Clear cell sarcoma of kidney in an adolescent and in young adults: a report of four cases with ultrastructural, immunohistochemical, and DNA flow cytometric analysis

Clear cell sarcoma of the kidney is a distinct, highly malignant pediatric neoplasm. Its occurrence in adults is extremely rare and the subject of isolated case reports. We present a series of four cases (three males and one female) identified in an adolescent and in young adults (16, 18, 20, and 25 years) with flank mass (three cases), hematuria (two cases), flank pain (two cases), and hypertension (one case). Three patients had stage III disease and one had stage I disease (National Wilms' Tumor Study staging system). All tumors had predominantly or exclusively the classic histology of a monotonous proliferation of uniform small round cells with evenly distributed fine chromatin, although focal microcyst formation (two cases) and spindled architecture (one case) (variant patterns) were also noted. Therapy in all cases consisted of surgery and chemotherapy with or without radiation. Follow-up data (29-202 months) showed distant metastases in all four cases, including the lung (four cases), bone (two cases), and the liver (two cases). Three patients died of disease at 29, 59, and 63 months (mean, 50.3 months), and one patient is alive with no evidence of disease at 202 months. Ultrastructural features included scattered primitive junctions, short and irregular cytoplasmic extensions, and scant to a moderate amount of mitochondria. Immunohistochemical study (three cases) showed immunoreactivity with vimentin (two cases) and no reaction with cytokeratin, epithelial membrane antigen, S-100 protein, or desmin. Flow cytometric analysis showed diploid DNA content in three primary tumors and tetraploidy in one metastatic tumor. The proliferative activity (S-phase fraction) was low to intermediate (mean, 9.8%). Our data suggest that clear cell sarcoma of the kidney in the young adult age group resembles its pediatric counterpart in ultrastructural and immunohistochemical characteristics, proclivity for skeletal and visceral metastasis, DNA diploid status with relatively low S-phase, and aggressive clinical course. Clear cell sarcoma of the kidney in adult patients, although rare, must be differentiated from sarcomatoid carcinoma, sarcomas, and round cell tumors because of its unique characteristics in comparison to other renal neoplasms.     

Targeted disruption of GAP-43 in P19 embryonal carcinoma cells inhibits neuronal differentiation. As well as acquisition of the morphological phenotype

GAP-43 is expressed in proliferating neuroblasts in vivo and in vitro, but its role during early neurogenesis has not been investigated. Here we show that neuroectodermal differentiation stimulated by retinoic acid (RA) in the embryonal carcinoma (EC) line P19 is accompanied by upregulation of GAP-43 expression in neuroepithelial precursor cells. In contrast, when upregulation of GAP-43 expression was prevented in 3 independent P19 lines because of a targeted insertion into the gene, generation of neuroepithelial precursors was inhibited. Consequently, neuronal number was significantly decreased, neuronal morphology was abnormal and fewer than 20% of all neurons were able to initiate neuritogenesis. Extracellular matrix (ECM) was unable to rescue initiation of neuritogenesis in the mutant cells, however those neurites that were extended responded normally to ECM-stimulated neurite outgrowth-promoting signals. These data suggest that GAP-43 function is required for commitment to a neuronal phenotype as well as initiation of neurite extension. However, stimulation of neurite outgrowth by ECM in P19s occurs independently of GAP-43.     

HPTLC method development, validation, and stress degradation studies for atorvastatin and ezetimibe in multicomponent tablet dosage form

A simple, precise, rapid, selective, and economic high performance thin-layer chromatography method has been established for simultaneous analysis of atorvastatin (ATV) and ezetimibe (EZE) in tablet dosage forms. The chromatography separation was performed on precoated silica gel 60 GF₂₅₄ plates with toluene–ethyl acetate–methanol 12:5:3 (v/v/v) as mobile phase. The plate was developed to a distance of 8.0?cm at ambient temperature. The retention factors for ATV and EZE were 0.31 and 0.57, respectively. The detection band was carried out at 254?nm. The calibration curve was linear in the concentration range of 200–1200?ng/spot for both ATV and EZE. For ATV, the recovery study results ranged from 99.44 to 99.54% with RSD value ranging from 0.067 to 0.107%. For EZE, the recovery results ranged from 98.88 to 99.00% with RSD value ranging from 0.154 to 1.756%. The assay was 99.89% for ATV and 99.84% for EZE. The calibration plots revealed a good linear relationship with r ²?=?0.9991 for ATV and 0.9992 for EZE. Both ATV and EZE were subjected to different stress conditions—acid, alkaline hydrolysis, oxidation, photo degradation, dry, and wet heat treatment—as prescribed by ICH. The degradation products were well resolved from the pure drug with significantly different R _f values. The method was validated for precision, accuracy, specificity, ruggedness, and robustness.     

Potassium-titanyl-phosphate laser assisted robotic partial nephrectomy in a porcine model: can robotic assistance optimize the power needed for effective cutting and hemostasis?

A potassium-titanyl-phosphate (KTP) laser through robotic endo-wrist instrument has been evaluated as an ablative and hemostatic tool in robotic assisted laparoscopic partial nephrectomy (RALPN). Ten RALPN were performed in five domestic female pigs. The partial nephrectomies were performed with bulldog clamping of the pedicle. Flexible glass fiber carrying 532-nm green light laser was used through a robotic endowrist instrument in two cases. Power usage from 4 to 10 W was tested. The laser probe was explored both as a cutting knife and for hemostasis. The pelvicalyceal system was closed with a running suture. Partial nephrectomies using KTP laser were performed without complications. Mean operative times and warm ischemia times for laser cases were 96 and 18 min, respectively. Mean estimated blood loss was 60 ml compared with 50 ml for non-laser cases. Complete hemostasis with the laser alone could be achieved with a power of 4 W and was found to be effective. In our hands the laser fiber powered up to 10 W was not effective as a quick cutting agent. Histopathologic analysis of the renal remnant revealed a cauterized surface effect with average laser penetration depth less than 1 mm and minimal surrounding cellular injury. The new robotic endowrist instrument carrying flexible glass fiber transmitting 532-nm green light laser is a useful addition to the armamentarium of the robotic urologic setup. Its control by the console surgeon enables quicker and more complete hemostasis of the cut surface in renal sparing surgery using a porcine model. Histologically proven lased depth of less than 1 mm suggests minimal parenchyma damage in an acute setting. Laser application as a cutting agent, however, requires further investigation with interval power settings beyond the limits of this preliminary study. We estimate that effective cutting should be possible with a setting lower than traditionally recommended for solid organs.     

Impact of neurocognitive function on academic difficulties in pediatric bipolar disorder: A clinical translation.

BACKGROUND: Previous research has demonstrated that academic and neuropsychological functions are compromised in pediatric bipolar disorder (PBD). Investigation of the degree to which neuropsychological deficits might contribute to those academic problems is needed to aid in the recognition and intervention for school achievement difficulties in PBD. METHODS: A sample of 55 children and adolescents with PBD with and without attention-deficit/hyperactivity disorder (ADHD) (PBD group, n = 28; PBD+ADHD group, n = 27) were tested with a computerized neurocognitive battery and standardized neuropsychological tests. Age range of subjects was 7-17 years, with the mean age of 11.97 (3.18) years. Parents completed a structured questionnaire on school and academic functioning. RESULTS: Logistic regression analyses indicated that executive function, attention, working memory, and verbal memory scores were poorer in those with a history of reading/writing difficulties. A separate logistic regression analysis found that attentional dysfunction predicted math difficulties. These relationships between neuropsychological function and academic difficulties were not different in those with PBD+ADHD than in those with PBD alone. CONCLUSIONS: In PBD neuropsychological deficits in the areas of attention, working memory, and organization/problem solving skills all contribute to academic difficulties. Early identification and intervention for these difficulties might help prevent lower academic achievement in PBD.     

Pelvic Lymph Node Dissection During Robot-assisted Radical Prostatectomy: Efficacy,Limitations, and Complications—A Systematic Review of the Literature

Context

Pelvic lymph node dissection (PLND) in prostate cancer is the most effective method for detecting lymph node metastases. However, a decline in the rate of PLND during radical prostatectomy (RP) has been noted. This is likely the result of prostate cancer stage migration in the prostate-specific antigen-screening era, and the introduction of minimally invasive approaches such as robot-assisted radical prostatectomy (RARP).

Objective

To assess the efficacy, limitations, and complications of PLND during RARP.

Evidence acquisition

A review of the literature was performed using the Medline, Scopus, and Web of Science databases with no restriction of language from January 1990 to December 2012. The literature search used the following terms: prostate cancer, radical prostatectomy, robot-assisted, and lymph node dissection.

Evidence synthesis

The median value of nodal yield at PLND during RARP ranged from 3 to 24 nodes. As seen in open and laparoscopic RP series, the lymph node positivity rate increased with the extent of dissection during RARP. Overall, PLND-only related complications are rare. The most frequent complication after PLND is symptomatic pelvic lymphocele, with occurrence ranging from 0% to 8% of cases. The rate of PLND-associated grade 3–4 complications ranged from 0% to 5%. PLND is associated with increased operative time. Available data suggest equivalence of PLND between RARP and other surgical approaches in terms of nodal yield, node positivity, and intraoperative and postoperative complications.

Conclusions

PLND during RARP can be performed effectively and safely. The overall number of nodes removed, the likelihood of node positivity, and the types and rates of complications of PLND are similar to pure laparoscopic and open retropubic procedures.