Testicular Metastasis of a Upper Urinary Tract High-grade Papillary Urothelial Carcinoma, 2 Years After Nephroureterectomy.

Urothelial carcinomas are the fourth most common tumors in men. Upper tract urinary carcinomas (UTUCs) are uncommon and represent only 5-10% of urothelial carcinomas.(1) Metastatic testicular cancers are rare and primary tumor sources are the prostate, lung, and gastrointestinal tract. We report the first case of testicular metastasis 2 years after initial curative surgery for a high-grade UTUC, all other reported cases weren't proceed by curative surgery.(3).

Breast lesions in reduction mammaplasty specimens: a histopathological pattern in 534 patients.

BACKGROUND: The prevalence of breast lesions (benign, precancerous and cancer lesions) in reduction mammaplasty (RM) specimens has rarely been reported in Europe and never in the Swiss population. METHODS: Personal and histopathological data from 534 female patients who underwent RM were reviewed. RESULTS: Benign and/or malignant lesions were detected in 76.2% of all patients. Benign breast lesions associated with an increased risk of developing breast cancer represented 2.8% of all lesions. Breast cancer in situ was identified in 5 (0.9%) patients. Patient age and previous history of breast cancer were risk factors for incidental breast cancer. CONCLUSION: The rate of incidental carcinoma in situ was higher for patients with breast cancer history. Probably due to preoperative breast cancer investigation, no occult invasive breast cancer was found in reduction mammary specimens. Therefore before RM, breast cancer evaluation should be considered for all patients, especially for those with breast cancer risk factors (e.g., patient age, personal history of breast cancer).

Advantages of bilayered vascular grafts for surgical applicability and tissue regeneration.

Nanofibrous scaffolds are part of an intense research effort to design the next generation of vascular grafts. With electrospinning, the production of micro- and nano-fiber-based prostheses is simple and cost effective. An important parameter for tissue regeneration in such scaffolds is pore size. Too small pores will impede cell infiltration, but too large pores can lead to problems such as blood leakage. In this study, bilayered grafts were made by electrospinning a high-porosity graft with a low-porosity layer on either the luminal or the adventitial side. Grafts were characterized in vitro for fiber size, pore size, total porosity, water and blood leakage, mechanical strength, burst pressure and suture retention strength, and were evaluated in vivo in the rat abdominal aorta replacement model for 3 and 12 weeks. In vitro blood leakage through these bilayered grafts was significantly reduced compared with a high-porosity graft. All grafts had an excellent in vivo outcome, with perfect patency and no thrombosis. Cell invasion and neovascularization were significantly reduced in the grafts with a low-porosity layer on the adventitial side, and there was no significant difference between the grafts in endothelialization rate or intimal hyperplasia. By tailoring the microarchitecture of biodegradable vascular prostheses, it is therefore possible to optimize the scaffold for tissue regeneration while preventing blood leakage, and thus facilitating applicability in the clinic.

Factorial design optimization and in vivo feasibility of poly(epsilon-caprolactone)-micro- and nanofiber-based small diameter vascular grafts.

Because of the severe increase of mortality by cardiovascular diseases, there has been rising interest among the tissue-engineering community for small-sized blood vessel substitutes. Here we present small diameter vascular grafts made of slow degradable poly(epsilon-caprolactone) nanofibers obtained by electrospinning. The process was optimized by a factorial design approach that led to reproducible grafts with inner diameters of 2 and 4 mm, respectively. Fiber sizes, graft morphology, and the resulting tensile stress and tensile strain values were studied as a function of various parameters in order to obtain optimal vascular grafts for implantation after gamma-sterilization. The influence of polymer concentration, solvent, needle-collector distance, applied voltage, flow rate, and spinning time has been studied. Consequently, an optimized vascular graft was implanted as an abdominal aortic substitute in nine rats for a feasibility study. Results are given following up a 12-week implantation period showing good patency, endothelization, and cell ingrowth.

Matching the diameter of ePTFE bypass prosthesis with a native artery improves neoendothelialization.

BACKGROUND AND AIM: The undersizing of the bypass graft diameter compared to native artery changes blood flow characteristics and velocity which may affect conduit neo-endothelialization, intimal hyperplasia reaction and patency. The aim of this study was to evaluate conduit neoendothelialization, intimal hyperplasia reaction and patency results between undersized and matched ePTFE grafts. MATERIAL AND METHODS: In 16 male Sprague-Dawley rats, undersized (1-mm internal diameter) and matched (2-mm internal diameter) ePTFE grafts were anastomosed end-to-end in the infrarenal abdominal aorta. Blood flow volume per minute was measured and wall shear stress was calculated for each group. After 3 weeks of follow-up, angiography was performed via the left carotid artery just before sacrifice. Conduit neoendothelialization and intimal hyperplasia reaction were measured by computer-assisted morphometry. RESULTS: Wall shear stress was 8 times higher for the undersized group (840.56 vs. 105.07 mPa). Three weeks after implantation, conduit neoendothelialization was better in matched grafts compared to undersized grafts (441 vs. 574 microm, p = 0.008). Intimal hyperplasia reaction was similar for both groups (8.7 vs. 6.7 microm(2)/microm for undersized and matched grafts, respectively). Patency rate was 7/8 for undersized and 8/8 for matched ePTFE grafts. CONCLUSION: Although the graft patency and the intimal hyperplasia reaction were not different between the two groups after 3 weeks, matched grafts had a significantly better endothelialization compared to undersized grafts. This short-term beneficial effect may influence long-term patency results.

First international consensus on the methodology of lymphangiogenesis quantification in solid human tumours.

The lymphatic system is the primary pathway of metastasis for most human cancers. Recent research efforts in studying lymphangiogenesis have suggested the existence of a relationship between lymphatic vessel density and patient survival. However, current methodology of lymphangiogenesis quantification is still characterised by high intra- and interobserver variability. For the amount of lymphatic vessels in a tumour to be a clinically useful parameter, a reliable quantification technique needs to be developed. With this consensus report, we therefore would like to initiate discussion on the standardisation of the immunohistochemical method for lymphangiogenesis assessment.

Expression and localization of VEGF-C and VEGFR-3 in glioblastomas and haemangioblastomas.

Primary human brain tumours account for approximately 2% of all cancers. High levels of expression of vascular endothelial growth factor-A (VEGF-A), a potent angiogenic factor, are linked to poor prognosis. In contrast, the potential role in human brain tumour biology of newer VEGF family members, VEGF-C and VEGF-D, both of which are lymphangiogenic factors, is poorly understood. In the present study, the expression of all VEGFs (VEGF-A, -B, -C, and -D) and their receptors (VEGFR-1, -2, and -3) has been assessed in 39 primary human brain tumours. The well-established findings were confirmed with VEGF-A. Surprisingly, however, VEGF-C and VEGF-D, as well as VEGFR-3, were expressed in some tumour types such as haemangioblastomas and glioblastomas, despite their lack of lymphatic vessels. VEGF-C and VEGFR-3 transcripts were localized to the tumour palisade around necrotic areas in glioblastomas and were evenly distributed throughout haemangioblastomas. VEGF-C protein was localized by immunohistochemistry to the palisade layer in glioblastomas. More than 50% of VEGF-C-positive cells also expressed the intermediate-stage inflammatory macrophage marker CD163; however, a significant proportion of VEGF-C-positive cells were CD163-negative. These data demonstrate the presence of molecules, primarily described as regulators of lymphangiogenesis, in normal human brain and brain tumours that are devoid of lymphatics. Their localization in macrophages points to a role in tumour-associated inflammation.

Improved neo-endothelialization of small diameter ePTFE grafts with titanium coating.

BACKGROUND: Patency of small synthetic bypass grafts is inferior compared to autologous grafts for revascularization procedures. Titanium coating of foreign surfaces has shown to decrease thrombogenicity, enhance biocompatibility and promote adhesion of endothelial cells. The aim of this study was to test the effect of titanium coating of small diameter ePTFE grafts on short term patency, neo-endothelialization and neointimal proliferation. METHODS: Bilateral carotid graft interposition was performed in 5 pigs with uncoated (n=5) and titanium-coated (n=5) ePTFE grafts (internal diameter=4 mm, length=5 cm), thus each pig served as its own control. At the end of the study (30 +/- 3 days), patency and stenosis severity was assessed by carotid angiography. Animals were sacrificed and grafts were excised for histology and scanning electron microscopy. Morphometry of histologic sections was carried out to determine neointimal proliferation and percentage of neo-endothelial coverage. RESULTS: Patency rate was 80% for uncoated and titanium-coated grafts. Quantitative angiography did not show any significant difference in lumen size between two groups. Morphometry revealed a significantly higher cellular coverage with CD31 positive endothelial cells for titanium-coated (84 +/- 19%) than uncoated grafts (48 +/- 26%, p<0.001). There was a non significant trend (p=0.112) towards increased neointimal proliferation in titanium-coated (94 +/- 61 micron2/micron) compared to uncoated grafts (60 +/- 57 micron2/micron). CONCLUSIONS: Patency rate in uncoated and titanium-coated ePTFE grafts is similar at one month. However, titanium coated grafts show a significant improvement in neo-endothelialization compared to uncoated grafts.

Hereditary vascular anomalies: new insights into their pathogenesis.

Increased understanding of the mechanisms of angiogenesis and lymphangiogenesis has provided a glimpse at some of the molecules involved in the pathophysiology of hemangiomas and vascular malformations. This review focuses on recent advances in our understanding of the mechanisms of angiogenesis/lymphangiogenesis and the differentiation of arterial, venous, and lymphatic vessels. We integrate this knowledge with new data obtained from genetic studies in humans, which have revealed a number of heretofore-unsuspected candidates involved in the development of familial vascular anomalies. We present a common infantile vascular tumor, hemangioma, and then focus on hereditary familial vascular and lymphatic malformations. We also summarize transgenic mouse models for some of these malformations. It seems reasonable to believe that novel therapeutic strategies will soon emerge for the treatment of hemangiomas and vascular malformations.

Familial predisposition to tufted angioma: identification of blood and lymphatic vascular components.

Tufted angioma is a rare benign vascular lesion of unknown etiology which mainly affects children under 5 years. It is characterized by nodules or tufts of capillary-sized vessels in the dermis. Here we report the second familial occurrence of tufted angioma, with a mode of inheritance compatible with a monogenic autosomal dominant trait with reduced penetrance. A preliminary investigation was performed to exclude association between the predisposition and certain candidate genes including KDR (kinase insert domain receptor), TEK (TEK tyrosine kinase endothelial), ACVRL1 (activin receptor-like kinase 1), ENG (endoglin) and FLT4 (fms-like tyrosine kinase 4). KDR, ENG and FLT4 were all compatible with linkage, with haplotypes being shared between three affected individuals and the one obligate carrier available for testing. TEK and ACVRL1 could essentially be excluded. Finally, we provide definitive evidence for the existence of both blood and lymphatic vascular elements in the lesion.

Vascular endothelial growth factor (VEGF) receptor-2 antagonists inhibit VEGF- and basic fibroblast growth factor-induced angiogenesis in vivo and in vitro.

Exponential tumor growth is angiogenesis-dependent. Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) are potent angiogenic inducers that act synergistically in vivo and in vitro. We assessed the effect of specific inhibitors of VEGF receptor (VEGFR)-2 tyrosine kinase activity in in vivo and in vitro models of VEGF- and bFGF-induced angiogenesis. In an implant mouse model of angiogenesis, VEGFR-2 inhibitors completely blocked angiogenesis induced by VEGF, and, surprisingly, also inhibited the effect of bFGF to various extents. In vitro, VEGF- and bFGF-induced bovine microvascular and aortic endothelial (BME and BAE) cell collagen gel invasion could be blocked by the VEGFR-2 inhibitors by 100 and approximately 90%, respectively. Similar results were obtained with VEGFR-1-IgG and VEGFR-3-IgG fusion proteins and with VEGFR-2 blocking antibodies. Both BME and BAE cells produce VEGF and VEGF-C, which is not modulated by bFGF. Thus, the unexpected inhibition of bFGF-induced angiogenesis by VEGFR-2 antagonists reveals a requirement for endogenous VEGF and VEGF-C in this process. These findings broaden the spectrum of mediators of angiogenesis that can be inhibited by VEGFR-2 antagonists and highlight the importance of these compounds as agents for inhibiting tumor growth sustained by both VEGF and bFGF.

Electrotonic interaction between muscle fibers in the rabbit ventricle.

Transmembrane potentials were recorded simultaneously from pairs of ventricular fibers in an isolated, regularly beating preparation. A double-barrelled microelectrode was used to record the potentials from, and to polarize, one fiber. A single microelectrode was used to record from a distant fiber. The existence of two systems of fibers, termed P and V, was confirmed. Histological evidence for the existence of two types of fibers is also presented. Electrotonic current spread was observed within both systems, electrotonic interaction between the two systems was rare and always weak. In the case of those pairs of fibers showing electrotonic interaction, the distance for an e-fold decrease in magnitude of the electrotonic potentials was found to be from 300 to 600 micro in P fibers and from 100 to 300 micro in V fibers. However, no electrotonic interaction could be observed in the majority of V fiber pairs. Moreover, the magnitude of the electrotonic potential did not decay monotonically with distance in any one direction. It is concluded that the rabbit ventricle cannot be regarded as a single freely interconnected syncytium.

Electrical properties of the smooth muscle membrane of the guinea-pig vas deferens.

1. The effects of polarizing current on single smooth muscle cells of the isolated guinea-pig vas deferens have been studied by means of a bridge circuit in which the same electrode was used to pass current and record membrane potential.2. Most cells had polarization resistances from 15 to 37 MOmega.3. Depolarizing currents caused graded spikes up to a maximum amplitude of 75 mV.4. Self-regenerative spikes occurred in some cells if the membrane was depolarized by > 35 mV.5. Currents of long duration and sufficient intensity caused a repetitive discharge.6. Spikes arising from excitatory junction potentials were always ;all-or-none' in contrast to the graded responses to intracellular stimulation.7. Electrotonic potentials declined much more rapidly than spontaneous excitatory junction potentials (EJPs); thus the time course of the EJP cannot be determined by the passive electrical properties of the smooth muscle cell membrane.