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1.  Role of ischemic preconditioning in hepatic ischemia-reperfusion injury 
Background
Investigation into less traumatic method of vascular occlusion during liver resection is the actual problem in hepatic surgery because of high level of complications such as liver failure. In this connection, the goal of our study was to determine the optimal model of vascular clamping. The research showed that vascular occlusion with ischemic preconditioning in the mode 5/10/15 the most delicate technique.
Methods
Forty white giant rabbits were divided randomly into four groups (n=10 in each group). In group I we used continuous Pringle maneuver by 30 min. In group II we used intermittent Pringle maneuver: 15 min of clamping/5 min of unclamping (reperfusion)/15 min of clamping. In group III we used intermittent Pringle maneuver with ischemic precondition: 5 min of ischemia/5 min of reperfusion, 10 min of ischemia/5 min of reperfusion/15 min of ischemia. Group IV (control group) is without hepatic ischemia. All animals were performed a liver biopsy at the end of the surgery. Five rabbits from each group underwent re-laparotomy on day 3 after surgery with biopsy samples being taken for studying reparative processes in liver parenchyma.
Results
Results of morphometric analysis were the best to illustrate different level of liver injury in the groups. Thus, there were 95.5% damaged hepatocytes after vascular occlusion in hepatic preparations in group I, 70.3% damaged hepatocytes in group II, and 42.3% damaged hepatocytes in group III. There were 5.3% damaged hepatocytes in the control group.
Conclusions
Vascular occlusion with ischemic preconditioning in the mode 5/10/15 the most delicate technique that does not involve major structural injuries and functional disorders in the remnant liver. Thus, it is amenable to translation into clinical practice and may improve outcomes in liver resection with inflow vascular occlusion.
doi:10.3978/j.issn.2304-3881.2014.06.03
PMCID: PMC4141290  PMID: 25202694
Liver resection; Pringle maneuver; ischemic preconditioning; vascular occlusion; ischemia-reperfusion injury
2.  Laparoscopic Left Liver Sectoriectomy of Caroli's Disease Limited to Segment II and III 
Caroli's disease is defined as a abnormal dilatation of the intra-hepatica bile ducts: Its incidence is extremely low (1 in 1,000,000 population) and in most of the cases the whole liver is interested and liver transplantation is the treatment of choice. In case of dilatation limited to the left or right lobe, liver resection can be performed. For many year the standard approach for liver resection has been a formal laparotomy by means of a large incision of abdomen that is characterized by significant post-operatie morbidity. More recently, minimally invasive, laparoscopic approach has been proposed as possible surgical technique for liver resection both for benign and malignant diseases. The main benefits of the minimally invasive approach is represented by a significant reduction of the surgical trauma that allows a faster recovery a less post-operative complications.
This video shows a case of Caroli s disease occured in a 58 years old male admitted at the gastroenterology department for sudden onset of abdominal pain associated with fever (>38C° ), nausea and shivering. Abdominal ultrasound demonstrated a significant dilatation of intra-hepatic left sited bile ducts with no evidences of gallbladder or common bile duct stones. Such findings were confirmed abdominal high resolution computer tomography. Laparoscopic left sectoriectomy was planned. Five trocars and 30° optic was used, exploration of the abdominal cavity showed no adhesions or evidences of other diseases.
In order to control blood inflow to the liver, vascular clamp was placed on the hepatic pedicle (Pringle s manouvre), Parenchymal division is carried out with a combined use of 5 mm bipolar forceps and 5 mm ultrasonic dissector. A severely dilated left hepatic duct was isolated and divided using a 45mm endoscopic vascular stapler. Liver dissection was continued up to isolation of the main left portal branch that was then divided with a further cartridge of 45 mm vascular stapler.
At his point the left liver remains attached only by the left hepatic vein: division of the triangular ligament was performed using monopolar hook and the hepatic vein isolated and the divided using vascular stapler.
Haemostatis was refined by application of argon beam coagulation and no bleeding was revealed even after removal of the vascular clamp (total Pringle s time 27 minutes).
Postoperative course was uneventful, minimal elevation of the liver function tests was recorded in post-operative day 1 but returned to normal at discharged on post-operative day 3.
doi:10.3791/1118
PMCID: PMC2762898  PMID: 19252471
3.  Total Intermittent Pringle Maneuver during Liver Resection Can Induce Intestinal Epithelial Cell Damage and Endotoxemia 
PLoS ONE  2012;7(1):e30539.
Objectives
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.
Methods
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.
Results
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.
Conclusion
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.
Trial Registration
ClinicalTrials.gov NCT01099475
doi:10.1371/journal.pone.0030539
PMCID: PMC3265485  PMID: 22291982
4.  Techniques of Inflow Occlusion for Liver Resection 
HPB Surgery  1996;9(3):188-189.
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 stability.
doi:10.1155/1996/84618
PMCID: PMC2443082  PMID: 8725464
5.  Comparing Outcomes of Two Vascular Inflow Occlusion Techniques and Treatment without Vascular Occlusion during Major Hepatectomy in Patients with Hepatitis B-Related Hepatocellular Carcinoma 
PLoS ONE  2014;9(9):e107303.
Background
Significant hemorrhage together with blood transfusion has negative impact on postoperative morbidity, mortality, and long-term survival of liver resection. Various techniques of vascular occlusion have been developed to reduce intraoperative blood loss. The objective of this study was to compare the outcomes of Pringle maneuver, hemi-hepatic vascular occlusion, and treatment without vascular occlusion used during liver resection.
Method
Data of 574 patients with Hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), who underwent major hepatectomy between January 2009 to March 2013 by Pringle maneuver (N = 158), hemi-hepatic vascular inflow occlusion (N = 216), or without any vascular occlusion (N = 200), were included in this retrospective study. Perioperative blood transfusion, intraoperative blood loss, and postoperative liver function, and surgical complications were analyzed and compared between the three groups.
Result
There were no significant difference observed in postoperative bilirubin, liver enzyme, and albumin levels between three groups (P>0.05). 5 patients (2.5%) in no occlusion group, 2 (1.3%) in Pringle group, and 8 (3.7%) in hemi-hepatic group had liver failure; but, there were no differences (P>0.05). The overall postoperative complications rate between three groups did not reach significant differences (33.5% vs 34.2% vs 42.6%, respectively; P>0.05). However, significant differences in intraoperative blood loss between no occlusion group (638.2±426.8 ml) and Pringle group (518.0±451.0 ml) or hemi-hepatic group (513.0±366.7 ml) (P<0.01).
Conclusion
Although there were no differences found between three groups regarding postoperative complications rate, no vascular occlusion group had more blood loss than the other two groups during liver resection.
doi:10.1371/journal.pone.0107303
PMCID: PMC4159310  PMID: 25203056
6.  Bone Flap Perfusion Assessment using Near-Infrared Fluorescence Imaging 
The Journal of surgical research  2012;178(2):e43-e50.
Background
Microsurgical vascularized bone flaps are a versatile technique for reconstructing large bone defects. However, assessment of perfusion is challenging, as clinical examination is difficult intra-operatively and often not possible post-operatively. Therefore, it is important to develop techniques to assess perfusion of vascularized bone flaps, and potentially improve surgical outcomes. Near-infrared (NIR) fluorescence imaging has been previously shown to provide real-time, intra-operative evaluation of vascular perfusion. This pilot study investigates the ability of NIR imaging to assess perfusion of vascularized bone flaps.
Materials and Methods
Vascularized bone flaps were created on female Yorkshire pigs using well-established models for porcine forelimb osteomyocutaneous flap allotransplantation (N = 8) and hindlimb fibula flaps (N = 8). Imaging of the bone flaps was performed during harvest using the FLARE™ intraoperative fluorescence imaging system following systemic injection of indocyanine green (ICG). Perfusion was also assessed using standard of care by clinical observation and Doppler. NIR fluorescence perfusion assessment was confirmed by intermittent clamping of the vascular pedicle.
Results
NIR fluorescence imaging can identify bone perfusion at the cut end of the osteotomy site. When the vascular pedicle is clamped or ligated, NIR imaging demonstrates no fluorescence when injected with ICG. With clamp removal, the osteotomy site emits fluorescence indicating bone perfusion. Results using fluorescence imaging show 100% agreement with clinical observation and Doppler.
Conclusion
Vascularized bone transfers have become an important tool in reconstructive surgery; however, no established techniques adequately assess perfusion. Our pilot study indicates that NIR imaging can provide real-time, intra-operative assessment of bone perfusion.
doi:10.1016/j.jss.2012.05.014
PMCID: PMC3435470  PMID: 22664132
Near-infrared imaging; vascularized bone flaps; bone perfusion; microsurgery; free flap; composite tissue allotransplantation
7.  Anesthetic Considerations in Hepatectomies under Hepatic Vascular Control 
HPB Surgery  2012;2012:720754.
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.
doi:10.1155/2012/720754
PMCID: PMC3368350  PMID: 22690040
8.  Outcomes of simple saline-coupled bipolar electrocautery for hepatic resection 
AIM: To evaluate the application of bipolar coagulation (BIP) in hepatectomy by comparing the efficacy of BIP alone, cavitron ultrasonic surgical aspirator (CUSA) + BIP and conventional clamp crushing (CLAMP).
METHODS: Based on our database of patient records, a total of 380 consecutive patients who underwent hepatectomy at our hospital were retrospectively studied for the efficacy of BIP alone, CUSA + BIP and CLAMP. Of all the patients, 75 received saline-coupled BIP (Group A), 53 received CUSA + BIP (Group B), and 252 received CLAMP (Group C). The pre-, mid-, and postoperative clinical manifestations were compared, and the effects of those maneuvers were evaluated.
RESULTS: There was no obvious difference among the preoperative indexes between the different groups. The operative time was longer in Groups A and B than in Group C (P < 0.001 for both). The amount of bleeding and the rate of transfusion during the operation were significantly higher in Group C than in Groups A and B (P < 0.001 for all). The incidence of postoperative complications in Group C (46.43%) was higher than that in Groups A (30.67%, P = 0.015) and B (28.30%, P = 0.016). The patients’ liver function recovery and postoperative hospital stay were not significantly different. BIP could decrease intraoperative hemorrhage and postoperative complications compared to CLAMP.
CONCLUSION: Simple saline-coupled BIP should be considered a safe and reliable technique for liver resection to decrease intraoperative hemorrhage and postoperative complications.
doi:10.3748/wjg.v20.i26.8638
PMCID: PMC4093715  PMID: 25024620
Hepatectomy; Surgical procedures; Blood loss; Complications; Hospital stay; Comparative study
9.  Hepatic blood inflow occlusion without hemihepatic artery control in treatment of hepatocellular carcinoma 
AIM: To investigate the clinical significance of hepatic blood inflow occlusion without hemihepatic artery control (BIOwHAC) in the treatment of hepatocellular carcinoma (HCC).
METHODS: Fifty-nine patients with HCC were divided into 3 groups based on the technique used for achieving hepatic vascular occlusion: group 1, vascular occlusion was achieved by the Pringle maneuver (n = 20); group 2, by hemihepatic vascular occlusion (HVO) (n = 20); and group 3, by BIOwHAC (n = 19). We compared the procedures among the three groups in term of operation time, intraoperative bleeding, postoperative liver function, postoperative complications, and length of hospital stay.
RESULTS: There were no statistically significant differences (P > 0.05) in age, sex, pathological diagnosis, preoperative Child’s disease grade, hepatic function, and tumor size among the three groups. No intraoperative complications or deaths occurrred, and there were no significant intergroup differences (P > 0.05) in intraoperative bleeding, hepatic function change 3 and 7 d after operation, the incidence of complications, and length of hospital stay. BIOwHAC and Pringle maneuver required a significantly shorter operation time than HVO; the difference in the serum alanine aminotransferase or aspartate aminotransferase levels before and 1 d after operation was more significant in the BIOwHAC and HVO groups than in the Pringle maneuver group (P < 0.05).
CONCLUSION: BIOwHAC is convenient and safe; this technique causes slight hepatic ischemia-reperfusion injury similar to HVO.
doi:10.3748/wjg.v16.i46.5895
PMCID: PMC3001983  PMID: 21155013
Hepatic blood inflow occlusion without hemihepatic artery control; Hepatocellular carcinoma; Intraoperative bleeding; Ischemia-reperfusion injury
10.  Clamp-Crushing versus stapler hepatectomy for transection of the parenchyma in elective hepatic resection (CRUNSH) - A randomized controlled trial (NCT01049607) 
BMC Surgery  2011;11:22.
Background
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.
Methods/Design
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.
Discussion
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.
Trial Registration
ClinicalTrials.gov: NCT01049607
doi:10.1186/1471-2482-11-22
PMCID: PMC3177759  PMID: 21888669
11.  IVC CLAMP: infrahepatic inferior vena cava clamping during hepatectomy - a randomised controlled trial in an interdisciplinary setting 
Trials  2009;10:94.
Background
Intraoperative haemorrhage is a known predictor for perioperative outcome of patients undergoing hepatic resection. While anaesthesiological lowering of central venous pressure (CVP) by fluid restriction is known to reduce bleeding during transection of the hepatic parenchyma its potential side effects remain poorly investigated. In theory it may have negative effects on kidney function and tissue perfusion and bears the risk to result in severe haemodynamic instability in case of profound intraoperative blood loss. The present randomised controlled trial evaluates efficacy and safety of infrahepatic inferior vena cava (IVC) clamping as an alternative surgical technique to reduce CVP during hepatic resection.
Methods/Design
The proposed IVC CLAMP trial is a single-centre randomised controlled trial with a two-group parallel design. Patients and outcome-assessors are blinded for the treatment intervention. Patients undergoing elective hepatic resection due to any reason are enrolled in IVC CLAMP. All patients admitted to the Department of General-, Visceral-, and Transplant Surgery, University of Heidelberg for elective hepatic resection are consecutively screened for eligibility and written informed consent is obtained on the day before surgery. The primary objective of this trial is to assess and compare the amount of blood loss during hepatic resection in patients receiving surgical CVP reduction by clamping of the IVC as compared to anaesthesiological CVP without infrahepatic IVC clamping reduction. In addition to blood loss a set of general as well as surgical variables are analysed.
Discussion
This is a randomised controlled patient and observer blinded two-group parallel trial designed to assess efficacy and safety of infrahepatic IVC clamping during elective hepatectomy.
Trial registration
ClinicalTrials NCT00732979
doi:10.1186/1745-6215-10-94
PMCID: PMC2770522  PMID: 19825186
12.  Hyperinsulinemic-euglycemic Clamps in Conscious, Unrestrained Mice 
Type 2 diabetes is characterized by a defect in insulin action. The hyperinsulinemic-euglycemic clamp, or insulin clamp, is widely considered the "gold standard" method for assessing insulin action in vivo. During an insulin clamp, hyperinsulinemia is achieved by a constant insulin infusion. Euglycemia is maintained via a concomitant glucose infusion at a variable rate. This variable glucose infusion rate (GIR) is determined by measuring blood glucose at brief intervals throughout the experiment and adjusting the GIR accordingly. The GIR is indicative of whole-body insulin action, as mice with enhanced insulin action require a greater GIR. The insulin clamp can incorporate administration of isotopic 2[14C]deoxyglucose to assess tissue-specific glucose uptake and [3-3H]glucose to assess the ability of insulin to suppress the rate of endogenous glucose appearance (endoRa), a marker of hepatic glucose production, and to stimulate the rate of whole-body glucose disappearance (Rd).
The miniaturization of the insulin clamp for use in genetic mouse models of metabolic disease has led to significant advances in diabetes research. Methods for performing insulin clamps vary between laboratories. It is important to note that the manner in which an insulin clamp is performed can significantly affect the results obtained. We have published a comprehensive assessment of different approaches to performing insulin clamps in conscious mice1 as well as an evaluation of the metabolic response of four commonly used inbred mouse strains using various clamp techniques2. Here we present a protocol for performing insulin clamps on conscious, unrestrained mice developed by the Vanderbilt Mouse Metabolic Phenotyping Center (MMPC; URL: www.mc.vanderbilt.edu/mmpc). This includes a description of the method for implanting catheters used during the insulin clamp. The protocol employed by the Vanderbilt MMPC utilizes a unique two-catheter system3. One catheter is inserted into the jugular vein for infusions. A second catheter is inserted into the carotid artery, which allows for blood sampling without the need to restrain or handle the mouse. This technique provides a significant advantage to the most common method for obtaining blood samples during insulin clamps which is to sample from the severed tip of the tail. Unlike this latter method, sampling from an arterial catheter is not stressful to the mouse1. We also describe methods for using isotopic tracer infusions to assess tissue-specific insulin action. We also provide guidelines for the appropriate presentation of results obtained from insulin clamps.
doi:10.3791/3188
PMCID: PMC3308587  PMID: 22126863
13.  Robotic Partial Nephrectomy Using Robotic Bulldog Clamps 
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.
Methods:
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.
Results:
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.
Conclusions:
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.
doi:10.4293/108680811X13176785204274
PMCID: PMC3340963  PMID: 22643509
Robotic partial nephrectomy; Robotic bulldog clamps; Laparoscopic bulldog clamps; Hilar clamping; Warm ischemia
14.  Whole-Cell Electrical Activity Under Direct Mechanical Stimulus by AFM Cantilever Using Planar Patch Clamp Chip Approach 
Patch clamp is a powerful tool for studying the properties of ion-channels and cellular membrane. In recent years, planar patch clamp chips have been fabricated from various materials including glass, quartz, silicon, silicon nitride, polydimethyl-siloxane (PDMS), and silicon dioxide. Planar patch clamps have made automation of patch clamp recordings possible. However, most planar patch clamp chips have limitations when used in combination with other techniques. Furthermore, the fabrication methods used are often expensive and require specialized equipments. An improved design as well as fabrication and characterization of a silicon-based planar patch clamp chip are described in this report. Fabrication involves true batch fabrication processes that can be performed in most common microfabrication facilities using well established MEMS techniques. Our planar patch clamp chips can form giga-ohm seals with the cell plasma membrane with success rate comparable to existing patch clamp techniques. The chip permits whole-cell voltage clamp recordings on variety of cell types including Chinese Hamster Ovary (CHO) cells and pheochromocytoma (PC12) cells, for times longer than most available patch clamp chips. When combined with a custom microfluidics chamber, we demonstrate that it is possible to perfuse the extra-cellular as well as intra-cellular buffers. The chamber design allows integration of planar patch clamp with atomic force microscope (AFM). Using our planar patch clamp chip and microfluidics chamber, we have recorded whole-cell mechanosensitive (MS) currents produced by directly stimulating human keratinocyte (HaCaT) cells using an AFM cantilever. Our results reveal the spatial distribution of MS ion channels and temporal details of the responses from MS channels. The results show that planar patch clamp chips have great potential for multi-parametric high throughput studies of ion channel proteins.
doi:10.1007/s12195-011-0160-4
PMCID: PMC3235648  PMID: 22174731
On-chip patch clamp; MEMS; Atomic force microscopy; Whole-cell recordings; Mechanosensitive ion channels
15.  Precautions in caudate lobe resection: Report of 11 cases 
AIM: To find the precautions against the safety in caudate lobe resection.
METHODS: The clinical data obtained from 11 cases of primary liver cancer in caudate lobe who received hepatectomy successfully were retrospectively analyzed. Four safe procedures were used in resection of primary liver cancer in caudate lobe: (1) selection of appropriate skin incision to obtain excellent exposure of operative field; (2) adequate mobilization of the liver to allow the liver to be displaced upwards to the left or to the right; (3) preparatory placement of tapes for total hepatic vascular exclusion, so that this procedure could be used to control the fatal bleeding of the liver when necessary; (4) selection of the ideal route for hepatectomy based on the condition of the tumor and the combined removal of multiple lobes if necessary. Among the 11 cases, simple occlusion of vessels of porta hepatis was used in caudate lobectomy for 6 cases, while in the other cases, the vessels were intermittently occluded several times or total hepatic vascular isolation was used in the caudate lobectomy. Combined partial right hepatectomy was done for 3 cases, combined left lateral lobectomy for 2 cases and caudate lobectomy alone for 6 cases.
RESULTS: Operation was successful for all the 11 cases. Intermittent inflow occlusion was performed for all patients for 15 min at 5-min intervals. Blockade was performed twice in 3 patients and total hepatic vascular exclusion was performed in one of the three patients. Blockade was performed three times in one patient, including a total hepatic vascular exclusion. Total hepatic vascular exclusion was performed only in one patient. The mean blood loss was 300 mL. Ascites and pleural effusion occurred in 4 patients, jaundice in 1 patient. Six patients died of tumor recurrence in 6, 11, 12, 13, 15, 19 mo after operation, respectively. The other 5 patients have survived more than 16 mo since the operation.
CONCLUSION: Caudate lobectomy for liver cancer in candidate lobe can be safely performed with the above procedures.
doi:10.3748/wjg.14.2767
PMCID: PMC2709046  PMID: 18461663
Caudate lobe; Primary liver cancer; Hepatectomy; Porta hepatis; Vascular exclusion
16.  Surgical treatment of neurological scoliosis using hybrid construct (lumbar transpedicular screws plus thoracic sublaminar acrylic loops) 
European Spine Journal  2011;20(Suppl 1):90-94.
In the nineties, most spinal surgeons supported the validity of segmental spine instrumentation, but this procedure has progressively been abandoned because difficult and with a high risk of neurological complications, in favor of the Cotrel-Dobousset (CD). The CD instrumentation is based on segmentation of curves, thus improving the angular correction and actuates sagittal profile. Sublaminar acrylic loops (Universal Clamp) shows the same resistance to stress as steel or titanium alloy sublaminar wires. The simple procedure and the tensioning of the strips allows re-tensioning and progressive correction. The increased contact area, improves corrective forces, thus reducing the risk of laminar fractures. The aim of this study was to verify the validity of this spinal fixation implant in the surgical treatment of a consecutive series of patients affected by neurologic scoliosis. The authors treated surgically 84 patients affected by neurologic scoliosis with an average age of 14 years (range 10–17). Universal Clamps associated with Socore TM spinal assembly, transpedicular lumbar screws and thoracic hooks at the upper end of the curve were used. The etiology of disease was cerebral palsy in 81 cases, Friedreich ataxia in two cases and Aicardi syndrome in one case. The average preoperative angular value was 73° ± 16°. It was implanted a mean of seven Clamps for each procedure (range 5–9). The average percentage of correction was 72%. Mean operative time was 240 ± 30 min with mean blood loss of 1200 ± 400 ml. No intra-operative complications occurred. Mean follow-up was 36 months. At one-year follow-up the mean loss of correction was 7° ± 2° with no re-intervention required. This is the first report on treatment of neurological scoliosis with this hybrid construct (lumbar screws, thoracic acrylic clamps, thoracic hooks at the upper end of the curve). In this group of patients the Universal Clamps technique appeared safe and effective and its mechanical performance is comparable to all-level screws construct. Furthermore, the kyphotic component can be better managed in case of thoracic lordosis. The most important aspect of this technique is a short operative time and low vascular and neurologic risks combined with a satisfying stability in the short-postoperative period. Nevertheless, it is important to value results on a long-term follow-up to analyze correction loss, pseudoarthrosis, and mechanical failure of the strips.
doi:10.1007/s00586-011-1751-4
PMCID: PMC3087050  PMID: 21404032
Neurological scoliosis; Cerebral palsy; Universal Clamp; Coronal correction; Sagittal balance; Operative time
17.  Immediately transcripted genes in various hepatic ischemia models 
Purpose
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).
Methods
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.
Results
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.
Conclusion
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.
doi:10.4174/jkss.2012.83.5.298
PMCID: PMC3491232  PMID: 23166889
Reperfusion injury; Ischemic preconditioning; Necrosis; Apoptosis; Microarray analysis
18.  Laparoscopic management of post-cholecystectomy sectoral artery pseudoaneurysm 
Vascular injuries during laparoscopic cholecystectomy can occur similar to biliary injuries and mostly represented by intraoperative bleeding. Hepatic artery system pseudoaneurysm are rare. It occurs in the early or late postoperative course. Patients present with pallor, signs of haemobillia and altered liver function. We report a case of right posterior sectoral artery pseudoaneurysm detected 2 weeks after laparoscopic cholecystectomy and successfully repaired laparoscopically. We also describe how laparoscopic pringle clamping saved the conversion. The actively bleeding right posterior sectoral artery pseudoaneurysm was diagnosed by CT angiogram. Embolisation, usually the treatment of choice, would have risked liver insufficiency as hepatic artery proper was at risk because the origin the bleeding artery was just after its bifurcation. Isolated right hepatic artery embolisation can also cause hepatic insufficiency. To our knowledge this is the first reported case of laparoscopic repair of post-laparoscopic cholecystectomy bleeding sectoral artery pseudoaneurysm.
doi:10.4103/0972-9941.124471
PMCID: PMC3902557  PMID: 24501508
Laparoscopic repair of aneurysm; pseudoaneurysm; post cholecystectomy vascular injury; right posterior sectoral artery
19.  Athermal Tension Adjustable Suture Ligation of the Vascular Pedicle During Robot-Assisted Prostatectomy* 
Journal of Endourology  2012;26(7):834-837.
Abstract
Purpose
We report a simple figure-of-eight tension adjustable suture to ligate the vascular pedicle (VP) during robot-assisted radical prostatectomy (RARP).
Materials and Methods
During nerve-sparing RARP, after the rectum has been mobilized, the VP is isolated and prepared for transection. Previous reports describe placing of hemostatic clips (metallic or Hem-o-lok™) or laparoscopic bulldog clamps (30 mm) to control and oversew the VP; both techniques are quite assistant dependent. We present a bulldog clamp alternative by placing a figure-of-eight fashion, a 6-cm 3-0 poliglecaprone on an SH needle with a small loop tied in the suture end. After the needle has been placed through the VP, it is then threaded through the preformed loop and then a small Hem-o-lok clip is placed and cinched down to occlude the blood vessels. Next, the VPs are transected. The clip can be further cinched, mimicking the technique used in partial nephrectomy, to control bleeding when encountered. Data were collected prospectively to demonstrate safety.
Results
We report on 74 men totaling 143 VPs using this new technique. The average operative time was reduced by 15 minutes compared with using bulldog clamps. In the initial 10 cases (20 attempts), inadvertent transection of the suture occurred three times. In these three cases, hemostasis was (easily) controlled with additional sutures.
Conclusions
The pedicle stitch technique offers an assistant independent alternative for a simple and precise athermal means to control the VP.
doi:10.1089/end.2011.0063
PMCID: PMC3727628  PMID: 22191496
20.  Intermittent selective clamping improves rat liver regeneration by attenuating oxidative and endoplasmic reticulum stress 
Cell Death & Disease  2014;5(3):e1107-.
Intermittent clamping of the portal trial is an effective method to avoid excessive blood loss during hepatic resection, but this procedure may cause ischemic damage to liver. Intermittent selective clamping of the lobes to be resected may represent a good alternative as it exposes the remnant liver only to the reperfusion stress. We compared the effect of intermittent total or selective clamping on hepatocellular injury and liver regeneration. Entire hepatic lobes or only lobes to be resected were subjected twice to 10 min of ischemia followed by 5 min of reperfusion before hepatectomy. We provided evidence that the effect of intermittent clamping can be damaging or beneficial depending to its mode of application. Although transaminase levels were similar in all groups, intermittent total clamping impaired liver regeneration and increased apoptosis. In contrast, intermittent selective clamping improved liver protein secretion and hepatocyte proliferation when compared with standard hepatectomy. This beneficial effect was linked to better adenosine-5′-triphosphate (ATP) recovery, nitric oxide production, antioxidant activities and endoplasmic reticulum adaptation leading to limit mitochondrial damage and apoptosis. Interestingly, transient and early chaperone inductions resulted in a controlled activation of the unfolded protein response concomitantly to endothelial nitric oxide synthase, extracellular signal-regulated kinase-1/2 (ERK1/2) and p38 MAPK activation that favors liver regeneration. Endoplasmic reticulum stress is a central target through which intermittent selective clamping exerts its cytoprotective effect and improves liver regeneration. This procedure could be applied as a powerful protective modality in the field of living donor liver transplantation and liver surgery.
doi:10.1038/cddis.2014.65
PMCID: PMC3973205  PMID: 24603335
oxidative and endoplasmic reticulum stress; ischemia reperfusion injury; unfolded protein response; mitochondrial damage
21.  Temporary extracorporeal axillo-iliac vascular prosthesis shunt in open repair of a pararenal aortic aneurysm 
INTRODUCTION
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.
DISCUSSION
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.
CONCLUSION
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.
doi:10.1016/j.ijscr.2012.12.022
PMCID: PMC3604714  PMID: 23500740
Pararenal aortic aneurysm; Temporary bypass; Arterial prosthesis
22.  Curative Resection of Hepatocellualr Carcinoma Using Modified Glissonean Pedicle Transection versus the Pringle Maneuver: A Case Control Study 
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.
doi:10.7150/ijms.4870
PMCID: PMC3498749  PMID: 23155358
Hepatocellualr carcinoma, large nodular; Pringle maneuver; Glissonean pedicel transection; Partial interruption of inferior vena cava; Surgical outcomes.
23.  Fenestrated Endovascular Grafts for the Repair of Juxtarenal Aortic Aneurysms 
Executive Summary
Endovascular repair of abdominal aortic aneurysm (AAA) allows the exclusion of the dilated aneurismal segment of the aorta from the systematic circulation. The procedure requires, however, that the endograft extends to the healthy parts of the aorta above and below the aneurysm, yet the neck of a juxtarenal aortic aneurysm (JRA) is too short for a standard endovascular repair. Fenestrated endovascular aortic repair (f—EVAR) provides a solution to overcome this problem by enabling the continuation of blood flow to the renal and visceral arteries through holes or ‘fenestrations’ in the graft. These fenestrations are designed to match the ostial diameter of the renal and visceral arteries.
There are three varieties fenestration, small, large, and scallop, and their location needs to be customized to fit the anatomy of the patient. If the device is not properly designed, if the alignment is inaccurate, or if the catheterization of the visceral arteries is not possible, the procedure may fail. In such cases, conversion to open surgery may become the only option as fenestrated endografts are not retrievable.
It is recommended that a stent be placed within each small fenestration to the target artery to prevent shuttering of the artery or occlusion. Many authors have noted an increased risk of vessel occlusion in unstented fenestrations and scallops.
Once placed in a patient, life-long follow-up at regular intervals is necessary to ensure the graft remains in its intended location, and that the components have adequate overlap. Should the need arise, routine follow-up allows the performance of timely and appropriate intervention through detection of events that could impact the long-term outcomes.
Alternative Technology
The technique of fenestrated endovascular grafting is still in evolution and few studies have been with published mid-term outcome data. As the technique become more common in vascular surgery practices, it will be important to determine if it can provide better outcomes than open surgical repair (OSR).
In an OSR approach, aortic clamping above one or both renal arteries, or above the visceral arteries, is required. The higher the level of aortic clamping, the greater the risk of cardiac stress and renal or visceral ischemia. During suprarenal or supraceliac aortic clamping, strain-induced myocardial ischemia may also occur due to concomitant rise in cardiac afterload and a decrease in cardiac output. Reports indicate that 6% of patients undergoing surgical repair develop myocardial infarction. The ideal level of clamp location remains controversial with conflicting views having been reported.
Method
A search of electronic databases (OVID MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, The Cochrane Library, and the International Agency for Health Technology Assessment [INAHTA] database was undertaken to identify evidence published from January 1, 2004 to December 19, 2008. The search was limited to English-language articles and human studies. The automatic search alerts were received and reviewed up to March 23, 2009.
The literature search and automatic search update identified 320 citations, of which 13 met inclusion/exclusion criteria. One comparative study presented at an international seminar, five single-arm studies on f—EVAR, and 7 studies on OSR (one prospective and six retrospective) were considered for this analysis.
To grade the strength of the body of evidence, the grading system formulated by the GRADE working group and adopted by MAS, was applied. The GRADE system classifies evidence quality as high (Grade A), moderate (Grade B), or low (Grade C) according to four key elements: study design, study quality, consistency across studies, and directness.
A summary of the characteristics of the f—EVAR and OSR studies found through the literature search is shown in Table ES-1.
Patient Characteristics: f–EVAR Studies versus OSR Studies
JRA, Juxtarenal aortic aneurysm; SRA, Suprarenal aortic aneurysm; TAA, Thoracic aortic aneurysm
Mortality Outcomes
The pooled estimate for 30-day mortality was 1.8% among the f—EVAR studies and 3.1% among the OSR studies that reported data for the repair of JRA separately. The pooled estimate for late mortality was 12.8% among the f—EVAR studies and 23.7% among the OSR studies that reported data for JRA separately.
Visceral Artery Events Reported in f—EVAR Studies
Renal Events during f-EVAR
A total of three main renal arteries and two accessory renal arteries became occluded during the procedure. These were all due to technical issues, except one accessory renal artery in which the artery was intentionally covered. One patient required open surgery following the procedure.
Renal Events During the follow-up
A total of 12 renal arteries (12 patients) were found to be occluded during follow-up. In two patients, the same side accessory renal artery was also occluded. Four (1.5%) patients lost one kidney and five (2.3%) patients underwent dialysis, three (1.4%) of which became permanent.
A total of 16 cases of renal artery stenosis (16 patients) occurred during follow-up. Eight of these were treated and eight were observed. Segmental renal infarcts were found in six patients but renal function was not impaired.
Mesenteric Events during f-EVAR
Three mesenteric events occurred during the f—EVAR procedures resulting in two deaths. One patient developed bowel ischemia due to embolization of the superior mesenteric artery (SMA); this patient died 13 days after the procedure from multiorgan failure. One patient died eights days after the procedure from mesenteric ischemia and bowel perforation. The third SMA event occurred during surgery with subsequent occlusion in early follow-up.
Mesenteric Events during Follow-up
During follow-up, five (1.8%) SMA occlusions/partial occlusions and one SMA stenosis were noted. Three of the five patients with SMA occlusion/partial occlusion remained asymptomatic and no further intervention was necessary. One patient underwent SMA bypass surgery and in two patients, the problem solved by SMA stenting. A summary of the outcomes reported in the f—EVAR and OSR studies is shown in Table ES-2.
Summary of Outcomes: Fenestrated Endovascular Graft Versus Open Surgical Repair for Treatment of Juxtarenal Aortic Aneurysm
Summary
Short- and medium-term results (up to 2 years) of f—EVAR for the repair of JRA showed that outcomes in f—EVAR series compare favourably with the figures for the OSR series; however, uncertainty remains regarding the long-term results. The following observations are based on low quality evidence.
F—EVAR has lower 30-day mortality than OSR (1.8% vs. 3.1%) and a lower late-mortality over the period of time that patients have been followed (12.8% vs. 23.7%).
There is a potential for the loss of target vessels during or after f—EVAR procedures. Loss of a target vessel may lead to loss of its respective end organ. The risk associated with this technique is mainly due to branch vessel ischemia or occlusion (primarily among the renal arteries and SMA). Ischemia or occlusion of these arteries can occur during surgery due to technical failure and/or embolization or it may occur during follow-up due to graft complications such as graft migration, component separation, or arterial thrombosis. The risk of kidney loss in this series of f—EVAR studies was 1.5% and the risk of mesenteric ischemia was 3.3%. In the OSR studies, the risk of developing renal insufficiency was 14.4% and the risk of mesenteric ischemia was 2.9%.
F—EVAR has a lower rate of postoperative cardiac and pulmonary complications.
Endoleak occurs in 22.5% of patients undergoing f—EVAR (all types) and about 8% of these require treatment. Most of the interventions performed to treat such endoleaks conducted using a minimally invasive approach.
Due to the complexity of the technique, patients must be appropriately selected for f—EVAR, the procedure performed by highly experienced operators, and in centers with advanced, high-resolution imaging systems to minimize the risk of complications.
Graft fenestrations have to be custom designed for each patient to fit and match the anatomy of their visceral arteries. Planning and sizing thus requires scrutiny of the target vessels with a high degree precision. This is important not only to prevent end organ ischemia and infarction, but to avoid prolonging procedures and subsequent adverse outcomes.
Assuming the average cost range of FEVAR procedure is $24,395-$30,070 as per hospital data and assuming the maximum number of annual cases in Ontario is 116, the average estimated cost impact range to the province for FEVAR procedures is $2.83M-$3.49M annually.
PMCID: PMC3377528  PMID: 23074534
24.  A novel method for troubleshooting vascular injury during anatomic thoracoscopic pulmonary resection without conversion to thoracotomy 
Surgical Endoscopy  2012;27(2):530-537.
Background
Massive bleeding caused by vascular injury is considered the most troublesome and dangerous complication during video-assisted thoracoscopic surgery (VATS) pulmonary resection and is an important reason for emergency conversion to thoracotomy. The purpose of this paper was to show the suction-compressing angiorrhaphy technique (SCAT) for troubleshooting this problem without conversion.
Methods
A total of 414 consecutive VATS anatomic pulmonary resections were performed between May 2006 and July 2011, among which 17 operations (4.11 %) encountered unexpected vascular injury. The procedure for troubleshooting vascular injury included bleeding control and angiorrhaphy. Bleeding was first controlled through side compression of the injured site with an endoscopic suction. Angiorrhaphy was then performed with running 5-0 Prolene suture using different procedures according to the size and location of the injuries, including direct suture upon suction compression, suture after substituting suction compression with clamping of the injured site, or suture after attaining proximal cross-clamping of the main pulmonary artery. Detailed information of these patients was carefully reviewed. The reasons for conversion to thoracotomy also were revealed.
Results
Fifteen cases (15/17, 88.24 %) were successfully managed without conversion. Two cases of left main pulmonary artery injury were converted to thoracotomy due to difficulties in proximal cross-clamping of the injured vessel. Blood loss of the 17 patients ranged from 60–935 (median, 350) ml. Two patients were administered with allogeneic blood. The postoperative chest CT scan showed normal blood flow on the injured vessels. The total conversion rate was 2.66 % (11/414). The most common reason for conversion was hilar lymphadenopathy.
Conclusions
The SCAT is an effective procedure for managing vascular injury during VATS anatomic pulmonary resection. In most cases, bleeding control and angiorrhaphy could be achieved using this method with acceptable blood loss, thereby avoiding emergency conversion to thoracotomy.
doi:10.1007/s00464-012-2475-1
PMCID: PMC3580039  PMID: 22806532
Thoracoscopy/VATS; Lung cancer surgery; Lobectomy; Bleeding; Angiorrhaphy
25.  Effect of the pringle maneuver on tumor recurrence of hepatocellular carcinoma after curative resection (EPTRH): a randomized, prospective, controlled multicenter trial 
BMC Cancer  2012;12:340.
Background
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.
Methods
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.
Discussion
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.
Trial registration
http://www.clinicaltrials.gov NCT00725335
doi:10.1186/1471-2407-12-340
PMCID: PMC3488001  PMID: 22862951
Hepatocellular carcinoma; Ischemia/reperfusion; Hepatectomy; Pringle maneuver

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