Clinicopathological and prognostic implications of endoglin (CD105) expression in hepatocellular carcinoma and its adjacent non-tumorous liver

Aim: The expression pattern of endoglin (CD105) in hepatocellular carcinoma (HCC) has not been reported so far. We hypothesized that CD105 could differentially highlight a subset of microvessels in HCC, and intratumoral microvessel density (IMVD) by CD105 immunostaining (IMVD-CD105) could provide better prognostic information than IMVD by CD34 immunostaining (IMVD-CD34). Methods: Paraffin blocks of tumor and adjacent non-tumorous liver tissues from 86 patients who underwent curative resection of HCC were used for this study. Serial sections were stained for CD105 and CD34, respectively, to highlight the microvessels. IMVD was counted according to a standard protocol. Results: In the HCC tissues, CD105 was either negatively or positively stained only in a subset of microvessels. In contrast, CD34 showed positive and more extensive microvessel staining in all cases examined. However, in the adjacent non-tumorous liver sections, CD105 showed a diffuse pattern of microvessel staining in 20 of 86 cases, while CD34 showed negative or only focal staining of the sinusoids around portal area. Correlation with clinicopathological data demonstrated that lower scores of IMVD-CD105 were found in larger sized tumors [mean 41.4/0.74 mm 2 (>5 cm tumor) vs 65.9/0.74 mm 2 (≤5 cm tumor), P = 0.043] and more aggressive tumors, as indicated by venous infiltration [36.8/0.74 mm 2 (present) vs 64.2/0.74 mm 2 (absent), P = 0.020], microsatellite nodules [35.1/0.74 mm 2 (present) vs 65.9/0.74 mm 2 (absent), P = 0.012], and advanced TNM tumor stage [38.8/0.74 mm 2 (stage 3 or 4) vs 68.3/0.74 mm 2 (stage 1 or 2), P = 0.014]. No prognostic significance was observed when median values were used as cut-off points using either IMVD-CD105 or IMVD-CD34. However, the presence of the diffuse pattern of CD105 expression in the adjacent non-tumorous liver tissues predicted a poorer disease-free survival (median 8.6 vs 21.5 mo, P = 0.026). Conclusion: Our data demonstrate that a lower IMVD-CD105 is associated with larger and more aggressive tumors. In this study, IMVD-CD105 did not provide significant prognostic information. However, active angiogenesis as highlighted by diffuse CD105 staining of the microvessels in the adjacent non-tumorous liver tissues is predictive of early recurrence. © 2005 The WJG Press and Elsevier Inc. All rights reserved.published_or_final_versio

Desensitization of T lymphocyte function by CXCR3 ligands in human hepatocellular carcinoma

Aim: Despite the presence of lymphocyte infiltration, human hepatocellular carcinoma (HCC) is typically a rapidly progressive disease. The mechanism of regulation of lymphocyte migration is poorly understood. In this study, we investigated various factors regulating T cell migration in HCC patients. We examined serum CXC chemokine levels in HCC patients and demonstrated the production of CXC chemokines by HCC cell lines. We determined the effect of both HCC patient serum and tumor cell conditioned supernatant upon lymphocyte expression of chemokine receptor CXCR3 as well as lymphocyte migration. Lastly, we examined the chemotactic responses of lymphocytes derived from HCC patients. Methods: The serum chemokines IP-10 (CXCL10) and Mig (CXCL9) levels were measured by cytometric bead array (CBA) and the tumor tissue IP-10 concentration was measured by ELISA. The surface expression of CXCR3 on lymphocytes was determined by flow cytometry. The migratory function of lymphocytes to the corresponding chemokines was assessed using an in vitro chemotactic assay. Phosphorylation of extracellular signal-regulated kinase (ERK) was determined by Western blot analysis. Results: Increased levels of IP-10 and Mig were detected in HCC patient serum and culture supernatants of HCC cell lines. The IP-10 concentration in the tumor was significantly higher than that in the non-involved adjacent liver tissues. HCC cell lines secreted functional chemokines that induced a CXCR3-specific chemotactic response of lymphocytes. Furthermore, tumor-cell-derived chemokines induced initial rapid phosphorylation of lymphocyte ERK followed by later inhibition of ERK phosphorylation. The culture of normal lymphocytes with HCC cell line supernatants or medium containing serum from HCC patients resulted in a significant reduction in the proportion of lymphocytes exhibiting surface expression of CXCR3. The reduction in T cell expression of CXCR3 resulted in reduced migration toward the ligand IP-10, and both CD4 + and CD8 + T cells from HCC patients exhibited diminished chemotactic responses to IP-10 in vitro compared to T cells from healthy control subjects. Conclusion: This study demonstrates functional desensitization of the chemokine receptor CXCR3 in lymphocytes from HCC patients by CXCR3 ligands secreted by tumor cells. This may cause lymphocyte dysfunction and subsequently impaired immune defense against the tumor. © 2005 The WJG Press and Elsevier Inc. All rights reserved.published_or_final_versio

Preconditioning with Porphyromonas gingivalis lipopolysaccharide may confer cardioprotection and improve recovery of the electrically induced intracellular calcium transient during ischemia and reperfusion

Background and Objective: Porphyromonas gingivalis lipopolysaccharide (LPS) is a ligand for cell surface toll-like receptors (TLR), TLR2 and TLR4 while stimulation of either leads to cardioprotection. We hypothesized that: (1) pretreatment with P. gingivalis LPS at appropriate concentrations would induce cardioprotection against injury induced by ischemia and reperfusion; and (2) P. gingivalis LPS pretreatment at cardioprotective concentrations may reduce Ca2+ overload, which is a precipitating cause of injury, and improve recovery of contractile function. Material and Methods: Male Sprague-Dawley rats were randomly selected to receive intraperitoneal saline or hot phenol-water-extracted P. gingivalis LPS at 0.2, 0.5, 1.0, 2.0 or 4.0 mg/kg 24 h before the experiment. The hearts were isolated and subjected to regional ischemia by coronary artery ligation followed by reperfusion. In isolated rat ventricular myocytes, the cytosolic Ca2+ level and the electrically induced intracellular calcium (E[Ca2+]i) transient, which reflects contractile function, were determined after pretreatment with a cardioprotective dose of P. gingivalis LPS. Results: Pretreatment with 0.5 mg/kg P. gingivalis LPS significantly reduced, while pretreatment with 1.0-4.0 mg/kg significantly increased infarct size. The Ca2+ overload induced by ischemia-reperfusion was attenuated in myocytes from rats pretreated with 0.5 mg/kg P. gingivalis LPS. Pretreated myocytes also showed an increased amplitude of the E[Ca2+]i transient, no prolongation of the time to reach the peak E[Ca2+]i transient and shorter 50% decay time during reperfusion. Conclusion: At a dosage of 0.5 mg/kg, P. gingivalis LPS confers cardioprotection against ischemia-reperfusion-induced injury and improved intracellular E[Ca2+]i transient recovery, hence improving myocyte contractile recovery. © 2009 John Wiley & Sons A/S.postprin

Radiofrequency ablation for controlling iatrogenic splenic injury

published_or_final_versionSpringer Open Choice, 21 Feb 201

Pancreaticoduodenectomy with vascular reconstruction for adenocarcinoma of the pancreas with borderline resectability

AIM: To analyze whether pancreaticoduodenectomy with simultaneous resection of tumor-involved vessels is a safe approach with acceptable patient survival. METHODS: Between January 2001 and March 2012, 136 patients received pancreaticoduodenectomy for adenocarcinoma at our hospital. Seventy-eight patients diagnosed with pancreatic head carcinoma were included in this study. Among them, 46 patients received standard pancreaticoduodenectomy (group 1) and 32 patients received pancreaticoduodenectomy with simultaneous resection of the portal vein or the superior mesenteric vein or artery (group 2) followed by reconstruction. The immediate surgical outcomes and survivals were compared between the groups. Fifty-five patients with unresectable adenocarcinoma of the pancreas without liver metastasis who received only bypass operations (group 3) were selected for additional survival comparison. RESULTS: The median ages of patients were 67 years (range: 37-82 years) in group 1, and 63 years (range: 35-86 years) in group 2. All group 2 patients had resection of the portal vein or the superior mesenteric vein and three patients had resection of the superior mes-enteric artery. The pancreatic fistula formation rate was 21.7% (10/46) in group 1 and 15.6% (5/32) in group 2 (P = 0.662). Two hospital deaths (4.3%) occurred in group 1 and one hospital death (3.1%) occurred in group 2 (P = 0.641). The one-year, three-year and five-year overall survival rates in group 1 were 71.1%, 23.6% and 13.5%, respectively. The corresponding rates in group 2 were 70.6%, 33.3% and 22.2% (P = 0.815). The one-year survival rate in group 3 was 13.8%. Pancreaticoduodenectomy with simultaneous vascular resection was safe for pancreatic head adenocarcinoma. CONCLUSION: The short-term and survival outcomes with simultaneous resection were not compromised when compared with that of standard pancreaticoduodenectomy. © 2014 Baishideng Publishing Group Inc. All rights reserved.published_or_final_versio

Management of spontaneously ruptured hepatocellular carcinomas in the radiofrequency ablation era

Background and aim: Spontaneous rupture of hepatocellular carcinoma (HCC) carries a high mortality. The use of radiofrequency ablation (RFA) in recent years has enriched the armamentarium for hemostasis of spontaneously ruptured HCCs but its results have not been documented. This study investigated the prognosis and outcome of spontaneous rupture of HCC as well as the results of using RFA for hemostasis. Patients and method: From January 1991 to December 2010, 5283 patients were diagnosed with HCC at our hospital, and 189 of them had spontaneous rupture of HCCs. They were grouped under two periods: period 1, 1991-2000, n = 70; period 2, 2001-2010, n = 119. RFA was available in period 2 only. Results: Hepatitis B virus infection was predominant in both periods. Surgical hemostasis was mainly achieved by hepatic artery ligation in period 1 and by RFA in period 2. The 30-day hospital mortality after surgical treatment was 55.6% (n = 18) in period 1 and 19.2% (n = 26) in period 2 (p = 0.012). Multivariate analysis identified 4 independent factors for better overall survival, namely, hemostasis by transarterial chemoembolization (hazard ratio 0.516, 95% confidence interval 0.354-0.751), hemostasis by RFA (hazard ratio 0.431, 95% confidence interval 0.236-0.790), having surgery as a subsequent treatment (hazard ratio 0.305, 95% confidence interval 0.186-0.498), and a serum total bilirubin level <19 umol/L (hazard ratio 1.596, 95% confidence interval 1.137-2.241). Conclusion: The use of RFA for hemostasis during laparotomy greatly reduced the hospital mortality rate when compared with conventional hepatic artery ligation. © 2014 Cheung et al.published_or_final_versio

High-intensity focused ultrasound for hepatocellular carcinoma: A single-center experience

Objective: This study aims to evaluate the outcome of patients with hepatocellular carcinoma (HCC) treated by high-intensity focused ultrasound (HIFU) in a single tertiary referral center. Background: HIFU is the latest developed local ablation technique for unresectable HCC. The initial experience on its efficacy is promising, but the survival benefit of patients undergoing HIFU for HCC is poorly defined. Methods: From October 2006 to December 2008, 49 patients received HIFU for unresectable HCC. Each patient underwent a single session of HIFU with a curative intent. Treatment efficacy and survival outcome were evaluated. Clinicopathologic factors affecting the primary technique effectiveness and overall survival rates were investigated by univariate analysis. Results: The median size of the treated tumors was 2.2 cm, ranging from 0.9 to 8 cm. The majority of patients had single tumors (n = 41, 83.6%). Thirty-one patients (63.2%) had artificial right pleural effusion during HIFU treatment to reduce damage to the lung and diaphragm. The hospital mortality rate was 2% (n = 1) and the complication rate was 8.1% (n = 4). The primary technique effectiveness rate was 79.5% (39 of 49 patients). It increased from 66.6% in the initial series to 89.2% in the last 28 patients. Tumor size (3.0 cm) was the significant risk factor affecting the complete ablation rate. The 1- and 3-year overall survival rates were 87.7% and 62.4%, respectively. Child-Pugh liver function grading was the significant prognostic factor influencing the overall survival rate. Conclusions: HIFU is an effective treatment modality for unresectable HCC with a high technique effectiveness rate and favorable survival outcome. © 2011 Lippincott Williams & Wilkins.postprin

Long Term Survival Analysis of Hepatectomy for Neuroendocrine Tumour Liver Metastases

Background. Liver is the commonest site for metastasis in patients with neuroendocrine tumour (NET). A vast majority of treatment strategies including liver directed nonsurgical therapy, liver directed surgical therapy, and nonliver directed therapy have been proposed. In this study we aim to investigate the outcome of liver resection in neuroendocrine tumour liver metastases (NELM). Method. 293 patients had hepatectomy for liver metastasis in our hospital between June 1996 and December 2010. Twelve patients were diagnosed to have NET in their final pathology and their data were reviewed. Results. The median ages of the patients were 48.5 years (range 20-71 years). Eight of the patients received major hepatectomy. Four patients received minor hepatectomy. The median operation time was 418 minutes (range 195-660 minutes). The median tumor size was 8.75 cm (range 0.9-21 cm). There was no hospital mortality. The overall one-year and three-year survivals were 91.7% and 55.6%. The one-year and three-year disease-free survivals were 33.3% and 16.7%. Conclusion. Hepatectomy is an effective and safe treatment for NELM. Reasonable outcome on long term overall survival and disease-free survival can be achieved in this group of patients with a low morbidity rate. © 2014 Tan To Cheung et al.published_or_final_versio

A HIV-1 heterosexual transmission chain in Guangzhou, China: a molecular epidemiological study

<p>Abstract</p> <p>Background</p> <p>We conducted molecular analyses to confirm four clustering HIV-1 infections (Patient A, B, C & D) in Guangzhou, China. These cases were identified by epidemiological investigation and suspected to acquire the infection through a common heterosexual transmission chain.</p> <p>Methods</p> <p><it>Env C2V3V4 </it>region, <it>gag p17/p24 </it>junction and partial <it>pol </it>gene of HIV-1 genome from serum specimens of these infected cases were amplified by reverse transcription polymerase chain reaction (RT-PCR) and nucleotide sequenced.</p> <p>Results</p> <p>Phylogenetic analyses indicated that their viral nucleotide sequences were significantly clustered together (bootstrap value is 99%, 98% and 100% in <it>env</it>, <it>gag </it>and <it>pol </it>tree respectively). Evolutionary distance analysis indicated that their genetic diversities of <it>env</it>, <it>gag </it>and <it>pol </it>genes were significantly lower than non-clustered controls, as measured by unpaired <it>t</it>-test (<it>env </it>gene comparison: <it>p </it>< 0.005; <it>gag </it>gene comparison: <it>p </it>< 0.005; <it>pol </it>gene comparison: <it>p </it>< 0.005).</p> <p>Conclusion</p> <p>Epidemiological results and molecular analyses consistently illustrated these four cases represented a transmission chain which dispersed in the locality through heterosexual contact involving commercial sex worker.</p

The interface between silicon and a high-k oxide

The ability to follow Moore's Law has been the basis of the tremendous success of the semiconductor industry in the past decades. To date, the greatest challenge for device scaling is the required replacement of silicon dioxide-based gate oxides by high-k oxides in transistors. Around 2010 high-k oxides are required to have an atomically defined interface with silicon without any interfacial SiO2 layer. The first clean interface between silicon and a high-K oxide has been demonstrated by McKee et al. Nevertheless, the interfacial structure is still under debate. Here we report on first-principles calculations of the formation of the interface between silicon and SrTiO3 and its atomic structure. Based on insights into how the chemical environment affects the interface, a way to engineer seemingly intangible electrical properties to meet technological requirements is outlined. The interface structure and its chemistry provide guidance for the selection process of other high-k gate oxides and for controlling their growth. Our study also shows that atomic control of the interfacial structure can dramatically improve the electronic properties of the interface. The interface presented here serves as a model for a variety of other interfaces between high-k oxides and silicon.Comment: 10 pages, 2 figures (one color