A case of pediatric live‐donor liver transplantation with a left lateral segment reduction by a linear stapler after reperfusion

In pediatric LDLT, graft reduction is sometimes required because of the graft size mismatch. Dividing the portal triad and hepatic veins with a linear stapler is a rapid and safe method of reduction. We herein present a case with a left lateral segment reduction achieved using a linear stapler after reperfusion in pediatric LDLT. The patient was a male who had previously undergone Kasai procedure for biliary atresia. We performed the LDLT with his father's lateral segment. According to the pre‐operative volumetry, the GV/SLV ratio was 102.5%. As the patient's PV was narrow, sclerotic and thick, we decided to put an interposition with the IMV graft of the donor between the confluence and the graft PV. The graft PV was anastomosed to the IMV graft. The warm ischemic time was 34 min, and the cold ischemic time was 82 min. The ratio of the graft size to the recipient weight (G/R ratio) was 4.2%. After reperfusion, we found that the graft had poor perfusion and decided to reduce the graft size. We noted good perfusion in the residual area after the lateral edge was clamped with an intestinal clamp. The liver tissue was sufficiently fractured with an intestinal clamp and then was divided with a linear stapler. The final G/R ratio was 3.6%. The total length of the operation was 12 h and 20 min. The amount of blood lost was 430 mL. No surgical complications, including post‐operative hemorrhage and bile leakage, were encountered. We believe that using the linear stapler decreased the duration of the operation and was an acceptable technique for reducing the graft after reperfusion.     

Optimal line of hepatotomy for left lateral living donor liver transplantation according to the anatomical variations of left hepatic duct system

Multiple duct anastomoses during LLS transplantation increase the incidence of biliary complications. The optimal plane of hepatotomy that results in the least number of bile ducts at the surface was investigated according to LHD variations. Ducts of 30 human livers were injected with resin and LHD branching on 3D‐CT reconstructions were analyzed. Ducts on the virtual hepatotomy surface were estimated in three splitting lines. Variations with subtypes were described. Ia (66.7%): ducts from segments (S.) II–III form a common trunk and S.IV duct joins it. Ib (10%): common trunk formed by ducts from S.II–S.III while S.IV duct joins the common hepatic duct. IIa (16.67%): S.IV duct drains into S.III duct. IIc (3.33%): S.IV duct drains into both S.II and S.III ducts. III (3.33%): trifurcation of S.II, S.III and S.IV ducts. When the virtual hepatotomy line was on the FL, there was a single duct for the anastomosis in 30% of cases but two, three, or four ducts in 53.3%, 10%, and 3.3%, respectively. Division 1 cm to the right of the FL resulted in one duct (70%), but S.IV duct injury may occur. LLS hepatotomy should not necessarily be performed along the FL. Variations must be taken into consideration to minimize the number of biliary anastomoses during liver implantation.     

Biliary reconstruction before clamp removal to avoid portal vein thrombosis in pediatric living‐donor liver transplantation using hyper‐reduced left lateral segment grafts: A novel technical strategy

LT has become the treatment of choice for children with end‐stage liver disease. The scarcity of donors and the considerable mortality on waiting lists have propelled the related living‐donor techniques, especially in small children. This population need smaller and good quality grafts and are usually candidates to receive a LLS from a related donor. Many times this grafts are still large and do not fit in the receptor's abdomen, so a further hyper‐reduction may be required. Despite all advances in LT field, vascular complications still occur in a considerable proportion remaining as a significant cause of morbidity, graft loss, and mortality. Technical issues currently play an essential role in its genesis. The widely spread technique for biliary and vascular reconstruction in living donor LT (LDLT) nowadays implies removal of the portal vein (PV) clamp after the venous anastomosis, then the arterial reconstruction is done, followed by the biliary reconstruction. However, due to the posterior location of the LLS bile duct, for its reconstruction, a rotation of the liver is required risking a potential transient PV occlusion leading to thrombosis afterward. We describe a new technique that involves performing biliary reconstruction after the PV anastomosis and before removing the vascular clamp, thus allowing to freely rotate the liver with less risk of PV occlusion and thrombosis.     

Liver graft volumetric changes after living donor liver transplantation with segment 2 graft for small infants

Urahashi T, Mizuta K, Sanada Y, Wakiya T, Yasuda Y, Kawarasaki H. Liver graft volumetric changes after living donor liver transplantation with segment 2 graft for small infants. Abstract: LT for small infants weighing <5 kg with liver failure might require innovative techniques for size reduction and transplantation of small grafts to avoid large‐for‐size graft, but little is known about post‐transplant graft volumetric changes. Five of 172 children who underwent LDLT received monosegment or reduced monosegment grafts using a modified Couinaud’s segment II (S2) graft for LDLT. Serial CT was used to evaluate the changes in the GV and other factors before LDLT and one and three months after LDLT. The shape of these grafts was classified into an OL type and an LL type. The GV increased in all patients one month after LDLT, whereas the GV decreased three months after LDLT in OL in comparison with one month after LDLT. The GRWR of the OL type has tended to decrease at three months, whereas the LL type showed a continuous increase with time, but finally they had adapted graft size for their body size. In conclusion, the volume of S2 grafts after LDLT had unique changes toward the ideal volume for the child weight when they received the appropriate liver volume.     

Modified triangular hepatic vein reconstruction for preventing hepatic venous outflow obstruction in pediatric living donor liver transplantation using left lateral segment grafts

HVOO can be a critical complication in pediatric LDLT. The aim of this study was to evaluate a modified triangular technique of hepatic vein reconstruction for preventing HVOO in pediatric LDLT. A total of 298 pediatric LDLTs were performed using a left lateral segment graft by 2 methods for reconstruction of the hepatic vein. In 177 recipients, slit‐shaped anastomosis was indicated with partial clamp of the IVC. A total of 121 recipients subjected to the modified triangular anastomosis with total clamp of the IVC. We compared the incidence of hepatic vein anastomotic complications between these 2 methods. Nine of the 177 cases (5.3%) treated with the conventional technique were diagnosed with outflow obstruction. All 9 cases underwent hepatic vein reconstruction with the slit‐shaped hepatic vein anastomosis. In contrast, there were no cases of outflow obstruction in the 121 cases treated with the modified triangular anastomosis. The modified triangular technique of hepatic vein reconstruction with total clamping of the IVC was useful for preventing HVOO in pediatric LDLT.     

Fibroadenoma in adolescent females after living donor liver transplantation

Breast FA is the most common breast tumor diagnosed in young women. Female renal transplant recipients on CsA have an increased risk of developing FA. However, reports of FA after LDLT have not been described. Our objectives were to determine the incidence of FA, analyze risk factors for FA, and evaluate treatment strategies in adolescent females after LDLT. A total of 18 female patients aged 10‐19 years who underwent LDLT and survived at least one year after transplantation were enrolled in our study. The incidence of FA was 11.1%. To determine pre‐ or post‐transplant conditions that are associated with FA after transplantation, the patients were divided into two groups according to the presence or absence of FA: FA group (n=2) and non‐FA group (n=16). There were no differences in mean age at LDLT, mean age at breast evaluation, and mean duration between transplantation and breast evaluation between the two groups. However, there was a difference in the immunosuppressive regimen between the two groups. The FA group was maintained on CsA, whereas the non‐FA group was maintained on tacrolimus. CsA might be implicated in FA development in adolescent females after LDLT.     

Heterozygote to homozygote related living donor liver transplantation in maple syrup urine disease: A case report

Liver transplantation is an accepted treatment modality in the management of MSUD. To our knowledge, ours is only the second successful case to date of a patient with MSUD receiving an allograft from an RLD who is a heterozygous carrier for the disease. In view of the worldwide shortage of available organs for transplantation, heterozygote to homozygote transplantation in the setting of MSUD may provide a viable alternative for those awaiting transplantation. We report on the case of a two‐yr‐old infant with MSUD, who received a left lateral segment (segments II and III) liver transplant from his mother, a heterozygote carrier of one of the three abnormal genes implicated in MSUD. Post‐operative BCAA levels normalized in our patient and remained so on an unrestricted protein diet and during times of physiological stress. To date, this is only the second case of a successful RLD liver transplant in a child with MSUD. Preliminary results indicate that RLD liver transplants are at least equivalent to deceased donor liver transplants in the treatment of MSUD, although longer term follow‐up is required. Heterozygote to homozygote RLD transplant in patients with MSUD presents a new pool of potential liver donors.     

Evaluation of the immune function assay in pediatric living donor liver transplantation

The immune function (ImmuKnow) assay is a measure of cell‐mediated immunity based on the peripheral CD4+ T cell ATP activity. The efficacy of ImmuKnow in pediatric LDLT is not well documented. The aim of this study was to assess the correlations between the ImmuKnow and the clinical status in pediatric LDLT recipients. A total of 716 blood samples were obtained from 60 pediatric LDLT recipients (one month to 16 yr of age). The recipient's status was classified as follows: stable, infection, or rejection. The ImmuKnow values in the pediatric LDLT recipients with a clinically stable status had a lower immune response (IQR 85–297 ATP ng/mL) than that previously reported in adults. Meanwhile, the ImmuKnow values of the stable patients were not correlated with age. Furthermore, a significant difference was found in the ImmuKnow values between the bacterial or fungal infection and stable groups, but not between the CMV or EBV infection and stable groups. The ImmuKnow levels in the pediatric LDLT were lower than those observed in the adult LDLT. The proposed reference value is between 85 and 297 ATP ng/mL in pediatric LDLT recipients. We conclude that the ImmuKnow assay could be helpful for monitoring pediatric LDLT recipients with bacterial or fungal infections.     

Cytokine concentrations and regulatory T cells in living donor and deceased donor liver transplant recipients

Outcomes of pediatric liver transplantation have constantly improved in the last decade. Living‐related liver transplantation does not seem to improve long‐term outcomes following liver transplantation, but few studies have evaluated immunological parameters of the alloimmune response after living vs. deceased donor organ transplantation. We analyzed numbers of regulatory T cells, lymphocyte subsets, and serum cytokine concentrations in 12 pediatric recipients of living‐related liver transplants and in 28 pediatric recipients of deceased donor organs during their annual follow‐ups. Transplant recipients who underwent living donor organ transplantation had significantly higher numbers of regulatory T cells and IL‐4 serum concentrations than recipients of deceased donor organs; both of these factors are associated with beneficial outcomes and transplantation tolerance. Living‐related liver transplantation may have potentially beneficial immunological aspects, although long‐term outcomes do not seem to be better in recipients of living donor organs than in recipients of deceased donor organs. Further studies are needed to compare immunological aspects of the two transplant procedures.     

Improvement in the prognosis and development of patients with methylmalonic acidemia after living donor liver transplant

Liver transplant is a treatment option for patients with MMA‐emia. While this therapy does not bring about a complete cure, it is expected to prolong survival and improve the QOL of patients. The aim of this study was to evaluate the significance of LDLT for patients with MMA‐emia in Japan. Clinical information on 13 patients with MMA‐emia who underwent LDLT was acquired using a self‐developed questionnaire sent to the doctors who provided medical care to patients with MMA‐emia after LDLT. Almost all of the patients continued on a protein‐restricted diet, and the number of acidosis attacks had significantly decreased. Physical growth had recovered to within the normal range by 2.5 years after LDLT, especially in patients who underwent LDLT before the age of 1 year. The average propionyl carnitine (C3) level had significantly decreased after LDLT, and the DQs had not worsened. Liver transplant should be performed for MMA‐emia in early life. This can be expected to maintain neurological development and improve the growth and QOL of patients. However, LDLT is not a curative treatment for MMA‐emia. A protein‐restricted diet should be continued, and renal function should be monitored closely, with consideration of a renal transplant.     

Diaphragmatic hernia in infants following living donor liver transplantation: report of three cases and a review of the literature

DH is a rare complication following LT. This report presents three cases of right-sided DH after LT using a left-sided graft. All of the patients were younger than one yr of age, and they were critically ill owing to their original disease, characterized by biliary atresia, progressive familiar intrahepatic cholestasis, and acute liver failure. DH occurred with sudden onset within three months after LT. All of the cases were promptly diagnosed and treated. A literature review of 24 cases of DH identified four factors associated with DH: left-sided graft, right-sided DH, relatively delayed onset of DH, and age-specific chief complaint. DH following LT should be considered as a potential surgical complication when a left-sided graft is used, especially in small infants with coagulopathy and malnutrition.     

Waiting list mortality for pediatric deceased donor liver transplantation in a Japanese living‐donor–dominant program

Living donor liver transplantation (LDLT) has become a major life‐saving procedure for children with end‐stage liver disease in Japan, whereas deceased donor liver transplantation (DDLT) has achieved only limited success. The annual number of pediatric liver transplantations is approximately 100‐120, with a patient 20‐year survival rate of 81.0%. In 2005, the liver transplantation program at the National Center for Child Health and Development in Tokyo, Japan, was initiated, with an overall number of 560 pediatric patients with end‐stage liver disease to date. In July 2010, our center was qualified as a pediatric DDLT center; a total of 132 patients were listed for DDLT up until February 2019. The indications for DDLT included acute liver failure (n = 46, 34.8%), metabolic liver disease (n = 26, 19.7%), graft failure after LDLT (n = 17, 12.9%), biliary atresia (n = 16, 12.1%), and primary sclerosing cholangitis (n = 10, 7.6%). Overall, 25.8% of the patients on the waiting list received a DDLT and 52.3% were transplanted from a living donor. The 5‐year patient and graft survivals were 90.5% and 88.8%, respectively, with an overall waiting list mortality of 3.0%. LDLT provides a better survival compared with DDLT among the recipients on the DDLT waiting list. LDLT is nevertheless of great importance in Japan; however, it cannot save all pediatric recipients. As the mortality of children on the waiting list has not yet been reduced to zero, both LDLT and DDLT should be implemented in pediatric liver transplantation programs.     

Hepatic venous reconstruction in pediatric living-related donor liver transplantation--experience of a single center

In pediatric patients submitted to living related liver transplantation, hepatic venous reconstruction is critical because of the diameter of the hepatic veins and the potential risk of twisting of the graft over the line of the anastomosis. The aim of the present study is to present our experience in hepatic venous reconstruction performed in pediatric living related donor liver transplantation. Fifty-four consecutive transplants were performed and two methods were utilized for the reconstruction of the hepatic vein: direct anastomosis of the orifice of the donor left or left and middle hepatic veins and the common orifice of the recipient left and middle hepatic veins (group 1-26 cases), and wide triangular anastomosis after creating a wide triangular orifice in the recipient inferior vena cava at the confluence of all the hepatic veins with an additional longitudinal incision in the inferior angle of the orifice (group 2-28 cases). In group 1, eight patients were excluded because of graft problems in the early postoperative period and five among the remaining 18 patients (27.7%) presented stricture at the site of the hepatic vein anastomosis. All these patients had to be submitted to two or three sessions of balloon dilatations of the anastomoses and in four of them a metal stent had to be placed. The liver histopathological changes were completely reversed by the placement of the stent. Among the 28 patients of the group 2, none of them presented hepatic vein stenosis (p = 0.01). The results of the present series lead to the conclusion that hepatic venous reconstruction in pediatric living donor liver transplantation must be preferentially performed by using a wide triangulation on the recipient inferior vena cava, including the orifices of the three hepatic veins. In cases of stenosis, the endovascular dilatation is the treatment of choice followed by stent placement in cases of recurrence.     

Early graft failure due to a veno-occlusive disease after a pediatric living donor liver transplantation

A 10-month-old boy with biliary atresia after Kasai procedure underwent a living donor liver transplantation (LDLT). Five days after the LDLT, high fever and increased ascites followed by poor bile drainage was accompanied by elevation of serum liver enzymes. Liver biopsy showed occlusion of the central veins by fibro-edematous endothelium and submassive necrosis of the parenchyma. Veno-occlusive disease (VOD) was suspected, and re-LDLT was urgently performed because of deterioration of hepatic failure. There are few cases of VOD after liver transplantation and this is the first one in an infant after LDLT.     

移植物体重比对左外叶小儿活体肝移植术后短期肝功能的影响

目的 探讨移植物体重比(Graft recipient body weight ratio,GRBW)对小儿活体左外叶肝移植术后短期肝功能恢复的影响.方法 2006年6月至2009年3月共施行活体肝移植25例,其中17例左外叶活体肝移植患儿作为研究对象.分别于术后1～7 d测量患儿肝脏功能,采用SPSS15.0统计软件分析了解GRBW与术后短期肝功能恢复的相关性.结果 ①肝移植术后肝功能恢复良好(P<0.000 1);②GRBW与术后谷丙转氨酶(ALT)变化呈正相关(P<0.05)、与AST变化呈负相关(P<0.05).结论 左外叶小儿活体肝移植GRBW对于术后肝功能恢复意义重大,移植术中应充分保证足够的GRBW比值.     

Hepatobiliary scintigraphy for the assessment of biliary stricture after pediatric living donor liver transplantation for hepaticojejunostomy reconstruction: the value of the excretion rate at 60 min

HBS is performed to determine the presence of biliary stricture after liver transplantation. We focused on the Ex-60 after an intravenous injection of tracer during HBS. The aim of this study was to review the cutoff values for the diagnosis of biliary stricture by HBS after pediatric LDLT. We analyzed 114 HBS studies using (99m) Tc-PMT in 80 cases after pediatric LDLT. HBS was performed three months after LDLT on a routine basis and/or was performed when ultrasonography and blood test findings indicated biliary stricture. A ROC curve analysis was performed to identify the cutoff value for the correlation between Ex-60 and biliary stricture. The Ex-60 (mean ± s.d.) in the cases diagnosed as having biliary stricture and in normal subjects were 49.1 ± 20.2% vs. 78.0 ± 9.7% (p < 0.01), respectively. As a result of an ROC curve analysis of the Ex-60, the recommended cutoff value to diagnose biliary stricture was set at 69.2% (sensitivity 87.0%, specificity 81.8%). In cases where the Ex-60 by (99m) Tc-PMT HBS is <69.2%, it is recommended that further treatment for biliary stricture should be provided.     

Technique advance to avoid hepatic venous outflow obstruction in pediatric living‐donor liver transplantation

HVOO represents a serious critical complication of pediatric living‐donor liver transplantation because open surgical repair is virtually impossible. Currently, despite several technical innovations and the introduction of triangulated anastomosis for hepatic vein reconstruction, the reported incidence of HVOO is still considerable. The aim of this study was to propose a new technique for hepatic venous reconstruction that avoids the original orifice of the recipient hepatic veins. Instead, anastomosis is performed in a newly created wide longitudinal orifice in the anterior wall of the recipient inferior vena cava. A total of 210 living related‐donor liver transplantations were performed using two methods for reconstruction of the hepatic vein. Group 1 included 69 patients subjected to direct anastomosis of the orifice of the graft hepatic vein and a wide orifice created in the recipient inferior vena cava by the confluence of the orifices of the right, left, and middle hepatic veins. Group 2 included 141 patients in whom the original orifices of the recipient hepatic veins were closed, the inferior vena cava was widely opened, and a long longitudinal anastomosis was performed using two lines of continuous sutures. Diagnosis of HVOO was suspected based on clinical findings and ultrasound studies and then confirmed by liver biopsy and interventional radiology examinations. Among the 69 recipients in group 1, 16 patients died due to graft problems during the postoperative period and eight of the survivors (15.1%) presented with HVOO. In group 2 (141 patients), 21 patients died, and there were no cases of HVOO. A comparison of the incidence of HVOO between groups revealed a significant difference (p = 0.01). Hepatic venous reconstruction during pediatric living‐donor liver transplantation should be performed using a wide longitudinal incision in the anterior wall of the recipient inferior vena cava because this technique eliminated anastomosis complications.     

Duct-to-duct biliary reconstruction in pediatric living donor liver transplantation

The results of duct-to-duct biliary reconstruction in six pediatric patients who received a living donor liver transplant aged from 2 months to 11 yr old are reported. The graft was either entire or a part of the left lateral segments. The orifice of the bile duct of the graft was anastomosed to the recipients' hepatic duct in an end-to-end fashion by interrupted suture using 6-0 absorbable material. A transanastomotic external stent tube (4 Fr) was passed through the stump of the recipients' cystic duct. Mean time for reconstruction was 24 min. All the recipients survived the operation and reinitiated oral intake on postoperative day 3. There were no early biliary complications. One 5-yr-old boy suffered from an anastomotic stenosis 9 months after transplantation. He underwent re-anastomosis by Roux-en Y (R-Y) procedure and recovered uneventfully. Duct-to-duct anastomosis in pediatric living donor liver transplantation has benefits while the complication rate is comparable to R-Y reconstruction.     

Interventional radiology for hepatic artery complications soon after living donor liver transplantation in a neonate

Early hepatic artery complications after liver transplantation in children, having undergone LDLT, can directly affect graft and recipient outcomes, making early diagnosis and treatment essential. In the past, laparotomy (thrombectomy or reanastomosis) was generally employed to treat early hepatic artery complications. Recently, favorable outcomes of IR have been reported. In children, however, the number of such reports is small. To the best of our knowledge, there is no published report on IR applied to neonates with early hepatic artery complications. We recently succeeded in safely using IR for a neonate with early hepatic artery complications after LDLT and obtained a favorable outcome. This case is presented herein.