Gross reporting of adult kidney tumor specimens: A comprehensive evidence-based review.

Renal tumors comprise a wide spectrum of benign and malignant tumors. The important prognostic factors in renal cell carcinoma include pathological stage, tumor grade, morphological type, sarcomatoid/rhabdoid differentiation, and tumor necrosis. Therefore, the pathologist needs to be fully aware of how to gross nephrectomy specimens to be able to accurately provide the above prognostic information while reporting adult kidney tumors. With the advent of nephron-sparing surgeries, due diligence should be exercised to assess and sample the parenchymal surgical margin. This article discusses the approach to grossing nephrectomy specimens, elaborates the significance of every step, and also sheds light on the importance of clinical and radiological information in providing a holistic approach to the diagnosis and staging of adult renal tumors.

Tuning the binding, release and cytotoxicity of hydrophobic drug by Bovine Serum Albumin nanoparticles: Influence of particle size.

To elucidate the effect of particle size of albumin nanoparticles on cellular uptake of a hydrophobic drug, herein we report the release kinetics and cytotoxicity of nanoparticle bound dimethylcurcumin (DMC) in A549 tumor cells. The bovine serum albumin (BSA) nanoparticles were prepared by thermal denaturation and characterized by dynamic light scattering (DLS), zeta (ζ) -potential, circular dichroism (CD) and transmission electron microscope (TEM). The preparation conditions were optimized to obtain nanoparticles with mean hydrodynamic diameters 28.0nm (BSAnp1) and 52.0nm (BSAnp2) and corresponding ζ- potential value of∼-7.0 and -6.0mV, respectively. Interaction of DMC with BSA nanoparticles was investigated by UV-vis, fluorescence and CD spectroscopy. CD studies indicated significant changes in the secondary structure of BSA upon particle formation, as revealed by decrease in the helicity. The cellular uptake of DMC increased with increase in particle size and the toxicity of DMC loaded nanoparticles to A549 cells were found to be consistent with their cellular uptake. Between the two formulations studied, BSAnp2 provided enhanced cellular uptake and can be used as an effective delivery system for hydrophobic drugs like DMC.

Peripheral primitive neuroectodermal tumor of the adrenal gland: A rare entity.

Peripheral primitive neuroectodermal tumor (PNET) is an uncommon tumor and the overall incidence is 1% of all sarcomas. PNET of the adrenal gland is an even rarer entity. A 37-year-old female was evaluated for an episode of loin pain. Ultrasonography showed a large heterogenous left adrenal mass with internal echogenic components. Computed tomography did not show any fat density within to suggest a myelolipoma. Biopsy suggested a poorly differentiated neoplasm with a possibility of PNET of the adrenal gland.

Primary renal angiosarcoma.

Primary angiosarcoma of the kidney is a rare tumor with only a few case reports in the literature. Management is not standardized and the prognosis is poor. However, clinicians need to be aware of this uncommon entity.

A rare case report: ovarian heterotopic pregnancy after in vitro fertilization.

OBJECTIVE: To report a case of ovarian heterotopic pregnancy after an IVF cycle. DESIGN: Case report. SETTING: Reproductive medicine unit, Christian Medical College Hospital, Vellore, India. PATIENT(S): A woman with an ovarian heterotopic pregnancy. INTERVENTION(S): Laparoscopic removal of ovarian ectopic pregnancy. MAIN OUTCOME MEASURE(S): Early detection and successful treatment of heterotopic pregnancy. RESULT(S): Successful laparoscopic management of ovarian pregnancy resulting in a single viable ongoing intrauterine pregnancy. CONCLUSION(S): Clinicians need to be aware of such rare and potentially fatal presentations after IVF, because early diagnosis and management in these cases can yield a favorable outcome.

Liquid embolisation material reduces the delivered radiation dose: a physical experiment.

OBJECTIVE: To test a new hypothesis that the glue/contrast admixture used for embolisation reduces the dose delivered to AVMs using an experimental model. METHOD: A model was created using a block of "solid water" (6 x 5 x 2 cm) with twelve wells of different depths. Different concentrations of the glue admixture (Enbucrilate + Lipiodol) were used. The model was irradiated using a 5MV beam with a clinical LINAC system and the dose was checked upstream and downstream. Dose was measured using Kodak XV film, a Vidar 16 bit film scanner and software for therapeutic film dosimetry measurements (RIT software). RESULTS: The radiation dose varied with the distance beyond the glue solid water interface. For distances of 0, 2 and 5 mm to the film, the mean reduction was 13.65% (SD = 2.94), 6.87% (SD = 1.95) and 1.75% (SD = 1.14), respectively. There was also correlation with the Lipiodol concentration in the mixture. The maximum reductions for 80, 50 and 20% Lipiodol concentrations were 16.1% (SD = 1.32), 14.85% (SD = 0.98) and 10% (SD = 1.21), respectively. There was no correlation between the glue depth and the dose delivered. CONCLUSION: The hypothesis that the glue mixture used for embolisation reduces the radiation dose delivered was experimentally confirmed with this study.

Splenic hemangiomas and hamartomas: MR imaging characteristics of 28 lesions.

PURPOSE: To determine the magnetic resonance (MR) imaging features of splenic hemangiomas and hamartomas, including their pattern of dynamic contrast material enhancement. MATERIALS AND METHODS: The appearance of 28 lesions in 18 patients was retrospectively reviewed on T2-weighted images (16 patients), unenhanced T1-weighted images (18 patients), and dynamic contrast-enhanced T1-weighted images (17 patients). Seventeen of 23 hemangiomas and all five hamartomas were proved at pathologic examination. RESULTS: Of the 22 hemangiomas imaged with T2-weighting, 19 were hyperintense, two were isointense, and one was hypointense relative to the spleen. Dynamic gadolinium-enhanced imaging demonstrated a progressive centripetal pattern of enhancement in 19 of 22 hemangiomas. On delayed images, 19 hemangiomas demonstrated uniform enhancement. Of the five hamartomas, four were imaged with T2-weighting; three were hyperintense and one was hypointense relative to the spleen. All hamartomas demonstrated diffuse heterogeneous enhancement on images obtained early after administration of contrast material and became more uniformly enhanced on delayed images. CONCLUSION: Splenic hemangiomas showed signal intensity characteristics and enhancement patterns similar to those described for hepatic hemangiomas. Since these features have been shown to reliably distinguish hemangiomas from other benign and malignant liver lesions, it may be reasonable to consider without histologic verification that lesions in the spleen with these imaging features represent hemangiomas.

Requiring on-line medical command for helicopter request prolongs computer-modeled transport time to the nearest trauma center.

INTRODUCTION: Rapid transport from scene to closest trauma center requires optimal use of public safety first responder (FR), basic life support (BLS), advanced life support (ALS), and transport resources (ground or air). In some parts of this regional emergency medical services (EMS) system, on-scene ALS requires contact with on-line medical command (OLMC) to obtain authorization for air medical helicopter (AMH) dispatch, because some EMS medical directors believe that this may decrease overutilization of AMH services. HYPOTHESIS: The hypothesis of this study was that requiring prior OLMC for AMH dispatch prolongs mean time to a trauma center versus either FR or BLS request for AMH. METHODS: Computer mapping programs were used to model the most rapid driving time to the closest trauma center from 167 actual AMH responses to the scene of a motor vehicle accident. In an OLMC-ALS model, only OLMC-ALS can request an AMH. In a BLS model, BLS units arrive on the scene and the crew requests simultaneous dispatch of an ALS response and an AMH. In the FR model, on arrival at the scene, a FR requests simultaneous dispatch of a BLS unit, an ALS unit, and an AMH. RESULTS: The OLMC-ALS model resulted in a longer mean value for time to trauma center by an AMH than did the computer model for all ground transport settings. The FR model yielded a shorter mean time for AMH compared with the mean values for time to trauma center for all settings. Differences in mean values for time in urban settings were small (ground: 42 minutes, air: 36 minutes), whereas those for the suburban (ground: 52 minutes, air: 41 minutes), and those for rural (ground: 69 minutes, air: 47 minutes) were significant clinically. For the BLS model, these differences persisted, but were significant clinically only in the rural setting (ground: 68 minutes, air: 53 minutes). CONCLUSIONS: Optimal use of AMH requires balancing the need for early helicopter dispatch to fully exploit its speed advantage with the disadvantage of expensive overutilization. This computer model indicates that the best person to request AMH varies by venue: in urban settings, the OLMC physician should request AMH dispatch; in suburban venues, BLS should request AMH dispatch; and in rural venues, FRs should request AMH dispatch.

Protein tyrosine kinase activation is required for LPS and PMA induction of tissue factor mRNA in human blood monocytes.

Tissue factor (TF) is a transmembrane glycoprotein which assembles with factor VIIa on cell surfaces to form a proteolytically active cofactor-enzyme complex; the TF/VIIa complex initiates the coagulation protease cascade. In response to bacterial lipopolysaccharide (LPS) and phorbol-12 myristate 13-acetate (PMA), monocytes synthesize and express TF on their surface. However, the mechanisms by which LPS and PMA activate TF synthesis by human blood monocytes are not fully understood. As it has been established that LPS and PMA activate protein tyrosine kinase (PTK) in monocytes, we studied the role of PTK in LPS and PMA induction of TF by human blood monocytes. Both LPS- and PMA-induced TF activity was inhibited in a concentration-dependent manner by the protein tyrosine kinase-specific inhibitors herbimycin A and genistein. TF antigen determination confirmed that LPS- and PMA-induced cell surface TF protein levels decreased in parallel to TF functional activity under herbimycin A and genistein treatment. Northern blot analysis of total RNA from LPS- and PMA-stimulated monocytes showed a concentration-dependent decrease in TF mRNA levels in response to herbimycin A and genistein. The rate of decay of LPS-induced TF mRNA, evaluated after the arrest of transcription by actinomycin D was not affected by genistein and herbimycin A, suggesting that the inhibitory effects occur at least partly at the transcriptional level. We conclude that LPS- and PMA-induced TF production by human monocytes is dependent on tyrosine kinase activation.

Interleukin-10 and pentoxifylline inhibit C-reactive protein-induced tissue factor gene expression in peripheral human blood monocytes.

Fibrin deposition is an integral feature of the inflammatory response. In response to C-reactive protein (CRP), an acute-phase reactant, blood monocytes synthesize and express tissue factor (TF), the main initiator of blood coagulation. We report the inhibitory effect of interleukin 10 (IL-10) and that of pentoxifylline, a methyl xanthine derivative, on monocyte expression of TF activity, TF protein and TF mRNA in response to CRP. These agents may be of use in diseases where a TF-induced prothrombotic state is detrimental.

Interleukin-10 inhibits endotoxin-induced tissue factor mRNA production by human monocytes.

In Gram-negative septic shock, human monocytes synthesize and express on their cytoplasmic membrane tissue factor (TF), a potent activator of the coagulation cascades. The role of TF in triggering disseminated intravascular coagulation (DIC) in these patients appears to be clear. We report the suppressive effect of interleukin-10 (IL-10) on endotoxin-induced TF activity and antigen levels, and on the expression of TF mRNA levels in human monocytes. These results emphasize the potential therapeutic value of this cytokine in septic shock, a condition still associated with a high mortality rate.

Interleukin 4 prevents the induction of tissue factor mRNA in human monocytes in response to LPS or PMA stimulation.

Increased expression of tissue factor (TF) procoagulant activity by blood monocytes and tissue macrophages is implicated in a number of thrombotic disorders, as well as in fibrin deposition associated with inflammatory lesions and immunological diseases. We found that interleukin 4 (IL-4), a T lymphocyte-derived cytokine known to regulate a number of monocyte functions, inhibited the production of TF by monocytes in response to endotoxin and phorbol myristate acetate (PMA) in vitro. IL-4 had a concentration-dependent inhibitory effect on functional TF procoagulant activity (PCA) and reduced the binding of an anti-TF antibody, as assessed by flow cytometry analysis. Moreover, IL-4 reduced LPS- and PMA-induced TF mRNA levels. TF mRNA stability was not modified by IL-4 after the arrest of transcription by actinomycin D. We thus conclude that mRNA suppression is mediated by an effect occurring at the transcriptional level. Our results also show that the suppressive effect of IL-4 is independent of an increase in the intracellular concentration of cyclic AMP, another established inhibitor of TF production. Locally produced IL-4 might thus contribute to limiting the consequences of monocyte activation.

Endotoxin-induced tissue factor in human monocytes is dependent upon protein kinase C activation.

Tissue factor (TF) is a transmembrane receptor which, in association with factors VII and VIIa, activates factor IX and X, thereby activating the coagulation protease cascades. In response to bacterial lipopolysaccharide (LPS) monocytes transcribe, synthesize and express TF on their surface. We investigated whether LPS-induced TF in human monocytes is mediated by protein kinase C (PKC) activation. The PKC agonists phorbol 12-myristate 13-acetate (PMA) and phorbol 12, 13 dibutyrate (PdBu) were both potent inducers of TF in human monocytes, whereas 4 alpha-12, 13 didecanoate (4 alpha-Pdd) had no such effect. Both LPS- and PMA-induced TF activity were inhibited, in a concentration dependent manner, by three different PKC inhibitors: H7, staurosporine and calphostin C. TF antigen determination confirmed that LPS-induced cell-surface TF protein levels decreased in parallel to TF functional activity under staurosporine treatment. Moreover, Northern blot analysis of total RNA from LPS- or PMA-stimulated monocytes showed a concentration-dependent decrease in TF mRNA levels in response to H7 and staurosporine. The decay rate of LPS-induced TF mRNA evaluated after the arrest of transcription by actinomycin D was not affected by the addition of staurosporine, suggesting that its inhibitory effect occurred at a transcriptional level. We conclude that LPS-induced production of TF and its mRNA by human monocytes are dependent on PKC activation.

High prevalence of skin cancer in World War II servicemen stationed in the Pacific theater.

BACKGROUND: A large proportion of our World War II patients with skin cancer had been stationed in the Pacific. OBJECTIVE: Our purpose was to determine whether a statistically greater number of World War II servicemen with skin cancer were stationed in the Pacific than the number stationed in Europe. METHODS: In a consecutive survey of 370 World War II servicemen with skin cancer who were stationed abroad, place of service, skin cancer types, skin type, ethnic background, and estimated average hours outdoors per day during their lifetime were determined. The number of veterans stationed in the Pacific and the number stationed in Europe with respect to these data were analyzed with the chi-square test. RESULTS: A statistically significantly greater number of Pacific veterans than Europe veterans had basal cell or squamous cell carcinomas. CONCLUSION: A few months to a few years of prolonged sun exposure in a high-sun-intensity area may result in skin cancer development many years after exposure.