Effects of Panax notoginseng (Chinese ginseng) and acute exercise on postprandial glycemia in non-diabetic adults.

The purpose of this study is to determine whether Panax Notoginseng (PNG) taken for 3 days and one 30-min cycling exercise can reduce postprandial hyperglycemia after ingesting a 75-mg oral glucose solution (OGTT) in untrained non-diabetic men, age 20-45 years. We randomly assigned 52 men to: 1) ginseng (G) + exercise (G+Ex, n=14), 2) ginseng (G, n=13), 3) placebo (C) + exercise (C+Ex, n=12), and 4) placebo control groups (C, n=13). The G and C groups took a daily 3g dose of PNG and cornstarch-placebo supplement for 3 days, respectively. The exercise groups also performed a 30-min cycling exercise on day 3 prior to OGTT. The daily 3g-dose of PNG supplementation significantly lowered postprandial plasma glucose (PG) concentration at 30 min post-OGTT in the G group, compared with C (mean Δ±SE: G vs. C = 26.3±11 mg/dl, p<0.05) and PG area under the curve (PG-AUC0-90) in the G and G+Ex groups, relative to the C (G vs. C = 96.5±42 and G+Ex vs. C = 85.2±41 mg/dl, both p<0.05). We conclude that a daily 3g-dose of PNG taken for 3 days, not one acute bout of 30-min cycling exercise at 60% VO2max, lowered postprandial glycemia at 30-min post-OGTT and PG-AUC 0-90 min in non-diabetic men, age 20-45 years.

Prospective randomized control study on the effect of branched-chain amino acids in patients with liver resection for hepatocellular carcinoma.

BACKGROUND: Aminoleban EN contains branched-chain amino acids (BCAA) and is known to be beneficial for the protein-energy malnutrition in cirrhotic patients. Patients suffering from hepatocellular carcinoma often have background cirrhosis, and the present study investigates the effect of Aminoleban EN on these patients after hepatic resection for the primary disease. METHODS: A prospective randomized controlled clinical trial, to which 50 patients were recruited, was carried out. The study group received Aminoleban EN in addition to normal diet for 12 weeks and the control group received an isonitrogenous and isocaloric diet only. RESULTS: After exclusions, there were 21 patients in the study group and 23 patients in the control. The study group had a shorter hospital stay, and had a significantly higher haemoglobin level, higher sodium level, higher albumin level and lower bilirubin during the postoperative course. There was no significant difference in terms of neuropsychiatric symptoms or Karnofsky performance score. There was no difference in gastrointestinal symptoms or other signs. No adverse reaction was associated with the administration of Aminoleban, and there was no significant difference in terms of morbidity and mortality between the two groups of patients. CONCLUSION: Aminoleban EN is safe to administer and does not have significant adverse effects. It contributes to a shorter hospital stay and quicker improvement of liver function in the early postoperative period. These beneficial results require only a 12-week period of administration of BCAA after operation.

Adjuvant intra-arterial iodine-131-labelled lipiodol for resectable hepatocellular carcinoma: a prospective randomised trial.

BACKGROUND: Resection of hepatocellular carcinoma is potentially curative, but local recurrence is common. In this prospective randomised trial, we aimed to find out if one dose of postoperative adjuvant intra-arterial iodine-131-labelled lipiodol could reduce the rate of local recurrence and increase disease-free and overall survival. METHODS: Patients who underwent curative resection for hepatocellular carcinoma and recovered within 6 weeks were randomly assigned one 1850 MBq dose of 131I-lipiodol or no further treatment (controls). We compared rates of recurrence and disease-free and overall survival (the primary endpoints) between the two groups by intention to treat. We planned an interim analysis when 30 patients (both groups together) had been followed up for a median of 2 years, with the intention of stopping early if the between-group difference in disease-free survival was significant (p=0.029). FINDINGS: Between April, 1992, and August, 1997, we recruited 43 patients: 21 received intra-arterial 131I-lipiodol and 22 received no adjuvant treatment. During a median follow-up of 34.6 (range 14.1-69.7) months, there were six (28.5%) recurrences among the 21 patients in the adjuvant treatment, compared with 13 (59%) in the controls (p=0.04). Median disease-free survival in the treatment and control groups was 57.2 (0.4-69.7) and 13.6 (2.1-68.3) months, respectively (p=0.037). 3-year overall survival in the treatment and control groups was 86.4% and 46.3%, respectively (p=0.039). The interim analysis showed a significant increase in disease-free survival in the treatment group compared with the controls (p=0.01), so we closed the trial early. 131I-lipiodol had no significant toxic effects. INTERPRETATION: In patients with hepatocellular carcinoma, one 1850 MBq dose of intra-arterial 131I-lipiodol given after curative resection significantly decreases the rate of recurrence and increases disease-free and overall survival.

Combating hepatocellular carcinoma with an integrated approach.

This short review summarizes an integrated approach to new methods of managing hepatocellular carcinoma (HCC) developed at our centre. HCC-specific isoforms of alpha-fetoprotein were detected by isoelectric focusing and their value in the differential diagnosis of early HCC on a background of chronic liver disease has been shown. Selective internal radiation therapy using yttrium-90 (90 Y) microspheres has been shown to be an effective treatment for inoperable HCC in a phase I and II study. A partition model for estimating the radiation doses from the 90 Y microspheres to the tumour and the non-tumorous liver during the therapy was then formulated, verified by correlating with intraoperative dosimetry, and evaluated in clinical settings. This permits 90 Y microspheres to be administered safely without the need of an open surgery and a randomized therapeutic controlled trial is in progress. Another randomized controlled trial using iodine-131 Lipiodol as a post-operative adjuvant therapy, aiming at reducing the recurrence rate is also on-going. HCC may be more effectively combated with a better understanding of its pathogenesis from chronic liver disease.

Internal radiation therapy for patients with primary or metastatic hepatic cancer: a review.

BACKGROUND: The limited efficacy of current approaches to the treatment of patients with hepatic cancer, including external beam radiation therapy and cytotoxic chemotherapy, has reawakened interest in the use of internal radiation therapy. METHODS: The authors reviewed series of patients with liver metastases or hepatocellular carcinoma (HCC) treated with 1) interstitial irradiation and direct intratumoral injection of 90Y microspheres, 2) intraarterial infusion of (131)I-Lipiodol, 3) intraarterial infusion of 90Y microspheres, or 4) parenteral administration of radiolabeled monoclonal antibodies. RESULTS: High dose rate interstitial irradiation with afterloading of (192)Ir resulted in local control of hepatic metastases for a median of 8 months and complete tumor eradication in 2 patients. Direct intratumoral injection of 90Y microspheres reduced the size of 90.6% of tumors and completely destroyed them in 8 patients. Treatment with arterial (131)I-Lipiodol resulted in a 17-92% response rate as well as a case of complete remission of unresectable HCC. It was found to be most effective against small tumors. No response was observed with liver metastases from colorectal carcinoma. Partial response was commonly achieved when patients with unresectable liver metastases or HCC were treated with intraarterial 9OY microspheres. Among four patients whose HCC became resectable following treatment with 90Y microspheres, two cases of complete remission were documented. In a prospective randomized trial, (131)I-antiferritin combined with chemotherapy was no more effective than chemotherapy alone. CONCLUSIONS: The different approaches to internal radiation therapy that are reviewed in this article represent several ways in which radiation can be selectively targeted to hepatic tumors without undue radiation to the nontumorous liver. However, the efficacy of each of these therapies still needs to be evaluated in randomized controlled trials.

Selective internal radiation therapy with intra-arterial iodine-131-Lipiodol in inoperable hepatocellular carcinoma.

UNLABELLED: From August 1990 to June 1993, 26 patients with inoperable hepatocellular carcinoma were treated with intra-arterial iodine-131-Lipiodol (131I-L). METHODS: Iodine-131-Lipiodol was given through either an implantable arterial port (9 patients) or during hepatic angiography (17 patients). All 26 patients had multiple lesions, 3 had involved resection margin after surgical resection and 1 had diffuse infiltrative lesions. The median size of the largest tumor among 22 patients with a measurable lesion was 4.5 cm (2-9.5 cm). The end points are tumor response in terms of tumor size, change in serum alpha-fetoprotein level, toxicity of treatment and overall survival. RESULTS: Twenty-three patients received a single treatment of 1.11-2.22 GBq (30-60 mCi)131I-L. Three patients received 2.22-4.44 GBq (60-120 mCi)131I-L in three fractions. Considering both radiological regression and reduction in serum alpha-fetoprotein level as objective response criteria, the overall response rate was 52% (13 out of 25 patients with evaluable disease). Ten out of 15 patients who had raised alpha-fetoprotein levels had more than 50% reduction and 8 patients had more than 90% reduction in alpha-fetoprotein level. Since analysis, 19 patients have died and 7 remain alive, giving a minimum median survival of 6 mo (range 1.2-16.6 mo), with 4 surviving more than 1 yr calculated from the day of treatment. There was only one patient who had late deterioration of liver function compatible with radiation hepatitis. There was no bone marrow toxicity documented in any patients. CONCLUSION: Treatment with intra-arterial 131I-L was well tolerated in patients with inoperable hepatocellular carcinoma and produced an objective response of 52% with median survival of 6 mo. A fractionated dose of 131I-L was feasible and the radiation dose could be escalated safely.

Hepatic intra-arterial lipiodol ultrasound guided biopsy in the management of hepatocellular carcinoma.

One hundred and fifty-one consecutive new patients with suspected hepatocellular carcinoma (HCC) were investigated from 1989 to 1990. Ultrasound showed the tumours to be inoperable in 111 patients. Selective hepatic angiography revealed 17 more patients with inoperable HCC. Hepatic intra-arterial lipiodol (HIAL) was injected in the remaining 23 patients. In 16 of them, a clinical decision could be reached basing on the radiological findings. Hepatic intra-arterial lipiodol ultrasound (HIAL/USG) guided biopsy was done in seven patients with suspicious lesions. Histology obtained with this method revealed hyperplastic cirrhotic nodules in four patients (two with suspected HCC and two with suspected secondaries). In another two patients, the suspected lesions were confirmed to be malignant. In the last patient who had received chemotherapy for extensive HCC, HIAL/USG guided biopsy revealed necrotic tissue only. At laparotomy, diffuse infiltrative abnormality was found and repeated biopsy confirmed residual malignancy in the necrotic tumour. We conclude that when there is radiological uncertainty as to the nature and extent of the HCC, HIAL/USG guided biopsy can help the clinician to make important decisions.

Disposition of epirubicin in an oily contrast medium after intravenous and intrahepato-arterial administration in liver cancer: a preliminary report.

The present study reports findings on the disposition of epirubicin after an intrahepato-arterial administration of the Lipiodol-drug complex, prepared by mixing the drug-aqueous phase with the iodized oil by ultra-sonification, in 14 patients with histologically proven hepatoma or hepatomegaly with serum alpha-fetoprotein level above 500 micrograms.l-1. The volume of Lipiodol used was 5 ml and the epirubicin dose was 50 mg.m-2. Blood samples were obtained at various time intervals up to 72 h post-dose. Serum concentrations of epirubicin were measured by liquid chromatography with fluorometric detection. The area under serum concentration-time curve (AUCinfinity0) was higher in the Lipiodol-epirubicin group (n = 8) while the clearance was faster and elimination t1/2 and mean residence time shorter in the plain epirubicin group (n = 3). However, interindividual variation in metabolism of epirubicin would affect serum level of the drug. In three patients who were given intravenous and intrahepato-arterial injections (90 mg.m-2) of plain epirubicin and Lipiodol-drug complex, the relative bioavailability of Lipiodol-epirubicin complex (F = 0.76 and 0.45) was lower than that of plain epirubicin (F = 0.80 and 0.73) in two patients while it was approximately 100% (F = 1.06 and 1.20) in one patient. It is likely that liver function of the patients might be modified by the disease state over a period of 3 months in the cross-over study. Further studies with larger patient samples are required to confirm if there is a targeting effect of the Lipiodol-drug complex toward hepatoma using a better formulation of the drug in Lipiodol.

Preoperative and intraoperative localisation of gastrointestinal bleeding of obscure origin.

In the past six years, 37 patients with gastrointestinal bleeding of obscure origin had their bleeding sites localised preoperatively or intraoperatively. Preoperative investigations followed a regime consisting of endoscopy, barium meal and follow through, small bowel enema, 99mTc pertechnetate scan, 99mTc-labelled red blood cell scan and selective coeliac and mesenteric angiography. Bleeding lesions were localised preoperatively in 36 patients. In one patient, diagnostic laparotomy had to be carried out immediately before any investigation because the bleeding was severe. At operation, angiosarcoma of ileum was found. Unless preoperative investigations showed the lesions to be in anatomically fixed organs like the duodenum or colon, the lesions had still to be found at operation. Palpation and transillumination detected the lesion intraoperatively in 21 patients while only some lesions were found in three patients with multiple lesions. Sigmoidoscopy through enterotomies was required in one patient. Intraoperative enteroscopy was done for small lesions not found grossly at operation in nine patients, to detect additional lesions in three patients or to rule out suspicious lesion shown on preoperative tests in one patient. In another patient with diffuse lymphoma of small bowel with bleeding from only a small segment of jejunum, injection of methylene blue intraoperatively through a previously placed angiographic catheter stained the bleeding segment of jejunum blue. This segment was identified easily and resected. These preoperative and intraoperative localisation procedures were simple and effective and we recommend them to be used more freely.

Intra-operative fibreoptic enteroscopy for bleeding lesions in the small intestine.

Twenty-five patients with gastrointestinal bleeding proved to have lesions in the small intestine. Intra-operative fibreoptic enteroscopy was performed on seven patients, in six patients through the anus and in one patient through an enterotomy and the anus. The indications for fibreoptic enteroscopy were inability to find the lesions in the 3 patients, multiple small lesions in 3 patients and to rule out suspicious pathology in the jejunum shown on a small bowel enema in a patient with ileal ulcers. In all instances, the fibreoptic enteroscopy was useful in localizing lesions, in detecting additional lesions and in ruling out the suspicious lesions. It can be performed easily and is safe. No complication developed from its use in this series.