liver transplantation. Transplantation Proceedings, 16, 1225-1227. PITT, H. A., POSTIER, R.G. & CAMOERON, J. L., 1980. Post
Cholangiography and interventional biliary radiology in adult liver transplantation. American Journal of Roentgenology, 144, 127-133.
operative T-tube cholangiography. Is antibiotic coverage necessary? Annals of Surgery, 191, 30-34. ROLLES, K., 1987. Biliary tract complications. In Liver Transplantation, ed. by R. Calne, (Grune and Stratton, London), pp. 473-483.
ZAJKO, A. B., CAMPBELL, W. L., LOGSDON, G. A., BRON, K. M., TZAKIS, A., ESQUIVEL, C. O. & STARZL, T. E., 1987.
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Cholangiographic findings in hepatic artery occlusion after liver transplantation. American Journal of Roentgenology, 149, 485-489. CAMPBELL, W. L., 1988. The role of sonography and transhepatic cholangiography in the diagnosis of biliary complications after liver transplantation. American Journal of Roentgenology, 151, 943-946.
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