Ameliorative effects of vitamins-loaded flavoured nanophytosomes fortified with star anise volatile oil against CsA-Induced liver and kidney injury in rats: Application in functional ice cream.

This study investigated the effect of flavoured nanophytosomes loaded with vitamins A, E, D, B complex, folic acid, and C, as well as zinc on the immunosuppressive cyclosporin A (CsA)-induced liver and kidney injury in male rats. The vitamins flavoured nanophytosomes (VFnPs) were characterized in terms of particle size, zeta potential, encapsulation efficiency. Ice cream was flavoured with star anise volatile oil to mask the VFnPs' flavour and unacceptable taste. The study found that treatment with CsA alone resulted in increased (P > 0.05) levels of creatinine, urea, and MDA, as well as the activities of AST and ALT, while the levels of SOD, CAT, GST, proteins, CD4, INF-ᵧ, IL-6, IL-1ß, and TLR4 decreased (P > 0.05). However, the group that received CsA simultaneously with VFnPs showed a significant (P > 0.05) decrease in the levels of creatinine, urea, and MDA, as well as the activities of AST and ALT, and increased (P > 0.05) levels of SOD, CAT, GST, proteins, CD4, INF-ᵧ, IL-6, IL-1ß, and TLR4. The increase in the ratio of VFnPs had little effect on the physiochemical and sensory evaluation of the ice cream. Finally, the study suggests that VFnPs could potentially protect against CsA-induced liver and kidney injury and serve as a promising natural therapy for treating such conditions.

A comparative study on flavour components and therapeutic properties of unfermented and fermented defatted soybean meal extract.

Microbial fermentation of plant material alters the composition of volatile and non-volatile plant natural products. We investigated the antioxidant, anticancer, and antiviral properties of extracts of defatted soybean meal fermented with Aspergillus fumigatus F-993 or A. awamori FB-133 using in vitro methods. Gas chromatography-mass spectrometry analysis of soybean meal fermented with A. awamori FB-133 and A. fumigatus F-993 identified 26 compounds with 11,14-octadecadienoic acid and methyl ester (63.63%) and 31 compounds with butylated hydroxytoluene (66.83%) and δ-myrcene (11.43%) as main constituents, respectively. The antioxidant activities of DSM extract were 3.362 ± 0.05 and 2.11 ± 0.02 mmol TE/mL, FDSM treated with A. awamori FB-133 were 4.763 ± 0.05 and 3.795 ± 0.03 mmol TE/mL and FDSM treated with A. fumigatus F-993 were 4.331 ± 0.04 and 3.971 ± 0.02 mmol TE/mL as determined by ABTS and FRAP assays, respectively. Both fermented extracts had better antioxidant activity than the unfermented extract as shown by multiple antioxidant activity assays. The concentration of fermented extracts required for 50% inhibition of cell viability was significantly lower than that of the unfermented extract when tested against the human liver cancer cell line HepG2 as shown by cell viability assays, indicating strong anticancer activity. The IC50 values for DSM, FDSM with A. fumigatusF-993 and FDSM with A. awamori FB-133 were27, 16.88 and 8.60 µg/mL, respectively. The extract of FDSM with A. awamori FB-133 showed the strongest anticancer activity, compared to DSM and FDSM with A. FumigatusF-993 extracts. Fermented extracts also reduced hepatitis A virus titres to a greater extent than unfermented extracts, thus showing strong antiviral property. Hepatitis A virus titres were reduced by 2.66 and 3 log10/0.1 mL by FDSM with A. fumigatusF-993 and FDSM by A.awamori FB-133, respectively, compared to DSM (5.50 log10/0.1 mL). Thus, the fermentation of soybean meal with A. fumigatusF-993 or A. awamori FB-133 improves the therapeutic effect of soybean extracts, which can be used in traditional medicine.

Perioperative use of continuous renal replacement therapy for orthotopic liver transplantation.

PURPOSE: We present a retrospective study describing the perioperative use of continuous renal replacement therapy (CRRT) for orthotopic liver transplantation (OLT). MATERIALS AND METHODS: We retrospectively reviewed the clinical course of patients who underwent OLT with the perioperative use of CRRT. The following variables were recorded: Gender, age, indication for transplantation, time when CRRT was initiated, postoperative need for CRRT, and the patient and organ (liver, kidneys) outcome up to 1 year after transplantation. RESULTS: Among 105 patients who underwent OLT from 2006 to 2010; we used CRRT in 12 cases (11.4%) perioperatively, including 9 (8.3%) patients intraoperatively. Perioperative CRRT was employed for volume, electrolyte, and/or pH management. All patients who underwent CRRT perioperatively were alive at 1 month, 10 (83.3%), at 3 and 6 months and 9 (75%) at 1 year after OLT. Only 1 surviving patient (8.3%) required renal replacement therapy at 1 month after surgery. Renal replacement therapy was not required in any surviving patient up to 12 months posttransplantation. CONCLUSION: Perioperative and especially intraoperative use of CRRT therapy can potentially improve the outcomes of patients undergoing OLT.

Liver transplantation for hepatitis C from donation after cardiac death donors: an analysis of OPTN/UNOS data.

Donation after cardiac death (DCD) liver transplantation is increasing largely because of a shortage of organs. However, there are almost no data that have specifically assessed the impact of using DCD livers for HCV patients. We retrospectively studied adult primary DCD liver transplantation (630 HCV, 1164 non-HCV) and 54 129 donation after brain death (DBD) liver transplantation between 2002 and 2009 using the UNOS/OPTN database. With donation after brain death (DBD) livers, HCV recipients had significantly inferior graft survival compared to non-HCV recipients (p < 0.0001). Contrary to DBD donors, DCD livers used in HCV patients showed no difference in graft survival compared to non-HCV patients (p = 0.5170). Cox models showed DCD livers and HCV disease had poorer graft survival (HR = 1.80 and 1.28, p < 0.0001, respectively). However, the hazard ratio of DCD and HCV interaction was 0.80 (p = 0.02) and these results suggest that DCD livers on HCV disease do not fare worse than DCD livers on non-HCV disease. The graft survival of recent years (2006-2009) was significantly better than that in former years (2002-2005) (p = 0.0482). In conclusion, DCD liver transplantation for HCV disease showed satisfactory outcomes. DCD liver transplantation can be valuable option for HCV related end-stage liver disease.

Lignan transformation by gut bacteria lowers tumor burden in a gnotobiotic rat model of breast cancer.

High dietary lignan exposure is implicated in a reduced breast cancer risk in women. The bacterial transformation of plant lignans to enterolignans is thought to be essential for this effect. To provide evidence for this assumption, gnotobiotic rats were colonized with the lignan-converting bacteria Clostridium saccharogumia, Eggerthella lenta, Blautia producta and Lactonifactor longoviformis (LCC rats). Germ-free rats were used as the control. All animals were fed a lignan-rich flaxseed diet and breast cancer was induced with 7,12-dimethylbenz(a)anthracene. The lignan secoisolariciresinol diglucoside was converted into the enterolignans enterodiol and enterolactone in the LCC but not in the germ-free rats. This transformation did not influence cancer incidence at the end of the 13 weeks experimental period but significantly decreased tumor numbers per tumor-bearing rat, tumor size, tumor cell proliferation and increased tumor cell apoptosis in LCC rats. No differences between LCC and control rats were observed in the expression of the genes encoding the estrogen receptors (ERs) α, ERß and G-coupled protein 30. The same was true for IGF-1 and EGFR involved in tumor growth. The activity of selected enzymes involved in the degradation of oxidants in plasma and liver was significantly increased in the LCC rats. However, plasma and liver concentrations of reduced glutathione and malondialdehyde, considered as oxidative stress markers, did not differ between the groups. In conclusion, our results show that the bacterial conversion of plant lignans to enterolignans beneficially influences their anticancer effects.

Fatal hyperammonemia after renal transplant due to late-onset urea cycle deficiency: a case report.

We present a case of severe hyperammonemia with subsequent brain herniation in an adult man after renal transplantation. After successful surgery and an initially uneventful postoperative course, the patient developed significant mental status changes associated with seizure activity. His condition rapidly deteriorated, requiring mechanical ventilation and cardiovascular support. Laboratory studies at that time demonstrated an increased serum ammonia level without evidence of liver or kidney dysfunction. Further investigation revealed an increased orotic acid level in the urine, suggesting a urea cycle disorder (UCD). Despite aggressive therapy, the patient's condition continued to deteriorate. Magnetic resonance imaging demonstrated severe brain edema with no cerebral perfusion; after consultation with the family, care was withdrawn. The combination of hyperammonemia and elevated urine orotic acid with normal liver and kidney function suggested a UCD. It is important to note that patients with a UCD may be free of symptoms for many years. Several factors are able to trigger the disease in adulthood, leading to encephalopathy and death. In this case, the patient's seizures were initially assumed to be a side effect of immunosuppressive therapy. Further diagnostic measures were only performed late in the course of the disease, which delayed the diagnosis of UCD.

F-18-fluorodeoxyglucose (FDG) positron-emission tomography of Echinococcus multilocularis liver lesions: prospective evaluation of its value for diagnosis and follow-up during benzimidazole therapy.

BACKGROUND: Long-term benzimidazole therapy benefits patients with non-resectable alveolar echinococcosis (AE). Methods to assess early therapeutic efficacy are lacking. Recently, AE liver lesions were reported to exhibit increased F-18-fluorodeoxyglucose (FDG) uptake in positron emission tomography (PET). To assess the value of FDG-PET for diagnosis and follow-up of AE patients. PATIENTS/METHODS: Twenty-six consecutive patients with newly diagnosed AE were enrolled. Baseline evaluation included CT and FDG-PET. Thirteen patients (11 women; median age 50 years, range 40-76) were resected, the remaining 13 (8 women; median age 60 years, range 39-72) had non-resectable disease, were started on benzimidazoles, and CT and FDG-PET were repeated at 6, 12 and 24 months of therapy. Twelve consecutive patients with newly diagnosed cystic echinococcosis (CE) of the liver were also subjected to baseline FDG-PET. RESULTS: In 21/26 AE patients, baseline PET scans showed multifocally increased FDG uptake in the hepatic lesions' periphery, while liver lesions were FDG negative in 11/12 CE patients. Thus, sensitivity and specificity of FDG-PET for AE vs. CE were 81% and 92%, respectively. In 5 of 10 non-resectable patients with increased baseline FDG uptake, the intensity of uptake decreased (or disappeared) during benzimidazole therapy, in 3 by >or=2 grades within the initial 6 months. CONCLUSIONS: FDG-PET is a sensitive and specific adjunct in the diagnosis of suspected AE and can help in differentiating AE from CE. The rapid improvement of positive PET scans with benzimidazole therapy in some patients indicates that absent FDG uptake does not necessarily reflect parasite viability.

Downstaging colorectal liver metastases by concomitant unilateral portal vein ligation and selective intra-arterial chemotherapy.

BACKGROUND: Although selective intrahepatic arterial chemotherapy successfully downstaged irresectable colorectal liver metastases in a previous study, curative resection was rarely possible, as the remnant healthy liver volume was inadequate. This pilot study evaluated the efficacy of concomitant unilateral portal vein ligation and selective intrahepatic arterial chemotherapy in downstaging such tumours. METHODS: The study included 11 patients with irresectable colorectal liver metastases. Selective intrahepatic arterial chemotherapy was delivered using a subcutaneous pump, and each patient underwent concomitant unilateral portal vein ligation of the hemiliver judged to have the higher tumour load. Chemotherapy involved serial administration of floxuridine for 2 weeks every 4 weeks. RESULTS: All patients developed significant atrophy of the hemiliver subjected to portal vein ligation and contralateral hypertrophy. There was no increase in tumour load within 6 months of therapy, and the load decreased by 60 per cent in the hemiliver ipsilateral to the ligated vein. At 3 months, six of 11 patients showed a significant response to chemotherapy. In four patients, downstaging allowed curative resection after only three cycles of chemotherapy. These patients survived at least 20 months afterwards. CONCLUSION: Combined unilateral portal vein ligation and selective intrahepatic arterial chemotherapy produced substantial atrophy of the ipsilateral hemiliver along with contralateral hypertrophy, without increased tumour growth in the regenerating hemiliver.

Evaluation of treatment and long-term follow-up in patients with hepatic alveolar echinococcosis.

BACKGROUND: Alveolar echinococcosis is a rare disorder, which makes a comparison of different treatment modalities within a clinical trial difficult to perform. Data prospectively recorded over a period of 25 years were used to evaluate three therapeutic strategies: benzimidazole therapy alone, complete 'curative' resection followed by 2 years of adjuvant benzimidazole treatment, and partial debulking resection followed by continuous administration of a benzimidazole. METHODS: Details of 113 patients with hepatic alveolar echinococcosis treated between 1976 and 2003 were analysed. Kaplan-Meier survival curves were constructed and, using a Cox regression model, patient age, year of initial treatment and PNM stage were entered as co-variates in the analysis. RESULTS: Kaplan-Meier overall survival curves stratified for treatment strategy indicated an improved long-term survival in patients undergoing the debulking procedure (P = 0.061) or curative resection (P = 0.002) compared with benzimidazole therapy alone. However, when PNM stage, patient age and year of initial treatment were introduced into the analysis, there was a trend for survival advantage only with curative resection (P = 0.07 versus benzimidazole alone). Debulking resulted in a higher rate of progression of hepatic echinococcosis than curative surgery (P = 0.008). The incidence of parasite-related complications was similar for debulking resection and benzimidazole therapy alone (P = 0.706). CONCLUSION: Debulking hepatic resections do not appear to offer any advantage in the treatment of patients with alveolar echinococcosis.

First clinical experience with Molecular Adsorbent Recirculating System (MARS) in six patients with severe acute on chronic liver failure.

UNLABELLED: Despite recent advances in general supportive care, the mortality rate of patients with severe liver insufficiency remains high. Recently a new artificial liver support system MARS has been used for selective removal of albumin-bound toxins. AIM: To assess the safety and efficacy of MARS treatment in patients with acute on chronic liver disease (n = 5) or liver failure after extended hepatic resection (n = 1). DESIGN/PATIENTS: Six patients, aged 34-58 years, with severe liver insufficiency (mean MELD-score 31 (range 24-35)) were treated one to 16 times with the MARS system. At baseline three patients were intubated, three were encephalopathic (HE) and three had multifactorial kidney failure requiring kidney replacement therapy. RESULTS AND CONCLUSION: In all the patients MARS treatment significantly reduced the serum bilirubin levels. In three patients encephalopathy improved. In two patients the extracorporeal treatment precipitated a disseminated intravascular coagulation with clinically significant bleeding. Bridging to liver transplantation was possible in one patient, the other five patients died 30 days (2-74 days) after starting MARS therapy. Our case series shows that MARS treatment in general can be safely performed in patients with severe liver disease. However, in patients with an activated clotting system severe bleeding complication can be triggered and MARS treatment should be used very cautiously in these situations. MARS seems to be a promising new treatment option for patients with acute on chronic liver failure. However, carefully conducted randomized controlled trials are necessary to define its potential place in the treatment of patients with severe liver disease.

Neoadjuvant and adjuvant therapies for resectable hepatocellular carcinoma (HCC) and palliation strategies.

Hepatocellular carcinoma (HCC) is the most common primary malignancy in the liver worldwide. The incidence of the tumor varies geographically. Thus, in the eastern area (China, Taiwan, and Japan) there are more than 20 cases per year per 100'000 population compared to less than 5 cases per 100'000 in most western countries [1]. The etiology of HCC is multifactorial. The two most important factors are the presence of cirrhosis and chronic hepatitis [2]. Early detection of HCC still remains a challenge. At the time of diagnosis, only 20-30% of all patients have tumors that are surgically resectable. Survival after curative resection is 30%-50% at five years. The poor outcome of the disease led to the development of different adjuvant and neoadjuvant therapies. There are numerous studies dealing with the treatment of HCC. Unfortunately, only few randomized controlled trials exist. In addition, there is no consensus on staging of HCC and no standardization of the outcome in the literature, which makes it difficult to compare the different procedures. This paper summarizes the current strategies in the treatment of HCC.

Treatment of primary and secondary liver malignancy.

The management of hepatic malignancy is one of the most controversial areas in medicine. It is a continuously evolving field which requires a multimodal approach and the inclusion of a medical oncologist, a hepatobiliary surgeon, a radiotherapist, an interventional radiologist and in some cases a transplant surgeon. In addition, the recent development of novel approaches such as neoadjuvant tumour therapy, cryosurgery, thermal ablative techniques as well as biological and immunological manipulation of malignant cells has added to the complexity of this field. Today, the availability of such innovative modalities, in the absence of an extrahepatic localisation of disease, allows the potential to cure many large primary and secondary hepatic tumours. However, the appropriate use of these various treatment modalities should be limited to centers with experience in treating patients with advanced disease where innovative study protocols are available. Experience of the surgeon with difficult hepatectomies is of paramount importance. Currently, mortality following major hepatectomies in non-cirrhotic patients is below 5% in centers of reference. For example, in the series from Duke University Medical Center there were no fatalities in more than 150 liver resections in patients with benign diseases and a 2% mortality in more than 300 patients with malignant diseases. Mortality, however, reached 5% in cirrhotic patients undergoing a resection involving more than 2 segments. This review will attempt to focus on an overview of the diagnosis and treatment of a selection of more common hepatic malignancies.

Transplant legislation: ethical and practical issues in liver allocation--The case of Switzerland.

Ethical and practical issues relating to liver allocation have been discussed in many countries. Several governments, including the United States, have attempted over the past few years to impose new legislation, which has resulted in virulent debates among individual centers, organ procurement agencies, states, and various groups of interest. This report discusses the current ongoing legislative process in Switzerland. In 1999, the people of Switzerland voted to develop transplant legislation. This reflected the need to regulate poorly defined practices to adapt to the rapid progress within the field of transplantation. The main issue facing the Swiss transplant community is whether new legislation will allow medical evolution in organ allocation criteria without creating regulations that may become outdated with time. In addition, public debate has been shown to have a negative impact on organ donation, thus emphasizing an ever-present penury in cadaveric allografts. This article discusses these issues within the context of liver transplantation in Switzerland and also raises the uniform ethical and practical constraints placed on the medical transplant community in the face of an organ shortage.

Obtaining a superficial femoral artery graft in adolescents and children with the deep femoral artery transposition.

A new technique to obtain a segment of the superficial femoral artery as an arterial conduit in young patients while an unobstructed peripheral blood flow is maintained by superficial femoral artery-deep femoral artery transposition is illustrated with two clinical examples. The explanted arterial autograft requires no replacement by another graft and provides a conduit of up to 10 cm in length. Excellent results were achieved in both patients at 1 year. This technique is recommended instead of saphenous vein conduits in very young patients because of the risk for late vein degeneration.

Polymyalgia rheumatica as a manifestation of a large hepatic cavernous hemangioma.

A 59-year-old woman presented with polymyalgia rheumatica which was refractory to conventional anti-inflammatory and steroid therapy. A full investigation for an underlying occult malignancy showed only the presence of a giant cavernous hepatic hemangioma. To our knowledge, polymyalgia rheumatica has never been described in association with giant cavernous hepatic hemangioma; resection of the latter lesion resulted in complete and, to this date, definite resolution of rheumatologic complaints in our patient.

Paediatric living related intestinal transplantation between two monozygotic twins: a 1-year follow-up.

We report on a syngeneic living related intestinal transplant in a paediatric setting with a 1-year follow-up. This procedure has allowed progressive growth and weight gain of a recipient patient and a resumption of normal activities with full social and familial reintegration.

[Small intestine transplantation]. / La transplantation d'intestin grêle.

Since the development of new immunosuppressive agents, as FK506, the results of small bowel transplantation have greatly improved. The patient survival at one year has increased from 25% during the cyclosporin era to 65% in 1995 and the graft survival from 19% to 57% respectively. Clearly, the postoperative complications are still frequent and severe and do not allow a wide generalisation of this method. However, total parental nutrition is not an appropriate solution for the long term management of patients with terminal intestinal insufficiency. In Switzerland, these patients survive for several years and finally die of problems that small bowel transplantation could already successfully overpass.