* 2014 Lippincott Williams & Wilkins
laparoscopic hepatectomy. The present transverse incisional hybrid method with or without a hand-port system has merits allowing operators to dissect the short hepatic veins and right inferior hepatic vein with direct vision and tactile sense meticulously. Laparoscopic devices can be used through the transverse wound with the double retraction technique. With direct vision, an operator can dissect the hilum, cephalic, and deep part of the liver and deal with a critical situation such as major vessel tear. The transverse scar of donors could be hidden under an abdominal skin fold and skin crease postoperatively. Figure 5 shows the wounds of patients who underwent transverse incisional hepatectomy and conventional method. As the photos, the transverse wound remained the fewer scars because it runs parallel along the Langer’s line corresponding to the alignment of collagen fibers within the dermis. Their postoperative AST, ALT, and total bilirubin were normal within 1 month and all patients fully recovered (Fig. 4). Laparoscopic and minimally invasive method had a less Grade I complications and few Grade II and III complications compared with a conventional method (Table 3). Therefore, it is technically feasible and safe. However, this technique still needs to be validated in terms of safety of the donor. REFERENCES 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17.
Raia S, Nery JR, Mies S. Liver transplantation from live donors. Lancet 1989; 2: 497. Cho EH, Suh KS, Lee HW, et al. Safety of modified extended right hepatectomy in living liver donors. Transpl Int 2007; 20: 779. Suh KS, Kim SH, Kim SB, et al. Safety of right lobectomy in living donor liver transplantation. Liver Transpl 2002; 8: 910. Yang HR, Jeng LB, Li PC, et al. Living donor right hepatectomy with inclusion of the middle hepatic vein: outcome in 200 donors. Transplant Proc 2012; 44: 460. Cherqui D, Soubrane O, Husson E, et al. Laparoscopic living donor hepatectomy for liver transplantation in children. Lancet 2002; 359: 392. Yi NJ, Suh KS, Cho JY, et al. Three-quarters of right liver donors experienced postoperative complications. Liver Transpl 2007; 13: 797. Suh KS, Yi NJ, Kim J, et al. Laparoscopic hepatectomy for a modified right graft in adult-to-adult living donor liver transplantation. Transplant Proc 2008; 40: 3529. Suh KS, Yi NJ, Kim T, et al. Laparoscopy-assisted donor right hepatectomy using a hand port system preserving the middle hepatic vein branches. World J Surg 2009; 33: 526. Koffron AJ, Kung R, Baker T, et al. Laparoscopic-assisted right lobe donor hepatectomy. Am J Transplant 2006; 6: 2522. Koffron AJ, Kung RD, Auffenberg GB, et al. Laparoscopic liver surgery for everyone: the hybrid method. Surgery 2007; 142: 463. Baker TB, Jay CL, Ladner DP, et al. Laparoscopy-assisted and open living donor right hepatectomy: a comparative study of outcomes. Surgery 2009; 146: 817. Soyama A, Takatsuki M, Hidaka M, et al. Standardized less invasive living donor hemihepatectomy using the hybrid method through a short upper midline incision. Transplant Proc 2012; 44: 353. Heisterkamp J, Marsman HA, Eker H, et al. A J-shaped subcostal incision reduces the incidence of abdominal wall complications in liver transplantation. Liver Transpl 2008; 14: 1655. Choi HJ, You YK, Na GH, et al. Single-port laparoscopy-assisted donor right hepatectomy in living donor liver transplantation: sensible approach or unnecessary hindrance? Transplant Proc 2012; 44: 347. Kim SH, Cho SY, Lee KW, et al. Upper midline incision for living donor right hepatectomy. Liver Transpl 2009; 15: 193. Lee KW, Kim SH, Han SS, et al. Use of an upper midline incision for living donor partial hepatectomy: a series of 143 consecutive cases. Liver Transpl 2011; 17: 969. Nagai S, Brown L, Yoshida A, et al. Mini-incision right hepatic lobectomy with or without laparoscopic assistance for living donor hepatectomy. Liver Transpl 2012; 18: 1188.
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SECTION 18. PROFESSIONAL FRAMEWORK FOR LIVER TRANSPLANTATION FOR OVERSEAS PATIENTS: TRAVELING FOR LIVING DONOR LIVER TRANSPLANTATION
Catherine S. Kabiling,1 Chao-Long Chen,1,4 Allan Concejero,1 Chih-Chi Wang,1 Shih-Ho Wang,1 Chih-Che Lin,1 Yueh-Wei Liu,1 Chee-Chien Yong,1 Bruno Jawan,2 and Yu-Fan Cheng3
Background. Liver transplantation (LT) in overseas patients is a sensitive issue because of the possibility of organ trafficking and transplant tourism. In the Istanbul Summit, there was a call to develop standardized professional frameworks to prevent these practices. Objectives. Our objectives are three-fold, to critically evaluate our professional framework, to study the demographic profiles, and to identify the outcome and impact of LT in overseas patients. Methods. Recipient and donor case records, e-mail communications, and medico-legal records were collected and analyzed for management strategy, demographic profile, donor and recipient characteristics, and outcome. Results. Only 5% of our total LT operations were for overseas patients. Forty-two (79%) were pediatric cases for which 39 (93%) were due to biliary atresia (PG0.001). Sixty-eight percent were from the Philippines. Thirty-seven (70%) of the donors were first-degree relative. The average hospital days of a pediatric living donor liver transplant (LDLT) recipient was 65.48T28.7, and average cost was 44,602 USD. An adult LDLT recipient stayed for 52.09T11.3 days and spent around 75, 013 USD. A donor of pediatric LDLT stayed in the hospital for 17.42T5 days and spent round 8,176 USD. A donor for adult LDLT was admitted for 15.5T4 days and spent an average 9,612 USD. The total cost for recipient and donor were 56,615 USD (range, 28,976Y82,056) for pediatric LDLT and 84,483 USD (range, 64,851Y108,467) for adult LDLT. Actuarial survival rates were 91% at 1 year, 88% at 3 years, and 86% at 5 years and 10 years. Conclusion. Travelling for LDLT may be a wise and cost-effective step for patients with end-stage liver disease seeking alternative ways from their country. Our professional framework is effective to prevent practice of organ trafficking and transplant tourism. It may be useful to develop international guidelines for the practice of LT in overseas patients. Keywords: Liver transplantation, Living donor liver transplantation, Medical tourism, Transplant tourism, Travel for transplantation.
The authors declare no funding or conflict of interest. 1 Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Taiwan. 2 Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital, Taiwan. 3 Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, Taiwan. 4 Address correspondence to: Chao-Long Chen, M.D., Liver Transplantation Program and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, 123 Ta-Pei Road, Niao-Sung, Kaohsiung 83305, Taiwan. E-mail: [email protected]
Copyright * 2014 by Lippincott Williams & Wilkins ISSN: 0041-1337/14/9708-00 DOI: 10.1097/TP.0000000000000060
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iver transplantation is a life-saving procedure for patients with end-stage liver failure. However, problems on decreased organ supply, high cost, and long waiting list has led many to seek other alternatives. In Asia, where living donor liver transplantation is primarily practised (1), success rate and survival rate are at par or, in some centers, had surpassed those in the Western side, at 91% to 93.2% (2Y4) and 81% 1-year survival (3), respectively. These Asian accomplishments plus the lower cost of the procedure it offers have attracted many patients with end-stage liver disease to travel to Asia to undergo living donor liver transplantation (LDLT). Liver transplantation (LT) in overseas patients is a sensitive issue because of the possibility of organ trafficking and transplant tourism. In the Istanbul Summit, need for developing standard professional framework was identified to prevent these practices. Our center is not an exception to this. Here, we report our series of our overseas LDLT recipients and their donors, focusing on the cost and duration of their stay in Taiwan.
L
PATIENTS AND METHODS All overseas nationals that had undergone LT at Kaohsiung Chang Gung Memorial Hospital 1984 until December 2012 were included in the study. Records were retrieved from the International Patient Coordinator of the Liver Transplant Center and were reviewed. There are 54 cases gathered, but one was deceased donor liver transplantation (DDLT). This was the first LT that was done to a nonlocal resident; the patient was a 5-year-old Japanese boy with biliary atresia (BA). He received a whole liver graft from a brain dead 6-year-old boy on 1998. This case was excluded for ease of analysis. The first overseas LDLT patient was done in 2001. At our center, all recipients must have living donor with compatible blood type, between 18 and 65 year old, and negative for HBV, HCV, and HIV to be eligible. Both donor and recipient should present legal documents proving their relationship within fifth degree. Recipient and donor data must be sent via email or courier, see Table 1 for list of requirements for donor and recipient. Once completed, the case is presented in the Liver Transplant conference for decision for acceptance. Arrangements are made once the case is accepted for transplantation. Upon arrival of the donor and recipient, another set of test is done to ascertain quality of the donor’s liver. If both donor and recipient’s condition are favorable for transplantation, they are scheduled for LDLT within the week. Once discharged, the recipient and the donor stayed in semi-furnished hostel within the hospital compound. Both were followed up every week. The donor’s follow-up is until all the biochemical tests are near normal, and no surgical complication is ascertained while the recipient is followed up until biochemical tests and immunosuppressant dosage have stabilized. Before recipient and donor are sent back to their country, a detailed medical record is furnished with the instruction to their local physician to contact the institution for further instructions and to give updates on the patient’s progress.
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Statistical Analysis Continuous data were reported as mean valuesTstandard deviations using two-tailed Student t test and comparison between groups were performed using the X2 test. Statistical significance was set at PG0.05. Statistical analyses were performed using SPSS 16.0.0.
RESULTS There are 54 cases of liver transplantation involving overseas nationals at the Kaohsiung Chang Gung Memorial Hospital from 1984 to December 2012. It comprises 5% of all the LT procedures that are being done in the hospital. The first foreign LT case is a DDLT procedure to a 5-year-old Japanese boy with BA, and who is still alive up to this day. The rest of the foreign LT cases are LDLT (n=53). Table 2 describes in detail the distribution of patients into pediatric and adult groups. Forty-two (79%) foreign LDLT cases are in the pediatric group, and 11 (21%) are adults. The mean age of the pediatric recipient is 2.59T2.8 and adult recipient 48.64T10.9 (PG0.001). With regard to sex distribution, Child-TurcottePugh (CTP) score, United network for organ sharing (UNOS) score and Model for End stage liver Disease (MELD) score, all recipients are evenly distributed. Most patients are from the Philippines, 68%, followed by those from China, 17% (PG0.001). Almost all of these patients had BA (n=40, 75%, PG0.001). Seventy percent of the donor are first-degree relative of the recipient, and only 4% (n=2) are spouses (P=0.011). For the pediatric recipients, 35 (83%) received left lateral segment graft, whereas 10 (91%) of the adult recipients had right side graft, PG0.001. A pediatric recipient after transplantation would usually stay in the hospital for 65.48T28.7 days, whereas an adult would stay for 52.09T11.3 days, and at discharge, they would have spent 44,602 USD (range, 20, 641Y73,622) for pediatric and 75, 013 (range, 54, 916Y99, 489) for adult LDLT operation. After discharge from the hospital, these patients would remain in a semi-furnished hostel within the hospital compound for outpatient follow-up for an average of 4.75T2.7 weeks for the pediatric group and 7.09T2.9 weeks for adult recipients. Donors of pediatric LDLT case would stay around 17.42T5.0 days and 15.5T4.4 days for adult LDLT cases. Their hospitalization would cost 8,176 (range, 5, 237Y13, 371) USD for pediatric cases and 9, 612 (range, 8, 525Y11, 826) USD for adult. Total hospital cost for both donor and recipient at the end of hospitalization are 56, 615 (range, 28, 976Y82, 956) USD and 84, 483 (range, 64, 851Y108,467) USD for pediatric and adult LDLT, respectively. There are five mortalities from the pediatric LDLT recipient, and the causes are portal vein thrombosis and hepatic artery thrombosis (1), acute respiratory distress syndrome (2), sepsis secondary to pneumonia (1), and spontaneous intracranial hemorrhage (1). In the adult LDLT cases, there are two mortalities. One had recurrence of hepatocellular carcinoma 2 years after the operation, and the other one developed gastric cancer and died of it after 5 years. Overall, the actuarial survival rates 91% at 1 year, 88% at 3 years, and 86% at 5 years and 10 years.
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TABLE 1.
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List of requirements for recipient and donor for LDLT
Recipient requirements Name Age, sex, birthday Body weight and height Blood type Updated clinical abstract Operations and treatments Medications Reason for transplant Hepatitis profile HBsAg Anti-HBs Anti-HBc Anti-HCV Anti-HIV Blood chemistry CBC, albumin, AST, ALT, total and direct bilirubin, BUN, creatinine, INR/Protime, AFP, CEA, CA 199 Liver ultrasound CT angiogram of the liver
One of the liver donors had poorly differentiated hepatocellular carcinoma 6 years after donation, despite strict screening pretransplantation. The donor donated left lateral segment (LLS) for a BA LDLT recipient. Albeit unremarkable yearly liver evaluation postliver donation, after 6 years, the patient already had multiple liver nodules ranging from 1 to 7 cm at segments 5, 6, 7, and 8 when evaluated for abdominal pain with right upper quadrant fullness. Because of tumor characteristics and location, salvage chemotherapy and target therapy were initiated, but after 3 months from onset of symptom, the patient died.
DISCUSSION Travelling abroad for cost-effective quality medical care has encouraged many. In Asia, there are hospitals with world-class facilities and capabilities that could offer cheaper procedures at prices more than 50% less of the price in United States. Physicians, especially surgeons, in these centers were usually trained in prestigious medical institutions and are known to deliver the best possible medical care (5). Solid organ transplantation has prolonged and improved lives of patients with end stage organ failure worldwide. However, procurement of solid organ for transplantation has raised many issues within the transplant community, at national and global levels, because of organ trafficking and transplant tourism. United Network for Organ Sharing (UNOS) has defined transplant tourism as the purchase of transplant organ abroad that includes access to an organ while bypassing laws, rules, or process of any or all countries involved (6). In the Istanbul Declaration, transplant tourism was differentiated from travel for transplantation. Although transplant tourism has all the negative connotations, travel for transplantation was defined as the movement of organs, donors, recipients, or transplant professionals across jurisdictional borders for transplantation purposes (7). Transplant tourism has received many criticisms.
Donor requirements Name Age, sex, birthday Body weight and height Blood type Hepatitis Profile HBsAg Anti-HBs Anti-HBc Anti-HCV Anti-HIV Blood chemistry CBC, albumin, AST, ALT, Total and direct bilirubin, BUN, Creatinine, INR/Protime, AFP, CEA, CA 199
Liver Ultrasound CT angiogram of the liver MRCP
Solid organ trafficking was rampant (6Y9), and the Korean Society for Transplantation made a survey on all Korean overseas transplant recipients and reported the suboptimal quality of care given to these transplant recipients (8). There are also many reports on lower success rates and higher risk for infectious disease transmission (8Y11) as well as poor communication with doctor and patient because of language barrier and no proper endorsement or documents after the procedure (8, 11). With all these issues, the medical community has still the moral obligation to provide standard medical care to all based on the principles of nonjudgmental regard, beneficence, and fiduciary responsibility (11). In Taiwan, legislation for human organ transplantation is very strict that a donation is only allowed for spouse who had born child or been married to the recipient for 2 years, and relatives within fifth degree, as was stipulated in the Organ transplant Act of Taiwan (12), and this has negated the issues on organ trafficking in the country. Also, the patient and their family are in constant communication with a coordinator, who can speak several languages, regarding the patient’s condition and progress. This coordinator also furnishes medical abstract for the receiving physician when the patient gets home. For patient coming from the Philippines, four surgeons had already trained at our Transplant Program, and these patients are advised to contact them upon returning to the country, thus bridging the communication gap. Patients around the globe are encouraged to travel for transplantation to Asia because of the fact LDLT centers in Asia are more adept, has more experience, and with better survival rates. Actual survival rates in Asia are 78.7% to 97.8% at 1 year and 76.1% to 97.8% at 5 years (13, 14) versus 81% at 1-year survival in the United States (4). At our center, our actual survival rate for overseas who had undergone LDLT are 91% at 1 year, 88% at 3 years, and 86% at 5 years and 10 years. This value may be lower than our overall 3 year survival of 91% (2) and 98% at 1- and 5-year
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TABLE 2.
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Demographics of foreign LDLT patients
Recipient Age Male/female CTP score UNOS 2a 2b 3 MELD/PELD Country of origin Philippines China Vietnam Indonesia United States Pakistan South Africa Diagnosis Biliary atresia (BA) BA, HCV BA, choledochal cyst Alagille’s syndrome Congenital hepatic fibrosis HCV HBV HCV, HCC HBV, HCC Alcohol-related liver failure Graft used Left lateral segment Right lobe Left lobe Total hospital stay (days) Total hospital cost (USD) Alive/expired OPD visits (weeks) Recipient-donor relationship 1st degree 2nd degree 3rd degree 5th degree Spouse Donor Total hospital stay (days) Hospital cost (USD) Total hospital cost (USD)
Pedia (n=43)
Adult (n=11)
P value
2.59T2.8 24/18 8.48T1.6
48.64T10.9 6/5 8.36T2.9
G0.001 0.877 0.112 0.088
1 23 18 12.83T6.2
0 10 1 15.27T8.2
33 9 0 0 0 0 0
3 0 3 2 1 1 1
37 1 1 2 1 0 0 0 0 0
1 0 0 0 0 2 1 1 5 1
35 0 6 65.48T28.7 44,602 (20,641Y73,620) 37/5 4.75T2.7
0 10 1 52.09T11.3 75,013 (54,916Y99,489) 9/2 7.09T2.9
33 1 4 4 0
4 1 3 1 2
17.42T5.0 8,176 (5, 237Y13,371) 56,615 (28,976Y82,056)
15.5T4.4 9, 612 (8,525Y11,826) 84,483 (64,851Y108,467)
0.074 G0.001
G0.001
G0.001
survival for BA recipients (15), because of the fact that these overseas patients are sicker than our local patients. Most recipients have already been optimized at their country before they arrive at our institution. For example, some BA patients had several Kasai revisions already, some had liver transplantation already, and some waited long to gather
0.910 0.397 0.793 0.425 0.011
0.552 0.435 0.435
money for transplantation. Different cases had different reasons, but in summary, they are generally complicated cases, intraoperatively and postoperatively. There was one donor mortality after 6 years because of aggressive hepatocellular carcinoma. Despite yearly liver evaluation, the lesion was not detected early to have room
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for surgical or interventional therapy. Because of advanced tumor stage at presentation, only salvage chemotherapy and targeted therapy was done, but still without improvement. After 3 months from onset of symptom, the donor died. With living donor liver transplantation, donor screening is very strict to make the procedure safe for the donor and to make certain that the donor has no predilection for any cancer or have any risk factors for developing liver problem in the future. However, as was presented, the donor has no risk factor and had regular liver evaluation but still developed hepatocellular carcinoma. Unlikely as it may seem, we should inform our patients, both the donor and the recipient, of this possibility after going through LDLT, as well as the importance of close follow-up (16). The low cost of the LDLT in the Asia also attracts many overseas patients. India boasts of its 40,000 to 65,000 USD for an LDLT procedure (17, 18). In the Philippines, an LDLT would cost around 135,000 USD (18); and in Korea, 220,000 to 280,000 (19). In the United States, LDLT would be around 500,000 to 523,400 USD (17, 19). In this article, the actual total cost of transplantation averages 56,615 (range, 28,976Y82,056) USD and 84,483 (range, 64,851Y108,467) USD for pediatric and adult LDLT, respectively. Still, it is very affordable as compared with other Asian counterparts and with the United States. We had two BA recipients with very complicated postoperative course both secondary to acute respiratory distress syndrome. One even has to be placed on Extracorporeal Membrane Oxygenation (ECMO) for 24 days, and the other one has several episodes of failed weaning from endotracheal intubation. The second patient also had vesico-ureteral reflux postoperatively and had to undergo ureteroneocystostomy for revision of previous ureter reimplantation surgery secondary to bladder diverticulum. Their hospitalization reached to 82 and 180 days. The cost of hospitalization for both patients was 54,136 USD and the total hospital cost, including their donors were 62,177 and 62,541 USD. Both recipients and their donors were doing well until present. Considering the complexity of the case, the amount that the parents had to shoulder was still very low. If these patients were in another institution, no one knows how much they could be spending; it could be up to the ceiling. Sixty-eight (n=36) of our patients are from the Philippines. Although the Philippines has three capable centers for doing the procedure, LDLT has only started in 2011 (20), and the cost is still twice as that in Taiwan (18). Usually, the family of the patients has already exhausted their resources, has researched extensively, and is ready to travel out of their country for a greater chance of survival at a lower cost. The price advantage and greater quality of LDLT in Asia are the main determining force that encourages overseas patients to travel to this part of the world. This reality plus the economic growth in Asia has included LDLT in medical brokerage business (21), as seen in India, Korea, and Singapore. In conclusion, travel for transplantation to Asia for living donor liver transplantation is a wise and cost-effective decision for patients with end-stage liver disease seeking other alternatives in their parent country.
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ACKNOWLEDGMENT The authors thank Linda Lin, RN, Kaohsiung Chang Gung Memorial Hospital International Patient Coordinator, for providing a listing and cost of hospitalization of all the overseas LDLT recipients and donors. REFERENCES 1. 2.
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de Villa V, Lo CM. Liver transplantation for hepatocellular carcinoma in Asia. Oncologist 2007; 12: 1321. Liver transplant survivals. Taiwan national health insurance. Available at: http://www.clchen.org.tw/english/media/20090401.htm. Accessed February 18, 2013. Chan SC, Fan ST, Lo CM, et al. A decade of right liver adult-to-adult living donor liver transplantation: the recipient midterm outcomes. Ann Surg 2008; 248: 411. Olthoff KM, Merion RM, Ghobrial RM, et al. Outcomes of 385 adult-to adult living donor liver transplant recipients. Ann Surg 2005; 242: 314. Issues monitor-medical tourism gaining momentum. KPMC International. May 2011. Issue 7. Available at: http://www.kpmg.com/CH/ en/Library/Articles-Publications/Documents/Sectors/pub-20120207issues-monitor-healthcare-medical-tourism-en.pdf. Accessed February 10, 2013. Budiani-Saberi DA, Delmonico FL. Organ trafficking and transplant tourism: a complementary on the Global Realities. Am J Transplant 2008; 8: 925. Delmonico FL. The Implications of Instanbul declaration on organ trafficking and transplant tourism. Curr Opin Organ Transplant 2009; 14: 116. Kwon CHD, Lee SK, Ha J. Trend and outcome of Korean patients receiving overseas solid organ transplantation between 1999 and 2005. J Korean Med Sci 2011; 26: 17. Biggins SW, Bambha K, Terrault N, et al. Transplant tourism to China: the impact on domestic patient-care decisions. Clin Transplant 2009; 23: 831. Kotton CN. Transplant tourism and donor-derived parasitic infections. Transplant Proc 2011; 43: 2448. Shiano TD, Rhodes R. The dilemma and reality of transplant tourism: an ethical perspective for liver transplant programs. Liver Transplant 2010; 16: 113. Concejero AM, Chen CL. Ethical perspective on living donor organ transplantation in Asia. Liver Transplant 2009; 15: 1658. Hwang S, Lee SG, Lee YJ, et al. Lessons learned from 1000 living donor liver transplantation in a single center: How to make living donations safe. Liver Transplant 2006; 12: 920. Chen CL, Fan ST, Lee SG, et al. Living donor liver transplantation: 12 years of experience in Asia. Transplantation 2003; 75: s6. Chen CL, Concejero AM, Wang CC, et al. Living donor liver transplantation for biliary atresia: a single-center experience with first 100 cases. Am J Transplant 2006; 6: 2672. Concejero AM, Chen CL, Labio ME. Donor death from hepatocellular carcinoma: an unusual cause. Liver Transplant 2012; 18: s158. Liver Transplant surgery abroad. Available at: http://www.medicaltourismco. com/organ-transplant/liver-transplant-surgery-abroad.php. Accessed February 13, 2013. Organ transplant Liver Transplant Prices. Placidway. Available at: http://www.placidway.com/cost-searchlist/Philippines,Liver_Transplant, Organ_Transplant/. Accessed February 14, 2013. Patients beyond borders, Focus on: Asan Medical Center. Healthy Travel Media. Available at: http://eng.amc.seoul.kr/lang/Down/Focus_ On.pdf. Accessed February 14, 2013. Manongdo JF, Usman EK. All-Filipino docs do first liver transplant. Manila Bulletin Newspaper Online. Available at: http://www.mb.com.ph/node/ 300376/allfilipino-doc#.URzf6h2gJlw. Accessed on February 11, 2013. Chin JJL, Campbell AV. Transplant tourism or International transplant medicine? A Case for marketing the distinction. Am J Transplant 2012; 12: 1700.
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
laparoscopic hepatectomy. The present transverse incisional hybrid method with or without a hand-port system has merits allowing operators to dissect the short hepatic veins and right inferior hepatic vein with direct vision and tactile sense meticulously. Laparoscopic devices can be used through the transverse wound with the double retraction technique. With direct vision, an operator can dissect the hilum, cephalic, and deep part of the liver and deal with a critical situation such as major vessel tear. The transverse scar of donors could be hidden under an abdominal skin fold and skin crease postoperatively. Figure 5 shows the wounds of patients who underwent transverse incisional hepatectomy and conventional method. As the photos, the transverse wound remained the fewer scars because it runs parallel along the Langer’s line corresponding to the alignment of collagen fibers within the dermis. Their postoperative AST, ALT, and total bilirubin were normal within 1 month and all patients fully recovered (Fig. 4). Laparoscopic and minimally invasive method had a less Grade I complications and few Grade II and III complications compared with a conventional method (Table 3). Therefore, it is technically feasible and safe. However, this technique still needs to be validated in terms of safety of the donor. REFERENCES 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17.
Raia S, Nery JR, Mies S. Liver transplantation from live donors. Lancet 1989; 2: 497. Cho EH, Suh KS, Lee HW, et al. Safety of modified extended right hepatectomy in living liver donors. Transpl Int 2007; 20: 779. Suh KS, Kim SH, Kim SB, et al. Safety of right lobectomy in living donor liver transplantation. Liver Transpl 2002; 8: 910. Yang HR, Jeng LB, Li PC, et al. Living donor right hepatectomy with inclusion of the middle hepatic vein: outcome in 200 donors. Transplant Proc 2012; 44: 460. Cherqui D, Soubrane O, Husson E, et al. Laparoscopic living donor hepatectomy for liver transplantation in children. Lancet 2002; 359: 392. Yi NJ, Suh KS, Cho JY, et al. Three-quarters of right liver donors experienced postoperative complications. Liver Transpl 2007; 13: 797. Suh KS, Yi NJ, Kim J, et al. Laparoscopic hepatectomy for a modified right graft in adult-to-adult living donor liver transplantation. Transplant Proc 2008; 40: 3529. Suh KS, Yi NJ, Kim T, et al. Laparoscopy-assisted donor right hepatectomy using a hand port system preserving the middle hepatic vein branches. World J Surg 2009; 33: 526. Koffron AJ, Kung R, Baker T, et al. Laparoscopic-assisted right lobe donor hepatectomy. Am J Transplant 2006; 6: 2522. Koffron AJ, Kung RD, Auffenberg GB, et al. Laparoscopic liver surgery for everyone: the hybrid method. Surgery 2007; 142: 463. Baker TB, Jay CL, Ladner DP, et al. Laparoscopy-assisted and open living donor right hepatectomy: a comparative study of outcomes. Surgery 2009; 146: 817. Soyama A, Takatsuki M, Hidaka M, et al. Standardized less invasive living donor hemihepatectomy using the hybrid method through a short upper midline incision. Transplant Proc 2012; 44: 353. Heisterkamp J, Marsman HA, Eker H, et al. A J-shaped subcostal incision reduces the incidence of abdominal wall complications in liver transplantation. Liver Transpl 2008; 14: 1655. Choi HJ, You YK, Na GH, et al. Single-port laparoscopy-assisted donor right hepatectomy in living donor liver transplantation: sensible approach or unnecessary hindrance? Transplant Proc 2012; 44: 347. Kim SH, Cho SY, Lee KW, et al. Upper midline incision for living donor right hepatectomy. Liver Transpl 2009; 15: 193. Lee KW, Kim SH, Han SS, et al. Use of an upper midline incision for living donor partial hepatectomy: a series of 143 consecutive cases. Liver Transpl 2011; 17: 969. Nagai S, Brown L, Yoshida A, et al. Mini-incision right hepatic lobectomy with or without laparoscopic assistance for living donor hepatectomy. Liver Transpl 2012; 18: 1188.
Chen et al.
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SECTION 18. PROFESSIONAL FRAMEWORK FOR LIVER TRANSPLANTATION FOR OVERSEAS PATIENTS: TRAVELING FOR LIVING DONOR LIVER TRANSPLANTATION
Catherine S. Kabiling,1 Chao-Long Chen,1,4 Allan Concejero,1 Chih-Chi Wang,1 Shih-Ho Wang,1 Chih-Che Lin,1 Yueh-Wei Liu,1 Chee-Chien Yong,1 Bruno Jawan,2 and Yu-Fan Cheng3
Background. Liver transplantation (LT) in overseas patients is a sensitive issue because of the possibility of organ trafficking and transplant tourism. In the Istanbul Summit, there was a call to develop standardized professional frameworks to prevent these practices. Objectives. Our objectives are three-fold, to critically evaluate our professional framework, to study the demographic profiles, and to identify the outcome and impact of LT in overseas patients. Methods. Recipient and donor case records, e-mail communications, and medico-legal records were collected and analyzed for management strategy, demographic profile, donor and recipient characteristics, and outcome. Results. Only 5% of our total LT operations were for overseas patients. Forty-two (79%) were pediatric cases for which 39 (93%) were due to biliary atresia (PG0.001). Sixty-eight percent were from the Philippines. Thirty-seven (70%) of the donors were first-degree relative. The average hospital days of a pediatric living donor liver transplant (LDLT) recipient was 65.48T28.7, and average cost was 44,602 USD. An adult LDLT recipient stayed for 52.09T11.3 days and spent around 75, 013 USD. A donor of pediatric LDLT stayed in the hospital for 17.42T5 days and spent round 8,176 USD. A donor for adult LDLT was admitted for 15.5T4 days and spent an average 9,612 USD. The total cost for recipient and donor were 56,615 USD (range, 28,976Y82,056) for pediatric LDLT and 84,483 USD (range, 64,851Y108,467) for adult LDLT. Actuarial survival rates were 91% at 1 year, 88% at 3 years, and 86% at 5 years and 10 years. Conclusion. Travelling for LDLT may be a wise and cost-effective step for patients with end-stage liver disease seeking alternative ways from their country. Our professional framework is effective to prevent practice of organ trafficking and transplant tourism. It may be useful to develop international guidelines for the practice of LT in overseas patients. Keywords: Liver transplantation, Living donor liver transplantation, Medical tourism, Transplant tourism, Travel for transplantation.
The authors declare no funding or conflict of interest. 1 Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Taiwan. 2 Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital, Taiwan. 3 Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, Taiwan. 4 Address correspondence to: Chao-Long Chen, M.D., Liver Transplantation Program and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, 123 Ta-Pei Road, Niao-Sung, Kaohsiung 83305, Taiwan. E-mail: [email protected]
Copyright * 2014 by Lippincott Williams & Wilkins ISSN: 0041-1337/14/9708-00 DOI: 10.1097/TP.0000000000000060
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iver transplantation is a life-saving procedure for patients with end-stage liver failure. However, problems on decreased organ supply, high cost, and long waiting list has led many to seek other alternatives. In Asia, where living donor liver transplantation is primarily practised (1), success rate and survival rate are at par or, in some centers, had surpassed those in the Western side, at 91% to 93.2% (2Y4) and 81% 1-year survival (3), respectively. These Asian accomplishments plus the lower cost of the procedure it offers have attracted many patients with end-stage liver disease to travel to Asia to undergo living donor liver transplantation (LDLT). Liver transplantation (LT) in overseas patients is a sensitive issue because of the possibility of organ trafficking and transplant tourism. In the Istanbul Summit, need for developing standard professional framework was identified to prevent these practices. Our center is not an exception to this. Here, we report our series of our overseas LDLT recipients and their donors, focusing on the cost and duration of their stay in Taiwan.
L
PATIENTS AND METHODS All overseas nationals that had undergone LT at Kaohsiung Chang Gung Memorial Hospital 1984 until December 2012 were included in the study. Records were retrieved from the International Patient Coordinator of the Liver Transplant Center and were reviewed. There are 54 cases gathered, but one was deceased donor liver transplantation (DDLT). This was the first LT that was done to a nonlocal resident; the patient was a 5-year-old Japanese boy with biliary atresia (BA). He received a whole liver graft from a brain dead 6-year-old boy on 1998. This case was excluded for ease of analysis. The first overseas LDLT patient was done in 2001. At our center, all recipients must have living donor with compatible blood type, between 18 and 65 year old, and negative for HBV, HCV, and HIV to be eligible. Both donor and recipient should present legal documents proving their relationship within fifth degree. Recipient and donor data must be sent via email or courier, see Table 1 for list of requirements for donor and recipient. Once completed, the case is presented in the Liver Transplant conference for decision for acceptance. Arrangements are made once the case is accepted for transplantation. Upon arrival of the donor and recipient, another set of test is done to ascertain quality of the donor’s liver. If both donor and recipient’s condition are favorable for transplantation, they are scheduled for LDLT within the week. Once discharged, the recipient and the donor stayed in semi-furnished hostel within the hospital compound. Both were followed up every week. The donor’s follow-up is until all the biochemical tests are near normal, and no surgical complication is ascertained while the recipient is followed up until biochemical tests and immunosuppressant dosage have stabilized. Before recipient and donor are sent back to their country, a detailed medical record is furnished with the instruction to their local physician to contact the institution for further instructions and to give updates on the patient’s progress.
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Statistical Analysis Continuous data were reported as mean valuesTstandard deviations using two-tailed Student t test and comparison between groups were performed using the X2 test. Statistical significance was set at PG0.05. Statistical analyses were performed using SPSS 16.0.0.
RESULTS There are 54 cases of liver transplantation involving overseas nationals at the Kaohsiung Chang Gung Memorial Hospital from 1984 to December 2012. It comprises 5% of all the LT procedures that are being done in the hospital. The first foreign LT case is a DDLT procedure to a 5-year-old Japanese boy with BA, and who is still alive up to this day. The rest of the foreign LT cases are LDLT (n=53). Table 2 describes in detail the distribution of patients into pediatric and adult groups. Forty-two (79%) foreign LDLT cases are in the pediatric group, and 11 (21%) are adults. The mean age of the pediatric recipient is 2.59T2.8 and adult recipient 48.64T10.9 (PG0.001). With regard to sex distribution, Child-TurcottePugh (CTP) score, United network for organ sharing (UNOS) score and Model for End stage liver Disease (MELD) score, all recipients are evenly distributed. Most patients are from the Philippines, 68%, followed by those from China, 17% (PG0.001). Almost all of these patients had BA (n=40, 75%, PG0.001). Seventy percent of the donor are first-degree relative of the recipient, and only 4% (n=2) are spouses (P=0.011). For the pediatric recipients, 35 (83%) received left lateral segment graft, whereas 10 (91%) of the adult recipients had right side graft, PG0.001. A pediatric recipient after transplantation would usually stay in the hospital for 65.48T28.7 days, whereas an adult would stay for 52.09T11.3 days, and at discharge, they would have spent 44,602 USD (range, 20, 641Y73,622) for pediatric and 75, 013 (range, 54, 916Y99, 489) for adult LDLT operation. After discharge from the hospital, these patients would remain in a semi-furnished hostel within the hospital compound for outpatient follow-up for an average of 4.75T2.7 weeks for the pediatric group and 7.09T2.9 weeks for adult recipients. Donors of pediatric LDLT case would stay around 17.42T5.0 days and 15.5T4.4 days for adult LDLT cases. Their hospitalization would cost 8,176 (range, 5, 237Y13, 371) USD for pediatric cases and 9, 612 (range, 8, 525Y11, 826) USD for adult. Total hospital cost for both donor and recipient at the end of hospitalization are 56, 615 (range, 28, 976Y82, 956) USD and 84, 483 (range, 64, 851Y108,467) USD for pediatric and adult LDLT, respectively. There are five mortalities from the pediatric LDLT recipient, and the causes are portal vein thrombosis and hepatic artery thrombosis (1), acute respiratory distress syndrome (2), sepsis secondary to pneumonia (1), and spontaneous intracranial hemorrhage (1). In the adult LDLT cases, there are two mortalities. One had recurrence of hepatocellular carcinoma 2 years after the operation, and the other one developed gastric cancer and died of it after 5 years. Overall, the actuarial survival rates 91% at 1 year, 88% at 3 years, and 86% at 5 years and 10 years.
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TABLE 1.
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List of requirements for recipient and donor for LDLT
Recipient requirements Name Age, sex, birthday Body weight and height Blood type Updated clinical abstract Operations and treatments Medications Reason for transplant Hepatitis profile HBsAg Anti-HBs Anti-HBc Anti-HCV Anti-HIV Blood chemistry CBC, albumin, AST, ALT, total and direct bilirubin, BUN, creatinine, INR/Protime, AFP, CEA, CA 199 Liver ultrasound CT angiogram of the liver
One of the liver donors had poorly differentiated hepatocellular carcinoma 6 years after donation, despite strict screening pretransplantation. The donor donated left lateral segment (LLS) for a BA LDLT recipient. Albeit unremarkable yearly liver evaluation postliver donation, after 6 years, the patient already had multiple liver nodules ranging from 1 to 7 cm at segments 5, 6, 7, and 8 when evaluated for abdominal pain with right upper quadrant fullness. Because of tumor characteristics and location, salvage chemotherapy and target therapy were initiated, but after 3 months from onset of symptom, the patient died.
DISCUSSION Travelling abroad for cost-effective quality medical care has encouraged many. In Asia, there are hospitals with world-class facilities and capabilities that could offer cheaper procedures at prices more than 50% less of the price in United States. Physicians, especially surgeons, in these centers were usually trained in prestigious medical institutions and are known to deliver the best possible medical care (5). Solid organ transplantation has prolonged and improved lives of patients with end stage organ failure worldwide. However, procurement of solid organ for transplantation has raised many issues within the transplant community, at national and global levels, because of organ trafficking and transplant tourism. United Network for Organ Sharing (UNOS) has defined transplant tourism as the purchase of transplant organ abroad that includes access to an organ while bypassing laws, rules, or process of any or all countries involved (6). In the Istanbul Declaration, transplant tourism was differentiated from travel for transplantation. Although transplant tourism has all the negative connotations, travel for transplantation was defined as the movement of organs, donors, recipients, or transplant professionals across jurisdictional borders for transplantation purposes (7). Transplant tourism has received many criticisms.
Donor requirements Name Age, sex, birthday Body weight and height Blood type Hepatitis Profile HBsAg Anti-HBs Anti-HBc Anti-HCV Anti-HIV Blood chemistry CBC, albumin, AST, ALT, Total and direct bilirubin, BUN, Creatinine, INR/Protime, AFP, CEA, CA 199
Liver Ultrasound CT angiogram of the liver MRCP
Solid organ trafficking was rampant (6Y9), and the Korean Society for Transplantation made a survey on all Korean overseas transplant recipients and reported the suboptimal quality of care given to these transplant recipients (8). There are also many reports on lower success rates and higher risk for infectious disease transmission (8Y11) as well as poor communication with doctor and patient because of language barrier and no proper endorsement or documents after the procedure (8, 11). With all these issues, the medical community has still the moral obligation to provide standard medical care to all based on the principles of nonjudgmental regard, beneficence, and fiduciary responsibility (11). In Taiwan, legislation for human organ transplantation is very strict that a donation is only allowed for spouse who had born child or been married to the recipient for 2 years, and relatives within fifth degree, as was stipulated in the Organ transplant Act of Taiwan (12), and this has negated the issues on organ trafficking in the country. Also, the patient and their family are in constant communication with a coordinator, who can speak several languages, regarding the patient’s condition and progress. This coordinator also furnishes medical abstract for the receiving physician when the patient gets home. For patient coming from the Philippines, four surgeons had already trained at our Transplant Program, and these patients are advised to contact them upon returning to the country, thus bridging the communication gap. Patients around the globe are encouraged to travel for transplantation to Asia because of the fact LDLT centers in Asia are more adept, has more experience, and with better survival rates. Actual survival rates in Asia are 78.7% to 97.8% at 1 year and 76.1% to 97.8% at 5 years (13, 14) versus 81% at 1-year survival in the United States (4). At our center, our actual survival rate for overseas who had undergone LDLT are 91% at 1 year, 88% at 3 years, and 86% at 5 years and 10 years. This value may be lower than our overall 3 year survival of 91% (2) and 98% at 1- and 5-year
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TABLE 2.
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Demographics of foreign LDLT patients
Recipient Age Male/female CTP score UNOS 2a 2b 3 MELD/PELD Country of origin Philippines China Vietnam Indonesia United States Pakistan South Africa Diagnosis Biliary atresia (BA) BA, HCV BA, choledochal cyst Alagille’s syndrome Congenital hepatic fibrosis HCV HBV HCV, HCC HBV, HCC Alcohol-related liver failure Graft used Left lateral segment Right lobe Left lobe Total hospital stay (days) Total hospital cost (USD) Alive/expired OPD visits (weeks) Recipient-donor relationship 1st degree 2nd degree 3rd degree 5th degree Spouse Donor Total hospital stay (days) Hospital cost (USD) Total hospital cost (USD)
Pedia (n=43)
Adult (n=11)
P value
2.59T2.8 24/18 8.48T1.6
48.64T10.9 6/5 8.36T2.9
G0.001 0.877 0.112 0.088
1 23 18 12.83T6.2
0 10 1 15.27T8.2
33 9 0 0 0 0 0
3 0 3 2 1 1 1
37 1 1 2 1 0 0 0 0 0
1 0 0 0 0 2 1 1 5 1
35 0 6 65.48T28.7 44,602 (20,641Y73,620) 37/5 4.75T2.7
0 10 1 52.09T11.3 75,013 (54,916Y99,489) 9/2 7.09T2.9
33 1 4 4 0
4 1 3 1 2
17.42T5.0 8,176 (5, 237Y13,371) 56,615 (28,976Y82,056)
15.5T4.4 9, 612 (8,525Y11,826) 84,483 (64,851Y108,467)
0.074 G0.001
G0.001
G0.001
survival for BA recipients (15), because of the fact that these overseas patients are sicker than our local patients. Most recipients have already been optimized at their country before they arrive at our institution. For example, some BA patients had several Kasai revisions already, some had liver transplantation already, and some waited long to gather
0.910 0.397 0.793 0.425 0.011
0.552 0.435 0.435
money for transplantation. Different cases had different reasons, but in summary, they are generally complicated cases, intraoperatively and postoperatively. There was one donor mortality after 6 years because of aggressive hepatocellular carcinoma. Despite yearly liver evaluation, the lesion was not detected early to have room
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for surgical or interventional therapy. Because of advanced tumor stage at presentation, only salvage chemotherapy and targeted therapy was done, but still without improvement. After 3 months from onset of symptom, the donor died. With living donor liver transplantation, donor screening is very strict to make the procedure safe for the donor and to make certain that the donor has no predilection for any cancer or have any risk factors for developing liver problem in the future. However, as was presented, the donor has no risk factor and had regular liver evaluation but still developed hepatocellular carcinoma. Unlikely as it may seem, we should inform our patients, both the donor and the recipient, of this possibility after going through LDLT, as well as the importance of close follow-up (16). The low cost of the LDLT in the Asia also attracts many overseas patients. India boasts of its 40,000 to 65,000 USD for an LDLT procedure (17, 18). In the Philippines, an LDLT would cost around 135,000 USD (18); and in Korea, 220,000 to 280,000 (19). In the United States, LDLT would be around 500,000 to 523,400 USD (17, 19). In this article, the actual total cost of transplantation averages 56,615 (range, 28,976Y82,056) USD and 84,483 (range, 64,851Y108,467) USD for pediatric and adult LDLT, respectively. Still, it is very affordable as compared with other Asian counterparts and with the United States. We had two BA recipients with very complicated postoperative course both secondary to acute respiratory distress syndrome. One even has to be placed on Extracorporeal Membrane Oxygenation (ECMO) for 24 days, and the other one has several episodes of failed weaning from endotracheal intubation. The second patient also had vesico-ureteral reflux postoperatively and had to undergo ureteroneocystostomy for revision of previous ureter reimplantation surgery secondary to bladder diverticulum. Their hospitalization reached to 82 and 180 days. The cost of hospitalization for both patients was 54,136 USD and the total hospital cost, including their donors were 62,177 and 62,541 USD. Both recipients and their donors were doing well until present. Considering the complexity of the case, the amount that the parents had to shoulder was still very low. If these patients were in another institution, no one knows how much they could be spending; it could be up to the ceiling. Sixty-eight (n=36) of our patients are from the Philippines. Although the Philippines has three capable centers for doing the procedure, LDLT has only started in 2011 (20), and the cost is still twice as that in Taiwan (18). Usually, the family of the patients has already exhausted their resources, has researched extensively, and is ready to travel out of their country for a greater chance of survival at a lower cost. The price advantage and greater quality of LDLT in Asia are the main determining force that encourages overseas patients to travel to this part of the world. This reality plus the economic growth in Asia has included LDLT in medical brokerage business (21), as seen in India, Korea, and Singapore. In conclusion, travel for transplantation to Asia for living donor liver transplantation is a wise and cost-effective decision for patients with end-stage liver disease seeking other alternatives in their parent country.
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ACKNOWLEDGMENT The authors thank Linda Lin, RN, Kaohsiung Chang Gung Memorial Hospital International Patient Coordinator, for providing a listing and cost of hospitalization of all the overseas LDLT recipients and donors. REFERENCES 1. 2.
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