Surgical strategy in grade II astrocytoma: a population-based analysis of survival and morbidity with a strategy of early resection as compared to watchful waiting

Background

We recently demonstrated a survival benefit of early resection in unselected diffuse low-grade gliomas (LGG). However, heterogeneity within the LGG entity warrants investigation in a homogenous subgroup. Astrocytoma represents the largest subgroup of LGG, and is characterized by diffuse growth and inferior prognosis. We aimed to study the effects of early resection compared to biopsy and watchful waiting in this subgroup.

Methods

Patient data was retrospectively reviewed in two neurosurgical departments with regional referral practice. In one hospital, initial diagnostic biopsies and watchful waiting was favored, while early resections guided with three-dimensional (3D) ultrasound were advocated in the other hospital. This created a natural experiment with patient management heavy influenced by residential address. In the hospitals’ histopathology databases, all adult patients diagnosed with supratentorial LGG from 1998 through 2009 were screened (n?=?169) and underwent blinded histopathological review. Histopathological review concluded with 117 patients with grade II astrocytomas that were included in the present study. The primary end-point was overall survival assessed by a regional comparison.

Results

Early resections were performed in 51 (82 %) versus 12 (22 %) patients in the respective hospitals (p?<?0.001). The two patient populations were otherwise similar. Median survival was 9.7 years (95 % CI 7.5–11.9) if treated in the hospital favoring early resections compared to 5.6 years (95 % CI 3.5–7.6) if treated at the hospital favoring biopsy and watchful waiting (p?=?0.047). No difference in surgical-related neurological morbidity was seen (p?=?0.843).

Conclusions

Early 3D ultrasound guided resections improve survival, apparently without increased morbidity, compared to biopsy and watchful waiting in patients with diffuse World Health Organization (WHO) grade II astrocytomas.     

Contrasting Hemodynamic Mechanisms of Losartan- vs. Atenolol-Based Antihypertensive Treatment: A LIFE Study

BackgroundPharmaceutical differences in central hemodynamics might influence cardiac response to antihypertensive treatment despite similar lowering of brachial blood pressure (BP).MethodsData from all patients with at least two echocardiographic examinations in the Losartan Intervention For Endpoint Reduction in Hypertension (LIFE) echocardiographic substudy (n = 801); high-risk patients on losartan- vs. atenolol-based antihypertensive therapy. Echocardiography was performed annually for 4 years to measure stroke index (SI), heart rate, cardiac index (CI), conduit artery stiffness assessed as pulse pressure/stroke index (PP/SI) and total peripheral resistance index (TPRI).ResultsAtenolol- and losartan-based therapy reduced BP similarly (cumulative difference in mean brachial blood pressure 0.3 mm Hg, P = 0.65). After 4 years the cumulative means of SI and heart rate were 1.8 ml/m(2) higher and 5.7 beats/min lower on atenolol-based treatment, respectively (both P < 0.001). This kept CI below baseline in atenolol-treated patients, whereas in the losartan group CI was unchanged from baseline throughout the study. TPRI was decreased more and remained lower in the losartan group (cumulative difference in mean TPRI 287 dynes/sec(-5)/cm/m(2), P < 0.001). These findings partly explained univariate differences in systolic- and diastolic function indices between the two treatments; fully adjusted losartan was only associated with a smaller left atrial diameter (cumulative mean difference 0.07 cm; 95% confidence intervals, -0.13 to -0.01, P = 0.03).ConclusionsContrasting hemodynamics impacted cardiac response to similar reductions in brachial BP on losartan- vs. atenolol-based therapy. The similar reduction of PP/SI suggests that the antihypertensive regimens used in the LIFE study had comparable effects on arterial stiffness (LIFE study; NCT00338260)American Journal of Hypertension, (2012); doi:10.1038/ajh.2012.81.     

MicroRNA expression profiling of carcinoma in situ cells of the testis

Testicular germ cell tumours, seminoma (SE) and non-seminoma (NS), of young adult men develop from a precursor cell, carcinoma in situ (CIS), which resembles foetal gonocytes and retains embryonic pluripotency. We used microarrays to analyse microRNA (miRNA) expression in 12 human testis samples with CIS cells and compared it with miRNA expression profiles of normal adult testis, testis with Sertoli-cell-only that lacks germ cells, testis tumours (SE and embryonal carcinoma (EC), an undifferentiated component of NS) and foetal male and female gonads. Principal components analysis revealed distinct miRNA expression profiles characteristic for each of the different tissue types. We identified several miRNAs that were unique to testis with CIS cells, foetal gonads and testis tumours. These included miRNAs from the hsa-miR-371-373 and -302-367 clusters that have previously been reported in germ cell tumours and three miRNAs (hsa-miR-96, -141 and -200c) that were also expressed in human epididymis. We found several miRNAs that were upregulated in testis tumours: hsa-miR-9, -105 and -182-183-96 clusters were highly expressed in SE, while the hsa-miR-515-526 cluster was high in EC. We conclude that the miRNA expression profile changes during testis development and that the miRNA profile of adult testis with CIS cells shares characteristic similarities with the expression in foetal gonocytes.     

On a heavy path – determining cold plasma-derived short-lived species chemistry using isotopic labelling

Cold atmospheric plasmas (CAPs) are promising medical tools and are currently applied in dermatology and epithelial cancers. While understanding of the biomedical effects is already substantial, knowledge on the contribution of individual ROS and RNS and the mode of activation of biochemical pathways is insufficient. Especially the formation and transport of short-lived reactive species in liquids remain elusive, a situation shared with other approaches involving redox processes such as photodynamic therapy. Here, the contribution of plasma-generated reactive oxygen species (ROS) in plasma liquid chemistry was determined by labeling these via admixing heavy oxygen ¹⁸O₂ to the feed gas or by using heavy water H₂¹⁸O as a solvent for the bait molecule. The inclusion of heavy or light oxygen atoms by the labeled ROS into the different cysteine products was determined by mass spectrometry. While products like cysteine sulfonic acid incorporated nearly exclusively gas phase-derived oxygen species (atomic oxygen and/or singlet oxygen), a significant contribution of liquid phase-derived species (OH radicals) was observed for cysteine-S-sulfonate. The role, origin, and reaction mechanisms of short-lived species, namely hydroxyl radicals, singlet oxygen, and atomic oxygen, are discussed. Interactions of these species both with the target cysteine molecule as well as the interphase and the liquid bulk are taken into consideration to shed light onto several reaction pathways resulting in observed isotopic oxygen incorporation. These studies give valuable insight into underlying plasma–liquid interaction processes and are a first step to understand these interaction processes between the gas and liquid phase on a molecular level.

Cold atmospheric plasmas (CAPs) are promising medical tools producing short-lived reactive species.     

Prostate cancer may trigger paraneoplastic limbic encephalitis: A case report and a review of the literature

We present a case of a previously healthy and active 64‐year‐old man who experienced a rapid neuropsychiatric decline. All tests for metabolic causes, neuroinfection, intracranial infarction or tumor were negative. By the means of magnetic resonance imaging, electroencephalography and the anti‐Hu antibody test the patient was diagnosed with paraneoplastic limbic encephalitis related to prostate cancer. The patient died within 6 months. We review the literature on prostate cancer‐related paraneoplastic limbic encephalitis. High‐risk prostate cancer can trigger paraneoplastic limbic encephalitis, a rapidly progressive neurological syndrome with a bad prognosis.     

Axillary Reverse Mapping: A Prospective Study in Women with Clinically Node Negative and Node Positive Breast Cancer

Background

The primary aim of axillary reverse mapping (ARM) is to prevent lymphedema by preserving arm versus breast axillary lymphatics. Concerns regarding feasibility and oncologic safety have limited the adoption of the technique. This prospective study was undertaken to investigate ARM in clinically node negative and node positive breast cancer patients.

Methods

A total of 184 patients underwent 212 ARM procedures: 155 sentinel lymph node biopsies (SLNB) without axillary lymph node dissection (ALND) (group 1) and 57 ALNDs with/without SLNB (group 2). ARM lymphatics were not preserved if they were a SLN, directly entered a SLN, or were within ALND boundaries during ALND.

Results

SLN with radioisotope alone was successful in 92 % of procedures (181 of 197). ARM identification was 47 % (73 of 155) in group 1. Criteria were met in 30 % (47 of 155) for preservation, and 25 % (38 of 155) were preserved. Of those who met preservation criteria, 81 % (38 of 47) were preserved. In group 2, ARM identification was 72 % (41 of 57); 7 met criteria for preservation and were preserved. Of the ARM nodes, 10 % (22 of 212) were SLNs (crossover). ARM nodes contained metastatic disease in one crossover and two nonsentinel ARM nodes in clinically node positive patients with N2/N3 disease.

Conclusions

ARM is a feasible technique for identification and preservation of axillary arm lymphatics with an acceptable incidence of SLN crossover. A larger sample size is needed to determine if ARM can reduce the incidence of lymphedema in patients undergoing SLNB alone and to confirm the absence of ARM metastases in clinically node negative patients undergoing ALND.