Pretreatment differentiation of renal cell carcinoma subtypes by CT: the influence of different tumor enhancement measurement approaches

Purpose

We conducted a retrospective study to evaluate the influence of different tumor enhancement measurement approaches on the ability of computed tomography (CT) to differentiate between solid forms of clear cell renal cell carcinoma (RCC), other RCC histologic subtypes and oncocytomas. Different RCC subtypes have a diverse range of malignant potential; consequently, the information about RCC subtype obtained using minimally invasive imaging method before the treatment could allow the more accurate therapy planning. Differentiation of ccRCCs from oncocytomas is important because oncocytomas are usually benign tumors which could be treated conservatively.

Methods

CT images of 113 patients with 118 solid renal tumors were evaluated. The imaging protocol consisted pre-contrast and post-contrast images during the arterial and nephrographic phases. Renal tumor attenuation values were measured using region of interest covering as much of the solid enhancing tumor tissue as possible. Tumor attenuation values and tumor enhancement ratios were correlated with histologic subtype. One hundred of tumors were diagnosed as clear cell RCC, nine as non-clear cell RCC and nine as oncocytoma.

Results

Tumor attenuation values of >74 HU on the arterial phase scans significantly correlated with clear cell RCC (Az 0.73). The tumor-to-aorta enhancement ratios calculated on tumor attenuation values measured on the arterial phase scans had a cutoff value of >0.29, which significantly correlated with clear cell RCC (Az 0.79). All ROC curves for differentiating the clear cell RCC from oncocytomas have area under the curve too small (0.5 or less) to have chose cutoff value with sensitivity and specificity that could be applied in clinical work.

Conclusion

Enhancement measurements of renal carcinomas on CT images in the arterial phase can be used as an auxiliary method in the pretreatment differentiation of solid forms of the most frequent RCC subtypes in patients not suitable for core biopsy but who are suitable for minimally invasive treatment methods and/or targeted therapy.     

Lumbar trabecular bone mineral density distribution in patients with and without vertebral fractures: a case–control study

Purpose

The proportion of load transmitted through the lumbar neural arch increases with aging, spinal degeneration, and lordosis, effectively shielding the lumbar vertebral bodies from load. This stress shielding may contribute to bone loss in the vertebral body, leading to increased fracture risk. To test his hypothesis, we performed a study to determine if vertebral body fractures were associated with a higher neural arch/vertebral body volumetric bone mineral density (vBMD) ratio.

Methods

Trabecular vBMD was calculated by quantitative CT in the L3 vertebral body and neural arch (pars interarticularis) of 36 women with vertebral compression fractures and 39 controls. Neural arch/vertebral body vBMD ratio was calculated, and its relationship to fracture status was determined using linear regression models adjusted for age and body mass index.

Results

Vertebral body trabecular vBMD was lower in fracture cases as compared to controls (mean ± SD, 49.0 ± 36.0 vs. 87.5 ± 36.8 mg/cm³, respectively; P < 0.001), whereas trabecular vBMD of the neural arch was similar (96.1 ± 57.6 in cases vs. 118.2 ± 57.4 mg/cm³ in controls; P = 0.182). The neural arch/vertebral body vBMD ratio was significantly greater in the fracture group than in controls (2.31 ± 1.07 vs. 1.44 ± 0.57, respectively; P < 0.001).

Conclusion

These results support the hypothesis that stress shielding is a contributor to vertebral body bone loss and may increase fracture risk. Although further studies are needed, there may be a role for interventions that can shift vertebral loading in the spine to help prevent fracture.     

Treatment of Lesch–Nyhan disease with S-adenosylmethionine: Experience with five young Malaysians,including a girl

Background: Lesch–Nyhan disease (LND) is a rare X-linked recessive neurogenetic disorder caused by deficiency of the purine salvage enzyme hypoxanthine phosphoribosyltransferase (HPRT, EC 2.4.2.8) which is responsible for recycling purine bases into purine nucleotides. Affected individuals have hyperuricemia leading to gout and urolithiasis, accompanied by a characteristic severe neurobehavioural phenotype with compulsive self-mutilation, extrapyramidal motor disturbances and cognitive impairment. Aim: For its theoretical therapeutic potential to replenish the brain purine nucleotide pool, oral supplementation with S-adenosylmethionine (SAMe) was trialed in 5 Malaysian children with LND, comprising 4 related Malay children from 2 families, including an LND girl, and a Chinese Malaysian boy. Results: Dramatic reductions of self-injury and aggressive behaviour, as well as a milder reduction of dystonia, were observed in all 5 patients. Other LND neurological symptoms did not improve during SAMe therapy. Discussion: Molecular mechanisms proposed for LND neuropathology include GTP depletion in the brain leading to impaired dopamine synthesis, dysfunction of G-protein-mediated signal transduction, and defective developmental programming of dopamine neurons. The improvement of our LND patients on SAMe, particularly the hallmark self-injurious behaviour, echoed clinical progress reported with another purine nucleotide depletion disorder, Arts Syndrome, but contrasted lack of benefit with the purine disorder adenylosuccinate lyase deficiency. This first report of a trial of SAMe therapy in LND children showed remarkably encouraging results that warrant larger studies.     

Prognostic Value of Diametrically Polarized Tumor-Associated Macrophages in Renal Cell Carcinoma

Background

As the most abundant tumor-infiltrating immune cells, tumor-associated macrophages (TAMs) are significant for fostering tumor progression. CD68⁺ TAMs display diversely polarized programs comprising CD11c⁺ proinflammatory macrophages (M1) and CD206⁺ immunosuppressive macrophages (M2). The aim of this study was to determine the survival impact of diametrically polarized TAMs in clear-cell renal cell carcinoma (ccRCC) and their application to stratification of patients according to their prognostic values.

Methods

The study included 185 consecutive patients with ccRCC who underwent nephrectomy between 1999 and 2001. CD68⁺ total and diametrically polarized (CD11c⁺ M1 and CD206⁺ M2) TAM densities were assessed by immunohistochemistry, and the relationships with clinicopathologic features and prognosis were evaluated.

Results

Low CD11c⁺ TAM density and high CD206⁺ TAM density were associated with reduced cancer-specific survival (P = 0.043 and P = 0.017, respectively), whereas CD68⁺ TAM density only had borderline prognostic significance (P = 0.062). Furthermore, combined analysis of CD11c⁺ and CD206⁺ TAMs (CD11c/CD206 signature) had a better power to predict patients’ outcome (P = 0.010). Together with TNM stage, tumor necrosis, and performance status, CD11c/CD206 signature was an independent prognostic factor (P = 0.010). When applied to the University of California Integrated Staging System intermediate-/high-risk group for localized ccRCC, CD11c/CD206 signature could further distinguish patients with dismal prognosis (P = 0.004).

Conclusions

Intratumoral balance of diametrically polarized TAMs is a novel independent predictor for survival in patients with ccRCC. Tipping the balance toward an antitumoral phenotype might be a promising target of postoperative adjuvant therapy.     

Prophylactic central neck disection in papillary thyroid cancer: a consensus report of the European Society of Endocrine Surgeons (ESES)

Background

There remains still no clear answer as to whether or not prophylactic central compartment neck dissection (pCCND) is indicated for the treatment of patients with papillary thyroid cancer.

Methods

The published studies, including single cohort, comparative studies and meta-analysis, were critically appraised. Aspects beyond postoperative complications and loco-regional recurrence rates in the analysis, as the impact of pre- and post-ablation thyroglobuline levels, multifocality, bilaterality and additional risk factors for recurrence, were also considered.

Results

Thirty studies and five meta-analyses were assessed. The lack of randomized clinical trials on the subject and the heterogeneity of study populations are the main limiting factors to draw clear conclusions, and a comprehensive list of bias sources has been identified. Recent comparative studies and systematic reviews all associate the pCCND with higher proportions of temporary postoperative hypocalcemia but not with significantly higher permanent hypoparathyroidism, recurrent laryngeal nerve injury or permanent vocal cord paralysis. The risk of recurrence appears to be reduced after pCCND, and the number of patients needed to treat to avoid a recurrence is between 20 and 31.

Conclusions

It is suggested that routine level 6 prophylactic dissections should be risk-stratified. Larger tumours (T3, T4), patients aged 45 years and older or 15 years and younger, male patients, patients with bilateral or multifocal tumours, and patients with known involved lateral lymph nodes could all be candidates for routine unilateral level 6 dissection. The operation should be limited to surgeons who have the available expertise and experience     

1H-MRS检测正常中老年人纹状体和黑质代谢功能

目的探讨中老年人纹状体和黑质1 H-MRS各参数值正常参考范围。方法纳入健康中老年志愿者32名,采用单体素PRESS序列对纹状体、多体素PRESS序列对黑质进行1 H-MRS扫描,分析N-乙酰天门冬氨酸(NAA)、胆碱(Cho)和肌酸(Cr)含量及各参数比值。结果左右侧纹状体和黑质NAA/Cr、Cho/Cr、NAA/Cho、NAA/(Cho+Cr)差异均无统计学意义(P均0.05)。综合两侧结果,纹状体NAA/Cr、Cho/Cr、NAA/Cho、NAA/(Cho+Cr)均值及95%CI分别为1.39(1.33~1.45)、0.90(0.86~0.94)、1.58(1.50~1.66)、0.73(0.70~0.76);黑质上述比值均值及95%CI分别为2.36(1.85~2.87)、1.38(1.12~1.65)、1.70(1.59~1.81)、0.93(0.86~1.00);纹状体及黑质中NAA/(Cho+Cr)比值均最稳定。结论正常中老年人黑质和纹状体1 H-MRS各参数中,NAA/(Cho+Cr)比值最稳定,可为研究累及黑质和纹状体区域的疾病提供正常参照。     

Interaction of citrate‐coated silver nanoparticles with earthworm coelomic fluid and related cytotoxicity in Eisenia andrei

Understanding the interaction of nanoparticles with biological fluid is important for predicting the behavior and toxicity of nanoparticles in living systems. The earthworm Eisenia andrei was exposed to citrate‐coated silver nanoparticles (cAgNPs), and the interaction of cAgNPs with earthworm coelomic fluid (ECF), the cytotoxicity of cAgNPs in earthworm coelomocytes was assessed. The neutral red retention assay showed a reduction in lysosomal stability after exposure. The toxicity of silver ions dissolved from cAgNPs in the soil medium was not significant. The aggregation and dissolution of cAgNPs increased in ECF, which contains various electrolytes that alter the properties of nanoparticles, and their subsequent toxicity. Microscopic and dissolution studies demonstrated that the aggregation of cAgNPs rapidly increased, and readily dissolved in ECF. The bioavailability of cAgNPs to earthworms induced lysosomal cytotoxicity. This is the first report to test the interaction and lysosomal cytotoxicity of nanoparticles in earthworm biofluids. Copyright © 2014 John Wiley & Sons, Ltd.