Modulation of human telomerase reverse transcriptase in hepatocellular carcinoma

AIM:Most cancer cells acquire immortal capability by telornerase activation. The human telornerase reverse transcriptase gene (hTERT) is considered to be the major determinant of the enzymatic activity of human telomerase,and the hTERTpromoter contains several c-lylyc binding sites that mediate hTERTtranscriptional activation. Few studies have examined the role of hTERTin hepatocarcinogenesis,and the relationship between c-Myc and telomerase in human hepatocellular carcinoma tissue is unknown.METHODS:We measured hTERTmRNA levels and c-Myc oncoprotein expression in 57 patients with hepatocellular carcinoma using in situhybridization and immunohistochemistry,respectively. The transcription regulation of hTERT was evaluated by transient transfection of pGL3-1375 into the human hepatocellular carcinoma cell line J5. To determine the relationship between c-Myc and the hTERTpromoter, a 1375-bp DNA fragment encompassing the promoter was placed upstream of the luciferase reporter gene and transiently transfected into the cell line. Two additional hTERT promoter constructs (-776 and -100 bp region) and an hTERT promoter-LUC construct containing 2 c-Myc mutations (pGL3-181 MycMT) were also used for luciferase assays.RESULTS:In 30 of 57 cases (52%), hTERTmRNA expression was associated with c-Myc protein expression. However,16 of 57 cases (28%) showed strong hTERTmRNA detection without c-Myc protein expression, and 11 cases (19%) showed weak hTERTmRNA expression and strong c-Myc expression.Although luciferase activity was decreased between upstream 1375 bp and 776 bp, there was no significant difference between upstream 776 bp and 100 bp. Finally, there was no significant decrease in activity after transfection of the hTERT promoter-LUC construct.CONCLUSION:The results indicate that c-Myc does not play a major role in gene regulation of the catalytic subunit of telomerase (hTERT) in human hepatocellular carcinoma.Other regulatory elements or epigenetic phenomena should be further investigated to understand hTERTgene regulation in human hepatocellular carcinoma.

Comparison of transcatheter arterial chemoembolization,laparoscopic radiofrequency ablation,and conservative treatment for decompensated cirrhotic patients with hepatocellular carcinoma

AIM:To compare the therapeutic effect of transcatheter arterial chemoembolization （TACE), laparoscopic radiofrequency ablation (LRFA), and conservative treatment for the therapy of decompensated liver cirrhosis patients with hepatocellular carcinomas (HCC).METHODS:Between October 2000 and July 2003, one hundred patients with histologically proven primary HCC and clinical decompensated liver cirrhosis (Child classification B or C) were included in this study. Forty patients received LRFA (LRFA group), twenty received TACE (TACE group),and forty received conservative treatment (control group).We compared the survival, recurrence, and complication rates in these three groups, making adjustment using the tumor metastastic node staging system.RESULTS:The major complication rate in the TACE group (9/20) was significantly higher than that in the LRFA group (7/40). For patients with TMN stage Ⅱ HCC, the survival rate of the LRFA group was better than that of the TACE and control groups (P=0.003) but the recurrence rates befween the LRFA and TACE groups did not differ.CONCLUSION: The LRFA group of patients had betterclinical outcomes in terms of survival and complication rates in comparison with the TACE group or conservative treatment in patients with decompensated liver cirrhosis, especially in TMN patients with stage Ⅱ HCC. LRFA is thus an appropriate alternative treatment for poor liver function among patientswith HCC.

Gallbladder contractility and volume characteristics in gallstone dyspepsia

AIM:It is difficult to differentiate gallstone dyspepsia and functional dyspepsia by clinical symptoms and signs. We hypothesized that gallstone dyspepsia was related to abnormal gallbladder motility. We aimed to differentiate gallstone dyspepsia from functional dyspepsia by measuring gallbladder motility.METHODS: We measured gallbladder volume changes in response to gastric distension (saline 500mL) and fatty meal in 10normal volunteers (controls) and 62 patients with gallstones and dyspepsia before cholecystectomy. Forty cholecystectomized patients were symptom free or had improvement (group I), while the remaining 22 patients had persistent dyspepsia (group Ⅱ). Gallbladder volume change and ejection fraction were analyzed and compared among the three groups.RESULTS:In group I, there were significant decreases in gallbladder volumes 5-25 rain after gastric distension,compared to fasting volumes. Compared to normal volunteers and group Ⅱ, group I had significantly decreased gallbladder volumes 10-20min after drinking 500mL of normal saline and 10 to 50min after eating fatty meal.CONCLUSION:Our results support the hypothesis that increased gallbladder contraction after gastric distension or fatty meal may be related to dyspeptic symptoms in uncomplicated gallstone disease. These findings may be useful in differentiating functional dyspepsia from gallstone dyspepsia, patients with the latter disease may benefit from laparoscopic cholecystectomy.

Effect of water-soluble contrast in colorectal surgery: A prospective randomized trial

AIM: Postoperative gastrointestinal-tract motility is normally delayed. Early feeding after colorectal surgery has been reported recently, but late feeding is common. Gastrografin not only enhances bowel peristalsis, but also decreases bowel-wall edema. Whether contrast medium allows early oral feeding and reduces the duration of hospitalization requires clarification. METHODS: Fifty patients underwent elective colorectal surgery In a regional medical center. Patients were prosp-ectively randomized into a Gastrografin group or control group (n=25 each). Patients in the Gastrografin group began their feeding schedule with 100 mL of 5% dextrose water with 100 mL of Gastrografin on postoperative d 3 and were advanced to a full liquid diet when the contrast reached the colon in 4 h. Patients in the control group began their feeding schedule with 200 mL of 5% dextrose water on postoperative d 3 and were advanced to a full liquid diet after the passage of flatus and stool. Nasogastric tubes were inserted for persistent postoperative vomiting. Fullness, nausea, vomiting, complications, time of anesthesia, time of operation, time of mobilization, time of oral feeding, and duration of hospital stay were recorded and analyzed with Student's t-test. RESULTS: In the Gastrografin group, one patient had aspiration pneumonia and one patient had anastomotic leakage resulting in sepsis and eventual death. This mortality was excluded from the subsequent statistical analysis. In the control group, two patients had wound infections. There was no significant difference between the two groups at the time of anesthesia, time of operation, or time of mobilization. There were significant differences between the two groups in the time of oral feeding (3.3±0.3 d in the Gastrografin group VS 4.8±0.4 d in the control group; P=odds ratio--, 95%CI [-0.5 to +0.7 d]) and in the length of hospital stay (7.6±1.1 d in the Gastrografin group VS 10.2±1.3 d in the control group; P=odds ratio--, 95% CI [-1.2 to +1.4 d]). CONCLUSION: Gastrografin not only allowed early oral feeding but also reduced the duration of hospitalization after elective colorectal surgery.