Hepatol Int DOI 10.1007/s12072-015-9628-y
ORIGINAL ARTICLE
Feasibility of liver graft procurement with donor gallbladder preservation in living donor liver transplantation Jia-Hong Dong1 • Sheng Ye1 • Wei-Dong Duan1 • Wen-Bing Ji1 • Yu-Rong Liang1
Received: 28 July 2014 / Accepted: 30 March 2015 Asian Pacific Association for the Study of the Liver 2015
Abstract Objective Cholecystectomy is routinely performed at most transplant centers during living donor liver transplantation (LDLT). This study was performed to evaluate the feasibility of liver graft procurement with donor gallbladder preservation in LDLT. Methods Eighty-nine LDLTs (from June 2006 to Dec 2012) were retrospectively analyzed at our hospital. The surgical approach for liver graft procurement with donor gallbladder preservation was assessed, and the anatomy of the cystic artery, the morphology and contractibility of the preserved gallbladder, postoperative symptoms, and vascular and biliary complications were compared among donors with or without gallbladder preservation. Results Twenty-eight donors (15 right and 13 left-liver grafts) successfully underwent liver graft procurement with gallbladder preservation. Among the 15 right lobectomy donors, for 12 cases (80.0 %) the cystic artery originated from right hepatic artery. From the left hepatic artery and proper hepatic artery accounted for 6.7 % (1/15), respectively. Postoperative symptoms among these 28 donors were slight, although donors with cholecystectomy often complained of fatty food aversion, dyspepsia, and diarrhea during an average follow-up of 58.6 (44–78) months. The morphology and contractibility of the preserved gallbladders were comparable with normal status; the rate of Jia-Hong Dong and Sheng Ye contributed equally to this article as joint first authors. & Sheng Ye [email protected] 1
Hospital and Institute of Hepatobiliary Surgery, Chinese PLA General Hospital, Chinese PLA Medical School, 28 Fuxin Road, Beijing 100853, China
contraction was 53.8 and 76.7 %, respectively, 30 and 60 min after ingestion of a fatty meal. Biliary and vascular complications among donors and recipients, irrespective of gallbladder preservation, were not significantly different. Conclusions These data suggest that for donors compliant with anatomical requirements, liver graft procurement with gallbladder preservation for the donor is feasible and safe. The preserved gallbladder was assessed as functioning well and postoperative symptoms as a result of cholecystectomy were significantly reduced during long-term follow-up. Keywords Liver transplantation Living donor Gallbladder preservation Abbreviations CBD Common bile duct CCK Cholecystokinin CHD Common hepatic duct CUSA Cavitron ultrasonic surgical aspiration Gd-BOPTA Gadobenate dimeglumine HTK Histidine–tryptophan–ketoglutarate IOC Intraoperative cholangiography IVC Inferior vena cava LHD Left hepatic duct LDLT Living donor liver transplantation MHA Middle hepatic artery MHV Middle hepatic vein MR Magnetic resonance PHA Proper hepatic artery PCS Post-cholecystectomy syndrome RHA Right hepatic artery RHV Right hepatic vein RHD Right hepatic duct RPV Right portal vein SOD Sphincter of Oddi dysfunction
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Introduction Living donor liver transplantation (LDLT) has become an effective therapeutic option for end-stage hepatic diseases. At most transplant centers, cholecystectomy is routinely performed during donor liver procurement, because intraoperative cholangiography (IOC) is conducted for definition of biliary anatomy and precise location of the site of bile duct division during left or right-liver graft procurement [1–3]. However, the gallbladder is an important organ with such diverse functions as bile storage, concentration, and secretion, and immunologic activity. The gallbladder concentrates bile 30-fold and the concentrated bile is excreted into the intestinal tract where it aids digestion of high-fat diets. After cholecystectomy, the bile is released continuously into the intestinal tract, and such dyspeptic symptoms as abdominal distention and diarrhea are observed after intake of high-fat diets, because of no or insufficient bile in the intestinal tract. In addition, the patients might suffer from postcholecystectomy syndrome (PCS) after the gallbladder removal [4] which could be related to sphincter of Oddi dysfunction (SOD) [5]. The lamina propria of cystic mucosa secretes white liquid mainly composed of immunoglobulin (IgA) which protects the biliary and intestinal mucosae against secondary bile acid and eliminates pathogenic bacteria. It has been suggested that cholecystectomy alters the drainage and residence time of bile in the intestinal tract, resulting in generation of more secondary cholic acid and an increased probability of mitosis and canceration of colon mucosal cells [6–8]. All liver donors are healthy individuals, and the safety of donors, including minimization of injury and maximum preservation of organ function, is a prerequisite for development of LDLT techniques. In this regard, liver graft procurement with gallbladder preservation for normal function in donors can enhance the postoperative quality of life and gastrointestinal function of donors.
The purpose of this study was to evaluate the feasibility of gallbladder preservation, guided by the anatomic and physiological features of the gallbladder, and to study longterm effects to ensure the safety of and minimum injury to donors. Herein, we present our initial results from assessment of the anatomical requirements of such donors and evaluation of postoperative symptoms, complications, morphology, and contractile functions of the gallbladder.
Patients and methods Study protocol Ninety-two grafts, 78 right-liver grafts and 14 left-liver grafts, were transplanted into 89 patients (three dual-graft transplants) at our hospital during the period from June 2006 to Dec 2012. Of the 78 right-lobe-graft LDLT (the MHV was included for 57 grafts), 15 donors (8 females and 7 males, average age 36.6 ± 7.2 years) met the anatomic requirements for gallbladder preservation (the MHV was included for seven grafts). Among 14 left-liver grafts, 13 were successfully performed with gallbladder preservation. The average postoperative follow-up period was 58.6 (44–78) months, and a total of six donors were lost to follow-up. The other 58 donors with cholecystectomy were regarded as controls, for comparison purposes. For both groups surgery was performed by the same group of surgeons. Clinical data for the two groups are as detailed in Table 1. Donor selection and evaluation The procedures involved in donor selection and evaluation conformed to the guidelines of the Regulation of Human’s Organ Transplantation of China and were approved by the
Table 1 Comparison of clinical data for right or left-graft lobectomy with or without gallbladder preservation Clinical data for donors
Graft procurement with donor gallbladder preservation Yes (n = 28)
p
No (n = 58)
Donor age (years)
36.8 ± 11.4
38.1 ± 12.2
NS
Remaining left liver/native liver volume (%)
37.2 ± 3.7
35.8 ± 5.7
NS NS
GRWR (%)
1.03 ± 0.28
0.96 ± 0.18
Operation time (min)
425.3 ± 53.8
408.2 ± 61.3
NS
Blood loss (ml)
358.3 ± 175.1
429.5 ± 123.9
NS
Transfusion dose of autoblood (ml)a
225.0 ± 35.4
249.3 ± 47.9
NS
Autoblood transfusion (%)
7.1 % (2/28)
8.6 % (5/58)
NS
Length of hospitalization (day)
10.3 ± 3.6
11.5 ± 2.9
NS
GRWR graft-to-recipient weight ratio, NS not significant a
Intraoperative red cell salvage
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hospital ethics committee. Among the 92 donors, 50 were male and 42 were female, aged from 19 to 56 years (average 37.5) with knowledge of civil rights. The evaluation was performed only after the donors expressed willingness to donate and had learned about the advantages and risks of the operation. The detailed evaluation methods followed those of Queen Mary Hospital, Hong Kong University [9] with some modification; MR imaging was the sole preoperative imaging technique for LDLT donor candidates [10– 13]. Our protocol includes: •
• •
T2 and T1-weighted imaging for detection and characterization of liver parenchymal and extraparenchymal disease; contrast-enhanced volumetric acquisition for evaluation of arterial and venous anatomy; and combination of T2-weighted MR cholangiography with gadobenate dimeglumine (MultiHance) enhanced T1weighted MR cholangiography for evaluation of biliary anatomy.
In this series, conventional IOC through the cystic duct was performed for the first five donors only. With accumulation of experience and on the basis of the literature, IOC is now no longer routinely performed and is reserved solely for problematic cases (when preoperative MRI is not sufficiently clear and biliary variation is suspected, which was encountered for two donors only (2.3 %) of our later cases). Surgical technique: right (or left)-graft lobectomy with gallbladder preservation
2.
3.
4.
5.
6.
7.
The feasibility of gallbladder preservation was confirmed by preoperative imaging of the donors and identification of origin of the intraoperative cystic artery (Fig. 1). The procedures were: 1.
Precise dissection of the right hepatic pedicle was performed. The RHA and the initial segment of the cystic artery originating from the RHA were then mobilized, and the anatomic relationship between the RHA and cystic artery, and the anatomic condition of
Fig. 1 Anatomic requirements shown for the 15 donors who underwent right hepatectomy with gallbladder preservation. a The cystic artery originates from a low position on the right hepatic artery (80.0 %, 12/15). b The cystic artery originates from the left hepatic artery (6.7 %, 1/15). c The cystic artery originates from the proper
8.
the RHA above the opening of cystic artery, were determined, to decide whether or not to perform rightgraft lobectomy with gallbladder preservation. The right portal vein (RPV) was then freed to the junction with the left portal vein, and main portal vein was clearly identified. The right liver was mobilized by dividing the perihepatic ligaments. Care was taken to isolate the right-side hepatic short veins, which were clamped, divided, and sutured. The RHA and RPV were temporarily occluded to produce the demarcation line between the right and left livers, or the Cantlie line was established by location of the MHV by use of intraoperative ultrasonography. The cystic artery was temporarily blocked with an atraumatic vascular bulldog clamp, the gallbladder located on the right of the hepatic transection plane from the liver cystic bed along the loose connective tissue between the gallbladder and liver–gallbladder bed was isolated, and the connection between the gallbladder located on the left of the hepatic transection plane and the liver–gallbladder bed was preserved as far as possible, so that the blood supply from the cystic fossa could be partly maintained. The hepatic parenchyma along the pre-determined cutting plane was transected by cavitron ultrasound surgical aspiration (CUSA) without inflow or outflow vascular occlusion. The loose tissue overlying the hilar plate was dissected meticulously to expose the confluence of left and right hepatic ducts, with the help of preoperative MR imaging, and the site of RHD division was determined. After the integrity of CHD and LHD was ensured, the anterior wall of the RHD was divided with a knife, the brisk arterial or venous bleeding from the hilar plate and ductal wall was controlled by use of 6/0 Prolene sutures, and the posterior wall of the RHD was then divided. The RHA, RPV, and RHV were divided in sequence and the right liver lobe was removed. All vessel stumps were sutured and closed, and the gallbladder at the
hepatic artery (13.3 %, 2/15). d The cystic artery originates from the gastroduodenal artery. If the cystic artery originates from a higher position on the RHA, or the RHA above the cystic artery is fine and close to the porta hepatis (e), it is not possible to preserve the gallbladder
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9.
right margo lateralis envelope of the left liver was also sutured and fixed (Fig. 2). The graft was implanted by use of a routine method, i.e. the modified outflow was end-to-side anastomosed to the IVC, then the liver blood flow was restored after RPV reconstruction. The RHA and RHD were anastomosed by microsurgery.
The procedures for left-graft procurement are similar to those for right-graft, but with an easier approach, because for most donors the gallbladder artery originates from the RHA.
Fig. 2 Precision graft liver procurement with gallbladder preservation for donor. a Do not dissect too much between the right hepatic artery and the bile duct, to preserve the hepatic artery branches that might be present there. b Transection line of the right-liver graft on the diaphragm and visceral surface (green arrow). c Remove the right graft, suture carefully, and close the stem of the hepatic vein, portal vein, and hepatic artery, to ensure the integrity of the cystic artery blood supply; pay attention to bile leakage from the right caudate lobe and the hepatic transection surface. d Suture and fix the preserved gallbladder to the incised margin of the left lobe; the falciform ligament is sutured to the anterior abdominal wall to prevent the left
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Follow-up: gallbladder morphology and function evaluation All donor and patient data were entered in the China Liver Transplant Registry (CLTR) hosted by Hong Kong University and their follow-up protocol was compiled with https://www.cltr.org/en/. Liver function tests, Doppler ultrasound, MRCP, or CT were routinely conducted to investigate vascular and biliary complications among both donors and recipients. The gallbladder and its contractile function, including morphology, size, thickness of gallbladder wall, and contractile and emptying functions, were
lobe from rotating into the right subphrenic cavity. e The liver transection-line on the diaphragm and visceral surface for the leftliver graft (green arrow). f, g The LHA, accessory LHA, and left portal vein are dissected free, and partial isolation of the left side of the gallbladder bed is also performed. h The left-liver graft is transected completely except for the inflow and outflow vessels. i Suture and attachment of the preserved gallbladder to the incised margin of the right liver after left-liver graft removal. a, gallbladder artery; b, RHA; c, LHA; d, accessory LHA; e, left portal vein; f, RHA. GB gallbladder. (Color figure online)
Hepatol Int
assessed by use of ultrasound. Subjective symptoms and complications among the two donor groups were followed up.
Postoperative symptoms among donors undergoing right hepatectomy with or without gallbladder preservation
Statistical analysis
Slight postoperative symptoms were observed for 28 donors with gallbladder preservation whereas donors with cholecystectomy often complained of epigastric pain, aversion to fatty foods, dyspepsia, and diarrhea during an average of 58.6 (44–78) months follow up, the difference between the two groups was significant. However, the 14.3 % (4/28) incidence of nausea and vomiting among donors with gallbladder preservation and 15.5 % (9/58) among donors with cholecystectomy was not significantly different. In addition, for two donors (3.4 %, 2/58) abdominal pain after cholecystectomy was attributed to SOD after endoscopic examination and one underwent endoscopic sphincterotomy (Table 2).
Results are expressed as x ± standard deviation. Values and variables were analyzed by use of the chi-square (v2) test for categorical values and Student’s t test for continuous variables. All data were analyzed by use of Stata 7.0 and SPSS 10.0 software and all p values \0.05 were regarded as statistically significant.
Results Anatomic evaluation of cystic artery for gallbladder preservation Anatomic evaluation of the cystic artery (Fig. 1) is of crucial importance when deciding whether or not to preserve the gallbladder. Among the 15 donors who underwent right lobectomy with gallbladder preservation, the cystic artery originated from the RHA in 80.0 % (type A; 12/15), from the left hepatic artery (LHA) in 6.7 % (type B; 1/15), and from the PHA in 6.7 % (type C; 1/15); a bibranch-type cystic artery that originated from the RHA and the middle hepatic artery (MHA) was found in 6.7 % (1/ 15). For type A or the bi-branch type cystic artery, if the length and diameter of the RHA above the cystic artery was suitable for graft hepatic artery reconstruction, preservation of the gallbladder was suggested. All 13 donors whose cystic artery originated from RHA underwent left lobectomy, so left-graft procurement with gallbladder preservation was achieved without difficulty. The blood supply for preserved gallbladders was in good condition and no dusky or swollen area was observed (Fig. 2). Ultrasound: cystic morphology and contractile function Cystic morphology and contractile function results are shown in Fig. 3. On ultrasound examination, the morphology and size of 26 preserved gallbladders were comparable with normal status, neither thickened cystic wall nor cholecystitis or cholelithiasis was found; however, two preserved gallbladders were found to have shrunk. During the fatty diet test, the contractile function of 26 preserved gallbladders was comparable with normal status; no contractile function was observed for two (7.1 %; 2/28) preserved gallbladders. Nevertheless, neither subjective symptoms nor necrosis or cholelithiasis was observed for these two donors during long-term follow-up.
Comparison of postoperative biliary and vascular complications among donors and recipients Among recipients who were implanted with a liver graft procured with gallbladder preservation in the donor, two suffered from biliary leakage. Among recipients who were implanted with a liver graft procured with cholecystectomy, one suffered from biliary leakage and the other suffered from anastomotic stricture. No significant difference was found between the two groups. Three donors, one with and two without gallbladder preservation, suffered from biliary leakage, and another donor with cholecystectomy suffered from biliary stricture; again there was no significant difference between the two groups. Vascular complications were not significantly different between the two groups (Table 3).
Discussion Cholecystectomy is commonly performed for symptomatic cholelithiasis or cholecystitis. Postcholecystectomy syndrome (PCS), i.e. the recurrence or persistence of abdominal pain or gastrointestinal symptoms months to years after cholecystectomy, which is frustrating for patient and surgeon alike, occurs in 5–47 % of patients [14, 15]. The reported 40 % incidence of PCS was partially related with functional impairment of Oddi’s sphincter [16], and SOD was diagnosed in 9–11 % of patients evaluated for postcholecystectomy pain [17, 18]. After cholecystectomy, 17–35.6 % of patients reported troublesome new-onset diarrhea [19–21], which could be associated with postoperative disturbance of bile metabolism and changes in the dynamics of bile release resulting in food intolerance and fat malabsorption.
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Hepatol Int Fig. 3 Morphology and contractile function of preserved donor gallbladders after graft procurement. The CT scan shows significant regeneration of the residual left lobe 29 months after right-graft lobectomy (a, b) with wellpreserved gallbladder morphology (red arrow). Ultrasonography shows the volume calculated from transverse, longitudinal, and anterior–posterior lengths before the fatty meal test. The pre-fat meal gallbladder volume is shown as control (c, e). Remarkable reduction in volume is observed 30 min (d) and 60 min (f) after consumption of the fatty meal. g Ultrasound evaluation of gallbladder contraction function after fatty meal ingestion shows contractile function of 26 preserved gallbladders comparable with normal status. Contractility (%) = (Volumepre-fat meal Volumefat meal 30min or 60 min)/ Volumepre-fat meal. (Color figure online)
a
b
c
d
e
f
Gallbladder volume (cm3)
Gallbladder contractility (%)᧟
Pre-fat meal
Fat meal 30 min.
Fat meal 60 min.
p
24.8±5.8
11.6±3.8
6.2±1.6
᧸0.05
᧩
53.8
76.7
᧸0.05
g Unlike routine symptomatic patients undergoing cholecystectomy with compromised gallbladder function because of gallstones, atrophy of the gallbladder, or cholecystitis, all living donors are healthy individuals with normal gallbladder function, and removal of normal gallbladder can lead to several functional disorders with potential injury to the donors.
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In our series, 17.2 % (10/58) of donors who underwent liver-graft lobectomy with cholecystectomy often complained of epigastric pain, aversion to fatty diet, abdominal distention after fatty meals, and diarrhea during an average of 58.6 (44–78) months follow-up. However, 28 donors with gallbladder preservation had few subjective symptoms; their frequent complaint of nausea and vomiting
Hepatol Int Table 2 Comparison of postoperative symptoms among donors with or without gallbladder preservation during follow-up Symptom
Upper abdominal painb
Gallbladder preservation (n = 28)
Cholecystectomya (n = 58)
Right graft (15)
Right graft (57)
Left graft (13)
0
Comparison of incidence
Clinical management
0 versus 5.2 % (3/58)*
Endoscopic intervention
0 versus 10.3 % (6/58)*
Relief by diet adjustment
0 versus 13.8 % (8/58)*
Medications
3.6 % (1/28) versus 12.1 % (7/58)*
Half self-relief, half medications
14.3 % (4/28) versus 15.5 % (9/58); NS
Medications
Left graft (1)
Mild: 1 Moderate: 2
Aversion to fatty foods
0
Diarrhea
0
Mild: 2 Moderate: 4 Mild: 2 Moderate: 5 Severe: 1
Dyspepsia
Mild: 1
Mild: 2
Nausea and Vomitingc
Mild: 2
Mild: 3
Moderate: 2
Moderate: 5
Moderate: 5
Severe: 1 NS not significant * p \ 0.05 a
One donor had pre-operative asymptomatic cholesterol gallstone
b
One case was attributed to CBD stones by ultrasound 29 months after surgery, and the stones were removed by ERCP; the other two were diagnosed as sphincter of Oddi dysfunction (SOD) by endoscopic manometry, one donor was relieved by use of the calcium-channel antagonist nifedipine and another underwent endoscopic sphincterotomy
c
All the symptoms were observed within the first week after hepatectomy when the patients began to eat
Table 3 Comparison of vascular and biliary complications among donors and recipients after graft procurement with or without gallbladder preservation Gallbladder preservation (n = 28)
Cholecystectomy (n = 58)
Donor
Recipient
Donor
Recipient
Biliary leakage
1
2
2
1
Biliary anastomotic stenosis
0
0
1
1
Comparison of incidence of complications (%)
Donor: 3.6 % (1/28) versus 5.2 % (3/58), NS; Recipient: 7.1 % (2/28) versus 3.4 % (2/58), NS
HAT or stenosis
0
0
0
2
Recipient: 0 versus 3.4 % (2/58), NS
PVT or stenosis
0
0
0
0
NS
Hepatic vein obstruction
0
1
1
2
Donor: 0 versus 1.7 % (1/58), NS; Recipient: 3.6 % (1/28) versus 3.4 % (2/58), NS
HAT hepatic artery thrombosis, PVT portal vein thrombosis, NS not significant
(14.3 %, 4/28), which was not significantly different from that of cholecystectomy donors (15.5 %, 9/58), was all observed within the first week after surgery (Table 1); this gastrointestinal symptom could be because of the major hepatectomy and was unrelated with gallbladder function. In agreement with previous studies [5, 16–18], our study confirmed that two donors with cholecystectomy suffered from SOD. Gallbladder and sphincter of Oddi (SO)
function are coordinated by hormonal and neuronal mechanisms; nerve fibers connect the gallbladder and SO via the cystic duct [22, 23]. Ingestion of a fatty meal is followed by release of cholecystokinin (CCK) which causes the gallbladder to contract and the SO to relax. Cholecystectomy may affect normal SO function by disrupting this nerve pathway and altering its response to CCK, which results in SO dyskinesia and SOD [24, 25].
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Notably, 12.1 % (7/58) donors suffered from new-onset postcholecystectomy diarrhea, this result is in agreement with previous findings for routine cholecystectomy patients [19–21]. However, no donor whose gallbladder was preserved had the distressing sequel. One of the major concerns about the use of this novel approach is cancellation of IOC and some critical queries must be addressed. First, how is the precise site of RHD division defined during right-graft procurement? Second, how is the integrity of the CBD and residual LHD ensured? In our practice, with the help of preoperative imaging and accumulation of LDLT experience, ‘‘all-in-one’’ MRI proved to be feasible and robust for evaluation of potential living-liver donors in a single diagnostic step [10–13]. In our series, Multihance-enhanced MR cholangiography accurately depicted potential donor biliary anatomy, and for our donors enough guidance was found for intraoperative precise definition of the site of RHD (or LHD) division, no LHD (or RHD), or CBD injury. (In our center IOC is now no longer routinely performed and is reserved for problematic cases only). This thus facilitates feasible right (or left)-graft lobectomy with gallbladder preservation. Another important concern about the use of this approach is cholecystic venous drainage. Does partial mobilization of the right (or left) side of the gallbladder bed affect cytic venous drainage? The cystic veins took either of two routes: one flowed out from the neck of the gallbladder, through the hilum, and into the liver, taken mainly by the portal branch for subsegment 4a (P4a) and by the umbilical portion of the portal branch; the other flowed out from the body of the gallbladder, through the hepatic bed, taken mainly by S4a sinusoid, S5 sinusoid, P4a, and P5 [26, 27]. In our practice, venous drainage of preserved gallbladders was in good condition after partial isolation of hepatic bed, and no dusky or swollen area was observed during intraoperative observation or postoperative followup. The preserved P4a or S4a cystic veins and later reconstructed collateral vessels may contribute to sufficient compensatory drainage for the gallbladder. A major aspect of suitability for gallbladder preservation is the origin of the cystic artery and cystic duct. The cystic artery usually originates from the RHA (73.5 %); however, 2.6–4.5 % of cystic arteries originate from the gastroduodenal artery [28, 29], 4.9 % from PHA [30], and 1–1.96 % from LHA [29, 31]. If the cystic artery originates from the LHA or PHA, or the lower cystic artery originates from the RHA such that the diameter and length of the RHA above the cystic artery are suitable for reconstruction of a graft hepatic artery, right-liver procurement with gallbladder preservation can be performed without difficulty. If the proximal right hepatic pedicle of the cystic artery originates from the RHA, the RHA that was above the opening of the cystic artery is tenuous and short, and the gallbladder
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is regarded as unsuitable for preservation. Two types of cystic duct variation are observed, i.e. it joins the upper position of the CHD or it joins the RHD; the occurrence of this is approximately 0.6–2.3 % [32], and the latter variation affects the surgical approach during right-graft procurement for gallbladder preservation. However, no cystic duct variation was observed among the 28 donors whose gallbladders were preserved in this study. Because the gallbladder is located at the boundary line of the left and right liver lobes, gallbladder preservation makes it inconvenient to dissect the right hepatic pedicle. For gallbladder preservation, it is important to first dissect precisely the right hepatic pedicle and cholecyst triangle, then confirm the origin of the cystic artery and the length and diameter of the upstream RHA, to ensure the integrity of cystic artery if the gallbladder is being preserved. Then, partially isolate the right side of the gallbladder bed and suspend the cystic ampulla to completely expose the RPV, etc. After satisfactory right hepatic pedicle dissection and under-right graft lobectomy conditions, isolate as little as possible of the cystic tissue to ensure sufficient compensatory cystic vessels and to avoid damage to the cystic duct. In this study, the function of most of the preserved gallbladders in donors was found to be good, as shown in Fig. 3. Moreover, the new surgical approach did not cause postoperative hepatic artery or biliary complications (Table 2) or affect the functional quality and rehabilitation of the individuals (Supplemental data(SD)). However, two donors with gallbladder preservation presented with cystic atrophy during follow-up. Although the donors did not report subjective symptoms, the contractile function of gallbladder was non-existent. This was probably because of excessive isolation of the gallbladder bed which led to obstruction of the drainage of the cystic vein. To avoid this complication, the division should deviate to the right side of the transection plane during right-graft procurement. Thus, the left-side serous membrane of the gallbladder will be as much preserved as possible to enable sufficient drainage of cystic vein. In conclusion, our initial results indicate that liver-graft lobectomy with gallbladder preservation is beneficial among donors who meet the anatomical requirements—the surgical approach does not increase postoperative vascular and biliary complications and, importantly, most of the preserved gallbladder remain fully functional during longterm follow-up. Another randomized control trial with a larger population and more long-term, evidence-based monitoring of outcomes will, however, be necessary to prove its efficacy and safety. Acknowledgements The authors would like to thank Ma Fen Xi for her excellent assistance with the schematic illustration. This study
Hepatol Int was sponsored by the Natural Sciences Foundation of China (Grant Nos. 30772136, 30972950 and 81070383). Compliance with ethical requirements and Conflict of interest All procedures followed were in accordance with the ethical standards of the responsible committees on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008. Informed consent was obtained from all the patients included in the study. Jia-Hong Dong, Sheng Ye, Wei-Dong Duan, Wen-Bing Ji, and Yu-Rong Liang declare that they have no conflict of interest.
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13. An SK, Lee JM, Suh KS, et al. Gadobenate dimeglumine-enhanced liver MRI as the sole preoperative imaging technique: a prospective study of living liver donors. AJR 2006;187: 1223–1233 14. Bisgaard T, Rosenberg J, Kehlet H. From acute to chronic pain after laparoscopic cholecystectomy: a prospective follow-up analysis. Scand J Gastroenterol 2005;40:1358–1364 15. Russello D, Di Stefano A, Scala R, et al. Does cholecystectomy always resolve biliary disease? Minerva Chir 1997;52:1435–1439 16. Zhou PH, Liu FL, Yao LQ, Qin XY. Endoscopic diagnosis and treatment of postcholecystectomy syndrome. Hepatobiliary Pancreat Dis Int 2003;2:117–120 17. Neoleptomenos JP, Bailey IS, Carr-Locke DL. Sphincter of Oddi dysfunction: results of treatment by endoscopic sphincterotomy. Br J Surg 1988;75:454–459 18. Roberts-Thompson IC, Toouli J. Is endoscopic sphincterotomy for disabling biliary type pain after cholecystectomy effective? Gastrointest Endosc 1985;31:370–373 19. Fisher M, Spillas DC, Tong LK. Diarrhoea after laparoscopic cholecystectomy: incidence and main determinants. ANZ J Surg 2008;78:482–486 20. Middelfart HV, Kristensen JU, Laursen CN, et al. Pain and dyspepsia after elective and acute cholecystectomy. Scand J Gastroenterol 1998;33:10–14 21. Lublin M, Crawford DL, Hiatt JR, Phillips EH. Symptoms before and after laparoscopic cholecystectomy for gallstones. Am Surg 2004;70:863–866 22. Thune A, Saccone G, Scicchitano JP, et al. Distension of the gallbladder inhibits sphincter of Oddi motility. Gut 1991;32:690–693 23. Padbury RTA, Furness JB, Baker RA, et al. Projections of nerve cells from the duodenum to the sphincter of Oddi and gallbladder of the Australian possum. Gastroenterology 1993;104:130–136 24. Luman W, Williams AJK, Pryde A, et al. Influence of cholecystectomy on sphincter of Oddi motility. Gut 1997;41:371–374 25. Behar J, Corazziari E, Guelrud M, et al. Functional gallbladder and sphincter of Oddi disorders. Gastroenterology 2006;130:1498–1509 26. Sugita M, Ryu M, Satake M, et al. Intrahepatic inflow areas of the drainage vein of the gallbladder: analysis by angio-CT. Surgery 2000;128(3):417–421 27. Kai K, Satoh S, Watanabe T, Endo Y. Evaluation of cholecystic venous flow using indocyanine green fluorescence angiography. J Hepatobiliary Pancreat Sci 2010;17:147–151 28. Balija M, Huis M, Nikolic V, et al. Laparoscopic visualization of the cystic artery anatomy. World J Surg 1999;23:703–707 29. Sarkar AK, Roy TS. Anatomy of the cystic artery arising from the gastroduodenal artery and its choledochal branch—a case report. J Anat 2000;197:503–506 30. Saidi H, Karanja TM, Ogengo JA. Variant anatomy of the cystic artery in adult Kenyans. Clin Anat 2007;20:943–945 31. Hugh TB, Kelly MD, Li B. Laparoscopic anatomy of the cystic artery. Am J Surg 1992;163:593–595 32. Lamah M, Karanjia ND, Dickson GH. Anatomical variations of the extrahepatic biliary tree: review of the world literature. Clin Anat 2001;14:167–172
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ORIGINAL ARTICLE
Feasibility of liver graft procurement with donor gallbladder preservation in living donor liver transplantation Jia-Hong Dong1 • Sheng Ye1 • Wei-Dong Duan1 • Wen-Bing Ji1 • Yu-Rong Liang1
Received: 28 July 2014 / Accepted: 30 March 2015 Asian Pacific Association for the Study of the Liver 2015
Abstract Objective Cholecystectomy is routinely performed at most transplant centers during living donor liver transplantation (LDLT). This study was performed to evaluate the feasibility of liver graft procurement with donor gallbladder preservation in LDLT. Methods Eighty-nine LDLTs (from June 2006 to Dec 2012) were retrospectively analyzed at our hospital. The surgical approach for liver graft procurement with donor gallbladder preservation was assessed, and the anatomy of the cystic artery, the morphology and contractibility of the preserved gallbladder, postoperative symptoms, and vascular and biliary complications were compared among donors with or without gallbladder preservation. Results Twenty-eight donors (15 right and 13 left-liver grafts) successfully underwent liver graft procurement with gallbladder preservation. Among the 15 right lobectomy donors, for 12 cases (80.0 %) the cystic artery originated from right hepatic artery. From the left hepatic artery and proper hepatic artery accounted for 6.7 % (1/15), respectively. Postoperative symptoms among these 28 donors were slight, although donors with cholecystectomy often complained of fatty food aversion, dyspepsia, and diarrhea during an average follow-up of 58.6 (44–78) months. The morphology and contractibility of the preserved gallbladders were comparable with normal status; the rate of Jia-Hong Dong and Sheng Ye contributed equally to this article as joint first authors. & Sheng Ye [email protected] 1
Hospital and Institute of Hepatobiliary Surgery, Chinese PLA General Hospital, Chinese PLA Medical School, 28 Fuxin Road, Beijing 100853, China
contraction was 53.8 and 76.7 %, respectively, 30 and 60 min after ingestion of a fatty meal. Biliary and vascular complications among donors and recipients, irrespective of gallbladder preservation, were not significantly different. Conclusions These data suggest that for donors compliant with anatomical requirements, liver graft procurement with gallbladder preservation for the donor is feasible and safe. The preserved gallbladder was assessed as functioning well and postoperative symptoms as a result of cholecystectomy were significantly reduced during long-term follow-up. Keywords Liver transplantation Living donor Gallbladder preservation Abbreviations CBD Common bile duct CCK Cholecystokinin CHD Common hepatic duct CUSA Cavitron ultrasonic surgical aspiration Gd-BOPTA Gadobenate dimeglumine HTK Histidine–tryptophan–ketoglutarate IOC Intraoperative cholangiography IVC Inferior vena cava LHD Left hepatic duct LDLT Living donor liver transplantation MHA Middle hepatic artery MHV Middle hepatic vein MR Magnetic resonance PHA Proper hepatic artery PCS Post-cholecystectomy syndrome RHA Right hepatic artery RHV Right hepatic vein RHD Right hepatic duct RPV Right portal vein SOD Sphincter of Oddi dysfunction
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Introduction Living donor liver transplantation (LDLT) has become an effective therapeutic option for end-stage hepatic diseases. At most transplant centers, cholecystectomy is routinely performed during donor liver procurement, because intraoperative cholangiography (IOC) is conducted for definition of biliary anatomy and precise location of the site of bile duct division during left or right-liver graft procurement [1–3]. However, the gallbladder is an important organ with such diverse functions as bile storage, concentration, and secretion, and immunologic activity. The gallbladder concentrates bile 30-fold and the concentrated bile is excreted into the intestinal tract where it aids digestion of high-fat diets. After cholecystectomy, the bile is released continuously into the intestinal tract, and such dyspeptic symptoms as abdominal distention and diarrhea are observed after intake of high-fat diets, because of no or insufficient bile in the intestinal tract. In addition, the patients might suffer from postcholecystectomy syndrome (PCS) after the gallbladder removal [4] which could be related to sphincter of Oddi dysfunction (SOD) [5]. The lamina propria of cystic mucosa secretes white liquid mainly composed of immunoglobulin (IgA) which protects the biliary and intestinal mucosae against secondary bile acid and eliminates pathogenic bacteria. It has been suggested that cholecystectomy alters the drainage and residence time of bile in the intestinal tract, resulting in generation of more secondary cholic acid and an increased probability of mitosis and canceration of colon mucosal cells [6–8]. All liver donors are healthy individuals, and the safety of donors, including minimization of injury and maximum preservation of organ function, is a prerequisite for development of LDLT techniques. In this regard, liver graft procurement with gallbladder preservation for normal function in donors can enhance the postoperative quality of life and gastrointestinal function of donors.
The purpose of this study was to evaluate the feasibility of gallbladder preservation, guided by the anatomic and physiological features of the gallbladder, and to study longterm effects to ensure the safety of and minimum injury to donors. Herein, we present our initial results from assessment of the anatomical requirements of such donors and evaluation of postoperative symptoms, complications, morphology, and contractile functions of the gallbladder.
Patients and methods Study protocol Ninety-two grafts, 78 right-liver grafts and 14 left-liver grafts, were transplanted into 89 patients (three dual-graft transplants) at our hospital during the period from June 2006 to Dec 2012. Of the 78 right-lobe-graft LDLT (the MHV was included for 57 grafts), 15 donors (8 females and 7 males, average age 36.6 ± 7.2 years) met the anatomic requirements for gallbladder preservation (the MHV was included for seven grafts). Among 14 left-liver grafts, 13 were successfully performed with gallbladder preservation. The average postoperative follow-up period was 58.6 (44–78) months, and a total of six donors were lost to follow-up. The other 58 donors with cholecystectomy were regarded as controls, for comparison purposes. For both groups surgery was performed by the same group of surgeons. Clinical data for the two groups are as detailed in Table 1. Donor selection and evaluation The procedures involved in donor selection and evaluation conformed to the guidelines of the Regulation of Human’s Organ Transplantation of China and were approved by the
Table 1 Comparison of clinical data for right or left-graft lobectomy with or without gallbladder preservation Clinical data for donors
Graft procurement with donor gallbladder preservation Yes (n = 28)
p
No (n = 58)
Donor age (years)
36.8 ± 11.4
38.1 ± 12.2
NS
Remaining left liver/native liver volume (%)
37.2 ± 3.7
35.8 ± 5.7
NS NS
GRWR (%)
1.03 ± 0.28
0.96 ± 0.18
Operation time (min)
425.3 ± 53.8
408.2 ± 61.3
NS
Blood loss (ml)
358.3 ± 175.1
429.5 ± 123.9
NS
Transfusion dose of autoblood (ml)a
225.0 ± 35.4
249.3 ± 47.9
NS
Autoblood transfusion (%)
7.1 % (2/28)
8.6 % (5/58)
NS
Length of hospitalization (day)
10.3 ± 3.6
11.5 ± 2.9
NS
GRWR graft-to-recipient weight ratio, NS not significant a
Intraoperative red cell salvage
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hospital ethics committee. Among the 92 donors, 50 were male and 42 were female, aged from 19 to 56 years (average 37.5) with knowledge of civil rights. The evaluation was performed only after the donors expressed willingness to donate and had learned about the advantages and risks of the operation. The detailed evaluation methods followed those of Queen Mary Hospital, Hong Kong University [9] with some modification; MR imaging was the sole preoperative imaging technique for LDLT donor candidates [10– 13]. Our protocol includes: •
• •
T2 and T1-weighted imaging for detection and characterization of liver parenchymal and extraparenchymal disease; contrast-enhanced volumetric acquisition for evaluation of arterial and venous anatomy; and combination of T2-weighted MR cholangiography with gadobenate dimeglumine (MultiHance) enhanced T1weighted MR cholangiography for evaluation of biliary anatomy.
In this series, conventional IOC through the cystic duct was performed for the first five donors only. With accumulation of experience and on the basis of the literature, IOC is now no longer routinely performed and is reserved solely for problematic cases (when preoperative MRI is not sufficiently clear and biliary variation is suspected, which was encountered for two donors only (2.3 %) of our later cases). Surgical technique: right (or left)-graft lobectomy with gallbladder preservation
2.
3.
4.
5.
6.
7.
The feasibility of gallbladder preservation was confirmed by preoperative imaging of the donors and identification of origin of the intraoperative cystic artery (Fig. 1). The procedures were: 1.
Precise dissection of the right hepatic pedicle was performed. The RHA and the initial segment of the cystic artery originating from the RHA were then mobilized, and the anatomic relationship between the RHA and cystic artery, and the anatomic condition of
Fig. 1 Anatomic requirements shown for the 15 donors who underwent right hepatectomy with gallbladder preservation. a The cystic artery originates from a low position on the right hepatic artery (80.0 %, 12/15). b The cystic artery originates from the left hepatic artery (6.7 %, 1/15). c The cystic artery originates from the proper
8.
the RHA above the opening of cystic artery, were determined, to decide whether or not to perform rightgraft lobectomy with gallbladder preservation. The right portal vein (RPV) was then freed to the junction with the left portal vein, and main portal vein was clearly identified. The right liver was mobilized by dividing the perihepatic ligaments. Care was taken to isolate the right-side hepatic short veins, which were clamped, divided, and sutured. The RHA and RPV were temporarily occluded to produce the demarcation line between the right and left livers, or the Cantlie line was established by location of the MHV by use of intraoperative ultrasonography. The cystic artery was temporarily blocked with an atraumatic vascular bulldog clamp, the gallbladder located on the right of the hepatic transection plane from the liver cystic bed along the loose connective tissue between the gallbladder and liver–gallbladder bed was isolated, and the connection between the gallbladder located on the left of the hepatic transection plane and the liver–gallbladder bed was preserved as far as possible, so that the blood supply from the cystic fossa could be partly maintained. The hepatic parenchyma along the pre-determined cutting plane was transected by cavitron ultrasound surgical aspiration (CUSA) without inflow or outflow vascular occlusion. The loose tissue overlying the hilar plate was dissected meticulously to expose the confluence of left and right hepatic ducts, with the help of preoperative MR imaging, and the site of RHD division was determined. After the integrity of CHD and LHD was ensured, the anterior wall of the RHD was divided with a knife, the brisk arterial or venous bleeding from the hilar plate and ductal wall was controlled by use of 6/0 Prolene sutures, and the posterior wall of the RHD was then divided. The RHA, RPV, and RHV were divided in sequence and the right liver lobe was removed. All vessel stumps were sutured and closed, and the gallbladder at the
hepatic artery (13.3 %, 2/15). d The cystic artery originates from the gastroduodenal artery. If the cystic artery originates from a higher position on the RHA, or the RHA above the cystic artery is fine and close to the porta hepatis (e), it is not possible to preserve the gallbladder
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9.
right margo lateralis envelope of the left liver was also sutured and fixed (Fig. 2). The graft was implanted by use of a routine method, i.e. the modified outflow was end-to-side anastomosed to the IVC, then the liver blood flow was restored after RPV reconstruction. The RHA and RHD were anastomosed by microsurgery.
The procedures for left-graft procurement are similar to those for right-graft, but with an easier approach, because for most donors the gallbladder artery originates from the RHA.
Fig. 2 Precision graft liver procurement with gallbladder preservation for donor. a Do not dissect too much between the right hepatic artery and the bile duct, to preserve the hepatic artery branches that might be present there. b Transection line of the right-liver graft on the diaphragm and visceral surface (green arrow). c Remove the right graft, suture carefully, and close the stem of the hepatic vein, portal vein, and hepatic artery, to ensure the integrity of the cystic artery blood supply; pay attention to bile leakage from the right caudate lobe and the hepatic transection surface. d Suture and fix the preserved gallbladder to the incised margin of the left lobe; the falciform ligament is sutured to the anterior abdominal wall to prevent the left
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Follow-up: gallbladder morphology and function evaluation All donor and patient data were entered in the China Liver Transplant Registry (CLTR) hosted by Hong Kong University and their follow-up protocol was compiled with https://www.cltr.org/en/. Liver function tests, Doppler ultrasound, MRCP, or CT were routinely conducted to investigate vascular and biliary complications among both donors and recipients. The gallbladder and its contractile function, including morphology, size, thickness of gallbladder wall, and contractile and emptying functions, were
lobe from rotating into the right subphrenic cavity. e The liver transection-line on the diaphragm and visceral surface for the leftliver graft (green arrow). f, g The LHA, accessory LHA, and left portal vein are dissected free, and partial isolation of the left side of the gallbladder bed is also performed. h The left-liver graft is transected completely except for the inflow and outflow vessels. i Suture and attachment of the preserved gallbladder to the incised margin of the right liver after left-liver graft removal. a, gallbladder artery; b, RHA; c, LHA; d, accessory LHA; e, left portal vein; f, RHA. GB gallbladder. (Color figure online)
Hepatol Int
assessed by use of ultrasound. Subjective symptoms and complications among the two donor groups were followed up.
Postoperative symptoms among donors undergoing right hepatectomy with or without gallbladder preservation
Statistical analysis
Slight postoperative symptoms were observed for 28 donors with gallbladder preservation whereas donors with cholecystectomy often complained of epigastric pain, aversion to fatty foods, dyspepsia, and diarrhea during an average of 58.6 (44–78) months follow up, the difference between the two groups was significant. However, the 14.3 % (4/28) incidence of nausea and vomiting among donors with gallbladder preservation and 15.5 % (9/58) among donors with cholecystectomy was not significantly different. In addition, for two donors (3.4 %, 2/58) abdominal pain after cholecystectomy was attributed to SOD after endoscopic examination and one underwent endoscopic sphincterotomy (Table 2).
Results are expressed as x ± standard deviation. Values and variables were analyzed by use of the chi-square (v2) test for categorical values and Student’s t test for continuous variables. All data were analyzed by use of Stata 7.0 and SPSS 10.0 software and all p values \0.05 were regarded as statistically significant.
Results Anatomic evaluation of cystic artery for gallbladder preservation Anatomic evaluation of the cystic artery (Fig. 1) is of crucial importance when deciding whether or not to preserve the gallbladder. Among the 15 donors who underwent right lobectomy with gallbladder preservation, the cystic artery originated from the RHA in 80.0 % (type A; 12/15), from the left hepatic artery (LHA) in 6.7 % (type B; 1/15), and from the PHA in 6.7 % (type C; 1/15); a bibranch-type cystic artery that originated from the RHA and the middle hepatic artery (MHA) was found in 6.7 % (1/ 15). For type A or the bi-branch type cystic artery, if the length and diameter of the RHA above the cystic artery was suitable for graft hepatic artery reconstruction, preservation of the gallbladder was suggested. All 13 donors whose cystic artery originated from RHA underwent left lobectomy, so left-graft procurement with gallbladder preservation was achieved without difficulty. The blood supply for preserved gallbladders was in good condition and no dusky or swollen area was observed (Fig. 2). Ultrasound: cystic morphology and contractile function Cystic morphology and contractile function results are shown in Fig. 3. On ultrasound examination, the morphology and size of 26 preserved gallbladders were comparable with normal status, neither thickened cystic wall nor cholecystitis or cholelithiasis was found; however, two preserved gallbladders were found to have shrunk. During the fatty diet test, the contractile function of 26 preserved gallbladders was comparable with normal status; no contractile function was observed for two (7.1 %; 2/28) preserved gallbladders. Nevertheless, neither subjective symptoms nor necrosis or cholelithiasis was observed for these two donors during long-term follow-up.
Comparison of postoperative biliary and vascular complications among donors and recipients Among recipients who were implanted with a liver graft procured with gallbladder preservation in the donor, two suffered from biliary leakage. Among recipients who were implanted with a liver graft procured with cholecystectomy, one suffered from biliary leakage and the other suffered from anastomotic stricture. No significant difference was found between the two groups. Three donors, one with and two without gallbladder preservation, suffered from biliary leakage, and another donor with cholecystectomy suffered from biliary stricture; again there was no significant difference between the two groups. Vascular complications were not significantly different between the two groups (Table 3).
Discussion Cholecystectomy is commonly performed for symptomatic cholelithiasis or cholecystitis. Postcholecystectomy syndrome (PCS), i.e. the recurrence or persistence of abdominal pain or gastrointestinal symptoms months to years after cholecystectomy, which is frustrating for patient and surgeon alike, occurs in 5–47 % of patients [14, 15]. The reported 40 % incidence of PCS was partially related with functional impairment of Oddi’s sphincter [16], and SOD was diagnosed in 9–11 % of patients evaluated for postcholecystectomy pain [17, 18]. After cholecystectomy, 17–35.6 % of patients reported troublesome new-onset diarrhea [19–21], which could be associated with postoperative disturbance of bile metabolism and changes in the dynamics of bile release resulting in food intolerance and fat malabsorption.
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Hepatol Int Fig. 3 Morphology and contractile function of preserved donor gallbladders after graft procurement. The CT scan shows significant regeneration of the residual left lobe 29 months after right-graft lobectomy (a, b) with wellpreserved gallbladder morphology (red arrow). Ultrasonography shows the volume calculated from transverse, longitudinal, and anterior–posterior lengths before the fatty meal test. The pre-fat meal gallbladder volume is shown as control (c, e). Remarkable reduction in volume is observed 30 min (d) and 60 min (f) after consumption of the fatty meal. g Ultrasound evaluation of gallbladder contraction function after fatty meal ingestion shows contractile function of 26 preserved gallbladders comparable with normal status. Contractility (%) = (Volumepre-fat meal Volumefat meal 30min or 60 min)/ Volumepre-fat meal. (Color figure online)
a
b
c
d
e
f
Gallbladder volume (cm3)
Gallbladder contractility (%)᧟
Pre-fat meal
Fat meal 30 min.
Fat meal 60 min.
p
24.8±5.8
11.6±3.8
6.2±1.6
᧸0.05
᧩
53.8
76.7
᧸0.05
g Unlike routine symptomatic patients undergoing cholecystectomy with compromised gallbladder function because of gallstones, atrophy of the gallbladder, or cholecystitis, all living donors are healthy individuals with normal gallbladder function, and removal of normal gallbladder can lead to several functional disorders with potential injury to the donors.
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In our series, 17.2 % (10/58) of donors who underwent liver-graft lobectomy with cholecystectomy often complained of epigastric pain, aversion to fatty diet, abdominal distention after fatty meals, and diarrhea during an average of 58.6 (44–78) months follow-up. However, 28 donors with gallbladder preservation had few subjective symptoms; their frequent complaint of nausea and vomiting
Hepatol Int Table 2 Comparison of postoperative symptoms among donors with or without gallbladder preservation during follow-up Symptom
Upper abdominal painb
Gallbladder preservation (n = 28)
Cholecystectomya (n = 58)
Right graft (15)
Right graft (57)
Left graft (13)
0
Comparison of incidence
Clinical management
0 versus 5.2 % (3/58)*
Endoscopic intervention
0 versus 10.3 % (6/58)*
Relief by diet adjustment
0 versus 13.8 % (8/58)*
Medications
3.6 % (1/28) versus 12.1 % (7/58)*
Half self-relief, half medications
14.3 % (4/28) versus 15.5 % (9/58); NS
Medications
Left graft (1)
Mild: 1 Moderate: 2
Aversion to fatty foods
0
Diarrhea
0
Mild: 2 Moderate: 4 Mild: 2 Moderate: 5 Severe: 1
Dyspepsia
Mild: 1
Mild: 2
Nausea and Vomitingc
Mild: 2
Mild: 3
Moderate: 2
Moderate: 5
Moderate: 5
Severe: 1 NS not significant * p \ 0.05 a
One donor had pre-operative asymptomatic cholesterol gallstone
b
One case was attributed to CBD stones by ultrasound 29 months after surgery, and the stones were removed by ERCP; the other two were diagnosed as sphincter of Oddi dysfunction (SOD) by endoscopic manometry, one donor was relieved by use of the calcium-channel antagonist nifedipine and another underwent endoscopic sphincterotomy
c
All the symptoms were observed within the first week after hepatectomy when the patients began to eat
Table 3 Comparison of vascular and biliary complications among donors and recipients after graft procurement with or without gallbladder preservation Gallbladder preservation (n = 28)
Cholecystectomy (n = 58)
Donor
Recipient
Donor
Recipient
Biliary leakage
1
2
2
1
Biliary anastomotic stenosis
0
0
1
1
Comparison of incidence of complications (%)
Donor: 3.6 % (1/28) versus 5.2 % (3/58), NS; Recipient: 7.1 % (2/28) versus 3.4 % (2/58), NS
HAT or stenosis
0
0
0
2
Recipient: 0 versus 3.4 % (2/58), NS
PVT or stenosis
0
0
0
0
NS
Hepatic vein obstruction
0
1
1
2
Donor: 0 versus 1.7 % (1/58), NS; Recipient: 3.6 % (1/28) versus 3.4 % (2/58), NS
HAT hepatic artery thrombosis, PVT portal vein thrombosis, NS not significant
(14.3 %, 4/28), which was not significantly different from that of cholecystectomy donors (15.5 %, 9/58), was all observed within the first week after surgery (Table 1); this gastrointestinal symptom could be because of the major hepatectomy and was unrelated with gallbladder function. In agreement with previous studies [5, 16–18], our study confirmed that two donors with cholecystectomy suffered from SOD. Gallbladder and sphincter of Oddi (SO)
function are coordinated by hormonal and neuronal mechanisms; nerve fibers connect the gallbladder and SO via the cystic duct [22, 23]. Ingestion of a fatty meal is followed by release of cholecystokinin (CCK) which causes the gallbladder to contract and the SO to relax. Cholecystectomy may affect normal SO function by disrupting this nerve pathway and altering its response to CCK, which results in SO dyskinesia and SOD [24, 25].
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Notably, 12.1 % (7/58) donors suffered from new-onset postcholecystectomy diarrhea, this result is in agreement with previous findings for routine cholecystectomy patients [19–21]. However, no donor whose gallbladder was preserved had the distressing sequel. One of the major concerns about the use of this novel approach is cancellation of IOC and some critical queries must be addressed. First, how is the precise site of RHD division defined during right-graft procurement? Second, how is the integrity of the CBD and residual LHD ensured? In our practice, with the help of preoperative imaging and accumulation of LDLT experience, ‘‘all-in-one’’ MRI proved to be feasible and robust for evaluation of potential living-liver donors in a single diagnostic step [10–13]. In our series, Multihance-enhanced MR cholangiography accurately depicted potential donor biliary anatomy, and for our donors enough guidance was found for intraoperative precise definition of the site of RHD (or LHD) division, no LHD (or RHD), or CBD injury. (In our center IOC is now no longer routinely performed and is reserved for problematic cases only). This thus facilitates feasible right (or left)-graft lobectomy with gallbladder preservation. Another important concern about the use of this approach is cholecystic venous drainage. Does partial mobilization of the right (or left) side of the gallbladder bed affect cytic venous drainage? The cystic veins took either of two routes: one flowed out from the neck of the gallbladder, through the hilum, and into the liver, taken mainly by the portal branch for subsegment 4a (P4a) and by the umbilical portion of the portal branch; the other flowed out from the body of the gallbladder, through the hepatic bed, taken mainly by S4a sinusoid, S5 sinusoid, P4a, and P5 [26, 27]. In our practice, venous drainage of preserved gallbladders was in good condition after partial isolation of hepatic bed, and no dusky or swollen area was observed during intraoperative observation or postoperative followup. The preserved P4a or S4a cystic veins and later reconstructed collateral vessels may contribute to sufficient compensatory drainage for the gallbladder. A major aspect of suitability for gallbladder preservation is the origin of the cystic artery and cystic duct. The cystic artery usually originates from the RHA (73.5 %); however, 2.6–4.5 % of cystic arteries originate from the gastroduodenal artery [28, 29], 4.9 % from PHA [30], and 1–1.96 % from LHA [29, 31]. If the cystic artery originates from the LHA or PHA, or the lower cystic artery originates from the RHA such that the diameter and length of the RHA above the cystic artery are suitable for reconstruction of a graft hepatic artery, right-liver procurement with gallbladder preservation can be performed without difficulty. If the proximal right hepatic pedicle of the cystic artery originates from the RHA, the RHA that was above the opening of the cystic artery is tenuous and short, and the gallbladder
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is regarded as unsuitable for preservation. Two types of cystic duct variation are observed, i.e. it joins the upper position of the CHD or it joins the RHD; the occurrence of this is approximately 0.6–2.3 % [32], and the latter variation affects the surgical approach during right-graft procurement for gallbladder preservation. However, no cystic duct variation was observed among the 28 donors whose gallbladders were preserved in this study. Because the gallbladder is located at the boundary line of the left and right liver lobes, gallbladder preservation makes it inconvenient to dissect the right hepatic pedicle. For gallbladder preservation, it is important to first dissect precisely the right hepatic pedicle and cholecyst triangle, then confirm the origin of the cystic artery and the length and diameter of the upstream RHA, to ensure the integrity of cystic artery if the gallbladder is being preserved. Then, partially isolate the right side of the gallbladder bed and suspend the cystic ampulla to completely expose the RPV, etc. After satisfactory right hepatic pedicle dissection and under-right graft lobectomy conditions, isolate as little as possible of the cystic tissue to ensure sufficient compensatory cystic vessels and to avoid damage to the cystic duct. In this study, the function of most of the preserved gallbladders in donors was found to be good, as shown in Fig. 3. Moreover, the new surgical approach did not cause postoperative hepatic artery or biliary complications (Table 2) or affect the functional quality and rehabilitation of the individuals (Supplemental data(SD)). However, two donors with gallbladder preservation presented with cystic atrophy during follow-up. Although the donors did not report subjective symptoms, the contractile function of gallbladder was non-existent. This was probably because of excessive isolation of the gallbladder bed which led to obstruction of the drainage of the cystic vein. To avoid this complication, the division should deviate to the right side of the transection plane during right-graft procurement. Thus, the left-side serous membrane of the gallbladder will be as much preserved as possible to enable sufficient drainage of cystic vein. In conclusion, our initial results indicate that liver-graft lobectomy with gallbladder preservation is beneficial among donors who meet the anatomical requirements—the surgical approach does not increase postoperative vascular and biliary complications and, importantly, most of the preserved gallbladder remain fully functional during longterm follow-up. Another randomized control trial with a larger population and more long-term, evidence-based monitoring of outcomes will, however, be necessary to prove its efficacy and safety. Acknowledgements The authors would like to thank Ma Fen Xi for her excellent assistance with the schematic illustration. This study
Hepatol Int was sponsored by the Natural Sciences Foundation of China (Grant Nos. 30772136, 30972950 and 81070383). Compliance with ethical requirements and Conflict of interest All procedures followed were in accordance with the ethical standards of the responsible committees on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008. Informed consent was obtained from all the patients included in the study. Jia-Hong Dong, Sheng Ye, Wei-Dong Duan, Wen-Bing Ji, and Yu-Rong Liang declare that they have no conflict of interest.
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