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P-A Clavien

Publications and source records attributed to P-A Clavien.

16 recordsLinked to original sources
PubMed2006

Distribution and dynamic changes of sphingolipids in blood in response to platelet activation.

BACKGROUND: Sphingolipids are signaling molecules in a range of biological processes. While sphingosine-1-phosphate (S1P) is thought to be abundantly stored in platelets and released upon stimulation, knowledge about the distribution and function of other sphingolipids in blood is lacking. OBJECTIVES: To analyze the sphingolipid content of blood components with special emphasis on dynamic changes in platelets. METHODS: Blood components from mice and humans were prepared by gradient centrifugation and analyzed by liquid chromatography-mass spectrometry. Additionally, murine platelets were activated in vitro and in vivo. RESULTS: Isolated non-activated platelets of mice were devoid of S1P, but instead contained dihydrosphingosine-1-phosphate (dhS1P), along with a high concentration of ceramide. Activation of platelets in vitro led to a loss of dhS1P and an increase in sphingosine, accompanied by a reduction of ceramide content. Platelet activation in vivo led to an immediate and continuous rise of dhS1P in plasma, while S1P remained stable. The sphingolipid distribution of human blood was markedly different from mice. Human platelets contained dhS1P in addition to S1P. CONCLUSIONS: Mouse platelets contain dhS1P instead of S1P. Platelet activation causes loss of dhS1P and breakdown of ceramide, implying ceramidase activation. Release of dhS1P from activated platelets might be a novel signaling pathway. Finally, the sphingolipid composition of mouse and human blood shows large differences, which must be considered when studying sphingolipid biology.

Animals↗
PubMed2006

Transarterial chemoembolization as a bridge to liver transplantation for hepatocellular carcinoma: an evidence-based analysis.

The aim of this review was to assess the impact of transarterial chemoembolization (TACE) as a neoadjuvant therapy prior to orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC). An electronic search on the Medline database (1990-2005) was used to identify relevant articles. The studies were reviewed and ranked according to their quality of evidence using the grading system proposed by the Oxford Centre for Evidence-based Medicine. As a bridge to OLT, pretransplant TACE does not improve long-term survival (grade C). There is currently no convincing evidence that TACE allows to expand the current selection criteria for OLT, nor that TACE decreases dropout rates on the waiting list (grade C). However, TACE does not increase the risk for postoperative complications (grade C). There is insufficient evidence that TACE offers any benefit when used prior to OLT, neither for early nor for advanced HCC. Well-designed randomized controlled trials are needed to define the role of TACE in OLT patients.

Carcinoma, Hepatocellular↗
PubMed2006

Cholestasis protects the liver from ischaemic injury and post-ischaemic inflammation in the mouse.

BACKGROUND AND HYPOTHESIS: Cholestasis is associated with high morbidity and mortality in patients undergoing major liver surgery, but the mechanisms responsible remain elusive. Increased ischaemic liver injury and inflammation may contribute to the poor outcome. METHODS: Common bile duct ligation (biliary obstruction with hyperbilirubinaemia) or selective ligation of the left hepatic duct (biliary obstruction without hyperbilirubinaemia) was performed in C57BL/6 mice before 1 h of hepatic ischaemia and 1, 4 or 24 h of reperfusion. Infection with the intracellular hepatic pathogen Listeria monocytogenes for 12 and 48 h was used to study ischaemia-independent hepatic inflammation. RESULTS: Cholestatic mice showed considerable protection from ischaemic liver injury as determined by transaminase release, histological liver injury and neutrophil infiltration. In cholestatic mice, reduced injury correlated with a failure to activate nuclear factor kappaB (NFkappaB) and tumour necrosis factor alpha (TNFalpha) mRNA synthesis, two key mediators of post-ischaemic liver inflammation. After selective bile duct ligation, both the ligated and the non-ligated lobes showed blocked activation of NFkappaB as well as reduced induction of TNFalpha mRNA synthesis and neutrophil infiltration. By contrast, infection with L monocytogenes showed comparable activation of NFkappaB and hepatic recruitment of neutrophils 12 h after infection. CONCLUSION: Cholestasis does not increase but rather dramatically protects the liver from ischaemic injury and inflammation. This effect is mediated by a systemic factor, but not bilirubin, and is associated with a preserved capacity to trigger an inflammatory response to other stimuli such as a bacterial pathogen.

Animals↗
PubMed2006

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.

Aged↗
PubMed2006

Outcome and cost analysis of sacral nerve stimulation for faecal incontinence.

BACKGROUND: Sacral nerve stimulation (SNS) may be successful in treating incapacitating faecal incontinence. The technique is expensive, and no cost analysis is currently available. The aim of this study was to assess clinical outcome and analyse cost-effectiveness. METHODS: Thirty-six consecutive patients underwent a two-stage SNS procedure. Outcome parameters and real costs were assessed prospectively. RESULTS: SNS was tested successfully in 33 of 36 patients, and 31 patients were stimulated permanently. In the first stage, eight of 36 patients reported minor complications (pain, infection or electrode dislocation), resulting in a cost of euro 4053 (range euro 2838-7273) per patient. For the second stage (permanent stimulation), eight of 33 patients had an infection, pain or loss of effectiveness, resulting in a cost of euro 11,292 (range euro 7406-20,274) per patient. Estimated costs for further follow-up were euro 997 per year. The 5-year cumulative cost for SNS was euro 22,150 per patient, compared with euro 33,996 for colostomy, euro 31,590 for dynamic graciloplasty and euro 3234 for conservative treatment. CONCLUSION: SNS is a highly cost-effective treatment for faecal incontinence. Options for further reduction of SNS costs include strict patient selection, treatment in an outpatient setting and using cheaper devices.

Adolescent↗
PubMed2006

A prospective comparison between clinical outcome and open-configuration magnetic resonance defecography findings before and after surgery for symptomatic rectocele.

BACKGROUND: The correlation between clinical symptoms and anatomical findings by conventional imaging is poor in patients with rectoceles. The aim of this prospective study was to assess and to correlate symptomatic changes after anterior levatorplasty with morphologic changes visualized by magnetic resonance defecography (MRD). METHOD: Fourteen women with a median age of 57 (range 37-83) accepted to participate. Seven of 14 had previous hysterectomy. Patients underwent MRD before surgery and again 6 months postsurgery. Pre- and postoperative symptoms and quality of life (QoL) (Eypasch) were assessed. Faecal and urinary incontinence were graded (Wexner- / Hanley-score). RESULTS: The median Eypasch-score improved from 90 (range 38-106) to 106 (range 29-133) after surgery (P = 0.016). Similarly, the Wexner-score ameliorated from 8 (range 0-20) to 4.5 (range 0-18; P = 0.02). Seven patients described new dyspareunia postoperatively. The median follow up was 16.5 months (range 9-45). The median rectocele size decreased from 37 mm (range 30-48) preoperatively to 12 mm (range 0-42) postoperatively (P = 0.004). Furthermore, enteroceles were corrected and pelvic floor descent was significantly reduced after surgery. Only the clinical symptom of incomplete evacuation strongly correlated with the respective radiological finding of contrast dye trapping (Rho = 0.822; P = 0.001). CONCLUSION: Anterior levatorplasty improved QoL in patients with symptomatic rectocele. Postsurgical correction of rectocele is accurately documented by MRD. Only moderate correlation between morphologic and clinical improvements was observed.

Adult↗
PubMed2006

How useful is PET/CT imaging in the management of post-transplant lymphoproliferative disease after liver transplantation?

Post-transplant lymphoproliferative disease (PTLD) is a serious and potentially life-threatening complication after solid organ transplantation. Here, we report our first experience with the use of PET/CT (positron emission tomography combined with computed tomogram) for the management of patients with PTLD after liver transplantation. Four patients with histologically proven PTLD were analyzed. Conventional work-up included physical examination and head-to-pelvis CT. PET/CT was used in one patient for initial staging and in all patients for follow-up. PET/CT positive findings underwent biopsy. Information provided by PET/CT resulted in a change of medical management in three of the four patients. Conventional work-up missed residual disease after surgery in one and failed to detect a tumor relapse in another patient. However, one patient disclosed a false positive PET/CT finding in the lungs. In conclusion, PET/CT may be a useful tool for staging and therapy monitoring of PTLD after liver transplantation.

Adolescent↗
PubMed2006

Blocking the path to death: anti-apoptotic molecules in ischemia/reperfusion injury of the liver.

This review highlights recent advances in our understanding of intracellular mechanisms underlying programmed cell death in hepatic ischemia/reperfusion injury. A range of molecules have been tested with the intention to block the pathways of programmed cell death at different levels and to thereby enhance viability of the liver in surgical procedures including liver transplantation. Cellular death receptors, the mitochondrial pathway of apoptosis, p53, mitogen-activated protein kinases (MAPKs) and intracellular proteases all present potential targets for pharmaceutical agents to prevent ischemia induced cell death in the liver. Although evidence has been provided for effective inhibition of injury and improvement of survival by such agents, an optimal treatment strategy remains to be developed.

Animals↗
PubMed2005

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.

Adult↗
PubMed2005

[Evidential basis in bariatric surgery].

Bariatric surgery is currently considered the best treatment option for morbid obesity. With the rapid development of laparoscopic techniques, a significant increase in the number bariatric procedures in recent years can be observed. Various surgical techniques to treat morbid obesity have been described, but only few prospective studies compare the different procedures, leading to a lack of evidence for their use. However, from the available literature some general recommendations can be given: (a) preoperative workup in an interdisciplinary team is mandatory, (b) primary bariatric procedures should be performed laparoscopically, and (c) the combination of restrictive and malabsorptive techniques is more efficient than a purely restrictive method, which is also true for the treatment of comorbid diabetes and arterial hypertension. In this paper, we present recent developments in bariatric surgery, with special emphasis on the available evidence for the best treatment of morbidly obese patients.

Bariatric Surgery↗
PubMed2004

Critical evaluation of the different staging systems for hepatocellular carcinoma.

BACKGROUND: Diagnostic and therapeutic options for hepatocellular carcinoma (HCC) have improved substantially in recent years. A number of new palliative and potentially curative treatment strategies are now available. However, evaluation of the therapeutic modalities and assessment of the prognosis of HCC remain difficult owing to the lack of consensus on a single staging system and the availability of a number of new staging systems, each claiming to be the most appropriate. METHODS: The most frequently used staging systems for HCC are presented here. Their ability to stratify patients into different treatment groups and to define prognosis are discussed. In addition, the advantages and disadvantages of each system are analysed. RESULTS AND CONCLUSION: None of the currently used staging systems fulfils all the requirements for stratification of patients with HCC into groups of different prognosis and therapeutic recommendations. An international agreement on a single staging system is urgently needed in order to permit comparable randomized clinical trials. Only in this way will the outcome for those with HCC be improved.

Carcinoma, Hepatocellular↗
PubMed2004

Water induces autocrine stimulation of tumor cell killing through ATP release and P2 receptor binding.

Although exposure of cells to extreme hypotonic stress appears to be a purely experimental set up, it has found an application in clinical routine. For years, surgeons have washed the abdominal cavity with distilled water to lyse isolated cancer cells left after surgery. No data are available supporting this practice or evaluating the potential mechanisms of cell injury under these circumstances. Recent evidence indicates that increases in cell volume stimulate release of adenosine triphosphate and autocrine stimulation of purinergic (P2) receptors in the plasma membrane of certain epithelial cell types. Under physiological conditions, purigenic stimulation can contribute to cell volume recovery through activation of solute efflux. In addition, adenosine triphosphate-P2 receptor binding might trigger other mechanisms affecting cell viability after profound hypotonic stress. This study demonstrates a novel pathway of cell death by apoptosis in human colon cancer cells following a short hypotonic stress. This pathway is induced by transitory cell swelling which leads to extracellular release of adenosine triphosphate (ATP) and specific binding of ATP to P2 receptors (probably P2X7). Extracellular ATP induced activation of caspases 3 and 8, annexin V, release of cytochrome c, and eventually cell death. The effect of ATP can be blocked by addition of (i) apyrase to hydrolyse extracellular ATP and (ii) suramin, a P2 receptor antagonist. Finally, (iii) gadolinium pretreatment, a blocker of ATP release, reduces sensitivity of the cells to hypotonic stress. The adenosine triphosphate-P2 receptor cell death pathway suggests that autocrine/paracrine signaling may contribute to regulation of viability in certain cancer cells disclosed with this pathway.

Adenosine Triphosphate↗
PubMed2004

Intravenous iloprost bridging to orthotopic liver transplantation in portopulmonary hypertension.

Portopulmonary hypertension (PPHTN) is associated with poor prognosis and high perioperative mortality after orthotopic liver transplantation. This study documents the first case of a patient with PPHTN who was successfully bridged to orthotopic liver transplantation with i.v. iloprost, a stable prostacyclin analogue. The PPHTN had resolved completely 4 months after successful transplantation. In conclusion, portopulmonary hypertension is a relative contraindication to orthotopic liver transplantation, which should be attempted only if pulmonary haemodynamics improve with prostanoids. In this context, iloprost may be a valuable alternative to epoprostenol.

Alcoholism↗
PubMed2003

Laparoscopic donor nephrectomy.

BACKGROUND: Living kidney donation represents an important source of organs for patients with end-stage renal failure. Over the past decade, laparoscopic donor nephrectomy has replaced the conventional open procedure in many transplant centres. Using evidence-based methods, this study examines the current status of laparoscopic donor nephrectomy. METHOD: A Medline literature search (PubMed database, 1999-2002) and manual cross-referencing were performed to identify all articles relating to laparoscopic donor nephrectomy. Safety and efficacy criteria were analysed systematically for each study. Studies included were categorized using an evidence-based level grading system. RESULTS: Of 687 publications, 20 studies with level I-II evidence and 12 with level III evidence were analysed. Only one level I study could be identified. Level I and level II evidence suggests superiority of the laparoscopic approach in regard to postoperative analgesic consumption, hospital stay and return to work. Other safety and efficacy criteria, including donor and recipient outcomes, were similar between the two techniques. CONCLUSION: Laparoscopic donor nephrectomy has gained community acceptance by physicians and patients over the past decade. Despite a lack of strong evidence, such as large prospective randomized studies, laparoscopic donor nephrectomy is likely to become the 'gold standard' for donor nephrectomy in the near future.

Analgesics↗