Objectives The unique feature of cholesteatoma is the hyperproliferation and accumulation of keratin debris within the middle ear and mastoid cavity, a process that leads to destruction of the surrounding structures in the temporal bone. The proliferation of keratin and the resulting bony destruction in the cholesteatoma matrix are associated with apoptosis. FasL, when conjugated with Fas, is known to trigger apoptosis. This study aimed to analyze the temporal bone patterns in patients with cholesteatoma and the expression of FasL in the cholesteatoma matrix.
Methods. From July 1999 to July 2001, all patients with cholesteatoma who received ear operations at the China Medical University Hospital were enrolled in this study. Surgical specimens from all patients were shown histopathologically to have cholesteatoma. The temporal bone patterns in these patients were reviewed by high resolution temporal bone computed tomography. Immunoperoxidase stain with a monoclonal antibody to FasL evaluated the expression of FasL in the cholesteatoma matrix. Postauricular skin, which was harvested during the same surgical procedure served as the control.
Result& The temporal bone patterns in the patients were classified as blunted scutum (58%), ossicular chain erosion (58%), erosion of tegmen mastoid-tympanicum (30%), erosion of the otic capsule (25%) and marked sclerosis (50%). Expression of FasL was not detected in the postauricular skin, cholesteatoma matrix or subepidermal granulation tissue.
Conclusions. The temporal bone patterns in the patients with cholesteatoma included bony destruction and new bone formation. No expression of FasL was detected in the cholesteatoma matrix or subepidermal granulation tissue. This indicates that apoptosis in the cholesteatoma matrix may not be through the FasL pathway. Therefore, the destruction of the temporal bone in patients with cholesteatoma may not be associated with FasL.
The current real-time PCR (polymerase chain reaction) platforms, which can detect and quantify several target DNA simultaneously, are equipped with discrete optics and detectors for different fluorescence wavelengths. However, the optical loss, due to the different lengths of the channels for several dyes, lowers the performance of fluorescence detection. Especially on the PCR platforms of lab-on-a-chip system, for the dispersion of the fluorescence in the micro fluidic channels, the received fluorescence is much lower than the emitted. To enhance the received intensity on the detection system is therefore a critical issue. The proposed fluorescence detection system, composing of an ultra-sensitive spectrometer, can provide continuous wavelength detection and can be employed for multiple DNA quantification and genotyping in a single reaction. For the tests to the genotyping ability, the melting temperatures of B type HBV and C type HBV can be distinguished by the difference of 1.1degC.The test results in this research show the same degree of sensitivity for DNA quantification and reproducibility within five intra assay samples as compared with a commercial one
Objectives: The relationship between the adenoids and otitis media has been well documented. The purpose of this study was to document the current trends in the bacteriology of the adenoids in children with otitis media with effusion (OME). Comparisons of bacteriology of the adenoids with that of the middle ear fluid are made, and the role of adenoidectomy in treating otitis media with effusion is discussed.
Methods: A prospective investigation of 44 patients with adenoid hyperplasia and OME was performed. All patients received transoral endoscopic adenoidectomy and insertion of tympanostomy tubes. The core adenoid tissue and middle ear fluid were cultured. Presumptive pathogens were identified using standard methods.
Results: The age range of the patients was 3 to 14 years with a mean age of 6.95years; 31 patients were male and 13 were female. Microorganisms were isolated in the core adenoid tissue in 84% (37/44) of the patients and more than two microorganisms were isolated in 41% (20/44) of the patients. Possible pathogenic microorganisms were present in 41% (29/70) of the samples. The most common pathogenic microorganisms were Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae and Pseudomonas aeruginosa. Possible nonpathogenic microorganisms were present in59% (41/70) of the samples. Streptococcus viridans, Neisseria species and coagulase(-) Staphylococcus were the most common. Only one isolate of Neisseria species(2.9%) was cultured from the middle ear effusion.
Conclusions: Our results suggest that the adenoidal reservoir of bacteria may be associated with otitis media with effusion. Although we did not find a significant association between bacteriology of the adenoids and that of middle ear effusion, a significant portion of the reservoir bacteria were pathogenic microorganisms and some of them were oxacillin-resistant or β-lactamase positive. The clinical benefits of adenoidectomy in the health management of children with otitis media with effusion should not be overlooked.
Intensity-modulated radiotherapy with simultaneous integrated boost (IMRT-SIB) reduces overall treatment duration and results in less radiotherapy (RT)-induced dermatitis. However, the use of traditional sequential approach or IMRT-SIB is still under debate since there is not enough evidence of long-term clinical outcomes. The present study investigated 216 patients who underwent breast conserving surgery (BCS) between 2010 and 2013. The median age was 51 years (range, 21-81 years). All patients received IMRT-SIB, 50.4 Gy at 1.8 Gy per fraction to the whole breast and 60.2 Gy at 2.15 Gy per fraction to the tumor bed by integral boost. Among 216 patients, 175 patients received post-operative RT with forward IMRT and 41 patients had Tomotherapy. The median follow-up was 6.4 years. Forty patients (97.6%) in the Tomotherapy arm and 147 patients (84%) in the IMRT arm developed grade 0-1 skin toxicity (P = 0.021). For the entire cohort, the 5-year and 7-year overall survival (OS) rates were 94.4% and 93.1% respectively. The 7-year distant metastasis-free survival rates were 100% vs 89.1% in the Tomotherapy and IMRT arm respectively (P = 0.028). In conclusion, Tomotherapy improved acute skin toxicity compared with forward IMRT-SIB. Chronic skin complication was 1.9%. IMRT-SIB resulted in good long-term survival.
Lung cancer is 1 of the most prevalent cancers globally. Definitive stereotactic ablative radiotherapy (SABR) is suggested for those who are unfit for or refuse surgical intervention. Here we present a patient with 2 lung cancer lesions who received SABR simultaneously with magnetic resonance Linear accelerator (Linac)-magnetic resonance (MR).A 46-years-old man had history of left lower lung cancer post lobectomy in 2018. Two recurrent tumors were found 2 years following, then became enlarged 4 months later.The recurrent tumors were found by computed tomography.SABR was indicated due to inoperability and small size. Simulation was done both by computed tomography and MR scan with ViewRay MRIdian Linac, with the prescription dose being 50 gray in 4 fractions performed every other day within 2 weeks. The 2 lesions were irradiated at the same time with a single isocenter with mean treatment time was 78 minutes.No acute side effect was noted. Follow-up chest computed tomography scan 14 months after SABR showed mild consolidation and pneumonitis over the upper irradiated site favoring radiation-related reasons, while pneumonitis was resolved over the lower irradiated site. Positron emission tomography showed no definite evidence of FDG-avid recurrence. The patient has survived over 18 months following SABR and more than 4 years from the first diagnosis of lung cancer without significant adverse effects.Simultaneous SABR for multiple lung lesions is quite challenging because tumor motion by breathing can increase the risk of missing the target. With help by MR-Linac, simultaneous SABR to multiple lung lesions can be performed safely with efficacy.
To analyze the prognostic factors associated with stage IB-IVA cervical cancer in patients who underwent concurrent chemoradiation therapy (CCRT) and to compare the clinical toxicities and dosimetric parameters of organs at risk between the different radiotherapy techniques.This retrospective study enrolled 93 patients with stage IB-IVA cervical cancer who underwent definitive CCRT between April 2009 and December 2017. Nine patients (9.7%) received 3DCRT, 43 patients (46.2%) underwent VMAT, and 41 patients (44.1%) received tomotherapy, and all of them followed by brachytherapy using a 2D planning technique. The treatment outcomes and related prognostic factors were analyzed. We also compared the clinical toxicities and dosimetric parameters between the different techniques used for the last 30 patients.With a median follow-up of 52.0 months, the 5-year overall survival (OS), progression-free survival (PFS), locoregional recurrence-free survival (LRRFS), and distant metastases-free survival (DMFS) were analyzed. In a Cox proportional hazards regression model, pretreatment SCC Ag > 10 ng/mL was a significant prognostic factor for PFS (hazard ratio [HR] 2.20; 95% confidence interval [CI] 1.03-4.70; P = 0.041), LRRFS (HR, 3.48; 95% CI 1.07-11.26; P = 0.038), and DMFS (HR 2.80; 95% CI 1.02-7.67; P = 0.045). Increasing the rectal volume receiving a radiation dose exceeding 30 Gy (V30 of rectum; odds ratio [OR] 1.15; 95% CI 1.10-1.30; P = 0.03) was associated with a higher possibility of ≥ Grade 2 acute radiation therapy (RT)-related diarrhea. The median rectal V30 values were 56.4%, 97.5%, and 86.5% for tomotherapy, 3-dimensional conformal radiation therapy (3DCRT), and volumetric modulated arc therapy (VMAT), respectively (P < 0.001). In addition, the chance of experiencing ≥ Grade 2 acute diarrhea were 10.0%, 66.7%, and 54.5% for tomotherapy, 3DCRT, and VMAT, respectively (P = 0.029).Patients with pretreatment SCC Ag ≤ 10 ng/mL have better PFS, LRRFS, and DMFS than those with pretreatment SCC Ag > 10 ng/mL. The rectal V30 is a significant predictor of severe acute diarrhea. Tomotherapy significantly decreased the rectal V30, reducing the severity of acute RT-related diarrhea during external beam RT. Trial registration This study was approved by the institutional review board at Kaohsiung Medical University Hospital. The registration number is KMUHIRB-E(I)-20190054 and retrospectively registered on 2019/3.
Aberrant neutrophil extracellular trap (NET) formation and the loss of barrier integrity in inflamed intestinal tissues have long been associated with inflammatory bowel disease (IBD). However, whether NETs alter intestinal epithelium permeability during colitis remains elusive. Here, we demonstrated that NETs promote the breakdown in intestinal barrier function for the pathogenesis of intestinal inflammation in mouse models of colitis. NETs were abundant in the colon of mice with colitis experimentally induced by dextran sulfate sodium (DSS) or 2,4,6-trinitrobenzene sulfonic acid (TNBS). Analysis of the intestinal barrier integrity revealed that NETs impaired gut permeability, enabling the initiation of luminal bacterial translocation and inflammation. Furthermore, NETs induced the apoptosis of epithelial cells and disrupted the integrity of tight junctions and adherens junctions. Intravenous administration of DNase I, an enzyme that dissolves the web-like DNA filaments of NETs, during colitis restored the mucosal barrier integrity which reduced the dissemination of luminal bacteria, and attenuated intestinal inflammation in both DSS and TNBS models. We conclude that NETs serve a detrimental factor in the gut epithelial barrier function leading to the pathogenesis of mucosal inflammation during acute colitis.
Increased neutrophil extracellular trap (NET) formation and abundant NET-associated proteins are frequently found in the inflamed colon of patients with inflammatory bowel disease. Peptidyl arginine deiminase 4 (PAD4) activation is essential for the generation of NET and NET-mediated pathogenesis. However, the role of PAD4-dependent NET formation in murine inflammatory bowel disease models and the molecular mechanisms responsible for the altered gut barrier function are unknown.Wild-type and Pad4 knockout (Pad4-/-) mice were administrated 3% dextran sulfate sodium (DSS) in their drinking water. Caco-2 monolayers were used to test the effect of NETs on intestinal barrier function and cytotoxicity. Histones were intrarectally administrated to wild-type mice to determine their effects on intestinal barrier function and cytotoxicity in vivo.PAD4 deficiency reduced the severity of DSS-induced colitis with decreased intestinal NET formation and enhanced gut barrier function and integrity in mice. NETs disrupted the barrier function in intestinal epithelial Caco-2 monolayers through their protein, rather than DNA, components. Pretreatment of NETs with histone inhibitors abrogated the effects on epithelial permeability. Consistent with these observations, adding purified histone proteins to Caco-2 monolayers significantly damaged epithelial barrier function, which was associated with the abnormal distribution and integrity of tight junctions as well as with increased cell death. Furthermore, intrarectal administration of histones damaged the intestinal barrier integrity and induced cytotoxicity in the mouse colon epithelium.PAD4-mediated NET formation has a detrimental role in acute colitis. NET-associated histones directly inhibit intestinal barrier function, resulting in cytotoxicity in vitro and in vivo.Peptidyl arginine deiminase 4–dependent neutrophil extracellular trap formation is detrimental to intestinal barrier function in acute colitis. Neutrophil extracellular trap–associated histones altered the integrity of tight junction and adherens junction proteins as well as induced intestinal epithelial cell death that resulted in increased gut epithelium permeability.
Large vestibular aqueduct syndrome (LVAS) may cause early-onset and progressive fluctuating sensorineural hearing loss (SNHL), and often leads to delayed speech in children. Previous head trauma, baro-trauma, air travel or an upper respiratory infection may lead to loss of hearing function which might recover spontaneously or develop into profound hearing loss. Early diagnosis and hearing aids are helpful to prevent speech disturbance. We present a 5-year-old boy who had had impaired hearing and speech disturbance since childhood. Fluctuating hearing function was demonstrated at another hospital when he was two years of age. CT scan of temporal bone revealed enlarged bilateral vestibular aqueducts. He had been admitted to hospital several times since 2 years of age. On each previous admission, he presented with vertigo and deafness; symptomatic treatment included mannitol and low dose prednisolone. He recovered within 3 days; however, it is unclear whether his recovery was due to the medication or whether it was spontaneous. We present this case to discuss the diagnosis, treatment, and probable pathophysiology of this syndrome.
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