Comparison of the Effects of Acellular Dermal Matrix and Montelukast on Radiation-Induced Peri-implant Capsular Formation in Rabbits.

PURPOSE: Capsular contracture (CC) is a troublesome complication after breast surgery with breast implants, and the risk increases in breast cancer patients after radiotherapy. Studies investigating leukotriene antagonists (eg, montelukast, zafirlukast) found that the acellular dermal matrix (ADM) can help prevent CC. We aimed to compare the effects of ADM and montelukast on CC after irradiation. METHODS: Eighteen New Zealand white rabbits were randomly divided into 3 groups of 6 each. Miniature cohesive gel implants were inserted into the pocket under the latissimus dorsi muscle. The lateral part was uncovered by the latissimus dorsi muscle. Six animals were included in the control group. In experimental group A (EG-A) (n = 6), the site was partially wrapped with ADM but not covered with muscle. Montelukast (Singulair, 0.2 mg/kg) was administered in experimental group B (EG-B) (n = 6) daily. Groups were irradiated at postoperative day 21 with Co-60 γ rays (25 Gy, single fraction) at the peri-implant area. Rabbits were sacrificed 12 weeks after surgery; implants with peri-implant capsule were harvested. Capsule thickness, collagen pattern, myofibroblast, and transforming growth factor (TGF) ß1/2 levels in the peri-implant capsule were evaluated. RESULTS: On histological evaluation, the capsule was thinner on the lateral aspect (covered with ADM) in EG-A (P = 0.004) and the entire capsule in EG-B (P = 0.004) than in the control group. However, there was no significant difference between EG-A and EG-B (P = 0.073). The collagen distribution pattern was more parallel with low density in the lateral capsular aspect in EG-A, but in the entire capsule in EG-B. The myofibroblast amount (EG-A, P = 0.031; EG-B, P = 0.016) and levels of TGF-ß1 and TGF-ß2 were reduced in the experimental groups (TGF-ß1, EG-A, P = 0.019; TGF-ß1, EG-B, P = 0.045; TGF-ß2, EG-A, P = 0.018; TGF-ß2, EG-B, P = 0.022). There was no significant difference between EG-A and EG-B (myofibroblast, P = 0.201; TGF-ß1, P = 0.665; TGF-ß2, P = 0.665). CONCLUSIONS: Acellular dermal matrix and montelukast have a prophylactic effect for CC even when the breast is irradiated. There was no significant difference between ADM and montelukast in preventing capsular formation. The difference is that ADM will only have the effect of covering the capsular formation with ADM and montelukast can cause systemic effects or complications.

Nanoporous silver cathode surface treated by atomic layer deposition of CeO(x) for low-temperature solid oxide fuel cells.

We evaluated the performance of solid oxide fuel cells (SOFCs) with a 50 nm thin silver (Ag) cathode surface treated with cerium oxide (CeO(x)) by atomic layer deposition (ALD). The performances of bare and ALD-treated Ag cathodes were evaluated on gadolinia-doped ceria (GDC) electrolyte supporting cells with a platinum (Pt) anode over 300 °C-450 °C. Our work confirms that ALD CeO(x) treatment enhances cathodic performance and thermal stability of the Ag cathode. The performance difference between cells using a Ag cathode optimally treated with an ALD CeO(x) surface and a reference Pt cathode is about 50% at 450 °C in terms of fuel cell power output in our experiment. The bare Ag cathode completely agglomerated into islands during fuel cell operation at 450 °C, while the ALD CeO(x) treatment effectively protects the porosity of the cathode. We also discuss the long-term stability of ALD CeO(x)-treated Ag cathodes related to the microstructure of the layers.

Atomic layer deposition of ruthenium on plasma-treated vertically aligned carbon nanotubes for high-performance ultracapacitors.

It is challenging to realize a conformal metal coating by atomic layer deposition (ALD) because of the high surface energy of metals. In this study, ALD of ruthenium (Ru) on vertically aligned carbon nanotubes (CNTs) was carried out. To activate the surface of CNTs that lack surface functional groups essential for ALD, oxygen plasma was applied ex situ before ALD. X-ray photoelectron spectroscopy and Raman spectroscopy confirmed surface activation of CNTs by the plasma pretreatment. Transmission electron microscopy analysis with energy-dispersive x-ray spectroscopy composition mapping showed that ALD Ru grew conformally along CNTs walls. ALD Ru/CNTs were electrochemically oxidized to ruthenium oxide (RuOx) that can be a potentially useful candidate for use in the electrodes of ultracapacitors. Electrode performance of RuOx/CNTs was evaluated using cyclic voltammetry and galvanostatic charge-discharge measurements.

Modified dose difference method for comparing dose distributions.

The quantitative comparison of two-dimensional dose distributions (e.g., calculated versus measured) has become a key issue in intensity-modulated radiotherapy (IMRT) QA. We proposed a new evaluation method referred to as modified dose difference (MDdiff) evaluation. Hereinafter, features and effectiveness of the MDdiff evaluation method will be described. In this work, the formalism of MDdiff was defined by introducing a dimensionless parameter ß(r)(DG)(r(-->)(r)). A new formalism is compared to a gamma method, and the MDdiff and the gamma method are respectively applied to patient-specific IMRT QA. The calculation of the evaluation of dose distributions was performed using a C++ program. Evaluations were performed by counting the number of data points satisfying MDdiff ≥ (1/2)δD°, γ ≥ 1. The evaluation result of dose distributions using the MDdiff method had the same tendency as the evaluation result using the gamma evaluation method. The modified dose difference tool also provides a quantitative method for comparing two dose distributions like the gamma evaluation. Furthermore, many problems of gamma evaluation are resolved.

Multi-institutional comparison of intensity modulated radiation therapy (IMRT) planning strategies and planning results for nasopharyngeal cancer.

The intensity-modulated radiation therapy (IMRT) planning strategies for nasopharyngeal cancer among Korean radiation oncology facilities were investigated. Five institutions with IMRT planning capacity using the same planning system were invited to participate in this study. The institutions were requested to produce the best plan possible for 2 cases that would deliver 70 Gy to the planning target volume of gross tumor (PTV1), 59.4 Gy to the PTV2, and 51.5 Gy to the PTV3 in which elective irradiation was required. The advised fractionation number was 33. The planning parameters, resultant dose distributions, and biological indices were compared. We found 2-3-fold variations in the volume of treatment targets. Similar degree of variation was found in the delineation of normal tissue. The physician-related factors in IMRT planning had more influence on the plan quality. The inhomogeneity index of PTV dose ranged from 4 to 49% in Case 1, and from 5 to 46% in Case 2. Variation in tumor control probabilities for the primary lesion and involved LNs was less marked. Normal tissue complication probabilities for parotid glands and skin showed marked variation. Results from this study suggest that greater efforts in providing training and continuing education in terms of IMRT planning parameters usually set by physician are necessary for the successful implementation of IMRT.

Incidence, Risk Factors, and Clinical Outcomes of Acute Kidney Injury Caused by Palliative Chemotherapy in Lung Cancer.

Purpose: Acute kidney injury (AKI) affects cancer therapy outcome and increases morbidity and mortality in cancer patients. We investigated the incidence, risk factors, and clinical outcomes of AKI caused by palliative chemotherapy in lung cancer patients. Materials and Methods: Between January 2005 and November 2014, 207 lung cancer patients who had been treated with first-line palliative chemotherapy were enrolled. Renal function was assessed during every cycle of chemotherapy. AKI was defined based on changes in serum creatinine levels as described in the Kidney Disease: Improving Global Outcomes guidelines. Clinical outcomes were evaluated depending on AKI occurrence during the first-line chemotherapy. Results: Of the 207 patients, 36 (17.4%) experienced AKI. Among the 36 patients who developed AKI during chemotherapy, 33 (91.8%) had AKI stage I. Although 19 patients (52.7%) with AKI during chemotherapy progressed to chronic kidney disease (CKD), no patients were reported to progress to end-stage renal disease (ESRD). The number of chemotherapy cycles was independently associated with chemotherapy-induced AKI in multivariate analysis (OR = 1.71, 95% CI 1.29-2.26, p < 0.001). The median follow-up duration was 83 months. Patients with AKI during chemotherapy (AKI group) showed significantly longer time to treatment failure than patients without AKI (non-AKI group) (4.2 vs. 2.5 months, p < 0.001). However, the median overall survival (11.7 vs. 8.8 months, p = 0.147) and progression-free survival (5.5 vs. 5.2 months, p = 0.347) were not different between the groups. Conclusions: AKI that developed during chemotherapy was mostly of mild degree and its prognosis was favorable. The occurrence of AKI was associated with the number of chemotherapy cycles administered. AKI did not adversely affect survival of lung cancer patients during chemotherapy.

Additional Chemotherapy with 5-FU plus Leucovorin between Preoperative Chemoradiotherapy and Surgery Improved Treatment Outcomes in Patients with Advanced Rectal Cancer.

Purpose: The aim of the preliminary study was to evaluate the efficacy and safety of 4-week chemotherapy with 5-Fluorouracil and leucovorin (LV5FU2) during the resting periods between preoperative CRT and surgery in patients with LARC. Materials and Methods: Standard preoperative CRT was delivered to the entire pelvis at a total dose of 5040 Gy of radiation with concurrent 5-FU or capecitabine for 6 weeks. Twenty-three patients received additional preoperative chemotherapy with two cycles of 5-FU and LV (LV 200 mg/m2 and 5-FU bolus 400 mg/m2 on day 1, and 5-FU infusion 2400 mg/m2 for 46 hrs, every 2 weeks) after preoperative CRT. Surgery was performed at 2-4 weeks following the completion of preoperative chemotherapy. Results: Between May 2013 and January 2015, 23 patients underwent preoperative CRT, with additional chemotherapy and surgery, and 23 patients completed the scheduled treatment. The median follow-up duration was 42.0 months. The tumor down-staging rate was observed in 65.2%, and pathologic complete remission (pCR) was noted in 5 patients (21.7%). T and N down-staging were observed in 16 (69.6%) and 14 (60.9%) patients, respectively. The four-year disease-free survival (DFS) rate was 73.9% and the four-year overall survival (OS) rate was 90.9% in patients who received additional chemotherapy. The four-year DFS rate was 100% in the tumor down-staging group vs. 25.0% in the non-down staging group treated with additional chemotherapy (P <0.001). There was also a significant difference of the four-year OS rate 100% in the tumor down-staging group compared with 71.4% in the non-down staging group (P = 0.031). Conclusions: This preliminary study showed that additional preoperative chemotherapy with LV5FU2 was well tolerable and had an improvement in the downstaging rate and survival. Randomized controlled trial of this strategy is encouraged for definitive conclusions.

The Association between Smoking Status and Influenza Vaccination Coverage Rate in Korean Adults: Analysis of the 2010-2012 Korea National Health and Nutrition Examination Survey.

BACKGROUND: Globally, smoking is one of the biggest challenges in public health and is a known cause of several important diseases. Influenza is preventable via annual vaccination, which is the most effective and cost-beneficial method of prevention. However, subjects who smoke have some unhealthy behaviours such as alcohol, low physical activity, and low vaccination rate. In this study, we analyzed the relationship between smoking status and factors potentially related to the influenza vaccination coverage rate in the South Korean adult population. METHODS: The study included 13,565 participants aged >19 years, from 2010 to 2012 from the Korea National Health and Nutrition Examination Survey data. Univariate analyses were conducted to examine the association between influenza coverage rate and related factors. Multivariate analysis was obtained after adjusting for variables that were statistically significant. RESULTS: The overall vaccination rate was 27.3% (n=3,703). Older individuals (P<0.0001), women (P<0.0001), non-smokers (P<0.0001), light alcohol drinkers (P<0.0001), the unemployed (P<0.0001), and subjects with diabetes mellitus (P<0.0001), hypercholesterolemia (P<0.0001), and metabolic syndrome (P<0.0001) had higher influenza vaccination coverage than the others. In multivariate analyses, current smokers and heavy smokers showed lower vaccination rates (odds ratio, 0.734; 95% confidence interval, 0.63-0.854). CONCLUSION: In the current study, smokers and individuals with inadequate health-promoting behaviors had lower vaccination rates than the others did.

A multi-center, open-label, randomized phase III trial of first-line chemotherapy with capecitabine monotherapy versus capecitabine plus oxaliplatin in elderly patients with advanced gastric cancer.

OBJECTIVES: More than half of cases of gastric cancer (GC) are diagnosed in elderly patients (≥70years). While doublet combination with fluoropyrimidines and platinum is currently considered standard first-line chemotherapy in advanced GC, the main goal of chemotherapy remains palliation. MATERIALS AND METHODS: In a multi-center phase III trial, patients with chemotherapy-naïve, metastatic GC, aged 70years or older were randomized 1:1 to receive X monotherapy (capecitabine 1000mg/m2 bid po on days one to fourteen) or XELOX (X plus oxaliplatin 110mg/m2 iv on D1). Treatment was repeated every 21days until disease progression, unacceptable toxicity, or withdrawal. Primary endpoint was overall survival (OS). RESULTS: In total, 50 patients with a median age of 77 (range, 70 to 84) were enrolled (X, n=26; XELOX, n=24). No treatment-related serious adverse events or unexpected toxicities were observed. The most frequently observed toxicities were nausea and hand-foot syndrome, with fatigue and peripheral neuropathy more common in XELOX than in X patients. Median OS was 11.1months for XELOX arm and 6.3months for X arm (HR 0.58, 95% CI 0.30-1.12, P=0.108). Although the difference was not significant, on the basis of evidence of superiority of XELOX seen in the first interim analysis, an independent data monitoring committee recommended early stopping of the trial. PFS was significantly longer (HR 0.32, 95% CI 0.17-0.61, P<0.001) with XELOX (7.1months) than with X (2.6months). CONCLUSION: Platinum-based combination chemotherapy was associated with survival benefit, as compared with X monotherapy in elderly patients with GC.

Role of cancer stem cell in radioresistant head and neck cancer.

OBJECTIVE: Radioresistance is the main determinant of treatment outcome in head and neck cancer. The aim of this study was to establish radioresistant head and neck cancer cell lines and isolate cancer stem cells from them to investigate the role of cancer stem cells in radioresistant head and neck cancer. METHODS: To induce radioresistant cell lines, radiation was delivered to SCC15, SCC25, and QLL1 cells with an accumulated dosage of 60Gy over 30 cycles of irradiation. After a total of 60Gy of irradiation, the radioresistance of irradiated cancer cells was verified by MTT assay. The radioresistant cells were cultured in serum-free medium in ultra-low-attachment culture flasks to induce sphere-forming cells. Then, sphere-forming cells were analyzed using Western blotting to identify the expression of stem cell markers, such as Nanog and Sox-2. RESULTS: The MTT assay of cell viability showed more radioresistance in the irradiated cancer cell lines than in the non-irradiated cancer cell lines. Sphere-forming cells were identified in all three cancer cell lines 3-5 days after serum deprivation. All sphere-forming cells from the three cancer cell lines expressed stem cell markers. Sphere-forming cells showed more radioresistance than monolayer cells after irradiation by colony forming assay. CONCLUSION: Cancer stem cells seem to play an important role in the radioresistance of head and neck cancer. Further research is required to find a precise mechanism of radioresistance related to cancer stem cells.

Determination of small-field correction factors for cylindrical ionization chambers using a semiempirical method.

A semiempirical method based on the averaging effect of the sensitive volumes of different air-filled ionization chambers (ICs) was employed to approximate the correction factors for beam quality produced from the difference in the sizes of the reference field and small fields.We measured the output factors using several cylindrical ICs and calculated the correction factors using a mathematical method similar to deconvolution; in the method, we modeled the variable and inhomogeneous energy fluence function within the chamber cavity. The parameters of the modeled function and the correction factors were determined by solving a developed system of equations as well as on the basis of the measurement data and the geometry of the chambers. Further, Monte Carlo (MC) computations were performed using the Monaco® treatment planning system to validate the proposed method.The determined correction factors () were comparable to the values derived from the MC computations performed using Monaco®. For example, for a 6 MV photon beam and a field size of 1 × 1 cm2, was calculated to be for a PTW 31010 chamber and for a PTW 31016 chamber. On the other hand, the values determined from the MC computations were 1.121 and 1.031, respectively; the difference between the proposed method and the MC computation is less than 2%. In addition, we determined the values for PTW 30013, PTW 31010, PTW 31016, IBA FC23-C, and IBA CC13 chambers as well.We devised a method for determining from both the measurement of the output factors and model-based mathematical computation. The proposed method can be useful in case the MC simulation would not be applicable for the clinical settings.

Effect of Temperature-Sensitive Poloxamer Solution/Gel Material on Pericardial Adhesion Prevention: Supine Rabbit Model Study Mimicking Cardiac Surgery.

OBJECTIVE: We investigated the mobility of a temperature-sensitive poloxamer/Alginate/CaCl2 mixture (PACM) in relation to gravity and cardiac motion and the efficacy of PACM on the prevention of pericardial adhesion in a supine rabbit model. METHODS: A total of 50 rabbits were randomly divided into two groups according to materials applied after epicardial abrasion: PACM and dye mixture (group PD; n = 25) and saline as the control group (group CO; n = 25). In group PD, rabbits were maintained in a supine position with appropriate sedation, and location of mixture of PACM and dye was assessed by CT scan at the immediate postoperative period and 12 hours after surgery. The grade of adhesions was evaluated macroscopically and microscopically two weeks after surgery. RESULTS: In group PD, enhancement was localized in the anterior pericardial space, where PACM and dye mixture was applied, on immediate post-surgical CT scans. However, the volume of the enhancement was significantly decreased at the anterior pericardial space 12 hours later (P < .001). Two weeks after surgery, group PD had significantly lower macroscopic adhesion score (P = .002) and fibrosis score (P = .018) than did group CO. Inflammation score and expression of anti-macrophage antibody in group PD were lower than those in group CO, although the differences were not significant. CONCLUSIONS: In a supine rabbit model study, the anti-adhesion effect was maintained at the area of PACM application, although PACM shifted with gravity and heart motion. For more potent pericardial adhesion prevention, further research and development on the maintenance of anti-adhesion material position are required.

Immunohistochemical study identifying prognostic biomolecular markers in nasopharyngeal carcinoma treated by radiotherapy.

BACKGROUND: We evaluated the predictive significance of 14 reported markers using immunohistochemical study in nasopharyngeal carcinoma. METHODS: Immunohistochemical stainings were done in 38 patients for Met, cyclooxygenase-2 (COX-2), nm23-H1, epidermal growth factor receptor (EGFR), p63, early growth response factor 1 (Egr1), chromosome segregation 1-like (CSE1L), cathepsin-D (aspartyl protease), C-erbB2, p53, signal transducers and activators of transcription (STAT3/STAT5), CD138 (Syndecan-1), and LIN28 with the usual methods. RESULTS: The median follow-up time was 30 months (11-83 months). High Met and CD138 expression were statistically significant negative prognostic factors on survival. The expression of Egr1 had a positive prognostic effect on survival. The combined score of these 3 markers, Met plus CD138 minus Egr1, was a strong prognostic factor. The median survival curve was distinctly separated in accord with this combined score. No prognostic value was revealed in COX-2, nm23-H1, EGFR, p63, CSE1L, cathepsin-D, C-erbB2, p53, STAT3, STAT5, and LIN28. CONCLUSIONS: The combined score of these markers could be used to stratify biomolecular risk groups.

Clinical outcomes of chemoradiotherapy for locally recurrent rectal cancer.

BACKGROUND: To assess the clinical outcome of chemoradiotherapy with or without surgery for locally recurrent rectal cancer (LRRC) and to find useful and significant prognostic factors for a clinical situation. METHODS: Between January 2001 and February 2009, 67 LRRC patients, who entered into concurrent chemoradiotherapy with or without surgery, were reviewed retrospectively. Of the 67 patients, 45 were treated with chemoradiotherapy plus surgery, and the remaining 22 were treated with chemoradiotherapy alone. The mean radiation doses (biologically equivalent dose in 2-Gy fractions) were 54.6 Gy and 66.5 Gy for the chemoradiotherapy with and without surgery groups, respectively. RESULTS: The median survival duration of all patients was 59 months. Five-year overall (OS), relapse-free (RFS), locoregional relapse-free (LRFS), and distant metastasis-free survival (DMFS) were 48.9%, 31.6%, 66.4%, and 40.6%, respectively. A multivariate analysis demonstrated that the presence of symptoms was an independent prognostic factor influencing OS, RFS, LRFS, and DMFS. No statistically significant difference was found in OS (p = 0.181), RFS (p = 0.113), LRFS (p = 0.379), or DMFS (p = 0.335) when comparing clinical outcomes between the chemoradiotherapy with and without surgery groups. CONCLUSIONS: Chemoradiotherapy with or without surgery could be a potential option for an LRRC cure, and the symptoms related to LRRC were a significant prognostic factor predicting poor clinical outcome. The chemoradiotherapy scheme for LRRC patients should be adjusted to the possibility of resectability and risk of local failure to focus on local control.

Gene expression of Clonorchis sinensis metacercaria induced by gamma irradiation.

Gamma-rays are a form of ionizing radiation and produce serious cellular damage to nuclei and organelles. Gamma irradiation induces the expressions of genes involved in DNA repair. Clonorchis sinensis resides in and provokes pathophysiologic changes in the bile ducts of mammals. The C. sinensis metacercariae are unsusceptible or resistant to gamma irradiation with LD50 of 16.5 Gy. Using the annealing control primer-based polymerase chain reaction (PCR) method, 19 genes were found to be up-regulated in C. sinensis metacercariae exposed to gamma rays. Contigs of up-regulated genes (URGs) were retrieved in a C. sinensis expressed sequence tag pool and extended by DNA-walking. Of the 13 URGs annotated putatively as functional genes, five URGs were associated with energy metabolism, six with protein processing, and the other two with DNA repair protein RAD23 and inhibitor of apoptosis protein. Four URGs were confirmed up-regulated by gamma irradiation by quantitative real-time PCR. One unknown gene, which was up-regulated to the greatest extent, might contribute to early recovery from gamma-irradiation-induced damage. The up-regulations of genes encoding DNA repair, protein processing, and energy metabolism proteins suggests that increases in gene products orchestrate DNA lesion repair and recover cellular functions in gamma-irradiated C. sinensis metacercariae.

Expression of cyclooxygenase (COX)-2 as a prognostic factor in nasopharyngeal cancer.

PURPOSE: To evaluate the relationship between treatment failure and COX-2 expression in nasopharyngeal cancer patients treated with chemotherapy and radiotherapy. MATERIALS AND METHODS: The subjects of this study were 22 nasopharyngeal cancer patients. The patients were treated with neoadjuvant chemotherapy, followed by radiotherapy, or with radiotherapy alone. The formalin-fixed, paraffin-embedded tissues of 11 patients who developed a locoregional recurrence (n=7) or distant metastasis (n=4) were compared with those of 11 disease free patients. Prognostic factors, including histological type, stage, radiation dose and chemotherapy, were well balanced between the two groups. The COX-2 expression was determined immunohistochemically. RESULTS: COX-2 expression was stronger in the patients with a locoregional recurrence or distant metastasis than in those free of disease. The COX-2 distribution scores of the control group were as follows: 0 in 7, 1 in 2 and 2 in 2 patients. In the recurrence group, the scores were as follows; 0 in 3, 1 in 1, 2 in 2 and 3 in 5 patients. COX-2 expression was shown to have a statistically significant influence on the treatment failure by the Mann-Whitney U test (p=0.024) and Mantel-Haenszel Chi-Square test (p=0.018). It also significantly influenced the treatment failure when an analysis was performed within patients with a undifferentiated histology (p=0.039 by the Mann-Whitney U test, p=0.037 by the Mantel-Haenszel Chi-Square test). CONCLUSION: COX-2 expression is believed to be one of the important factors associated with a locoregional recurrence or distant metastasis.

Solitary dural extramedullary plasmacytoma with inv(9)(p13q21).

The authors report the case of a 24-year-old man who presented with a solitary dural extramedullary plasmacytoma (EMP) with inv(9)(p13q21). Chromosome 9 aberrations may be associated with the pathogenesis. This is the first reported case of solitary dural EMP associated with inv(9)(p13q21).