Middle-ear or mastoid granulation pathology associated with retraction of the pars flaccida and low-pitched tinnitus.

OBJECTIVE: This study aimed to evaluate the clinical features and outcomes of patients with middle-ear granulation pathologies associated with attic retractions. METHOD: The clinical records of adult patients with middle-ear granulation pathologies and attic retractions confirmed via computed tomography and surgical exploration between January 2012 and January 2019 were retrospectively reviewed. RESULTS: A total of 59 patients were included. Endoscopic examination showed a normal pars tensa but retraction of the pars flaccida in all patients. No granulation tissue or debris were observed. Low-pitched tinnitus was the principal complaint of 55 patients (100 per cent), followed by ear fullness (14 patients, 23.7 per cent). Of the 59 patients, 52 patients (88.1 per cent) underwent canal wall up mastoidectomy and 7 patients (11.9 per cent) underwent endoscopic endaural atticoantrotomy. No ossicular chain destruction was evident. All patients were followed up for 12 months. Tinnitus disappeared completely in 48 patients (81.4 per cent), improved significantly in 9 patients (15.3 per cent) and improved mildly in 2 patients (3.3 per cent). CONCLUSION: A granulation tissue pathology should be considered when a patient complains of low-pitched tinnitus and exhibits retraction of the pars flaccida. Computed tomography and surgical exploration should be scheduled.

Scanning Electron Microscopy in the Evaluation of Defects to the Ossicular Chain in the Course of Chronic Otitis Media.

OBJECTIVE: Chronic otitis media is a heterogeneous disorder. Chronic suppurative otitis media with cholesteatoma and, to a lesser extent, chronic otitis media with granulation lead to the destruction of bone structures within the middle ear. Bone loss may appear in the prominence of the horizontal semicircular canals and the bony canal of the facial nerve. The inflammatory process may spread to the bony labyrinth of the sigmoidal sinuses and the cranial cavities. MATERIALS AND METHODS: The analysis comprised the examination of fragments of auditory ossicles removed during surgery in 21 patients with various types of chronic inflammation of the middle ear. The purpose of this study was to evaluate the usefulness of scanning electron microscopy in evaluating the erosion of middle ear ossicles in different types of chronic otitis media. Images captured at various magnifications were used for the best possible illustration of the observed lesions in bone tissue. RESULTS: The observed lesions and the degree of bone surface damage were dependent on the type of chronic inflammation of the middle ear. The largest destructive changes in the ossicular chain were observed in chronic otitis media with cholesteatoma; smaller changes were observed in chronic otitis media with granulation. CONCLUSION: In the case of damage to the ossicles inflicted by inflammation, the use of a modeled bone block made of a temporal bone taken from outside the tympanic cavity or a biomaterial prosthesis is a good choice in ossiculoplasty.

Tissue damage in herniated brain parenchyma into giant arachnoid granulations: demonstration with high resolution MRI.

BACKGROUND: Brain herniation (BH) into arachnoid granulation has been remarkable in recent years. PURPOSE: To evaluate the damage in herniated parenchyma into the giant arachnoid granulation (GAG) and to investigate the clinical-demographic importance of this damage. MATERIAL AND METHODS: Patients with BH into GAG were retrospectively included in the study. Each of the patients had at least one high-resolution 3D magnetic resonance imaging (MRI) sequence. The arachnoid granulation dimensions, locations, and origin of herniated parenchyma were evaluated by two experienced radiologists. The demographic and symptomatic features of the patients were recorded from the hospital database. RESULTS: A total of 27 patients (21 females, 6 males; age range 6-71 years; mean age 41.3 years) were found to contain BH into GAG. It was most commonly seen in the transverse sinus (67%); the origin was most common in the cerebellar parenchyma (56%). Abnormal signal and morphology were detected in herniated parenchyma in 11 (47%) patients, atrophy in six, and atrophy and gliosis in five. The most common complaints were headache (47%), while other frequent symptoms were vertigo (15%) and blurred vision (11%). There was a statistically significant positive correlation between frequency of damage in herniated brain parenchyma and the maximal size of GAG (P<0.05). CONCLUSION: In patients with BH into GAG, parenchymal damage may be associated with various symptoms, such as headache and vertigo, although they have not been statistically proven. It is important to carefully evaluate hernia tissue, as the risk of tissue damage may increase in larger GAGs.

Protuberancia ósea con adelgazamiento cortical / Bone protuberance with cortical thinning

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Development of a computer-based quantification method for immunohistochemically-stained tissues and its application to study mast cells in equine wound healing (proof of concept).

BACKGROUND: There is a growing interest in the scientific community to use computer-based software programs for the quantification of cells during physiological and pathophysiological processes. Drawbacks of computer-based methods currently used to quantify immunohistochemical staining are the complexity of use, expense of software and overly-simplified descriptions of protocol thereby limiting reproducibility. The precise role of mast cells in equine cutaneous wound healing is unknown. Given the contribution of mast cells to the chronic inflammation observed in human keloid, a pathology similar to exuberant granulation tissue (EGT) in horses, mast cells might be present in high numbers in equine limb wounds predisposed to EGT. The main goal of this study was to develop a reliable and reproducible quantification method for immunostained tissues using a computer software that is widely available, at no cost, to the scientific community. A secondary goal was to conduct a proof of concept using the newly-established method to quantify mast cells during wound healing at different anatomical sites (body and limb) in horses to see if a different pattern is observed in limb wounds, which are predisposed to EGT. RESULTS: A good intraclass correlation coefficient (ICC, 0.67 p < 0.05) was found between the computer-based ImageJ method and manual counting. An excellent intra-operator ICC of 0.90 (p < 0.01) was found for the ImageJ quantification method while a good interoperator ICC of 0.69 (p < 0.01) was measured. No significant difference was observed between the variation of the ImageJ and that of the manual counting method. Mast cells were localized below the epidermis, around cutaneous appendages and blood vessels. Mast cell numbers did not differ significantly in relation to anatomical location or time of healing. CONCLUSIONS: The computer-based quantification method developed is reliable, reproducible, available, cost-free and could be used to study different physiological and pathological processes using immunohistochemistry.

Absceso glúteo y malformación sacrocoxígea compleja / Gluteal abscess and complex sacrococcygeal malformation

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Reliability of diffusion-weighted magnetic resonance imaging in differentiation of recurrent cholesteatoma and granulation tissue after intact canal wall mastoidectomy.

OBJECTIVE: To assess the reliability of diffusion-weighted magnetic resonance imaging in differentiating recurrent cholesteatoma from granulation tissue after intact canal wall mastoidectomy. METHODS: A prospective study was conducted of 56 consecutive patients with suspected cholesteatoma recurrence after intact canal wall mastoidectomy who underwent diffusion-weighted imaging and delayed contrast magnetic resonance imaging of the temporal bone. The final diagnosis was recurrence in 38 patients and granulation tissue in 18 patients. RESULTS: Cholesteatoma detection on diffusion-weighted imaging based on two sets of readings had sensitivity of 94.7 and 94.7 per cent, specificity of 94.4 and 88.9 per cent, and accuracy of 94.6 and 92.8 per cent, with good intra-observer agreement (Κ = 0.72, p = 0.001). Cholesteatoma detection on delayed contrast magnetic resonance imaging had sensitivity of 81.6 and 78.9 per cent, specificity of 77.8 and 66.7 per cent, and accuracy of 80.4 and 75.0 per cent, with fair intra-observer agreement (Κ = 0.57, p = 0.001). The mean cholesteatoma diameter on diffusion-weighted imaging was 7.7 ± 1.8 and 7.9 ± 1.8 mm, with excellent intra-observer agreement (Κ = 0.994, p = 0.001). CONCLUSION: Diffusion-weighted imaging is a reliable method for differentiating recurrent cholesteatoma and granulation tissue after intact canal wall mastoidectomy.

Evaluation of giant arachnoid granulations with high-resolution 3D-volumetric MR sequences at 3T.

PURPOSE: To evaluate the contribution to the diagnosis of the giant arachnoid granulations (AGs) of three-dimensional (3D) high-resolution magnetic resonance (MR) imaging sequences such as T2-weighted sampling perfection with application optimized contrasts using different flip-angle evolution (SPACE) and post-contrast T1-weighted magnetization prepared rapid gradient echo (MPRAGE). MATERIALS AND METHODS: Patients with 45 giant AGs were included in this retrospective study. All the patients were performed 3D T2-weighted SPACE and contrast enhanced MR venography sequences, as well as conventional cerebral MR imaging sequences. Post-contrast T1 weighted MPRAGE sequence were performed on 38/45 patients. All cerebral MR examinations were reviewed by the 2 neuroradiologists. Each GA was evaluated carefully to assess location and mean diameter. RESULTS: The most common location for giant AGs was at both transverse sinuses. Fluid signal feature within the giant AGs was not isointense to CSF on SE T1 and FLAIR MR imaging in 32 of 45 giant AGs. There were cerebral herniation into AG in 10 (22.2 %) of 45 giant AGs. 33 (73.3 %) of 45 giant AGs had central vein finding into AG in contrast enhanced MR venography. Signal void phenomenon into AG in 3D T2-weighted SPACE MR sequence was identified in 28 (62.2 %) of 45 giant AGs. CONCLUSIONS: Fluid within giant AGs had no completely CSF-like signal intensity on conventional and 3D high-resolution MR imaging sequences. Majority of CSF-incongruent fluid within giant AGs on conventional sequences is mostly due to intra-AG CSF flow.

The diagnosis and management of supernumerary nasal teeth.

OBJECTIVE: To discuss the reasons for misdiagnosis of supernumerary nasal teeth. METHODS: Clinical data of four supernumerary nasal tooth patients were analysed retrospectively at visits to our otolaryngology department between 2005 and 2018. RESULTS: All four patients were male and had a supernumerary nasal tooth in the right nasal cavity. Three of the four patients had previously been misdiagnosed. All the supernumerary nasal teeth were surrounded by granulation tissue or hypertrophic nasal mucosa, and were subsequently confirmed by computed tomography and endoscopy. The granulation tissue or hypertrophic nasal mucosa was removed using microwave ablation, and the supernumerary nasal teeth successfully removed by endoscopy. CONCLUSION: Supernumerary nasal teeth are rare, and are usually misdiagnosed because such teeth are surrounded by hypertrophic nasal mucosa or granulation tissue. They can be confirmed by computed tomography and endoscopy.

A Design-Based Stereologic Method to Quantify the Tissue Changes Associated with a Novel Drug-Eluting Tracheobronchial Stent.

BACKGROUND: Granulation tissue is a common complication of airway stenting, but no published methods can quantify the volume and type of tissue that develops. OBJECTIVE: To use design-based stereology to quantify changes in tissue volume and type associated with airway stenting. METHODS: We compared drug-eluting stents (DES) filled with gendine to standard silicone stents in pigs in an assessor-blinded randomized trial. Tracheal stents were placed via rigid bronchoscopy. After 1 month, animals were euthanized and necropsies were performed. Antimicrobial effects of the DES were assessed in trachea tissue samples, on the DES surface, and with residual gel from the DES reservoir. Tracheal thickness was measured using orthogonal intercepts. Design-based stereology was used to quantify the volume density of tissues using a point-counting method. The volume of each tissue was normalized to cartilage volume, which is unaffected by stenting. RESULTS: Pigs were randomized to DES (n = 36) or control stents (n = 9). The drug was successfully eluted from the DES, and the stent surface showed antibacterial activity. DES and controls did not differ in tissue microbiology, tracheal thickness, or granulation tissue volume. Compared to nonstented controls, stented airways demonstrated a 110% increase in soft-tissue volume (p = 0.005). Submucosal connective tissue (118%; p < 0.0001), epithelium (70%; p < 0.0001), submucosal glands (47%; p = 0.001), and smooth muscle (41%; p < 0.0001) increased in volume. CONCLUSION: Stenting doubles the volume of soft tissue in the trachea. Design-based stereology can quantify the tissue changes associated with airway stenting.

Post-transplantation laryngeal actinomycosis.

A case of laryngeal actinomycosis occurred after bone marrow transplantation was reported. The patient was a 14-year-old girl who had a history of bone marrow transplantation for the treatment of acute lymphocytic leukemia 4month before the onset of the disease. She was referred to our hospital complaining persistent sore throat since 2weeks ago. Fiberscopic observation proved the presence of white tumor-like mass on her right arytenoid of the larynx. As CT image demonstrated that the mass was localized at the arytenoid region with central low-density area surrounded by granulation tissue, we underwent biopsy under local anesthesia. Excision of the mass proved it to be a soft granulation including sulfur granules. Oral administration of amoxicillin 750mg per day was initiated as a postoperative medication. On day 17, histological study confirmed that the tumor-like mass was Actinomyces granuloma, and therefore amoxicillin administration continued. The medication was effective to subside the disease and the arytenoid lesion healed on day 31. Amoxicillin was further administered until day 70 to prevent recurrence. At 6month after the biopsy, she was free from the disease.

Cholesteatoma vs granulation tissue: a differential diagnosis by DWI-MRI apparent diffusion coefficient.

PURPOSE: To diagnose cholesteatoma when it is not visible through tympanic perforation, imaging techniques are necessary. Recently, the combination of computed tomography and magnetic resonance imaging has proven effective to diagnose middle ear cholesteatoma. In particular, diffusion weighted images have integrated the conventional imaging for the qualitative assessment of cholesteatoma. Accordingly, the aim of this study was to obtain a quantitative analysis of cholesteatoma calculating the apparent diffusion coefficient value. So, we investigated whether it could differentiate cholesteatoma from other inflammatory tissues both in a preoperative and in a postoperative study. METHODS: This study included 109 patients with clinical suspicion of primary or residual/recurrent cholesteatoma. All patients underwent preoperative computed tomography and magnetic resonance imaging with diffusion sequences before primary or second-look surgery to calculate the apparent diffusion coefficient value. RESULTS: We found that the apparent diffusion coefficient values of cholesteatoma were significantly lower than those of non cholesteatoma. In particular, the apparent diffusion coefficient median value of the cholesteatoma group (0.84 × 10- 3 mm2/s) differed from the inflammatory granulation tissue (2.21 × 10- 3 mm2/s) group (p < 2.2 × 10- 16). Furthermore, we modeled the probability of cholesteatoma by means of a logistic regression and we determined an optimal cut-off probability value of ~ 0.86 (specificity = 1.0, sensitivity = 0.97), corresponding to an apparent diffusion coefficient cut-off value of 1.37 × 10- 3 mm2/s. CONCLUSIONS: Our study has demonstrated that apparent diffusion coefficient values constitute a valuable quantitative parameter for preoperative differentiation of cholesteatomas from other middle ear inflammatory diseases and for postoperative diagnosis of recurrent/residual cholesteatomas.

ADC Benchmark Range for Correct Diagnosis of Primary and Recurrent Middle Ear Cholesteatoma.

OBJECTIVES: Magnetic resonance imaging (MRI) and in particular diffusion-weighted imaging (DWI) have been broadly proven to be the reference imaging method to discriminate between cholesteatoma and noncholesteatomatous middle ear lesions, especially when high tissue specificity is required. The aim of this study is to define a range of apparent diffusion coefficient (ADC) values within which the diagnosis of cholesteatoma is almost certain. METHODS: The study was retrospectively conducted on a cohort of 124 patients. All patients underwent first- or second-look surgery because primary or secondary acquired cholesteatoma was clinically suspected; they all had preoperative MRI examination 15 days before surgery, including DWI from which the ADC maps were calculated. RESULTS: Average ADC value for cholesteatomas was 859,4 × 10-6 mm2/s (range 1545 × 10-6 mm2/s; IQR = 362 × 10-6 mm2/s; σ = 276,3 × 10-6 mm2/s), while for noncholesteatomatous inflammatory lesions, it was 2216,3 × 10-6 mm2/s (range 1015 × 10-6 mm2/s; IQR = 372,75 × 10-6 mm2/s; σ = 225,6 × 10-6 mm2/s). Interobserver agreement with Fleiss' Kappa statistics was 0,96. No overlap between two groups' range of values was found and the difference was statistically significant for p < 0.0001. CONCLUSIONS: We propose an interval of ADC values that should represent an appropriate benchmark range for a correct differentiation between cholesteatoma and granulation tissue or fibrosis of noncholesteatomatous inflammatory lesions.

An In-vivo Prospective Study of the Diagnostic Yield and Accuracy of Optical Biopsy Compared with Conventional Renal Mass Biopsy for the Diagnosis of Renal Cell Carcinoma: The Interim Analysis.

BACKGROUND: Lack of accuracy in preoperative imaging leads to overtreatment of benign renal masses (RMs) or indolent renal cell carcinomas (RCCs). Optical coherence tomography (OCT) is real time and high resolution, enabling quantitative analysis through attenuation coefficient (µOCT, mm-1). OBJECTIVE: To determine the accuracy and diagnostic yield of OCT and renal mass biopsy (RMB) for the differentiation of benign RMs versus RCC and oncocytoma versus RCC. DESIGN, SETTING, AND PARTICIPANTS: From October 2013 to June 2016, 95 patients with solid enhancing RMs on cross-sectional imaging were prospectively included. All patients underwent subsequent excision or ablation. INTERVENTION: Percutaneous, image-guided, needle-based OCT followed by RMB in an outpatient setting under local anaesthesia. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Accuracy and diagnostic yield, µOCT correlated to resection pathology or second biopsy during ablation. Tables (2×2) for RMB, receiver operating characteristic curve for OCT. Mann-Whitney test to differentiate µOCT of RMs. RESULTS AND LIMITATIONS: RMB diagnostic yield was 79% with sensitivity, specificity, positive predictive value, and negative predictive value (NPV) of 100%, 89%, 99%, and 100%, respectively. Diagnostic yield and added value of OCT to differentiate RCC from benign was 99% and 15%, respectively. Significant difference was observed in median µOCT between benign RMs (3.2mm-1, interquartile range [IQR]: 2.65-4.35) and RCCs (4.3mm-1, IQR: 3.70-5.00), p=0.0171, and oncocytomas (3.38mm-1, IQR: 2.68-3.95) and RCCs (4.3mm-1, IQR: 3.70-5.00), p=0.0031. OCT showed sensitivity, specificity, positive predictive value. and NPV of 91%, 56%, 91%, and 56%, respectively, to differentiate benign RMs from RCCs and 92%, 67%, 95%, and 55%, respectively, to differentiate oncocytoma from RCC. Limitations include two reference standards and heterogeneity benign RMs. CONCLUSIONS: Compared with RMB, OCT has a higher diagnostic yield. OCT accurately distinguishes benign RMs from RCCs, and oncocytoma from RCCs, although specificity and NPV are lower. PATIENT SUMMARY: Optical coherence tomography, a new optical scan, exhibits similar sensitivity and positive predictive value than renal mass biopsy, although lower specificity and negative predictive value. Optical coherence tomography has a higher diagnostic yield for diagnosing renal cell carcinoma.

Dimensional Changes of Fresh Sockets With Reactive Soft Tissue Preservation: A Cone Beam CT Study.

PURPOSE: The aim of this study was to assess dimensional changes of the fresh sockets grafted with collagen sheets and maintenance of reactive soft tissue, using cone beam computed tomography (CBCT). MATERIALS AND METHODS: Tooth extractions were performed with maximum preservation of the alveolar housing, reactive soft tissue was left into the sockets and collagen sheets filled bone defects. Cone beam computed tomography were performed before and 3 months after extractions. RESULTS: One hundred forty-five teeth, 60 monoradiculars and 85 molars, were extracted. In total, 269 alveoli were evaluated. In Group A, not statistically significant differences were found between monoradiculars, whereas statistically significant differences (P < 0.05) were found between molars, both for mesial and distal alveoli. In Group B, not statistically significant differences were found between maxillary and mandibular bone changes values (P > 0.05) for all types of teeth. CONCLUSIONS: This study reported an atraumatic tooth extraction, reactive soft tissue left in situ, and grafted collagen sponge may be helpful to reduce fresh socket collapse after extraction procedures.

EW-7197, an activin-like kinase 5 inhibitor, suppresses granulation tissue after stent placement in rat esophagus.

BACKGROUND AND AIMS: Self-expanding metallic stent (SEMS) placement is a well-established method for treating malignant esophageal strictures; however, this procedure has not gained widespread acceptance for treating benign esophageal strictures because of granulation tissue formation. The aim of the present study was to investigate whether EW-7197, a novel per-oral transforming growth factor-ß type I receptor kinase inhibitor, suppressed granulation tissue formation after SEMS placement in the rat esophagus. METHODS: Sixty rats underwent SEMS placement and were randomly divided into 4 groups. Group A (n = 20) received vehicle-treated control for 4 weeks. Group B (n = 20) received 20 mg/kg/day EW-7197 for 4 weeks. Group C (n = 10) received 20 mg/kg/day EW-7197 for 4 weeks followed by vehicle-treated control for 4 weeks. Group D (n = 10) received 20 mg/kg/day EW-7197 for 8 weeks. RESULTS: SEMS placement was technically successful in all rats. Eleven rats, however, were excluded because of stent migration (n = 9) and procedure-related death (n = 2). The luminal diameter in group A was significantly smaller than those in groups B, C, and D (all P < .001). The percentage of granulation tissue area, number of epithelial layers, thickness of submucosal fibrosis, percentage of connective tissue area, and degree of collagen deposition were significantly higher in group A than in groups B, C, and D (all P < .001); however, there were no significant differences among groups B, C, and D. EW-7197 decreased the expression levels of phospho-Smad 3, N-cadherin, fibronectin, α-smooth muscle actin, and transforming growth factor-ß1 and increased the expression level of E-cadherin (all P < .01). CONCLUSIONS: EW-7197 suppressed granulation tissue formation after SEMS placement in the rat esophagus.

Attic cholesteatoma with closure of the entrance to pars flaccida retraction pocket.

We report three patients with pars flaccida-type cholesteatoma (attic cholesteatoma) with closure of the entrance to the cholesteatoma at the time of surgery. These patients were diagnosed with attic cholesteatoma requiring surgery on the basis of abnormal findings of the pars flaccida, audiometry, and temporal bone computed tomography during the clinical course. Intraoperatively, cholesteatoma matrix and granulation tissue were observed behind the intact pars flaccida epithelium, which suggested that the entrance had apparently closed and the continuity with the cholesteatoma matrix disappeared after resolution of inflammation at the pars flaccida. In such patients, a normal pars flaccida may cause cholesteatoma to be initially overlooked, or misdiagnosed as congenital cholesteatoma. The diagnosis should be carefully made on the basis of the clinical course and the results of various examinations.