Journal of Pediatric Surgery 49 (2014) 1734–1737

Contents lists available at ScienceDirect

Journal of Pediatric Surgery journal homepage: www.elsevier.com/locate/jpedsurg

Recipient body size does not matter in pediatric liver transplantation Patrick Ho Yu Chung a, See Ching Chan b,⁎, Vivian Way Kay Mok c, Paul Kwong Hang Tam a, Chung Mau Lo b a b c

Division of Paediatric Surgery, Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China Division of Liver Transplantation, Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China Division of Plastic and Reconstructive Surgery, Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China

a r t i c l e

i n f o

Article history: Received 20 August 2014 Accepted 5 September 2014 Key words: Liver transplantation Pediatric Living donor Deceased donor

a b s t r a c t Background and purpose: It is controversial whether small size recipient is associated with adverse outcome in liver transplantation. This study aims to evaluate the outcomes of pediatric liver transplantation according to body weight of recipients. Methods: Liver transplant recipients (age b 18 years, from 1993 to 2011) were studied retrospectively. They were categorized according to the body size at the time of transplantation (A: b6 kg; B: between 6 kg to 10 kg; C: N10 kg). Results: A total of 113 patients (83 LDLTs and 30 DDLTs) were studied. Thirteen (11.5%) belonged to group A, 56 (49.6%) belonged to group B, and 44 (38.9%) belonged to group C. The best graft and patient survivals were found in group A (Figs. 1 and 2), and none of the patients required re-laparotomy for general surgical complications, while 32 patients (32%) in groups B and C did. Regarding transplant-related complications, although group A patients had the highest incidence of biliary tract complications (38.5%, n = 5), the incidence of vascular complications (hepatic artery: 7%, portal vein: 0%, hepatic vein: 0%) in this group was the lowest among the three groups. Conclusion: Outcomes of small-sized recipients are not inferior. Less technical-related vascular complications, which may lead to early graft loss, were observed. This could be patient-related (less advanced cirrhosis) or surgeonrelated (additional attention paid). © 2014 Elsevier Inc. All rights reserved.

Despite the advancement in the treatment of liver diseases in children, liver transplant is still indicated in some diseases that progress to acute or chronic liver failure. Transplantation surgery in children is always challenging and technically demanding. Meticulous hemostasis and accurate anastomosis are required for successful outcomes. Some studies have reported a worse outcome in liver transplant for young children when compared to adults [1–3]. In our opinion, a lower body weight is probably more reflective of the underlying nutritional status and body reserve. In this study, we evaluate the outcomes of pediatric liver transplantation with reference to their body weights at the time of surgery. 1. Patients and methods The first pediatric liver transplantation in our center was performed in 1993. Since then, a total of 120 cases (primary transplantation and retransplantation) have been completed. Techniques for living donor liver transplant (LDLT) and deceased donor liver transplant (DDLT) are standardized and have been described previously [4,5]. In both procedures, after total hepatectomy, vascular and biliary anastomoses were performed using fine absorbable sutures. In the early postoperative

⁎ Corresponding author at: Department of Surgery, Queen Mary Hospital, 102, Pokfulam Road, Hong Kong, China. Tel.: +852 225 53025; fax: +852 281 75475. E-mail addresses: [email protected] (P.H.Y. Chung), [email protected] (S.C. Chan), [email protected] (V.W.K. Mok), [email protected] (P.K.H. Tam), [email protected] (C.M. Lo). http://dx.doi.org/10.1016/j.jpedsurg.2014.09.010 0022-3468/© 2014 Elsevier Inc. All rights reserved.

period, patients would stay in the intensive care unit with management under our standard protocol. Bedside Doppler ultrasound to assess vascular flow was performed at least once daily within the first two weeks after operation. Upon discharge, all patients have lifelong follow-up in our outpatient clinic at regular intervals. In this study, the medical records of liver transplant recipients (age at operation b18 years, from 1993 to 2011) were reviewed retrospectively. Cases of retransplantation were excluded. This study has been approved by the institutional review board of our hospital. To evaluate the outcomes of these patients with respect to their body size, they were categorized according to the body weight (BW) at the time of operation (A = less than or equal to 6 kg; B = between 6 kg to 10 kg; C = above 10 kg). As previous reports have shown a higher complication rate and more surgical difficulties in vascular reconstruction at 6 kg and 10 kg recipients [6,7], these two body weight values were chosen as the landmarks for comparison in this study. Demographic data including body weight, gender, indications for operation, pretransplant Paediatric End-stage Liver Disease (PELD) score and general status before transplantation would be presented. The main outcomes to be evaluated include general surgical complications, vascular complications, biliary complications as well as graft and patient survival. Statistical analysis was done using IBM Statistical Package for Social Science, version 20.0. Continuous variables were expressed as median (range) and compared using the Kruskal–Wallis test. Categorical variables were compared using the chi-square test. A p-value of less than 0.05 was considered to be statistically significant. Graft and patient survival after liver transplantation were estimated by the Kaplan–Meier survival method.

P.H.Y. Chung et al. / Journal of Pediatric Surgery 49 (2014) 1734–1737

1735

Fig. 1. Indications for liver transplantation in pediatric patients.

2. Results During the study period, there were 120 liver transplantations performed. However, 7 cases were excluded from the present study because they were retransplantations. Among the 113 cases, 83 were living donor liver transplants (LDLTs) and 30 cases were deceased donor liver transplant (DDLTs). There were slightly more female than male patients (female/male = 58:55). The youngest patient at the time of transplantation was a full term baby girl at the age of 46 days with body weight 4.4 kg. The median follow-up period was 8.5 years (range, 3 months to 17 years). The indications for liver transplant included biliary atresia (n = 78), fulminant hepatic failure (n = 18), metabolic diseases (n = 8), hepatitis (n = 4), tumor (n = 2) and others (n = 3) (Fig. 1). Background information of the studied patients is summarized in Table 1. Of the 113 patients, 13 (11.5%) belonged to group A (BW ≤ 6 kg); 56 (49.6%) belonged to group B (BW 6 kg to 10 kg) and 44 (38.9%) belonged to group C (BW N 10 kg). For the pretransplant status, the median PELD scores were 10 (range: 8 to 20), 12 (−10 to 23) and 14 (8 to 32) in group A, B and C respectively (p = 0.67). The highest median bilirubin level (μmol/L) before transplantation was found in group C (154, range: 34 to 334), followed by group B (92, range: 10 to 224) and group A (86, range: 56 to 154) (p = 0.26). As expected, group A has the lowest median graft weight (gram) (225, range: 185–364). However, there is no statistical significance difference in the estimated standard liver volume among the three groups. Twenty-six (23.0%) patients needed intensive care unit admission before transplantation. While the overall one-year graft survival was 84.1.7% (95/113), the results in different groups (A/B/C) were 100%, 80.4% and 84.1% respectively (p = 0.07) (Fig. 2). The overall patient survival at 1 year was 88.5% (100/113). The results in different groups were 100% in group A, 85.7% in group B and 88.6% in group C (p = 0.08) respectively (Fig. 3).

Fig. 2. Graft survival curve in groups A, B and C.

Incidence of surgical complications was summarized in Table 2. Regarding the incidence of general surgical complications, none of the patient in group A required relaparotomy for surgical complications while 32 patients in groups B and C did. For complications specific to liver transplantation, the overall incidence was 37.2% (42/113). There were 5 patients who suffered from hepatic artery thrombosis in the early postoperative period. Three came from group C and the other two patients were from group A and B respectively. They all required reoperation and this resulted in one graft loss in group C. Portal vein complications (stenosis/thrombosis) (n = 13) were most common in group B (n = 9). The remaining 4 patients belonged to group C. On the other hand, there were no patients from group A suffering from portal vein complications. There were only two patients in group C who suffered from hepatic vein/vena caval complications. Incidence of biliary complications (stricture and leakage) was 19.4% (22/113). Seventeen cases were stricture and five cases were leakage. The highest incidence of biliary tract complication was found in group A (38.5%, n = 5), followed by group B (21.4%, n = 12) and group C (11.4%, n = 5), (p = 0.25).

Table 1 Demographic and characteristics of patients in groups A, B and C.

Body weight No. of patients Body weight (kg)a Indications Biliary atresia Nonbiliary atresia Pretransplant bilirubin level (umol/L)a PELD score before transplantationa Graft weight (g)a Estimated standard liver volume (%) a

Median (range).

Group A

Group B

Group C

≤6 kg 13 5.4 (4.4–5.9)

6 kg to 10 kg 56 8.6 (6.1–9.9)

≥10 kg 44 14.8 (10.1–68.9) 0.02

8 5 86 (56–154)

40 16 92 (10–224)

30 14 154 (56–334)

0.26

10 (8–20)

12 (−10-23)

14 (8–34)

0.67

225 (185–364) 295 (165–450) 385 (200–1385) 120 (106–165) 103 (60–205) 85 (39–150)

p Value

0.03 0.07 Fig. 3. Recipient survival curve in groups A, B and C.

1736

P.H.Y. Chung et al. / Journal of Pediatric Surgery 49 (2014) 1734–1737

Table 2 Incidence of transplant related and general surgical complications after liver transplantation.

Transplant-related complications (Leakage or obstruction; n = 42) Hepatic artery (n = 5) Hepatic vein or vena cava (n = 2) Portal vein (n = 13) Biliary tract (n = 22) General surgical complications (n = 55) Wound infection (n = 14) Intraabdominal collection (n = 8) Intraabdominal bleeding (n = 5) Intestinal obstruction (n = 11) Bowel perforation (n = 8) Others (n = 9)

Group A

Group B

Group C

p Value

1 (7%) 0 (0%) 0 (0%) 5 (38.5%)

1 (7%) 0 (0%) 9 (16.1%) 12 (21.4%)

3 (6.8%) 2 (4.5%) 4 (9.1%) 5 (11.4%)

0.85 0.9 0.05 0.25

3 (23.1%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%)

6 (10.7%) 4 (7.1%) 3 (5.4%) 5 (8.9%) 5 (8.9%) 6 (10.7%)

5 (11.4%) 4 (9.1%) 2 (4.5%) 6 (13.6%) 3 (6.8%) 3 (6.8%)

0.76 0.21 0.48 0.43 0.66 0.39

3. Discussion Our current study shows that liver transplant in the smallest-sized patient (body weight less than 6 kg) is feasible though technically demanding. The outcomes in terms of patient and graft survival are at least comparable, if not superior, to the larger-sized recipients in our series. Incidence for vascular complications which may potentially lead to early graft loss is also less in the small-sized patients. Liver transplantation remains the only curative treatment for patients with end-staged liver diseases. Although the incidence of liver disease related to viral hepatitis or alcoholism is less common in children, there are other diagnoses specific to pediatric patients which subject them to the need of liver transplantation. The most common indication for liver transplant in children is biliary atresia. It is a congenital disease resulting in fibrosis and sclerosis of the biliary tract. The disease remained fatal until development of the Kasai operation in 1957 [8]. Despite an uneventful operation, there are still a considerable number of patients in need of transplantation because of progressive liver failure or the development of portal hypertension and growth retardation [9–11]. Some of these patients may have disease progression that happens in the early period after Kasai operation and require liver transplantation when their body size is still small. Other indications for liver transplant in early age include congenital metabolic diseases, drug-induced or idiopathic hepatitis. All these conditions are potentially fatal or leading to significant morbidity. Therefore, liver transplantation is sometimes inevitable even in young infants. Being a complex and highly specialized operation, liver transplant requires meticulous surgical skills in vascular and biliary reconstructions. There is no doubt that performing such procedures in smallsized recipients is more technically demanding than in large-sized recipients. In addition, the tolerance to blood loss is also less in pediatric patients and hence an even better hemostasis is needed. All these are additional challenges to the operating surgeons when compared with transplantation surgery in adults. Some surgeons have hesitation when considering liver transplantation for small-sized babies. There were a few early reports on the outcome of liver transplantation in young patients. In the 1990s, Dunn et al. [12] and Vázquez et al. [13] reported their experience in liver transplantation in small babies. While the results of Dunn et al.'s study revealed a worse allograft survival in patients young than 1 year, Vázquez et al. concluded that small babies are a high-risk group in a pediatric liver transplant program. However, in almost the same year, Beath et al. from Birmingham reported their successful experience in liver transplantation in babies within infantile period [14]. The study on the relationship between age or body size with clinical outcomes continued in the 2000s. With the advancement in surgical technology and intensive care support, an improvement in

results has been noted. Iglesias et al. [15] reported that in recipients less than 7 kg, an 82% patient survival rate and 72% graft survival rate could be achieved. It was concluded that weight alone (under 7 kg) should not be considered as a contraindication for liver transplantation. Noujaim et al. [16] carried out a retrospective review on the outcome of patients less than 5 kg. He reported that the survival rate in patients less than 5 kg could be compared favorably with older patients. More recently, a retrospective review based on UNOS database has been published [17]. In this report, patients with body weight less than 5 kg were studied. It was concluded that transplantation in recipients less than 5 kg had relatively high rate of mortality and graft loss. Nevertheless, an improvement in survival was observed over the last decade. Risk factors analysis showed that being on life support at transplant was associated with worse outcomes in terms of death and graft loss. In the study, we try to evaluate the outcome of our small-sized recipients by a retrospective analysis. There is a shortage of deceased donor graft in our locality and therefore, most recipients received liver grafts from living donors. In most of our cases, a left lateral section graft or left lobe graft would suffice. The most common indication in our series was biliary atresia and almost all patients had undergone Kasai operation. With this, the majority of our patients did not have a virgin abdomen to start with. This was one of the major challenges to the operating surgeons who have to overcome the intraabdominal adhesion during operation. However, the complication rate was not particularly high in our small-sized recipients and none of them required re-laparotomy for surgical complications. For transplantrelated complications, the potential problems which may lead to early graft loss are portal vein- and hepatic artery-related. Performing portal vein anastomosis is always difficult in a small-sized recipient since there is usually a discrepancy in the caliber between the native and graft portal vein. Given the very small sized hepatic artery, arterial anastomosis is also challenging in pediatric liver transplant. However, in our current series, the incidence of complications relating to these two vascular anastomoses were actually lowest in group A patients and hence difficulty in performing vascular anastomosis should not be used an argument against transplantation in small-sized recipients Although we could not conclude that group A patients had the best survival because of statistical insignificance, it can be noted that the overall patient and graft survivals in group A patients were at least not inferior to the others. We believe that this is related to the extra care and attention paid during operations for small-sized recipients. In fact, the technique for total hepatectomy and implantation are standard and similar to operations in adults. Surgeons, however, have to pay attention to gentle tissue handling when operating on small-sized recipients as their tissues are fragile and can easily be torn. Hemostasis has to be meticulous as even a tiny blood clot can potentially dampen the vascular flow in small-sized patients owing to their extremely small-sized vessels. Another reason that we postulate for favorable outcomes in small-size recipients is the less advanced cirrhosis found in this group of patients, evidenced by a more favorable pretransplant liver function. Although the incidence of biliary stricture appears higher in small-sized patients, most strictures can be treated with interventional radiology nowadays and re-operation rarely needed and hence, surgical trauma to patients is less extensive. Post-operative caring is another cornerstone for success. Each member of the managing team, including surgeons, physicians and nurses, should be familiar with a standard protocol so that any deviations from usual recovery can be determined early before irreversible damage happens. In summary, performing liver transplantation is not contraindicated in small-sized recipients. However, surgeons performing the operation should have ample experience and be prepared to pay extra-effort. Furthermore, a good understanding in pediatric anatomy and physiology will facilitate the operation. Lastly, we believe that a successful operation has to be supported by a group of dedicated pediatric anesthetists as well as intensivists for perioperative support.

P.H.Y. Chung et al. / Journal of Pediatric Surgery 49 (2014) 1734–1737

References [1] Bouchut JC, Stamm D, Boillot O, et al. Postoperative infectious complications in paediatric liver transplantation: a study of 48 transplants. Paediatr Anaesth 2001; 11(1):93–8. [2] Sokal EM, Veyckemans F, de Ville de Goyet J, et al. Liver transplantation in children less than 1 year of age. J Pediatr 1990;117(2 Pt 1):205–10. [3] Colombani PM, Cigarroa FG, Schwarz K, et al. Liver transplantation in infants younger than 1 year of age. Ann Surg 1996;223(6):658–62 [discussion 62–4. PubMed PMID: 8645039]. [4] Saing H, Fan ST, Chan KL, et al. Liver transplantation in infants. J Pediatr Surg 1999;34 (11):1721–4. [5] Fan ST. Living donor liver transplantation. 2nd ed. Takungpao: Shenzhen; 2007. [6] Cheng YF, Chen CL, Huang TL, et al. Risk factors for intraoperative portal vein thrombosis in pediatric living donor liver transplantation. Clin Transpl 2004;18(4):390–4. [7] Shirouzu Y, Kasahara M, Morioka D, et al. Vascular reconstruction and complications in living donor liver transplantation in infants weighing less than 6 kilograms: the Kyoto experience. Liver Transpl 2006;12(8):1224–32. [8] Kasai MSS. A new operation for ‘non-correctable’ biliary atresia: hepatic portoenterostomy. Shujutsu 1959;13:733–9.

1737

[9] Nio M, Ohi R. Biliary atresia. Semin Pediatr Surg 2000;9(4):177–86. [10] Wildhaber BE, Majno P, Mayr J, et al. Biliary atresia: Swiss national study, 1994–2004. J Pediatr Gastroenterol Nutr 2008;46(3):299–307. [11] Mohammad S, Grimberg A, Rand E, et al. Long-term linear growth and puberty in pediatric liver transplant recipients. J Pediatr 2013;163(5):1354–60 [e1-7]. [12] Dunn SP, Weintraub W, Vinocur CD, et al. Is age less than 1 year a high-risk category for orthotopic liver transplantation? J Pediatr Surg 1993;28(8): 1048–50. [13] Vazquez J, Gamez M, Santamaria ML, et al. Liver transplantation in small babies. J Pediatr Surg 1993;28(8):1051–3. [14] Beath SV, Brook GD, Kelly DA, et al. Successful liver transplantation in babies under 1 year. BMJ 1993;307(6908):825–8. [15] Iglesias J, Lopez JA, Ortega J, et al. Liver transplantation in infants weighing under 7 kilograms: management and outcome of PICU. Pediatr Transplant 2004;8(3): 228–32. [16] Noujaim HM, Mayer DA, Buckles JA, et al. Techniques for and outcome of liver transplantation in neonates and infants weighing up to 5 kilograms. J Pediatr Surg 2002; 37(2):159–64. [17] Arnon R, Annunziato R, Miloh T, et al. Liver transplantation in children weighing 5 kg or less: analysis of the UNOS database. Pediatr Transplant 2011;15(6): 650–8.

Recipient body size does not matter in pediatric liver transplantation.

It is controversial whether small size recipient is associated with adverse outcome in liver transplantation. This study aims to evaluate the outcomes...
314KB Sizes 0 Downloads 5 Views