Acute-on-chronic liver failure treated by split liver transplantation:a single-center experience on 9 cases / 中华普通外科杂志

Objective:To evaluate the short-term efficacy of split liver transplantation (SLT) in patients with acute-on-chronic liver failure (ACLF).Methods:The clinical data of 9 ACLF patients receiving SLT in our center from Mar 2021 to May 2022 were retrospectively analyzed to evaluate its safety and efficacy.Results:The preoperative APASL ACLF Research consortium (AARC) score of the 9 ACLF patients was 8 points in 1 case, 9 points in 3 cases, 10 points in 3 cases, 11 points in 1 case and 12 points in 1 case, 7 cases were in AARC-ACLF grade 2, and 2 cases in grade 3.In-situ liver splitting was performed in 9 deceased donors, including 4 classical split cases, 5 full size split cases. Among these 9 ACLF patients, 2 received left half liver transplantation, 3 received right half liver transplantation, and 4 received extended right lobe liver transplantation. After transplantation, all 9 recipients were discharged fully recovered, 1 case developed Clavien grade Ⅳa complication and 2 cases developed Clavien grade Ⅲb complication.After SLT treatment the median postoperative hospital stay was 27 days, the 1-year survival rate was 100%, and the organ survival rate was 88.9%.Conclusion:Split liver transplantation is a safe and feasible treatment method for ACLF patients.

Patients with perihilar cholangiocarcinoma resection combined with portal vein resection and reconstruction / 中华肝胆外科杂志

Objective:To study the safety and efficacy of combining portal vein resection and reconstruction (PVR) with resection of perihilar cholangiocarcinoma (PHC).Methods:A total of 104 patients with PHC who underwent hepatectomies for either biliary resection alone or biliary resection combined with PVR from October 2006 to December 2019 at the Department of Hepatopancreatobiliary, Ningbo Medical Center of Lihuili Hospital entered into this study. There were 63 males and 41 females, with the age of (64.4±10.4) years. The control group consisted of 75 patients who underwent biliary resection alone, while the PVR group consisted 29 patients with biliary resection combined with PVR. The patient characteristics and the follow-up outcomes of the two groups were analyzed and compared. Survival analyses were performed using the Kaplan Meier method with the log-rank test.Results:Wedge resection of portal vein, side to side anastomosis in 2 cases, segmental resection and end to end anastomosis in 27 cases. The time taken for PVR and portal vein resection were (12.7±2.9)(range 8 to 18)min and (20.7±7.3)(range 8 to 38) mm, respectively. The estimated blood loss for the PVR group was significantly more than the control group [ M( Q1, Q3)] 800.0 (600.0, 1 500.0) ml vs. 600.0(500.0, 1 000.0) ml ( P<0.05). Based on postoperative pathological studies, the proportion of lymph node metastasis was significantly higher in the PVR group than the control group (58.6% vs. 32.0%, P<0.05). Clavien-Dindo grade Ⅲ and above complications were 30.7%(23/75) and 34.5%(10/29) in the control and PVR groups, respectively ( P>0.05). The re-operation and postoperative 90 days mortality rates were 9.3%(7/75) and 2.7%(2/75) in the control group, compared with 3.4%(1/29) and 0 in the PVR group, respectively (both P>0.05). The 1-, 3- and 5-year survival rates were 81.1%, 44.8% and 36.4% respectively for the control group and 78.1%, 35.9% and 31.4% for the PVR group (χ 2=0.33, P=0.570). Conclusion:When compared to biliary resection alone, biliary resection combined with PVR did not significantly increase postoperative complication and mortality rates, but with comparable long-term survival outcomes. Combined biliary resection with PVR was safe and improved the resection rate in selected patients with locally advanced PHC.

Modification and innovation of in-situ full-left/full-right liver splitting technique / 中华器官移植杂志

Objective:To explore the feasibility of technological modification and innovation of full-left/full-right liver splitting in situ for donors and examine the safety of clinical application for liver transplantation (LT).Methods:From March 2021 to June 2022, clinical and surgical data are retrospectively reviewed for 27 donors undergoing full-left/full-right liver splitting in situ and the corresponding 49 recipients undergoing full-left/full-right LT.According to the split liver technique used in donor liver surgery, they are divided into conventional split group(group A, 13 cases)and innovative split group(group B, 14 cases). The corresponding recipients are divided into two groups of recipient C(25 cases)and recipient D(24 cases). General profiles, intraoperative findings, type of vascular allocation and short-term outcomes in two groups are compared.After full-size split liver transplantation(fSLT), follow-ups continued until the end of September 2022.Results:There are 23 males and 4 females in donors.The causes of mortality for donors are traumatic head injury(12 cases)cerebrovascular accident(13 cases)and anoxia encephalopathy(2 cases). Baseline characteristics of two groups indicate that body weight and body mass index(BMI)are higher in group B and blood sodium level is lower than that in group A( P<0.05). No statistical differences exist for the others.Liver splitting time is significantly shorter in group B than that in group A(175 vs.230 min, P=0.022). No significant inter-group difference exists in type of vascular allocation.Retrohepatic inferior vena cava(IVC)is split in one case in group A and 10 cases in group B( P=0.001). Among 20 cases of right hemiliver requiring a reconstruction of segment Ⅴ/Ⅷ venous outflow, 12 cases in group A and 3 cases in group B are reconstructed with conventional independent bridging method(independent type)while another 5 cases in group B reconstruct with innovated technique by bridging Ⅴ/Ⅷ vein for splitting IVC with iliac vessel and molding all outflows as one for anastomosis(combined typ e). There is significant inter-group difference( P=0.004). No significant differences exist in operative duration, anhepatic phase or blood loss between groups C and B, except for T tube retaining in 7 cases of group A and 14 cases of group D( P=0.032). Twelve cases developed a total of 26 instances of≥Clavien-Dindo grade Ⅲ complications.Of which, 7 cases in group C and 5 cases in group D show no significant difference in postoperative morbidity.However, for serious biliary complications(≥Clavien Dindo grade Ⅲ), there are 6 cases in group C versus none in group D( P=0.016). Two cases died from postoperative complication with a postoperative mortality rate of 4.1%.Postoperative hospital stay is similar in two groups.And accumulates 6/12-month survivals were 95.9% and 87.7% for grafts and 95.9% and 92.4% for recipients respectively. Conclusions:Operative duration of full-left/full-right liver splitting in situ tends to shorten with an accumulation of a certain amount of cases.Technological modification and innovation in IVC splitting and segment Ⅴ/Ⅷ vein reconstruction should be further validated as both feasible and safe by short-term outcomes of the corresponding recipients.

Influencing factors in predicting conversion of laparoscopic liver tumor resection to open surgery / 中华肝胆外科杂志

Objective:To study the influencing factors in predicting conversion of laparoscopic liver tumor resection to open surgery to provide references for selection of patients for laparoscopic hepatectomy.Methods:The clinical data of 222 patients who were planned to undergo laparoscopic liver tumor resection at Ningbo Medical Center Lihuili Hospital from December 2015 to November 2018 were analyzed retrospectively. There were 146 males and 76 females, with an average age of 58.1 years. These patients were divided into the conversion group ( n=24) and the laparscopic group ( n=198) according to whether intraoperative conversion to open surgery was carried out. Chi-square test was used to evaluate relevant factors of conversion. Logistic regression analysis was used for multivariate analysis and to find out independent risk factors of conversion. Results:The conversion rate was 10.8% (24/222). Univariate analysis showed that hypertension, history of abdominal surgery, liver cirrhosis, tumors located at posterosuperior segments and major liver resection were significantly associated with conversion (all P<0.05). Multivariate analysis showed that the risk factors which were independently associated with conversion were liver cirrhosis ( OR=2.611, 95% CI: 1.018-6.701), tumors located at posterosuperior segments ( OR=6.115, 95% CI: 2.207-16.941), and major liver resection ( OR=3.361, 95% CI: 1.150-9.825)(all P<0.05). Conclusion:Patients who were planned for laparoscopic liver tumor resection with liver cirrhosis, tumors at posterosuperior segments or major liver resection were at higher risks of conversion to open surgery.

Molecular subtyping of cholangiocarcinoma and its potential clinical application / 中华肝胆外科杂志

Intrahepatic cholangiocarcinoma (ICC) has a high degree malignancy, and its incidence has gradually increased in recent years. Surgery is still the only curative treatment for ICC to achieve long-term survival, but its onset is hidden, and most patients have lost the opportunity of operation when they are diagnosed. ICC shows significant heterogeneity. With the development of the second generation sequencing technology, the tumor patterns of ICC, such as DNA, RNA, epigenetic, protein, microenvironment and so on, have been gradually discovered. The purpose of this article is to review the research progress of molecular typing and clinical application of ICC in recent years.

Increasing the thermostability of glutamate decarboxylase from Lactobacillus brevis by introducing proline / 生物工程学报

Glutamate decarboxylase, a unique pyridoxal 5'-phosphate-dependent enzyme, catalyzes α-decarboxylation of L-glutamate to γ-aminobutyrate. However, glutamate decarboxylase from different sources has the common problem of poor thermostability that affects its application in industry. In this study, proline was introduced at 13 different positions in glutamate decarboxylase by using the design strategy of homologous sequence alignment between Thermococcus kodakarensis and Lactobacillus brevis CGMCC No.1306. A mutant enzyme G364P with higher thermostability was obtained. Compared to the wild type, thermostability of the mutant G364P was significantly improved, the half-life time (t1/2) at 55 °C and the semi-inactivation temperature (T₅₀ ¹⁵) of the mutant G364P increased 19.4 min and 5.3 °C, respectively, while kcat/Km of the mutant enzyme remained nearly unchanged. Further analysis of their thermostability by molecular dynamics simulations were performed. The root mean square deviation of G364P and root mean square fluctuation in the loop region including G364 were lower than the wild type at 313 K for 10 ns, and G364P increased one hydrophobic interaction in the loop region. It proves that mutation of flexible 364-Gly to rigid proline endows glutamate decarboxylase with enhanced thermostability.

Liver transplantation using donation after cardiac death: A single-center experience of 115 cases / 中华普通外科杂志

Objective To investigate the clinical outcomes of liver transplantation by using donation after cardiac death (DCD) in single center.Methods The clinical data of 115 DCD donors and recipients of liver transplantation from Jan 2012 to Sep 2017 at our institution were analyzed,including preoperative general data,intraoperative status,and postoperative early complications.Patients were followed up to Oct 30th,2017.The measurement data with normal distribution were analyzed by t test,the enumeration data were analyzed by chi-square test or Fisher exact probability test,and the Kaplan-Meier method was used for survival analysis.Results All of the 115 donors were within China category Ⅲ using the classification of China donor after cardiac death.Donor graft mean warm ischemic time and cold ischemic time was (10 ± 4) min and (6.1 ± 1.7) h,respectively.All of the recipients underwent liver transplantation successfully.The mean preoperation MELD score was 14 ± 7.Seven patients were ABO-incompatible liver transplantation (A→O,3 cases,B→O 2 cases,AB→O 1 case,AB→A 1 case).19 patients (16.5％) had postoperative complications (Clavien-Dindo classification grade Ⅲ-Ⅴ).The perioperative mortality was 2.6％ (3 cases).All patients were followed up for an average (21 ± 17) mon.Patients 1-,3-,and 5-year survival rates were 93.6％,81.8％,and 77.5％,respectively.Conclusion The outcome of DCD liver transplantation is favorable at our institution under careful donor and recipient selection and intensive perioperative management.

Risk factors for delayed gastric emptying after pancreaticoduodenectomy / 中华胰腺病杂志

Objective To analyze the related risk factors for delayed gastric emptying ( DGE) after pancreaticoduodenectomy .Methods Clinical data on 308 patients who underwent pancreaticoduodenectomy at Ningbo Lihuili hospital from January 2009 to December 2014 were retrospectively analyzed , and patients were divided into DGE group and non-DGE group.Univariate analysis and multivariate logistic regression analysis were used to study the risk factors associated with DGE during perioperative period .Results DGE occurred in 55 patients (17.9%).The incidences of grade A, grade B and grade C DGE were 7.1%(22/308), 6.2%(19/308) and 4.5%(14/308), respectively.The univariate analysis showed the method of pancreatic digestive tract reconstruction ( pancreaticogastrostomy or pancreaticojejunostomy ) , postoperative pancreatic fistula, postoperative biliary fistula and postoperative intraabdominal infection were risk factors for DGE after surgery. Multivariate analysis indicated that the method of pancreatic digestive tract reconstruction (OR=1.19, P=0.046), postoperative pancreatic fistula ( OR=1.33, P=0.014), postoperative biliary fistula (OR=1.43, P=0.047) and postoperative intraabdominal infection (OR=1.51, P=0.001) were independently associated with DGE . Postoperative pancreatic fistula (OR=3.692, P=0.021) and intraabdominal infection (OR=3.725,P=0.003)were also the independent risk factors for Grade B and Grade C DGE. Conclusions DGE after pancreaticoduodenectomy was strongly related to the postoperative complications .Postoperative pancreatic fistula , biliary fistula and intraabdominal infection were associated with increased risk of DGE , while pancreaticogastrostomy reduced the incidence of DGE by decreasing the incidence of pancreatic or biliary fistula .

Enhancing glutamate decarboxylase activity by site-directed mutagenesis: an insight from Ramachandran plot / 生物工程学报

Glutamate decarboxylase (GAD) can catalyze the decarboxylation of glutamate into γ-aminobutyrate (GABA) and is the only enzyme of GABA biosynthesis. Improving GAD activity and thermostability will be helpful for the highly efficient biosynthesis of GABA. According to the Ramachandran plot information of GAD 1407 three-dimensional structure from Lactobacillus brevis CGMCC No. 1306, we identified the unstable site K413 as the mutation target, constructed the mutant GAD by site-directed mutagenesis and measured the thermostability and activity of the wide type and mutant GAD. Mutant K413A led to a remarkably slower inactivation rate, and its half-life at 50 °C reached 105 min which was 2.1-fold higher than the wild type GAD1407. Moreover, mutant K413I exhibited 1.6-fold higher activity in comparison with the wide type GAD1407, although it had little improvement in thermostability of GAD. Ramachandran plot can be considered as a potential approach to increase GAD thermostability and activity.

Rectification procedures for patients after nonstandard cholangioenterostomy and improper endoscopic retrograde biliary drainage / 中华肝胆外科杂志

Objective To discuss the harm and the rectification procedures for patients who have received nonstandard cholangioenterostomy and improper endoscopic retrograde biliary drainage.Method The clinical data of 55 patients who had received nonstandard cholangioenterostomy and improper endoscopic retrograde biliary drainage seen at the Ningbo LiHuiLi Hospital between 2004.6 to2011.12 were retrospectively analyzed.Results There were 23 patients who had stones located intrahepatically which had not been dealt with in the previous operation; 16 patients received choledochoduodenostomy; 5 patients received side-to-side or side-to-end cholangiojejunostomy (with no division of the common bile duct) ; 2 patients developed anastomotic stricture after nonstandard cholangioenterostomy; 3 patients had a short efferent loop of jejunum; and 6 patients had improper endoscopic retrograde biliary drainage.Through reoperative rectification,all patients had satisfactory therapeutic outcomes.Conclusions For hepatolithiasis patients,nonstandard cholangioenterostomy and improper endoscopic retrograde biliary drainage not only cause harm to the patients,but also force patients to have a reoperation.Thus,following strict operative indications,choosing the right operation and improving on the operative skills are the keys to prevent a reoperation.

Intrahepatic biliary papillomatosis:a report of 9 cases / 中华肝胆外科杂志

Objective Intrahepatic biliary papillomatosis(IBP)is a rare disease that is characterized by multiple numerous papillary adenomas in the intrahepatic biliary duct(IBD).The clinical features and outcome,however,are not well known.The clinicopathologic features,treatments and follow-up results were retrospectively analyzed in order to improve the efficiency of diagnosis and treatment for the disease.Methods Between August 2006 and October 2008,9 patients were diagnosed with IBP by histological findings at a tertiary referral center,Ningbo Medical Center(University of Ningbo,College of Medicine,Ningbo,China).The authors retrospectively reviewed the medical records to obtain clinical,radiological and pathologic data.The therapeutic results and follow-up data were also reviewed.Results The ratio of male to female was 2:7 and the middle age was 59 years.Repeated episodes of fever and right upper quadrant abdominal pain with or without jaundice were the common clinical manifestations.There were intrahepatic choledocholithiasis and/or history of previous biliary operation in 8 cases.The level of CA19-9 and CEA were almost normal.Imaging workup demonstrated cyst-like dilatation of intrahepatic biliary tree with or without liver atrophy,which were more obvious in the mucin-hypersecreting IBP.All of the 9 cases underwent curative resection with an adequate resection margin.Macroscopic findings demonstrated that the tumors of 9 cases were all located in the left lobe with mucin-hypersecreting type in 7 cases.The diameter of numerous papillary granular was usually less than 10 mm(from 2 to 5 mm.frequently)and friable,that filled the dilated IHD dispersive.Fine fibrovascular cores lined by dysplastic epithelial cells were frequently found under microscope.Few foci of stromalinvasion were noticed in the two cases with malignant transformation.All of the 9 cases survived and there was no recurrence.Conclusion IBP occurs more often in middle and old women who have history of biliary disease. Repeated episodes of cholangitis are the common clinical manifestations. Extra- and intrahepatic biliary tract dilatation is the common imaging finding.MRCP/ERCP is more valuable than others in diagnosis. Clinical and histological finding shows that IBP is a premalignant disease with high malignant potential. Curative resection should be done as earlyas possible for the long-term survival rate. The use of cholangioscopy in operation and rapid biopsy of resection margin will benefit the curative resection.

Reduced liver toxicity and drug leakage during chemotherapy of retrograde isolated hepatic perfusion in rat liver / 中华肝胆外科杂志

Objective The retrograde isolated hepatic perfusion (RIHP) model was used to compare with the isolated hepatic perfusion (IHP) model in reducing the rate of normal hepatic tissue toxicity and peripheral drug leakage during chemotherapy in rat liver. Methods A total of 90 male Sprague-Dawley rats weighing 300-350 g were randomized into 3 groups with 30 rats in each. Group A: perfusion with Lactated Ringer'S Solution through arteria hepatica (RA) and portal vein (PV),the inferior vena cava was used as an outflow tract of perfusate. Group B: For isolated hepatic perfusion (IHP), Fluorouracil (5-FU) was added into the perfusate at a dose of 350mg/kg and introduced in to the liver through arteria hepatica, portal vein was perfused by Lactated Ringer'S Solution, and the inferior vena cava was used as an outflow tract of perfusate. Group C: by using retrograde isolated hepatic perfusion (RIHP), the solution which contains 350 mg/kg Fluorouracil (5-FU) was also introduced through arteria hepatica, the inferior vena cava was introduced with Lactated Ringer'S Solution;the portal vein was used as an outflow tract of the perfusate. On day 1, 3, 5 and 7 after the perfusion in all groups, blood serum ALT test and liver histopathology test were performed. The peripheral blood drug levels were measured with high performance liquid chromatographic(HPLC) system in group B and group C. Results The survival rate was 90%, 86.7% and 90% in group A, B and C,respectively. No statistically significant difference was observed in the survival rate among the 3groups. In all the three groups, serum ALT levels were the highest on the first day after IHP: (481.6±207.6)μmol/LingroupA;(1641. 6±658.0) μmol/LingroupBand( 913. 0±353. 5)μmol/Lin group C. Significant higher serum ALT levels were observed by comparing group B and C with A(P＜0. 05). Meanwhile, the serum ALT levels were significantly higher in group B than in group C (P＜0.05). The peaks of peripheral blood drug concentration during the perfusion were 131.2±29.4μg/ml in group B and 65.3±28. 4μg/ml in group C. Significant difference was observed (P＜0. 05). Liver biopsies of group A showed mild changes on the first day after IHP and returned to normal after 7 days. Group B showed severe changes on the first day after IHP and local necrosis still existed after 7 days. Group C showed moderate changes as compared with group B on the first day after IHP and also returned to normal after 7 days. Conclusion Retrograde isolated hepatic perfusion (RIHP) can reduce the liver toxicity compared to isolated hepatic perfusion (IHP). Hopefully, RIHP will be considered as a safer way in regional chemotherapy in liver cancer.