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The purpose of this study was to evaluate the dosimetry of single fraction, single-isocenter intensity-modulated radiosurgery (IMRS) plans for multiple intracranial metastases and to compare Helical Tomotherapy (HT). Ten treatment plans with 3-6 brain metastases treated with IMRS were re-planned with HT. The mean number of lesions was 5 and mean PTV 22 cm(3). The prescribed dose was 16-20 Gy. The mean V100% was similar for IMRS and HT, and the mean conformity index was 1.4, mean Paddick confirmity index was 0.7, and mean MDPD was 1.1 for both. The mean gradient index was similar for both. The mean 50% &#95;isodose volume was 179.2 cm(3) for IMRS and 277.0 cm(3) for HT (p=0.01). The mean maximum doses to organs at risk were lower for IMRS except brainstem and right optic nerve. For brain, the integral dose was 5.1 and 6.8 Gy-kg (p<0.001) and mean dose 4.0 and 5.4 Gy (p<0.001) for IMRS and HT, respectively. The mean treatment times were 23 (IMRS) and 41 (HT) minutes. Conformity and homogeneity indices were equivalent and sparing of the organs at risk was clinically acceptable for both IMRS and HT. Though the gradient index was similar for IMRS and HT, the mean 50% isodose volume and integral dose to normal brain were lower for IMRS as was treatment time.

Background: Tumors are composed of subpopulations of cells with heterogeneous characteristics that allow for tumor progression and development of treatment resistance. The purpose of this study was to determine if there is heterogeneity in the in vitro chemosensitivity in different invasive sections of a single tumor., Materials and Methods: Chemosensitivity in advanced colorectal cancer specimens was examined using an ATP-based chemotherapy response assay. Four chemotherapeutic agents (5-fluorouracil (5-FU), oxaliplatin, irinotecan, and mitomycin) were used for chemosensitivity studies. Tumor tissues were obtained from the superficial (mucosa/submucosa) and deep parts (muscle/subserosa/serosa), respectively. Twenty patients who had results for both the superficial and deep parts were evaluated., Results: The chemosensitivity study showed variable cell death rates in both parts of the tumor. Regression analysis showed some correlations with 5-FU and irinotecan, but not with oxaliplatin or mitomycin. With the exception of three patients in whom no drug was recommended, at least one chemotherapeutic drug showed some consistency between the superficial and deep parts of the tumor. Mitomycin was the most frequently active agent for the superficial part. In the deep part, oxaliplatin and mitomycin were the most active agents., Conclusions: There may be heterogeneity in the responses to anti-chemotherapeutic agents in advanced colorectal cancer, according to the depth of invasion. Therefore, in clinical situations, chemosensitivity test specimens should be mixed with various parts of the whole tumor in order to obtain representative chemosensitivity and chemoresistance profiles.

Background/aims: This study analyzed the patients who died of recurrent colorectal cancer and determined the clinicopathologic indicators that were associated with the survival time., Methodology: The study included 282 patients who died of recurrent colorectal cancer after resection. The clinicopathologic findings were compared between 162 patients who died within 3 years after resection (the short-term survival group) and 120 patients who died more than 3 years after resection (the long-term survival group). Multivariate analysis was performed to determine the independent factors correlated with the timing of death., Results: When compared with the long-term survival group, the short-term survival group was characterized by a tumor size >5 cm (51.2% in the short-term survival group vs. 39.2% in the long-term survival group), poorly differentiated tumor (13.3% vs. 0.9%), invasion through the muscularis propria (98.8% vs. 88.3%), positive lymphatic invasion (43.2% vs. 20.8%), positive vascular invasion (34.0% vs. 16.7%), positive perineural invasion (17.9% vs. 8.3%), extended lymph node metastasis and Dukes' stage C disease (80.9% vs. 60.8%). The mean survival time was significantly influenced by the histologic grade, the depth of wall invasion, the presence of lymphatic or vascular invasion, the level of lymph node metastasis and the Dukes' stage. On multivariate analysis, however, histologic grade was the only independent factor associated with the survival time., Conclusions: The histological grade was the only significant factor influencing the survival time after resection of colorectal cancer. The patients with poorly differentiated adenocarcinoma frequently died of recurrence within 3 years after colorectal resection.

Background: For patients with T3N0M0 colon cancer without known risk factors, the necessity of chemotherapy has no definite consensus., Methods: From 1994 to 2004, we retrospectively analyzed 247 patients who had pathologically confirmed T3N0M0 colon cancer without risk factors., Results: Among the 247 patients, 198 (80.2%) received chemotherapy and 49 (19.8%) underwent surgery alone. The 5-year survival rate was 92.8% for patients with T3N0M0 colon cancer without risk factors. Only chemotherapy increased survival (P = .032) by multivariate analysis. The 5-year survival rates were 85.4% in the surgery-only group and 94.2% in the group that received surgery with chemotherapy. There was no difference in the therapeutic efficacy of 5-fluorouracil, capecitabine, and uracil/tegafur (P = .424) for survival., Conclusion: The results of this study showed that chemotherapy improved the survival of patients with T3N0M0 colon cancer without risk factors.

This study was designed to investigate the possibility that mtDNA mutations might arise in inflammatory or chronically damaged nasal polyp tissue from 23 patients. Thirteen patients (57%) displayed nasal polyp tissue-specific mtDNA mutations in the hypervariable segment of the control region and cytochrome b gene, which were not found in the corresponding blood cells and/or adjacent normal tissue. Nasal polyp tissue-specific length heteroplasmic mutations were also detected in nucleotide position (np) 303-315 homopolymeric poly C track (39%), np 514-523 CA repeats (17%) and np 16184-16193 poly C track (30%). The average mtDNA copy number was about three times higher in nasal polyp tissue than in the corresponding peripheral blood cells and adjacent non-polyp tissues. The level of reactive oxygen species (ROS) was significantly higher in the nasal polyp tissues compared to those from the corresponding samples. High level of ROS in nasal polyp tissue may contribute to development of mtDNA mutations, which may play a crucial role in the vicious cycle of pathophysiology of nasal polyps.

Intramembranous tympanic membrane cholesterol granuloma (CG) occurs infrequently. Here, the authors report a case of CG in the tympanic membrane presenting as a blue eardrum in the right ear. In addition, a pinhole perforation noted in the anterosuperior area revealed a brown discharge. High-resolution temporal bone CT showed a bulging mass shadow in the middle ear and a soft tissue dense lesion that filled both the epitympanum and mastoid cavity. Tympanomastoidectomy was performed under general anesthesia. New bone formation was confirmed in the mastoid antrum and epitympanum, and the epitympanum was blocked by new bone. The tympanic membrane revealed a round, brownish mass with a glistening surface and a severely thickened pars tensa. We herein report this case and review pertinent medical literature.

Purpose: To determine the feasibility and benefits of optimized magnetic resonance imaging (MRI)-guided brachytherapy (BT) for cancer of the cervix., Methods and Materials: A total of 20 patients with International Federation of Gynecology and Obstetrics Stage IB-IV cervical cancer had an MRI-compatible intrauterine BT applicator inserted after external beam radiotherapy. MRI scans were acquired, and the gross tumor volume at diagnosis and at BT, the high-risk (HR) and intermediate-risk clinical target volume (CTV), and rectal, sigmoid, and bladder walls were delineated. Pulsed-dose-rate BT was planned and delivered in a conventional manner. Optimized MRI-based plans were developed and compared with the conventional plans., Results: The HR CTV and intermediate-risk CTV were adequately treated (the percentage of volume treated to >or=100% of the intended dose was >95%) in 70% and 85% of the patients with the conventional plans, respectively, and in 75% and 95% of the patients with the optimized plans, respectively. The minimal dose to the contiguous 2 cm(3) of the rectal, sigmoid, and bladder wall volume was 16 +/- 6.2, 25 +/- 8.7, and 31 +/- 9.2 Gy, respectively. With MRI-guided BT optimization, it was possible to maintain coverage of the HR-CTV and reduce the dose to the normal tissues, especially in patients with small tumors at BT. In these patients, the HR percentage of volume treated to >or=100% of the intended dose approached 100% in all cases, and the minimal dose to the contiguous 2-cm(3) of the rectum, sigmoid, and bladder was 12-32% less than with conventional BT planning., Conclusion: MRI-based BT for cervical cancer has the potential to optimize primary tumor dosimetry and reduce the dose to critical normal tissues, particularly in patients with small tumors.

Aim: The value of multi-visceral resection (MVR) for treating primary advanced colon cancer infiltrating into the neighboring organs had been debated because of the high mortality., Methods: We reviewed 1288 patients who underwent curative resection for pT3-4 colon cancer without distant metastasis from 1994 to 2004., Results: Eighty four patients (6.5%) with colon cancer infiltrating into the neighboring organs (cT4) underwent MVR. The accuracy of the intra-operative decision for true invasion (pT4) was 35.7%. Major surgical morbidity occurred in 11 patients of the standard resection group (0.9%) and in 2 patients of the MVR group (2.3%) (p = 0.206). Most of the recurrence was distant metastasis (20 patients, 23.8%). Local recurrence was occurred in five patients (6.0%). The prognostic factors for recurrence and survival were pathologic tumor invasion (p = 0.033 and p = 0.016, respectively) and lymph node metastasis (p = 0.010 and p < 0.001, respectively)., Conclusion: Multi-visceral resection was a safe and curative procedure as compared with standard resection for patients with advanced colon cancer. The cause of a poor prognosis in MVR was not local recurrence but distant metastasis. Pathologic tumor invasion and lymph node metastasis were the potential prognostic factors.

This investigation involves quantifying the extent of intracranial peripheral dose arising from simulated targets situated in the skull-base or upper-spine region using the Leksell GammaKnife Perfexion treatment unit. For each of three spherical target volumes--denoted as Vs (4 cm3), VM (18 cm3), and VL (60 cm3)--three treatment plans were manually generated, one for each of the three collimator sizes--4, 8, and 16 mm. Each of the plans was delivered to a spherical dosimetry phantom with an insert containing EBT Gafchromic film. The total dose at 70 mm from the targets' edges, %D(70 mm), was measured as a function of elevation angle and expressed as a percentage of the prescription dose. The film insert was placed centered in the median sagittal plane (Leksell X = 100) and %D(70 mm) was measured for the angular range from 0 degree (superior/along Z axis) to 90 degrees (anterior/along Y axis). For a given collimator i, the irradiation time ti to treat a spherical target of volume V using the 50% isodose line was observed to follow a power-law relationship of the form ti = Ai(V/ Vi)n where Ai was the maximum dose divided by collimator dose rate and Vi was the volume encompassed by the 50% isodose line for a single shot. The mean value of n was 0.61 (range: 0.61-0.62). Along the superior (Z) direction (angle=0 degree) and up to angles of around 30 degrees, the %D(70 mm) was always highest for the 4 mm plans, followed by the 8 mm, followed by the 16 mm. In this angular range, the maximum measured %D(70 mm) was 1.7% of the prescription dose. The intracranial peripheral dose along the superior direction (combined scatter and leakage dose) resulting from irradiation of upper-spine or base-of-skull lesions is measured to be less than 2% of the prescription dose, even for very large (60 cm3) targets. The results of this study indicate that, for a given target volume, treatment plans consisting of only 4 mm shots yield larger peripheral dose in the superior direction than 8 mm shot only plans, which in turn yield larger peripheral dose than 16 mm shot only plans.

Nur, a member of the Fur family, is a nickel-responsive transcription factor that controls nickel homeostasis and anti-oxidative response in Streptomyces coelicolor. Here we report the 2.4-A resolution crystal structure of Nur. It contains a unique nickel-specific metal site in addition to a nonspecific common metal site. The identification of the 6-5-6 motif of the Nur recognition box and a Nur/DNA complex model reveals that Nur mainly interacts with terminal bases of the palindrome on complex formation. This contrasts with more distributed contacts between Fur and the n-1-n type of the Fur-binding motif. The disparity between Nur and Fur in the conformation of the S1-S2 sheet in the DNA-binding domain can explain their different DNA-recognition patterns. Furthermore, the fact that the specificity of Nur in metal sensing and DNA recognition is conferred by the specific metal site suggests that its introduction drives the evolution of Nur orthologs in the Fur family.

Osteomas of the middle ear are rare benign tumors. They commonly arise from the promontory. To date, a total of three cases of osteomas of the ossicles, inseparable from malleus and incus, have been described in the English literature. Among them, only one case osteoma with congenital cholesteatoma has been reported. Recently a 6-year-old boy with osteoma associated with congenital cholesteatoma presented to our service. The osteoma and congenital cholesteatoma were removed successfully by canal wall up mastoidectomy with staging operation. A rock-hard mass was separated from the footplate. The malleus and short process of incus were intact. Histopathological examination confirmed the presence of the osteoma.

Purpose: Whole pelvic intensity-modulated radiotherapy (IMRT) is increasingly being used to treat cervix cancer and other gynecologic tumors. However, tumor and normal organ movement during treatment can substantially detract from the benefits of this approach. This study explored the effect of internal anatomic changes on the dose delivered to the tumor and organs at risk using a strategy integrating deformable soft-tissue modeling with simulated dose accumulation., Methods and Materials: Twenty patients with cervix cancer underwent baseline and weekly pelvic magnetic resonance imaging during treatment. Interfraction organ motion and delivered (accumulated) dose was modeled for three treatment scenarios: four-field box, large-margin whole pelvic IMRT (20-mm planning target volume, but 10 mm inferiorly) and small-margin IMRT (5-mm planning target volume)., Results: Individually, the planned dose was not the same as the simulated delivered dose; however, when taken as a group, this was not statistically significant for the four-field box and large-margin IMRT plans. The small-margin IMRT plans yielded adequate target coverage in most patients; however, significant target underdosing occurred in 1 patient who displayed excessive, unpredictable internal target movement. The delivered doses to the organs at risk were significantly reduced with the small-margin plan, although substantial variability was present among the patients., Conclusion: Simulated dose accumulation might provide a more accurate depiction of the target and organ at risk coverage during fractionated whole pelvic IMRT for cervical cancer. The adequacy of primary tumor coverage using 5-mm planning target volume margins is contingent on the use of daily image-guided setup.

Background and Aims: The incidence of double primary malignancies (DPM) is known to be higher in colorectal cancer patients than the general population. And, the role of microsatellite instability (MSI) in DPM has been previously studied. We evaluated the clinical features and association between MSI and colorectal cancer patients with DPM., Materials and Methods: From September 1994 to May 2004, we reviewed 2,301 colorectal cancer patients with regard to secondary primary malignancies. A subgroup analysis was performed for MSI after January 2003., Results: One hundred forty-five patients (6.3%) had a DPM identified. In DPM group, 57 patients had a synchronous DPM (39.3%), and 88 patients had a metachronous malignancy (60.7%). Male gender (p<0.001) and colon cancer (p<0.001) were the factors related with the development of the DPM. Most of the second malignancies occurred within 3 years after the primary operation. The common second malignancies were stomach (58 patients, 40%) and lung (21 patients, 14.5%). In the subgroup analysis, there was a higher frequency of DPM in the MSI group when compared to the microsatellite stable group (p=0.021)., Conclusions: The careful pre- and postoperative evaluation should be paid for detecting DPM as well as for detecting recurrence in colorectal cancer patients. The results of this study suggest that MSI might be a useful marker for the detection of DPM in colorectal cancer patients.

Purposes: This study is a prospective randomized clinical trial to evaluate the clinical safety and the effect of a sodium hyaluronate-based bioresorbable membrane (Seprafilm; Genzyme, Cambridge, MA, USA) for reducing adhesive intestinal obstruction after colorectal cancer surgery., Materials and Methods: Between November 2002 and December 2003, 504 patients underwent radical resection for sigmoid or rectal cancer. Among these patients, 427 patients were enrolled in this study. The patients were randomized into the Seprafilm group (N = 185) and the control group (N = 242). All the patients in the Seprafilm) group received one sheet of Seprafilm over the pelvic inlet where the peritoneum was denuded due to pelvic dissection. Intestinal obstruction was defined when there were symptoms of nausea, vomiting, and abdominal distension combined with an obstructive bowel pattern on the radiologic evaluation., Results: The median follow-up period was 25.0 months. There were no significant differences between the Seprafilm and the control groups for the clinicopathologic parameters. There were no differences in the incidence of complications between the two groups; however, the incidence of early postoperative intestinal obstruction was significantly less in the Seprafilm group than in the control group (2.7% vs 7.0%, respectively, p = 0.045). Five patients in the Seprafilm group experienced postoperative intestinal obstruction (2.7%) compared with 11 patients in the control group (4.6%) during the follow-up period; however, there was no statistical difference., Conclusions: Seprafilm appears to be effective in preventing early postoperative intestinal obstruction and there was a trend for reduced intestinal obstruction after lower abdominal surgery for colorectal cancer.

In the present study, the anti-cancer effects of ginseng fermented with Phellinus linteus (GFPL) extract were examined through in vitro and in vivo assays. GFPL was produced by co-cultivating ginseng and Phellinus linteus together. Ginsenoside Rg3, Rh1 and Rh2 are important mediators of anti-angiogenesis and their levels in GFPL were enriched 24, 19 and 16 times, respectively, more than that of ginseng itself through the fermentation. GFPL exhibited distinct anti-cancer effects, including growth inhibition of the human lung carcinoma cell line A549, and promotion of immune activation by stimulating nitric oxide (NO) production in Raw 264.7 cells. Further evidence supporting anti-cancer effects of GFPL was its significant prolongment of the survival of B16F10 cancer cell-implanted mice. These results suggest that the GFPL may be a candidate for cancer prevention and treatment through immune activation and anti-angiogenic effects by enriching Rg3, Rh1 and Rh2.

Background & Objective: It has been suggested that increased inner ear pressure can affect the stiffness of the tympano-ossicular conductive system. However, the published literature contains few studies on changes of middle ear mechanics caused by increased inner ear pressure. In this study, we evaluated the effects of increased inner ear pressure on tympanic membrane vibration in guinea pigs using a laser Doppler vibrometer (LDV)., Materials and Methods: We used 10 male guinea pigs (weighing 250 g each) with normal eardrums and Preyer reflexes were used for the experiment. Inner ear pressure was modified by two approaches--directly via a tube placed in the inner ear (n=5) and indirectly via a tube placed in the subaracnoid space (n=5). Slow uniform pressure (microl/min) was infused until constant pressure was maintained. At this time, an artificial endolymph or perilymph was injected with a constant pressure of 100 and 300 mm H2O. We measured the umbo velocity using a LDV., Results: A positive pressure load decreased the umbo vibration at low frequencies but did not change the umbo vibration at mid and high frequencies. The umbo velocity had a greater reduction for an endolymphatic pressure load than for a perilymphatic pressure load. The largest change in velocity was noted at a frequency of 0.1 kHz. There was no significant change in velocity at higher frequencies, except for 5 kHz., Conclusion: LDV is a good tool to analyze middle ear function and it has the potential indirectly to diagnose an increase in endolymphatic or perilymphatic pressure.

Background and Objective: Bacterial biofilm formation has been implicated in the high rate of persistent otorrhea after tympanostomy tube insertion. It has been suggested that the tube material may be an important factor in the development of otorrhea. Recently we reported the presence of ciprofloxacin-resistant Pseudomonas aeruginosa (CRPA) biofilms on infected tympanostomy tubes following the use of intractable post-tympanostomy tubes and the onset of otorrhea. In this study, we have evaluated the resistance of piperacillin-tazobactam coated with chitosan on a tympanostomy tube to prevent CRPA biofilm formation in vitro., Materials and Methods: Three sets each of piperacillin-tazobactam coated silicone tubes (n=5), commercial silver-oxide coated silicone tubes (Activent, Silic) (n=5) and control uncoated tympanostomy tubes (Paparella type 1) (n=5) were processed for evaluation. The piperacillin-tazobactam coated tympanostomy tubes were compared with the silver-oxide coated tubes and the uncoated control tubes for resistance to CRPA biofilm formation after in vitro incubation., Results: Scanning electron microscopy showed that the surface of the silver-oxide coated tube (Activent) formed a thick biofilm with crusts as well as an uncoated tube. In contrast, the surface of a piperacillin-tazobactam coated tympanostomy tube showed virtually no CRPA biofilm formation., Conclusion: The piperacillin-tazobactam coated tympanostomy tube showed resistance to CRPA biofilm formation. The piperacillin-tazobactam coating may be useful to reduce CRPA biofilm formation; however, further in vivo studies are necessary.

Cholesterol granuloma (CG) may erode into the middle ear, the mastoid bone and the petrous apex. However, aggressive erosion into the cranial cavity is extremely rare. Here we report a case of huge CG extending to the middle cranial fossa. Temporal bone computerized tomography showed a soft tissue mass which destroyed the bony plate of the posterior and middle cranial fossa. On magnetic resonance imaging, the mass revealed a high signal on both T1 and T2-weighted images. The mass compressed the middle cranial fossa without invasion into the brain. The CG was removed by extended cortical mastoidectomy. The postoperative course was uneventful and there were no neurological complications.

The occurrence of postoperative secondary cholesterol cysts in the mastoid has been previously reported, however the occurrence of a primary large cholesterol cyst in the mastoid with bony destruction of the facial nerve has rarely been reported. The case report of a 17-year-old female patient with a primary large cholesterol cyst with dysgeusia is presented. Computed tomography and magnetic resonance imaging findings for the lesion distinguish a cholesterol granuloma, cholesteatoma and vascular tumor. The patient underwent a canal wall down mastoidectomy with mastoid obliteration. A dehiscent portion of the mastoid segment of the facial nerve was visible within the cavity; the gross finding of the facial nerve was edematous in appearance. Five years later, there has been no recurrence of disease.

Post-transplant lymphoproliferative disorder (PTLD) is a life-threatening complication of any organ transplantation. It is more common in children than in adults, and the risk factors include Epstein-Barr virus (EBV) infection and immunosuppression. We report a case of colonic marginal zone B-cell lymphoma occurring 4 years after liver transplantation in a 52-year-old man who had been taking immunosuppressive agents, namely, cyclosporin, mycophenolate mofetil (MMF), and prednisolone. A routine follow-up colonoscopy showed a 2.0-cm diffuse nodular transverse colon polyp covered with erosive mucosa. Snare polypectomy was done without any complications. Immunohistochemical staining was positive for CD3 and CD20 in the interstitially scattered small lymphocytes and negative for Bcl-2, revealing marginal zone B-cell lymphoma. EBV quantitative polymerase chain reaction was less than the detection limit (<10 copies/5 microl whole blood). Extraintestinal whole-body screening was negative. The patient underwent right hemicolectomy after colonoscopic tattooing for positive resection margins on snare polypectomy. Surgical pathology revealed no evidence of residual lymphoma. Treatment consisted of colonic resection and reduction of the doses of immunosuppressants. The patient is currently under close surveillance without any signs of recurrence.

Background: There has been a steady increase in the number of cases of ciprofloxacin-resistant Pseudomonas aeruginosa (CRPA) otorrhea; this is a growing medical concern. For otological surgery in children, octylcyanoacrylate can be an alternative method of closure for surgical incisions. Recent in vitro studies have shown that octylcyanoacrylate is effective as an antimicrobical barrier. To date, there have been only rare reports on the antibacterial effect of octylcyanoacrylate against CRPA. The purpose of this study is to determine the antimicrobial effects of octyl-cyanoacrylate against the CRPA that was isolated from patients with chronic suppurative otitis media., Patients and Methods: Clinical CRPA (n=20) bacteria and ciprofloxacin-sensitive PA (CSPA) (n=20) were obtained from patients. The susceptibilities to various antibiotics were determined by disk diffusion method., Result: Both CSPA and CRPA were resistant to octylcyanoacrylate., Conclusion: Results demonstrated that octylcyanoacrylate has no antibacterial activity against CSPA and CRPA.

The classic presentation of congenital cholesteatoma is a pearl behind the anterior-superior quadrant of an intact tympanic membrane. Idiopathic hemotympanum is characterized by a dark blue eardrum, the most prominent feature of which is the presence of cholesterol granulomas. Blue eardrum is associated with eustachian tube dysfunction. Despite the well-established relationship between eustachian tube dysfunction and the development of pediatric cholesteatoma, little has been written concerning the appropriate timing of tympanostomy tube placement. To date, there are no reports of congenital cholesteatoma associated with blue eardrum. A recent case of advanced congenital cholesteatoma (stage IV) associated with blue eardrum was treated using preoperative tympanostomy tube insertion. Tympanostomy tubes were helpful in preventing recurrence of the cholesteatoma after surgery. The case is presented along with a review of the literature.

Background and Objective: With the increased use of ototopical ciprofloxacin solution, newly evolved bacterial fluoroquinolone resistance has also become more of a problem. The emergence of ciprofloxacin-resistant Pseudomonas aeruginosa (CRPA) has created a new therapeutic challenge in otology. We evaluated the ototoxicity of topical fortified piperacillin-tazobactam solution by performing experiments in young male albino guinea pigs (weight, 250-300 g each)., Materials and Methods: Antimicrobial assay by direct contact test using scanning electron microscope was performed. Twenty guinea pigs (250-300 g) were treated with fortified piperacillin-tazobactam solution. In experimental group 1 (n=10), a gelfoam ball impregnated with 120 microl of fortified piperacillin-tazobactam was implanted on the round window membrane by a posterior approach. In experimental group 2 (n=10), 20 microl of fortified piperacillin-tazobactam was injected into the middle ear cavity via silicone tube with a small hole placed in the superior aspect of the bulla by drilling. The drug application through the tube was performed for 7 consecutive days. In control group (n=5), a gelfoam ball impregnated with 120 microl of gentamicin solution (80 mg/2 ml) was implanted on the round window membrane., Results: The fortified piperacillin-tazobactam 20 microl treated CRPAs showed destruction of their cell membrane in antimicrobial assay by direct contact test. No significant difference in the mean auditory brainstem response (ABR) thresholds before and after drug administration was found for the experimental group. However, significant elevation of the mean ABR thresholds was found for the control group. In experimental group, scanning electron microscopy showed almost normal sterociliary arrangements and surface structure on the inner and outer hair cells. However, significant destruction of outer hair cells was identified in control group., Conclusion: This present study's data suggests that fortified piperacillin-tazobactam solution can be effectively used for topically treating CRPA otorrhea in those patients who suffer with chronic suppurative otitis media.

Contrast injection protocol is known to affect the estimation of kinetic parameters in functional CT. A novel method is proposed to maximize the precision of parameter estimates by modulating the contrast injection scheme. The method models the intravenous contrast bolus to be dispersed by a "patient function" to give rise to the arterial input function, which, in turn, carries the contrast agent to tissue leading to contrast enhancement. The covariance matrix analysis was applied to calculate the uncertainty of parameter estimates as the coefficients of variation (CV) in the adiabatic tissue homogeneity (ATH), two-compartment, and the modified Kety model in which tumor pathophysiology is modeled. An optimization scheme was used to determine the optimal injection protocol which would minimize the CV of a particular kinetic parameter. For clinical utility, a recommended injection protocol was suggested from a statistical analysis with the optimal injection protocols obtained from the first group of 12 patients with cervix cancer. The efficacy of the recommended injection protocol was tested with a second group of 12 patients. In addition, the robustness of the recommended injection protocol to longitudinal study has been investigated in the presence of variations in arterial input function and tumor pathophysiology. Based on the data of the second group of patients, and using the ATH model, the recommended biphasic injection of two boluses improves the precision in the estimation of blood flow and mean transit time (MTT), by 36.9% and 38.4%, respectively, compared to the standard uniphasic injection protocol in the CV. However, measurement of the permeability surface area product and extravascular extracellular space volume favors a single fast bolus of the same contrast amount. The two-compartment model and the modified Kety model also benefited from the single fast bolus. The effect of variation in the arterial input function and tumor pathophysiology on the applicability of the recommended injection was also investigated. Based on computer simulation for a range of variations in the arterial input function and pathophysiology, the recommended biphasic injection was found to improve the precision in blood flow and MTT estimates by 31.4% and 36.5% on average, respectively, compared to the uniphasic injection.

The lengths of the surgical rectum and peritoneal reflection were important factors in treatment modality of rectal tumor. To evaluate the surgical length of rectum, we measured the length of the peritoneal reflections, sacral promontory and termination of the taenia coli from the anal verge by rigid sigmoidoscope in 23 male and 23 females during operation. The mean lengths of the sacral promontory were 16.5+/- 2.2 cm and 16.1+/-2.2 cm in the males and females, respectively. As for the peritoneal reflection, the results were anterior (8.8+/-2.2 cm, 8.1+/-1.7 cm), lateral (10.8+/-2.7 cm, 11.4+/-1.9 cm) and posterior (13.8+/-2.5 cm, 14.0+/-1.9 cm), respectively. There were no statistically significant differences between male and female. And only height had a correlation with the length of sacral promontory both in male and female (p=0.015 and p=0.018, respectively). For all the estimated lengths, the length of the sacral promontory had a correlation with the lengths of the anterior (p<0.001 and p=0.001) and posterior (p<0.001 and p<0.001) peritoneal reflections in males and females, respectively. We suggest that the intra-operative lengths of the rectum and peritoneal reflection will be useful information for treatment modality of rectal tumor clinically in Korean.

Background/aims: The androgen dehydroepiandrosterone (DHEA) attenuates allergic inflammatory airway reactions by down-regulating the Th2 response in mice. The purpose of this study was to investigate whether DHEA suppresses Th2 cytokine production in cultured peripheral blood mononuclear cells (PBMCs) from asthmatic patients., Methods: Sixty-one consecutive suspected asthmatic or non-asthmatic men underwent tests for asthma. PBMCs from each subject were cultured with and without DHEA (0.01~10 microM) for 48 h. The concentrations of interferon (IFN)-gamma, interleukin (IL)-5, and IL-10 in the culture supernatant were measured via an enzyme-linked immunosorbent assay., Results: In PBMCs from subjects exhibiting methacholine airway hyperresponsiveness (AHR), DHEA significantly suppressed IL-10, IL-5, and IFN-gamma production in a dose-dependent manner (all p<0.001) and tended to increase the IFN-gamma/IL-5 ratio (p=0.087). DHEA (10 microM) suppressed cytokine production to a greater degree in subjects with AHR compared with those without AHR (IL-5: 24.0+/-7.8% vs. 40.9+/-3.6%, p<0.01; IFN-gamma: 29.7+/-7.0% vs. 54.5+/-5.1%, p<0.01). Cytokine suppression was significantly related to AHR, serum total IgE levels, and skin reactivity to house dust mites., Conclusions: DHEA suppressed both Th1 and Th2 responses, with a Th1 bias, and the degree of suppression was associated with the severity of AHR or atopy. Therefore, DHEA may be a useful therapy for asthma.

Background & Objective: The presence of adhesions after middle ear surgery is not uncommon. Fibrosis can cause conductive hearing loss and it contributes to retraction of the tympanic membrane in the post-surgery patient. The purpose of this study was to evaluate the anti-adhesive effect of Seprafilm and MeroGel in the abraded mucosa of a guinea pig's middle ear., Materials and Methods: Fifteen pathogen-free adult male albino guinea pigs weighing 250-300g each were used. Under an aseptic condition, the middle ear mucosa was abraded using a pick through a myringotomy incision. Seprafilm, MeroGel and Gelfoam, respectively, were then packed into guinea pigs' middle ear cavities. Auditory brainstem responses (ABRs) were assessed preoperatively and 3 weeks after operation., Results: The ABR results at postoperative week 3 showed no statistically significant difference for the myringotomy and postpacking, except for the MeroGel packing. However, there was no significant threshold on the 6 weeks' postoperative ABR. The Gelfoam group demonstrated extensive fibrosis and adhesion within the bulla cavity. The Seprafilm and MeroGel groups showed no adhesion in the middle ear cleft after abrasion of the mucosa., Conclusion: From these results, we suggest the use of Seprafilm and MeroGel to improve the results of otosurgery.

Unlabelled: There has been a steady increase in the number of cases of methicillin-resistant Staphylococcus aureus (MRSA) otorrhea; this is a growing medical concern. For otological surgery in children, octylcyanoacrylate can be an alternative method of closure for surgical incisions. Recent in vitro studies have shown that octylcyanoacrylate is effective as an antimicrobical barrier. To date, there have been only rare reports on the antibacterial effect of octylcyanoacrylate against MRSA. The purpose of this study is to determine the antimicrobial effects of octylcyanoacrylate against the MRSA that was isolated from patients with chronic suppurative otitis media., Materials and Methods: Clinical MRSA (n=20) bacteria and methicillin-sensitive SA (MSSA) (n=20) were obtained from patients. The susceptibilities to various antibiotics were determined by disk diffusion method., Results: MSSA was sensitive to octylcyanoacrylate. The antibacterial activity of octylcyanoacrylate was weak against MRSA., Conclusion: Our results demonstrated that octylcyanoacrylate has slight antibacterial activity against MRSA.

Background and Objective: The aim of this study was to evaluate whether a combination of expanded human mesenchymal stem cells (hMSCs) with hyaluronic acid gel in human demineralized bone matrix (hDBM) can promote osteogenesis in a mastoid obliteration procedure, with using the guinea pig as an animal model., Materials and Methods: Fourteen male guinea pigs were used for the experiment. Bulla obliteration using 6-diamidino-2-phenylindole (DAPI)-labeled hMSCs (2x10(6)) loaded into hDBM with hyaluronic acid hydrogel was performed in the experimental group (n=7). The control group was obliterated using hDBM only (n=7). The histologic findings and microCT images were obtained from each bulla at 3 and 7 weeks postsurgery., Results: The increased soft tissue intensity caused by chondrogenic differentiation around the implanted hMSCs-loaded hDBM was identified, as compared to the hMSCs-free hDBM group. All the hMSCs-loaded hDBM at 7 weeks post-implantation displayed greater amounts of bone filling the bulla space, as compared to the hMSCs-free hDBM implanted group. In the hMSCs-free hDBM group, microCT shows incomplete new bone formation, as compared to the hyaluronic acid gel-hMSCs treated group., Conclusion: The successful formation of bone using allogeneic hMSCs loaded onto hDBM and hyaluronic acid hydrogel to repair critically sized bulla defects in the guinea pig model was accompanied with the absence of any local response to the foreign cells. The use of hMSCs-loaded hDBM and hyaluronic acid hydrogel is appropriate for performing clinical mastoid obliteration.

Background and Aims: There are a range of rates and a number of prognostic factors associated with the local recurrence of colorectal cancer after curative resection. The aim of this study was to identify the potential prognostic factors of local recurrence in patients with colon and rectal cancers., Materials and Methods: A retrospective review of 1,838 patients who underwent curative resection of non-metastatic colorectal cancer was conducted. The patients were treated between 1994 and 2004, and had a minimum follow-up of 3 years., Results: There were 994 patients with colon cancer and 844 patients with rectal cancer. The median duration of follow-up was 60.9 +/- 24.5 months. With respect to colon cancer, the local recurrence rate was 6.1% (61 patients). With respect to rectal cancer, 95 patients had a local recurrence (11.3%), the rate of which was statistically greater than the local recurrence rate for colon cancer (p < 0.001). The overall recurrence rate was 16.4% (301 patients), and the local recurrence rate, with or without systemic metastases, was 8.5% (156 patients). Local recurrences occurred within 2 and 3 years in 59.9% and 82.4% of the patients, respectively. In patients with colon and rectal cancer, the pathologic T stage (p = 0.044 and p = 0.034, respectively), pathologic N stage (p = 0.001 and p < 0.001, respectively), and lymphovascular invasion (p = 0.013 and p = 0.004, respectively) were adverse risk factors for local recurrence. The level of the anastomosis from the anal verge was an additional prognostic factor (p = 0.007) in patients with rectal cancer., Conclusion: Compulsive follow-up care of patients with colon and rectal cancers is needed for 3 years after curative resection, especially in patients who have adverse risk factors for local recurrence.

Background and Objective: Interceed (oxidized regenerated cellulose) has been used to prevent postoperative abdominal adhesion. However, the efficacy and safety of using Interceed in middle ear surgery have not been thoroughly studied., Materials and Methods: The animals were divided into two groups: the Interceed group and the Gelfoam (Gelatin sponge) group. In every group, the study was performed on five guinea pigs (ten ears). Under the aseptic condition, the middle ear mucosa was abraded using a pick through a myringotomy incision. Interceed and Gelfoam were then packed into the guinea pigs' middle ear cavities. The auditory brainstem responses (ABRs) were assessed preoperatively and at 3 weeks after the operation with the animals under general anesthesia. Histopathologic study was performed 3 weeks after the operation., Results: The ABR results on postoperative week 3 showed no statistically significant difference for myringotomy and postpacking. The fibrosis, middle ear mucosa thickening and adhesion formation appeared to be less in the Interceed group compared with the Gelfoam group. Any foreign body reaction was not observed in the Interceed group., Conclusion: Our results show that Interceed is nonototoxic and biocompatible with the guinea pig's middle ear cavity. Therefore, these results suggest that Interceed could be used safely in the middle ear as a middle ear packing agent during otosurgery.

Background: KHU14, an ethanolic extract of Radix Gentianae Macrophyllae (Qinjiao), Rhizoma Coptidis (Huanglian) and Citri Unshiu Pericarpium (Wenzhou migan) was tested for its anti-inflammatory effects., Methods: Three out of 20 herbs were found to have anti-inflammatory effects. The formulation of these herbs, i.e. KHU14 was tested for croton oil-induced ear edema, carrageenan-induced paw edema, acetic acid-induced capillary permeability, cotton pellet and delayed type hypersensitivity., Results: KHU14 exhibited anti-inflammatory effects in animal models of acute and chronic inflammation. The anti-inflammatory activity of KHU14 observed was comparable to that of celecoxib. KHU14 inhibited the production of NO and PGE2 in LPS/IFN-gamma-stimulated peritoneal macrophages, and reduced edema and the amount of infiltrated cells in animal models., Conclusion: KHU14 exhibited anti-inflammatory effects as demonstrated in typical immunological tests for anti-inflammation in vitro and in vivo.

We report here on a case of congenital cholesteatoma that extended into the internal auditory meatus and cochlea. A 17-year-old boy underwent surgery for a very large cholesteatoma, which was discovered behind an intact tympanic membrane. Pure tone audiometry revealed an unresponsive ear. High resolution temporal bone computed tomography showed perilabyrinthine extension with its absence in the vestibular area, and destruction of the bony cochlea at the basal turn, the tegmen and the posterior cranial fossa. Magnetic resonance imaging revealed no intracranial extension. Surgical exploration of the middle ear and the mastoid cavity revealed that both the vestibule and the basal turn of the cochlea were filled with a noninfected cholesteatoma. The cholesteatoma extended into the internal auditory meatus through translabyrinthine destruction; it extended into the basal turn of the cochlea through the infralabyrinthine route. The bony segment of the facial nerve canal demonstrated near total dehiscence. The cholesteatoma was removed by the transotic approach. Congenital cholesteatoma is characterized by no specific history. Therefore, early detection of this malady can be challenging, but it is important to prevent such complications as were observed in this reported case.

Background: The recent outcome of adult-to-adult living donor liver transplantation (ALDLT) using small-for-size grafts (SFSGs; GRWR <0.8%) has been excellent after right grafts were exclusively used in large-volume ALDLT centers., Methods: We compared the outcome of ALDLTs using 11 right SFSGs (group R) with that using 18 left SFSGs (group L) of our center. The dysfunction of graft was defined dysfunction as hyperbilirubinemia (>5 mg/dl), prolonged prothrombin time (>2 INR), or uncontrolled ascites (>1,000 ml/day) on 3 consecutive days in posttransplant 7 days, and the dysfunction score (DS; the sum of points given per each sign) of the graft was used to describe the SFSG dysfunction severity., Results: The pretransplant recipient status was similar between the groups, but the 1-year mortality rate was 0% in group R and 33.3% (n = 6) in group L (p = 0.038). The ICU stay was longer in group L (20 days) than in group R (11 days; p = 0.004). Hyperbilirubinemia in group R vs. L was noted in 54.5% vs. 50%, prolonged prothrombin time in 18.2% vs. 50%, and uncontrolled ascites in 54.5% vs. 100%. The DS was lower in group R than in group L (1.3 vs. 2; p = 0.007). The DS was zero in four right liver recipients. On multivariate analysis, the only factor affecting DS was the graft side., Conclusion: The clinical signs of SFSG dysfunction were less arduous and there was no 1-year mortality in cases in group R. Therefore, the right SFSG may be used for ALDLT in the future base on the transplant center's experience.

We propose a novel on-line functional imaging method with which tumor microenvironment can be quantified at the treatment unit. It is an X-ray contrast enhanced method based the (kv) cone beam CT (CBCT) platform and it promises to provide a surrogate measurement of tumor perfusion. The method was tested with 6 rabbits implanted with VX2 tumor. The technique involves a baseline CBCT followed by a contrast enhanced CBCT synchronized with contrast injection. The scan time for each CBCT is approximately 2 minutes during which a set of projections are acquired. The conventional reconstruction approach of contrast enhanced CBCT will give a single volumetric image with no temporal signature. On the other hand, the proposed technique makes use of a mathematical expression to parameterize the wash-in and wash-out behavior of contrast uptake in each voxel. Based on the projection data, the new method uses non-linear optimization to solve for the parameters describing the dynamic characteristics of injected contrast with which tumor perfusion can be derived. In our rabbit study, dynamic contrast enhanced images were reconstructed with the CBCT projections by the proposed method. Results show that the estimated contrast enhancement with the proposed CBCT method is in excellent agreement with the measured enhancement by CT. The proposed CBCT method is sensitive for detecting changes in the tumor microenvironment as a result of radiation treatment., (© 2008 American Association of Physicists in Medicine.)

Background/aims: The purpose of this study was to assess the long-term prognosis of patients with carcinoma obstruction of the left colon and determine the associated clinical and pathological characteristics to identify independent prognostic factors., Methodology: From 1996 to 2003, 915 patients who underwent curative resection for left-sided colon carcinoma were classified as either the obstruction group (n = 169) or the non-obstruction group (n = 746). Clinical and pathological findings were compared between the 2 groups. Univariate and multivariate analyses were performed to identify independent prognostic factors correlated with survival and disease recurrence., Results: Distribution of tumor location, tumor size, macroscopic type and histological grade were found to be different in comparisons between the 2 groups. The tumor stage was more advanced in the obstruction group. The overall and disease-free survival rates were significantly lower in the obstruction group compared to the non-obstruction group. However, the results of the multivariate analysis demonstrated that obstruction itself was not an independent prognostic factor. Instead, patient age, serum carcinoembryonic antigen (CEA) level and tumor stage were significant prognostic indicators for long-term outcome., Conclusions: Obstruction in left-sided colon cancer was not an independent risk factor for long-term patient outcome. The study results confirmed the conventional prognostic factors of patient age, serum CEA level and tumor stage.

Background: Anastomosis leakage is a major complication of rectal surgery. The aim of this study was to identify risk factors for anastomotic leakage after low anterior resection (LAR) in rectal cancer patients and study its impact on long-term prognosis and disease-free survival and overall survival in rectal cancer patients., Methods: Consecutive patients who underwent rectal resection with primary anastomosis below the pelvic peritoneal reflexion for rectal cancer between October 1996 to February 2006 were included., Results: Anastomosis leakage after LAR occurred in 51 patients (4.0%). The median time to leakage was 4 days (range = 2-30 days). In univariate analysis, gender, level of anastomosis less than 4 cm, preoperative concomitant chemoradiation (CCRT), and length of operation greater than 120 min were significantly associated with anastomosis leakage. In a multivariate analysis, gender (p = 0.041; relative risk = 2.007; 95% CI = 1.030-3.912) and preoperative CCRT (p = 0.003; relative risk = 2.861; 95% CI = 1.417-5.778) were identified as independent prognostic factors. The overall survival of the nonleakage group and the leakage group was 80.2% and 64.9%, respectively (p = 0.170). The 5-year disease-free survival rates were not significantly different between the nonleakage and leakage groups (78.1% vs. 65.9%, p = 0.166)., Conclusions: The incidence of anastomotic leakage after low anterior resection is relatively low. Male gender and preoperative CCRT were associated with increased risk for anastomotic leakage after rectal cancer surgery. No effect of anastomosis leakage on local recurrence was found in this series.

Some members of lactic acid bacteria are known to synthesize glutathione (GSH) or to import it from growth medium, whereas others are not. Analysis of the genome sequences of several Leuconostoc spp. indicate the presence of the gene gshA that encodes gamma-glutamylcysteine synthetase, but not the gene gshB encoding glutathione synthetase. We report here that, in cells of Leuconostoc kimchii and Leuconostoc mesenteroides, gamma-glutamylcysteine (gamma-GC) is present in large amount, whereas GSH is not detectable. The level of gamma-GC was higher at the stationary phase than at the exponential phase. Expression of the gshA gene in Leuconostoc spp. analyzed by S1 mapping showed the increased mRNA level upon hydrogen peroxide treatment. From high-resolution S1 mapping, the transcriptional start site was mapped and the putative promoter elements were suggested. This work suggests that gamma-GC has a significant role in Leuconostoc spp. as the major low-molecular-weight thiol.

A geometric calibration method that determines a complete description of source-detector geometry was adapted to a mobile C-arm for cone-beam computed tomography (CBCT). The non-iterative calibration algorithm calculates a unique solution for the positions of the source (X(s), Y(s), Z(s)), detector (X(d), Y(d), Z(d)), piercing point (U(o), V(o)), and detector rotation angles (phi, theta, eta) based on projections of a phantom consisting of two plane-parallel circles of ball bearings encased in a cylindrical acrylic tube. The prototype C-arm system was based on a Siemens PowerMobil modified to provide flat-panel CBCT for image-guided interventions. The magnitude of geometric nonidealities in the source-detector orbit was measured, and the short-term (approximately 4 h) and long-term (approximately 6 months) reproducibility of the calibration was evaluated. The C-arm exhibits large geometric nonidealities due to mechanical flex, with maximum departures from the average semicircular orbit of deltaU(o) = 15.8 mm and deltaV(o) = 9.8 mm (for the piercing point), deltaX and deltaY = 6-8 mm and deltaZ = 1 mm (for the source and detector), and deltaphi approximately 2.9 degrees, deltatheta approximately 1.9 degrees, and delta eta approximately 0.8 degrees (for the detector tilt/rotation). Despite such significant departures from a semicircular orbit, these system parameters were found to be reproducible, and therefore correctable by geometric calibration. Short-term reproducibility was < 0.16 mm (subpixel) for the piercing point coordinates, < 0.25 mm for the source-detector X and Y, < 0.035 mm for the source-detector Z, and < 0.02 degrees for the detector angles. Long-term reproducibility was similarly high, demonstrated by image quality and spatial resolution measurements over a period of 6 months. For example, the full-width at half-maximum (FWHM) in axial images of a thin steel wire increased slightly as a function of the time (delta) between calibration and image acquisition: FWHM=0.62, 0.63, 0.66, 0.71, and 0.72 mm at delta = 0 s, 1 h, 1 day, 1 month, and 6 months, respectively. For ongoing clinical trials in CBCT-guided surgery at our institution, geometric calibration is conducted monthly to provide sufficient three-dimensional (3D) image quality while managing time and workflow considerations of the calibration and quality assurance process. The sensitivity of 3D image quality to each of the system parameters was investigated, as was the tolerance to systematic and random errors in the geometric parameters, showing the most sensitive parameters to be the piercing point coordinates (U(o), V(o)) and in-plane positions of the source (X(s), Y(s)) and detector (X(d), Y(d)). Errors in the out-of-plane position of the source (Z(s)) and detector (Z(d)) and the detector angles (phi, theta, eta) were shown to have subtler effects on 3D image quality.

Purpose: Internal tumor and organ movement is important when considering intensity-modulated radiotherapy for patients with cancer of the cervix because of the tight margins and steep dose gradients. In this study, the internal movement of the tumor, cervix, and uterus were examined using serial cinematic magnetic resonance imaging scans and point-of-interest analysis., Methods and Materials: Twenty patients with Stage IB-IVA cervical cancer underwent pelvic magnetic resonance imaging before treatment and then weekly during external beam radiotherapy. In each 30-min session, sequential T(2)-sagittal magnetic resonance imaging scans were obtained. The points of interest (cervical os, uterine canal, and uterine fundus) were traced on each image frame, allowing the craniocaudal and anteroposterior displacements to be measured. The mean displacements and trends were analyzed using mixed linear models. Prediction intervals were calculated to determine the internal target margins., Results: Large interscan motion was found for all three points of interest that was only partially explained by the variations in bladder and rectal filling. The intrascan motion was much smaller. Both inter- and intrascan motion was greatest at the fundus of the uterus, less along the canal, and least at the cervical os. The isotropic internal target margins required to encompass 90% of the interscan motion were 4 cm at the fundus and 1.5 cm at the os. In contrast, smaller margins of 1 cm and 0.45 cm, respectively, were adequate to encompass the intrascan motion alone., Conclusion: Daily soft-tissue imaging with correction for interfractional motion or adaptive replanning will be important if the benefits of intensity-modulated radiotherapy are to be maximized in women with cervical cancer.

Both BCG and dehydroepiandrosterone (DHEA) induce Th1 immune responses and suppress Th2 allergic reactions. To investigate whether the combination of BCG and DHEA has an additive effect on asthma prevention, BALB/c mice (n = 10 per group) were given an intraperitoneal injection of BCG at the beginning of sensitization, and fed mice chow containing DHEA throughout the study. In female mice, the combined administration of 2 x 10(4) CFUs BCG and 0.01% DHEA effectively suppressed the ovalbumin-induced increase in airway sensitivity to methacholine (56.5 vs. 8.2 mg/mL, p < 0.01), while BCG (13.9 mg/mL) or DHEA (17.9 mg/mL) alone did not. However, the addition of high dose (0.1%) DHEA decreased the efficacy of high dose (2 x 10(5) CFUs) BCG in suppressing the airway responsiveness and eosinophilia. In male mice, the treatments with BCG and/or DHEA were less effective, and the interferon-gamma/interleukin-4 ratio in the splenocyte supernatant was significantly higher and the ovalbumin-specific IgE concentration in the serum was significantly lower as compared to female mice. In conclusion, the combination of low doses of BCG and DHEA had an additive effect in suppressing the development of airway hypersensitivity. Androgens in males and DHEA overdose might reduce the efficacy of BCG.

Purpose: To measure regression of cancer of the uterine cervix during external beam radiotherapy using magnetic resonance imaging, derive radiobiologic parameters from a mathematical model of tumor regression, and compare these parameters with the pretreatment measurements of tumor hypoxia., Methods and Materials: A total of 27 eligible patients undergoing external beam radiotherapy for cervical cancer underwent weekly magnetic resonance imaging scans. The tumor volume was assessed on each of these scans and the rate of regression plotted. A radiobiologic model was formulated to simulate the effect on tumor regression of the surviving proportion of cells after 2 Gy (SP(2)), the cell clearance constant (clearance of irreparably damaged cells from the tumor [T(c)]), and accelerated repopulation. Nonlinear regression analysis was used to fit the radiobiologic model to the magnetic resonance imaging-derived tumor volumes and to derive the estimates of SP(2) and T(c) for each patient. These were compared to the pretreatment hypoxia measurements., Results: The initial tumor volume was 8-209 cm(3). The relative reduction in volume during treatment was 0.02-0.79. The simulations using representative values of the independent biologic variables derived from published data showed SP(2) and T(c) to strongly influence the shape of the volume-response curves. Nonlinear regression analysis yielded a median SP(2) of 0.71 and median T(c) of 10 days. Tumors with a high SP(2) >0.71 were significantly more hypoxic at diagnosis (p = 0.02)., Conclusion: The results of our study have shown that cervical cancer regresses during external beam radiotherapy, although marked variability is present among patients and is influenced by underlying biologic processes, including cellular sensitivity to radiotherapy and proliferation. Better understanding of the biologic mechanisms might facilitate novel adaptive treatment strategies in future studies.

Background: Some sporadic colon cancers and hereditary nonpolyposis colorectal cancer (HNPCC) have been known by a constitutional defect in mismatch gene repair (MMR) and dysfunction in of this MMR system, which lead to an aberrant phenotype that can cause microsatellite instability. However, the clinicopathologic features of still existing microsatellite stable (MSS) colon cancer remain to be investigated., Method: We compared the gene expression patterns of nine tumor tissues of HNPCC and nine tumor tissues of sporadic colon cancer with their adjacent pathologically normal, MSS tissues by modified differential display-polymerase chain reaction, selected four potential marker genes, and confirmed their reproducibility by reverse transcriptase-polymerase chain reaction., Results: Reg I, MLCK, and MYH11 in tumors of MSS HNPCC showed significant differences in gene expression pattern compared with the adjacent pathologically normal tissues (P = 0.028, P = 0.002, and P = 0.001, respectively). Similar differences in expression patterns for the same set of genes were seen between the sporadic colon cancer group and their adjacent pathologically normal tissues (P = 0.012, P = 0.003, and P = 0.002, respectively)., Conclusion: We suggest that the three cancer-associated differentially expressed genes in MSS sporadic colon cancer or MSS HNPCC might be potential tumor markers.

The nasal cavity is a rare site of origin of neuroendocrine tumors. They can be classified typical carcinoid, atypical carcinoid and small cell carcinoma, neuroendocrine type. The tumor histology and prognosis correlate closely. The typical carcinoid tumors are well differentiated with benign course. The treatment of the typical carcinoid is a conservative surgery and the prognosis is good. But, typical carcinoid tumor of the nasal cavity was extremely rare, so the treatment has not been established. We report a case of typical carcinoid tumor of the nasal cavity in a 76-year-old man who treated by conservative surgery using sinus endoscopy. To the best of our knowledge this is the first report on an typical carcinoid in the nasal cavity.

Reversion-inducing cysteine-rich protein with Kazal motifs (RECK) is a novel membrane-anchored matrix metalloproteinase (MMP) inhibitor. RECK, MMP-2, and MMP-9 are believed to play crucial roles in tumor progression. This study was designed to examine the prognostic value of RECK, MMP-2, and MMP-9 in conjunction with other clinicopathologic factors in patients of T3-T4 node-negative colorectal cancer. RECK and MMP expression was observed using immunohistochemical analysis of the primary tumor from 89 patients with curatively resected T3-4 N0 colorectal cancer retrospectively. High RECK expression was observed in 51 cases, whereas expression was low in the other 38 cases. MMP-2 and MMP-9 expression was positive in cancer cells in 24 and 33 cases, respectively. RECK and MMP-2 expression was not significantly associated with any clinicopathologic factors. However, expression of MMP-9 was correlated with tumor location. A statistically significant inverse correlation was found between RECK and MMP-2 expression, and a statistically significant correlation was found between MMP-2 and MMP-9 expression. However, no association between RECK and MMP-9 expression was observed. Univariate analysis demonstrated that rectal tumor location, preoperative carcinoembryonic antigen more than 5 ng/mL, positive lymphatic invasion, less than 12 dissected lymph nodes, and positive MMP-9 expression were poor prognostic factors of disease-free survival. A multivariate analysis confirmed that enhanced MMP-9 expression was an independent and significant factor for prediction of a poor prognosis. In addition, positive lymphatic invasion and less than 12 dissected lymph nodes were significant negative prognostic factors. In conclusion, MMP-9 status represents a novel prognostic factor in evaluation of T3-T4 node-negative colorectal cancer.

Unlabelled: Sensorineural hearing loss, which is limited to the cochlear basal turn, due to acute or chronic otitis media has been reported in clinical and experimental studies. In the present study, the effect of intratympanic dexamethasone on endotoxin-induced cochlear damage was investigated by measuring the cochlear blood flow and hearing., Materials and Methods: Ten male Sprague-Dawley rats were inoculated with lipopolysaccharide (LPS), and divided into 2 groups of five rats each. One hour after intratympanic inoculation, the group A received 40 microl of phosphate-buffered saline (PBS) in the right middle ear cavity, group B received 40 microl of dexamethasone. The treated animals were examined 24 h after inoculation using auditory brainstem response (ABR) and cochlear blood flow (CBF)., Results: The elevated threshold decreased significantly after intratympanic dexamethasone administration compared to the PBS-treated group. Intratympanic dexamethasone administration to the round window of rats led to a statistically significant increase in CBF compared to the PBS-treated group (p <0.05). The response to round window application of prostaglandin E1 (PGE1) in the dexamethasone-treated group was better than in the PBS-treated group., Conclusion: Our results showed that intratympanic dexamethasone treatment was effective in protecting the function of the cochlea against endotoxin-induced otitis media.

Background and Aims: Approximately 20% of patients with colorectal cancer are initially diagnosed with stage IV. The majority has non-curative metastases, and their chances of survival are pitiful. This study evaluated the prognostic factors of survival and the access to the effective treatment in accordance with patients., Materials and Methods: We retrospectively analyzed 503 patients for demographics, tumor characteristics, the treatment modality, and the survival outcome. Curative operation was performed in 127 patients and palliative operation in 376 patients., Results: For the curative operation group, the 5-year survival rate was 34.5%, and the prognostic factors of survival and recurrence were male gender (p = 0.003, 0.009), pathologic N stage (p < 0.001, p = 0.002), and perineural invasion (p = 0.003, p = 0.026), respectively. For the non-curative operation group, the 5-year survival rate was 0%, and the median survival duration was 16.5 months. The potential predictors of survival for the palliative operation group were carcinoembryonic antigen level (p = 0.013), differentiation of tumor (p = 0.011), resection of primary tumor (p < 0.001), and chemotherapy (p < 0.001). But for the 131 patients with asymptomatic incurable disease, only chemotherapy was related to survival (p < 0.001)., Conclusions: The potential predictors of survival for curative stage IV colorectal cancer were male gender, pathologic N stage, and perineural invasion. Resection of the primary tumor and chemotherapy showed benefit for the incurable patients. But for the asymptomatic incurable patients, only chemotherapy prolonged the survival.

Unlabelled: The antibacterial effects of tea-tree oil against the formation of methicillin-resistant Staphylococcus aureus (MRSA) biofilm on the surface of the tympanostomy tubes was evaluated., Materials and Methods: Silicone tympanostomy tubes were pretreated with normal saline for 12 hours, the control group (n=4), with 100% tea-tree oil, experimental group A (n=3), or with 50% tea-tree oil, experimental group B (n=3). All the tubes were incubated in a MRSA solution for 2 days and then processed for evaluation using scanning electron microscopy., Results: The development of the biofilm mode of growth of MRSA was observed in the saline-treated control group. In contrast, only focal biofilms were present on the tube surface in experimental group A and considerable reduction of biofilm with destruction of the MRSA cells was shown in experimental group B., Conclusion: From these results, the antimicrobial effect of tea-tree oil against biofilm formation on tympanostomy tubes in vitro has been verified.