Changes of electrical impedance characteristics with the radiation induced damage on biological tissue constituents.

This study analyzes the response of increasing radiation dose to the pork tenderloin tissue. Considering its significant cell structure, pork tenderloin tissue samples are selected for the experimental objects to measure their electrical impedance characteristics. This study proposes and investigates an effective approach to characterize the variation of the internal change of the components of pork tenderloin tissues caused by radiation. Changes in the pork tenderloin tissues are that the gap of the myotome is more far apart with increase of radiation dose because of the destroyed Myofibrils under the damage. With the increase of radiation dose, the impedance value of the pork tenderloin tissue decreases. Each of mean differences in the impedance values before and after irradiation dose under 1 Gy, 2 Gy and 4 Gy show 0.55±0.03, 1.09±0.14 and 1.97±0.14, respectively. However, the mean difference substantially increases to 13.08±0.16 at irradiation dose of 10 Gy. Thus, the cell membrane shows the most severe rupture at a radiation dose of 10 Gy. Changes in the microstructure of the irradiated pork tenderloin tissue samples are also checked and validated by a transmission electron microscope.

Gene Signature for Sorafenib Susceptibility in Hepatocellular Carcinoma: Different Approach with a Predictive Biomarker.

BACKGROUND/AIM: Uniform treatment of hepatocellular carcinoma (HCC) with molecular targeted drugs (e.g., sorafenib) results in a poor overall tumor response when tumor subtyping is absent. Patient stratification based on actionable gene expression is a method that can potentially improve the effectiveness of these drugs. Here we aimed to identify the clinical application of actionable genes in predicting response to sorafenib. METHODS: Through quantitative real-time reverse transcription PCR, we analyzed the expression levels of seven actionable genes (VEGFR2, PDGFRB, c-KIT, c-RAF, EGFR, mTOR, and FGFR1) in tumors versus noncancerous tissues from 220 HCC patients treated with sorafenib. Our analysis found that 9 responders did not have unique clinical features compared to nonresponders. A receiver operating characteristic curve evaluated the predictive performance of the treatment benefit score (TBS) calculated from the actionable genes. RESULTS: The responders had significantly higher TBS values than the nonresponders. With an area under the curve of 0.779, a TBS combining mTOR with VEGFR2, c-KIT, and c-RAF was the most significant predictor of response to sorafenib. When used alone, sorafenib had a 0.7-3% response rate among HCC patients, but when stratifying the patients with actionable genes, the tumor response rate rose to 15.6%. Furthermore, actionable gene expression is significantly correlated with tumor response. CONCLUSIONS: Our findings on patient stratification based on actionable molecular subtyping potentially provide a therapeutic strategy for improving sorafenib's effectiveness in treating HCC.

Availability of preoperative systemic steroids on endoscopic sinus surgery for chronic rhinosinusitis with nasal polyposis.

PURPOSE: To analyze the outcome of endoscopic sinus surgery (ESS) after preoperative systemic steroid (PSS) treatment for chronic rhinosinusitis (CRS) with nasal polyposis (NP) and to investigate and compare clinicopathological factors associated with the outcome. MATERIALS AND METHODS: We performed a retrospective chart review of 468 patients with CRS with NP who underwent primary ESS between January 2005 and October 2011. 124 patients who met the inclusion criteria were included. Beginning from 2008, our clinic administered steroid preoperatively in patients of CRS with NP, thus there were 84 patients with preoperative systemic steroid (PSS group) and another 40 patients without such regimen (no PSS group). To evaluate the outcome after ESS, poor outcome and complication were analyzed according to the following parameters: age, sex, follow-up duration, eosinophilic infiltration, atopy, asthma, Lund-Mackay score, and polyp grade. RESULTS: There was no significant difference in poor outcome rates between the PSS and no PSS group (35.0% vs. 47.6%, p=0.185). There was no significant difference in complication rates between the PSS and no PSS group (10% vs. 6%, p=0.468). As with the multivariate analysis of the clinicopathological factors to the poor outcome rate, presence of asthma and eosinophilic infiltration were significantly related (odds ratio as 6.555 and 4.505, respectively), whereas PSS was confirmed as less likely related (odds ratio 0.611). CONCLUSION: Low dose PSS administration does not seem to have an effect on the outcome after ESS in patients who have CRS with NP. Eosinophilic infiltration and presence of asthma are important predictors of surgical outcome.

Expression of cell-cycle regulators (cyclin D1, cyclin E, p27kip1, p57kip2) in papillary thyroid carcinoma.

OBJECTIVE: To evaluate the expression of cell-cycle regulators in papillary thyroid carcinoma in relation to lymph node metastatic features, and to determine whether immunohistochemical staining of cell-cycle markers can predict lymph node metastasis. STUDY DESIGN: Cross-sectional study of prior surgical specimens. SETTING: Academic tertiary referral center. SUBJECTS AND METHODS: We reviewed the clinical records of patients who had undergone surgery for thyroid cancer and follicular adenoma between January 2005 and May 2008 at our clinic. Among these cases, 92 patients, comprising 28 patients with follicular adenoma, 32 with papillary thyroid carcinoma without lymph node metastasis, and 32 with papillary thyroid carcinoma with lymph node metastasis, were selected randomly. Formalin-fixed, paraffin-embedded tissues from the 92 patients were immunohistochemically stained for cyclin D1, cyclin E, p27(kip1), and p57(kip2), and protein expression levels were quantified and compared among the groups. RESULTS: Tumor specimens from the papillary thyroid carcinoma group had significantly higher expression levels of cyclin D1 and cyclin E, and cytoplasmic expression of p57(kip2) than the other two groups (P < 0.05). In particular, all malignant cases expressed cyclin D1, and cytoplasmic p57(kip2) was expressed only in malignant cases. Furthermore, differences in the grade of cyclin D1 expression according to lymph node metastasis were statistically significant (P < 0.05). CONCLUSION: Our results suggest that immunohistochemistry of certain cell-cycle regulators may be helpful in the diagnosis of papillary thyroid carcinoma, and that cyclin D1 in particular may be a useful marker for evaluating lymph node metastasis.

Anatomical variations of the spinal accessory nerve and its relevance to level IIb lymph nodes.

OBJECTIVE: This study was conducted to identify anatomical variations of the spinal accessory nerve (SAN) in the upper neck, the landmark of the anterior and inferior border of level IIb, and to evaluate the nerve's effect on the border and the number of lymph nodes (LNs) in level IIb. STUDY DESIGN AND SETTING: Case series with planned data collection. SUBJECTS AND METHODS: A total of 181 neck dissections (NDs) were prospectively enrolled in this study. The relation between the SAN and adjacent structures (internal jugular vein [IJV], sternocleidomastoid muscle [SCM], cervical plexus) and the number of LNs in level IIb was investigated. RESULTS: The SAN crossed the IJV ventrally in 72 cases (39.8%) and dorsally in 104 cases (57.4%), and passed through the IJV in five cases (2.8%). The SAN ran along the inner surface of the SCM and sent branches to the SCM without penetration of the muscle in 83 cases (45.9%), whereas in 98 cases (54.1%) the nerve sent branches to the SCM by penetration. Cervical plexus contribution to the SAN was seen from C2 in 96 cases (53.1%), C2 and C3 in 69 cases (38.1%), and C3 in 16 cases (8.8%). The mean number of LNs of level IIa and level IIb was 6.5 and 8.2 in cases in which the SAN crossed the IJV ventrally, and 6.8 and 5.4 in dorsally crossing cases. LNs included in the neck level IIb in ventrally crossing SAN cases were significantly larger than the dorsally crossing cases (P < 0.05). CONCLUSIONS: Our results may help to minimize the incidence of injuring the SAN in the upper neck during ND. Neck level IIb would contain more LNs if the course of the nerve leans toward the ventral side.

Medial fracturing of the inferior turbinate: effect on the ostiomeatal unit and the uncinate process.

It is apparently a common practice to fracture the inferior turbinate medially and superiorly to facilitate the fenestration of the inferior meatus, and to fracture medially and lateralize the inferior turbinate during turbinoplasty. However, it is also known that medial fracturing of the inferior turbinate may induce lateral displacement of the uncinate process. We investigated medial fracturing of the inferior turbinate to see whether it had any effect on changing the position of the uncinate process. A retrospective study was done on 23 patients who underwent medial fracturing of the inferior turbinate during submucosal turbinoplasty or turbinectomy from January 2004 through September 2006. By analyzing ostiomeatal-unit computed tomography, we measured the angle of the uncinate process, the minimal width of the ethmoid infundibulum, and the size of the maxillary sinus ostium. The angle of the uncinate process was 14.19-32.45 degrees , the minimal width of the ethmoid infundibulum was 0.61-2.45 mm, and the size of the maxillary sinus ostium was 2.14-6.77 mm. After the surgery, the angle of the uncinate process was 15.56-32.51 degrees , the minimal width of the ethmoid infundibulum was 0.53-2.52 mm, and the size of the maxillary sinus ostium was 2.18-7.01 mm. Pathologic change in the ostiomeatal-unit was not observed for an average period of 14.9 months (range 10.3-21.8 months) follow-up period. Our report suggests that the medial fracturing of the inferior turbinate does not alter the position of the uncinate process and the size of the maxillary sinus ostium. Clinically, it does not seem to affect normal physiology of the sinus function nor does it cause sinusitis.

Transcutaneous injection laryngoplasty through the cricothyroid space in the sitting position: anatomical information and technique.

A variety of approaches have been introduced to perform injection laryngoplasty under local anesthesia. Among these reported methods, transcutaneous injection through the cricothyroid space offers many advantages, but it possesses some technical difficulties during access to the vocal fold. The aim of this study was to assess the anatomic references related to transcutaneous injection laryngoplasty through cricothyroid space using 3-dimensionally reconstructed computed tomography to provide guidelines and to achieve higher efficacy during the procedure. The study group consisted of 14 patients (7 male, 7 female) with unilateral vocal fold paralysis and who had undergone multi-detector array computed tomography (MDCT) between January 2004 and December 2005. Assumption was made that transcutaneous injection is approached from the surface at lower margin of the thyroid cartilage and 7 mm lateral to the midline through the cricothyroid membrane and spot at the posterior 1/3 of true vocal cord is the target for injection laryngoplasty. From the surface of the injection point to the target, a line was drawn. Its length and the angle formed between it and the approach direction of needle was measured. Based on these measurements, 15 patients (8 male, 7 female) with unilateral vocal fold paralysis received 15 trials of transcutaneous injection laryngoplasty through the cricothyroid space. The average length from the surface of the injection point (7 mm lateral to the midline) to the posterior 1/3 of the true vocal cord (target of the injection) was 15.75 mm in men and 13.91 mm in women. The average of the angle in medial direction at the surface needed to reach the target of the injection was 10.57 degrees in men and 12.71 degrees in women, and in superior direction was 47.57 degrees in men and 47.43 degrees in women. Injection laryngoplasty performed under acquired reference measurements were successful in 14 trials (93.3%) out of 15 trials in 15 patients. We suggest that knowledge of the anatomic references regarding the transcutaneous injection laryngoplasty through cricothyroid space will provide guidelines for beginners and improve the understanding of the procedure, eventually leading to easier and more precise access to the vocal cord.

Glycerol pure tone audiometry and glycerol vestibular evoked myogenic potential: representing specific status of endolymphatic hydrops in the inner ear.

This prospective study attempts to explore the effect of glycerol on vestibular evoked myogenic potential (VEMP) in patients with definite unilateral Meniere's disease (MD) and to investigate whether the test reflects different pathologic states of endolymphatic hydrops (EH) in the inner ear by comparing the results of glycerol pure tone audiometry (PTA). Twenty-eight patients with definite unilateral MD were studied. As a control group, 11 patients with vestibular neuritis were selected. Sixteen ears of normal volunteers were enrolled to acquire normal range of the test. Each MD patient underwent glycerol testing measure with both conventional PTA and VEMP testing. Eleven vestibular neuritis patients also underwent glycerol-VEMP testing. The difference ratio was adopted to compare the changes in p1-n1 amplitude and latency of VEMP after the administration of glycerol (1.3 g/kg). Significant changes in the VEMP wave after the glycerol loading were seen in amplitude, but not in latency with MD patients. On the affected side, the amplitude of the p1-n1 biphasic wave significantly increased in 11 of 28 (39.3%) ears and decreased in 2 (7.1%) ears. On the unaffected side, 5 (17.9%) ears showed significant increase in amplitude. Significant changes in PTA were noted after administration of glycerol in 14 of 28 (50%) patients with MD. However, there was no statistically significant correlation between the test results. Glycerol administration had no significant effect on VEMP in patients with vestibular neuritis. The amplitude of VEMP in some patients with MD was increased, but the latency was not influenced by oral administration of glycerol. The severity of EH appears to vary in different parts of the inner ear. Glycerol-VEMP test results in patients with vestibular neuritis suggest that the VEMP reflects potential abnormality in the sacculocollic pathway, while glycerol-VEMP identifies the existence of EH in the saccule. VEMP and PTA after glycerol administration provide potential status of MD.

Basaloid squamous cell carcinoma of the external auditory canal: case report.

Basaloid squamous cell carcinoma (BSCC) is a rare malignancy, with features of both basal cell carcinoma and squamous cell carcinoma. The tumor has a predilection for the upper aerodigestive tract, and has been suggested to behave more aggressively than squamous cell carcinoma (SCC). To the author's knowledge, BSCC confined to the external auditory canal (EAC) has not been previously described. BSCC of EAC manifests similar characteristics as the conventional EAC cancer, presenting a mass with chronic otorrhea and itching sense. Excision of the tumor was accomplished by modified lateral temporal bone resection. This report describes the first case of BSCC in this location, and includes reviews of the pathologic and clinical aspects of this disease.

Activation of selective transcription factors and cytokines by water-soluble extract from Lentinus lepideus.

We isolated a water-soluble extract, PG101, from cultured mycelia of Lentinus lepideus. Treatment of human peripheral blood mononuclear cells (PBMCs) with PG101 increased levels of TNF-alpha, IL-1beta, IL-10, and IL-12 by 100- to 1000-fold, whereas GM-CSF and IL-18 were activated by an order of magnitude. On the contrary, IFN-gamma and IL-4 were not affected. The response to PG101 occurred in a dose- and time-dependent manner. From the human PBMCs treated with PG101, TNF-alpha was a first cytokine to be activated, detectable at 2 hr post-treatment followed by IL-1beta at 6 hr post-treatment. IL-12 and IL-10 were the next to follow. GM-CSF and IL-18 both showed significant increases 24 hr after treatment. When PBMCs were sorted into various cell types, monocyte/macrophages, but not T and B cells, were the major target cell type responsive to PG101. Consistent with this result, the profile of cytokine expression upon PG101 treatment was comparable between PBMCs and a human promonocytic cell line (U937), whereas cell lines of T cell and myeloid origins did not respond to PG101. Data from a transient transfection assay involving specific reporter plasmids indicated that cellular transcription factor such as NF-kappaB, but not AP-1, was highly activated by PG101. Results from a gel retardation assay and the experiment involving a specific NF-kappaB inhibitor confirmed the involvement of NF-kappaB. Despite its significant biological effect on various cytokines, PG101 remained nontoxic in both rats and PBMCs even at a biological concentration approximately 20 times greater. PG101 demonstrates great potential as a therapeutic immune modulator.

Enhancement of repopulation and hematopoiesis of bone marrow cells in irradiated mice by oral administration of PG101, a water-soluble extract from Lentinus lepideus.

PG101 is a water-soluble extract from Lentinus lepideus. It is a potential biological response modifier that activates selective cytokines in vitro, mainly by controlling cellular transcription factor NF-kappaB. Effects of PG101 were tested on bone marrow cells in irradiated mice. Mice were irradiated with a dose of 6 Gy and were given PG101 by gavages daily for 24 days. In PG101-treated mice, the number of colony-forming cells, including colony-forming units (CFU)-granulocytes/macrophages (GM) and erythroid burst-forming units (BFU-E), were increased to almost the levels seen in nonirradiated control as early as 8 days after irradiation. Two-color flow cytometric analysis using antibodies to ER-MP12 and ER-MP20 suggested that in the bone marrow cell population, PG101 increased the number of granulocytes (ER-MP12(-)20(med)) and myeloid progenitors (ER-MP12(+)20(+)). Analysis of surface c-Kit and Gr-1 proteins in bone marrow cells indicated that PG101 might induce differentiation of progenitor cells to granulocytes and/or proliferation of the committed cells. Lastly, oral administration of PG101 highly increased serum levels of GM-CSF, IL-6, and IL-1beta. Interestingly, the level of TNF-alpha was elevated by irradiation in control mice, but was maintained at the background level in PG101-treated mice, suggesting that PG101 might effectively suppress TNF-alpha-related pathologic conditions. Our results strongly suggest the great potential of PG101 as an immune enhancer during radiotherapy and/or chemotherapy.