An effective assessment of cluster tendency through sampling based multi-viewpoints visual method.

Social networks are the rich sources to people for sharing the knowledge on health-related issues. Nowadays, Twitter is one of the great significant social platforms to the people for a discussion on topics. Analyzing the clusters for the tweets concerning terms is a complex process due to the sparsity problem. Topic models are useful or avoiding this problem with derivations of topic clusters. Finding pre-cluster tendency is the major problem in many clustering methods. Existing methods, such as visual access tendency (VAT), cosine-based VAT (cVAT), multi viewpoints-based cosine similarity VAT (MVS-VAT) majorly used to access the prior information about clusters tendency problem. Solution of cluster tendency indicates the tractable number of clusters. The MVS-VAT enables the cluster tendency for the tweet documents effectively than other visual methods. However, it takes a higher number of viewpoints, thus requiring more computational time for the clustering of tweets data. Therefore, sampling-based visual methods are proposed to overcome the computational problem. Several standard health keywords are used for the extraction of health tweets to illustrate the effectiveness of proposed work in the experimental study.

CD105 is a prognostic marker and valid endothelial target for microbubble platforms in cholangiocarcinoma.

PURPOSE: The current treatment outcomes in cholangiocarcinoma are poor with cure afforded only by surgical extirpation. The efficacy of targeting the tumoural endothelial marker CD105 in cholangiocarcinoma, as a basis for potential microbubble-based treatment, is unknown and was explored here. METHODS: Tissue expression of CD105 was quantified using immunohistochemistry in 54 perihilar cholangiocarcinoma samples from patients who underwent resection in a single centre over a ten-year period, and analysed against clinicopathological data. In vitro flow assays using microbubbles functionalised with CD105 antibody were conducted to ascertain specificity of binding to murine SVR endothelial cells. Finally, CD105-microbubbles were intravenously administered to 10 Balb/c nude mice bearing heterotopic subcutaneous human extrahepatic cholangiocarcinoma (TFK-1 and EGI-1) xenografts after which in vivo binding was assessed following contrast-enhanced destruction replenishment ultrasound application. RESULTS: Though not significantly associated with any examined clinicopathological variable, we found that higher CD105 expression was independently associated with poorer patient survival (median 12 vs 31 months; p = 0.002). In vitro studies revealed significant binding of CD105-microbubbles to SVR endothelial cells in comparison to isotype control (p = 0.01), as well as in vivo to TFK-1 (p = 0.02) and EGI-1 (p = 0.04) mouse xenograft vasculature. CONCLUSION: Our results indicate that CD105 is a biomarker eminently suitable for cholangiocarcinoma targeting using functionalised microbubbles.

Neutrophil Gelatinase-associated Lipocalin as a Theragnostic Marker in Perihilar Cholangiocarcinoma.

BACKGROUND/AIM: Platforms using valid molecular targets can provide concurrent diagnostic and treatment (theragnostic) options in perihilar cholangiocarcinoma (PHC). Neutrophil gelatinase-associated lipocalin (NGAL) is a biomarker in the biliary secretome of PHC. Its potential as a theragnostic target and its prognostic significance in this cancer was, therefore, explored. MATERIALS AND METHODS: In-vitro studies were used to determine NGAL localization in several cholangiocarcinoma cell lines. Tissue expression of NGAL was quantified in PHC resection cases from 2000-2010 by immunohistochemistry. RESULTS: NGAL was expressed in the majority of tested cell lines and localized to their membranes. Tissues from 54 patients underwent NGAL immunohistochemistry. Median tumoral NGAL expression was significantly higher than that in matched liver controls (p<0.001). Higher NGAL tumor expression was associated with nodal metastasis (p=0.021), although no significant association with survival was observed. CONCLUSION: The expression and localization of NGAL in PHC make it a valid candidate biomarker for exploitation in theragnostic platforms.

Radical operation for hilar cholangiocarcinoma in comparable Eastern and Western centers: Outcome analysis and prognostic factors.

BACKGROUND: Extensive resection for hilar cholangiocarcinoma is the most effective treatment, but high morbidity and poor prognosis remain concerns. Previous data have shown marked differences in outcomes between comparable Eastern and Western centers. We compared the outcomes of the management for hilar cholangiocarcinoma at one Japanese and one British institution with comparable experience. METHODS: Of 298 consecutive patients with hilar cholangiocarcinoma evaluated at Hirosaki University Hospital, Japan and St. James's University Hospital, Leeds, UK, 183 underwent radical resection. Clinicopathologic variables and postoperative outcomes were compared. RESULTS: Significant differences were not observed between the Hirosaki and Leeds cohorts in overall outcomes despite several differences in the patient characteristics. Although there was a difference in 90-day mortality (2.5% vs 13.6%, respectively), disease-specific 5-year survival rates were 32.8% and 31.9%, respectively (P = .767). Multivariate analysis identified trisectionectomy (odds ratio = 2.32; P = .010), combined pancreatoduodenectomy (odds ratio = 7.88; P = .010), and perioperative blood transfusion (odds ratio = 1.88; P = .045) were associated with postoperative major complications, while preoperative biliary drainage associated with postoperative major complications, while preoperative biliary drainage (risk ratio = 2.21; P = .018), perioperative blood transfusion (risk ratio = 1.58; P = .029), lymph node metastasis (risk ratio = 2.00; P = .002), moderate/poorly differentiated tumor (risk ratio = 1.72; P = .029), microvascular invasion (risk ratio = 1.63; P = .046), and R1 resection (risk ratio = 1.90; P = .005) were risk factors for poor survival. CONCLUSION: Disease-specific survival and prognostic factors were similar in both centers. Meticulous operative technique to avoid perioperative blood transfusion may improve long-term survival.

Phytochemical investigation of sesquiterpenes from the fruits of Schisandra chinensis and their cytotoxic activity.

Phytochemical investigation of ethanolic extract from the fruits of Schisandra chinensis led to the isolation of four new sesquiterpenes (1-4); their structures were determined by a combination of NMR (1D and 2D) and MS spectroscopic techniques. In addition, all these isolates were screened for their cytotoxic activities against MCF-7, Caco-2, Hela, Lncap, Hep G2 and MDA-MB231 cancer cell lines. Results indicated that compounds 2 and 3 displayed potent cytotoxic activity against Caco2 cell lines with IC50 values of 17.10 µg/mM and 16.46 µg/mM, respectively.

Metal free oxidative coupling of aryl formamides with alcohols for the synthesis of carbamates.

A direct transformation of N-aryl formamides to the corresponding carbamates via the formation of isocyanate intermediates is achieved in good yields using hypervalent iodine as an oxidant.

Methyl angolensate and mexicanolide-type limonoids from the seeds of Cipadessa baccifera.

Six new methyl angolensate type (1-6) and three new mexicanolide-type (7-9) limonoids, along with six known limonoids (10-15), were isolated from the seeds of Cipadessa baccifera. The structures of all these compounds were established by extensive 1D, 2D NMR, and HRESIMS experiments, and structures of 11 and 13 were further confirmed by a single crystal X-ray diffraction analysis, which are reported for the first time. The cytotoxic activities of these isolates were also studied against A549, MCF7, ME-180, HT-29, B-16, ACHN cancer cell lines using MTT assay, and results indicated that compounds 4, 10, and 14 displayed potent cytotoxic activity against B-16, ACHN cell lines with an IC50 values of 8.51 and 7.0 µg/mL, respectively.

Repeat liver resection after a hepatic or extended hepatic trisectionectomy for colorectal liver metastasis.

OBJECTIVE: A right and left hepatic trisectionectomy and an extended trisectionectomy are the largest liver resections performed for malignancy. This report analyses a series of 23 patients who had at least one repeat resection after a hepatic trisectionectomy for colorectal liver metastasis (CRLM). METHODS: A retrospective analysis of a single-centre prospective liver resection database from May 1996 to April 2009 was used for patient identification. Full notes, radiology and patient reviews were analysed for a variety of factors with respect to survival. RESULTS: Twenty-three patients underwent up to 3 repeat hepatic resections after 20 right and 3 left hepatic trisectionectomies. In 18 patients the initial surgery was an extended trisectionectomy. Overall 1-, 3- and 5-year survival rates after a repeat resection were 100%, 46% and 32%, respectively. No factors predictive for survival were identified. CONCLUSION: A repeat resection after a hepatic trisectionectomy for CRLM can offer extended survival and should be considered where appropriate.

Subtotal hepatectomy and whole graft auxiliary transplantation for acetaminophen-associated acute liver failure.

BACKGROUND: An acetominophen overdose (AOD) is the leading cause of acute liver failure (ALF) in the UK and USA. For patients who meet the King's College Hospital criteria, (mortality risk > 85%), an emergency orthotopic liver transplantation (OLT) is conventionally performed with subsequent life-long immunosuppression. A new technique was developed in 1998 for AOD-induced ALF where a subtotal hepatectomy (right hepatic trisectionectomy) and whole graft auxiliary liver transplant (WGALT) was performed with complete withdrawal of immunosupression during the first year post-operatively. RESULTS: During 1998-2010, 68 patients were listed for an emergency transplantation for AOD ALF at our institution: 28 died waiting, 16 underwent OLT and 24 a subtotal hepatectomy with WGALT. Eight OLT (50%) and 16 WGALT remain alive (67%); actuarial survival at 5 years OLT 50%, WGALT 63%, P = 0.37. All patients who had successful WGALT are off immunosuppression. Poor prognostic factors in the WGALT group included higher donor age (40.4 versus 53.9, P = 0.043), requirements for a blood transfusion (4.3 versus 7.6, P = 0.0043) and recipient weight (63.1 versus 54 kg, P = 0.036). CONCLUSION: Although OLT remains standard practice for AOD-induced ALF, life-long immunosuppression is required. A favourable survival rate using a subtotal hepatectomy and WGALT has been demonstrated, and importantly, all successful patients have undergone complete immunosuppression withdrawal. This technique is advocated for patients who have acetominophen hepatotoxicity requiring liver transplantation.

Operative terminology and post-operative management approaches applied to hepatic surgery: Trainee perspectives.

Outcomes in hepatic resectional surgery (HRS) have improved as a result of advances in the understanding of hepatic anatomy, improved surgical techniques, and enhanced peri-operative management. Patients are generally cared for in specialist higher-level ward settings with multidisciplinary input during the initial post-operative period, however, greater acceptance and understanding of HRS has meant that care is transferred, usually after 24-48 h, to a standard ward environment. Surgical trainees will be presented with such patients either electively as part of a hepatobiliary firm or whilst covering the service on-call, and it is therefore important to acknowledge the key points in managing HRS patients. Understanding the applied anatomy of the liver is the key to determining the extent of resection to be undertaken. Increasingly, enhanced patient pathways exist in the post-operative setting requiring focus on the delivery of high quality analgesia, careful fluid balance, nutrition and thromboprophlaxis. Complications can occur including liver, renal and respiratory failure, hemorrhage, and sepsis, all of which require prompt recognition and management. We provide an overview of the relevant terminology applied to hepatic surgery, an approach to the post-operative management, and an aid to developing an awareness of complications so as to facilitate better confidence in this complex subgroup of general surgical patients.

Pre-liver transplant biopsy in hepatocellular carcinoma: a potential criterion for exclusion from transplantation?

BACKGROUND: In cirrhotic patients with hepatocellular carcinoma (HCC), poor differentiation in pre-liver transplantation (LT) biopsy of the largest tumour is used as a criterion for exclusion from LT in some centres. The potential role of pre-LT biopsy at one centre was explored. METHODS: A prospective database of patients undergoing orthotopic LT for radiologically diagnosed HCC at St James's University Hospital, Leeds during 2006-2011 was analysed. RESULTS: A total of 60 predominantly male (85.0%) patients with viral hepatitis were identified. There were discrepancies between radiological and histopathological findings with respect to the number of tumours identified (in 27 patients, 45.0%) and their size (in 63 tumours, 64.3%). In four (6.7%) patients, the largest lesion, which would theoretically have been targeted for biopsy, was not the largest in the explant. Nine (31.0%) patients with multifocal HCC had tumours of differing grades. In two (6.9%) patients, the largest tumour was well differentiated, but smaller tumours in the explant were poorly differentiated. In one patient, the largest lesion was benign and smaller invasive tumours were confirmed histologically. CONCLUSIONS: The need to optimize selection for LT in HCC remains. In the present series, the largest tumour was not always representative of overall tumour burden or biological aggression and its potential use to exclude patients from LT is questionable.

Cytotoxic sesquiterpenes from Hedychium spicatum: isolation, structure elucidation and structure-activity relationship studies.

Phytochemical investigation of chloroform extract from rhizomes of Hedychium spicatum resulted in the isolation of six new sesquiterpenes (1-6) along with fifteen known compounds (7-21). Their structures were elucidated on the basis of the extensive spectroscopic analyses (IR, Mass and NMR) and by comparison of the data with those reported in the literature. Further, cytotoxic activities of all the isolates were evaluated by determining their inhibitory effects against A-549, B-16, Hela, HT-29, NCI-H460, PC-3, IEC-6 and L-6 cancer cell lines. Results indicated that compounds 1 and 3 may serve as an important natural lead compounds for future development as they showed potent cytotoxic activity against Hela cell lines with an IC50 value of 0.3 µg/mL and 1.80 µg/mL, respectively.

Ischaemic Preconditioning and Intermittent Clamping Does not Influence Mediators of Liver Regeneration in a Human Liver Sinusoidal Endothelial Cell Model of Ischaemia-Reperfusion Injury.

BACKGROUND: The role of surgical technique on liver regeneration following surgery remains inconclusive. The aim of the study was to assess the effect of ischaemic preconditioning (IPC) and intermittent clamping (IC) on mediators of regeneration produced by human liver sinusoidal endothelial cells (SECs), using an in vitro hypoxia-reoxygenation model to mimic ischaemia-reperfusion injury (IRI). METHODS: Following extraction from samples obtained from liver resection (n = 5), confluent culture flasks of SECs were subjected to IRI (1 hour hypoxia + 1 hour reoxygenation), IPC prior to IRI (10 minutes hypoxia + 10 minutes reoxygenation + 1 hour hypoxia + 1 hour reoxygenation), IC (15 minutes hypoxia + 5 minutes reoxygenation x 3 + 1 hour reoxygenation) and compared to controls. The production of various mediators was determined over 48 hours. RESULTS: Interleukin (IL)-6, IL-8, granulocyte-colony stimulating factor (G-CSF) and hepatocyte growth factor (HGF) were produced by SECs. Both IPC and IC did not significantly influence the profile of IL-6, IL-8, G-CSF and HGF by SECs compared to IRI over the study period. CONCLUSION: IPC and IC did not influence the production of pro-regenerative mediators in a SECs model of IRI. The role of surgical technique on liver regeneration remains to be determined.

Role of quantification of hepatic steatosis and future remnant volume in predicting hepatic dysfunction and complications after liver resection for colorectal metastases: a pilot study.

OBJECTIVES: Accurate prediction of safe remnant liver volume to minimize complications following liver resection remains challenging. The aim of this study was to assess whether quantification of steatosis improved the predictive value of preoperative volumetric analysis. METHODS: Thirty patients undergoing planned right or extended right hemi-hepatectomy for colorectal metastases were recruited prospectively. Magnetic resonance imaging was used to assess the level of hepatic steatosis and future remnant liver volume. These data were correlated with data on postoperative hepatic insufficiency, complications and hospital stay. Correlations of remnant percentage, remnant mass to patient mass and remnant mass to body surface area with and without steatosis measurements were assessed. RESULTS: In 10 of the 30 patients the planned liver resection was altered. Moderate-severe postoperative hepatic dysfunction was seen in 17 patients. Complications arose in 14 patients. The median level of steatosis was 3.8% (range: 1.2-17.6%), but was higher in patients (n= 10) who received preoperative chemotherapy (P= 0.124), in whom the median level was 4.8% (range: 1.5-17.6%). The strongest correlation was that of remnant liver mass to patient mass (r= 0.77, P < 0.001). However, the addition of steatosis quantification did not improve this correlation (r= 0.76, P < 0.001). CONCLUSIONS: This is the first study to combine volumetric with steatosis quantifications. No significant benefit was seen in this small pilot. However, these techniques may be useful in operative planning, particularly in patients receiving preoperative chemotherapy.

Development and validation of HPTLC method for the determination of mycophenolate mofetil in bulk and pharmaceutical formulation.

AIM: Described in this manuscript is the first ever reported, new, simple, high-performance thin-layer chromatographic method for the determination of mycophenolate mofetil in bulk and tablet dosage form. MATERIALS AND METHODS: The drug was separated on aluminum plates precoated with silica gel 60 F254 with toluene, acetone, and methanol in the ratio of 6:2:2 (v/v/v) as the mobile phase. Quantitative analysis was performed by densitometric scanning at 254 nm. RESULTS: The method was validated for linearity, accuracy, precision, and robustness. The calibration plot was linear in the range of 100-500 ng band(-1) for mycophenolate mofetil. The method was successfully applied to the analysis of the drug in a pharmaceutical dosage form.

Hepatocellular carcinoma within a noncirrhotic, nonfibrotic, seronegative liver: surgical approaches and outcomes.

BACKGROUND: Hepatocellular carcinoma (HCC) most commonly arises in patients with chronic liver disease. Data on outcomes after liver resection in patients with noncirrhotic, nonfibrotic, seronegative, referred to as a "normal" liver are limited. We aimed to investigate differences in prognostic factors and outcomes between patients presenting with HCC arising in "normal" liver (NLHCC) and that arising in "diseased" liver (DLHCC). STUDY DESIGN: All patients undergoing resection for HCC between 1994 and 2008 were assessed. Multivariable analysis of clincopathologic data from the NLHCC group was performed by comparing them with data from the group who had surgery for DLHCC during this period. RESULTS: During the 15-year study period, 142 patients underwent liver resection for HCC: 81 for NLHCC and 61 for DLHCC. NLHCCs were more often solitary but were larger and required more major resections. There was no significant difference in survival outcomes between patients who had NLHCC or DLHCC, with overall and recurrence-free 5-year survivals of 60% and 51% in NLHCC and 55% and 33% in DLHCC, respectively. In patients with NLHCC, significant factors predicting overall survival were blood transfusion requirement (p = 0.003) and age (p = 0.009), and the only significant factor at predicting recurrence-free survival was presence of multiple tumors (p = 0.025). In contrast, in DLHCC, the only significant prognostic variables were a preoperative tumor biopsy (p = 0.017) or a high neutrophil-to-lymphocyte ratio (p = 0.001), both of which predicted a poorer recurrence-free survival. CONCLUSIONS: HCC presenting in patients with a normal background liver parenchyma appears to present a different spectrum of the disease. However, excellent outcomes can be achieved after liver resection, although this often requires the use of advanced techniques due to late presentation.

Inferior vena cava resection with hepatectomy: challenging but justified.

OBJECTIVE: The aim of this study was to evaluate the clinical outcome of hepatectomy combined with inferior vena cava (IVC) resection and reconstruction for treatment of invasive liver tumours. METHODS: From February 1995 to September 2010, 2146 patients underwent liver resections in our hospital's hepatopancreatobiliary unit. Of these, 35 (1.6%) patients underwent hepatectomy with IVC resection. These patients were included in this study. Data were analysed from a prospectively collected database. RESULTS: Resections were carried out for colorectal liver metastasis (CRLM) (n= 21), hepatocellular carcinoma (n= 6), cholangiocarcinoma (n= 3) and other conditions (n= 5). Resections were carried out with total vascular occlusion in 34 patients and without in one patient. In situ hypothermic perfusion was performed in 13 patients; the ante situm technique was used in three patients, and ex vivo resection was used in six patients. There were four early deaths from multiple organ failure. Postoperative complications occurred in 14 patients, three of whom required re-operation. Median overall survival was 29 months and cumulative 5-year survival was 37.7%. Rates of 1-, 2- and 5-year survival were 75.9%, 58.7% and 19.6%, respectively, in CRLM patients. CONCLUSIONS: Aggressive surgical management of liver tumours with IVC involvement offers the only hope for cure in selected patients. Resection by specialist teams affords acceptable perioperative morbidity and mortality rates.

Evolution of the surgical management of perihilar cholangiocarcinoma in a Western centre demonstrates improved survival with endoscopic biliary drainage and reduced use of blood transfusion.

BACKGROUND: Perihilar cholangiocarcinoma (PHCCA) remains a surgical challenge for which few large Western series have been reported. The aims of this study were to investigate the results of surgical resection for PHCCA and assess how practice has evolved over the past 15 years. METHODS: A prospectively maintained database was interrogated to identify all resections. Clinicopathological data were analysed for impact on survival. Subsequently, data for resections carried out during the periods 1994-1998, 1999-2003 and 2004-2008 were compared. RESULTS: Eighty-three patients underwent resection. Trisectionectomy was required in 67% of resections. Overall survival was 70%, 36% and 20% at 1, 3 and 5 years, respectively. Size of tumour, margin (R0) status, lymph node status, distant metastasis, tumour grade, portal vein resection, microscopic direct vascular invasion, T-stage and blood transfusion requirement significantly affected outcome on univariate analysis. Distant metastasis (P = 0.040), percutaneous biliary drainage (P = 0.015) and blood transfusion requirement (P = 0.026) were significant factors on multivariate analysis. Survival outcomes improved and blood transfusion requirement was significantly reduced in the most recent time period. DISCUSSION: Blood transfusion requirement and preoperative percutaneous biliary drainage were identified as independent indicators of a poor prognosis following resection of PHCCA. Longterm survival can be achieved following the aggressive surgical resection of this tumour, but the emergence of a clear learning curve in our analyses indicates that these patients should be managed in high-volume centres in order to achieve improved outcomes.