Biomedical subjects
Publications and source records attributed to Pierre-Alain Clavien.
There is no worldwide consensus of an algorithm for the radical treatment of hepatocellular carcinoma (HCC). Surgical resection, liver transplantation and, recently, local ablation therapies achieve high curative rates in selected patients. However, recurrence of HCC remains a major problem. This review provides an overview of the current surgical treatment options available for patients with HCC.
OBJECTIVE: We sought to determine the impact of positron emission tomography/computed tomography (PET/CT) on the management of presumed resectable pancreatic cancer and to assess the cost of this new staging procedure. SUMMARY BACKGROUND DATA: PET using 18F-fluorodeoxyglucose (FDG) is increasingly used for the staging of pancreatic cancer, but anatomic information is limited. Integrated PET/CT enables optimal anatomic delineation of PET findings and identification of FDG-negative lesions on computed tomography (CT) images and might improve preoperative staging. MATERIAL AND METHODS: Patients with suspected pancreatic cancer who had a PET/CT between June 2001 to April 2004 were entered into a prospective database. Routine staging included abdominal CT, chest x-ray, and CA 19-9 measurement. FDG-PET/CT was conducted according to a standardized protocol, and findings were confirmed by histology. Cost benefit analysis was performed based on charged cost of PET/CT and pancreatic resection and included the time frame of staging and surgery. RESULTS: Fifty-nine patients with a median age of 61 years (range, 40-80 years) were included in this analysis. Fifty-one patients had lesions in the head and 8 in the tail of the pancreas. The positive and negative predictive values for pancreatic cancer were 91% and 64%, respectively. PET/CT detected additional distant metastases in 5 and synchronous rectal cancer in 2 patients. PET/CT findings changed the management in 16% of patients with pancreatic cancer deemed resectable after routine staging (P = 0.031) and was cost saving. CONCLUSIONS: PET/CT represents an important staging procedure prior to pancreatic resection for cancer, since it significantly improves patient selection and is cost-effective.
OBJECTIVE: To identify the most efficient parenchyma transection technique for liver resection using a prospective randomized protocol. SUMMARY BACKGROUND DATA: Liver resection can be performed by different transection devices with or without inflow occlusion (Pringle maneuver). Only limited data are currently available on the best transection technique. METHODS: A randomized controlled trial was performed in noncirrhotic and noncholestatic patients undergoing liver resection comparing the clamp crushing technique with Pringle maneuver versus CUSA versus Hydrojet versus dissecting sealer without Pringle maneuver (25 patients each group). Primary endpoints were intraoperative blood loss, resection time, and postoperative liver injury. Secondary end points included the use of inflow occlusion, postoperative complications, and costs. RESULTS: The clamp crushing technique had the highest transection velocity (3.9 +/- 0.3 cm/min) and lowest blood loss (1.5 +/- 0.3 mL/cm) compared with CUSA (2.3 +/- 0.2 cm/min and 4 +/- 0.7 mL/cm), Hydrojet (2.4 +/- 0.3 cm/min and 3.5 +/- 0.5 mL/cm), and dissecting sealer (2.5 +/- 0.3 cm/min and 3.4 +/- 0.4 mL/cm) (velocity: P = 0.001; blood loss: P = 0.003). Clamp crushing technique was associated with the lowest need for postoperative blood transfusions. The degree of postoperative reperfusion injury and complications were not significantly different among the groups. The clamp crushing technique proved to be most cost-efficient device and had a cost-saving potential of 600 to 2400 per case. CONCLUSIONS: The clamp crushing technique was the most efficient device in terms of resection time, blood loss, and blood transfusion frequency compared with CUSA, Hydrojet, and dissecting sealer, and proved to be also the most cost-efficient device.
Mast cells (MC) can undergo significant changes in number and phenotype; these alterations result in the differential expression of growth factors and cytokines. Kit ligand (KL; stem cell factor) is produced by mesenchymal cells, and in the liver by biliary epithelial cells. Recent studies suggest that KL, and its receptor c-kit, may be involved in liver regeneration after loss of liver mass. However, KL is also the major growth, differentiating, chemotactic, and activating factor for MC. The aim of our study was to elucidate the dynamics and phenotype of hepatic MC and KL/c-kit expression during liver regeneration after partial (70%) hepatectomy in the rat. Regenerating livers were harvested after 1, 3, 7, and 14 days, respectively (n = 6 each day). MC were stained for naphthol-AS/D-chloroacetate esterase and counted as MC per bile ductule. MC phenotype was assessed by rat MC protease (RMCP)-1 and -2 immunofluorescence staining, in order to distinguish RMCP-1 positive connective tissue MC (CTMC) from RMCP-2 positive mucosa MC (MMC). mRNA expression of RMCP, c-kit, and the differentially spliced variants of KL was quantified by RT-PCR. MC counts per bile ductule decreased in regenerating rat liver tissue at day 3, compared with native livers, and became normal thereafter. Hepatic MC were predominantly of a CTMC phenotype expressing RMCP-1, as previously published; after hepatectomy, between 76 and 99% of all MC double-expressed RMCP-1 and -2, compatible with an MMC phenotype. The ratio of the two alternatively spliced mRNAs for KL (KL-1 : KL-2), and c-kit mRNA expression did not differ significantly between regenerating livers and the livers of sham operated animals. These results suggest that hepatic mast cells are restored during liver regeneration after partial hepatectomy in the rat. Restored MC express an MMC phenotype, suggesting migration from outside into the regenerating liver. Alternative splicing of KL is affected by the surgical procedure in general, and, together with its receptor c-kit, doesn't seem to be involved in liver regeneration after partial hepatectomy in the rat. Further functional studies, and studies in regenerating human livers might offer the possibility of elucidating the role of the hepatic mast cell, and its different protease phenotypes during liver regeneration after surgical loss of liver mass.
While pancreas transplantation has evolved within two decades from a frustrating and poorly-accepted therapeutic option to a highly successful procedure, the respective benefits of the successive surgical and immunosuppressive developments have remained unclear. The aim of this study was to determine using an evidence-based methodology, which novel approaches have contributed to the current results and whether pancreas transplantation is cost-effective. Out of 2481 articles, 102 analyzed either surgical or immunosuppressive aspects of pancreas transplantation. Urological complications were more frequent in bladder over enteric drainage (range: 62-63% vs. 12-20%, p = 0.0001), but without significant difference in patient or graft survival. Portal drainage was associated with a trend toward fewer complications and better hyperinsulinemia control over systemic drainage in retrospective studies. Immunosuppression combining induction therapy, a calcineurin inhibitor, mycophenolate mophetil (MMF) and corticosteroids were associated with a 40% decreased incidence of rejection (p = 0.01) and an increase in graft survival above 90% at 1 year (p < 0.05). Pancreas transplantation is highly cost-effective compared to conservative alternatives. We conclude that despite a paucity of large studies, enteric drainage should be recommended but the benefits of portal venous drainage remain debated. Quadruple immunosuppression protocols including induction therapy should be the standard regimen.
Widespread application of cadaveric split or living donor liver transplantation bears considerable potential to increase the pool of available organs and thus alleviate the problem of organ shortage. Although splitting of a cadaveric liver into two grafts for adult recipients can be performed successfully, sufficient function of undersized grafts is a major concern. To minimize the risk for living donors, transplant surgeons aim at procuring the least necessary liver volume, also leading to potentially small grafts. When small partial grafts are unable to meet the functional demands, the recipients can develop a so-called small-for-size syndrome (SFSS). There is currently limited data on the pathogenesis of SFSS, with clinical studies mainly focusing on portal hyperperfusion. Additional aspects include graft-related factors such as functional and regenerative capacity, as well as recipient-related factors, such as overall health status and severity of cirrhosis. However, there is currently no consensus on the definition of SFSS. We propose a novel definition, based on simple clinical criteria, which divides the syndrome into either nonfunction or dysfunction of a small graft after the exclusion of other causes. This definition should ease comparability of future clinical trials, and thus improve understanding of the pathogenesis of SFSS.
BACKGROUND: With a dramatically increasing number of bariatric operations performed world-wide in the recent years, more late complications have been noticed. Proximal gastric pouch dilatation is a known late complication after laparoscopic or open restrictive surgery for morbid obesity. In the present paper, we report our experience with laparoscopic re-operation of enlarged gastric pouches after laparoscopic gastric bypass, with emphasis on technique and outcome. METHODS: Data were retrieved from a prospective database of 334 patients who underwent a laparoscopic gastric bypass operation at the University Hospital of Zurich from July 2000 to December 2004. Five laparoscopic revisions for pouch dilatation after primary bypass were performed. RESULTS: 3 female and 2 male patients with median age 40 years (range 32-55) underwent a laparoscopic pouch resizing. At the time of the re-operation, the median BMI was 32.0 kg/m(2) (range 28.4-48.4). All procedures were performed laparoscopically with no conversion to open surgery. The median operating-time was 110 minutes (95-120). The median hospital stay was 6 days (range 5-14). The median BMI in the follow-up of 12 months (9-14) was 28.0 kg/m(2) (25.5-45.8). Diabetes mellitus improved in 4 cases during follow-up. CONCLUSION: Laparoscopic pouch resizing with redo of the gastro-jejunal anastomosis was feasible, safe and effective in this small series. It led to further weight loss and improved symptoms of poor pouch emptying.
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Hepatitis C virus (HCV) infection invariably recurs after liver transplantation (LT), and sequels of chronic hepatitis of the graft are a significant cause of morbidity and mortality. In an uncontrolled trial, 31 patients with histologically confirmed hepatitis C after LT received, sequentially, ribavirin (10 mg/kg body weight q.d.) for 12 weeks, followed by ribavirin at the same dose q.d. plus interferon-alpha (IFN-alpha) [3 million units three times a week (3 MU TIW)] for another 48 weeks. Based on an intent-to-treat analysis, the percentages of patients with undetectable HCV RNA in their serum were 0%, 38.7% and 45.2% after 12, 36 and 60 weeks of therapy, respectively. A sustained virological response, as defined by undetectable serum HCV RNA 24 weeks after the end of treatment, was observed in 9/31 patients (29%). Sustained responders had a significant improvement of their liver inflammatory activity score (P=0.025), but not of their liver fibrosis score. The chances of sustained virological response correlated with the length of treatment, but not with the HCV genotype or baseline HCV RNA level. In conclusion, patients with recurrent hepatitis C after LT might benefit from ribavirin/IFN-alpha therapy, provided that the treatment is tolerated for a sufficient duration of time.
The aim of this study was to evaluate whether the protective effect of intermittent clamping and ischemic preconditioning is related to an improved hepatic microcirculation after ischemia/reperfusion injury. Male C57BL/6 mice were subjected to 75 or 120 min of hepatic ischemia and 1 or 3 hours of reperfusion. The effects of continuous ischemia, intermittent clamping, and ischemic preconditioning before prolonged ischemia on sinusoidal perfusion, leukocyte-endothelial interactions, and Kupffer cell phagocytic activity were analyzed by intravital fluorescence microscopy. Kupffer cell activation was measured by tissue levels of tumor necrosis factor (TNF)-alpha, and the integrity of sinusoidal endothelial cells and Kupffer cells were evaluated by electron microscopy. Continuous ischemia resulted in decreased sinusoidal perfusion rate and phagocytic activity of Kupffer cell, increased leukocyte-endothelial interactions and TNF-alpha levels. Both protective strategies improved sinusoidal perfusion, leukocyte-endothelial interactions and phagocytic activity of Kupffer cells after 75-minutes of ischemia, and intermittent clamping also after 120 minutes ischemia. TNF-alpha release was significantly reduced and sinusoidal wall integrity was preserved by both protective procedures. In conclusion, both strategies are protective against ischemia/reperfusion injury by maintaining hepatic microcirculation and decreasing Kupffer cell activation for clinically relevant ischemic periods, and intermittent clamping appears superior for prolonged ischemia.
We designed this experimental study to determine the optimal cycle for intermittent inflow occlusion during liver resection. A cycle of intermittent clamping (IC) for 15 minutes of ischemia followed by reperfusion for 5 minutes during liver resection is currently the most popular protocol used by experienced liver centers. As each period of reperfusion is associated with bleeding, longer periods of clamping would be advantageous. However, the longest safe duration of successive ischemia is unknown. Three groups of mice were subjected to a total liver ischemic period for 90 minutes; 2 groups underwent IC for 15 or 30 minutes, respectively, followed by 5 minutes of reperfusion, while the control group was subjected to continuous inflow occlusion only. The degree of tissue injury was assessed using biochemical and histological markers, as well as animal survival. While serious injury was observed in the continuous clamping group, both IC groups were associated with minimal injury, including lesser degrees of apoptosis and necrosis. All animals survived in the IC groups, while all animals died following 90 minutes of continuous inflow occlusion. In conclusion, intermittent portal pedicle clamping with 15- or 30-minute cycles is highly protective. A period of 30 minutes clamping should be preferred, since this would decrease the amount of blood loss associated with each cycle. This data should be confirmed in humans, and may represent a change in the current practice of hepatic surgery.
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We present a 25-year-old, HIV-negative patient from Kosovo, with no significant past medical history, who was admitted to a local hospital for nonspecific upper abdominal discomfort. He was transferred to us after a retroperitoneal mass with contact to the right colonic flexure had been found during workup. Colonoscopy demonstrated an edemateous area with a central fistula in the right flexure, and histology showed caseous necrosis. Although neither bacteriology nor histology could detect any germs, gastrointestinal tuberculosis seemed to be very probable. Laparotomy with a segmental resection of the colon was performed to remove the fistula-bearing segment, and histologic examination of the resected specimen confirmed the intraoperative suspect of a retroperitoneal colonic perforation. Again, all cultures from the specimen were negative for tuberculosis, but polymerase chain reaction of a regional lymph node revealed acid-fast bacilli of the Mycobacterium tuberculosis/bovis species. Although the patient had no other sites of tuberculosis infection like pulmonary or urinary, he received adjuvant standard tuberculosis treatment for six months. At control examination one year after the operation, the patient was free of recurrence and in very good general condition. We report this extremely rare presentation of gastrointestinal tuberculosis to sensitize physicians to tuberculosis again, because incidence rates are increasing and this disease will certainly play a more important role in the future.
OBJECTIVE: Although quality assessment is gaining increasing attention, there is still no consensus on how to define and grade postoperative complications. This shortcoming hampers comparison of outcome data among different centers and therapies and over time. PATIENTS AND METHODS: A classification of complications published by one of the authors in 1992 was critically re-evaluated and modified to increase its accuracy and its acceptability in the surgical community. Modifications mainly focused on the manner of reporting life-threatening and permanently disabling complications. The new grading system still mostly relies on the therapy used to treat the complication. The classification was tested in a cohort of 6336 patients who underwent elective general surgery at our institution. The reproducibility and personal judgment of the classification were evaluated through an international survey with 2 questionnaires sent to 10 surgical centers worldwide. RESULTS: The new ranking system significantly correlated with complexity of surgery (P < 0.0001) as well as with the length of the hospital stay (P < 0.0001). A total of 144 surgeons from 10 different centers around the world and at different levels of training returned the survey. Ninety percent of the case presentations were correctly graded. The classification was considered to be simple (92% of the respondents), reproducible (91%), logical (92%), useful (90%), and comprehensive (89%). The answers of both questionnaires were not dependent on the origin of the reply and the level of training of the surgeons. CONCLUSIONS: The new complication classification appears reliable and may represent a compelling tool for quality assessment in surgery in all parts of the world.
OBJECTIVE: To define whether laparoscopic gastric banding or laparoscopic Roux-en-Y gastric bypass represents the better approach to treat patients with morbid obesity. SUMMARY BACKGROUND DATA: Two techniques, laparoscopic gastric bypass or gastric banding, are currently widely used to treat morbid obesity. Since both procedures offer certain advantages, a strong controversy exists as to which operation should be proposed to these patients. Therefore, data are urgently needed to identify the best therapy. METHODS: Since randomized trials are most likely not feasible because of the highly different invasiveness and irreversibility of these procedures, a matched-pair design of a large prospectively collected database appears to be the best method. Therefore, we used our prospective database including 678 bariatric procedures performed at our institution since 1995. A total of 103 consecutive patients with laparoscopic gastric bypass were randomly matched to 103 patients with laparoscopic gastric banding according to age, body mass index, and gender. RESULTS: Both groups were comparable regarding age, gender, body mass index, excessive weight, fat mass, and comorbidites such as diabetes, heart disease, and hypertension. Feasibility and safety: All gastric banding procedures were performed laparoscopically, and one gastric bypass operation had to be converted to an open procedure. Mean operating time was 145 minutes for gastric banding and 190 minutes for gastric bypass (P < 0.001). Hospital stay was 3.3 days for gastric banding and 8.4 days for gastric bypass. The incidence of early postoperative complications was not significantly different, but late complications were significantly more frequent in the gastric banding group (pouch dilatation). There was no mortality in both groups. Efficiency: Body mass index decreased from 48.0 to 36.8 kg/m in the gastric banding group and from 47.8 to 31.9 kg/m in the gastric bypass group within 2 years of surgery. These differences became significant from the first postoperative month until the end of the follow-up (24 months). The gastric bypass procedure achieved a significantly better reduction of comorbidities. CONCLUSIONS: Laparoscopic gastric banding and laparoscopic gastric bypass are feasible and safe. Pouch dilatations after gastric banding are responsible for more late complications compared with the gastric bypass. Laparoscopic gastric bypass offers a significant advantage regarding weight loss and reduction of comorbidities after surgery. Therefore, in our hands, laparoscopic Roux-en-Y gastric bypass appears to be the therapy of choice.
OBJECTIVE: To compare the diagnostic value of contrast-enhanced CT (ceCT) and 2-[18-F]-fluoro-2-deoxyglucose-PET/CT in patients with metastatic colorectal cancer to the liver. BACKGROUND: Despite preoperative evaluation with ceCT, the tumor load in patients with metastatic colorectal cancer to the liver is often underestimated. Positron emission tomography (PET) has been used in combination with the ceCT to improve identification of intra- and extrahepatic tumors in these patients. We compared ceCT and a novel fused PET/CT technique in patients evaluated for liver resection for metastatic colorectal cancer. METHODS: Patients evaluated for resection of liver metastases from colorectal cancer were entered into a prospective database. Each patient received a ceCT and a PET/CT, and both examinations were evaluated independently by a radiologist/nuclear medicine physician without the knowledge of the results of other diagnostic techniques. The sensitivity and the specificity of both tests regarding the detection of intrahepatic tumor load, extra/hepatic metastases, and local recurrence at the colorectal site were determined. The main end point of the study was to assess the impact of the PET/CT findings on the therapeutic strategy. RESULTS: Seventy-six patients with a median age of 63 years were included in the study. ceCT and PET/CT provided comparable findings for the detection of intrahepatic metastases with a sensitivity of 95% and 91%, respectively. However, PET/CT was superior in establishing the diagnosis of intrahepatic recurrences in patients with prior hepatectomy (specificity 50% vs. 100%, P = 0.04). Local recurrences at the primary colo-rectal resection site were detected by ceCT and PET/CT with a sensitivity of 53% and 93%, respectively (P = 0.03). Extrahepatic disease was missed in the ceCT in one third of the cases (sensitivity 64%), whereas PET/CT failed to detect extrahepatic lesions in only 11% of the cases (sensitivity 89%) (P = 0.02). New findings in the PET/CT resulted in a change in the therapeutic strategy in 21% of the patients. CONCLUSION: PET/CT and ceCT provide similar information regarding hepatic metastases of colorectal cancer, whereas PET/CT is superior to ceCT for the detection of recurrent intrahepatic tumors after hepatectomy, extrahepatic metastases, and local recurrence at the site of the initial colorectal surgery. We now routinely perform PET/CT on all patients being evaluated for liver resection for metastatic colorectal cancer.
OBJECTIVE: To determine the evidence-based value of prophylactic drainage in gastrointestinal (GI) surgery. METHODS: An electronic search of the Medline database from 1966 to 2004 was performed to identify articles comparing prophylactic drainage with no drainage in GI surgery. The studies were reviewed and classified according to their quality of evidence using the grading system proposed by the Oxford Centre for Evidence-based Medicine. Seventeen randomized controlled trials (RCTs) were found for hepato-pancreatico-biliary surgery, none for upper GI tract, and 13 for lower GI tract surgery. If sufficient RCTs were identified, we performed a meta-analysis to characterize the drain effect using the random-effects model. RESULTS: There is evidence of level 1a that drains do not reduce complications after hepatic, colonic, or rectal resection with primary anastomosis and appendectomy for any stage of appendicitis. Drains were even harmful after hepatic resection in chronic liver disease and appendectomy. In the absence of RCTs, there is a consensus (evidence level 5) about the necessity of prophylactic drainage after esophageal resection and total gastrectomy due to the potential fatal outcome in case of anastomotic and gastric leakage. CONCLUSION: Many GI operations can be performed safely without prophylactic drainage. Drains should be omitted after hepatic, colonic, or rectal resection with primary anastomosis and appendectomy for any stage of appendicitis (recommendation grade A), whereas prophylactic drainage remains indicated after esophageal resection and total gastrectomy (recommendation grade D). For many other GI procedures, especially involving the upper GI tract, there is a further demand for well-designed RCTs to clarify the value of prophylactic drainage.
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