In Vivo Anti-Hepatocellular Carcinoma Effects of the Chloroform Root Extract of Clausena excavata Burm.

Liver cancer is the most common cancer among males in Africa. The disease has a poor prognosis and its treatment is associated with toxicity and resistance. For this reason, numerous herbal combinations are being subjected to anticancer screening to circumvent the shortcomings of the conventional anticancer drugs. In the current study, the in vivo anti-cancer effects of the chloroform root extract of the herb, Clausena excavata Burm were investigated. Liver cancer was induced in mice by a single intraperitoneal injection of diethylnitrosamine (DEN) followed by oral administration of the promoter of carcinogenesis, 2-aminoacetyl fluorine that was mixed with the mice feed. The cytotoxicity of the root extract of C. excavata on liver cancer cells was investigated using liver enzyme, histology, DNA fragmentation and caspases assays. Real time qPCR was conducted to evaluate the effect of the extract on apoptotic genes. The findings revealed that the extract of C. excavata significantly decreased the progression of hepatocarcinogenesis and the toxicity-induced production of the liver enzymes, alanine and aspartate aminotransferases. The histological analyses of the liver tissues revealed evidence of apoptotic cell death. The extract also provoked significant (p < .05) expressions of caspase 9 protein and gene as well as other apoptotic genes (P53, P27, Apaf-1, cytochrome C, bax and bid). Therefore, we postulate that the chloroform root extract of C. excavata induces apoptosis of liver cancer in mice.

Oncolytic virus V937 in combination with PD-1 blockade therapy to target immunologically quiescent liver and colorectal cancer.

V937 is an investigational, genetically unmodified Kuykendall strain of coxsackievirus A21, which has been evaluated in the clinic for advanced solid tumor malignancies. V937 specifically infects and lyses tumor cells that overexpress intercellular adhesion molecule-1 (ICAM-1). Intratumoral V937 as a monotherapy and in combination with anti-PD-1 antibody pembrolizumab has shown clinical response in patients with metastatic melanoma, which overexpresses ICAM-1. Here, we investigate in preclinical studies the potential bidirectional cross-talk between hepatocellular carcinomas (HCC) or colorectal carcinomas (CRC) and immune cells when treated with V937 alone or in combination with pembrolizumab. We show that while V937 treatment of tumor cell lines or organoids or peripheral blood mononuclear cells (PBMCs) alone induced a minimal immunological response, V937 treatment of non-contact co-cultures of tumor cell lines or CRC organoids with PBMCs led to robust production of proinflammatory cytokines and immune cell activation. In addition, both recombinant interferon-gamma and pembrolizumab increased ICAM-1 on tumor cell lines or organoids and, in turn, amplified V937-mediated oncolysis and immunogenicity. These findings provide critical mechanistic insights on the cross-talk between V937-mediated oncolysis and immune responses, demonstrating the therapeutic potential of V937 in combination with PD-1 blockade to treat immunologically quiescent cancers.

The timing phase affected the inconsistency of APHE subtypes of liver observations in patients at risk for HCC on the multi-hepatic arterial phase imaging.

OBJECTIVE: To investigate whether liver observations in patients at risk for hepatocellular carcinoma (HCC) display inconsistent arterial phase hyperenhancement (APHE) subtypes on the multi-hepatic arterial phase imaging (mHAP) and to further investigate factors affecting inconsistent APHE subtype of observations on mHAP imaging. METHODS: From April 2018 to June 2021, a total of 141 patients at high risk of HCC with 238 liver observations who underwent mHAP MRI acquisitions were consecutively included in this retrospective study. Two experienced radiologists reviewed individual arterial phase imaging independently and assessed the enhancement pattern of each liver observation according to LI-RADS. Another two experienced radiologists identified and recorded the genuine timing phase of each phase independently. When a disagreement appeared between the two radiologists, another expert participated in the discussion to get a final decision. A separate descriptive analysis was used for all observations scored APHE by the radiologists. The Kappa coefficient was used to determine the agreement between the two radiologists. Univariate analysis was performed to investigate the factors affecting inconsistent APHE subtype of liver observations on mHAP imaging. RESULTS: The interobserver agreement was substantial to almost perfect agreement on the assessment of timing phase (κ = 0.712-0.887) and evaluation of APHE subtype (κ = 0.795-0.901). A total of 87.8% (209/238) of the observations showed consistent nonrim APHE and 10.2% (24/238) of the observations showed consistent rim APHE on mHAP imaging. A total of 2.1% (5/238) of the liver observations were considered inconsistent APHE subtypes, and all progressed nonrim to rim on mHAP imaging. 87.9% (124/141) of the mHAP acquisitions were all arterial phases and 12.1% (17/141) of the mHAP acquisitions obtained both the arterial phase and portal venous phase. Univariate analysis was performed and found that the timing phase of mHAP imaging affected the consistency of APHE subtype of liver observations. When considering the timing phase and excluding the portal venous phase acquired by mHAP imaging, none of the liver observations showed inconsistent APHE subtypes on mHAP imaging. CONCLUSION: The timing phase which mHAP acquisition contained portal venous phase affected the inconsistency of APHE subtype of liver observations on mHAP imaging. When evaluating the APHE subtype of liver observations, it's necessary to assess the timing of each phase acquired by the mHAP technique at first.

2023 Update of Indian National Association for Study of the Liver Consensus on Management of Intermediate and Advanced Hepatocellular Carcinoma: The Puri III Recommendations.

Hepatocellular carcinoma (HCC) presents significant treatment challenges despite considerable advancements in its management. The Indian National Association for the Study of the Liver (INASL) first published its guidelines to aid healthcare professionals in the diagnosis and treatment of HCC in 2014. These guidelines were subsequently updated in 2019. However, INASL has recognized the need to revise its guidelines in 2023 due to recent rapid advancements in the diagnosis and management of HCC, particularly for intermediate and advanced stages. The aim is to provide healthcare professionals with evidence-based recommendations tailored to the Indian context. To accomplish this, a task force was formed, and a two-day round table discussion was held in Puri, Odisha. During this event, experts in their respective fields deliberated and finalized consensus statements to develop these updated guidelines. The 2023 INASL guidelines offer a comprehensive framework for the diagnosis, staging, and management of intermediate and advanced HCC in India. They represent a significant step forward in standardizing clinical practices nationwide, with the primary objective of ensuring that patients with HCC receive the best possible care based on the latest evidence. The guidelines cover various topics related to intermediate and advanced HCC, including biomarkers of aggressive behavior, staging, treatment options, and follow-up care.

ATR-dependent ubiquitin-specific protease 20 phosphorylation confers oxaliplatin and ferroptosis resistance.

Oxaliplatin (OXA) resistance is a major clinic challenge in hepatocellular carcinoma (HCC). Ferroptosis is a kind of iron-dependent cell death. Triggering ferroptosis is considered to restore sensitivity to chemotherapy. In the present study, we found that USP20 was overexpressed in OXA-resistant HCC cells. High expression of USP20 in HCC was associated with poor prognosis. USP20 contributes OXA resistance and suppress ferroptosis in HCC. Pharmacological inhibition or knockdown of USP20 triggered ferroptosis and increased the sensitivity of HCC cells to OXA both in vitro and in vivo. Coimmunoprecipitation results revealed that the UCH domain of USP20 interacted with the N terminal of SLC7A11. USP20 stabilized SLC7A11 via removing K48-linked polyubiquitination of SLC7A11 protein at K30 and K37. Most importantly, DNA damage-induced ATR activation was required for Ser132 and Ser368 phosphorylation of USP20. USP20 phosphorylation at Ser132 and Ser368 enhanced its stability and thus conferred OXA and ferroptosis resistance of HCC cells. Our study reveals a previously undiscovered association between OXA and ferroptosis and provides new insight into mechanisms regarding how DNA damage therapies always lead to therapeutic resistance. Therefore, targeting USP20 may mitigate the development of drug resistance and promote ferroptosis of HCC in patients receiving chemotherapy.

Development of a deep-learning model for classification of LI-RADS major features by using subtraction images of MRI: a preliminary study.

PURPOSE: Liver Imaging Reporting and Data System (LI-RADS) is limited by interreader variability. Thus, our study aimed to develop a deep-learning model for classifying LI-RADS major features using subtraction images using magnetic resonance imaging (MRI). METHODS: This single-center retrospective study included 222 consecutive patients who underwent resection for hepatocellular carcinoma (HCC) between January, 2015 and December, 2017. Subtraction arterial, portal venous, and transitional phase images of preoperative gadoxetic acid-enhanced MRI were used to train and test the deep-learning models. Initially, a three-dimensional (3D) nnU-Net-based deep-learning model was developed for HCC segmentation. Subsequently, a 3D U-Net-based deep-learning model was developed to assess three LI-RADS major features (nonrim arterial phase hyperenhancement [APHE], nonperipheral washout, and enhancing capsule [EC]), utilizing the results determined by board-certified radiologists as reference standards. The HCC segmentation performance was assessed using the Dice similarity coefficient (DSC), sensitivity, and precision. The sensitivity, specificity, and accuracy of the deep-learning model for classifying LI-RADS major features were calculated. RESULTS: The average DSC, sensitivity, and precision of our model for HCC segmentation were 0.884, 0.891, and 0.887, respectively, across all the phases. Our model demonstrated a sensitivity, specificity, and accuracy of 96.6% (28/29), 66.7% (4/6), and 91.4% (32/35), respectively, for nonrim APHE; 95.0% (19/20), 50.0% (4/8), and 82.1% (23/28), respectively, for nonperipheral washout; and 86.7% (26/30), 54.2% (13/24), and 72.2% (39/54) for EC, respectively. CONCLUSION: We developed an end-to-end deep-learning model that classifies the LI-RADS major features using subtraction MRI images. Our model exhibited satisfactory performance in classifying LI-RADS major features.

An Insight into the Novel Immunotherapy and Targeted Therapeutic Strategies for Hepatocellular Carcinoma and Cholangiocarcinoma.

Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) constitute highly malignant forms of primary liver cancers. Hepatocellular and bile duct carcinogenesis is a multiplex process, caused by various genetic and epigenetic alterations, the influence of environmental factors, as well as the implication of the gut microbiome, which was undervalued in the previous years. The molecular and immunological analysis of the above malignancies, as well as the identification of the crucial role of intestinal microbiota for hepatic and biliary pathogenesis, opened the horizon for novel therapeutic strategies, such as immunotherapy, and enhanced the overall survival of cancer patients. Some of the immunotherapy strategies that are either clinically applied or under pre-clinical studies include monoclonal antibodies, immune checkpoint blockade, cancer vaccines, as well as the utilization of oncolytic viral vectors and Chimeric antigen, receptor-engineered T (CAR-T) cell therapy. In this current review, we will shed light on the recent therapeutic modalities for the above primary liver cancers, as well as on the methods for the enhancement and optimization of anti-tumor immunity.

Mutations in TP53 and PIK3CA genes in hepatocellular carcinoma patients are associated with chronic Schistosomiasis.

The purpose of this study was to evaluate the genetic variation of the PIK3CA gene and the histopathological changes in liver tissue of patients with chronic Schistosomiasis to predict hepatocellular carcinoma. In this retrospective, the study samples were taken from 20 patients, divided into chronic schistosomiasis infected group of people (S) and chronic schistosomiasis uninfected group of people (C). The liver tissue biopsy samples for histological examinations were obtained only from chronic Schistosomiasis patients (n = 9). The blood samples were obtained from groups S and C for the mutational analysis of the PIK3CA and TP53 genes. The results suggest that the patients diagnosed with chronic Schistosomiasis were 9 (55%), and healthy patients without Schistosomiasis were 11 (45%). Histological results found that proliferation of fibrosis was observed in the hepatocytes of schistosomiasis patients. A total of 8 mutations (5 male, 3 female) were detected in PIK3CA and TP53 genes. Including 1634 A > G substitution mutations in PIK3CA, which was the only mutation found in males and females among the 8 mutations, accounting 22.22%. PIK3CA gene mutations were found more predominant in male groups as compared to other TP53 gene mutations. In conclusion, this study found that patients with chronic Schistosomiasis are at risk of PIK3CA gene mutations, eventually leading to hepatocytes fibrosis and liver cancer.

Regenerative Liver Surgery - ALPPS and Associated Techniques.

Hepatectomy is the only potentially curative treatment of hepatic tumors, but remains challenging in case of multiple, bilobar lesions and those located in the vicinity of the hepatic hilum and hepatic veins. Regenerative liver surgery utilizes the unique ability of the liver to re-grow after tissue loss and vascular deprivation. All concepts subsumed under this term aim to increase the resectability of hepatic tumors by stimulating growth of future liver remnant. Many of these techniques have evolved over the last decades. ALPPS (associated liver partition and portal vein ligation for staged hepatectomy) is an advanced technique combining portal vein ligation and parenchymal transection which gave rise to many variants, all with the common goal of extending resectability. This article reviews techniques currently available for regenerative liver surgery focusing on ALPPS, its mechanisms of liver regeneration, indications, advantages, drawbacks, results and future perspectives.

Up to Date and Perspectives for Hepatocellular Carcinoma\'s Intraoperative Ultrasound.

With all the technological progress registered so far, hepatocellular carcinoma is still a diagnostic and therapeutic challenge, the optimal management being ensured only by a personalized attitude, offered by a multidisciplinary approach. Ultrasound plays an essential role in the guidelines for this neoplasm, the intraoperative application being mandatory to increase the survival of these patients, when the surgical approach is possible and indicated. This paper highlights the main indications for intraoperative ultrasound in the diagnosis and treatment of hepatocellular carcinoma, along with areas that have developmental potential.

Is There a Role for Surgery in BCLC B Hepatocellular Carcinoma?

Intermediate stage hepatocarcinoma, classified b Barcelona Clinic Liver Cancer (BCLC) comprises a large number of patients, with diverse characteristics, being defined by multiple tumours, preserved liver function and good performance status. The recommended treatment for this stage is transarterial chemoembolization (TACE), but there are a few studies that discuss the role of surgery in this stage. We report a case of a 59-year-old woman diagnosed with BCLC B hepatocarcinoma (two tumours of 34 and 25 mm, in liver segments 5 and 6) who was successfully treated with surgical resection. This patient had additional risk factors like morbid obesity, clinically significant portal hypertension, and thrombocytopenia. Despite these characteristics, the evolution was favourable. In conclusion, we believe that surgery has an important role in the treatment of well-selected BCLC B patients and a good preoperative assessment of the patient can minimize the perioperative risk.

Preoperative prediction of pathologic grade of HCC on gadobenate dimeglumine-enhanced dynamic MRI.

PURPOSE: To evaluate the value of gadobenate dimeglumine-enhanced MRI in predicting the pathologic grade of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Patients with pathologically proven HCC who underwent preoperative gadobenate dimeglumine-enhanced dynamic MRI were included. Two radiologists blinded to pathology results evaluated images in consensus. Lesions were evaluated quantitatively in terms of ratio of enhancement (RE), and qualitatively based on image features related to tumor aggressiveness. Logistic regression and ROC analyses were used to determine the value of these parameters to predict pathologic grade. RESULTS: In total, 221 patients (194 males, 27 females, aged 52.9 ± 11.7 years) with 49 poorly differentiated HCCs and 172 well/moderately differentiated HCCs were evaluated. Features significantly related to poorer pathologic grade at univariate analysis included lower RE in the early arterial phase (EAP) (p = 0.001), nonsmooth margins (p = 0.001), absence of capsule (p < 0.001), arterial peritumoral hyperenhancement (p < 0.001), higher AFP (p = 0.004), multiple tumors (p = 0.026), and larger tumor size (p = 0.028). At multivariate analysis, lower RE (EAP) (OR = 0.144, p = 0.002), absence of capsule (OR = 0.281, p = 0.004), and arterial peritumoral hyperenhancement (OR = 4.117, p < 0.001) were independent predictive factors for poorer pathologic grade. ROC analysis showed lower RE (EAP) was predictive of poorer pathologic grade (AUC = 0.667). AUC increased to 0.797 when combined with absence of capsule and presence of peritumoral hyperenhancement. CONCLUSIONS: Lower RE (EAP), absence of capsule, and arterial peritumoral hyperenhancement were predictive biomarkers for poorer pathologic grade of HCC on gadobenate dimeglumine-enhanced dynamic MRI. KEY POINTS: • Gadobenate dimeglumine-enhanced dynamic MRI was a useful quantitative biomarker for preoperative prediction of pathologic grade in patients with HCC. • Lower RE in the early arterial phase, absence of capsule, and arterial peritumoral hyperenhancement were potential imaging indicators for preoperative prediction of poorer pathologic grade of HCC on gadobenate dimeglumine-enhanced MRI. • A lower RE in the early arterial phase was effective at predicting poorer pathologic grade of HCCs but prediction is improved when combined with absence of capsule and presence of peritumoral hyperenhancement.

Cyanidin 3-glucoside modulated cell cycle progression in liver precancerous lesion, in vivo study.

BACKGROUND: Cyanidin-3-O-glucoside (cyan) exhibits antioxidant and anticancer properties. The cell cycle proteins and antimitotic drugs might be promising therapeutic targets in hepatocellular carcinoma. AIM: To investigate the effect of cyan administration on cell cycle in hepatic precancerous lesion (PCL) induced by diethylnitrosamine/2-acetylaminofluorene (DEN/2-AAF) in Wistar rats. METHODS: In vivo, DEN/2-AAF-induced hepatic PCL, rats were treated with three doses of cyan (10, 15, and 20 mg/kg/d, for four consecutive days per week for 16 wk). Blood and liver tissue samples were collected for measurement of the followings; alpha fetoprotein (AFP) liver function and RNA panel differential expression was evaluated via real time polymerase chain reaction. Histopathological examination of liver sections stained with H&E and immunohistochemical study using glutathione S-transferase placental (GSTP) and proliferating cell nuclear antigen (PCNA) antibodies were assessed. RESULTS: Cyan administration mitigated the effect of DEN/2-AFF induced PCL, decreased AFP levels, and improved liver function. Remarkably, treatment with cyan dose dependently decreased the long non-coding RNA MALAT1 and tubulin gamma 1 mRNA expressions and increased the levels of miR-125b, all of which are involved in cell cycle and mitotic spindle assembly. Of note, cyan decreased GSTP foci percent area and PCNA positively stained nuclei. CONCLUSION: Our results indicated that cyan could be used as a potential therapeutic agent to inhibit liver carcinogenesis in rat model via modulation of cell cycle.

Balloon occluded TACE (B-TACE) vs DEM-TACE for HCC: a single center retrospective case control study.

BACKGROUND: To compare oncological results and safety profile of balloon micro-catheter trans-arterial chemoembolization (b-TACE) and drug-eluting-microsphere (DEM-TACE) in patients with hepatocellular-carcinoma (HCC). METHODS: This is a case-control, retrospective, single-center study. Between January-2015/March-2019, 149 patients (131 males [87.9%]) with 226 HCC were treated, 22 patients (35 HCC; 19 [86.4%] males) with b-TACE and 127 with DEM-TACE (191 HCC, 112 [88.2%] males). Embolization protocol was standardized (sequential 100 ± 25 and 200 ± 25 µm microspheres). Results were evaluated by modified-response-evaluation-criteria-in-solid-tumor [mRECIST] at 1, 3-6 and 9-12 months and time to recurrence after complete response [TTR] at 1 years. Cox's regression weighted with tumor dimensions was performed. Adverse events (AEs) were recorded. RESULTS: mRECIST oncological response at all time points (1, 3-6 and 9-12 months) for both treatments were similar, with the exception of Objective response rate at 9-12 months. Objective response at 1 and 3-6 months between b-TACE vs DEM-TACE [23/35 (65.7%) vs 119/191 (62.3%), 21/29 (72.4%) vs 78/136 (57.4%) (p > 0.05), respectively]. On the contrary, at 9-12 months, it was significantly higher in b-TACE subgroup than DEM-TACE (15/19 [78.9%] vs 48/89 [53.9%], p = 0.05). TTR for complete response at 1 year had a better trend for b-TACE vs DEM-TACE (278.0 days [196.0-342.0] vs 219.0 days [161.0-238.0], OR 0.68 [0.4-1.0], p = 0.10). The use of balloon micro-catheter reduced the relative risk of the event of recurrence by 0.63 [CI95% 0.38-1.04]; p = 0.07). No significant differences were found in AEs rate. CONCLUSION: b-TACE showed a trend of better oncological response over DEM-TACE with and longer TTR with a similar adverse events rate, in patients presenting with larger tumors.

Carbon ion radiotherapy for patients with hepatocellular carcinoma in the caudate lobe carbon ion radiotherapy for hepatocellular carcinoma in caudate lobe.

AIM: The treatment of hepatocellular carcinoma in the caudate lobe (HCCCL) is technically challenging. We aimed to investigate the efficacy and toxicity of carbon ion radiotherapy (C-ion RT) for HCCCL. METHODS: Patients with HCCCL treated with C-ion RT at our hospital between January 2011 and December 2018 were evaluated. The total dose was 52.8 or 60 Gy (relative biological effectiveness) in four or 12 fractions depending on the distance between the tumor and the gastrointestinal tract. The survival outcome, the presence or absence of recurrence (local recurrence, intrahepatic recurrence outside the irradiation field, or extrahepatic recurrence), and acute/late adverse events were evaluated. RESULTS: Nine patients were included. The median tumor size was 3.4 cm, and the median follow-up duration was 18.3 months for all patients. No patient developed local recurrence during follow-up. Five patients subsequently developed intrahepatic recurrence outside the irradiation field and two had extrahepatic metastasis. Five patients died of hepatocellular carcinoma. No acute adverse events of grade ≥2 were observed. Two patients experienced grade 2 or 3 late adverse events, including obstructive jaundice, hepatic encephalopathy, ascites, and edema. CONCLUSION: Carbon ion radiotherapy for HCCCL achieved excellent local control with acceptable adverse events and can thus be a curative treatment option for HCCCL.

Can Hematological Inflammatory Parameters Predict Mortality in Hepatocellular Carcinoma?

PURPOSE: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. Inflammatory and hematological parameters such as neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) provided useful information especially in the diagnosis, treatment, and follow-up of malignancies. In this study, we planned to demonstrate the efficacy of NLR and PLR levels in the evaluation of the prognosis of patients with HCC in our clinic. MATERIAL AND METHODS: This study was planned as a prospective observational cohort study. The study included 105 patients with HCC on the base of cirrhosis. Our study group was classified according to Barcelona Clinic Liver Cancer (BCLC), Okuda staging system, and Milan criteria at the time of admission. RESULTS: The mean age of all cases was 60.6 ± 12.4 years, and 77 (73.3%) of the patients were male. The mean life expectancy of all patients was 7.7 ± 4.3 months. During 1-year follow-up, 61 (58.1%) HCC patients died. The mean survival of the patients who died was 4.6 ± 3.0 months. In our study, patients with NLR > 2.7, patients with PLR > 100.29, BCLC advanced stage, and Okuda advanced stage, and patients who did not meet the Milan criteria had shorter survival duration. NLR > 2.7, BCLC advanced stage, and Child C were determined as independent risk factors affecting mortality. CONCLUSION: There was a strong correlation between NLR-PLR levels and mortality. PLR and NLR levels can be used in conjunction with other staging systems to regulate, monitor, and predict the survival of HCC patients.

JSH Guidelines for the Management of Hepatitis C Virus Infection, 2019 Update; Protective Effect of Antiviral Therapy against Hepatocarcinogenesis.

The Drafting Committee for Hepatitis Management Guidelines established by the Japan Society of Hepatology (JSH) drafted the first version of the clinical practice guidelines for the management of hepatitis C virus (HCV) infection in 2012. Since then, we have been publishing updates as new drugs for hepatitis C become available and new indications for existing drugs are added. The new approval of sofosbuvir/velpatasvir prompted us to publish the seventh version of the guidelines in Japanese in March 2019. We also published the first English-language version of the JSH guidelines in 2013 and English versions of updates made to the Japanese-language guidelines in 2014 and 2016. In 2020, the committee has decided to publish a new English version, covering general information about treatment for hepatitis C, drugs used, recommended treatments for chronic hepatitis and cirrhosis, and special populations, such as patients who have renal impairment, are on dialysis, or have developed recurrence of hepatitis C after liver transplantation. Furthermore, the committee has released a separate publication covering the protective effect of antiviral therapy against hepatocarcinogenesis.

In vivo induction of hepatocellular carcinoma by diethylnitrosoamine and pharmacological intervention in Balb C mice using Bergenia ciliata extracts / Indução in vivo de carcinoma hepatocelular por dietilnitrosoamina e intervenção farmacológica em camundongos balb c usando extratos de Bergenia ciliata

Abstract Background Hepatocellular carcinoma is the most frequent primary malignancy of liver and accounts for as many as one million deaths worldwide in a year. Objectives The aim of the present study was to evaluate the anti-cancerous efficiency of Bergenia ciliata rhizome against diethylnitrosoamine induced hepatocarcinogenesis in Balb C mice. Methods One percent diethylnitrosoamine was prepared by using 99 ml of normal saline NaCl (0.9 percent) solution to which was added 1 ml of concentrated diethylnitrosoamine (DEN) solution (0.01 μg/μl). Extract of Bergenia ciliata was prepared by maceration technique. Mice were classified into four groups as follows: Group 1 a control group (N=7) received saline solution (3.5 μl/mg), group 2 (N=14) received diethylnitrosoamine (3.5 μl/mg) intraperitoneally once in a week for eight consecutive weeks, group 3 (N=7) received plant extract (150 mg/kg (Body weight)) once in a week, while group 4 (N=7) was given combination of diethylnitrosoamine (3.5 μl/mg) and plant extract (150 mg/kg (Body weight)). After eight weeks of DEN induction group 2 mice were divided into two subgroups containing seven mice each, subgroup 1 was sacrificed while subgroup 2 was treated with plant extract (150 mg/kg (Body weight)) once in a week for eight consecutive weeks. Results The model of DEN injected hepatocellular carcinomic (HCC) mice elicited significant decline in levels of albumin with concomitant significant elevations in tumor markers aspartate aminotransferase, alanine aminotransferase (ALT), lactate dehydrogenase (LDH), alpha feto protein (AFP), gamma glutamyl transferase (Y-GT), 5 nucleotidase (5NT), glucose-6-phosphate dehydrogenase (G6PDH) and bilirubin. The intraperitoneal administration of B. ciliata as a protective agent, produced significant increase in albumin levels with significant decrease in the levels of tumor markers aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), alpha feto protein (AFP), gamma glutamyl transferase (Y-GT), 5 nucleotidase (5NT), glucose-6-phosphate dehydrogenase (G6PDH) and bilirubin. Conclusion Bergenia ciliata has potent antioxidant activity, radical scavenging capacity and anticancerous properties. Bergenia ciliata extracts may provide a basis for development of anti-cancerous drug.

Resumo Antecedentes O carcinoma hepatocelular é a neoplasia primária mais frequente do fígado e é responsável por até um milhão de mortes em todo o mundo em um ano. Objetivos O objetivo do presente estudo foi avaliar a eficiência anticancerígena do rizoma de Bergenia ciliata contra a hepatocarcinogênese induzida por dietilnitrosoamina em camundongos balb c. Métodos Um por cento de dietilnitrosoamina foi preparado usando 99 ml de solução salina normal (0,9 por cento) à qual foi adicionado 1 ml de solução concentrada de dietilnitrosoamina (DEN) (0,01 μg / μl). O extrato de Bergenia ciliata foi preparado pela técnica de maceração. Os ratos foram classificados em quatro grupos: Grupo 1 grupo controle (N = 7) recebeu solução salina (3,5 mL / mg), grupo 2 (N = 14) recebeu dietilnitrosoamina (3,5 mL / mg) por via intraperitoneal uma vez por semana para oito semanas consecutivas, o grupo 3 (N = 7) recebeu extrato vegetal (150 mg / kg (peso corporal)) uma vez por semana, enquanto o grupo 4 (N = 7) recebeu combinação de dietilnitrosoamina (3,5 μl / mg) e extrato (150 mg / kg (peso corporal). Após oito semanas do grupo de indução DEN 2 ratos foram divididos em dois subgrupos contendo sete ratos cada, subgrupo 1 foi sacrificado enquanto subgrupo 2 foi tratado com extrato vegetal (150 mg / kg)) uma vez por semana durante oito semanas consecutivas. Resultados O modelo de camundongos hepatocelulares carcinômicos (CHC) injetados com DEN provocou declínio significativo nos níveis de albumina com elevações significativas concomitantes nos marcadores tumorais: aspartato aminotransferase, alanina aminotransferase (ALT), lactato desidrogenase (LDH), proteína alfa feto (AFP), gama glutamiltransferase (Y-GT), 5 nucleotidase (5NT), glicose-6-fosfato ehidrogenase (G6PDH) e bilirrubina. A administração intraperitoneal de B. ciliata como agente protetor produziu um aumento significativo nos níveis de albumina com uma diminuição significativa nos níveis dos marcadores tumorais: aspartato aminotransferase, alanina aminotransferase (ALT), lactato desidrogenase (LDH), proteína alfa feto (AFP), gama glutamiltransferase (Y-GT), 5 nucleotidase (5NT), glicose-6-fosfato desidrogenase (G6PDH) e bilirrubina. Conclusão Bergenia ciliata possui atividade antioxidante potente, capacidade de eliminação de radicais livres e propriedades anticancerígenas. Extratos de Bergenia ciliata podem fornecer uma base para o desenvolvimento de drogas anti-cancerígenas.

Preoperative albumin-bilirubin grade combined with aspartate aminotransferase-to-platelet count ratio index predict outcomes of patients with hepatocellular carcinoma within Milan criteria after liver resection.

There is little information concerning the prognostic significance of combined albumin- bilirubin (ALBI) grade and aspartate aminotransferase-to-platelet count ratio index (APRI) in hepatocellular carcinoma (HCC). Therefore, we performed this study to assess the prognostic utility of combining ALBI and APRI (ALBI-APRI score) for predicting the prognosis of patients with HCC within Milan criteria after liver resection. Two hundred thirty-nine patients were involved in this study. Patients with a high APRI score were allocated a score of 1, whereas patients with a low APRI score were allocated a score of 0. The ALBI-APRI score is the summation of APRI score and ALBI grade. The area under the receiver operating characteristic curve (AUC) was used to estimate the predictive accuracy of different models. During the study period, 132 patients experienced recurrence, and 52 patients died. Multivariate analysis revealed the ALBI-APRI score (HR = 1.753, 95% CI = 1.293-2.377, p < 0.001), presence of microvascular invasion (MVI, HR = 2.693, 95%CI = 1.832-3.960, p < 0.001) and multiple tumors (HR = 1.973, 95% CI = 1.300-2.995, p = 0.001) were all associated with recurrence. In addition, blood transfusion (HR = 3.113, 95% CI = 1.677-5.778, p < 0.001), high preoperative alpha-fetoprotein (AFP, HR = 2.272, 95% CI = 1.298-3.976, p = 0.004), ALBI-APRI score (HR = 2.046, 95% CI = 1.237-3.382, p = 0.005) and presence of MVI (HR = 4.524, 95% CI = 2.514-8.140, p < 0.001) were correlated with postoperative mortality. The AUCs of ALBI-APRI score were significantly higher than either ALBI or APRI alone for predicting both postoperative recurrence and mortality. ALBI-APRI score may be a predictor for the prognosis of patients with HCC within Milan criteria following liver resection. A more well-designed and large-scale study are warranted to prove our findings.

PreoperativePredictionoftheExpressionofCK19inHepatocellularCarcinomaby Gd-EOB-DTPAEnhancedMRI / 中山大学学报(医学科学版)

@#【Objective】 To investigate the predictive value of preoperative Gd- EOB- DTPA enhanced MRI in the expression of cytokeratin 19（CK19）in hepatocellular carcinoma（HCC）.【Methods】A total of 102 patients，including 94 male and 8 female，with single HCC confirmed by pathology after operation who underwent preoperative enhanced MRI were retrospectively analyzed. A total of 25 were CK19-positive HCC and 77 were CK19-negative HCC. Two radiologists evaluated MR features including tumor size，tumor margin，intratumoral vessels，signal intensity（SI）on arterial phase （AP） ，enhancement pattern ，arterial rim enhancement ，peritumoral enhancement ，internal cystic or necrotic portion，hemorrhage，intratumoral fat，tumor capsule，vascular invasion，lymph node metastasis，intratumoral septum， target sign on diffusion weighted imaging（DWI）or hepatobiliary phase（HBP），peritumor hypointensity，SI on ADC，SI on HBP ，T1 relaxation times and T1 reduction rate between pre- and post- contrast enhancement. The associations between these imaging features and CK19 expression were investigated. 【Results】SI on AP（P = 0.013），arterial rim enhancement（P = 0.018），target sign on DWI（P = 0.001）and target sign on HBP（P = 0.005）were significantly associated with CK19 expression. Delayed enhanced intratumoral septum（P = 0.042）was associated with CK19 expression between HCCs less than 5 cm. Target sign on DWI（P = 0.001，OR = 4.875，95%CI：1.838~12.927）were independent significant factors of CK19- positive HCC.【Conclusion】Preoperative enhanced MRI with Gd- EOB- DTPA is helpful to predict CK19 expression of HCC.