Living Donor Liver Transplantation. Kyung-Suk Suh, M.D. Department of Surgery, Seoul National University College of Medicine

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Living Donor Liver Transplantation Kyung-Suk Suh, M.D. Department of Surgery, Seoul National University College of Medicine

Liver Transplantation in Korea 700 118 600 64 66 500 400 37 28 50 480 530 559 300 200 84 42 186 286 335 364 100 111 0 88 93 95 97 99 '01 '03 '05 LDLT (n=2949) DDLT (n=669) Total : 3618

Today s topic MHV reconstruction Outcome of 300 live donors Small-for-size graft LDLT for HCC

Anatomical Consideration in Donor Hepatectomy INFLOW = OUTFLOW (portal v. hepatic a) (hepatic v.) bile duct in both donor and recipient Inflow > Outflow Congestion Outflow > Inflow Ischemia

AN ARTIFICIAL VASCULAR GRAFT IS A USEFUL INTERPOSITION MATERIAL FOR ANTERIOR SECTION DRAINAGE OF A RIGHT LIVER GRAFT Liver Transplantation in press

(%) Patency Rate 100 80 60 40 RHV+MHV PTFE 20 0 1 month 4 months (Months after LT)

6-mo Patient Survival Rate Cumulative Patient Survival Rate 1.1 1.0.9.8.7.6.5.4.3.2 PTFE (n=26), 100% RHV+MHV (n=17), 100% RHV (n=85), 84.7%.1 0.0 0 2 4 6 8 10 P=.028 12 14 Post-Transplant Months

One- and 4-mo patency rate of the eptfe graft was 80.8% and 38.5%. No symptom ass. with the late eptfe graft obstruction No infectious complication of the eptfe graft An artificial eptfe grafts can be a used an interposition vessel graft for anterior drainage without serious complications.

Clinical Outcome of 300 Consecutive Living Liver Donors Kyung-Suk Suh, Eung-Ho Cho, Sung Hoon Yang, Hae Won Lee, Jai Young Cho, Yong Beom Cho, Nam-Joon Yi, Kuhn Uk Lee Department of Surgery Seoul National University, College of Medicine, Seoul, Korea in submission

Annual Cases of LDLT (n=300) Start point of prospective investigation for donor complication No. 70 Early group n=100 Late group n=200 60 50 40 56 50 61 30 20 10 21 35 42 39 0 1999 2000 2001 2002 2003 2004 2005 Nov. Years

Results of 300 Donors No mortality No reoperation No intraop. transfusion of blood product

Comparison of Outcomes Between Early and Late Groups

Clinical Data Early group (n=100) Late group (n=200) p value Male/Female 59/41 141/59 0.052 Age (years) 30.0 ±7.8 31.6 ± 8.9 0.131 Graft (Rt. : Lt.) 45 : 55 141 : 59 <0.001 Operation time (min) Intraop. blood loss (ml) Postop. hospital stay (days) 314.8 ±66.8 285.2 ±49.0 0.002 423.1± 205.4 383.0 ±201.9 0.317 13.1 ±3.6 11.6 ±3.0 0.778

Complication Rate Early group (n=100) Late group (n=200) p value Complications 4 (4%) 95 (47.5%) Grade I 0 57 (28.5%) Grade II 1 (1.0%) 35 (17.5%) <0.05 Grade III 3 (3.0%) 3 (1.5%)

Complications in Early Group (4 patients) Grade II (1 patient) Complication Postoperative ascites Management Conservative management Grade III (3 patients) Iatrogenic pneumothorax Fluid collection at op. site Closed thoracotomy Percutaneous drainage Rt. subphrenic abscess Percutaneous drainage

Complications in Late Group Modified Clavien Grade (I) Hyperbilirubinemia 1 42 Abdominal fluid collection 18 Grade I (57 patients) Wound problems Pleural effusion Ascites Voice change Hepatic vein stenosis 13 13 6 3 2 1 Hyperbilirubinemia : total bilirubin > 3mg/dL > 3 days or > 1.3 mg/dl after POD 7

Complications in Late Group Modified Clavien Grade (II) Bile leak 1 17 Ileus 7 Grade II (35 patients) Bleeding Antibiotics 8 5 Accidental postoperative transfusion 2 1 Bile leak : drain fluid bilirubin > 2 x serum bilirubin, sustained mort than POD 7

Complications in Late Group Modified Clavien Grade (III) Anaphylactic reaction due to CT dye 1 Grade III (3 patients) Pelvic abscess of unknown origin 1 Bile leak with percutaneous drainage 1

Summary In our series, no donor mortality, reoperation, or intraoperative transfusion occurred. In chronological analysis, Minor complications were ignored under retrospective review (4.0% in early group vs 47.5% in late group). Recently, right liver donation is more frequent than left liver (right liver donor: 45.0% in early group vs 70.5% in late group).

Small-for-Size Syndrome Recognizable clinical syndrome which occurs in the presence of a reduced mass of liver insufficient to maintain normal liver function Poor bile production Delayed synthetic function Prolonged cholestasis Intractable ascites septic complication mortality Graft-to-recipient weight ratio (GRWR) > 0.8~1.0% Graft selection of the living donor: left liver graft right liver graft Dahm et al. Am J Transplant. 2005; 5: 2605-10

Survival of small-for-size graft Suguwara et al, J Am Coll Surg 2001 GV/SLV <40% : 80% >40% : 96% Kiuchi et al, Transplantation 1999 GRWR <0.8 : 58% 0.8 1 : 76% >1 : 83% Nichizaki et al, Ann Surg 2001 GV/SLV <30% : 100% 30-40% : 75% >40% : 90%

Small-for-size partial liver graft in an adult recipient; a new transplant technique. Boillot O, Delafosse B,Mechet I,Boucaud C,Pouyet M. We report a new technique of adult liver transplantation using a smallfor-size graft. In order to avoid graft congestion and failure by overperfusion, we completely diverted the superior mesenteric venous flow by a mesocaval shunt with downstream ligation of the superior mesenteric vein. The recipient recovered well, and the graft had normal histology and function at 5 months follow-up. Given the current scarcity of cadaveric donors, this technique may increase the numbers of adult recipients by using left lobes from cadaveric split liver grafts. Lancet. 2002 Feb 2;359(9304):406-7.

Auxiliary Partial Orthotopic LT(APOLT) (living or cadaveric)

Auxiliary Partial Orthotopic LT(APOLT) (living or cadaveric)

Outcome of SFSG in SNUH 29 recipients with a SFSG (GRWR <0.8%) One-year patient survival rate Rt. (100%) vs. Lt. liver graft (66.6%) Cause of death: Graft failure & sepsis More significant SFSS in left SFSG Hyperbilirubinemia and uncontrolled ascites was more common in left liver recipient. All left liver recipients had SFSS. One-third right liver recipients with good graft condition had no SFSS.

Anti-tumor effect, hepatic function and viral clearance in treatment modalities for HCC Antitumor effect Removal of carcinogenic liver Hepatic function Viral clearance Surgery > 100% some No, even aggravate TACE 40-80% PEI 80% No No No No Liver TPL > 100% Yes Yes, in Hep B No, even aggravate in Hep C Disadvantage of TPL : graft failure, infection, donor organ shortage, high cost, risk of life long immunosuppression

Survival according to Milan criteria P = 0.023 1YSR 3YSR 5YSR Meet (n=58) 89.7% 80.6% 72.3% Exceed (n=20) 75.0% 46.6% 46.6%

Strategy of Liver Transplantation For HCC Early HCC Advanced HCC Poor LFT Good LFT Poor LFT Good LFT Prevention of tumor 1 o LDLT progress No waiting time RFA, TACE are effective Expand or limit criteria Surgical LT resection Better DFS in LT Selection (tumor bilolgy) Tumor differentiation Molecular marker Tumor downstage Sometimes possible with TACE, etc DDLT ( Intention-to-Treat Biologic selection process Analysis) 2 o LT (Salvage or Rescue) Can be done with variable risk 1 o LT is better?? LT LT Early : within Milan, Advanced : Beyond Milan

Cumulative recurrence -free survival curve according to 18 F-FDG-PET imaging Recurrence-free Survival Rate (%) 100 90 80 70 60 50 40 30 20 10 0 0 1 2-yr Recurrence-free survival rate = 85.1% PET (-) p = 0.0005 2-yr Recurrence-free survival rate = 46.1% 2 3 PET (+) 4 Years Yang et al, Liver Transplantation 2006

Surgery in press

Beyond Milan Survival according to serum AFP, 400 ng/ml (n=15/4) 1.0.9.8.7.6.5 1Yr SR 92.9% 1Yr SR 50% 2Yr SR 85.1% Preop AFP 400 n=14.4.3.2 2Yr SR 0% p = 0.0006 Preop AFP > 400 n=5.1 0.0 0 12 24 36 48 60 72 84 96 survival period

Scoring criteria Tumor Factors Number of Points* 1 2 3 4 Size (cm) 3 > 3, 5 > 5, 6.5 > 6.5 Number (nodules) 1 2, 3 4, 5 6 AFP (ng/ml) 20 > 20, 200 > 200, 1000 > 1000 *: 3-6 points : Select as the candidates for LT, 7-12 points : Exclude from the candidates for LT : Diameter of the largest tumor

Cumulative survival rate according to criteria based on pre-op data Milan Scoring

Summary Safe remnant volume in live liver donor Remnant <35% is relatively safe MHV reconstruction PTFE graft is safe and useful Modifed extended right graft guarenttees good flow Outcome of 300 live donors No mortality, No transfusion, No reoperation Small-for-size graft Excellent outcome especially in Right graft LDLT for HCC New criteria are needed.