Abstract

Intrahepatic cholangiocellular carcinoma (ICC) is an uncommon but lethal cancer. The aim of this study is to assess the factors affecting the survival of ICC patients and to evaluate the benefit of these factors when various therapeutic modalities are used. Between October 2007 and June 2012, 66 ICC cases among 2255 liver cancer patients were identified by pathology and divided into two groups: Group I (surgery group, n = 17) and Group II (nonsurgery group, n = 49). Group II was further divided into Group IIa (those receiving palliative treatment, n = 19) and Group IIb (no treatment received, n = 30). Factors affecting patient survival over the study period were assessed (3- and 6-month results were reported) and therapeutic benefits identified within each of the groups were evaluated. Of the 66 patients identified (male/female = 36/30), 10.6% (7/66) were in the early stages of illness. Overall, the mean patient survival duration was 3.50 ± 0.92 months (1.69–5.31 months). The mean survival duration of Group I patients was 10.50 ± 2.84 months (4.94–16.06 months). The mean survival duration of Group II patients was 3.50 ± 0.65 months (2.24–4.76 months) with Group IIa patients surviving on average 9.50 ± 3.27 months (3.10–15.90 months) and Group IIb patients surviving on average 1.50 ± 0.12 months (1.26–1.74 months). Better survival outcomes were observed in the groups receiving treatment, Group I and Group IIa, than in Group Iib, which did not receive treatment [9.50 ± 1.73 months (6.12–12.89 months) vs. 1.50 ± 0.12 months (1.26–1.74 months), p < 0.001]. Lower albumin, higher bilirubin, higher CA19-9, advanced tumor stage, and no treatment were identified as important predictors of patient mortality at the 3- and 6-month time-points. These factors remained relevant throughout the entire study period (p = 0.002, 0.029, 0.027, 0.028, < 0.001, respectively). This study identified surgery as the treatment that provided the best survival prognosis for patients with ICC. Treatment involving either chemotherapy or radiotherapy could also prolong ICC patient survival. Better liver preservation, lower CA19-9, and less aggressive tumor conditions were identified as factors which play crucial roles in enhancing patient survival.

Abstract

Glucose-6-phosphate dehydrogenase (G6PD), a key regulatory enzyme of the pentose phosphate pathway, catalyses the first rate-limiting reaction to produce ribose-5-phosphate for nucleic acid synthesis and NADPH to use in reductive biosynthesis. The available studies indicate an antioxidant role for G6PD and variation in its levels as a result of cellular insult. In this study, the activity of G6PD was monitored during Nʹ-nitrosodiethylamine (NDEA)-induced hepatic damage in Wistar rats. NDEA generates hepatotoxicity and possesses mutagenic effects. To induce hepatic damage, NDEA was administered at doses of 100 mg kg− 1 body weight week− 1 (i.p.) for 14 days. The animals of the control and treated groups were sacrificed each week. The extent of liver damage was ensured by LFT biomarkers, such as transaminases, ALP, bilirubin and the hepato-somatic index (HSI) along with histopathological observations of H&E and Massons trichrome stained liver specimens. The results of the present study show that at the selected doses, NDEA significantly elevates LFT proteins and bilirubin and damages the lobular architecture in a dose-dependent manner. Software analysis of zymograms indicates maximum activity of the hepatic G6PD levels in day-14 NDEA-treated animals. Our spectrophotometry data further support the above findings on hepatic G6PD levels and demonstrate an approximately 1.63 × and 1.66 × fold increase in day-7 and day-14 NDEA intoxicated animals (P < 0.05). It is concluded that elevation in the G6PD activity is apparently the consequence of NDEA-induced intoxication or oxidative stress, leading to hepatic damage to provide sufficient NADPH for microsomal detoxification and ribose-5-phosphate for DNA synthesis and repair, respectively, to maintain the cellular redox status.