摘要:
BACKGROUND: Gadolinium chloride (GdCl3) selectively in-activates Kupffer cells and protects against ischemia/reperfu-sion and endotoxin injury. However, the effect of Kupffer cell inactivation on liver regeneration after partial liver transplan-tation (PLTx) is not clear. This study was to investigate the role of GdCl3 pretreatment in graft function after PLTx, and to explore the potential mechanism involved in this process.
METHODS: PLTx (30% partial liver transplantation) was per-formed using Kamada's cuff technique, without hepatic artery reconstruction. Rats were randomly divided into the control low-dose (5 mg/kg) and high-dose (10 mg/kg) GdCl3 groups. Liver injury was determined by the plasma levels of alanine aminotransferase and aspartate aminotransferase, liver regen-eration by PCNA staining and BrdU uptake, apoptosis by TU-NEL assay. IL-6 and p-STAT3 levels were measured by ELISA and Western blotting.
RESULTS: GdCl3 depleted Kupffer cells and decreased animal survival rates, but did not significantly affect alanine amino-transferase and aspartate aminotransferase (P>0.05). GdCl3 pretreatment induced apoptosis and inhibited IL-6 overex-pression and STAT3 phosphorylation after PLTx in graft tissues.
CONCLUSION: Kupffer cells may contribute to the liver re-generation after PLTx through inhibition of apoptosis and activation of the IL-6/p-STAT3 signal pathway.
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BACKGROUND:?In? order? to? preserve? functional? liver? paren-chyma,?extended?central?hepatectomy?(segments?4,?5,?7?and?8?resection)?was?proposed?for?the?management?of?centrally?lo-cated?hepatocellular?carcinoma?invading?the?right?and?middle?hepatic?veins,?reconstructing?segment?6?outflow?in?the?absence?of?the?thick?inferior?right?hepatic?vein.?The?present?study?was?to?describe?our?surgical?techniques?of?extended?central?hepa-tectomy.
METHODS:?Between?2008?and?2012,?5?patients?with?centrally?located?hepatocellular?carcinoma?invading?or?in?the?vicinity?of? the? right? and? middle? hepatic? veins? underwent? extended?central?hepatectomy.?The?thick?inferior?right?hepatic?vein?was?preserved?during?dissection.?Gore-Tex?graft?was?used?for?seg-ment?6?outflow?reconstruction?in?the?absence?of?the?thick?infe-rior?right?hepatic?vein.
RESULTS:?The? mean? future? remnant? liver? volume? for? seg-ments?2?and?3?was?28%?versus?45%?on?segment?6?preservation.?The?mean?tumor?diameter?was?7.4?cm.?The?thick?inferior?right?hepatic?vein?was?found?in?1?patient.?Outflow?reconstruction?from? segment? 6? was? performed? in? 4? patients.? Postoperative?complications? included? bile? leakage? (1? patient),? pleural? effu-sion?(2)?and?liver?failure?(1).?The?rate?of?graft?patency?was?75%.?There?was?no?perioperative?mortality.
CONCLUSION:?Extended?central?hepatectomy?is?a?safe?alter-native? for? extended? hepatic? resection? in? selected? patients? at-tempting?to?preserve?the?functional?liver?parenchyma. -
BACKGROUND: Gadolinium chloride (GdCl3) selectively in-activates Kupffer cells and protects against ischemia/reperfu-sion and endotoxin injury. However, the effect of Kupffer cell inactivation on liver regeneration after partial liver transplan-tation (PLTx) is not clear. This study was to investigate the role of GdCl3 pretreatment in graft function after PLTx, and to explore the potential mechanism involved in this process.
METHODS: PLTx (30% partial liver transplantation) was per-formed using Kamada's cuff technique, without hepatic artery reconstruction. Rats were randomly divided into the control low-dose (5 mg/kg) and high-dose (10 mg/kg) GdCl3 groups. Liver injury was determined by the plasma levels of alanine aminotransferase and aspartate aminotransferase, liver regen-eration by PCNA staining and BrdU uptake, apoptosis by TU-NEL assay. IL-6 and p-STAT3 levels were measured by ELISA and Western blotting.
RESULTS: GdCl3 depleted Kupffer cells and decreased animal survival rates, but did not significantly affect alanine amino-transferase and aspartate aminotransferase (P>0.05). GdCl3 pretreatment induced apoptosis and inhibited IL-6 overex-pression and STAT3 phosphorylation after PLTx in graft tissues.
CONCLUSION: Kupffer cells may contribute to the liver re-generation after PLTx through inhibition of apoptosis and activation of the IL-6/p-STAT3 signal pathway. -
BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Most of the patients with HCC lose the surgical opportunity at the time of diagno-sis. Some novel therapeutic modalities, like gene therapy, are promising for the treatment of HCC. However, the success of gene therapy depends on two aspects: efficient gene materials and gene delivery vectors. The present study was to develop new chitosan-based nanoparticles for a midkine-siRNA (anti-HCC gene drug) delivery.
METHODS: The novel gene delivery vector (MixNCH) was syn-thesized by hybrid-type modification of chitosan with 2-chloro-ethylaminehydrochlorideandN,N-dimethyl-2-chloroethylamine hydrochloride. The chemical structure of MixNCH was char-acterized by FT-IR and 1HNMR. The cytotoxicity of MixNCH was determined by MTS assay. The gene condensation ability and size, zeta potential and morphology of MixNCH/MK-siRNA nanoparticles were measured. The in vitro transfection and gene knockdown efficiency of midkine by MixNCH/MK-siRNA nanoparticles was detected by qRT-PCR and Western blotting. Gene knockdown effect at the molecule level on the proliferation of HepG2 in vitro was determined by MTS assay.
RESULTS: MixNCH was successfully acquired by aminoalkyl-ation modification of chitosan. The MixNCH could condense MK-siRNA well above the weight ratio of 3. The average size of MixNCH/MK-siRNA nanoparticles was 100-200 nm, and the surface charge was about +5 mV. Morphologically, MixNCH/MK-siRNA nanoparticles were in regular spherical shape with no aggregation. Regarding to the in vitro transfection of nanoparticles, the MixNCH/MK-siRNA nanoparticles reduced MK mRNA level to 14.03%±4.03%, which were comparable to Biotrans (8.94%±3.77%). MixNCH/MK-siRNA effectively inhibited the proliferation of HepG2 in vitro.
CONCLUSION: MixNCH/MK-siRNA nanoparticles could be effective for the treatment of hepatocellular carcinoma. -
BACKGROUND:?At?the?time?of?diagnosis,?most?patients?with?gallbladder? cancer? are? in? advanced? stage? and? the? cancer? is?unresectable.?Long-term?survivors?are?usually?seen?in?a?small?number? of? patients? with? incidental? gallbladder? cancer.? This?study?aimed?to?identify?preoperative?predictors?of?incidental?gallbladder?cancer?in?elderly?patients.
METHODS:?A?total?of?4014?patients?of?more?than?44?years?old?who?had?undergone?cholecystectomy?at?our?department?from?January?2000?to?December?2010?were?retrospectively?reviewed.?Univariate?and?multivariate?modalities?were?used?to?identify?the?predictive?factors?of?incidental?gallbladder?cancer.
RESULTS:?Twenty-nine? of? the? 4014? patients? who? had? under-gone? cholecystectomy? for? benign? gallbladder? diseases? were?histologically?diagnosed?as?having?incidental?gallbladder?can-cer.?Multivariate?analysis?identified?that?elevated?carbohydrate?antigen? 19-9? combined? with? carcinoembryonic? antigen? and/or? carbohydrate? antigen? 125? (P=0.045),? a? gallbladder? polyp?greater?than?or?equal?to?1.2?cm?(P=0.043)?and?focal?gallblad-der?wall?thickening?of?more?than?or?equal?to?5?mm?(P=0.002)?were?predictive?factors?of?incidental?gallbladder?cancer.
CONCLUSION:?Cholecystectomy? is? suggested? for? patients?with?these?predictive?factors?and?intraoperative?frozen?section?should?be?considered?to?rule?out?carcinoma. -
BACKGROUND: Liver resection is currently the most efficient curative approach for a wide variety of liver tumors. The ap-plication of modern techniques and new surgical devices has improved operative outcomes. Radiofrequency ablation is used more often for liver parenchymal transection. This study aimed to assess the efficacy and safety of radiofrequency abla-tion-assisted liver resection.
METHODS: A retrospective study of 145 consecutive patients who underwent radiofrequency ablation-assisted liver resec-tion was performed. Intraoperative blood loss, need for trans-fusion or intraoperative Pringle maneuver, the duration of liver parenchymal transection, perioperative complications, and postoperative morbidity and mortality were all evaluated.
RESULTS: Fifty minor and ninety-five major liver resections were performed. The mean intraoperative blood loss was 251 mL, with a transfusion rate of 11.7%. The Pringle maneuver was necessary in 12 patients (8.3%). The mean duration for parenchymal transection was 51.75 minutes. There were 47 patients (32.4%) with postoperative complications. There is no mortality within 30 days after surgery.
CONCLUSIONS: Radiofrequency ablation-assisted liver re-section permits both major and minor liver resections with minimal blood loss and without occlusion of hepatic inflow. Furthermore it decreases the need for blood transfusion and reduces morbidity and mortality. -
BACKGROUND:?The?mitogen-activated?protein?kinases?(MAPKs)?signaling?pathway?is?involved?in?inflammatory?process.?However,?the?mechanism?is?not?clear.?The?present?study?was?to?investi-gate?the?role?of?p38?MAPK?in?acute?pancreatitis?in?mice.
METHODS:?Mice?were?divided?into?4?groups:?saline?control;?acute? pancreatitis? induced? with? repeated? injections? of? ceru-lein;? control? plus? p38? MAPK? inhibitor? SB203580;? and? acute?pancreatitis?plus?SB203580.?The?pancreatic?histology,?pancre-atic?enzymes,?cytokines,?myeloperoxidase?activity,?p38?MAPK?and?heat?shock?protein?(HSP)?60?and?70?were?evaluated.
RESULTS:?Repeated? injections? of? cerulein? resulted? in? acute?pancreatitis? in? mice,? accompanying? with? the? activation? of?p38? MAPK? and? overexpression? of? HSP60? and? HSP70? in? the?pancreatic?tissues.?Treatment?with?SB203580?significantly?in-hibited?the?activation?of?p38?MAPK,?and?furthermore,?inhib-ited?the?expression?of?HSP60?and?HSP70?in?the?pancreas,?the?inflammatory? cytokines? in? the? serum,? and? myeloperoxidase?activity?in?the?lung.
CONCLUSION:?The?p38?MAPK?signaling?pathway?is?involved?in? the? regulation? of? inflammatory? response? and? the? expres-sion?of?HSP60?and?HSP70?in?acute?pancreatitis. -
BACKGROUND: Pancreaticobiliary maljunction is a high risk factor of pancreatitis and biliary tract cancer. How this mal-junction affects the liver remains obscure. This study aimed to examine the effects of pancreaticobiliary maljunction on the liver, pancreas and gallbladder in a cat model.
METHODS: A model of choledocho-pancreatic side-to-side ductal anastomosis was created in ten cats.Before the procedure, a small piece of tissue from the liver, pancreas and gallbladder was collected as a control. The common channel formation was checked by cholecystography. The livers, pancreases and gall-bladders of these cats were harvested for histological examina-tion. The expression of proliferating cell nuclear antigen in the gallbladder was examined with immunohistochemistry.
RESULTS: Seven of the 10 cats survived for 6 months after surgery. The color of the liver was darker in the PBM model than the control specimen, with nodules on the surface. His-tological examination showed ballooning changes and inflam-matory infiltrations and the histopathological score increased significantly (P<0.05). Also, mitochondria swelling and lipid droplet in cytoplasm were observed under an electron micro-scope. The pancreas also appeared darker in the PBM model than the control specimen and dilated pancreatic ducts were found in three cats. Histopathological examination revealed vascular proliferation and inflammatory infiltration with nu-merous neutrophils. Gallbladder epithelial cells were featured by expanded endoplasmic reticulum, increased intercellular space and cellular nucleus deformation. The positive cells of proliferating cell nuclear antigen were increased significantly (P<0.05).
CONCLUSION: The present study demonstrated that pancreatico-biliary maljunction can lead to the injuries of the liver, pancreas and gallbladder. -
BACKGROUND: Donor shortage is the biggest obstacle in organ transplantation. Living donor liver transplantation (LDLT) has been considered as a valuable approach to short-ening waiting time. The objectives of this study were to inves-tigate the feasibility of utilizing donors older than 50 years in LDLT and to evaluate the graft function and recipient survival.
METHODS: All LDLT cases (n=159) were divided into the older (donor age ≥50 years, n=10) and younger (donor age <50 years, n=149) donor groups. Donor graft and recipient condition pre-, intra- and post-operation were compared between the two groups. Inparticular,graftfunctionsandrecipientsurvivalswereanalyzed.
RESULTS: The median donor age was 58.5 (52.5-60.0) years in the older donor group and 25.0 (23.0-32.0) in the younger do-nor group. There was no significant difference in cold ischemic time, anhepatic phase and operation time between the older and younger donor groups (P>0.05). However, the volume of red blood cell transfused in operation was greater in the older donor group than in the younger donor group (1900 vs 1200 mL, P=0.023). The 1-, 3- and 5-year graft survival rates were 90%, 80% and 80% for the older donor group, and 92%, 87%and 87% for the younger donor group, respectively (P=0.459). The 1-, 3- and 5-year survival rates were 100%, 90% and 90%for recipients with older grafts, and 93%, 87% and 87% for those with younger grafts, respectively (P=0.811).
CONCLUSION: It is safe for a LDLT recipient to receive liver from donors older than 50 years, and there is no significant adverse effect on graft function and long-term patients' survival. -
BACKGROUND: The prognostic prediction of liver transplan-tation (LT) guides the donor organ allocation. However, there is currently no satisfactory model to predict the recipients' outcome, especially for the patients with HBV cirrhosis-re-lated hepatocellular carcinoma (HCC). The present study was to develop a quantitative assessment model for predicting the post-LT survival in HBV-related HCC patients.
METHODS: Two hundred and thirty-eight LT recipients at the Liver Transplant Center, First Affiliated Hospital, Zhejiang University School of Medicine between 2008 and 2013 were included in this study. Their post-LT prognosis was recorded and multiple risk factors were analyzed using univariate and multivariate analyses in Cox regression.
RESULTS: The score model was as follows: 0.114×(Child-Pugh score)-0.002×(positive HBV DNA detection time)+0.647× (number of tumor nodules)+0.055×(max diameter of tumor nodules)+0.231×lnAFP+0.437×(tumor differentiation grade). The receiver operating characteristic curve analysis showed that the area under the curve of the scoring model for predict-ing the post-LT survival was 0.887. The cut-off value was 1.27, which was associated with a sensitivity of 72.5% and a speci-ficity of 90.7%, respectively.
CONCLUSION: The quantitative score model for predicting post-LT survival proved to be sensitive and specific. -
BACKGROUND: A preoperative diagnosis of primary hepatic lymphoma (PHL) can have profound therapeutic and prognos-tic implications. Because of the rarity of PHL, however, there are few reports on diagnostic imaging.We reviewed the clinical and radiologic findings of 29 patients with PHL, the largest series to date, to evaluate the diagnostic features of this disease.
METHODS: Clinical data and radiologic findings at presen-tation were retrospectively reviewed for 29 patients with pathologically confirmed PHL from January 2005 to June 2013. Imaging studies, including ultrasound (US) (n=29) and contrast-enhanced computed tomography (CECT) (n=24), were performed within 2 weeks before biopsy or surgery.
RESULTS: Among the 29 patients, 23 (79%) were positive for hepatitis B virus (HBV) and 26 (90%) had a significantly ele-vated level of serum lactate dehydrogenase (LDH). There were two distinct types of PHL on imaging: diffuse (n=5) and nodu-lar (n=24). Homogeneous or heterogeneous hepatomegaly was the only sign for diffuse PHL on both US and CECT, without any definite hepatic mass. For the nodular type, 63% (15/24) of patients had solitary lesions and 38% (9/24) had multiple lesions. On US, seven patients displayed patchy distribution with an indistinct tumor margin and a rich color flow signal. CECT showed rim-like enhancement (n=3) and slightly ho-mogeneous or heterogeneous enhancement (n=14) in the arte-rial phase and isoenhancement (n=5) and hypoenhancement (n=12) in the portal venous and late phases. Furthermore, in five patients, CT revealed that hepatic vessels passed through the lesions and were not displaced from the abnormal area or appreciably compressed.
CONCLUSIONS: The infiltration type of PHL was associated with the histologic subtype. Considered together with HBV positivity and elevated LDH, homogeneous or heterogeneous hepatomegaly may indicate diffuse PHL, whereas patchy dis-tribution with a rich color flow signal on US or normal vessels extending through the lesion on CECT may be the diagnostic indicators of nodular PHL.