Cerebellar Abscess Induced by Cochlear Fistula due to Chronic Suppurative Otitis Media.

Cochlear fistulas with cholesteatoma as the primary disease have been reported frequently in the relevant literature. However, there are no reports of cochlear fistula without cholesteatoma due to chronic suppurative otitis media with intracranial complications. We report a case of cochlear fistula due to chronic otitis media that was diagnosed after the onset of a cerebellar abscess. The patient was a 25-year-old man with severe autism. He was admitted to our hospital with otorrhea from his left ear, emesis, and impaired consciousness. Computed tomography (CT) of the head showed left suppurative otitis media, left cerebellar abscess, and brainstem compression due to hydrocephalus. Right extra-ventricular drainage and brain abscess drainage were urgently performed. The next day, foramen magnum decompression and abscess drainage with partial resection of the swollen cerebellum were performed for decompression purposes. He was subsequently treated with antimicrobial therapy, but magnetic resonance imaging of the head showed an increase in the size of the cerebellar abscess. Re-examination of the temporal bone CT scans revealed a bony defect in the left cochlear promontory angle. We assumed that the cochlear fistula was responsible for the otogenic brain abscess. Thus, the patient underwent surgical closure of the cochlear fistula. After the operation, the cerebellar abscess lesion gradually shrank, and his general condition stabilized. Cochlear fistula should be considered in the management of patients with inflammatory middle ear disease associated with otogenic intracranial complications in the middle ear.

Correction: Integrated Multiregional Analysis Proposing a New Model of Colorectal Cancer Evolution.

[This corrects the article DOI: 10.1371/journal.pgen.1005778.].

Histological and immunohistochemical characteristics of undifferentiated small round cell sarcomas associated with CIC-DUX4 and BCOR-CCNB3 fusion genes.

CIC-DUX4 and BCOR-CCNB3 fusion-gene-associated small round cell sarcomas account for a proportion of pediatric small round cell sarcomas, but their pathological features have not been sufficiently clarified. We reviewed a large number of soft tissue tumors registered at our institution, retrieved the cases of unclassified tumors with a small round cell component, and subjected them to histopathological, immunohistochemical, and gene profile analysis. We reviewed 164 cases of unclassified tumors with a small round cell component and analyzed them by RT-PCR and FISH. Tumors positive for a specific fusion-gene were also subjected to histopathological and immunohistochemical examinations. We identified 16 cases of BCOR-CCNB3/CIC-associated (CIC-DUX4 or CIC gene rearrangement-positive) sarcomas. These included seven BCOR-CCNB3 sarcomas and nine CIC-associated sarcomas. Heterogeneous elements included a myxoid spindle cell component in three BCOR-CCNB3 sarcomas and an epithelioid cell component in two CIC-associated sarcomas (one CIC-DUX4-positive and one CIC-DUX4-negative sarcomas). Mitotic activity was low in both heterogeneous components. By immunohistochemistry, in seven BCOR-CCNB3 sarcomas expression of EMA was positive in two cases, of p63 in three, of CD56 in six, of TLE1 in seven, of NKX2.2 in two, of CCNB3 in seven, and of BCOR in six cases (one case could not be tested for BCOR). In nine cases of CIC-associated sarcoma, CD56 was expressed in five, alpha-smooth muscle actin in one, ERG in three, and CD99, WT1 and TLE1 each in eight cases. Both sarcoma types showed not only a small round cell component, but also a myxoid/epithelioid component with low mitotic activity.

A microsensing system for the in vivo real-time detection of local drug kinetics.

Real-time recording of the kinetics of systemically administered drugs in in vivo microenvironments may accelerate the development of effective medical therapies. However, conventional methods require considerable analyte quantities, have low sampling rates and do not address how drug kinetics correlate with target function over time. Here, we describe the development and application of a drug-sensing system consisting of a glass microelectrode and a microsensor composed of boron-doped diamond with a tip of around 40 µm in diameter. We show that, in the guinea pig cochlea, the system can measure-simultaneously and in real time-changes in the concentration of bumetanide (a diuretic that is ototoxic but applicable to epilepsy treatment) and the endocochlear potential underlying hearing. In the rat brain, we tracked the kinetics of the drug and the local field potentials representing neuronal activity. We also show that the actions of the antiepileptic drug lamotrigine and the anticancer reagent doxorubicin can be monitored in vivo. Our microsensing system offers the potential to detect pharmacological and physiological responses that might otherwise remain undetected.

[A Case of Pneumocystis Pneumonia after Cetuximab-based Bioradiotherapy].

Reports of drug-induced interstitial pneumonia caused by Cetuximab have been increasing. Pneumocystis pneumonia is important as a differential diagnosis of drug-induced interstitial pneumonia. We report herein on a 64-year-old man with pneumocystis pneumonia after cetuximab-based bioradiotherapy for laryngeal cancer. After radiotherapy, the patient developed multi-drug resistant pneumonia. Chest CT imaging revealed diffuse ground-glass opacities in the lung field. He was diagnosed as having pneumocystis pneumonia based on the bronchoalveolar lavage (BAL) findings, and then his symptoms improved after treatment with Trimethoprim/Sulfamethoxazole. It is important to assess the risk factor for pneumocystis pneumonia for early its detection and treatment.

Molecular subclassification determined by human papillomavirus and epidermal growth factor receptor status is associated with the prognosis of oropharyngeal squamous cell carcinoma.

Human papillomavirus (HPV) infection is an indicator of good response to chemoradiotherapy in oropharyngeal squamous cell carcinoma (OPSCC), and epidermal growth factor receptor (EGFR) is a molecular-therapeutic target in head and neck squamous cell carcinoma. Here we investigated the prevalence and prognostic significance of HPV infection and EGFR alteration in OPSCC. We analyzed the presence of high-risk HPV using in situ hybridization, protein expressions of p16 and EGFR using immunohistochemistry, and the EGFR gene copy number gain using chromogenic in situ hybridization (CISH) in 105 cases of OPSCC. The biopsy specimens before chemoradiotherapy were used for these analyses. HPV infection and p16 protein overexpression were detected in 53.3% and 52.4% of the OPSCCs, and each factor was associated with better overall survival (P = .0026 and P = .0026) and nonkeratinizing histology (P = .0002 and P = .0004), respectively. EGFR gene copy number gain (high polysomy or amplification) was detected in 12.4% of the OPSCCs and was correlated with EGFR protein overexpression (P = .0667) and worse overall survival (P < .0001). HPV infection and EGFR gene copy number gain (EGFR CISH positive) were mutually exclusive. The HPV-negative/EGFR CISH-positive OPSCCs had significantly worse overall survival than did the HPV-positive/EGFR CISH-negative OPSCCs and HPV-negative/EGFR CISH-negative OPSCCs (P < .0001 and P < .0001, respectively). The EGFR CISH-negative OPSCCs had favorable prognosis irrespective of HPV infection. Our results suggest that EGFR gene copy number gain-positive tumors represent an HPV-negative, aggressive subgroup of OPSCCs. The molecular subclassification of OPSCCs based on HPV infection and EGFR status may serve as important information for appropriate therapeutic strategy.

Integrated Multiregional Analysis Proposing a New Model of Colorectal Cancer Evolution.

Understanding intratumor heterogeneity is clinically important because it could cause therapeutic failure by fostering evolutionary adaptation. To this end, we profiled the genome and epigenome in multiple regions within each of nine colorectal tumors. Extensive intertumor heterogeneity is observed, from which we inferred the evolutionary history of the tumors. First, clonally shared alterations appeared, in which C>T transitions at CpG site and CpG island hypermethylation were relatively enriched. Correlation between mutation counts and patients' ages suggests that the early-acquired alterations resulted from aging. In the late phase, a parental clone was branched into numerous subclones. Known driver alterations were observed frequently in the early-acquired alterations, but rarely in the late-acquired alterations. Consistently, our computational simulation of the branching evolution suggests that extensive intratumor heterogeneity could be generated by neutral evolution. Collectively, we propose a new model of colorectal cancer evolution, which is useful for understanding and confronting this heterogeneous disease.

Tracheobronchomegaly associated with laryngo-tracheal amyloidosis: First case report.

Tracheobronchomegaly (TBM) is a rare enlargement of the tracheal cartilage, also known as Mounier-Kuhn syndrome (MKS). Here, we describe an unusual case of acquired TBM in an adult, caused by amyloid regeneration and associated tracheal weakening, rather than by MKS. CT scan and fiberscopic examination of a 55-year-old woman suffering from severe dyspnea revealed TBM and subglottic stenosis, which was caused by deposition of amyloid tissue. We performed a tracheostomy and vaporized the subglottic stenosis with a CO2 laser, after which we installed a silicone T-tube. After the first operation, re-stenosis occurred, and the procedure was repeated; stenosis was subsequently cured and the dyspnea disappeared, after which the tracheostomy could be closed. This is the first report of adult TBM associated with amyloid deposition in the subglottis and trachea. This diagnosis is very difficult, as amyloid deposition in the trachea can have various clinical presentations.

Surgical approaches to jugular foramen schwannomas: An anatomic study.

BACKGROUND: The variety of surgical approaches to jugular schwannomas makes selection of an approach difficult. The purpose of this study was to define the anatomic elements of these approaches. METHODS: Ten adult cadaveric heads were examined. RESULTS: There are lateral, posterior, and anterior routes that access various parts of the jugular foramen. Removal of the jugular process of the occipital bone provides access to the posterior aspect of the foramen, the infralabyrinthine mastoidectomy provides access to the lateral edge and dome of the jugular bulb, and the preauricular approaches provide access to the anterior margin of the bulb and foramen. Additions to these approaches may include cervical and vertebral artery exposure, facial nerve transposition, foramen magnum exposure, and external canal and condylar resection. CONCLUSION: An understanding of the anatomy of the jugular foramen is crucial in achieving total tumor removal while minimizing risk. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1041-E1053, 2016.

Dual gain of HER2 and EGFR gene copy numbers impacts the prognosis of carcinoma ex pleomorphic adenoma.

We investigated the potential roles of HER2 and EGFR and evaluated their prognostic significance in carcinoma ex pleomorphic adenoma (CXPA). We analyzed HER2 and EGFR overexpression status using immunohistochemistry (IHC) and gene copy number gain by chromogenic in situ hybridization (CISH) in 50 cases of CXPA (40 ductal-type and 10 myoepithelial-type CXPAs). Salivary duct carcinoma was the most common histologic subtype of malignant component (n = 21). Immunohistochemistry positivity and chromogenic in situ hybridization positivity were closely correlated in both HER2 and EGFR. HER2 CISH positivity (mostly gene amplification) and EGFR CISH positivity (mostly gene high polysomy) were present in 19 (40%) and 21 (44%) cases, respectively, and were each significantly correlated with poor outcome (P = .0009 and P = .0032, respectively). Dual gain of HER2 and EGFR gene copy numbers was present in 11 cases (23%) and was the most aggressive genotype. HER2 CISH positivity was more frequently present in ductal-type CXPAs (47%) than in myoepithelial-type CXPAs (10%), whereas the prevalence of EGFR CISH positivity was similar in both histologic subtypes (42% and 50%, respectively). Our results suggest that HER2 and EGFR gene copy number gains may play an important role in the progression of CXPA, in particular ductal-type CXPAs. HER2 CISH-positive/EGFR CISH-positive tumors may be the most aggressive subgroup in CXPA. The molecular subclassification of CXPA based on the HER2 and EGFR status may be helpful for prognostic prediction and decisions regarding the choice of therapeutic strategy.

NKCCs in the fibrocytes of the spiral ligament are silent on the unidirectional K⁺ transport that controls the electrochemical properties in the mammalian cochlea.

Unidirectional K(+) transport across the lateral cochlear wall contributes to the endocochlear potential (EP) of +80 mV in the endolymph, a property essential for hearing. The wall comprises two epithelial layers, the syncytium and the marginal cells. The basolateral surface of the former and the apical membranes of the latter face the perilymph and the endolymph, respectively. Intrastrial space (IS), an extracellular compartment between the two layers, exhibits low [K(+)] and a potential similar to the EP. This IS potential (ISP) dominates the EP and represents a K(+) diffusion potential elicited by a large K(+) gradient across the syncytial apical surface. The K(+) gradient depends on the unidirectional K(+) transport driven by Na(+),K(+)-ATPases on the basolateral surface of each layer and the concomitant Na(+),K(+),2Cl(-)-cotransporters (NKCCs) in the marginal cell layer. The NKCCs coexpressed with the Na(+),K(+)-ATPases in the syncytial layer also seem to participate in the K(+) transport. To test this hypothesis, we examined the electrochemical properties of the lateral wall with electrodes measuring [K(+)] and potential. Blocking NKCCs by perilymphatic perfusion of bumetanide suppressed the ISP. Unexpectedly and unlike the inhibition of the syncytial Na(+),K(+)-ATPases, the perfusion barely altered the electrochemical properties of the syncytium but markedly augmented [K(+)] of the IS. Consequently, the K(+) gradient decreased and the ISP declined. These observations resembled those when the marginal cells' Na(+),K(+)-ATPases or NKCCs were blocked with vascularly applied inhibitors. It is plausible that NKCCs in the marginal cells are affected by the perilymphatically perfused bumetanide, and these transporters, but not those in the syncytium, mediate the unidirectional K(+) transport.

Template-guided implantation of the Bonebridge: clinical experience.

The surgical procedure for Bonebridge implantation cannot be done in some cases without exposing the dura mater or sigmoid sinus. Surgical simulation technology can help to identify such difficulties prior to surgery and be used to clarify the optimal location and orientation of the device to be implanted. However, there has not been a simple strategy to drill the temporal bone at exactly the same location as that simulated on the computer. Based on our previous development of the surface template-assisted marker positioning (STAMP) method for performing image-guided otologic surgery, we recently developed a noninvasive guiding method, the BB-STAMP method, for performing image-guided Bonebridge implantation. Three patients underwent Bonebridge implantation at our surgical center during the years of 2013-2014. The authors in the simulation center supported the surgery using the BB-STAMP method. The time and effort required to prepare for the surgery were evaluated. In addition, a postoperative analysis was performed to assess the accuracy of placing the device in the planned location. The BB-STAMP method enabled the surgeon to precisely replicate the computer simulation in the real patient with submillimetric accuracy without complexity. Thus, the use of experienced and elaborative simulation coupled with the creation of a tailor-made three-dimensional template (BB-STAMP) enables surgeons to perform quick, precise and safe surgical procedures at distant institutions.

Hyalinizing clear cell carcinoma with EWSR1-ATF1 fusion gene: report of three cases with molecular analyses.

Hyalinizing clear cell carcinoma (HCCC) is a low-grade salivary gland carcinoma characterized by clear cells and hyalinized stroma. Recently, the EWSR1-ATF1 fusion gene was found in HCCCs. We herein describe three cases of HCCC identified in one male and two females, ranging in age from 27 to 67 years. The tumors were located in the root of tongue, nasopharynx, and soft palate. They were composed of nested or cord-like proliferations of epithelial cells with clear to pale eosinophilic cytoplasm, embedded in hyalinized and focally fibroedematous stroma. Tumor-associated lymphoid proliferation and pseudoepitheliomatous hyperplasia were also observed in each one case. MAML2 fusions specific to mucoepidermoid carcinoma were not detected in any of the three cases. We found EWSR1-ATF1 in two of three HCCCs using reverse transcription polymerase chain reaction (RT-PCR) with our original primer sets designed to detect the fusion gene transcripts in formalin-fixed paraffin-embedded (FFPE) tissues. EWSR1 rearrangement was also confirmed by fluorescence in situ hybridization (FISH) on FFPE sections in two cases. There was a good concordance between the two methods (two positive cases and one negative case by both RT-PCR and FISH). Therefore, RT-PCR and FISH using FFPE tissue may be ancillary tools to confirm the diagnosis of HCCC.

A clinical experience of 'STAMP' plate-guided Bonebridge implantation.

CONCLUSION: The surface template-assisted marker positioning (STAMP) method is useful for successful Bonebridge™ (BB) implantation on a planned site while avoiding dangerous positions. OBJECTIVES: To confirm the usefulness of the STAMP method for the safe operation of BB. METHODS: From a patient's temporal bone CT data, a guide plate and confirmation plate were generated by the STAMP method. The guide plate is used to mark the correct place for implantation, while the confirmation plate lets us know the correct angle and depth of the hole. RESULTS: With the guide plate, the correct place for BB implantation was easily found. The hole was made to be an appropriate size with the confirmation plate while exposing only a small part of sigmoid sinus as simulated. Finally, the BB implant was successfully placed exactly at the planned site.

A surgical navigation system for guiding exact cochleostomy using auditory feedback: a clinical feasibility study.

In cochlear implantation (CI), the insertion of the electrode array into the appropriate compartment of the cochlea, the scala tympani, is important for an optimal hearing outcome. The current surgical technique for CI depends primarily on the surgeon's skills and experience level to achieve the correct placement of the electrode array, and the surgeon needs to confirm that the exact placement is achieved prior to completing the procedure. Thus, a surgical navigation system can help the surgeon to access the scala tympani without injuring important organs in the complex structure of the temporal bone. However, the use of a surgical microscope has restricted the effectiveness of the surgical navigation because it has been difficult to deliver the navigational information to the surgeon from outside of the surgeon's visual attention. We herein present a clinical feasibility study of an auditory feedback function developed as a computer-surgeon interface that can guide the surgeon to the preset cochleostomy location. As a result, the surgeon could confirm that the drilling point was correct, while keeping his or her eyes focused on the microscope. The proposed interface reduced the common frustration that surgeons experience when using surgical navigation during otologic surgeries.

Microsurgical anatomy of subtotal temporal bone resection en bloc with the parotid gland and temporomandibular joint.

BACKGROUND: Subtotal temporal bone resection (STBR) has been used for half a century to remove temporal bone malignancies. However, there are few reports on the detailed anatomy involved in the resection. OBJECTIVE: To describe the microsurgical anatomy of STBR combined en bloc with the resection of the parotid gland and temporomandibular joint (TMJ). METHODS: Cadaveric specimens were dissected in a stepwise manner using 3× to 40× magnification. RESULTS: STBR can be combined with the total parotidectomy and the resection of the TMJ if the tumor extends into the parotid gland, TMJ, or facial nerve. In this study, we describe the step-by-step microsurgical anatomy of STBR en bloc with the parotid gland and TMJ. The surgical technique described combines 3 approaches: the high cervical, subtemporal-infratemporal fossa, and retromastoid-paracondylar approaches. Combining these 3 approaches aided in efficiently completing this modified approach. CONCLUSION: STBR is a complicated and technically challenging procedure. This study highlights the importance of understanding the surgical anatomy of STBR and will serve as a catalyst for improvement of the surgical technique for temporal bone resection.

Image-guided placement of the Bonebridge™ without surgical navigation equipment.

PURPOSE:    Most of the current Bonebridge surgeries undergo preoperative simulation planning in a computer. However, surgeons usually use the landmarks on the bone surface to determine the location where to implant the device, using the simulation image in the computer only as a reference (conventional method). We developed an image-guided method for precisely replicating simulation surgery upon performing Bonebridge implantation. METHODS:    Based on our previous development of the surface template-assisted marker positioning (STAMP) method for performing image-guided otologic surgery, we fabricated templates that fit only at the designated location on the patient's temporal bone surface. The Bonebridge STAMP (BB-STAMP) plate shows the exact location where to start drilling. The BB-STAMP was also combined with a perforator-guiding sleeve, so that the location, direction and depth of the cylindrical well could be precisely replicated as simulated. We also created a STAMP plate for confirmation that fits only after sufficient drilling at the correct location is finished. To evaluate the proposed methods, we performed simulation surgery on four cadaveric temporal bones and their 12 replicas (three each for four bones). The time used and the degree of mismatch between the simulated location and the drilled location were compared. RESULTS:    A feasibility study was successfully conducted using the proposed BB-STAMP methods and the conventional method. The amount of time required for the procedure did not differ significantly between the surgical methods, although using the BB-STAMP and perforator guide was always quicker. The degree of mismatch between the simulation and resected models had tendency to be smaller when the surgery was guided by the BB-STAMP with or without a perforator guide, although the difference was not statistically significant. CONCLUSIONS:    The proposed BB-STAMP is a promising method for replicating exactly what is performed during simulation without using a surgical navigation system.

Neuromagnetic detection of the laryngeal area: Sensory-evoked fields to air-puff stimulation.

The sensory projections from the oral cavity, pharynx, and larynx are crucial in assuring safe deglutition, coughing, breathing, and voice production/speaking. Although several studies using neuroimaging techniques have demonstrated cortical activation related to pharyngeal and laryngeal functions, little is known regarding sensory projections from the laryngeal area to the somatosensory cortex. The purpose of this study was to establish the cortical activity evoked by somatic air-puff stimulation at the laryngeal mucosa using magnetoencephalography. Twelve healthy volunteers were trained to inhibit swallowing in response to air stimuli delivered to the larynx. Minimum norm estimates was performed on the laryngeal somatosensory evoked fields (LSEFs) to best differentiate the target activations from non-task-related activations. Evoked magnetic fields were recorded with acceptable reproducibility in the left hemisphere, with a peak latency of approximately 100ms in 10 subjects. Peak activation was estimated at the caudolateral region of the primary somatosensory area (S1). These results establish the ability to detect LSEFs with an acceptable reproducibility within a single subject and among subjects. These results also suggest the existence of laryngeal somatic afferent input to the caudolateral region of S1 in human. Our findings indicate that further investigation in this area is needed, and should focus on laryngeal lateralization, swallowing, and speech processing.

A preregistered STAMP method for image-guided temporal bone surgery.

OBJECTIVES: Image-guided otological surgeries require minimal invasiveness and high accuracy, and these two factors usually compete with each other. Our recently developed registration method, called the STAMP method, showed minimal invasiveness with accuracy comparable to that of the current more invasive registration methods used in image-guided temporal bone surgery. However, surgeons perceived the STAMP method as complex and time-consuming. METHODS: We modified our STAMP method to further simplify the surgeon's tasks in the operating room. We attached an optical tracking target on the STAMP plate and registered the plate in an IGS system before surgery, outside the operating room. The registration was completed in the operating room by finishing the final simple task, which was to hold the preregistered STAMP plate still on the patient's temporal bone. We tested this modified preregistered STAMP method in simulation surgery and actual surgeries. The registration times and errors of the STAMP method and preregistered STAMP method were compared. RESULTS: The proposed new preregistered STAMP method significantly reduced the registration time in the operating room without compromising the registration accuracy. CONCLUSIONS: The preregistered STAMP method significantly improved the original STAMP method in terms of time and convenience. It is now considered to be one of the easiest and quickest registrations for image-guided temporal bone surgery. Because most of the critical processes of registration can be completed in the laboratory, the registration task in the operating room is therefore greatly simplified, thus allowing surgeons to concentrate more on the surgery itself.

Inflammatory pseudotumor in head and neck.

BACKGROUND: Inflammatory pseudotumor (IPT) is a tumefactive lesion characterized by fibroblastic proliferations and a prominent inflammatory component. It behaves as a locally benign or aggressive lesion, clinically and radiologically mimicking a neoplastic process. Numerous entities can be diagnosed as IPT, from reactive lesions to true neoplasms. The diagnosis of IPT requires further elaboration, and IPT should be distinguished from other similar entities such as inflammatory myofibroblastic tumor and IgG4-related sclerosing disease. CASE SUMMARY: We report two cases of IPT arising from the head and neck region. One occurred at the orbit and the other at the parapharyngeal space. Histologically, they showed aggregates of myofibroblasts and inflammatory cells. Immunohistochemically, the number of IgG4-positive cells was less than 40% of the number of IgG positive cells, and the myofibroblastic cells were negative for anaplastic lymphoma kinase. The diagnosis was IPT/not otherwise specified. One patient was treated by systemic administration of corticosteroid and had good response. The other, who was treated by local administration of corticosteroid, partially responded and is currently stable with limited disease. DISCUSSION: IPT has been reported to occur in various anatomical sites, most commonly in the lungs. The incidence in the head and neck area is extremely rare. Treatment of IPT is controversial and may involve corticosteroids or surgical resection, or both. Other chemotherapeutic agents and radiotherapy may be considered in steroid-resistant patients. The pathological subtype, safety of resection, and safety of corticosteroid use must be included in the decision-making process for treatment.