Hepatocellular carcinoma: Current management and future trends

Carr, Brian I.

doi:10.1053/j.gastro.2004.09.036

Cited by 224 publications

(169 citation statements)

References 35 publications

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“…11 Cases of HCC have occurred in a number of metabolic diseases, but Many forms of curative and palliative therapy have been attempted with varying success, and optimal treatment strategies are still controversial. 12,13 Surgical resection works best for small tumors in patients with no underlying liver disease. For patients with multiple small tumors and compensated cirrhosis, liver transplantation offers the possibility of curing the underlying liver disease as well as the tumor.…”

Section: Risk Factors For Hcc and Suspected Etiologiesmentioning

confidence: 99%

Neoplasms of the liver

2007

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Section: Risk Factors For Hcc and Suspected Etiologiesmentioning

confidence: 99%

Neoplasms of the liver

2007

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“…3) In addition, HCC frequently recurs after radical surgery in the residual liver tissue because of progressive disease. 4) Although chemotherapy has been applied to treat the advanced or recurrent HCC, most of anticancer drugs cannot exert the desired effect on HCC because of high chemoresistance rate. 5,6) Local therapies such as percutaneous ethanol injection, 7,8) intratumoral injection [9][10][11] and intra-arterial infusion 12) have been performed to enhance the therapeutic effect of anticancer drugs on HCC.…”

mentioning

confidence: 99%

Effect of Metabolic Inhibitors on the Hepatic Disposition of 5-Fluorouracil after Application to the Rat Liver Surface

Shimokawa

Wakasugi

Tomonaga

et al. 2016

Biological & Pharmaceutical Bulletin

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We evaluated the effects of 5-fluorouracil (5-FU) metabolic inhibitors, gimeracil or uridine, on the hepatic disposition of 5-FU after application to the liver surface in rats, aiming to enhance the availability of 5-FU in the liver. 5-FU solution with or without metabolic inhibitors was applied to the rat liver surface using a cylindrical diffusion cell. The liver, blood and the remaining solution in the diffusion cell were collected at specified times, and assayed for 5-FU content. 5-FU absorption properties were not altered by addition of gimeracil and uridine. The 5-FU concentration in the diffusion cell attachment site of the rat liver (site 1) at 0.1-0.4 M ratios of gimeracil to 5-FU was significantly higher than that of the control. On the contrary, the addition of uridine did not increase the 5-FU concentration at site 1. At a 0.1 M ratio of gimeracil to 5-FU, the maximum 5-FU plasma concentration was the lowest, and the area under the 5-FU concentration-time curve at site 1 was 3.4 times greater than that of the control. We demonstrated that applying 5-FU with gimeracil to the rat liver surface could increase the availability of 5-FU in the liver.Key words liver surface; 5-fluorouracil; disposition; dihydropyrimidine dehydrogenase; gimeracil; uridine Hepatocellular carcinoma (HCC) is the second most frequent cause of cancer-related death worldwide. 1) In many cases, chronic hepatitis and hepatic cirrhosis trigger the development of HCC. 2) Even radical surgery, a potentially curative treatment for HCC, is limited by cancer progression and hepatic functional reserve. 3) In addition, HCC frequently recurs after radical surgery in the residual liver tissue because of progressive disease. 4) Although chemotherapy has been applied to treat the advanced or recurrent HCC, most of anticancer drugs cannot exert the desired effect on HCC because of high chemoresistance rate. 5,6) Local therapies such as percutaneous ethanol injection, 7,8) intratumoral injection 9-11) and intra-arterial infusion 12) have been performed to enhance the therapeutic effect of anticancer drugs on HCC. However, optimal delivery of anticancer drugs to HCC lesion is difficult through these routes because of distribution in the normal surrounding tissue or rapid efflux into the systemic circulation from the injection site.Therefore, we have proposed that the liver surface is a new drug administration route, and investigated the absorption and disposition characteristics of several marker compounds after direct application to the rat liver surface. [13][14][15][16][17][18] To use this route as a local HCC therapy, we showed that 5-fluorouracil (5-FU), a pyrimidine anticancer drug, was site-selectively and continuously delivered in the liver after application to the liver surface in rats. 19,20) We have also investigated other organs as an administration route of 5-FU. 21,22) Although viscous additives to 5-FU solution improved site-selective accumulation of 5-FU, 23) the increase in 5-FU concentration at the application site was not large ...

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“…It is believed that surgical resection or liver transplantation remain to be the mainstays for HCC therapy. [13][14][15][16] With surgical removal, the five-year survival rate of 20-40% can be expected, but local recurrence is highly likely. 17 In well-selected patients, the five-year survival rate after surgical resection can be as high as 70%.…”

mentioning

confidence: 99%

“…[14][15][16] Newer therapeutic approaches are under continuous investigation and development, especially for patients with non-resectable, nontransplantable, and recurrent HCC. While biological therapies such as gene therapy and immunotherapy are largely in their experimental stages, local tumor ablation therapy such as radiofrequency ablation (RFA), ethanol injection, cryotherapy, PDT are potentially useful palliative approaches with variable efficacies.…”

mentioning

confidence: 99%