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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.  Evaluation of the Safe Ischemic Time of Clamping During Intermittent Pringles Maneuver in Rabbits 
Archives of Trauma Research  2015;4(4):e30244.
Background:
The liver is the most commonly injured organ in blunt abdominal trauma. Although major hepatic bleeding may be partially controlled with portal triade clamping (the Pringle’s maneuver), continuous prolonged clamping results in liver ischemia.
Objectives:
The purpose of this study was to determine the safe time of Pringle maneuver based on pathologic changes of liver in rabbit models.
Materials and Methods:
In an experimental study, 20 New-Zealand white rabbits were selected. In laparotomy, a blunt dissector was passed through the foramen of Winslow and the hepato-duodenal ligament encircled with an umbilical tape. En masse Pringle maneuver was performed using atraumatic flexible clamps. Rabbits were divided into four groups based on Pringle maneuver time (30 minutes, 45 minutes, 60 minutes, and 75 minutes). A hepatic biopsy was performed at the beginning of operation. The degree of tissue injury was evaluated using blood markers.
Results:
There were five rabbits in each group. At the end of 60 minutes ischemia, only minor alterations were observed in pathological specimens. At the end of 75 minutes, hepatocyte damage and necrosis were observed. The serum levels of alanine aminotransferase (Group A: P = 0.02; Group B: P = 0.01; Group C: P = 0.0002; Group D: P = 0.01) and Aspartate aminotransferase (Group A: P = 0.03; Group B: P = 0.002; Group C: P = 0.0004; Group D: P = 0.0003) were significantly increased post-operatively. The maximum level was in the first day after operation.
Conclusions:
Continuous portal triade clamping (the Pringle maneuver) during liver ischemia (30 and 45 minutes) in rabbits resulted in no ischemic change. Increasing time of clamping to 30 minutes was safe in intermittent Pringle maneuver.
doi:10.5812/atr.30244
PMCID: PMC4733517  PMID: 26848477
Liver; Pringle’s Maneuver; Ischemia
4.  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
5.  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
6.  Selective vascular isolation of the liver as part of initial damage control for grade 5 liver injuries: Shouldn’t we use it more frequently?☆ 
Highlights
•Patients with severe liver injury may as part of the initial damage control operation, concurrently with intermittent Pringle maneuver, and intra- and perihepatic packing.•For patient unstable to undergo embolization in the intervention radiology suite, or if there is no such service in the hospital, selective vascular isolation of various liver vessels performed by the trauma surgeon should be an option.•Trauma surgeons should be able and trained to perform selective vascular isolation for liver injuries.
Background
Severe liver trauma (grade 4 and 5) carries mortality greater than 40%. It represents a major surgical challenge in patients with hemodynamic instability who require an immediate exploratory laparotomy. Perihepatic packing and damage control can sometimes work, but for severe liver injuries, adjunct maneuvers might be needed (such as early embolization or hepatic artery ligation). During a patient’s first operation for severe liver trauma, anatomic resection is rarely tolerated.
Materials and methods
We managed a 31 year-old male with a blunt grade 5 right-lobe liver injury in severe hypovolemic shock.
Results
As part of the initial damage control operation, concurrently with intermittent Pringle maneuver, he underwent intra- and perihepatic packing; selective isolation and ligation of the right portal vein, right hepatic artery, and right hepatic vein; and repair of the retrohepatic inferior vena cava. Then, 36 h later, the patient underwent a right hepatectomy.
Conclusion
For patients with severe liver injuries, selective vascular isolation and ligation may be considered as part of damage control (in addition to intermittent Pringle maneuver) and might enable anatomic resection at a later stage.
doi:10.1016/j.ijscr.2014.12.021
PMCID: PMC4334949  PMID: 25569195
Severe liver injury; Selective vascular isolation for liver injury; Embolization; Damage control
7.  BiClamp® forcep liver transection versus clamp crushing technique for liver resection: study protocol for a randomized controlled trial 
Trials  2015;16:201.
Background
Blood loss and the requirement of blood transfusions during liver transection have been shown to correlate well with higher morbidity and mortality rates and a worse prognosis. Various devices for liver parenchymal transection have been developed to reduce intraoperative blood loss. The goal of this study is to evaluate the safety and effectiveness of BiClamp® forcep transection compared to a clamp crushing technique in patients undergoing liver resection.
Methods/Design
This study will include patients 18 years and older scheduled for hepatectomy with hepatic vascular exclusion who give informed consent. A sample size of 48 patients in each randomization arm will be calculated to detect a difference in the reduction of blood loss of approximately 200 ml (90% power and α = 0.05 (two-tailed)). The primary efficacy endpoint of the trial will be the total intraoperative blood loss based on the randomized dissection technique. The statistical analysis is based on the intention-to-treat population. Patients will be followed up on for three months for complications and adverse events.
Discussion
This prospective, single-center, randomized controlled, single-blinded, two-group parallel trial is designed to assess the efficacy and safety of BiClamp forcep hepatectomy versus clamp crushing for parenchymal transection during elective hepatic resection.
Trial registration
This trial was registered with Clinicaltrials.gov (identifier: NCT02197481) on 15 July 2014.
doi:10.1186/s13063-015-0722-1
PMCID: PMC4434524  PMID: 25925431
Clamp crushing; BiClamp® forcep transection; Blood loss; Randomized controlled trial
8.  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
9.  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
10.  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
11.  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
12.  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
13.  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
14.  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
15.  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
16.  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
17.  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
18.  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
19.  Salvage with a Secondary Infrahepatic Cavocavostomy of the Occluded Modified Piggyback Anastomosis during Split Liver Transplantation: A Case Report 
Hepatic venous outflow obstruction following liver transplantation is rare but disastrous. Here we described a 14-year-old boy who underwent a split right lobe liver transplantation with modified (side-to-side) piggyback technique which resulted in hepatic venous outflow obstruction. When the liver graft was lifted up, the outflow drainage returned to normal but when it was placed back into the abdomen, the outflow obstruction recurred. Because reanastomosis would have resulted in hepatic reischemia, alternatively, a second infrahepatic cavocavostomy was planned without requiring hepatic reischemia. During this procedure, the first assistant hung the liver up to provide sufficient outflow and the portal inflow of the graft continued as well. We only clamped the recipient's infrahepatic vena cava and the caudal cuff of the graft cava. After the second end-to-side cavocaval anastomosis, the graft was placed in its orthotopic position and there was no outflow problem anymore. The patient tolerated the procedure well and there were no problems after three months of follow-up. A second cavocavostomy can provide an extra bypass for some hepatic venous outflow problems after piggyback anastomosis by avoiding hepatic reischemia.
doi:10.1155/2014/740802
PMCID: PMC4055404  PMID: 24959369
20.  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
21.  Safe upper limit of intermittent hepatic inflow occlusion for liver resection in cirrhotic rats 
AIM: To evaluate the effects of varying ischemic durations on cirrhotic liver and to determine the safe upper limit of repeated intermittent hepatic inflow occlusion.
METHODS: Hepatic ischemia in cirrhotic rats was induced by clamping the common pedicle of left and median lobes after non-ischemic lobes resection. The cirrhotic rats were divided into six groups according to the duration and form of vascular clamping: sham occlusion (SO), intermittent occlusion for 10 (IO-10), 15 (IO-15), 20 (IO-20) and 30 (IO-30) minutes with 5 minutes of reflow and continuous occlusion for 60 minutes (CO-60). All animals received a total duration of 60 minutes of hepatic inflow occlusion. Liver viability was investigated in relation of hepatic adenylate energy charge (EC). Triphenyltetrazollum chloride (TTC) reduction activities were assayed to qualitatively evaluate the degree of irreversible hepatocellular injury. The biochemical and morphological changes were also assessed and a 7-day mortality was observed.
RESULTS: At 60 min after reperfusion following a total of 60 min of hepatic inflow occlusion, EC values in IO-10 (0.749 ± 0.012) and IO-15 (0.699 ± 0.002) groups were rapidly restored to that in SO group (0.748 ± 0.016), TTC reduction activities remained in high levels (0.144 ± 0.002 mg/mg protein, 0.139 ± 0.003 mg/mg protein and 0.121 ± 0.003 mg/mg protein in SO, IO-10 and IO-15 groups, respectively). But in IO-20 and IO-30 groups, EC levels were partly restored (0.457 ± 0.023 and 0.534 ± 0.027) accompanying with a significantly decreased TTC reduction activities (0.070 ± 0.005 mg/mg protein and 0.061 ± 0.003 mg/mg protein). No recovery in EC values (0.228 ± 0.004) and a progressive decrease in TTC reduction activities (0.033 ± 0.002 mg/mg protein) were shown in CO-60 group. Although not significantly different, the activities of the serum aspartate aminotransferase (AST) on the third postoperative day (POD3) and P OD7 and of the serum alanine aminotransferase (ALT) on POD3 in CO-60 group remained higher than that in intermittent occlusion groups. Moreover, a 60% animal mortality rate and more severe morphological alterations were also shown in CO-60 group.
CONCLUSION: Hepatic inflow occlusion during 60 min for liver resection in cirrhotic rats resulted in less hepatocellular injury when occlusion was intermittent rather than continuous. Each period of 15 minutes was the safe upper limit of repeated intermittent vascular occlusion that the cirrhotic liver could tolerate without undergoing irreversible hepatocellular injury.
doi:10.3748/wjg.v7.i5.713
PMCID: PMC4695581  PMID: 11819861
hepatic inflow occlusion/intermittent/continuous; liver resection; cirrhosis; rat; energy charge; triphennyltetrazollum chloride
22.  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
23.  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
24.  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
25.  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

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