Dynamics of cellular immune responses in recipients of renal allografts positive for hepatitis B surface antigen.

BACKGROUND/PURPOSE: Hepatitis B surface antigen (HBsAg)-positive renal transplantation recipients must take lifelong immunosuppressants and nucleotide analogues (NAs). We investigated the cellular immune responses of HBsAg-positive renal transplantation recipients taking immunosuppressants and NAs. METHODS: Blood samples were collected from HBsAg-positive individuals with end-stage renal disease on the transplant waiting list (Group 1) and renal transplantation recipients taking immunosuppressants and NAs (Group 2) or immunosuppressants without NAs (Group 3). Hepatitis B virus (HBV)-specific pentamers were used to quantify circulating HBV-specific CD8+ T cells. RESULTS: Groups 2 and 3 had higher cellular immune responses, as indicated by significantly lower regulatory T (Treg)/CD8+ T cell ratios than Group 1. With undetectable viral loads under both immunosuppressant and NAs, the CD8+ T cell and HBV-specific CD8+ T cell frequencies were similar in Group 2 and Group 1. Patients in Group 3 did not use NAs and had an elevated viral load and higher HBV-specific CD8+ T cell and IFN-γ-producing HBV-specific CD8+ T cell frequencies, but lower a frequency of programmed death-1 (PD-1)+ HBV-specific CD8+ T cells than the other groups. Increased viral replication in Group 3 resulted in significantly higher CD8+ T cell and IFN-γ-producing CD8+ T cell frequencies than Group 1. CONCLUSION: Immunosuppressant therapy increases viral replication in HBsAg-positive renal transplant recipients due to disabling or dysregulation of virus-specific CD8+ T cells. The higher cellular immune responses due to lower Treg/CD8+ T cell ratios in HBsAg-positive renal transplant recipients may be one of the reasons to induce liver pathology because of uncontrolled viral replication.

Prognostic significance of positive surgical margins for scalp angiosarcoma.

BACKGROUND: Scalp angiosarcomas (AS) are aggressive soft tissue sarcomas that present with outcomes different from other AS of the head and neck region. Due to the rarity of the disease, limited data on the clinical outcome of scalp AS are available. In particular, the prognostic significance of surgical margins remains controversial and the impact of margin status on survival has not been documented. METHODS: We retrospectively reviewed 41 scalp AS patients, including 30 patients with localized disease and 11 patients with initial distant metastasis, treated in our institution between 1997 and 2017. Survival was determined by Kaplan-Meier analysis. In the 30 patients without distant metastasis (localized disease), univariate and multivariate analysis using the Cox proportional hazards model were used to determine clinicopathologic characteristics associated with recurrence free survival (RFS), locoregional control (LRC), and overall survival (OS). RESULTS: Totally 41 patients diagnosed with scalp AS were identified, including 30 patients with localized disease and 11 patients with initial distant metastasis on diagnosis. Overall, the median follow-up period was 19.3 (range 0.3-128.5) months. The median survival time was 16.6 (range 0.3-144.3) months and the 5-year OS (95% Confidence Interval (CI)) rate was 22% (12%-42%). In the 30 patients with localized disease, univariate analysis showed that positive margins, either lateral-side or deep-side, were significant prognostic factors for RFS, LRC, and OS (p < 0.05). On multivariate analysis, positive margins emerged as adverse prognostic factors for RFS (Hazard Ratio (HR) 4.29, 95% CI, 1.71-10.75, p = 0.002), LRC (HR 6.35, 95% CI, 2.19-18.37, p = 0.001), and OS (HR 4.73, 95% CI, 1.71-13.07, p = 0.003). CONCLUSION: Scalp AS is associated with high local recurrence rates and poor survival outcomes. Positive surgical margins are adverse prognostic factors for survival.

Telbivudine for renal transplant recipients with chronic hepatitis B infection: a randomized controlled trial with early termination.

BACKGROUND: The aim of this study was to analyze changes in renal function in HBsAg-positive renal transplant recipients receiving lamivudine who did or did not switch to telbivudine. METHODS: In this prospective randomized clinical trial (RCT), HBsAg-positive renal transplant recipients who had received lamivudine prophylaxis for at least 6 months were 1:2 randomized to receive either lamivudine or telbivudine for another 24 months. Renal function was evaluated by creatinine level and estimated glomerular filtration rate (eGFR) at the time of randomization (baseline), 6, 12, 18, and 24 months respectively. RESULTS: This RCT was prematurely terminated after recruiting only 17 patients due to a high incidence (61.5%; 8/13) of clinical myalgia in the telbivudine group. Cox's proportional hazards model revealed that there was no independent predictor of myalgia. Based on intention-to-treat and per protocol analyses using generalized estimating equations, the patients in the randomized telbivudine group had a significantly increased eGFR and the patients in the lamivudine group had a significantly decreased eGFR at the end of follow-up compared to the values at study enrollment. However, there was no significant difference between the lamivudine and telbivudine groups. CONCLUSIONS: The renal protective effect of telbivudine for HBsAg positive renal transplant recipients was uncertain for high incidence of myalgia and only patients who were on telbivudine for 24 months had renal function maintenance.

The impacts of intra-arterial chemotherapy on head and neck microvascular reconstruction.

BACKGROUND: For locally advanced head and neck cancers, intra-arterial (IA) chemotherapy is utilized for locoregional control with favorable results. The study aimed to evaluate the surgical outcomes of microsurgical reconstruction in head and neck cancer patients with IA chemotherapy METHODS: This cohort study retrospectively reviewed patients who underwent head and neck microsurgical reconstruction from January 2014 to August 2018. Patients with prior history of chemotherapy were included and categorized into two groups according to history of IA chemotherapy (IA group)/intravenous chemotherapy (IV group). Flap survival was evaluated along with microsurgical revision rates and complications. Recipient vessel specimens were analyzed by histological examination. A 1:1 propensity score matched analysis was performed. RESULTS: The study cohort included 45 patients with IA chemotherapy and 201 patients with IV chemotherapy. After propensity score matching, the difference in total flap loss and microsurgical revision rates were nonsignificant between two groups. However, the IA group had significantly higher rates of arterial thrombosis (Odds ratio [OR] 4.98; 95%CI, 1.28-19.38; p = 0.021), wound-related complications (OR 3.30; 95%CI, 1.21-9.02; p = 0.02) and revision surgery within one month (OR 3.73; 95%CI, 1.10-12.64; p = 0.035). Based on histology, IA group vessels showed a higher intima/media ratio than the IV group (0.45 ± 0.06 versus 0.23 ± 0.03, p = 0.02) CONCLUSION: Despite treating local advanced head and neck cancers with good results, IA chemotherapy may cause subsequent deleterious effects on local tissue due to the high concentration of cytotoxic chemotherapeutic agents. Surgeons should be cautious in selection of recipient vessels when performing microvascular reconstruction.

B-Cell Activating Factor Enhances Hepatocyte-Driven Angiogenesis via B-Cell CLL/Lymphoma 10/Nuclear Factor-KappaB Signaling during Liver Regeneration.

B-cell activating factor (BAFF) is found to be associated with the histological severity of nonalcoholic steatohepatitis (NASH). BAFF was also found to have a protective role in hepatic steatosis via down regulating the expression of steatogenesis genes and enhancing steatosis in hepatocytes through BAFF-R. However, the roles of BAFF during liver regeneration are not well defined. In this study, C57/B6 mice with 70% partial hepatectomy were used as a liver regeneration model. BAFF expression was determined by enzyme immunoassay, and anti-BAFF-neutralizing antibodies were administered to confirm the effects of BAFF on liver regeneration. Western blotting, immunohistochemistry, and florescence staining determined the expression of B-cell CCL/lymphoma 10 (BCL10). The angiogenesis promoting capability was evaluated after the transfection of cells with siRNA targeting BCL10 expression, and the role of NF-κB was assessed. The results revealed that the BAFF and BCL10 levels were upregulated after partial hepatectomy. Treatment with anti-BAFF-neutralizing antibodies caused death in mice that were subjected to 70% partial hepatectomy within 72 h. In vitro, recombinant BAFF protein did not enhance hepatocyte proliferation; however, transfection with BCL10 siRNA arrested hepatocytes at the G2/M phase. Interestingly, conditioned medium from BAFF-treated hepatocytes enhanced angiogenesis and endothelial cell proliferation. Moreover, Matrix metalloproteinase-9 (MMP-9), Fibroblast growth factor 4 (FGF4), and Interleukin-8 (IL-8) proteins were upregulated by BAFF through BCL10/NF-κB signaling. In mice that were treated with anti-BAFF-neutralizing antibodies, the microvessel density (MVD) of the remaining liver tissues and liver regeneration were both reduced. Taken together, our study demonstrated that an increased expression of BAFF and activation of BCL10/NF-κB signaling were involved in hepatocyte-driven angiogenesis and survival during liver regeneration.

Robotic Versus Open Hepatectomy for Hepatocellular Carcinoma: A Matched Comparison.

BACKGROUND: Robotic hepatectomy has been suggested to be a safe and effective approach for liver disease; however, studies comparing robotic hepatectomy with the conventional open approach regarding oncologic outcomes for hepatocellular carcinoma (HCC) are limited. Accordingly, we performed a matched comparison of surgical and oncological outcomes between robotic and open hepatectomy. METHODS: Between January 2012 and October 2015, a total of 183 patients underwent robotic hepatectomy and 275 patients underwent open hepatectomy by the same surgical team in our center. Eighty-one newly diagnosed HCC cases in each group were compared under propensity score matching (PSM) in a 1:1 ratio. RESULTS: With robotic hepatectomy, the conversion rate was 1.6 % and the complication rate was 4.4 %. On PSM, the groups had a comparable percentage of major liver resections (41.9 vs. 39.5 %) and liver cirrhosis (45.7 vs. 46.9 %). Compared with the open group, the robotic group required longer operation times (343 vs. 220 min), shorter hospital stays (7.5 vs. 10.1 days), and lower dosages of postoperative patient-controlled analgesia (350 vs. 554 ng/kg). The 3-year disease-free survival of the robotic group was comparable with that of the open group (72.2 % vs. 58.0 %; p = 0.062), as was the 3-year overall survival (92.6 vs. 93.7 %; p = 0.431). CONCLUSIONS: This is the first oncological study comparing robotic liver resection for HCC with open resection. Robotic hepatectomy can be applied for challenging major resections in patients with cirrhotic liver disease with less postoperative pain and shorter hospital stays without compromising oncological outcomes.

Targeted Delivery of C/EBPα -saRNA by Pancreatic Ductal Adenocarcinoma-specific RNA Aptamers Inhibits Tumor Growth In Vivo.

The 5-year survival rate for pancreatic ductal adenocarcinoma (PDAC) remains dismal despite current chemotherapeutic agents and inhibitors of molecular targets. As the incidence of PDAC constantly increases, more effective multidrug approaches must be made. Here, we report a novel method of delivering antitumorigenic therapy in PDAC by upregulating the transcriptional factor CCAAT/enhancer-binding protein-α (C/EBPα), recognized for its antiproliferative effects. Small activating RNA (saRNA) duplexes designed to increase C/EBPα expression were linked onto PDAC-specific 2'-Fluropyrimidine RNA aptamers (2'F-RNA) - P19 and P1 for construction of a cell type-specific delivery vehicle. Both P19- and P1-C/EBPα-saRNA conjugates increased expression of C/EBPα and significantly suppressed cell proliferation. Tail vein injection of the saRNA/aptamer conjugates in PANC-1 and in gemcitabine-resistant AsPC-1 mouse-xenografts led to reduced tumor size with no observed toxicity. To exploit the specificity of the P19/P1 aptamers for PDAC cells, we also assessed if conjugation with Cy3 would allow it to be used as a diagnostic tool on archival human pancreatic duodenectomy tissue sections. Scoring pattern from 72 patients suggested a positive correlation between high fluorescent signal in the high mortality patient groups. We propose a novel aptamer-based strategy for delivery of targeted molecular therapy in advanced PDAC where current modalities fail.

Risk factors for complications following immediate tissue expander based breast reconstruction in Taiwanese population.

BACKGROUND/PURPOSE: Breast cancer patients in Asia show considerable disparities from Caucasian patients, such as younger age of onset and lower rates of smoking, obesity, and diabetes. Findings of prior studies regarding risk factors associated with complications in tissue expander may not hold for Asian populations, since most of these studies involved Caucasian patients. In this study, we surveyed risk factors in the Taiwanese population, providing additional evidence about the important differences and discuss the implications for clinical practice. METHODS: Patients who underwent immediate, two-stage, tissue expander breast reconstruction from December 2008 to August 2014 in the National Taiwan University Hospital, Taipei, Taiwan were included. Follow-up observations of all patients were conducted until December 2014. Complications occurring during the tissue expander stage were evaluated. Multivariate regression modeling was used to identify risk factors for complications. RESULTS: A total of 246 consecutive, immediate, smooth round tissue expander placements were performed for breast reconstruction. The most common complication was skin necrosis (4.9%), followed by wound dehiscence (4.1%). In the multivariate model, body mass index (BMI) ≥ 24 kg/m2 was the only risk factor that reached statistical significance (odds ratio: 2.41, 95% confidence interval: 1.17-4.96). CONCLUSION: We provided evidence that racial disparities have an impact on the risk factors for complications associated with tissue expander breast reconstruction. BMI≥24 kg/m2 was the only risk factor significantly associated with complications. Clinically, BMI≥24 kg/m2, rather than the standard definition of obesity (BMI > 30 kg/m2), may be a more suitable cutoff point for risk in patients of Asian ethnicity.

Study of poly-ɛ-caprolactone membranes for pleurodesis.

BACKGROUND/PURPOSE: Pleurodesis with biomaterial membrane is an emerging treatment method for pneumothorax. However, the ideal one for the common disease is still under debate. METHODS: We investigate the Poly-ε-caprolactone (PCL) membrane pleurodesis by using New Zealand White rabbits, which was sacrificed for examination one month later. Moreover, inflammation and fibrosis scoring were done under microscopic evaluation, as well as Western blot analysis in vitro and in vivo. RESULTS: Gross evaluation of pleurodesis score revealed that dense PCL membrane produced moderate pleural adhesion, while porous PCL membrane exhibited significantly higher pleurodesis scores. CONCLUSION: PCL membrane induced significant degree of adhesion, both within the abdomen and chest of the rabbits. The porous PCL membrane produces more intensive adhesion than dense one. Fibronectin plays an important role in the process of pleurodesis. Further study is required for the clinical application of the promising material.

Extracorporeal membrane oxygenation for neonatal congenital diaphragmatic hernia: The initial single-center experience in Taiwan.

BACKGROUND/PURPOSE: Extracorporeal membrane oxygenation (ECMO) is a treatment option for stabilizing neonates with congenital diaphragmatic hernia (CDH) in a critical condition when standard therapy fails. However, the use of this approach in Taiwan has not been previously reported. METHODS: The charts of all neonates with CDH treated in our institute during the period 2007-2014 were reviewed. After 2010, patients who could not be stabilized with conventional treatment were candidates for ECMO. We compared the demographic data of patients with and without ECMO support. The clinical course and complications of ECMO were also reviewed. RESULTS: We identified 39 neonates with CDH with a median birth weight of 2696 g (range, 1526-3280 g). Seven (18%) of these patients required ECMO support. The APGAR score at 5 minutes differed significantly between the ECMO and non-ECMO groups. The survival rate was 84.6% (33/39) for all CDH patients and 57.1% (4/7) for the ECMO group. The total ECMO bypass times in the survivors was in the range of 5-36 days, whereas all nonsurvivors received ECMO for at least 36 days (mean duration, 68 days). Surgical bleeding occurred in four of seven patients in the ECMO group. CONCLUSION: The introduction of ECMO rescued some CDH patients who could not have survived by conventional management. Prolonged (i.e., > 36 days) ECMO support had no benefit for survival.

Postoperative Showering for Clean and Clean-contaminated Wounds: A Prospective, Randomized Controlled Trial.

OBJECTIVE: To evaluate wound infection rates, pain scores, satisfaction with wound care, and wound care costs starting 48 hours after surgery. BACKGROUND: Showering after surgery is a controversial issue for wound care providers and patients. We investigated the benefits and detriments of showering for postoperative wound care. METHODS: Patients undergoing thyroid, lung, inguinal hernia, and face and extremity surgeries with clean or clean-contaminated wounds were included. The patients were randomized to allow showering (shower group) or to keep the wound dry (nonshower group) for postoperative wound care starting 48 hours after surgery. The primary endpoint was the rate of surgical wound infection. The secondary endpoints included the wound pain score, satisfaction with wound care, and cost of wound care. RESULTS: Between May 2013 and March 2014, there were 222 patients randomized to the shower group and 222 to the nonshower group. Two patients in each group were lost to follow-up. There were 4 superficial surgical site infections in the shower group and 6 in the nonshower group (4/220, 1.8% vs 6/220, 2.7%, P = 0.751). Postoperative pain scores were comparable between the 2 groups. Patients in the shower group were more satisfied with their method of wound care, and their wound care costs were lower when compared with the nonshower group. CONCLUSIONS: Clean and clean-contaminated wounds can be safely showered 48 hours after surgery. Postoperative showering does not increase the risk of surgical site complications. It may increase patients' satisfaction and lower the cost of wound care.

Robotic liver donor right hepatectomy: A pure, minimally invasive approach.

Right hepatectomy for a living liver donor via a pure minimally invasive approach is a challenging procedure and only a few cases have been reported. Between May 2013 and August 2015, 13 patients underwent robotic living donor right hepatectomy in our institute, and 54 patients received open surgery. In this series, no conversion was conducted for robotic donor right hepatectomy. The 2 groups shared similar blood loss (169 versus 146 mL), complication rates (7.7% versus 9.3%), and recovery of donor liver function (peak alanine aminotransferase, 269 versus 252 IU/mL). The robotic group needed longer operation time (596 versus 383 minutes) but less postoperative patient-controlled analgesia (0.58 versus 0.84 ng/kg) and a shorter period before returning to work/school (52.9 versus 100.0 days) and sex (100.0 versus 156.0 days). For recipient outcomes regarding the donor procedure, the robotic group shared similar experiences in early allograft dysfunction, complications, and 1-year recipient liver function with the open group. With respect to documented benefits of minimally invasive left-sided liver donor procedure, the development of right donor hepatectomy is slow. In conclusion, with substantial improvements in patient recovery after the minimally invasive approach, the robotic platform would be a big step toward completing pure minimally invasive liver donor surgery. Liver Transplantation 22 1509-1518 2016 AASLD.

Increased Autophagy Markers Are Associated with Ductular Reaction during the Development of Cirrhosis.

Autophagy is a regulatory pathway in liver fibrosis. We investigated the roles of autophagy in human cirrhotic livers. Cirrhotic and noncirrhotic liver tissues were obtained from patients with hepatocellular carcinoma, and liver tissues from live donors served as control. Patients with cirrhotic livers had significantly increased levels of various essential autophagy-related genes compared with noncirrhotic livers. In addition, colocalization of autophagy marker microtubule-associated protein 1 light chain 3B (LC3B) with lysosome-associated membrane protein-1, increased levels of lysosome-associated membrane protein-2, and increased maturation of lysosomal cathepsin D were observed in cirrhotic livers. By using dual-immunofluorescence staining, we demonstrated that increased LC3B was located mainly in the cytokeratin 19-labeled ductular reaction (DR) in human cirrhotic livers and in an experimental cirrhosis induced by 2-acetylaminofluorene (AAF) with carbon tetrachloride (CCl4), indicating a conserved response to chronic liver damage. Furthermore, an AAF/CCl4-mediated increase in DR and fibrosis were attenuated after chloroquine treatment, suggesting that the autophagy-lysosome pathway was essential for AAF/CCl4-induced DR-fibrosis. In conclusion, we demonstrated that increased autophagy marker positively correlated with DR during the development of cirrhosis. Therefore, targeting autophagy may hold therapeutic value for liver cirrhosis.

High glucose-induced reactive oxygen species generation promotes stemness in human adipose-derived stem cells.

BACKGROUND AIMS: Adipose-derived stem cells (ASCs) represent an important source of cell therapy to treat diabetic complications. However, hyperglycemia may alter several cellular functions, so the present study aimed to investigate the influence of a diabetic environment on the stemness and differentiation capabilities of ASCs. METHODS: Human ASCs were obtained from subcutaneous adipose tissues of diabetic (dASCs) and nondiabetic donors (nASCs) and characterized. To reproduce an in vitro hyperglycemia environment, the nASCs were also cultured under prolonged high-glucose (HG; 4.5 g/L) or low-glucose (LG; 1.0 g/L) conditions. RESULTS: The expression of cell surface markers in dASCs and nASC was similar and characteristic of mesenchymal stem cells. Although dASCs or HG-treated nASCs exhibited decreased proliferation, enhanced expression of the pluripotent markers Sox-2, Oct-4, and Nanog was observed. Moreover, HG-treated nASCs exhibited decreased cell migration, enhanced senescence, and significantly higher intracellular reactive oxygen species (ROS), whereas their adipogenic and osteogenic differentiation capacities remained comparable to LG-treated cells. With antioxidant treatment, HG-treated nASCs showed improved cell proliferative activity without stemness enhancement. This HG-induced biological response was associated with ROS-mediated AKT attenuation. When cultured in an appropriate induction medium, the HG-treated nASCs and dASCs exhibited enhanced potential of transdifferentiation into neuron-like cells. DISCUSSION: Despite lower proliferative activity and higher senescence in a diabetic environment, ASCs also exhibit enhanced stemness and neurogenic transdifferentiation potential via a ROS-mediated mechanism. The information is important for future application of autologous ASCs in diabetic patients.

PET/MRI in pancreatic and periampullary cancer: correlating diffusion-weighted imaging, MR spectroscopy and glucose metabolic activity with clinical stage and prognosis.

PURPOSE: To correlate the clinical stage and prognosis of pancreatic or periampullary cancer with the imaging biomarkers on diffusion-weighted imaging, magnetic resonance spectroscopy and glucose metabolic activity derived from integrated PET/MRI. METHODS: This prospective study was approved by the institutional review board and informed consent was obtained. The study group comprised 60 consecutive patients with pancreatic or periampullary cancer who underwent PET/MRI before treatment. The imaging biomarkers were the minimal apparent diffusion coefficient (ADCmin), choline levels, standardized uptake values, metabolic tumour volume (MTV), and total lesion glycolysis (TLG) of the tumours. The relationships between these biomarkers and clinical TNM stage were evaluated using the Pearson test and the Mann-Whitney U test. The area under the receiver operating characteristic curve (AUROC) was used to evaluate accuracy. The correlation between the imaging biomarker and progression-free survival (PFS) was investigated using the Cox proportional hazards model. RESULTS: ADCmin was significantly lower in N1 and TNM stage 3+ tumours. Choline levels significantly higher in T4 tumours. TLG was significantly higher in T4, N1 and TNM stage 3+ tumours. MTV was significantly higher in T4, N1, M1, and TNM stage 3+ tumours (all P < 0.05). The MTV/ADCmin ratio exhibited the highest AUROC for predicting T4, N1, M1, and advanced TNM stages tumours, and was an independent predictor of PFS (P = 0.018) after adjustment for age, sex, tumour size and stage. CONCLUSION: The imaging biomarkers from integrated PET/MRI may predict clinical stage and PFS in patients with pancreatic or periampullary cancer.

Clinical Application of Different Surgical Navigation Systems in Complex Craniomaxillofacial Surgery: The Use of Multisurface 3-Dimensional Images and a 2-Plane Reference System.

BACKGROUND: Intraoperative navigation is a tool that provides surgeons with real-time guidance based on patients' preoperative imaging studies. The application of intraoperative navigation to neurosurgery and otolaryngology has been well documented; however, only isolated reports have analyzed its potential in the field of craniomaxillofacial surgery. METHODS: From November 2010 to July 2014, 15 patients were operated on for complex craniomaxillofacial surgery with assistance by 3 different navigation systems, which used either infrared or electromagnetic technologies. We imported fine-cut (0.625-mm) computed tomographic scan images of the patients to the navigation systems whose software processed them into multisurface 3-dimentional models used as guiding material for the surgical navigation. We also developed a simple "2-plane reference system" to ensure that the final results were symmetric to the normal half of the face. Appearance outcome was evaluated by questionnaire. RESULTS: Of these 15 cases, 3 cases were performed with infrared-based navigation, and the remaining 12 cases were accomplished by electromagnetic technology. Most of these cases resulted in satisfactory outcomes after tumor resection, posttraumatic reconstruction, and postablative reconstruction. CONCLUSION: Navigation systems offer highly valuable intraoperative assistance in complex craniomaxillofacial surgery. Not only can these systems pinpoint deep-seated lesions as neurosurgeons or otolaryngologists do, but they can also use a simple 2-plane reference system for accurate bone alignment. Moreover, advancements in multisurface 3-D models provide us more reliable intuitive image guidance. The application of electromagnetic technology, with its smaller reference obviation of the line-of-sight problem, makes the manipulation of craniomaxillofacial surgery more comfortable.

Assessing hepatic fibrosis: comparing the intravoxel incoherent motion in MRI with acoustic radiation force impulse imaging in US.

OBJECTIVES: This study compared the diagnostic performance of intravoxel incoherent motion (IVIM) in magnetic resonance imaging (MRI) and acoustic radiation force impulse imaging (ARFI) in ultrasound (US) for liver fibrosis (LF) evaluation. METHODS: A total of 49 patients scheduled for liver surgery were recruited. LF in the non-tumorous liver parenchyma at the right lobe was estimated using a slow diffusion coefficient, fast diffusion coefficient (D fast), perfusion fraction (f) of the IVIM parameters, the total apparent diffusion coefficient of conventional diffusion-weighted imaging and the shear wave velocity (Vs) of ARFI. LF was graded using the Metavir scoring system on histological examination. The Spearman rank correlation coefficient for correlation and analysis of variance was used for determining difference. The diagnostic performance was compared using receiver operating characteristic curve analysis. RESULTS: LF exhibited significant correlation with the three parameters D fast, f, and Vs (r = -0.528, -0.337, and 0.481, respectively, P < 0.05). The D fast values in the F4 group were significantly lower than those in the F0, F1 and F2 groups. D fast exhibited a non-inferior performance for diagnosing all fibrosis grades compared with that of Vs. CONCLUSIONS: Both IVIM and ARFI provide reliable estimations for the noninvasive assessment of LF. KEY POINTS: • Liver fibrosis can be diagnosed and graded using noninvasive imaging modalities. • ARFI and IVIM can be incorporated into routine examinations. • IVIM can differentiate liver cirrhosis from none to moderate liver fibrosis. • The diagnostic performances of IVIM and ARFI are equal.

Connective tissue growth factor inhibits gastric cancer peritoneal metastasis by blocking integrin α3ß1-dependent adhesion.

BACKGROUND: Connective tissue growth factor (CTGF) plays important roles in normal and pathological conditions. The aim of this study was to investigate the role of CTGF in peritoneal metastasis as well as the underlying mechanism in gastric cancer progression. METHODS: CTGF expression levels for wild-type and stable overexpression clones were determined by Western blotting and quantitative polymerase chain reaction (Q-PCR). Univariate and multivariate analyses, immunohistochemistry, and survival probability analyses were performed on gastric cancer patients. The extracellular matrix components involved in CTGF-regulated adhesion were determined. Recombinant CTGF was added to cells or coinoculated with gastric cancer cells into mice to evaluate its therapeutic potential. RESULTS: CTGF overexpression and treatment with the recombinant protein significantly inhibited cell adhesion. In vivo peritoneal metastasis demonstrated that CTGF-stable transfectants markedly decreased the number and size of tumor nodules in the mesentery. Statistical analysis of gastric cancer patient data showed that patients expressing higher CTGF levels had earlier TNM staging and a higher survival probability after the surgery. Integrin α3ß1 was the cell adhesion molecule mediating gastric cancer cell adhesion to laminin, and blocking of integrin α3ß1 prevented gastric cancer cell adhesion to recombinant CTGF. Coimmunoprecipitation results indicated that CTGF binds to integrin α3. Coinoculation of recombinant CTGF and gastric cancer cell lines in mice showed effective inhibition of peritoneal dissemination. CONCLUSIONS: Our results suggested that gastric cancer peritoneal metastasis is mediated through integrin α3ß1 binding to laminin, and CTGF effectively blocks the interaction by binding to integrin α3ß1, thus demonstrating the therapeutic potential of recombinant CTGF in gastric cancer patients.

Necrotizing fasciitis in patients with diabetes mellitus: clinical characteristics and risk factors for mortality.

BACKGROUND: Necrotizing fasciitis (NF) is a rapidly progressive and life-threatening infection. This study aimed to investigate the clinical characteristics and mortality- associated factors in diabetic patients. METHODS: Detailed clinical information of 165 NF cases was retrospectively collected and analyzed in National Taiwan University Hospital between January 1997 and February 2013. We documented and compared the clinical features according to the presence of underlying diabetes mellitus, and we identified risk factors associated with mortality. RESULTS: There were 84 patients (51 %) with diabetes. The overall case fatality rate was 29.7 %, and we found no significant difference between the patients with or without diabetes. Compared with the nondiabetic patients, diabetic patients were older and exhibited higher serum levels of glucose and potassium on admission. Polymicrobial infection and monomicrobial NF caused by Klebsiella pneumoniae were also more frequently associated with diabetic patients. Moreover, diabetic NF patients exhibit a significantly higher chance of limb loss during hospitalization. In the combined diabetic and nondiabetic cohort, a high serum level of potassium (odds ratio, 2.2; 95 % confidence interval, 1.2 to 4.02; P = 0.011) on admission was independently associated with mortality, whereas positive blood culture on admission was associated with mortality in the diabetic cohort (odds ratio, 7.36; 95 % confidence interval, 1.66 to 32.54; P = 0.009). CONCLUSIONS: Diabetic patients are more susceptible to NF caused by polymicrobial infection or K. pneumoniae, and they are more likely to receive limb amputation for infection control. Bacteraemia on admission is a significant risk factor for mortality in diabetic NF patients.

Long-term oncologic results of laparoscopic D3 lymphadenectomy with complete mesocolic excision for right-sided colon cancer with clinically positive lymph nodes.

BACKGROUND/AIM: To assess surgical outcomes of patients undergoing D3 lymph node dissection and complete mesocolic excision for the treatment of right-sided colon cancer in the context that both procedures were performed laparoscopically. METHODS: 244 consecutive patients with clinically staged III right-sided colon cancer were recruited to undergo the laparoscopic D3 lymph node dissection with complete mesocolic excision. Postoperatively, the patients were stratified as N0, N1, N2, and N3 groups according to the level of lymph node metastasis, prospectively followed up for more than 5 years, and compared. RESULTS: The 5-year cumulative recurrence rate and the estimated time-to-recurrence [mean (95 % confidence interval)] was 16.6 % (n = 7/42), 113.8 (101.4-126.2) months in N0 group; 21.3 % (n = 17/80), 108.9 (99.1-118.7) months in N1 group; 43.2 % (n = 32/74), 85.4 (73.0-97.8) months in N2 group; and 52.0 % (n = 25/48), 65.2 (49.0-81.4) months in N3 group. When N1 and N0 groups of patients were lumped together, and compared with patients with N2 or N3 metastasis, we found that the latter were with a significantly higher recurrence rate (p < 0.0001). D3 lymph node dissection with complete mesocolic excision could assure the harvest of sufficient number (n = 34.4 ± 8.4) of lymph nodes for precise pathologic cancer staging. Skip lymph node metastasis was detected in 19.8 % (n = 40/202) of patients, and such surgical procedures facilitated up-staging in 4.5 % (n = 11/244) of patients. CONCLUSION: The present study encourages the dissemination of such concepts to surgical oncologists dealing with colorectal cancer through didactic education, and international consensus meeting is therefore mandatory to optimize the surgery of colon cancer.