Mucinous tubular and spindle cell carcinoma of the kidney: cytopathologic findings

A 54-year-old woman was hospitalized for flank pain and acute renal failure when imaging studies revealed a 5.2 cm mass in the left kidney. She was referred for fine needle aspiration of the lesion, which showed an epithelial tumor with round to oval nuclei associated with strands of metachromatic stromal tissue. Cytopathologic diagnosis was consistent with renal cell carcinoma. Subsequent nephrectomy was performed and the surgical pathology specimen showed a mucinous tubular and spindle cell carcinoma of the kidney. The patient has done well post-operatively with 10 months of benign follow-up.     

Microfluidic assisted synthesis of PLGA drug delivery systems

Poly(lactic-co-glycolic acid) (PLGA) is a biocompatible and biodegradable polymer that recently attracted attention for use as part of drug delivery systems (DDS). In this context, there is an emerging need for a rapid, reliable and reproducible method of synthesis. Here, microfluidic systems provide great opportunities for synthesizing carriers in a tightly controlled manner and with low consumption of materials, energy and time. These miniature devices have been the focus of recent research since they can address the challenges inherent to the bulk system, e.g. low drug loading efficiency and encapsulation, broad size distribution and burst initial release. In this article, we provide an overview of current microfluidic systems used in drug delivery production, with a special focus on PLGA-based DDS. In this context, we highlight the advantages associated with the use of microchip systems in the fabrication of nanoparticles (NPs) and microparticles (MPs), e.g. in achieving complex morphologies. Furthermore, we discuss the challenges for selecting proper microfluidics for targeted DDS production in a translational setting and introduce strategies that are used to overcome microfluidics shortcomings, like low throughput for production.

Poly(lactic-co-glycolic acid) (PLGA) is a biocompatible and biodegradable polymer that recently attracted attention for use as part of drug delivery systems (DDS).     

Comparing cystatin C changes as a measure of renal function before and after radiotherapy in patients with stomach cancer

The objective of this study was to determine and compare cystatin C changes before and after radiotherapy in patients with stomach cancer who were candidate for radiotherapy. This study was conducted as a prospective cohort one. Eighteen patients with definite diagnosis of stomach cancer under treatment by radiotherapy who presented to Radiotherapy-Oncology Center of Imam Hossein Hospital, Tehran-Iran, and the treatment in all cases was simultaneous chemoradiation with Xeloda were included. In all patients before radiotherapy and after radiotherapy serum creatinine (Cr) and cystatin C were measured simultaneously. Mean cystatin level before treatment (1.2 ± 0.4) was significantly lower than that of post-treatment (1.6 ± 0.36), (P=0.001). Serum Cr level before treatment was 1.15 ± 0.33 and after radiotherapy was 1.08 ± 0.24 and did not show significant difference. Glomerular filtration rate (GFR) of the patients before radiotherapy was -46.8 ± 21.0 and after radiotherapy was 43.8 ± 15.8 that did not have significant difference (P=0.146) and also blood urea nitrogen (BUN) before radiotherapy was 20.72 ± 3.7 and 20 ± 6.38 after radiotherapy that did not have significant difference (P=0.6). Comparison of the cystatin C difference with total radiation dose of the kidneys that are put in three dose groups in radiotherapy field had association that in dose of less that 18 gray (Gy) the cystatin C change showed significant and positive association (P=0.027; r=0.52) and about 18-24 Gy the cystatin C difference showed significant and negative association (P=0.023, r=-0.53). It seems that for evaluating the renal function, serum cystatin C measurement is preferable than serum Cr. level.     

Molecular Confirmation of t(6;11)(p21;q12) Renal Cell Carcinoma in Archival Paraffin-embedded Material Using a Break-apart TFEB FISH Assay Expands its Clinicopathologic Spectrum

A subset of renal cell carcinomas (RCCs) is characterized by t(6;11)(p21;q12), which results in fusion of the untranslated Alpha (MALAT1) gene to the TFEB gene. Only 21 genetically confirmed cases of t(6;11) RCCs have been reported. This neoplasm typically demonstrates a distinctive biphasic morphology, comprising larger epithelioid cells and smaller cells clustered around basement membrane material; however, the full spectrum of its morphologic appearances is not known. The t(6;11) RCCs differ from most conventional RCCs in that they consistently express melanocytic immunohistochemical (IHC) markers such as HMB45 and Melan A and the cysteine protease cathepsin K but are often negative for epithelial markers such as cytokeratins. TFEB IHC has been proven to be useful to confirm the diagnosis of t(6;11) RCCs in archival material, because native TFEB is upregulated through promoter substitution by the gene fusion. However, IHC is highly fixation dependent and has been proven to be particularly difficult for TFEB. A validated fluorescence in situ hybridization (FISH) assay for molecular confirmation of the t(6;11) RCC in archival formalin-fixed, paraffin-embedded material has not been previously reported. We report herein the development of a break-apart TFEB FISH assay for the diagnosis of t(6;11)(p21;q12) RCCs. We validated the assay on 4 genetically confirmed cases and 76 relevant expected negative control cases and used the assay to report 8 new cases that expand the clinicopathologic spectrum of t(6;11) RCCs. An additional previously reported TFEB IHC-positive case was confirmed by TFEB FISH in 46-year-old archival material. In conclusion, TFEB FISH is a robust, clinically validated assay that can confirm the diagnosis of t(6;11) RCC in archival material and should allow a more comprehensive clinicopathologic delineation of this recently recognized neoplastic entity.     

Fibroblast growth factor 2 regulation of mitral valve interstitial cell repair in vitro

OBJECTIVE: Because elongated mitral valve interstitial cells have features of myofibroblasts, it is likely that these cells are essential for the repair of injured valve leaflets. We characterized the cellular morphology and pattern of repair of these interstitial cells in wounds produced in vitro and tested the hypothesis that fibroblast growth factor 2 enhances interstitial cell repair. METHODS: Mitral valve interstitial cells were plated onto glass coverslips, reached confluence after 1 week, and were wounded by passage of a spatula along the center of a monolayer, which created a linear wound with two edges. The wounds were observed from 0 to 96 hours by phase-contrast microscopy. Wounds were also fixed at 0, 2, and 24 hours and stained for fibroblast growth factor 2 and fibroblast growth factor receptor 1 by means of immunofluorescence and laser confocal microscopy. RESULTS: Cells in confluent monolayers and in the monolayer behind the wound edge formed a multilayered orthogonal pattern of elongated cells similar to fibroblasts. Cells along the wound edge migrated into the wound after 4 hours, and at 24 hours single cells with prominent lamellipodia and tails were present within the wound. There was overlapping of cells as well, similar to smooth muscle cells. Fibroblast growth factor 2 and fibroblast growth factor receptor 1 were present in the cells of the undisturbed confluent monolayer. They were upwardly regulated relative to the unwounded monolayer in the cells along the wound edge at 2 hours and in the monolayer behind the wound edge at 24 hours. In single cells that migrated into the wound, fibroblast growth factor 2 and fibroblast growth factor receptor 1 were prominent. Fibroblast growth factor 2 showed a 6-fold increase in concentration relative to unwounded cultures in conditioned medium from wounded cultures at 2 hours after wounding. Addition of a neutralizing antibody to fibroblast growth factor 2 significantly delayed wound closure at 24 to 96 hours. Addition of exogenous fibroblast growth factor 2 to cultures at the time of wounding did not enhance wound repair. CONCLUSION: Mitral valve interstitial cells have the ability to repair wounds, and fibroblast growth factor 2 is a modulator of these repair processes.