In biliary atresia (BA), efforts to prevent premature liver transplantation (LT) are aimed at early diagnosis, timing of Kasai-portoenterostomy (KPE), and centralization of care. This report presents the clinical picture, treatment strategies, and outcomes of BA patients with no previous treatment. A retrospective cohort study (Jan/2001 to Jan/2021) was conducted to evaluate the outcome of patients with BA referred to a single team. Study groups were: 1) Kasai-only group (K-only) n=9), 2) LT-only group (n=7), and 3) Kasai+LT group (K+LT) (n=23). Survival with native liver and overall survival were 22.9 and 94.8%, respectively, at 120 months of follow-up. There was no difference in age at KPE in the K-only group (46.8±21.8 days) vs K+LT (52.1±22 days), P=0.4. Ten (25.6%) patients were babies conceived through in vitro fertilization (IVF). Four IVF patients (40%) presented associated congenital heart disease vs 5 patients (17%) in the remaining group (P=0.14). Two of the IVF patients were premature (<37 weeks). Median maternal age at birth was 35 years (33 to 41 years). Excellent patient survival is expected for patients with BA with the available treatment strategies. IVF+BA was an unexpected prevalent association in this cohort, and further studies are required to better understand these findings.

Maple syrup urine disease (MSUD) is an autosomal recessive disease associated with high levels of branched-chain amino acids. Children with MSUD can present severe neurological damage, but liver transplantation (LT) allows the patient to resume a normal diet and avoid further neurological damage. The use of living related donors has been controversial because parents are obligatory heterozygotes. We report a case of a 2-year-old child with MSUD who underwent a living donor LT. The donor was the patient's mother, and his liver was then used as a domino graft. The postoperative course was uneventful in all three subjects. DNA analysis performed after the transplantation (sequencing of the coding regions of BCKDHA, BCKDHB, and DBT genes) showed that the MSUD patient was heterozygous for a pathogenic mutation in the BCKDHB gene. This mutation was not found in his mother, who is an obligatory carrier for MSUD according to the family history and, as expected, presented both normal clinical phenotype and levels of branched-chain amino acids. In conclusion, our data suggest that the use of a related donor in LT for MSUD was effective, and the liver of the MSUD patient was successfully used in domino transplantation. Routine donor genotyping may not be feasible, because the test is not widely available, and, most importantly, the disease is associated with both the presence of allelic and locus heterogeneity. Further studies with this population of patients are required to expand the use of related donors in MSUD.

Split liver transplantation is considered the most effective method for increasing the human liver graft pool. Two techniques are currently in use for splitting liver grafts. In the classic "ex situ" technique the division of the hilar structures as well as of the liver parenchyma is performed on the back table, after harvesting. Since the first case reported by Pichlmayr et al. (1) in 1988, this method has been performed in several centers (2-4). Although increasing experience has been achieved during these years, the results obtained with the ex situ technique are inferior when compared with other procedures such as whole, reduced, and living donor graft transplantation (5). Two major problems can be identified in the ex situ technique: the difficulty to properly recognize the hilar structures during bench dissection, particularly the arterial and biliary elements, which may lead to bile duct devascularization and biliary complications in the recipient, and the extended cold ischemia time expended during the back table work, which includes the usual whole graft preparation, dissection and division of hilar structures after a cholangiogram, and the complete separation of liver parenchyma. Recently, Rogiers et al. (6) described the "in situ" technique in which hilar and parenchymal division are completed before graft perfusion, without vascular supply interruption, as in the living donor operation. This method provided excellent results with significant lower graft dysfunction and biliary complication rates (7, 8). The clear advantages of the in situ technique are: appropriate observation of hilar anatomy, allowing preservation of the bile duct and/or hepatic duct irrigation, reduction of cold ischemia time, and less bleeding from the cut surfaces of both grafts. Nevertheless, the major problem for the routine utilization of the in situ procedure is the significant extension of operation time, which can be harmful to the multiorgan donor, leading to a low rate of acceptance by other organ transplant teams. We devised a combined technique for splitting liver grafts that is carried out with minimal in situ dissection, followed by multiorgan perfusion and completion of hilar and parenchymal separation on the back table. The aim of this approach is to properly recognize the anatomic structures with minimal increase of donor operation time and an easier back table division of the graft, associating the advantages of both methods currently used. After standard preparation for multiorgan perfusion, the hepatic hilum is approached. The left hepatic artery and the left branch of the portal vein are carefully identified. However, these vessels are not completely dissected at this moment. Next, a small portion of liver parenchyma is sectioned starting from the hepatic edge toward the hilum, down to the hepatic duct. A cholangiogram is performed through the cystic duct for biliary anatomy evaluation and choosing the best site for sectioning. The left hepatic duct is severed, and the stump is closed at the common hepatic duct level. Next, multiorgan perfusion and harvesting are carried out as usual. Back table preparation is performed in the same way as for whole grafts. Hilar dissection, previously initiated in situ, is now completed. The left hepatic artery is sectioned at the point determined during the in situ dissection, and the portal vein left branch is severed at the portal bifurcation level. These maneuvers are quite facilitated by previous in situ dissection. Parenchymal cleavage is continued toward the left hepatic vein, which is identified and sectioned, completing the graft division. Hemostatic sutures are placed on the cut surfaces of both grafts followed by fibrin glue spray. Two stable donors, weighing 75 and 65 kg each, were operated on by the above-described technique on November 96 and April 97, respectively, resulting in four grafts implanted in two adults weighing 64 and 75 kg and two children weighing 16.5 and 7.9 kg. Because in one donor no anatomic variation was observed, biliary and vascular divisions were performed at the common duct, hepatic artery, and portal vein respective bifurcations. In the other case, the right hepatic artery originated from the superior mesenteric artery, and sections were performed only at the biliary and portal vein bifurcation levels. Donor operation extra time required for partial in situ dissection was of 65 and 45 min for each case. Segments II+III were transplanted in both children after "piggy-back" hepatectomy. Implantation was carried out starting by an end-to-side anastomosis between the left hepatic vein and inferior vena cava, followed by portal vein anastomosis without interposition grafts. Due to the left hepatic artery small diameter, in one case the arterial anastomosis was performed by microsurgical technique. Roux en Y hepatojejunal anastomosis was performed on both children. Segments I+IV-VIII were transplanted in the adult recipients by standard orthotopic technique, followed by duct to duct biliary anastomosis. Cold ischemia times were 270 and 240 min for left grafts and 540 and 510 min for right grafts. All allografts had good postoperative function with aspartate aminotransferase and alanine aminotransferase postoperative peak levels ranging from 252 to 1474 IU and 200 to 1303 IU, respectively. One child died on the seventh postoperative day, due to cerebral edema and ischemia, but with no graft dysfunction. The other three patients had uneventful outcomes and are now 19 months (two patients) and 24 months (one patient) after transplantation, with good graft function. Organ scarcity is the main obstacle to fulfill the worldwide increasing liver transplantation demand. Because other graft sources, such as xenotransplantation, are not yet available, surgeons have to innovate to face the increasing mortality and morbidity on the liver transplant waiting lists. Although split liver transplantation is considered the most rational policy for expanding the human liver donor pool, technical and logistic difficulties, observed in the early experience with the classic ex situ technique, have discouraged its wide utilization. Despite improvement in patient and graft survival rates, reported in a recent series, a significant incidence of biliary complications, ranging from 16 to 25%, is still observed with the ex situ technique (4, 9, 10). This is due to the difficulty in identifying and correctly dividing the biliary tract and hepatic arterial branches during bench dissection, which may cause bile duct devascularization leading to anastomotic leakage and/or stenosis in the recipient. Another unfavorable feature of the ex situ method is the longer cold ischemia time and frequent warming up of the graft imposed by extensive back table work. This can be responsible for the higher graft dysfunction rate observed with this technique, mainly on right grafts (7, 8). Recently, Rogiers et al. (6) introduced the in situ technique. This procedure is carried out as in the living liver donor, allowing proper anatomic observation and division of the hilar structures. Complete dissection of the left hepatic artery and of the left portal vein is performed in situ, keeping the right hilar elements untouched. The left hepatic duct is sectioned during the parenchymal division without entering the periductal tissue, to preserve its irrigation. After completing the parenchymal separation and left hepatic vein isolation and section, the left graft is removed and flushed on the back table, ready for implantation. During the in situ procedure the right liver blood supply is maintained uninterrupted until multiorgan harvesting is performed. Therefore, cold ischemia time is considerably decreased for both grafts. The experience with the in situ splitting, recently reported by Rogiers et al. (7) and Goss et al. (8), demonstrated better results with 6-month patient and graft survival rates of 92% and 86%, respectively. On both series primary nonfunction was reduced and no vascular nor biliary complications were observed. Despite these results, the in situ technique has some limitations that preclude its wider use. It has to be performed preferably by surgeons experienced with living donor operation. Even when carried out by trained teams, removal of the left graft requires from 1 to 4.5 additional hours to the regular harvesting procedure (7, 8). This may cause donor instability and refusal by other organ transplant teams. The objective of the combined procedure proposed herein is to keep the anatomic precision of the in situ method without a significant increase in donor operation time. For this purpose, the left hepatic artery and the left branch of the portal vein are not fully dissected and just the small portion of liver tissue necessary to identify and section the left bile duct is divided in situ. After preliminary in situ dissection, division of the graft on the back table is quite facilitated and cold ischemia time is decreased. Although good graft function and acceptable donor operation and cold ischemia times were accomplished in these two cases, no definitive conclusion can be drawn from this preliminary experience. A large series will be necessary to confirm the theoretical advantages of the proposed technical modifications. Eduardo Carone1 Paulo Chapchap Vincenzo Pugliese Gilda Porta Irene Miura Edison R. Parise Mário Kondo Department of Surgery; Division of Liver Transplantation; Hospital Sírio Libanês; São Paulo, Brasil