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Enhancer of zeste homolog 2 (EZH2) is the catalytic core of polycomb repressive complex 2 (PRC2), which primarily methylates lysine 27 on histone H3 (H2K27me3), generating transcriptionally suppressed heterochromatin. Since EZH2 suppresses expression of genes involved in dentin formation, we examined the role of EZH2 in tooth development. Intriguingly, microCT analysis of teeth from mice with conditional Ezh2 knockout in uncommitted mesenchymal cells showed hyper-mineralization of enamel, which is produced by the epithelial-lineage cells, ameloblasts. Scanning electron microscopy analysis and nano-indentation of the incisor enamel from knockout mice revealed smaller inter-rod spaces and higher hardness compared to wild type enamel, respectively. Interestingly, expression of the calcium channel subunit gene, Orai2, was decreased compared to its competitor, Orai1, both in knockout mouse incisors and the ex vivo culture of ameloblasts with the surrounding tissues under EZH2 inhibition. Moreover, histological analysis of incisor from knockout mice showed decreased ameloblastin and expedited KLK4 expression in the ameloblasts. These observations suggest that EZH2 depletion in dental mesenchymal cells reduces enamel matrix formation and increases enamel protease activity from ameloblasts, resulting in enamel hyper-mineralization. This study demonstrates the significant role of the suppressive H3K27me3 mark for heterochromatin on enamel formation.

External auditory canal (EAC) carcinoma is a rare and unusual malignancy. The complex anatomy and relationship between the tumor and surrounding tissues in a limited space render it difficult to attain safe resection margins during surgery. A high jugular bulb (HJB) is one such anatomical variation that has important surgical implications that complicate the surgical procedure for EAC carcinoma. A 73-year-old woman presented with a 3-month history of right ear pain. Pathological findings and computed tomography (CT) revealed EAC carcinoma, which was expanding to the middle ear (ME). Although there was no cavity inside the ME, an HJB was detected. Surgical treatment using a temporal incision for temporal craniotomy achieved complete resection of the tumor and preserved facial nerve function. The patient recovered without complications and was discharged 17 days after the operation. Temporal incision and temporal craniotomy is a useful approach for EAC carcinoma with HJB.

We recently reported that tetraphenylethene-appended poly(acrylic acid) derivatives (e.g., PAA-TPE

The aim of this paper is to describe a safe and effective surgical technique for neck dissection under local anesthesia. An increasing number of patients cannot undergo general anesthesia due to systemic complication arising from old age. Moreover, the long-term survival of patients with recurrent or metastatic cancer due to advances in chemotherapy has increased the necessity of neck dissection under local anesthesia. Appropriate pain control and selection of medical devices are important factors for success of the surgery under local anesthesia. In addition to the usual subcutaneous infiltration anesthesia for pain control, nerve blocks for each cervical nerve encountered during surgery are extremely effective. Since muscle relaxants are not available, sharp devices such as knife or scissors, instead of electric scalpel, should be used to prevent unexpected muscle contractions caused by electric current. This video presents well-proven techniques and technical tips for superselective neck dissection under local anesthesia.

Background: To determine factors that delay surgical recovery and increase intraoperative hemorrhage in skull base surgery. Methods: Factors related to delayed postoperative recovery were retrospectively reviewed in 33 patients who underwent open skull base surgery. Early and late recovery phases were assessed as “days required to walk around the ward (DWW)” and “length of hospital stay (LHS),” respectively. Intraoperative blood loss was cal­culated every hour and analyzed in 4 steps, i.e., craniotomy and intracranial manipulation, cranial fossa osteotomy, extracranial osteotomy, and reconstruction. Results: More than 4,000 mL of blood loss (B = 2.7392, Exp[B] = 15.4744; 95% CI 1.1828–202.4417) and comorbidi­ty (B = 2.3978, Exp[B]) = 10.9987; 95% CI 1.3534–98.3810) significantly prolonged the DWW; the occurrence of postoperative complications significantly delayed the LHS (p = 0.0316). Tumor invasion to the hard palate, the maxillary sinus, the pterygopalatine fossa, the base of the pterygoid process, the sphenoid sinus, the middle cranial fossa, and the cavernous sinus and a long operation time (>13 h) were associated with increased total hemorrhage. The optimal cut-off hemorrhage volume associated with total massive blood loss in craniotomy and intracranial manipulation (AUC = 0.8364), cranial fossa osteotomy (AUC = 0.8000), and extracranial osteotomy (AUC = 0.8545) was 1,111, 750, and 913 mL, respectively. Persistent infection (6%) and neuropsychiatric disorder (6%) are direct causes of delayed LHS. Conclusion: Blood loss, comorbidity, and postoperative complications were risk factors for delayed surgical recovery. Meticulous preoperative planning, intraoperative surefire hemostasis, and perioperative holistic management are prerequisites for safe skull base surgery.

This paper describes the development of a novel dry film-type dielectric material with low loss tangent (D f ) and the demonstration of a low-loss filter substrate using the dielectric material for high-frequency transmission applications. This paper also presents the evaluation results of the small filter characteristics of the substrate in the 28 GHz and 39 GHz 5G millimeter-wave (mmWave) band. We have recently developed a dry film dielectric material with outstanding electrical properties and excellent mechanical properties (Material P). This new material is based on polyphenylene ether (PPE) that has extremely low D f . PPE is commonly known as a thermoplastic polymer, henceforth a new chemical design was applied to modify the polymer structure into a thermosetting polymer. The new dielectric material can be processed at a low temperature about 200°C and is compatible to the standard substrate manufacturing processes, such as semi additive process (SAP). Material characterization revealed that D k /D f of Material P is 3.1 /0.0013 at 10 GHz, and glass transition temperature (T g ) is 200°C. In this work, RF filter performance of the Material P was characterized to demonstrate the benefit of the low loss material. As the reference, the performance of epoxy dielectric was additionally characterized and compared. Electrical characterization of the filter structures showed low transmission losses < 1.0 dB at 28 GHz and < 0.8 dB at 39 GHz with Material P, verifying applicability of the material for high frequency applications.

In traditional craniofacial resection of tumors invading the anterior skull base, the bilateral olfactory apparatus is resected. Recently, transnasal endoscopy has been used for olfactory preservation in resections of unilateral low-grade malignancies. However, for tumors that invade the orbita or for high-grade malignancies, the transnasal endoscopic skull base surgery has been controversial. This video demonstrates the surgical techniques of olfactory preservation during craniofacial resection of a high-grade malignancy invading the hemianterior skull base and orbita.We present the case of a 32-year-old woman with osteosarcoma in the right ethmoid sinus. The tumor invaded the ipsilateral cribriform plate, dura menta, and orbital periosteum; however, the nasal septum and crista galli were intact (Fig. 1A, B). Because the tumor was a high-grade malignancy and the orbita had been invaded, we performed craniofacial resection instead of endoscopic resection (Fig. C2A). We drilled into the right side of the crista galli, midline of the cribriform plate, and perpendicular plate of the ethmoid bone via craniotomy. As a result, we accessed the nasal cavity directly (Fig. 2B). To preserve the nasal septum, we detached the remaining right septal mucosa through the transfacial approach (Fig. 2C). Because of the high risk of cerebrospinal fluid leakage as a result of previous irradiation, we performed vascularized free flap reconstruction of the skull base instead of pericranial flap.Postoperative computed tomography revealed no evidence of tumor (Fig. 1C, D). The patient's sense of smell returned after 1 postoperative day, and she was discharged on the postoperative day 14.The link to the video can be found at: https://youtu.be/XzPABYwzkjs.

Background While transoral robotic surgery (TORS) is widely used for the management of lateral wall oropharyngeal carcinomas (OPC), open surgical techniques are still used in some cases. A pull-through method for open surgical resections of OPC has recently been introduced. We improved on this method by eliminating the need for subsequent free-flap reconstruction. Methods 16 patients with lateral wall OPC underwent pull-through resections. After resection, we used the digastric muscle, stylohyoid muscles, submandibular gland and the surrounding tissues to block the neck and oral cavity and to avoid reconstruction. Results This novel technique was performed without major complications or morbidities. The average post-operative hospital stay was 14.6 ± 6.1 days, and the average duration until initiation of oral intake post-operation was 6.5 ± 2.9 days. Oncological outcomes, post-operative course and function were acceptable. Conclusions Our novel method provides an efficient and less invasive surgical technique than conventional open approaches.

We recently reported that tetraphenylethene-appended poly(acrylic acid) derivatives (e.g., PAA-TPE0.02) can serve as fluorescent Ca2+ sensors in the presence of physiological concentrations of biologically relevant ions, amino acids, and sugars. However, in the presence of basic proteins such as albumins, the Ca2+-sensing property of the polymer is significantly impaired due to the nonspecific adsorption of protein molecules, which competes with binding to Ca2+. To solve this problem, we explored new designs by focusing on the polymer-chain topology of PAA-TPE0.02 with biocompatible segments. Here, we report the Ca2+-sensing and protein-adsorption-resistance properties of various types of PAA-TPE0.02 copolymers with a poly(oligoethylene glycol acrylate) (polyOEGA) segment, featuring a random, diblock, triblock, or 4-armed-star-block structure. Through this study, we show an interesting topology effect; i.e., a branch-shaped PAA-TPE0.02-co-polyOEGA with biocompatible segments at every terminal (i.e., 4-armed-star-block copolymer) exhibits both good Ca2+-sensing and protein-adsorption-resistance properties.

We recently reported that tetraphenylethene-appended poly(acrylic acid) derivatives [PAA-TPEx (x = 0.01–0.05)] provide a fluorescent Ca2+ sensor, where aggregation-induced emission (AIE) of the TPE pendants occurs in conjunction with Ca2+-triggered polymer-chain folding. On the basis of dynamic and static light-scattering data, here we discuss the hydrodynamic radius and molar mass of PAA-TPE0.01 in the presence of Ca2+, Mg2+, or Na+ at various concentrations and elucidate the origin of the Ca2+ selectivity. In contrast to Na+, which exclusively triggered nonfluorescent interpolymer aggregation of PAA-TPE0.01, Ca2+ and Mg2+ induced polymer-chain folding associated with AIE from the TPE pendants. Importantly, Ca2+ caused polymer-chain folding more effectively than Mg2+. Consequently, polymer aggregates formed in the presence of Ca2+ possessed a much higher inner density than those formed in the presence of Mg2+, leading to a more pronounced AIE behavior and, in turn, the Ca2+ ion selectivity over Mg2+.

Background Schwannoma originating from the esophageal branch of the recurrent laryngeal nerve is clinically rare event. The best approach to preoperative pathological diagnosis, surgery, and airway management for this submucosal tumor in the tracheal membranous portion remains controversial. Methods and results A 69-year-old man had developed dyspnea for 6 months. Transnasal endoscopy revealed a submucosal tumor in the tracheal membranous portion, obstructing the airway. CT revealed that the tumor was located between the trachea and esophagus. Needle biopsy using ultrasonic bronchoscope diagnosed the submucosal tumor as schwannoma. Intercapsular resection was performed by a transtracheal approach under local anesthesia. The tumor was completely resected and the patient's symptoms completely improved. Conclusions We report the treatment of a rare schwannoma originating from the esophageal branch of the recurrent laryngeal nerve. A needle biopsy using an ultrasonic bronchoscope was successfully used for diagnosis. Intercapsular resection by a transtracheal approach was effective.

BACKGROUND Carotid blowout syndrome (CBS) is among the fatal complications in head and neck cancer treatment. However, the optimal treatment for CBS has not been established yet. This study aimed to describe our experience with two patients at high risk of CBS who underwent common carotid artery (CCA) ligation at the proximal side of the bleeding point under local anesthesia and before CCA rupture, and to review and compare the medical records of these two patients against 10 CBS cases treated in our department. METHODS The institutional electronic medical record was searched, and clinical information was extracted for all patients who showed CBS from 2007 to 2017. Our treatment method was performed as follows. Ligation of the proximal side of the CCA was performed under local anesthesia. The CCA was identified and clamped with two bulldog forceps for 10 minutes to check for any adverse neurological symptoms. Subsequently, the CCA was ligated using 2-0 silk threads and sutured with an absorbable suture between the silk threads. However, ligation or occlusion of the external carotid artery by previous treatment is a prerequisite for this method. RESULTS Eight patients received interventions, with six patients undergoing prophylactic interventions before rupture. Four patients who did not undergo treatment died owing to CBS. Two patients who underwent treatment with the novel method did not experience re-bleeding, but their conditions deteriorated owing to cancer progression. CONCLUSION The present method is one of the treatment choices for CBS, especially in patients with an 'impending' risk of CBS.

This study elucidates the clinical impact of surgical treatment of head and neck squamous cell carcinoma (HNSCC) based on a detailed search of all exons of the TP53 gene and p53 protein phenotypic analysis using formalin-fixed paraffin-embedded (FFPE) specimens. Clinically well-annotated FFPE specimens from 317 patients with HNSCC treated by surgery were examined by all-exon TP53 sequencing using a next-generation sequencer and p53 protein phenotype by immunohistochemistry. After excluding human papillomavirus-associated oropharyngeal carcinomas, two risk categories were classified as “p53 adverse function” and “p53 favorable function” based on TP53 mutation status and p53 protein phenotype. Mutation in PIK3CA, AKT, and HRAS was also evaluated by target sequence. Cox proportional hazards regression models were used for statistical analysis of clinical outcomes. Receiver operating characteristic curve analysis was used to determine the optimal surgical margin cutoff for local recurrence. Local control rates were compared between the risk groups using Fisher’s exact test. Multivariate analysis identified “p53 adverse function” as an independent poor predictor of overall survival, local control, and distant metastasis-free survival. In oral cavity cancer, the optimal surgical margin cutoff associated with local recurrence was 6 mm. In patients with surgical margin > 6 mm, the “p53 adverse function” group demonstrated significantly higher local recurrence rate than the “p53 favorable function” group. PIK3CA, AKT, or HRAS mutation did not correlate with improved overall survival. All-exon TP53 sequencing and p53 protein phenotype analysis using FFPE specimens can accurately predict clinical outcomes.

Key Clinical Message Peritoneal pregnancy may cause severe abdominal bleeding without genital bleeding as early as the fifth week of gestation. Awareness that pregnancy can exist in unusual locations is imperative.

Solitary fibrous tumors (SFT) are uncommon neoplasm that arises in most cases from the pleura. SFT has been rarely observed in the head and neck, but SFT of the paranasal sinuses is especially rare, with 39 previously reported cases to date including those reported in this abstract. Herein we describe three cases of SFT in the paranasal sinuses that were successfully treated endoscopically. Two of the three cases involved patients with no previous history of SFT. The lesion of one of the patients was pathologically diagnosed as SFT preoperatively, but the other was diagnosed as an angiogenic tumor without any biopsies. The tumors were completely resected after arterial embolization by a transnasal endoscopic procedure. The third case involved a 43-year old man, who had undergone medial maxillectomy through a lateral rhinotomy incision to resect SFT four years and seven months before. The tumor relapsed intracranially and, therefore, a craniotomy procedure followed by endoscopic skull base surgery was performed. Radiation therapy was performed postoperatively because the recurrent tumor was pathologically identified as malignant SFT, which had been classified benign at the time of the first resection. All three patients are presently alive with no evidence of disease.

Objective This study aimed to determine the adequate resection margin in skull base surgery for head and neck sarcoma. Design We retrospectively reviewed 22 sarcomas with skull base invasion. Induction chemotherapy, followed by surgery and postoperative radiotherapy and adjuvant chemotherapy, was performed in 18 patients with chemosensitive sarcomas, and surgery with or without postoperative radiotherapy was performed in four patients with chemoresistant sarcomas. Radical resection was performed in patients with chemosensitive sarcomas with a poor response to induction chemotherapy and in patients with chemoresistant sarcomas. Conservative resection with close surgical margin was performed in patients with chemosensitive sarcomas with a good response to induction chemotherapy. Setting and Participants This single-centered retrospective study included patients from the National Cancer Center Hospital, Japan. Results The response to induction chemotherapy was significantly associated with the 3-year local control rate (LCR; good response versus poor response: 100% versus 63%, p = 0.048). Patients with a good response to chemotherapy had a favorable local prognosis even when the local therapy was conservative resection. In radical skull base surgery, patients whose surgical margins were classified as “wide margin positive” had significantly poorer 3-year LCR than did patients with “margin negative” or “micro margin positive” margins (25% versus 83%, p = 0.014). Conclusion Conservative resection with close surgical margins might be acceptable for chemosensitive sarcomas with a good response to chemotherapy. Resection margin status was an important predictive factor for local recurrence after radical skull base surgery. Microscopic microresidual tumor might be controlled by postoperative treatment.

Background Lymph node metastasis with extranodal extension represents one of the most important adverse prognostic factors for survival in patients with head and neck squamous cell carcinoma. We propose that extranodal extension occurs to differing extents. The aim of this study was to determine the prognostic significance of extranodal extension in patients with head and neck squamous cell carcinoma. Methods Two hundred and ninety-eight patients with head and neck squamous cell carcinoma who underwent surgical resection and neck dissection were included. Cervical lymph nodes were classified into four categories: (i) pathological N negative, (ii) extranodal extension negative, (iii) non-surgical extranodal extension and (iv) surgical extranodal extension. Results Lymph node metastases were detected in 67.1% of laryngeal/hypopharyngeal cancer patients and 52.7% of oral cancer patients. The 3-year disease-specific survival rates for patients in the pathological N negative, extranodal extension negative, non-surgical extranodal extension and surgical extranodal extension groups were 90.9%, 79.6%, 63.8% and 48.3%, respectively. In laryngeal/hypopharyngeal cancer patients, surgical extranodal extension was associated with a significantly poorer disease-specific survival than a pathological N negative, extranodal extension negative or non-surgical extranodal extension status. In oral cancer patients, no significant differences were observed between the non-surgical and surgical extranodal extension groups. However, non-surgical extranodal extension was associated with a poorer disease-specific survival than a pathological N negative or extranodal extension negative status. Conclusions Surgical extranodal extension was a poor prognostic factor in patients with head and neck squamous cell carcinoma. The prognostic significance of surgical extranodal extension differed between laryngeal/hypopharyngeal and oral cancer patients. The clinical significance of surgical extranodal extension was much greater for patients with laryngeal/hypopharyngeal cancer than oral cancer.

Bacterial biofilms have emerged as potential critical triggers in the pathogenesis of bisphosphonate (BP)-related osteonecrosis of the jaw (ONJ) or BRONJ. BRONJ lesions have shown to be heavily colonized by oral bacteria, most of these difficult to cultivate and presents many clinical challenges. The purpose of this study was to characterize the bacterial diversity in BRONJ lesions and to determine host immune response. We examined tissue specimens from three cohorts (n=30); patients with periodontal disease without a history of BP therapy (Control, n=10), patients with periodontal disease having history of BP therapy but without ONJ (BP, n=5) and patients with BRONJ (BRONJ, n=15). Denaturing gradient gel electrophoresis of polymerase chain reaction (PCR)-amplified 16S rRNA gene fragments revealed less bacterial diversity in BRONJ than BP and Control cohorts. Sequence analysis detected six phyla with predominant affiliation to Firmicutes in BRONJ (71.6%), BP (70.3%) and Control (59.1%). Significant differences (P

Background Sarcomas of the larynx are uncommon tumors, and osteosarcoma is the rarest. Only 24 cases of osteosarcoma of the larynx have been reported. The only case reported in Asia was from Thailand in 1981. Methods A 55-year-old male patient was referred to our hospital because of an 8-month history of odynophagia and a gradually enlarging left neck mass. A neck CT scan was performed. A literature review was also performed for this report. Results The CT scan revealed extensive calcification with enlargement of the thyroid cartilage. The patient was diagnosed with osteosarcoma and was successfully treated by surgery alone. Conclusion Adequate surgical resection is required for successful treatment of laryngeal sarcomas. Adjuvant therapy is not contraindicated, but chemotherapy may improve the prognosis in patients with high-grade tumors or metastatic disease. © 2014 Wiley Periodicals, Inc. Head Neck 37: E26-E29, 2015

Prostate cancer (PCa) is the second leading cause of cancer-related death in American men and many PCa patients develop skeletal metastasis. Current treatment modalities for metastatic PCa are mostly palliative with poor prognosis. Epidemiological studies indicated that patients receiving the diabetic drug metformin have lower PCa risk and better prognosis, suggesting that metformin may have antineoplastic effects. The mechanism by which metformin acts as chemopreventive agent to impede PCa initiation and progression is unknown. The amplification of c-MYC oncogene plays a key role in early prostate epithelia cell transformation and PCa growth. The purpose of this study is to investigate the effect of metformin on c-myc expression and PCa progression. Our results demonstrated that (i) in Hi-Myc mice that display murine prostate neoplasia and highly resemble the progression of human prostate tumors, metformin attenuated the development of prostate intraepithelial neoplasia (PIN, the precancerous lesion of prostate) and PCa lesions. (ii) Metformin reduced c-myc protein levels in vivo and in vitro. In Myc-CaP mouse PCa cells, metformin decreased c-myc protein levels by at least 50%. (iii) Metformin selectively inhibited the growth of PCa cells by stimulating cell cycle arrest and apoptosis without affecting the growth of normal prostatic epithelial cells (RWPE-1). (iv) Reduced PIN formation by metformin was associated with reduced levels of androgen receptor and proliferation marker Ki-67 in Hi-Myc mouse prostate glands. Our novel findings suggest that by downregulating c-myc, metformin can act as a chemopreventive agent to restrict prostatic neoplasia initiation and transformation. Summary: Metformin, an old antidiabetes drug, may inhibit prostate intraepithelial neoplasia transforming to cancer lesion via reducing c-MYC, an ‘old’ overexpressed oncogene. This study explores chemopreventive efficacy of metformin in prostate cancer and its link to cMYC in vitro and in vivo.

Objective The orbital periosteum is considered to be a barrier to tumor spread; however, it is difficult to evaluate microscopic tumor spread during surgery. This study aimed to assess the impact of pathological status in orbital preservation surgery. Methods We retrospectively analyzed the 3-year local control rate and treatment outcomes of patients with malignant tumors invading the orbit who were treated between 2006 and 2012. Results In total, 27 patients were reviewed over a median follow-up period of 36 months. Pathologically, 19 had carcinomas and 8 had sarcomas. Treatment was by orbital exenteration in 6 patients and orbital preservation surgery in 21 patients. After orbital preservation surgery, poorer 3-year local control rates were significantly associated with positive surgical margins (negative vs. positive: 91% vs. 41%, P = 0.040) and microscopic orbital periosteum invasion (negative vs. positive: 90% vs. 39%, P = 0.010). These factors were independent risk factors in multivariate analysis. The locations of the positive margin were most common at the horizontal and vertical margins of the orbital periosteum and the posterior margin of the orbital apex. Moreover, in 24% of patients, invasion evaluation by preoperative imaging study was underestimated compared with postoperative microscopic evaluation. Conclusions The positive surgical margin and microscopic orbital periosteum invasion were the risk factors of orbital recurrence. It is difficult to determine the indications for orbital preservation surgery by preoperative imaging studies because of the unpredictable accurate pathological status before surgery and the limitations of preoperative imaging evaluation.

Although the role of extracellular Ca2+ draws increasing attention as a messenger in intercellular communications, there is currently no tool available for imaging Ca2+ dynamics in extracellular regions. Here we report the first solid-state fluorescent Ca2+ sensor that fulfills the essential requirements for realizing extracellular Ca2+ imaging. Inspired by natural extracellular Ca2+-sensing receptors, we designed a particular type of chemically-crosslinked polyacrylic acid gel, which can undergo single-chain aggregation in the presence of Ca2+. By attaching aggregation-induced emission luminogen to the polyacrylic acid as a pendant, the conformational state of the main chain at a given Ca2+ concentration is successfully translated into fluorescence property. The Ca2+ sensor has a millimolar-order apparent dissociation constant compatible with extracellular Ca2+ concentrations and exhibits sufficient dynamic range and excellent selectivity in the presence of physiological concentrations of biologically relevant ions, thus enabling monitoring of submillimolar fluctuations of Ca2+ in flowing analytes containing millimolar Ca2+ concentrations.

Objectives The purpose of this study was to assess the value of the apparent diffusion coefficient (ADC) in the differential diagnosis between benign and malignant thyroid nodules, particularly those found to have indeterminate cytology with fine needle aspiration (FNA). Methods Thirty-eight patients with 42 thyroid nodules underwent neck magnetic resonance imaging consisting of T1-, T2-, and diffusion-weighted imaging. The final diagnosis of all nodules was confirmed by surgery, revealing 23 with benign and 19 with malignant lesions. Preoperative FNA cytology was performed in 38 of 42 nodules, including 15 of indeterminate cytology. The mean ADC values in benign and malignant groups were compared. Results There was a significant difference between mean ADC values in benign and malignant nodules and between mean ADC in benign and malignant nodules of indeterminate cytology. A cutoff value for malignant nodules of 1.60 × 10 −3 mm 2 /s yielded sensitivity, specificity, and accuracy of 94.73%, 82.60%, and 88.09%, respectively. Conclusion The present study revealed that ADC measurements could potentially quantitatively differentiate between benign and malignant thyroid nodules, even those of indeterminate cytology. We propose that diffusion-weighted imaging evaluation should be used for the assessment of thyroid nodules in addition to FNA cytology.

体幹臓器を原発とする悪性腫瘍の頭頸部領域転移は，その大部分は遠隔転移扱いとされ，予後不良である。今回，われわれは自験例35例の臨床的検討を行ったので報告する。原発部位は3例以上が肺10例，乳腺6例，腎4例，胸部食道3例であった。初診時未治療例は23例，治療後再発例が12例であった。頸部リンパ節転移が28例，その他頭頸部転移が13例16箇所に存在した。頭頸部転移が判明した時点で15例22臓器にその他部位にも転移を認めた。5例で外科切除が行われていた。これら頭頸部領域転移例について外科切除を必要とする場合はまれではあるが存在し，その適応の判断については症例毎に検討していく必要があると考えられた。

Nonfibrillar assemblies of amyloid β-protein (Aβ) are considered to play primary roles in Alzheimer disease (AD). Elucidating the assembly pathways of these specific aggregates is essential for understanding disease pathogenesis and developing knowledge-based therapies. However, these assemblies cannot be monitored in vivo, and there has been no reliable in vitro monitoring method at low protein concentration. We have developed a highly sensitive in vitro monitoring method using fluorescence correlation spectroscopy (FCS) combined with transmission electron microscopy (TEM) and toxicity assays. Using Aβ labeled at the N terminus or Lys(16), we uncovered two distinct assembly pathways. One leads to highly toxic 10-15-nm spherical Aβ assemblies, termed amylospheroids (ASPDs). The other leads to fibrils. The first step in ASPD formation is trimerization. ASPDs of ∼330 kDa in mass form from these trimers after 5 h of slow rotation. Up to at least 24 h, ASPDs remain the dominant structures in assembly reactions. Neurotoxicity studies reveal that the most toxic ASPDs are ∼128 kDa (∼32-mers). In contrast, fibrillogenesis begins with dimer formation and then proceeds to formation of 15-40-nm spherical intermediates, from which fibrils originate after 15 h. Unlike ASPD formation, the Lys(16)-labeled peptide disturbed fibril formation because the Aβ(16-20) region is critical for this final step. These differences in the assembly pathways clearly indicated that ASPDs are not fibril precursors. The method we have developed should facilitate identifying Aβ assembly steps at which inhibition may be beneficial.

甲状腺乳頭癌は生命予後良好な癌腫であり，その根治治療は治癒切除が原則である。従って進行癌であっても生命予後改善が見込めるため拡大切除の適応となりうる。今回われわれは初診時に両側反回神経麻痺，右総頸動脈浸潤，単発肺転移を来し，右総頸動脈および左内頸静脈の再建を要した進行甲状腺乳頭癌の切除を経験した。症例は69歳女性で主訴は嗄声。術前診断甲状腺乳頭癌cT4bN1bM1stage IVCに対し甲状腺全摘術（右総頸動脈合併切除）＋喉頭全摘術＋両側頸部郭清術＋右総頸動脈再建＋左内頸静脈再建施行した。拡大切除に際して，術前から合併症回避および治療完遂のために必要十分な手術戦略を建てることが重要と再認識した。

Recruitment of effector T cells to inflamed peripheral tissues is regulated by chemokines and their receptors, but the factors regulating recruitment to tumors remain largely undefined. Ionizing radiation (IR) therapy is a common treatment modality for breast and other cancers. Used as a cytocidal agent for proliferating cancer cells, IR in combination with immunotherapy has been shown to promote immune-mediated tumor destruction in preclinical studies. In this study we demonstrate that IR markedly enhanced the secretion by mouse and human breast cancer cells of CXCL16, a chemokine that binds to CXCR6 on Th1 and activated CD8 effector T cells, and plays an important role in their recruitment to sites of inflammation. Using a poorly immunogenic mouse model of breast cancer, we found that irradiation increased the migration of CD8+CXCR6+ activated T cells to tumors in vitro and in vivo. CXCR6-deficient mice showed reduced infiltration of tumors by activated CD8 T cells and impaired tumor regression following treatment with local IR to the tumor and Abs blocking the negative regulator of T cell activation, CTLA-4. These results provide the first evidence that IR can induce the secretion by cancer cells of proinflammatory chemotactic factors that recruit antitumor effector T cells. The ability of IR to convert tumors into “inflamed” peripheral tissues could be exploited to overcome obstacles at the effector phase of the antitumor immune response and improve the therapeutic efficacy of immunotherapy.

Hypopharyngeal squamous cell carcinoma (HPSCC) is an aggressive disease with poor prognosis; but has no established biomarkers on the order of human papilloma virus and p16 in oropharyngeal carcinoma. This study investigated pre-treatment serum markers, including the combination of platelet count and neutrophil–lymphocyte ratio (COP-NLR) as a prognosis predictor in patients with HPSCC treated in our hospital. We retrospectively reviewed electronic medical records of 118 consecutive patients treated with curative intent at our hospital between 2007 and 2013. Of these 118 patients, we enrolled 100 patients for whom we had sufficient data to analyze relationships between clinico-laboratory characteristics and survival, including the prognostic significance of pre-treatment serum markers and previous reported clinical factors. Multivariate analysis of clinico-laboratory characteristics associated COP-NLR with cancer-specific survival, as were lymph node metastases. Kaplan–Meier analysis and log-rank tests showed that the COP-NLR could stratify those patients into three independent groups (P = 0.003). COP-NLR might be a useful predictor of survival in patients with HPSCC.