Objective To investigate the clinical efficacy and experiences of laparoscopic hepatectomy (LH) for segment Ⅶ and Ⅷ liver tumors.Methods The retrospective cross-sectional study was conducted.The clinicopathological data of 94 patients who underwent LH for segment lⅦ or Ⅷ liver tumors in the Sir Run Run Shaw Hospital Affiliated to Zhejiang University School of Medicine from June 2010 to August 2016 were collected.The operating space for operation was built under laparoscopy.According to liver cirrhosis grading,tumor size,adjacent relationship with major blood vessels and residual liver volume,non-anatomical and anatomical hepatectomies were selected by patients.During the operation,tumors were precisely pinpointed and plane of liver resection was determined,and then proper instruments of liver partition and techniques of hepatic inflow occlusion were selected.Observation indicators:(1) surgical and postoperative recovery situations;(2) postoperative pathological examination;(3) follow-up and survival situation.Follow-up using outpatient examination and telephone interview was performed to detect the patients' survival up to July 2017.Measurement data with normal distribution were represented as (x)±s.Measurement data with skewed distribution were described as M (interquartile range).Survival rate was caculated by the Kaplan-Meier method.Results (1) Surgical and postoperative recovery situations:all 94 patients received successful operations,without perioperative death,including 73undergoing non-anatomical hepatectomy and 21 undergoing anatomical hepatectomy.Fourteen patients had conversion to open surgery and 27 received hepatic inflow occlusion.The median operation time,median volume of intraoperative blood loss and cases with intraoperative blood transfusion were respectively 187.5 minutes (75.0minutes),200 mL (200 mL) and 15.Eighteen patients had postoperative complications,including 6 with pleural effusion,6 with abdominal effusion,1 with wound infection,1 with abdominal infection,1 with venous thrombosis,1 with bleeding,1 with coagulation disorders and 1 with hepatic insufficiency.Clavien-Dindo classification of complications:11,1,5 and 1 patients were detected in grade Ⅰ,lⅡ,Ⅲ and Ⅳ,respectively.All complications were improved by symptomatic treatment.The median duration of hospital stay was 7 days (6 days).(2) Postoperative pathological examination:results of tumor pathological examination showed that 45,5,9 and 35 patients were respectively confirmed as hepatocellular carcinoma,cholangiocarcinoma,metastatic hepatic carcinoma and benign liver tumor.(3) Follow-up and survival situation:59 patients with malignant tumors were followed up for 6.0-52.0 months,with a median time of 42.6 months.Postoperative 1-and 3-year overall survival rates of 59 patients with malignant tumors were 98.3％ and 84.7％,respectively.Conclusions LH for segment Ⅶ and Ⅷ liver tumors which is conducted in experienced medical center is safe and feasible,with definite effects.Building operating space for operation under laparoscopy,determining precise positioning of the tumor and plane of liver resection,and selecting proper instruments of liver partition and techniques of hepatic inflow occlusion are the key points of successful operation.

Objective To evaluate the application value of three-dimensional (3D) reconstruction technique in laparoscopic hepatectomy.Methods The retrospective cohort study was conducted.The clinicopathological data of 189 patients with liver cancer who were admitted to the Sir Run Run Shaw Hospital Affiliated to Zhejiang University School of Medicine from January 2014 to December 2018 were collected.There were 142 males and 47 females,aged from 27 to 86 years,with an average age of 60 years.According to the difficulty score of surgery,50 of 189 patients underwent laparoscopic complex hepatectomy,including 23 with preoperative 3D reconstruction in the complex reconstruction group and 27 with no preoperative 3D reconstruction in the complex control group;other 139 patients underwent laparoscopic non-complex hepatectomy,including 25 with preoperative 3D reconstruction in the non-complex reconstruction group and 114 with no preoperative 3D reconstruction in the non-complex control group.Observation indicators:(1) vascular assessment of patients who received 3D reconstruction;(2) surgical and postoperative situations;(3) typical case analysis.Measurement data with normal distribution were presented as Mean±SD,and comparison between groups was done using the t test.Measurement data with skewed distribution were presented as M (range),and comparison between groups was done using the Mann-Whitney U test.Count data were represented as absolute number or percentage,and comparison between groups was analyzed using the chi-square test or Fisher exact probability.Results (1) Vascular assessment of patients who received 3D reconstruction:48 of 189 patients were performed preoperative 3D reconstruction.Vascular assessment of 48 patients showed 41 of hepatic arterial Michels Ⅰ type,4 of Michels Ⅱ type,1,1,and 1 of Michels Ⅲ,Ⅳ,Ⅷ type,respectively.There were 35 belonging to hepatic venous Ⅰ type and 12 belonging to hepatic venous Ⅱ type and 1 with unclear distribution of hepatic vein.There were 5 and 3 belonging to portal venous Ⅰ type and Ⅱ type,38 with normal distribution of portal vein,and 2 with unclear distribution of portal vein,respectively.(2) Surgical and postoperative situations:50 of 189 patients underwent laparoscopic complex hepatectomy,and 139 underwent laparoscopic non-complex hepatectomy.The operation time and volume of intraoperative blood loss were (234±64)minutes and 200 mL (range,100-408 mL) in the complex reconstruction group,and (289±80)minutes and 500 mL (range,400-800 mL) in the complex control group,respectively,showing statistically significant differences between the two groups (t=-2.474,Z=-2.981,P＜ 0.05).Cases with postoperative complications and duration of postoperative hospital stay of complex reconstruction group were 8 and 6 days (range,4-12 days),respectively,versus 13 and 8 days (range,6-13 days) of complex control group.There was no significant difference (x2=0.911,Z =-1.634,P＞0.05).The operation time,volume of intraoperative blood loss,cases of postoperative complications and duration of postoperative hospital stay were 160.0 minutes (range,117.5-221.0 minutes),100 mL (range,75-200 mL),8,5 days (range,4-8 days) in the non-complex reconstruction group,157.5 min (range,100.0-222.5 minutes),100 mL (range,50-200 mL),43,6 days (range,4-7 days) in the non-complex control group,showing no significant difference between the two groups (Z=-0.525,-0.797,x2 =0.289,Z=-0.011,P＞0.05).(3) Typical case analysis:one 48-year-old male patient with primary liver cancer developed a personalized hepatectomy plan through simulation function of vascular drainage area in 3D reconstruction.One 49-year-old female patient achieved indirect intraoperative navigation through emulation function of 3D reconstruction.Conclusions The 3D reconstruction of liver in preoperative assessment is beneficial to choice of surgical options and personalized surgical plan in the precise hepatectomy.Especially in the laparoscopic complex hepatectomy,preoperative 3D reconstruction can shorten operation time,and reduce volume of intraoperative blood loss.

Objective To study the optimal timing of preoperative injection of indocyanine green in laparoscopic liver tumor resection under indocyanine green fluorescent navigation to obtain the most satisfactory fluorescence imaging effects.Methods 60 patients with liver tumors who underwent laparoscopic hepatectomy from April 2017 to October 2018 were retrospectively studied on the intraoperative fluorescence imaging effects.A simple grading of the fluorescence imaging effects was developed.The ICG R15 and preoperative injection times of ICG were correlated with the intraoperative fluorescence imaging effects.Results Of 60 patients with liver tumors,59 patients underwent laparoscopic liver resection and one patient was converted to open surgery.The overall satisfaction rate of intraoperative fluorescence imaging was 73.4％ (44/60).In the patients with an ICG R15 rate ≤ 7％,it was easier to obtain good fluorescence imagings when the preoperative administration time was longer than 48 hours.Even when the preoperative administration time was longer than 5 days,satisfactory fluorescence imaging effect could still be obtained in these patients.In the patients with an ICG R15 rate ＞ 7％,intraoperative fluorescence imagings were unsatisfactory when the administration time was less than 6 days.Relative better imagings were obtained in these patients when the preoperative administration time was more than 6 days.Conclusions When the pre-operative ICG injection dose was not changed,the preoperative administration time should be adjusted according to the value of the ICG R15 to obtain better intraoperative fluorescence imaging effects of the liver tumors.The optimal timing needs to be further studied by a large case study.

Objective To evaluate the effect of mild hypothermia on inositol-requiring enzyme 1 (IRE1) signaling pathway during myocardial injury after cardiac arrest and resuscitation in swine.Methods Twenty-one healthy male white swine,weighing 33-41 kg,were divided into 3 groups using a random number table method:sham operation group (group S,n =5),cardiac arrest-cardiopulmonary resuscitation group (group CA-CPR,n=8),and mild hypothermia group (group MH,n=8).The model of cardiac arrest and resuscitation was established based on the previously reported method.The catheters placed in the left femoral artery and right internal jugular vein were connected to the PiCCO Monitor system,and another pacing catheter was advanced from the right external jugular vein into the right ventricle.Ventricular fibrillation was induced by using a 1 mA alternating current through the pacing catheter.Once ventricular fibrillation was successfully induced,mechanical ventilation was discontinued for 8 min,and then cardiopulmonary resuscitation was initiated.Epinephrine 20 μg/kg was administered at 2.5 min of resuscitation followed by repetition every 3 min.Defibrillation was delivered at 5 min of resuscitation,and then spontaneous circulation was evaluated.If return of spontaneous circulation was not achieved,cardiopulmonary resuscitation was immediately resumed for 2 min and then defibrillation was delivered again.Mechanical ventilation was continued for 30 h after successful resuscitation.Animals in group S only underwent surgical preparation without experiencing cardiac arrest and resuscitation.At 5 min after successful resuscitation,body temperature was cooled down to 33 ℃ by using a cooling blanket,and then maintained at this level until 24 h after resuscitation,followed by 5 h of re-warming at a rate of 1 ℃/h in group MH.The temperature was maintained at 37.5-38.5 ℃ with the aid of surface cooling blanket in the other two groups.At 1,6,12,24 and 30 h after resuscitation (T1-5),the values of stroke volume (SV) and global ejection fraction (GEF) were recorded,and meanwhile 2 ml of blood samples was obtained via the femoral vein to measure the concentration of serum cardiac troponin Ⅰ (cTnI) (by enzyme-linked immunosorbent assay) and activity of serum creatine kinase-MB (CK-MB) (by immunosuppression).The swine were sacrificed at 30 h after resuscitation,and then myocardial specimens from the left ventricle were obtained for determination of the expression of caspase-3 (by immunohistochemistry),cell apoptosis (by TUNEL),and expression of IRE1 and casepase-12 (by Western blot).Apoptosis index was calculated.Results Compared with group S,SV and GEF were significantly decreased and the serum CK-MB activity was increased at T1-5,the concentration of serum cTnI was increased at T2-5,the expression of IRE1,caspase-12 and caspase-3 in myocardium was up-regulated,and apoptosis index was increased in CA-CPR and MH groups (P＜0.05).Compared with group CA-CPR,the SV and GEF were significantly increased and the concentration of serum cTnI was decreased at T2-5,the activity of serum CK-MB was decreased at T3-5,the expression of IRE1,caspase-12 and caspase-3 in myocardium was down-regulated,and apoptosis index was decreased in group MH (P＜0.05).Conclusion The mechanism by which mild hypothermia mitigates myocardial injury after cardiac arrest and resuscitation may be related to inhibiting IRE1 signaling pathway in swine.

Objective To investigate the effects of rapid hypothermia induced via esophagus on intestinal mucous injury in early stage after cardiopulmonary resuscitation (CPR) in a swine model of cardiac arrest.Methods Twenty-seven male domestic pigs weighing (36±2)kg were utilized.The animals were randomly crandom number divided into 3 groups (n=9 in each):normothermia group (NT group),surface cooling group (SC group),and esophageal cooling group (EC group).The pig model was established by 8 mins of untreated ventricular fibrillation and then 5 mins of CPR.At 5 mins after restoration of spontaneous circulation (ROSC),therapeutic hypothermia was applied by either an esophageal cooling device in the EC group or a surface cooling blanket in the SC group to reach a targeted temperature of 33 ℃ maintained for 24 h after ROSC,and then followed by warming up in a rate of 1 ℃ / hr for 5 hrs.A normal temperature of (38.0±0.5)℃ was maintained throughout the experiment in the NT group.The core temperature was continuously monitored during a period of 30 h after ROSC.At 3 h,6 h,12 h,24 h and 30 h after ROSC,intestinal fatty acid binding protein (IFABP) content and diamine oxidase (DAO) activity in serum were measured by ELISA.At 30 h after ROSC,the pigs were sacrificed,and then intestinal tissue was rapidly obtained for the determination of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) contents by ELISA,cell apoptosis by TUNEL,and caspase-3 expression by immunohistochemistry.Results The rate of temperature decrease was 2.8 ℃/h and the time required for target temperature was 102 min in the EC group,while the rate of temperature decrease was 1.5 /h and the time consumed for target temperature was 185 mins in the SC group,which suggested the efficacy of cooling was significantly better in the EC group than that in the SC group (both P＜0.05).Compared with the NT group,serum IFABP content and DAO activity were significantly decreased at 3 hrs after ROSC in the EC group and at 6 hrs after ROSC in the SC group.Compared with the SC group,serum IFABP content at 6 hrs after ROSC and DAO activity at 12 h after ROSC were significantly decreased in the EC group IFABP (pg/mL):(710±32) vs.(777±52) at 6 h,(870±49) vs.(960±64) at 12 h,(1 022±65)vs.(1 143±63) at 24 h,(882±71) vs.(1 006±45) at 30 h DAO (U/mL):(39.9±1.9) vs.(43.4±3.2) at 12 h,(30.6±2.4) vs.(34.0±3.1) at 24 h,(26.1±2.7) vs.(29.4±2.2) at 30 h,all P＜0.05.In the intestinal tissue,TNF-α and IL-6 contents were significantly reduced,and cell apoptosis index and caspase-3 expression were significantly decreased in the SC and EC groups compared with the NT group.Additionally,inflammatory response and cell apoptosis in intestinal tissue were further significantly lesser in the EC group compared with the SC group TNF-α (pg/mL):(721±94) vs.(922±125);IL-6(pg/mL):(454±69) vs.(697±132);Apoptotic index(％):(6.2±2.6)vs.(12.8±3.0);caspase-3 expression (IOD):(8.9±1.6) vs.(15.9±1.9),all P＜0.05.Conclusions In a swine model of cardiac arrest,rapid hypothermia could be successfully induced via esophagus and consequently produced a greater protective effect on post-resuscitation intestinal injury compared with the conventional surface cooling.The protective mechanisms are associated with the inhibition of inflammatory response and cell apoptosis.

OBJECTIVE: To investigate the protective effect and potential mechanism of tubastatin A (TubA), a specific inhibitor of histone deacetylase 6 (HDAC6), on renal and intestinal injuries after cardiopulmonary resuscitation (CPR) in swine. METHODS: Twenty-five healthy male white swine were divided into Sham group (n = 6), CPR model group (n = 10) and TubA intervention group (n = 9) using a random number table. The porcine model of CPR was reproduced by 9-minute cardiac arrest induced by electrical stimulation via right ventricle followed by 6-minute CPR. The animals in the Sham group only underwent the regular operation including endotracheal intubation, catheterization, and anesthetic monitoring. At 5 minutes after successful resuscitation, a dose of 4.5 mg/kg of TubA was infused via the femoral vein within 1 hour in the TubA intervention group. The same volume of normal saline was infused in the Sham and CPR model groups. Venous samples were collected before modeling and 1, 2, 4, 24 hours after resuscitation, and the levels of serum creatinine (SCr), blood urea nitrogen (BUN), intestinal fatty acid binding protein (I-FABP) and diamine oxidase (DAO) in serum were determined by enzyme-linked immunoadsordent assay (ELISA). At 24 hours after resuscitation, the upper pole of left kidney and terminal ileum were harvested to detect cell apoptosis by TdT-mediated dUTP-biotin nick end labeling (TUNEL), and the expression levels of receptor-interacting protein 3 (RIP3) and mixed lineage kinase domain-like protein (MLKL) were detected by Western blotting. RESULTS: After resuscitation, renal dysfunction and intestinal mucous injury were observed in the CPR model and TubA intervention groups when compared with the Sham group, which was indicated by significantly increased levels of SCr, BUN, I-FABP and DAO in serum. However, the serum levels of SCr and DAO starting 1 hour after resuscitation, the serum levels of BUN starting 2 hours after resuscitation, and the serum levels of I-FABP starting 4 hours after resuscitation were significantly decreased in the TubA intervention group when compared with the CPR model group [1-hour SCr (μmol/L): 87±6 vs. 122±7, 1-hour DAO (kU/L): 8.1±1.2 vs. 10.3±0.8, 2-hour BUN (mmol/L): 12.3±1.2 vs. 14.7±1.3, 4-hour I-FABP (ng/L): 661±39 vs. 751±38, all P < 0.05]. The detection of tissue samples indicated that cell apoptosis and necroptosis in the kidney and intestine at 24 hours after resuscitation were significantly greater in the CPR model and TubA intervention groups when compared with the Sham group, which were indicated by significantly increased apoptotic index and markedly elevated expression levels of RIP3 and MLKL. Nevertheless, compared with the CPR model group, renal and intestinal apoptotic indexes at 24 hours after resuscitation in the TubA intervention group were significantly decreased [renal apoptosis index: (21.4±4.6)% vs. (55.2±9.5)%, intestinal apoptosis index: (21.3±4.5)% vs. (50.9±7.0)%, both P < 0.05], and the expression levels of RIP3 and MLKL were significantly reduced [renal tissue: RIP3 protein (RIP3/GAPDH) was 1.11±0.07 vs. 1.39±0.17, MLKL protein (MLKL/GAPDH) was 1.20±0.14 vs. 1.51±0.26; intestinal tissue: RIP3 protein (RIP3/GAPDH) was 1.24±0.18 vs. 1.69±0.28, MLKL protein (MLKL/GAPDH) was 1.38±0.15 vs. 1.80±0.26, all P < 0.05]. CONCLUSIONS TubA has the protective effect on alleviating post-resuscitation renal dysfunction and intestinal mucous injury, and its mechanism may be related to inhibition of cell apoptosis and necroptosis.
Male ; Animals ; Swine ; Abdominal Injuries ; Apoptosis ; Cardiopulmonary Resuscitation ; Kidney Diseases