Safety of ramucirumab treatment in patients with advanced hepatocellular carcinoma and elevated alpha-fetoprotein.

INTRODUCTION: Hepatocellular carcinoma (HCC) is the second most common cause of cancer-induced deaths worldwide, and limited therapeutic options are available for patients with advanced disease. Ramucirumab, a monoclonal antibody that blocks the vascular endothelial growth factor (VEGF) receptor-2, is the first biomarker-selected systemic agent with therapeutic efficacy, tolerability, and favorable patient-reported outcomes in patients with advanced HCC and elevated serum α-fetoprotein levels ≥400 ng/mL, who are resistant or intolerant to sorafenib therapy. However, treatment-induced adverse events (AEs), such as hypertension, proteinuria, bleeding, thromboembolism, and gastrointestinal perforation remain challenging and potentially fatal concerns. AREAS COVERED: This review discusses the published or ongoing studies and subgroup analyses on ramucirumab therapy in patients with advanced HCC. We present information on the risks of ramucirumab-induced common or rare AEs and their management. EXPERT OPINION: Ramucirumab toxicity secondary to VEGF inhibition is similar to the AEs that are known to be associated with other VEGF-blocking antibodies. Common AEs can be safely treated using conventional measures; however, rare and potentially fatal AEs necessitate close monitoring. With regard to the safety profile, more promising ramucirumab-containing combination therapies are likely to pave the future path for effective HCC treatment.

Dietary Melatonin and Glycine Decrease Tumor Growth through Antiangiogenic Activity in Experimental Colorectal Liver Metastasis.

Despite multimodal treatment strategies, clinical outcomes of advanced stage colorectal cancer (CRC) patients remain poor. Neoadjuvant/adjuvant chemotherapy efficacy is limited due to chemoresistance, toxicity, and negative side effects. Since both melatonin and glycine have anti-cancer activities without relevant side effects, this study was designed to investigate their combined effects in experimental CRC liver metastases. CRC metastasis with CC531 cells were induced in male Wistar rats. Melatonin and glycine alone or their combination were supplemented for 14 days (n = 100). Blood parameters, a micro-computed tomography scan (tumor volume over time), and immunohistochemistry for Ki67 and CD31 expression in tumor tissue were compared between groups. Melatonin and glycine alone significantly reduced the tumor volume by 63.2% (p = 0.002) and 43% (p = 0.044) over time, respectively, while tumor volume increased by 8.7% in the controls. Moreover, treatment with melatonin and glycine alone reduced the tumor proliferation index. Most interestingly, the combination therapy did not have any influence on the above-mentioned tumor parameters. The leukocyte count was significantly increased with melatonin at the end of the experiment (p = 0.012) which was due to a high lymphocytes count. Tumor microvascular density was significantly reduced in all treatment groups. The results of this study suggest an inhibitory function for melatonin and glycine alone in the case of CRC liver metastasis growth by acting as natural antiangiogenic molecules, followed by angiogenesis-dependent cancer proliferation and immunomodulation.

YIV-906 potentiated anti-PD1 action against hepatocellular carcinoma by enhancing adaptive and innate immunity in the tumor microenvironment.

YIV-906 (PHY906) is a standardized botanical cancer drug candidate developed with a systems biology approach-inspired by a traditional Chinese herbal formulation, historically used to treat gastrointestinal symptoms including diarrhea, nausea and vomiting. In combination with chemotherapy and/or radiation therapy, preclinical and clinical results suggest that YIV-906 has the potential to prolong survival and improve quality of life for cancer patients. Here, we demonstrated that YIV-906 plus anti-PD1 could eradicate all Hepa 1-6 tumors in all tumor bearing mice. YIV-906 was found to have multiple mechanisms of action to enhance adaptive and innate immunity. In combination, YIV-906 reduced PD1 or counteracted PD-L1 induction caused by anti-PD1 which led to higher T-cell activation gene expression of the tumor. In addition, YIV-906 could reduce immune tolerance by modulating IDO activity and reducing monocytic MDSC of the tumor. The combination of anti-PD1 and YIV-906 generated acute inflammation in the tumor microenvironment with more M1-like macrophages. YIV-906 could potentiate the action of interferon gamma (IFNg) to increase M1-like macrophage polarization while inhibiting IL4 action to decrease M2 macrophage polarization. Flavonoids from YIV-906 were responsible for modulating IDO activity and potentiating IFNg action in M1-like macrophage polarization. In conclusion, YIV-906 could act as an immunomodulator and enhance the innate and adaptive immune response and potentiate anti-tumor activity for immunotherapies to treat cancer.

Uveal Melanoma Metastasis to the Contralateral Eye Structures: A Retrospective Comparative Analysis of 13 Consecutive Patients.

PURPOSE: To report uveal melanoma (UM) metastasis to the contralateral ocular and periocular structures. DESIGN: Retrospective study. PARTICIPANTS: Thirteen patients with UM metastasis to the contralateral ocular and periocular structures were included. METHODS: Clinical records were reviewed retrospectively. MAIN OUTCOME MEASURES: The development and time to onset of contralateral ocular and periocular metastasis, systemic metastasis, and death. RESULTS: Of the 13 000 treated UM patients, 13 patients were diagnosed with UM metastasis to the contralateral ocular and periocular structures. Mean patient age at primary UM diagnosis was 60 years (median, 60 years; range, 37-87 years). The primary uveal melanoma was in the choroid (n = 11) or ciliary body (n = 2) and was treated with brachytherapy (n = 11), proton beam radiotherapy (n = 1), or enucleation (n = 1). Systemic metastasis developed in 11 patients (85%) at a mean of 66 months (median, 34 months; range, 12-216 months) after diagnosis of the primary UM. All 11 patients (100%) showed liver metastasis and 8 patients (62%) also showed extrahepatic metastasis. The sites of metastasis to the contralateral ocular or periocular structures included the choroid in 4 patients (31%), the orbit in 7 patients (54%), and the eyelid in 2 patients (15%). One patient with eyelid metastasis demonstrated concurrent conjunctival nodule. Mean time to diagnosis of contralateral ocular or periocular metastasis was 94 months (median, 48 months; range, 9-375 months). Contralateral choroidal metastasis was multifocal in 3 of 4 patients (75%). Of 7 patients with orbital metastasis, 5 showed extraocular muscle involvement with restricted ocular motility. Treatment for contralateral choroidal metastasis included brachytherapy (n = 2), transpupillary thermotherapy (n = 1), and observation (n = 1). Treatment for contralateral periocular (orbit or eyelid) metastasis was excision (n = 5), external beam radiotherapy (n = 2), and observation (n = 2). Of 13 patients, death was documented in 11 patients at a mean of 17 months (median, 9 months; range, 3-54 months) as a result of systemic UM metastasis (n = 10) or unrelated cause (n = 1). CONCLUSIONS: Metastasis resulting from UM to the contralateral ocular and periocular structures is rare and generally occurs in patients with disseminated metastasis. Orbital tissue is the most common site of involvement, and these patients have short life expectancy.

Quality diet indexes and risk of hepatocellular carcinoma: Findings from the Singapore Chinese Health Study.

There is limited research on the effect of dietary quality on hepatocellular carcinoma (HCC) risk in populations with relatively high risk of HCC. Using data from Singapore Chinese Health Study, a prospective cohort study, of 63 257 Chinese aged 45 to 74, we assessed four diet-quality index (DQI) scores: the Alternative Health Eating Index-2010 (AHEI-2010), Alternate Mediterranean Diet (aMED), Dietary Approaches to Stop Hypertension (DASH) and Heathy Diet Indicator (HDI). We identified 561 incident HCC cases among the cohort participants after a mean of 17.6 years of follow-up. Cox proportional hazard regression model was used to estimate hazard ratio (HR) and 95% confidence interval (CI) for HCC in relation to these DQI scores. Unconditional logistic regression method was used to evaluate the associations between DQIs and HCC risk among a subset of individuals who tested negative for hepatitis B surface antigen (HBsAg). High scores of AHEI-2010, aMED and DASH, representing higher dietary quality, were associated with lower risk of HCC (all Ptrend < .05). Compared with the lowest quartile, HRs (95% CIs) of HCC for the highest quartile of AHEI-2010, aMED and DASH were 0.69 (0.53-0.89), 0.70 (0.52-0.95) and 0.67 (0.51-0.87), respectively. No significant association between HDI and HCC risk was observed. Among HBsAg-negative individuals, similar inverse associations were observed, and the strongest inverse association was for aMED (HRQ4vsQ1 = 0.46, 95% CI: 0.23-0.94, Ptrend = .10). These findings support the notion that adherence to a healthier diet may lower the risk of HCC, suggesting that dietary modification may be an effective approach for primary prevention of HCC.

Effects of Protein and Calorie Restriction on the Metabolism and Toxicity Profile of Irinotecan in Cancer Patients.

Preclinical data suggests that protein and calorie restriction (PCR) might improve treatment tolerability without impairing antitumor efficacy. Therefore, we have studied the influence of PCR on irinotecan pharmacokinetics and toxicity. In this crossover trial, patients with liver metastases of solid tumors were included and randomized to treatment with irinotecan preceded by 5 days of PCR (~ 30% caloric and ~ 70% protein restriction) during the first cycle and a second cycle preceded by a normal diet or vice versa. Pharmacokinetic blood sampling and biopsies of both healthy liver and liver metastases were performed. The primary end point was the relative difference in geometric means for the active metabolite SN-38 concentration in healthy liver analyzed by a linear mixed model. No significant differences were seen in irinotecan (+ 16.8%, P = 0.22) and SN-38 (+ 9.8%, P = 0.48) concentrations between PCR and normal diet in healthy liver, as well as in liver metastases (irinotecan: -38.8%, P = 0.05 and SN-38: -13.8%, P = 0.50). PCR increased irinotecan plasma area under the curve from zero to 24 hours (AUC0-24h ) with 7.1% (P = 0.04) compared with normal diet, whereas the SN-38 plasma AUC0-24h increased with 50.3% (P < 0.001). Grade ≥ 3 toxicity was not increased during PCR vs. normal diet (P = 0.69). No difference was seen in neutropenia grade ≥ 3 (47% vs. 32% P = 0.38), diarrhea grade ≥ 3 (5% vs. 21% P = 0.25), and febrile neutropenia (5% vs. 16% P = 0.50) during PCR vs. normal diet. In conclusion, plasma SN-38 exposure increased dramatically after PCR, whereas toxicity did not change. PCR did not alter the irinotecan and SN-38 exposure in healthy liver and liver metastases. PCR might therefore potentially improve the therapeutic window in patients treated with irinotecan.

Coffee and nonalcoholic fatty liver disease: A review.

Nonalcoholic fatty liver disease (NAFLD) is widely prevalent globally and has no effective treatment. Coffee is one of the most popular beverages in the world and can therefore have a significant impact on public health on account of its health-promoting properties. Evidence from observational, clinical, and animal studies suggests that coffee may play an important role in human health. This article summarizes the effects of coffee on liver health, especially on nonalcoholic fatty liver disease (NAFLD) and its progression: liver fibrosis, cirrhosis and hepatocellular carcinoma. In addition, this article describes the pathogenesis, prevalence, diagnosis, and nutrition guidelines relating to NAFLD. Possible mechanisms responsible for the effects of coffee on the liver are also suggested.

Procyanidin B1, a novel and specific inhibitor of Kv10.1 channel, suppresses the evolution of hepatoma.

Recently, we and other groups revealed that aberrant expression of Kv10.1 channel, a voltage-gated potassium ion channel, contributes to a variety of tumorigenesis process.Potent and selective inhibitor of Kv10.1 is urgently needed, both as pharmacological tools for studying the physiological functions of this enigmatic channel and as potential leads for development of anti-tumor drugs. In this study, Procyanidin B1, a natural compound extracted from the grape seed, was identified as a potent, specific inhibitor, which can inhibit the Kv10.1 channel in a concentration-dependent manner (IC50 = 10.38 ± 0.87 µM), but has negligible effects on other potassium channels, including Kir2.1, HERG or KCNQ1. It was demonstrated that Procyanidin B1 directly binds to Kv10.1 channel and inhibits its currents, without increasing intracellular Ca2+. Further, three amino acids, I550, T552, and Q557 in the C-linker domain of Kv10.1 were found critical for forming the binding pocket of Procyanidin B1 with Kv10.1 channel.In addition, Procyanidin B1 inhibits migration and proliferation of liver cancer cells (HuH-7 cells, HepG2 cells) through inhibiting Kv10.1, but not in Kv10.1 negatively expressed cell lines. Next, we assayed the tumor suppressing effect of Procyanidin B1 on cell line-derived xenograft mouse model. Our data showed that 15 mg/kg Procyanidin B1 can significantly suppress the growth of the tumor (HepG2) with an inhibition rate of about 60.25%. Compared with cisplatin, Procyanidin B1 has no side effect on the normal metabolismof the mice. The present work indicated that Procyanidin B1 is a proming liver cancer anti-tumor drug, and also confirmed that Kv10.1 can serve as a potential, tumor-specific drug target.

Association between Dietary Tomato Intake and the Risk of Hepatocellular Carcinoma: The Singapore Chinese Health Study.

BACKGROUND: Intake of tomato and/or lycopene has been associated with reduced risk of several cancers, but there is no report on the association with risk of hepatocellular carcinoma (HCC). METHODS: The associations of tomato and lycopene consumption with risk of HCC were examined in the Singapore Chinese Health Study, a prospective cohort of 63,257 Chinese ages 45 to 74 years at enrollment. Diet was assessed using a validated semiquantitative food frequency questionnaire. Cox proportional hazard regression models were used to estimate HR and its 95% confidence interval (CI) of HCC with the consumption of tomato and lycopene among all cohort participants, and unconditional logistic regression was used to assess the association by hepatitis B surface antigen (HBsAg) positivity in a nested case-control study. RESULTS: After a mean follow-up of 17.6 years, 561 incident HCC cases were identified. Higher tomato intake was associated with lower risk of HCC after adjustment for potential confounders (P trend < 0.001). Compared with the lowest quartile, HRs (95% CIs) of HCC for the second, third, and fourth quartile of tomato intake were 0.70 (0.56-0.88), 0.73 (0.58-0.92), and 0.63 (0.49-0.81). Among HBsAg-negative individuals, the inverse association remained (P trend = 0.03). There was no association between lycopene intake and HCC risk (P trend = 0.54). CONCLUSIONS: Tomato intake may offer protection against the development of HCC, particularly among individuals without chronic infection with hepatitis B virus. IMPACT: Tomato intake is a low-cost preventative measure against HCC that may help reduce risk due to increasing rates of nonalcoholic fatty liver disease.

Prediagnostic dietary intakes of vitamin A and ß-carotene are associated with hepatocellular-carcinoma survival.

Vitamin A and its precursor (ß-carotene) have been linked with cancer incidence and mortality. However, the relationship between vitamin A and the prognosis of hepatocellular-carcinoma (HCC) is still unknown. Therefore, we investigated whether dietary intakes of vitamin A, retinol, and ß-carotene were associated with survival in patients with HCC who participated in the Guangdong Liver Cancer Cohort (GLCC) study. Patients aged 18-80 years with a diagnosis of incident Primary Liver Cancer (PLC) were enrolled within one month of diagnosis prior to cancer treatment at the Sun Yat-sen University Cancer Center. Dietary information one year before diagnosis of HCC was obtained using a 79-item, validated semiquantitative food frequency questionnaire (FFQ). We restricted the present analysis to 877 HCC patients enrolled in the GLCC between September, 2013 and April, 2017 who had completed FFQ. Cox proportional hazard regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CIs) for overall and HCC-specific survival. After a median follow-up of 797 days, 384 deaths were documented, 343 of which died from HCC. The multivariable-adjusted HRs (95% CI) of overall and HCC-specific survival for the highest versus the lowest quartile were 0.70 (0.53-0.94) and 0.68 (0.50-0.92) for vitamin A, and 0.72 (0.54-0.96) and 0.69 (0.51-0.94) for ß-carotene, respectively. However, no significant association of dietary retinol intakes with survival outcomes was observed. Our observations suggest that higher prediagnostic dietary intakes of vitamin A and ß-carotene were associated with improved overall and HCC-specific survival.

Impact of Branched-Chain Amino Acid Granule Therapy in Patients with Hepatocellular Carcinoma Who Have Normal Albumin Levels and Low Branched-Chain Amino Acid to Tyrosine Ratios.

Serum albumin has been reported to be a useful indicator of liver function and branched-chain amino acid (BCAA) therapy is associated with a lower incidence of hepatocellular carcinoma (HCC). We investigated the impact of BCAA granule therapy on overall survival and disease-specific survival in patients with normal albumin levels and low BCAA to tyrosine ratio (BTR)s who had treatment-naïve HCC. Overall survival and disease-specific survival was analyzed in 78 patients with HCC who were treated (n = 27) or not treated (n = 51) with BCAAs. Twenty-six patients died during the follow-up period. There were 19, 5, and 2 patients who died due to HCC, hepatic failure, and non-liver-related disease, respectively. Multivariate analysis for factors associated with overall survival indicated that BCAA therapy was independently associated with good prognosis in patients with HCC (hazard ratio [HR], 0.317; 95% confidence interval [CI], 0.123-0.813; P = 0.017). In addition, multivariate analysis using competing risks methods indicated that BCAA therapy is independently associated with reduction of disease-specific mortality (HR, 0.216; 95% CI, 0.068-0.689; P = 0.001). In conclusion, BCAA therapy improved both overall survival and disease-specific survival in HCC patients with low BTRs despite having normal albumin levels.

Pre-Operative vs. Peri-Operative Nutrition Supplementation in Hepatic Resection for Cancer: A Systematic Review.

Despite improvements in safety of hepatic resection post-operative complications occur in up to a half of patients. A systematic review was undertaken to compare the effect of pre-operative and peri-operative nutritional supplementation on post-operative outcomes in patients undergoing hepatic resection for malignancy. Included studies were identified through a search of PubMed (1966 to November 2016), Embase (1947 to November 2016) and the Cochrane Library (1993 to November 2016). Eleven studies involving a total of 725 patients were included in this systematic review. BCAA supplementation in the pre-operative and peri-operative period was reported to reduce the overall complication rate by 26.9% (P = 0.01) in one cohort study while pre-operative immunonutrition was shown to reduce post-operative ascites by 25.4% (P =0.012) in another cohort study without affecting the overall complication rate. Four further studies on enteral supplementation failed to show a benefit with regards to post-operative complications. Post-operative mortality was unaffected by pre-operative and peri-operative BCAA. Both pre-operative and peri-operative nutritional supplementation have shown promising results regarding the post-operative course of patients undergoing hepatic resection for malignancy. No randomized controlled study exists directly comparing pre-operative and peri-operative nutrition and this needs to be focused on in future research.

Protective effects of coffee consumption following liver transplantation for hepatocellular carcinoma in cirrhosis.

BACKGROUND: Increasing evidence suggests that coffee consumption might protect against hepatocellular carcinoma (HCC) and liver cirrhosis-associated death risk. Caffeine is a natural antagonist to extracellular adenosine and exhibits experimental tumoricidal activity. AIM: To evaluate if coffee consumption has beneficial effects on HCC recurrence after orthotopic liver transplantation (OLT). METHODS: Coffee consumption of patients before and after OLT for HCC was assessed and correlated with HCC recurrence. HepG2 cells were analysed for proliferation and metastasis potential after treatment with adenosine, in the presence or absence of adenosine receptor antagonists. Expression of adenosine receptors was determined, and known adenosine-mediated cancer pathways inclusive of MAPK and NF-kappa B were tested. RESULTS: Ninety patients underwent OLT for HCC. Sixteen (17.8%) patients experienced HCC recurrence after median time of 11.5 months (range 1-40.5). For overall survival postoperative coffee intake emerged as major factor of hazard reduction in a multivariate analysis (HR = 0.2936, 95% CI = 0.12-0.71, P = 0.006). Those with such postoperative coffee intake (≥3 cups per day) had a longer overall survival than those who consumed less or no coffee: M = 11.0 years, SD = 0.52 years vs. M = 7.48 years, SD = 0.76 years = 4.7, P = 0.029). CONCLUSIONS: Coffee consumption is associated with a decreased risk of HCC recurrence and provides for increased survival following OLT. We suggest that these results might be, at least in part, associated with the antagonist activity of caffeine on adenosine-A2AR mediated growth-promoting effects on HCC cells.

Cytostatic and Anti-tumor Potential of Ajwa Date Pulp against Human Hepatocellular Carcinoma HepG2 Cells.

Ajwa dates (Phoenix dactylifera L.) are used by traditional therapeutic practitioners for several health benefits but most remain to be scientifically validated. In this study, we evaluated the apoptosis-inducing effect of ethanolic extract of Ajwa date pulp (ADP) on human hepatocellular carcinoma (HCC) HepG2 cells. High performance liquid chromatography analysis revealed the presence of polysaccharide ß-D-glucan in ADP extract. Treated HCC cells revealed morphological characteristics of apoptosis under phase contrast microscopy. MTT assay demonstrated significant (p < 0.05) dose- and time-dependent inhibition of HCC cell growth. HCC cells were found to be in late apoptotic stage on treatment with higher doses of ADP extract as depicted by acridine orange/ethidium bromide and Annexin V-FITC/PI double stain. Importantly, ADP extract increased the reactive oxygen species level and decreased the mitochondrial membrane potential in treated HCC cells. Flow cytometry analysis demonstrated that ADP extract induced elevation of S and G2/M phases of cell cycle. Moreover, ADP extract induced apoptosis in HCC cells independent of tumor suppressor genes viz. CHEK2, ATM and TP53. Interestingly, ADP extract did not display any significant effect on normal cell line Vero. This study provides validation that ADP extract can be considered as a safe and natural potential drug candidate against human liver cancer.

Dietary intake of genistein suppresses hepatocellular carcinoma through AMPK-mediated apoptosis and anti-inflammation.

BACKGROUND: Women have a lower risk of hepatocellular carcinoma (HCC) than men, and the decreased possibility of HCC in women is thought to depend on estrogen levels. As a soybean-isoflavone product, genistein has estrogenic activity in various reproductive tissues, because it mimics 17ß-estradiol and binds the estrogen receptor. Though genistein is a known liver cancer suppressor, its effects have not been studies in long-term experiment, where genistein is fed to a female animal model of HCC. METHODS: Mice were treated with diethylnitrosamine (DEN) to induce HCC at 2 weeks of age and fed with supplemental genistein for 5 months, from 40 to 62 weeks of age. RESULTS: The dietary intake of genistein decreased the incidence of HCC and suppressed HCC development. Genistein induced phospho-AMPK in total liver extracts, Hep3B cells, and Raw 264.7 cells, and phospho-AMPK promoted apoptosis in liver and Hep3B cells. Moreover, phospho-AMPK down-regulated pro-inflammatory responses and ameliorated liver damage. A suppressed pro-inflammatory response with increased mitochondrial respiration was concomitantly observed after genistein treatment. CONCLUSIONS: Genistein-mediated AMPK activation increases hepatocyte apoptosis through energy-dependent caspase pathways, suppresses the inflammatory response in resident liver macrophages by increased cellular respiration, and consequently inhibits the initiation and progression of HCC.

Diet Supplementation with Soy Protein Isolate, but Not the Isoflavone Genistein, Protects Against Alcohol-Induced Tumor Progression in DEN-Treated Male Mice.

Diethylnitrosamine-treated male mice were assigned to 4 groups: a casein-based 35% high fat ethanol liquid diet (EtOH), an EtOH diet made with soy protein isolate protein (EtOH/SOY), an EtOH liquid diet supplemented with genistein (EtOH/GEN) and a chow group. EtOH feeding, final concentration 5% (v/v), continued for 16 wks. EtOH increased incidence and multiplicity of basophilic lesions and adenomas compared to the chow group, (p < 0.05). The EtOH/SOY group had reduced adenoma progression when compared to the EtOH and EtOH/GEN group, (p < 0.05). Genistein supplementation had no protective effect. Soy feeding significantly reduced serum ALT concentrations (p < 0.05), decreased hepatic TNFα and CD-14 expression and decreased nuclear accumulation of NFκB protein in EtOH/SOY-treated mice compared to the EtOH group (p < 0.05). With respect to ceramides, high resolution MALDI-FTICR Imaging mass spectrometry revealed changes in the accumulation of long acyl chain ceramide species, in particular C18, in the EtOH group when compared to the EtOH/SOY group. Additionally, expression of acid ceramidase and sphingosine kinase 1 which degrade ceramide into sphingosine and convert sphingosine to sphingosine-1-phosphate (S1P) respectively and expression of S1P receptors S1PR2 and S1PR3 were all upregulated by EtOH and suppressed in the EtOH/SOY group, p < 0.05. EtOH feeding also increased hepatocyte proliferation and mRNA expression of ß-catenin targets, including cyclin D1, MMP7 and glutamine synthase, which were reduced in the EtOH/SOY group, p < 0.05. These findings suggest that soy prevents tumorigenesis by reducing inflammation and by reducing hepatocyte proliferation through inhibition of EtOH-mediated ß-catenin signaling. These mechanisms may involve blockade of sphingolipid signaling.

[Is preoperative systemic chemotherapy recommended for resectable colorectal liver metastases? Oncosurgical aspects]. / Reszekábilis colorectalis eredetu májáttét esetén javasolt-e a preoperatív szisztémás kezelés? Onkosebészeti nézopont.

Surgical resection is still the only curative treatment for colorectal liver metastases, but this is one part of a complex therapy. Nowadays a patient with colorectal liver metastasis is not treated only by a surgeon or by an oncologist or even only by an invasive radiologist. Collective decisions, complement treatments give the only chance to treat these patients for longer time. Patients with colorectal liver metastases could be regarded as patients with chronic disease. Specially interesting are the various treatment options of resectable colorectal liver metastases. The efficiency and necessity of preoperative chemotherapy are still a hot spot in the treatment of resectable liver metastases. In this study, we try to summarize the international and local experiences and the current evidence of the use of preoperative chemotherapy in the treatment of colorectal liver metastases. Orv Hetil. 2018; 159(21): 823-830.

Primary hepatic marginal zone lymphoma: A rare coincidence.

Primary hepatic lymphoma (PHL) is an extremely rare disease and is often misdiagnosed. The optimal therapy is still unclear and the outcomes are uncertain. Among PHLs, a primary hepatic low-grade marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue is still rarer. The present study reports the case of an elderly female diagnosed with PHL (mucosa-associated lymphoid tissue) and treated with single agent rituximab. After 18 months, she had a progressive disease and developed Waldenstorms macroglobulinemia concomitantly. To date, the patient has received 2 cycles of the RCOP (rituximab, cyclophosphamide, vincristine, and prednisone) regimen and patient's condition is presently stable. This case is reported for its rarity and to convey the importance of the meticulous examination of the tissue. Diagnosis of this condition is important, because the disease is treatable.