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Biomedical subjects

Pierre-Alain Clavien

Publications and source records attributed to Pierre-Alain Clavien.

At least 37 records · Page 2Linked to original sources
PubMed2006

A prospective, randomized, controlled trial comparing intermittent portal triad clamping versus ischemic preconditioning with continuous clamping for major liver resection.

OBJECTIVE: To evaluate whether ischemic preconditioning (IP) with continuous clamping or intermittent clamping (IC) of the portal triad confers better protection during liver surgery. SUMMARY BACKGROUND DATA: IP and IC are distinct protective approaches against ischemic injury. Since both strategies proved to be superior in randomized controlled trials (RCTs) to continuous inflow occlusion alone, we designed a RCT to compare IP and IC in patients undergoing major liver resection. METHODS: Noncirrhotic patients undergoing major liver resection were randomized to receive IP with inflow occlusion (n = 36) or IC (n = 37). Primary endpoints were postoperative liver injury and intraoperative blood loss. Postoperative liver injury was assessed by peak values of AST (alanine aminotransferase) and ALT (aspartate aminotransferase), as well as the area under the curve (AUC) of the postoperative transaminase course. Secondary endpoints included resection time, the need of blood transfusion, ICU, and hospital stay as well as postoperative complications and mortality. RESULTS: Both groups were comparable regarding demographics, ASA score, type of hepatectomy, duration of inflow occlusion (range, 30-75 minutes), and resection surface. The transection-related blood loss was 146 versus 250 mL (P = 0.008), and when standardized to the resection surface 1.2 versus 1.8 mL/cm (P = 0.01) for IP and IC, respectively. Although peak AST, AUCAST, and AUCALT were lower for IC, the differences did not reach statistical significance. Overall (42% vs. 38%) and major (33 vs. 27%) postoperative complications as well as median ICU (1 vs. 1 day) and hospital stay (10 vs. 11 days) were similar between both groups. CONCLUSIONS: Both IP and IC appear to be equally effective in protecting against postoperative liver injury in noncirrhotic patients undergoing major liver resection. However, IP is associated with lower blood loss and shorter transection time. Therefore, both strategies can be recommended for noncirrhotic patients undergoing liver resection.

Age Factors↗
PubMed2006

Assessment of complications after pancreatic surgery: A novel grading system applied to 633 patients undergoing pancreaticoduodenectomy.

OBJECTIVE: To define a simple and reproducible classification of complications following pancreaticoduodenectomy (PD) based on a therapy-oriented severity grading system. BACKGROUND: While mortality is rare after PD, morbidity rates remain high. The lack of standardization in evaluating morbidity after PD has severely hampered meaningful comparisons over time and among centers. We adapted a novel classification of complication to stratify morbidity by severity after PD, to test whether the incidence of pancreatic fistula has changed over time, and to identify risk factors in a single North American center. METHODS: The classification was applied to a consecutive series of 633 patients undergoing PD between February 2003 and August 2005. Another series of 141 patients treated between 1987 and 1990 was also analyzed to identify changes in the incidence and severity of fistula. Univariate and multivariate analyses were performed to link respective complications with preoperative and intraoperative parameters, length of hospital stay, and long-term survival. RESULTS: A total of 263 (41.5%) patients did not develop any complication, while 370 (58.5%) had at least one complication; 62 (10.0%) patients had only grade I complications (no need for specific intervention), 192 patients (30.0%) had grade II (need for drug therapy such as antibiotics), 85 patients (13.5%) had grade III (need for invasive therapy), and 19 patients (3.0%) had grade IV complications (organ dysfunction with ICU stay). Grade V (death) occurred in 12 patients (2.0%). A total of 57 patients (9.0%) developed pancreatic fistula, of which 33 (58.0%) were classified as grade II, 17 (30.0%) as grade III, 5 (9.0%) as grade IV, and 2 (3.5%) as grade V. Delayed gastric emptying was documented in 80 patients (12.7%); half of them were scored as grade II and the other half as grade III. A significant decrease in the incidence of fistula was observed between the 2 periods analyzed (14.0% vs. 9.0%, P < 0.001), mostly due to a decrease in grade II fistula. Cardiovascular disease was a risk factor for overall morbidity and complication severity, while texture of the gland and cardiovascular disease were risk factors for pancreatic fistula. CONCLUSION: This study demonstrates the applicability and utility of a new classification in grading complications following pancreatic surgery. This novel approach may provide a standardized, objective, and reproducible assessment of pancreas surgery enabling meaningful comparison among centers and over time.

Adult↗
PubMed2006

Novel short-term hypothermic oxygenated perfusion (HOPE) system prevents injury in rat liver graft from non-heart beating donor.

OBJECTIVE: To assess a machine perfusion system in rescuing liver grafts from non-heart-beating donors (NHBD). SUMMARY BACKGROUND DATA: The introduction of extracorporeal liver perfusion systems in the clinical routine depends on feasibility. Conceivably, perfusion could be performed during recipient preparation. We investigated whether a novel rat liver machine perfusion applied after in situ ischemia and cold storage can rescue NHBD liver grafts. METHODS: We induced cardiac arrest in male Brown Norway rats by phrenotomy and ligation of the subcardial aorta. We studied 2 experimental groups: 45 minutes of warm in situ ischemia + 5 hours cold storage versus 45 minutes of warm in situ ischemia + 5 hours cold storage followed by 1 hour hypothermic oxygenated extracorporeal perfusion (HOPE). In both groups, livers were reperfused in a closed sanguineous isolated liver perfusion device for 3 hours at 37 degrees C. To test the benefit of HOPE on survival, we performed orthotopic liver transplantation in both experimental groups. RESULTS: After cold storage and reperfusion, NHBD livers showed necrosis of hepatocytes, increased release of AST, and decreased bile flow. HOPE improved NHBD livers significantly with a reduction of necrosis, less AST release, and increased bile flow. ATP was severely depleted in cold-stored NHBD livers but restored in livers treated by HOPE. After orthotopic liver transplantation, grafts treated by HOPE demonstrated a significant extension on animal survival. CONCLUSIONS: We demonstrate a beneficial effect of HOPE by preventing reperfusion injury in a clinically relevant NHBD model.

Animals↗
PubMed2006

Cationic long-chain ceramide LCL-30 induces cell death by mitochondrial targeting in SW403 cells.

Ceramides are sphingolipid second messengers that are involved in the mediation of cell death. There is accumulating evidence that mitochondria play a central role in ceramide-derived toxicity. We designed a novel cationic long-chain ceramide [omega-pyridinium bromide D-erythro-C16-ceramide (LCL-30)] targeting negatively charged mitochondria. Our results show that LCL-30 is highly cytotoxic to SW403 cells (and other cancer cell lines) and preferentially accumulates in mitochondria, resulting in a decrease of the mitochondrial membrane potential, release of mitochondrial cytochrome c, and activation of caspase-3 and caspase-9. Ultrastructural analyses support the concept of mitochondrial selectivity. Interestingly, levels of endogenous mitochondrial C16-ceramide decreased by more than half, whereas levels of sphingosine-1-phosphate increased dramatically and selectively in mitochondria after administration of LCL-30, suggesting the presence of a mitochondrial sphingosine kinase. Of note, intracellular long-chain ceramide levels and sphingosine-1-phosphate remained unaffected in the cytosolic and extramitochondrial (nuclei/cellular membranes) cellular fractions. Furthermore, a synergistic effect of cotreatment of LCL-30 and doxorubicin was observed, which was not related to alterations in endogenous ceramide levels. Cationic long-chain pyridinium ceramides might be promising new drugs for cancer therapy through their mitochondrial preference.

Antibiotics, Antineoplastic↗
PubMed2006

Immunoprivileged status of the liver is controlled by Toll-like receptor 3 signaling.

The liver is known to be a classical immunoprivileged site with a relatively high resistance against immune responses. Here we demonstrate that highly activated liver-specific effector CD8+ T cells alone were not sufficient to trigger immune destruction of the liver in mice. Only additional innate immune signals orchestrated by TLR3 provoked liver damage. While TLR3 activation did not directly alter liver-specific CD8+ T cell function, it induced IFN-alpha and TNF-alpha release. These cytokines generated expression of the chemokine CXCL9 in the liver, thereby enhancing CD8+ T cell infiltration and liver disease in mice. Thus, nonspecific activation of innate immunity can drastically enhance susceptibility to immune destruction of a solid organ.

Adaptor Proteins, Signal Transducing↗
PubMed2006

New device for the introduction of a circular stapler in laparoscopic gastric bypass surgery.

BACKGROUND: In laparoscopic Roux-en-Y gastric bypass (LRYGBP) surgery, the anastomosis between the gastric pouch and the jejunum can be performed using a circular stapler, as described in the original publication by Wittgrove in 1994. The introduction of the circular stapler through the thick abdominal wall in morbidly obese patients can be challenging. To overcome the difficulties of this task, a new device was developed and its use is presented. METHOD: The new device has the shape of a trocar tip which can be mounted on the circular stapler, giving it the properties of a trocar. Therefore, easier introduction into the abdominal cavity is feasible. The use of the device was assessed analyzing the data of a prospective database, comparing patient groups operated without the device (n=301) and patients operated with the device (n=100). RESULTS: The groups were comparable in age, sex, BMI and number of previous abdominal operations. The wound infection rate at the site of stapler introduction decreased from 6.6% to 1% (P=0.035). The overall operating time, hospital stay and complication rate were unchanged. CONCLUSION: The new device proved to be useful in daily practice and enabled an easier stapler introduction with fewer wound infections.

Adult↗
PubMed2005

Mouse livers with macrosteatosis are more susceptible to normothermic ischemic injury than those with microsteatosis.

BACKGROUND/AIMS: Fatty livers are increasingly used for transplantation due to the dramatic organ shortage. While steatosis is an established risk factor for post-operative complications, the impact of macro- vs. microvesicular steatosis on ischemic injury is unclear. METHODS: The effects of ischemia and reperfusion were tested in two different models of steatotic mice: ob/ob as a model disclosing predominantly macrovesicular steatosis and choline deficient diet having mainly microvesicular steatosis. Steatotic and lean livers were subjected to 45 min of ischemia. Serial markers of hepatocellular injury, animal survival were measured. Hepatic tissue blood flow and portal vein perfusion were assessed. RESULTS: Ob/ob mice had a significantly lower tolerance to hepatic ischemia. with increased AST release and decreased survival in comparison to the choline deficient mice. No difference in ATP content was found between both steatosis models, but hepatic perfusion and portal vein flow were significantly lower after reperfusion in the ob/ob mice when compared to the choline deficient animals. Ischemic pre-conditioning significantly improved liver reperfusion and injury in both models of steatosis. CONCLUSIONS: Livers with macrovesicular steatosis have a lower tolerance to ischemic injury than those with microvesicular steatosis. Low intrahepatic and portal vein perfusion in macrovesicular fatty livers is, at least partially, responsible for the poorer outcome.

Adenosine Triphosphate↗
PubMed2005

Abdominal compartment syndrome after liver transplantation.

The abdominal compartment syndrome is a well-known complication after abdominal trauma and is increasingly recognized as a potential risk factor for renal failure and mortality after adult orthotopic liver transplantation (OLT). We present a case report of a young patient who presented with acute liver failure complicated by an acute pancreatitis. The patient developed an acute abdominal compartment syndrome after OLT. Transurethral measurement of intraabdominal pressure indicated an abdominal compartment syndrome associated with impaired abdominal vascular perfusion, including liver perfusion. Renal insufficiency was immediately reversed after decompressive bedside laparotomy. The abdominal compartment syndrome is a potential source of posttransplant renal insufficiency and liver necrosis in OLT. It remains, however, a rarely described complication after liver transplantation, despite the presence of significant factors that contribute to elevated intraabdominal pressure.

Adult↗
PubMed2005

Corticosteroid-free immunosuppression with tacrolimus following induction with daclizumab: a large randomized clinical study.

This open, randomized (1 : 1), multicenter, 3-month study compared a dual tacrolimus plus steroids (Tac / steroids) regimen with a steroid-free immunosuppressive regimen of tacrolimus following daclizumab induction therapy (Tac / Dac) in adult liver transplant recipients. The full analysis set comprised 347 patients in the Tac / steroids group and 351 in the Tac / Dac group. Mean tacrolimus dose during month 3 was 0.11 mg/kg/day in both groups; mean whole-blood trough levels during month 3 were 10.9 ng/mL (Tac / steroids) and 10.6 ng/mL (Tac / Dac). The incidence of biopsy-confirmed acute rejection that required treatment was similar in both groups: 26.5% in the Tac / steroids group and 25.4% in the Tac / Dac group (P = .727). However, the incidence of biopsy-confirmed corticosteroid-resistant acute rejection was higher in the Tac / steroids group than in the Tac / Dac group (6.3 vs. 2.8%; P = .027). Kaplan-Meier estimates of graft survival (92.2 vs. 90.5%) and patient survival (94.5 vs. 93.7%) were similar in both groups. While also the overall adverse event profiles were similar, the incidences of diabetes mellitus (15.3 vs. 5.7%, respectively; P < .001) and cytomegalovirus infection (11.5 vs. 5.1%, respectively; P = .002) were higher in the Tac / steroids group compared with the Tac / Dac group. Mean cholesterol levels increased by 16% in the Tac / steroids group, but were unchanged in the Tac / Dac group during the study. In conclusion, tacrolimus monotherapy following daclizumab induction is an effective and safe regimen, with an advantage over concomitant steroid-maintenance therapy in terms of a lower incidence of diabetes and viral infection, and a lower incidence of steroid-resistant acute rejection.

Acute Disease↗
PubMed2005

Should we deny surgery for malignant hepato-pancreatico-biliary tumors to elderly patients?

Malignant hepato-pancreatico-biliary (HPB) tumors have their highest incidence within the sixth to eighth decades of life. The aging of the world population has resulted in a dramatic increase in the number of elderly patients considered for resection of malignant HPB tumors. Because elderly patients are more likely to have more co-morbidities, cognitive impairment, and decreased life expectancy, the benefit and appropriateness of these procedures must be scrutinized for geriatric patients. Therefore, many surgeons have compared the perioperative and long-term outcome of hepatic and pancreatic resections for elderly and younger patients. In most series the elderly population was defined by an age of 70 years or older. The results demonstrate that hepatic resection for hepatocellular carcinoma and colorectal liver metastases can be safely performed in well-selected elderly patients with long-term outcome comparable to younger patients. Similar findings are also reported for pancreatic resection in elderly patients with either ampullary or pancreatic cancer. Although the survival benefit of pancreatico-duodenectomy is limited in all age groups, the absence of competitive therapy justifies this procedure as the sole curative option in younger as well as older patients. Data on resection of gallbladder cancer and hilar bile duct cancer in the elderly are sparse, but there is evidence from large series on resection of these types of tumors that advanced age per se is not a risk factor for reduced outcome. Therefore, surgical options should not be denied to elderly patients with a malignant HPB tumor, and the evaluation should include surgeons expert in HPB surgery.

Age Factors↗
PubMed2005

Fatal esophageal perforation caused by invasive candidiasis.

Instrumental lesions, spontaneous rupture, and trauma cause most esophageal perforations. Transmural fungal infection is extremely rare, although Candida may be detected in as many as 25% of normal esophagus. In this report we present a case of fatal esophageal perforation due to transmural Candida infection in a 76-year-old woman. The patient died from septic shock and multiorgan failure, despite esophageal resection and systemic antifungal therapy. Pathogenetic aspects and treatment strategies are discussed.

Aged↗