bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanical Complications of Long-Term Tesio Catheters
Authors: Ndzengue A. , Kessaris N. , Dosani T. , Mustafa N. , Papalois V. , Hakim N.S.
Published: January 2018

Vascular access catheters such as Tesio-Caths are preferentially inserted in the internal jugular vein and serve as access for hemodialysis. Complications related to the removal of these types of lines are uncommon. We report four patients in whom the tip of the Tesio-Cath broke and was left stuck in the superior vena cava. Although there is no defined limit to the maximum length of stay of vascular access catheters for dialysis, the possibility of catheter entrapment should be considered. It remains to be determined whether removing Tesio-Caths every 16–18 months is beneficial in avoiding this complication.
Rescue of an Axillary-Axillary Arteriovenous Graft not Amenable to Endovascular Intervention by Formation of an Axillary Loop: A Case Report
Authors: Frampton A.E. , Hossain M. , Jahromi A.H. , Morsy M. , Chemla E.S.
Published: January 2018

Central venous obstruction associated with a distal arteriovenous fistula can result in massive swelling of the affected extremity and venous hypertension. We present the surgical rescue of an axillary-axillary arterio-venous access ((necklace graft) between the left axillary artery to the contralateral axillary vein), compromised by central venous stenosis, by conversion into an arteriovenous axillary loop graft (AVALG) as an additional “exotic” grafting procedure in the anterior chest. This procedure resulted in the salvage of the patient's access and rapid resolution of the associated upper extremity swelling.
Prosthetic Arteriovenous Grafts for Hemodialysis
Authors: Akoh Jacob A.
Published: January 2018

Introduction

Prosthetic arteriovenous (AV) grafts are indicated in patients with failed AV fistula (AVF), exhausted superficial veins or unsuitable vessels. Increasing the proportion of prevalent hemodialysis (HD) patients using autogenous AVF should reduce the need for AV grafts and associated morbidity. This paper reviews the current role of prosthetic AV grafts in vascular access for HD.

Technical considerations

Prior to the insertion of a prosthetic AV graft, a comprehensive review of previous access procedures and full physical examination in addition to vessel mapping is required. Anastomotic technique should take into account the flow diffuser concept, graft geometry and an anastomotic angle of 15° in order to reduce the incidence of intimal hyperplasia.

Results

Many authors report 1 and 2-yr cumulative graft patency rates of 59–90% and 50–82%, respectively. The major drawbacks with synthetic grafts include: thrombosis, a five-fold increase in infection risk and steal syndrome. The choice between surgical and percutaneous methods of dealing with blocked AV grafts remains controversial, though percutaneous techniques are assuming an increasingly important role. Percutaneous strategies are successful in declotting access in 67–95% of cases. Stenting of stenotic lesions following thrombectomy improves secondary patency rates. Strategies for dealing with AV graft infection include antibiotic prophylaxis, partial, subtotal or total graft excision and the use of biological prosthesis.

Conclusions

Though more prone to complications than autogenous AVFs, AV grafts offer a short maturation period and are more amenable to thrombectomy by radiological or surgical means. Complex AV grafts may be appropriate in patients with exhausted access sites.
Surgical Excision of Infected Arteriovenous Grafts: Technique and Review
Authors: Ceppa Eugene P. , Sileshi Bantayehu , Beasley Georgia M. , Lawson Jeffrey H.
Published: January 2018

Infected prosthetic arteriovenous grafts for hemodialysis present a profound risk to patient well being. Here we present five recent cases and describe our technique for total graft excision. We also review the literature and discuss the much debated role of partial, subtotal, and total graft excision.
Benefits of Intraoperative Digital Subtraction Angiography in Primary Arteriovenous Fistula Creation
Authors: Förster Rolf , Scholz Johannes
Published: January 2018

Digital subtraction angiography (DSA) is an ideal procedure for improving vascular surgery results, not yet in use for arteriovenous fistula (AVF) creation. In a prospective study, the practicability and benefits of intraoperative completion DSA (CDSA) for this purpose were investigated. When the arteriovenous anastomosis was completed and clinically judged as running, DSA via percutaneous or open-site puncture was conducted. Findings and consequences were prospectively documented. From July 2005 to September 2006 a primary AVF was created in 54 patients. Fifty of these could be included in the study (68, 39–91 yrs). In 44 a forearm fistula, and in six patients an elbow fistula was newly created. In two cases we were unable to insert a cannula into the A. brachialis (study escape). In the remaining 48 cases, CDSA visualized afferent artery, anastomosis and draining vein. No complications occurred associated with CDSA; 3.5, 2–12 ml, contrast agent were required per patient. In 13 cases, CDSA revealed problems with the AVF that could be corrected immediately: the vein was freed from restraining soft tissue (n=4), a stealing venous branch was ligated (n=6), transluminal thrombectomy was conducted (n=1) or anastomosis was newly created (n=3). AVF could be successfully created proven by ongoing dialysis in 30 cases, and in eight cases as demonstrated by clinical and sonographic evaluations, resulting in a primary 1-yr patency rate of 79.2%. CDSA in AVF surgery is practicable and reveals conditions that can be corrected immediately, thus improving surgical outcome. Long since standard in other areas of vascular surgery, CDSA should become a routine procedure in AVF creation.
Graft for Immediate use as First Stage of a Native Fistula
Authors: Schuman Earl
Published: January 2018

The majority of patients in the United States begin hemodialysis with a catheter. Many have immature or inadequate fistulae. At 90 days 77% of these patients are still using a catheter or a graft. The morbidity and mortality from prolonged catheter use have been well delineated. Although most of us adhere to the DOQI and Fistula First tenets, a fistula at all costs can seem counterproductive. A new paradigm is needed. The techniques described in this paper offer a novel approach to circumvent the problems of increasing catheter use and long fistula maturation times. The graft for immediate use is placed in the forearm and allows the proximal vessels to mature while providing dialysis access without a catheter. When these vessels meet maturation guidelines, or when surveillance indicates impending graft failure, a native fistula can be constructed and used in a 2–3 week period. This approach minimizes or circumvents catheter use altogether.
Hybrid Management of a False Aneurysm Complicating an Arteriovenous Graft in a Patient with Critical Limb Ischemia
Authors: Kouvelos George N. , Xanthopoulos Dimitrios K. , Harissis Haralampos V. , Arnaoutoglou Helen M. , Matsagas Miltiadis I.
Published: January 2018

End-stage renal diabetic patients undergoing dialysis through an arteriovenous graft (AVG) often present with multiple graft complications which demand a combined therapeutic approach. We report a case of a male suffering from a pseudoaneurysm and venous outflow stenosis of his thigh AVG, as well as from critical limb ischemia caused by multiple significant stenoses of the femoropopliteal arterial segment. The patient was managed in a single session with a combination of classic open surgical and endovascular techniques in order to treat his aneurysm, salvage the AVG and to revascularize his leg. This case illustrates the prospect of combining classic open surgical and endovascular techniques for the optimal management of complicated AVGs. Using the hybrid approach in these cases one can succeed in optimizing the result, while simultaneously minimizing the overall risk for the patient.
Surgical Anatomy of Upper Arm: What is Needed for AVF Planning
Authors: Shenoy Surendra
Published: January 2018

The majority of patients with end-stage renal disease (ESRD) have anatomy suitable for arteriovenous fistula creation. Clinical examination supplemented with duplex Doppler vessel mapping plays a crucial role in evaluation of the anatomy to plan dialysis access in a given patient. Access planning should take into consideration the overall health status and longevity of the ESRD patient on dialysis and potential for the access failure. Accordingly, access planning should involve not only a plan for the initial procedure, but include an algorithm to provide an access sequence to support the patient through the entire ESRD life.
Financial journalism in today’s high-frequency news and information era
Authors: Strauß Nadine
Published: January 2018

This study relies on 22 expert interviews and a survey among 40 financial journalists in the United States to reassess the role of financial journalists for financial markets in today’s high-frequency information and news era. Findings point to a discrepancy between the ideal active watchdog role journalists picture for themselves and their actual role enactment. Furthermore, the process of constructing and distributing financial news has been found to be self-referential within the financial system, leaving little room for alternative voices. In this sense, the influence of regular financial reporting in driving stock market prices has been found to be limited but contingent on various factors such as unexpected news, repeatedly negative reporting, or news about a merger. Eventually, facing the proliferation of online news, journalists have raised a general concern regarding the loss of journalistic values, but they also see potentials for their discipline in light of automated reporting and online news.
Development as resistance and translation: Remaking norms and ideas of the Gates Foundation
Authors: Fejerskov Adam Moe
Published: January 2018

This article explores how ideas and practices manifested in a Bill and Melinda Gates Foundation-funded project on women’s access to land are continuously remade and transformed as they move through the many layers towards implementation. The article builds a theoretical framework that lets us understand development projects as systems of continuous meaning negotiation and translation. It then discusses the particular project’s three dominant reconfigurations of gender and women—from instrumentalizing, to legal-institutional, to transformative and deeply political understandings of the project—as it is continuously remade on its way from headquarter and towards implementation in the Indian state of Odisha.
Measuring young children’s word knowledge: A conceptual review
Authors: Hadley Elizabeth Burke , Dickinson David K
Published: January 2018

The importance of early vocabulary development to later reading comprehension has been well-established. However, there have been a number of criticisms that the assessments typically used to measure oral vocabulary knowledge do not adequately capture the complexity of this construct. This conceptual review works towards a more robust theoretical framework for vocabulary knowledge, focusing especially on the understudied dimension of vocabulary depth, which can be used to evaluate and design measures for early childhood learners. This framework is then used to review measures commonly used for preschool to 1st grade learners in the context of vocabulary interventions and observational studies. Recommendations are made for the use of existing measures and the design of future measures.
Boosting for statistical modelling-A non-technical introduction
Authors: Mayr Andreas , Hofner Benjamin
Published: January 2018

Boosting algorithms were originally developed for machine learning but were later adapted to estimate statistical models—offering various practical advantages such as automated variable selection and implicit regularization of effect estimates. The interpretation of the resulting models, however, remains the same as if they had been fitted by classical methods. Boosting, hence, allows to use an advanced machine learning scheme to estimate various types of statistical models. This tutorial aims to highlight how boosting can be used for semi-parametric modelling, what practical implications follow from the design of the algorithm and what kind of drawbacks data analysts have to expect. We illustrate the application of boosting in the analysis of a stunting score from children in India and a high-dimensional dataset of tumour DNA to develop a biomarker for the occurrence of metastases in breast cancer patients.
Targeting Comorbid Anxiety and Depression Using the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders in Adolescents
Authors: Sherman Jamie A. , Tonarely Niza A. , Ehrenreich-May Jill
Published: January 2018

This article presents the use of an emotion-focused, transdiagnostic therapy approach designed for adolescents with a range of anxiety, obsessive-compulsive, depressive, and related disorders, referred to here as emotional disorders. Preliminary work suggests that emotional disorders share underlying temperament factors, such as high neuroticism and low extroversion in adults and adolescents, possibly influencing the development and maintenance of emotional disorders across the life span. The Unified Protocol for Transdiagnostic Treatment of Emotional Disorders in Adolescents (UP-A) and similar core dysfunction-focused, transdiagnostic therapy approaches may lead to successful treatment by targeting higher order factors that cut across an array of emotional disorders The utility of UP-A for adolescents experiencing a variety of emotional disorder symptoms is demonstrated here through the case illustration of Tony, a 15-year-old adolescent male with severe social and generalized anxiety and mild levels of depression. After 16 individual treatment sessions, Tony demonstrated significant reductions in anxiety and depressive symptoms, as well as an ability to respond more adaptively to a range of emotional experiences. This case study illustrates how short-term, transdiagnostic treatment using the UP-A can effectively ameliorate a wide range of emotional disorder symptoms in adolescents and may also lead to changes in core features of neuroticism, potentially preventing development of further emotional difficulties over time.
Analysis of National Institutes of Health Funding in Hand Surgery
Authors: Silvestre Jason , Ruan Qing Z. , Chang Benjamin
Published: January 2018

Background: Federal research dollars help investigators develop biomedical therapies for human diseases. Currently, the state of funding in hand surgery is poorly understood. This study defines the portfolio of National Institutes of Health (NIH) grants awarded in hand surgery. Methods: This was a cross-sectional study of hand surgeons in the US. Faculty members of accredited hand surgery fellowships and/or members of the American Society for Surgery of the Hand were queried in the NIH RePORT database for awards obtained during 2005-2015. Results: Of 2317 hand surgeons queried, only 18 obtained an NIH grant (0.8%). Thirty-eight unique grants were identified totaling $42 197 375. R01 awards comprised the majority of funding (78.0%) while K08 awards accounted for 1.1%. The K-to-R transition rate was zero. The National Institute of Arthritis and Musculoskeletal and Skin Disease supported the most funding (65.2%), followed by the National Institute of Neurological Disorders and Stroke (30.8%). There was no statistically significant difference in NIH funding totals with hand surgeon characteristics. Funding supported translational (46.0%), basic science (29.6%), clinical (21.0%), and education-based (3.4%) research. Peripheral nerve (33.3%) and bone and joint disease (30.1%) received the most research funding. Conclusions: Less than 1% of hand surgeons obtain NIH research grants. Of the 2 identified K08 awards, none led to a subsequent R award. Future research should identify barriers to grant procurement to design effective policies to increase NIH funding in hand surgery.
Eyelid arteriovenous malformation treated with pre-surgical embolization: A case report
Authors: Juszkat Robert , Żabicki Bartosz , Stanistawska Katarzyna , Szepelak Karolina , Kądziołka Bartosz , Sosnowski Piotr , Kocięcki Jarosław
Published: January 2018

Background

Arteriovenous malformations are potentially serious vascular anomalies that are rarely encountered in the eyelid and require a multidisciplinary approach.

Objectives

We would like to describe the technical and clinical aspects related to the treatment of palpebral arteriovenous malformation with selective embolization, followed by surgical resection.

Methods

A 40-year-old patient presented with an isolated high-flow palpebral arteriovenous malformation. Transarterial embolization, using a liquid embolic agent (PHIL™), was performed in this patient.

Results

Angiographic and clinical follow-up revealed good results with clinical regression of the mass.

Conclusion

Although endovascular treatment of palpebral arteriovenous malformations is technically challenging, good functional and cosmetic result was achieved. Arteriovenous malformation embolization using PHIL™ seems to be very effective and makes subsequent surgical procedure safe and feasible.

Level IV

Evidence obtained from multiple time series with or without the intervention, such as case studies. Dramatic results in uncontrolled trials might also be regarded as this type of evidence.
New Biotechnologies: Spin-off on Health and Society
Authors: Carbone A.
Published: January 2018

New biotechnologies and the new biology deriving from them are having a revolutionary impact on economy and society and are consequently transforming the role of researchers, which is changing continually to meet the competence required. The advances in human genetics on the other hand make it necessary to look for different approaches and new rules in bioethics. Comprehensive views and careful considerations are therefore needed in order that this new biology may have a positive impact on health, being respectful of the social and ethical principles of human beings.
Prognostic Significance of Plasminogen Activator Inhibitor-1 in Breast Cancer, with Special Emphasis on Locoregional Recurrence-Free Survival
Authors: Cufer T. , Vrhovec I. , Borštnar S.
Published: January 2018

The independent prognostic value of protease uPA and its inhibitor PAI-1 for survival in breast cancer patients is firmly established. However, there is very little data on the prognostic value of serine proteases and their inhibitors for locoregional recurrence in breast cancer. The prognostic value of PAI-1 for local control in a group of 766 patients treated at our institute with either breast conserving treatment or modified radical mastectomy was evaluated. The locoregional recurrence-free survival (LRFS) of patients with PAI-1 values above the median value was significantly worse than that of patients with PAI-1 values below the median value (log-rank; p=0.0078). In multivariate analysis PAI-1 levels proved to be of independent statistical significance for LRFS (p=0.0401, relative risk 2.28, 95% confidence interval 1.04–5.02). The independent prognostic value of PAI-1 for metastasis-free survival and overall survival was also confirmed. In addition, our data suggest that PAI-1 antigen levels in tumor tissue might be of prognostic value for survival after locoregional recurrence (log-rank; p=0.0618). According to our findings, PAI-1 levels could be used as a biological marker that could facilitate the identifation of patients with a higher risk of local relapse already at the time of primary treatment. These patients should then be offered more aggressive treatment.
Effect of Antibiotic Treatment on Serum PSA and Percent Free PSA Levels in Patients with Biochemical Criteria for Prostate Biopsy and Previous Lower Urinary Tract Infections
Authors: Lorente J.A. , Arango O. , Bielsa O. , Cortadellas R. , Gelabert-Mas A.
Published: January 2018

Background

Controversy exists as to the influence of inflammatory foci on total and free prostate-specific antigen (PSA) concentrations. The objective was to analyze the biological variations of PSA and percent free PSA (%f-PSA) in patients with biochemical criteria for prostate biopsy (PSA higher than 4 ng/mL and normal rectal examination) and compare them with the variation induced by antibiotic treatment in a cohort of patients with a history of lower urinary tract infections and no clinical evidence of prostatitis.

Methods

Ninety patients with a history of lower urinary tract infections, non-suspicious digital rectal examination and PSA between 4 and 20 ng/mL were analyzed. PSA concentration and %f-PSA were determined. Forty-five patients were treated with three weeks of ofloxacin, following which marker determination was repeated. All patients underwent ultrasound-controlled transrectal six-core prostate biopsy.

Results

Sixty-seven patients presented benign prostatic hyperplasia (BPH) (30 with prostatitic foci) and 23 cancer. Significant variations in PSA (6.97 ng/mL vs. 5.82 ng/mL, p=0.001) and %f-PSA (14.84% vs. 17.53%, p=0.01) were found only in the treated patients. These differences were significant for patients with BPH-associated prostatitic foci and not for patients with BPH or cancer. The tendency was for PSA to decrease (15 treated patients with PSA <4 ng/mL vs. six non-treated patients) and for %f-PSA to increase. The median variation of %f-PSA was greater than that of PSA. When the cutoff for %f-PSA was set at 25%, 18.9% of unnecessary biopsies after the first determination and 20% after the second could be avoided. By associating the reduction in PSA, up to 46% could be avoided in treated patients.

Conclusion

Biochemical criteria for prostate biopsy may be modified in patients with a history of lower urinary tract infections due to variations greater than those explained by intraindividual biological variations, and may be influenced by the antibiotic treatment. These results suggest that subclinical inflammatory foci may influence PSA and %f-PSA.
Prognostic Value of Plasminogen Activator Inhibitors in Breast Cancer
Authors: Borstnar S. , Vrhovec I. , Cufer T.
Published: January 2018

The prognosis of cancer is primarily dependent on its potential to invade and metastasize. Data from both pre-clinical and clinical studies strongly suggest that serine proteases, as well as their inhibitors and receptor, play a central role in the processes leading to metastasis. We therefore investigated the prognostic value of plasminogen activator inhibitors type 1 (PAI-1) and type 2 (PAI-2) and the combination of both inhibitors in 332 patients with operable breast cancer. PAI-1 and PAI-2 content was measured in the primary tumor cytosols using an enzyme-linked immunosorbent assay. For PAI-1 the median value (3.9 ng/mg protein) was used as cutoff, while the optimized cutoff for PAI-2 (6.5 ng/mg protein) was obtained using the log-rank statistic. After a median follow-up of 46 months 96 (29%) patients relapsed. In univariate analysis patients with a high PAI-1 or a low PAI-2 content had an increased risk of relapse. The difference was statistically significant for PAI-1 (p<0.0001) and almost statistically significant for PAI-2 (p=0.057). Stage, tumor size, differentiation grade, lymph node status and hormone receptor status also showed significant univariate impact on disease-free survival (DFS). In multivariate analysis (Cox model) PAI-1 (p<0.0001, RR=2.78), PAI-2 (p=0.0075, RR=2.17), UICC stage (p=0.0014, RR=2.2), differentiation grade (p=0.0097, RR=1.91) and nodal status (p<0.0001, RR=2.9) retained their significance. When both inhibitors were combined the worst prognosis was observed in patients with simultaneous high PAI-1 and low PAI-2 levels, whereas low PAI-1 in combination with high PAI-2 values indicated a very favorable prognosis. In conclusion, our study showed that both PAI-1 and PAI-2 had independent prognostic value in breast cancer. Combination of both inhibitors further improved the differentiation of patients with respect to prognosis.
Cathepsin D Expression in Colorectal Adenocarcinomas and Adenomas
Authors: Kanber Y. , Demirbag N.R. , Sam A.D. , Aydin N.
Published: January 2018

The aim of this study was to investigate the role of cathepsin D in colorectal cancer. For this purpose cathepsin D expression was evaluated by means of immunohistochemistry in stromal and tumor cells of 31 colorectal carcinomas and 29 adenomas. Cytoplasmic cathepsin D expression of tumor cells was present in 90.3% of the carcinoma cases and various degrees of stromal cell cathepsin D expression were present in all cases. In the adenomas, the epithelial cells and stromal cells expressed cathepsin D in 68.96% and 96.55% of cases, respectively. The staining intensity was always weaker in the adenomas. When the stromal and tumor cell cathepsin D expression in the adenocarcinoma and adenoma cases were compared, a statistically significant difference was observed in the staining of stromal cells. Furthermore, stromal cathepsin D expression in the adenocarcinomas was related to tumor stage when the carcinomas were divided into low and high stage. Cathepsin D expression in stromal cells may be an important indicator of poor prognosis in colorectal adenocarcinomas.
Osteoprotegerin and Receptor Activator of Nuclear Factor-κB Ligand (RANKL) in the Serum of Healthy Adults
Authors: Jung K. , Lein M. , Hösslin K. v. , Grosse A. , Roth S. , Possinger K. , Lüftner D.
Published: January 2018

Aims

Osteoprotegerin and the receptor activator of the nuclear factor-κB ligand (RANKL) are decisive factors for maintaining the balance between bone formation and bone resorption. As new, sensitive ELISAs have been developed recently, reference serum ranges should be established to use these analytes for possible diagnostic purposes.

Methods

Measurements were performed in serum samples of 142 healthy adults (82 women, 60 men) between 20 and 70 years of age (mean age: 46 years) using ELISA kits from Immundiagnostik, Bensheim, Germany.

Results

Serum concentrations of osteoprotegerin were age and gender independent and showed a Gaussian distribution, while RANKL concentrations were also age independent but differed between males and females, with a non-Gaussian distribution. For osteoprotegerin a gender-independent upper 97.5 percentile limit of 3.6 pmol/L was calculated while the corresponding limits for RANKL and the ratio of RANKL to osteoprotegerin amounted to 3.29 pmol/L and 2.78 in women and 1.66 pmol/L and 2.18 in men, respectively.

Conclusions

Both osteoprotegerin and RANKL were quantifiable in serum of healthy adults, which means that these compounds can be used as potential diagnostic tools.
Quantitative Analysis of Urinary Daidzein and Equol by Gas Chromatography after Solid-Phase Extraction and High-Performance Liquid Chromatography
Authors: Venturelli E. , Rinaldi S. , Cambiè M. , Cavalleri A. , Secreto G.
Published: January 2018

Daidzein and its main metabolite equol are isoflavone phytoestrogens. Several studies have suggested that intake of an isoflavone-rich diet may prevent hormone-related cancer and estrogen-related disorders (cardiovascular disease, osteoporosis and menopausal symptoms). To better understand the role of isoflavones in preventing such severe disease, several methods have been developed to measure these compounds in biological fluids. However, the analytical procedures to measure isoflavones are often time-consuming and require highly skilled technicians. In this paper we describe a method for urinary daidzein and equol measurement that combines solid phase extraction and HPLC purification before gas chromatographic determination. The specificity of the method was confirmed by the gas chromatography-mass spectrometry technique. The mean recovery of daidzein and equol was 94.6% and 97.0%, respectively. The repeatability of the method was in the range of 2.0–7.4% for daidzein and 1.3–4.9% for equol. A linear relationship between observed and expected values was found in the dilution (r2=0.9983 for daidzein; r2=0.9982 for equol) and addition (r2=0.9984 for daidzein; r2=0.9989 for equol) assays. The method is suitable to measure changes in the urinary excretion of isoflavones and to investigate urinary isoflavonoids as biomarkers of isoflavone exposure.
Mutation Analysis in the Coding Sequence of Thymidine Kinase 1 in Breast and Colorectal Cancer
Authors: Gilles S.I. , Romain S. , Casellas P. , Ouafik L'h. , Fina F. , Combes T. , Vuaroquaux V. , Seitz J.-F. , Bonnier P. , Galiègue S. , Carayon P. , Martin P.-M.
Published: January 2018

We report the first mutational study of thymidine kinase 1 (TK1) performed in human solid tumors. We sequenced cDNAs representing the complete coding region of TK1 in human breast (n=22) and colorectal (n=26) cancer. Codon 106 near the ATP binding site constantly differed (ATG → GTG; Met → Val) from the one deposited by Bradshaw and Deininger in the Genbank database (Accession number NM_003258). Silent polymorphisms at codon 11 (CCC → CCT; Pro → Pro) and codon 75 (GCG → GCA; Ala → Ala) were frequently detected in tumors as well as in normal tissues. In breast cancer the two polymorphisms were observed in 63.6% of the samples analyzed. No significant association could be found between polymorphisms and TK activity. In colorectal cancer the incidence of the two changes was 73.1% and 69.2%, respectively. Interestingly, one colon cancer with high cytosolic TK activity displayed two missense mutations located in and near the putative phosphorylation site by tyrosine kinase (s) (TAT → CAT; Tyr → His) and by cAMP-, cGMP-dependent protein kinase (TAC → TGC; Tyr → Cys), respectively; adjacent normal mucosa showed no mutation. This may open new avenues that imply TK1 activity in tumor cell proliferation.
Overall Survival in Advanced Breast Cancer: Relevance of Progesterone Receptor Expression and DNA Ploidy in Fine-Needle Aspirates of 392 Patients
Authors: Pinto A.E. , André S. , Mendonça E. , Silva G. , Soares J.
Published: January 2018

Fine-needle aspiration cytology (FNAC) is essential for making a diagnosis in advanced breast cancer. The determination of hormone receptors in the material obtained is useful for predicting patient response to endocrine therapy, but the prognostic value of hormone receptor expression as well as the clinical utility of DNA flow cytometry are controversial. The aim of this prospective study with long-term follow-up (median: 81 months) was to evaluate these biomarkers in relation to overall survival in a series of 392 patients with advanced breast cancer (stage IIB, n=106; IIIA, n=66; IIIB, n=174; and IV, n=46) using FNAC. Estrogen and progesterone receptor expression was found in 65.1% and 46.1% of the tumors, respectively. Hormone receptors were not found to be associated with clinical staging. DNA aneuploidy was present in 70.9% of the cases and the median S-phase fraction (SPF) was 9.4%. There was a significant correlation of aneuploidy and high SPF with lack of hormone receptors. In univariate analysis, advanced disease stage, absence of hormone receptors, DNA aneuploidy and high SPF showed a statistically significant correlation with poor clinical outcome. In multivariate analysis, disease stage, progesterone receptors and DNA ploidy retained independent prognostic significance in relation to overall survival. These data indicate that progesterone receptor expression and DNA ploidy are independent prognostic factors in advanced breast cancer.
Negative CEA values in Metastatic Colorectal Carcinoma and the Likelihood of Complete Chemotherapy Response
Authors: Tomasevic Z. , Jelic S. , Nikolic L. , Filipovic I. , Stamatovic L. , Radosavljevic D.
Published: January 2018

Introduction

Experimental results reported in the literature have suggested that CEA might inhibit host defense mechanisms and that immunotolerance to CEA could play an important role in the development of metastases in colorectal carcinoma. It might therefore be assumed that negative CEA values during metastatic disease represent a favorable prognostic factor. Surprisingly, there are very few data available about negative CEA. The aim of this study was to determine the significance of negative initial CEA values in patients with metastatic colorectal carcinoma.

Patients and Methods

Initial CEA values were determined in 114 patients with metastatic colorectal carcinoma. The patients were divided into three groups according to these values: I (n=22) <5 ng/mL; II (n=33) 5-100 ng/mL; III (n=59) >100 ng/mL.

Results

Seven/114 complete responses (CR), 22/114 partial responses (PR), 45/114 instances of stable disease (SD) and 38/114 of progressive disease (PD) were registered, while two patients were not evaluable. There were six long-lasting CRs (median 24 months, range 10–37 months) in the CEA-negative patient subset, while in the CEA-positive subset there was only one CR, in a patient with an initial CEA level of 18 ng/mL. The mean initial CEA values in the different response categories were: CR: 4.0 ng/mL; PR: 436 ng/mL; SD: 1442 ng/mL; PD: 6071 ng/mL. The likelihood of response, in particular CR, was highly dependent upon CEA levels (Fisher's exact test, 0.00001). The median survival decreased significantly with increased values of CEA (p=0.006).

Conclusion

Negative CEA in metastatic disease was the main characteristic of the patient subset capable of attaining CR. When relapsing, all patients but one became CEA positive.
CD44v10: An Antimetastatic Membrane Glycoprotein for Pancreatic Cancer
Authors: Navaglia F. , Fogar P. , Greco E. , Basso D. , Stefani A.L. , Mazza S. , Zambon C.-F. , Habeler W. , Altavilla G. , Amadori A. , Cecchetto A. , Plebani M.
Published: January 2018

Aims

The aims of this study were 1) to investigate the mRNA pattern of CD44 variants in three primary (MIA PaCa 2, PANC-1, PSN-1) and two metastatic (CAPAN-1, SUIT-2) pancreatic cancer (PC) cell lines; 2) to ascertain whether the genetic transfer of CD44s and CD44v10 modifies the adhesion of PC cells to the extracellular matrix (ECM) in vitro and their metastatic behavior in vivo.

Methods

CD44 mRNA analysis was done by means of RT-PCR. Adhesion to ECM the was assessed using coated microtiter plates. For the study of CD44v10 insertion in the CAPAN-1 line, liposome-mediated DNA transfer was used. SCID mice were employed for in vivo experiments.

Results

CD44v10 mRNA was not expressed by the CAPAN-1 nor by four of the six SUIT-2-derived clones. The stable expression of CD44v10 by modified CAPAN-1 significantly enhanced fibronectin adhesion. Mice without either liver or pancreatic metastases were more frequently found among the animals injected with modified (CD44v10 expressing) than with non-modified CAPAN-1.

Conclusions

1) It is possible to differentiate between metastatic and non-metastatic PC cells on the basis of CD44v10 expression; 2) CD44v10 seems to be involved in mediating fibronectin adhesion in vitro and in counteracting metastases in vivo.
The Effect of EGFR-Related Tyrosine Kinase Activity Inhibition on the Growth and Invasion Mechanisms of Prostate Carcinoma Cell Lines
Authors: Ünlü A. , Leake R.E.
Published: January 2018

Increased urokinase plasminogen activator (uPA) levels and epidermal growth factor receptor (EGFR)-related tyrosine kinase activity are associated with poor prognosis in several cancers. We studied the effect of epidermal growth factor (EGF) and a specific inhibitor of EGFR, ZM252868, on the growth and invasiveness of the prostate cancer cell lines PC3 and DU145. PC3 cell growth was stimulated by exogenous EGF but DU145 cell growth was not. EGFR-specific tyrosine kinase inhibitor significantly inhibited the growth of both cell types. EGF increased uPA protein level and uPA activity in both cell types. EGF stimulation also resulted in increased uPAR transcript in both cell lines. uPA production and activity were suppressed by the inhibitor to well below the levels in control cells. Matrigel invasion of PC3 cells was increased by EGF. ZM252868 also reversed the EGF-stimulated matrigel invasion by PC3 cells. Our results indicate that EGF is a potent stimulative agent for both growth and invasion in prostate cancer cells, and that targeting the EGFR function inhibits not only tumor growth but also invasiveness.
Transforming Growth Factor β1 Stimulates Urokinase Plasminogen Activator System on Prostate Cancer Cells
Authors: Ünlü A. , Leake R.E.
Published: January 2018

The effect of TGFβ1 on the proliferation and plasminogen activator system (PA) of two prostate carcinoma cell lines, PC3 and DU145, was investigated. PA, particularly urokinase plasminogen activator (uPA), has been implicated in extracellular proteolysis, local invasiveness, metastatic spread and angiogenesis. High levels of uPA and plasminogen activator inhibitor-1 (PAI-1) correlate with poor prognosis in several cancers. TGFβ1 had no significant effect on the proliferation of either cell line. TGFβ1 increased the production of uPA in PC3 and DU145 cells. Despite the very low PAI-1 protein levels in both cell lines, TGFβ1 treatment resulted in a remarkable increase in PAI-1 secretion. PAI-2 protein was also increased by 59% in the PC3 cells. A divergent effect of TGFβ1 on the uPA enzyme activity was observed (28% decrease in PC3 and 131% increase in DU145 cells). Overall, TGFβ1 treatment did not affect the invasion of reconstituted basement membrane of PC3 cells. In addition to the uPA:PAI-1 ratio, the presence of PAI-2 may be an important factor in the determination of metastatic sites for prostate cancer cells. In conclusion, the potential contribution of TGFβ1 to tumor invasion may be considered as positive, based on both loss of growth inhibition and stimulation of components of the invasive system of prostate carcinoma.
Changes in Circulating VEGF Levels in Relation to Clinical Response during Chemotherapy for Metastatic Cancer
Authors: Lissoni P. , Rovelli F. , Malugani F. , Brivio F. , Fumagalli L. , Gardani G.S.
Published: January 2018

Abnormally high blood levels of vascular endothelial growth factor (VEGF) appear to be associated with a poor prognosis in advanced cancer, probably as a consequence of its angiogenic and immunosuppressive effects. The prognostic significance of changes in VEGF secretion during cancer chemotherapy is still unknown. This study aimed to investigate the relation between VEGF variations and therapeutic results during chemotherapy in advanced malignancies. The study included 90 metastatic cancer patients, 59 with non-small cell lung cancer and 31 with colorectal carcinoma. Chemotherapy consisted of cisplatin plus etoposide for NSCLC and camptothecin for colorectal cancer. Abnormally high (>2 SD with respect to values in healthy controls) pretreatment VEGF levels were found in 38/90 (42%) patients. The percentage of non-progressive disease in response to chemotherapy was significantly higher in patients with normal levels of VEGF prior to therapy than in those with elevated pretreatment values of VEGF (10/32 vs 4/27; p<0.05). Moreover, the percentage of VEGF level normalization during chemotherapy was significantly higher in patients with objective tumor response or stable disease than in progressing patients (10/18 vs 0/20; p<0.001). Finally, among patients with tumor response or disease stabilization, the one-year survival rate was significantly higher in patients with chemotherapy-induced normalization of VEGF than in those with persistently high VEGF blood levels (9/10 vs 3/8; p<0.05). These results suggest that changes in VEGF levels during chemotherapy may represent a useful biomarker to predict the effect of chemotherapy in terms of tumor response and survival in patients with metastatic solid neoplasms.
Epidermal Growth Factor Receptor and c-erbB-2 Contents in Unresectable (UICC R1 or R2) Gastric Cancer
Authors: García I. , Del Casar J.M. , Corte M.D. , Allende M.T. , García-Muñiz J.L. , Vizoso F.
Published: January 2018

Background

Epidermal growth factor receptor (EGFR) and c-erbB-2 are membrane receptors expressed in a variety of solid human cancers and directly correlated with poor prognosis. The objective of this work was to evaluate the EGFR and c-erbB-2 levels in non-resectable gastric carcinomas, their possible relationship with a variety of clinicopathological tumor parameters, and their prognostic significance.

Methods

This was a prospective analysis of 65 patients with unresectable gastric carcinomas (UICC R1 or R2), who underwent palliative surgery and were followed up for a median period of 13 months. Membranous EGFR levels were examined by radioligand binding assays and cytosolic c-erbB-2 levels by means of an immunoenzymatic assay.

Results

There was a wide variability in EGFR (80.3-2910 fmol/mg of protein) and c-erbB-2 (0.4-10071 NHU/mg of protein) levels in neoplastic tissues from patients with unresectable gastric carcinomas. Median c-erbB2 was significantly higher in tumors of the intestinal type than in tumors of the diffuse type (p=0.035) and in R2 than in R1 tumors (p=0.016). Statistical analysis showed that there was no relationship between tumor c-erbB-2 or EGFR content and any other patient or tumor characteristics. However, high levels of EGFR were significantly associated with a shorter overall survival (p=0.01).

Conclusion

Our data suggest a role of both transmembrane proteins in the progression of gastric cancer. EGFR and c-erbB-2 contents in unresectable gastric cancer could be utilized as appropriate biological markers for selecting candidates for treatment based on EGFR and/or c-erbB-2 inhibition.
Cytosolic Levels of An Estrogen-Induced Breast Cancer-Associated Peptide (TFF1/pS2) in Colorectal Cancer: Clinical Significance and Relationship with Steroid Receptors
Authors: Vizoso F.J. , Fagilde M.C. , Corte M.D. , Corte M.G. , Gava R. , Bongera M. , Allende M.T. , García-Muñiz J.L.
Published: January 2018

Background

The Trefoil Factor 1 (TFF1/pS2), a peptide consisting of 60 amino acids, is the most abundant estrogen-induced messenger RNA in MCF-7 breast cancer cells and is also expressed by colorectal carcinomas. The objective of this work was to evaluate the cytosolic TFF1 content in colorectal carcinomas, its possible relationship with estrogen and progesterone receptors as well as with clinicopathological tumor parameters, and its potential prognostic significance.

Methods

Cytosolic TFF1 levels were examined by immunoradiometric assay in 178 patients with resectable colorectal cancer. The mean follow-up period was 32 months.

Results

There was a wide variability of cytosolic TFF1 levels in tumor-surrounding mucosa samples (0.09-42.5 ng/mg protein) as well as in tumors (0.01-270 ng/mg protein). Comparison of paired mucosa and carcinoma samples showed significantly higher TFF1 levels in tumors (mean: 17.1 ng/mg protein) than in mucosa samples (10 ng/mg protein) (p=0.027). TFF1 levels were significantly higher in mucosa samples surrounding distal colon and rectal tumors (p=0.0001) and in tumor samples obtained from older patients (p=0.007). However, there were no significant differences in tumor TFF1 levels with respect to clinicopathological parameters such as the patient's sex, tumor location, stage, histological grade, ploidy, S-phase, or tumor estrogen and progesterone receptors. In addition, there was no significant relationship between tumor TFF1 levels and disease outcome.

Conclusions

TFF1 may play an as yet undetermined role in the tumorigenesis of colorectal carcinomas. However, cytosolic levels of TFF1 do not seem to have any prognostic significance in colorectal carcinomas.
Questioning the Utility of Pooling Samples in Microarray Experiments with Cell Lines
Authors: Lusa L. , Cappelletti V. , Gariboldi M. , Ferrario C. , De Cecco L. , Reid J.F. , Toffanin S. , Gallus G. , McShane L.M. , Daidone M.G. , Pierotti M.A.
Published: January 2018

We describe a microarray experiment using the MCF-7 breast cancer cell line in two different experimental conditions for which the same number of independent pools as the number of individual samples was hybridized on Affymetrix GeneChips. Unexpectedly, when using individual samples, the number of probe sets found to be differentially expressed between treated and untreated cells was about three times greater than that found using pools. These findings indicate that pooling samples in microarray experiments where the biological variability is expected to be small might not be helpful and could even decrease one's ability to identify differentially expressed genes.
Evaluation of Diagnostic Accuracy of Screening by Fecal Occult Blood Testing (FOBT). Comparison of FOB Gold and OC Sensor Assays in a Consecutive Prospective Screening Series
Authors: Rubeca T. , Rapi S. , Confortini M. , Brogioni M. , Grazzini G. , Zappa M. , Puliti D. , Castiglione G. , Ciatto S.
Published: January 2018

We evaluated a new immunological fecal occult blood testing assay (FOB Gold, Sentinel = SENT) compared to the assay currently employed in the Florence screening program (OC-Hemodia, Eiken = OC). A total of 4,133 subjects were screened with both tests and underwent colonoscopy if positive (100 ng/mL Hb cutoff) to either test: 190 (4.59%) were positive (OC =140 (3.4%); SENT = 131 (3.2%)). The relative sensitivity for 7 cancers was 100% with OC and 67.9% with SENT, and for 48 high-risk adenomas (HRAs) it was 77.0% with OC and 66.6% with SENT. The positive predictive value (PPV) for cancer+HRA was 31.4% for OC and 28.2% for SENT and the specificity was 97.7 for both. The differences were not statistically significant. Adding SENT to OC increased the positivity rate by 32% and the cancer+HRA detection rate by 25%, and decreased the PPV by 10%. Both tests were performed on the same tubes in 1,601 cases, and in 18 of 47 cases they differed on different tubes but not on the same tube, suggesting inhomogeneous Hb content or varying fecal matrix influence in different samples. SENT has practical advantages for screening (fully automated, high output, requires no dedicated instrument), a comparable specificity and a lower sensitivity, though the latter difference may be partially ascribed to differences in sampling and not to the assay itself. Because of the statistical insignificance of the differences, further studies are needed for confirmation.
Prognostic value of Carcinoma-associated Antigen MK-1 in Urinary Bladder Carcinoma
Authors: EL-Kenawy A. EL-Meghawry , El-kott A.F. , Hamed S.M. , Kuroki M.
Published: January 2018

Background

The present study has been performed to evaluate the expression of MK-1 in schistosomiasis-associated squamous cell carcinoma of the urinary bladder and to correlate this new marker with the conventional histopathological parameters.

Patients and methods

Paraffin sections of 5-μm thickness from 81 cases were prepared for hematoxylin and eosin staining and immunohistochemical analysis of MK-1 expression was carried out.

Results

Forty-six cases (56.8%) were positive for MK-1 protein expression. Significant correlations between MK-1 expression and tumor grade (p=0.004), schistosoma (p=0.031), DNA ploidy (p=0.001), and tumor recurrence (p<0.001) were observed. MK-1, sex, tumor grade, stage, schistosoma, DNA ploidy, and recurrence were evaluated in relation to outcome. Univariate and multivariate analysis of survival were performed. The overall 5-year survival was 51.85%. In univariate analysis, MK-1 expression, tumor grade, DNA ploidy, and recurrence had a significant impact on the survival of these patients. In a Cox proportional hazards model, recurrence maintained its significant impact on survival.

Conclusions

These findings suggest that MK-1 is a prognostic marker for recurrence: 34 (87.2%) of 39 recurrent cases were positive for MK-1 expression. However, only recurrence was an independent prognostic factor in patients with schistosomiasis-associated squamous cell carcinoma of the bladder.