bluuebunny/crossref_metadata_2025 huggingface dataset:
Primary Patency Rates of AV Fistulae and the Effect of Patient Variables
Authors: Field M. , Mcnamara K. , Bailey G. , Jaipersad A. , Morgan R.H. , Pherwani A.D.
Published: March 2018

Background

DOQI (The Dialysis Outcomes Quality Initiative) recommend 40% of prevalent renal failure patients should be undergoing hemodialysis (HD) using autogenous arteriovenous fistulae (AVF). The aim of this study is to assess the primary patency rates of wrist and elbow fistulae, and to examine how patient variables influence the success of a fistula. In addition, an attempt has been made to address the main issue of survival rates in this high risk patient population.

Methods

A retrospective study was performed on all patients in the University Hospital of North Staffordshire who underwent creation of a wrist or elbow fistula for HD. During the study period 289 primary AVFs were created. In all, 210 AVF were sited at the wrist and 79 at the elbow. Follow-up ranged from 3 months to 4 yrs. Primary patency and patient death, transplant and transfer were taken as end points. Patient survival was defined as time of fistula creation to patient death. Actuarial survival was calculated using Kaplan-Meier survival analyses, with differences between groups determined using log rank analysis, and statistical significance obtained using X2 tests.

Results

Primary patency for wrist fistulae was 49, 41 and 32% at 6, 12 and 24 months, respectively, and 57, 51 and 38% for elbow fistulae. Regression analysis showed fistula survival to be significantly greater in males than in females (p=0.023). Fistula survival rates in non-diabetics patients were higher than in patients with diabetes however, this was not significant (p=0.11); (54, 48 and 34% in diabetics compared to 45, 35 and 26% in non-diabetics at 6, 12 and 24 months, respectively). Age did not influence fistula survival; however, it did affect patient survival. Patient survival was 90, 74 and 56% at 1, 2 and 3 yrs, respectively, and in >60s fell to 86, 71 and 50%. Overall 74/245 (30%) patients died.

Conclusion

These results suggest that overall primary patency rates for wrist and elbow fistulae are comparable to similar studies at 6, 12 and 24 months. Fistula survival after this period is dictated by poor patient survival. Our findings suggest that creation of primary vascular access at the elbow in older females and diabetics may be associated with better results.
Peripheral Venous Hypertension of the Hand: A Complication of a Proximal Radial Artery Arteriovenous Fistula
Authors: Anaya-Ayala J.E. , Charlton-Ouw K.M. , Cardon A.L. , Peden E.K.
Published: March 2018

Venous hypertension due to dialysis access is usually secondary to outflow obstruction. The bidirectional proximal radial artery arteriovenous fistula (PRAVF) has been proposed as a procedure to increase autogenous fistula utilization and is rarely reported to cause peripheral venous hypertension. We report here a case of peripheral venous hypertension from a PRAVF, the first report to our knowledge caused by a peripheral outflow obstruction. A proximal occlusion in the medial cephalic vein led to retrograde flow through the median antebrachial vein into the hand. We briefly discuss this complication and considerations of its management in relation to the bidirectional PRAVF creation.
Pseudostenosis of Axillary Vein Due to Adduction of the Upper Limb
Authors: Fabbian F. , Bortot A. , Galeotti R. , Dall'Ara S. , Galdi A. , Bergami M. , Catizone L.
Published: March 2018

Axillary vein stenosis is a well-documented complication in hemodialysis (HD) patients, but in adipose or athletic subjects, pseudostenosis of the axillary vein can be detected. We report a case of pseudostenosis in a fit dialysis patient who underwent phlebography of the right upper limb, performed to create a new vascular access (VA). The investigation demonstrated that the axillary vein appeared sharpened with a reduced lumen. Based on this exam, angioplasty of the right axillary vein was planned. The new phlebographic study, performed abducting the arm, demonstrated that the previously marked stenosis of the axillary vein disappeared. Our case illustrates how the reduction of the axillary vein lumen was secondary to “muscular print” and was present only if the arm was adducted. In uremic patients, the squeezing of the vascular nervous bundle of the upper limb is possible in fit patients at the time of phlebography, an examination that should be performed with the arm both in adduction and abduction.
Ulno-Basilic Arteriovenous Fistulae: Indications and Surgical Technique
Authors: Cavatorta F. , Galli S. , Zollo A. , Crespi E. , Carnabuci A.
Published: March 2018

Ulnar-basilic fistula is a vascular access option for hemodialysis first reported in 1967. There is no inherent reason why the ulnar artery cannot be used to create a fistula at the wrist; however, a few reports dealing with its complications and survival rates have been published in the literature. In the present work the results of 9 ulnar-basilic fistulae done in 9 adults patients on chronic hemodialysis, are reported. Two fistulae were created as primary access and the remaining 7 fistulae as secondary access after thrombosis of an ipsilateral and controlateral radiocephalic fistula in 6 cases and in a case of high-flux brachiocephalic fistula. No episodes of surgical complications were observed. This fistula is an additional option to create a distal vascular access for hemodialysis before constructing a proximal access.
Cross-Talk between Inflammation, Coagulation/Fibrinolysis and Vascular access in Hemodialysis Patients
Authors: Costa E. , Rocha S. , Rocha-Pereira P. , Castro E. , Reis F. , Teixeira F. , Miranda V. , Faria M. Do Sameiro , Loureiro A. , Quintanilha A. , Belo L. , Santos-Silva A.
Published: March 2018

This work aimed to study the association between fibrinolytic/endothelial cell function and inflammatory markers in chronic kidney disease (CKD) patients undergoing hemodialysis (HD) and recombinant human erythropoietin (rhEPO) therapies, and its relationship with the type of vascular access (VA) used for the HD procedure. As fibrinolytic/endothelial cell function markers we evaluated plasminogen activator inhibitor type-1 (PAI-1), tissue plasminogen activator (tPA) and D-dimers, and as inflammatory markers; C-reactive protein (CRP), soluble interleukin (IL)-2 receptor (s-IL2R), IL-6 and serum albumin levels. The study was performed in 50 CKD patients undergoing regular HD, 11 with a central venous dialysis catheter (CVC) and 39 with an arteriovenous fistula (AVF), and in 25 healthy controls. Compared to controls, CKD patients presented with significantly higher levels of CRP, s-IL2R, IL-6 and D-dimers, and significantly lower levels of PAI-1. The tPA/PAI-1 ratio was significantly higher in CKD patients. We also found statistical significant correlations in CKD patients between D-dimers levels and inflammatory markers: CRP, albumin, s-IL2R and IL-6. When comparing the two groups of CKD patients, we found that those with a CVC presented statistically significant lower levels of hemoglobin concentration and albumin, and higher levels of CRP, IL-6, D-dimers and tPA. Our results showed an association between fibrinolytic/endothelial cell function and increased inflammatory markers in CKD patients. The increased levels of D-dimer, tPA and inflammatory markers in CKD patients using a CVC, led us to propose a relationship between the type of VA chosen for HD, and the risk of thrombogenesis.
Successful AV Fistula Creation does not Lead to Higher Catheter Use: The Experience by the Northwest Renal Network 16 Vascular access Quality Improvement Program. Four Years follow-up
Authors: Nguyen V.D. , Griffith C.N. , Reus J. , Barclay C. , Alford S. , Treat L. , Hanthorn M. , Ball L. , Lawson L. , Ledeen M. , Buss J.
Published: March 2018

Background

In 2002, the Center for Medicare and Medicaid Services (CMS) required all 18 Renal Networks to participate in a Vascular Access Quality Improvement Program (QIP). The Northwest Renal Network (NWRN 16) chose to increase arteriovenous fistula (AVF) use. NWRN 16 hypothesized that strategies which targeted the improvement of AVF rate and the reduction of catheter use were the same. In December 2001, 44.2% of hemodialysis (HD) patients in the NWRN 16 received HD using an AVF which met the Dialysis Outcome Quality Initiative (K/DOQI) 40% AVF guideline for prevalent patients. However, 43% of HD facilities (2869 patients) had less than 40% of AVF and higher HD catheter rates than the average Network catheter rates (25.0 vs. 20.3%). To address the needs of underperforming facilities, NWRN 16 provided education and tools for their vascular access decision makers to promote AVF creation and catheter reduction.

Methods

In 2002, NWRN 16 sponsored four regional workshops targeted at nephrologists, vascular surgeons, HD nurses, and interventional radiologists.

Results

Percentage of AVFs in use in invited facilities increased from 31.3% pre-intervention to 56.2% at 4 yrs: 78% increase (99% confidence interval: 77.8% to 81.5%). Percentage of catheters increased from 25% to 25.8%: 3.2% change over 4 yrs (99% confidence interval: 2.5% to 4%).

Conclusion

The success of Network 16's AVF interventions demonstrates the effectiveness of Network education promoting multidisciplinary teamwork, and innovative strategies to increase dramatically AVF use without substantial increase in catheter use.
Contrast-Enhanced Magnetic Resonance Angiography Findings Prior to Hemodialysis Vascular access Creation: A Prospective Analysis
Authors: Planken R.N. , Leiner T. , Nijenhuis R.J. , Duijm L.E. , Cuypers P.W. , Douwes-Draaijer P. , Van Der Sande F.M. , Kessels A.G. , Tordoir J.H.
Published: March 2018

Purpose

To determine prospectively the clinical value of contrast-enhanced magnetic resonance angiography (CE-MRA) for assessment of the arterial inflow and venous outflow prior to vascular access (VA) creation.

Methods

Seventy-three patients underwent duplex ultrasonography (DUS) and CE-MRA prior to VA creation for detection of stenoses and occlusions. Two observers read the CE-MRA images for determination of inter-observer agreement. A VA was considered functional if it could be used for successful two-needle hemodialysis therapy within 2 months after creation.

Results

CE-MRA detected 6 stenosed, 8 occluded arterial vessel segments and 12 stenosed and 41 occluded venous vessel segments in 70 patients. Inter-observer agreement for detection of upper extremity arterial and venous stenoses and occlusions with CE-MRA was substantial to almost perfect (kappa values 0.76–0.96). CE-MRA detected lesions, not detected by DUS, that were associated with VA early failure and non-maturation in 33% of patients (7/21). Accessory veins detected preoperatively were the cause of VA non-maturation in a substantial group of patients (47%: 7/15).

Conclusion

CE-MRA enables accurate detection of upper extremity arterial and venous stenosis and occlusions prior to VA creation. Preoperative CE-MRA identified arterial and venous stenoses, not detected by DUS that were associated with VA early failure and non-maturation. However, the use of gadolinium containing contrast media is currently contraindicated due the reported incidence of nephrogenic systemic fibrosis.
Multi-Slice Computed Tomographic Angiography for Stenosis Detection in Forearm Hemodialysis Arteriovenous Fistulas
Authors: Rooijens P.P.G.M. , Serafino G.P , Vroegindeweij D. , Dammers R. , Yo T.I. , De Smet A.A.E.A. , Tordoir J.H.M.
Published: March 2018

Purpose

A method of diagnosing the extent and severity of arteriovenous fistula (AVF) stenoses is multi-slice computed tomographic angiography (MS-CTA). The aim of this prospective study was to assess the accuracy of MS-CTA for the detection and grading of stenoses in AVF in comparison to digital subtraction angiography (DSA), which was used as the gold standard of reference.

Methods

Fifteen hemodialysis (HD) patients with dysfunctioning forearm AVF were included. These AVFs were evaluated by both DSA and MS-CTA and were read in a prospective, blinded manner by two radiologists experienced in vascular imaging.

Results

ROC analysis revealed areas under the curve of 0.90 ± 0.07 for observer I and 0.87 ± 0.08 for observer II at a stenosis cut-off level of ≥50% diameter reduction. The combined results for MS-CTA showed sensitivity, specificity and positive and negative predictive values of 82%, 98%, 82% and 98% for stenoses ≥50% and 71%, 99%, 77% and 98% for stenoses ≥75%. Inter-observer agreement for the detection of stenoses ≥50% diameter reduction was 0.70 and 1.0, for MS-CTA and DSA, respectively.

Conclusion

MS-CTA can provide good visualization of forearm HD access AVF and has moderate sensitivity, but high specificity for the detection of flow-limiting stenoses.
Quantitative Evaluation of the Systemic Effects of Transposed Basilic Vein to Brachial Artery Arteriovenous Fistula: A Prospective Study
Authors: Saratzis N. , Saratzis A. , Sarafidis P.A. , Melas N. , Ktenidis K. , Kiskinis D.
Published: March 2018

Background

The transposed basilic vein to brachial artery arteriovenous fistula (BBAVF) constitutes an alternative autogenous vascular access (VA) site for chronic hemodialysis (HD); however, the hemodynamic effects of this procedure have not been adequately studied. The purpose of this study is to evaluate the effects of BBAVF on systemic arterial pressure, cardiac function, and upper limb ischemia (ischemic steal syndrome) utilizing reproducible quantitative methods.

Methods

Ten consecutive patients (eight males; mean age: 65.10 ± 2.87 yrs) scheduled to undergo a brachial-basilic vein transposition were included, excluding patients with cardiac failure. Blood flow volume at the level of the AVF, systemic arterial pressure (SAP), cardiac output (CO) and digital brachial index (DBI) were measured intra-operatively, before and after the creation of the BBAVF, and post-operatively on the 30th post-operative day and on the 3rd post-operative month.

Results

SAP and DBI at 30 days and 3 months post-operatively were significantly lower compared to baseline. CO at 30 days and 3 months post-operatively was significantly higher compared to baseline; however, none of the patients developed cardiac failure. DBI remained ≥0.6 at 3 months, except in one case (0.59). Blood flow volume at the level of the AVF was positively correlated with CO levels on the 30th post-operative day. Mean clinical follow-up was 12 months (range: 4–15 months). In two cases (20%) the AVF was thrombosed (4th and 10th post-operative month).

Conclusion

This prospective quantitative study proves that the BBAVF does impact significantly upon SAP, CO, and DBI; however, it is safe in terms of high-output cardiac failure and ischemic steal syndrome. The authors state that they do not have any commercial, proprietary, or financial interest in any products or companies described in this article.
Percutaneous transluminal angioplasty for central venous stenosis or occlusion in hemodialysis patients
Authors: Horita Yuki
Published: March 2018

The objectives of central venous percutaneous transluminal angioplasty are to dilate the venous lesion and to extend the life of arteriovenous fistula for hemodialysis. It is reasonable to perform percutaneous transluminal angioplasty for central venous lesions if this interventional therapy is required to maintain stable dialysis therapy. However, the presence of large fresh thrombus at central venous lesion site represents a contraindication to percutaneous transluminal angioplasty unless the thrombus can first be removed by thrombectomy. Balloon angioplasty is a basic treatment for central venous lesion, but stent implantation is sometimes required. The self-expandable or balloon-expandable stent is chosen by the lesion location and characteristics. The lesion in subclavian vein is generally treated by self-expandable stent and right brachiocephalic vein is treated by balloon-expandable stent. The organic lesion of innominate vein with plaque is treated by self-expandable stent. Note that the innominate venous stenosis is sometimes caused by compression between the right brachiocephalic artery and the sternum, and this lesion is treated by balloon-expandable stent because the radial force of balloon-expandable stent is stronger than self-expandable stent. It is important to understand the indication and stent selection for central venous percutaneous transluminal angioplasty.
Validity of administrative database code algorithms to identify vascular access placement, surgical revisions, and secondary patency
Authors: Al-Jaishi Ahmed A , Moist Louise M , Oliver Matthew J , Nash Danielle M , Fleet Jamie L , Garg Amit X , Lok Charmaine E
Published: March 2018

Background:

We assessed the validity of physician billing codes and hospital admission using International Classification of Diseases 10th revision codes to identify vascular access placement, secondary patency, and surgical revisions in administrative data.

Methods:

We included adults (≥18 years) with a vascular access placed between 1 April 2004 and 31 March 2013 at the University Health Network, Toronto. Our reference standard was a prospective vascular access database (VASPRO) that contains information on vascular access type and dates of placement, dates for failure, and any revisions. We used VASPRO to assess the validity of different administrative coding algorithms by calculating the sensitivity, specificity, and positive predictive values of vascular access events.

Results:

The sensitivity (95% confidence interval) of the best performing algorithm to identify arteriovenous access placement was 86% (83%, 89%) and specificity was 92% (89%, 93%). The corresponding numbers to identify catheter insertion were 84% (82%, 86%) and 84% (80%, 87%), respectively. The sensitivity of the best performing coding algorithm to identify arteriovenous access surgical revisions was 81% (67%, 90%) and specificity was 89% (87%, 90%). The algorithm capturing arteriovenous access placement and catheter insertion had a positive predictive value greater than 90% and arteriovenous access surgical revisions had a positive predictive value of 20%. The duration of arteriovenous access secondary patency was on average 578 (553, 603) days in VASPRO and 555 (530, 580) days in administrative databases.

Conclusion:

Administrative data algorithms have fair to good operating characteristics to identify vascular access placement and arteriovenous access secondary patency. Low positive predictive values for surgical revisions algorithm suggest that administrative data should only be used to rule out the occurrence of an event.
Skin Studies
Authors: Lafrance Marc
Published: March 2018

In this article, I introduce the critical study of the skin in three parts. I start with a reflection on what makes the skin such a suggestive and, arguably, special phenomenon. I then provide a brief overview of the key works, recurring themes and ongoing debates that characterize the skin studies subfield. And finally, I end with a presentation of the articles that make up Body and Society’s special issue on the skin, taking care to highlight how they both contribute to the subfield as it currently stands while orienting it towards new questions, concerns and challenges.
Retained primitive reflexes: Perceptions of parents who have used Rhythmic Movement Training with their children
Authors: Grigg Tessa M , Fox-Turnbull Wendy , Culpan Ian
Published: March 2018

This article reports on a qualitative phenomenological research project that investigated the use of Rhythmic Movement Training (RMT) as an intervention for retained primitive reflexes. Participants were from seven families who each had a child between the ages of 7 years and 12 years. Through semi-structured interviews, parents described their reasons for seeking additional help with their child’s development issues. They talked about finding RMT, using RMT within their family routine and their views on the costs and the benefits they experienced, both financial and time. While there has been a small amount of research into movement programmes targeting retained primitive reflexes, to date there appears to have been no studies completed on RMT. The data collected described searches for help, the stress and frustrations associated with the search and the range of interventions these parents tried. The families in this research found that RMT was easy to use within their daily routine and that it was a cost-effective, low-impact intervention. The families noticed a range of benefits for children who had completed the movements. The findings provide encouraging evidence to proceed with further study that will investigate the academic, social and emotional development of children using RMT.
A new method for estimating the scale of fluctuation in reliability assessment of reinforced concrete structures considering spatial variability
Authors: Yang Yiming , Peng Jianxin , Zhang Jianren , Cai CS
Published: March 2018

The scale of fluctuation ( θ) of the material and geometrical parameters is the basis of studying the spatial variability of reinforced concrete structures. In this article, a new estimation method for the scale of fluctuation based on Bayesian information criterion is proposed. And based on the analysis of experimental data recorded on the three 36-year-old beams of the Jianggong Bridge and 246 corroded steel bars, the scale of fluctuation ( θ) of concrete compressive strength ( fc) and steel pitting factor ( R) are estimated. The theoretical bending moment of three test beams are calculated considering the influence of the spatial distributions of fc, R, and other relative variables. The reasonableness and superiority of the Bayesian information criterion model than the auto-correlation function method and the semivariogram function model are verified by comparing the theoretical results with the measured bending moment of the three beams mentioned above.
Combining Ultrasound-Guided Vascular Access With Ultrasound-Guided Analgesia for Single Skin and Vessel Puncture
Authors: Murray Timothy E. , O’Neill Damien C. , Lee Michael J.
Published: March 2018

Purpose: To describe a single skin puncture technique combining subcutaneous injection of anesthetic to the depth of the vessel wall with venipuncture in the same movement. Technique: Using ultrasound guidance, controlled anesthetic instillation along the needle tract and outer vessel wall with a 21-G vascular access needle can be combined with vessel puncture. This technique reduces the number of skin punctures and ensures accurate anesthetic instillation. The maximum inadvertent intravascular dose of commercial local anesthetic preparations that can be delivered with a small syringe is far below toxicity thresholds. Conclusion: A technique for combining anesthetic administration and vascular access with a 21-G needle and ultrasound guidance is feasible.
Ethical Research Practice or Undue Influence? Symbolic Power in Community- and Individual-Level Informed Consent Processes in Community-Based Participatory Research in Swaziland
Authors: Brear Michelle
Published: March 2018

In community-based participatory research (CBPR), community-level consent is assumed to enhance ethical rigor, when obtained prior to individual informed consent. However, community leaders’ permission to conduct research may influence individuals’ agency to decline participation. This article presents findings of a Bourdieusian analysis of ethnographic data documenting CBPR in rural Swaziland. The findings reveal that the “symbolic power” of leaders who provide community-level consent constrains individual agency and reproduces existing relations of power, if individual informed consent is simply a procedure. However, when informed consent is a process that introduces notions of autonomy and rights, it can disrupt power relations. Implications for ethical CBPR practice, and ethnography’s value for developing theory from real-world research ethics practice, are discussed.
Circulating Immature and Mature Dendritic Cells in Relation to Lymphocyte Subsets in Patients with Gastrointestinal Tract Cancer
Authors: Lissoni P. , Brivio F. , Ferrante R. , Vigore L. , Vaghi M. , Fumagalli E. , Bucovec R. , Malugani F. , Fumagalli L.
Published: March 2018

Cancer-related deficiency in circulating dendritic cells (DC), whose important anticancer role is well established, has been proven to be associated with lymphocytopenia. This study was performed to evaluate which lymphocyte subset is most markedly related to the failure of the DC system. The study included 30 patients with gastrointestinal tract cancer, 10 of whom had distant organ metastases. Immature and mature DCs were measured by FACS and monoclonal antibodies against CD123 and CD11c antigens, respectively. Low levels of immature and mature DCs were observed in 63% and 43% of patients, respectively. Patients with low levels of circulating mature DCs had significantly lower values of T lymphocytes, T helper lymphocytes and NK cells than those with normal mature DC levels. In contrast, no significant difference was seen between patients with normal or abnormally low values of immature DCs. Conversely, patients with a decreased number of T lymphocytes, T helper lymphocytes and NK cells showed significantly lower values of circulating mature DCs than those with lymphocyte subsets within the normal range, whereas no difference was seen in immature DC amounts. This study suggests that only mature DC deficiency may be associated with important lymphocyte subset alterations in cancer patients, whereas deficiency in immature DCs does not seem to be related to other immune cell disorders.
Tumor-Biological Factors Upa and PAI-1 as Stratification Criteria of a Multicenter Adjuvant Chemotherapy Trial in Node-Negative Breast Cancer
Authors: Prechtl A. , Harbeck N. , Thomssen C. , Meisner C. , Braun M. , Untch M. , Wieland M. , Lisboa B. , Cufer T. , Graeff H. , Selbmann K. , Schmitt M. , JÄnicke F.
Published: March 2018

In axillary node-negative primary breast cancer, 70% of the patients will be cured by locoregional treatment alone. Therefore, adjuvant systemic therapy is only needed for those 30% of node-negative patients who will relapse after primary therapy and eventually die of metastases. Traditional histomorphological and clinical factors do not provide sufficient information to allow accurate risk group assessment in order to identify node-negative patients who might benefit from adjuvant systemic therapy. In the last decade various groups have reported a strong and statistically independent prognostic impact of the serine protease uPA (urokinase-type plasminogen activator) and its inhibitor PAI-1 (plasminogen activator inhibitor type 1) in node-negative breast cancer patients. Based on these data, a prospective multicenter therapy trial in node-negative breast cancer patients was started in Germany in June 1993, supported by the German Research Association (DFG). Axillary node-negative breast cancer patients with high levels of either or both proteolytic factors in the tumor tissue were randomized to adjuvant CMF chemotherapy versus observation only. Recruitment was continued until the end of 1998, by which time 684 patients had been enrolled. Since then, patients have been followed up in order to assess the value of uPA and PAI-1 determination as an adequate selection criterion for adjuvant chemotherapy in node-negative breast cancer patients. This paper reports on the rationale and design of this prospective multicenter clinical trial, which may have an impact on future policies in prognosis-oriented treatment strategies.
Cysteine Proteinases and Their Inhibitors in Extracellular Fluids: Markers for Diagnosis and Prognosis in Cancer
Authors: Kos J. , Werle B. , Lah T. , Brunner N.
Published: March 2018

Cathepsins B, H and L have been shown to participate in processes of tumor growth, vascularization, invasion and metastasis. Their levels in tumor tissue extracts can provide useful clinical information to predict disease-free and overall survival in breast, lung, colorectal, brain and head and neck cancer patients. Recently we have found that both cysteine cathepsins and their endogenous protein inhibitors stefins and cystatin C can also predict prognosis when measured extracellularly. In melanoma and colorectal cancer patients high serum levels of cathepsins B and H correlated with shorter survival. Similarly, increased extracellular levels of stefins A and B and cystatin C correlated significantly with high risk of adverse outcome in cancer patients. However, the cathepsin B/cystatin C complex was found to be less abundant in sera of patients with malignant tumors than in those with benign diseases or in healthy controls, suggesting an imbalance between the enzyme and its inhibitor in cancer patients.
Modulation of EGFR Gene Transcription by a Polymorphic Repetitive Sequence – a Link between Genetics and Epigenetics
Authors: Gebhardt F. , BÜrger H. , Brandt B.
Published: March 2018

The epidermal growth factor receptor (EGFR) plays a crucial role in growth, differentiation and motility of normal as well as tumor cells. The transduction of extracellular signals to the cytoplasm via the receptor not only depends on ligand binding, but is also determined by the receptor density on the cell surface. Therefore, with regard to cancer diagnosis and therapeutic approaches targeting EGFR it is important to know how the expression level of EGFR is controlled. We found that transcription activity declines with increasing numbers of CA dinucleotides of a highly polymorphic CA repeat in the first intron of the epidermal growth factor receptor gene. In vivo data from cultured cell lines support these findings, although other regulation mechanisms can compensate this effect. In addition, we showed that RNA elongation terminates at a site closely downstream of the simple sequence repeat (SSR) and that there are two separate major transcription start sites. Model calculations for the helical DNA conformation revealed a high bendability in the EGFR polymorphic region, especially if the CA stretch is extended. These data suggest that the CA-SSR can act like a joint, bringing the promoter in proximity to a putative repressor protein bound downstream of the CA-SSR. The data indicate that this polymorphism may be a marker for cancer, linking genetic and epigenetic risk factors. Furthermore, in breast cancer, heterozygous tumors with short CA-SSR showed an elevated EGFR-expression in contrast to tumours with longer CA-SSR. Tumours with loss of heterozygosity in intron 1 of egfr revealed an increased EGFR expression if the longer allele was lost. Moreover, decreased EGFR gene levels were significantly correlated with poor prognosis in breast cancer.
Detection of Estrogen Receptor-Beta mRNA in Breast Cancer Using RT-PCR
Authors: Cullen R. , Maguire T. , Diggin P. , Hill A. , McDermott E. , O'Higgins N. , Duffy M.J.
Published: March 2018

The estrogen receptor (ER) is the most useful marker currently available for breast cancer, being used both to predict response to therapy and assess prognosis. Recently, a new form of the ER, known as ER-beta, was identified. In this preliminary study we show that ER-beta mRNA was expressed less frequently in breast cancers than ER-alpha. ER-alpha but not ER-beta levels correlated with ER protein as determined by ELISA. We conclude that ER-beta is expressed in approximately 50% of breast cancers but it does not appear to be detected by a widely available ELISA.
A Lysosomal Pepstatin-Insensitive Proteinase as a Novel Biomarker for Breast Carcinoma
Authors: Junaid M. A. , Clark G. M. , Pullarkat R. K.
Published: March 2018

Lysosomal proteinases play an important role in the turnover of intracellular proteins, and acidic proteinases such as cathepsin D are known to be increased in breast carcinoma. In the present study the activity of a newly discovered acidic lysosomal pepstatin-insensitive proteinase (CLN2p) was measured in breast tissues by the most sensitive and highly specific assay that we had developed for the diagnosis of late-infantile neuronal ceroid lipofuscinosis (LINCL) (2). Samples from eight normal subjects undergoing reductive mammoplasty and 200 patients with primary breast carcinoma were analyzed. The results suggest a two- to seventeen-fold higher CLN2p activity in tumors, which was significantly and positively correlated with already known breast cancer biomarkers such as levels of cathepsin D, estrogen receptor and progesterone receptor. These results suggest a diagnostic and prognostic potential for this novel acid proteinase in breast cancer.
Changes in Circulating Dendritic Cells and IL-12 in Relation to the Angiogenic Factor VEGF during IL-2 Immunotherapy of Metastatic Renal Cell Cancer
Authors: Bonfanti A. , Lissoni P. , Bucovec R. , Rovelli F. , Brivio F. , Fumagalli L.
Published: March 2018

Angiogenesis and immunosuppression are the main biological mechanisms responsible for cancer progression. Moreover, recent observations suggesting a negative influence of angiogenesis on anticancer immunity have shown that some angiogenic factors, such as VEGF, may induce immunosuppression. In addition, the evidence of abnormally high blood levels of VEGF has been proven to be associated with resistance to IL-2 immunotherapy. The present study was performed to establish a possible relation ship between the efficacy of IL-2 cancer immunotherapy and changes in circulating levels of VEGF, IL-12, mature and immature dendritic cells (DC). The study included 25 metastatic renal cell cancer patients who underwent subcutaneus low-dose IL-2 immunotherapy (6 MIU/day for 6 days/week for 4 weeks). Immature and mature DCs were identified as CD123+ and CD11c+ cells, respectively. The clinical response consisted of partial response (PR) in five, stable disease (SD) in 11 and progressive disease (PD) in the remaining nine patients. The mean IL-12 levels observed during IL-2 immunotherapy were significantly higher in patients with PR or SD than in those with PD, whereas the mean VEGF concentrations were significantly higher in patients who had PD than in those with PR or SD. Finally, a significant increase in the mean number of circulating mature DCs occurred only in patients with PR or SD, whereas no significant change was seen in patients with PD. By contrast, no significant change was observed in the mean number of immature DCs. This study shows that the efficacy of IL-2 immunotherapy is associated with a significant increase in circulating mature DCs and IL-12, without any concomitant increase in VEGF concentrations. Further studies will be required to better define the relationship between activation of anticancer immunity and control of angiogenesis-related mechanisms.
CCND1 mRNA Overexpression is Highly Related to Estrogen Receptor Positivity but not to Proliferative Markers in Primary Breast Cancer
Authors: Spyratos F. , Andrieu C. , Vidaud D. , Briffod M. , Vidaud M. , Lidereau R. , Bièche I.
Published: March 2018

To elucidate the role of CCND1 alterations in sporadic breast cancer we investigated the possible link between CCND1 mRNA levels versus estrogen-receptor (ER) status and a proliferation marker, S-phase fraction (SPF), measured by flow cytometry. CCND1 expression was quantified by means of real-time quantitative RT-PCR in a well-characterized series of 33 primary breast cancer patients. Eighteen tumors (54.5%) showed CCND1 overexpression ranging from 3.3 to 29.5 times the level observed in normal breast tissue. Seventeen (94.4%) of the 18 cases with CCND1 overexpression were ER-positive compared to seven (46.7%) of the 15 cases with normal CCND1 expression (p=0.0074). CCND1 overexpression was independent of SPF and DNA-ploidy status. These data suggest that the CCND1 gene does not act as an oncogene responsible for more rapid cell proliferation in breast cancer, but could be involved in the regulation of hormone sensitivity associated with ER.
BTA-TRAK Combined with Urinary Cytology is a Reliable Urinary Indicator of Recurrent Transitional Cell Carcinoma (TCC) of the Bladder
Authors: Mattioli S. , Seregni E. , Caperna L. , Botti C. , Savelli G. , Bombardieri E.
Published: March 2018

This study evaluated the diagnostic accuracy of BTA-TRAK in combination with urinary cytology (UC) in the follow-up of patients with a history of transitional cell carcinoma (TCC) of the bladder. The overall sensitivity of BTA-TRAK, UC and the two tests combined for the detection of recurrences was 82.7% (48/58), 84.2% (48/57) and 91.2% (52/57), respectively. BTA and UC showed comparable sensitivity for superficial recurrences (76.7% (33/43) and 78.5% (33/42), respectively) and for invasive recurrences (100% (15/15)); when the two tests were used in combination, the sensitivity for superficial lesions increased to 88% (37/42). BTA-TRAK was more sensitive than UC for G1 recurrences (81.2% (13/16) vs. 68.7% (11/16)), and when the two tests were combined the sensitivity increased to 87.5% (14/16). The sensitivity of the combination was 100% (15/15) for G3 lesions. The differences in urinary BTA-TRAK levels between patients with recurrences and those without evidence of disease were statistically significant (Wilcoxon's test, p<0.05); among patients with recurrences BTA levels were significantly higher in the invasive and poorly differentiated subtypes. In the series of patients studied by us, BTA-TRAK combined with UC was shown to be a non-invasive, accurate test to predict TCC recurrences. Periodic measurement of BTA-TRAK combined with urinary cytology seems to provide additional information for the monitoring of patients treated for TCC; however, due to the presence of false positive and false negative results, this test cannot replace cystoscopy. In a selected group of patients it could, if combined with cytology and ultrasonography and if correctly used and interpreted, orient the timing and indication for cystoscopy.
Elevated Serum Endothelin-1 Levels in Patients with Colorectal Cancer; Relevance for Prognosis
Authors: Peeters C.F. , Thomas C.M. , Sweep F.C. , Span P.N. , Wobbes T. , Ruers T.M.
Published: March 2018

Background

It has been demonstrated that the Doppler Perfusion Index (DPI) is increased in patients who are at risk of developing liver metastases from colorectal cancer. It has been postulated that a circulating hormonal factor is involved in the relative vasoconstriction throughout the splanchnic bed. Endothelin-1 (ET-1), a potent vasoconstrictor which has been associated with tumor growth and is produced by colorectal tumors, may play an important role in this phenomenon. In this paper the prognostic value of serum ET-1 in colorectal cancer is discussed.

Methods

Preoperative serum levels of ET-1 were assessed in three groups of patients: group A underwent resection of the colorectal tumor and remained free of recurrence (n=20); group B developed metachronous liver metastases at least six months after colorectal resection (n=14); and group C presented with colorectal cancer and synchronous liver metastases (n=22).

Results

The mean (SD) serum ET-1 levels in groups A, B and C were 1.59 (0.41) pmol/L, 1.70 (0.32) pmol/L and 1.85 (0.47) pmol/L, respectively. These values were significantly different from those of healthy controls (1.22 (0.31), p<0.05). Kaplan-Meier analyses revealed no prognostic value of preoperative serum ET-1 levels.

Conclusions

These preliminary results demonstrate that serum ET-1 levels are raised in patients with colorectal cancer. Serum ET-1 levels do not seem to be of prognostic value for survival.
Expression and Clinical Significance of Pepsinogen C in Resectable Pancreatic Cancer
Authors: Truan N. , Vizoso F. , Fresno M.F. , Fernández R. , Quintela I. , Alexandre E. , Martínez A.
Published: March 2018

Pepsinogen C is an aspartyl-proteinase usually involved in the digestion of proteins in the stomach, and an androgen- inducible protein in breast cancer cells. In this study we evaluated its expression and clinical significance in patients with resectable pancreatic cancer. Pepsinogen C expression was examined by immunohistochemical methods in a series of 73 pancreatic carcinomas. The prognostic value of pepsinogen C was retrospectively evaluated by multivariate analysis. A total of 21 (28.8%) pancreatic carcinomas stained positively for pepsinogen C. The percentage of pepsinogen C-positive tumors was significantly higher in well-differentiated tumors (38.3%) than in moderately differentiated (15.8%) and poorly differentiated (0%) tumors (p<0.05). In addition, statistical analysis revealed that pepsinogen C expression was associated with clinical outcome. Thus, patients with pepsinogen C-negative tumors have a poorer overall survival than those with pepsinogen C-positive tumors. Our results led us to consider that the expression of pepsinogen C may represent a useful biological marker in pancreatic cancer. Expression of this protein may be a marker of gastric-type differentiation of the tumors and it might also reflect the existence of a complete hormone receptor pathway in a subset of pancreatic carcinomas.
Prognostic Significance of Cytosolic pS2 Protein Content in Gastric Cancer
Authors: Suárez C. , Vizoso F. , Rodríguez J.C. , García I. , Raigoso P. , Allende M.T. , García-Muñiz J.L. , García-Morán M.
Published: March 2018

pS2, a 60-amino-acid chain peptide which is the most widespread estrogen-induced RNA messenger in MCF-7 breast cancer cells, is normally detected in the epithelium of gastric mucosa. The aims of this work were to evaluate the cytosolic pS2 content and its clinical significance in gastric carcinomas. Cytosolic pS2 levels were examined by immunoradiometric methods in 108 patients with primary gastric adenocarcinomas. The mean follow-up period was 23.3 months. The cytosolic pS2 levels of the tumors ranged widely, i.e., from 0.1 to 3217 ng/mg protein. There were no significant differences in pS2 content between tumors (mean ± standard error: 137.2±31.4 ng/mg protein) and paired adjacent mucosa samples (n=84; mean ± standard error: 249.6±32.6 ng/mg protein), nor were there any significant differences in tumoral pS2 levels with respect to clinicopathologic parameters such as patient age and sex or tumor location, stage, histologic type or grade. However, the results indicated that high intratumoral pS2 levels were significantly and independently associated with an unfavorable outcome in the overall group of patients (p=0.0266) and in patients with resectable gastric cancer (p=0.003). In conclusion, pS2 may represent a useful biological marker in gastric cancer.
Prognostic Significance of the Combined Expression of Matrix Metalloproteinase-9, Urokinase Type Plasminogen Activator and its Receptor in Breast Cancer as Measured by Northern Blot Analysis
Authors: Pacheco M.M. , Nishimoto I.N. , Neto M. Mourão , Mantovani E.B. , Brentani M.M.
Published: March 2018

Using Northern blot analysis we have measured the co-expression of the matrix metalloprotease MMP-9, plasminogen activator urokinase type (uPA) and its receptor (uPAR) mRNAs in 81 biopsies of breast carcinomas with the objective of analyzing the impact of these factors on the overall survival probability of the patients (median follow-up time: 4 years). Individual mRNA levels of either uPA or uPAR showed parallel variations with MMP-9 mRNA, suggesting a coordinate transcription of these markers. When median values were used as cutoff points to discriminate between high and low factor expression, no association was found with patient outcome and MMP-9 or uPA mRNA distribution. However, increased uPAR mRNA levels were associated with poor prognosis (p = 0.01). The combination of MMP-9 and uPAR mRNA measurements has not enhanced prognostic information compared to information supplied by the receptor alone (p = 0.01). The combination of MMP-9 and high levels of uPA mRNA led to a significant association with poor outcome (p = 0.03). Multivariate analysis supported the notion that increased uPAR mRNA production in primary breast cancer may be a predictor of overall survival.
Clinical Evaluation of Lentil Lectin-Reactive Alpha-Fetoprotein-L3 in Histology-Proven Hepatocellular Carcinoma
Authors: Khien V.V. , Mao H.V. , Chinh T.T. , Ha P.T. , Bang M.H. , Lac B.V. , Hop T.V. , Tuan N.A. , Don L.V. , Taketa K. , Satomura S.
Published: March 2018

Introduction

Serum alpha-fetoprotein (AFP) is a useful marker of hepatocellular carcinoma (HCC), although the serum AFP concentration is also increased in patients with chronic liver diseases (CLD). The analysis of AFP glycoforms has been known to be of diagnostic value. We applied the lectin-affinity electrophoresis and antibody-affinity blotting techniques to HCC patients in Vietnam in order to better understand the role of lentil lectin-affinity AFP-L3 in the diagnosis and differential diagnosis of HCC, and its relationship with the biological characteristics of HCC.

Methods

Lens culinaris agglutinin-reactive AFP (AFP-L3) was measured in 65 patients with histologically proven HCC and 25 patients with CLD. All patients had serum AFP levels above 54 ng/mL. AFP-L3 levels were determined by lectin affinity electrophoresis coupled with antibody-affinity blotting. The diagnosis of HCC was confirmed histologically by ultrasound-guided biopsy.

Results

The mean value of AFP-L3 in the HCC patients was 49.6 ± 21.6%, which was significantly higher (p<0.001) than that in the 25 CLD patients (10.7 ± 4.3%). When the cutoff level for AFP-L3 was set at 15% (mean ± SD), the sensitivity was 96.9%, the specificity 92.0% and the accuracy 95.5% in the 65 HCC patients. There was no clear correlation between serum AFP level and AFP-L3 percentage (r=0.16). There was no correlation between AFP-L3 and the maximum diameter of HCC nodules (r=0.05). However, the mean AFP-L3 value was higher in moderately or poorly differentiated HCC than in well differentiated tumors (p<0.001).

Conclusions

AFP-L3 is potentially a clinically useful marker for the differentiation of increased AFP levels in hepatocellular carcinoma and chronic liver diseases. The AFP-L3 percentage is closely related to HCC differentiation. We consider the analysis of AFP-L3 a useful adjunct in the diagnosis of HCC.
Detection of Circulating Mammary Mucin (MUC1) and MUC1 Immune Complexes (MUC1-CIC) in Healthy Women
Authors: Croce M.V. , Isla-Larrain M.T. , Price M.R. , Segal-Eiras A.
Published: March 2018

There is convincing epidemiological evidence that multiparity provides protection against the development of breast cancer. In the present study we evaluated the levels of MUC1 and MUC1 circulating immune complexes (MUC1-CIC) in 135 serum samples obtained from healthy women. The study population included 13 women who had never been pregnant, 31 primiparous pregnant women, 36 multiparous pregnant women who had lactated, 5 multiparous pregnant women who had never lactated, 24 multiparous non-pregnant women who were lactating at the time of the study, 24 multiparous non-pregnant women who had lactated, and 2 multiparous non-pregnant women who had never lactated. The purpose of this work was to detect MUC1 variations during pregnancy and lactation as well as to study the possible induction of a humoral immune response against MUC1 in these conditions. We employed ELISA techniques to measure MUC1 (CASA test) and MUC1-CIC (IgM and IgG) using two anti-MUC1 monoclonal antibodies (MAbs): C595 and SM3. Statistical analysis was performed using the ANOVA test. The pooled results pertaining to pregnant versus non-pregnant women were compared and significant differences were observed in MUC1 and MUC1-CIC-IgM levels detected with both MAbs; the MUC1-CIC-IgG levels detected with C595 were increased in the pregnant group while the MUC1-CIC-IgG levels detected with SM3 did not show any significant differences. When the results were compared between lactating and non-lactating women, no significant differences were found. In conclusion, MUC1 and MUC1-CIC-IgM, detected with both MAbs, and MUC1-CIC-IgG levels detected with the MAb C595 are apparently induced by pregnancy.