Comparative Effectiveness of Neoadjuvant Chemoradiation Versus Upfront Surgery in the Management of Recto-Sigmoid Junction Cancer

Introduction

The optimal management of locally advanced recto-sigmoid cancer is unclear. Although some experts advocate for upfront surgery, others recommend neoadjuvant chemoradiation followed by surgery. We used the National Cancer Database to characterize patterns-of-care and overall survival (OS) associated with these treatment strategies.

In vitro interference of the red cell substitute pyridoxalated hemoglobin-polyoxyethylene with blood compatibility, coagulation, and clinical chemistry testing

Pyridoxalated hemoglobin-polyoxyethylene (PHP) is a prototypical red cell substitute approved for phase I studies. Peripheral blood smears of human blood mixed with PHP in 1 to 4 g/dL concentrations showed dose-dependent red cell aggregation and rouleaux. Whether this aggregation limits interpretation of blood compatibility testing and whether the intense coloration of serum or plasma containing PHP affects routine coagulation and clinical chemistry measurements was tested. In vitro studies. University hospital laboratory. Four healthy volunteers, blood types A, B, AB, and O. All were Rh+.

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ABO typing, Rh typing, and antibody screening and coagulation studies were performed on blood: PHP admixtures having final concentrations of 1, 2, and 4 g/dL. For clinical chemistry interference studies, known concentrations of analytes were added to a serum matrix containing PHP ABO (forward) and Rh typing showed no interference in the three concentrations tested. Reverse ABO typing and antibody screening showed rouleaux at 4 g/dL, which corrected with routine saline replacement. Partial thromboplastin time (PTT), prothrombin time (PT), and fibrinogen showed no clinically significant differences from the controls. Results for electrolytes, renal function analytes, and markers of cardiac injury were acceptable by standard laboratory methods. However, results of liver function tests were unacceptable in PHPcontaining specimens. PHP-induced aggregation was observed with high PHP concentration; however, compatibility testing was not affected because agglutination was corrected by saline replacement, which is standard practice. Although routine blood banking, coagulation, and most clinical chemistry analytes can be measured reliably, alternative methods and strategies are needed for assessing liver function in the presence of PHP.     

Endothelium-dependent contractile actions of proteinase-activated receptor-2-activating peptides in human umbilical vein: release of a contracting factor via a novel receptor

1. The contractile actions of the proteinase-activated receptor-2-activating peptides (PAR₂APs), SLIGRL-NH₂ (SL-NH₂), SLIGKV-NH₂ (KV-NH₂), trans-cinnamoyl-LIGRLO-NH₂ (tc-NH₂), and the PAR₁-AP, TFLLR-NH₂ (TF-NH₂) as well as trypsin and thrombin were studied in endothelium-denuded and intact human umbilical vein (HUV) ring preparations.
2. In HUV rings with, but not without an intact endothelium, PAR₂APs caused a concentration-dependent contractile response, whereas LSIGRL-NH₂ trypsin and PAR₁APs were inactive. The contractile response was not affected by the endothelin ET_A receptor antagonist, BQ123, the cyclooxygenase inhibitor, indomethacin, the leukotriene synthesis inhibitor, MK886, or the epoxygenase/P450 inhibitor, SKF-525A. Other pharmacological antagonists (prazosin, Losartan®) were similarly inactive.
3. The order of potencies of the PAR₂APs to cause a contraction in the endothelium-intact preparation was: SL-NH₂>>KV-NH₂⩾tc-NH₂.
4. Using an endothelium-free rat aorta ring as a reporter tissue, surrounded with endothelium-intact HUV as a donor tissue in a `sandwich assay,'' we also monitored the ability of SL-NH₂, TF-NH₂, trypsin and thrombin to release either contractile (EDCF) or relaxant (EDRF) factors.
5. In the `sandwich assay'' done in the presence of L-NAME (0.1 mM), the endothelium-intact HUV tissue (but not endothelium-denuded HUV) released a contractile factor (EDCF) in response to SL-NH₂ (50 μM) but not to trypsin or LSIGRL-NH₂. The SL-NH₂-mediated release/action of the EDCF was not affected by BQ123, indomethacin, MK886 or SKF-525A.
6. In the `sandwich assay'', trypsin (4–10 nM), SL-NH₂, KV-NH₂ and tc-NH₂ caused the release of a relaxant activity (EDRF) from the endothelium-intact (but not the denuded) HUV preparation. The release of EDRF was blocked by 0.1 mM ^ωnitro-L-arginine-methylester (L-NAME). Neither thrombin (10 u ml⁻¹, 100 nM) nor TF-NH₂ (50 μM) were active in this EDRF-release assay.
7. The relative potencies of the PAR₂ agonists for causing the release of EDRF in the HUV sandwich assay were: trypsin>>SL-NH₂>>tc-NH₂>KV-NH₂. This order of potencies differed from the one observed for the same agonists in the HUV contraction assay (above) and in an intracellular calcium signalling assay, conducted with cloned human PAR₂ that was expressed in cultured rat kidney KNRK cells: trypsin>>SL-NH₂=tc-NH₂>KV-NH₂.
8. We conclude that PAR₂APs (but not PAR₁APs) via a receptor distinct from PAR₂, can cause a contractile response in endothelium-intact HUV tissue via the release of a diffusable EDCF, that is different from previously recognized smooth muscle agonists (e.g. prostanoid metabolites, endothelin, noradrenaline, angiotensin-II, acetylcholine).

     

HCV associated glomerulopathy in Egyptian patients: clinicopathological analysis

BACKGROUND: Hepatitis C virus (HCV) infection in Egypt has reached an epidemic proportion and is associated with many extra hepatic manifestations; Glomerulonephritis (GN) is one of the most consequences of HCV infection often resulting in end stage renal disease in some cases. Detection of viral genome or particles within the kidney biopsies from HCV-infected patients has proven to be difficult. Histological characterization of renal lesions still represents a major challenge. The aim of our work was to describe the histological pattern of HCV-associated nephropathy. METHODS: Fifty Patients--out of 233--presented to Mansoura Urology and Nephrology clinic with manifestations of glomerular disease were screened for HCV antibodies by a 3rd generation ELISA test. Those tested positive for HCV antibodies were confirmed by PCR for HCV-RNA and subjected to more detailed clinical, biochemical and histological study. Kidney biopsies and in appropriate cases liver biopsies were examined by LM and electron microscopy (EM). RESULTS: Histological study of renal biopsies revealed membranoproliferative (MPGN) type 1 to be the most common lesion encountered (54%), followed by focal segmental glomerulosclerosis (FSGS) (24%), mesangioproliferative GN (18%), membranous nephropathy (MN) (4%) in that order. EM examinations of renal biopsies were successful in identifying HCV like particles in frozen renal tissue. CONCLUSION: HCV-associated glomerulopathy is a distinct category of glomerulonephritis. Results of LM showed some peculiar features. In addition, we were successful in location and detection of HCV particles in renal tissues by EM.     

Renal cell carcinoma metastatic to Hurthle cell adenoma of thyroid

Metastases to the thyroid gland are a common finding at autopsy in patients who died of malignancy and are often misdiagnosed as primary thyroid neoplasms clinically. We present a patient with a rare, unusual case of renal cell carcinoma (RCC) metastatic to a Hurthle cell adenoma of the thyroid. A 53-year-old woman was admitted to a University of Texas Medical Branch Hospital (Galveston, TX) for a large right thyroid mass that was present for 3 months. A fine needle aspiration of the thyroid mass was performed and interpreted as suggestive of a Hurthle cell neoplasm. A total thyroidectomy revealed Hurthle cell adenoma containing clusters of cytologically atypical cells with clear cytoplasm. Subsequent patient evaluation and computed tomography revealed a renal mass. Left radical nephrectomy was performed at a later date for left renal mass and the microscopic examination confirmed the diagnosis of primary clear cell carcinoma of the kidney. Further studies confirmed that the thyroid mass was metastases from RCC. Although carcinoma of the kidney is responsible in most instances of metastatic disease to the thyroid, metastatic RCC to a thyroid neoplasm is extremely rare, with only two reports found in the English literature. The possibility of metastatic RCC should always be taken under consideration, especially when nests of clear cells are seen infiltrating into the thyroid parenchyma or neoplasm.     

Five-year outcomes of the PYTHAGORAS U.S. clinical trial of the Aorfix endograft for endovascular aneurysm repair in patients with highly angulated aortic necks

Objective

Early and midterm outcomes of the Prospective Aneurysm Trial: High Angle Aorfix Bifurcated Stent Graft (PYTHAGORAS) trial in patients with highly angulated aortic necks (≥60 degrees) have already been published and shown comparable outcomes to other endografts in normal anatomy. Herein, we present the long-term outcomes of the PYTHAGORAS trial of Aorfix (Lombard Medical, Irvine, Calif) for patients with highly angulated aortic neck anatomy.

Bovine carotid artery biologic graft outperforms expanded polytetrafluoroethylene for hemodialysis access

Objective

Arteriovenous grafts remain reliable substitutes for permanent hemodialysis access in patients without a suitable autogenous conduit. Advances in conduit design and endovascular management of access-related complications question the preference for synthetic conduits over biologic grafts in contemporary practice. In this study, we compared outcomes between a bovine carotid artery (BCA) biologic graft and expanded polytetrafluoroethylene (ePTFE) grafts for hemodialysis access in a recent cohort of patients.