Cancer burden in the year 2000. The global picture.

Free radicals are ubiquitous in our body and are generated by normal physiological processes, including aerobic metabolism and inflammatory responses, to eliminate invading pathogenic microorganisms. Because free radicals can also inflict cellular damage, several defences have evolved both to protect our cells from radicals--such as antioxidant scavengers and enzymes--and to repair DNA damage. Understanding the association between chronic inflammation and cancer provides insights into the molecular mechanisms involved. In particular, we highlight the interaction between nitric oxide and p53 as a crucial pathway in inflammatory-mediated carcinogenesis.

Radical causes of cancer

The roots and rhizomes of licorice (Glycyrrhiza) species have long been used worldwide as a herbal medicine and natural sweetener. Licorice root is a traditional medicine used mainly for the treatment of peptic ulcer, hepatitis C, and pulmonary and skin diseases, although clinical and experimental studies suggest that it has several other useful pharmacological properties such as antiinflammatory, antiviral, antimicrobial, antioxidative, anticancer activities, immunomodulatory, hepatoprotective and cardioprotective effects. A large number of components have been isolated from licorice, including triterpene saponins, flavonoids, isoflavonoids and chalcones, with glycyrrhizic acid normally being considered to be the main biologically active component. This review summarizes the phytochemical, pharmacological and pharmacokinetics data, together with the clinical and adverse effects of licorice and its bioactive components.

Review of Pharmacological Effects of Glycyrrhiza sp. and its Bioactive Compounds

https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1053/jhep.2001.25087

Increasing incidence and mortality of primary intrahepatic cholangiocarcinoma in the United States.

Cholangiocarcinoma (CCA) is a heterogeneous group of malignancies with features of biliary tract differentiation. CCA is the second most common primary liver tumour and the incidence is increasing worldwide. CCA has high mortality owing to its aggressiveness, late diagnosis and refractory nature. In May 2015, the "European Network for the Study of Cholangiocarcinoma" (ENS-CCA: www.enscca.org or www.cholangiocarcinoma.eu) was created to promote and boost international research collaboration on the study of CCA at basic, translational and clinical level. In this Consensus Statement, we aim to provide valuable information on classifications, pathological features, risk factors, cells of origin, genetic and epigenetic modifications and current therapies available for this cancer. Moreover, future directions on basic and clinical investigations and plans for the ENS-CCA are highlighted.

/pdf/expert-consensus-document-cholangiocarcinoma-current-1ot5rctd8a.pdf

Expert consensus document: Cholangiocarcinoma: current knowledge and future perspectives consensus statement from the European Network for the Study of Cholangiocarcinoma (ENS-CCA)

BACKGROUND

Hepatocellular carcinoma (HCC) occurs in patients with hepatitis C virus-RNA positive chronic liver disease. It is important to prevent HCC with drug administration.



METHODS

A retrospective study was undertaken to evaluate the long term preventive effect of Stronger Neo-Minophagen C (SNMC) on HCC development. SNMC is a Japanese medicine that is commonly administered to patients with chronic hepatitis C to improve the serum alanine aminotransferase (ALT) level. Of 453 patients diagnosed with chronic hepatitis C retrospectively in the study hospital between January 1979 and April 1984, 84 patients (Group A) had been treated with SNMC; SNMC was given at a dose of 100 mL daily for 8 weeks, then 2-7 times a week for 2-16 years (median, 10.1 years). Another group of 109 patients (Group B) could not be treated with SNMC or interferon for a long period of time (median, 9.2 years) and were given other herbal medicine (such as vitamin K). The patients were retrospectively monitored, and the cumulative incidence of HCC and risk factors for HCC were examined.



RESULTS

The 10th-year rates of cumulative HCC incidence for Groups A and B were 7% and 12%, respectively, and the 15th-year rates were 12% and 25%. By Cox regression analysis, the relative risk of HCC incidence in patients not treated with SNMC (Group B) was 2.49 compared with that of patients treated with SNMC (Group A).



CONCLUSIONS

In this study, long term administration of SNMC in the treatment of chronic hepatitis C was effective in preventing liver carcinogenesis. Cancer 1997; 79:1494-500. © 1997 American Cancer Society.

The long term efficacy of glycyrrhizin in chronic hepatitis C patients

Methods. Eighty-three patients with hepatocellular carcinoma (HCC) were treated with curative surgical resection during the past 8 years.



Results. No operative deaths occurred. The cumulative recurrence rates after resection at the ends of years 1, 2, and 3 were 37.0%, 57.1%, and 71.6%, respectively. After adjusting the imbalance in clinical factors among patients by using a Cox proportional-hazards model, it was shown that multiplicity, histologic classification, and absence of antibody to hepatitis C virus were associated significantly with recurrence after resection. The size of the tumor did not affect the incidence of recurrence. Thirty-eight of 41 patients with intrahepatic tumor recurrence had undergone at least one of the following three therapies against HCC: surgical reresection, percutaneous ethanol injection (PEI), and transcatheter arterial embolization (TAE). The most significant factor affecting the survival time of patients with tumor recurrence was the total number of tumor nodules at the time of recurrence. Although surgery and PEI were thought to be more effective treatments than TAE in prolonging life, multivariate analysis showed that they were not significant factors of survival time because choices in the method of treatment were correlated closely with the number of cancer nodules. A 65.3% 5-year survival rate from the time of first surgery was accomplished through vigorous therapy when tumors recurred.



Conclusion. In conclusion, despite the high recurrence rate after resection of HCC, the use of multiple therapies can achieve increased survival rates. Cancer 1993; 71:19-25.

Risk factors for tumor recurrence and prognosis after curative resection of hepatocellular carcinoma.

BACKGROUND

Hepatitis C virus (HCV) infection is a major risk factor for the development of hepatocellular carcinoma. However, the risk factors for primary cholangiocellular carcinoma of the liver (PCC-L) have not been fully investigated. The authors determined the incidence of PCC-L in patients with HCV-related cirrhosis.



METHODS

Between 1980 and 1997, the authors prospectively studied 600 consecutive patients for the appearance of PCC-L; these patients were positive for HCV and later developed cirrhosis. The follow-up period ranged from 0 to 18.5 years (median, 7.2 years).



RESULTS

During the observation period, PCC-L developed in 14 patients (2.3%). Among these, 11 (1.8%) had cholangiocellular carcinomas and the other 3 (0.5%) had a combined type of hepatocellular and cholangiocellular carcinoma. Within the same period, hepatocellular carcinoma (HCC) developed in 206 patients (34.3%). The cumulative rates of newly diagnosed PCC-L were 1.6% at 5 years and 3.5% at 10 years, which was about 1000 times higher than the estimated incidence of PCC-L in the general population of Japan. PCC-L was treated by surgical resection in 3 patients who survived for > 3 years. However, the other 11 patients received palliative therapy or chemotherapy. The survival rates among PCC-L patients were 39.3%, 23.6%, and 16.5% at the end of 1, 3, and 5 years, respectively, and were significantly lower than those of HCC (P = 0.0001).



CONCLUSIONS

The results of this study show a relatively high incidence of PCC-L in patients with HCV-related cirrhosis, and also show that this type of liver cancer is associated with a relatively poor prognosis. These results indicate that HCV-related cirrhosis is a major risk factor for PCC-L in Japanese patients. Cancer 2000;88:2471–7. © 2000 American Cancer Society.

https://acsjournals.onlinelibrary.wiley.com/doi/pdf/10.1002/1097-0142%2820000601%2988%3A11%3C2471%3A%3AAID-CNCR7%3E3.0.CO%3B2-T

Kazuaki Chayama

Papers

The long term efficacy of glycyrrhizin in chronic hepatitis C patients

Risk factors for tumor recurrence and prognosis after curative resection of hepatocellular carcinoma.

Incidence of primary cholangiocellular carcinoma of the liver in Japanese patients with hepatitis C virus–related cirrhosis