The intermittent Pringle maneuver (IPM) is frequently applied to minimize blood loss during liver transection. Clamping the hepatoduodenal ligament blocks the hepatic inflow, which leads to a non circulating (hepato)splanchnic outflow. Also, IPM blocks the mesenteric venous drainage (as well as the splenic drainage) with raising pressure in the microvascular network of the intestinal structures. It is unknown whether the IPM is harmful to the gut. The aim was to investigate intestinal epithelial cell damage reflected by circulating intestinal fatty acid binding protein levels (I-FABP) in patients undergoing liver resection with IPM.
Patients who underwent liver surgery received total IPM (total-IPM) or selective IPM (sel-IPM). A selective IPM was performed by selectively clamping the right portal pedicle. Patients without IPM served as controls (no-IPM). Arterial blood samples were taken immediately after incision, ischemia and reperfusion of the liver, transection, 8 hours after start of surgery and on the first post-operative day.
24 patients (13 males) were included. 7 patients received cycles of 15 minutes and 5 patients received cycles of 30 minutes of hepatic inflow occlusion. 6 patients received cycles of 15 minutes selective hepatic occlusion and 6 patients underwent surgery without inflow occlusion. Application of total-IPM resulted in a significant increase in I-FABP 8 hours after start of surgery compared to baseline (p<0.005). In the no-IPM group and sel-IPM group no significant increase in I-FABP at any time point compared to baseline was observed.
Total-IPM in patients undergoing liver resection is associated with a substantial increase in arterial I-FABP, pointing to intestinal epithelial injury during liver surgery.
Hepatic resection is currently still the best choice of therapeutic strategies for liver cancer, but the long-term survival rate after surgery is unsatisfactory. Most patients develop intra- and/or extrahepatic recurrence. The reasons for this high recurrence rate are not entirely clear. Recent studies have indicated that ischemia-reperfusion injury to the liver may be a significant factor promoting tumor recurrence and metastasis in animal models. If this is also true in humans, the effects of the Pringle maneuver, which has been widely used in hepatectomy for the past century, should be examined. To date, there are no reported data or randomized controlled studies examining the relationship between use of the Pringle maneuver and local tumor recurrence. We hypothesize that the long-term prognosis of patients with liver cancer could be worsened by use of the Pringle maneuver due to an increase in the rate of tumor recurrence in the liver remnant. We designed a multicenter, prospective, randomized surgical trial to test this hypothesis.
At least 498 eligible patients from five participating centers will be enrolled and randomized into either the Pringle group or the non-Pringle group in a ratio of 1:1 using a permuted-blocks randomization protocol. After the completion of surgical intervention, patients will be included in a 3-year follow-up program.
This multicenter surgical trial will examine whether the Pringle maneuver has a negative effect on the long-term outcome of hepatocellular carcinoma patients. The trial will also provide information about prognostic differences, safety, advantages and disadvantages between Pringle and non-Pringle surgical procedures. Ultimately, the results will increase the available information about the effects of ischemia-reperfusion injury on tumor recurrence, which will be of immense benefit to general surgery.
Hepatocellular carcinoma; Ischemia/reperfusion; Hepatectomy; Pringle maneuver
To elucidate the characteristic gene transcription profiles among various hepatic ischemia conditions, immediately transcribed genes and the degree of ischemic injury were compared among total ischemia (TI), intermittent clamping (IC), and ischemic preconditioning (IPC).
Sprague-Dawley rats were equally divided into control (C, sham-operated), TI (ischemia for 90 minutes), IC (ischemia for 15 minutes and reperfusion for 5 minutes, repeated six times), and IPC (ischemia for 15 minutes, reperfusion for 5 minutes, and ischemia again for 90 minutes) groups. A cDNA microarray analysis was performed using hepatic tissues obtained by partial hepatectomy after occluding hepatic inflow.
The cDNA microarray revealed the following: interleukin (IL)-1β expression was 2-fold greater in the TI group than in the C group. In the IC group, IL-1α/β expression increased by 2.5-fold, and Na+/K+ ATPase β1 expression decreased by 2.4-fold. In the IPC group, interferon regulatory factor-1, osteoprotegerin, and retinoblastoma-1 expression increased by approximately 2-fold compared to that in the C group, but the expression of Na+/K+ ATPase β1 decreased 3-fold.
The current findings revealed characteristic gene expression profiles under various ischemic conditions. However, additional studies are needed to clarify the mechanism of protection against IPC.
Reperfusion injury; Ischemic preconditioning; Necrosis; Apoptosis; Microarray analysis
When a long aortic clamp time is expected or when upper body to lower body collateral arteries are sparse, temporary lower body perfusion may be needed to reduce ischemic injury during supraceliac clamping in open repair of pararenal aortic aneurysms. The use of conventional extracorporeal perfusion techniques carry extra risks and is not in the armamentarium of most vascular surgeons. An axillo-femoral or -iliac shunt using a vascular prosthesis does not require the same degree of anticoagulation and causes less activation of blood components.
PRESENTATION OF CASE
A patient, who had extensive vascular stenotic disease and large bowel ischemia, was operated on for a pararenal aortic aneurysm while the lower body was perfused via a temporary extracorporeal vascular prosthesis axillo-iliac shunt. Copious backbleeding encountered while suturing the proximal anastomosis testified to the efficacy of the temporary shunt. A left hemicolectomy had to be performed for gangrene of the sigmoid colon and he needed 2 days of respiratory support; otherwise the postoperative course was uneventful.
In our case more ischemic injury than that observed might have been expected without the temporary bypass but significant backbleeding may have negated some of the beneficial effect of the shunt.
A temporary axillo-femoral or -iliac shunt prevents lower limb ischemia and provides an ample amount of collateral blood flow to the torso. It does not need to be buried subcutaneously as previously described. Occlusive balloons should be used where possible to prevent backbleeding and to further increase available collateral blood supply.
Pararenal aortic aneurysm; Temporary bypass; Arterial prosthesis
Hepatic resection is still associated with significant morbidity. Although the period of parenchymal transection presents a crucial step during the operation, uncertainty persists regarding the optimal technique of transection. It was the aim of the present randomized controlled trial to evaluate the efficacy and safety of hepatic resection using the technique of stapler hepatectomy compared to the simple clamp-crushing technique.
The CRUNSH Trial is a prospective randomized controlled single-center trial with a two-group parallel design. Patients scheduled for elective hepatic resection without extrahepatic resection at the Department of General-, Visceral- and Transplantation Surgery, University of Heidelberg are enrolled into the trial and randomized intraoperatively to hepatic resection by the clamp-crushing technique and stapler hepatectomy, respectively. The primary endpoint is total intraoperative blood loss. A set of general and surgical variables are documented as secondary endpoints. Patients and outcome-assessors are blinded for the treatment intervention.
The CRUNSH Trial is the first randomized controlled trial to evaluate efficacy and safety of stapler hepatectomy compared to the clamp-crushing technique for parenchymal transection during elective hepatic resection.
Limited resection can be a therapeutic approach in patients with cirrhosis with very low
remnant hepatic function after resection. In this study, two hilar vascular clamping
methods (hilar selective clamping [n=13] and hilar lobar clamping method [n=8]), which were used for resection ofhepatocellular carcinoma in patients with cirrhosis, were
compared based on cardiovascular stability during clamping, intraoperative bleeding,
operative time and postoperative course. In the past, the Pringle method had been used
(n=19) and those instances were included for comparison. The mean operation time of
the lobar clamping group was 209 ± 44 minutes, which was significantly less than that of
the selective clamping group (259 ± 44 minutes, p < 0.05). Furthermore, the mean
intraoperative blood loss of the lobar clamping group was 920 ± 400 milliliters, which
was significantly less than that of the selective clamping group (1,640 ± 590 milliliters,
p < 0.01). The postoperative total bilirubin and glutamine-oxaloacetic transaminase
levels tended to be high in the Pringle group, but there was no significant difference
between the groups. Although the blood pressure during clamping significantly decreased
in all groups, the decrease was profound in the Pringle group as compared with those in
the other two groups. Thus, as a method for controlling afferent bloodflow during hepatic
resection in patients with cirrhosis, we recommend the lobar clamping method as a
simple, safe and effective way to minimize bleeding and maintain cardiovascular
Background. Hazards of liver surgery have been attenuated by the evolution in methods of hepatic vascular control and the anesthetic management. In this paper, the anesthetic considerations during hepatic vascular occlusion techniques were reviewed. Methods. A Medline literature search using the terms “anesthetic,” “anesthesia,” “liver,” “hepatectomy,” “inflow,” “outflow occlusion,” “Pringle,” “hemodynamic,” “air embolism,” “blood loss,” “transfusion,” “ischemia-reperfusion,” “preconditioning,” was performed. Results. Task-orientated anesthetic management, according to the performed method of hepatic vascular occlusion, ameliorates the surgical outcome and improves the morbidity and mortality rates, following liver surgery. Conclusions. Hepatic vascular occlusion techniques share common anesthetic considerations in terms of preoperative assessment, monitoring, induction, and maintenance of anesthesia. On the other hand, the hemodynamic management, the prevention of vascular air embolism, blood transfusion, and liver injury are plausible when the anesthetic plan is scheduled according to the method of hepatic vascular occlusion performed.
Intra-operative tumor rupture is a serious complication during resection of large hepatocellular carcinoma (HCC) leading to more blood loss. We report our experience in applying continuous Pringle maneuver with in situ hypothermic perfusion via inferior mesenteric vein catheterization to the portal vein of the remnant liver for resection during an extended left lobectomy of a large HCC which ruptured intraoperatively. Using this method, we successfully managed the patient without any further morbidity. This technique provides easier accessibility of in situ perfusion, decreases operative blood loss and prevents warm ischemic injury to the remnant liver during parenchymal transection. This method could be effective for the resection of large ruptured HCC.
Hepatectomy; In situ hypothermic perfusion; Continuous pringle maneuver
During liver resection clamping of the hepato-duodenal ligament (the Pringle maneuver) is performed to reduce intraoperative blood-loss. During this maneuver acute portal hypertension may lead to spontaneous splenic rupture requiring rapid splenectomy in order to control blood loss. We present 2 case of patients with hemorrhage from the spleen during clamping for liver surgery. A review of the literature with an emphasis on the pathophysiology of splenic hemorrhage is presented.
Spleen; Rupture; Pringle maneuver; Liver surgery
Haemangiomas are the most common solitary benign neoplasm of the liver with an incidence ranging from 5% to 20%. Although usually small and asymptomatic, they may reach considerable proportions and rarely give rise to life-threatening complications. Surgical intervention is required for incapacitating symptoms, established complications, and diagnostic uncertainty. The resection of haemangiomas demands meticulous surgical technique, owing to their high vascularity and the concomitant risk of intra-operative haemorrhage. Laparoscopic resection of giant haemangiomas is even more challenging, and has only been reported twice. We here report the case of a giant 10 cm liver haemangioma which was successfully resected laparoscopically using the laparoscopic HabibTM 4×, a bipolar radiofrequency device, without clamping major vessels and with minimal blood loss. Transfusion of blood or blood products was not required. The patient had an uneventful recovery and was asymptomatic at 7-mo follow-up.
Giant; Haemangioma; Habib™ 4×; Laparoscopic; Liver resection
Ischemic preconditioning (IP) decreases severity of liver necrosis and has anti-apoptotic effects in previous studies using liver regeneration in normal rats. This study assessed the effect of IP on liver regeneration after hepatic resection in cirrhotic rats.
To induce liver cirrhosis, thioacetamide (300 mg/kg) was injected intraperitoneally into Sprague-Dawley rats twice per week for 16 weeks. Animals were divided into four groups: non-clamping (NC), total clamping (TC), IP, and intermittent clamping (IC). Ischemic injury was induced by clamping the left portal pedicle including the portal vein and hepatic artery. Liver enzymes alanine transaminase (ALT) and aspartate aminotransferase (AST) were measured to assess liver damage. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) staining for apoptosis and proliferating cell nuclear antigen (PCNA) staining for cell replication were also performed.
Day-1 ALT and AST were highest in IP, however, levels in NC and IC were comparably low on days 1-7. There was no significant correlation of AST or ALT with experimental groups (P=0.615 and P=0.186). On TUNEL, numbers of apoptotic cells at 100× magnification (cells/field) were 31.8±24.2 in NC, 69.0±72.3 in TC, 80.2±63.1 in IP, and 21.2±20.8 in IC (P<0.05). When regeneration capacity was assessed by PCNA staining, PCNA-positive cells (cells/field) at 400× were 3.4±6.0 in NC, 16.9±69 in TC, 17.0±7.8 in IP and 7.4±7.6 in IC (P<0.05).
Although regeneration capacity in IP is higher than IC, the liver is vulnerable to ischemic damage in cirrhotic rats. Careful consideration is needed in applying IP in the clinical setting.
Liver cirrhosis; Ischemic preconditioning; Liver regeneration; Hepatectomy; Apoptosis
The patient with a patent, infected vascular graft presents a dilemma to the surgeon, who must decide whether revascularization is necessary in addition to removal of the infected graft. When a graft infection points superficially or requires drainage, the graft may be well enough exposed to provide easy access. A technique to determine preoperatively the need for revascularization in two patients with patent, exposed grafts is discussed. Following therapeutic anticoagulation, the exposed grafts were occluded with a screw clamp. Within 1 hour, one patient developed ischemic rest pain, associated with a fall in ankle blood pressure to < 60 mm Hg. Consequently, the patient underwent excision of the infected graft and revascularization with another extraanatomic bypass graft. The second patient, who had moderate intermittent claudication, tolerated clamping of the graft without ischemic symptoms at rest. Revascularization was performed through noninfected tissue, with the knowledge that the graft could be removed if necessary, without causing ischemic rest pain. This technique helps to determine preoperatively whether patients with exposed, infected grafts require revascularization as well as graft excision.
Robotically applying bulldog clamps was found to be a safe and feasible method of hilar occlusion during robotic partial nephrectomy.
Background and Objectives:
The need for a skilled assistant to perform hilar clamping during robotic partial nephrectomy is a potential limitation of the technique. We describe our experience using robotic bulldog clamps applied by the console surgeon for hilar clamping.
A total of 60 consecutive patients underwent robotic partial nephrectomy, 30 using laparoscopic bulldog clamps applied by the assistant and 30 using robotic bulldog clamps applied with the robotic Prograsp instrument. Perioperative outcomes were compared between groups.
All 30 patients underwent successful hilar clamping during robotic partial nephrectomy using robotic bulldog clamps with no intraoperative complications and without the need for readjustment/reclamping. Robotic bulldog clamps provided adequate ischemia even for tumors >4 cm, hilar, endophytic, multiple tumors, and multiple renal arteries. Both groups had similar baseline characteristics. Perioperative outcomes with robotic bulldog clamps were at least comparable to the laparoscopic bulldog group, with a trend to lower console time, warm ischemia time, and estimated blood loss.
Use of robotically applied bulldog clamps is a safe and feasible method of hilar occlusion during robotic partial nephrectomy; they perform at least as well as laparoscopic bulldog clamps while allowing the console surgeon greater autonomy and precision for hilar clamping.
Robotic partial nephrectomy; Robotic bulldog clamps; Laparoscopic bulldog clamps; Hilar clamping; Warm ischemia
Clamp loaders are pentameric ATPases of the AAA+ family that operate to ensure processive DNA replication. They do so by loading onto DNA the ring-shaped sliding clamps that tether the polymerase to the DNA. Structural and biochemical analysis of clamp loaders has shown how, despite differences in composition across different branches of life, all clamp loaders undergo the same concerted conformational transformations, which generate a binding surface for the open clamp and an internal spiral chamber into which the DNA at the replication fork can slide, triggering ATP hydrolysis, release of the clamp loader, and closure of the clamp round the DNA. We review here the current understanding of the clamp loader mechanism and discuss the implications of the differences between clamp loaders from the different branches of life.
Objective: The Glissonean pedicle transection method of liver resection has been found to shorten operative time and minimize intraoperative bleeding during liver segmentectomy. We have compared the feasibility, effectiveness, and safety of the Glissonean pedicle transection method with the Pringle maneuver in patients undergoing selective curative resection of large hepatocellualr carcinoma (HCC).
Methods: Eligible patients with large (> 5 cm) nodular HCC (n = 50) were assigned to undergo curative hepatectomy using the Glissonean pedicle transection method (n = 25) or the Pringle maneuver (n = 25). Partial interruption of the infrahepatic inferior vena cava was incorporated to further reduce bleeding from liver transection. The primary outcome measure was postoperative changes in liver function from baseline. Secondary outcomes included operating time, volume of intraoperative blood loss/transfusion, and time to resolution of ascites.
Results: The two groups were comparable in age, sex, site and size of the liver tumor, segment or lobe intended to be resected, and liver function reserve, and the results were not significant statistically. All patients underwent successful major hepatectomies using the assigned method, with the extent of major hepatectomy comparable in the two groups (P = 0.832). The Glissonean approach was associated with shorter hepatic inflow interruption (30.0 ± 12.0 min vs. 45.0 ± 13.0 min, P < 0.001), lower volume of blood loss (145.0 ± 20.0 mL vs. 298.0 ± 109.0 mL, P < 0.001), reduced requirement for transfusion (0.0 ± 0.0 mL vs. 200.0 ± 109.0 mL, P < 0.0001), and more rapid resolution of ascites (9.5 ± 1.2 d vs. 15.3 ± 2.4 d, P < 0.001). Postoperative liver function measures were comparable in the two groups, and the results were not significant statistically.
Conclusion: The Glissonean pedicle transection method is a feasible, effective, and safe technique for hepatic inflow control during the curative resection of large nodular HCCs.
Hepatocellualr carcinoma, large nodular; Pringle maneuver; Glissonean pedicel transection; Partial interruption of inferior vena cava; Surgical outcomes.
To date, elective nephron-sparing surgery is an established method for the exstirpation of renal tumors. While open partial nephrectomy remains the reference standard of the management of renal masses, laparoscopic partial nephrectomy (LPN) continues to evolve. Conventional techniques include clamping the renal vessels risking ischaemic damage of the clamped organ. Thus, new techniques are needed that combine a sufficient tissue incision for exstirpation of the tumor with an efficient coagulation to assure haemostasis and abandon renal vessel clamping in LPN. Laser-excision of renal tumors during laparoscopic surgery seems to be a logical solution.
We performed nephron-sparing surgery without clamping of the renal vessels in 11 patients with a renal tumor in exophytic position (mean size 32 mm, ranging 8–45 mm) by laser-supported LPN.
Regular ultrasound monitoring and insertion of a temporary drainage showed no evidence of postoperative hemorrhage. All tumors were removed with a histopathologically confirmed surrounding margin of normal renal tissue (R0 resection). Serum creatinine, hemoglobin, and hematocrit were nearly unaltered before and after surgery.
The experience won in these patients have confirmed that laser-assisted LPN without clamping of the renal vessels could be a safe and gentle alternative to classic partial nephrectomy in patients with exophytic position of renal tumors.
Laser partial nephrectomy; Laparoscopic partial nephrectomy; Renal resection without ischaemia; Ischaemia; Laser
Renal vascular clamping with ensuing warm ischemia is typically needed during robotic or laparoscopic partial nephrectomy. We developed a technique for angiographic delivery of the novel intra-arterial reverse thermoplastic polymer LeGoo-XL™ that allows temporary selective vascular occlusion with normal perfusion of the remaining kidney.
Materials and Methods
Eight pigs underwent a total of 16 selective angiographic occlusions of the lower pole segmental artery using gel polymer. The technical feasibility of 2 hemostatic techniques, perfusion hemostasis and local plug formation, was assessed in 4 pigs each. Selective ischemia time was recorded and the vascular occlusion site was noted radiographically and laparoscopically. The feasibility of reversing the polymer from solid back to liquid state to allow reperfusion was determined. Pathological analysis of the kidney was completed in these acute model pigs. In the last 2 cases lower pole robotic partial nephrectomy was done using the da Vinci® surgical system.
Selective lower pole ischemia was achieved in all 8 cases. Perfusion hemostasis yielded an inconsistent duration of occlusion (zero to greater than 60 minutes). Vascular occlusion time using local plug formation was more reliable (17 to 30 minutes) with consistent ability to reverse the plug to liquid state by cold saline flush. Two lower pole robotic partial nephrectomies were completed with minimal blood loss.
We developed a reliable technique of angiographic delivery of gel polymer for temporary vascular occlusion of selective renal artery branches using local plug formation. Ongoing studies are under way to assess technique consistency and the long-term effects of the polymer.
kidney; nephrectomy; robotics; laparoscopy; polymers
To evaluate the safety and feasibility of a simplified zero ischemia technique using kidney donor computed tomographic (CT) angiography and conventional laparoscopic bulldog clamps.
Materials and Methods
We conducted a review of seven robot-assisted partial nephrectomies (RAPNs) performed by a single surgeon from January 2012 to May 2012. Using a simplified protocol of 3-dimentional reconstruction, tertiary arterial branches supplying the tumor were selectively clamped prior to resection. We used conventional laparoscopic bulldog clamps instead of microsurgical vessel clamps. The patients' demographic information, perioperative outcomes, pathologic outcomes and pre- and postoperative renal functions up to 3 months follow-up were analyzed.
RAPN were successfully performed for seven complex renal hilar tumors. There were no significant differences in the total operation time, estimated blood loss or postoperative outcomes compared with published literature on standard RAPN. Negative surgical margins were reported in all cases.
We presented a simplified-zero ischemia technique using kidney Donor CT angiography and conventional laparoscopic bulldog clamps. We have also demonstrated its safety and feasibility in patients with complex renal hilar tumors. This modified technique can be easily adopted by most surgeons who are currently performing RAPN.
Kidney cancer; Nephrectomy; Robotics; Three-dimensional image
Background. Metabolomics studies can quantitatively detect the dynamic metabolic response of living systems. Objective. To detect urinary metabolomics after hepatic ischemia/reperfusion (I/R) injury induced by the Pringle maneuver using gas chromatography-mass spectrometry (GC-MS). Methods. Male Sprague-Dawley rats (N = 80) were randomly divided into 4 groups (n = 20/group): sham operation, day 1, day 3, and day 5. Rats in the day 1, day 3, and day 5 groups underwent the Pringle maneuver. Serum alanine transaminase (ALT) and total bilirubin (TBIL) were measured, and hematoxylin and eosin (HE) staining of the liver tissue was performed. GC-MS was used to detect urinary metabolomics. Results. Compared with the sham group, the serum ALT and TBIL levels at day 1 were significantly elevated (P < 0.01) and then decreased and reached close to normal levels at day 5. GC-MS detected 7 metabolites which had similar changes as those of liver tissue revealed by histological examination. Significant differences in lactic acid, pyruvic acid, alanine, serine, and glycerol-3-phosphate were found among the groups (P < 0.001). Principle component analysis showed that 7 metabolites distinguished the day 1 and day 3 groups from the sham group. Conclusions. Noninvasive urinary metabolomic analysis is a potential means for the early detection and diagnosis of hepatic I/R injury.
Centres with high volumes of high-risk surgery have significantly better outcomes than low-volume centres for pancreatic resection, oesophagectomy and pelvic exenteration. However, this has not to date been conclusively demonstrated for hepatic resection. With increased experience, operative practice can change. The use of the Pringle manoeuvre reduced substantially over a 12-year period in a single centre as it was felt anecdotally that its use increased the incidence of hepatic insufficiency and operative mortality. This study was designed to review 12 years of experience in a single hepatobiliary centre
PATIENTS AND METHODS
Data regarding 526 consecutive liver resections were prospectively recorded and retrospectively analysed in a high-volume referral unit over a 12-year period. Patients' demographics, operative mortality and morbidity were analysed on an annual basis.
Overall peri-operative mortality was 1.9%. Operative mortality in the first 6 years compared to the latter 6 years was 4.1% and 1.2%, respectively (P = 0.13). The morbidity rate was 26.8% and 20.3% in the first and second halves of the study, respectively (P = 0.15). With increased experience, intra-operative blood loss and patients receiving blood transfusions decreased (P = 0.047 and 0.03, respectively) while the number of intra-operative Pringle manoeuvres also decreased (P < 0.0001). Hospital stay decreased significantly over the 12 years (P = 0.049).
High-volume centres are the safest environment for hepatic resection. With increased experience, it may be possible to reduce the intra-operative use of the Pringle manoeuvre without increasing the intra-operative blood loss. This may be associated with a decrease in hepatic insufficiency and peri-operative mortality.
Hepatic resection; Operative mortality; Blood loss; Pringle manoeuvre
The objective of this study was to investigate the role of endothelial progenitor cells (EPCs) in the modulation of ischemia-reperfusion injury (IRI) in a partial nephrectomy (PN) rat model using early-phase ischemic preconditioning (IPC).
Materials and Methods
Ninety male Sprague-Dawley rats were randomly divided into three groups following right-side nephrectomy: Sham-operated rats (surgery without vascular clamping); PN rats (renal blood vessels were clamped for 40 min and PN was performed); and IPC rats (pretreated with 15 min ischemia and 10 min reperfusion). At 1, 3, 6, 12, 24 h, and 3 days after reperfusion, the pool of circulating EPCs and kidneys were harvested. The extent of renal injury was assessed, along with EPC number, cell proliferation, angiogenesis, and vascular growth factor expression.
Pretreated rats exhibited significant improvements in renal function and morphology. EPC numbers in the kidneys were increased at 12 h following reperfusion in the IPC group as compared to the PN or Sham groups. Cell proliferation (including endothelial and tubular epithelial cells) and angiogenesis in peritubular capillaries were markedly increased in kidneys treated with IPC. In addition, vascular endothelial growth factor-A (VEGF-A) and stromal cell-derived factor-1α (SDF-1α) expression in the kidneys of pretreated rats was increased compared to rats subjected to PN.
Our investigation suggested that: (1) the early phase of IPC may attenuate renal IRI induced by PN; (2) EPCs play an important role in renal protection, involving promotion of cell proliferation and angiogenesis through release of several angiogenic factors.
AIM: To investigate the risk factors for postoperative liver insufficiency in patients with Child-Pugh class A liver function undergoing liver resection.
METHODS: A total of 427 consecutive patients undergoing partial hepatectomy from October 2007 to April 2011 at a single center (Department of Hepatic SurgeryI, Eastern Hepatobiliary Surgery Hospital, Shanghai, China) were included in the study. All the patients had preoperative liver function of Child-Pugh class A and were diagnosed as having primary liver cancer by postoperative histopathology. Surgery was performed by the same team and hepatic resection was carried out by a clamp crushing method. A clamp/unclamp time of 15 min/5 min was adopted for hepatic inflow occlusion. Patients’ records of demographic variables, intraoperative parameters, pathological findings and laboratory test results were reviewed. Postoperative liver insufficiency and failure were defined as prolonged hyperbilirubinemia unrelated to biliary obstruction or leak, clinically apparent ascites, prolonged coagulopathy requiring frozen fresh plasma, and/or hepatic encephalopathy. The incidence of postoperative liver insufficiency or liver failure was observed and the attributing risk factors were analyzed. A multivariate analysis was conducted to determine the independent predictive factors.
RESULTS: Among the 427 patients, there were 362 males and 65 females, with a mean age of 51.1 ± 10.4 years. Most patients (86.4%) had a background of viral hepatitis and 234 (54.8%) patients had liver cirrhosis. Indications for partial hepatectomy included hepatocellular carcinoma (391 patients), intrahepatic cholangiocarcinoma (31 patients) and a combination of both (5 patients). Hepatic resections of ≤ 3 and ≥ 4 liver segments were performed in 358 (83.8%) and 69 (16.2%) patients, respectively. Seventeen (4.0%) patients developed liver insufficiency after hepatectomy, of whom 10 patients manifested as prolonged hyperbilirubinemia unrelated to biliary obstruction or leak, 6 patients had clinically apparent ascites and prolonged coagulopathy, 1 patient had hepatic encephalopathy and died on day 21 after surgery. On univariate analysis, age ≥ 60 years and prealbumin < 170 mg/dL were found to be significantly correlated with postoperative liver insufficiency (P = 0.045 and P = 0.009, respectively). There was no statistical difference in postoperative liver insufficiency between patients with or without hepatitis, liver cirrhosis and esophagogastric varices. Intraoperative parameters (type of resection, inflow blood occlusion time, blood loss and blood transfusion) and laboratory test results were not associated with postoperative liver insufficiency either. Age ≥ 60 years and prealbumin < 170 mg/dL were selected on multivariate analysis, and only prealbumin < 170 mg/dL remained predictive (hazard ratio, 3.192; 95%CI: 1.185-8.601, P = 0.022).
CONCLUSION: Prealbumin serum level is a predictive factor for postoperative liver insufficiency in patients with liver function of Child-Pugh class A undergoing hepatectomy. Since prealbumin is a good marker of nutritional status, the improved nutritional status may decrease the incidence of liver insufficiency.
Prealbumin; Hepatectomy; Liver insufficiency; Child-Pugh class A; Primary liver cancer
Adenoviral gene therapy in liver transplantation has many potential applications, but current vector delivery methods to grafts lack efficiency and require high titers. In this study, we attempted to improve gene delivery efficacy using three different delivery methods to liver grafts with adenoviral vector encoding the LacZ marker gene (AdLacZ).
AdLacZ was delivered to cold preserved rat liver grafts by: (1) continuous perfusion via the portal vein (portal perfusion), (2) continuous perfusion via both the portal vein and hepatic artery (dual perfusion), and (3) trapping viral perfusate in the liver vasculature by clamping outflow (clamp technique).
Using 1 × 109 plaque-forming units of AdLacZ (multiplicity of infection of 0.4), transduction rate in 3-hr preserved liver grafts, determined by 5-bromo-4-chromo-3-indolyl-β-d-galactopyranoside staining and β-galactosidase assay 48 hr after transplantation, was best with clamp technique (21.5±2.7% 5-bromo-4-chromo-3-indolyl-β-d-galactopyranosidepositive cells and 81.1±3.6 U/g β-galactosidase), followed by dual perfusion (18.5±1.8%, 66.6±19.4 U/g) and portal perfusion (8.8±2.5%, 19.7±15.4 U/g). Further studies using clamp technique demonstrated a near-maximal gene transfer rate of 30% at multiplicity of infection of 0.4 with prolonged cold ischemia to 18 hr. Transgene expression was stable for 2 weeks and slowly declined to 7.8±12.1 % at day 28. Lack of inflammatory response was confirmed by histopathological examination and liver enzymes. Transduction was selectively induced in hepatocytes with nearly no extrahepatic transgene expression in the lung and spleen.
The clamp technique provides a highly efficient viral gene delivery method to cold preserved liver grafts. This method offers maximal infectivity of adenoviral vector with minimal technical manipulation.
We evaluated the efficacy of parenchymal compression in open partial nephrectomies (OPNs) compared with that of the conventional vascular clamping method.
Materials and Methods
OPNs were conducted by means of the parenchymal compression technique at our institution from April 2006. Among these, the operative outcomes of 20 consecutive patients with normal preoperative renal function (Group 1) were matched with those of 20 control patients from the database of previous operations who underwent OPN with a conventional vascular clamping method (Group 2).
All preoperative characteristics were similar in both groups. The operative time was significantly higher for Group 2 (132.4±17.7 vs. 151.4±21.4 minutes, p=0.031). Estimated blood loss was slightly higher for Group 2, with marginal statistical significance (173.7±11.5 vs. 211.2±43.8 ml, p=0.06). Histologic examination revealed that over 80% of the tumors in both groups were renal cell carcinomas. For all patients, the pathology results of specimens were negative. Serum creatinine, checked at 1, 3, and 7 days after the operation, was significantly increased in both groups to a similar degree. However, 30 days after surgery, the patterns of serial serum creatinine levels demonstrated statistically significant differences by repeated-measures ANOVA (p<0.001), with a trend of more elevated in Group 2 than in Group 1, although values were within the normal range. No major complications occurred in either group.
OPN using the parenchymal compression method had acceptable outcomes in terms of complete tumor control, avoiding warm ischemic time, and minimizing blooding, with good preservation of renal function and minimal complications.
Kidney neoplasms; Organ preservation; Nephrectomy
A critical shortage of donors exists for liver transplantation, which non-heart-beating cadaver donors could help ease. This study evaluated ischemic preconditioning to improve graft viability after non-heart-beating liver donation in rats. Ischemic preconditioning was performed by clamping the portal vein and hepatic artery for 10 min followed by unclamping for 5 min. Subsequently, the aorta was cross-clamped for up to 120 min. After 2 h of storage, livers were either transplanted or perfused with warm buffer containing trypan blue. Aortic clamping for 60 and 120 min prior to liver harvest markedly decreased 30-day graft survival from 100% without aortic clamping to 50% and 0%, respectively, which ischemic preconditioning restored to 100 and 50%. After 60 min of aortic clamping, loss of viability of parenchymal and nonparenchymal cells was 22.6 and 5.6%, respectively, which preconditioning decreased to 3.0 and 1.5%. Cold storage after aortic clamping further increased parenchymal and non-parenchymal cell killing to 40.4 and 10.1%, respectively, which ischemic preconditioning decreased to 12.4 and 1.8%. In conclusion, ischemic preconditioning markedly decreased cell killing after subsequent sustained warm ischemia. Most importantly, ischemic preconditioning restored 100% graft survival of livers harvested from non-heart-beating donors after 60 min of aortic clamping.