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Expression of the solute carrier (SLC) transporter SLC22A3 gene is associated with overall survival of pancreatic cancer patients. This study tested whether genetic variability in SLC22A3 associates with pancreatic cancer risk and prognosis. Twenty four single nucleotide polymorphisms (SNPs) tagging the SLC22A3 gene sequence and regulatory elements were selected for analysis. Of these, 22 were successfully evaluated in the discovery phase while six significant or suggestive variants entered the validation phase, comprising a total study number of 1,518 cases and 3,908 controls. In the discovery phase, rs2504938, rs9364554, and rs2457571 SNPs were significantly associated with pancreatic cancer risk. Moreover, rs7758229 associated with the presence of distant metastases, while rs512077 and rs2504956 correlated with overall survival of patients. Although replicated, the association for rs9364554 did not pass multiple testing corrections in the validation phase. Contrary to the discovery stage, rs2504938 associated with survival in the validation cohort, which was more pronounced in stage IV patients. In conclusion, common variation in the SLC22A3 gene is unlikely to significantly contribute to pancreatic cancer risk. The rs2504938 SNP in SLC22A3 significantly associates with an unfavorable prognosis of pancreatic cancer patients. Further investigation of this SNP effect on the molecular and clinical phenotype is warranted.

There are excellent guidelines for clinicians to manage venous diseases but few reviews to assess their hemodynamic background. Hemodynamic concepts that evolved in the past have largely remained unchallenged in recent decades, perhaps due to their often complicated nature and in part due to emergence of new diagnostic techniques. Duplex ultrasound scanning and other imaging techniques which evolved in the latter part of the 20th century have dominated investigation. They have greatly improved our understanding of the anatomical patterns of venous reflux and obstruction. However, they do not provide the physiological basis for understanding the hemodynamics of flow, pressure, compliance and resistance. Hemodynamic investigations appear to provide a better correlation with post-treatment clinical outcome and quality of life than ultrasound findings. There is a far better prospect for understanding the complete picture of the patient's disability and response to management by combining ultrasound with hemodynamic studies. Accordingly, at the instigation of Dr Angelo Scuderi, the Union Internationale de Phlebologie (UIP) executive board commissioned a large number of experts to assess all aspects of management for venous disease by evidence-based principles. These included experts from various member societies including the European Venous Forum (EVF), American Venous Forum (AVF), American College of Phlebology (ACP) and Cardiovascular Disease Educational and Research Trust (CDERT). Their aim was to confirm or dispel long-held hemodynamic principles and to provide a comprehensive review of venous hemodynamic concepts underlying the pathophysiology of lower limb venous disorders, their usefulness for investigating patients and the relevant hemodynamic changes associated with various forms of treatment. Chapter 1 is devoted to basic hemodynamic concepts and normal venous physiology. Chapter 2 presents the mechanism and magnitude of hemodynamic changes in acute deep vein thrombosis indicating their pathophysiological and clinical significance. Chapter 3 describes the hemodynamic changes that occur in different classes of chronic venous disease and their relation to the anatomic extent of disease in the macrocirculation and microcirculation. The next four chapters (Chapters 4-7) describe the hemodynamic changes resulting from treatmen by compression using different materials, intermittent compression devices, pharmacological agents and finally surgical or endovenous ablation. Chapter 8 discusses the unique hemodynamic features associated with alternative treatment techniques used by the CHIVA and ASVAL. Chapter 9 describes the hemodynamic effects following treatment to relieve pelvic reflux and obstruction. Finally, Chapter 10 demonstrates that contrary to general belief there is a moderate to good correlation between certain hemodynamic measurements and clinical severity of chronic venous disease. The authors believe that this document will be a timely asset to both clinicians and researchers alike. It is directed towards surgeons and physicians who are anxious to incorporate the conclusions of research into their daily practice. It is also directed to postgraduate trainees, vascular technologists and bioengineers, particularly to help them understand the hemodynamic background to pathophysiology, investigations and treatment of patients with venous disorders. Hopefully it will be a platform for those who would like to embark on new research in the field of venous disease.

The thyrocytes are exposed to high levels of oxidative stress which could induce DNA damages. Base excision repair (BER) is one of the principal mechanisms of defense against oxidative DNA damage, however recent evidences suggest that also nucleotide excision repair (NER) could be involved. The aim of present work was to identify novel differentiated thyroid cancer (DTC) risk variants in BER and NER genes. For this purpose, the most strongly associated SNPs within NER and BER genes found in our previous GWAS on DTC were selected and replicated in an independent series of samples for a new case-control study. Although a positive signal was detected at the nominal level of 0.05 for rs7689099 (encoding for an aminoacid change proline to arginine at codon 117 within NEIL3), none of the considered SNPs (i.e. rs7990340 and rs690860 within RFC3, rs3744767 and rs1131636 within RPA1, rs16962916 and rs3136166 in ERCC4, and rs17739370 and rs7689099 in NEIL3) was associated with the risk of DTC when the correction of multiple testing was applied. In conclusion, a role of NER and BER pathways was evoked in the susceptibility to DTC. However, this seemed to be limited to few polymorphic genes and the overall effect size appeared weak., (Copyright © 2016. Published by Elsevier B.V.)

The first part of this review article provides the physiologic background that sustained the CHIVA principles development. Then the venous networks anatomy and flow patterns are described with pertinent sonographic interpretations, leading to the shunt concept description and to the consequent CHIVA strategy application. An in depth explanation into the hemodynamic conservative cure approach follows, together with pertinent review of the relevant literature.

Background: Leukapheresis for autologous stem cell transplantation represents an efficient technique for the reconstitution of haematopoietic system in patients subjected to a high-dose chemotherapy for the treatment of haematological malignancies. The current regulations emphasise first steps of leukapheresis procedure but do not recommend methods for thawing, only suggesting that it must be performed as soon as possible in a 37 °C thermostatic bath., Aim of the Study: We compared the classic method of thawing with an innovative and fully traceable method that uses WSCFD(®) Stem Cell Fast Thawer KW., Materials and Methods: The first part of the study was focused on the thermodynamic process of the two methods, thawing 6 "simulated" leukapheresis (buffy coats of healthy donors cryopreserved with saline solution, 5% HSA and 5% DMSO) and analysing the thawing curve obtained, by using an inside probe. In the second part, we focused on the recovery of viable CD34+ cells and leukocytes, thawing 20 real leukapheresis from paediatric patients. In this phase we also analyse final core bag temperature, time of procedure, cellular recovery with ISHAGE single platform flow cytometry assay and clonogenic potential performing a CFU assay., Results: We found no significant differences between the two methods, both for thermodynamic aspect and cellular recovery. Thawing curves were similar and the paired Student's-t test used for statistical analysis showed a CD34+ cells recovery of 92.2% ± 11.4 using WSCFD(®) versus 90% ± 11.1 of thermostatic bath. Data were similar even for leukocytes recovery (80.8% ± 9.5 with WSCFD(®) and 79.2% ± 14.4 with thermostatic bath). All thawed products never exceeded the core temperature of 30 °C and no differences were found about the post-thaw clonogenic potential (614 × 10(4) ± 98.3 total CFU using WSCFD(®) versus 592 × 10(4) ± 78.5 using thermostatic bath). The only difference observed was about the thawing time: WSCFD method requires a slightly longer time but, on the other hand, it correlates with reduced mean increase in temperature per minute, as a result of a more linear thawing curve., Conclusions: WSCFD(®) can replace the 37 °C thermostatic bath thawing procedure for leukapheresis, providing more security and fully traceable process data., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Tattoo is going to be a very common practice especially among young people and we are witnessing a gradual increase of numerous potential complications to tattoo placement which are often seen by physicians, but generally unknown to the public. The most common skin reactions to tattoo include a transient acute inflammatory reaction due to trauma of the skin with needles and medical complications such as superficial and deep local infections, systemic infections, allergic contact dermatitis, photodermatitis, granulomatous and lichenoid reactions, and skin diseases localized on tattooed area (eczema, psoriasis, lichen, and morphea). Next to these inflammatory skin reactions we have to consider also the possibility of the development of cutaneous conditions such as pseudolymphomatous reactions and pseudoepitheliomatous hyperplasia. The aim of this study is to underline the importance of an early diagnosis by performing a histological examination especially when we are in front of suspected papulonodular lesions arising from a tattoo, followed by a proper treatment, since cutaneous neoplastic evolution is known to be a rare but possible complication.

Aim: A significant relationship between great saphenous vein (GSV) caliber at the thigh and function of the terminal valve of the sapheno-femoral junction (SFJ) has already been demonstrated. Yet, the function of the proximal common femoral valve (FV), which is missing in 20-24% of cases, might also play a significant role in SFJ reflux. The aim of this paper was to verify whether GSV caliber also predicts the function/presence of FV., Methods: Using a high-resolution duplex scanner we selected 572 GSVs showing clear-cut SFJ incompetence. Then, by positioning the probe on the inguinal skin fold and orientating the probe upward, we tested FV function. Valve incompetence was diagnosed when a retrograde flow lasting longer than 0.5 s was elicited by both calf squeezing with sudden release and Valsalva maneuver, with the patient standing. Finally, in all patients we measured GSV caliber 15 cm below the groin in the standing position., Results: GSV caliber =7 was not predictive of FV function/presence (51.9% competence vs 48.1% incompetence/absence). In contrast, GSV caliber < or = 6 mm and GSV caliber > or = 8 mm were highly predictive of FV competence and incompetence/absence, respectively (sensibility 98.6%, specificity 80.4%, positive predictive power 88.2%, negative predictive power 97.4%, diagnostic accuracy 91.3%)., Conclusions: Our data strengthen the relationship between GSV caliber at the thigh and hemodynamics of the whole sapheno-femoral complex, including in this definition the FV also.

Aim: The detection of reflux elicited by the compression/release test with the PW Doppler sample at the level of the sapheno-femoral arch might not be sufficient by itself to diagnose the incompetence of the whole sapheno-femoral junction (SFJ). The aim of this study was to further refine the diagnosis by positioning the PW Doppler sample at different levels of SFJ and eliciting reflux both by squeezing and with the Valsalva manoeuvre. In addition, the relationship of the findings with the vein diameter was taken into consideration., Methods: By using a high resolution duplex scanner, 1 294 great saphenous veins (GSV) found to be incompetent by the compression/release test at duplex investigation of the saphenous arch, were also tested at the same level by the Valsalva manoeuvre. Subsequently, the tests were repeated by positioning the PW Doppler sample at the femoral side of the terminal valve, at the saphenous arch tributaries, and at the pre-terminal valve level. Furthermore, the GSV diameter in the standing position was measured at 15 cm from the groin in all patients, and correlated with the hemodynamic patterns found at the junction level., Results: Comparing to compression/release test at the level of the saphenous arch, the Valsalva manoeuvre was negative in 259 (20%) lower limbs and positive in 1 035 (80%). Among the 1 294 GSV found to be incompetent at compression/release test at the level of the saphenous arch, only 710 (55%) lower limbs showed incompetence of the terminal valve. A total of 124 patients (10%), presenting with a competent terminal valve but with a positive Valsalva manoeuvre in the arch, showed a downward flow from a pelvic tributary of the GSV. Finally, a significant statistical correlation between the presence of a competent terminal valve and a GSV diameter <5 mm has been found (p<0.001)., Conclusion: Our data show that the detection of reflux elicited by compression/release test at the level of the saphenous arch is insufficient to diagnose the incompetence of the terminal valve. Our results, together with the correlation between the saphenous trunk diameter at the thigh and the competence or the incompetence of the terminal valve, present significant clinical implications when sapheno-femoral surgical disconnection is contemplated.

This report describes the results of our 3-year experience using ambulatory conservative hemodynamic management (ACHM) for lower extremity venous insufficiency involving the greater saphenous vein (GSV), with specific analysis of recurrence due to neoformation of vessels. We performed 289 ACHM procedures in 259 consecutive patients with GSV-related varicose veins. Follow-up clinical examination and Doppler ultrasound imaging was carried out at 3, 6, 12, 24, and 36 months in all cases to assess formation of neovessels supplied either by the superficial (A) or deep (B) venous system. Our data showed that ACHM achieved excellent improvement, with complete disappearance of varicose veins in 41.2% of cases, good improvement in 43%, fair improvement in 14.1%, and no improvement in 1.7%. The only predictor of outcome was the quality of drainage from the GSV vein. Poor drainage leads to neoformation of vessels supplied by the superficial (A) venous system. In about 50% of cases, drainage appeared spontaneously within 1 year, with a subsequent reduction in formation of neovessels. Neoformation of vessels supplied by the deep (B) venous system (10%) was independent of the quality drainage. This finding suggests that formation of these neovesseis is unrelated to the surgical method used to treat varicose veins. In patients with poor drainage of the saphenous network, neoformation of vessels supplied by the superficial (A) venous system is predictable with regard to both topography and delay. ACHM is a good tool for treatment of varicose veins, as reliable statistical prediction of mid-term results is possible using available models.

Gene targeting techniques and early mouse embryos have been used to produce immortalized fibroblasts genetically deficient in phospholipase C (PLC)-gamma1, a ubiquitous tyrosine kinase substrate. Plcg1(-/-) embryos die at embryonic day 9; however, cells derived from these embryos proliferate as well as cells from Plcg1(+/+) embryos. The null cells do grow to a higher saturation density in serum-containing media, as their capacity to spread out is decreased compared with that of wild-type cells. In terms of epidermal growth factor receptor activation and internalization, or growth factor induction of mitogen-activated protein kinase, c-fos, or DNA synthesis in quiescent cells, PLcg1(-/-) cells respond equivalently to PLcg1(+/+) cells. Also, null cells are able to migrate effectively in a wounded monolayer. Therefore, immortalized fibroblasts do not require PLC-gamma1 for many responses to growth factors.

Objective: To assess three-year results following "CHIVA"., Design: Comparison between our results and data in the literature following stripping., Setting: Phlebologic Surgery, 46 Datini Street, Florence, Italy., Patients: 148 consecutive operated patients suffering from varicose veins (166 procedures)., Interventions: "CHIVA", as described by Franceschi and Bailly., Main Outcome Measures: The presence of visible varicose veins, graded in three categories, according to Hobbs and Einarsson, as shown by clinical examination., Results: Very good results were obtained in 100 cases, who presented without any finding of varicose veins throughout the follow-up. Of the remaining 66, in 1 case we found a new varicose network completely developed, whereas in 65 cases only some visible residual or recurrent vessels were present., Conclusions: Significantly better results were observed in the CHIVA group compared with stripping groups (P < 0,001).