br Conclusions br Introduction Liver transplantation LT


Liver transplantation (LT) is the mainstay of treatment for end stage liver diseases, including inherited liver disorders. Organ donation, however, has not kept up with the demand, leading to increased morbidity and mortality. Alternatives to LT have been sought over the last decade to overcome the shortage of donor organs, and cell therapy has emerged as a highly effective “bridging therapy” to LT or even as a curative option in some reported experiments on inherited liver disorders (Dhawan et al. 2010; Forbes and Rosenthal 2014; Stéphenne et al. 2006).
To adequately restore the liver function, delivery of a large number of NS-398 (approximately 5%–10% of the liver mass or transplantation of 200–400 million cells/kg weight) is necessary over a short period of time and often needs repetition. It is challenging to effectively deliver such a large number of cells by the intra-portal approach (Baccarani et al. 2005). When the cells are injected into the vascular compartments (portal vein/artery), the liver engraftment efficiency ranges from 5%–30% depending on the type and size of the cells and the majority of the cells end up in a different organ (Hoppo et al. 2011; Puppi et al. 2012). The cell engraftment and retention might increase when they are directly injected into the liver parenchyma (Turner et al. 2013). A possible mismatch between the cell size and the sinusoidal endothelial pore size, resistance to the uptake and integration of injected cells in a histologically normal liver and occurrence of portal venous thrombosis are thought to be the possible hurdles (Kocken et al. 1997). Cell therapy is much more challenging unless the recipient liver is damaged by iatrogenic methods. Liver irradiation, reperfusion injury and types of noxious chemical agents have been used to create damage to the recipient liver to increase the integration of transfused cells with excellent outcomes in reported experiments (Malhi et al. 2002; Morán-Jiménez et al. 2008; Stéphenne et al. 2006; Turner et al. 2011). However, so far the overall clinical outcomes have been mixed. For instance, radiation-induced liver disease is a concern when whole-liver radiation at doses above 30 Gy is used (Jorns et al. 2012; Schlachterman et al. 2015). With portal vein embolization-mediated ischemia reperfusion injury, NS-398 an increase in portal pressure and the risk of portal thrombosis are possible (Jorns et al. 2012). Administration of noxious chemical agents such as carbon tetrachloride (CCl4) can lead to liver fibrosis, cirrhosis and hepatocellular carcinoma (Fujii et al. 2010).
High intensity focused ultrasound (HIFU) has been traditionally used for non-invasive tumor ablation (Aubry et al. 2013). In recent years, significant interest has been garnered in alternative applications of HIFU. HIFU techniques can be used to mechanically fractionate soft tissue with a high degree of precision (Khokhlova et al. 2011; Kieran et al. 2007). This is known as histotripsy. A well-defined lesion in the form of a cavity could be produced by histotripsy without any significant thermal damage at the periphery of the cavity. In soft tissues, the distortion of an initially harmonic acoustic waveform due to tissue non-linearity causes enhanced heating. This is because the absorption of ultrasound energy in tissue increases with frequency (ter Haar and Coussios 2007). Significant wave distortion in tissue leads to the generation of a shock wavefront, which contains tens of harmonics of the fundamental frequency. Once shockwaves are developed at the focal point of the HIFU transducer, where the non-linear propagation effects are the strongest, the heating rate can be increased significantly. In the case of plane harmonic waves, for example, heat deposition is proportional to the acoustic pressure amplitude squared whereas for shock waves the heating rate is proportional to the shock pressure amplitude cubed. This localized super-heating by the shock waves can raise tissue temperature to 100°C in a few milliseconds (Canney et al. 2010; Maxwell et al. 2012). A boiling vapor bubble is subsequently formed and grows to millimeter size at the focus followed by the production of tissue fractionation. The growth of this millimeter-sized bubble is likely to be due to the asymmetry in the shock waveforms (Kreider et al. 2011). As the peak positive pressure phase has a shorter duration than the negative pressure part in the shockwaves, the bubble has a relatively longer time to undergo expansion rather than collapsing leading to an explosive growth within a few acoustic cycles.

br Material and methods br Result and discussion br Conclusions

Material and methods

Result and discussion

This study demonstrates that ultrasonic treatment can control the growth rate of L. sakei as evident from growth model parameters obtained by fitting the Gompertz model. Second order polynomial models for SGR and lag phase showed strong dependency of L. sakei growth on both the level of ultrasonic power and sonication time. Cell-free extracts obtained from MRS broth and meat extract after 24h fermentation period showed inhibition against selected pathogenic microorganisms. Hence, ultrasound can be employed for stimulation and/or retardation of L sakei growth depending on the sonication conditions which can be extended to other probiotics. Additionally, cell-free extracts obtained could be further exploited for food bio-preservation purposes.

Organic dyes widely present in wastewater of textiles, paper, plastics, leather, food, antiseptics, cosmetics, fungicides following entrance to the aquatic environment [1–3] cause toxicity, carcinogenicity and mutagenic points [2,4–6]. Therefore, their removal from wastewater is great demand and achieved by application of conventional physicochemical, chemical and biological principles that classified to coagulation and flocculation [7], adsorption [8], biosorption [9], electrochemical techniques [10] and fungal decolonization [11], while more harpagoside is possible in adsorption [12]. The simple design, nontoxic and low cost adsorbents, low treatment cost and mild conditions are criterion for selection of best mode and adsorbent in this approach [13]. Growing researches interest and effort lead exporting carbon-based materials that simply were modified by novel nanoscale materials. This combination is associated whit enhance in surface area porosity and rate of mass transfer [14–16]. AC as sole adsorbent due to presence of non-localized n electrons and also fictional reactive centers like OH, COOH, NH2 and amide group seems to attract various species through Л-Л, hydrogen bonding and charge electrostatic force deepened on working pH [17,18]. On the other hands, compounded like CuO nanoparticles eagerly like to bind on AC surface through binding copper center to the functional group or non-localized M-electron through ion dipole interaction, while presence of its oxygen reactive center also favor loading process through hydrogen bonding via hard-hard interaction [18,19]. Therefore, it seems and expectable that CuO-NP-AC has greater and favorable reactive sites toward AC and/or CuO-NP as sole adsorbent. Probable back distribution of copper (ions and atoms) to environments do not generate harmful problem for living things is related to its high threshold limit suggested by world health organization (WHO) [20–22].
Procedures using ultrasonic waves are very efficient at removing chemicals and eliminating toxic contamination. Therefore, techniques using hybrid ultrasonic waves, together with other methods such as adsorption process are the most common uses of ultrasonic waves [23–25]. In this case the using of ultrasound waves its well-known to accelerate chemical process due to the phenomenon of acoustic cavitation, that is, the formation, growth and collapse of micrometrical bubbles, formed by the propagation of a pressure wave through a liquid [26]. As well as, ultrasound waves and its secondary effect, cavitation (nucleation, growth and transient collapse of tiny gas bubbles) improve the mass transfer harpagoside and breaking the affinity between adsorbate and adsorbent through convection pathway that is emerged from physical phenomena without significant change in equilibrium characteristics of the adsorption/desorption system [27–29].
Simultaneous removal of dyes due to their absorption peak overlap is big problem that limit the simultaneous clean up procedures. The derivative spectrophotometric are good choice that cope with these problems [30,31].
Experimental design methods widely used as the efficient way for modeling, analyzing and interpreting experimental data. This method permits efficient optimization and give useful subject about individual and cooperation contribution as main and interaction on response. As well as, improve characteristics performance with at least number of experiments while minimize error of experiments [32,33].

Recently it has been argued that by performing

Recently it has been argued that by performing valence order SQ 22536 energy-loss spectroscopy (VEELS) at primary electron energies below the Čerenkov limit band gap energies can be observed directly and that the Kramers–Kronig analysis can be carried out directly in order to locally measure optical properties of the material (see, e.g., [6,7] and references therein). In this short article, we employ simulations to show that working below the Čerenkov limit is an insufficient condition to observe the true band gap signal and that performing the Kramers–Kronig analysis can be problematic even when working below the Čerenkov limit. The inadequacy of the Čerenkov-limit criterion is based in the occurrence of retardation losses and the excitation of guided light modes which are present even if the primary electron energy is below the Čerenkov limit.

Valence electron energy-loss spectra of GaAs and corresponding plots of the scattering probability as a function of energy-loss and scattering angle were calculated based on the dispersion bracket formalism of Bolton and Chen (see, e.g., [8]) which is an extension of the “Kröger formula” [9] to multilayered systems. In the present case, i.e. for single-slice models, the dispersion bracket formalism provides identical results to the Kröger formula [10]. The dielectric function of GaAs was taken from Ref. [11], resampled on an energy scale of 0.01eV increments, and the imaginary part of the dielectric function below 1.37eV was set equal zero.
The Čerenkov limit, i.e. the threshold electron energy for the generation of Čerenkov photons, is given by EČerenkov [keV]=511keV ([ε1,max/(ε1,max−1)]0.5−1) with the rest mass energy of an electron of 511keV. The Čerenkov limit is calculated by using the maximum order SQ 22536 of the real part ε1,max of the dielectric function which yields for GaAs 11keV. To analyze the spectrum characteristics below the Čerenkov limit, calculations were performed for 10keV electrons.

Results and discussion
Fig. 1 shows calculated inelastic scattering plots of GaAs for 10keV electrons. The plots show on a logarithmic (color) scale the scattering probability of electrons as a function of energy loss and scattering angle. The energy loss between and 10eV is plotted along the vertical axis and the scattering angle between and 0.2mrad is plotted along the horizontal axis. The plots were calculated for GaAs slices of thickness 5, 25, 50 and 100nm. Looking at Fig. 1 the most apparent feature in all four plots is the light line [4] which reveals that the inelastic scattering probability in front of the band gap signal (Eg(GaAs)=1.42eV [11]) does not vanish. Moreover, for a slice thickness of 50nm, the occurrence of an intensity peak with a distinct dispersion is observable. This branch, which moves to lower energies with increasing sample thickness, is clearly identifiable in the simulation for a slice thickness of 100nm and corresponds to the energy loss due to the excitation of a guided light mode. In addition, the appearance of a second mode is observable in the plot for 100nm GaAs. The inset in the plot of the 100nm slice shows enlarged the area surrounded by the white frame. The enlargement clearly reveals that the first guided light mode shows a faint line in front of the band gap and thus further increases the background intensity in front of the band gap signal. The presence of the light line and the faint branch of the guided light mode cannot be explained (classically) based on the energy-loss function. Relativistic correction of the electron–specimen interaction and retardation, in particular, are needed to explain these spectral contributions. The excitation of the guided light mode is not a surface loss. The energy range and the number of (excitable) guided light modes depend on the thickness of the material and should not be confused with a surface effect.
Fig. 2 shows calculated low-loss spectra of GaAs for 10keV electrons for slice thicknesses of 5, 25, 50 and 100nm. The calculated spectra show the energy range in front and the intensity onset at the band gap energy. Fig. 2 reveals that the apparent band gap onset shifts to lower energies with increasing slice thickness, even for the chosen primary electron energy below the Čerenkov limit. This shows that the shift of the apparent band gap onset is affected by the presence of the guided light mode, as seen in Fig. 1. Although the shift of the apparent band gap onset between the 5nm and the 100nm slices is only about 50meV, it follows the same trend as when materials are investigated at electron energies above the Čerenkov limit [4]. The reason for this is that the guided light mode, which shifts the apparent band gap signal to lower energies, is excited independent from whether the primary electron energy is above or below the Čerenkov limit. A band gap shift of 50meV is small, but it might be critical for device properties. Moreover, determining an intensity onset with a precision of 50meV seems quite feasible with monochromated microscopes which recently showed energy resolutions of 10–20meV [12,13]. As the inelastic mean free path of 10keV in GaAs is of the order of 20nm, one might argue that a sample of 100nm exceeds the suitable thickness for electron energy-loss spectroscopy. However, the calculations show that guided light modes can be excited below the Čerenkov limit and they potentially can impact precise band gap measurements. Moreover, this observation is particularly important for materials whose Čerenkov limit is not as low as in GaAs, like, e.g., GaN, Si3N4, ZnO or SiO2 with a Čerenkov limit of about 40keV and higher, and thus tolerate larger sample thicknesses when one aims at working below the Čerenkov limit.

Introduction In contrast to high resolution

In contrast to high-resolution transmission electron microscopy (TEM) in materials science, where a broad transfer band up to high spatial frequencies is generated at Scherzer defocus, structure determination of phase objects such as biological macromolecules depends on contrast at low-resolution, which is indispensible for the detection and proper alignment of particles. In conventional TEM, phase contrast is generated by defocusing the objective lens up to several micrometers. The contrast transfer function (CTF) for TEM imaging of a phase object is given by
is the defocus; is the wavelength; is the spatial frequency; is the spherical aberration; is the damping due to spatial and temporal coherence.
It was recognized early on that defocus contrast for low spatial frequencies is poor and generates image artefacts due to CTF oscillation. In his original proposal, as early as 1947, Boersch proposed two designs for physical phase plates that enable in-focus TEM imaging of phase objects when placed in the back focal plane of a TEM [1]. One design, referred to as the Boersch phase plate (BPP), consists of an electrostatic einzel lens shifting the phase of the unscattered electrons. An einzel lens is an electrostatic lens, which does not alter the energy of the propagating electrons. But Boersch suggested also a much simpler device, consisting of a thin amorphous carbon film with a central hole shifting the phase of the scattered electrons by 90° [1]. This PP type is today referred to as Zernike PP. In the last decade, BPPs, Zernike PPs, and a variety of other PP designs have been fabricated and implemented into TEMs [2–12]. Although generation of in-focus contrast for ice-embedded biological specimens has been demonstrated [3,8,13,14], progress has been slow. Electrostatic charging of physical PPs has so far prevented their routine use in electron cryo-microscopy (cryo-EM) of biological specimens [15–17]. Due to their complex multilayer design, electrostatic PPs are more prone to charging than thin film PPs [16]. More progress has been made with the simple design of Zernike PPs. Zernike PPs have been successfully used solely for electron cryo-tomography of large biological structures, such as viruses [18], phages [19], and Exendin-3 (9-39) amide [20]. Recently, a new thin film phase plate has been developed, the so-called Volta PP, which is superior to the Zernike PP with respect to lifetime and reliability [21,22]. Therefore, it is very likely that thin film phase plates will be routinely used for PP cryo-EM of biological specimens in the near future. It is worth noting that current hole-free thin film PP designs are closely related to a PP proposed and fabricated by Nigel Unwin as early as 1970 [23]. In his original proposal, Unwin generated phase contrast by beam-induced electrostatic charging of a gold-coated spider thread mounted in the back focal plane of a TEM [23].
Inelastic scattering of electrons propagating through the ~30nm thick carbon film causes loss of high-resolution information. Currently, the resolution achieved with Zernike PPs is worse than 8Å [19]. To facilitate cryo-EM of small single particles at atomic resolution, the high signal-to-noise ratio of direct electron detectors [24–26] should be combined with in-focus imaging using a thin film PP. The main function of a physical PP is to enhance contrast at low spatial frequencies, and thus to facilitate particle picking and alignment or sub-tomogram averaging with cryo-EM. In this work, a new type of thin film phase plate is proposed that imparts a phase shift only to electrons scattered to low angles, thereby maximizing contrast transfer at low spatial frequencies and avoiding damping of high-resolution information. Furthermore, the fabrication of such a device is discussed.

Results and discussion

An improved design for a thin film phase plate has been proposed, consisting of a disk of a phase-shifting material, deposited on an ultrathin support film, imparting a phase shift to low spatial frequencies only. Furthermore, the work provides a guideline for the fabrication of an Exendin-3 (9-39) amide improved hole-free phase plate. The experimental results indicate that the fabrication of such devices from a 2D material is feasible. What remains to be tested is the stability of a SAPP during operation in a TEM. 2D materials, such as graphene, are sensitive towards intensive electron irradiation [43] and special care must be taken during centring of the phase plate in the back focal plane of the TEM. Automatic procedures should be developed ensuring that the unscattered electron beam hits the phase-shifting material of the SAPP only. Once fabricated and implemented into a TEM, the SAPP holds great potential to facilitate cryo-EM of small single particles at atomic resolution.

For valence electron scattering eV

For valence-electron scattering (1eV < E < 50eV), L(E) can be shown to be a few nm by recording the inelastic signal as a STEM probe is scanned across the edge of a specimen [4–8] or a sharp internal boundary [9]. Similar measurements for vibrational losses (0.1–0.5eV) have given values of several tens of nm [1]. The general situation is illustrated in Fig. 1, which includes L(E) values estimated from various kinds of TEM measurements (filled data points) . The data is scattered (due to experimental error and the different methods, geometry and definitions used) but demonstrates how the delocalization distance is inversely related to Sunitinib Malate Supplier loss.
For core-electron excitation, giving rise to an ionization edge at some hundreds of eV, L(E) has subatomic dimensions but is important for the interpretation of channeling measurements on crystalline specimens [14–20]. This delocalization has been calculated using Bloch-wave or multislice methods [21–30] and is complicated by the influence of elastic scattering, which occurs on a length scale similar to that of the core-loss scattering.
The lines in Fig. 1 are based on relatively simple considerations. For example, we can use the Heisenberg uncertainty principle Δpx Δx ≈ h to estimate a delocalization distance Δx, taking the momentum uncertainty as Δpx=±(h/λ)θ50, h being Planck\’s constant, λ the primary-electron wavelength and θ50 the angular width containing 50% of the scattering. Assuming an inverse correlation between impact parameter and scattering angle, the length containing half of the inelastic scattering is:

Except for Cerenkov and surface-mode losses, inelastic scattering is dominated by a dipole component with a Lorentzian angular distribution of half-width θE ≈ E/2E0 but with a cutoff around an angle θc, giving θ50 ≈ (θEθc)1/2. A Bethe-ridge cutoff at θc ≈ (2θE)1/2 leads to:
as indicated by the dashed line in Fig. 1. In this figure, the black dash-dot curve represents Eq. (2) combined (by quadrature addition) with the diffraction limit imposed by a 10mrad spectrometer-collection aperture. The aperture effect is important only for large energy losses; for E < 50eV, θE < 1mrad and almost all the inelastic signal passes through a typical aperture. Invoking Fourier optics, we can compare the inelastic scattering of electrons with the diffraction of electrons of wavelength λ from a circular aperture of radius a. Observed on a distant screen, the first minimum in the Airy-function intensity corresponds to a deflection angle of θ1 = 0.61λ/a, which forms the basis of the Rayleigh criterion for resolution: Δx = 0.61λ/θ1. However, the angular range containing half of the photons is θ50 = 0.263(λ/a) and the diameter from which these photons emerge is d50=(2a)/21/2, giving a value: that is slightly smaller than Eq. (1). Using Δpx Δx ≈ h and similar arguments, Pennycook [17] obtained an expression for the root-mean-square (RMS) impact parameter bRMS (weighted over the Lorentzian angular distribution) that can also be interpreted as a delocalization length:
Eq. (4) predicts an energy-loss dependence close to E−1 rather than E−3/4 but provides an equally good fit to experimental data, as shown in Fig. 1.

Point spread function for inelastic scattering
The success of Eq. (3) in predicting delocalization suggests using the methods of Fourier optics to relate the spatial distribution of the scattering (here denoted as a point-spread function, PSF) to its angular distribution, easily recorded as an intensity variation at a distant plane (Frauhofer diffraction pattern). In light optics, the PSF is related to the Fourier transform of the angular distribution of scattered intensity or scattered amplitude, depending on the lateral coherence length of the illumination [31]. For the elastic scattering of electrons, the lateral coherence exceeds atomic dimensions and the object-plane potential is related to the scattered amplitude[32,33]. Extending this idea to the inelastic scattering of electrons suggests:

br Conclusion br Acknowledgment br Bladder cancer is



Bladder cancer is primarily a disease of the elderly; 71% of patients are diagnosed after the age of 65 years. Radical cystectomy (RC) with regional lymphadenectomy and urinary diversion remains a part of standard management of muscle-invasive urothelial carcinoma of the bladder.
Studies addressing mortality and morbidity of RC in the elderly report mixed results. A large single-institution study revealed no differences in perioperative survival or complication rates in patients aged >80 years. A multi-institutional study of 888 consecutive RC patients, however, found worse pathologic and disease-specific outcomes in patients aged >80 years, and a collaborative review corroborated higher morbidity and mortality in elderly patients. Elderly patients are more likely to suffer comorbidities and frailty that might disqualify them from surgery or increase the risk of complications, as evidenced in the Surveillance, Epidemiology, and End Results program and in systematic reviews. In addition, perioperative chemotherapy is used less frequently in elderly patients, including those with muscle-invasive disease.

Male circumcision (MC) is defined as removal of the redundant prepuce. It has been demonstrated to be an effective surgical procedure to reduce the incidence of human immunodeficiency ck1 inhibitor transmission through heterosexual intercourse by approximately 60%. Several studies have also demonstrated that MC can significantly reduce the risk of human papillomavirus, herpes simplex virus 2, as well as other sexually transmitted infections. In addition, it assists in the prevention of urinary tract infections, penile cancer, prostate cancer, and cervical cancer of female partners.
Conventional circumcision (CC) is the standard procedure currently used in most MC programs. However, it is time consuming, painful, and requires stitches. In addition, operative incision visibility lacks controllability. Furthermore, evidence suggests that practitioners must complete an average of 100 circumcisions before they are considered adequately trained to perform safe and effective conventional open MC.
In recent years, there has been an increase in the use of MC devices, such as the Shang Ring that do not require suturing and hemostasis. The emergence of such devices has significantly reduced operative time. Furthermore, less surgical skill is required, and highly cosmetic results are achieved. Indeed, the lower degree of technical skill required to provide Shang Ring circumcision (SRC) translates into a shorter learning curve for newly trained clinicians to achieve competency. Nevertheless, controversy exists as to whether the efficacy and safety of SRC is superior to those of CC. However, thus far, no overwhelming evidence of its benefits in MC practice has been presented. For these reasons, we have conducted beta decay systematic review and meta-analysis to assess the safety and efficacy of SRC in MC in English.
Materials and Methods

We formulated a comprehensive and exhaustive search strategy in an attempt to identify all relevant studies. All the selected trials were RCTs; after quality assessment, we ultimately included 8 RCTs. Study selection was based on Preferred Reporting Items for Systematic Reviews and Meta-analysis criteria ( A flow diagram of evidence acquisition is illustrated in Figure 1. All uncircumcised men seeking circumcision in the included trials were randomly assigned to one of the 2 treatment groups. There were 3314 male patients in the 8 study trials: 1815 who received SRC and 1499 who received CC. Although these RCTs were inadequate in allocation concealment and blinding because of ethical issues and properties of surgery studies, quality assessment revealed that the included studies were of high quality. The basic characteristics and quality assessments of the included studies are summarized in Table 1.

SRC as a new surgical technique for MC was first reported in 2008 by Peng et al. Since then, SRC has increased in popularity worldwide. Although CC is still widely accepted and performed, the weaknesses of CC are clear—operative time, intraoperative pain, and postoperative PA are all inferior relative to SRC. Comparing both methods will help to provide high-quality evidence-based medicine for MC. RCTs are considered the gold standard trial design for estimating and comparing interventions because bias is minimal. Therefore, we excluded non-RCTs, case studies, and lower quality studies to maximize quality control. Eventually, 8 high-quality RCTs met the inclusion criteria of this systematic review and meta-analysis. To our knowledge, this is the first systematic review and meta-analysis to compare SRC with CC for MC in English.

UMI-77 Supplier br A year old patient presented

A 45-year-old patient presented with prostate-specific antigen (PSA) relapse (0.3 ng/mL) 20 months after radical prostatectomy for organ-confined prostate cancer. A whole body F-NaF positron emission tomography (PET) revealed no evidence of bone metastases (). Pelvic magnetic resonance imaging, however, identified a suspicious 26 × 20 mm left-sided pararectal nodule (). Ga-labeled prostate-specific membrane antigen-targeted ligand PET/computed tomography (PSMA-PET/CT) revealed tracer uptake of the lesion apparently confirming a lymph node metastasis (). This assumption was, however, falsified by scintigraphy with Tc pertechnetate-labeled heat-damaged autologous UMI-77 Supplier that revealed pelvic splenosis after trauma-related splenectomy 34 years earlier ().
PSMA-PET/CT relies on the overexpression of PSMA on the surface of prostate cancer cells. With its high specificity even at very low PSA levels, nodules with tracer uptake are likely being interpreted as prostate cancer recurrences particularly if located at typical site and associated with a detectable PSA level. Due to seeding to unexpected anatomical locations, splenosis may mimic various diseases. Of the visceral organs, the spleen has the second highest Ga-labeled PSMA-targeted ligand uptake (highest uptake in kidneys). Splenunculi may, therefore, masquerade as PSMA-positive lymph node metastases.

A 77-year-old man was diagnosed with a Gleason 8 prostate adenocarcinoma. He already had skeletal metastases. He underwent surgical castration and 2 months later, he presented with gradual decreased visual acuity of the right eye, left eye blurred vision, and painless bilateral eye redness. The examination revealed a tumor formation of the right iris, not pigmented, neovascularized, invading the iridocorneal angle and distorting the pupil, highly suggestive of metastasis (), and a left neovascularized choroidal lesion, also suggestive of metastasis. Computed tomography scan confirmed these 2 orbital localizations (). A fine-needle aspiration biopsy of the iris was performed and revealed poorly differentiated adenocarcinoma. Taxane-based chemotherapy and bilateral eye radiation therapy were decided upon tumor multidisciplinary board, but the patient was lost to follow-up.
Less than 10 cases of iris metastasis and 16 cases of metastatic prostate carcinoma to the choroid have been reported. The standard method for diagnosis is fine-needle biopsy, which is positive in 88% of the cases. The recommended treatment for uveal metastasis is radiation therapy. Indeed, these tumors are very radiosensitive, and surgery alone appears to be insufficient. The prognosis is generally poor with an overall median survival rate from the time of orbital localization diagnosis between 7.4 and 10.5 months.

A 66-year-old-woman underwent a laparoscopic left partial nephrectomy for a 3 cm tumor with a RENAL nephrometry score of 7p. Following laparoscopic mobilization of the kidney, a single renal artery was clamped. The tumor was excised without entry into the collecting system and no segmental vessels were noted. The kidney was reconstructed with an absorbable barbed suture and sliding-clip renorrhaphy using polyglactin sutures on tapered needles. Warm ischemia time was 28 minutes. The final pathological analysis confirmed renal cell carcinoma (clear cell type) with negative margins and a Leibovich score of 1. Surveillance computed tomography performed 6 months postoperatively found a 4 cm lesion in the left kidney that is avidly enhanced in the arterial phase, consistent with a pseudoaneurysm (). The patient was asymptomatic and denied any visible hematuria. Urgent angiography and embolization of the pseudoaneurysm using a combination of N-butyl cyanoacrylate and endovascular coiling were performed (). Postembolization computed tomography imaging showed satisfactory thrombosis of the pseudoaneurysm (). Renal pseudoaneurysm is a rare complication of partial nephrectomy and typically presents in the early postoperative period with visible hematuria. This case illustrates that this rare complication may also present as an asymptomatic incidental finding and is amenable to successful angioembolization.

Limited to the nature of cryoablation and preservation

Limited to the nature of cryoablation and preservation of vital ceramide kinase nearby, tumor locations in prostate would interfere with the successful rate of prostate cryoablation. To improve oncological outcomes, detailed and accurate tumor locations is essential for prostate patients who plan to receive cryoablation.

We investigated the treatment outcome of testicular cancer in Taiwan, given globally rise in incidence in recent decades.
From February 2010 to October 2015, we retrospectively collected patients with the confirmed diagnosis of testicular cancer. Clinical data, pathological details and treatment outcomes were analyzed by reviewing medical records.
A total of 81 patients with testicular cancer were enrolled; 40 (49.4%) had seminoma and 41(50.6%) had non-seminoma germ cell cancer. The median age was 51 years old in seminoma and 30 years old in non-seminoma group. The median follow up period was 30 months (range 1 to 70).

Ketamine is the most commonly abused psychotropic substance among youngsters in Taiwan. Long-term ketamine use can cause chronic cystitis and severe lower urinary tract symptoms (LUTS). We conducted an in-depth epidemiological study to better understand the correlation between ketamine abuse and LUTS.
The survey was conducted in two private rehabilitation centers in Taiwan. Through self-administered questionnaires (OABSS, IPSS, ICSI, ICPI and VAS), records of inmates, such as gender, age, and details of using ketamine, including the way, amount, duration of using ketamine as well as symptoms of urinary tract were obtained. Data processing and statistical analysis were performed using statistical software SPSS v.17. We analyzed all kinds of relative factors causing ketamine cystitis and off factor, and established an occurrence and severity forecasting module.
106 ketamine abusers completed the questionnaires, including 11 women and 95 men. LUTS occurred after using ketamine for 24.67±26.36 (mean±SD) months. Most of them combined snoring and smoking of the ketamine. Leading symptoms included frequency (67.3%), incomplete voiding (66.3%) and nocturia (61.2%). The scores of OABSS, IPSS, ICSI, ICPI and VAS were 5.23±4.37, 13.11±10.62, 11.47±6.78, 9.92±5.65, 2.89±3.48, respectively. 79.2% of ketamine abusers admitted a history of polysubstance abuse, although none of them had taken drugs other than ketamine regularly. Smoking of ketamine was negatively correlated with symptom scores in IPSS-S, ICSI and ICPI (P<0.05). OABSS significantly increased while combine using ketamine and Marijuana (P=0.016). Combination with 3,4-methylenedioxy-methamphetamine (MDMA) usage significantly increased the ICPI score (P=0.034). Ketamine abuse can induce severe storage symptoms depending on the duration of using ketamine. Snorting of ketamine may cause worsen LUTS than smoking. Combine using ketamine and certain substances may exacerbate LUTS. With this model as a platform, further prospective studies are warranted to investigate the appropriate choice of treatment for this new clinical entity.
In Hong Kong, the prevalence of Female urinary incontinence is around 35% and around 18% (∼60,000 female) suffered from serve incontinence. However, due to the fact that many women have poor coordination of pelvic floor muscle it leads to unsatisfactory treatment outcomes. Few studies have compared the effectiveness of biofeedback pelvic floor muscle training against intra-vaginal electrical stimulation in treating urinary incontinence.

Bladder outlet obstruction (BOO) is a common cause of overactive bladder (OAB) symptoms in men, but not all men with OAB symptoms have BOO. The strategies for treatment of OAB symptoms are different in men with BOO and those without BOO. Pressure-flow studies are considered the reference standard to diagnose BOO. However, the procedure is invasive, expensive and time-consuming. A non-invasive diagnostic method for BOO in men with OAB symptoms is warranted. The nomogram creates a simple graphical representation of a statistically predictive model which generates a numerical probability of a clinical event. In this study, we want to develop a nomogram for detection of BOO in male patients with OAB symptoms.

To assess the clinical usefulness and safety we used a

To assess the clinical usefulness and safety, we used a subcutaneous xenograft tumor model. In this model, MK2206 was administered intraperitoneally at 50mg/kg once per week. This dose was lower than that reported previously [19], which used the dose of 100mg/kg once per week, but this low concentration could still enhance cancer-specific CDDP-induced cytotoxicity, and significant tendency of tumor growth inhibition was found in the combination therapy group. However, statistical differences could not be observed among groups. When we consider the clinical application of MK2206 at a low concentration with chemotherapeutic agents, a combination with CDDP, which is one of the most frequently used agents for UC, is a very attractive choice.


Renal cell carcinoma (RCC), which accounts for approximately 3% of all human malignancies, is the most common malignant cancer in the adult kidney. According to the World Health Organization (WHO) classification, clear cell subtype (ccRCC) represents 80% to 90% of all RCCs [1]. At present, owing to the increased application of radiological diagnostic techniques and the interest in regular checkups, the clinical diagnosis of early-stage RCC has increased. RCC could be cured surgically if diagnosed at an early stage; however, approximately 30% of patients undergoing nephrectomy for localized RCC will have local recurrence or distant metastasis [2]. Patients who at a higher risk of recurrence or progression need to undergo a closer follow-up.
Recent studies revealed that molecular predictors can not only assist in outcome prediction but also have the potential to serve as practical targets for development of therapeutic strategies. Thegalectins (Gals) are a structurally related family of proteins that function as animal lectins with at least one highly conserved carbohydrate recognition domain and an affinity for β-galactosides [3]. They are involved in various biological processes including cell growth, apoptosis, angiogenesis, cell migration, and inflammation [4,5]. Previous studies have indicated that elevated Tubacin of Gal-1 might serve as a potential marker for RCC and is implicated in ccRCC progression via the hypoxia-inducible factors (HIF)/mammalian target of rapamycin (mTOR) signaling axis [6,7]. According to the previous studies, Gal-3 is also highly expressed in ccRCC and involved in tumor progression [8,9].
Similar to Gal-1 and Gal-3, Gal-8 is implicated in modulation of cell matrix and cell-cell interactions [10,11]. Studies have shown that Gal-8 expression is markedly related with certain neoplasms in tissues such as the pancreas, the colon, the skin, and the liver [12–15]. In the prostate and bladder carcinomas, there have been conflicting data documented so far. On one hand, high expression of Gal-8 might give neoplasms some growth or metastasis-related advantages [16,17]. On the other hand, Danguy et al. [12] showed that the expression level of Gal-8 is very low in normal prostatic tissues as well as in benign hyperplasias or adenocarcinomas. Another work reported that decreased Gal-8 is a marker for recurrence in bladder carcinoma [18]. Regarding the expression of Gal-8 in the kidney, no statistically significant differences of staining intensity were observed between RCC and normal tissues [12]. However, the low number of specimens and intertumoral and intratumoral heterogeneity prevent any final conclusion [12,19].

Patients and methods


It has been reported that the expression of Gal-1 and Gal-3 could be regulated by HIF1 [22,23]. In addition, von Hippel–Lindau (VHL) inactivation is a common event in ccRCC. Because Gal-8 exerts functions similar to Gal-1 and Gal-3 in Tubacin certain tumors and has been validated to play a critical role in ccRCC in this study, we consider that Gal-8 expression might also be modulated by HIF1 and involved in VHL/HIF/HRG (hypoxia responsive gene) signaling axis.
As presented in this study, Gal-8 expression could be applied as an independent prognostic factor in patients with early-stage ccRCC, especially in T1b stage. The profound molecular roles of Gal-8 in ccRCC tumorigenesis await further investigation. Besides the well-documented ability to mediate cell adhesion [10], Gal-8 could modulate endothelial cell migration and promote angiogenesis [24]. The proangiogenesis properties of Gal-8 further indicated its potential role in VHL/HIF/vascular endothelial growth factor (VEGF) signaling pathway. Another study reported that Gal-8 could promote cytoskeletal rearrangement via activation of Rho signaling [25]. A recent study concluded that Gal-8 exerted immunosuppressive function not only by inducing apoptosis of activated T cells but also via negatively mediating the critical function of lymphocyte function-associated antigen-1 in the immune system [26]. Numerous researches have determined that cytotoxic T-lymphocyte antigen-4 and programmed death-1 expressed on T cells, functioning as immune checkpoints, also exert immunosuppressive actions. Nowadays, anti-cytotoxic T-lymphocyte antigen-4 and anti-programmed death-1 monoclonal antibodies have presented striking antitumor activity in large phase I studies [27,28]. So Gal-8 expression might also be identified as a potential predictive biomarker on treatment response of these immune checkpoints inhibitors, which needs further explorations.

IL expression in RCC cell

IL-6 serine protease in RCC cell lines also correlates with human plasma membrane-associated sialidase (NEU3) expression (Fig.2) [64]. NEU3 is unique in specifically hydrolyzing gangliosides and is thought to participate in cellular differentiation and transmembrane signaling, thereby playing a crucial role in the regulation of cell surface function [61]. NEU3 sensitizes IL-6 signaling mainly via the phosphatidylinositol 3-kinase (PI3K) pathway in a positive feedback manner, leading to suppression of apoptosis accompanied by enhanced cell migration. Suppression of apoptosis and promotion of cell motility is induced by NEU3 overexpression and potentiation of IL-6 effects. Results from in vitro modeling demonstrated that PI3K activation might be responsible for the suppression of apoptosis and increased motility caused by NEU3ʼs overexpression and by IL-6 treatment [64].

IL-6 as a prognostic marker in RCC
Serum IL-6 was undetectable in most of the tumor-free patients, but was present in many patients with metastatic RCC [65]. Higher levels of IL-6 measured before surgery correlated with worse survival outcomes. Normal IL-6 levels in patientsʼ serum before nephrectomy correlated with longer survival time and longer cancer-specific survival time [66] and without nephrectomy [65]. In a large the Cancer Renal Cytokine (CRECY) trial of IL-2 (arm A) or IFN-α (arm B) or a combination of IL-2 and IFN-α (arm C) serum IL-6 levels was significantly correlated with PFS and overall survival (OS). It was therefore shown to have prognostic potential [67]. However, in other studies, serum IL-6 levels did not correlate with survival in RCC [41].
At the same time, patients with increased IL-6 expression have greater incidence of lymph node metastases [45] and distant metastases [68]. There was no significant correlation between the tumor size or grade and IL-6 expression; however relatively large number of high-grade tumors expressed a high level of IL-6 [69]. In a clinical study, a significant association between serum IL-6 level and anemia; elevated platelet count; decreased serum albumin and elevated alkaline phosphatase levels [41]; and higher serum C-reactive protein (CRP), haptoglobin, and gammaglutamyl transferase levels [70] was found in patients with RCC. In patients with RCC after nephrectomy, a strong correlation was found between the maximal concentrations of IL-6 and CRP, but not total fibrinogen or high-molecular-weight fibrinogen [71]. IL-6 levels were also found to be significantly higher in patients presenting with paraneoplastic fever and weight loss [70] (summarized in Table 1).
Pazopanib is a tyrosine kinase inhibitor (TKI) that blocks angiogenesis. IL-6 was the only individual cancer-associated fibroblasts with significant predictive value for PFS benefit, and patients with high IL-6 concentrations had a greater relative benefit from pazopanib when compared with that of patients who received placebo [72]. Hence, IL-6 is 1 of 5 factors with continuous tumor shrinkage or PFS in patients treated with pazopanib [72], but not together with IL-2 treatment [41]. It was reported that pretreatment serum concentrations of IL-6 is higher in patients who do not respond to IL-2 treatment and who experience progressive disease at first follow-up. Patients with detectable IL-6 levels had a shorter OS after IL-2 treatment than patients without circulating IL-6 had, and the difference in median survival was as high as 8 vs. 16 months [39] (summarized in Table 1).

IL-6 pathway serine protease as drug target in RCC
RCC is resistant to conventional radiotherapy and chemotherapy, but complete responses have been observed after immunotherapy with high-dose IL-2 and IFN-α. The first immunotherapy trial for renal cancer was conducted in 1914, when New York surgeon WB Cooley published a study assessing the long-term effects of application of a bacterial toxins mixture in patients with renal tumors [73]. Immunotherapy using IL-2 or IFN-α is now registered in RCC treatment in the United States and the European Union [74–77]. The 2 recombinant forms rIFN-α-2a and rIFN-α-2b are available for clinical use; Roferon (rIFN-α2a) is more immunogenic than Intron A (rIFN-α2b) is. Th1 cytokine production is induced by IFN-α, and it promotes antitumor cytotoxicity [78]. For natural killer cells and T cells, IL-2 is a growth/differentiation factor that induces and maintains cytotoxicity [79]. Unfortunately, clinical studies demonstrated that IL-2 gave response rates of 15% to 30% with approximately 5% being complete responses; the median survival was reported between 6 and 19 months [80,81]. Consequently, use of IFN-α or IL-2 treatment regimens may result in a reduction of tumor burden by more than 50%. Unfortunately, the objective response rates (partial or complete response) are in the range of 5% to 20% [82–85], and the median OS of responding patients is only extended by approximately 4 months [86]. Combined therapy with IL-2 and IFN-α exhibited longer median recurrence-free survival in comparison with that in a single-agent treatment, but OS did not differ between treatment arms [81]. However, further trials did not reveal clinical benefits of synergistic usage of other immune stimulants in RCC treatment [81]. Hence, new immunological targets for RCC treatment should be investigated.