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\begin{document}

\title{Diagnostic and Therapeutic Management Algorithm for Biliary
Complications in Living Liver Donors}



\author[1]{Sezai Yilmaz}%
\author[1]{Sami Akbulut}%
\author[1]{Sertac Usta}%
\author[1]{Oguzhan Ozsay}%
\author[1]{Tevfik Tolga Sahin}%
\author[1]{Kemal Baris Sarici}%
\author[1]{Adil Baskiran}%
\author[1]{Fatih Gonultas}%
\author[1]{Fatih Ozdemir}%
\author[1]{Veysel Ersan}%
\author[1]{Burak Isik}%
\author[2]{Ramazan Kutlu}%
\author[1]{Abuzer Dirican}%
\author[2]{Murat Harputluoglu}%
\affil[1]{Inonu University}%
\affil[2]{Inonu University Faculty Of Medicine}%


\vspace{-1em}



  
  \date{June 06, 2024}


\begingroup
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\selectlanguage{english}
\begin{abstract}
Background: Complications in living liver donors are one of the main
concerns about living donor liver transplantation and the most important
of all are biliary complications. Objective: To present the diagnostic
and therapeutic algorithm developed for the postoperative biliary
complications in living liver donors (LLDs). Methods: Between September
2005 and October 2019, 2120 living liver donor candidates underwent
living donor hepatectomy and postoperative biliary complications
developed in 167 (7.87\%). Management algorithm for various biliary
complications and living liver donors who required hepaticojejunostomy
were evaluated for this retrospective cohort study. Results: Fifty-one
LLDs underwent 53 relaparotomy procedures due to biliary peritonitis.
Endoscopic retrograde cholangiopancreatography (sphincterotomy\selectlanguage{ngerman}±
stenting) was performed in 104 donors but due to persistent bile duct
stricture ± bile leaks, percutaneous transhepatic biliary tract drainage
catheter was inserted in six donors following a failed endoscopic
retrograde cholangiopancreatography assisted treatment. Ninety-seven
LLDs underwent interventional radiologic procedure and twelve of them
were percutaneous transhepatic biliary tract drainage. HJ was performed
in 10 LLDs with right lobe LDH and 2 LLDs with left lobe LDH. Ten of the
12 LLDs underwent percutaneous transhepatic biliary tract drainage
catheter assisted HJ in a median of 50 days after LDH. Following HJ, 11
LLDs did not have any complication along the median of 978 days
(min-max: 139-3578) of follow-up. Conclusion: As living donor liver
transplantation will continue to be performed in countries with low
cadaveric organ supply and biliary complications will be encountered
following LDH. Timing of management of the biliary complication is vital
and HJ procedure is the ultimate treatment modality for biliary
complications that cannot be solved by other minimally invasive methods
especially percutaneous transhepatic biliary tract drainage.%
\end{abstract}\selectlanguage{ngerman}%



\sloppy


\textbf{ORIGINAL ARTICLE}

\textbf{Diagnostic and Therapeutic Management Algorithm for Biliary
Complications in Living Liver Donors}

\textbf{Running Head:} Management algorithm for donor biliary
complications

Sezai Yilmaz\textsuperscript{1}, Sami Akbulut\textsuperscript{1}, Sertac
Usta\textsuperscript{1}, Oguzhan Ozsay\textsuperscript{1}, Tevfik Tolga
Sahin\textsuperscript{1}, Kemal Baris Sarici\textsuperscript{1}, Adil
Baskiran\textsuperscript{1}, Fatih Gonultas\textsuperscript{1}, Fatih
Ozdemir\textsuperscript{1}, Veysel Ersan\textsuperscript{1}, Burak
Isik\textsuperscript{1}, Ramazan Kutlu\textsuperscript{2}, Abuzer
Dirican\textsuperscript{1}, Murat Harputluoglu\textsuperscript{3}

\textsuperscript{1} Liver Transplant Institute, Inonu University Faculty
of Medicine, Malatya 44280, Turkey

\textsuperscript{2} Department of Radiology, Inonu University Faculty of
Medicine, 44280, Malatya, Turkey

\textsuperscript{3} Department of Gastroenterology and Hepatology, Inonu
University Faculty of Medicine, 44280, Malatya, Turkey

\textbf{Corresponding author:}

Prof Sami Akbulut, MD, PhD, FACS,

Department of Surgery and

Liver Transplant Institute,

Inonu University Faculty of Medicine,

Elazig Yolu 10. Km,

Malatya 44280, Turkey.

Telephone: +90-422-3410660

Email: akbulutsami@gmail.com

\textbf{Authors ORCID ID Email}

Sezai Yilmaz 0000-0002-8044-0297 sezai.yilmaz@inonu.edu.tr

Sami Akbulut 0000-0002-6864-7711 akbulutsami@gmail.com

Sertac Usta 0000-0003-0446-7073 sertacusta44@gmail.com

Oguzhan Ozsay 0000-0001-6291-2652 oguzhanozsay@gmail.com

Tevfik Tolga Sahin 0000-0002-9132-6115 tevfiktolgaa@gmail.com

Kemal Baris Sarici 0000-0001-8237-9701 kemal.sarici@inonu.edu.tr

Adil Baskiran 0000-0002-7536-1631 dr.adil.baskiran@gmail.com

Fatih Gonultas 0000-0001-7771-3891 fatnih44@gmail.com

Fatih Ozdemir 0000-0003-0292-3602 fatihup@hotmail.com

Veysel Ersan 0000-0002-1510-0288 veysersan@gmail.com

Burak Isik 0000-0002-2395-3985 isik\_burak@yahoo.com

Ramazan Kutlu 0000-0001-7941-7025 ramazan.kutlu@inonu.edu.tr

Abuzer Dirican 0000-0002-8647-3268 abuzerdirican@hotmail.com

Murat Harputluoglu 0000-0002-9415-147X mharputluoglu@hotmail.com

\textbf{ABBREVIATIONS}

LDH- Living donor hepatectomy; LLD- Living liver donors; LDLT- Living
donor liver transplantation; ERCP- Endoscopic retrograde
cholangiopancreatography; PTBD- Percutaneous transhepatic biliary tract
drainage; HJ - Hepaticojejunostomy; MDCT- Multidetector computed
tomography; MRCP- Magnetic resonance cholangio pancreatography; US-
Ultrasonography; ALP- Alkaline phosphatase; GGT- Gamma-glutamyl
transferase; BMI- Body mass index

\textbf{ABSCTRACT}

\textbf{Background:} Complications in living liver donors are one of the
main concerns about living donor liver transplantation and the most
important of all are biliary complications.

\textbf{Objective:} To present the diagnostic and therapeutic algorithm
developed for the postoperative biliary complications in living liver
donors (LLDs).

\textbf{Methods:} Between September 2005 and October 2019, 2120 living
liver donor candidates underwent living donor hepatectomy and
postoperative biliary complications developed in 167 (7.87\%).
Management algorithm for various biliary complications and living liver
donors who required hepaticojejunostomy were evaluated for this
retrospective cohort study.

\textbf{Results:} Fifty-one LLDs underwent 53 relaparotomy procedures
due to biliary peritonitis. Endoscopic retrograde
cholangiopancreatography (sphincterotomy\selectlanguage{ngerman}± stenting) was performed in 104
donors but due to persistent bile duct stricture ± bile leaks,
percutaneous transhepatic biliary tract drainage catheter was inserted
in six donors following a failed endoscopic retrograde
cholangiopancreatography assisted treatment. Ninety-seven LLDs underwent
interventional radiologic procedure and twelve of them were percutaneous
transhepatic biliary tract drainage. HJ was performed in 10 LLDs with
right lobe LDH and 2 LLDs with left lobe LDH. Ten of the 12 LLDs
underwent percutaneous transhepatic biliary tract drainage catheter
assisted HJ in a median of 50 days after LDH. Following HJ, 11 LLDs did
not have any complication along the median of 978 days (min-max:
139-3578) of follow-up.

\textbf{Conclusion:} As living donor liver transplantation will continue
to be performed in countries with low cadaveric organ supply and biliary
complications will be encountered following LDH. Timing of management of
the biliary complication is vital and HJ procedure is the ultimate
treatment modality for biliary complications that cannot be solved by
other minimally invasive methods especially percutaneous transhepatic
biliary tract drainage.

\textbf{Key Words;} Living donor liver transplantation; Living Donor
Hepatectomy; Biliary Complications; Percutaneous transhepatic biliary
tract drainage; Hepaticojejunostomy

\textbf{INTRODUCTION}

Living donor liver transplantation (LDLT) is the method of choice for
expanding the liver donor pool in many countries where the cadaveric
organ supply is insufficient. \textsuperscript{1,2} The most important
advantages of LDLT are an easily available liver graft, ability to
perform a planned and elective surgery, and a shorter cold ischemia
time. \textsuperscript{1,2} Despite of these advantages, safety of
living liver donors (LLDs) is still a matter of debate. Increase in the
number of studies addressing with morbidity and mortality in LLDs
reduced the interest and a motivation in performing LDLT in the western
world; significantly. Studies in current literature reported an overall
morbidity and mortality following living donor hepatectomy (LDH) as
0-67\% and 0.1-1\%, respectively. \textsuperscript{1-3} Biliary
complications following the LDH procedure are the most common of all the
complications. Management of intraoperative or postoperative biliary
complications vary from a strategy of ``wait and see'' to a complex and
technically demanding surgical procedure such as hepaticojejunostomy
(HJ). Percutaneous transhepatic biliary tract drainage (PTBD:
external-internal, external), percutaneous perihepatic bilioma drainage
(transhepatic or transperitoneal) and endoscopic retrograde
cholangiopancreatography (ERCP) are among the treatment options for
biliary complications. However, there is a lack of consensus regarding
timing and choice of treatment algorithm and which LLDs should undergo
HJ. This study aims to present our treatment algorithm of biliary
complications in LLDs and our technique for PTBD catheter assisted HJ in
necessary cases.

\textbf{MATERIAL AND METHODS}

\textbf{Study Design}

Demographic, clinical and radiological data of 2120 LLDs who underwent
LDH at the Inonu University Liver Transplant Institute between September
2005 and October 2019 were prospectively collected and retrospectively
analyzed (retrospective cohort). This study was designed to emphasize
two major points. First, to assess the diagnostic and therapeutic
management algorithm for biliary complications following LDH. Second, to
present our interventional radiology assisted HJ technique for biliary
stricture and bile leaks which were not successfully treated with
endoscopic and interventional radiologic procedures.

\textbf{Donor Evaluation Protocol}

Turkish Ministry of Health allows living organ donation from the first
to fourth relatives of the recipient. Any relative beyond the fourth
degree or non-next of kin donor (samaritan donors) are evaluated by the
state ethic committee in order to rule out commercial organ donation.
Our detailed donor evaluation scheme and information regarding our
aborted donor hepatectomies were emphasized in a recent study from our
institute. \textsuperscript{4} Currently, LLDs are chosen among
individuals aged between 18 to 60 years of age with normal renal and
liver functions. However, in the early years of our experience, donors \selectlanguage{english}[?]
60 years old were used. The individuals must also have negative viral
serology (except for those individuals that have antibody against the
hepatitis B core antigen) and matched blood group compatible. We
routinely perform multi-detector computerized tomography to determine
the volume of the graft and the future remnant liver, to delineate the
vascular anatomy of the intended vascular graft. Also, we routinely
perform magnetic resonance assisted cholangiography and dynamic magnetic
resonance imaging to evaluate the biliary anatomy and the quality of the
liver parenchyma.

\textbf{Donor Hepatectomy Technique}

The technique for LDH that we prefer was described in the previous
studies from our liver institution. \textsuperscript{5-7} The procedure
starts with cholecystectomy and we perform intraoperative
cholangiography routinely. It is performed as the initial step of the
procedure in order to decide to proceed with LDH. We also perform
intraoperative cholangiography as the last step the procedure following
hemostasis in order to determine any unrecognized injuries to the
biliary tract.

\textbf{Data acquisition}

Data of 167 (7.87 \%) LLDs with postoperative biliary complications (one
intraoperative) diagnosed clinically and radiologically were reviewed in
terms of age, sex, body mass index (BMI: kg/m2), blood group, relation
of LLDs to the recipient, type of LDH (right, left, segment II-III),
time from LDH to ERCP, time from LDH to interventional radiologic
procedures, time from LDH to relaparotomy or HJ. In the following
sections we will define LDH related biliary complications and PTBD
catheter assisted HJ technique in accordance with the objectives of the
present study. Ethical approval was obtained from the Inonu University
Institutional Review Board for non-interventional studies (Approval No:
2019/10-23).

\textbf{Definition of Biliary Complications}

Physical examination findings, biochemical parameters, ultrasonography
(US), multidetector computed tomography (MDCT), magnetic resonance
cholangiopancreatography (MRCP) and ERCP were used to identify and
classify biliary complications following LDH. All of the components
listed below are regarded as postoperative biliary complications: (i)
radiologic diagnosis of fluid collection suggesting perihepatic bilioma
in LLDs with cholangitis or abscess formation with abdominal pain,
fever, chills or rarely, bilioma incidentally detected in LLDs without
clinical findings (ii) prolonged biliary fluid drainage from surgically
inserted drainage tube more than 5 days after the LDH, (iii) prolonged
postoperative elevations in serum alkaline phosphatase (ALP),
gamma-glutamyl transferase (GGT) and bilirubin levels, or a new onset
postoperative elevation of the afore mentioned tests (iv) diagnosis of
biliary peritonitis with acute abdominal findings.

\textbf{Management Algorithm for Biliary Complications (Graphic-1)}

\textbf{(I)} Majority of the LLDs who had a radiological perihepatic
bilioma with findings of cholangitis or abscess without acute abdomen
underwent percutaneous transhepatic drainage and in rare occasions
(Fig.1a), a percutaneous transperitoneal (non-hepatic) drainage was
performed (Fig.1b). A drainage catheter was not placed in the
perihepatic fluid collections or perihepatic abscess like fluid
collections without abdominal findings when there is no bile in the
aspirated fluid and these cases were generally followed-up with US. In
rare cases with recurrent collection, the procedure was repeated. LLDs
who received a drainage catheter were controlled with pouchography
following couple of days to provide a decrease of pressure in the
collection and reduction of the edema. In cases without any bile duct
connection, ``wait and see'' strategy was chosen (Fig.1c). In majority
of these cases the bilioma was caused by minor bile duct draining the
caudate lobe (Fig.1d). Cases with a bile duct connection were evaluated
and treated according to the communication of the bile leaks either to
the main or isolated major segmental branches of hepatic duct (Fig.2).
Cases with a communication with the main bile ducts were treated
primarily with ERCP+ sphincterotomy +- stent placement. If ERCP failed
due to technical reasons or bile leaks persisted despite ERCP, an
external-internal or external PTBD catheter was inserted. In LLDs with
bile leaks from an isolated segmental bile duct located on the cut
surface of remnant liver without any communication with a major bile
duct, treatment method is chosen according to daily amount of bile
drainage. In LLDs with bile drainage less than 50 mL/day are mostly
related to minor segmental bile duct; thus close follow-up without any
invasive intervention is preferred but very rarely fibrin glue plug is
applied to the bile duct through percutaneous placed catheter in cases
with prolonged low volume drainage less than 20ml/days. In LLDs with
prolonged bile drainage more than 50 ml/days can be related to major
segmental bile duct which require PTBD catheter. If bile leaks was
communicated with major segmental bile duct in PTC, PTBD assisted HJ can
be considered. Even if the external-internal PTBD catheter is inserted,
the most appropriate approach is PTBD guided HJ in cases with persistent
bile leaks from the site of bile duct stumps. The reason for this is due
to the fact that ischemic defects in the bile duct stump that often
unsuitable for primary repair.

\textbf{(II)} For LLDs with a biliary drainage from the perihepatic
surgical drain without acute abdomen, wait and see for first
postoperative five days is the preferred management strategy. Early
relaparotomy is beneficial in cases with pure bile flow more than 300
ml/day within the postoperative first two days, which we preferred in
two cases in the present study. In LLDs with persistent biliary drainage
prolonged (\selectlanguage{english}[?]5 days), bile duct injury is usually evaluated with MRCP
and/or occasionally with fluoroscopy enhanced with contrast media
delivered from surgical drain where placed in the perihepatic space. In
patients whose MRCP was unsuccessful to show the remnant biliary tract,
diagnostic ERCP was considered and, stent was inserted in necessary
cases. Wait and see strategy was chosen in LLDs without any evident
relation with the bile ducts. If any relation with the bile ducts was
diagnosed, first column of the algorithm was chosen (see Graphic-1).

\textbf{(III)} For LLDs with isolated enzyme elevation and without any
clinical or ultrasonographic findings, MRCP is utilized to evaluate the
biliary tract. LLDs without any biliary stricture diagnosed with MRCP
require further investigation for evaluation of any possible parenchymal
disease (transient elastography, biopsy, genetic analysis etc). LLDs
with biliary stricture on MRCP undergo ERCP+- sphincterotomy and a stent
is inserted for the treatment of the stricture. In LLDs whom ERCP
failed, PTBD is performed and external-internal PTBD catheter is
inserted and during the follow-up period stent `renewal is performed
with ERCP. If external-internal PTBD procedure failed to pass through
the stricture, external PTBD catheter is inserted and re-evaluated a few
days later. If the repeated attempt fails again, PTBD catheter assisted
HJ is performed.

\textbf{(IV)} Relaparotomy was performed for LLDs with acute abdomen.
Following irrigation of abdominal cavity, cut surface of remnant liver,
left or right hepatic duct stumps, cystic duct stump and main bile duct
are evaluated thoroughly and minor bile leaks points on cut surface of
the remnant liver are sutured with polypropylene. Cholangiography is
performed via catheter inserted into cystic duct. When major bile leaks
are detected during cholangiography, catheter is sent through the cystic
duct to the remnant liver bile ducts. After this procedure, bile leaks
points are repaired with polypropylene suture materials. Postoperative
cholangiography is performed two to four weeks later and catheter was
withdrawn if no bile leak is observed.

\textbf{Definition of Hepaticojejunostomy Procedure}

Laparotomy is performed through the previous Makuuchi incision and
cholangiography is performed following catheterization of cystic duct
stump. In LLDs with an external PTBD catheter, radiologist place a
guide-wire through the catheter. The PTBD catheter is withdrawn with
care and the rigid guide-wire is pushed-forward slowly under
fluoroscopic observation (Fig.3a). The bile duct is determined by the
bulging at the closest point on the cut surface. A bile duct orifice
that is wide enough to perform an anastomosis is obtained using cavitron
ultrasonic surgical aspirator to dissect the periductal liver
parenchyma. Following retraction of guide-wire, PTBD catheter was
inserted and HJ anastomosis was performed. In cases that have
external-internal PTBD catheter, it is easy to see the catheter after
the damaged extrahepatic bile duct is explored. In these cases, HJ is
performed over the PTBD catheter and distal end of the catheter was
advanced into the Roux limb (Fig.3b). HJ anastomoses are performed with
interrupted suture using 6/0 monofilament polydioxanone sutures, stiches
remained outside. Following the anastomosis, patency of bile ducts is
controlled with intraoperative cholangiography via PTBD catheter. PTBD
catheters are with-drawn in LLDs without bile leaks on cholangiography
performed on postoperative week 4-6.

\textbf{Postoperative follow-up of LLDs with Hepaticojejunostomy}

A surgical drain is inserted to the perihepatic or perianastomotic site
and these drainage tubes were withdrawn postoperatively when drainage is
not bilious and the output volume is \textless{} 50 mL/day. PTBD
catheters are irrigated at least once each day with 5-10 cc saline
solution. A cholangiography is performed between on postoperative 5th to
7th days and LLDs without clinical, laboratory and radiological findings
of bile leaks are discharged. Another cholangiography is performed on
postoperative fourth and sixth weeks and catheters are withdrawn in LLDs
without any biliary leaks.

\textbf{RESULTS}

\textbf{General Assessment}

A total of 167 (7.87 \%) LLDs (male: 103, female: 64, median age: 30,
min-max: 18-63 yr) developed biliary complications. Right hepatectomy
was performed in 134 LLDs while segment II-III resection was performed
in 25 LLDs. Left hepatectomy was performed in the remaining 8 LLDs. No
statistically difference was found between the LLDs with (n=167) and
without (n=1953) biliary complications in terms of liver graft type
(n=0.153), preoperative Anti HBc total positivity (p=0.716), sex
(p=0.403), age (p=0.328), BMI (p=0.443) and preoperative total bilirubin
level (p=0.280).

\textbf{Assessment of the ERCP Results}

ERCP was performed in 104 LLDs in a median of 21 days (min-max: 5-104
days) following LDH for one to eight sessions. Among these 104 LLDs, six
LLDs underwent PTBD +- stenting due to unsuccessful ERCP or persistent
biliary leak despite ERCP. Due to persistent bile duct stricture or bile
leaks, two of these six LLDs underwent PTBD catheter assisted HJ
thereafter. Six of twelve LLDs who underwent HJ had a history of failed
ERCP attempts. One ERCP session resulted in duodenal perforation,
management report of this LLD is previously
published.\textsuperscript{8} Five LLDs with biliary complications had
mild-to-moderate pancreatitis following ERCP, all of which recovered
with fluid resuscitation and medical treatment. No other complications
were observed all along median of 1119 days (min-max: 15-3536) of
follow-up after ERCP.

\textbf{Assessment of the Percutaneous Procedures Results}

Ninety-seven LLDs with biliary complications underwent one to four
sessions of interventional radiology assisted percutaneous procedures.
Eighty-five of them underwent transhepatic or transperitoneal
perihepatic bilioma drainage and no any drainage catheter was placed in
18 of these patients because the aspirated fluid was serous/purulent
rather than bilious. Median time from LDH to percutaneous bilioma
drainage was 21 days (min-max: 6-317 days). Median time from LDH to PTBD
catheter insertion was 33 days (min-max: 24-78 days). Among 12 LLDs had
a PTBD catheter insertion, ten underwent PTBD catheter assisted HJ, of
which 7 had external and 3 had internal-external PTBD catheters.

\textbf{Assessment of the Hepaticojejunostomy Results}

HJ procedure was performed in 12 LLDs who had postoperative (n=11) or
intraoperative (n=1) biliary complications. (i) Intraoperative biliary
complication consisted of iatrogenic segment IV bile duct injury. In
this patient, HJ anastomosis was performed to the bile duct draining
segment 4 and the main bile duct was left intact (Fig.4). (ii) Isolated
major segmental duct obstruction was present in 4 LLDs and there was no
problem in the main bile duct. In these LLDs, these isolated bile ducts
were probably unnoticed in the first operation and ligated accidentally.
HJ anastomosis was performed in these patients as described above. (iii)
Two patients had obstruction in the main bile duct that could not be
resolved by percutaneous interventional procedures and the treatment
required HJ. In the above-mentioned 7 LLDs, single orifice HJ was
performed. (iv) In 3 patients, large ischemic defective area was found
on the ductal stump area which was caused by an obstruction in the main
biliary tract. Side-to-side HJ was performed and ductal continuity was
achieved in these 3 cases (Fig.5). (v) Two patients had both major
biliary tract and isolated segmental major biliary tract obstruction.
These patients underwent double orifice HJ (Fig.6). In other words,
there were 14 HJ ostium in 12 cases. One of these 12 cases was
unfortunate. Isolated major segmental duct obstruction was noticed after
HJ was performed to the main biliary tract in the re-operation. Another
HJ was performed to this bile duct on the same Roux limb in the second
reoperation.

Ten LLDs underwent PTBD catheter assisted HJ and the distal tip of the
catheters were advanced through the anastomosis into the Roux limb. In
one patient who received an emergency laparotomy in the postoperative
early period and did not have a PTBD catheter, a trans-anastomotic
catheter was inserted and distal tip of the catheter was advanced into
the intrahepatic bile ducts (Fig.7). In the remaining one patient with
HJ, it was found that there was an iatrogenic injury to the segment 4
bile duct during parenchymal transection. Therefore, end-to-side HJ was
performed between Roux limb and bile duct that drained segment IV and a
trans-anastomotic catheter was used to protect the anastomosis in this
patient. The details of the of the patients underwent HJ are given in
Graphic-2.

Twelve LLDs with biliary complications underwent HJ at a median of 50
days (min-max: 0-97 days) after the LDH. HJ was performed in 10 LLDs
with right lobe LDH and 2 LLDs with left lobe LDH. None of the LLDs
underwent segment II-III resection required HJ anastomosis. There was no
statistically significant difference between LLDs, who have biliary
complications, with (n=12) and without (n=155) HJ procedure in terms of
sex (p=0.805), age (p=0.714), graft type (right vs left; p=0.820), BMI
(p=0.330), bile duct anatomy (p=0.066) and bile leaks (p=0.137). LLDs
with a biliary complication following LDH were followed-up for a median
of 1141 days (min-max: 21-4201 days). Following HJ, 11 LLDs did not have
any complication all along the median 978 days (min-max: 139-3578 days)
of follow-up. For a patient who suffered from HJ anastomosis stricture
on long-term follow-up, an internal biliary drainage catheter was
inserted and then the catheter was withdrawn following three sessions of
balloon dilation.

\textbf{Assessment of the Relaparotomy Results}

Fifty-one LLDs (2.4 \%) with a median age 27 years (min-max: 20-51
years) underwent 53 relaparotomy due to various biliary complications. A
sum of 107 relaparotomy procedures were performed and 53 of them were
related with various biliary complications. Median time from LDH to
relaparotomy was 20 days (min-max: 1-97 days). Thirteen of the
relaparotomies received HJ (one LLD had twice relaparotomy for a second
HJ). Only two LLDs underwent HJ during relaparotomy for acute biliary
peritonitis. One of these two LLDs underwent early relaparotomy due to a
bilioma which was 10 cm in diameter resulted in peritonitis. An ischemic
section consisting right ductal stump of the main bile duct was
diagnosed, and a HJ was performed between the ischemic section of the
bile duct and a jejunal Roux limb, preserving the continuity of bile
flow via common bile duct. Although external-internal PTBD catheter was
inserted in another LLD to prevent postoperative bile leaks, bile leaks
persisted and acute abdomen findings developed. Therefore, PTBD catheter
assisted HJ was performed in the laparotomy performed for acute abdomen
findings. Remaining 40 patients that underwent re-laparotomy, the
indications were biliary peritonitis, drainage of fluid/bilioma, high
output bile leaks in the early postoperative period (\selectlanguage{english}[?]300 cc pure bile
leaks) and duodenal perforation due to ERCP. A biliary drainage catheter
extending from the cystic duct stump to the intrahepatic bile ducts was
placed in 13 LLDs for bile leaks from cut surface or bile duct stump.
Procedure for repair of bile leaks was mentioned above. Following
bilioma drainage and a drainage tube placement, surgical procedure was
finalized in 26 LLDs. Remaining one LLD underwent relaparotomy due to
duodenal perforation following ERCP.

\textbf{DISCUSSION}

Biliary complications following LDH are common and the incidence has
been reported to range from 0 \% to 38.6 \%. \textsuperscript{9}Ghobrial
and colleagues \textsuperscript{10} have reported a retrospective study
conducted by the A2ALL study group conducted in conjunction with 9
centers that perform LDLT and they have reported that complications are
the second most common complications that are encountered in LLDs in the
postoperative period with an incidence of 9.2\%. Our complications are a
bit lower than that has been reported in their study. However, a recent
review by Simoes and colleagues\textsuperscript{11} have stated that the
incidence of biliary complications among the donors ranged between 6\%
to 18\%. Wide variations of biliary complications in LLDs reported in
various studies may be due to the lack of uniform definition of these
complications. In centers who report low postoperative biliary
complications can be due to low rate of abdominal drains use, negligence
of the subclinical bile leaks, and early discharges because of cost
problems in these centers.\textsuperscript{12-14} In the present study,
overall postoperative biliary complications following LDH is 7.8 \%.
Total biliary complication rates in LLDs have been shown to be higher in
right lobe harvesting (6.6 \% versus 2.9 \%).\textsuperscript{9} Biliary
anatomic variations of the right lobe of the liver are more frequently
encountered which may explain the high complication rates observed in
the present study. In our study, no statistically significant difference
between right and left lobe donors in terms of biliary complications may
be due to advanced experience of approximately 250-300 LDLTs annually.

The algorithm for the management of postoperative biliary complications
presented in our study is the result of extensive experience of our
institute, obtained through a long period of time. In some studies,
flowchart-like diagrams are presented for the diagnosis and treatment of
biliary complications; however, in these studies an development of an
algorithm was attempted based on results obtained from low volume
experience. \textsuperscript{2,15} We think that our flowchart
(Graphic-1) is a study that results from a high patient volume series
and clearly demonstrates the treatment methods. To give an example, our
management algorithm is very clear in the cases with low output bile
leaks that stem from isolated minor bile ducts. It is noteworthy to
emphasize that 30 years have passed since the first LDLT procedure and
little has been published to guide the physicians regarding the
management of biliary complications following LDH. We believe that the
present study will provide a useful algorithm for management of
postoperative living donor biliary complications in centers performing
LDLT.

The necessity of HJ for management of the biliary complications in cases
that cannot be treated by the interventional methods following LDH is a
reality. The publications from centers that perform LDLT have major
shortcomings regarding the extent of LLDs that receive HJ following
biliary complications. For example, it is not clear whether ``the
surgical repair'' and ``repeat biliary reconstruction'' referred to in
these studies is in fact HJ or not. \textsuperscript{15,16} We do not
see much emphasis on this issue in the literature. To date, we have
tried to find cases of HJ reported in LLDs. A total of 15 HJs were
reported in 9 published studies except four cases of HJ that was
reported from our institute (Table 1) \textsuperscript{4-6,14,17-24} In
the present study, the rate of HJ among those who experience biliary
complications was 0.56\%.

HJ is a major operation performed for the management of biliary
complications following LDH. This has emotionally adverse effects on the
LLD surgeons. Nevertheless, it is noteworthy that HJ is a life-saving
procedure in the management of biliary complications because biliary
complications may result in death of the donor. \textsuperscript{2,25}Of
course, all non-surgical methods should be used to treat biliary
complications especially in LLDs. However, unnecessary waiting of the
cases that do not recover will only result in a disaster. In biliary
leaks that are not resolved with percutaneous radiologic interventions,
HJ should be kept in mind as a last resort for the management. In other
words, we think that after a few unsuccessful attempts of minimally
invasive procedures, we should not underestimate the success of a HJ
procedure.

In the operations for biliary stricture, the most difficult part of this
operation was to reveal the obstructed biliary duct on the dens
structured hepatic hilum. We believe that this difficulty can be
overcome with the percutaneous transhepatic biliary drainage catheter
assisted HJ described in this study.

Furthermore, if HJ is chosen to treat a biliary complication in an LLD,
it should be performed as one step procedure during the reoperation. In
the present study, another procedure was needed in one LLD who was
operated for biliary complication and HJ was performed. In this LLD, HJ
was performed to a sufficiently wide bile duct. Intraoperative
cholangiography was performed through a PTBD catheter that has been
inserted prior to operation and bile ducts were visualized and the
operation was ended. In fact, the visualized bile ducts belong to
segment II and IV. Segment III hepatic duct remained obstructed and were
not visualized. Unfortunately, we did not compare the final
intraoperative cholangiography images with donor MRCP or intraoperative
cholangiography images obtained at the beginning of the LDH procedure.
Therefore, this patient required re-laparotomy for a second HJ
anastomosis.

In LLDs with early-recognized biliary complication, presence of a
skilled endoscopists and interventional radiologists has paramount
importance. In this study, we mentioned 12 LLDs whose biliary
complications had to be treated with HJ although we had endoscopists and
interventional radiologists with extensive experience. Of course, minor
bile ducts originating from the cut surface of the remnant liver should
be evaluated with extreme caution during the operation. Intraoperative
cholangiography should be examined diligently to evaluate any
misinterpreted major biliary tract injuries and if necessary,
cholangiography should be repeated from different flip angles.

This is the largest LLDs series in the literature and we have described
the treatment algorithm for biliary complications and we have frankly
presented HJ cases. The results of this study show that postoperative
biliary complications are still a major problem following LDH.
Furthermore, about 7 \% of the LLDs with biliary complications require
HJ for management of this complication. Donor safety during LDLT is
imperative, however if this concern leads to improper transection of the
graft donor, the results may be devastation for the recipient.
Therefore, a good balance should be obtained during the LDH procedures.
Necessary precautions should be taken to avoid damage to the donor bile
ducts but we should also provide sufficient bile ducts for safe
anastomosis in the recipient. However, occasionally this balance can be
disrupted leading to unfavorable outcome in the donor. In countries with
insufficient cadaveric organ supply, LDLT will still continue to be the
major source of organ supply and biliary complications will be
encountered in the LLDs. In centers performing LDLT, it should be a
priority to employ early and accurate management protocol for
postoperative donor biliary complications.

\textbf{AUTHOR CONTRIBUTIONS}

Development of the project: Akbulut S, Sahin TT, Yilmaz S and Ozsay O;
data collection: Sarici KB, Baskiran A, Gonultas F, Ozdemir F and Ersan
V; writing: Akbulut S, Isik B and Yilmaz S; drawing of figures: SU;
radiological interventions: Kutlu R; endoscopic interventions:
Harputluoglu M; editing; Akbulut S, Isik B, Sahin TT and Yilmaz S

\textbf{DATA AVAILABILITY STATEMENT}

The data that support the findings of this study are avaiable from the
corresponding author, (SA), upon a reasonable request

\textbf{DISCLOSURE}

The authors report no conflict of interest.

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\textbf{TABLE, GRAPHIC AND FIGURE LEGENDS}

\textbf{Table-1} Summarized of the literature about Living liver donors
who underwent Roux-en-Y HJ or Choledochojejunostomy due to major biliary
complications following living donor hepatectomy

\textbf{Graphic-1} Diagnostic and therapeutic algorithm for
postoperative biliary complications in living liver donors

\textbf{Graphic-2} Classification of living liver donors undergoing HJ
according to anastomosis techniques

\textbf{Figure-1} Different contrast-enhanced tomography images of
postoperative biliary complications. Extrahepatic biloma (a), drainage
of extrahepatic biloma via PTBD catheter (b), no communication between
the biloma and the bile ducts (c), communication between the biloma and
the minor segmnetal bile duct (d).

\textbf{Figure-2} Pouchography showed that the contrast medium passes
both to the left hepatic duct and to the common bile duct.

\textbf{Figure-3} Demonstration regarding the search of obstructed or
ligated bile duct via interventional radiological instruments (a). then,
HJ was performed over the PTBD catheter (b).

\textbf{Figure-4} Demonstration of intraoperative iatrogenic segment IV
bile duct injury. HJ was performed over the transanastomotic biliary
drainage catheter

\textbf{Figure-5} Demonstration of the persistent bile leaks from stump
despite PTBD catheter placement (a). then, side-to-side HJ was performed
over the PTBD catheter (b). Thus, the common bile duct was preserved.

\textbf{Figure-6} Demonstration of two separate HJ anastomosis on the
same Roux limb

\textbf{Figure-7} Demonstration of end-to-side HJ between roux limb and
common bile duct . HJ was performed over the transanastomotic biliary
drainage catheter

\textbf{Hosted file}

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