The influence of liver fibrosis on the rate of liver regeneration and complications following ALPPS has yet to be fully understood. This study aimed to scrutinize the effects of liver fibrosis on the postoperative complications, and prognosis subsequent to ALPPS. Clinical data were collected from patients with primary liver cancer who underwent ALPPS at Peking Union Medical College Hospital between May 2014 and October 2022. The degree of liver fibrosis was assessed using haematoxylin-eosin staining and Sirius red staining. This study encompassed thirty patients who underwent ALPPS for primary liver cancer, and there were 23 patients with hepatocellular carcinoma, 5 with cholangiocarcinoma, and 2 with combined hepatocellular-cholangiocarcinoma. The impact of severe liver fibrosis on the rate of liver regeneration was not statistically significant (P = 0.892). All patients with severe complications belonged to the severe liver fibrosis group. Severe liver fibrosis exhibited a significant association with 90 days mortality (P = 0.014) and overall survival (P = 0.012). Severe liver fibrosis emerges as a crucial risk factor for liver failure and perioperative mortality following the second step of ALPPS. Preoperative liver function impairment is an important predictive factor for postoperative liver failure.

Therapeutic options for large or locally advanced hepatocellular carcinoma (HCC) have limited efficacy. This study investigated the efficacy and safety of drug-eluting beads trans-arterial chemo-embolization (dTACE), portal vein embolization (PVE), tyrosine kinase inhibitor (TKI), and immune checkpoint inhibitors (ICI) compared to Associating Liver Partition and Portal vein ligation for Staged hepatectomy (ALPPS) for large or locally advanced HCC.Data regarding clinicopathological details, safety, and oncological outcomes were reviewed for the quadruple therapy (dTACE-PVE-TKI-ICI) and compared with ALPPS.From 2019 to 2020, 10 patients with large or locally advanced HCC underwent future remnant liver (FRL) modulation (dTACE-PVE-TKI-ICI: 5; ALPPS: 5). All five dTACE-PVE-TKI-ICI cases responded well, with patients #4 and #5 achieving complete tumor necrosis. The overall response rate (ORR) was 5/5. Patients #1-4 underwent hepatectomy, while #5 declined surgery due to complete tumor necrosis. Mean FRL volume increased by 75.3% (range 60.0%-89.4%) in 2-4 months, compared to 104.6% (range 51.3%-160.8%) in 21-37 days for ALPPS (P = 0.032). Major postoperative complications occurred in 1/5 ALPPS patients. Resection rates were 4/4 for quadruple therapy and 5/5 for ALPPS. 2-year progression free survival for dTACE-PVE-TKI-ICI and ALPPS were 5/5 and 3/5, respectively.Quadruple therapy is a feasible, effective strategy for enhancing resectability by downsizing tumors and inducing FRL hypertrophy, with manageable complications and improved long-term prognosis. In addition, it provokes the re-examination of the application of ALPPS in an era of molecular and immune treatments.

Post-hepatectomy liver failure (PHLF) leads to poor prognosis in patients undergoing hepatectomy, with hepatic vascular reconstitution playing a critical role. However, the regulators of hepatic vascular reconstitution remain unclear. In this study, we aimed to investigate the regulatory mechanisms of hepatic vascular reconstitution and identify biomarkers predicting PHLF in patients undergoing hepatectomy.
Candidate genes that were associated with hepatic vascular reconstitution were screened using adeno-associated virus vectors in Alb-Cre-CRISPR/Cas9 mice subjected to partial hepatectomy. The biological activities of candidate genes were estimated using endothelial precursor transfusion and associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) models. The level of candidates was detected in biopsies from patients undergoing ALPPS. Risk factors for PHLF were also screened using retrospective data.
Downregulation of Gata3 and upregulation of Ramp2 in hepatocytes promoted the proliferation of liver sinusoidal endothelial cells and hepatic revascularization. Pigment epithelium-derived factor (PEDF) and vascular endothelial growth factor A (VEGFA) played opposite roles in regulating the migration of endothelial precursors from bone marrow and the formation of new sinusoids after hepatectomy. Gata3 restricted endothelial cell function in patient-derived hepatic organoids, which was abrogated by a Gata3 inhibitor. Moreover, overexpression of Gata3 led to higher mortality in ALPPS mice, which was improved by a PEDF-neutralizing antibody. The expression of Gata3/RAMP and PEDF/VEGFA tended to have a negative correlation in patients undergoing ALPPS. A nomogram incorporating multiple factors, such as serum PEDF/VEGF index, was constructed and could efficiently predict the risk of PHLF.
The balance of Gata3 and Ramp2 in hepatocytes regulates the proliferation of liver sinusoidal endothelial cells and hepatic revascularization via changes in the expression of PEDF and VEGFA, revealing potential targets for the prevention and treatment of PHLF.
In this study, we show that the balance of Gata3 and Ramp2 in hepatocytes regulates hepatic vascular reconstitution by promoting a shift from pigment epithelium-derived factor (PEDF) to vascular endothelial growth factor A (VEGFA) expression during hepatectomy- or ALLPS (associating liver partition and portal vein ligation for staged hepatectomy)-induced liver regeneration. We also identified serum PEDF/VEGFA index as a potential predictor of post-hepatectomy liver failure in patients who underwent hepatectomy. This study improves our understanding of how hepatocytes contribute to liver regeneration and provides new targets for the prevention and treatment of post-hepatectomy liver failure.

UNASSIGNED: Insufficient post-operative future liver remnant (FLR) limits the feasibility of hepatectomy for patients. Staged hepatectomy is an effective surgical approach that can improve the resection rate of hepatocellular carcinoma (HCC). This study aimed to compare the safety and efficacy of laparoscopic microwave ablation and portal vein ligation for staged hepatectomy (LAPS) and classical associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) in the treatment of hepatitis B virus (HBV)-related HCC.
UNASSIGNED: Clinical data of patients with HBV-related HCC who underwent LAPS or ALPPS in our institute between January 2017 and May 2022 were retrospectively analysed.
UNASSIGNED: A total of 18 patients with HBV-related HCC were retrospectively analysed and divided into the LAPS group (n = 9) and ALPPS group (n = 9). Eight patients in the LAPS group and eight patients in the ALPPS group proceeded to a similar resection rate (88.9% vs 88.9%, P = 1.000). The patients undergoing LAPS had a lower total comprehensive complication index than those undergoing ALPPS but there was not a significant different between the two groups (8.66 vs 35.87, P = 0.054). The hypertrophy rate of FLR induced by ALPPS tended to be more rapid than that induced by LAPS (24.29 vs 13.17 mL/d, P = 0.095). The 2-year recurrence-free survival (RFS) was 0% for ALPPS and 35.7% for LAPS (P = 0.009), whereas the 2-year overall survival for ALPPS and LAPS was 33.3% and 100.0% (P = 0.052), respectively.
UNASSIGNED: LAPS tended to induce lower morbidity and FLR hypertrophy more slowly than ALPPS, with a comparable resection rate and better long-term RFS in HBV-related HCC patients.

OBJECTIVE: Associating liver partition and portal vein ligation (PVL) for staged hepatectomy (ALPPS) is a creative strategy for enlarging the future liver remnant (FLR) and increasing the tumor resectability rate. However, the indications for ALPPS must have a certain limit when the FLR is too small. We aimed to establish a modified ALPPS model with more widen applicability in rats.
METHODS: An extreme ALPPS model was established in rodents with only a 6.5% FLR. The portal vein (PV) was subjected to restriction to different degrees, then the portal vein pressure (PVP) was measured. Then, different modifications of ALPPS, including hepatic artery restriction (HAR), gradual portal vein restriction (GPVR), and GPVR-associated HAR (HAR+GPVR), were applied in the extreme ALPPS models.
RESULTS: PVL or PVR provoked an immediate increase in the PVP. The PVP in the PVR -1.28 mm, PVR -0.81 mm, PVR -0.63 mm, and PVL groups was 11.05±1.57 cmH2O, 16.18±1.92 cmH2O, 20.66±1.99 cmH2O, and 24.10±3.33 cmH2O, respectively, and the corresponding 3-day survival rate was 100%, 90.09%, 36.33% and 0, respectively. Then, in the extreme ALPPS model, the growth ratio of the FLR in the control, HAR, GPVR, and HAR+GPVR groups was 0.43±0.21, 0.50±0.16, 4.80±0.86, and 7.40±2.56, and as a consequence, the corresponding 30-day survival rate was 9.09%, 15.38%, 84.61% and 92.90%, respectively.
CONCLUSIONS: ALPPS itself has a limit, and high PVP after PVL contributes to postoperative death in the extreme ALPPS model. Furthermore, a modified method for extreme ALPPS is proposed, i.e., GPVR+HAR in place of PVL, which significantly improves the survival rate of extreme hepatectomy in rat models.

BACKGROUND: Despite the ALPPS technique remains a controversy, various ALPPS techniques have made many attempts.1-6 This video discusses the technical tips for L-ALPPS after conversion therapy.
METHODS: A 56-year-old, HCC patient who performed the abdominal CT showed a 6.0*5.7-cm-sized mass with intrahepatic metastasis. After four cycles of conversion therapy, the patient achieved a radiologic complete response. However, the standardized, remnant liver volume ratio (SRLVR) was only 34%. Thus, L-ALPPS was contemplated.
RESULTS: After full mobilization, intraoperative ultrasonography marked the main trunk of MHV. The concept of \"Laennec membrane anatomy\" was introduced.7 The anterior pedicle (AP) and the posterior pedicle (PP) were elastically suspended along the Laennec membrane. The conventional hilar dissection approach was used to isolate and suspend RHA and the right portal vein (RPV). Then, IRHV and short hepatic vein were clipped and cut. The Pringle maneuver was used intermittently during the parenchymal transection. Hepatic resection was performed from the caudal to the cranial side along MHV after RPV was ligated. The RHV was elastically suspended after hepatic resection. The omentum was used to cover the resection surface. Stage 2, preoperative SRLVR increased to 68.3%. The adhesion of the right hemiliver was bluntly separated. AP, PP, and RHV were divided by the stapler respectively. Operation time and bleeding volume for stage-1 surgery and stage-2 surgery were 240 min and 80 min, 200 ml and 250 ml, respectively. The postoperative recovery was uneventful.
CONCLUSIONS: L-ALPPS as a surgical option seems to be feasible and safe for intermediate-advanced HCC after conversion therapy.

UNASSIGNED: To evaluate the efficacy of ultrasound-guided percutaneous microwave ablation (PMA) combined with portal vein embolization (PVE) for planned hepatectomy.
UNASSIGNED: We retrospectively reviewed data of 18 patients with multiple right liver tumors or hilar tumor of liver invades the surrounding tissue and insufficient future liver remnant (FLR) for hepatectomy from July 2015 to March 2017. Ultrasound-guided PMA was performed by using PMCT cold circulation microwave treatment apparatus. PVE was performed after PMA. The increase of FLR was evaluated by computed tomography (CT) 6-22 days after PVE. The proportion of FLR, increase in the amplitude of FLR, procedure-related complications, perioperative morbidity and mortality, and overall survival (OS) rates, the median survival time were analyzed.
UNASSIGNED: The median volume of FLR before PMA and PVE was 369.7 ml (range: 239.4-493.1 ml). After a median waiting period of 11.5 days (range: 6-22 days), the median volume of FLR was increased to 523.4 ml (range: 355.4-833.3 ml). The changes in FLR before and after PMA and PVE were statistically significant (p<0.001). No serious perioperative complications or mortality were found. After a median follow-up time of 51.0 months (range: 2-54 months), the 6-month, 1-year, 2-year, 3-year and 4-year survival rates were 88.9%, 72.2%, 44.4%, 33.3%, 22.2%, respectively, and the median survival time was 15.0 ± 7.1 months.
UNASSIGNED: PMA combined with PVE increases FLR rapidly, avoids touching malignant tumors, and produces fewer procedure-related complications. It appears safe and efficacious for planned hepatectomy.

UNASSIGNED: The impact of sarcopenia on the future liver remnant (FLR) growth after portal vein occlusion, including portal vein embolization (PVE) and associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) has gained increasing interest. This systematic review aimed to explore whether sarcopenia was associated with insufficient FLR growth after PVE/ALPPS stage-1.
UNASSIGNED: A systematic literature search was performed in PubMed, Embase, Web of Science, and Cochrane Library up to 05 July 2022. Studies evaluating the influence of sarcopenia on FLR growth after PVE/ALPPS stage-1 in patients with liver cancer were included. A predefined table was used to extract information including the study and patient characteristics, sarcopenia measurement, FLR growth, post-treatment complications and post-hepatectomy liver failure, resection rate. Research quality was evaluated by the Newcastle-Ottawa Scale.
UNASSIGNED: Five studies consisting of 609 patients were included in this study, with a sample size ranging from 42 to 306 (median: 90) patients. Only one study was multicenter research. The incidence of sarcopenia differed from 40% to 67% (median: 63%). Skeletal muscle index based on pretreatment computed tomography was the commonly used parameter for sarcopenia evaluation. All included studies showed that sarcopenia impaired the FLR growth after PVE/ALPPS stage-1. However, the association between sarcopenia and post-treatment complications, post-hepatectomy liver failure, and resection rate remains unclear. All studies showed moderate-to-high quality.
UNASSIGNED: Sarcopenia seems to be prevalent in patients undergoing PVE/ALPPS and may be a risk factor for impaired liver growth after PVE/ALPPS stage-1 according to currently limited evidence.
UNASSIGNED: https://inplasy.com/, identifier INPLASY202280038.

OBJECTIVE: To evaluate the safety and efficacy of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) in the treatment of initially unresectable hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) and to preliminarily explore the mechanism of rapid growth of the future liver remnant (FLR).
METHODS: Twenty-four patients with HBV-associated HCC who underwent ALPPS in our hospital from August 2014 to January 2021 were retrospectively studied. Propensity score matching was used to compare oncologic outcomes of patients treated with ALPPS and transarterial chemoembolization (TACE). The expression of YAP and JNK in liver tissue after two stages of ALPPS were detected.
RESULTS: The median standard liver volume (SLV) was 1471.4 ml. Before second stage of ALPPS, the median FLR increased by 74.4%, and the median FLR/SLV increased from 26.1 to 41.6%. Twenty-two patients (91.7%) received staged hepatectomy after a median interval of 15 (9-24) d. The total incidence of postoperative complications in ALPPS group was 54.5%, and of Clavien-Dindo ≥ IIIb postoperative complications (requiring surgical, endoscopic or radiological intervention under general anesthesia) was 9.1%. There was no significant difference in total complications between ALPPS group and TACE group, but there were lower rate of above grade III complications in the TACE group than that in the ALPPS group. The incidence of complications was lower in laparoscopic-ALPPS than that in open surgery. In ALPPS group, the 1-year, 2-year and 5-year overall survival rate were respectively 71.4%, 33.3% and 4.8%. Interval time was an independent risk factor associated with overall survival rate. There was no significant difference in overall survival rate between ALPPS group and TACE group. For advanced HCC (BCLC stage B and C), ALPPS group was not superior to TACE group in overall survival rate. The expression of YAP and p-JNK in the residual liver tissue after second stage procedure was higher than that after first stage procedure, and the co-expression of YAP and p-JNK was observed in the residual liver tissue.
CONCLUSIONS: ALPPS is a safe and effective treatment for initially unresectable HBV-associated HCC. Laparoscopic technique might improve the effect of ALPPS. YAP and JNK pathway might take a role in rapid FLR increase in ALPPS procedure.

Liver cancer is one of the most lethal malignant tumors in the world, and surgical resection is the main treatment for liver cancer. Liver failure due to insufficient residual liver volume is a fatal complication after hepatectomy. How to effectively increase the residual liver volume after hepatectomy and improve the safety of hepatectomy has always been a problem to be solved in liver surgery. Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) effectively reduces the occurrence of liver failure due to insufficient residual liver volume after hepatectomy, thereby increasing the probability of radical resection by inducing rapid proliferation of residual liver tissue. However, the molecular mechanism of residual liver tissue regeneration after primary ALPPS (combined liver partition and portal vein ligation) remains unclear. Here, we found that lots of circular RNAs (circRNAs) are upregulated after ALPPS in pig liver cells; then, we identified the orthologous circRNA in humans and pigs to detect their function in liver regeneration. The results showed that loss of circ-0067724 and circ-0016213 could suppress liver cell proliferation. Together, these findings suggest that circ-0067724 and circ-0016213 play an important role in liver cell proliferation, and this may help us to find new strategies to promote liver regeneration.