Routine microsurgical biliary reconstruction decreases early anastomotic complications in living donor liver transplantation

Authors

  • Tsan-Shiun Lin,

    1. Liver Transplantation Program, Chang Gung Memorial Hospital–Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan
    2. Department of Surgery, Chang Gung Memorial Hospital–Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan
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    • These authors contributed equally to this study.

  • Allan M. Concejero,

    1. Liver Transplantation Program, Chang Gung Memorial Hospital–Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan
    2. Department of Surgery, Chang Gung Memorial Hospital–Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan
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    • These authors contributed equally to this study.

  • Chao-Long Chen,

    Corresponding author
    1. Liver Transplantation Program, Chang Gung Memorial Hospital–Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan
    2. Department of Surgery, Chang Gung Memorial Hospital–Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan
    • Department of Surgery, Chang Gung Memorial Hospital–Kaohsiung Medical Center, 123 Ta-Pei Road, Niao-Sung, Kaohsiung 833, Taiwan
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    • Telephone: +886-7-731-7123, extension 8097; FAX: +887-7-732-4855

  • Yuan-Cheng Chiang,

    1. Liver Transplantation Program, Chang Gung Memorial Hospital–Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan
    2. Department of Surgery, Chang Gung Memorial Hospital–Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan
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  • Chih-Chi Wang,

    1. Liver Transplantation Program, Chang Gung Memorial Hospital–Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan
    2. Department of Surgery, Chang Gung Memorial Hospital–Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan
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  • Shih-Ho Wang,

    1. Liver Transplantation Program, Chang Gung Memorial Hospital–Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan
    2. Department of Surgery, Chang Gung Memorial Hospital–Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan
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  • Yueh-Wei Liu,

    1. Liver Transplantation Program, Chang Gung Memorial Hospital–Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan
    2. Department of Surgery, Chang Gung Memorial Hospital–Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan
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  • Chin-Hsiang Yang,

    1. Liver Transplantation Program, Chang Gung Memorial Hospital–Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan
    2. Department of Surgery, Chang Gung Memorial Hospital–Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan
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  • Chee-Chien Yong,

    1. Liver Transplantation Program, Chang Gung Memorial Hospital–Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan
    2. Department of Surgery, Chang Gung Memorial Hospital–Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan
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  • Bruno Jawan,

    1. Liver Transplantation Program, Chang Gung Memorial Hospital–Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan
    2. Department of Anesthesiology, Chang Gung Memorial Hospital–Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan
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  • Yu-Fan Cheng

    1. Liver Transplantation Program, Chang Gung Memorial Hospital–Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan
    2. Department of Diagnostic Radiology, Chang Gung Memorial Hospital–Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan
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Abstract

Biliary reconstruction using a microsurgical technique in living donor liver transplantation was routinely performed on 88 grafts primarily transplanted into 85 patients. All procedures were performed under a microscope by a single microsurgeon. Except for biliary atresia and Alagille syndrome, duct-to-duct reconstruction was performed. Stents were not used. The outcomes with microsurgical biliary reconstruction (MB) were compared with the outcomes of a cohort of 86 grafts in 85 patients that underwent conventional biliary reconstruction (CB). The identification of complications included only up to 12 months of follow-up for each recipient in both groups. The average graft duct sizes were 2.8 mm for MB and 3.4 mm for CB. Most complications occurred in the first 15 cases with MB, and these cases were considered to constitute the learning curve phase. The MB complication rate was 46.7% in the first 15 cases, 20.0% in the next 15 cases, and 5.4% in the last 55 cases. When the learning curve phase was excluded, the overall complication rate over time with MB (8.9%) was significantly lower than that with CB (21.9%). CB increased the risk of biliary complications by 2.5 times (relative risk: 2.5; attributable risk: 128; odds ratio: 2.9). In conclusion, routine MB is a technical innovation that leads to decreased early anastomotic complications in living donor liver transplantation. Liver Transpl 15:1766–1775, 2009. © 2009 AASLD.

Liver transplantation (LT) has become the standard treatment for patients with end-stage liver disease. With improvements made in surgical techniques, immunosuppressive agents, and intensive and anesthesia care, the complications of LT have been reduced.1 However, biliary reconstruction remains the Achilles' heel of LT because of the high incidence of reported complications that cause a myriad of graft problems associated with significant recipient morbidity and mortality.2–4

Biliary complications can be generally grouped and analyzed according to the time of occurrence (early versus late), type (leak versus stricture), and contributing technical factors (anastomotic versus nonanastomotic). Anastomotic complications are mostly related to operative reasons and often occur early. Nonanastomotic (intrahepatic) complications are commonly preservation-related, ischemia-related, or reperfusion injury–related and usually manifest later.

In living donor liver transplantation (LDLT), the 2 generally accepted methods of biliary reconstruction are the Roux-en-Y hepaticojejunostomy and duct-to-duct anastomosis.5–12 A modification of both methods includes the use of stents.13, 14 Our center has gone through an evolutionary change in our biliary reconstruction methods over the years. Currently, we perform routine microsurgical biliary reconstruction (MB) without a stent in the recipient. To our knowledge, routine biliary reconstruction using a microsurgical technique in LT has not been reported, and the results have not been elucidated. Our objective is to describe our institutional experience with routine biliary reconstruction using a microsurgical technique in LDLT.

Abbreviations

CB, conventional biliary reconstruction; HA, hepatic artery; HBV, hepatitis B virus; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; HD, hepatic duct; LDLT, living donor liver transplantation; LT, liver transplantation; MB, microsurgical biliary reconstruction; MELD, Model for End-Stage Liver Disease; PELD, Pediatric End-Stage Liver Disease.

PATIENTS AND METHODS

From March 22, 2006 to November 30, 2007, 88 grafts were primarily transplanted into 85 patients (including 3 dual graft transplants) at the Chang Gung Memorial Hospital–Kaohsiung Medical Center (Taiwan). All biliary reconstructions were performed under a microscope by a single microsurgeon who also did the hepatic artery (HA) reconstruction with a microsurgical technique. Except for biliary atresia and Alagille syndrome, duct-to-duct reconstruction was performed. A stent or T-tube was not used. All recipients and donors were blood type–identical or ABO-compatible. Data were collected with a prospective database, and the biliary reconstruction characteristics, complications, and outcomes were analyzed retrospectively.

Because the occurrence of biliary complications is time-dependent, we defined a perioperative biliary complication as either a bile leak or a stricture occurring within 90 days of surgery and an early biliary complication as a complication occurring within 12 months of transplant. Bile leakage was defined as the presence of bile material in the closed-suction drain that persisted beyond 3 days after transplantation or as the presence of a biloma within the area of the anastomosis. An anastomotic biliary stricture was defined as a narrowing of the extrahepatic bile duct to >50% of the initial duct caliber or intrahepatic biliary dilatation > 3 mm in the presence of a notable extrahepatic biliary narrowing at the area of the anastomosis. A stricture was diagnosed on the basis of magnetic resonance imaging, percutaneous transhepatic biliary imaging, or endoscopic retrograde cholangiography. The outcomes with MB were compared with the outcomes of a historical cohort in which the last 86 grafts, primarily transplanted into 85 patients (including 1 dual graft), underwent conventional biliary reconstruction (CB) before March 22, 2006. The minimum follow-up among surviving patients in the MB group was 12 months. The identification of complications included only up to 12 months of follow-up for each recipient in both groups.

CB Technique

The biliary reconstructions in the CB group were performed by 2 senior experienced LT surgeons (but not microsurgeons) who alternately took cues in reconstructing the bile duct during the transplant operation (C.-L.C. and C.-C.W.) and were involved in our LDLT program since its inception in 1994. We have elucidated our donor evaluation and graft procurement techniques in previous publications.15 Here, we summarize the salient points with an emphasis on biliary reconstruction.

In right graft procurement, hilar dissection was performed with identification and isolation of the right portal vein and HA. The small portal branches to the caudate lobe and segment 4 were divided between ligatures to allow subsequent encirclement of the right hilar plate and hepatic ducts (HDs). Once two-thirds of the parenchymal transection was completed, the entire right hilar plate together with the HD, Glissonian sheath, and periductal tissue was dissected and isolated with a tonsil clamp and then encircled and tagged by a regular vessel loop. The HD was not dissected free from the hilar plate. The right HA and portal vein were tagged by a regular vessel loop to avoid injury during the encircling of the hilar plate. Transcystic intraoperative cholangiography to delineate the biliary anatomy and decide on the level of transection of the right HD was routinely performed. After a cholangiography scout film with 2 radiopaque loops was taken, 2 short pieces of radiopaque loops were lightly sutured onto the planned biliary transection line (Fig. 1), and another cholangiograph was taken. These steps were carried out with precision to avoid multiple ducts in the graft, if possible, and to prevent injuries to the remaining liver biliary tree. The corresponding author of this article (C.-L.C.) developed this complete hilar plate encircling technique, which has been applied since the start of our LDLT program in 1994 [it was presented in video format at invited lectures during the 6th World Congress of the International Hepato-Pancreato-Biliary Association (Washington, DC) and the 10th Congress of the International Liver Transplant Society (Kyoto, Japan)]. This technique was used in both the CB and MB groups. Furthermore, all donor hepatectomies were performed by an experienced LT surgeon (C.-L.C.).

Figure 1.

Complete hilar plate encircling technique in right graft procurement: the entire hilar plate together with the hepatic duct, Glissonian sheath, and periductal tissue is encircled with a white vessel loop. For precise mapping of the transection line, 2 short pieces of radiopaque loops are lightly sutured onto the planned biliary cutting plane, and another cholangiogram is taken.

In left graft procurement, hilar dissection was performed in a fashion similar to that used in a right graft with the complete hilar plate encircling technique. Routine cholecystectomy was not done unless intraoperative cholangiography was indicated. Intraoperative cholangiography was indicated if preoperative magnetic resonance cholangiography showed bile duct branching within 1 cm of the confluence, a right sectoral duct draining into the left HD, or trifurcation of the HD, if the donor had previous biliary surgery (ie, cholecystectomy),16 or if there were equivocal preoperative imaging findings. Similarly, the periductal tissue and its arteriovenous plexus were untouched and preserved. The entire hilar plate with the left HD, Glissonian sheath, and periductal tissue was divided sharply with scissors (Fig. 2).

Figure 2.

Complete hilar plate encircling technique and transection during left graft procurement.

In the recipient, total hepatectomy with preservation of the inferior vena cava was performed as described previously.17, 18 In order to ensure no disruption of the HD blood supply, the hilar dissection was kept to a minimum with preservation of as much connective tissue around the native HD as possible. The recipient's common bile duct was not dissected away from the proper HA to keep the duct blood supply from the proper HA intact. At the end of the recipient hepatectomy, the bile duct was cut at the hilum, usually intraparenchymally above the HD confluence. In biliary atresia patients who had previously undergone a Kasai operation, the Roux loop was disconnected and was again used for biliary enteric anastomosis. Whenever it was possible, duct-to-duct anastomosis for biliary reconstruction without a stent or T-tube was performed, except for biliary atresia and Alagille syndrome recipients, who underwent duct-to-jejunum anastomosis, and under certain conditions in which duct-to-duct anastomosis was not feasible or was contraindicated.

When there were 2 or 3 separate ducts in the graft, ductoplasty was performed if the ducts could be approximated without tension. The ductoplasty was performed via the placement of interrupted 6-0 absorbable, monofilament, polydioxanone sutures (PDS II, Ethicon, Inc., Somerville, NJ) to gently appose the separate ducts together. The intervening tissue between the separate ducts was not dissected or cut during the ductoplasty. The apposition of these separate ducts without complex manipulation of the ducts further ensured that the blood supply was not compromised. If the ducts were far apart or could not be approximated without tension, a separate anastomosis for each duct opening was performed. Biliary reconstruction was done with interrupted 6-0 absorbable, monofilament sutures with or without surgical loupes. There had to be troublesome bleeding in the recipient bile duct before the anastomosis was performed. If there was poor or no bleeding, we cut back the bile duct until there was brisk bleeding. Tension during the anastomosis procedure was avoided. Nerve hooks were used to expose the bile ducts instead of forceps to minimize crushing of the duct edges. All suture knots were tied extraluminally.

MB Technique

Since March 22, 2006, all biliary reconstructions were performed by an experienced microsurgeon (T.-S.L.). All biliary reconstructions were performed under an operating microscope (Carl Zeiss, Jena, Germany) with a magnification of 10 to 20×. The graft bile duct was not dissected for additional length for anastomosis. The recipient bile duct was not dissected far off from the HA. The ducts were inspected for quality, vascularity, and size of the lumen. The technique of ductoplasty for multiple small duct openings was similar to that used in the conventional method but under a microscope.

The microsurgical biliary anastomosis was performed with 6-0 Prolene sutures (Johnson and Johnson, Somerville, NJ) on a 6-0 gauge cardiovascular-point needle. The interrupted suturing technique was used for the posterior wall anastomosis first, and then the continuous suture and interrupted tie technique or combined microvascular anastomosis was used for the anterior wall. The combined microvascular anastomosis method was described in an earlier report.19 This technique was simple to use, decreased the operative time, and avoided suturing into the posterior wall as all the sutures were put into place before the knots were tied and all suture knots were tied extraluminally (Fig. 3).

Figure 3.

Continuous suture and interrupted tie technique applied to microsurgical biliary reconstruction.

Follow-Up

A routine Doppler ultrasound examination of the portal vein, hepatic vein, and HA was conducted upon completion of all vascular anastomoses, after closure of the abdomen, and daily for 1 week. It was decreased to every other day in the second week post-transplant and then to twice a week until the patient was discharged from the hospital. This was done for the early detection of any possible vascular problems. Particular attention was also given to biliary dilatation. After discharge, a Doppler ultrasound examination was performed every 3 months in hepatocellular carcinoma patients and every 6 months in non–hepatocellular carcinoma patients. If there was any indication of a biliary problem, magnetic resonance cholangiography was requested to delineate the biliary tree, and if any intervention was required, percutaneous transhepatic cholangiography or endoscopic retrograde cholangiography was performed initially.

Immunosuppression and Posttransplant Management

In adults, basiliximab induction (Simulect, Novartis, Basel, Switzerland) was routinely administered 6 hours after portal reperfusion and on day 4 post-transplant, and the main immunosuppression consisted of tacrolimus (Prograft, Fujisawa, Osaka, Japan) in combination with steroids. In children, immunosuppression included cyclosporine (Neoral, Novartis), azathioprine (GlaxoWellcome, Auckland, New Zealand), and a steroid. Mycophenolate (Roche, Basel, Switzerland) was used in both groups when indicated.20 Steroids were tapered and discontinued within 3 months in the majority of recipients, except for those with autoimmune disorders.

All rejections were biopsy-proven and managed with either increased immunosuppression or intravenous pulse methylprednisolone (10 mg/kg/body weight).

Statistical Analysis

All values were expressed as means and ranges when appropriate. The t test and chi-square test with Yates' correction were used to compare recipients and outcomes between the MB and CB groups. A P value < 0.05 was considered significant. The analysis was done with SPSS computer software (SPSS version 13 for Windows, SPSS, Inc., Chicago, IL).

RESULTS

Table 1 summarizes the demographic and pretransplant clinical characteristics of the patients who underwent CB and MB. There was no significant difference in the 2 groups in terms of gender, diagnosis, mean age, height, weight, Child-Pugh score and classification (except in Child A and B), or Model for End-Stage Liver Disease or Pediatric End-Stage Liver Disease scores. There were almost equal numbers of males and females as well as pediatric and adult patients in both groups. It can be inferred on the basis of the demographic and pretransplant characteristics that the 2 groups were nearly identical.

Table 1. Demographic and Pretransplant Clinical Characteristics of the Patients
CharacteristicConventional Group (n = 85)Microsurgical Group (n = 85)P Value
  1. Abbreviations: HBV, hepatitis B virus; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; MELD, Model for End-Stage Liver Disease; PELD, Pediatric End-Stage Liver Disease.

Patient   
 Male6362 
 Female2223 
 Adult5863 
 Pediatric2722 
Diagnosis   
 Biliary atresia1918 
 Neonatal hepatitis10 
 Alagille11 
 Polycystic liver10 
 Wilson's disease22 
 Glycogen storage disease51 
 Urea cycle disorder01 
 HBV ± HCC3841 
 HCV ± HCC912 
 HBV ± HCV14 
 Primary biliary cirrhosis20 
 Cryptogenic20 
 Alcoholic cirrhosis45 
    
Mean age (years)35.4 (0.7–64.2)39.4 (0.5–67.7) 
Mean height (cm)140.9 (68.0–175.5)142.8 (62.0–180.9) 
Mean weight (kg)53.0 (7.8–98.0)54.0 (6.1–97.2) 
Child-Pugh classification   
 A1021<0.05
 B5240<0.05
 C2324 
Mean Child-Pugh score8.7 (5–15)8.1 (5–14) 
Mean MELD-PELD score12.6 (−11 to 45)12.1 (−7 to 32) 

Table 2 summarizes the operative data for the CB and MB groups. Besides dual-graft LDLT (once with CB and 3 times with MB), the significant differences between the 2 groups included the cold ischemia time, total operative time, and amount of transfused packed red cells. There were 7 early and late deaths in each group (CB: LDLT 173, veno-occlusive disease of the liver; 180, small-for-size syndrome; 198, perioperative bleeding; 230, pancreatitis; 233, portal vein thrombosis; 236, perioperative bleeding; and 239, septic complications; MB: LDLT 256, acute myocardial infarction; 260, perioperative bleeding; 269, septic complications; 291, HA thrombosis; 292, hepatitis C recurrence; 299, microangiopathic thrombocytopenic purpura; and 303, lung metastasis). The deaths were not related to any biliary complication.

Table 2. Operative Data and Outcomes
Operative FactorConventional GroupMicrosurgical GroupP Value
  1. Abbreviation: LDLT, living donor liver transplantation.

Mean donor age (years)31.5 (19.4–54.6)30.6 (18.0–55.0) 
Type of LDLT   
 Single graft8482 
 Dual graft13 
Graft usedTotal n = 86Total n = 88 
 Right lobe5561 
 Extended right lobe52 
 Left lobe46 
 Extended left lobe20 
 Left lateral segment1715 
 Extended left lateral segment34 
Mean graft weight to recipient weight ratio1.4 (0.7–4.2)1.6 (0.6–4.8) 
Mean cold ischemia time (minutes)70.7 (25.0–287.0)56.2 (18.0–153.0)<0.05
Mean warm ischemia time (minutes)54.6 (25.0–93.0)53.7 (29.0–115.0) 
Mean operative time (minutes)639.3 (413.0–1163.0)684.4 (465.0–980.0)<0.05
Mean recipient blood loss (mL)3247.1 (15.0–53,850.0)3392.7 (30.0–18,300.0) 
Mean recipient packed red cell transfusion (g)1804.2 (0–10,714.0)2381.8 (0–12,038.0)<0.05
Number of early and late recipient deaths77 

The mean graft duct size was 3.4 mm (range, 1.0-7.0 mm) in CB and 2.8 mm (range, 1.0-7.0 mm) in MB. The stratified biliary reconstruction characteristics, outcomes, and complications are summarized in Tables 3 to 5. A stent or T-tube was not used in any patient in either group. The most common complication was a stricture (9.4%) in CB and a leak (9.4%) in MB. The overall biliary complication rates in the CB and MB groups were 18.8% (16/85) and 15.3% (13/85), respectively. There was no relationship between the occurrence of biliary complications and the number of duct openings or liver lobe used (P > 0.05). As shown in Table 3, there were 3 strictures and 2 leaks followed by a stricture in the multiple duct group that underwent MB. In the 3 patients with primary strictures, 1 had a stricture confined to only 1 duct (LDLT 280; the stricture was in the right posterior segmental duct), and 2 had strictures involving all reconstructed ducts (LDLT 256 and 281; 2-in-1 duct-to-duct reconstruction). In the 2 leaks followed by a stricture, the stricture involved the entire anastomosis, and all ducts were obstructed. All biliary complications in the MB group were isolated biliary complications and were not associated with any major vascular (HA, portal vein, and hepatic vein) complications. In the CB group, only 1 (LDLT 228) was associated with both HA thrombosis and a biliary stricture. The overall incidence of HA thrombosis was 2.3% (2/88) in the MB group and 3.5% (3/86) in the CB group. In addition, the gastroepiploic artery was used in 2 patients in the MB group (2/88; 2.3%) and in 2 patients in the CB group (2/86; 2.3%) because of the poor quality of the native HA assessed at the time of transplantation.

Table 3. Stratification of Complications Based on the Patient and Graft Types
CharacteristicConventional Group (n = 16)Microsurgical Group (n = 13)
Type of graft  
 Left lobe35
 Right lobe138
Type of patient  
 Pediatric42
 Adult1211
Table 4. Stratification of Complications Based on the Type of Complication and Lobe Used
ComplicationConventional Group (n = 16)Microsurgical Group (n = 13)
Left LobeRight LobeLeft LobeRight Lobe
Leak1444
Stricture1712
Leak followed by stricture1202
Total31358
Table 5. Stratification of Complications Based on the Type of Complication and Duct Reconstruction
ComplicationConventional Group (n = 16)Microsurgical Group (n = 13)
Single Duct (n = 40)Multiple Ducts (n = 25)Roux-Y (n = 21)Single Duct (n = 46)Multiple Ducts (n = 20)Roux-Y (n = 22)
Leak221512
Stricture620030
Leak followed by stricture120020
Total9 (22.5%)6 (24%)1 (5%)5 (10.7%)6 (30%)2 (9.1%)

In the MB group, the first HA thrombosis patient (LDLT 291) underwent thrombectomy and re-anastomosis of the HA 7 days after transplantation. This patient succumbed to complications of HA thrombosis and is listed under deaths. The second patient (LDLT 297) underwent radial artery interposition grafting 6 days after transplantation. This patient survived without biliary complications. Both thromboses occurred in pediatric patients. In the CB group, the first HA thrombosis patient (LDLT 203) underwent revascularization with the left gastric artery 11 days after transplantation. This patient survived without biliary complications. The second patient (LDLT 228) developed HA thrombosis on the second posttransplant day and underwent thrombectomy and re-anastomosis of the HA. This patient developed a biloma and multiple biliary strictures and required retransplantation 20 months later. The third patient (LDLT 233) was a pediatric patient who developed HA thrombosis after multiple laparotomies for portal vein thrombosis. This patient died from severe liver necrosis as a complication of portal vein thrombosis and is listed under deaths.

In the CB group, 13 complications developed within 90 days after transplantation, and 3 developed beyond 90 days but within 12 months. In the MB group, all complications occurred within 90 days after transplantation. When the biliary complications rates were stratified on the basis of the time of occurrence (Table 6), there was an increasing trend in complications in the CB group and a decreasing trend in complications in the MB group as identified against time. When the first 15 cases in the MB groups (the learning curve phase) were considered and excluded from further analysis and the first 15 cases in the CB group were excluded to equalize the number of cases in the 2 arms, the MB group showed a significantly lower incidence of biliary complications (8.3% versus 21.1%). Further analysis of this cohort study showed that CB increased the risk of biliary complications by 2.5 times (relative risk: 2.5; attributable risk: 128; odds ratio: 2.9; Table 7).

Table 6. Stratification of Biliary Complications According to the Time of Occurrence (n = 85)
Period of OccurrenceConventional GroupMicrosurgical Group
First 15 cases1 (6.7%)7 (46.7%)
Next 15 cases3 (20.0%)3 (20.0%)
Last 55 cases12 (21.8%)3 (5.4%)
Table 7. Risk of Developing Complications Based on the Method of Biliary Reconstruction
 With ComplicationsWithout ComplicationsTotal
  1. NOTE: The 15 learning curve cases were excluded. The relative risk (risk ratio) was 2.5; the conventional reconstruction increased the risk of complications by 2.5 times. The attributable risk (risk difference) was 128 (the absolute increase in risk). Compare this to the odds ratio of 2.9.

Conventional Group15 (21.1%)56 (78.8%)71 (1 dual)
Microsurgical Group6 (8.3%)66 (91.7%)72 (2 dual)

DISCUSSION

The causes of biliary complication are multifactorial.21 In general, the causes of biliary complications can be grouped into 3 main categories: recipient factors, graft factors, and techniques of reconstruction. The recipient factors include technical considerations, vascular problems, re-explorations, and previous biliary disease. The graft factors include the surgical technique, use of either the right or left lobe, number of ducts, duct size, donor age, ischemia time, and preservation technique. The techniques of reconstruction include duct-to-duct and duct-to-jejunum techniques, the use of stents, suturing techniques and materials, and ductoplasty techniques.

Heffron et al.22 reported a higher incidence of biliary complications in their initial experience with LDLT in comparison with deceased donor and split LT. In LDLT and particularly in right lobe LDLT, we sometimes deal with small and multiple duct openings that are thin and thus make the biliary reconstruction more difficult than deceased donor LT, for which there is a single, large anastomosis between 2 better vascularized bile ducts of the donor and recipient.23 As such, biliary reconstruction in LDLT requires refinement and precision in technique.

Aside from physical characteristics, there are other risk factors for biliary complications, which include prolonged cold and warm ischemic times, arterial thrombosis, chronic rejection, ABO incompatibility, and cytomegalovirus infection.24 With LDLT, the cold ischemic time is kept to a minimum, human leukocyte antigen is usually haplo-identical, and ABO-compatible grafts are used most of the time except for an emergency. The use of a stent or T-tube in LDLT is still not resolved, unlike in deceased donor LT. Marcos and coworkers25, 26 found that there is a decrease in biliary complications when transanastomotic stenting is used. However, Gondolesi et al.27 found no difference in the rates of complications in patients with or without a stent. Liu et al.14 found that it was safe to perform duct-to-duct anastomosis in right lobe LDLT without a stent. On the basis of our earlier experience, we found that there was an increase in complications when a stent or T-tube was used in duct-to-duct anastomosis. Hence, we abandoned the routine use of a stent or T-tube in October 2001. In this study, all biliary reconstructions were performed without a stent or T-tube.

Earlier in our series (the CB group), the cold ischemia time was longer because we do not routinely incorporate the middle hepatic vein into the graft,18 so more time at the back-table is needed to reconstruct the middle hepatic vein tributaries, including any significantly sized (>5 mm) right inferior hepatic veins. With skill and experience (the MB group) at the back-table, our cold ischemia time has shortened. The relatively longer operative time in the MB group can be attributed to the longer time to reconstruct the bile duct during the initial application of this technique. Again, with experience, the time to reconstruct the bile ducts has shortened. Despite the longer operative time in the MB group, we did not encounter problems related to recipient hypothermia, coagulopathy, delayed extubation, or respiratory or infection complications in this group.

The feasibility of using microsurgical reconstruction in biliary ducts was established in an experimental study involving animals.28 This animal study found that microsurgery offers an interesting perspective for reconstructive and transplantation surgery. Microsurgical techniques in biliary reconstruction have been applied in clinical LT in cases of neonatal and infant recipients for whom monosegment grafts have been used. Its first introduction to LDLT for both adult and pediatric recipients was reported by Yan et al.,29 who found its use to be beneficial, especially in the setting of hepaticojejunostomy for a small HD (≤2 mm). However, the outcome of the routine use of microsurgical techniques in LDLT has not been elucidated.

Our complete hilar plate encircling technique has been the same in all donors since we started our LDLT program in 1994; if we assume that the 2 groups were identical or nearly identical in terms of their demographic profiles and pretransplant clinical characteristics and that the techniques have been standardized over time with experience, the application of routine MB has been proved to be beneficial in decreasing biliary complications. Although the overall rates of complications in the 2 groups were not significantly different, the stratified results (Table 5) and the effect of the learning curve (Tables 6 and 7) clearly demonstrate that MB has the advantage. It is clear that there was a reduction in the complication rate among the single duct reconstructions. However, as far as ducts reconstructed with Roux-en-Y are concerned, there was no difference in the 2 groups. The gray area lies in multiple ducts. The CB and MB groups seemed to have the same complication rate as far as the reconstruction of multiple ducts is concerned. However, there were only 20 multiple duct cases in the MB group, and 6 had complications. Four of the 6 cases occurred during the learning curve phase. Because the CB complications occurred at random, MB has an advantage over CB for the reconstruction of multiple ducts because with experience fewer complications occurred in the multiple duct group that underwent MB.

The heterogeneity of the patients may have contributed to the overall statistical power observed in risk occurrence because highly heterogeneous groups would more likely yield unbiased data. Assuming that experience leads to refinement and perfection, we did not see this in the CB group as more complications were seen over a period of time in the latter cases (Table 6). However, in the MB group, we surmise that the first 15 cases constituted the learning curve phase as complications greatly decreased afterwards. With increasing variability in donor biliary anatomy, there was even an increase in the risk of developing complications when CB was used.

From our first LDLT operation in June 17, 1994 until the end of this study period, we performed 339 primary LDLT procedures (including 5 dual graft transplants). When we take the very first 88 cases in our series and compare them with the 85 cases (88 grafts) performed with the microsurgical technique to elaborate on the experience and learning curve, we find that the compositions of the groups to be compared are not balanced, and there is a significant difference. In the beginning of our series, there were more pediatric patients than adult patients, and more left lobe grafts (64; including left lateral segments) were used than right lobe grafts (24). In the MB group, the opposite occurred: there was more right lobe grafts (63) than left lobe grafts (25). Further analyses of the very first 88 cases showed that the first 15 cases were all pediatric patients who received left lobes; and in the next 15 cases, there was only 1 adult right lobe case. The biliary complication rates in the first 15 cases and in the next 15 cases were 20% (3/15), and 6.7% (1/15), respectively. Overall, the biliary complication rate in this group, including 7 right lobe and 4 left lobe biliary complications, was 12.5% (11/88); the adult right lobes were used during the later part of the series. Hence, we included only the last 88 historical cases before the start of MB because these consecutive cases (the CB group) represented numbers of left-side and right-side grafts and of pediatric and adult patients almost comparable to those of the MB group. Therefore, the CB group approximated the characteristics of the MB group. Although we did not expect this, even the deaths in the 2 groups turned out to approximate one another.

What factors may have played to the advantage of MB over CB? The identified factors are as follows:

  • 1We can avoid injury or trauma to the bile duct epithelium by not grasping the inside of the structure.
  • 2Obstruction should be less because the field is well visualized under magnification.
  • 3Posterior wall first reconstruction followed by the continuous suture and interrupted tie technique is useful in small orifices.
  • 4All knots are placed extraluminally.
  • 5More precisely placed stitches can be added in case of a leak because of the magnified field.

MB is more difficult than microvascular reconstruction of the HA for the following reasons:

  • 1Because of troublesome bile and bleeding from the edges, clamps cannot be applied during the reconstruction, and suction may traumatize the tissues; hence, only copious saline irrigation is used to visualize the field or orifice.
  • 2The bile duct is fixed to the graft edge; therefore, there is less flexibility in manipulating the duct.
  • 3A leak may not be evident immediately after anastomosis, unlike in vascular reconstruction; one has to wait for some minutes to check for bile staining.

In contrast, microsurgical vascular reconstruction is easier to perform for the following reasons:

  • 1The orifices are nonbleeding once the vascular clamps have been applied.
  • 2The vessel is not fixed, so it can be lengthened by traction, pulling, or further dissection.
  • 3It is easier to check for leaks after anastomosis as they manifest immediately.

There were several problems encountered during the early introductory phase of MB. These problems may have contributed to the high complication rate during the learning phase. These problems were as follows:

  • 1Positioning: the use of the microscope was a limitation affecting dexterity and movement.
  • 2Visualization of the field: no clamps were used, and troublesome bleeding was encountered. To overcome the bleeding, direct sutures over the bleeder with 8-0 Prolene under magnification to avoid blind suturing (this had to be done before the reconstruction was started) and the use of copious irrigation to visualize the field were maneuvers considered to be useful.
  • 3Suture material: the first 2 cases used PDS 6-0 sutures. The PDS curled after use, and this made it technically difficult to use under magnification, especially during the tying or securing of the knots. From the third case onward, we used Prolene 6-0.

The bile ducts are tougher and thicker than visceral blood vessels, particularly in ducts that may have developed recurrent cholangitis. For tensile strength, we preferred to use 6-0 sutures. The reconstruction technique was interrupted, and all the knots were placed extraluminally to avoid anastomotic/orifice blockade. Although nonabsorbable, Prolene is made of an inert material; hence, there is likely less tissue reaction. Furthermore, the interrupted placement of sutures is less likely to contribute to stricture formation than a continuously placed suture, which may cause a purse-string effect.

Comparing the demographic data in the first 15 cases in the CB and MB groups, we found that there were more pediatric cases in the CB group (5 versus 2), and there were more left lobe grafts used in the CB group (5 versus 3). These characteristics may have favored a low complication rate in the first 15 cases in the CB group because in pediatric LDLT, in which left-side grafts are mostly used, the reported rates are approximately 4% to 6%, and these have significantly decreased since the initial learning experience, during which the biliary complication rates ranged from 15% to 20%.30–32 Furthermore, taking into consideration the learning curve in the MB group as another form of bias, we decided to exclude the first 15 cases in both groups in the final analysis. We persisted with the MB technique despite the seemingly high complication rate in the early cases because we were modifying the technique and looking for better ways to refine the technique when we analyzed the possible cause(s) of the complications. The last 55 cases in the MB group proved that our persistence with the new technique led to better results.

What factors may have caused the increased number of complications in the CB group? A significant factor may have been the number and size of the bile ducts. There were more multiple duct openings encountered in the latter cases in the CB group, but this was not statistically significant. Although the overall duct orifice size was bigger in CB than MB (3.4 versus 2.8 mm), there were also smaller duct orifice sizes encountered in the latter cases that were similar to the MB group. Thus, donor biliary anatomy variability may have played a factor in the occurrence of more complications in the latter cases in the CB group.

In conclusion, bile duct reconstruction in small graft duct openings and in multiple duct openings is technically demanding in LDLT. The routine use of MB is a technical innovation that may lead to a decreased number of early anastomotic biliary complications. Longer patient follow-up is needed to evaluate the outcome of this innovation in the long-term.

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