Research article Open Access
Utility of Bone Scan in Pre-Liver Transplant Work-Up of Patients with hepatocellular carcinoma
Ahmed Alqarni1, Monther Kabbani1, Faisal Abaalkhail1,2, Alicia Chorley1, Hany Elbeshbeshy1, Waleed Al-Hamoudi1,3, Saleh Alabbad1, Mark Stuarduvant1, Mohammad Alsofayan1, Wael Al- Kattan2, Baderaldeen Ahmed1, Mohamed Al Sebayel1, HussienElsiesy1, 2*
1Liver Transplantation, King Faisal Specialist Hospital & Research Center
2Alfaisal University
3Gastroenterology, King Saud University, Riyadh, Saudi Arabia
*Corresponding author: Hussien Elsiesy, King Faisal Specialist Hospital & Research Center and Department of Liver transplantation, Altakhasusi Street, Riyadh, 11211, Saudi Arabia, Tel: +966114647272;E-mail: @
Received: October 2, 2016; Accepted: November 30, 2016; Published: January 14, 2017
Citation: Alqarni A, Kabbani M, Abaalkhail F, Chorley A, Elsiesy H, et al. (2017) Utility of Bone Scan in Pre-Liver Transplant Work-Up of Patients with hepatocellular carcinoma. Gastroenterol Pancreatol Liver Disord 4(1): 1-3. DOI: http://dx.doi.org/10.15226/2374- 815X/4/1/00179
Abstract
Background and Aims: Our program utilizes bone scan routinely as part of liver transplant (LT) evaluation of patients with hepatocellular carcinoma (HCC). The aim of this study is to evaluate the utility of bone scan in the pre-transplant workup.
Methods: This is a retrospective chart review of our LT database from January 2011 to December 2014 of all patients with HCC who had LT. Collected data include age , gender, etiology of liver disease , imaging (CT or MRI ) , bone scan, explants tissue pathology , type of transplant and transplant outcome.
Results: During the study period, 275 LTs were performed. Fifty-two patients had HCC, of whom 34 underwent bone scan. The average age was 58(22-72), and 20 patients were males. The etiology of liver disease was hepatitis C (21 patients), cryptogenic cirrhosis (7 patients) and HBV (6 patients). Sixteen patients had HCC within the Milan criteria, 12 within University of California at San Francisco (UCSF) criteria, and 6 patients were beyond the UCSF criteria. Twenty four patients underwent Living donor liver transplantation (LDLT), whereas 10 patients underwent Deceased donor liver transplantation (DDLT). Of the 34 patients, 1 patient had positive suspicious bone scan (2.9%). The remaining 33 patients had negative bone scan (97 %). One patient within UCSF criteria had false positive bone scan (negative PET-CT and no recurrence after liver transplant).
Conclusions: Bone scan has low utility in patients with HCC within the Milan criteria and should not be routinely used as part of the liver transplant workup.
Key Words: Bone scan; Hepatocellular carcinoma; Bone
Introduction
Hepatocellular carcinoma (HCC) is the most common primary liver tumor accounts for over 80 % [1, 2] and the burden of this devastating disease is expected to increase. HCC is the second leading cause of cancer-related death worldwide [3]. Incidence rates are not uniform across different geographical regions, but vary in accordance with the frequency of risk factors [4]. Each year, approximately 750,000 new cases are diagnosed, risk factors include pre-existing infection with hepatitis B or C viruses and cirrhosis [5, 6].
The diagnosis of HCC in our study was made based on radiological criteria according to the AASLD guidelines [7, 8].
Bone metastases (BM) are rare in patients with early-stage hepatocellular carcinoma (HCC) [9]. In some centers, liver transplantation (LT) policies require patients with HCC to undergo bone scans.
Bone scintigraphy was performed using a dual-head gamma camera equipped with general-purpose collimators. Anterior and posterior whole-body images were acquired approximately 3 hours after intravenous administration of 925 MBq 99mTchydroxymethane diphosphonate (HDP). Additional static planar images were acquired at the discretion of the attending nuclear physician. The results of each bone scan were classified as follows: (i) positive for metastases (defined as focal uptake of the radiotracer in non-physiologic locations that could not be explained by other conditions, such as trauma, known degenerative diseases, or inflammation); (ii) negative for metastases (physiologic uptake alone or uptake with a distribution consistent with recent trauma or known degenerative diseases); or (iii) suspicious for BM (increased uptake in non-physiologic locations without characteristics of metastases, such as isolated focal uptake) [10]
Our program utilizes bone scan routinely in the pretransplant evaluation of patients with hepatocellular carcinoma (HCC). The aim of our study is to evaluate the utility of bone scan in the setting of the pre-transplant liver workup in HCC patient.
Method
This is a retrospective chart review of our liver transplant (LT) database of all patients with HCC who underwent bone scan prior to liver transplantation. From January 2011 to December 2014, 275 LTs were performed, including 183 LDLTs and 92 DDLTs. Fifty-two patients had HCC, of whom bone scan was performed on 34 patients. The data collected include the following: age, gender, etiology of liver disease, tumor size and number on CT or MRI, bone scan results, explant tissue analysis, type of transplant [living donor (LDLT) versus deceased donor (DDLT)] and transplant outcome. Patients within Milan criteria received a MELD exception of 22 on cadaveric waiting list, patients within UCSF criteria were allowed to undergo LDLT, and patients beyond UCSF criteria received liver transplantation only if they were successfully down staged using loco-regional therapy.
Results
During the study period, 275 LTs were performed, including 183 LDLTs and 92 DDLTs. Fifty-two patients had HCC, of whom bone scan was performed in 34 patients. The average age was 58 (22-72), and 20 patients were males. The etiology of liver disease was hepatitis C (21 patients), cryptogenic cirrhosis (7 patients), and HBV (6 patients). The median follow up was 38 months. Sixteen patients had HCC within Milan criteria and 12 patients within University of California at San Francisco criteria (UCSF), and 6 patients were beyond UCSF criteria. Twenty-four patients underwent LDLT, whereas 10 patients underwent DDLT (Figure 1).
Of the 34 patients, 33 patients had negative bone scan. One patient with suspicious positive bone scan had negative PET scan and no clinical evidence of bone metastases on follow up and she still alive. she was 61 years old with NASH and MRI report showed liver cirrhosis with two HCC both located in segment 4A one 3.4cm x 2.7cm and the second HCC 1.4cm x 1.6cm within UCSF criteria, she was underwent living-related liver transplant (Right Lobe) and histopathology showed moderately differentiated, hepatocellular carcinoma largest focus measures 3cm in maximum dimension, no vascular invasion, uninvolved liver shows macro and micro liver cirrhosis, vascular resection margins are free of tumor (Table 1).
The explant showed well differentiated HCC in 16 patients, moderately differentiated HCC in 10 patients, poorly differentiated in 1 patient, combined HCC & cholangiocacinoma in 1 patient and complete necrosis after the loco-regional therapy in 6 patients.
Three patients died, one within UCSF criteria and two beyond UCSF criteria, two due to hepatic artery thrombosis and one due to sepsis and multi organ failure.
Discussion
Technetium-99m methylene diphosphonate (Tc-99m MDP) bone scintigraphy (BS) has been widely used to detect skeletal metastasis in practice. The advantage of BS lies in its ability to effectively survey the entire skeletal system in a single scan, which takes only a short period of time [11].
Figure 1:
Table 1: Bone Scan result in relation to tumor size.

Beyond UCSF

UCSF

MILAN

PATIENTS

6

12

16

Total

0

1

0

Positive

6

11

16

Negative

0%

8%

0%

Percentage

Once a diagnosis of HCC has been confirmed, disease staging is essential for treatment selection [1]. Curative treatments, such as resection or liver transplantation (LT), are offered to patients with early stage tumors according to the Barcelona Clinic Liver Cancer Group (BCLC) classification [1], that is, patients with a single lesion < 5 cm or up to three lesions ≤3 cm without macrovascular invasion. These criteria, known as the Milan criteria [12], identify a group of patients with HCC who may experience good disease-free survival after LT and outcomes comparable to those of patients receiving LT for other indications. Therefore, the majority of transplantation programs use these criteria

For selection of patients with HCC. The Milan criteria are used as part of our policy for selection of patients with HCC as candidates for LT. To identify possible subclinical metastases, our program requires that all patients with HCC undergo computed tomography (CT) of the chest and a bone scan to be included on the LT waiting list. However, the recommendation to screen for metastasis in patients with early-stage HCC as a requirement for inclusion on the LT waiting list is not evidence-based. Recently, some research groups investigated the frequency of bone metastases (BM) and the utility of bone scans (BSs) in the pre- LT assessment of this patient population [13, 14]. These studies showed that, in view of the low frequency of metastases, BSs should only be performed in this setting in patients with clinical signs or symptoms indicative of bone metastasis. Rodríguez S, etal. [15], Koneru et al. [16] and Witjes et al. [14] also concluded that BSs are not cost-effective and do notimprove selection of LT candidates We report our experience in evaluating the role of bone scan in detecting HCC bone metastases in pre-liver transplant patients and find that our results are in agreement with other reports evaluating the role of bone scan in patients with HCC.

We have shown that bone scan has no utility in patients with HCC within Milan criteria and should not be routinely used as part of the liver transplant work-up.
Conclusion
We have shown that bone scan has low utility in patients with HCC within Milan criteria and should not be routinely used as part of the liver transplant work-up.
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