RESUMO
Oxaliplatin is a key drug in the treatment of colorectal cancer, but it causes acute and chronic neuropathies in patients. Goshajinkigan (GJG) is a Kampo medicine that is used for the treatments of several neurological symptoms including pain and numbness. More recently, GJG has been reported to prevent the oxaliplatin-induced peripheral neuropathy in clinical studies. No experimental study, however, has been conducted to date to determine the effect of GJG on pain behaviour in a rat model of oxaliplatin-induced neuropathy. Moreover, the impact on the anti-tumour effect of oxaliplatin remains unknown. In the present study, we examined the effects of GJG on the peripheral neuropathy and anti-tumour activity of oxaliplatin in rodents. Repeated administration of oxaliplatin caused cold hyperalgesia from days 3 to 37 and mechanical allodynia from days 21 to 28. Repeated administration of GJG prevented the oxaliplatin-induced cold hyperalgesia but not mechanical allodynia and axonal degeneration in rat sciatic nerve. Single administration of GJG reduced both cold hyperalgesia and mechanical allodynia after the development of neuropathy. In addition, GJG did not affect the anti-tumour effect of oxaliplatin in the tumour cells or tumour cells-implanted mice. These results suggest that GJG relieves the oxaliplatin-induced cold hyperalgesia and mechanical allodynia without affecting anti-tumour activity of oxaliplatin, and, therefore, may be useful for the oxaliplatin-induced neuropathy in clinical practice.
Assuntos
Antineoplásicos/efeitos adversos , Medicamentos de Ervas Chinesas/administração & dosagem , Interações Ervas-Drogas , Compostos Organoplatínicos/efeitos adversos , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/prevenção & controle , Animais , Antineoplásicos/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Hiperalgesia/induzido quimicamente , Hiperalgesia/tratamento farmacológico , Hiperalgesia/prevenção & controle , Masculino , Medicina Kampo , Camundongos , Camundongos Endogâmicos BALB C , Compostos Organoplatínicos/farmacologia , Oxaliplatina , Dor/induzido quimicamente , Dor/tratamento farmacológico , Dor/prevenção & controle , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Ratos , Ratos Sprague-Dawley , Células Tumorais CultivadasRESUMO
BACKGROUND/AIMS: Whether or not generalists and specialist physicians can make an appropriate adaptation of their practice patterns when caring for their patients currently remains a matter of debate. The present study was undertaken to explore whether the clinical characteristics of hepatocellular carcinoma at its time of detection, the initial treatment options and the survival vary between patients with hepatocellular carcinoma associated with cirrhosis who were treated by hepatologists and those who were treated by non-hepatologists. METHODOLOGY: A retrospective study with 626 patients with hepatocellular carcinoma associated with cirrhosis was performed. The patients were stratified into three groups as follows; 1) a hepatologist group: 280 patients followed up and treated consistently by hepatologists, 2) a non-hepatologist group: 126 patients followed up and treated consistently by non-hepatologists, and 3) the other group: 220 patients either followed up by hepatologists and treated by non-hepatologists, or vice versa, or those identified to have tumors incidentally without any follow-up. To confirm the clear difference between generalists and specialists, the gender ratio, age, hepatitis B and C virus markers, serum alpha-fetoprotein level, tumor size, the number of tumors, Child's grade, portal thrombosis at the initial detection, the types of follow-up until the initial detection of hepatocellular carcinoma, the initial treatments chosen, and survival were compared between the hepatologist group and the non-hepatologist group. RESULTS: There were no statistically significant differences between the two groups with respect to gender ratio, age, hepatitis virus markers and the alpha-fetoprotein level. However, the tumor size, the number of tumors, Child's grade and portal thrombosis at the initial detection were more advanced in the non-hepatologist group, which was most likely due to the poorer follow-up until the detection of hepatocellular carcinoma compared with that in the hepatologist group (p value: 0.0237). Regarding therapy for hepatocellular carcinoma, intensive therapies were more often performed in the hepatologist group and, in addition, non-treated cases were less frequently found in the hepatologist group. Consequently, the 1-, 3- and 5-year survivals of the patients in the hepatologist group were 84.7, 61.1 and 35.1%, respectively, which were significantly longer than those in the non-hepatologist group, which were 80.7, 45.8 and 31.8%, respectively (p value: 0.0434). CONCLUSIONS: Hepatocellular carcinoma patients with cirrhosis who were treated by hepatologists can expect to obtain a longer survival because hepatocellular carcinoma tends to be detected at a smaller size, while such patients also usually receive more appropriate treatment modalities.