Evaluation of Pringle Maneuver During Liver Resection in a Rat Model of Surgical Obstructive Jaundice

Temporary portal triad clamping (Pringle maneuver) during liver resection reduces intraoperative blood loss. A normal liver can safely tolerate normothermic ischemia for up to 60 min. However, its safety in patients with surgical obstructive jaundice (SOJ) is not known. Therefore, we investigated the effect of hepatic ischemia in an experimental rat model of SOJ created by ligating the bile duct. Four groups of rats were created: Group I (sham operation, 10 days later, liver resection); Group II (sham operation, 10 days later, liver resection with 5 min of hepatic ischemia); Group III (bile duct ligation, 10 days later, liver resection); and Group IV (bile duct ligation, 10 days later, liver resection with 5 min of hepatic ischemia). The ischemic injury was assessed by the survival of rats, liver tissue malondialdehyde and total glutathione (markers of free radical injury), serum alanine aminotransferase, aspartate aminotransferase, and liver histology. The results showed decreased survival (47.6% vs. 90% [p =. 046]), increased liver tissue malondialdehyde (161 ± 35 vs. 129 ± 33 μg/gm liver tissue [p ≤. 05]), and decreased liver tissue total glutathione (565 ± 169 vs. 1075 ± 276 nmol/gm liver tissue [p ≤. 05]) in rats with SOJ subjected to hepatic ischemia when compared to nonjaundiced rats. The changes in serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase showed an increasing trend in the SOJ group but were not statistically significant. Ischemic changes in liver histology were seen more often in the SOJ group but were not statistically significant. These data suggest that temporary portal triad clamping in an experimental model of SOJ is detrimental to the outcome of liver resection.     

Bile duct exclusion from selective vascular inflow occlusion in rat liver: role of ischemic preconditioning and N-acetylcysteine on hepatic reperfusion injury

AIM: To study the effects of N-acetylcysteine and ischemic preconditioning on the portal triad clamping compared to arterial and portal clamping alone. METHODS: Eighty EPM 1-Wistar rats were randomized into two groups, depending on inclusion (Group 1) or not (Group 2) of the bile duct in the hepatic vascular pedicle occlusion. Each group was divided into four subgroups as follows. IR 1: 20 minutes after celiotomy, the pedicle containing vascular elements and bile duct to the left lateral and median liver lobes was occluded for 40 minutes, followed by 30 minutes of reperfusion. IPC 1: after 10 minutes of ischemia and 10 minutes of reperfusion, the ischemic preconditioning period, the rats were submitted to the same procedure described for IR 1 Group. NAC 1: the rats received N-acetylcysteine (150 mg/kg) 15 minutes before 40 minutes of ischemia and 5 minutes before 30 minutes of reperfusion. SHAM 1: The hepatic pedicle for the lateral and median liver lobes was dissected after 20 minutes, the bile duct alone was clamped for 40 minutes, and released for an additional 30 minutes. In the IR 2, IPC 2, and NAC 2 groups, ischemia was achieved with an exclusive vascular occlusion. SHAM 2: dissection and observation for 90 minutes. The blood was sampled for liver enzyme levels. Statistical analysis was done (P 相似文献   

高原地区大鼠常温下耐受入肝血流阻断安全时限的研究

目的研究在高原地区(海拔3000米)大鼠常温下耐受入肝血流阻断安全时限。方法分为单纯入肝血流阻断50、40、30、20、15、10分钟6组及假手术组。首先按50、40、30、20、10分钟实验,测定死亡率,然后按死亡率较低组开始实验,于12 h、24 h、48 h、72 h分别开腹,取心脏血及肝脏标本行肝功、病理检查。结果发现大鼠在高原地区(海拔3 000米)可以耐受10 min的肝门阻断,超过20 min肝门阻断肝功损伤严重,肝脏病理改变明显,死亡率升高。结论可以确认10分钟是高原地区(海拔3 000米)大鼠能耐受的最大缺血安全时限。     

Establishment of an animal model of biliary ischemic stenosis with clamping in mice

OBJECTIVE: The objective of this study was to explore a method to establish biliary ischemic stenosis in mice. METHODS: After the optimal time of biliary ischemia was determined, 20 Kunming mice were equally divided into 2 groups. In the experimental group a 0.4-cm length of common bile duct was clamped for 90 minutes with 2 micro-vessel clamps (width = 0.1 cm). The common bile duct was not clamped in the control group. Twenty-one days later, biliary tract visualization was performed in all mice. Blood samples were collected from the inferior vena cava to determine the serum levels of total bilirubin (TBIL) and alanine aminotransferase (ALT). Meanwhile, samples of the common bile duct and liver tissue were extracted for microscopic examination to observe morphological changes. RESULTS: In the experimental group, obvious dilatation of the common bile duct appeared over the clamp site. There was no dilatation of the common bile duct in the control group. Twenty-one days later, serum levels of TBIL and ALT were significantly higher among the experimental compared with the control group. Microscopic examination showed that the part of common bile duct at the clamp site was significantly expanded, with a smaller or occluded bile duct lumen necrotic mucosa with determination, and tubular wall with fibrosis and excrustation. A few dead liver cells and many inflammatory cells were observed in liver tissue samples. CONCLUSIONS: A biliary ischemic stenosis model was established using a clamping method in mice, which may provide a reliable technique for basic and clinical research into mechanisms of biliary ischemic stenosis after liver transplantation.     

Allopurinol plus pentoxifilline in hepatic ischaemia/reperfusion injury

OBJECTIVES: Ischaemia/reperfusion injury of the liver is the major cause of liver dysfunction and cellular death in transplantation and in liver resection with hepatic pedicle clamping. Many agents are used to prevent this phenomenon, which occurs following interaction of different mediators during both ischaemia and reperfusion. In this study, we aimed to assess the effects of allopurinol, a xanthine oxidase inhibitor, and pentoxifilline, on liver ischaemia/reperfusion injury when used together and to compare these with the effects of using these agents singly. METHODS: Thirty-two rats were divided into four groups consisting of eight rats: Group C, control; Group P, pentoxifilline; Group A, allopurinol; and Group PA, pentoxifilline + allopurinol. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) levels were measured before hepatic pedicle clamping, on the 45th minute of ischaemia and 15 and 45 minutes after reperfusion. Group P rats were injected with 50 mg/kg pentoxifilline, Group A rats 50 mg/kg allopurinol and Group PA rats were injected with both agents 15 minutes before hepatic pedicle clamping. RESULTS: Ischaemia/reperfusion injury was produced by hepatic pedicle clamping, as demonstrated by AST, ALT and LDH increase. Injury prevention occurred in Groups P, A and PA. No significantly different (better) prevention was provided by giving allopurinol plus pentoxifilline to the rats. Furthermore, no difference was observed between the allopurinol and pentoxifilline injected groups in terms of preventing ischaemia/reperfusion injury. CONCLUSIONS: Pretreatment with allopurinol or pentoxifilline resulted in significantly lower hepatic enzyme elevation than that in controls in the rat liver ischaemia/reperfusion model. Using both agents does not provide better protection than using either agent alone.     

Protective effects of thromboxane A2 synthetase inhibitor (OKY-046) on hepatic ischemia-reperfusion injury in rats with obstructive jaundice

The effects of OKY-046, a thromboxane A₂ synthetase inhibitor, on complete hepatic ischemia with obstructive jaundice were studied in male Wistar rats in vivo. The objective of this study was to investigate the influence of OKY-046 (i) on the hepatic microcirculation, as measured by tissue partial oxygen pressure (tPO₂), and (ii) on the release of interleukin-8 (IL-8) in hepatic tissue after reperfusion. Fourteen days after bile duct clamping, the rats were subjected to 30-min warm complete liver ischemia and then reperfusion. The rats were divided into three groups; one group received no treatment (controls, group C), one group received OKY-046 from 15 min before hepatic ischemia to the end of the experiment (group OKY), and the third group received gadolinium chloride (group Gd), injected intravenously to evaluate the contribution of the Kupffer cell to IL-8 production. Group OKY maintained significantly higher tPO₂ levels 5, 10, and 15 min after declamping compared to group C (P<0.05). The IL-8 level in liver tissue in group OKY was lower than that in group C, but the difference was not significant. Group Gd exhibited the lowest IL-8 level of the three groups (P < 0.05). These findings demonstrated that OKY-046 improved the hepatic microcirculation during the reperfusion period, influenced the Kupffer cells in terms of the avoidance of hypoxia, and depressed the concentration of IL-8 in liver tissue.     

Prolonged continuous or intermittent vascular inflow occlusion during hemihepatectomy in pigs

OBJECTIVE: To assess ischemia and reperfusion (I/R) injury in a hemihepatectomy model in pigs after prolonged continuous or intermittent vascular inflow occlusion in the liver. SUMMARY BACKGROUND DATA: Massive intraoperative blood loss during liver resections can be prevented by temporary vascular inflow occlusion, consequently leading to ischemia and reperfusion injury in the remnant liver. Previously, in a pig liver resection model in which only limited I/R injury was induced during brief (90 min) vascular inflow occlusion, the authors demonstrated reduced I/R injury after continuous (CNT) occlusion, compared to intermittent (INT). This liver resection study on pigs was undertaken to assess I/R injury after prolonged (120 min) CNT or INT occlusion. METHODS: In pigs (37.0 +/- 1.5 kg), liver ischemia during 2 hours was CNT (n = 6) or INT (n = 6) (eight subsequent periods of 12 min ischemia and 3 min recirculation), followed by 6 hours of reperfusion. A left hemihepatectomy (45.5% +/- 1.4%) was performed within the first 12 minutes of ischemia. No hepatic pedicle clamping or liver resection was performed in control experiments (n = 6). Microvascular damage was assessed by hyaluronic acid (HA) uptake capacity of the liver (parameter of early sinusoidal endothelial cell damage) and restoration of intrahepatic tissue pO2 during reperfusion. Hepatocellular damage was tested by plasma concentrations of aspartate aminotransferase (AST), alanine aminotransferase, and lactate dehydrogenase (LDH). RESULTS: Hyaluronic acid uptake after 6 hours of reperfusion, compared to preischemic uptake, was unaltered in the control group, but was significantly reduced in both resection groups. However, more HA was taken up after INT occlusion, compared to CNT (60.4% +/- 5.6% and 39.5% +/- 3.7%, respectively; ANOVA: p = 0.001). Intrahepatic tissue pO2 distribution after 6 hours of reperfusion more closely returned to preischemic configuration in the INT group than in the CNT group, indicating reduced microcirculatory disturbances after INT occlusion. Release of AST and LDH after 6 hours of reperfusion was significantly increased in both CNT and INT groups. Lower AST levels, however, were found after INT occlusion than after CNT occlusion (267.0 +/- 74.7 U/l and 603.3 +/- 132.4 U/l, respectively; p = 0.06). CONCLUSIONS: Intermittent hepatic vascular inflow occlusion during prolonged liver ischemia in pigs resulted in less microcirculatory and hepatocellular injury, compared to continuous occlusion. Intermittent clamping is preferable when prolonged periods of vascular inflow occlusion are applied during liver resections.     

大黄素对大鼠肝脏缺血再灌注损伤的预防作用

目的:探讨大黄素对肝脏缺血-再灌注损伤的保护作用及其机制.方法:将45只成年雄性SD大鼠随机分成三组:假手术对照组(A组)15只,肝缺血30 min、再灌注90min组(B组)15只,术前5 d给予大黄素灌胃60mg/(kg·d),5次 肝缺血30 min、再灌注90min(C组)15只;观察血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、透明质酸酶(HA)、肝组织丙二醛(MDA)含量的变化及肝脏组织病理学改变情况,同时测定各组大鼠胆汁流量情况.结果:C组与B组相比,MDA含量显著降低(P＜0.05),HA浓度明显降低(P＜0.01),胆汁流量显著增加(P＜0.01),同时C组的肝细胞功能明显改善,且肝脏超微结构改变也较轻.结论:大黄素对肝脏缺血-再灌注损伤具有保护作用,该作用与减轻肝脏缺血再灌注后脂质过氧化程度和肝窦内皮细胞损伤有关.     

Protective effect of resveratrol against oxidative stress in cholestasis

BACKGROUND: We investigated the protective role of resveratrol in rat liver injuries induced by chronic biliary obstruction. MATERIALS AND METHODS: Secondary biliary cirrhosis was induced by bile duct ligation for 28 days. Swiss albino rats were divided into the three following groups: group 1: sham (n = 7); group 2: bile duct ligation (n = 7); group 3: bile duct ligation plus resveratrol (n = 7). Bile duct ligation plus resveratrol group received 10 mg/kg dose of resveratrol intraperitoneally daily for 28 days. Liver damage and cholestasis were determined by the biochemical and the pathologic examination. RESULTS: The present data showed a decrease in both plasma bilirubin levels and aspartate aminotransferase and alanine aminotransferase levels in the resveratrol-treated rats, when compared with bile duct ligation group (P < 0.05). In the resveratrol-treated rats, tissue levels of malondialdehyde and nitric oxide were significantly lower than that of the bile duct ligation (P < 0.002). The levels of glutathione in resveratrol-treated rats were significantly higher than that in bile duct ligation group (P < 0.004). The levels of interleukin-1alpha, interleukin-6, and tumor necrosis factor-alpha in resveratrol group were significantly lower than that in bile duct ligation group (P < 0.004, P < 0.001, P < 0.001, respectively). Administration of resveratrol in the rats with biliary obstruction resulted in inhibition of ductular proliferation and lymphocytic inflammation. CONCLUSION: The present study demonstrates that intraperitoneal administration of resveratrol in bile duct ligated rats maintained antioxidant defenses and reduces liver oxidative damage and ductular proliferation. This effect of resveratrol may be useful in the preservation of liver function in cholestasis.     

Liver resection under total vascular isolation. Variations on a theme.

Total vascular isolation (TVI) of the liver was employed during parenchymal transection in 16 patients undergoing hepatic resection for large tumors (mean diameter, 10.7 cm) located near hilar structures, hepatic veins, or the inferior vena cava (IVC). In 14 cases, TVI was achieved by clamping the suprahepatic and infrahepatic IVC and the porta hepatis, with or without aortic occlusion; in two, selective hepatic vein clamping was possible, obviating IVC occlusion. Procedures included standard and extended right and left lobectomies and caudate lobe resections. Concomitant resection and reconstruction of the portal vein (one case), IVC (one case), and bile duct (three cases) was required. Postoperative hepatic and renal failure did not occur. Mean intensive care unit and hospital stays were 2.8 +/- 1.9 and 12.5 +/- 5.2 days, respectively. There were two perioperative deaths. Total vascular isolation permits safe resection of large, critically located tumors that would otherwise present prohibitive operative risks.     

肝切除联合肝动脉切除对梗阻性黄疸大鼠肝细胞再生和凋亡的影响

目的 探索在梗阻性黄疸时,不同范围肝切除联合肝动脉切除对肝细胞再生和凋亡的影响.方法 155只雄性SD大鼠行胆总管结扎制备梗阻性黄疽模型,5 d后二次手术分为:胆肠再通内引流组;肝切除(42%、70%)联合胆肠再通内引流组;肝切除(42%,70%)联合肝固有动脉切除、胆肠再通内引流组.动态观察二次手术后24 h、72 h、7 d肝组织HGF、bcl-2 mRNA含量及蛋白表达、肝细胞增殖和凋亡指数的变化,并统计各组死亡率.结果 高胆红素血症、行胆肠冉通内引流的同时,大鼠肝切除或肝切除联合肝动脉切除后,肝再生均受抑制,凋亡增多;较之肝切除组和42%肝切除联合肝固有动脉切除组.70%肝切除联合肝固有动脉切除组术后肝组织HGF、bcl-2 mRNA含量显著减少,肝细胞再生明显受抑而凋亡显著增多,死亡率显著增高(P<0.05).结论 高胆红素血症时,肝切除量是影响大鼠肝切除联合肝动脉切除实施安全性的重要因素,42%肝切除联合肝固有动脉切除、胆肠再通内引流,对肝细胞再生和凋亡影响较小,安全町行;70%肝切除联合肝动脉切除、胆肠再通内引流后肝细胞再生显著受抑制,凋亡增多,死亡率高,应避免实施.     

The development of a pyogenic liver abscess following radical resection of cholangiocellular carcinoma with ligation of the right hepatic artery: Report of a case

We present herein the case of a pyogenic liver abscess developing from hepatic ischemia caused by resection of the right hepatic artery when a left hemihepatectomy with caudate lobectomy and extrahepatic bile duct resection was performed for cholangiocellular carcinoma. Postoperative cholangiography revealed communication between the abscess cavity and the intrahepatic bile duct. The liver abscess was successfully treated by percutaneous transhepatic drainage. Thus, breakdown of the intrahepatic bile duct due to ischemia may play an important role in the development of a pyogenic liver abscess following hepatic arterial occlusion.     

Complete versus selective portal triad clamping for minor liver resections: a prospective randomized trial

OBJECTIVE: To evaluate the feasibility, safety, efficacy, amount of hemorrhage, postoperative complications, and ischemic injury of selective clamping in patients undergoing minor liver resections. SUMMARY BACKGROUND DATA: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.     

Late Biliary Obstruction in Wistar Rats After Intermittent Hepatic Pedicle Clamping

Introduction

The temporary vascular occlusion of hepatic flow is one of the essential procedures in hepatic surgery.

Aim

Evaluate the late liver alterations after intermittent pedicle hepatic clamping (IHPC) in Wistar rats.

Methods

Male Wistar rats (n = 14) with average weight of 281.1 g, were anesthetized with intraperitoneal ketamine 5%. The IHPC group (n = 7) was submitted to U-shaped abdominal incision; the hepatic pedicle was isolated and submitted to IHPC ischemia 4 times, 5 minutes each, followed by reperfusion 4 times, 5 minutes each. The simulated operation group (n = 7) was subjected to anesthesia, laparotomy, and manipulation of the hepatic pedicle. On day 35, after fasting for 12 hours, liver biopsies were collected and blood was tested for liver aminotransferases (aspartate aminotransferase/alanine aminotransferase).

Results

All the IHPC group animals had a dilated common bile duct and increased liver enzymes (P < .05 by Mann-Whitney test). Ductular proliferation (100% of cases), porta-porta septa (42.8%), formation of lumps (42.8%), foci of necrosis (14.2%), and bile plugs (14, 2%) were observed only in the IHPC group.

Conclusion

In rats, IHPC caused morphologic features leading to biliary obstruction.     

Highly anatomically systematized hepatic resection with Glissonean sheath code transection at the hepatic hilus

We have developed a new method of hepatic resection, in which the cancer-bearing Glissonean code (G-code) branches are served using a hilar approach for an anatomically systematized resection. Since the hepatic artery, portal vein and bile duct are surrounded by connective tissue, the portal triad can be treated as a fibroid code both outside and inside the liver. Compared to the ramification pattern of the hepatic artery, portal vein and bile duct, that of the G-code is simpler. In all our surgical procedures of hepatic resections, the cancer bearing G-code branch is selectively cut using a hilar approach before the dissection of the parenchyma of the liver. We have experienced 168 cases of several types of hepatic resection for hepatocellular carcinoma. Only in three cases was it impossible to accomplish the transection of some third branches using a hilar approach.     

Pioglitazone Attenuates Ischemia/Reperfusion–Induced Liver Injury in Rats

Introduction

Hepatic ischemia/reperfusion (I/R) injury leads to free radical generation and acute inflammatory responses that cause liver damage, an important problem for liver transplantation. Pioglitazone is known to protect I/R injury in various tissues; however, the mechanism of cytoprotection is not well understood. This study investigated the effects of pioglitazone administration in a warm hepatic I/R model on tumor necrosis factor (TNF)-α level, tissue injury, and antioxidant enzyme activity.

Materials and Methods

Eighty wistar strain rats were divided into 4 groups (n = 20): Group 1 sham hosts; Group 2 hepatic I/R; Group 3 hepatic I/R + pioglitazone (10 mg/kg); and Group 4 hepatic I/R + vehicle. Rat livers were subjected to 30 minutes of ischemia followed by 6 hours of reperfusion. After reperfusion rats were humanely killed to obtain liver tissue to study glutathione peroxidase (GPx), superoxide dysmutase (SOD), malondialdehyde (MDA) levels and for histopathologic assessment. TNF-α, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were measured in serum.

Results

Pioglitazone pretreatment significantly reduced liver enzyme content (ALT, 176.80 ± 13.75 vs 235.28 ± 31.92 and AST, 748.20 ± 79.29 vs 944.85 ± 101.87) and TNF-α level (9:8.60 ± 8.67 vs 138.28 ± 9.99) after I/R compared with the control group. MDA level (3.02 ± 0.37 vs 4.36 ± 0.38) and hepatocytic degeneration were reduced in the pioglitazone-treated group. GPx (2.40 ± 0.25 vs 1.36 ± 0.31) and SOD activity (2.22 ± 0.30 vs 1.40 ± 0.35) were significantly higher in the pioglitazone-treated group compared with the control group.

Conclusion

The present study showed that pioglitazone administration improved hepatic I/R injury that was associated with enhanced antioxidant enzyme activities and suppression of TNF-α, ALT, and AST levels. Because peroxisome proliferator-activated receptor-γ agonists are widely used to treat diabetic patients, it may be relatively easy to expand their clinical indication. However, further investigations will be required to delineate protective mechanisms by which pioglitazone attenuates hepatic tissue injury after I/R.     

Evaluation of graft viability in heterotopic auxiliary liver transplantation in the rat.

In the rat model of heterotopic auxiliary liver transplantation, the coexistence of the engrafted liver and the recipient's native liver makes it difficult to evaluate the posttransplant graft viability. In this study, auxiliary liver transplantation was performed in Wistar rats, in which the recipient's native liver was handicapped with a 68% partial hepatectomy and a common bile duct ligation. Serum biochemistry of the liver was analyzed and compared with that of the selected control group. The surgical handicap of the liver showed severe damaging effects: the handicapped native livers appeared atrophic at autopsy, and no long-term animal survival could be achieved without an auxiliary liver transplantation. As the engrafted liver corrected the cholestasis of the handicapped native liver, significant differences of serum biochemistry were found between the transplanted group and the control group: for bilirubin concentration and gamma glutamyl transferase activity from postoperative day 3 to 28 (p < .05); for alkaline phosphatase on days 3, 7, 14, and 28 (p < .05); for alanine aminotransferase activity on days 3 and 14 (p < .05); and for aspartate aminotransferase activity on day 14 (p < .05). The efficiency to induce hepatic failure and to hamper its regeneration capacity in the native liver makes animal survival and liver biology as reliable parameters to evaluate the posttransplant graft viability in this rat model.     

Impaired bacterial clearance and trapping in obstructive jaundice.

Sepsis is a major cause of mortality in patients with common bile duct obstruction. To define possible contributing factors to this phenomenon, this study evaluates the effect of biliary obstruction on the intravascular clearance and organ trapping of viable Escherichia coli using a rat model. Adult male Sprague-Dawley rats were placed in three groups: Group I controls had sham operation, Group II had division and ligation of common bile duct (CDL), and Group III underwent splenectomy. At 21 days following operation 10(9) radiolabeled E. coli were injected intravenously. At varying intervals after infusion, blood samples were obtained for clearance study. At 10 minutes, bacterial distribution in the liver, spleen, kidneys, and lungs was determined (expressed as the mean percentage of injected viable E. coli). Intravascular clearance was similar in all groups. There was a significant decrease in the trapping of bacteria by the liver of CDL rats 14.5% +/- 4.95 (vs. control = 70.0% +/- 13.3) (p less than 0.005). A significant increase of bacterial trapping by the lung was observed in the CDL animals: 63.1% +/- 7.06 (vs. controls 1.4% +/- 0.82) (p less than 0.005). There was no significant change in bacterial localization in splenectomized rats. These data suggest that biliary obstruction decreases hepatic phagocytosis and increases pulmonary localization of viable E. coli. As the Kupffer cells of the liver are usually effective in removal of blood borne bacteria, this phagocytic dysfunction may contribute to the increased susceptibility to infection noted in instances of biliary obstruction.     

Liver ischemia for hepatic resection: where is the limit?

BACKGROUND. A consecutive series of 50 patients who submitted to 53 hepatic resections with use of continuous normothermic liver ischemia is reported. METHODS. Portal triad clamping has been used in 28 cases, with associated inferior vena caval clamping above and below the liver (hepatic vascular exclusion) in 25 patients. The size of the tumor required major hepatic resection in 38 cases (71.7%). Malignant tumors (83%) were the most common indication for liver resection. Patients were placed in three groups according to the duration of liver ischemia: group A, less than 30 minutes (9 patients); group B, 30 to 60 minutes (29 patients); and group C, 60 or more (15 patients). RESULTS. No differences in mortality rates (5.7% in the entire series and 0% in group C) and morbidity rate could be shown. No significant difference was found in postoperative liver test results, and no persistent alteration remained thereafter. Liver biopsy at 6 and 12 months after operation did not reveal any chronic damage. Liver capability to regenerate was maintained as documented by postoperative computerized tomography scan or magnetic resonance imaging. CONCLUSIONS. Because interruption of hepatic blood flow in normothermia is safe for at least 60 minutes (up to 85 minutes in this study), vascular clamping is recommended for hazardous liver resections to minimize blood loss, which appears to be the main factor of death and morbidity.     

Regional hepatic arterial infusion of degradable starch microspheres increases fluorodeoxyuridine (FUdR) tumor uptake

Hepatic metastases of colorectal carcinoma demonstrate a dose response to chemotherapy. In animal studies hepatic arterial infusion of chemotherapeutic agents with degradable starch microspheres (DSMs) produces a redistribution of blood flow between tumor and liver and an increase in tumor drug levels. In this prospective clinical study in patients with colorectal metastases, we evaluated the effect of DSMs on liver and tumor levels of fluoropyrimidines after intraoperative administration through the hepatic artery. Fourteen patients underwent infusion of radiolabeled fluorodeoxyuridine, 14C-FUdR (0.15 mg/kg, 0.5 microCi/kg), followed 2 to 5 minutes later by infusion of 3H-FUdR (0.15 mg/kg, 1.0 microCi/kg) without (n = 3) or with (n = 11) DMS. Seven of the later patients underwent major hepatic resection and tissue mapping of drug distribution, and four patients underwent biopsy procedures to remove specimens of liver and tumor 5 minutes after microsphere infusion. Administration of DSMs with FUdR increased tumor drug levels as measured by 3H-FUdR (5.9 +/- 4.4 vs 17.1 +/- 9.4 nmol/gm, p = 0.07) without altering hepatic drug levels (35.7 +/- 10.9 vs 30.2 +/- 20.9 nmol/gm, p = NS) and significantly increased the tumor/liver drug ratio of tritiated fluoropyrimidines (0.16 +/- 0.09 to 0.63 +/- 0.13, p = 0.03). Fluoropyrimidine levels in tumor and liver correlated with blood flow as measured by technetium-99m macroaggregated albumin retention. Thus, hepatic arterial administration of DSMs in human beings enhances tumor FUdR levels and may be useful in increasing tumor cytotoxicity and decreasing systemic toxicity during regional hepatic infusion.