Polymorphism of genes encoding drug-metabolizing and inflammation-related enzymes for susceptibility to cholangiocarcinoma in Thailand

BACKGROUND Cholangiocarcinoma(CCA)is an intractable cancer,and its incidence in north eastern Thailand is the highest worldwide.Infection with the liver fluke Opisthorchis viverrini(OV)has been associated with CCA risk.However,animal experiments have suggested that OV alone does not induce CCA,but its combination with a chemical carcinogen like nitrosamine can cause experimentally induced CCA in hamsters.Therefore,in humans,other environmental and genetic factors may also be involved.AIM To examine relations between risk for CCA and genetic polymorphisms in carcinogenmetabolizing and inflammation-related genes.METHODS This hospital-based case-control study enrolled 95 case-control pairs matched by age(±5 years)and sex.We examined relations between risk for CCA and genetic polymorphisms in carcinogenmetabolizing and inflammation-related genes,serum anti-OV,alcohol consumption,and smoking.Polymorphisms of CYP2E1,IL-6(-174 and-634),IL-10(-819),and NF-κB(-94)and their cooccurrence with polymorphisms in the drug-metabolizing enzyme gene GSTT1 or GSTM1 were also analyzed.RESULTS Although CCA risk was not significantly associated with any single polymorphism,persons with the GSTT1 wild-type and CYP2E1 c1/c2+c2/c2 genotype had an increased risk(OR=3.33,95%CI:1.23-9.00)as compared with persons having the GSTT1 wild-type and CYP2E1 c1/c1 wild genotype.The presence of anti-OV in serum was associated with a 7-to 11-fold increased risk,and smoking level was related to an OR of 1.5-1.8 in multivariable analyses adjusted for each of the seven genetic polymorphisms.CONCLUSION In addition to infection with OV,gene-gene interactions may be considered as one of the risk factors for CCA development.

A Moxa Stimulation on the Leg Affected the Function of Stomach via Autonomic Nerve System and Polymodal Receptors

The moxa therapy is a popular traditional hyperthermia therapy in East Asia. The moxa is made from dried mugwort (Artemisiaargyi). The moxa is usually put on a meridian point and then is burnt on to obtain a hyperthermic stimulation to the skin. However, very few researches have been studied in the effects and mechanism of the moxa therapy. Therefore, in this study, we gave the moxa stimulation to healthy subjects. In the moxa group, the moxa was lit on the ST36 (Zusanli: an acupuncture point in anterior tibialis of the leg) for 5 minutes. Their responses were traced with electrogastrogram (EGG) and assessed the change of gastric function. At the same time, their heart rate (HR) was recorded and observed to study the mechanism of moxa treatment. And then their results were compared with those of the control group. After the moxa stimulation, EGG showed significant increase and stayed 3.0 - 3.1 cpm while HR prominently decreased. On the other hand, the control group did not indicate such results. Those results are common to the re-sponse of acupuncture-like stimulation by the reflex arc which consists of receptor, sensory neuron, central nervous system, motor neuron and effector. It may be explained as below: the elements of the acupuncture-like stimulation and the moxa are pain and hyperthermia respectively and they both are received by polymodal receptors. Thus the moxa stimulation applied on ST36 may be ef-fective to enhance stomach function.

Reuse of liver grafts following the brain death of the initial recipient

AIM: To determine if there is a reasonable prospect of success of a re-use liver transplantation.METHODS: We systematically searched for reports of liver graft re-use using electronic searches of PubMed and Web of Knowledge. We performed hand searches of references lists of articles reporting re-use of grafts.RESULTS: A systematic review of the literature reveals 28 liver transplantations using previously transplanted grafts. First and second recipients ranged in age from 4 to 72 years and 29 to 62 years respectively. Liver disease in the first recipient was varied including 5(18%) patients with fulminant liver failure who died subsequently of cerebral edema. The second transplanta-tion was performed after a median interval of 5 d(one day-13 years). Viral hepatitis was present in 3(11%) of the initial recipients and in 8(29%) of final recipients. Hepatocellular carcinoma was present in 6(21%) of the final recipients. Early survival after the final transplantation was 93%, whereas long-term survival was 78% with a mean follow-up of 23.3(3-120) mo.CONCLUSION: Outcomes of transplantation using previously transplanted grafts in this select population are similar to those seen with conventional grafts.

Effect of branched-chain amino acids in patients receiving intervention for hepatocellular carcinoma

AIM:To investigate the usefulness of branched-chain amino acids(BCAA)before transarterial chemoembolization(TACE)or radiofrequency ablation(RFA).METHODS:We investigated the usefulness of preintervention with BCAAs by comparing patients treated with BCAAs at 12.45 g/d orally for at least 2 wk before TACE or RFA and those not receiving such pretreatment.A total of 270 patients with hepatocellular carcinoma complicated by cirrhosis were included in the study.Mean changes from baseline(Δ)in serum albumin(Alb),C-reactive protein(CRP),and transaminase levels,as well as peak body temperature were also determined and compared at days 2,5,and 10 after the start of TACE or RFA.RESULTS:In patients who underwent TACE or RFA,BCAA pre-intervention significantly suppressed the development of post-intervention hypoalbuminemia and reduced inflammatory reactions during the subsequent clinical course.After TACE,theΔAlb peaked on day 2,remained constantly lower in BCAA-treated patients,compared to the control group,and was-0.13±0.42g/dL in BCAA-treated patients and-0.33±0.51 g/dL in untreated patients on day 10.TheΔCRP was also significantly lower in BCAA-treated patients on days2,5 and 10 after TACE.Like the trends noted after TACE,a similar tendency was noted as to theΔAlb andΔCRP after RFA.The changes in serum Alb level were inversely correlated with CRP changes;therefore,a possible involvement of the anti-inflammatory effect of BCAAs was inferred as a factor contributory to the suppression of decrease in serum Alb level.CONCLUSION:Pre-intervention with BCAAs may hasten the recovery of serum Alb level and mitigate postoperative complications in patients undergoing TACE or RFA.

Effect of Iron-Mediated Oxidative Stress on Insulin Resistance Through the Forkhead Box-Containing Protein O Subfamily-1 (FOXO-1) Pathway in Chronic Hepatitis C

Aims: Chronic hepatitis C virus (HCV) infection is often associated with glucose metabolic disorders and iron overload. It has recently been shown that reactive oxygen species (ROS) increase gluconeogenesis in hepatocytes through the forkhead box-containing protein O subfamily-1 (FOXO1)-dependent pathway. The aim of this study is proving a cause-and-effect relationship between iron-mediated ROS production and insulin resistance (IR) in chronic hepatitis C (CH-C) patients. Methods: The study included 42 patients with CH-C (22 males and 20 females, median age 53 years). Homeostasis model assessment of insulin resistance (HOMA-IR) value was assessed for each patient at entry. Gene expression levels in the biopsied liver tissues were determined by quantitative reverse transcription-polymerase chain reaction (RT- PCR). In addition, the effect of ROS on gluconeogenesis was assessed using HepG2 cells treated with a well-known ROS generator, diethylmaleate (DEM). Results: The serum ferritin levels were significantly correlated with the serum aspartate aminotransferase level, alanine aminotransferase level, HOMA-IR value, grade of fatty accumulation, total hepatic iron score, and 8-OH-deoxy-2’-guanosine (8-OHdG)-positive cell count. FOXO1 expression was correlated with 8-OHdG-positive cell count, phosphoenolpyruvate carboxykinase (PEPCK) expression, and HOMA-IR. In HepG2 cells, the gene transcription of FOXO1 and PEPCK was increased by DEM treatment, which was associated with an increase in non-phosphorylated FOXO1 protein in the nuclear fraction. Conclusions: Iron-mediated ROS production enhances gluconeogenesis through the FOXO1-mediated pathway and is an affecting factor to IR in patients with CH-C.

Cecal volvulus associated with mobile cecum in Cornelia de Lange syndrome: Report of a case

We report a case of cecal volvulus in an 11-year-old girl who had been diagnosed with Cornelia de Lange syndrome. She had undergone operative fundoplication several years earlier and was referred to our institute for treatment of intestinal obstruction. A severely dilated colon was detected on abdominal roentgenogram, and abdominal CT and colonic enema strongly suggested cecal volvulus. Emergency operation was performed and cecal volvulus with mobile cecum was ascertained;the volvulus was corrected and the mobile cecum was fixed to the peritoneum on the right side. Neurologically handicapped patients sometimes suffer from cecal volvulus, and patients with Cornelia de Lange syndrome are at especially high risk. Moreover, operative fundoplication promotes intestinal dilatation and it may be another risk factor for cecal volvulus.