Ji-Cho Tng , Wng-Jie Suolng , Chong Yng , Yi Wng , Ming-Wu Tin , b , Yu Zhng , *

a Organ Transplantation Center, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu 610072, China

b School of Clinical Medical Sciences, Southwest Medical University, Luzhou 6460 0 0, China

c NHC Key Laboratory of Echinococcosis Prevention and Control, Lhasa 850 0 0 0, China

Hepatic alveolar echinococcosis (HAE) is a lethal infectious dis- ease caused by the larval stage ofEchinococcusmultilocularis. To date, radical resection combined with albendazole is considered the major treatment for patients with HAE. However, many pa- tients miss the best time for diagnosis and resection due to pa- tient delay, doctor delay, or long distances to specialized centers. Allogeneic liver transplantation is an important method for the treatment of end-stage HAE, but its application is limited due to the shortage of organ donors, long-term use of immunosuppressive agents and high recurrence rates [1] . Recently,exvivoliver resec- tion and autotransplantation has been used for end-stage HAE with invasion of multiple intrahepatic structures that could not be re- constructedinvivo[ 2 , 3 ]. However, the insufficient future liver rem- nant (FLR), which may cause posthepatectomy liver failure, makesexvivoliver resection and autotransplantation unfeasible for some patients. For patients suffering from end-stage HAE with insuf- ficient FLR and infiltration of the hepatocaval confluence or the retrohepatic vena cava, we developed a novel strategy that con- sists of monosegmental associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) and ante-situm liver re- section.

A 38-year-old woman was diagnosed with HAE. A computed to- mography (CT) scan revealed that the intrahepatic structures were invaded by multiple masses. The largest was 9.1 × 9.4 cm in diam- eter and had eroded three hepatic veins and wrapped around the inferior vena cava (IVC) ( Fig. 1 A and C) and a large inferior right hepatic vein (IRHV) that drained segment 6 directly into the IVC ( Fig. 1 B). Segment 6 received inflow from the right posterior por- tal pedicle. The FLR volume measured by three-dimensional (3D) imaging was 256.6 mL (FLR/total liver volume: 15.3%; FLR/standard liver volume: 27.5%; FLR/body weight: 0.49%), indicating that nor- mal metabolic needs could not be met after one-time resection with a high risk of posthepatectomy liver failure.

In stage 1, the Glissonian sheath entering the right hemiliver was identified through an extraglissonian ultrasound-guided ap- proach through the liver parenchyma and marked with a vessel loop. Using the same approach, the Glissonian pedicle from the right posterior segment was identified and encircled with a vessel loop. Then the right anterior pedicle was identified and clamped. Surface demarcation of the limits between the right anterior and posterior sector and of the limits beside the falciform ligament was marked with cautery, followed by partial transection of the liver parenchyma along the two lines. In the hilum of the liver, the left portal vein was dissected, identified, and ligated. Then, the right anterior portal vein was ligated ( Fig. 2 A). Six months af- ter stage 1, a CT scan revealed that the FLR (565.2 mL) had sig- nificantly increased, minimizing the risk of posthepatectomy liver failure (FLR/total liver volume: 30.2%; FLR/standard liver volume: 60.6%; FLR/body weight: 1.09%). There was no obvious progression of the mass during the interval ( Fig. 1 D and F). The right por- tal vein and the IRHV were kept intact ( Fig. 1 E). In stage 2, the infra- and suprahepatic vena cava were exposed as much as possi- ble. Surface demarcation of segment 6 was performed with cautery followed by transection along this line. Care was given to maintain the intactness of the IRHV and the Glissonian pedicle from seg- ment 6. Then, the Glissonian pedicle to the left liver, the right an- terior liver and segment 7 were transected. The infrahepatic vena cava was clamped, and the suprahepatic vena cava was clamped and transected, followed by ante-situm liver resection of the infil- tration at the posterior peritoneum. At this time, segment 6 was detached from the rest of the liver, and the reconstruction of the IVC with a polytetrafluoroethylene graft was performed ( Figs. 1 I and 2 B).

Fig. 1. A: Infiltration of the hepatocaval confluence shown on CT before stage 1; B: the right portal vein and the IRHV remain intact before stage 1; C: the coronal diagram of the liver shows invasion of multiple liver segments before stage 1; D: infiltration of the hepatocaval confluence without obvious progress of the mass before stage 2; E: the right portal vein and the IRHV were kept intact, and hypertrophy of the right posterior lobe before stage 2 can be seen; F: the coronal diagram of the liver shows invasion of multiple liver segments and hypertrophy of the FLR before stage 2; G: the inflow and outflow of the remnant liver remained unobstructed without recurrence after two years; H: the coronal diagram of the liver shows the unobstructed right portal vein and hypertrophy of the remnant liver after two years; I: the reconstruction of the IVC was completed. IRHV: inferior right hepatic vein; FLR: future liver remnant; IVC: inferior vena cava.

In stage 1 surgery, the total operative time was 300 min and the bleeding volume was 500 mL. The pathology confirmed the di- agnosis of alveolar hydatid disease. Moderate anemia occurred and 1.5 units of red blood cell suspension was infused after surgery. The right hydrothorax occurred and thoracic close drainage was performed. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were close to normal on postoperative day (POD) 8, and there were no bleeding, biliary fistula, infection or other major complications (grade II of Clavien–Dindo classifica- tion). The patient was discharged on POD 16.

In stage 2 surgery, the total operative time was 700 min, the bleeding volume was 3500 mL and the blood transfusion was 3910 mL. The total vascular occlusion (TVO) time was 30 min. The coagulant function abnormality occurred after surgery, and 7 units of cryoprecipitate and 300 mL of fresh frozen plasma were infused. AST and ALT were close to normal on POD 9 and there was no major complication (grade II of Clavien–Dindo classification). The patient was discharged on POD 10, and long-term treatment with anticoagulation therapy and albendazole was administered. Two years after surgery, the patient was in good condition with unob- structed blood vessels and no recurrence visible on the CT scan ( Fig. 1 G and H).

Fig. 2. Schematization of the surgical procedure. A: The left portal vein and the right anterior portal vein were ligated, and partial splitting of the liver was performed along the surface demarcation of the limits between right anterior and posterior sectors and the limits beside the falciform ligament (yellow lines); B: ante-situm liver resection followed by reconstruction of the inferior vena cava with polytetrafluoroethylene graft (2 cm).

In the present study, we introduce our experience concerning monosegmental ALPPS and ante-situm liver resection while avoid- ing cold perfusion and veno-venous bypass. To our knowledge, this is the first report on a surgery that combines these two complex techniques. Although end-stage HAE is characterized by tumor-like infiltrative growth and invasion of multiple intrahepatic structures, the FLR is often in good condition, and the mass slowly progresses, making it possible to treat with innovative and complex surgical procedures.

ALPPS has initiated hot debates on its safety and efficacy among experienced hepatobiliary surgeons. One major drawback of this procedure is the high incidence of complications and early mor- tality. Initial problems have drastically decreased in recent years due to adjustment of patient selection, technical modification, and interstage management. There was a significant decrease in the annual 90-day mortality starting from 17% in the early period to 3.8%. This development was parallelly accompanied by a steady re- duction of the annual overall and major interstage complication rates with 78% and 10% in the early period to 56% and 3%, respec- tively [4] . Patient selection is one of the key principles for improv- ing outcome in surgery [5] . Age has been reported as crucial factor for mortality in ALPPS [ 6 , 7 ]. Liver fibrosis/cirrhosis is closely re- lated to liver reserve function [8] and its severity is negatively cor- related with the rate of hypertrophy of the FLR [9] . Moreover, sev- eral technical modifications of the ALPPS operation have been de- veloped. All variants have in common less invasive stage 1 surgery aiming to avoid major interstage complications and to improve safety of the procedure. Despite the less invasiveness, rapid hyper- trophy is not considerably impaired in ALPPS variants compared with the classical procedure [10] . In the present study, partial split of the liver parenchyma to the surface of the mass was performed, further blocking the blood flow in the branch due to the large vol- ume of the mass, which is basically equivalent to complete split. This split strategy simplifies the operation and reduces the diffi- culty of surgery and the risk of postoperative complications. Fur- thermore, following stage 1 surgery, greatest attention needs to be directed to the interstage course. Interstage complications are mainly influenced by patient selection and ALPPS technique. In the present study, hepatorenal function, liver volume, Child-Pugh score, and indocyanine green test, were regularly measured, and a comprehensive assessment based on the general condition of the patient was performed to guide the safe progression of stage 2 surgery. No long-term surgery-related adverse events or recurrence occurred during the 2-year follow-up period.

The mass had invaded the entirety of the traditional outflow of the liver except for segment 6, which was drained by a large IRHV, a known form of anomalous anatomy with a reported prevalence of 6% -67% in a previous study [11] . The presence of an IRHV has implications for various surgical procedures, such as partial hepa- tectomy and living-donor liver transplantation. It provided the pos- sibility for hepatectomy with a single peripheral segment without traditional hepatic venous outflow in this study. In addition, during the monosegment ALPPS reported by Schadde et al. [12] , the left hepatic portal vein, the right anterior portal vein, and the segment 7 portal vein were all ligated in stage 1. Considering the “small- for-flow” syndrome caused by elevated portal vein pressure after ligation of most portal vein branches [13] as well as the preser- vation of the physiological function of segment 7, these steps may further reduce the risk of postoperative complications. Our team conservatively retained the right posterior hepatic portal vein, and only ligated the right anterior lobe portal vein and the left hepatic portal vein. Its safety and effectiveness need to be confirmed by further studies.

In the case of masses infiltrating the hepatocaval confluence or the retrohepatic vena cava, the ante-situm procedure is superior toexsituliver resection, providing the surgeon sufficient visualiza- tion of the hepatic vein confluence for reconstruction and allowing complete resection of the mass without transecting the common bile duct and hepatic artery. It has been shown that TVO is well tolerated for 60–90 min in patients with normal liver parenchyma, and a cirrhotic liver still can tolerate 30 min of warm ischemia without significant impairment [ 14 , 15 ]. Accordingly, the hepatic perfusion, as well as veno-venous bypass, can be avoided in con- ventional ante-situm liver resection, as long as the duration of TVO is controlled within a reasonable range and the liver is in good condition without cirrhosis. However, Matsuo et al. [16] reported that hepatocytes were immature during an ALPPS procedure, indi- cating the presence of a functional gap despite successful stimu- lation of regeneration. Therefore, for liver resection with only sin- gle liver segment, it is necessary to extend the interstage interval until the hypertrophic liver function reaches normal range [6] , so as to improve the tolerance to hypoxia and ischemia in stage 2 surgery. The average interstage interval for patients with end-stage HAE who underwent routine ALPPS surgery in our hospital is 3 months. In addition to the above reasons, it is also related to the patients themselves. Most patients with HAE live in nomadic ar- eas with poor traffic and are far away from medical institutions, which make it difficult for them to get medical treatment in time. Fortunately, the characteristics of HAE allow a relatively long wait. Therefore, our team decided against the use of hepatic perfusion and veno-venous bypass based on our long-term experience in the field of orthotopic liver transplantation at our institution. We also prepared for the use of cold perfusion to prevent prolonging the duration of warm ischemia due to unexpected difficulties.

In conclusion, monosegmental ALPPS combined with ante- situm liver resection represents a novel strategy for patients suf- fering end-stage HAE with insufficient FLR and infiltration of the hepatocaval confluence or the retrohepatic vena cava. This proce- dure should be performed at experienced hepatopancreatobiliary centers with careful patient selection, and allows the opportunity for cold perfusion in case of unexpectedly prolonged TVO. A large- scale and long-term follow-up study is necessary to further evalu- ate this treatment strategy.

Acknowledgments

None.

CRediTauthorshipcontributionstatement

Ji-ChaoTang:Data curation, Formal analysis, Writing – origi- nal draft.Wang-JieSuolang:Data curation, Formal analysis, Writ- ing – original draft.ChongYang:Formal analysis, Methodology.YiWang:Formal analysis, Methodology.Ming-WuTian:Formal anal- ysis, Methodology.YuZhang:Conceptualization, Funding acquisi- tion, Supervision, Writing – review & editing.

Funding

This study was supported by a grant from the Non-profit Cen- tral Research Institute Fund of Chinese Academy of Medical Sci- ences (No. 2019PT320 0 04).

Ethicalapproval

This study was approved by the Ethics Committee of Sichuan Provincial People’s Hospital (No. 2016-24). Written informed con- sent was obtained from the reported patient.

Competinginterest

No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the sub- ject of this article.