Resection For Hepatocellular Carcinoma Research Articles

Prognostic Implications of MRI-assessed Intratumoral Fat in Hepatocellular Carcinoma: An Asian and European Cohort Study.

Background The clinicopathologic-radiologic and prognostic characteristics of intratumoral fat in hepatocellular carcinoma (HCC) are critical for personalized treatment but remain understudied. Purpose To investigate the clinicopathologic-radiologic associations and prognostic implications of MRI-assessed intratumoral fat in HCCs. Materials and Methods This retrospective cohort study included consecutive adult patients who underwent resection for solitary HCCs and preoperative contrast-enhanced MRI from two tertiary-care hospitals in East Asia (March 2011 to December 2021) and Western Europe (September 2012 to December 2019). MRI scans were independently evaluated by three radiologists at each hospital. Based on Liver Imaging Reporting and Data System (LI-RADS) version 2018, intratumoral fat was defined as "fat in mass more than adjacent liver," and the homogeneous subtype was defined as intratumoral fat "in absence of mosaic and nodule-in-nodule architecture." Recurrence-free survival (RFS) and overall survival (OS) were estimated using the Kaplan-Meier method and compared using the log-rank test. Cox regression analyses were conducted to identify factors associated with RFS and OS. Results A total of 933 patients were included in the Asian (n = 736; median age, 53 years [IQR, 45-62 years]; 626 male) and European (n = 207; median age, 64 years [IQR, 55-70 years]; 161 male) cohorts. MRI-assessed intratumoral fat was detected in 30% (215 of 726) and 31% (64 of 207) of patients in the Asian and European cohorts, respectively (P = .72). In both cohorts, the steatohepatitic subtype, nonperipheral washout, enhancing capsule, and mosaic architecture were more frequent in tumors with intratumoral fat (P value range, <.001 to .04). Intratumoral fat in general was not associated with RFS or OS in either cohort (P value range, .48-.97). However, in the Asian cohort, homogeneous intratumoral fat was associated with longer RFS (hazard ratio [HR], 0.60; P = .009) and OS (HR, 0.33; P = .008) in multivariable Cox regression analyses. Conclusion MRI-assessed intratumoral fat was more frequent in steatohepatitic HCCs and associated with nonperipheral washout, enhancing capsule, and mosaic architecture. Although intratumoral fat was generally nonprognostic, homogeneous intratumoral fat was associated with longer RFS and OS in the Asian cohort. Published under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Harmath in this issue.

The impact of tumor burden score on prognosis in patients after radical resection of hepatocellular carcinoma: a single-center retrospective study

The impact of tumor burden score on prognosis in patients after radical resection of hepatocellular carcinoma: a single-center retrospective study

Role of Serum Alpha-fetoprotein in Assessing the Resectability of Hepatocellular Carcinoma

Background: Serum AFP is a well-established tumor marker of hepatocellular carcinoma (HCC) which has already proved its acceptability in confirming the diagnosis and predicting the prognosis of HCC. Objective: The current study is aimed to evaluate the role of serum alpha-fetoprotein in assessing the resectability of HCC. Methods: This was a single-center, cross-sectional study done from September 2020 to August 2021 at the department of Hepatobiliary, pancreatic, and liver transplantation surgery at BSMMU. A total of 27 HCC patients who met the inclusion criteria were enrolled in the study. Clinical, laboratory, and imaging findings were obtained using a standardized data collecting sheet with the patients' informed agreement. AFP was measured by automated chemiluminescence analyzer (LIAISON XL, DiaSorin, Italy) in the Department of Biochemistry &amp; Molecular Biology, BSMMU. Based on the ROC curve of this study, the patients were divided into group 1 with AFP levels 38.45 ng/ml and group 2 with AFP levels &gt;38.45 ng/ml. According to the resectable criteria (TNM stage: I, II, BCLC stage: 0, A, B, CTP grade: A, B, ECOG PS: 0) established for the study, each AFP group was further subdivided into resectable and unresectable subgroups. Finally, the parameters (tumor size, number, location, CTP grade, fibrosis score, performance status, HBV positive, HBV DNA, BCLC and TNM stage) of the resectable and unresectable patients in each AFP group were evaluated. Statistical analyses were performed using SPSS version 22. Quantitative variables were expressed as mean±standard deviation and examined using an unpaired t-test. The qualitative data were represented by frequencies and percentages, and the Chi-Square test and Fisher exact test (where applicable) were used to determine any correlation. The statistical tests were conducted with a 95% confidence interval, and P0.05 was deemed statistically significant. Results: In this study, thirty seven percent (37%) patients ...........

Perioperative Tislelizumab plus intensity modulated radiotherapy in resectable hepatocellular carcinoma with macrovascular invasion: a phase II trial

Hepatocellular carcinoma (HCC) patients with macrovascular invasion (MVI) have dismal prognosis and there are no standard perioperative therapies. This phase 2 trial (ChiCTR2000036385) aimed to investigate the activity and safety of perioperative tislelizumab plus intensity modulated radiotherapy (IMRT) for resectable HCC with MVI. Thirty treatment-naïve patients with MVI received 3 cycles of tislelizumab intravenously (200 mg, every three weeks) and concurrent IMRT (45 Gray in 15 fractions). Primary endpoints were the overall response rate (ORR) and overall survival (OS). Secondary endpoints were the proportion of patients with a complete or major pathological response (pCR or MPR), recurrence-free survival (RFS) and safety. Of patients enrolled, 15 (50%) underwent curative surgery followed by adjuvant tislelizumab. The ORR was 30.0% (90% CI 16.6%-46.5%) and the median OS was 18.7 months. Of the 15 patients underwent surgical resection, 10 (66.7%) achieved pCR or MPR and 8 (53.3%) remained recurrence-free. The median RFS were not reached with a median follow-up of 21.77 months (95% CI 12.50-31.03) post-surgery. 4 (13.3%) patients experienced grade 3 treatment-related adverse events. The most common events were thrombocytopenia, leukopenia, and anemia. The trial has met the pre-specified endpoints, and these results support further studies of perioperative immunotherapy plus radiotherapy in HCC.

Prognostic significance of early and multiple recurrences after curative resection for hepatocellular carcinoma

BackgroundIn hepatocellular carcinoma (HCC), postoperative recurrence remains high. This study aimed to evaluate the recurrence patterns and prognosis of HCC after curative hepatectomy.MethodsAmong 352 patients with primary HCC who underwent initial hepatectomy between January 2002 and December 2022, 151 with recurrence were assessed for the relationship between recurrence pattern and prognosis.ResultsThe early recurrence group (within 6 months postoperatively; n = 38) had significantly higher serum alpha-fetoprotein (p = 0.002), des-γ-carboxyprothrombin (DCP; p = 0.004) levels and Barcelona Clinic Liver Cancer (BCLC) stage (p < 0.001), larger tumor size (p < 0.001), higher incidence of multiple tumors (p = 0.002) and lower overall survival (OS) (p < 0.001) than the late recurrence group (> 6 months postoperatively; n = 113). The tumor size (p = 0.013) and BCLC stage (p = 0.001) were independent risk factors for early recurrence within 6 months in multivariate analysis.The multiple recurrence group (intrahepatic multinodular recurrence or distant metastasis; n = 89) had significantly lower prognostic nutritional index (p = 0.026), larger tumor size (p = 0.017), lower incidence of liver cirrhosis (p = 0.03) than the single recurrence group (single nodule recurrence; n = 62). The multiple recurrence group, especially patients with ≥ three intrahepatic nodules and distant metastases, had lower postoperative OS (p < 0.001) and shorter time to recurrence (p < 0.001) than the single recurrence group.When the patients were classified into three groups: late recurrence with one or two tumors (Group A; n = 74), early recurrence or three or more tumors or distant metastasis (Group B; n = 54), and early recurrence with three or more tumors or distant metastasis (Group C; n = 23), OS was significantly lower in Groups B and C than Group A (p < 0.001).ConclusionsPatients with early recurrence within 6 months after surgery and three or more recurrence nodule or distant metastasis exhibited poor prognosis after initial recurrence, and they should be carefully followed up.

Challenges in Adjuvant Immunotherapy after Resection or Ablation for High-Risk Hepatocellular Carcinoma at High-Risk of Recurrence

Challenges in Adjuvant Immunotherapy after Resection or Ablation for High-Risk Hepatocellular Carcinoma at High-Risk of Recurrence

A Decade of Experience Between Open and Minimally Invasive Hepatectomies for Hepatocellular Carcinoma

Background and Objectives: Hepatic resection offers promising outcomes for patients with hepatocellular carcinoma (HCC) but can be constrained by factors like patient suitability. Continuous advancements in laparoscopic and robotic technologies have made minimally invasive hepatectomies (MIHs) a viable alternative to open hepatectomies with benefits in terms of recovery and complications. Materials and Methods: We completed a retrospective review on 138 HCC patients who underwent OH or MIH between 2010 and 2020 at the Hume-Lee Transplant Center. Univariate and multivariate analyses were completed on demographic, clinical, and tumor-specific data to assess the impact of these variables on overall and disease-free survival at 1, 3, and 5 years. Preoperative metrics like length of hospital stay (LOS) and operation duration were also evaluated. Results: Of the 109 OH and 29 MIH patients, MIH patients demonstrated shorter LOS and operative times. However, overall survival (OS) and disease-free survival (DFS) were similar between groups, with no significant variations in 1-, 3-, and 5-year survival rates. Age &gt; 60 years and a lack of preoperative transcatheter arterial chemoembolization (TACE) were significant predictors of inferior OS and DFS in multivariate analyses. Conclusions: MIH is an efficient substitute for OH with comparable survival, even in older patients. The reduced LOS and operation time enhance its feasibility, and older patients previously denied for curative resection may qualify for MIH. Preoperative TACE also enhances survival outcomes, emphasizing its general role in managing resectable HCCs. Both robotic and laparoscopic hepatectomies offer acceptable short- and long-term clinical outcomes, highlighting MIH as the standard choice for HCC patients.

Prognostic impact of aspirin in patients with hepatocellular carcinoma after liver resection: propensity-score-matched analysis.

The association between aspirin and hepatocellular carcinoma (HCC) has been reported to prevent carcinogenesis caused by hepatitis B or C virus infection. The objective of this study was to investigate the prognostic impact of aspirin in patients who underwent liver resection for HCC. Data for 1032 patients who underwent primary resection for HCC between 2000 and 2019 were reviewed. There were 87 patients (8.4%) who took aspirin (aspirin group) and 945 (91.6%) who did not (non-aspirin group). Short-term outcomes, recurrence-free survival (RFS), and overall survival (OS) were compared between two groups in the matched cohort using propensity-score matching. The median patient follow-up was 42.6months (95% confidence interval 3.12-136.8months). There was no significant difference in short-term outcomes, including bleeding events. RFS and OS after liver resection in the aspirin group were significantly better than those in the non-aspirin group in the unmatched cohort [5-year RFS rate: 50.3% vs 31.4%, hazard ratio (HR) 0.55, P = 0.0002; 5-year OS rate: 82.9% vs 70.2%, HR 0.46, P = 0.002]. In the matched cohort, RFS and OS after liver resection in the aspirin group were also significantly better than those in the non-aspirin group (5-year RFS rate: 50.3% vs 32.0%, HR 0.60, P = 0.003; 5-year OS rate: 82.9% vs 74.6%, HR 0.56, P = 0.03). Use of aspirin was associated with better prognosis for patients who underwent primary resection for HCC.

Tissue and imaging biomarkers of response to neoadjuvant nivolumab or nivolumab plus ipilimumab in patients with resectable hepatocellular carcinoma.

Perioperative immunotherapy has shown promise in some patients with early-stage hepatocellular carcinoma (HCC). This study examined tissue and imaging biomarkers associated with pathologic response in a phase II clinical trial in patients with resectable HCC. Analysis included 18 patients with biopsy-proven resectable HCC treated with neoadjuvant nivolumab plus ipilimumab or nivolumab alone in a phase II clinical trial at MD Anderson Cancer Center (NCT03222076). Liver MRE (to measure tissue fibrosis) and biopsies (to evaluate immune activation markers) were obtained serially pretreatment and after completing neoadjuvant immunotherapy. A major pathologic response (MPR) was defined as tumor necrosis of more than 70%. Data comparing patients with MPR versus those without was summarized using descriptive statistics and compared using the Wilcoxon rank sum test. Patients with MPR after neoadjuvant immunotherapy tended to have larger tumors (mean 9.52 vs. 4.99 centimeters; p = 0.050). They had a significant reduction in tumor size post-treatment (14.67% reduction vs. 9.15% increase in size; p = 0.042) and a non-significant decrease in serum AFP (-24.20% vs -14.00%; p = 0.085). Further, patients with MPR had a greater increase in intratumoral expression levels of CD8 (26.92% vs -0.04%; p = 0.026), Granzyme B (15.56% vs -2.24%; p = 0.011), and PD-1 (20.17% vs 0.40%; p = 0.048) but not PD-L1 (7.69% vs 0.57%; p = 0.26). Tumor and liver fibrosis were comparable before and after neoadjuvant therapy in patients with MPR versus non-responders. Changes in tumor size and immune cell infiltration and activation are candidate predictive markers of pathologic response to neoadjuvant immunotherapy in patients with resectable HCC.

The value of postoperative contrast-enhanced ultrasound parameters in lymph node metastasis, tumor node metastasis, and treatment response evaluation of resected hepatocellular carcinoma.

To explore the application value of postoperative contrast-enhanced ultrasound (CEUS) parameters for lymph node metastasis (LNM), tumor, node, metastasis staging, and treatment response evaluation of resected hepatocellular carcinoma (HCC). We retrospectively analyzed 100 patients with liver cancer who underwent liver CEUS at our hospital between October 2020 and October 2022. The patient's LNM, pathological staging, and therapeutic effects were recorded based on the histopathological results. CEUS parameters were analyzed and compared CEUS parameters between different lymph node metastases, pathological stages, and therapeutic effects. Twenty-three patients experienced LNM, 77 patients did not experience LNM; and the rise time (RT), peak intensity (PI), and area under the curve (AUC) of the metastatic group were significantly smaller than those of the nonmetastatic group (P < .05). 44 cases were classified into groups I to II by pathological staging, and 56 cases were classified into groups III to IV. The RT, PI, and AUC of groups III to IV were significantly lower than those of groups I-II (P < .05). Seventy-nine cases were complete necrosis, 21 cases were residual or recurrent; The RT, PI, and AUC of the residual or recurrent group were significantly lower than those of the complete necrosis group (P < .05). The receiver operating characteristic curve shows that RT, PI, and AUC have a certain value in evaluating LNM, pathological staging, and treatment response of HCC, and the combined evaluation/evaluation value of these 3 factors is relatively high. The postoperative CEUS parameters RT, PI, and AUC can be used for LNM, pathological staging evaluation, and treatment response evaluation of HCC. Moreover, the combination of the 3 parameters is feasible and valuable in evaluating LNM, tumor, node, metastasis staging, and treatment response of HCC.

Spatial Dynamics of T and B Cell Response Predicts Clinical Outcome of Resectable and Unresectable Hepatocellular Carcinoma.

Immunotherapies have led to a paradigm shift in the treatment of hepatocellular carcinoma (HCC). Studies have revealed the single-cell catalogues of tumor-infiltrating immune cells and the trajectories of their differentiation. Nevertheless, the spatial distribution of these immune cells with distinct phenotypes in tumor microenvironment and their clinicopathological significance in resectable and unresectable HCCs are still largely unclear. We analyzed the spatial dynamics of intratumoral CD4 and CD8 T cells and their association with B and plasma cells using 283 surgically resected HCCs, 58 unresectable HCC samples before combined immunotherapy (atezolizumab plus bevacizumab [Atezo+Bev]), and autopsy specimens from 50 cases of advanced-stage HCCs through multiplex immunohistochemistry combined with transcriptomic and driver gene mutation analysis. Classification based on the spatial dynamics of T and B cell responses (refined immunosubtype) was developed and its clinicopathological significance was analyzed. We found that stem-like CD4 and CD8 T cells were mainly observed in T cell aggregates. Differentiation of T follicular helper cells were associated with the development of tertiary lymphoid structures, whereas differentiation of CD4 TCXCL13 cells with phenotype resembling T peripheral helper cells were associated with the development of lymphoplasmacytic microenvironment. The refined immunosubtype could predict clinical outcomes of resectable HCC after surgery and unresectable HCC after Atezo+Bev therapy. The immune microenvironment of metastatic lesions tended to reflect those of primary lesions. We revealed the spatial dynamics of T and B cell response in HCC, which is closely associated with the clinical outcome after surgical resection or Atezo+Bev therapy.

Prognostic Impact of the Cholangiolar Component in Combined Hepatocellular-Cholangiocarcinoma: Insights From a Western Single-Center Study.

Primary liver malignancies, such as hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), and combined hepatocellular-cholangiocarcinoma (cHCC-CCA), represent significant contributors to global cancer-related mortality. The diagnostic challenges associated with distinguishing cHCC-CCA from HCC and ICC stem from their rarity and overlapping histological features. This study aimed to reclassify primary liver tumors resected at a Western center and to compare clinicopathological features and prognosis among patients with HCC, ICC, and cHCC-CCA. A retrospective analysis was conducted on patients undergoing resection for HCC, ICC, or cHCC-CCA between 2007 and 2017. Clinical and perioperative data were collected, and pathological specimens were reclassified by a specialized pathologist. Statistical analysis was employed to compare clinical features and survival outcomes among the different tumor types. Out of the initially identified 192 patients, 140 were included in the analysis. Following reclassification, 71.42% were diagnosed with HCC, 12.14% with ICC, and 16.42% with cHCC-CCA. Patients with HCC were predominantly male and exhibited a higher incidence of isolated liver recurrence. ICC patients more frequently underwent open procedures. Additionally, patients with HCC and cHCC-CCA showed higher rates of cirrhosis, elevated alpha-fetoprotein levels, and extrahepatic recurrence, while those with ICC and cHCC-CCA demonstrated elevated CA 19-9 levels. Overall survival and disease-free survival were longer for HCC compared to cases with a cholangiolar component (ICC and cHCC-CCA). Histological evaluation should actively incorporate the search for a cholangiolar component in primary liver tumors to prevent misdiagnosis, as its presence indicates a poorer prognosis.

Textbook outcome and nomogram-guided approaches for enhancing surgical success in elderly HCC patients: Deciphering the influence of sarcopenia.

Sarcopenia, serving as a surrogate for frailty, is clinically significant in liver resection (LR) for elderly hepatocellular carcinoma (HCC) patients. Our study aims to assess sarcopenia's impact, measured by Psoas Muscle Index (PMI), on postoperative outcomes. We retrospectively studied patients aged ≥ 60years who underwent LR for HCC between 2014 and 2018. PMI, derived from preoperative CT scans, and Textbook Outcome (TO) for LR were assessed. A nomogram predicting overall survival (OS) was developed via multivariable analysis. Of the 149 eligible HCC patients, the median PMI was 7.225 cm2/m2 in males and 4.882 cm2/m2 in females, with 37 (24.8%) patients identified as sarcopenic. Mortality was significantly associated with sarcopenia (HR 2.15; p = 0.032), MELD ≥ 10 (HR 3.13; p = 0.001), > 3 HCC nodules (HR 4.97; p = 0.001), and Clavien-Dindo ≥ 3 complications (HR 3.38; p < 0.001). Sarcopenic patients had a 5-year OS of 38.8% compared to 61% for non-sarcopenic individuals (p = 0.085). Achieving TO correlated with higher OS (p = 0.01). In sarcopenic cases, the absence of postoperative complications emerged as a limiting factor. Sarcopenic patients failing to achieve TO had worse OS compared to non-sarcopenic and TO-achieving counterparts (5-year OS 18.5%; p = 0.00039). Sarcopenia emerges as a prognostic factor for LR outcomes in elderly HCC patients. Postoperative complications in sarcopenic patients may compromise oncological outcomes.

Body mass index is a risk factor for postoperative morbidity after laparoscopic hepatectomy of hepatocellular carcinoma: a multicenter retrospective study

PurposeThe aim of this study was to determine whether preoperative body mass index (BMI) was associated with postoperative morbidity after laparoscopic liver resection (LLR) for hepatocellular carcinoma (HCC).MethodsA total of three groups of patients were categorized based on preoperative BMI: low-BMI (≤ 18.4 kg/m2), normal-BMI (18.5–24.9 kg/m2) and high-BMI (≥ 25.0 kg/m2). Baseline clinicopathological characteristics, operative variables, and postoperative 30-day mortality and morbidity were recorded and compared among the three groups. The independent risk factors for postoperative morbidity, including surgical site infection (SSI), were identified using univariate and multivariate analyses.ResultsAmong 226 included patients, 20 (8.8%), 122 (54%), and 84 (37.2%) patients had low, normal, and high BMI, respectively. There were no significant differences in postoperative 30-day mortality rates in patients with low BMI and high BMI compared with those with normal BMI (5% and 1.2% vs. 0%, P = 0.141 and P = 0.408, respectively). However, postoperative morbidity rates were significantly higher in patients with low BMI and high BMI compared to those with normal BMI (40% and 32.1% vs. 17.2%, P = 0.032 and P = 0.020, respectively). According to multivariate analysis, both low and high BMI were independent risk factors of increased postoperative morbidity (OR: 5.03, 95% CI: 1.02–25.6, P = 0.047, and OR: 4.53, 95% CI: 1.75–12.8, P = 0.003, respectively). Low and high BMI were also identified as independent risk factors of increased postoperative SSI rates (OR: 6.25, 95% CI: 1.60–23.8, P = 0.007, and OR: 2.89, 95% CI: 1.04–8.77, P = 0.047, respectively).ConclusionA higher incidence of postoperative morbidity including SSI after LLR for HCC was found in low-BMI and high-BMI patients compared to normal-BMI patients.Clinical trials registrationNot applicable because this is a retrospective observational study.

Persistent acute kidney injury: Postoperative impact and predictors in patients undergoing liver resection.

Persistent acute kidney injury (AKI) has not been investigated in patients undergoing liver resection. We aimed to identify the predictors of persistent AKI, its effect on postoperative outcomes and long-term renal function in patients following liver resection, and its impact on survival in patients with hepatocellular carcinoma (HCC). We examined 990 patients who underwent liver resection, including a subgroup analysis of 384 patients with curative resection for initial HCC. Persistent AKI was defined as residual impairment of serum creatinine≥0.3mg/dL or≥50% from baseline 1month after surgery. The persistent AKI group had significantly worse postoperative outcomes, including overall morbidity, major morbidity, longer hospital stay, and 90-day mortality. In the subgroup analysis of patients with HCC, persistent AKI was associated with a significantly poorer overall survival (OS) rate (p<0.001), and the multivariate analysis confirmed persistent AKI as an independent poor prognostic factor for OS (p=0.005). The long-term postoperative estimated glomerular filtration rate decline was significantly greater in the persistent AKI group than in the no AKI and transient AKI groups (p<0.001 for both). Chronic kidney disease, albumin-bilirubin grade ≥2, and anatomical resection were independent predictors of persistent AKI (p=0.001, p=0.039, and p=0.015, respectively). Persistent AKI adversely affects postoperative outcomes and long-term renal function in patients undergoing liver resection. Furthermore, it is associated with poor prognosis in patients with HCC. Therapeutic strategies to prevent persistent AKI are critical for improving postoperative outcomes in these patients.

Robotic liver resection for hepatocellular carcinoma: a new dawn?

Robotic liver resection for hepatocellular carcinoma: a new dawn?

Pre-operative evaluation of spontaneous portosystemic shunts as a predictor of post-hepatectomy liver failure in patients undergoing liver resection for hepatocellular carcinoma

BackgroundPost-hepatectomy liver failure (PHLF) can significantly compromise outcomes, especially in cirrhotic patients. The identification of accurate and non-invasive pre-operative predictors is of paramount importance to appropriately stratify patients according to their estimated risk and select the best treatment strategy. Materials and methodsConsecutive patients undergoing liver resection for HCC on cirrhosis between 1-2015 and 12–2020 at 10 international Institutions were enrolled and their pre-operative CT scans were evaluated for the presence of spontaneous portosystemic shunts (SPSS) to identify predictors of PHLF and develop a nomogram. ResultsThe analysis of the CT scans identified SPSS in 74 patients (17.4 %). PHLF was developed in 27 out of 425 cases (6.4 %), with grades B/C observed in 17 patients (4 %). At the multivariable analysis, the presence of SPSS resulted an independent risk factor for all-grades PHLF (OR 6.83, 95%CI 2.39–19.51, p < 0.001) and clinically significant PHLF development (OR 7.92, 95%CI 2.03–30.85, p = 0.003) alongside a patient's age ≥74 years, a pre-operative platelets count <106x103/μL, a multiple-segments liver resection, and an intraoperative blood loss ≥1200 mL. The 30- and 90-days mortality in patients with and without SPSS resulted 2.7 % vs 0.3 % (p = 0.024) and 5.4 % vs 1.1 % (p = 0.014). The accuracy of SPSS in predicting PHLF development was 0.847 (95%n CI 0.809–0.880). The internally validated nomogram showed excellent performance in predicting grades B/C PHLF (c-statistic = 0.933 (95%CI 0.888–0.979)). ConclusionThe pre-operative presence of SPSS assessed on the pre-operative imaging proved to be a valuable radiological biomarker able to predict PHLF development in patients undergoing liver resection for HCC.

HCC spatial transcriptomic profiling reveals significant and potentially targetable cancer-endothelial interactions.

HCC is a highly vascular tumor, and many effective drug regimens target the tumor blood vessels. Prior bulk HCC subtyping data used bulk transcriptomes, which contained a mixture of parenchymal and stromal contributions. We utilized computational deconvolution and cell-cell interaction analyses to cell type-specific (tumor-enriched and vessel-enriched) spatial transcriptomic data collected from 41 resected HCC tissue specimens. We report that the prior Hoshida bulk transcriptional subtyping schema is driven largely by an endothelial fraction, show an alternative tumor-specific schema has potential prognostic value, and use spatially paired ligand-receptor analyses to identify known and novel (LGALS9 tumor-HAVCR2 vessel) signaling relationships that drive HCC biology in a subtype-specific and potentially targetable manner. Our study leverages spatial gene expression profiling technologies to dissect HCC heterogeneity and identify heterogeneous signaling relationships between cancer cells and their endothelial cells. Future validation and expansion of these findings may validate novel cancer-endothelial cell interactions and related drug targets.

A classification model for resectability in hepatocellular carcinoma patients.

Some patients undergoing liver resection for hepatocellular carcinoma (HCC) have poor outcomes. Therefore, we aimed to propose a new resectability classification for patients with HCC. We classified patients into three categories: resectable (R), borderline resectable (BR), and unresectable (UR). Patients (n=409) who underwent hepatectomy for HCC were assigned to the non-UR (R and BR classes combined; n=285) and UR-HCC classes (n=68; training cohort). Patient characteristics in the BR-HCC and R-HCC groups were compared. The new criteria were tested in a validation cohort (n=295). Of the 285 patients, 229 and 56 were classified into the R- and BR-HCC classes, respectively, using macrovascular invasion, tumor size, and future liver remnant/modified albumin-bilirubin scores. Patients with BR-HCC demonstrated significantly worse progression-free and overall survival (p<0.0001 and p<0.0001, respectively) than patients with R-HCC in the training cohort. Similar results were observed in the validation cohort. Multivariate analysis of the non-UR-HCC group in the training cohort revealed that the tumor number and BR-HCC were independent predictive factors for poor overall survival. This classification can help select patients with BR-HCC for preoperative treatment before considering surgery.

Ultrasound-based Radiomics Analysis for Assessing Risk Factors Associated With Early Recurrence Following Surgical Resection of Hepatocellular Carcinoma

ObjectiveThe aim of this study was to explore the value of ultrasound-based radiomics analysis for early recurrence (ER) after surgical resection of hepatocellular carcinoma (HCC). MethodsThis retrospective study included 127 patients who underwent primary surgical resection for HCC between October 2019 and November 2021. The patients were subsequently divided into training and validation sets (7:3 ratio). All patients received preoperative routine ultrasound and contrast-enhanced ultrasound (CEUS), with postoperative pathological confirmation of HCC. Radiomics features were extracted from maximum section of two-dimensional ultrasound image. The least absolute shrinkage and selection operation (LASSO) logistic regression algorithm with 10-fold cross-validation was employed to establish ultrasonic radiomics features. Logistic regression modeling was employed to build models based on clinical and ultrasonic features (model 1, clinical-ultrasonic model), radiomics signature (model 2, ultrasonic radiomics model), and the combination (model 3, clinical-ultrasonic-radiomics model). Then a nomogram model was established to predict the risk of ER, and the application value of nomogram through internal verification was evaluated. ResultsModel 3 showed optimal diagnostic performance in both training set (AUC=0.907) and validation set (AUC=0.925), followed by the model 1 in training set (AUC=0.846) and validation set (AUC=0.855), both above two models performed better than model 2 in training set (AUC=0.751) and validation set (AUC=0.702) (p<0.05). In training set and validation set of model 3, the sensitivity were 83.3%, 77.8%, the specificity ware 95.8%, 100.0% and the C-index were 0.791, 0.778. ConclusionThe preoperative clinical-ultrasonic-radiomics model is anticipated to be a reliable tool for predicting the ER of surgical resection of HCC.