Clinicopathological characteristics and prognosis of solid pseudopapillary neoplasm of the pancreas: comparison between tumors ≤5 cm and larger tumors / 南方医科大学学报

<p><b>OBJECTIVE</b>To compare the clinicopathological characteristics and prognosis of patients with small (≤5 cm) solid pseudopapillary neoplasm of the pancreas (SPN) and those with large (>5 cm) SPNs.</p><p><b>METHODS</b>We retrospectively analyzed the clinical characteristics, laboratory findings, radiological features, treatment and prognosis of 148 patients with histologically confirmed SPN between August, 2006 and December, 2014 and compared the data between patients with small SPNs (≤5 cm) and those with large SPNs (>5 cm).</p><p><b>RESULTS</b>In the large SPN group, the female-to-male ratio was significantly higher than that in small SPN group (61/8 vs 56/23, P=0.009) and the patients were significantly younger in large SPN group (28.3±12.3 vs 33.0±11.4 years, P=0.016). Small SPNs (≤5 cm) typically presented as inhomogeneous solid or cystic tumors, while large SPNs (>5 cm) often appeared as homogeneous solid and cystic tumors, but they did not show any significant difference in aggressive behaviors (P=0.288). The 5-year disease-free survival of patients with small SPNs was 100%, and the 1-, 3-, and 5-year disease-free survival of patients with large SPNs was 98.6%, 94.9%, and 89.3%, respectively (P=0.030), showing no significant differences in the overall survival between the two groups.</p><p><b>CONCLUSION</b>Small SPNs and large SPNs have different clinical characteristics. Even with complete resection, tumors larger than 5 cm are more likely to have tumor recurrence and metastasis, and close follow-up is recommended for these patients.</p>

A Single-institution Experience with Open Irreversible Electroporation for Locally Advanced Pancreatic Carcinoma / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Locally advanced pancreatic carcinoma (LAPC) is characterized by poor prognosis despite recommended concurrent chemoradiotherapy. Irreversible electroporation (IRE) has emerged as a potential option for the management of unresectable pancreatic cancer. This study was conducted to evaluate the safety and short-term efficacy of open IRE for the treatment of LAPC.</p><p><b>METHODS</b>Retrospective data of 25 consecutive patients receiving IRE for T3 lesions from July 2015 to June 2016 at a single center were analyzed. The perioperative and long-term IRE-related complications were reviewed to evaluate the safety of the procedure. The tumor reduction and biological response were analyzed through computed tomography/magnetic resonance imaging; the serum level of CA19-9 was measured as a secondary endpoint to evaluate the short-term efficacy of IRE.</p><p><b>RESULTS</b>All patients were successfully treated; the median tumor size was 4.2 cm and the median IRE time was 36 min. Four intraoperative procedure-related complications were observed (16%): two transient hypertensive episodes, one hypotension case, and one transient supraventricular tachycardia case. Nine postoperative complications were described, including three Grade A pancreatic fistulas, three delayed gastric emptying, one acute pancreatitis, one upper gastrointestinal hemorrhage, and one portal vein thrombosis. The overall rate of stable disease was 28%, 36% achieved partial response, and lower serum CA19-9 levels were recorded in all patients at discharge.</p><p><b>CONCLUSIONS</b>IRE is feasible for the treatment of LAPC and is a reasonable intervention strategy owing to its combined attributes of safety and efficacy.</p>

The therapeutic mechanisms of sirolimus treatment for ischemic-type biliary lesions after liver transplantation / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the pathogenesis of ischemic-type biliary lesions (ITBLs) in post-liver transplant patients and the possible therapeutic mechanisms of sirolimus.</p><p><b>METHODS</b>The clinic data of 32 post-liver transplant patients with ITBLs from May 2004 to December 2010 was analyzed. There were including 25 male and 7 female patients with a median age of 46 years (ranging from 19 to 61 years). Patients were divided into those who received sirolimus (sirolimus group) and those who did not (control group). The expression of IL-2, FoxP3, and IL-10 in the portal area, liver function indexes, and bile duct injury score were assessed pre-ITBL, when ITBLs were identified, and after 6 months of sirolimus treatment.</p><p><b>RESULTS</b>Compared with pre-ITBL optical density (OD) values, there was a significantly increase in IL-2 OD(0.138 ± 0.050 in control group and 0.141 ± 0.052 in sirolimus group), but not FoxP3 and IL-10 OD in both groups at the time ITBLs were diagnosed. After 6 months of treatment, the IL-2, FoxP3, and IL-10 OD values in the control group were not different from those when ITBLs were diagnosed. There was a significant reduction in post-therapy IL-2 OD(0.107 ± 0.043, t = 2.087, P = 0.044), and a significant elevation in FoxP3(0.213 ± 0.039) and IL-10 OD(0.187 ± 0.048) in sirolimus group as compared with those when ITBLs were diagnosed(t = -3.822 and -4.350, both P < 0.01). There was a significant increase in serum levels of ALT, AST, total bilirubin, γ-glutamyl transpeptidase and ALP at the time ITBLs were diagnosed compared with pre-ITBL levels in both groups. After 6 months of treatment, the above indexes had not changed in the control group, but significantly improved in the sirolimus group, and the bile duct injury score in the sirolimus group had significantly decreased(4.4 ± 2.4, Z = -2.568, P = 0.010). The 1-year and 3-year graft survival rates in the control group were 6/13 and 5/13, respectively, and 17/19 and 13/19, respectively, in the sirolimus group (χ(2) = 7.166, P = 0.007; χ(2) = 5.398, P = 0.020, respectively).</p><p><b>CONCLUSIONS</b>Sirolimus can downregulate IL-2 expression and upregulate FoxP3 and IL-10 expression, thereby stimulating FoxP3+ Treg cells, suppressing immunopathological damage, and promoting epithelial repair in bile ducts.</p>

A quantitative real time polymerase chain reaction for detection of HBV covalently closed circular DNA in livers of the HBV infected patient / 中华流行病学杂志

Objective To establish and optimize a sensitive and specific quantitative realtime polymerase chain reaction(PCR)method for detection of hepatitis B virus covalently closed circular DNA(HBV cccDNA)in liver tissue. Methods Specific primers and probes were designed to detect HBV DNA(tDNA)and cccDNA. A series of plasmids(3.44 × 100-3.44 × 109 copies/μl)containing a full double-stranded copies of HBV genome(genotype C)were used to establish the standard curve of real-time PCR. Liver samples of 33 patients with HBV related hepatocellular carcinoma(HCC), 13 Chronic hepatitis B patients(CHB)and 10 non-HBV patients were collected to verify the sensitivity and specificity of the assay. A fraction of extracted DNA was digested with a Plasmid-Safe ATP-dependent Dnase(PSAD)for HBV cccDNA detection and the remaining was used for tDNA and β-globin detection. The amount(copies/cell)of HBV cccDNA and tDNA were measured by a real-time PCR, using β-globin housekeeping gene as a quantitation standard. Results The standard curves of real-time PCR with a linear range of 3.44 × 100 to 3.44 × 109 copies/μl were established for detecting HBV cccDNA and tDNA, and both of the lowest detection limits of HBV cccDNA and tDNA were 3.44 × 100 copies/μl. The lowest quantitation levels of HBV cccDNA in liver tissues tested in 33 HBV related HCC patients and 13 CHB patients were 0.003 copies/cell and 0.031copies/cell, respectively. HBV cccDNA and tDNA in liver tissue of 10 non-HBV patient appeared to be negative. The true positive rate was increasing through the digestion of HBV DNA by PSAD, and the analytic specificity of cccDNA detection improved by 7.24 × 102 times. Liver tissues of 2 patients were retested 5 times in the PCR for detecting cccDNA and the coefficience of variations on cycle threshold (Ct)were between 0.224%-0.609%. Conclusion A highly sensitive and specific quantitative real time PCR method for the detection of HBV cccDNA in liver tissue was established and could be used for clinical and epidemiological studies.

Immunosuppressant dexamethasone can significantly extend the expression of hepatitis B virus antigens in the HBV mouse model by hydrodynamic transfection method / 病毒学报

To develop a HBV infection mouse model by hydrodynamic-based transfection and further to optimize the method of development of HBV infection mouse model. We first developed a construct which contained inverted terminal repeat elements (ITR) of adeno-associated virus (AAV) and 1. 3 copies of HBV genome (ayw subtype). The pAAV-HBV1. 3 DNA was then injected hydrodynamically into the tail veins of C57BL/6 mice in 5 seconds. The virus load in serum and liver was assayed by ELISA and Real-time PCR. The expression of virus antigen and the pathologic changes of liver were analyzed by HE and immunohistochemical staining. Meanwhile, to develop HBV transfected immunosuppressied mouse, mice were injected intraperitoneally triple with 0.2 ml dexamethason (50 mg/kg) every two days before HBV transfection. The levels of HBsAg and HBeAg were assayed by ELISA. Our data showed: (1) HBsAg and HBeAg were positive (100%) in serum and liver of experimental normal mouse at day 10 after HBV transfection, and became negative at day 30 and day 60. Meanwhile the viral load in serum and liver in experimental group was significantly higher than that in control group at day 10, 30 and 60 after HBV transfection (P < 0.01, P < 0.05, respectively). (2) HBsAg and HBeAg in serum in immunosuppressed mouse model were positive until 60 days. In conclusion, a HBV infection mouse model was developed successfully by hydrodynamic-based transfection. By suppressing the immune status of mice injected with dexamethasone, the expression of HBV antigens was extended longer than that in normal adult mice. These models pave a way for HBV research and evaluation of HBV vaccine and drug development.

Emergency right lobe adult-to-adult live-donor liver transplantation for the treatment of acute liver failure following severe hepatitis / 中华外科杂志

<p><b>OBJECTIVE</b>To research the clinical feasibility of emergency right lobe adult-to-adult live-donor liver transplantation in treating acute liver failure following severe hepatitis.</p><p><b>METHODS</b>Consecutive ten severe hepatitis patients (4 acute-on-chronic severe hepatitis and 6 acute severe hepatitis; 9 caused by HBV and 1 with drug-induced acute liver failure) underwent emergency right lobe adult-to-adult live-donor liver transplantation in our hospital from April 2007 to December 2007. The +/- s of model for end-stage liver disease score was 33.22 +/- 6.55. The outcomes of these recipients were prospectively analyzed.</p><p><b>RESULTS</b>Among them, 8 ABO blood group were identical and 2 compatible. One was Rh sub-group negative. Except 2 recipients died (1 acute renal failure caused by veno cava thrombosis, 1 liver graft lose caused by hepatic artery thrombosis), the rest of recipients (80%) and all donors were safe. The mean graft-to-recipient weight ratio was (1.19 +/- 0.14)%, and graft volume to recipient estimated standard liver volume ratio was (65.13 +/- 8.75)%. Right lobe grafts with middle hepatic vein (MHV) 3 cases, without MHV 4 cases, without MHV but followed by V and VIII hepatic vein outflow reconstruction 3 cases. Encouraging outcome was achieved in this group of recipient: elevated serum creatinine, serum endotoxin, decreased serum prothrombin activity (PTA) and total bilirubin returned to normal about on postoperative day (POD) 3, POD 7, POD 14 and POD 28, respectively.</p><p><b>CONCLUSIONS</b>Outcomes of emergency right lobe adult-to-adult live-donor liver transplantation for acute hepatic failure following severe hepatitis are fairly encouraging and acceptable. emergency right lobe adult-to-adult live-donor liver transplantation is an effective and life-saving modality for acute liver failure following severe hepatitis.</p>

Prophylaxsis against recurrance of hepatitis B virus after liver transplantation / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To summarize the clinical data in preventing HBV recurrence after liver transplantation and explore a optimal individual protocol in prophylaxis of HBV recurrence.</p><p><b>METHODS</b>We retrospected outcomes in 195 recipients who underwent a liver transplantation for HBV-related liver disease between June 2004 and July 2008. According to the anti-virus protocol these recipients are divided into two groups as following: group A received a protocol of combination treatment of lamivudine with HBIG, and group B with combination treatment of adefovir with HBIG. With mean follow-up of 23.7 months, HBV recurrent rate was observed in overall and each group separately.</p><p><b>RESULTS</b>A total of 195 liver transplant recipients were identified that met the study criteria. At the sixth and eleventh month after operation, HBV recurrence appeared in 2 recipients, each in two groups, which were due to LAM cessation and HBV mutation respectively. Recurrent rate was 0.6% in group A, 3.7% in group B and 1% in total. There was no significant difference in HBV recurrent rate between group A and B.</p><p><b>CONCLUSION</b>Lamivudine combined with HBIg should be considered as a reliable method in preventing HBV recurrence after liver transplantation. Better outcomes can be achieved by individual anti-virus protocol and HBIg administration according to HBV status in recipient.</p>

Enhancing active immunity against hepatitis B virus by HBV vaccine immunization in patients with HBV-related end-stage liver diseases treated with liver transplantation / 中华肝脏病杂志

<p><b>OBJECTIVES</b>To study the active immunity response of liver transplant patients for HBV-related diseases after hepatitis B virus (HBV) vaccine immunization and to investigate the factors that influence the effectiveness of the vaccination in order to find measures to increase its success.</p><p><b>METHODS</b>Thirteen patients who had liver transplants because of HBV-related end-stage liver diseases received hepatitis B virus immunoglobulin and lamivudine for an average of 38 months (range 27-77 months). They received double intramuscular doses (40 microg) of a recombinant vaccine at months 0, 1, 2 and 6. The anti-HBs titers were tested regularly at months 1, 2, 3, 6 and 7.</p><p><b>RESULTS</b>Seven of the 13 patients (53.8%) developed higher serum titers of anti-HBs compared with their titers prior to the vaccinations, 2 patients of the 13 (15.4%) developed an increase by 100 U/L and in 4 patients (30.8%) their base levels were doubled. Those responding patients were followed-up for another 8 months after the fourth vaccination, and only 1 patient among them had a decrease of the anti-HBs titers below the level prior to the vaccination.</p><p><b>CONCLUSION</b>Hepatitis B vaccine immunization can be used to enhance the active immunity against HBV in patients who had liver transplants for HBV-related diseases.</p>

Establishment of hepatocellular carcinoma multidrug resistant monoclone cell line HepG2/mdr1 / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The multidrug resistance (MDR) associated with the expression of the mdr1 gene and its product P-glycoprotein is a major factor in the prognosis of hepatocellular carcinoma cell (HCC) patients treated with chemotherapy. Our study was to establish a stable HCC MDR cell line where a de novo acquisition of multidrug resistance specifically related to overexpression of a transgenic mdr1.</p><p><b>METHODS</b>The 4.5-kb mdr1 cDNA obtained from the plasmid pHaMDR1-1 was cloned into the PCI-neo mammalian expression vector, later was transferred by liposome to human hepatocarcinoma cell line HepG2. Then the transfected HepG2 cells resisting G418 were clustered and cultured and the specific fragment of mdr1 cDNA, mRNA and the P-glycoprotein (Pgp) in these HepG2 cells were detected by PCR, RT-PCR and flow cytometry, respectively. The accumulation of the daunorubicin was determinated by flow cytometry simultaneously. The nude mice model of grafting tumour was established by injecting subcutaneously HepG2/mdr1 cells in the right axilla. When the tumour diameter reached 5 mm, adriamycin was injected into peritoneal cavity. The size and growth inhibition of tumour were evaluated.</p><p><b>RESULTS</b>The mdr1 expression vector was constructed successfully and the MDR HCC line HepG2/mdr1 developed. The PCR analysis showed that the specific fragment of mdr1 cDNA in HepG2/mdr1 cells, but not in the control group HepG2 cells. Furthermore, the content of the specific fragment of mdr1 mRNA and Pgp expression in HepG2/mdr1 cells were (59.7 +/- 7.9)% and (12.28 +/- 2.09)%, respectively, compared with (16.9 +/- 3.2)% and (3.07 +/- 1.06)% in HepG2 cells. In the nude mice HCC model, the tumour genes of both groups were identified. After ADM therapy, the mean size of HepG2 cell tumours was significantly smaller than HepG2/mdr1 cell tumours.</p><p><b>CONCLUSION</b>The approach using the transfer of mdr1 cDNA may be applicable to the development of MDR hepatocarcinoma cell line, whose MDR mechanism is known. This would provide the experimental basis of MDR research.</p>

An analysis of long term prophylaxis of virus recurrence with antiviral treatment in HBV infected liver transplant recipient patients / 中华肝脏病杂志

<p><b>OBJECTIVE</b>No optimal prophylactic protocol of hepatitis B immunoglobulin (HBIG) combined with nucleos(t)ide analogue for HBV recurrence has been established yet. By investigating the alterations of HBV markers in HBV related liver disease patients, recipients of a liver transplant, under lamivudine or/and HBIG prophylaxis, we aim to explore the possible HBV recurrence mechanism involved and to find a new option in the prophylaxis of HBV recurrence and to tailor individualized therapy.</p><p><b>METHODS</b>Serial liver biopsy specimens and sera were obtained intraoperationally and at definite time points during follow-up. ELISA and chemiluminescent microparticle immunoassay, HBV DNA fluorescent quantification, immunohistochemistry staining and HBV DNA in situ hybridization were performed. Alterations of HBV markers in specimens of 96 liver transplant recipients were investigated retrospectively.</p><p><b>RESULTS</b>All 17 cases had HBV recurrence (median 37 months) which occurred in the follow-up period after liver transplantation. The overall actual HBV recurrence rate at 2 years was 22% with a significant difference between that of the active and inactive groups (P<0.05); 82.4% HBV recurrence took place within the first 3 years after the operation, and the recurrence ratio of first 3 years to 3 years later after transplantation was 4.7 (P<0.01). The HBV DNA positive patients accounted for 78.6% of the total number of recurrences within the first 3 years. HBcAb and HBeAb positive rates went down with time, but their positivity remained.</p><p><b>CONCLUSION</b>HBV recurrence happens after liver transplantation. In inactive HBV replicative patients with strictly combined prophylaxis and availability of other medications and using 3 years after liver transplantation as a point of time, we think that tapering down the dosage of HBIG and tailoring individualized treatment methods based on virological and immunological situations of each recipient are worth trying.</p>

Liver transplantation for chronic hepatitis B patients with lamivudine monotherapy or lamivudine combined with individualized low-dose hepatitis B immunoglobulin treatment / 中华肝脏病杂志

<p><b>OBJECTIVE</b>The aim of this study was designed to evaluate the outcomes of liver transplant recipients with chronic hepatitis B (CHB) receiving either lamivudine monotherapy or lamivudine combined with individualized low-dose hepatitis B immunoglobulin (HBIG) therapy.</p><p><b>METHODS</b>A total of 111 liver transplant recipients with CHB were divided not randomly into two groups according to the availability of HBIG before liver transplantation (LT). Thirty-two patients received lamivudine monotherapy (100 mg/d) and 79 patients received lamivudine (100 mg/d) combined with individualized low-dose HBIG (intramuscular administration) to maintain the titer of antibody to hepatitis B virus (HBV) surface antigen (anti-HBs) not less than 100 U/L. The patients were followed-up for a median time of 32 months (1 to 88 months).</p><p><b>RESULTS</b>In the lamivudine monotherapy group, 5 patients hepatitis B relapsed (3/5 developed YMDD mutants of HBV), with 1-, 2-, and 3-year cumulative recurrence rates of 7.1%, 14.3% and 17.9% and survival rates of 87.5%, 84.4% and 74.6%. In the lamivudine and HBIG combination therapy group, 2 patients hepatitis B relapsed (2/2 developed YMDD mutants of HBV), with 1-, 2-, and 3-year cumulative recurrence rates of 0, 1.8% and 5.7% (P < 0.01) and survival rates of 83.5%, 80.9% and 77.6% (P > 0.05).</p><p><b>CONCLUSIONS</b>Compared with lamivudine monotherapy, lamivudine combined with individualized low-dose HBIG can further reduce the recurrence risk of hepatitis B in liver transplant recipients. This combined therapy could be used as a rational strategy for prophylaxis of hepatitis B recurrence in such patients.</p>

Diagnosis and treatment of bacterial pneumonia in liver transplantation recipients: report of 33 cases / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Bacterial pneumonia in the recipients of liver transplantation (LTX) is a common postoperative complication influencing the prognosis greatly. In this article, the diagnosis and treatment of bacterial pneumonia in 33 LTX recipients are reported.</p><p><b>METHODS</b>From February 1999 to January 2003, a total of 103 patients underwent allogeneic LTX at our center; afterwards, a retrospective analysis was made on their postoperative clinical manifestations, including symptoms (expectoration, panting and fever), sign (rale), results of laboratory examinations (white blood cell count and sputum culture of tracheal secretions or pleural fluid culture), and chest X-ray films. The following data of the pneumonia and non-pneumonia groups were collected, and the rank sum test (SPSS 11.0, Wilcoxon's method) was used to analyze the duration of postoperative respirator utilization and the volume of pleural effusion through pleurocentesis or pleural drainage.</p><p><b>RESULTS</b>In the 103 patients, 33 experienced 53 episodes of bacterial pneumonia during their hospital stay after transplantation, 14 of them (42.42%) had more than three manifestations of the seven mentioned above. The pathogens causing bacterial pneumonia included Pseudomonas aeruginosa (17.48%), Klebsiella pneumoniae (15.53%), Acinetobacter baumannii (10.68%), and Staphylococcus aureus (7.77%). Amilkacin, tienam, ciprofloxacin, vancomycin, etc. were the antibiotics of choice against those bacteria. Acute rejection occurred during the treatment of bacterial pneumonia in 16 patients, and 5 of them died. Wilcoxon's rank sum test of the data indicated that the pneumonia group had longer duration of postoperative ventilator treatment and larger volume of pleural effusion than the non-pneumonia group (P < 0.05).</p><p><b>CONCLUSIONS</b>The clinical manifestations of pneumonia after LTX might be atypical, and special attention should be paid to the respiratory symptoms and signs within 2 months after LTX. Whenever the diagnosis of bacterial pneumonia is confirmed, consideration should be given to reasonable use of antibiotics and regulation of immunity in addition to other routine therapies.</p>

Investigation on the alteration of hepatitis B virus (HBV) markers in liver allograft of HBV related recipients in perioperative period / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the alteration of HBV markers in liver allograft of HBV related recipients pre and post liver transplantation under Lamivudine or combination of Lamivudine with HBIG prophylaxis and explore the mechanism of HBV de nova infection in liver allograft after orthotopic liver transplantation, as well as seek to establish a optimal prophylactic protocol.</p><p><b>METHODS</b>The serial liver biopsy specimens of 90 liver allograft and sera of 78 liver transplant recipients during operation and after 1 week, 1 month, 3 months, 6 months, 12 months, 24 months post transplantation have been collected and detected for HBV markers with enzyme-linked radioimmunoassay, fluorescent quantitative assay for HBV-DNA in serology and with immunohistochemistry stain, HBV-DNA in situ hybridization in histology for detection of HBV markers in liver allograft samples.</p><p><b>RESULTS</b>Whether recipients with active replicative or inactive replicative HBV preoperatively, none of positive HBV-DNA, HBsAg and HBcAg in 100% liver biopsy specimens with HBV-DNA hybridization in situ and immunohistochemistry stains in histology within 2 hours after reperfusion.</p><p><b>CONCLUSION</b>Whatever HBV replicative status the recipients have before surgery, no evidence of HBV particles direct invasion to the liver allograft from HBV related cirrhotics during operation under current prophylactic measures. However, the further supposed mechanism and its significance in HBV de nova infection of liver allograft remained to be disclosed further.</p>

Diagnosis and treatment of lung aspergillosis after liver transplantation / 中华外科杂志

<p><b>OBJECTIVE</b>To assess the diagnosis and treatment of invasive lung aspergillosis after liver transplantation.</p><p><b>METHODS</b>Routine sputum culture was performed. Itraconazole and fluconazole were used to prevent fungal infection prophylactically. Amphyotericin B was only used on aspergillosis. In 54 patients receiving, liver transplantation, 3 patients with lung aspergillosis were reviewed.</p><p><b>RESULTS</b>Of the 3 patients 2 died and 1 recovered.</p><p><b>CONCLUSIONS</b>Over-immunosuppression is a main risk factor for aspergillosis. Amphotericin B is still the best choice for the treatment of aspergillosis and its gradual, interrupted, low concentration administration, cooperated with itraconazole can ease the side effects.</p>