Thorotrast-induced ruptured hepatic angiosarcoma

The use of Thorotrast as a contrast medium is now of historical interest. Thorotrast-induced angiosarcoma, though rare, still generates considerable clinical interest because of the characteristic opacification of the liver, spleen, and lymph nodes, and the long latency period between exposure and the onset of the tumor. We present a case of hepatic angiosarcoma which developed 37 years after the administration of Thorotrast.     

Long-Term Haematological Complications of Thorotrast

Six cases representing the spectrum of haematological complicationsdue to systemic administration of Thorotrast are reposted. Twopatients suffered from acute leukaemia, one patient had marrowfailure and three patients presented with haematological featuresof hyposplenism; two of these also had solid tumours. The literatureis reviewed.     

Thorotrast-induced cholangiocarcinoma: case report

Thorotrast, a contrast medium used extensively before being banned in 1950s, delivers a densely ionizing, high linear energy transfer type of radiation that predisposes to malignancies. We report a case of peripheral cholangiocarcinoma and describe its computed tomographic and magnetic resonance imaging features in a patient who developed it 48 years after exposure to Thorotrast.     

华蟾素辅助治疗晚期消化系统肿瘤近期疗效观察

目的:总结中药抗癌针剂华蟾素辅助治疗晚期消化系统肿瘤的效果。方法:用华蟾素15~20mL加入生理盐水250mL静脉滴注,连续20d为1个疗程,一般连用1~3个疗程;同时配合中医辨症论治口服中药。其中10例同时接受了CF+5FU+L-OHP方案化疗,1例接受了CF+5FU方案化疗。结果:CR为0,PR为2,NC12例,PD12例,其中2例PR病例均接受了化疗;病人腹胀、肝区痛、食欲不振、神疲乏力等症状明显改善,肝功能明显改善,生活质量明显提高。结论:静脉滴注华蟾素应是目前治疗晚期消化系统肿瘤一项比较合适的辅助措施。     

The effects of adrenalin, glucagon, insulin and dibutyryl cyclic AMP on liver and serum alpha-amylase activities in the rat

The effects of the injection of adrenalin, glucagon, insulin and dibutyryl cyclic AMP on the α-amylase activities of liver and serum were investigated. In rats aged 5–8 days, but not in adult rats, the intraperitoneal injection of adrenalin caused an increase in serum amylase activity and a decrease in liver amylase activity. Insulin produced a decrease in serum amylase and an increase in liver amylase activity. Glucagon and dibutyryl cyclic AMP had no effect on serum amylase but, like adrenalin, decreased the liver amylase activity.     

Hydatid liver cyst: an 11-year experience of treatment with percutaneous aspiration and ethanol injection.

OBJECTIVE: To report an 11-year experience of treatment of hydatid liver cysts with double percutaneous aspiration and injection of alcohol. METHODS: Of the 129 patients with 174 hydatid liver cysts admitted to our department between January 1988 and January 1999, 79 patients with 119 vital hydatid liver cysts were selected for double percutaneous aspiration and injection of alcohol. Under ultrasonographic guidance, cystic cavities were first drained through fine needles, and then 95% sterile ethanol was injected and left in situ. The same procedure was repeated 3 days later without reaspiration of the injected alcohol. General anesthesia without endotracheal intubation was performed in 21 selected cases. RESULTS: Double percutaneous aspiration and injection of alcohol was completed in 78 patients with 118 hydatid liver cysts. In 1 case the procedure could not be accomplished because of an intracystic hemorrhage. A total of 254 punctures were performed, and the ethanol injected per session ranged between 12 and 250 mL. The mean hospital stay was 2.9 days (range, 2-7 days). The overall median follow-up was 48 months (range, 6-122 months). At the last ultrasonographic examination, 45.8% of the treated hydatid liver cysts had a solid pattern, 47.4% were no longer appreciable, and 6.8% had a minimal liquid component. Intracystic relapse occurred in 5% of the patients. In no case were any new cysts observed either in different hepatic segments or in any extrahepatic location. The morbidity rate was 9%, and 1 death occurred (mortality rate, 1.3%). CONCLUSIONS: Over a long period, double percutaneous aspiration and injection of alcohol proved to be a substantially safe, effective, and low-cost procedure for hydatid liver cyst treatment.     

Pulse inversion sonography in the early phase of the sonographic contrast agent Levovist: differentiation between benign and malignant focal liver lesions.

OBJECTIVE: To determine whether examination of focal liver lesions by pulse inversion sonography in the early perfusion phase of the contrast agent Levovist (SH U 508A; Schering AG, Berlin, Germany) enables distinction between benign and malignant lesions. METHODS: Seventy-two patients were examined. The cause of the lesion was confirmed by liver biopsy, computed tomography, or both or by hepatic iminodiacetic acid-enhanced scintigraphy. Forty-two patients had malignant liver lesions, and 30 had benign liver lesions. After injection of 2 g of Levovist intravenously, analysis of Levovist arrival was performed by the interval delay imaging technique for 60 seconds. RESULTS: The early arrival of Levovist less than 30 seconds after injection was used as an indicator for malignancy and had specificity of 67% and sensitivity of 60% (P < .05). The central starlike fill-in as a sign for focal nodular hyperplasia had specificity of 100% and sensitivity of 67% (P < .001). The rimlike pattern followed by centripetal fill-in as a sign for hemangioma had specificity of 100% and sensitivity of 18% (P < .01). In contrast, the early diffuse stippled arrival pattern was found in 60% of malignant lesions and also in 33% of cases of focal nodular hyperplasia and in 1 patient with an adenoma. CONCLUSIONS: Analysis of Levovist arrival time cannot distinguish between a malignant or benign lesion in individual cases. However, the central starlike arrival pattern is characteristic of focal nodular hyperplasia.     

Contrast-enhanced power Doppler sonography: improved detection of characteristic flow patterns in focal liver lesions

PURPOSE: The aim of this study was to evaluate whether intravenous injection of an ultrasound contrast agent aids in the visualization of focal liver lesions on power Doppler images. METHODS: Fifty patients with focal liver lesions were studied by B-mode and power Doppler sonography before and after intravenous injection of the contrast agent Levovist (galactose-based microbubbles; 10 ml of a concentration of 300 mg/ml). Thirty-two patients had malignant liver lesions (19 metastases, 12 hepatocellular carcinomas, 1 cholangiocellular carcinoma), while 18 had benign lesions (12 hemangiomas, 2 focal nodular hyperplasias, 4 others). RESULTS: After contrast medium injection, the number of lesions with no intralesional flow dropped from 18 to 9. Flow signal intensity was rated subjectively as marked on contrast-enhanced images in 17 patients; only 4 patients had marked flow on precontrast images. On precontrast studies, central flow in 10 lesions and peripheral flow in 29 lesions could be observed. After enhancement, the numbers increased to 18 and 34 lesions, respectively. CONCLUSIONS: On power Doppler images, a greater number of intratumoral vessels are seen in focal liver lesions after contrast medium administration.     

Cervical thorotrast granuloma: An iatrogenic cause of dysphagia

Thorotrast granuloma of the neck is an extensive benign connective tissue overgrowth secondary to localized extravasation of contrast. This can present with dysphagia secondary to mass effect or motor disorder of swallowing related to demyelinization of the ninth through twelfth cranial nerves. The radiographic appearance is characteristic in both location and density.     

Antitumor effect of a splenic injection of 5-fluorouracil on metastatic liver cancer in mice

The regional administration of 5-fluorouracil (5-FU) has been the fundamental therapy against liver metastases for the improvement of patient prognosis; however, there have been few reports about the immunological effects of this agent. It is also unknown whether it affects the spleen, one of the major lymphoid organs. The objective of the present study was to determine the immunological effect of an intrasplenic injection of 5-FU against liver metastases. We investigated the effect of an intrasplenic injection of 5-FU on the formation of experimental liver metastasis resulting from an intraportal vein injection of colon 26 carcinoma cells in BALB/c mice and elucidated some of the underlying mechanisms involving the effects of this on cellular immunity. Liver metastases were significantly diminished by the splenic injection of 5-FU, particularly in comparison with the portal injection or systemic administration. This was followed by augmentation of the interleukin-12 (IL-12) level in the spleen and activation of hepatic mononuclear cells. In those cells, NK1.1+ (NKT) cells played a central role against metastases. A splenic injection of 5-FU is more effective on the involution of liver metastases than portal or systemic injection. This effect may be attributed to the augmentation of the IL-12 level in the spleen and of NKT cells in the liver rather than to the original effect of 5-FU, which is the so-called inhibition of DNA synthesis.     

Hepatotoxicity induced by a single ip injection of ruthenium red.

Ruthenium red (RR) has been used as a marker in morphological observations of the glycocalix because it interacts with polyanionic mucopolysaccharides. This fact may explain its agglutinating effect on rat blood red cells following a single 20 mg/kg intraperitoneal injection, which increases with time post-injection. This study was performed to determine whether such an effect was due to a direct effect of the RR on the blood cells, to interference with coagulation, or to the non-specific general toxicity of this dye. Male rats were injected with 20 mg/kg RR ip and the enzymatic and coagulation parameters, plus the liver morphology were examined. Alanine aminotransferase (ALAT) activity was increased at 30, 60 and 120 min, and aspartic aminotransferase (ASAT) activity was increased 60, 120 and 480 min after RR injection. The prothrombin time (PT) and partially activated thromboplastin time (PTT) were significantly decreased, particularly after 60-120 min. The liver had an external granular appearance with clear signs of congestion and oedema, and showed degenerative changes very soon after RR injection. A single administration of RR induces serious functional and structural changes in the liver. Such a toxicity, and these changes must be taken into consideration, particularly with regard to neurological studies.     

Severe thrombocytopenia due to hypersplenism successfully treated with partial splenic embolization in preoperative management

Hypersplenism is a known complication of portal hypertension secondary to cirrhosis of the liver. Although thrombocytopenia secondary to hypersplenism does not cause clinically significant hemostatic defect, it may need to be addressed in selective circumstances, such as preoperative preparation for a surgery. This report describes a 30-year-old male with a history of cirrhosis of the liver and hypersplenism who had a recurrence of craniopharyngioma. A platelet count of 40 x 10(9)/L limited his treatment options. A stereotactic injection of radioactive P32 into the tumor was planned but was thought not to be feasible because of the thrombocytopenia. The thrombocytopenia responded favorably to partial splenic embolization, and the patient underwent successful stereotactic injection of radioactive P32 into the tumor.     

Hepatic CT enhancement: effect of the rate and volume of contrast medium injection in an animal model

Background: To evaluate the relative effect of rate of injection and volume of contrast medium on aortic, portal, and hepatic enhancement during computed tomography (CT). Methods: Thirty-eight nonincremental CT examinations were performed in three mini-pigs by using a combination of three different volumes (1.5, 2, and 3 mL/kg) and five different rates (1.5, 3, 4.5, 6, and 7.5 mL/s) of contrast material injection. Time-density enhancement curves of the aorta, portal vein, and liver were plotted over time for each rate of injection, each volume of contrast, and each volume–rate combination. In addition, aortic, portal, and liver peak enhancements, time-to-peak enhancements, optimal scanning intervals, and contrast enhancement indices were calculated for each volume–rate combination. Results: Higher rates of injection increased peak aortic enhancement but had no effect on peak portal or hepatic enhancement. This result may be explained by the dilution of the bolus of contrast medium in the splanchnic circulation. When the results of a 6-mL/s injection of 1.5 mL/kg of contrast material were compared with a 3-mL/s injection of 2 mL/kg, maximum aortic enhancement increased by 32%, whereas maximum liver enhancement decreased by 35%. Conclusion: An increase in the rate of contrast injection results in an increase of peak aortic enhancement even when the total iodine load is decreased. However, an increase of the rate of contrast injection does not increase maximum liver enhancement, which is related to the total iodine dose injected. Therefore, one cannot compensate a decrease in the iodine load by an increase in injection rate in contrast-enhanced CT of the liver. Received: 3 September 1997/Revision accepted: 13 January 1999     

Characterization and function of the bovine kidney epithelial angiotensin receptor subtype 4 using angiotensin IV and divalinal angiotensin IV as receptor ligands

A polymeric prodrug of prostaglandin E(1) (PGE(1)) was synthesized using galactosylated poly(L-glutamic acid hydrazide) (Gal-HZ-PLGA) as a biodegradable and targetable carrier to hepatocytes. Poly(L-glutamic acid hydrazide) was prepared by reacting poly(gamma-benzyl-L-glutamate) with hydrazine monohydrate, followed by reaction with 2-imino-2-methoxyethyl-1-thiogalactosides to obtain Gal-HZ-PLGA after i.v. injection. (111)In-labeled galactosylated poly(L-glutamic acid hydrazide) ((111)In-Gal-HZ-PLGA) rapidly accumulated in the liver in a dose-dependent manner, whereas (111)In-poly(L-glutamic acid hydrazide) did not, indicating the involvement of a galactose-specific mechanism in the uptake of (111)In-Gal-HZ-PLGA. Fractionation of liver cells revealed that (111)In-Gal-HZ-PLGA was preferentially taken up by liver parenchymal cells. After being taken up by the liver, (111)In-Gal-HZ-PLGA was gradually degraded, and radioactive metabolites with low molecular weight were detected within 10 min after injection. Then, PGE(1) or [(3)H]PGE(1) was coupled to Gal-HZ-PLGA via a hydrazone bond under mild conditions to obtain PGE(1) conjugate. After i.v. injection, [(3)H]PGE(1) conjugate was rapidly taken up by the liver (more than 80% of the dose). After injection of the conjugate, (3)H radioactivity remained in the liver, representing about 70% of the dose, even at 24 h, whereas little radioactivity remained in the organ at 1 h after the injection of free [(3)H]PGE(1). Finally, its pharmacological activity was examined in mice with fulminant hepatitis induced by peritoneal injection of carbon tetrachloride. The i.v. injection of PGE(1) conjugate at a dose of 1 mg (0.074 mg PGE(1))/kg effectively inhibited the increase of plasma glutamic pyruvic transaminase activity, whereas twice this dose (0.15 mg/kg) of free PGE(1) had little effect. These results suggest that the PGE(1) conjugate is an excellent polymeric prodrug of PGE(1) for hepatitis therapy.     

Injection sclerotherapy of oesophageal variceal haemorrhage. A prospective long-term follow-up study

One-hundred-seventy-five patients with oesophageal variceal bleeding and liver cirrhosis who underwent long-term injection sclerotherapy were prospectively followed for 44 +/- SD 17 months. While aetiology (alcoholic vs. non-alcoholic cirrhosis) had no influence on survival, the Child status assessed at the time of initiation of sclerotherapy was of important prognostic value (mortality rate after a mean follow-up of 44 months: Child A 5%, Child B 45%, and Child C 83%). Initiation of sclerotherapy (elective vs. emergency) had no influence on survival in the A/B patients, whereas electively treated Child C patients had a somewhat better outcome than those in whom sclerotherapy was started during active bleeding. Rebleeding, especially within the first two months after starting repeat sclerotherapy, was significantly influenced by the Child status of the patients. About one-fourth of all deaths were combined with rebleeding in the Child B and C patients, but none of the A patients had intestinal bleeding prior to death. It is concluded that Child A patients have an excellent long-term prognosis after variceal haemorrhage treated by repeated endoscopic injection of the varices.     

Hepatic artery administration of degradable starch microspheres

The effects of hepatic artery administration of degradable starch microspheres on liver energy charge and nucleic acid anabolism were studied in rats. Liver energy charge was evaluated 20 and 60 min after the injection of degradable starch microspheres. As compared to controls the microspheres had no effect on liver energy charge. The incorporation of orotic acid, uracil, and thymidine into liver RNA or DNA was studied 1 h after hepatic artery injection of precursor alone or together with degradable starch microspheres. Orotic acid and uracil incorporation into RNA was studied in normal rats and the DNA incorporation of thymidine in animals with regenerating livers. Orotic acid and thymidine were given in trace amounts. Uracil was given in amounts corresponding to a therapeutic dose of 5-fluorouracil. The addition of microspheres had no effects on the incorporation of the nucleic acid precursors into RNA or DNA. Thus, in the normal liver degradable starch microspheres administered by the hepatic artery had no influence on liver energy charge or RNA anabolism in the liver. Also the microspheres had no negative effects on the DNA anabolism in proliferating liver cells.     

Rapid Kupffer cell death after intravenous injection of adenovirus vectors.

When adenovirus vectors are injected intravenously, they are quickly taken up by Kupffer cells in the liver. We report that this causes rapid necrosis of Kupffer cells in mice at doses of 10(11) particles/kg or higher. By 10 min after intravenous vector injection, Kupffer cells were permeable to propidium iodide and trypan blue. This coincided with a sharp rise in serum lactate dehydrogenase. Ultrastructural examination showed degeneration of Kupffer cells, including complete disappearance of chromatin by 1 h. After an initial intravenous injection of vector, dead Kupffer cells were unable to take up a second dose of vector, and hepatic transgene expression from the second dose was augmented. Death of Kupffer cells did not affect serum levels of IL-6 or IL-12. There was no immediate change in the number of Kupffer cells in the liver, but a significant decline was found by 4 h after injection of vector. Interestingly, substantial numbers of vector-containing Kupffer cells were found in pulmonary capillaries, indicating that they had been swept out of the liver. Together these results show that an intravenous injection of adenovirus vector causes synchronous and surprisingly rapid Kupffer cell death.     

Flumazenil in the treatment of hepatic encephalopathy in children with fulminant liver failure

Objective To evaluate the effect of flumazenil on hepatic encephalopathy complicating fulminant liver failure in children.Design Uncontrolled prospective study.Setting Pediatric Intensive Care Unit, tertiary care center.Patients 9 children with fulminant liver failure and hepatic encephalopathy awaiting emergency liver transplantationInterventions Changes in hepatic encephalopathy grade and in electroencephalogram were recorded during the injection of a bolus of flumazenil (0.01 mg/kg/IV bolus) followed by a continuous infusion of flumazenil (0.01mg/kg/h).Measurements and main results Before flumazenil, 7 children had grade 2 and 2 had grade 3 hepatic encephalopathy. Flumazenil injection mediated an arousal effect in 1 child in whom encephalopathy improved from grade 3 to grade 2. This effect lasted 30 min. No clinical response was observed in other children. An improvement of EEG anomalies was observed lasting 3 min in one child. Despite continuous infusion of flumazenil, encephalopathy worsened in all children.Conclusion The effect of intravenous administration of flumazenil on hepatic encephalopathy in children with fulminant liver failure is inconsistent. Its efficacy is transient. The therapeutic value of flumazenil in children with fulminant liver failure awaiting a liver graft is minimal at this dosage.     

超声引导下醋酸注射治疗兔肝VX2肿瘤的实验研究

目的 探讨超声引导下醋酸注射治疗肝肿瘤的效果。方法 在超声引导下对20只家兔肝组织注射不同浓度及剂量的醋酸,分别于即刻1d、3d及1周后观察超声图像,之后处死动物进行病理检查,同时测量其凝固区直径。采用兔肝VX2肿瘤模型8只（10个结节）进行醋酸瘤内注射。注射后即刻及注射后1d处死动物观察其病理变化。另有对照组动物6只（8个结节）同期处死,比较生长情况。结果 注射醋酸后动物肝脏立即发生凝固性坏死,坏死区呈椭球形。坏死区大小与其浓度及剂量呈正比。超声引导下醋酸瘤内注射24h后8个结节肿瘤细胞发生完全凝固性坏死,而注射后12h内2个结节肿瘤原发灶大部分发生变性及凝固性坏死,边缘有少量肿瘤残存,而对照组肿瘤结节的平均直径为1．3cm,两组差异有显著性意义。结论 醋酸对兔肝VX2肿瘤有极强的杀伤作用,治疗后24h完全坏死。