Combination of IL-34 and AFP improves the diagnostic value during the development of HBV related hepatocellular carcinoma

Abstract Background IL34 involves in host immunity regulated carcinogenesis. Alpha-fetoprotein (AFP) is related to the development of HCC. We explored if combination of IL-34 and APF could improve the diagnostic value in HBV related hepatocellular carcinoma (HBVHCC). Methods Serum was obtained from HBV patients or healthy control. Liver tissue was obtained from liver biopsy in CHB, HBV related cirrhosis patients or curative resection in HBVHCC patients. Serum IL34 and MCSF were measured. Hepatic IL34, MCSF and CD68+ tumor associate macrophages (TAMs) were determined. Results Serum IL34 was 1.7, 1.3 or 2.3-fold higher in HBVHCC than that of CHB, HBV related cirrhosis, or healthy control, which was inhibited following transhepatic arterial chemoembolization (TACE) in HBVHCC patients. Intrahepatic IL34 was higher in HBVHCC than that of the other three groups. Intra-hepatic IL34 was associated with high HBVDNA, HBeAg−, poor differentiation and small tumor size of HBVHCC patients. Intra-hepatic TAMs in HBVHCC were increased 1.7 or 1.3-fold, compared to that from CHB or HBV-cirrhosis patients. Intra-hepatic TAMs were associated with high HBVDNA, high tumor differentiation, small tumor size, abnormal AFP and more tumor number. AFP plus serum IL-34, showed the highest AUC (0.837) with sensitivity (0.632) and highest specificity (0.931), suggesting that AFP plus IL-34 enhances the reliability for prediction of the development of HBVHCC among CHB patients. Conclusions Circulating and intra-hepatic IL34 was upregulated gradually in HBV disease progression from CHB, cirrhosis and HCC. IL-34 may be used as a diagnostic biomarker and potential therapeutic target for the management of HBVHCC.

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Interleukin-34 is associated with hepatocellular carcinoma in chronic hepatitis B patients

10.21203/rs.3.rs-68883/v1 ◽

2020 ◽

Author(s):

Kehui Liu ◽

Yezhou Ding ◽

Yun Wang ◽

Qingqing Zhao ◽

Lei Yan ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Hepatitis B ◽

Tumor Size ◽

Hbv Dna ◽

The Other ◽

Tumor Differentiation ◽

Tumor Number ◽

Control Serum ◽

B Virus ◽

Healthy Control

Abstract Backgrounds: IL‑34 is involved in a number of auto-immunities and cancers. We explored the relationship between serum/hepatic IL‑34 and hepatitis B virus (HBV) related hepatocellular carcinoma (HBV‑HCC) patients.Methods: Serum was obtained from the HBV patients or healthy control with written consents. Liver tissue was obtained from liver biopsy in CHB, HBV related cirrhosis patients or curative resection in HBV‑HCC patients. Serum IL‑34 and MCSF were measured, using ELISA. HepaticIL‑34, MCSF and CD68 were determined, using immunohistochemistry.Results: Serum IL‑34 was 1.7, 1.6 or 1.7 fold higher in HBV‑HCC than that of the other three groups (CHB, HBV related cirrhosis, and healthy control). Serum IL‑34 was significantly reduced after trans‑hepatic arterial chemoembolization (TACE) in HBV‑HCC patients. There was significant correlation between the incidence of HBV‑HCC and IL‑34 (rs=0.160, p<0.05) as well as AFP (rs=0.442, p<0.01). Furthermore, intra-hepatic IL‑34 was higher in HBV‑HCC than that of the other three groups. Intra-hepatic IL‑34 was associated with high HBV‑DNA, HBeAg-, low tumor differentiation and small tumor size of HBV‑HCC patients. Intra-hepaticCD68+ TAMs were increased 1.6 or 1.3 fold in HBV‑HCC compared to that from CHB or HBV-cirrhosis. Intra-hepatic CD68+ TAMs were associated with high HBV‑DNA, high tumor differentiation, big tumor size, abnormal AFP and more tumor number.Conclusions: IL‑34, correlated with HBV‑HCC and IL‑34, may be used as a therapeutic target in precise medicine for management of HBV‑HCC.

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A Real-World Comparative Study of Microwave and Radiofrequency Ablation in Treatment-Naïve and Recurrent Hepatocellular Carcinoma

Journal of Clinical Medicine ◽

10.3390/jcm11020302 ◽

2022 ◽

Vol 11 (2) ◽

pp. 302

Author(s):

Soon Kyu Lee ◽

Dong Jin Chung ◽

Se Hyun Cho

Keyword(s):

Hepatocellular Carcinoma ◽

Radiofrequency Ablation ◽

Survival Rate ◽

High Risk ◽

Complication Rate ◽

Tumor Size ◽

Small Tumor ◽

Recurrent Hepatocellular Carcinoma ◽

Treatment Naïve ◽

Small Tumor Size

The efficacy and safety of microwave ablation (MWA) compared to radiofrequency ablation (RFA) for patients with treatment-naïve and recurrent hepatocellular carcinoma (HCC) has not been clarified in Korea. There were 150 HCC patients (100 in the RFA group and 50 in the MWA group) enrolled in our study. The primary outcome was one- and two-year disease-free survival (DFS). Secondary outcomes were complete response (CR) rate, two-year survival rate, risk factors for DFS and complication rate. Treatment outcomes were also assessed using propensity-score matching (PSM). The MWA group had better one- and two-year DFS than the RFA group (p = 0.035 and p = 0.032, respectively), whereas the CR rate, two-year survival rate, and complication rate were similar between the two groups with fewer major complications in the MWA group (p = 0.043). Patients with perivascular tumors, high risk of recurrence, and small tumor size (≤3 cm) were more suitable for MWA than RFA. MWA was also an independent factor for favorable one- and two-year DFS. Finally, the MWA group still showed better one- and two-year DFS than the RFA group after PSM. In conclusion, MWA could be an alternative treatment to RFA especially in patients with a high risk of recurrence, perivascular tumors, and small tumor size.

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Radiofrequency Ablation With or Without Transcatheter Arterial Chemoembolization in the Treatment of Hepatocellular Carcinoma: A Prospective Randomized Trial

Journal of Clinical Oncology ◽

10.1200/jco.2012.42.9936 ◽

2013 ◽

Vol 31 (4) ◽

pp. 426-432 ◽

Cited By ~ 236

Author(s):

Zhen-Wei Peng ◽

Yao-Jun Zhang ◽

Min-Shan Chen ◽

Li Xu ◽

Hui-Hong Liang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Overall Survival ◽

Prognostic Factors ◽

Transcatheter Arterial Chemoembolization ◽

Recurrence Free Survival ◽

Treatment Allocation ◽

Free Survival ◽

End Point ◽

Tumor Number ◽

Arterial Chemoembolization

Purpose To compare radiofrequency ablation (RFA) with or without transcatheter arterial chemoembolization (TACE) in the treatment of hepatocellular carcinoma (HCC). Patients and Methods A randomized controlled trial was conducted on 189 patients with HCC less than 7 cm at a single tertiary referral center between October 2006 and June 2009. Patients were randomly asssigned to receive TACE combined with RFA (TACE-RFA; n = 94) or RFA alone (n = 95). The primary end point was overall survival. The secondary end point was recurrence-free survival, and the tertiary end point was adverse effects. Results At a follow-up of 7 to 62 months, 34 patients in the TACE-RFA group and 48 patients in the RFA group had died. Thirty-three patients and 52 patients had developed recurrence in the TACE-RFA group and RFA group, respectively. The 1-, 3-, and 4-year overall survivals for the TACE-RFA group and the RFA group were 92.6%, 66.6%, and 61.8% and 85.3%, 59%, and 45.0%, respectively. The corresponding recurrence-free survivals were 79.4%, 60.6%, and 54.8% and 66.7%, 44.2%, and 38.9%, respectively. Patients in the TACE-RFA group had better overall survival and recurrence-free survival than patients in the RFA group (hazard ratio, 0.525; 95% CI, 0.335 to 0.822; P = .002; hazard ratio, 0.575; 95% CI, 0.374 to 0.897; P = .009, respectively). There were no treatment-related deaths. On logistic regression analyses, treatment allocation, tumor size, and tumor number were significant prognostic factors for overall survival, whereas treatment allocation and tumor number were significant prognostic factors for recurrence-free survival. Conclusion TACE-RFA was superior to RFA alone in improving survival for patients with HCC less than 7 cm.

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Outcome of multidisciplinary treatment of peripheral primitive neuroectodermal tumor

Scientific Reports ◽

10.1038/s41598-020-72680-6 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Yidi Liu ◽

Yan Yuan ◽

Fuquan Zhang ◽

Ke Hu ◽

Jie Qiu ◽

...

Keyword(s):

Overall Survival ◽

Tumor Size ◽

Therapeutic Approach ◽

Univariate Analysis ◽

Multidisciplinary Treatment ◽

College Hospital ◽

Small Tumor ◽

Medical College ◽

Treatment Plans ◽

Small Tumor Size

Abstract Peripheral primitive neuroectodermal tumors (PNETs) constitute very rare and aggressive malignancies. To date, there are no standard guidelines for management of peripheral PNETs due to the paucity of cases arising in various body sites. Therapeutic approach is derived from Ewing sarcoma family, which currently remains multimodal. Our study retrospectively analyzed 86 PNET patients from February 1, 1998 to February 1, 2018 at Peking Union Medical College Hospital with an additional 75 patients from review of literature. The clinicopathologic and treatment plans associated with survival was investigated. Surgery, chemotherapy, female sex, small tumor size, no lymph node metastasis, R0 surgical resection, (vincristine + doxorubicin + cyclophosphamide)/(isophosphamide + etoposide) regimen, and more than 10 cycles of chemotherapy were associated with improved overall survival in univariate analysis. Surgery, more than 10 cycles of chemotherapy, and small tumor size were independent prognostic factors for higher overall survival. Our data indicates that multimodal therapy is the mainstay therapeutic approach for peripheral PNET.

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Balloon-Occluded Trans-Arterial Chemoembolization Technique with Alternate Infusion of Cisplatin and Gelatin Slurry for Small Hepatocellular Carcinoma Nodules Adjacent to the Glisson Sheath

BioMed Research International ◽

10.1155/2019/8350926 ◽

2019 ◽

Vol 2019 ◽

pp. 1-9 ◽

Cited By ~ 3

Author(s):

Toshiyuki Irie ◽

Nobuyuki Takahashi ◽

Toshiro Kamoshida

Keyword(s):

Hepatocellular Carcinoma ◽

Contrast Medium ◽

Drug Carrier ◽

Objective Response ◽

Small Hepatocellular Carcinoma ◽

Small Tumor ◽

Study Results ◽

Significant Difference ◽

Tace Group ◽

Arterial Chemoembolization

Objective. It is difficult to control small hepatocellular carcinoma (HCC) nodules adjacent to the Glisson sheath (GS) by trans-arterial chemoembolization (TACE) probably due to multiple small tumor feeders directly branching from the trunk artery. The purpose of this study was to conduct a retrospective evaluation of a new TACE technique called the repeated alternate infusion of cisplatin solution and gelatin slurry distal to balloon occlusion (RAIB-TACE), for the treatment of small HCC nodules adjacent to GS. Materials and Methods. Small nodules less than 4 cm attached to proximal portion of the subsegmental to lobar level portal branch were retrospectively selected. Between January 2011 and April 2014, 29 nodules in 29 patients were treated by super-selective lipiodol TACE/balloon-occluded TACE (B-TACE) (Lip-TACE group). Since April 2014, treatment protocols for small nodules adjacent to GS were changed, and 14 nodules in 12 patients were treated by RAIB-TACE (RAIB-TACE group). In RAIB-TACE group, alternate infusion of cisplatin solution and sparse gelatin slurry (mixture of 80 mg of gelatin fragments and 20 mL of contrast medium) were repeated until arterial flow was ceased. In Lip-TACE group, lipiodol was used as drug carrier and dense gelatin slurry (mixture of 80 mg of gelatin fragments and 2 mL of contrast medium) as embolization material. Dynamic CT/MRI was obtained 1-3 months after TACE, and response of each nodule was evaluated basing on modified RECIST criteria. Results. In RAIB-TACE group, all 14 nodules (100%) were diagnosed as CR or PR. In Lip-TACE group, 18 of 29 (62.1%) were diagnosed as CR or PR. There was a statistically significant difference in objective response ratio between the groups (p=0.008, Fisher’s test). Biloma (n=1) and benign stricture of the right hepatic duct (n=1) were seen in RAIB-TACE group. The biloma shrunk without treatment and the patient had no symptom, but the patient with biliary stricture repeated cholangitis and was treated by administration of antibiotics. Conclusion. The study results show that RAIB-TACE is more effective than lipiodol TACE/B-TACE for small hepatocellular carcinoma adjacent to GS. We speculate that one of the reasons to explain why Lip-TACE is inferior to RAIB-TACE is that viscous lipiodol or dense gelatin slurry could not flow into small tumor feeders effectively.

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P31 Prognostic significance of vascular tumor emboli in 1518 breast carcinoma patients with small tumor size (≤3 cm)

European Journal of Cancer ◽

10.1016/s0959-8049(97)89249-0 ◽

1998 ◽

Vol 34 ◽

pp. S21

Author(s):

J.-Y. Pierga ◽

A. Vincent-Salomon ◽

M. Cousineau ◽

B. Zafrani ◽

B. Asselain ◽

...

Keyword(s):

Breast Carcinoma ◽

Tumor Size ◽

Prognostic Significance ◽

Vascular Tumor ◽

Small Tumor ◽

Tumor Emboli ◽

Small Tumor Size

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The Effect of Transarterial Chemoembolization in Combination With Kang’ai Injection on Patients With Intermediate Stage Hepatocellular Carcinoma: A Prospective Study

Integrative Cancer Therapies ◽

10.1177/1534735417734913 ◽

2017 ◽

Vol 17 (2) ◽

pp. 477-485 ◽

Cited By ~ 7

Author(s):

Yue-Meng Wan ◽

Yu-Hua Li ◽

Zhi-Yuan Xu ◽

Hua-Mei Wu ◽

Ying Xu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Tumor Size ◽

Transarterial Chemoembolization ◽

Intermediate Stage ◽

Primary Endpoints ◽

Tumor Number ◽

Tace Group ◽

Extrahepatic Metastases ◽

A Prospective Study ◽

Postembolization Syndrome

Background: The outcome of patients with intermediate stage hepatocellular carcinoma (HCC) treated by transarterial chemoembolization (TACE) remains poor. Search for a more effective therapy is still necessary. Objective: This study aimed to investigate the effect of combining TACE with Kang’ai (KA) injection for treating patients with intermediate stage HCC. Methods: A total of 89 patients with intermediate stage HCC were enrolled and divided into TACE +KA group (n = 48) receiving repeated TACE plus KA injection, and TACE group (n = 41) receiving repeated TACE alone. All patients were prospectively studied. Primary endpoints were overall survival (OS) and time to radiologic progression (TTP). Results: The TACE + KA group had significantly longer median OS (27.0 vs 21.0 months, P = .038) and TTP (12.0 vs 10.0 months, P = .028) than TACE group. The 1-, 2-, and 3-year OS rates in the TACE + KA group were markedly higher than in TACE group (88.5%, 58.8%, and 20.8% vs 81.3%, 44.9%, and 6.7%, respectively, P = .038), while the 1- and 2-year TTP rates in the TACE + KA group were significantly lower than in TACE group (49.3% and 86.9% vs 75.3% and 100%, P = .028). TACE + KA group displayed significantly lower incidences of intrahepatic and extrahepatic metastases, as well as postembolization syndrome than TACE group ( P < .05). Multivariate analyses revealed group ( P = .023), maximum tumor size ( P = .019), and tumor number ( P = .034) as significant predictors for OS, and group ( P = .046), maximum tumor size ( P = .002) and α-fetoprotein level ( P = .020) as significant predictors for TTP. Both TACE and KA injection were well tolerated. Conclusion: TACE plus KA injection is more effective than TACE alone for treating patients with intermediate stage HCC in this nonrandomized study. Further research is warranted.

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Diagnostic Test of PIVKA-II as A Tumor Marker for Hepatocellular Carcinoma (HCC)

INDONESIAN JOURNAL OF CLINICAL PATHOLOGY AND MEDICAL LABORATORY ◽

10.24293/ijcpml.v26i2.1436 ◽

2020 ◽

Vol 26 (2) ◽

Author(s):

Dwi Priyadi Djatmiko ◽

I Putu Adi Santosa ◽

Elvin Richela Lawanto ◽

Bogi Pratomo ◽

Hani Susianti

Keyword(s):

Hepatocellular Carcinoma ◽

Tumor Marker ◽

Diagnostic Test ◽

Method Comparison ◽

Normal Liver ◽

Diagnostic Value ◽

Roc Curve Analysis ◽

Healthy Control ◽

Cirrhotic Patients ◽

Sensitivity Specificity

Introduction. Alpha-Fetoprotein (AFP) is a tumor marker that has been widely used for HCC, but there has been no increased AFP in 35-45% patients with HCC. Protein induced by vitamin K absence or antagonist II (PIVKA-II) is an abnormal prothrombin secreted in HCC and is expected can be used for HCC diagnostic marker. The objective of this study was to compare serum PIVKA-II levels in the patients with HCC, cirrhosis and healthy control and determine the diagnostic value of PIVKA-II for hepatocellular carcinoma. Methods. This was a cross-section analytic observational study to identify the diagnostic value of PIVKA-II for HCC diagnosis. The diagnosis of 20 cirrhotic patients and 15 patients with HCC was established by history taking, physical examination, and additional examination according to the diagnosis criteria. A group of 12 individuals with normal liver function were used as healthy control subjects. Serum PIVKA-II levels were analyzed with immunoassay method. Comparison study used the Independent-Samples Kruskal Wallis Test. ROC curve analysis and 2x2 contingency table was used to calculate sensitivity, specificity, positive and negative predictive value (PPV and NPV).Results. The serum PIVKA-II level in the patients with HCC was significantly higher than in cirrhotic (p = 0,000) and healthy control patients (p = 0,000). Sensitivity, specificity, PPV, and NPV of PIVKA-II for diagnosis of HCC in cirrhotic patients at a cut-off value of 140.85 mAU/mL were 93.33%, 75%, 73.68%, and 93.75%, respectively (AUC = 0.87).Conclusions and Suggestions. PIVKA-II has high diagnostic value for HCC diagnosis. Diagnostic test that compare serum PIVKA-II level in any size of HCC nodules may be needed in the future.

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Improvement of the primary efficacy of microwave ablation of malignant liver tumors by using a robotic navigation system

Radiology and Oncology ◽

10.2478/raon-2020-0033 ◽

2020 ◽

Vol 54 (3) ◽

pp. 295-300

Author(s):

Jan Schaible ◽

Benedikt Pregler ◽

Niklas Verloh ◽

Ingo Einspieler ◽

Wolf Bäumler ◽

...

Keyword(s):

Tumor Size ◽

Microwave Ablation ◽

Liver Tumors ◽

Multiple Logistic Regression Analysis ◽

Percutaneous Ablation ◽

Primary Efficacy ◽

Robotic Navigation ◽

Liver Malignancies ◽

Small Tumor ◽

Small Tumor Size

AbstractBackgroundThe aim of the study was to assess the primary efficacy of robot-assisted microwave ablation and compare it to manually guided microwave ablation for percutaneous ablation of liver malignancies.Patients and methodsWe performed a retrospective single center evaluation of microwave ablations of 368 liver tumors in 192 patients (36 female, 156 male, mean age 63 years). One hundred and nineteen ablations were performed between 08/2011 and 03/2014 with manual guidance, whereas 249 ablations were performed between 04/2014 and 11/2018 using robotic guidance. A 6-week follow-up (ultrasound, computed tomography and magnetic resonance imaging) was performed on all patients.ResultsThe primary technique efficacy outcome of the group treated by robotic guidance was significantly higher than that of the manually guided group (88% vs. 76%; p = 0.013). Multiple logistic regression analysis indicated that a small tumor size (≤ 3 cm) and robotic guidance were significant favorable prognostic factors for complete ablation.ConclusionsIn addition to a small tumor size, robotic navigation was a major positive prognostic factor for primary technique efficacy.

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