Scattered and rapid intrahepatic recurrences after radio frequency ablation for hepatocellular carcinoma

AIM： To evaluate a series of patients with hepatocellular carcinoma （HCC） treated with several different protocols and devices. METHODS： We treated 138 patients [chronic hepatitis/ liver cirrhosis （Child-Pugh A/B/C）, 3/135 （107/25/3）] with two different devices and protocols： cool-tip needle [initial ablation at 60 W （standard method） （n = 37） or at 40 W （modified method） （n = 28）] or; ablation with a LeVeen needle using a standard single-step, full expansion （single-step） method （n = 39） or a multi-step, incremental expansion （multi-step） method. RESULTS： Eleven patients experienced rapid and scattered recurrences 1 to 7 mo after the ablation. Nine patients were treated by the cool-tip original protocol （60 W） （9/37 = 24%） and the other two by the LeVeen single-step method （2/39 = 5%）. The location of the recurrence was surrounding and limited to the site of ablation segment in three cases, and spread over one Iobule or both Iobules in the other eight cases. There was no recurrence in the patients treated with the modified cool-tip modified method （40 W） or the LeVeen multi-step method. CONCLUSION： There is a risk of rapid and scattered recurrence after RFA, especially when the standard cool- tip procedure is used. Because such recurrence would worsen the prognosis, we recommend that modified protocols for the cool-tip and LeVeen needle methods should be used in clinical practice.

Drug sensitivity and drug resistance profiles of human intrahepatic cholangiocarcinoma cell lines

AIM: To study the effect of a number of chemotherapeutic drugs on five human intrahepatic cholangiocarcinoma (CCA) cell lines. The expressions of genes that have been proposed to influence the resistance of chemotherapeutic drugs including thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), glutathione-S-transferase PI (GSTP1), multidrug resistance protein (MDR1) and multidrug resistance-associated proteins (MRPs) were also determined. METHODS: Five human CCA cell lines (KKU-100, KKU-M055, KKU-M156, KKU-M214 and KKU-OCA17) were treated with various chemotherapeutic drugs and growth inhibition was determined by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay. Semi-quantitative levels of gene expression were determined by a reverse transcriptase polymerase chain reaction (RT-PCR). Results of IC_(50) values and the ratios of gene expression were analyzed by linear regression to predict their relationship. RESULTS: Among five CCA cell lines, KKU-M055 was the most sensitive cell line towards all chemotherapeutic drugs investigated, particularly taxane derivatives with IC_(50) values of 0.02-3 nmol/L, whereas KKU-100 was apparently the least sensitive cell line. When compared to other chemotherapeutic agents, doxorubicin and pirarubicin showed the lowest IC_(50) values (＜5 μmol/L) in all five CCA cell lines. Results from RT-PCR showed that TS, MRP1, MRP3 and GSTP1 were highly expressed in these five CCA cell lines while DPD and MRP2 were only moderately expressed. It should be noted that MDR1 expression was detected only in KKU-OCA17 cell lines. A strong correlation was only found between the level of MRP3 expression and the IC_(50) values of etoposide, doxorubicin and pirarubicin (r=0.86-0.98, P＜0.05). CONCLUSION: Sensitivity to chemotherapeutic agents is not associated with the histological type of CCA. Choosing of the appropriate chemotherapeutic regimen for the treatment of CCA requires knowledge of drug sensitivity. MRP3 was correlated with resistance of CCA cell lines to etoposide, doxorubicin and pirarubicin, whereas other chemotherapeutic drugs showed no association. The role of this multidrug resistance-associated protein, MRP3, in chemotherapeutic resistance in CCA patients needs to be further investigated.

COMBINED SURGICAL THERAPY FOR HEPATOLITHIASIS

Objective To evaluate the combined surgical therapy for calculi of intrahepatic duct. Methods One hundred and eight cases of hepatolithiasis treated in our hospital from January 1986 to September 2003 were summarized and analyzed retrospectively. The primary surgery included 57 cases of biliary tract exploration and cholangiolithotomy, 26 cases of cholangiojejunostomy, and 25 cases of partial hepatectomy. Of these cases, 156 operations were performed totally. There were 36 patients undergoing two or more operations for cholangiolithiasis problem. Fiberoptic choledochoscopy was employed to examine and remove the residual stones during and after operation in all cases. Results The residual stone rates were 57.89% (33/57), 26.92% (7/26), and 24.0% (6/25) for biliary tract exploration and cholangiolithotomy, cholangiojejunostomy, and partial hepatectomy, respectively. Fiberoptic choledochoscopy was utilized pre- and post-operatively for each patient, which was performed 2 to 9 times on each case. Following the combined treatment, the rate of residual stone after operation decreased to 12.96% (14/108). Conclusions The combined surgical therapy is valuable for resolving the problem of hepatolithiasis in most of the patients. Regarding the clinical outcomes of different surgical procedures, partial hepatectomy is superior to cholangiojejuno- stomy or biliary tract exploration and cholangiolithotomy. Fiberoptic choledochoscopy is also important to reduce the occurrence of residual stones and the rate of reoperation.

The hepatic sinusoidal endothelial lining and colorectal liver metastases

Colorectal cancer (CRC) is a common malignant disease and the severe nature of cases in men and women who develop colorectal cancer makes this an important socio-economic health issue. Major challenges such as understanding and modeling colorectal cancer pathways rely on our understanding of simple models such as outlined in this paper. We discuss that the development of novel standardized approaches of multidimensional (correlative) biomolecular microscopy methods facilitates the collection of (sub) cellular tissue information in the early onset of colorectal liver metastasis and that this approach will be crucial in designing new effective strategies for CRC treatment. The application of X-ray micro-computed tomography and its potential in correlative imaging of the liver vasculature will be discussed.

Intracellular transport of hepatitis B virus

For genome mulUplication hepadnaviruses use the transcriptional machinery of the cell that is found within the nucleus. Thus the viral genome has to be transported through the cytoplasm and nuclear pore. The intracytosolic translocation is facilitated by the viral capsid that surrounds the genome and that interacts with cellular microtubules. The subsequent passage through the nuclear pore complexes （NPC） is mediated by the nuclear transport receptors importin α andβ. Importin α binds to the C-terminus of the capsid protein that comprises a nuclear localization signal （NLS）. The exposure of the NLS is regulated and depends upon genome maturation and/or phosphorylation of the capsid protein. As for other karyophilic cargos using this pathway importin α interacts with importin β that facilitates docking of the import complex to the NPC and the passage through the pore. Being a unique strategy, the import of the viral capsid is incomplete in that it becomes arrested inside the nuclear basket, which is a cage-like structure on the karyoplasmic face of the NPC. Presumably only this compartment provides the factors that are required for capsid disassembly and genome release that is restricted to those capsids comprising a mature viral DNA genome.

Endoscopic therapy of benign biliary strictures

Benign biliary strictures are being increasingly treated with endoscopic techniques. The benign nature of the stricture should be first confirmed in order to ensure appropriate therapy. Surgery has been the traditional treatment, but there is increasing desire for minimally invasive endoscopic therapy. At present, endoscopy has become the first line approach for the therapy of post- liver transplant anastomotic strictures and distal （Bismuth ! and I） post-operative strictures. Strictures related to chronic pancreatitis have proven more difficult to treat, and endoscopic therapy is reserved for patients who are not surgical candidates. The preferred endoscopic approach is aggressive treatment with gradual dilation of the stricture and insertion of multiple plastic stents. The use of uncovered self expandable metal stents should be discouraged due to poor long-term results. Treatment with covered metal stents or bioabsorbable stents warrants further evaluation. This area of therapeutic endoscopy provides an ongoing opportunity for fresh research and innovation.

Update of endoscopy in liver disease:More than just treating varices

The management of complications in liver disease is often complex and challenging.Endoscopy has undergone a period of rapid expansion with numerous novel and specialized endoscopic modalities that are of increasing value in the investigation and management of the patient with liver disease.In this review,relevant literature search and expert opinions have been used to provide a brief overview and update of the current endoscopic management of patients with liver disease and portal hypertension.The main areas covered are safety of endoscopy in patients with liver disease,the use of standard endoscopy for the treatment of varices and the role of new endoscopic modalities such as endoscopic ultrasound,esophageal capsule,argon plasma coagulation,spyglass and endomicroscopy in the investigation and treatment of liver-related gastrointestinal and biliary pathology.It is clear that the role of the endoscopy in liver disease is well beyond that of just treating varices.As the technology in endoscopy expands,so does the role of the endoscopist in liver disease.

Percutaneous Ethanol Intratumoral Injection for Treatment of Small Primary Liver Cancer：Summary of 240 Cases

Objective To evaluate the therapeutic effects of percutaneous ethanol intratumoral injection (PEIT) for treatment of small primary liver cancer (SPLC).Methods 240 patients with surgically or pathologically proved SPLC ( < 3 cm in diameter) were treated by PEIT ( under the guidance of B-ultrasound) . Of the" 240 patients, 163 had recurrent liver cancer, 55 had inoperable liver cancer because of cardiac, pulmonary, hepatic and renal dysfunctions or due to the close proximity of tumor to the major vessels, and 22 refused to receive surgical resection. In 40 patients who received surgical resection after PEIT treatment, the resected tumors were pathologically evaluated for necrotic status and the patients were followed up postoperatively.Results Postoperative 1-, 2- and 3-year survival rate of the 240 patients was 94.9% , 84.2% and 66.3% respectively. Conclusion PEIT can be used as a non-invasive treatment for SPLC, and preoperative PEIT appears to be helpful in reducing recurrence of postoperative liver cancer.

Dynamic changes and mechanism of intestinal endotoxemia in partially hepatectomized rats

AIM： To explore the mechanism of intestinal endotoxemia （IETM） formation and its changes in partially hepatectomized （PH） rats. METHODS： One-hundred and two adult male Wistar rats were randomly divided into three groups： normal control （NC） group, partially hepatectomized （PH） group and a sham-operated （SO） group. To study the dynamic changes, rats were sacrificed before and at different time points after partial hepatectomy or the sham-operation （ 6 h, 12 h, 24 h, 36 h, 48 h, 72 h, 120 h and 168 h）. NC group was used as Oh time point in observation, namely 0 h group. For each time point indicated, six rats were used in parallel. Endotoxin （ET） and diamine oxidase （DAO） levels were determined in serum using Limulus Lysate test with chromogenic substrate and spectrophotometry. Intestinal mucosa barrier was observed under opticcal or electron microscope. The number and functional state of Kupffer cells （KCs） in the remnant regenerating liver were measured by immunohistochemical staining. RESULTS： Serum ET levels significantly increased during 6-72 h period after PH compared with NC and SO groups, and there were two peak values at 12 and 48 h while serum DAO level significantly increased at 12 and 24 h. There was positive correlation （r = 0.757, P 〈 0.05） between the levels of DAO and ET dynamic changes. The optical examination showed neutrophil margination and superficial necrosis of the villi in the intestinal mucosa during 6-24 h period after PH. The penetrated electron microscope examination showed thatthe gaps between intestinal mucosa cells were increased and the Lanthanum （La） particles were observed among the intestinal mucosa cells during 6-48 h period, The numbers of KCs in the remnant regenerating liver were significantly increased during 24-168 h period after PH, However, the activation of KCs was predominantly observed at 48 h after PH. CONCLUSION： The mechanism of IETM in PH rats might be the injury of intestinal mucosa barrier and the decrease of the absolute number of KCs as well as the depression of functional state of KCs, This observation is of potential value in patients undergoing liver resection,

Endoscopic naso-pancreatic drainage for the treatment of pancreatic fistula occurring after LDLT

Pancreatic fistula is a quite rare complication in patients who undergo living donor liver transplantation(LDLT).However,in the cases that show pancreatic fistula,the limited volume of the graft and the resultant inadequate liver function may complicate the management of the fistula.As a result,the pancreatic fistula may result in the death of the patient.We present 2 cases in whichendoscopic treatment was effective against pancreatic fistulas that developed after LDLT.In case 1,a 61-yearold woman underwent LDLT for primary biliary cirrhosis.Because of a portal venous thrombus caused by a splenorenal shunt,the patient underwent portal vein reconstruction,and a splenorenal shunt was ligated on postoperative day(POD)7.The main pancreatic duct was injured during the manipulation to achieve hemostasis,thereby necessitating open drainage.However,discharge of pancreatic fluid continued even after POD 300.Endoscopic naso-pancreatic drainage(ENPD)was performed,and this procedure resulted in a remarkable decrease in drain output.The refractory pancreatic fistula healed on day 40 after ENPD.In case 2,a 58-year-old man underwent LDLT for cirrhosis caused by the hepatitis C virus.When the portal vein was exposed during thrombectomy,the pancreatic head was injured,which led to the formation of a pancreatic fistula.Conservative therapy was ineffective;therefore,ENPD was performed.The pancreatic fistula healed on day 38 after ENPD.The findings in these 2 cases show that endoscopic drainage of the main pancreatic duct is a less invasive and effective treatment for pancreatic fistulas that develop after LDLT.

Serum HIF-1α and VEGF Levels Pre-and Post-TACE in Patients with Primary Liver Cancer

Objective To investigate the expression levels of serum hypoxia inducible factor 1 alpha(HIF-1α) and vascular endothelial growth factor(VEGF) pre-and post-transcatheter arterial chemoembolization(TACE) in patients with primary liver cancer(PLC),and correlations between prognosis factors and serum HIF-1α as well as VEGF levels.Methods Forty consecutive patients fulfilling diagnostic criteria for PLC undergoing TACE from March 2008 to May 2009 were enrolled into the study.The serum HIF-1α and VEGF levels of PLC patients pre-and 1 day,1 week,1 month post-TACE were analyzed using ELISA,and compared with that of 20 healthy volunteers.Patients were divided into complete response(CR) and partial response(PR),stable disease(SD),progressive disease(PD) groups according to the therapeutic efficacy.Pearson correlation was used to analyze the correlation between different clinical variables and serum HIF-1α and VEGF levels before TACE,and correlation between serum HIF-1α and VEGF levels was also evaluated.Results The expression levels of serum HIF-1α and VEGF in PLC patients were 154.94±83.29 and 264.00±148.10 pg/mL pre-TACE,and both of them were significantly higher than those in control group(23.84±8.15 and 69.78±21.42 pg/mL,all P<0.01).One day after TACE,both serum HIF-1α(570.64± 230.87 pg/mL) and VEGF levels(362.07±102.25 pg/mL) reached the peak values(all P<0.01).One week post-TACE,expression levels of them were decreased(198.62±92.11 and 283.52±145.46 pg/mL respectively),but still significantly higher than those before TACE(all P<0.01).The levels of both HIF-1α(133.96±57.02 vs.255.74±123.44 pg/mL) and VEGF(150.96±84.89 vs.368.95±161.90 pg/mL) in CR group 1 month post-TACE were significantly lower than those in PR+SD+PD group(all P<0.01).The level of serum HIF-1α was positively correlated with serum VEGF level(r=0.42,P<0.001).Both serum HIF-1α and VEGF levels were observed to be correlated with portal vein tumor thrombi(P<0.05) and metastasis(P<0.05).

An uncommon cause of gastro-duodenal ulceration

Gastrointestinal ulcers occur frequently and are mainly caused by H pylori infection. In this report, we present a rare case of gastro-duodenal ulcer following selective internal radiation therapy (SIRT). SIRT is a palliative treatment for unresectable liver tumours. During SIRT, 90Y-microspheres are infused into the hepatic artery. Pre- treatment evaluation for the presence of arterial shunts to neighbouring organs should be determined in order to avoid complications of SIRT.

Why more attentions to fetus in cases of intrahepatic cholestasis of pregnancy?

Intrahepatic cholestasis of pregnancy(ICP) is a peculiar disease in middle-late pregnancy with the pathological characteristics of hepatic capillary bile duct silts and is accompanied by clinical presentations of pruritus and bile acid(BA) elevation in serum. Maternal outcomes for patients diagnosed with ICP are usually good. However, fetal outcomes can be devastating with high frequencies of perinatal complications. Patients with ICP generally have an early delivery due to fetal complications. The current hypothesis is that ICP has higher frequencies of fetal complications due to high concentrations of BA which has toxic cellular effects to many organs. In lungs, it destroys the AT-II cells, decreasing phospholipids synthesis leading to the alveolar capillary permeability to increase and pulmonary surfactant to decrease. In heart, cholate can cross into the fetal compartment and causing fetal arrhythmias and decreased contractility. In the nervous system, high BAs can cause nerve cell denaturation and necrosis, mitochondria edema and membrane dissolve. In the placenta, high BA concentration can cause edema of the villous, decrease number of villous, intervillous thickening and balloon formation.In addition, high total BA can result in chorionic vein constriction and impaired fetal adrenal function.

Malignant Hemangioendothelioma of the Liver： a Case Report

A male patient, 50 years old, was hospitalized in our department because of repeated vague pain under the right rib for more than 3 months. Two weeks prior to his hospitalization the pain became severe accompanied by fever. The right subcostal vague pain and discomfort occurred 3 months before admission, with no radiating pain elsewhere, no vomiting, no diarrhea or jaundice but with chilis and pyrexia. In the afternoon the fever intensified, with a body temperature of about 38.5℃. There was the vague pain and discomfort under the right rib, which was paroxysmally intensified.

Experimental research of relationship between doses and biological effect of ^(32)P-GMS by percutaneous intra-tumor injection to treat liver cancer

Objection： To study the relationship between different doses and biological effect of 32p-glass microspheres （32P-GMS） by percutaneous intra-tumor injection at different times and provide proofs of theory for clinical therapy. Methods： 36 Zealand rabbits and Vx-2 were used to establish the animal model of liver tumor. Six groups were randomly designed. The suspension of different radiative doses of 32p-GMS combined with lipiodol-ultrafluid （0.1 mL） was respectively injected by percutaneous intra-tumor. The tumor tissues were examined by light microscope. MRI examination of liver tumors were performed before and after the injection. Results： C and D groups were observed that the tumor volume was decreased and the rate of restrained tumor was gradually increased after injection of 32p-GMS. The living tumor tissues of E group completely disappeared after the injection for two weeks. MRI examination showed that the tumor signal of E group was equal as T2 as the signal of normal liver parenchyma. The living tumor tissues were not found in F group after the injection for three weeks. Conclusion： 111 MBq was the best radiative dose of ~2p-GMS for treatment of 1 cm liver cancer by percutaneous intra-tumor injection. MRI examination was very valuable to evaluate the result and follow up after the injection to treat liver cancer.

The first report of treatment of liver abscess due to Candida albicans with intra-abscess and intravenous administration of liposomal amphotericin B (Amphotec)

Increasing reports on application and safety of liposomal amphotericin B (Amphotec) in the treatment of deep fungal infections have been described recently. This is the first report that a case of liver abscess due to Candida albicans was completely cured with intra-abscess and intravenous administration of liposomal amphotericin B without recurrence in three-year follow-up period.

Perioperative insulin therapy using a closed-loop artificial endocrine pancreas after hepatic resection

Postoperative hyperglycemia is common in critically ill patients, even in those without a prior history of diabetes mellitus. It is well known that hyperglycemia induced by surgical stress often results in dysregulation of liver metabolism and immune function, impairing postoperative recovery. Current evidence suggests that maintaining normoglycemia postoperatively improves surgical outcome and reduces the mortality and morbidity of critically ill patients. On the basis of these observations, several large randomized controlled studies were designed to evaluate the benefit of postoperative tight glycemic control with intensive insulin therapy. However, intensive insulin therapy carries the risk of hypoglycemia, which is linked to serious neurological events. Recently, we demonstrated that perioperative tight glycemic control in surgical patients could be achieved safely using a closed-loop glycemic control system and that this decreased both the incidence of infection at the site of the surgical incision, without the appearance of hypoglycemia, and actual hospital costs. Here, we review the benefits and requirements of perioperative intensive insulin therapy using a dosed-loop artificial endocrine pancreas system in hepatectomized patients. This novel intensive insulin therapy is safe and effectively improves surgical outcome after hepatic resection.

妊娠期肝内胆汁淤积症48例分析

目的探讨妊娠期肝内胆汁淤积症对围产儿预后的影响及终止妊娠时机的选择。方法回顾性分析焦作市妇幼保健院2009-01-2011-01住院分娩的48例妊娠期肝内胆汁淤积症患者的临床资料。结果48例妊娠期肝内胆汁淤积症孕妇发生新生儿轻度窒息8例，胎死宫内1例，胎儿窘迫34例，早产18例。结论加强孕期保健．对高危孕产妇进行系统管理，对已确诊的妊娠期肝内胆汁淤积症的孕妇加强治疗和胎儿监测，适时终止妊娠，降低围产儿患病率和病死率。

Variceal bleeding in cirrhotic patients

Variceal bleeding is one of the major causes of death in cirrhotic patients.The management during the acute phase and the secondary prophylaxis is well defined.Recent recommendations(2015 Baveno VI expert consensus)are available and should be followed for an optimal management,which must be performed as an emergency in a liver or general intensive-care unit.It is based on the early administration of a vasoactive drug(before endoscopy),an antibiotic prophylaxis and a restrictive transfusion strategy(hemoglobin target of 7 g/dL).The endoscopic treatment is based on band ligations.Sclerotherapy should be abandoned.In the most severe patients(Child Pugh C or B with active bleeding during initial endoscopy),transjugular intrahepatic portosystemic shunt(TIPS)should be performed within 72 hours after admission to minimize the risk of rebleeding.Secondary prophylaxis is based on the association of non-selective beta-blockers(NSBBs)and repeated band ligations.TIPS should be considered when bleeding reoccurs in spite of a well-conducted secondary prophylaxis or when NSBBs are poorly tolerated.It should also be considered when bleeding is refractory.Liver transplantation should be discussed when bleeding is not controlled after TIPS insertion and in all cases when liver function is deteriorated.