• Annals of Hepato-Biliary-Pancreatic Surgery
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• v.26 no.4
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• pp.386-394
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• 2022

Splenic artery steal syndrome (SASS) is a cause of graft hypoperfusion leading to the development of biliary tract complications, graft failure, and in some cases to retransplantation. Its management is still controversial since there is no universal consensus about its prophylaxis and consequently treatment. We present a case of SASS that occurred 48 hours after orthotopic liver transplantation (OLTx) in a 56-year-old male patient with alcoholic cirrhosis and severe portal hypertension, and who was successfully treated by splenic artery embolization. A literature search was performed using the PubMed database, and a total of 22 studies including 4,789 patients who underwent OLTx were relevant to this review. A prophylactic treatment was performed in 260 cases (6.2%) through splenic artery ligation in 98 patients (37.7%) and splenic artery banding in 102 (39.2%). In the patients who did not receive prophylaxis, SASS occurred after OLTx in 266 (5.5%) and was mainly treated by splenic artery embolization (78.9%). Splenic artery ligation and splenectomies were performed, respectively, in 6 and 20 patients (2.3% and 7.5%). The higher rate of complications registered was represented by biliary tract complications (9.7% in patients who received prophylaxis and 11.6% in patients who developed SASS), portal vein thrombosis (respectively, 7.3% and 6.9%), splenectomy (4.8% and 20.9%), and death from sepsis (4.8% and 30.2%). Whenever possible, prevention is the best way to approach SASS, considering all the potential damage arising from an arterial graft hypoperfusion. Where clinical conditions do not permit prophylaxis, an accurate risk assessment and postoperative monitoring are mandatory.

• Archives of Plastic Surgery
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• v.36 no.1
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• pp.33-37
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• 2009

Purpose: Liver transplantation is considered as the treatment of choice in many acute and chronic liver diseases, and it is becoming more common. Since successful microscopic anastomosis of hepatic artery is a crucial requirement of successful liver transplantation, we studied and analyzed the result of hepatic artery anastomosis of liver transplantation in our liver transplantation center. Methods: 145 liver transplantations were performed between February 2005 and May 2008. Male to female ratio of the liver transplantation recipients was 3.4 : 1. Anastomosis of portal vein, hepatic vein and biliary tract was performed by the general surgeon, and anastomosis of hepatic artery was performed by the plastic surgeon under the loupe or microscopic vision. After the hepatic artery was reconstructed, anastomosed site status and flow were checked with Doppler ultrasonography intraoperatively and with contrast enhanced CT or angiography postoperatively if necessary. Results: Out of 145 liver transplantations, cadaveric liver donor was used 37 cases and living donor liver transplantation was performed 108 cases including the 2 dual donor liver transplantations. As for the baseline diseases that resulted in the liver transplantation, there were 57 cases of liver cirrhosis and hepatocellular carcinoma due to hepatitis B, taking up the greatest proportion. Single donor hepatic artery was used in 114 cases, and mean artery diameter was 2.92 mm and mean artery length was 24.25 mm. Hepatic artery was used as the recipient artery in every case except the 8 cases in which gastroepiploic artery was used as alternative. Out of 145 cases of hepatic artery anastomosis, 3 cases resulted in the thrombosis of the hepatic artery, requiring thrombectomy and re - anastomosis. In all 3 cases, thrombosis was found in left hepatic artery and there was no past history of hepatic artery chemoembolization. Conclusion: Incidence of hepatic artery thrombosis after the anastomosis of hepatic artery during liver transplantation was 2.1%, which is considered sufficiently low.

• Journal of Pharmaceutical Investigation
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• v.31 no.4
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• pp.265-271
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• 2001

In order to elucidate the influence of intestinal and hepatic first-pass effect on the pharmacokinetics of triflusal, the biotransformation of triflusal in the gastrointestinal tract and liver was designed. Moreover, we tried to establish an HPLC method applicable for bioassay and available to pharmacokinetics, not only with the simultaneous determination of triflusal and its active metabolite, 2-hydroxy-4-trifluoromethyl benzoic acid (HTB), but also with improving sensitivity. After the administration of triflusal (10 mg/kg) and HTB (10 mg/kg) into femoral vein, portal vein (only triflusal) and oral route (only triflusal), pharmacokinetic parameters were investigated from the plasma concentration-time profiles of triflusal and HTB in rats. An HPLC method was developed for the simultaneous determination of triflusal and HTB in rat plasma, urine and bile. The HPLC analysis was carried out using a C18 column and acetonitrile-methanol-water (25:10:65, v/v/v) as the mobile phase and UV detection at 234 nm. Furosemide was used as the internal standard. The calibration curves were linear over the concentration range $0.05-5.0\;{\mu}g/ml$ for triflusal and $0.2-200.0\;{\mu}g/ml$ for HTB with correlation coefficients greater than 0.999 and with intra-day or inter-day coefficients of variation not exceeding 10.0%. This assay procedure was applied to the study of metabolite pharmacokinetics of triflusal and HTB in rats. It was supposed that triflusal was almost metabolized in vivo because urinary and biliary excreted amounts of triflusal could be ignored as it was lower than 1.2% of the administered dose. According to the gastrointestinal and hepatic biotransformation pathways of triflusal, it was found that triflusal was hydrolyzed by about 5% in intestine and metabolized by about 53% in liver, and that the bioavailability of triflusal after oral administration of triflusal was 0.44, and also that the fraction of total elimination rate of triflusal which formed HTB in liver $(F_{mi},\;%)$ was about 98%. These results showed that triflusal was almost metabolized in liver, and the total elimination of triflusal in the body was dependent to the formation rate of HTB from triflusal in liver.

• Korean Journal of Radiology
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• v.23 no.3
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• pp.322-332
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• 2022

Objective: CT plays a central role in determining the resectability of pancreatic cancer, which directs the use of neoadjuvant therapy. This study aimed to assess the diagnostic accuracy of CT in predicting circumferential resection margin (CRM) involvement in patients with resectable or borderline resectable pancreatic head cancer. Materials and Methods: Seventy-seven patients who were scheduled for upfront surgery for resectable or borderline resectable pancreatic head cancer were prospectively enrolled, and 75 patients (38 male and 37 female; mean age ± standard deviation, 68 ± 11 years) were finally analyzed. The CRM status was evaluated separately for the superior mesenteric artery (SMA) and posterior and superior mesenteric vein/portal vein (SMV/PV) margins. Three independent radiologists reviewed the preoperative CT images and evaluated the resection margin status. The reference standard for CRM status was pathologic examination of pancreaticoduodenectomy specimens in an axial plane perpendicular to the axis of the second portion of the duodenum. The diagnostic accuracy of CT was assessed for overall CRM involvement, defined as involvement of the SMA or posterior margins (per-patient analysis), and involvement of each of the three resection margins (per-margin analysis). The data were pooled using a crossed random effects model. Results: Forty patients had pathologically confirmed overall CRM involvement in pancreatic cancer, while CRM involvement was not seen in 35 patients. For overall CRM involvement, the pooled sensitivity and specificity were 15% (95% confidence interval: 7%-49%) and 99% (96%-100%), respectively. For each of the resection margins, the pooled sensitivity and specificity were 14% (9%-54%) and 99% (38%-100%) for the SMA margin, 12% (8%-46%) and 99% (97%-100%) for the posterior margin; and 37% (29%-53%) and 96% (31%-100%) for the SMV/PV margin, respectively. Conclusion: CT showed very high specificity but low sensitivity in predicting pathological CRM involvement in pancreatic cancer.

• Asian-Australasian Journal of Animal Sciences
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• v.20 no.8
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• pp.1222-1228
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• 2007

The aim of this experiment was to compare the characterization of fatty acid digestion of Beijing Fatty (BF) and Arbor Acres (AA) chickens. One-day-old male AA and BF chickens were raised in the same house, and fed with the same diet. We first evaluated utilization of dietary fatty acids in chickens by the total collection procedure, and chickens were then killed to compare the abundance of intestinal mRNA expression of liver-fatty acid binding protein (L-FABP) and intestinal-fatty acid binding protein (I-FABP) by Real-time PCR, and also the pH of intestinal mucosa at 3 and 6 weeks of age. Another group of chickens were sampled at 6 weeks of age to compare the total bile acid concentration in serum, and lipase activity in contents of the small intestine. Results showed that compared to AA chickens, BF chickens had higher lipase activity in the content of the small intestine (p<0.05), greater total bile acid content in portal vein blood (p<0.05) at 6 weeks of age, lower intestinal mucosal pH at both 3 weeks (p<0.05) and 6 weeks (p<0.05) of age, and higher abundance of liver-fatty acid binding protein (L-FABP) mRNA expression in intestine tissues at 6 weeks of age (p<0.05), and higher digestibility of fatty acids at both 3 and 6 weeks (p<0.05) of age. There was no difference in I-FABP mRNA expression between AA and BF chickens at either age. Thus, BF chickens had greater fatty acids utilization than AA chickens that was associated with L-FABP, lipase activity, bile acid content and intestinal mucosal pH.

• Journal of Yeungnam Medical Science
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• v.33 no.2
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• pp.155-158
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• 2016

Sorafenib (Nexavar) has been regarded as a treatment for unresectable hepatocellular carcinoma (HCC), with side effects that include hand-foot skin reaction, diarrhea, rash, fatigue, hypertension, nausea, anorexia, weight loss, and alopecia. Thyroid disorder, such as endocrine side effect, has also been reported. However no case involving adrenal insufficiency has been reported. Here, we report a case of adrenal insufficiency which occurred after taking sorafenib in a patient with HCC. A 56-year-old man visited our hospital due to right upper quadrant abdominal pain and he was diagnosed as multiple disseminated and unresectable HCCs with portal vein invasion; therefore transarterial chemoembolization was performed and sorafenib administration was started. Two months later, he was admitted to the hospital complaining of severe fatigue. The laboratory results showed cortisol of <$0.2{\mu}g/dL$ and adrenocorticotropic hormone of <1.00 pg/mL. The patient had no history of taking steroids or herbal medications. Secondary adrenal insufficiency was diagnosed and prednisolone 10 mg per day was started immediately; as a result, fatigue remarkably improved. This may be the first report indicating a possible association between sorafenib and adrenal insufficiency and it implies that the possibility of adrenal insufficiency should be considered in patients taking sorafenib who complain of severe fatigue.

• Toxicological Research
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• v.32 no.2
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• pp.133-140
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• 2016

Sulfasalzine is a widely administered drug against inflammatory-based disorders in human. However several cases of liver injury are associated with its administration. There is no stabilized safe protective agent against sulfasalazine-induced liver injury. Current investigation was designed to evaluate if N-acetylcysteine (NAC) and dithioteritol (DTT) as thiol reducing agents and/or vitamins C and E as antioxidants have any protective effects against sulfasalazine-induced hepatic injury in an ex vivo model of isolated rat liver. Rat liver was canulated and perfused via portal vein in a closed recirculating system. Different concentrations of sulfasalazine and/or thiol reductants and antioxidants were administered and markers of organ injury were monitored at different time intervals. It was found that 5 mM of sulfasalazine caused marked liver injury as judged by rise in liver perfusate level of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) (p < 0.05). A significant amount of lipid peroxidation and hepatic glutathione depletion were detected in drug-treated livers, accompanied with significant histopathological changes of the organ. Administration of NAC ($500{\mu}M$), DTT (${400\mu}M$), Vitamin C ($200{\mu}M$), or vitamin E ($200{\mu}M$) significantly alleviated sulfasalazine-induced hepatic injury in isolated perfused rat liver. The data obtained from current investigation indicate potential therapeutic properties of thiol reductants and antioxidants against sulfasalazine-induced liver injury.

• Journal of Pharmaceutical Investigation
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• v.22 no.4
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• pp.301-306
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• 1992

The influence of phenobarbital (PB) pretreatment (75 mg/kg/day, i.p. for 4 days) on the metabolite kinetics of diltiazem (DTZ) was studied in rats in order to elucidate the effect of esterase induced by PB on the formation of DTZ to desacetyldiltiazem (DAD), DAD was injected via portal vein (3 mg/kg) to the control and PB-pretreated rats, The intrinsic hepatic clearance of DAD was significantly increased by PB pretreatment and the absolute bioavailability of DAD was significantly decreased in the PB-pretreated rats. According to the hepatic biotransformation model of DTZ, the fraction of systemic clearance of DTZ which forms DAD $(G_{mi})$ was different from that of DTZ which furnishes the available DAD to the systemic circulation $(F_{mi})$ in control rats. This result shows that DTZ was suspected of the sequential hepatic first-pass metabolism. On the other hand, PB pretreatment enhanced the $G_{mi}$ value of DTZ by 44%. It may be concluded that the deacetylation of DTZ to DAD in rats is increased by the esterase induced by PB but the transfer rate of DAD immediately formed from DTZ into systemic circulation is not affected by PB due to the 27% decreased absolute bioavailability of DAD resulting from PB pretreatment.

• Toxicological Research
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• v.28 no.1
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• pp.57-65
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• 2012

In this study, the 4-week oral toxicity and anti-cancer activity of the hexane layer of Melia azedarach L. var. japonica Makino's bark extract were investigated. We carried out a hollow fiber (HF) assay and 28-day repeated toxicity study to confirm the anti-cancer effect and safety of the hexane layer. The HF assay was carried out using an A549 human adenocarcinoma cell via intraperitoneal (IP) site with or without cisplatin. In the result, the 200 mg/kg b.w of hexane layer with 4 mg/kg b.w of cisplatin treated group, showed the highest cytotoxicity aginst A549 carcinoma cells. For the 28-day repeated toxicity study, 6 groups of 10 male and female mice were given by gavage 200, 100, or 50 mg/kg b.w hexane layer with or without 4 mg/kg b.w of cisplatin against body weight, and were then sacrificed for blood and tissue sampling. The subacute oral toxicity study in mice with doses of 200, 100, and 50 mg/kg b.w hexane layer showed no significant changes in body weight gain and general behavior. The cisplatin-treated group significantly decreased in body weight compared to the control group but regained weight with 100 and 200 mg/kg b.w of hexane layer. The biochemical analysis showed significant increase in several parameters (ALT, total billirubin, AST, creatinine, and BUN) in cisplatin-treated groups. However, in the group given a co-treatment of hexane layer (200 mg/kg b.w), levels of these parameters decreased. In hematological analysis, cisplatin induced the reduction of WBCs and neutrophils but co-treatment with hexane layer (100 and 200 mg/kg b.w) improved these toxicities caused by cisplatin. The histological profile of the livers showed eosinophilic cell foci in central vein and portal triad in cisplatin treated mice. These results show that hexane layer might have an anti-cancer activity and could improve the toxicity of cisplatin.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.9
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• pp.3709-3713
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• 2015

Background: Many factors, including molecular ones, were demonstrated to be associated with long-term prognosis of hepatocellular carcinoma (HCC). Thus far, the expression and clinicopathologic and prognostic significance of the carboxyl terminus of Hsp70-interacting protein (CHIP) in B-type hepatitis virus (HBV)-related HCC remain unknown. Materials and Methods: CHIP expression was detected by immunohistochemical staining of surgical samples from 79 patients with HCC with HBsAg positivity. In addition, correlations with clinicopathologic parameters and patient survival were evaluated. Results: It was found that positive CHIP staining was observed in tumor, but not non-tumor, tissues. High expression of CHIP was significantly related to larger tumor size, with marginally significant associations noted for presence of portal vein invasion and higher serum a-fetoprotein level. In addition, univariate analysis showed that high CHIP expression was a powerful predictor for dismal overall and disease-free survival. However, independent prognostic implications of CHIP were not proven in multivariate Cox regression test. Conclusions: CHIP is overexpressed in HBV-related HCC and is associated with unfavorable biological behavior as well as poor prognosis. However, its prognostic role needs to be further validated.