Ischemic preconditioning versus intermittent vascular occlusion in liver resections performed under selective vascular exclusion: a prospective randomized study. Occlusion of hepatic blood inflow for complex central liver resections in cirrhotic patients: a randomized comparison of hemihepatic and total hepatic occlusion techniques. Complete versus selective portal triad clamping for minor liver resections: a prospective randomized trial. A prospective, randomized, controlled trial comparing intermittent portal triad clamping versus ischemic preconditioning with continuous clamping for major liver resection. Portal triad clamping or hepatic vascular exclusion for major liver resection. A controlled study. Treatment of liver metastases from colorectal cancer with hepatic artery occlusion, intraportal 5-fluorouracil infusion, and oral allopurinol. A randomized clinical trial. Ischemic preconditioning improves postoperative outcome after liver resections: a randomized controlled study. [Experiences with adjuvant prostaglandin therapy in vascular surgery interventions]. Ischemic preconditioning for major liver resection under vascular exclusion of the liver preserving the caval flow: a randomized prospective study.
The aim of this study was to compare ischemic preconditioning with the intermittent vascular occlusion technique in liver resections performed under inflow and outflow occlusion.
                Fifty-four patients with resectable liver tumors assigned were randomly to undergo surgery with either ischemic preconditioning (IP group, n = 27) or with intermittent vascular occlusion (IVO group, n = 27). Both groups were compared regarding surgical parameters, aspartate transaminase levels, and apoptosis.
                For warm ischemic time less than 40 minutes, no significant difference was noticed between the 2 groups apart from caspase-3 activity, which was higher in the IVO group than in the IP group (17.2 +/- 3.4 vs. 10.3 +/- 5.2, P < .05). When warm ischemia exceeded 40 minutes, the IP group showed higher levels in blood aspartate transaminase levels on day 3 (442 +/- 178 IU/L vs. 305 +/- 104 IU/L, P < .05) and higher caspase-3 levels (26.5 +/- 5.7 count/high-power field [hpf] vs. 20.7 +/- 3.6 count/hpf, P < .05) and apoptotic activity (28.5 +/- 7.5 count/hpf vs. 20.2 +/- 4.1 count/hpf, P < .05), as compared with the IVO group.
                Although both techniques showed comparable efficacy for short ischemic times, intermittent vascular occlusion provided better cytoprotection when ischemia exceeded 40 minutes. Intermittent occlusion of hepatic blood inflow by means of a hemihepatic or total hepatic occlusion technique is essential for reducing operative blood loss. Central liver resection to preserve more functioning liver parenchyma is mandatory for centrally located liver tumors in patients with cirrhosis, but it requires a longer overall hepatic ischemic time because of a wide transection plane. No controlled comparison has been performed for the 2 techniques in these operations.
                Hemihepatic inflow occlusion may be beneficial in cirrhotic patients who undergo complex central hepatectomy with a wide liver transection plane.
                A prospective, randomized study.
                University hospital and tertiary referral center.
                During liver parenchymal transection, 58 cirrhotic patients who underwent complex central liver resections with a wide transection plane were prospectively randomized into 2 groups. In the group undergoing total hepatic inflow clamping (group T; n = 28), occlusion of hepatic blood inflow was performed for 15 minutes with declamping for 5 minutes. In the group undergoing selective clamping of ipsilateral blood inflow (group H; n = 30), clamping was performed for 30 minutes with declamping for 5 minutes.
                Comparison of patient backgrounds, operative procedures, and early postoperative results.
                Operative blood loss, need for blood transfusion, and postoperative morbidity.
                The patients' backgrounds, operative procedures, and area of liver transection plane were not significantly different between the 2 groups. In all patients, the liver transection areas were greater than 60 cm(2) and overall liver ischemic times were greater than 60 minutes. The amount of operative blood loss and incidence of blood transfusion were significantly greater in group T because of greater blood loss during declamping. Overall liver ischemic and total operative times, postoperative morbidity, and postoperative changes in liver enzyme levels were not significantly different between groups. No in-hospital deaths occurred in either group.
                Intermittent hemihepatic and total occlusion of hepatic blood inflow are safe in cirrhotic patients with an overall ischemic time of greater than 60 minutes. However, for complex liver resections with an estimated liver transection plane of greater than 60 cm(2), hemihepatic occlusion of blood inflow, if feasible, may be recommended in cirrhotic patients to reduce operative blood loss and the incidence of blood transfusion under our defined occlusion time. To evaluate the feasibility, safety, efficacy, amount of hemorrhage, postoperative complications, and ischemic injury of selective clamping in patients undergoing minor liver resections.
                Inflow occlusion can reduce blood loss during hepatectomy. However, Pringle maneuver produces ischemic injury to the remaining liver. Selective hemihepatic vascular occlusion technique can reduce the severity of visceral congestion and total liver ischemia.
                Eighty patients undergoing minor hepatic resection were randomly assigned to complete clamping (CC) or selective clamping (SC). Hemodynamic parameters, including portal pressure and the hepatic venous pressure gradient (HVPG), were evaluated. The amount of blood loss, measurements of liver enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST), and postoperative evolution were also recorded.
                No differences were observed in the amount of hemorrhage (671 +/- 533 mL versus 735 +/- 397 mL; P = 0.54) or the patients that required transfusion (10% versus 15%; P = 0.55). There were no differences on postoperative morbidity between groups (38% versus 29%; P = 0.38). Cirrhotic patients with CC had significantly higher ALT (7.7 +/- 4.6 versus 4.5 +/- 2.7 mukat/L, P = 0.01) and AST (10.2 +/- 8.7 versus 4.9 +/- 2.1 mukat/L; P = 0.03) values on the first postoperative day than SC. The multivariate analysis demonstrated that high central venous pressure, HVPG >10 mm Hg, and intraoperative blood loss were independent factors related to morbidity.
                Both techniques of clamping are equally effective and feasible for patients with normal liver and undergoing minor hepatectomies. However, in cirrhotic patients selective clamping induces less ischemic injury and should be recommended. Finally, even for minor hepatic resections, central venous pressure, HVPG, and intraoperative blood loss are factors related to morbidity and should be considered. To evaluate whether ischemic preconditioning (IP) with continuous clamping or intermittent clamping (IC) of the portal triad confers better protection during liver surgery.
                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.
                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.
                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.
                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. The authors compared operative course of patients undergoing major liver resections under portal triad clamping (PTC) or under hepatic vascular exclusion (HVE).
                Reduced blood loss during liver resection is achieved by PTC or HVE. Specific complications and postoperative hepatocellular injury mediated with two procedures have not been compared.
                Fifty-two noncirrhotic patients undergoing major liver resections were included in a prospective randomized study comparing both the intraoperative and postoperative courses under PTC (n = 24) or under HVE (n = 28).
                The two groups were similar at entry, but eight patients were crossed over to the other group during resection. In the HVE group, hemodynamic intolerance occurred in four (14%) patients. In the PTC group, pedicular clamping was not efficient in four patients, including three with involvement of the cavohepatic intersection and one with persistent bleeding due to tricuspid insufficiency. Intraoperative blood losses and postoperative enzyme level reflecting hepatocellular injury were similar in the two groups. Mean operative duration and mean clampage duration were significantly increased after HVE. Postoperative abdominal collections and pulmonary complications were 2.5-fold higher after HVE but without statistical significance, whereas the mean length of postoperative hospital stay was longer after HVE.
                This study shows that both methods of vascular occlusion are equally effective in reducing blood loss in major liver resections. The HVE is associated with unpredictable hemodynamic intolerance, increased postoperative complications with a longer hospital stay, and should be restricted to lesions involving the cavo-hepatic intersection. Regional therapy for colorectal liver metastases aimed at prolonging survival has not been tested fully in a randomized trial with untreated control subjects. This study explored the efficacy of temporary hepatic artery occlusion followed by intraportal infusion of 5-fluorouracil (5-FU) and oral allopurinol as biochemical modulators in prolonging the survival of patients with nonresectable liver metastases and no extrahepatic cancer.
                Eighty-four patients were considered for randomization, of whom 24 were excluded at laparotomy because of extrahepatic cancer (n = 17) or resectable lesions (n = 5). In two patients, no cancer was identified in the liver. Thirty-two patients were allocated to receive treatment, and 28 were allocated to receive no regional or systemic treatment. Six patients were excluded after randomization because of major protocol violations.
                The median survival time for patients was 17 months (range, 0-66), and for control subjects, the median was 8 months (range, 0-31). Log rank analysis demonstrated a significant survival benefit for treatment versus no treatment (P = 0.0039). (In two patients, early death was due to toxicity from the wrong dose of 5-FU and the wrong route of administration, respectively; the mean and median survival were reduced by 1 month).
                This study identified a treatment modality that prolongs survival in patients with nonresectable liver metastases and no extrahepatic metastases from colorectal cancer, suggesting that control subjects receiving no therapy may not be necessary in future randomized trials. Clamping of the portal triad (Pringle maneuver) prevents blood loss during liver resection, but leads to liver injury upon reperfusion. Ischemic preconditioning (IP) has been shown to protect the liver against prolonged ischemic injury in animal models. However, the clinical value of this procedure has not yet been established.
                61 Patients undergoing hepatic resection under inflow occlusion were randomized to either to receive (Group-A n = 30) or not to receive (Group-B n = 31) an IP (10 minutes of ischemia followed 10 minutes of reperfusion).
                Mean (+/- SD)/ Group-A vs. Group-B. Pringle time of 34 +/- 14 and 33 +/- 12 minutes and the extent of resected liver tissue (2.7 +/- 1.3 vs. 2.7 +/- 1.1 segments) were comparable in both groups. Complications, including death, severe liver dysfunction and biliary leakage occurred in 6 patients of Group-A vs. 14 patients of Group-B (p<0.05). Intraoperative blood loss was significantly lower in Group-A (1.28 +/- 0.91 l vs. 1.94 +/- 0.76 l; p<0.001) with 5 vs. 15 patients requiring transfusions (p<0.01). In a multivariate analysis the duration of the Pringle maneuver (p<0.05) and the absence of preconditioning (p<0.05) were independent predictors for the occurrence of postoperative complications.
                IP protects against reperfusion injury, reduces the incidence of complications after hepatic resection under inflow occlusion and is simple to use in clinical practice. Two prospective randomized trials were referred. In the first study 50 patients with femorotibial greater saphenous vein in situ bypasses were treated intraarterially with 0.2 ng PGE 1/kg body weight/min and 15,000 i.U. of heparine continuously. The control group of 50 patients also got 15,000 i.U. of heparine and 3 x 0.5 g of Aspirin. We observed 2 (4%) immediate occlusions in the PGE 1 group and 7 (14%) immediate occlusions in the control group. This difference proved to be statistically significant. In the second study 83 patients with three level occlusions (ilio-femoro-tibial) in stage III and IV were treated with a profundaplasty. 42 patients received 60 micrograms PGE 1 in 250 ml saline twice daily. The control group of 41 patients only got twice 250 ml saline over a period of three weeks. In the PGE 1 group 26 patients (61%) showed disappearance of rest pain and healing of necrotic lesions, whereas in the control group this could only be achieved in 15 patients (35%). The difference proved to be statistically significant. Two randomized prospective studies suggested that ischemic preconditioning (IP) protects the human liver against ischemia-reperfusion injury after hepatectomy performed under continuous clamping of the portal triad. The primary goal of this study was to determine whether IP protects the human liver against ischemia-reperfusion injury after hepatectomy under continuous vascular exclusion with preservation of the caval flow.
                Sixty patients were randomly divided into two groups: with (n=30; preconditioning group) and without (n=30; control group) IP (10 minutes of portal triad clamping and 10 minutes of reperfusion) before major hepatectomy under vascular exclusion of the liver preserving the caval flow. Serum concentrations of aspartate transferase, alanine transferase, glutathione-S-transferase, and bilirubin and prothrombin time were regularly determined until discharge and at 1 month. Morbidity and mortality were determined in both groups.
                Peak postoperative concentrations of aspartate transferase were similar in the groups with and without IP (851 +/- 1,733 IU/L and 427 +/- 166 IU/L respectively, p=0.2). A similar trend toward a higher peak concentration of alanine transferase and glutathione-S-transferase was indeed observed in the preconditioning group compared with the control group. Morbidity and mortality rates and lengths of ICU and hospitalization stays were similar in both groups.
                IP does not improve liver tolerance to ischemia-reperfusion after hepatectomy under vascular exclusion of the liver with preservation of the caval flow. This maneuver does not improve postoperative liver function and does not affect morbidity or mortality rates. The clinical use of IP through 10 minutes of warm ischemia in this technique of hepatectomy is not currently recommended.
Intermittent vascular occlusion seems safe in liver resection. However, it does not seem to decrease morbidity. More randomised trials seem to be needed.