Assessing response in breast cancer with dynamic contrast-enhanced magnetic resonance imaging: Are signal intensity–time curves adequate?

Quantitative DCE-MRI parameters including K^trans (transfer constant min^?1) can predict both response and outcome in breast cancer patients treated with neoadjuvant chemotherapy (NAC). Quantitative methods are time-consuming to calculate, requiring expensive software and interpretive expertise. For diagnostic purposes, signal intensity–time curves (SITCs) are used for tissue characterisation. In this study, we compare the ability of NAC-related changes in SITCs with K^trans to predict response and outcomes. 73 women with primary breast cancer underwent DCE-MRI studies before and after two cycles of NAC. Patients received anthracycline and/or docetaxel-based chemotherapy. At completion of NAC, patients had local treatment with surgery & radiotherapy and further systemic treatments. SITCs for paired DCE-MRI studies were visually scored using a five-curve type classification schema encompassing wash-in and wash-out phases and correlated with K^trans values and to the endpoints of pathological response, OS and DFS. 58 paired patients studies were evaluable. The median size by MRI measurement for 52 tumours was 38 mm (range 17–86 mm) at baseline and 26 mm (range 10–85 mm) after two cycles of NAC. Median baseline K^trans (min^?1) was 0.214 (range 0.085–0.469), and post-two cycles of NAC was 0.128 (range 0.013–0.603). SITC shapes were significantly related to K^trans values both before (χ ² = 43.3, P = 0.000) and after two cycles of NAC (χ ² = 60.5, P = 0.000). Changes in curve shapes were significantly related to changes in K^trans (χ ² = 53.5, P = 0.000). Changes in curve shape were significantly correlated with clinical (P = 0.005) and pathological response (P = 0.005). Reductions in curve shape of ≥1 point were significant for overall improved survival using Kaplan–Meier analysis with a 5-year OS of 80.9 versus 68.6 % (P = 0.048). SITCs require no special software to generate and provide a useful method of assessing the effectiveness of NAC for primary breast cancer.     

Environmental health in Egypt

Egypt shares most of the environmental problems of developing countries. One of the most important health and environmental problems is air pollution resulting from using fuel, burning operations, and the increase of automobile exhaust in cities. Moreover, the deficiency of efficient sanitation services and water pollution caused by the breaking down of old and consumed water networks, as well as the various problems in construction, designing and maintenance of sewage system resulted in the appearance and prevalence of communicable and non-communicable diseases. There are several examples of exposure to chemical genotoxicants, and lifestyle exposures in the population, which create unique combinations of environmental risk factors for diseases such as cancer. Environmental factors may interact with infection and lead to enhancement of carcinogenicity processes. Currently, there is a growing interest in environmental mutagenicity and carcinogenicity research. The use of different biomarkers and genetic susceptibility testing can contribute effectively to risk assessment. The Government of Egypt recognizes and deals seriously with these problems. The State Ministry of Environment has initiated new policies that include risk minimization, law enforcement, treatment of pollution at source, mitigation procedures and inter-sectorial collaboration. The Ministry of Health and Population recognized the link between economic development, environment and health. It elaborated a national environment health strategy in accordance with the format of the regional and global environmental health policy. This strategy identified priority areas, which requires further action to be taken and to be implemented. Environmental health was included as one of the four main objectives of the strategic Healthy Egyptians 2010 Initiative. Specific objectives and plans for the initiative are presented.     

Quality-of-life (QoL) as a predictive biomarker in patients with advanced pancreatic cancer (APC) receiving chemotherapy: results from a prospective multicenter phase 2 trial

Purpose

Pancreatic cancer is rapidly fatal with median survival of only 6 months (mo). Quality-of-life (QoL) was analyzed prospectively in a phase 2 study of gemcitabine (G), capecitabine (C) and bevacizumab (B) in APC patients.

Methods

A total of 50 patients with APC received B 15 mg/kg, C 1,300 mg/m² daily for 2 weeks and G 1,000 mg/m² weekly 2 times; cycles were repeated every 21 days. Endpoints: progression free survival (PFS), overall survival (OS) and assessment of QoL prior to each cycle using the European organization for research and treatment of cancer (EORTC) PAN-26 QoL questionnaire. An exact 95% confidence interval (CI) (Clopper-Pearson method) was used to assess rate of improved QoL (defined as >5% decrease in two consecutive scores compared with baseline).

Results

Patient characteristics- Stage IIB/III/IV: 3/5/42; Sex: 28 M/22 F; Median age: 64 years. QoL in patients- improved: 56%, no improvement: 24%; unevaluable: 20%. Median PFS: 5.8 mo, OS: 9.8 mo. QoL improvement rate: 28/40=0.7 (95% CI: 0.53-0.83) in evaluable patients. Using QoL improvement rate, no significant difference was seen in patients with OS ≥6 mo compared to OS <6 mo. However QoL scores at 3 and 6 weeks from start of treatment correlated strongly with ≥6 mo survival (P value 0.0092 and 0.0081, respectively).

Conclusions

Baseline score and change in QoL scores of patients on G, C and B were not predictive of survival ≥6 mo. Post treatment scores at 3 and 6 weeks from start of therapy however, were predictive of survival ≥6 mo suggesting the potential predictive value of this tool for use in future studies.     

Controlling Ca2+-Activated K+ Channels with Models of Ca2+ Buffering in Purkinje Cells

Intracellular Ca(2+) concentrations play a crucial role in the physiological interaction between Ca(2+) channels and Ca(2+)-activated K(+) channels. The commonly used model, a Ca(2+) pool with a short relaxation time, fails to simulate interactions occurring at multiple time scales. On the other hand, detailed computational models including various Ca(2+) buffers and pumps can result in large computational cost due to radial diffusion in large compartments, which may be undesirable when simulating morphologically detailed Purkinje cell models. We present a method using a compensating mechanism to replace radial diffusion and compared the dynamics of different Ca(2+) buffering models during generation of a dendritic Ca(2+) spike in a single compartment model of a PC dendritic segment with Ca(2+) channels of P- and T-type and Ca(2+)-activated K(+) channels of BK- and SK-type. The Ca(2+) dynamics models used are (1) a single Ca(2+) pool; (2) two Ca(2+) pools, respectively, for the fast and slow transients; (3) detailed Ca(2+) dynamics with buffers, pump, and diffusion; and (4) detailed Ca(2+) dynamics with buffers, pump, and diffusion compensation. Our results show that detailed Ca(2+) dynamics models have significantly better control over Ca(2+)-activated K(+) channels and lead to physiologically more realistic simulations of Ca(2+) spikes and bursting. Furthermore, the compensating mechanism largely eliminates the effect of removing diffusion from the model on Ca(2+) dynamics over multiple time scales.     

Surgical specialization and training – its relation to clinical outcome for colorectal cancer surgery

Rationale, aims and objectives Surgical sub‐specialization has been considered to be a major factor in improving cancer surgery‐related outcomes in terms of 5‐year survival and disease‐free intervals. In this article we have looked at the evidence supporting the improvement in colorectal cancer outcomes with ‘colorectal specialists’ performing colon and rectal surgery. Methods A literature review was carried out using search engines such as Pubmed, Ovid and Cochrane Databases. Only studies looking at colorectal cancer outcome related to surgery were included in our review. Results Specialist surgeons performing a high volume of colorectal cancer surgery demonstrated better 5‐year survival rates in patients, with less local recurrence. This was most evident in surgery for rectal cancer, where an association with increased sphincter saving surgery was also seen. Total mesorectal excision is now the accepted treatment for rectal cancer and has markedly improved survival rates and decreased local recurrence. Conclusion The outcomes in colorectal surgery continue to steadily improve. The training of specialized colorectal surgeons is a major contributing factor towards this improvement.     

Population-based estimates of neuroendovascular procedures: results of a state-wide study

Background: The Brain Attack Coalition identified the availability of neuroendovascular procedures as an essential component of a comprehensive stroke center. Objective: To provide population-based estimates of neuroendovascular procedures. Methods: State-wide estimates of cervicocerebral angiograms, endovascular ischemic stroke treatments, carotid angioplasty and stent placements, intracranial angioplasty and stent placements, endovascular treatment of intracranial aneurysms, and endovascular treatment of intracranial arteriovenous malformations (AVMs) were obtained. We calculated the annual incidence rates of various neuroendovascular and neurosurgical procedures (per 100,000 persons). For the denominator, total persons in each year were categorized in 10-year age intervals. Results: The incidence of carotid endarterectomy (387.6 per 100,000 persons) and carotid stent placement (34.7 per 100,000 persons) peaked at 75-84 years. The incidence of aneurysm embolization also peaked in that population bracket (67.9 per 100,000 persons), yet there was a dramatic reduction in the incidence of surgical aneurysm treatment (3.6 per 100,000 persons) in those aged 75-84 years. There was a prominent reduction in the incidence of all procedures in the population aged ≥85 years, except for intravenous/intra-arterial thrombolytic use in ischemic stroke. The incidence of ischemic stroke increased almost by 50% in the population aged ≥85 years compared to those aged 75-84 years. However, the incidence of endovascular procedures for acute ischemic stroke decreased from 22.8 per 100,000 persons in the population aged 75-84 years to 13.2 per 100,000 persons in the population aged ≥85 years. Conclusions: A marked disproportion of neuroendovascular procedures performed and disease prevalence was noted in persons aged ≥85 years, an increasing segment of the population according to recent Census.     

The reduction of superoxide dismutase activity is associated with the severity of neurological soft signs in patients with schizophrenia

This study aimed to explore the relationship between antioxidant enzyme activities and neurological soft signs (NSS) in a sample of patients with schizophrenia. Sixty clinically stable patients with schizophrenia treated mostly by first-generation antipsychotics and 30 matched healthy controls were recruited. NSS were assessed in two groups by a standardized neurological examination (Krebs et al., 2000). The red blood cell (RBC) antioxidant activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) were measured by spectrophotometry. RBC activities of all enzymes studied: SOD, GSH-Px and CAT, were significantly lower in the patients compared to control group. All NSS scores were significantly higher in the patients compared to healthy controls' scores. In the patients, a negative correlation was found between RBC SOD activity and NSS total score and motor coordination and motor integration sub-scores. The association between low SOD activity as a marker of oxidative stress and NSS in schizophrenic patients suggests a common pathological process of these abnormalities.