- Email: [email protected]
Hepatobiliary Scintigraphy in the Preoperative Evaluation of Potential Living Liver Donors
Hepatobiliary Scintigraphy in the Preoperative Evaluation of Potential Living Liver Donors M. Serenaria,*, C. Pettinatob, C. Bonattia, L. Zanonic, F. Odaldia, A. Cucchettia, M. Ravaiolia, S. Fantic, A.D. Pinnaa, and M. Cescona a Department of Medical and Surgical Sciences e DIMEC, S.Orsola-Malpighi Hospital, Alma Mater Studiorum, University of Bologna, Bologna, Italy; bMedical Physics Unit, Radiology Unit, S.Orsola-Malpighi Hospital, Bologna, Italy; and cDepartment of Nuclear Medicine, S.Orsola-Malpighi Hospital, Bologna, Italy
ABSTRACT Background. Graft selection strategy in living donor liver transplantation (LDLT) is usually multifactorial, but special attention is paid to the determination of donor liver volumes to minimize any risk of posthepatectomy liver failure (PHLF). Hepatobiliary scintigraphy (HBS) with single-photon-emission computed tomography allows for the measurement of total and future liver remnant function (FLR-F) and has been shown to predict the risk of PHLF more accurately than liver volumetry. Methods. Since November 2016, HBS has been performed at our Institution in every candidate to major hepatectomy, including potential living liver donors. Results. Thirty-seven consecutive patients were submitted to HBS, of whom 7 were potential living liver donors. After completed hepatectomy (n ¼ 27), the median FLR-F of patients who developed PHLF (n ¼ 9) was 1.72%/min/m2 (range 1.40e2.78) compared to that of patients who did not (n ¼ 18), which was 4.02%/min/m2 (range 1.15e12.08). Three donors underwent operations (1 right hepatectomy and 2 left hepatectomies). In the only donor who developed PHLF, the FLR accounted for the 37% of the total liver volume, whereas the FLR represented only the 31% of the total liver function (TL-F ¼ 11.29%/min) with a resulting FLR-F of 2.05%/min/m2. Conclusions. The present study suggests that a non-invasive low-cost exam such as HBS may be a promising tool to predict PHLF not only in neoplastic patients but also to evaluate potential living donors. Larger studies are needed to draw any conclusion regarding the benefits of HBS in the living liver donor workup.
T
HE FIRST aim of graft selection strategies in living donor liver transplantation (LDLT) is donor safety. The decision to use left-lobe (LL) or right-lobe (RL) grafts is usually multifactorial, including both donor and recipient considerations [1]. In this regard, future liver remnant (FLR) volume is known to be a major concern in donor surgery, especially for patients undergoing right hepatectomy, and the LL, which is normally smaller than the RL, may be preferred to reduce the risk of posthepatectomy liver failure (PHLF) in the donor [2]. However, donor anatomy, as well as the risk of small-for-size syndrome in the recipient, may require the donation of the RL. Although volumetry is the standard method for determining whether a patient can safely undergo a major hepatectomy, many ª 2018 Elsevier Inc. All rights reserved. 230 Park Avenue, New York, NY 10169
Transplantation Proceedings, 51, 167e170 (2019)
studies have demonstrated that there is not always a linear correlation between liver volume and function [3]. Recently, Kuramitsu et al [4] reported that right hepatectomy also carries a non-negligible risk for PHLF in LDLT setting. In this sense, hepatobiliary scintigraphy (HBS) with singlephoton-emission computed tomography (SPECT) allows for the measurement of regional distribution of liver
*Address correspondence to Matteo Serenari, MD, Department of Medical and Surgical Sciences e DIMEC, S.Orsola-Malpighi Hospital, Alma Mater Studiorum, University of Bologna, Via Massarenti 9, 40138, Bologna, Italy. E-mail: matteo. [email protected] 0041-1345/18 https://doi.org/10.1016/j.transproceed.2018.04.087
167
168
function [5] and has been shown to predict the risk of PHLF before major hepatectomy more accurately than liver volumetry [6]. Herein we report our preliminary experience of HBS before major hepatectomy, including potential living liver donors. MATERIALS AND METHODS Since November 2016, HBS has been performed before major hepatectomy according to Associazione Italiana di Medicina Nucleare ed Imaging’s 2017 guidelines (https://www.aimn.it/site/ page/attivita/linee-guida), and was done for every donor candidate entered in our LDLT program. The preoperative donor workup at our institution includes computed tomography (CT), magnetic resonance cholangiography (MRCP), liver biopsy, blood tests, and viral serology as standard practices. If donors are selected for surgery, 3 multi-disciplinary conferences are held before the operation to review and discuss the case, plan the surgery, and review imaging investigations. All members of the team (surgeons, radiologists, hepatologists, coordinators, and nurses) participate in these meetings. PHLF was defined according to the International Study Group of Liver Surgery criteria [7].
Hepatic Volumetry Liver volumes were assessed using MeVis software (Fraunhofer MeVis, Bremen, Germany) in living donors. MeVis uses a 3-phasic CT scan to extract the individual vessel territories of the patient’s liver [8]. Based on this segmentation, it is possible to draw a resection line in the model, showing the loss of vascular territories with each cut. Both the FLR and the measured total liver volume (TLV) were calculated. We aim to leave donors with a FLR/TLV 30%.
Hepatobiliary Scintigraphy Patients were in supine position, with a large field-of-view SPECT camera (Discovery NM/CT 670 ES, GE Healthcare, Eindhoven, the Netherlands) over the liver and heart region. The SPECT camera was equipped with low-energy high-resolution collimators. First, a dual-head dynamic acquisition (36 frames at 10s/frame, 128 matrix), was obtained immediately after the intravenous administration of 200 MBq freshly prepared 99mTc-labeled iminodiacetic acid (99m Tc-mebrofenin, Bridatec, GE Healthcare), which was used to calculate the hepatic mebrofenin uptake rate (TL-F) using geometric mean datasets. Subsequently, a fast SPECT acquisition was performed (60 projections of 5s/projection, 128 matrix), centered on the peak of the hepatic time-activity curve, which was used to calculate the 3-dimensional distribution of function within the future liver remnant (FLR-C). Directly after SPECT, a low-dose, non-contrast-enhanced CT scan was acquired for attenuation correction and anatomic mapping. FRL function (FRL-F) was calculated as TL-F multiplied by FLR-C, expressed as %/min and corrected for body surface area [5].
Donor Surgical Technique The graft procurement technique starts with a small hockey-stick incision. After inspection and palpation of the liver, the liver is fully mobilized. The hepatic hilum is encircled with a tourniquet for Pringle maneuver. Posterior segment venous tributaries are preserved for re-implantation in the recipient depending on the estimated congestive area, calculated preoperatively using MeVis. After the cholecystectomy, a small cholangiogram catheter is introduced into the cystic duct and biliary anatomy is verified,
SERENARI, PETTINATO, BONATTI ET AL correlating any intraoperative observations with the preoperative MRCP images. To define the bile duct transection line, a large metal clip is used. Dissection of the portal vein and the hepatic artery is cautiously performed in order to avoid ischemic damage of the bile duct. After visualization of the middle hepatic vein using intraoperative ultrasound and securing the right/left hepatic vein, the transection line is marked through a transient right/left vascular occlusion and a parenchymal transection is then performed with ultrasonic dissector plus harmonic scalpel. At our center, the middle hepatic vein is not routinely taken along with the graft. Bleeding is controlled mainly with bipolar electrocautery supplemented with hemostatic clips. Before dividing the right/left bile duct, the cholangiogram is repeated to ensure that the marking clip placed is in a good position. Heparin is normally not administered prior to graft removal. The right/left hepatic artery and the right/left portal vein are divided with a small Satinsky vascular clamp, as well as the right/ left hepatic vein. The hepatic artery is flushed with heparin using a small catheter and the entire graft is then flushed through the portal vein with 1e1.5 L of Celsior solution. The liver is packed on ice and transferred to the recipient operating room.
RESULTS
Between November 2016 and November 2017, 37 consecutive patients who were candidates for major hepatectomy were submitted to preoperative HBS. Of these, 7 were potential living donors (Table 1). After the hepatectomy was completed, PHLF occurred in 9 out of 27 patients (33.3%, 5 of grade A and 4 of grade B). The median FLR-F of patients who developed PHLF was 1.72%/min/m2 (range 1.40e2.78) compared to that of patients who did not, which was 4.02%/min/m2 (range 1.15e12.08). Focusing on the donor operations, 3 patients underwent operations (1 right hepatectomy and 2 left hepatectomies) and discharged without any complications, except for 1 patient who developed grade A PHLF and ascites. This donor was a 59-year-old woman who donated her right hemi-liver (segments 5-6-7-8) to her husband. Her preoperative laboratory tests and liver biopsy were normal but with antibody to hepatitis B core antigen positivity. The FLR (segments 1-2-3-4) was 407 cm3 and accounted for 37% of the TLV, whereas the FLR represented functionally (FLR-C) only 31% of the total liver function (TL-F ¼ 11.29%/min) with a resulting FLR-F of 2.05%/min/m2. We decided to use the RL since the LL would have been provided a graft weightto-body weight ratio of only 0.58% compared to 0.96% if RL had been used. Furthermore, the LL would have required that 3 arteries had been reconstructed: the left branch of the hepatic artery, 1 accessory left hepatic artery arising from the left gastric artery, and a middle hepatic artery arising from the proper hepatic artery. The recipient had bilateral colorectal liver metastases and his MELD was 7. The other 4 patients were not suitable for the donor procedure: the recipient of patient 4 (Table 1) was transplanted with a cadaveric donor graft. We ruled out patient 5 due to a factor V mutation. Among the last 2 LDLT procedures that had to be performed, the recipient of patient 6 showed progression of disease (colorectal liver metastases)
HEPATOBILIARY SCINTIGRAPHY
169
Table 1. Characteristics of Donor Candidates Evaluated With Hepatobiliary Scintigraphy Patient
1 2 3 4 5 6 7
Age (y)
Sex
BMI (kg/m2)
Graft
FLR/TLV (%)
FLR-C (%)
TL-F (%/min)
FLR-F (%/min/m2)
Type of Surgery
PHLF*
59 48 46 40 31 35 39
F F M M F M M
23.5 23.8 24.4 32.6 22.3 24 23.1
RL LL LL LL RL LL RL
37 71.6 67.5 65.6 36.7 67.9 30.7
31.1 83.5 71 76.4 29 64.8 29.3
11.29 19.21 17.10 14.28 14.83 15.24 17.90
2.05 8.97 5.52 4.95 2.61 5.24 2.77
RH LH LH -
Yes No No -
Abbreviations: BMI, body mass index; F, female; FLR, future liver remnant; FLR-C, percentage of distribution of function within the future liver remnant; FLR-F, future liver remnant function; LH, left hepatectomy; LL, left lobe; M, male; PHLF, post-hepatectomy liver failure; RH, right hepatectomy; RL, right lobe; TL-F, total liver function; TLV, total liver volume. *According to International Study Group of Liver Surgery criteria.
at the follow-up imaging, and patient 7 is still waiting for donor surgery.
DISCUSSION
Donor safety is mandatory in LDLT and every effort must be made to minimize the risk of donor complications. This study aimed to show the potential role of a non-invasive, low-cost exam such as HBS in the workup of living liver donors to predict PHLF before donor hepatectomy. In the recent past, selection of graft shifted from LL to RL with a demonstrated increased rate of complications for the donors [9]. Indeed, RL represents about the 60% of the whole liver and its use may provide more adequate volumes in the recipient; however, this increases the risk of PHLF in the donor [1]. In 2013 Cheah et al performed a worldwide survey where they analyzed 71 LDLT programs and reported 23 donor deaths out of 11,553 LDLT procedures (0.2%) [10]. Of those 23 deaths, 8 (34.8%) were due to liver failure. More recently, Kuramitsu et al [4] reported a rate of PHLF of 8% (21 patients) according to the International Study Group of Liver Surgery criteria in their 12 years of LDLT experience, without any demonstrated association between PHLF and FLR volume revealed by uni- or multivariate analysis. The risk of PHLF should therefore not be underestimated even if volumetric criteria are met, normally with a FLR ranging between 30% and 35% of the TLV depending on the age of the donor [11]. Indeed, many studies have demonstrated that there is not always a linear correlation between function and volume, especially in the presence of an underlying liver disease [5]. Thus, the “healthy” volunteers who are selected for donation may be in some cases not healthy at all but preoperative laboratory tests fail to measure liver function comprehensively. Invasive and costly liver biopsies may be also be of little use, as they are prone to frequent sampling errors. In this sense, HBS is a non-invasive low-cost exam which has been shown to be able to measure total liver function as indocyanine green clearance does, but unlike indocyanine green clearance it can also measure residual liver function, which is helpful in cases of borderline remnant liver volumes. For instance, in the only patient who developed PHLF, the FLR represented in our series, 37% of the TLV, but 31% was a
very low TL-F (11.29%/min) with a resulting FLR-F of 2.05%/min/m2 (FLR-F ¼ TL-F/BSA FLR-C). This value was lower than the cut-off established in 2010 for a safe liver resection (2.69%/min/m2) [6]. Although this cutoff has been recently called into question [12], at present HBS can be used as a confirmatory test together with CT volumetry in clinical decision-making, especially with borderline remnant liver volumes. This finding needs to be studied within a larger group of patients who are candidates for living donor hepatectomy to draw any conclusion of the benefits of HBS in the living liver donor workup. However, despite the low number of cases of living donors reported in the current series, we recently started to perform HBS at our institution before every major hepatectomy. Interestingly, 5 of the 9 PHLFs were represented by patients who underwent right hepatectomy with normal preoperative remnant liver volumes and liver function exams. In conclusion, the present study suggests that a noninvasive, low-cost exam such as HBS may also be helpful to prevent PHLF in LDLT settings and may be included in the standard preoperative workup of donors. Future research should focus on role of HBS in matching between functional demand of graft recipient and donor organ, thus helping simplify the very complex graft selection strategy.
REFERENCES [1] Roll GR, Parekh JR, Parker WF, Siegler M, Pomfret EA, Ascher NL, et al. Left hepatectomy versus right hepatectomy for living donor liver transplantation: shifting the risk from the donor to the recipient. Liver Transpl 2013;19:472e81. [2] Halazun KJ, Przybyszewski EM, Griesemer AD, Cherqui D, Michelassi F, Guarrera JV, et al. Leaning to the left: increasing the donor pool by using the left lobe, outcomes of the largest singlecenter North American experience of left lobe adult-to-adult living donor liver transplantation. Ann Surg 2016;264:448e56. [3] Nilsson H, Karlgren S, Blomqvist L, Jonas E. The inhomogeneous distribution of liver function: possible impact on the prediction of post-operative remnant liver function. HPB (Oxford) 2015;17:272e7. [4] Kuramitsu K, Fukumoto T, Kobayashi T, Fukushima K, Okimoto S, Iwasaki T, et al. The incidence of posthepatectomy liver failure defined by the international study group of liver surgery among living donors. J Gastrointest Surg 2016;20:757e64. [5] De Graaf W, Van Lienden KP, Van Gulik TM, Bennink RJ. (99m) Tc-Mebrofenin hepatobiliary scintigraphy with SPECT for
170 the assessment of hepatic function and liver functional volume before partial hepatectomy. J Nucl Med 2010;51:229e36. [6] de Graaf W, van Lienden KP, Dinant S, Roelofs JJTH, Busch ORC, Gouma DJ, et al. Assessment of future remnant liver function using hepatobiliary scintigraphy in patients undergoing major liver resection. J Gastrointest Surg 2010;14:369e78. [7] Rahbari NN, Garden OJ, Padbury R, Brooke-Smith M, Crawford M, Adam R, et al. Posthepatectomy liver failure: a definition and grading by the International Study Group of Liver Surgery (ISGLS). Surgery 2011;149:713e24. [8] Radtke A, Nadalin S, Sotiropoulos GC, Molmenti EP, Schroeder T, Valentin-Gamazo C, et al. Computer-assisted operative planning in adult living donor liver transplantation: a new way to resolve the dilemma of the middle hepatic vein. World J Surg 2007;31:175e85.
SERENARI, PETTINATO, BONATTI ET AL [9] Lo CM. Complications and long-term outcome of living liver donors: a survey of 1,508 cases in five Asian centers. Transplantation 2003;75:S12e5. [10] Cheah YL, Simpson MA, Pomposelli JJ, Pomfret EA. Incidence of death and potentially life-threatening near-miss events in living donor hepatic lobectomy: a world-wide survey. Liver Transpl 2013;19:499e506. [11] Hwang S, Lee SG, Lee YJ, Sung KB, Park KM, Kim KH, et al. Lessons learned from 1,000 living donor liver transplantations in a single center: how to make living donations safe. Liver Transpl 2006;12:920e7. [12] Serenari M, Collaud C, Alvarez FA, de Santibañes M, Giunta D, Pekolj J, et al. Interstage assessment of remnant liver function in ALPPS using hepatobiliary scintigraphy. Ann Surg 2018;267:1141e7.
ABSTRACT Background. Graft selection strategy in living donor liver transplantation (LDLT) is usually multifactorial, but special attention is paid to the determination of donor liver volumes to minimize any risk of posthepatectomy liver failure (PHLF). Hepatobiliary scintigraphy (HBS) with single-photon-emission computed tomography allows for the measurement of total and future liver remnant function (FLR-F) and has been shown to predict the risk of PHLF more accurately than liver volumetry. Methods. Since November 2016, HBS has been performed at our Institution in every candidate to major hepatectomy, including potential living liver donors. Results. Thirty-seven consecutive patients were submitted to HBS, of whom 7 were potential living liver donors. After completed hepatectomy (n ¼ 27), the median FLR-F of patients who developed PHLF (n ¼ 9) was 1.72%/min/m2 (range 1.40e2.78) compared to that of patients who did not (n ¼ 18), which was 4.02%/min/m2 (range 1.15e12.08). Three donors underwent operations (1 right hepatectomy and 2 left hepatectomies). In the only donor who developed PHLF, the FLR accounted for the 37% of the total liver volume, whereas the FLR represented only the 31% of the total liver function (TL-F ¼ 11.29%/min) with a resulting FLR-F of 2.05%/min/m2. Conclusions. The present study suggests that a non-invasive low-cost exam such as HBS may be a promising tool to predict PHLF not only in neoplastic patients but also to evaluate potential living donors. Larger studies are needed to draw any conclusion regarding the benefits of HBS in the living liver donor workup.
T
HE FIRST aim of graft selection strategies in living donor liver transplantation (LDLT) is donor safety. The decision to use left-lobe (LL) or right-lobe (RL) grafts is usually multifactorial, including both donor and recipient considerations [1]. In this regard, future liver remnant (FLR) volume is known to be a major concern in donor surgery, especially for patients undergoing right hepatectomy, and the LL, which is normally smaller than the RL, may be preferred to reduce the risk of posthepatectomy liver failure (PHLF) in the donor [2]. However, donor anatomy, as well as the risk of small-for-size syndrome in the recipient, may require the donation of the RL. Although volumetry is the standard method for determining whether a patient can safely undergo a major hepatectomy, many ª 2018 Elsevier Inc. All rights reserved. 230 Park Avenue, New York, NY 10169
Transplantation Proceedings, 51, 167e170 (2019)
studies have demonstrated that there is not always a linear correlation between liver volume and function [3]. Recently, Kuramitsu et al [4] reported that right hepatectomy also carries a non-negligible risk for PHLF in LDLT setting. In this sense, hepatobiliary scintigraphy (HBS) with singlephoton-emission computed tomography (SPECT) allows for the measurement of regional distribution of liver
*Address correspondence to Matteo Serenari, MD, Department of Medical and Surgical Sciences e DIMEC, S.Orsola-Malpighi Hospital, Alma Mater Studiorum, University of Bologna, Via Massarenti 9, 40138, Bologna, Italy. E-mail: matteo. [email protected] 0041-1345/18 https://doi.org/10.1016/j.transproceed.2018.04.087
167
168
function [5] and has been shown to predict the risk of PHLF before major hepatectomy more accurately than liver volumetry [6]. Herein we report our preliminary experience of HBS before major hepatectomy, including potential living liver donors. MATERIALS AND METHODS Since November 2016, HBS has been performed before major hepatectomy according to Associazione Italiana di Medicina Nucleare ed Imaging’s 2017 guidelines (https://www.aimn.it/site/ page/attivita/linee-guida), and was done for every donor candidate entered in our LDLT program. The preoperative donor workup at our institution includes computed tomography (CT), magnetic resonance cholangiography (MRCP), liver biopsy, blood tests, and viral serology as standard practices. If donors are selected for surgery, 3 multi-disciplinary conferences are held before the operation to review and discuss the case, plan the surgery, and review imaging investigations. All members of the team (surgeons, radiologists, hepatologists, coordinators, and nurses) participate in these meetings. PHLF was defined according to the International Study Group of Liver Surgery criteria [7].
Hepatic Volumetry Liver volumes were assessed using MeVis software (Fraunhofer MeVis, Bremen, Germany) in living donors. MeVis uses a 3-phasic CT scan to extract the individual vessel territories of the patient’s liver [8]. Based on this segmentation, it is possible to draw a resection line in the model, showing the loss of vascular territories with each cut. Both the FLR and the measured total liver volume (TLV) were calculated. We aim to leave donors with a FLR/TLV 30%.
Hepatobiliary Scintigraphy Patients were in supine position, with a large field-of-view SPECT camera (Discovery NM/CT 670 ES, GE Healthcare, Eindhoven, the Netherlands) over the liver and heart region. The SPECT camera was equipped with low-energy high-resolution collimators. First, a dual-head dynamic acquisition (36 frames at 10s/frame, 128 matrix), was obtained immediately after the intravenous administration of 200 MBq freshly prepared 99mTc-labeled iminodiacetic acid (99m Tc-mebrofenin, Bridatec, GE Healthcare), which was used to calculate the hepatic mebrofenin uptake rate (TL-F) using geometric mean datasets. Subsequently, a fast SPECT acquisition was performed (60 projections of 5s/projection, 128 matrix), centered on the peak of the hepatic time-activity curve, which was used to calculate the 3-dimensional distribution of function within the future liver remnant (FLR-C). Directly after SPECT, a low-dose, non-contrast-enhanced CT scan was acquired for attenuation correction and anatomic mapping. FRL function (FRL-F) was calculated as TL-F multiplied by FLR-C, expressed as %/min and corrected for body surface area [5].
Donor Surgical Technique The graft procurement technique starts with a small hockey-stick incision. After inspection and palpation of the liver, the liver is fully mobilized. The hepatic hilum is encircled with a tourniquet for Pringle maneuver. Posterior segment venous tributaries are preserved for re-implantation in the recipient depending on the estimated congestive area, calculated preoperatively using MeVis. After the cholecystectomy, a small cholangiogram catheter is introduced into the cystic duct and biliary anatomy is verified,
SERENARI, PETTINATO, BONATTI ET AL correlating any intraoperative observations with the preoperative MRCP images. To define the bile duct transection line, a large metal clip is used. Dissection of the portal vein and the hepatic artery is cautiously performed in order to avoid ischemic damage of the bile duct. After visualization of the middle hepatic vein using intraoperative ultrasound and securing the right/left hepatic vein, the transection line is marked through a transient right/left vascular occlusion and a parenchymal transection is then performed with ultrasonic dissector plus harmonic scalpel. At our center, the middle hepatic vein is not routinely taken along with the graft. Bleeding is controlled mainly with bipolar electrocautery supplemented with hemostatic clips. Before dividing the right/left bile duct, the cholangiogram is repeated to ensure that the marking clip placed is in a good position. Heparin is normally not administered prior to graft removal. The right/left hepatic artery and the right/left portal vein are divided with a small Satinsky vascular clamp, as well as the right/ left hepatic vein. The hepatic artery is flushed with heparin using a small catheter and the entire graft is then flushed through the portal vein with 1e1.5 L of Celsior solution. The liver is packed on ice and transferred to the recipient operating room.
RESULTS
Between November 2016 and November 2017, 37 consecutive patients who were candidates for major hepatectomy were submitted to preoperative HBS. Of these, 7 were potential living donors (Table 1). After the hepatectomy was completed, PHLF occurred in 9 out of 27 patients (33.3%, 5 of grade A and 4 of grade B). The median FLR-F of patients who developed PHLF was 1.72%/min/m2 (range 1.40e2.78) compared to that of patients who did not, which was 4.02%/min/m2 (range 1.15e12.08). Focusing on the donor operations, 3 patients underwent operations (1 right hepatectomy and 2 left hepatectomies) and discharged without any complications, except for 1 patient who developed grade A PHLF and ascites. This donor was a 59-year-old woman who donated her right hemi-liver (segments 5-6-7-8) to her husband. Her preoperative laboratory tests and liver biopsy were normal but with antibody to hepatitis B core antigen positivity. The FLR (segments 1-2-3-4) was 407 cm3 and accounted for 37% of the TLV, whereas the FLR represented functionally (FLR-C) only 31% of the total liver function (TL-F ¼ 11.29%/min) with a resulting FLR-F of 2.05%/min/m2. We decided to use the RL since the LL would have been provided a graft weightto-body weight ratio of only 0.58% compared to 0.96% if RL had been used. Furthermore, the LL would have required that 3 arteries had been reconstructed: the left branch of the hepatic artery, 1 accessory left hepatic artery arising from the left gastric artery, and a middle hepatic artery arising from the proper hepatic artery. The recipient had bilateral colorectal liver metastases and his MELD was 7. The other 4 patients were not suitable for the donor procedure: the recipient of patient 4 (Table 1) was transplanted with a cadaveric donor graft. We ruled out patient 5 due to a factor V mutation. Among the last 2 LDLT procedures that had to be performed, the recipient of patient 6 showed progression of disease (colorectal liver metastases)
HEPATOBILIARY SCINTIGRAPHY
169
Table 1. Characteristics of Donor Candidates Evaluated With Hepatobiliary Scintigraphy Patient
1 2 3 4 5 6 7
Age (y)
Sex
BMI (kg/m2)
Graft
FLR/TLV (%)
FLR-C (%)
TL-F (%/min)
FLR-F (%/min/m2)
Type of Surgery
PHLF*
59 48 46 40 31 35 39
F F M M F M M
23.5 23.8 24.4 32.6 22.3 24 23.1
RL LL LL LL RL LL RL
37 71.6 67.5 65.6 36.7 67.9 30.7
31.1 83.5 71 76.4 29 64.8 29.3
11.29 19.21 17.10 14.28 14.83 15.24 17.90
2.05 8.97 5.52 4.95 2.61 5.24 2.77
RH LH LH -
Yes No No -
Abbreviations: BMI, body mass index; F, female; FLR, future liver remnant; FLR-C, percentage of distribution of function within the future liver remnant; FLR-F, future liver remnant function; LH, left hepatectomy; LL, left lobe; M, male; PHLF, post-hepatectomy liver failure; RH, right hepatectomy; RL, right lobe; TL-F, total liver function; TLV, total liver volume. *According to International Study Group of Liver Surgery criteria.
at the follow-up imaging, and patient 7 is still waiting for donor surgery.
DISCUSSION
Donor safety is mandatory in LDLT and every effort must be made to minimize the risk of donor complications. This study aimed to show the potential role of a non-invasive, low-cost exam such as HBS in the workup of living liver donors to predict PHLF before donor hepatectomy. In the recent past, selection of graft shifted from LL to RL with a demonstrated increased rate of complications for the donors [9]. Indeed, RL represents about the 60% of the whole liver and its use may provide more adequate volumes in the recipient; however, this increases the risk of PHLF in the donor [1]. In 2013 Cheah et al performed a worldwide survey where they analyzed 71 LDLT programs and reported 23 donor deaths out of 11,553 LDLT procedures (0.2%) [10]. Of those 23 deaths, 8 (34.8%) were due to liver failure. More recently, Kuramitsu et al [4] reported a rate of PHLF of 8% (21 patients) according to the International Study Group of Liver Surgery criteria in their 12 years of LDLT experience, without any demonstrated association between PHLF and FLR volume revealed by uni- or multivariate analysis. The risk of PHLF should therefore not be underestimated even if volumetric criteria are met, normally with a FLR ranging between 30% and 35% of the TLV depending on the age of the donor [11]. Indeed, many studies have demonstrated that there is not always a linear correlation between function and volume, especially in the presence of an underlying liver disease [5]. Thus, the “healthy” volunteers who are selected for donation may be in some cases not healthy at all but preoperative laboratory tests fail to measure liver function comprehensively. Invasive and costly liver biopsies may be also be of little use, as they are prone to frequent sampling errors. In this sense, HBS is a non-invasive low-cost exam which has been shown to be able to measure total liver function as indocyanine green clearance does, but unlike indocyanine green clearance it can also measure residual liver function, which is helpful in cases of borderline remnant liver volumes. For instance, in the only patient who developed PHLF, the FLR represented in our series, 37% of the TLV, but 31% was a
very low TL-F (11.29%/min) with a resulting FLR-F of 2.05%/min/m2 (FLR-F ¼ TL-F/BSA FLR-C). This value was lower than the cut-off established in 2010 for a safe liver resection (2.69%/min/m2) [6]. Although this cutoff has been recently called into question [12], at present HBS can be used as a confirmatory test together with CT volumetry in clinical decision-making, especially with borderline remnant liver volumes. This finding needs to be studied within a larger group of patients who are candidates for living donor hepatectomy to draw any conclusion of the benefits of HBS in the living liver donor workup. However, despite the low number of cases of living donors reported in the current series, we recently started to perform HBS at our institution before every major hepatectomy. Interestingly, 5 of the 9 PHLFs were represented by patients who underwent right hepatectomy with normal preoperative remnant liver volumes and liver function exams. In conclusion, the present study suggests that a noninvasive, low-cost exam such as HBS may also be helpful to prevent PHLF in LDLT settings and may be included in the standard preoperative workup of donors. Future research should focus on role of HBS in matching between functional demand of graft recipient and donor organ, thus helping simplify the very complex graft selection strategy.
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