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A systematic review of contralateral liver lobe hypertrophy after unilobar selective internal radiation therapy with Y90. - HPB : the official journal of the International Hepato Pancreato Biliary Association
A curative liver resection is the treatment of choice for both primary and secondary liver malignancies. However, an inadequate future liver remnant (FLR) frequently precludes successful surgery. Portal vein embolization is the gold-standard modality for inducing hypertrophy of the FLR. In recent times, unilobar Yttrium-90 selective internal radiation therapy (SIRT) has been reported to induce hypertrophy of the contralateral, untreated liver lobe. The aim of this study was to review the current literature reporting on contralateral liver hypertrophy induced by unilobar SIRT.A systematic review of the English-language literature between 2000 and 2014 was performed using the search terms 'Yttrium 90' OR 'selective internal radiation therapy' OR 'radioembolization' AND 'hypertrophy'.Seven studies, reporting on 312 patients, were included. Two hundred and eighty-four patients (91.0%) received treatment to the right lobe. Two hundred and fifteen patients had hepatocellular carcinoma (HCC), 12 had intrahepatic cholangiocarcinoma and 85 had liver metastases from mixed primaries. Y90 SIRT resulted in contralateral liver hypertrophy that ranged from 26% to 47% at 44 days to 9 months. All studies were retrospective in nature, and heterogeneous, with substantial variations relative to pathology treated, underlying liver disease, dosage and delivery of Y90, the number of treatment sessions and time to measurement of hypertrophy.Unilobar Y90 SIRT results in significant hypertrophy of the contralateral liver lobe. The rate of hypertrophy seems to be slower than that achieved by other methods.Â© 2015 International Hepato-Pancreato-Biliary Association.
Targeting the WNT Signaling Pathway in Cancer Therapeutics. - The oncologist
The WNT signaling cascade is integral in numerous biological processes including embryonic development, cell cycle regulation, inflammation, and cancer. Hyperactivation of WNT signaling secondary to alterations to varying nodes of the pathway have been identified in multiple tumor types. These alterations converge into increased tumorigenicity, sustained proliferation, and enhanced metastatic potential. This review seeks to evaluate the evidence supporting the WNT pathway in cancer, the therapeutic strategies in modulating this pathway, and potential challenges in drug development.Â©AlphaMed Press.
Are preoperative blood neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios useful in predicting malignancy in surgically-treated mucin-producing pancreatic cystic neoplasms? - Journal of surgical oncology
The aim of this study was to determine if neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were predictive of malignancy in mucin-producing pancreatic cystic neoplasms (MpPCN).One hundred and twenty patients with MpPCN were retrospectively reviewed. Malignant neoplasms were defined as neoplasms harbouring invasive carcinoma or high grade dysplasia. A high NLR and PLR were defined as â‰¥2.551 and â‰¥208.1, respectively.High NLR was significantly associated with symptomatic tumors, larger tumors, solid component, main-duct IPMN, and Sendai high risk category. High PLR was significantly associated with jaundice and Sendai high risk category. On univariate analyses, symptomatic tumors, jaundice, solid component, dilated pancreatic duct, and both a high NLR and PLR were significant predictors of malignant and invasive MpPCN. On multivariate analyses, solid component and dilated pancreatic duct were independent predictors of malignant and invasive MpPCN. PLR was an independent predictor for invasive MpPCN. When MpPCN were stratified by the Fukuoka and Sendai Guidelines, both a high NLR and PLR were significantly associated with malignant neoplasms within the high risk categories.PLR is an independent predictor of invasive carcinoma. The addition of PLR as a criterion to the FCG and SCG significantly improved the predictive value of these guidelines in detecting invasive neoplasms.Â© 2015 Wiley Periodicals, Inc.
Phase II study of trastuzumab in combination with S-1 and cisplatin in the first-line treatment of human epidermal growth factor receptor HER2-positive advanced gastric cancer. - Cancer chemotherapy and pharmacology
The use of trastuzumab, a monoclonal antibody targeting the HER2 protein, in combination with 5-fluorouracil/platinum-based chemotherapy improves survival in patients with HER2-positive advanced gastric cancer. In addition, TS-one (S-1)/platinum is also used as a standard of care in Asian countries. However, little is known about the combination of S-1/cisplatin chemotherapy and trastuzumab in patients with HER2-positive advanced gastric/gastroesophageal junction (GEJ) cancer.We conducted a single-arm, two-stage, open-label, multicenter phase II study. Trastuzumab was administered intravenously on day 1 of the first cycle at 8 mg/kg and 6 mg/kg on day 1 of subsequent cycles. Cisplatin was administered intravenously at 60 mg/m(2) on day 1 of each cycle after trastuzumab. S-1 was administered orally [based on body surface area (BSA)] twice a day for 14 days in a 3-weekly cycle. Patients with BSA of <1.25 received a total of 80 mg of S-1, those with BSA â‰¥1.5 received 120 mg, and the remaining received 100 mg daily in two divided doses.All evaluable patients experienced tumor reduction during the trial. The primary end point (overall survival rate) was 59.3 %, with a clinical benefit rate of 66.7 %. Median progression-free survival was 7.4 months; 62.6 % patients were free from disease progression at 6 months. Median overall survival was 14.6 months, and the median time to treatment failure was 6.0 months.The combination of trastuzumab with S-1 and cisplatin demonstrated good activity, was generally well tolerated, and is a feasible treatment option in the first-line treatment of HER2-positive advanced gastric/GEJ cancers.
ChemCom: A Software Program for Searching and Comparing Chemical Libraries. - Journal of chemical information and modeling
An efficient chemical comparator, a computer application facilitating searching and comparing chemical libraries, is useful in drug discovery and other relevant areas. The need for an efficient and user-friendly chemical comparator prompted us to develop ChemCom (Chemical Comparator) based on Java Web Start (JavaWS) technology. ChemCom provides a user-friendly graphical interface to a number of fast algorithms including a novel algorithm termed UnionBit Tree Algorithm. It utilizes an intuitive stepwise mechanism for selecting chemical comparison parameters before starting the comparison process. UnionBit has shown approximately an 165% speedup on average compared to its closest competitive algorithm implemented in ChemCom over real data. It is approximately 11 times faster than the Open Babel FastSearch algorithm in our tests. ChemCom can be accessed free-of-charge via a user-friendly website at http://bioinformatics.org/chemcom/.
New oral anti-coagulants: Implications for neurosurgery. - British journal of neurosurgery
New oral anti-coagulants such as the direct thrombin inhibitor, Dabigatran, and the activated factor X inhibitors, Rivaroxaban and Apixaban, are rapidly gaining clinical popularity in North America and Europe following a number of seminal randomised control trials comparing their efficacy to Warfarin and Enoxaparin. In the coming years these agents are set to replace Warfarin use for the primary prevention of stroke in non-valvular atrial fibrillation, post-operative thromboprophylaxis and the treatment of deep vein thrombosis. The main trials have shown superior anti-coagulant effects over warfarin and low-molecular-weight heparin with the added benefits of lower bleeding complications (including intracranial haemorrhages) and no requirement for monitoring. Case reports are now appearing in the literature, highlighting some of the complications of their use, namely the lack of a uniform normalised anti-coagulation test and the paucity in clinical experience with reversing the anti-coagulant effects when emergent surgery is mandated. This review has been written for the neurosurgeon who will shortly be confronted with increasing numbers of patients taking new oral anti-coagulants and intracranial complications. Hospital clinicians will need to understand the pharmacokinetics of drug administration, the laboratory tests to measure the level of anti-coagulation and the treatment of patients who are therapeutically anti-coagulated and require urgent surgical intervention.
Identification of properties important to protein aggregation using feature selection. - BMC bioinformatics
Protein aggregation is a significant problem in the biopharmaceutical industry (protein drug stability) and is associated medically with over 40 human diseases. Although a number of computational models have been developed for predicting aggregation propensity and identifying aggregation-prone regions in proteins, little systematic research has been done to determine physicochemical properties relevant to aggregation and their relative importance to this important process. Such studies may result in not only accurately predicting peptide aggregation propensities and identifying aggregation prone regions in proteins, but also aid in discovering additional underlying mechanisms governing this process.We use two feature selection algorithms to identify 16 features, out of a total of 560 physicochemical properties, presumably important to protein aggregation. Two predictors (ProA-SVM and ProA-RF) using selected features are built for predicting peptide aggregation propensity and identifying aggregation prone regions in proteins. Both methods are compared favourably to other state-of-the-art algorithms in cross validation. The identified important properties are fairly consistent with previous studies and bring some new insights into protein and peptide aggregation. One interesting new finding is that aggregation prone peptide sequences have similar properties to signal peptide and signal anchor sequences.Both predictors are implemented in a freely available web application (http://www.abl.ku.edu/ProA/). We suggest that the quaternary structure of protein aggregates, especially soluble oligomers, may allow the formation of new molecular recognition signals that guide aggregate targeting to specific cellular sites.
Conservative management of L-asparaginase-induced hypertriglyceridemia in an adult patient: a case report and review of the literature. - Onkologie
L-Asparaginase (L-Asp) may induce hypertriglyceridemia; however, this has been mainly observed among pediatric patients. Treatment for L-Asp-induced hypertriglyceridemia is not standardized, ranging from fasting and diet restriction to the invasive plasmapheresis procedure.We describe a 53-year-old male patient who presented with L-Asp-induced severe hypertriglyceridemia. He was receiving L-Asp as part of his chemotherapy regimen for natural killer T-cell lymphoma. After the 20th dose, his serum triglyceride level was 3,552 mg/dl, with a total cholesterol of 418 mg/dl. Despite the high triglyceride, the patient did not present with acute pancreatitis symptoms. Treatment comprising fasting, fenofibrate, and omega-3 fatty acids was initiated. Triglyceride levels dropped rapidly to 1,000 mg/dl within 2 days, and to 268 mg/dl after 10 days. The chemotherapy regimen was subsequently switched to exclude L-Asp.L-Asp-induced severe hypertriglyceridemia may occur in adults and may be conservatively managed with fasting, fibrates, and omega-3 fatty acids. Plasmapheresis or continuous insulin infusion may be used for symptomatic patients with high triglyceride levels. Lipidlowering agents should be continued for patients previously treated for hyperlipidemia. Regular monitoring of lipid levels for patients receiving L-Asp is important, especially for those with a prior history of dyslipidemia. Re-challenge with L-Asp can be undertaken on an individual basis.Copyright Â© 2012 S. Karger AG, Basel.
The impact of irritable bowel syndrome on health-related quality of life: a Singapore perspective. - BMC gastroenterology
Irritable bowel syndrome (IBS) is a common gastrointestinal disorder. The prevalence of IBS in Asian countries varies from 2.9% to 15.6%. IBS does not result in increased mortality, but is associated with psychological distress and disruption of work and sleep. Consequently, the evaluation of health-related quality of life (HRQoL) is an important outcome measure for patients with IBS since it provides a holistic assessment of the patient's emotional, social and physical function. However, some HRQoL tools can be time-consuming to apply. EQ-5D is a brief HRQoL tool which has been validated in the Western IBS population but has thus far not been used in Asia. This study was conducted to determine whether persons with self-reported symptoms that met the Rome III criteria for IBS had a poorer quality of life than those without these symptoms. We also aimed to determine which specific aspects of quality of life were most affected and whether any risk factors distinguished those with and without IBS.Self-administered questionnaires which included the Rome III diagnostic questionnaire modules for IBS and the EQ-5D questionnaire were obtained from participants of a health symposium in Singapore on 31th October 2010. IBS was diagnosed based on the Rome III Criteria. The main outcome measure was the EQ-5D index score. The relationship between the presence of IBS and the EQ-5D index score, individual dimensions of EQ-5D and demographic risk factors were examined.449 completed questionnaires were analyzed. The mean EQ-5D index score for IBS was 0.739 which was a significant reduction compared to non-IBS participants [-0.11 (95% CI: -0.15 to -0.07), p<0.001]. Multivariate analysis showed that IBS was significantly associated with younger age and higher education level. Of the five EQ-5D dimensions, IBS sufferers were significantly affected in mobility, anxiety or depression, usual activity and pain. There was a "dose related" increase in likelihood of having IBS with increased severity of pain and anxiety or depression.IBS sufferers have significantly poorer quality of life. Assessment of HRQoL in IBS using the EQ-5D should be considered in further studies and routine clinical practice.
SymDex: increasing the efficiency of chemical fingerprint similarity searches for comparing large chemical libraries by using query set indexing. - Journal of chemical information and modeling
The large sizes of today's chemical databases require efficient algorithms to perform similarity searches. It can be very time consuming to compare two large chemical databases. This paper seeks to build upon existing research efforts by describing a novel strategy for accelerating existing search algorithms for comparing large chemical collections. The quest for efficiency has focused on developing better indexing algorithms by creating heuristics for searching individual chemical against a chemical library by detecting and eliminating needless similarity calculations. For comparing two chemical collections, these algorithms simply execute searches for each chemical in the query set sequentially. The strategy presented in this paper achieves a speedup upon these algorithms by indexing the set of all query chemicals so redundant calculations that arise in the case of sequential searches are eliminated. We implement this novel algorithm by developing a similarity search program called Symmetric inDexing or SymDex. SymDex shows over a 232% maximum speedup compared to the state-of-the-art single query search algorithm over real data for various fingerprint lengths. Considerable speedup is even seen for batch searches where query set sizes are relatively small compared to typical database sizes. To the best of our knowledge, SymDex is the first search algorithm designed specifically for comparing chemical libraries. It can be adapted to most, if not all, existing indexing algorithms and shows potential for accelerating future similarity search algorithms for comparing chemical databases.
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