Independent Poor Prognostic Factors for True Progression after Radiation Therapy and Concomitant Temozolomide in Patients with Glioblastoma: Subependymal Enhancement and Low ADC Value

BACKGROUND AND PURPOSE:Subependymal enhancement and DWI have been reported to be useful MR imaging markers for identifying true progression. Our aim was to determine whether the subependymal enhancement pattern and ADC can differentiate true progression from pseudoprogression in patients with glioblastoma multiforme treated with concurrent chemoradiotherapy by using temozolomide.MATERIALS AND METHODS:Forty-two patients with glioblastoma multiforme with newly developed or enlarged enhancing lesions on the first follow-up MR images obtained within 2 months of concurrent chemoradiotherapy completion were included. Subependymal enhancement was analyzed for the presence, location, and pattern (local or distant relative to enhancing lesions). The mean ADC value and the fifth percentile of the cumulative ADC histogram were determined. A multiple logistic regression analysis was performed to identify independent factors associated with true progression.RESULTS:Distant subependymal enhancement (ie, extending >1 cm or isolated from the enhancing lesion) was significantly more common in true progression (n = 24) than in pseudoprogression (n = 18) (P = .042). The fifth percentile of the cumulative ADC histogram was significantly lower in true progression than in pseudoprogression (P = .014). Both the distant subependymal enhancement and the fifth percentile of the cumulative ADC histogram were independent factors associated with true progression (P = .041 and P = .033, respectively). Sensitivity and specificity for the diagnosis of true progression were 83% and 67%, respectively, by using both factors.CONCLUSIONS:Both the distant subependymal enhancement and the fifth percentile of the cumulative ADC histogram were significant independent factors predictive of true progression.

Glioblastoma multiforme (GBM) is the most common form of malignant primary brain tumor in adults,¹ which is notorious for its intrinsic aggressiveness and a dismal prognosis.^2,3 The current standard treatment for GBM is maximal safe tumor resection followed by radiation therapy with concurrent temozolomide (TMZ) and adjuvant TMZ.⁴Recently, the criteria for assessing therapeutic responses in high-grade gliomas have been updated by the Response Assessment in Neuro-Oncology (RANO) Working Group to address the limitations of the previous guideline.⁵ For instance, contrast enhancement, which has been regarded as a surrogate marker for tumor progression, has been reassessed as a nonspecific finding merely reflecting the passage of contrast material across a disrupted blood-tumor barrier.^6–11 In particular, radiologists and clinicians have increasingly recognized the occurrence of progressive MR imaging lesions immediately after completion of concurrent chemoradiotherapy (CCRT) with TMZ, which spontaneously improved without further treatment other than the adjuvant TMZ.^12–14 The treatment-related reaction is termed pseudoprogression and has received attention as a potential pitfall in the response evaluation. At present, owing to the lack of established findings in conventional contrast-enhanced MR imaging for the differential diagnosis of true progression from pseudoprogression,^9,10 RANO stresses that the diagnosis of true progression can be made within the first 12 weeks after completion of radiation therapy only if most of the new enhancement is located outside the radiation field or if there is pathologic confirmation of progressive disease.⁵During the past few decades, there has been extensive effort to identify imaging biomarkers for tumor progression. Among the many parameters derived from advanced MR imaging techniques, DWI has been consistently reported to be helpful in differentiating tumor progression from treatment-related changes or necrosis.^15–22 Meanwhile, most previous studies pertaining to the role of conventional MR imaging have not shown promising results.^9,23 Nevertheless, a recent study focusing on the conventional MR imaging findings has proposed subependymal enhancement as a useful MR imaging marker for differentiating true progression from pseudoprogression.²⁴ To our knowledge, however, no previous studies have conducted in-depth analysis of the subependymal enhancement, and its potential as an independent predictor for true progression remains elusive.The purpose of the present study was to determine whether the subependymal enhancement pattern and ADC can differentiate true progression from pseudoprogression in patients with GBM treated with radiation therapy and concomitant TMZ.     

IL-10 promoter gene polymorphism associated with the occurrence of chronic GVHD and its clinical course during systemic immunosuppressive treatment for chronic GVHD after allogeneic peripheral blood stem cell transplantation

BACKGROUND: The current study attempted to evaluate the association between IL-10 promoter gene polymorphism and transplant outcomes including the occurrence of chronic graft-versus-host disease (GVHD) and its clinical course during systemic immunosuppressive treatment (IST) among 60 recipients of cytokine-mobilized peripheral blood stem cell (PBSC) from HLA-matched sibling donors. METHODS: We analyzed 3 single-nucleotide polymorphisms in proximal region of IL-10 promoter gene (-1082/-819/-592). RESULTS: In the current study, only two haplotypes (1082*A/819*T/592*A [ATA] and 1082*A/819*C/592*C [ACC]) were found. An increased occurrence of chronic GVHD was noted dependent on the IL-10 haplotypes (43% vs. 68% vs. 96% in ACC/ACC vs. ATA/ACC vs. ATA/ATA haplotype, P=0.003). In a logistic regression based on multinomial model, ATA/ATA homozygote had 7-fold increasing risk of the development of chronic GVHD compared with ACC/ACC homozygote. The incidence of chronic GVHD at 1 year was 46%+/-20%, 64%+/-10%, and 82%+/-5% in ACC/ACC, ATA/ACC and ATA/ATA group, respectively (P=0.0266). Plus, the duration of systemic IST was significantly shorter in recipients without ATA-haplotype comparing with those with ATA haplotype (339 days vs. 1,146 days, P=0.0091). CONCLUSION: IL-10 promoter gene polymorphism was found to be apparently associated with chronic GVHD after allogeneic peripheral blood stem cell transplantation from HLA-matched sibling donors.     

Etomidate attenuates phenylephrine-induced contraction in isolated rat aorta

PURPOSE: A previous study has shown that etomidate inhibits the angiotensin II-induced calcium influx in rat aortic smooth muscle cells. The goals of our current in vitro study were to investigate the effect of etomidate on phenylephrine-induced contraction in rat aorta, and to elucidate the associated signalling pathway. METHODS: Endothelium-denuded aortic rings were suspended for isometric tension recording. Concentration-response curves for phenylephrine (10(-9) to 10(-6) M), 5-hydroxytryptamine (10(-7) to 10(-4) M) and potassium chloride (10 to 60 mM) were generated in the presence and absence of etomidate (5 x 10(-6), 3 x 10(-5), 5 x 10(-5) M). For the rings pretreated with verapamil (10(-5) M), the phenylephrine concentration-response curves were generated in the presence and absence of etomidate (5 x 10(-5) M). In the rings exposed to calcium-free isotonic depolarizing solution, the contractile response induced by the addition of calcium was assessed in the presence and absence of etomidate (5 x 10(-5) M). RESULTS: Etomidate (5 x 10(-5) M) produced a significant rightward shift in the concentration-response curves for phenylephrine, 5-hydroxytryptamine and potassium chloride. Etomidate (5 x 10(-5) M) did not alter phenylephrine-induced contraction in the rings pretreated with verapamil. Etomidate (5 x 10(-5) M) significantly attenuated the contractile response induced by the addition of calcium in the calcium-free isotonic depolarizing solution. CONCLUSION: The results suggest that etomidate, which exceeds the clinically relevant concentration, attenuates the phenylephrine-induced contraction by having an inhibitory effect on the calcium influx by blocking the L-type calcium channels in the rat aortic vascular smooth muscle.     

Prähospitale geburtshilfliche Notfälle in einem bodengebundenen städtischen Notarztsystem

Background

In the German emergency medical system (EMS) obstetrical emergencies are rarely encountered, but are highly emotional situations for all concerned and form a special challenge for the emergency physician. The aim of this study was to evaluate the incidence, the course and the performance of rescue missions in a ground-based EMS system.

Methods

In a retrospective study the prehospital emergency charts concerning obstetrical emergencies over a 5-year period (10/2002–09/2007) were analysed.

Results

A total of 40 physician-staffed rescue missions with obstetrical emergencies were identified. On average seven rescue missions were performed per year. The majority of cases with 73% of the rescue missions was performed during the night service (16:00–07:00 h). On average the emergency patients (26th–41st week of gestation) were classified by the National Advisory Committee for Aeronautics (NACA) score as NACA III. Of the 40 obstetrical emergencies delivery occurred out of hospital in 18 cases (33rd–41st week of gestation), while the emergency physician was present in only 3 cases during childbirth. In 15 cases prehospital childbirth took place in the domestic environment of the patient, in 2 cases in an ambulance and in 1 case in the medical office of a gynecologist. In 20 cases the pregnant women were transported to hospital while labor had already begun. The emergency physicians on scene applied intravenous access, guided through labor and delivery, and administered tocolysis and in cases of prehospital delivery the emergency physicians also applied oxytocin, cut the umbilical cord and performed primary care of the newborn.

Conclusions

Obstetrical emergencies are rare but recurrent in the ground-based EMS. However, prehospital management of women in labor, supervision of spontaneous prehospital delivery and the initial management of a newborn form a challenge for the emergency physician responsible. Consequently, prehospital management of obstetrical emergencies needs intensive consideration during education and training of emergency medical personnel.     

Robotic tumor-specific mesorectal excison of rectal cancer: short-term outcome of a pilot randomized trial

Background  Laparoscopic colorectal resection has become popular. The recently developed da Vinci Surgical System promises to facilitate endoscopic surgery and overcome its disadvantages. This study therefore aimed to compare the short-term results between robotic tumor-specific mesorectal excision (R-TSME) using the da Vinci Surgical System and conventional laparoscopic tumor-specific mesorectal excision (L-TSME) in rectal cancer patients. Methods  Between April 2006 and February 2007, 36 patients were randomly assigned to receive R-TSME or L-TSME. During the study, 18 patients underwent robotic low anterior resection using the da Vinci Surgical System, and 18 patients had conventional laparoscopic low anterior resection. Patient characteristics, perioperative clinical results, complications, and pathologic details were compared between the two groups. Results  The patient characteristics were not significantly different between the two groups. The mean operating time, hemoglobin change, and conversion rate were not significantly different between the groups. Complications were treated conservatively and did not require surgical intervention in the R-TSME group. The average length of stay was 6.9 ± 1.3 days in the R-TSME group and 8.7 ± 1.3 days in the L-TSME group (p < 0.001). The specimen quality of the R-TSME group was acceptable. Conclusion  Tumor-specific mesorectal excision was performed safely and effectively using the da Vinci Surgical System and the perioperative outcomes were acceptable.     

Range of motion of standard and high-flexion posterior stabilized total knee prostheses. A prospective, randomized study

BACKGROUND: The restoration of posterior femoral translation has been shown to be an important factor in enhancing knee flexion after total knee arthroplasty. The purpose of this study was to compare the ranges of motion associated with standard and high-flexion posterior stabilized total knee prostheses in patients managed with simultaneous bilateral total knee arthroplasty. METHODS: Fifty patients (mean age, sixty-eight years) received a standard fixed-bearing knee prosthesis in one knee and a high-flexion fixed-bearing knee prosthesis in the contralateral knee. Two patients were men, and forty-eight were women. At a mean of 2.1 years postoperatively, the patients were assessed clinically and radiographically with use of the knee-rating systems of the Knee Society and The Hospital for Special Surgery. RESULTS: The mean postoperative Hospital for Special Surgery knee score was 90 points for the knees treated with the standard fixed-bearing prosthesis and 89.4 points for those treated with the high-flexion prosthesis. At the time of the final follow-up, the knees with the standard prosthesis had a mean range of motion of 135.8 degrees (range, 105 degrees to 150 degrees ) and those with a high-flexion prosthesis had a mean range of motion of 138.6 degrees (range, 105 degrees to 150 degrees ) (p = 0.41). No knee had aseptic loosening, revision, or osteolysis. CONCLUSIONS: After a minimum duration of follow-up of two years, we found no significant differences between the groups with regard to range of motion or clinical and radiographic parameters, except for posterior femoral condylar offset.     

Effect of 5% fluoride varnish application on caries among school children in rural Brazil: a randomized controlled trial

Arruda AO, Senthamarai Kannan R, Inglehart MR, Rezende CT, Sohn W. Effect of 5% fluoride varnish application on caries among school children in rural Brazil: a randomized controlled trial. Community Dent Oral Epidemiol 2011. © 2011 John Wiley & Sons A/S Abstract – Objectives: To determine the efficacy of 5% sodium fluoride (NaF) varnish application in reducing caries increments in the permanent dentition of rural Brazilian school children over the course of 12 months. Methods: A double‐blind, randomized, placebo‐controlled trial was conducted with 379 children aged 7–14 years who attended three schools in Brazil between January 2006 and December 2007. During this period, each school was visited four times at 6‐month interval for recruitment, dental examinations, and fluoride varnish applications. Recruited children were randomly assigned to either a treatment (5% NaF varnish, n = 198) or a control group (placebo, n = 181). Trained interviewers collected data on oral health habits and sociodemographic characteristics from the children. Information on the child’s diet was collected through a 7‐day food frequency diary. Caries examinations were conducted using the International Caries Detection and Assessment System (ICDAS). The efficacy of fluoride varnish application on caries prevention was reported as a preventive fraction (PF). Crude caries increments of decayed and filled surfaces (DFS) were compared between fluoride varnish and placebo groups. A generalized linear model (GLM) was constructed to test the differences in DFS increments between the groups after accounting for confounding factors. Results: Of the total sample (N = 379), 210 (55.4%) children had completed 12 months of follow‐up including one or two applications of fluoride varnish or placebo. At the baseline examination, the children in the treatment and control groups presented on average 6.2 and 5.6 DFS, respectively (P < 0.001). After 12 months of follow‐up, the children in the varnish group showed significantly lower DFS increments than did children in the control group (10.8 versus 13.3; P < 0.007), with PF of 40% (95% CI: 34.3–45.7%; P < 0.0001). Conclusions: The results of this study suggest that applications of 5% NaF varnish can be recommended as a public health measure for reducing caries incidence in this high‐caries‐risk population.     

Role of protein kinase C delta in X-ray-induced apoptosis of keratinocyte

Abstract:  In this study, we investigated the process of X-ray-induced apoptosis of skin keratinocyte, and the functional role of protein kinase C delta (PKCδ) and downstream signalling cascade. High-dose X-ray irradiation (10 Gy) led to the apoptosis of HaCaT keratinocyte, accompanied by PKCδ cleavage. Treatment with PKCδ inhibitor and adenoviral transduction of dominant-negative PKCδ clearly inhibited the X-ray-induced apoptosis of keratinocyte. In addition, X-ray induced the phosphorylation of extracellular signal-regulated kinases 1/2 (ERK1/2) and inhibition by ERK1/2 inhibitor abrogated the X-ray-induced apoptosis. Interestingly, overexpression of dominant-negative PKCδ markedly blocked the X-ray-induced phosphorylation of ERK1/2, suggesting that ERK1/2 is the functional downstream effector of PKCδ. Next, we investigated the difference between UVB and X-ray response. UVB induced the apoptosis of keratinocyte in a PKCδ-dependent manner, similar to X-ray response. However, UVB irradiation induced the phosphorylation of c-jun N-terminal kinases (JNK) and inhibition of JNK significantly protected the UVB-induced apoptosis. These results demonstrate that PKCδ is a key regulator in X-ray-induced apoptosis of keratinocyte and suggest that there is subtle difference in downstream signalling cascade between UVB and X-ray response of keratinocyte.     

Melasma: histopathological characteristics in 56 Korean patients

BACKGROUND: Melasma is a common acquired symmetrical hypermelanosis characterized by irregular light to dark brown macules and patches on sun-exposed areas of the skin. Its histopathological characteristics are not fully understood. OBJECTIVES: To characterize the histopathological features of facial melasma skin in comparison with adjacent normal skin. METHODS: Biopsies were taken from both melasma lesional skin and adjacent perilesional normal skin in 56 Korean women with melasma. The sections were stained using haematoxylin and eosin, Fontana-Masson, diastase-resistant periodic acid-Schiff, Masson trichrome and Verhoeff-van Gieson stains, and immunostaining for melanocytes. Data on the changes in number of melanocytes and melanin contents of the epidermis were analysed by a computer-assisted image analysis program. The ultrastructure of the skin was also examined. RESULTS: The amount of melanin was significantly increased in all epidermal layers in melasma skin. The staining intensity and number of epidermal melanocytes increased in melasma lesions. Lesional skin showed more prominent solar elastosis compared with normal skin. Melanosomes increased in number and were more widely dispersed in the keratinocytes of the lesional skin. Lesional melanocytes had many more mitochondria, Golgi apparatus, rough endoplasmic reticulum and ribosomes in their cytoplasm. A dihydroxyphenylalanine reaction was apparent in the cisternae and vesicles of the trans-Golgi network in melanocytes from lesional skin. CONCLUSIONS: Melasma is characterized by epidermal hyperpigmentation, possibly caused both by an increased number of melanocytes and by an increased activity of melanogenic enzymes overlying dermal changes caused by solar radiation.