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Pierre-Alain Clavien

Publications and source records attributed to Pierre-Alain Clavien.

At least 73 records · Page 4Linked to original sources
PubMed2003

Living donor liver transplantation and tolerance: a potential strategy in cholangiocarcinoma.

BACKGROUND: Donor-specific immune tolerance has been reported in isolated cases of kidney transplantation associated with bone marrow transplantation. The following is a description of a living donor liver transplantation for a hilar cholangiocarcinoma in a previous recipient of an allogeneic bone marrow transplant. METHOD: A right hemi-liver transplantation was performed using a liver allograft obtained from the same previous bone marrow donor. A neoadjuvant chemo-irradiation protocol was implemented before the procedure. Because of the presence of full chimerism, no immunosuppression has been necessary for the last 22 months. RESULTS: Liver graft function has remained excellent, and a magnetic resonance imaging scan at one and a half years has shown no tumor recurrence. A control liver biopsy at 1 year showed no rejection. CONCLUSIONS: Neoadjuvant chemo-irradiation therapy and removal of all immunosuppression after liver transplantation formed the basic structure of this approach. Additional benefits provided by living donor liver transplantation included limitation of tumor progression by diminishing the pretransplantation waiting time, radical excision of the tumor through a complete hepatectomy, and optimal timing of the transplant procedure within a neoadjuvant chemo-irradiation protocol.

Adult↗
PubMed2003

Obesity in general elective surgery.

BACKGROUND: Obese patients are generally believed to be at a higher risk for surgery than those who are not obese, although convincing data are lacking. METHODS: We prospectively investigated a cohort of 6336 patients undergoing general elective surgery at our institution to assess whether obesity affects the outcome of surgery. Exclusion criteria were emergency, vascular, thoracic, and bariatric operations; transplantation procedures; patients under immunosuppression; and operations done under local anaesthesia. Postoperative morbidity was analysed for non-obese and obese patients (body-mass index <30 kg/m(2) vs >or=30 kg/m(2)). Obesity was further stratified into mild obesity (30.0-34.9 kg/m(2)) and severe obesity (>or=35 kg/m(2)). Risk factors were analysed with univariate and multivariate models. FINDINGS: The cohort consisted of 6336 patients, of whom 808 (13%) were obese, 569 (9%) were mildly obese, and 239 (4%) had severe obesity. The morbidity rates in patients who were obese compared with those who were not were much the same (122 [15.1%] of 808 vs 901 [16.3%] of 5528; p=0.26), with the exception of an increased incidence of wound infections after open surgery in patients who were obese (17 [4%] of 431 vs 92 [3%] of 3555, p=0.03). Incidence of complications did not differ between patients who were mildly obese (91 [16.0%] of 569), severely obese (36 [15.1%] of 239), and non-obese (901 [16.3%] of 5528; p=0.19). In multivariate regression analyses, obesity was not a risk factor for development of postoperative complications. Of note, the additional medical resource use as estimated by a new classification of complications showed no differences between patients who were and were not obese. INTERPRETATION: Obesity alone is not a risk factor for postoperative complications. The regressive attitude towards general surgery in obese patients is no longer justified.

Adult↗
PubMed2003

Right living donor hepatectomy in the presence of celiac artery stenosis.

BACKGROUND: Incidental celiac artery stenosis has been cited as an exclusion criterion for adult donor right hepatectomy. METHODS: We report our experience involving right donor hepatectomy performed in the presence of isolated high-grade (greater than 80%) celiac trunk stenosis in two young healthy and asymptomatic adult living liver donors. RESULTS: The immediate postoperative course was complicated by a superficial wound infection in one patient and a transient median nerve palsy caused by intraoperative positioning, which spontaneously resolved, in the second patient. Both were discharged within 7 to 10 days postoperatively. They are doing well at 1 year follow-up without any complaints and have both returned to 100% full employment. CONCLUSIONS: Our results show that right donor hepatectomy can be safely performed in the presence of significant celiac artery stenosis. However, careful long-term follow-up will be required to monitor for any future progression of mesenteric vascular disease.

Adult↗
PubMed2003

Protective strategies against ischemic injury of the liver.

This article summarizes strategies to protect the liver from injuries caused by ischemia and reperfusion. Three different sections (i.e., surgical and pharmacologic strategies and gene therapy) present approaches to enhance the survival and viability of the liver in various surgical procedures including liver transplantation. The first section reviews approaches using surgical interventions such as ischemic preconditioning and intermittent clamping. Their protective effects are discussed with respect to the mechanism of injury. In the second section, pharmacologic agents targeting microcirculation, oxidative stress, proteases, and inflammation are described. Mechanisms of injury and their suppression by a wide variety of drugs are discussed. The third section focuses on gene therapy. Potential target genes have been identified (e.g., superoxide dismutase or heme oxygenase). Animal experiments in which the liver injury is reduced successfully may pave the way to novel strategies applied to different liver diseases in humans.

Animals↗
PubMed2003

Ischemic preconditioning protects the steatotic mouse liver against reperfusion injury: an ATP dependent mechanism.

BACKGROUND/AIMS: Hepatic steatosis is a major risk factor for liver surgery and transplantation. The increased susceptibility of fatty livers to ischemic injury is associated with a necrotic form of cell death as opposed to apoptosis in lean animals, and is possibly related to low contents of ATP. Ischemic preconditioning, a brief period of ischemia prior to a prolonged period, protects the lean liver against ischemia through anti-apoptotic properties. We evaluated whether ischemic preconditioning also confers protection in the fatty liver and whether it protects against the ATP loss. METHODS: The effect of ischemic preconditioning was tested in steatotic and lean livers subjected to 75 min of ischemia and 4 or 24 h of reperfusion. Tissue ATP contents were assessed at various times, and a model of low hepatic ATP contents (starvation) was studied to assess the type of injury following ischemia and the effects of preconditioning. RESULTS: Ischemic preconditioning protected steatotic livers against massive necrosis. ATP levels were significantly higher before and after reperfusion in liver subjected to preconditioning when compared to controls. Liver with low baseline ATP levels (starvation) were also associated with necrosis, and were protected by ischemic preconditioning. CONCLUSIONS: Ischemic preconditioning mainly protects the fatty liver against necrosis possibly through preservation and restoration of tissue ATP contents.

Adenosine Triphosphate↗
PubMed2003

Sub-lethal oxidative stress triggers the protective effects of ischemic preconditioning in the mouse liver.

BACKGROUND/AIMS: While ischemic preconditioning confers significant protection against subsequent prolonged periods of ischemia, the mechanisms triggering protection remain speculative. We hypothesize that a sub-lethal oxidative stress during ischemic preconditioning induces defense mechanisms preventing subsequent lethal injury. METHODS: We used mouse models of partial and total hepatic ischemia for 75 min. Ischemic preconditioning consisted of 10-min ischemia and 15-min reperfusion prior to the prolonged ischemic insult. RESULTS: Tissue levels of peroxides increased about three times after 10 min of ischemia and normalized within 15 min of reperfusion. This limited oxidative stress during ischemic preconditioning prevented the negative effects of subsequent prolonged ischemia as assessed by AST-levels, TUNEL-staining of hepatocytes and animal survival. N-Acetylcysteine inhibited the mild oxidative burst of ischemic preconditioning, and fully reversed the protective effects of preconditioning. The protective role of a sub-lethal oxidative stress was supported by the benefit of delivery of an H2O2-analog through the portal vein prior to a long ischemic insult. This challenge conferred similar protection as ischemic preconditioning. CONCLUSIONS: We conclude that the mild burst of oxidative stress generated during ischemic preconditioning triggers protective mechanisms against subsequent, otherwise lethal, ischemic injury. The pathway possibly includes enhancement of natural anti-oxidative stress mechanisms.

Animals↗
PubMed2003

ICAM-1 triggers liver regeneration through leukocyte recruitment and Kupffer cell-dependent release of TNF-alpha/IL-6 in mice.

BACKGROUND & AIMS: Tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 mediate hepatocyte proliferation in vivo, suggesting that local and systemic inflammatory reactions may trigger hepatic regeneration after major tissue loss. METHODS: Wild-type, intercellular adhesion molecule (ICAM)-1-/-, and neutropenic-induced mice were subjected to 70% hepatectomy. Three different approaches to block and/or deplete liver macrophages (Kupffer cells) were used. RESULTS: We found that liver from ICAM-1-deficient mice exhibited impaired regeneration after partial hepatectomy. This finding is associated with dramatic decrease in leukocyte recruitment and tissue TNF-alpha and IL-6 levels. All markers of hepatocyte proliferation were restored in ICAM-/- mice by injections of recombinant IL-6. Neutropenic animals and liver macrophage (Kupffer cell) depletion resulted in similar failure of regeneration with low levels of TNF-alpha and IL-6. CONCLUSIONS: The data suggest a novel pathway in which ICAM-1 binds to leukocytes after hepatectomy, triggering hepatocyte proliferation through Kupffer cell-dependent release of TNF-alpha and IL-6.

Animals↗
PubMed2003

Arterialized partial orthotopic liver transplantation in the mouse: a new model and evaluation of the critical liver mass.

The availability of a model of partial orthotopic liver transplantation (OLT) in the mouse would be an important tool for studying injuries associated with transplantation. The goals of this study were three-fold: (1). to develop a model of partial OLT in the mouse, (2). to determine the minimal graft volume in this model, and (3). to define the injury associated with small volume incompatible with animal survival. Putative grafts of 30% and 50% were prepared. Their weight was 30 +/- 5% and 45 +/- 10%, respectively. Subsequently, 30% and 45% syngeneic partial liver grafts were orthotopically transplanted into C57BL/6 mice. Each recipient receiving a 45% graft survived permanently, whereas those receiving only a 30% graft volume died within 2 to 4 days of surgery. Serum transaminase levels normalized in the 45% graft group within 14 days after surgery. In this group, small foci of necrosis and mild steatosis were noted on histology at postoperative day 2, but no abnormalities were noted after 14 days and 100 days. In contrast, recipients who underwent transplantation with a 30% graft volume showed a comparable amount of necrosis and significant microvesicular steatosis in most hepatocytes 2 days after surgery. Hepatocyte proliferation was reduced in this group when compared with animals who underwent transplantation with a 45% graft volume. In conclusion, partial liver transplantation is feasible in the mouse with a critical graft volume ranging between 30% and 45%. Small liver grafts develop massive microvesicular steatosis and impaired regeneration rapidly leading to animal death.

Animals↗
PubMed2003

A prospective randomized study in 100 consecutive patients undergoing major liver resection with versus without ischemic preconditioning.

OBJECTIVE: To evaluate the protective effects of ischemic preconditioning in a prospective randomized study involving a large population of unselected patients and to identify factors affecting the protective effects. SUMMARY BACKGROUND DATA: Ischemic preconditioning is an effective protective strategy in several animal models. Protection has also been suggested in a small series of patients undergoing a hemihepatectomy with 30 minutes of inflow occlusion. Whether preconditioning confers protection in other types of liver resection and longer periods of ischemia is unknown. Therefore, we conducted a prospective randomized study to evaluate the impact of ischemic preconditioning in liver surgery. METHODS: A total of 100 unselected patients undergoing major liver resection (> bisegmentectomy) under inflow occlusion for at least 30 minutes were randomized during surgery to either receive or not receive an ischemic preconditioning protocol (10 minutes of ischemia followed by 10 minutes of reperfusion). Univariate and multivariate analyses were performed to identify independent factors affecting the protective effects of ischemic preconditioning. ATP contents in liver were measured as a possible mechanism of protection. RESULTS: Both groups (n = 50 in each) were comparable regarding age, gender, duration of inflow occlusion, and resected liver volumes. Postoperative serum transaminase levels were significantly lower in preconditioned than in control patients (median peak AST 364 U/L vs. 520 U/L, P = 0.028; ALT 406 vs. 519 U/L, P = 0.049). Regression multivariate analysis revealed an increased benefit of ischemic preconditioning in younger patients, in patients with longer duration of inflow occlusion (up to 60 minutes), and in cases of lower resected liver volume (<50%). Patients with steatosis were also particularly protected by ischemic preconditioning. ATP content in liver tissue was preserved by ischemic preconditioning in young but not older patients. CONCLUSIONS: This study establishes ischemic preconditioning as a protective strategy against hepatic ischemia in humans. The strategy is particularly effective in young patients requiring a prolonged period of inflow occlusion, and in the presence of steatosis, and is possibly related to preservation of ATP content in liver tissue. Other strategies are needed in older patients.

Adult↗
PubMed2003

Laparoscopic Roux-en-Y gastric bypass, but not rebanding, should be proposed as rescue procedure for patients with failed laparoscopic gastric banding.

OBJECTIVE: To define whether laparoscopic rebanding or Roux-en-Y gastric bypass represents the best approach for failed laparoscopic gastric banding in patients with morbid obesity. SUMMARY BACKGROUND DATA: Countless laparoscopic gastric bandings have been implanted during the recent years worldwide. Despite excellent short-term results, long-term failures and complications have been reported in more than 20% of patients. Which rescue procedures should be used remains controversial. Therefore, we analyzed our experience with the use of laparoscopic rebanding versus laparoscopic Roux-en-Y gastric bypass after failed gastric banding. METHODS: Using a prospectively collected database, we analyzed the feasibility, safety, and effectiveness of laparoscopic rebanding versus laparoscopic conversion to Roux-en-Y gastric bypass after failed laparoscopic gastric banding. RESULTS A total of 62 consecutive patients were treated in our institution between May 1995 and December 2002 for failed primary laparoscopic gastric banding, including 30 laparoscopic rebandings and 32 laparoscopic conversions to Roux-en-Y gastric bypass. Rebandings were preferably done during the initial period of the study and Roux-en-Y gastric bypass in the last period. Both groups were comparable before the initial banding procedures. At the time of redo surgery, patients receiving a gastric bypass had more esophageal dysmotility (47% vs. 7%, P = 0.002) and higher body mass index (BMI) than those elected for rebanding procedures (BMI 42.0 vs. 38.4 kg/m2, P = 0.015). Feasibility and safety: Each procedure was performed laparoscopically. Mean operating time was 215 minutes for gastric bypass and 173 minutes for rebanding (P = 0.03). Early complications occurred in one case in the rebanding group and in 2 cases in the bypass group; all underwent a laparoscopic reexploration without the need for open surgery. There was no mortality in this series. Effectiveness: BMI in the gastric bypass group decreased from 42.0 to 31.8 kg/m2 (P = 0.02) within 1 year of surgery, while it remained unchanged in the rebanding group. CONCLUSIONS: Laparoscopic conversion to a gastric bypass as well as laparoscopic rebanding are feasible and safe. Conversion to gastric bypass offers a significant advantage in terms of further weight loss after surgery. Therefore, this procedure should be considered as the rescue therapy of choice after a failed laparoscopic gastric banding.

Adult↗
PubMed2002

Comparison of arterialized and nonarterialized orthotopic liver transplantation in mice: prowess or relevant model?

BACKGROUND: New insights into mechanisms of injury in orthotopic liver transplantation (OLT) often come from experiments in small animal models. Mice are particularly suitable because of the growing availability of gene-altered animals and specific antibodies. A validated model of OLT in mice is not available and, in particular, the role of rearterialization is unknown. Therefore, we developed a new model of OLT in mice, and we compared liver injury and animal survival in the presence and the absence of arterial blood supply. METHODS: Syngenic OLT was performed in male Balb/c mice. An arterial segment was removed en bloc with the graft in the donor animal and subsequently implanted in a recipient animal using a combination of suture and cuff technique. In some animals, rearterialization was performed with an end-to-side anastomosis between the recipient aorta and the graft artery using a running suture. Rewarming ischemia time was consistently kept below 20 min. RESULTS: All animals (8/8) survived permanently in the presence of a rearterialized graft, whereas only 50% (4/8) were alive at 2 weeks in the absence of arterial supply ( P=0.025). Serum aspartate aminotransferase levels were significantly lower in the presence of arterial supply at 1 and 3 days and 2 weeks after OLT. Serum levels of alkaline phosphatase normalized within 2 weeks in animals with arterialized grafts, whereas levels remained high (3x normal values) in nonarterialized animals. Histologic examination supported a primary injury to the small bile ducts. Viability of arterialized grafts preserved for 16 hr in cold University of Wisconsin solution was 100%. CONCLUSIONS: This study established a new model of arterialized OLT in mice, which opens new avenues for research.

Animals↗
PubMed2002

Living donor liver transplantation in patients with portal vein thrombosis: a survey and review of technical issues.

BACKGROUND: Unlike cadaveric liver transplantation, current attitudes in living donor liver transplantation (LDLT) quote increased risk factors in the potential recipient such as retransplantation, multiple previous surgeries, or preexisting recipient portal vein thrombosis (PVT) as absolute or relative contraindications to this procedure. METHODS: An international survey was performed to examine the attitude of transplant teams relative to LDLT in the setting of preexisting PVT in the potential recipient. A questionnaire was sent to a total of 80 transplant centers performing LDLT in the United States, Europe, Canada, Japan, Southeast Asia, and Australia. RESULTS: A response was obtained from 47 transplant centers (59% response rate). This included 2146 LDLT procedures that combined both left and right lobe allografts. The incidence of acute preexisting recipient PVT was 18 (0.8%) and of chronic PVT was 26 (1.2%). Thrombectomy was performed in 28 (64%), a jump graft in 13 (29.5%), and a combination of both thrombectomy and a jump graft in 2 (4.5%) cases. With reference to the presence of preexisting PVT in the potential recipient, 5 centers considered this to be an absolute contraindication (10.7%), 24 centers as a relative contraindication (51%), and 18 as not being a contraindication (38.3%) to LDLT. CONCLUSIONS: The overall response to our questionnaire reflected a cautious attitude within the transplant community. Ethical criteria pertaining to risk undertaken by a healthy donor in situations of higher recipient morbidity risk does seem to impact on the decision to undertake LDLT in this group of patients.

Health Surveys↗
PubMed2002

Kidney transplantation from donors without a heartbeat.

BACKGROUND: The dramatic shortage of kidney donors has triggered interest in other sources of organs, such as donors without a heartbeat. Accumulating evidence suggests that the short-term survival of cadaveric kidneys from such donors is similar to that of cadaveric kidneys from donors with a heartbeat. However, no data from large, matched studies with long-term follow-up are available. We conducted a matched, single-center study of kidney transplants obtained from donors without a heartbeat and those from donors with a heartbeat, with a 15-year follow-up period. METHODS: Between 1985 and 2000, 122 kidney transplantations involving donors without a heartbeat were performed at the University of Zurich, in Switzerland. Outcomes of these procedures were compared with those of 122 transplantations of kidneys from donors with a heartbeat. The recipients were matched according to age, sex, number of transplantations, and calendar period of transplantation. RESULTS: The characteristics of the recipients did not differ significantly between the two groups. We observed a significantly higher incidence of delayed graft function among the patients who received kidneys from donors without a heartbeat (48.4 percent) than among the patients who received kidneys from donors with a heartbeat (23.8 percent) (P<0.001). However, the long-term rate of graft survival was similar in the two groups (P=0.98): at 10 years, the rate of graft survival was 78.7 percent for kidneys from donors without a heartbeat and 76.7 percent for kidneys from donors with a heartbeat. CONCLUSIONS: Although the incidence of delayed graft function is significantly higher with kidneys from donors without a heartbeat than with kidneys from donors with a heartbeat, there is no difference in long-term outcome between the two types of graft.

Adult↗
PubMed2002

Stapled vs excision hemorrhoidectomy: long-term results of a prospective randomized trial.

HYPOTHESIS: Stapled hemorrhoidectomy offers several advantages over excision hemorrhoidectomy, including reduced postoperative pain, a reduced hospital stay, and an earlier recovery time. Furthermore, stapled hemorrhoidectomy is associated with lower hemorrhoidal recurrence on long-term follow-up. DESIGN: A randomized prospective trial. Patients were blinded to the operation technique used. Follow-up occurred at 1 and 3 weeks and 12 months postoperatively. SETTING: A university hospital providing primary, secondary, and tertiary care. PATIENTS: Forty patients with second- and third-degree hemorrhoid disease were randomized to undergo either stapled or excision hemorrhoidectomy. Two patients were excluded. All patients were subject to a follow-up examination. INTERVENTIONS: Stapled hemorrhoidectomy (Longo technique) vs excision hemorrhoidectomy (Ferguson technique). MAIN OUTCOME MEASURES: Operating time, postoperative pain (measured by the visual analog scale), hospital stay, histologic features, morbidity, defecation habit, continence, recovery time (return to work), and hemorrhoid recurrence at 1 year. RESULTS: Stapled vs excision hemorrhoidectomy was associated with a significantly reduced operating time (30 vs 43.25 minutes; P<.001), reduced postoperative pain scores (visual analog score) on the first 4 postoperative days (day 1: 2.7 vs 6.3; day 2: 1.7 vs 6.3; day 3: 0.8 vs 5.4; and day 4: 0.5 vs 4.8, where 0 indicates no pain, and 10, maximum pain; P < or = .001), and an earlier return to work (6.7 vs 20.7 days;P =.001). There were no differences for stapled vs excision hemorrhoidectomy in length of hospital stay (2.4 vs 2.1 days), complications (3 [15%] of 20 patients vs 5 [25%] of 20 patients), and recurrence rate (1 [5%] of 20 patients vs 1 [5%] of 20 patients). CONCLUSIONS: Stapled hemorrhoidectomy is associated with reduced postoperative pain, earlier recovery time and return to work, and a similar recurrence rate compared with the excision technique. Provided further clinical trials confirm these findings, stapled hemorrhoidectomy may become a future gold standard.

Adult↗
PubMed2002

Contrast-enhanced three-dimensional magnetic resonance angiography for visualization of ectopic varices.

We report the case of a 62-year-old male with portal hypertension and recurrent bleeding refractory to surgical intervention from varices in a sigmoid stoma. Although stomal varices were detected neither by physical examination, stomal endoscopy, nor duplex sonography, contrast-enhanced three-dimensional magnetic resonance angiography of the portal vein and its collateral branches demonstrated their presence. Surgical revisions of the stoma failed to prevent bleeding, but implantation of a transjugular intrahepatic shunt successfully prevented recurrent hemorrhage. This case indicates that contrast-enhanced, three-dimensional magnetic resonance angiography is useful to detect this rare complication of portal hypertension and helps to tailor adequate treatment in patients with recurrent bleeding from stomal varices.

Contrast Media↗