Cryoablation combined with radiotherapy for hepatic malignancy:Five case reports

BACKGROUND The survival of patients treated with monotherapy for hepatic malignancies is not ideal.A comprehensive program of cryoablation combined with radiotherapy for the treatment of hepatic malignancies results in less trauma to the patients.It may provide an option for the treatment of patients with advanced hepatic malignancies.CASE SUMMARY We reported 5 cases of advanced-stage hepatic malignancies treated in our hospital from 2017-2018,including 3 cases of primary hepatocellular carcinoma and 2 cases of metastatic hepatic carcinoma.They first received cryoablation therapy on their liver lesions.The procedure consisted of 2 freeze-thaw cycles,and for each session,the duration of freezing was 13-15 min,and the natural rewarming period was 2-8 min.Depending on the tumor size,the appropriate cryoprobes were selected to achieve complete tumor ablation to the greatest extent possible.After cryoablation surgery,intensity-modulated radiotherapy(IMRT)for liver lesions was performed,and the radiotherapy regimen was 5400 cGy/18f and 300 cGy/f.None of the 5 patients had adverse events above grade II,and their quality of life was significantly improved.Among them,4 patients were free of disease progression in the liver lesions under local control,and their survival was prolonged;3 patients are still alive.CONCLUSION Our clinical practice demonstrated that cryoablation combined with IMRT could be implemented safely.The definitive efficacy for hepatic malignancies needs to be confirmed in larger-size sample prospective studies.

Is hepatic neoplasm-related pyogenic liver abscess a distinct clinical entity?

AIM: To compare the clinical characteristics of pyogenic liver abscess (PLA) in patients with and without hepatic neoplasm (HN). METHODS: We performed a retrospective analysis involving patients with PLA. The demographic, clinical features, laboratory and imaging findings, management and outcome of patients with and without HN were studied. RESULTS: From January 2000 to December 2009 inclusive, 318 patients (35 with HN) had PLA, and mean age and comorbidity were comparable between the two groups. More patients with HN experienced right upper quadrant pain (68.6% vs 52.7%, P < 0.04), developed jaundice (14.3% vs 5.7%, P < 0.03) and hepatomegaly (17.1% vs 3.9%, P < 0.01), and had higher serum total bilirubin level (43.3 μmol/L vs 30.0 μmol/L, P = 0.05). Most patients in both groups had PLAs in the right hepatic lobe, and biliary tract disorder was the most common underlying cause (71.4% and 61.8%). However, more PLAs in the HN group were associated with thicker abscess wall (37.1% vs 19.4%, P < 0.01), septal lobulation (77.1% vs 58%, P < 0.02), gaseous cavitation (17% vs 7.8%, P = 0.03), portal thrombophlebitis (11.4% vs 1.8%, P < 0.01) and aerobilia (25.9% vs 5.5%, P < 0.01). Mixed bacterial growth (40% vs 15.2%, P < 0.01) and Gram-negative bacilli (22.8% vs 60.4%, P < 0.01) were dominant isolates in PLAs with and without HN, respectively. Although incidence of the complications was comparable between the two groups, patients with HN had a higher mortality rate than those without (71.4% vs 8.8%, P < 0.01). Multivariate logistic regression analysis revealed underlying active malignancy [odds ratio (OR): 40.45, 95% CI: 14.76-111.65], hypoalbuminemia (OR: 1.22, 95% CI: 1.14-1.38), disseminated intravascular coagulation (OR: 3.32, 95% CI: 1.19-9.69) and acute coronary syndrome (OR: 4.48, 95% CI: 1.08-17.8) were independent risk factors associated with mortality. However, several HN cases, presented concurrently with PLAs, were found to have curative resectable tumors and had good prognosis after surgery. CONCLUSION: PLA associated with HN tends to form a distinct clinical syndrome with a different extent of clinical manifestations, radiological and microbiological features and complications.

Isolated hepatic perfusion for unresectable hepatic malignancies:A systematic review and meta-analysis

AIMTo investigate the effcacy and safety of isolated hepatic perfusion （IHP） in the management of unresectable liver malignancies.METHODSStudies were identified manually and on-line by using PubMed and EMBASE database. We formulate the eligibility criteria according to the PICOS elements, and accessed the quality of studies using the MINORS instrument. Data from all included studies were carefully investigated. We calculated the pooled response rate and incidences of mortality reported from all eligible studiesby using the Meta-Analyst software, and we computed a pooled relative risk （RR） and 95%CI by using the Comprehensive Meta-Analysis software. Heterogeneity was quantifed evaluated using I2 statistic.RESULTS Eight studies, including 502 patients, were selected. Of these, six studies performed IHP, while the other two studies performed percutaneous IHP. The results showed that the pooled response rate was 60.8% （95%CI： 53.1%-68%）, I2 = 37.1%. The median overall survival was 20 mo （range： 12.1 to 25 mo） following IHP or PIHP. The pooled mortality rate was 5.4% （95%CI： 2.5%-11.2%）, I2 = 37.5%. Prognostic factors predict the response to IHP or survival, and were reported in six studies. Meta-analysis demonstrated that Gender was not associated with overall survival （RR = 0.877, 95%CI： 0.564-1.365）; however, carcino-embryonic antigen ≤ 30 ng/mL was associated with a signifcant improvement in survival outcomes with colorectal cancer patients （RR = 2.082, 95%CI： 1.371-3.163）, and there was no signifcant heterogeneity.CONCLUSIONThe present systemic review and meta-analysis suggest that IHP and PIHP are potentially efficient and safe techniques for unresectable liver primary and secondarymalignancies.

Malignant hepatic vascular tumors in adults: Characteristics,diagnostic difficulties and current management

Malignant vascular tumors of the liver include rare primary hepatic mesenchymal tumors developed in the background of a normal liver parenchyma. Most of them are detected incidentally by the increased use of performing imaging techniques. Their diagnosis is challenging, involving clinical and imaging criteria, with final confirmation by histology and immunohistochemistry. Surgery represents the mainstay of treatment. Liver transplantation(LT) has improved substantially the prognosis of hepatic epithelioid hemangioendothelioma(HEHE), with 5-year patient survival rates of up to 81%, based on the European Liver Intestine Transplantation AssociationEuropean Liver Transplant Registry study. Unfortunately, the results of surgery and LT are dismal in cases of hepatic angiosarcoma(HAS). Due to the disappointing results of very short survival periods of approximately 6-7 mo after LT, because of tumor recurrence and rapid progression of the disease, HAS is considered an absolute contraindication to LT. Recurrences after surgical resection are high in cases of HEHE and invariably present in cases of HAS. The discovery of reliable prognostic markers and the elaboration of prognostic scores following LT are needed to provide the best therapeutic choice for each patient.Studies on a few patients have demonstrated the stabilization of the disease in a proportion of patients with hepatic vascular tumors using novel targeted antiangiogenic agents, cytokines or immunotherapy. These new approaches,alone or in combination with other therapeutic modalities, such as surgery and classical chemotherapy, need further investigation to assess their role in prolonging patient survival. Personalized therapeutic algorithms according to the histopathological features, behavior, molecular biology and genetics of the tumors should be elaborated in the near future for the management of patients diagnosed with primary malignant vascular tumors of the liver.

Differentiation of pyogenic hepatic abscesses from malignant mimickers using multislice-based texture acquired from contrast-enhanced computed tomography

BACKGROUND： Pyogenic hepatic abscess may mimic primary or secondary carcinoma of the liver on contrast-enhanced computed tomography（CECT）. The present study was to explore the usefulness of the analysis of multislice-based texture acquired from CECT in the differentiation between pyogenic hepatic abscesses and malignant mimickers.METHODS： This retrospective study included 25 abscesses in 20 patients and 33 tumors in 26 subjects who underwent CECT. To make comparison, we also enrolled 19 patients with hepatic single simple cyst. The images from CECT were analyzed using a Laplacian of Gaussian band-pass filter（5 filter levels with sigma weighting ranging from 1.0 to 2.5）. We also quantified the uniformity, entropy, kurtosis and skewness of the multislice-based texture at different sigma weightings. Statistical significance for these parameters was tested with oneway ANOVA followed by Tukey honestly significant difference（HSD） test. Diagnostic performance was evaluated using the receiver operating characteristic（ROC） curve analysis.RESULTS： There were significant differences in entropy and uniformity at all sigma weightings（P〈0.001） among hepatic abscesses, malignant mimickers and simple cysts. The significant difference in kurtosis and skewness was shown at sigma 1.8 and 2.0 weightings（P=0.002-0.006）. Tukey HSD testshowed that the abscesses had a significantly higher entropy and lower uniformity compared with malignant mimickers（P=0.000-0.004）. Entropy（at a sigma 2.0 weighting） had the largest area under the ROC curve（0.888） in differentiating abscesses from malignant mimickers, with a sensitivity of 81.8% and a specificity of 88.0% when the cutoff value was set to 3.64.CONCLUSION： Multislice-based texture analysis may be useful for differentiating pyogenic hepatic abscesses from malignant mimickers.

Liver transplant for large hepatocellular carcinoma in Malatya: Therole of gamma glutamyl transferase and alpha-fetoprotein, aretrospective cohort study

BACKGROUND There is increasing interest in transplanting patients with hepatocellularcarcinoma (HCC) with tumors greater than 5 cm (Milan criteria).AIM To investigate possible prognostically-useful factors for liver transplantation inHCC patients with large tumors.METHODS In this clinical study, 50 patients with HCC who were transplanted at our LiverTransplant Center between April 2006 and August 2019 and had tumors greaterthan 6 cm maximum diameter were retrospectively analyzed. Their survival andfull clinical characteristics were examined, with respect to serum alphafetoprotein(AFP) and gamma glutamyl transpeptidase (GGT) levels. Kaplan-Meier survival estimates were used to determine overall survival and disease-freesurvival in these patients. The inclusion criterion was evidence of HCC. Exclusioncriteria were the presence of macroscopic portal vein thrombosis or metastasisand a follow-up period of less than 90 d.RESULTS Using receiver operating characteristic curve (ROC) analysis, cutoff values of AFP200 ng/mL and GGT 104 IU/L were identified and used in this study.Significantly longer overall survival (OS) and disease-free-survival (DFS) were found in patients who had lower values of either parameter, compared withhigher values. Even greater differences in survival were found when the 2parameters were combined. Two tumor size bands were identified, in searchingfor the limits of this approach with larger tumors, namely 6-10 cm and > 10 cm.Combination parameters in the 6-10 cm band reflected 5-year OS of 76.2% inpatients with low AFP plus low GGT vs 0% for all other groups. Patients withtumors greater than 10 cm, did not have low AFP plus low GGT. The mostconsistent clinical correlates for longer survival were degree of tumordifferentiation and absence of microscopic portal venous invasion.CONCLUSION Serum levels of AFP and GGT, both alone and combined, represent a simpleprognostic identifier in patients with large HCCs undergoing liver transplantation.

Atezolizumab plus bevacizumab versus sorafenib or atezolizumab alone for unresectable hepatocellular carcinoma:A systematic review

BACKGROUND Despite the use of current standard therapy,the prognosis of patients with unresectable hepatocellular carcinoma(HCC)is poor,with median survival times of 40 mo for intermediate HCC(Barcelona Clinic Liver Cancer[BCLC]stage B)and 6-8 mo for advanced HCC(BCLC stage C).Although patients with earlystage HCC are usually suitable for therapies with curative intention,up to 70% of patients experience relapse within 5 years.In the past decade,the United States Food and Drug Administration has approved different immunogenic treatment options for advanced HCC,the most common type of liver cancer among adults.Nevertheless,no treatment is useful in the adjuvant setting.Since 2007,the multikinase inhibitor sorafenib has been used as a first-line targeted drug to address the increased mortality and incidence rates of HCC.However,in 2020,the IMbrave150 trial demonstrated that combination therapy of atezolizumab(antiprogrammed death-ligand 1[PD-L1])and bevacizumab(anti-vascular endothelial growth factor[VEGF])is superior to sorafenib,a single anti-programmed death 1/PD-L1 antibody inhibitor used as an anti-cancer monotherapy for HCC treatment.AIM To conduct a systematic literature review to evaluate the evidence supporting the efficacy and safety of atezolizumab/bevacizumab as preferred first-line drug therapy over the conventional sorafenib or atezolizumab monotherapies,which are used to improve survival outcomes and reduce disease progression in patients with unresectable HCC and non-decompensated liver disease.METHODS A comprehensive literature review was conducted using the PubMed,Scopus,ScienceDirect,clinicaltrials.gov,PubMed Central,Embase,EuropePMC,and CINAHL databases to identify studies that met the inclusion criteria using relevant MeSH terms.This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and risk of bias(RoB)were assessed using the Cochrane RoB 2 tool and Sevis.RESULTS In the atezolizumab/bevacizumab group,an improvement in overall tumor response,reduction of disease progression,and longer progression-free survival were observed compared to monotherapy with either sorafenib or atezolizumab.Hypertension and proteinuria were the most common adverse events,and the rates of adverse events were comparable to those with the monotherapy.Of the studies,there were two completed trials and two ongoing trials analyzed using high quality and low bias.A more thorough analysis was only performed on the completed trials.CONCLUSION Treatment of HCC with atezolizumab/bevacizumab combination therapy was confirmed to be an effective first-line treatment to improve survival in patients with unresectable HCC and non-decompensated liver disease compared to monotherapy with either sorafenib or atezolizumab.

Intrahepatic biliary injuries associated with radiofrequency ablation of hepatic malignancies

Background Biliary injury after radiofrequency ablation can cause serious consequences including death. However, there are limited data regarding bile duct changes with or without complications associated with radiofrequency ablation of hepatic malignancies. This study aimed to assess the incidence, prognosis and risk factors of intrahepatic biliary injury associated with radiofrequency ablation. Methods Between June 2001 and January 2009, 638 patients with hepatic malignancies （405 with hepatocellular carcinoma, and 233 with liver metastasis） who had 955 treatment sessions were enrolled in this study. Imaging and laboratory data, the course of treatment, and patient outcomes were reviewed retrospectively. The risk factors of biliary injury and the impact on overall survival of patients were analyzed. The chi-square test, Fisher＇s exact test, Kaplan-Meier curves and stepwise Logistic regression model were used for statistical analysis where appropriate. Results Biliary injury was observed in 17 patients after 17 ablation sessions based on imaging findings. The overall incidence of biliary injury was 1.8% （17/955） with an average onset time of 12 weeks （2-36 weeks）. Mild, moderate and severe complications of biliary injury were identified in 9, 6 and 2 cases, respectively. The median survival time after detection of biliary injury was 40 months. There seemed no notable difference in overall survival between patients with and those without biliary injuries. By multivariate analysis, vessel infiltration （P=-0.034） and treatment session 〉4 times （P=0.025） were independent risk factors for biliary injury of hepatocellular carcinoma; while tumor located centrally was the only independent risk factor in the metastasis group （P=0.043）. Conclusions The incidence of biliary injury was not frequent （1.8%）. Through appropriate treatment, intrahepatic bile duct injuries seemed not affect the patients＇ long-term survival. Additionally, risk factors may be helpful for selecting radiofrequency ablation candidates and predicting biliary complications.