Background
Presently, according to different difficulty scoring systems, there is no difference in complexity estimation of laparoscopic liver resection (LLR) of segments 7 and 8. However, there is ...no published data supporting this assumption. To date, no studies have compared the outcomes of laparoscopic parenchyma‐sparing resection of the liver segments 7 and 8.
Methods
A post hoc analysis of patients undergoing LLR of segments 7 and 8 in 46 centers between 2004 and 2020 was performed. 1:1 Propensity score matching (PSM) was used to compare isolated LLR of segments 7 and 8. Subset analyses were also performed to compare atypical resections and segmentectomies of 7 and 8.
Results
A total of 2411 patients were identified, and 1691 patients met the inclusion criteria. Comparison after PSM between the entire cohort of segment 7 and segment 8 resections revealed inferior results for segment 7 resection in terms of increased blood loss, blood transfusions, and conversions to open surgery. Subset analyses of only atypical resections similarly demonstrated poorer outcomes for segment 7 in terms of increased blood loss, operation time, blood transfusions, and conversions to open surgery. Conversely, a subgroup analysis of segmentectomies after PSM found better outcomes for segment 7 in terms of a shorter operation time and hospital stay.
Conclusion
Differences in the outcomes of segments 7 and 8 resections suggest a greater difficulty of laparoscopic atypical resection of segment 7 compared to segment 8, and greater difficulty of segmentectomy 8 compared to segmentectomy 7.
Abstract
Chronic hepatitis B virus (HBV) infection can cause oxidative stress and induce cell death. The mechanisms by which cells overcome oxidative stress to survive remain largely unknown. Here, ...we used human sera, liver tissues and cell lines to study how HBV modulates cellular pathways to counteract oxidative stress-induced cell death. We found high-mobility group AT-hook 2 (HMGA2), an architectural transcription factor is upregulated in hepatocellular carcinoma (HCC) tissues and cell lines. Elevated serum HMGA2 is significantly associated with viral load in HBV carriers, and HBV-related HCC. We showed that HBV X protein (HBx) encoded by HBV-induced cell growth via HMGA2 activation. The growth-promoting effect is abolished when HMGA2 is suppressed. Ectopic HBx expression induced DNA damage and oxidative stress. HMGA2 silencing reduced oxidative stress in HBx-expressing cells. Cytoprotective stanniocalcin 2 (STC2) protein is a downstream target of HMGA2. Consistent with the findings in HMGA2, STC2 mRNA and protein expression are upregulated in HCC tissues. Elevated serum STC2 is also associated with viral load in HBV carriers, and HCC. STC2 is transcriptionally upregulated by HBx and HMGA2 to elicit cytoprotection against apoptosis. STC2 knockdown disrupted Bax/Bcl-2 balance that increased cytochrome c release, caspase 3/7 activity and apoptosis, and thus abolished the growth-promoting effect of HMGA2. Clinical relevance of HBx/HMGA2/STC2 signaling is evidenced by the significant correlation of serum HMGA2/STC2 in active HBV infection and HCC. These findings reveal a novel HBx regulatory HMGA2/STC2 pathway in counteracting reactive oxygen species-induced cell death. HMGA2 and STC2 may be therapeutic targets for prevention of hepatocarcinogenesis in chronic HBV infection.
HBx protein encoded by HBV induced HMGA2 and STC2 expression. The HBx/HMGA2/STC2 signaling promotes hepatocarcinogenesis by protecting cells from ROS-induced apoptosis.
Graphical Abstract
BackgroundProgrammed cell death protein 1 (PD-1) pathway blockade with immune checkpoint inhibitors (ICIs) is a standard therapy in advanced hepatocellular carcinoma (HCC) nowadays. No strategies to ...overcome ICI resistance have been described. We aimed to evaluate the use of ipilimumab and anti-PD-1 ICIs (nivolumab or pembrolizumab) combinations in patients with advanced HCC with progression on prior ICIs.MethodsPatients with advanced HCC with documented tumor progression on prior ICIs and subsequently received ipilimumab with nivolumab/pembrolizumab were analyzed. Objective response rate (ORR), median duration of response (DOR), time-to-progression (TTP), overall survival (OS), and treatment-related adverse events (TRAEs) were assessed.ResultsTwenty-five patients were included. The median age was 62 (range: 51–83). About 68% were of Child-Pugh (CP) Grade A and 48% had primary resistance to prior ICI. At median follow-up of 37.7 months, the ORR was 16% with a median DOR of 11.5 months (range: 2.76–30.3). Three patients achieved complete response. The median TTP was 2.96 months (95% CI: 1.61 to 4.31). Median OS was 10.9 months (95% CI: 3.99 to 17.8) and the 1 year, 2 year and 3 year survival rates were 42.4%, 32.3% and 21.6%, respectively. The ORR was 16.7% in primary resistance group and 15.4% in acquired resistance group (p=1.00). All responders were of CP A and Albumin-Bilirubin (ALBI) Grade 1 or 2. CP and ALBI Grades were significantly associated with OS (p=0.006 and p<0.001, respectively). Overall, 52% of patients experienced TRAEs and 12% experienced Grade 3 or above TRAEs.ConclusionsIpilimumab and nivolumab/pembrolizumab can achieve durable antitumor activity and encouraging survival outcomes with acceptable toxicity in patients with advanced HCC who had prior treatment with ICIs.
OBJECTIVE:The aim of this study was to determine the outcomes of living donor liver transplantation (LDLT) according to various graft-to-recipient weight ratio (GRWR).
BACKGROUND:The standard GRWR in ...LDLT is >0.8%. Our center accepted predicted GRWR ≥0.6% in selected patients.
METHODS:Data from patients who underwent LDLT from 2001 to 2017 were included. Patients were stratified according to actual GRWR (Group 1:GRWR ≤0.6%; Group 20.6%<GRWR≤ 0.8%; Group 3:GRWR >0.8%).
RESULTS:There were 545 LDLT (group 1 = 39; group 2 = 159; group 3 = 347) performed. Pretransplant predicted GRWR showed good correlation to actual GRWR (R = 0.834) and these figures differed within a ± 10%margin (P = 0.034) using an equivalence test. There were more left lobe grafts in group 1 (33.3%) than group 2 (10.7%) and 3 (2.9%). Median donor age was <35 years and steatosis >10% was rare.There was no difference in postoperative complication, vascular and biliary complication rate between groups. Over one-fifth (20.5%) of group 1 patients required portal flow modulation (PFM) and was higher than group 2 (3.1%) and group 3 (4%) (P = 0.001). Twenty-six patients developed small-for-size syndrome (SFSS)5 of 39 (12.8%) in group 1 and 21 of 159 (13.2%) in group 2 and none in group 3 (P < 0.001). There were 2 hospital mortalities; otherwise, the remaining patients 24/26 (92.3%) survive with a functional liver graft. The 5-year graft survival rates were 85.4% versus 87.8% versus 84.7% for group 1, 2, and 3, respectively (P = 0.718). GRWR did not predict worse survivals in multivariable analysis.
CONCLUSIONS:Graft size in LDLT can be lowered to 0.6% after careful recipient selection, with low incidence of SFSS and excellent outcomes. Accurate graft weight prediction, donor-recipient matching, meticulous surgical techniques, appropriate use of PFM, and vigilant perioperative care is important to the success of such approach.
Immune checkpoint blockade (ICB) has improved cancer treatment, yet why most hepatocellular carcinoma (HCC) patients are resistant to PD-1 ICB remains elusive. Here, we elucidated the role of a ...programmed cell death protein 1 (PD-1) isoform, Δ42PD-1, in HCC progression and resistance to nivolumab ICB.
We investigated 74 HCC patients in three cohorts, including 41 untreated, 28 treated with nivolumab and 5 treated with pembrolizumab. Peripheral blood mononuclear cells from blood samples and tumour infiltrating lymphocytes from tumour tissues were isolated for immunophenotyping. The functional significance of Δ42PD-1 was explored by single-cell RNA sequencing analysis and validated by functional and mechanistic studies. The immunotherapeutic efficacy of Δ42PD-1 monoclonal antibody was determined in HCC humanised mouse models.
We found distinct T cell subsets, which did not express PD-1 but expressed its isoform Δ42PD-1, accounting for up to 71% of cytotoxic T lymphocytes in untreated HCC patients. Δ42PD-1
T cells were tumour-infiltrating and correlated positively with HCC severity. Moreover, they were more exhausted than PD-1
T cells by single T cell and functional analysis. HCC patients treated with anti-PD-1 ICB showed effective PD-1 blockade but increased frequencies of Δ42PD-1
T cells over time especially in patients with progressive disease. Tumour-infiltrated Δ42PD-1
T cells likely sustained HCC through toll-like receptors-4-signalling for tumourigenesis. Anti-Δ42PD-1 antibody, but not nivolumab, inhibited tumour growth in three murine HCC models.
Our findings not only revealed a mechanism underlying resistance to PD-1 ICB but also identified anti-Δ42PD-1 antibody for HCC immunotherapy.
Hepatocellular carcinoma (HCC) is a major public health burden in Hong Kong, and chronic hepatitis B is the most common HCC etiology in our region. With the high case load, extensive local expertise ...on HCC has been accumulated. This article summarized local guidelines and real-life practice on HCC management in Hong Kong. For HCC surveillance, liver ultrasound and serum alpha-fetoprotein for periodic screening is recommended in viral hepatitis or cirrhotic patients, and this is adhered to in clinical practice. HCC diagnosis is not covered in local guidelines, yet our practice is in-line with regional guidelines, where diagnosis is usually achieved by cross-sectional imaging and without the need for histology. Our guidelines recommend using the Hong Kong Liver Cancer Staging for pre-treatment staging, yet we routinely use other widely-adopted systems such as the Barcelona Clinic Liver Cancer Staging and the Tumor-Node-Metastasis Staging as well. Our local guidelines have provided clear treatment algorithms for the whole range of HCC therapies, including resection, ablation, transplant, transarterial chemoembolization, transarterial radioembolization, stereotactic body radiation therapy, targeted therapy, and immunotherapy. Real-life treatment choices are largely in line with the guidelines, although treatment protocols are individualized, and availability of specific therapies can vary between centers. Overall, HCC guidelines in Hong Kong are tailored based on local expertise and our unique patient population. The guidelines are up-to-date and provide practical pathways to assist our routine practice. Regular updates of local guidelines are warranted to account for the rapidly evolving paradigm of HCC management.
Background
The concept of minimally invasive anatomic liver resection (MIALR) is gaining popularity. However, specific technical skills need to be acquired to safely perform MIALR. The “Expert ...Consensus Meeting: Precision Anatomy for Minimally Invasive HBP Surgery (PAM‐HBP Surgery Consensus)” was developed as a special program during the 32nd meeting of the Japanese Society of Hepato‐Biliary‐Pancreatic Surgery (JSHBPS).
Methods
Thirty‐four international experts gathered online for the consensus. A Research Committee performed a comprehensive literature review, classifying studies according to the Scottish Intercollegiate Guidelines Network method. Based on the literature review and experts’ opinions, tentative recommendations were drafted and circulated among experts using online Delphi Rounds. Finally, formulated recommendations were presented online in the Expert Consensus Meeting of the JSHBPS on February 23rd, 2021. The final recommendations were validated and finalized by the 2nd Delphi Round in May 2021.
Results
Seven clinical questions were selected, and 22 recommendations were formulated. All recommendations reached more than 85% consensus among experts at the final Delphi Round.
Conclusions
The Expert Consensus Meeting for safely performing MIALR has presented a set of clinical guidelines based on available literature and experts’ opinions. We expect these guidelines to have a favorable effect on the safe implementation and development of MIALR.
Highlight
Gotohda and colleagues report on the minimally invasive anatomic liver resection recommendations formulated in the Expert Consensus Meeting: PAM‐HBP Surgery Project held as a special program during the 32nd meeting of the Japanese Society of Hepato‐Biliary‐Pancreatic Surgery in February 2021 and finalized after a second Delphi round in May 2021.
This study compared outcomes of nonresectable hepatocellular carcinoma (HCC) who had transarterial chemoembolization (TACE) vs. stereotactic body radiation therapy (SBRT) after TACE (TACE + SBRT).
...This was a retrospective study of 2 centers in Hong Kong. There were 49 patients who had TACE + SBRT and 202 patients who had TACE alone. Propensity score matching was used to adjust for differences in patients’ demographics and tumor characteristics between the 2 groups. The primary outcome was overall survival (OS) and secondary outcomes were progression-free survival (PFS) and treatment-related toxicity.
After matching, 49 patients were in the TACE + SBRT group and 98 patients in the TACE group with similar baseline characteristics. The 1-&3-year OS were better in TACE + SBRT group (67.2 vs. 43.9% and 36.5 vs. 13.3%, p = 0.003). The 1-&3-year PFS was also better in TACE + SBRT group (32.5 vs. 21.4% and 15.1 vs. 5.1%, p = 0.012). Radiological disease control was better in the TACE + SBRT group (98 vs. 56.7%). Risk of severe toxicity was uncommon in both treatment arms. TACE + SBRT was an independent good prognostic factor for OS and PFS in multivariate analysis, whereas AFP>200 ng/ml, large tumor and multiple tumors predicted worse OS.
TACE + SBRT is safe and results in better survivals in nonresectable HCC patients.
To compare the outcomes between robotic major hepatectomy (R-MH) and laparoscopic major hepatectomy(L-MH).
Robotic techniques may overcome the limitations of laparoscopic liver resection. However, it ...is unknown whether robotic major hepatectomy (R-MH) is superior to laparoscopic major hepatectomy (L-MH).
This is a post hoc analysis of a multicenter database of patients undergoing R-MH or L-MH at 59 international centers from 2008 to 2021. Data on patient demographics, center experience/ volume, perioperative outcomes and tumor characteristics were collected and analyzed. 1:1 propensity score matched (PSM) and coarsened-exact matched (CEM) analysis was performed to minimize selection bias between both groups.
A total of 4822 cases met the study criteria, of which 892 underwent R-MH and 3930 underwent L-MH. Both 1:1 PSM, (841 R-MH vs. 841 L-MH) and CEM (237 R-MH vs. 356 L-MH) were performed. R-MH was associated with significantly less blood loss (PSM:200.0 IQR:100.0, 450.0 ml vs. 300.0 IQR:150.0, 500.0 ml; P=0.012; CEM:170.0 IQR: 90.0, 400.0 ml vs. 200.0 IQR:100.0, 400.0 ml; P=0.006), lower rates of Pringle maneuver application (PSM: 47.1% vs. 63.0%; P<0.001; CEM: 54.0% vs 65.0%; P=0.007) and open conversion (PSM: 5.1% vs. 11.9%; P<0.001; CEM: 5.5% vs. 10.4%, P=0.04) compared to L-MH. On subset analysis of 1273 cirrhotic patients, R-MH was associated with a lower postoperative morbidity rate (PSM: 19.5% vs. 29.9%; P=0.02; CEM 10.4% vs. 25.5%; P=0.02) and shorter postoperative stay (PSM: 6.9 IQR: 5.0, 9.0 days vs. 8.0 IQR: 6.0 11.3 days; P<0.001; CEM 7.0 IQR: 5.0, 9.0 days vs. 7.0 IQR: 6.0, 10.0 days; P=0.047).
This international multicenter study demonstrated that R-MH was comparable to L-MH in safety and was associated with reduced blood loss, lower rates of Pringle maneuver application and conversion to open surgery.
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