Abstract: H19 is a maternally expressed oncofetal gene, which is expressed at substantial levels in embryonic tissues and various human tumor types, but marginally or not expressed in the corresponding tissue of the adult. Dramatic increase in H19 mRNA was found in hepatocytes following the initiation of their proliferation by hepatectomy. H19 is a target gene for HGF, which also sharply increases after hepatectomy. The growth of liver metastases after hepatectomy and it's correlation with levels of the H19 and HGF RNA were evaluated on an orthotopic model of rat colon liver metastases. Significant increase in tumor growth was found after 70% hepatectomy. HGF and H19 RNAs levels in tumors were substantially elevated after hepatectomy compared to those observed in tumors with no hepatectomy. A direct positive correlation between the level of H19 RNA and the extent of liver resection was found. HGF has an important role in overexpression of H19 resulting in a rapid growth of metastases in the remaining liver after hepatectomy. These findings may have important clinical applications, when decisions regarding partial hepatectomy, two stage hepatectomy procedure or staged radiofrequency ablation prior to hepatectomy has to be taken.
Abstract: ABSTRACT: BACKGROUND: Ovarian cancer ascites fluid (OCAF), contains malignant cells, is usually present in women with an advanced stage disease and currently has no effective therapy. Hence, we developed a new therapy strategy to target the expression of diphtheria toxin gene under the control of H19 regulatory sequences in ovarian tumor cells. H19 RNA is present at high levels in human cancer tissues (including ovarian cancer), while existing at a nearly undetectable level in the surrounding normal tissue. METHODS: H19 gene expression was tested in cells from OCAF by the in-situ hybridization technique (ISH) using an H19 RNA probe. The therapeutic potential of the toxin vector DTA-H19 was tested in ovarian carcinoma cell lines and in a heterotopic animal model for ovarian cancer. RESULTS: H19 RNA was detected in 90% of patients with OCAF as determined by ISH. Intratumoral injection of DTA-H19 into ectopically developed tumors caused 40% inhibition of tumor growth. CONCLUSION: These observations may be the first step towards a major breakthrough in the treatment of human OCAF, while the effect in solid tumors required further investigation. It should enable us to identify likely non-responders in advance, and to treat patients who are resistant to all known therapies, thereby avoiding treatment failure.
Abstract: BACKGROUND: Octanoate (also known as sodium octanoate), a medium-chain fatty acid metabolized in the liver, is a potential substrate for non-invasive breath testing of hepatic mitochondrial beta-oxidation. METHODS: We evaluated the (13)C-octanoate breath test (OBT) for assessing injury in acute hepatitis and two rat models of liver cirrhosis, first testing octanoate absorption (per os or intraperitoneally (i.p.)) in normal rats. We then induced acute hepatitis with thioacetamide (300 mg/kg/i.p., 24-h intervals). Liver injury end points were serum aminotransferase levels and (13)C-OBT (24 and 48 h following initial injection). Thioacetamide (200 mg/kg/i.p., twice per week, 12 weeks) was used to induce liver cirrhosis. OBT and liver histological assessment were performed every 4 weeks. Bile duct ligation (BDL) was used to induce cholestatic liver injury. We completed breath tests with (13)C-OBT and (13)C-methacetin (MBID), liver biochemistry, and liver histology in BDL and sham-operated rats (baseline, 6, 14, 20 days post-BDL). RESULTS: Octanoate absorbs well by either route. Peak amplitudes and cumulative percentage dose recovered at 30 and 60 min (CPDR30/60), but not peak time, correlated with acute hepatitis. Fibrosis stage 3 at week 8 significantly correlated with each OBT parameter. Cholestatic liver injury (serum bilirubin, ALP, gamma-GT, liver histology) was associated with significant suppression of the maximal peak values and CPDR30/60, respectively (P < 0.05), using MBID but not (13)C-octanoate. CONCLUSIONS: OBT is sensitive for potentially evaluating liver function in rat models of acute hepatitis and thioacetamide-induced liver cirrhosis but not in cholestatic liver injury. The MBID test may be better for evaluation of cholestatic liver disease in this model.
Abstract: BACKGROUND AND AIM: Methacetin is thought to be a good substrate for the evaluation of different cytochrome P450 enzymatic systems of liver microsomes because of its rapid metabolism and lack of toxicity in small doses. Recent studies indicate that a methacetin breath test may be a non-invasive alternative for the evaluation of liver function since it correlates well with the severity of liver damage. It may also discriminate between different stages of liver cirrhosis and correlates with the Child-Pugh score. The application of this test in experimental liver damage in animal models has not yet been examined. This study aimed to evaluate the efficacy of the (13)C-methacetin breath test in assessing the extent of hepatic injury in models of acute liver failure, liver cirrhosis, and fatty liver in rats. METHODS: Absorption of methacetin given per os or intraperitoneally in normal rats was evaluated. The association between liver mass and (13)C-methacetin breath test results was assessed in a 70% hepatectomy rat model. Fulminant hepatic failure was induced by three consecutive intraperitoneal injections of thioacetamide, 300 mg/kg, at 24 h intervals. For induction of liver cirrhosis, rats were given intraperitoneal injections of thioacetamide, 200 mg/kg, twice a week for 12 weeks. A methionine-choline deficient diet was used for the induction of fatty liver. Rats were analyzed for (13)C-methacetin by BreathID (MBID) using molecular correlation spectrometry. BreathID continuously sampled the animal's breath for 60 min and displayed the results on the BreathID screen in real-time. RESULTS: Methacetin was absorbed well irrespective of the administration method in normal rats. Liver mass was associated with peak amplitude, complete percent dose recovery (CPDR) at 30 and 60 min and MBID peak time. A high degree of association was also demonstrated with MBID results in acute hepatitis (peak amplitude, 19.6 +/- 3.4 vs 6.3 +/- 1.63.4; CPDR30, 6.0 +/- 3.3 vs 1.2 +/- 0.5; CPDR60, 13.3 +/- 4.5 vs 3.2 +/- 1.4; and peak time, 31.0 +/- 14.9 vs 46.9 +/- 10.8 min) and liver cirrhosis (peak amplitude, 24.4 +/- 2.3 vs 15.6 +/- 6.4; CPDR30, 7.9 +/- 1.2 vs 2.7 +/- 1.0; CPDR60, 17.8 +/- 2.6 vs 8.8 +/- 2.1; and peak time, 30.2 +/- 1.5 vs 59.6 +/- 14.5 min), but not with grade of liver steatosis. CONCLUSIONS: Methacetin is well absorbed and exclusively metabolized in the liver. MBID is a sensitive test and may be a useful tool for the evaluation of functional liver mass in animal models of acute liver failure and cirrhosis. However, MBID could not distinguish between fatty liver and normal liver in rats.
Abstract: A 74-year-old patient who has developed fecal incontinence following continuous ambulatory peritoneal dialysis (CAPD) is presented. Incontinence was caused by elevated intra-abdominal pressure during peritoneal dialysis, which correlated with the volume of dialysate and position of the patient. The lowest pressure was found in the recumbent position. A change of dialysis schedule to continuous cycler peritoneal dialysis (CCPD) with "dry day" resulted in a disappearance of the symptoms.
Abstract: BACKGROUND: Now that the laparoscopic treatment of symptomatic liver cystic disease has proven feasible and safe, it is gaining wide acceptance. However, due to diagnostic pitfalls and a relatively high recurrence rate, further improvements and refinement of the procedure are still needed. We have evaluated the contribution of laparoscopic ultrasound in the diagnosis and management of patients with symptomatic liver cysts. METHODS: Twelve patients with single or multiple cysts of the liver and two patients with polycystic liver disease were managed laparoscopically. Laparoscopic ultrasound served as an integral part of the procedure in all patients. RESULTS: Patients underwent either complete cyst excision (two cases) or resection of the extrahepatic cystic component (eight cases). Additionally, in two patients, deep cysts not demonstrated by preoperative imaging studies were detected and treated with a combination of laparoscopy and laparoscopic ultrasound. In one patient with a cystobiliary fistula, conversion to an open cystjejunostomy was necessary. Patients with polycystic liver disease underwent a combination of excision and unroofing of both superficial and deeper cysts using laparoscopic contact ultrasound throughout the procedure. Laparoscopic ultrasonography was found to have a significant impact on the operative strategy in five patients (36%) with multiple cysts or polycystic disease. The postoperative course was uneventful in all cases. Thirteen patients remained asymptomatic throughout the follow-up period of 30 months; one patient with polycystic liver disease developed recurrent symptoms after 5 months and was treated with left hepatectomy. CONCLUSION: Additional use of laparoscopic ultrasound enables the detection, differentiation, and treatment of deep, nonvisualized cystic lesions (two patients, 16.6%) and validation of the adequacy of the laparoscopic procedure.
Abstract: Solitary and multiple hepatic cysts are now more commonly found because of advances in imaging techniques. Most hepatic cysts are asymptomatic, but when they do cause symptoms they require surgical intervention. The advent of laparoscopy and of laparoscopic ultrasonography allow comprehensive evaluation and treatment of the cysts. 12 patients with hepatic cysts were treated laparoscopically. 8 with single cysts underwent successful subtotal cyst resection without signs of recurrence (up to 20 years of follow-up). 4 with polycystic liver disease underwent sub-total resection of superficial cysts. Deep cysts were unroofed and drained under laparoscopic ultrasound guidance. In this group, 1 experienced recurrence of symptoms and required partial hepatectomy of the involved segment. In another, a connection between a deep cyst and bile ducts was demonstrated and cystojejunostomy was performed. The laparoscopic approach in the management of patients with liver cysts is effective and safe, and we recommend it as the procedure of choice for single hepatic cysts. In polycystic liver disease the procedure is much less successful.
Abstract: Silver plating of nucleoli was used to study the activity of nucleolar organizers (NO) in the cells of one-layer prismatic epithelium of the gastric and duodenal mucosae. The activity of NO was established to be lowered in patients suffering from ulcer disease and in patients with compression stenosis of the celiac trunk, which may point to the impairment of protein synthetic processes in the cells. Factor of ischemia as the most probable cause of the enumerated changes is under discussion.
Abstract: By means of a polarographic method, the decrease in the rate of blood flow in the gastric and duodenal mucosa at the period of exacerbation of ulcer disease, and its normalization at the period of ulcer healing were revealed. The role of the impaired blood supply of the mucosa in ulcer formation is discussed.
