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Markus Selzner

Publications and source records attributed to Markus Selzner.

16 recordsLinked 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↗
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

How should transection of the liver be performed?: a prospective randomized study in 100 consecutive patients: comparing four different transection strategies.

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.

Analysis of Variance↗
PubMed2004

Does the novel PET/CT imaging modality impact on the treatment of patients with metastatic colorectal cancer of the liver?

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.

Colorectal Neoplasms↗
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

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

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

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↗
PubMed2002

Transgenic mice overexpressing human Bcl-2 are resistant to hepatic ischemia and reperfusion.

BACKGROUND/AIMS: Apoptosis is a key mechanism of reperfusion injury in the ischemic liver. The apoptotic pathway is highly regulated by anti-apoptotic factors, such as Bcl-2. We evaluated the effect of Bcl-2 overexpression on apoptosis and the activation of the apoptotic cascade after hepatic ischemia and reperfusion. METHODS: Ninety minutes of ischemia and reperfusion was performed in Bcl-2 transgenic and non-transgenic mice. Bcl-2 overexpression was determined by immunohistochemistry and Western blot. Liver injury was determined by aspartate aminotransferase (AST), Tunel test and the activation of the apoptotic cascade and animal survival. RESULTS: Bcl-2 overexpression was present in all hepatocytes and non-parenchymal liver cells in transgenic mice. Bcl-2 overexpression resulted in significant decreased AST levels after ischemic injury, and complete inhibition of apoptosis. After 90 min of total hepatic ischemia all control mice died, while four transgenic mice survived permanently. Bcl-2 overexpression was associated with inhibition of caspase 3 activation after reperfusion and increased baseline levels of cytoplasmic cytochrome c, caspase 3, and a reduction of Bcl-x(L) production. CONCLUSIONS: Bcl-2 overexpression protects against ischemic injury by inhibiting apoptosis. Extensive overproduction of Bcl-2 is associated with a compensatory increase of baseline levels of cytoplasmic cytochrome c and caspase 3, and a deletion of Bcl-x(L).

Animals↗
PubMed2002

Cold ischemia decreases liver regeneration after partial liver transplantation in the rat: A TNF-alpha/IL-6-dependent mechanism.

New strategies of partial liver transplantation such as cadaveric split or living related liver transplantation have been developed to overcome organ shortage. Thus, studies on the ability of small partial grafts to regenerate to normal size while maintaining adequate function have become important. Here, we evaluated the effects of cold preservation on hepatocyte proliferation and function in a novel model of partial liver transplantation in rats. Lewis rats subjected to 70% liver resection (control) were compared with rats that underwent total hepatectomy and 30% partial liver transplantation (recipient). Livers were preserved at 4 degrees C for 30 minutes, 10 hours, or 16 hours in University of Wisconsin solution. Seventy percent liver resection was associated with 100% survival, whereas 30-minute, 10-hour, and 16-hour preservation before 30% transplantation resulted in 80%, 40%, and 20% animal survival, respectively. Prolonged time of cold preservation (10 and 16 hours) was associated with a dramatic decrease of all markers of regeneration (P <.05). Tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) levels were also significantly decreased in recipient rats compared with the control group. Finally, pretreatment of recipients with recombinant IL-6 (rIL-6) normalized all markers of regeneration and significantly improved survival in the 10-hour group (90% vs. 40%; P <.05). In conclusion, sustained periods of cold preservation significantly impaired TNF-alpha and IL-6 production, the regenerative ability of the liver, and animal survival. rIL-6 reversed impaired regeneration in the 10-hour cold ischemia group and suggests a primary role of nonparenchymal cells in modulating hepatocyte proliferation in the ischemic liver.

Animals↗
PubMed2002

Downstaging of hepatocellular carcinoma and liver metastases from colorectal cancer by selective intra-arterial chemotherapy.

BACKGROUND: Although resection is the sole chance of cure in patients with hepatocellular carcinoma (HCC) or metastatic colorectal cancer to the liver, most patients are not candidates for surgery at the time of diagnosis. Strategies aiming at downstaging large or multifocal tumors to enable curative resection are appealing. The aim of this study was to evaluate the effects of neoadjuvant selective intra-arterial chemotherapy in noncirrhotic patients with unresectable HCC or metastatic colorectal cancer to the liver in the absence of extrahepatic disease. METHODS: Selective chemotherapy was provided by using a subcutaneous pump device via a catheter placed in the gastroduodenal artery. Chemotherapy regimen included floxuridine (0.2 mg/kg/day for 14 days) in each patient with additional boluses of cisplatin and doxorubicin on day 1 of each cycle in the presence of HCC. Patients were evaluated at 3, 6, 9, and 12 months for possible curative resection. Complete follow-up was available for each patient. RESULTS: Twenty-eight patients with unresectable liver tumors (5 HCC and 23 metastatic colorectal cancer) were included in this study. There were no surgical complications related to pump insertion, and local chemotherapy was started within 1 week of surgery in each patient. The median follow-up in survivors was 31 months (range, 30 months to 5 years). Chemotherapy was well tolerated in 18 (64%) patients. Chemotherapy was discontinued in 4 patients because of abnormal liver function test results, and 2 of them required a biliary stent to relieve a biliary stricture. In 9 patients downstaging enabled curative resection (3 HCC, 6 colorectal metastasis). Seven of these patients were alive and tumor free at the completion of the study, with at least 2 years of follow-up. The actuarial survival rates at 3 years for HCC and colorectal metastases were 60% and 50%, respectively. CONCLUSIONS: About one third of patients with unresectable liver tumors can be successfully treated by neoadjuvant intra-arterial chemotherapy followed by curative resection. This strategy appears particularly promising in patients with large HCC. This approach should be investigated further.

Adult↗