Resection For Hepatocellular Carcinoma Research Articles

Diabetes Mellitus Following Resection of a Hepatocellular Carcinoma in a Dog Presented with Hypoglycemia.

A 5 yr old male neutered Labradoodle presented for an episode of acute collapse. Point-of-care blood work showed hypoglycemia and abdominal ultrasonography revealed a liver mass arising from the caudate liver lobe. The dog underwent a partial liver lobectomy, and histopathology confirmed a fully resected hepatocellular carcinoma. Blood glucose levels normalized initially after surgery, but 1 wk later, the patient was diagnosed with diabetes mellitus based on the development of polyuria, polydipsia, hyperglycemia, and glucosuria. Appropriate treatment with insulin was initiated, and 1 yr following the diagnosis, the dog was still requiring administration of insulin twice daily. This case describes the uncommon development of diabetes mellitus in a dog following surgical resection of a hepatocellular carcinoma initially associated with hypoglycemia. Although very unusual, this should be considered as a potential complication of surgical treatment of such tumors, and affected patients may require long-term medical management.

A prospective, phase II clinical study of tislelizumab monotherapy or in combination with lenvatinib for neoadjuvant treatment of resectable hepatocellular carcinoma

A prospective, phase II clinical study of tislelizumab monotherapy or in combination with lenvatinib for neoadjuvant treatment of resectable hepatocellular carcinoma

Prognosis of Neoadjuvant HAIC and Lenvatinib Followed by Surgery versus Direct Resection for Resectable or Borderline Resectable Hepatocellular Carcinoma: A Real-World Study.

This research aims to compare the efficacy of neoadjuvant hepatic arterial infusion chemotherapy (HAIC) combined with Lenvatinib (Len) to direct liver resection (LR) in patients with resectable or borderline resectable hepatocellular carcinoma (HCC). This retrospective study included 154 patients with hepatocellular carcinoma (HCC) treated at the a large-scale hepatocellular carcinoma Research Center between March 2019 and June 2023. Patients were assigned to one of two groups: 63 received neoadjuvant hepatic arterial infusion chemotherapy (HAIC) combined with Lenvatinib followed by liver resection (HAIC+Len→LR), while 91 received direct liver resection (LR). The primary outcomes assessed were median overall survival (mOS), median progression-free survival (mPFS), median duration of response (mDOR), and adverse events (AEs). Patients in the HAIC+Len→LR group demonstrated significantly longer median overall survival (mOS) (40.1 months vs 35.9 months, P=0.001) and median progression-free survival (mPFS) (32.8 months vs 23.8 months, P=0.0023) compared to the LR group. Preoperative complete response (CR) to HAIC was associated with better median duration of response (mDOR) and mOS compared to partial response (PR) (not reached vs 28.9 months, P=0.006; 40.0 vs 29.1 months, P=0.037). Subgroup analysis revealed no significant difference in OS or PFS between the HAIC+Len→LR and LR groups in early Barcelona Clinic Liver Cancer (BCLC) stages. However, in late BCLC stages, the HAIC+Len→LR group exhibited significantly improved OS and PFS (HR 0.471, P=0.016; HR 0.551, P=0.022). Treatment-related grade ≥3 adverse events were comparable between the two groups. For patients with resectable or marginally resectable HCC in the intermediate to advanced stages of BCLC, surgery after neoadjuvant HAIC+Len may offer improved long-term prognosis.

Artificial Intelligence-assisted Raman Spectroscopy for Liver cancer diagnosis

Hepatocellular carcinoma (HCC), the most common form of primary liver cancer, represents a global health challenge due to its complexity and the limitations of current diagnostic techniques. By combining Raman spectroscopy and Artificial Intelligence (AI), we have succeeded in classifying tumor cells. In fact, we have performed a first Raman spectral analysis based on the characterization and differentiation between uncultured primary human liver cells derived from resected HCC tumor tissue and the adjacent non-tumor counterpart. Biochemical analysis of the collected Raman spectra revealed that there is more DNA in the nuclei of the tumor cells than in non-tumor cells. We then develop three machine learning approaches, including multivariate models and neural networks, to rapidly automate the recognition and classification of the Raman spectra of both cells. To evaluate the performance of the developed AI models, we prepared and analyzed two additional cell samples with a ratio of 4:1 and 3:1 between tumor and non-tumor cells and compared the obtained results with the nominal percentages (accuracy of 80 and 60%, respectively). These results confirm that the models are able to make classifications at the level of a single spectrum, indicating the possibility of rapidly analysing and classifying a primary HCC cell.

Challenges in performing liver resection for HCC in SubSaharan Africa

Challenges in performing liver resection for HCC in SubSaharan Africa

The impact of portal hypertension assessment method on the outcomes of hepatocellular carcinoma resection: a meta-analysis of matched cohort and prospective studies

The impact of portal hypertension assessment method on the outcomes of hepatocellular carcinoma resection: a meta-analysis of matched cohort and prospective studies

Feasibility of novel intraoperative navigation for anatomical liver resection using real-time virtual sonography combined with indocyanine green fluorescent imaging technology.

To analyze the feasibility and clinical effect of novel intraoperative navigation of real-time virtual sonography (RVS) combined with indocyanine green (ICG) fluorescent imaging technology in anatomical liver resection (ALR) for hepatocellular carcinoma. The clinical data of 41 patients who underwent ALR using RVS intraoperative navigation combined with ICG fluorescent imaging technology in the Department of Hepatobiliary Surgery of Peking University International Hospital from January 2020 to May 2022 were retrospectively analyzed. RVS was applied to guide the surgical plane through fusing real-time intraoperative ultrasound images with corresponding preoperative CT or MRI images. Operation methods, operation time, intraoperative blood loss, operative margin, hospital stay and postoperative complications were analyzed. The 1-year overall survival rate and tumor-free survival rate of patients were followed up by outpatient review or telephone calls. ALR surgery was performed on each of 41 patients. There were no deaths during perioperative period and postoperative complications occurred in 7 cases (17.1%). The postoperative pathological examinations demonstrated all cases of hepatocellular carcinoma and negative operative margins. The 41 patients were followed up for 12 to 20 months, with a median follow-up time of 14 months. The overall survival rate 1 year after surgery was 100.0% (41/41), 3 patients (7.3%) experienced tumor recurrence, and the tumor-free survival rate of 1 year after surgery was 92.7% (38/41). In conclusion, novel intraoperative navigation of RVS combined with ICG fluorescent imaging technology is safe and feasible in anatomical segmental hepatectomy of hepatocellular carcinoma.

Peri-operative score for elderly patients with resectable hepatocellular carcinoma.

Liver resection is the mainstay for a curative treatment for patients with resectable hepatocellular carcinoma (HCC), also in elderly population. Despite this, the evaluation of patient condition, liver function and extent of disease remains a demanding process with the aim to reduce postoperative morbidity and mortality. To identify new perioperative risk factors that could be associated with higher 90- and 180-d mortality in elderly patients eligible for liver resection for HCC considering traditional perioperative risk scores and to develop a risk score. A multicentric, retrospective study was performed by reviewing the medical records of patients aged 70 years or older who electively underwent liver resection for HCC; several independent variables correlated with death from all causes at 90 and 180 d were studied. The coefficients of Cox regression proportional-hazards model for six-month mortality were rounded to the nearest integer to assign risk factors' weights and derive the scoring algorithm. Multivariate analysis found variables (American Society of Anesthesiology score, high rate of comorbidities, Mayo end stage liver disease score and size of biggest lesion) that had independent correlations with increased 90- and 180-d mortality. A clinical risk score was developed with survival profiles. This score can aid in stratifying this population in order to assess who can benefit from surgical treatment in terms of postoperative mortality.

The Impact of Portal Hypertension Assessment Method on the Outcomes of Hepatocellular Carcinoma Resection: A Meta-Analysis of Matched Cohort and Prospective Studies.

Examine portal hypertension (PHT) impact on postoperative and survival outcomes in hepatocellular carcinoma (HCC) patients after liver resection (LR), specifically exploring distinctions between indirect signs and invasive measurements of PHT. PHT has historically discouraged LR in individuals with HCC due to the elevated risk of morbidity, including liver decompensation (LD). A systematic review was conducted using 3 databases to identify prospective-controlled and matched cohort studies until December 28, 2022. Focus on comparing postoperative outcomes (mortality, morbidity, and liver-related complications) and overall survival in HCC patients with and without PHT undergoing LR. Three meta-analysis models were utilized: for aggregated data (fixed-effects inverse variance model), for patient-level survival data (one-stage frequentist meta-analysis with gamma-shared frailty Cox proportional hazards model), and for pooled data (Freeman-Tukey exact and double arcsine method). Nine studies involving 1124 patients were analyzed. Indirect signs of PHT were not significantly associated with higher mortality, overall complications, PHLF or LD. However, LR in patients with hepatic venous pressure gradient (HVPG) ≥10mmHg significantly increased the risk of overall complications, PHLF, and LD. Despite elevated risks, the procedure resulted in a 5-year overall survival rate of 55.2%. Open LR significantly increased the risk of overall complications, PHLF, and LD. Conversely, PHT did not show a significant association with worse postoperative outcomes in minimally invasive LR. LR in the presence of indirect signs of PHT poses no increased risk of complications. Yet, in HVPG ≥10mmHg patients, LR increases overall morbidity and liver-related complications risk. Transjugular HVPG assessment is crucial for LR decisions. Minimally invasive approach seems to be vital for favorable outcomes, especially in HVPG ≥10mmHg patients.

Inflammation-related prognostic markers in resected hepatocellular carcinoma.

Hepatocellular carcinoma is usually detected late and therapeutic options are unsatisfactory. Despite marked progress in patient care, HCC remains among the deadliest cancers world-wide. While surgical resection remains a key option for early-stage HCC, the 5-year survival rates after surgical resection are limited. One reason for limited outcomes is the lack of reliable prognostic biomarkers to predict HCC recurrence. HCC prognosis has been shown to correlate with different systemic and pathological markers which are associated with patient survival and HCC recurrence. Liver inflammatory processes offer a large variety of systemic and pathological markers which may be exploited to improve the reliability of prognosis and decision making of liver surgeons and hepatologists. The following review aims to dissect the potential tools, targets and prognostic meaning of inflammatory markers in patients with resectable HCC. We analyze changes in circulant cellular populations and assess inflammatory biomarkers as a surrogate of impaired outcomes and provide an overview on predictive gene expression signatures including inflammatory transcriptional patterns, which are representative of poor survival in these patients.

Zinc transporter 1 expression in hepatocellular carcinoma correlates with prognosis: A single-center retrospective study

ObjectivesZinc is crucial in the pathogenesis of hepatocellular carcinoma; however, no reports have examined its association with clinical parameters and zinc transporter 1 (ZNT1) expression intensity. This study aimed to assess the association between ZNT1 expression and prognosis in patients with hepatocellular carcinoma. MethodsThis retrospective study included 65 patients who underwent surgical hepatocellular carcinoma resection at a single center between January 2011 and June 2015. ZNT1 expression on hepatocellular carcinoma cells from specimens was assessed using immunohistochemistry, and the relationship between its intensity and various clinical indexes was examined with univariate and multivariable analyses and the Mann–Whitney U, Kruskal–Wallis, Bonferroni, and log-rank tests. ResultsZNT1 expression on the hepatocellular carcinoma cell membrane was negative in 31 patients and positive in 34 patients, including nine patients showing strongly positive expression. Patients with and without ZNT1 expression had similar blood zinc concentrations, α-fetoprotein levels, protein induced by vitamin K absence-antagonist-II levels, gross classification, maximal tumor diameters, and background liver disease. The blood zinc concentrations were significantly lower in patients with strongly positive ZNT1 expression (57.0 ± 22.1 μg/dL) than in those with positive ZNT1 expression (71.1 ± 14.2 μg/dL; P = 0.015) or those with no ZNT1 expression (72.9 ± 14.1 μg/dL; P = 0.043). Overall survival was significantly shorter in ZNT1-expressing patients than in non-expressing patients (log-rank test, P = 0.024). Multivariable analysis using the Cox proportional hazards model identified maximal tumor diameter (hazard ratio, 1.018; 95% confidence interval, 1.002–1.034; P = 0.026) and ZNT1 expression status (hazard ratio, 2.082; 95% confidence interval, 1.196–3.621; P = 0.010) as prognostic contributing factors.

Surgical Decision-Making Considerations in Hepatocellular Carcinoma Resection: Safety and Efficacy.

Surgical Decision-Making Considerations in Hepatocellular Carcinoma Resection: Safety and Efficacy.

Treatment strategy for lymph node metastasis of hepatocellular carcinoma using an ICG navigation system: a case report

BackgroundSince indocyanine green (ICG) accumulates selectively in hepatocellular carcinoma (HCC) cells, it can be used to detect metastatic lesions. Lymph node metastasis of HCC is rarely observed, both simultaneously and metachronously. Therefore, it is sometimes difficult to identify metachronous lymph nodes during salvage surgery because of prior surgery. Herein, we report a case in which lymph node metastasis of HCC was successfully resected using an ICG navigation system.Case presentationThe patient was a 62-year-old man who had undergone radical liver resection for HCC 8 years ago. During surveillance, contrast-enhanced computed tomography (CT) revealed a mass in the hepatic hilum. Various diagnostic modalities suggested that the patient had a solitary metastatic lymph node of HCC, and extirpation of the tumor was planned. Intraoperative ICG fluorescence imaging allowed surgeons to clearly identify the target lesion. Histopathologically, the tumor was confirmed to be a lymph node metastasis of HCC. The patient’s postoperative course was uneventful, and he remains alive without recurrence 2 years after the second surgery.ConclusionIntraoperative navigation surgery by ICG fluorescence imaging was useful for the safe resection of extrahepatic metastasis of HCC in a complicated situation.

Prediction of macrotrabecular-massive hepatocellular carcinoma by using MR-based models and their prognostic implications.

To evaluate the efficacy of MRI-based radiomics and clinical models in predicting MTM-HCC. Additionally, to investigate the ability of the radiomics model designed for MTM-HCC identification in predicting disease-free survival (DFS) in patients with HCC. A total of 336 patients who underwent oncological resection for HCC between June 2007 and March 2021 were included. 127 patients in Cohort1 were used for MTM-HCC identification, and 209 patients in Cohort2 for prognostic analyses. Radiomics analysis was performed using volumes of interest of HCC delineated on pre-operative MRI images. Radiomics and clinical models were developed using Random Forest algorithm in Cohort1 and a radiomics probability (RP) of MTM-HCC was obtained from the radiomics model. Based on the RP, patients in Cohort2 were divided into a RAD-MTM-HCC (RAD-M) group and a RAD-non-MTM-HCC (RAD-nM) group. Univariate and multivariate Cox regression analyses were employed to identify the independent predictors for DFS of patients in Cohort2. Kaplan-Meier curves were used to compare the DFS between different groups pf patients based on the predictors. The radiomics model for identifying MTM-HCC showed AUCs of 0.916 (95% CI: 0.858-0.960) and 0.833 (95% CI: 0.675-0.935), and the clinical model showed AUCs of 0.760 (95% CI: 0.669-0.836) and 0.704 (95% CI: 0.532-0.843) in the respective training and validation sets. Furthermore, the radiomics biomarker RP, portal or hepatic vein tumor thrombus, irregular rim-like arterial phase hyperenhancement (IRE) and AFP were independent predictors of DFS in patients with HCC. The DFS of RAD-nM group was significantly higher than that of the RAD-M group (p < .001). MR-based clinical and radiomic models have the potential to accurately diagnose MTM-HCC. Moreover, the radiomics signature designed to identify MTM-HCC also can be used to predict prognosis in patients with HCC, realizing the diagnostic and prognostic aims at the same time.

An Overview of Traditional Chinese Medicine in the Treatment After Radical Resection of Hepatocellular Carcinoma.

According to the Barcelona Clinic Liver Cancer (BCLC) system, radical resection of early stage primary hepatocellular carcinoma (HCC) mainly includes liver transplantation, surgical resection, and radiofrequency ablation (RFA), which yield 5-year survival rates of about 70-79%, 41.3-69.5%, and 40-70%, respectively. The tumor-free 5-year rate for HCC patients undergoing radical resection only reach up to 13.7 months, so the prevention of recurrence after radical resection of HCC is very important for the prognosis of patients. The traditional Chinese medicine (TCM) takes the approach of multitarget and overall-regulation to treat tumors, it can also independently present the "component-target-pathway" related to a particular disease, and its systematic and holistic characteristics can provide a personalized therapy based on symptoms of the patient by treating the patient as a whole. TCM as postoperative adjuvant therapy after radical resection of HCC in Barcelona Clinic liver cancer A or B stages, and the numerous clinical trials confirmed that the efficacy of TCM in the field of HCC has a significant effect, not only improving the prognosis and quality of life but also enhancing patient survival rate. However, with the characteristics of multi-target, multi-component, and multi-pathway, the specific mechanism of Chinese medicine in the treatment of diseases is still unclear. Because of the positive pharmacological activities of TCM in combating anti-tumors, the mechanism studies of TCM have demonstrated beneficial effects on the regulation of immune function, chronic inflammation, the proliferation and metastasis of liver cancer cells, autophagy, and cell signaling pathways related to liver cancer. Therefore, this article reviews the mechanism of traditional Chinese medicine in reducing the recurrence rate of HCC after radical resection.

LBA4 Low-dose stereotactic body radiotherapy prior to pre-operative cemiplimab for patients with resectable hepatocellular carcinoma

LBA4 Low-dose stereotactic body radiotherapy prior to pre-operative cemiplimab for patients with resectable hepatocellular carcinoma

Ablation versus Radiation Segmentectomy for Small Liver Tumors.

Hepatocellular carcinoma (HCC) is a liver malignancy that affects more than a million people worldwide with a complex multifactorial etiology. After the diagnosis of HCC is made, physicians establish management using the Barcelona Clinic Liver Cancer (BCLC) guidelines revolving around tumor stage, liver function, performance status, and patient preferences. According to recent updates to these guidelines, thermal ablation is the second-best curative option apart from surgical resection for small HCC (< 2 cm). While thermal ablation is standard of care, recent studies have suggested that radiation segmentectomy (RS) has similar outcomes, limited hepatotoxicity, and ultimately a cost-efficient approach. Although there is limited literature on RS, this article compares ablation techniques against radiation segmentectomy for small HCC tumors.

A Multicenter Phase 2 Trial Evaluating the Efficacy and Safety of Preoperative Lenvatinib Therapy for Patients with Advanced Hepatocellular Carcinoma (LENS-HCC Trial)

Introduction: The phase III REFLECT trial demonstrated that lenvatinib was superior to sorafenib in terms of progression-free survival (PFS), time to progression, and objective response rate (ORR) for patients with unresectable hepatocellular carcinoma (HCC). This study assessed the efficacy and safety of preoperative lenvatinib therapy for patients with oncologically or technically unresectable HCC. Methods: In this multicenter single-arm phase II trial, patients with advanced HCC and factors suggestive of a poor prognosis (macroscopic vascular invasion, extrahepatic metastasis, or multinodular tumors) were enrolled. Patients with these factors, even with technically resectable HCC, were defined as oncologically unresectable because of the expected poor prognosis after surgery. After 8 weeks of lenvatinib therapy, the patients were assessed for resectability, and tumor resection was performed if the tumor was considered technically resectable. The primary endpoint was the surgical resection rate. The secondary endpoints were the macroscopic curative resection rate, overall survival (OS), ORR, PFS, and the change in the indocyanine green retention rate at 15 min as measured before and after lenvatinib therapy. The trial was registered with the Japan Registry of Clinical Trials (s031190057). Results: Between July 2019 and January 2021, 49 patients (42 oncologically unresectable patients and 7 technically unresectable patients) from 11 centers were enrolled. The ORR was 37.5% based on mRECIST and 12.5% based on RECIST version 1.1. Thirty-three patients underwent surgery (surgical resection rate: 67.3%) without perioperative mortality. The surgical resection rate was 76.2% for oncologically unresectable patients and 14.3% for technically unresectable patients. The 1-year OS rate and median PFS were 75.9% and 7.2 months, respectively, with a median follow-up period of 9.3 months. Conclusions: The relatively high surgical resection rate seen in this study suggests the safety and feasibility of lenvatinib therapy followed by surgical resection for patients with oncologically or technically unresectable HCC.

Correlation between preoperative systemic immune inflammation index, nutritional risk index, and prognosis of radical resection of liver cancer.

Radical surgery is the most commonly used treatment for hepatocellular carcinoma (HCC). However, the surgical effect remains not ideal, and prognostic evaluation is insufficient. Furthermore, clinical intervention is rife with uncertainty and not conducive to prolonging patient survival. To explore correlations between the systemic immune inflammatory index (SII) and geriatric nutritional risk index (GNRI) and HCC operation prognosis. This retrospective study included and collected follow up data from 100 HCC. Kaplan-Meier survival curves were used to analyze the correlation between SII and GNRI scores and survival. SII and GNRI were calculated as follows: SII = neutrophil count × platelet count/lymphocyte count; GNRI = [1.489 × albumin (g/L) + 41.7 × actual weight/ideal weight]. We analyzed the predictive efficacy of the SII and GNRI in HCC patients using receiver operating characteristic (ROC) curves, and the relationships between the SII, GNRI, and survival rate using Kaplan-Meier survival curves. Cox regression analysis was utilized to analyze independent risk factors influencing prognosis. After 1 year of follow-up, 24 patients died and 76 survived. The area under the curve (AUC), sensitivity, specificity, and the optimal cutoff value of SII were 0.728 (95% confidence interval: 0.600-0.856), 79.2%, 63.2%, and 309.14, respectively. According to ROC curve analysis results for predicting postoperative death in HCC patients, the AUC of SII and GNRI combination was higher than that of SII or GNRI alone, and SII was higher than that of GNRI (P < 0.05). The proportion of advanced differentiated tumors, tumor maximum diameter (5-10 cm, > 10 cm), lymph node metastasis, and TNM stage III-IV in patients with SII > 309.14 was higher than that in patients with SII ≤ 309.14 (P < 0.05). The proportion of patients aged > 70 years was higher in patients with GNRI ≤ 98 than that in patients with GNRI > 98 (P < 0.05). The 1-year survival rate of the SII > 309.14 group (compared with the SII ≤ 309.14 group) and GNRI ≤ 98 group (compared with the GNRI > 98 group) was lower (P < 0.05). The prognosis after radical resection of HCC is related to the SII and GNRI and poor in high SII or low GNRI patients.

EpCAM-positive circulating tumor cells and serum AFP levels predict outcome after curative resection of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) has high recurrence rates exceeding 50% despite curative resection. The serum biomarker alpha-fetoprotein (AFP) is a well-known prognostic marker for HCC. EpCAM-positive circulating tumor cells (CTC) have a high predictive value for early HCC recurrence after curatively intended resection, most likely indicating micro-metastases at the time of resection. However, sensitivity remains low. The objective of this study was to evaluate a composite test comprising both CTC and AFP to identify patients at high risk for early HCC recurrence. We prospectively enrolled 58 patients undergoing curative intended resection for HCC at a tertiary referral center. Blood specimens were obtained prior to resection and analyzed for EpCAM-positive CTC and serum AFP levels. A positive result was defined as either detection of CTC or AFP levels ≥ 400 ng/ml. Eight patients tested positive for CTC, seven for AFP, and two for both markers. A positive composite test was significantly associated with shorter early recurrence-free survival (5 vs. 16 months, p = 0.005), time to recurrence (5 vs. 16 months, p = 0.011), and overall survival (37 vs. not reached, p = 0.034). Combining CTC and AFP identified patients with poor outcome after surgical resection, for whom adjuvant or neoadjuvant therapies may be particularly desirable.