Primary Liver Carcinoma Patients Research Articles

Adjuvant therapy with Huatan Sanjie Granules improves the prognosis of patients with primary liver cancer: a cohort study and the investigation of its mechanism of action based on network pharmacology.

Objective: Nowadays, primary liver carcinoma (PLC) is one of the major contributors to the global cancer burden, and China has the highest morbidity and mortality rates in the world. As a well-known Chinese herbal medicine (CHM) prescription, Huatan Sanjie Granules (HSG) has been used clinically for many years to treat PLC with remarkable efficacy, but the underlying mechanism of action remains unclear. Methods: A clinical cohort study was conducted to observe the overall survival of PLC patients with vs. without oral administration of HSG. Meanwhile, the BATMAN-TCM database was used to retrieve the potential active ingredients in the six herbs of HSG and their corresponding drug targets. PLC-related targets were then screened through the Gene Expression Omnibus (GEO) database. The protein-protein interaction (PPI) network of targets of HSG against PLC was constructed using Cytoscape software. The cell function assays were further carried out for verification. Results: The results of the cohort study showed that the median survival time of PLC patients exposed to HSG was 269days, which was 23days longer than that of the control group (HR, 0.62; 95% CI, 0.38-0.99; p = 0.047). In particular, the median survival time of Barcelona Clinic Liver Cancer stage C patients was 411days in the exposure group, which was 137days longer than that in the control group (HR, 0.59; 95% CI, 0.35-0.96; p = 0.036). Meanwhile, the enrichment analysis result for the obtained PPI network consisting of 362 potential core therapeutic targets suggest that HSG may inhibit the growth of liver cancer (LC) cells by blocking the PI3K-Akt/MAPK signaling pathways. Furthermore, the above prediction results were verified by a series of in vitro assays. Specifically, we found that the expressions TP53 and YWHA2, the targets of the hepatitis B virus signaling pathway, were significantly affected by HSG. Conclusion: HSG shows promising therapeutic efficacy in the adjuvant treatment of PLC.

Diagnostic value of hepatic artery perfusion fraction combined with TGF-β in patients with hepatocellular carcinoma

Diagnostic value of hepatic artery perfusion fraction (HAF) combined with transforming growth factor-β (TGF-β) in the diagnosis of primary liver carcinoma (PLC) was evaluated. The clinical data of 128 PLC patients undergoing radical hepatectomy in Affiliated Hospital of Jining Medical University were regarded as the study group. Seventy-four healthy volunteers examined in Affiliated Hospital of Jining Medical University were collected as the control group. Double-antibody sandwich enzyme-linked immunosorbent assay was used to detect the expression level of serum TGF-β. The upper abdomen of the subjects was scanned by a 64-slice spiral CT, and the perfusion parameters were analyzed and calculated. According to the HAF and the expression level of TGF-β in the two groups, single and combined detection of TGF-β and HAF parameters were detected, respectively, by ROC curve. The expression of TGF-β in serum of the study group was higher than that of the control group (P<0.05). The expression level of serum TGF-β was closely related to total bilirubin, ascites, TNM stage, prothrombin time and tumor diameter. Blood flow (BF), blood volume (BV), permeability surface (PS), HAF and other perfusion parameters in the study group were higher than those in the control group (P<0.05). The specificity and sensitivity of TGF-β expression level in diagnosing PLC were 73 and 93%, respectively; the specificity and sensitivity of HAF parameter in diagnosing PLC were 73 and 100%, respectively; the specificity and sensitivity of HAF parameter combined with TGF-β expression level were 84 and 100%, respectively. TGF-β is highly expressed in serum of PLC patients; HAF parameter combined with TGF-β expression level can improve the specificity and has an important value in the diagnosis of PLC, which is worthy of clinical promotion.

Caregiver reaction of primary liver carcinoma patients and its influencing factors

Objective To explore the current situation and influencing factors of caregiver reaction of primary liver carcinoma patients. Methods From January 2016 to June 2017, we selected 220 caregivers of primary liver carcinoma patients of hepatobiliary and pancreatic surgery in Tumor Hospital, Affiliated to Xinjiang Medical University, as subjects by convenience sampling. All of the patients were investigated with the Caregiver Reaction Assessment (CRA). Results The scores of four dimensions (self-esteem, health and time load, financial load, lack of family support) of CRA were (3.81±0.24), (3.62±0.12), (3.31±0.09) and (2.72±0.03). The influencing factors of self-esteem of caregivers included sexes, family monthly income and education; the influencing factors of health and time load consisted of relationship with patients, family monthly income and education; the relationship with patients, family monthly income and education were the influencing factors of lack of family support; the family monthly income and payment mode of cost were the influencing factors of financial load (P<0.05). Conclusions Clinical medical staff should strengthen the psychological assessment of caregivers and provide targeted intervention with a variety of ways. Key words: Liver neoplasms; Caregiver reaction; Influencing factors

Multi-omics study revealing the complexity and spatial heterogeneity of tumor-infiltrating lymphocytes in primary liver carcinoma.

Intratumoral heterogeneity has been revealed in primary liver carcinoma (PLC). However, spatial heterogeneity of tumor-infiltrating lymphocytes (TILs), which reflects one dimension of a tumor's spatial heterogeneity, and the relationship between TIL diversity, local immune response and mutation burden remain unexplored in PLC. Therefore, we performed immune repertoire sequencing, gene expression profiling analysis and whole-exome sequencing in parallel on five regions of each tumor and on matched adjacent normal tissues and peripheral blood from five PLC patients. A significantly higher cumulative frequency of the top 250 most abundant TIL clones was observed in tumors than in peripheral blood. Besides, overlap rates of T cell receptor (TCR) repertoire for intratumor comparisons, significant higher than those for tumor-adjacent normal tissue comparisons and tumor-blood comparisons, which provide evidence for antigen-driven clonal expansion in PLC. Analysis of the percentage of ubiquitous TCR sequences, regional frequencies of each clone and TIL diversity suggested TIL clones varying between distinct regions of the same tumor, which indicated weak TCR repertoire similarity within a single tumor. Furthermore, correlation analysis revealed that TIL diversity significantly correlated with the expression of immune response genes rather than the mutation load. We conclude that intratumoural T-cell clones are spatially heterogeneous, which can lead to underestimate the immune profile of PLC from a single biopsy sample and may present challenge to adoptive cell therapy using autologous TILs. TIL diversity provides a reasonable explanation for the degree of immune response, implied TIL diversity can serve as a surrogate marker to monitor the effect of immunotherapy.

Gross Tumor Volume is a Better Prognostic Factor than Greatest Tumor Diameter in Primary Liver Carcinoma Patients Treated with Radiotherapy

Gross tumor volume (GTV) should be an independent prognostic factor affecting patients' survival. However, the value of GTV in predicting the prognosis remains to be established. This study evaluated the prognostic significance of GTV and the greatest tumor diameter (GTD) in patients with Child-Pugh A primary liver carcinoma (PLC) who had been treated with radiotherapy.

Dosimetric predictor identification for radiation-induced liver disease after hypofractionated conformal radiotherapy for primary liver carcinoma patients with Child–Pugh Grade A cirrhosis

PurposeRadiation-induced liver disease (RILD) is the most severe complication in liver cancer treatment. The aim of this study was to identify dosimetric predictors for RILD in primary liver carcinoma (PLC) patients with Child–Pugh Grade A cirrhosis after hypofractionated conformal radiotherapy (CRT). Methods and materialsA total of 114 eligible patients (mean age 45years old) were enrolled and treated. The mean gross tumor volume (GTV) was (378.3±308.1) cm3. A median dose of 53Gy was delivered to the PLC by hypofractionated CRT (three fractions/week) with a median fraction size of 4.6Gy (range: 4–6Gy). ResultsPatients were followed up for 1–79months (median 19months) after the completion of irradiation. RILD was diagnosed in nine (7.9%) patients. Univariate analyses revealed that GTV and the percentage of normal liver volume receiving more than 5–40Gy irradiations (V5–40) were related to the risk of developing RILD. Multivariate analyses demonstrated that only GTV and V20 were independent predictors. Using V20 as the predictor for RILD, the accuracy, sensitivity, and specificity was 76.3%, 88.9%, and 75.2%, respectively. ConclusionsOur data suggest that V20 is the unique significant dosimetric predictor for RILD risks in PLC patients with Child–Pugh Grade A cirrhosis after hypofractionated CRT.

Prediction of radiation-induced liver disease by Lyman normal-tissue complication probability model in three-dimensional conformal radiation therapy for primary liver carcinoma

To describe the probability of RILD by application of the Lyman-Kutcher-Burman normal-tissue complication (NTCP) model for primary liver carcinoma (PLC) treated with hypofractionated three-dimensional conformal radiotherapy (3D-CRT). A total of 109 PLC patients treated by 3D-CRT were followed for RILD. Of these patients, 93 were in liver cirrhosis of Child-Pugh Grade A, and 16 were in Child-Pugh Grade B. The Michigan NTCP model was used to predict the probability of RILD, and then the modified Lyman NTCP model was generated for Child-Pugh A and Child-Pugh B patients by maximum-likelihood analysis. Of all patients, 17 developed RILD in which 8 were of Child-Pugh Grade A, and 9 were of Child-Pugh Grade B. The prediction of RILD by the Michigan model was underestimated for PLC patients. The modified n, m, TD50 (1) were 1.1, 0.28, and 40.5 Gy and 0.7, 0.43, and 23 Gy for patients with Child-Pugh A and B, respectively, which yielded better estimations of RILD probability. The hepatic tolerable doses (TD5) would be MDTNL of 21 Gy and 6 Gy, respectively, for Child-Pugh A and B patients. The Michigan model was probably not fit to predict RILD in PLC patients. A modified Lyman NTCP model for RILD was recommended.

Association between Helicobacter infection in liver tissue and primary liver carcinoma

To investigate the relationship between Helicobacter species and primary liver carcinoma (PLC). The liver samples resected during operation from 21 patients with PLC diagnosed by histopathology and 12 patients with other liver diseases as controls were studied. Helicobacter species in liver specimens from the studied subjects were examined by PCR with Helicobacter specific 16SrRNA primers. The amplified products were identified by Southern hybridization and nucleic acid hybridization in situ and sequencing. The specimens were made slices to undergo in situ hybridization of cDNA-mRNA of Helicobacter. Qualitative and quantitative studies were used to assess the correlation of liver tissue helicobacter infection with PLC. Thirteen of the 21 samples (62%) of PLC were positive for Helicobacter specific 16SrRNA gene, while none was positive in the controls (P < 0.01). In situ hybridization results demonstrated a highly Helicobacter 16SrRNA-mRNA positive rate in the PLC group (62%) and none of positive specimen in the control group (P < 0.01). Nine of the Helicobacter specific PCR applicants were sequenced and a homology of 97.80% in comparison with 16SrRNA of H p was found. Helicobacter infection may exist in the liver tissues of PLC patients with a high infection rate, suggesting an association between Helicobacter infection and PLC.

Pharmacokinetics of controlled release morphine (MST) in patients with liver carcinoma

There are no studies reported on the pharmacokinetics of controlled release morphine (MST) in patients with hepatocellular carcinoma, the fifth most common cancer in the world. We have studied the pharmacokinetic profile of MST (30 mg) in 15 patients with liver carcinoma (eight with primary carcinoma on top of chronic hepatitis C, and seven with secondary metastatic liver malignancy as a result of other primary) compared with our previously published data for 10 healthy controls. Plasma morphine concentrations were measured in venous blood samples at intervals up to 12 h by high-pressure liquid chromatography. Total body clearance (Cl) and systemic bioavailability were estimated using a compartmental method. Morphine bioavailability showed a substantial increase in patients with primary liver and secondary metastatic carcinoma than that of controls (64.8, 62.1, and 16.8%, respectively). The area under the serum concentration-time curve increased 4-fold in primary carcinoma (416 [sem25] microg h(-1) litre(-1)) and 3-fold (303 [21] microg h(-1) litre(-1)) in metastatic liver patients compared with healthy control (92.5 [3] microg h(-1) litre(-1)). No significant difference was found in T(max) between the two malignant groups but C(max) was significantly greater in primary liver carcinoma patients. Impaired morphine elimination was noted in primary carcinoma only (t(1/2) 5.99 [0.39] h). Careful administration of morphine is recommended in patients with liver cancer.

Radiation-induced liver disease in three-dimensional conformal radiotherapy for primary liver carcinoma

To identify the risk factors of radiation-induced liver disease (RILD) in three-dimensional conformal radiotherapy (3DCRT) for primary liver carcinoma (PLC) and find a dosimetric threshold for RILD. Between April 1999 and August 2003, 128 patients with PLC were treated by 3DCRT at Cancer Hospital, Guangxi Medical University. All of the patients were technical unresectable or medical inoperable due to poor liver function or cardiovascular diseases. The clinical characteristics of these patients were as follows: 113male, 15 female; median age of 48.2(27–72); with portal vein thrombosis (PVT) in 34 cases, without in 94 cases; liver cirrhosis of Child-Pugh grade A in 108 cases, Child-Pugh grade B 20 cases. 3DCRT was carried out by 8MV x-ray with Topslane treatment planning system. In 48 patients transarterial chemoembolization (TACE) was performed prior to 3DCRT with DDP, ADM and MMC. 3DCRT was delivered by4.88 ± 0.47Gy(4-8Gy)/fraction, three fractions per week (Mon., Wed. Fri.) with a median total dose of 53.6Gy. The mean value of gross target volume (GTV) was 458.92 ± 429.8 cm3. RILD was defined as either anicteric elevation of alkaline phosphatase level of at least twofold and non-malignant ascites (classic RILD), or elevated transaminases of at least fivefold the upper limit of normal or of pre-treatment level(non-classic RILD). The diagnosis of RILD should be distinguished from the progression of PLC, which occurred within 4 months. Parameters evaluated for the occurrence of RILD included: gender, age, GTV, AFP level, HBV, PVT, TACE, Child-Pugh grade of liver cirrhosis. Among 128 patients, 84 patients had complete 3-dimensional dose-volume data, and these dosimetric parameters, including DVH were also analyzed. During a median follow-up time of 17.2 months (4–56) after 3DCRT, 19 patients were diagnosed as RILD with the incidence of 14.8%(19/128). Classic RILD 13cases,non-classic RILD 6 cases. 16 cases died of hepatic failure, 8 of them died within 4 months after completion of radiation with the median survival time of 5.2 (1–14) months. GTV, PVT and Child-Pugh grade of liver cirrhosis had correlation with occurrence of RILD, in favor of small GTV, without PVT and Child-Pugh grade A (p = 0.000, 0.002, 0.001, respectively). The Grade of hepatic toxicity of Common Toxicity Criteria (Version 2.0) during 3DCRT also related to RILD (p = 0.000). Ten of 84 patients, who had 3DCRT dosimetric data developed RILD after treatments. When whole liver volume was taken as a single organ, which included normal liver and tumors, the mean whole liver dose was significantly higher in patients with RILD than those without (27.5Gy ± .8.5Gy vs.33.9Gy ± 5.9Gy,p = 0.027). Multivariate analysis demonstrated that only Child-Pugh grade of liver cirrhosis played an independent factor (p = 0.000, RR = 29.7) for occurrence of RILD with much high incidence for Child-Pugh B patients. In Child-Pugh grade A patients, the threshold of dosimetric parameters, which would not produce >5% of RILD was 81% for V5, 69% for V10, 51% for V15, or 42% for V20.For Child-Pugh A patients, when mean normal liver (excluding tumors) dose was ≤19Gy(33 cases), there was no case of RILD (0%),whereas, when mean normal liver dose was over 19Gy,the incidence of RILD was 2/36(5.6%).The incidence of RILD were 0/38(0%) and 2/31(6.5%), respectively for mean whole liver dose of ≤28Gy and >28Gy. In Child-Pugh grade B patient, the probability of developing RILD was 53% (8/15),which implied that the doses used in this study was not tolerable. Liver cirrhosis was the most critical risk factor for occurrence of RILD when PLC was treated by irradiation. For Child-Pugh grade A patients, the safe threshold dose could be 81% for V5, 69% for V10, 51% for V15, or 42% for V20, and mean normal liver dose of 19Gy or mean whole liver dose of 28Gy when 3DCRT was carried out by fractionation used in this study. The fractionation and total doses implemented in this study was not tolerable for PLC patients with liver cirrhosis of Child-Pugh grade B, and not recommended for the further clinical trials

Radiation-induced liver disease in three-dimensional conformal radiotherapy for primary liver carcinoma

To identify the risk factors of radiation-induced liver disease (RILD) in three-dimensional conformal radiotherapy (3DCRT) for primary liver carcinoma (PLC) and find a dosimetric threshold for RILD. Between April 1999 and August 2003, 128 patients with PLC were treated by 3DCRT at Cancer Hospital, Guangxi Medical University. All of the patients were technical unresectable or medical inoperable due to poor liver function or cardiovascular diseases. The clinical characteristics of these patients were as follows: 113male, 15 female; median age of 48.2(27–72); with portal vein thrombosis (PVT) in 34 cases, without in 94 cases; liver cirrhosis of Child-Pugh grade A in 108 cases, Child-Pugh grade B 20 cases. 3DCRT was carried out by 8MV x-ray with Topslane treatment planning system. In 48 patients transarterial chemoembolization (TACE) was performed prior to 3DCRT with DDP, ADM and MMC. 3DCRT was delivered by4.88 ± 0.47Gy(4-8Gy)/fraction, three fractions per week (Mon., Wed. Fri.) with a median total dose of 53.6Gy. The mean value of gross target volume (GTV) was 458.92 ± 429.8 cm3. RILD was defined as either anicteric elevation of alkaline phosphatase level of at least twofold and non-malignant ascites (classic RILD), or elevated transaminases of at least fivefold the upper limit of normal or of pre-treatment level(non-classic RILD). The diagnosis of RILD should be distinguished from the progression of PLC, which occurred within 4 months. Parameters evaluated for the occurrence of RILD included: gender, age, GTV, AFP level, HBV, PVT, TACE, Child-Pugh grade of liver cirrhosis. Among 128 patients, 84 patients had complete 3-dimensional dose-volume data, and these dosimetric parameters, including DVH were also analyzed. During a median follow-up time of 17.2 months (4–56) after 3DCRT, 19 patients were diagnosed as RILD with the incidence of 14.8%(19/128). Classic RILD 13cases,non-classic RILD 6 cases. 16 cases died of hepatic failure, 8 of them died within 4 months after completion of radiation with the median survival time of 5.2 (1–14) months. GTV, PVT and Child-Pugh grade of liver cirrhosis had correlation with occurrence of RILD, in favor of small GTV, without PVT and Child-Pugh grade A (p = 0.000, 0.002, 0.001, respectively). The Grade of hepatic toxicity of Common Toxicity Criteria (Version 2.0) during 3DCRT also related to RILD (p = 0.000). Ten of 84 patients, who had 3DCRT dosimetric data developed RILD after treatments. When whole liver volume was taken as a single organ, which included normal liver and tumors, the mean whole liver dose was significantly higher in patients with RILD than those without (27.5Gy ± .8.5Gy vs.33.9Gy ± 5.9Gy,p = 0.027). Multivariate analysis demonstrated that only Child-Pugh grade of liver cirrhosis played an independent factor (p = 0.000, RR = 29.7) for occurrence of RILD with much high incidence for Child-Pugh B patients. In Child-Pugh grade A patients, the threshold of dosimetric parameters, which would not produce >5% of RILD was 81% for V5, 69% for V10, 51% for V15, or 42% for V20.For Child-Pugh A patients, when mean normal liver (excluding tumors) dose was ≤19Gy(33 cases), there was no case of RILD (0%),whereas, when mean normal liver dose was over 19Gy,the incidence of RILD was 2/36(5.6%).The incidence of RILD were 0/38(0%) and 2/31(6.5%), respectively for mean whole liver dose of ≤28Gy and >28Gy. In Child-Pugh grade B patient, the probability of developing RILD was 53% (8/15),which implied that the doses used in this study was not tolerable. Liver cirrhosis was the most critical risk factor for occurrence of RILD when PLC was treated by irradiation. For Child-Pugh grade A patients, the safe threshold dose could be 81% for V5, 69% for V10, 51% for V15, or 42% for V20, and mean normal liver dose of 19Gy or mean whole liver dose of 28Gy when 3DCRT was carried out by fractionation used in this study. The fractionation and total doses implemented in this study was not tolerable for PLC patients with liver cirrhosis of Child-Pugh grade B, and not recommended for the further clinical trials

Clinical course and prognosis of one hundred and two patients with hepatic coma 1958 through 1975.

The clinical course and prognosis of hepatic coma were examined in 102 patients treated in the period from 1958 to 1975. The diagnoses included 9 fulminant hepatitis, 7 subacute hepatitis, 53 liver cirrhosis without liver carcinoma (40 cases of the acute type, 10 cases of the chronic type and 3 cases of another type, according to Sherlock's classification of hepatic coma) and 33 liver cirrhosis with primary liver carcinoma. Four of 9 fulminant hepatitis patients gained consciousness within 1 week and recovered completely. Seven subacute hepatitis patients died within 2 weeks after onset of hepatic coma. In the period from 1958 to 1969, 20% of liver cirrhosis patients with the acute type of coma recovered from coma, and in the period from 1970 to 1975, 45% of patients recovered. Seven of 10 patients with the chronic type of coma died between 4 months and 9 years after the onset of coma. Three other patients are presently still alive. The median survival time was 2.5 years. Nine primary liver carcinoma patients with coma were hospitalized from 1958 to 1969 and 24 from 1970 to 1975. Hepatorenal syndrome was present in 31 of 71 examined patients. Twenty-three patients with hepatorenal syndrome were in the period from 1970 to 1975.