Wenyan Liu

Using a decellularized splenic matrix as a 3D scaffold for hepatocyte cultivation in vitro: a preliminary trial.

Using a decellularized liver matrix (DLM) to reengineer liver tissue is a promising therapy for end-stage liver disease. However, the limited supply of donor organs still hampers its potential clinical application, while a xenogenic decellularized matrix may bring a risk of zoonosis and immunological rejection. Therefore, an appropriate alternative scaffold is needed. In this research, we established a decellularized splenic matrix (DSM) in a rodent model, which preserved the 3D ultrastructure, the components of the extracellular matrix (ECM) and the native vascular network. The DSM and DLM had similar components of ECM, and similar mechanical properties. Hepatocytes were seeded to the DSM and DLM for dynamic culturing up to 6 d, and distributed both in decellularized sinusoidal spaces and around the vessels. The TUNEL-positive cell percentage in a dynamic culturing decellularized splenic matrix (dDSM) was 10.7%  ±  3.6% at 3d and 25.8%  ±  5.6% at 5d, although 14.2%  ±  4.5% and 24.8%  ±  2.9%, respectively, in a dynamic culturing decellularized liver matrix (dDLM) at the same time point (p  >  0.05). Primary hepatocytes in the dDSM and dDLM expressed albumin, G6pc and Ugt1a1. The gene expression of Cyp2b1, Cyp1a2 and HNF1α in the gene transcription level revealed hepatocytes had lower gene expression levels in the dDSM compared with the dDLM at 3d, but better than those in a sandwich culture. The cumulative albumin production at 6 d of culture was 80.7   ±   9.6 μg per million cells in the dDSM and 89.6   ±   4.6 μg per million cells in the dDLM (p  >  0.05). In summary, the DSM is a promising 3D scaffold for hepatocyte cultivation in vitro.

Extrahepatic portacaval shunt via a magnetic compression technique: A cadaveric feasibility study

AIM To explore the anatomical feasibility of portacaval shunt using a magnetic compression technique (MCT) in cadavers. METHODS Computed tomography (CT) images of 30 portal hypertensive patients were obtained. The diameters of the portal vein (PV), the inferior vena cava (IVC), and distance between the two structures were measured. Similar measurements were performed on 20 adult corpses. The feasibility of portacaval shunt based on those measurements was analyzed. First stage of the extrahepatic portacaval shunt using MCT was performed on five cadavers. Specifically, the PV and IVC were exposed through an abdominal incision of the cadavers. The parent magnet was introduced from the femoral vein and was delivered into the IVC by an anchor wire and a 5F Cook catheter. The daughter magnet was introduced into the PV through the splenic vein using an interventional guide wire. When the daughter magnet met the parent magnet, they automatically clipped together and the first stage of the portacaval shunt was set up. RESULTS The average diameters of the PV and the IVC measured from the 30 CT image were 14.39 ± 2.36 mm and 18.59 ± 4.97 mm, respectively, and the maximum and minimum distances between the PV and the IVC were 9.79 ± 4.56 mm and 9.50 ± 4.79 mm, respectively. From 20 cadavers, the average diameters of the PV and the IVC were 14.48 ± 1.47 mm and 24.71 ± 2.64 mm, and the maximum and minimum distances between the PV and the IVC were 10.14 ± 1.70 mm and 8.93 ± 1.17 mm, respectively. The distances between the PV and the IVC from both the CT images and the cadavers were within the effective length of portacaval anastomosis using MCT (30.30 ± 4.19 mm). The PV and IVC are in close proximity to each other with no intervening tissues or structures in between. Simulated surgeries of the first stage using MCT on five cadavers was successfully performed. CONCLUSION Anatomically, extrahepatic portacaval shunt employing MCT is highly feasible in humans.

Magnet compression technique: a novel method for rectovaginal fistula repair.

Dear Editor: Though the morbidity of rectovaginal fistula (RVF) is not high in humans, surgical repair is difficult to finish and does not work well actually. As the statistical data shows, when the RVF is repaired firstly, its success rate is 70–79 %, but when the fistula is repaired for a second or more times, its success rate is decreased to 40–85%. In clinic, there are many ways to repair the RVF, but until now, the standard therapy is still uncertain, so the fistula was almost repaired clinically according to its surrounding conditions. Magnetic compression technique (MCT) can be applied to the anastomosis between two hollow organs based on the noncontact magnetism from two magnets. As far, based on MCT, there were repor ts about vascular anas tomosis , choledochojejunostomy, and gastroenteric anastomosis continuously. It is a simple and effective method which can accomplish many kinds of anastomoses with no suture. Most of all, it can finish the one-stage anastomosis even when the tissues are inflammatory. This time, the MCT is successfully applied to repair of RVF. The details are as follows. A 38-year-old female’s chief complaint was that she received vaginal tightening surgery for 2 years with vagina defecating stool-like object. Two years ago, the patient received vaginal tightening surgery for her flabby vagina. One week after the operation, she found there was gas defecated via vagina with stool. Then she was diagnosed with rectovaginal fistula. One year ago, she was operated on to repair the rectovaginal fistula. Unfortunately, the symptom above recurred 1 week after the operation. Six months ago, the patient received the same repair operation which turned to be a failure that the rectovaginal fistula appeared again 1 week after the second repair operation. The two repair operations both failed to close the fistula. Now, the patient came to the hospital for a radical therapy. The physical examination was done. At the lithotomy position, at the direction of 7 o’clock, 2 cm far from the bottom of vagina, there was a 2-mm in diameter fistula, which is firm and solid, with tissue around the boarder red and swollen and granulation tissue hypertrophying but without apparent inflammatory exudate. The body and the neck of uterus and the adnexa of the uterus were all normal. Considering the experience of the two former operations, we decided to repair the fistula with magnet compression technique. The entire study was carried out in strict accordance with protocols approved by the Medical Ethics Committee of The First Affiliated of Xi’an Jiaotong University (Permit Number: 2014-57). We designed an embowedmagnet which is 50 mm in length, 12 mm in chord length, and 4 mm thick in accordance with the size of the fistula. The magnet is made from N45 neodymium-iron-boron permanent magnet and covered with titanium nitride coating. The magnet weighs 7.81 g. And the magnetic intensity is 3400GS. Xiao-Peng Yan and Yu-Liang Zou contributed equally to this work.

The FIB-4 score predicts postoperative short-term outcomes of hepatocellular carcinoma fulfilling the milan criteria.

BACKGROUND The fibrosis score 4 (FIB-4) score is a useful tool to determine the degree of hepatic fibrosis. Liver fibrosis and cirrhosis are well-known predictors of postoperative complications after hepatectomy. This study examined the impact of FIB-4 on postoperative short-term outcomes of patients with hepatocellular carcinoma (HCC). METHODS Three hundred and fifty patients undergoing hepatectomy for HCC between 2008 and 2013 were enrolled. The receiver operating characteristic (ROC) curve analysis was performed to determine the cutoff value of the FIB-4. Univariate and multivariate analysis was performed to identify the risk factors. The correlation of the preoperative FIB-4 value with clinicopathological parameters was examined. RESULTS Postoperative complications were observed in 202 (57.7%) patients. The optimal cutoff value of the FIB-4 was set at 2.88 and 3.85 for postoperative complications and intraoperative blood loss respectively. It was also an independent prognostic factor for postoperative complications (hazard ratio [HR], 1.202; 95% CI, 1.076-1.344; P = 0.001) and intraoperative blood loss (HR, 1.196; 95% CI, 1.091-1.343; P < 0.001) by multivariate analysis. The FIB-4 was significantly correlated with age, liver function, coagulation function, blood loss, intraoperative blood transfusion (all P < 0.05). CONCLUSION Preoperative FIB-4 is a useful index to predict postoperative outcomes in patients with HCC. The FIB-4 should be assessed routinely for hepatocellular carcinoma patients.

Collagen I promotes hepatocellular carcinoma cell proliferation by regulating integrin β1/FAK signaling pathway in nonalcoholic fatty liver

Nonalcoholic fatty liver disease (NAFLD) has become a major risk factor for hepatocellular carcinoma (HCC) worldwide. However, the underlying mechanism remains insufficiently elucidated. The expression of Collagen I, an important component of extracellular matrix (ECM), was increased during the progression from simple steatosis to NASH. The purpose of this study was to investigate the role of Collagen I in NAFLD-related HCC. To study this, the decellularized liver matrix, which preserves the pathological changes of ECM, was prepared from the human fatty liver (FLM) and human normal liver (NLM). HepG2 cells cultured in FLM had a higher proliferation rate than those in NLM. SMMC-7721 and HepG2 cells cultured on Collagen I-coated plates grew faster than those on either Collagen IV- or fibronectin-coated plates. This effect was dose-dependent and associated with elevated integrin β1 expression and activation of downstream phospho-FAK. Knocking down the expression of integrin β1 significantly decreased the proliferation of HCC cells. Additionally, an orthotopic tumor model was established in NAFLD mice at different stages. The over-expressed Collagen I in the mice liver increased the expression of integrin β1 and downstream phospho-FAK, resulting in the proliferation of HCC cells. This proliferation could be inhibited by blocking the integrin β1/FAK pathway. In summary, our study demonstrated that Collagen I promoted HCC cell proliferation by regulating the integrin β1/FAK pathway. Decellularized liver matrix can be used as a platform to three-dimensionally culture HCC cells and reproduce the impact of changed ECM on the progression of NAFLD-related HCC.

Splenorenal shunt via magnetic compression technique: a feasibility study in canine and cadaver

Abstract Introduction: The concept of magnetic compression technique (MCT) has been accepted by surgeons to solve a variety of surgical problems. In this study, we attempted to explore the feasibility of a splenorenal shunt using MCT in canine and cadaver. Material and methods: The diameters of the splenic vein (SV), the left renal vein (LRV), and the vertical interval between them, were measured in computer tomography (CT) images obtained from 30 patients with portal hypertension and in 20 adult cadavers. The magnetic devices used for the splenorenal shunt were then manufactured based on the anatomic parameters measured above. The observation of the anatomical structure showed there were no special structural tissues or any important organs between SV and LRV. Then the magnetic compression splenorenal shunt procedure was performed in three dogs and five cadavers. Seven days later, the necrotic tissue between the two magnets was shed and the magnets were removed with the anchor wire. Results: The feasibility of splenorenal shunt via MCT was successfully shown in both canine and cadaver, thus providing a theoretical support for future clinical application.

Racial disparities in the survival time of patients with hepatocellular carcinoma and intrahepatic cholangiocarcinoma between Chinese patients and patients of other racial groups: A population‑based study from 2004 to 2013

The aim of the present study was to investigate the racial disparities in the presentation, treatment and survival time of patients with hepatocellular carcinoma (HCC) or intrahepatic cholangiocarcinoma (ICC) between Chinese and other racial groups from the Surveillance, Epidemiology, and End Results (SEER) database between January 1st 2004, and December 31st 2013. Key covariates, including clinical presentation, treatment and survival time, were recorded and compared, demonstrating the racial differences. Kaplan-Meier analysis and Cox regression models were performed to identify these disparities in survival time. A total of 30,954 patients were identified in the SEER database. Among these, 27,767 (89.7%) had HCC and 3,187 (10.3%) had ICC. In the HCC cohort, Chinese patients had the highest survival time. Compared with the mortality risk of Chinese patients, the mortality risk of Other Asian, non-Hispanic white, Hispanic and African-American patients increased by 16.8, 35.1, 28.3 and 33.3%, respectively. Compared with other groups, Chinese patients were more likely to present with localized stage, and without vascular invasion, adjacent invasion and metastasis. In the ICC cohort, the Chinese group had improved survival time, compared with the other groups following univariate analysis, although no significant differences were observed between Chinese and Other Asian and Hispanic patients following adjusting for contributing factors. Furthermore, there was no significant differences in the presentation between the groups, which differed from the HCC analysis. In conclusion, race/ethnicity was a significant independent prognostic factor in the HCC cohort, whereas it was not significant in the ICC cohort. The synergistic effect of contributing factors, including demographic, socioeconomic, biological and treatment differences, caused the racial disparity observed in primary liver cancer survival time.

Operation or non-operation: strategy of managing multi-magnets in digestive tract

Dear Editor: If there is a single magnet swallowed into one’s digestive tract, it can be discharged by human body, which needs no surgical intervention. However, if there are multi-magnets in the same situation, it is a consensus that the sooner the operation is done, the better result will be gotten. But is it really that simple? We report a case that multi-magnets were discharged without any surgical intervention. The patient was a 29-year-old male who complained that he swallowed eight magnets by accident 3 h ago. He had no relevant symptoms and signs during physical examination. X-ray of abdomen showed there was a high-density foreign body in stomach. Combing the sample of the magnet and interpretation of the X-ray, we concluded the foreign body consisted of eight cylindrical magnets attracting each other. What is the strategy? How to pull out the magnets? Whether to do endoscopy or operation or perhaps do nothing? We measured the magnetic sample provided by the patient. The shape of the single magnetic body is cylindrical. The diameter and height is 4 and 5 mm, respectively. Field strength on surface is 2700Gs. The eight magnetic bodies attracting each other formed a whole which was 10 mm×11 mm at maximum size. According to above analysis, we speculated that the probability the eight magnets separate and re-attract to form a new shape was fairly small. Otherwise, the whole magnetic body was quite small. Thus, it was of great probable that the eight magnets can be discharged as a whole by the patient himself. The patient agreed with our nonoperation strategy after understanding the reasons. However, we still require the patient to have a liquid diet in case of the failure, preparing for surgical intervention. X-rays of abdomen were done intermittently to check the position of the magnets. After 48 h, the magnets had passed the ileocecum. Then, the patient returned to the normal diet. After 73 h, the patient discharged the eight magnets. Many previous articles reported it is better to operate early when there are several magnets in digestive tract in order to avoid the complication of obstruction, perforation, and internal fistula in gastrointestinal tract. Nevertheless, we suggest that doctors should make different decisions based on different situations. I: when the patient swallows several magnets by accident which scatter over the gastrointestinal tract, the internal fistula caused by magnets attracting each other has great probability to occur. Thus, the earlier intervention doctors do, the better recovery patients will get. II: there are two situations when magnets attracting each other form a whole. A: it is possible that the attracted magnets can separate and reform. The intervention should be done as early as possible under this situation. B: the attracted Xiao-Peng Yan and Wen-Yan Liu contributed equally to this work.