Clinical implications of APEX1 and Jagged1 as chemoresistance factors in biliary tract cancer

PURPOSE: Biliary cancer is a highly malignant neoplasm with poor prognosis and most patients need to undergo palliative chemotherapy, however major clinical problem associated with the use of chemotherapy is chemoresistance. So far, we aimed at investigating clinical implications of apurinic/apyrimidinic endodeoxyribonuclease 1 (APEX1) and Jagged1 as chemoresistance factors in biliary tract cancer. METHODS: We used 5 human biliary tract cancer cell lines (SNU-245, SNU-308, SNU-478, SNU-1079, and SNU-1196), and investigated the chemosensitivity of APEX1 and Jagged1 through 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay and Western blot. Alternately, the 10 patients of advanced biliary cancer consist of 2 group according to the chemotherapy response examined by immunohistochemistry using APEX1 and Jagged1 antibody, and protein expression level was scored for staining intensity and percent positive cell. RESULTS: The result of MTT assay after APEX1 knockdown showed that strong coexpression of APEX1 and Jagged1 cell line (SNU-245, SNU-1079, and SNU-1196) showed a greater decrease in IC₅₀ of chemotherapeutic agent (5-fluorouracil, gemcitabine and cisplatin). The Western blot analysis of APEX1 and Jagged1 expression in biliary cancer cell lines after APEX1 knockdown definitively demonstrated decreased Jagged1 expression. The APEX1 and Jagged1expression level of immunohistochemistry represented that chemorefractory patients had higher than chemoresponsive patients. CONCLUSION: These results demonstrate that simultaneous high expression of APEX1 and Jagged1 is associated with chemoresistance in biliary cancer and suggest that is a potential therapeutic target for chemoresistance in advanced biliary cancer.

Guidelines for the Surgical Management of Laryngeal Cancer: Korean Society of Thyroid-Head and Neck Surgery

Korean Society of Thyroid-Head and Neck Surgery appointed a Task Force to develop clinical practice guidelines for the surgical treatment of laryngeal cancer. This Task Force conducted a systematic search of the EMBASE, MEDLINE, Cochrane Library, and KoreaMed databases to identify relevant articles, using search terms selected according to the key questions. Evidence-based recommendations were then created on the basis of these articles. An external expert review and Delphi questionnaire were applied to reach consensus regarding the recommendations. The resulting guidelines focus on the surgical treatment of laryngeal cancer with the assumption that surgery is the selected treatment modality after a multidisciplinary discussion in any context. These guidelines do not, therefore, address non-surgical treatment such as radiation therapy or chemotherapy. The committee developed 62 evidence-based recommendations in 32 categories intended to assist clinicians during management of patients with laryngeal cancer and patients with laryngeal cancer, and counselors and health policy-makers.

Preoperative Lymph Node Staging by FDG PET/CT With Contrast Enhancement for Thyroid Cancer: A Multicenter Study and Comparison With Neck CT

OBJECTIVES: The purpose of this study was to compare lymph node (LN) staging using ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) with contrast-enhancement (CE) PET/CT and contrast-enhanced neck CT (neck CT) in patients with thyroid cancer with level-by-level comparison with various factors. METHODS: This was a retrospective multicenter study. A total of 85 patients were enrolled. Patients who underwent a preoperative evaluation by CE PET/CT and neck CT for thyroid cancer were enrolled. The gold standard for LN was the combination of surgical pathology and clinical follow-up. We compared CE PET/CT with neck CT using a level-by-level method. Factors, including age, sex, camera, arm position, tumor size, extra-thyroidal extension, tumor location, number of primary tumors, primary tumor maximum standardized uptake value, and the interval from scan to operation were also analyzed. RESULTS: Overall accuracy was 81.2% for CE PET/CT and 68.2% for neck CT. CE PET/CT was more sensitive than neck CT (65.8% vs. 44.7%). Also, CE PET/CT showed higher negative predictive value (77.2% vs. 66.1%). CE PET/CT showed good agreement with the gold standard (weighted kappa [κ], 0.7) for differentiating N0, N1a, and N1b, whereas neck CT showed moderate agreement (weighted κ, 0.5). CE PET/CT showed better agreement for the number of levels involved with the gold standard (weighted κ, 0.7) than that of neck CT with the gold standard (weighted κ, 0.5). The accuracies for differentiating N0, N1a, and N1b were 81.2% for CE PET/CT and 68.2% for neck CT. Level-by-level analysis showed that CE PET/CT was more sensitive and has higher negative predictive value for detecting ipsilateral level IV and level VI LNs than neck CT. Other analyzed factors were not related to accuracies of both modalities. CONCLUSION: CE PET/CT was more sensitive and reliable than neck CT for preoperative LN staging in patients with thyroid cancer.

Differential Diagnosis of Chronic Coughing

Cough, the most common symptom, encountered in the outpatient clinic can be caused by various underlying diseases. It defines as chronic cough that the duration of cough is more than 8 weeks with a normal chest X-ray findings. The cause of cough can be found out for more than 90% through the appropriate diagnostic approach and Upper airway cough syndrome, Asthma and Gastroesophageal reflex disease are the most common causes of disease to non-smokers. Chronic cough can be due to not one reason but various reasons and achieve good results by a systematic approach to diagnosis and a concrete treatment on the basis of the sufficient understanding of the underlying disease.

Unusual Presentation of Second Branchial Cleft Cyst: Case Reports and Literature Review / 대한이비인후과학회지

Second branchial cleft cysts are the most common neck masses found in adults. However, the parapharyngeal presence of branchial cleft cyst is very rare. We report three cases of parapharyngeal branchial cleft cyst in adults. They suffered from frequent oropharyngeal infection or abscess. We performed a transoral resection without any surgical complications. Biopsy revealed a squamous lined epithelial wall with lymphoid aggregation, which is characteristic of branchial cleft cyst. No evidence of recurrence was observed in 2 years.

A Case of Pharyngitis Caused by Clinostomum complanatum / 대한이비인후과학회지

A 13-year-old female patient visited the otolaryngology clinic with complaints of a moving foreign body sensation in her throat. The patient used to eat raw fish and she had eaten mullet sashimi a week before. During laryngoscopy for the pharynx and larynx, a motile fluke was found attached to the posterolateral nasopharyngeal wall. The worm was easily removed and identified as Clinostomum complanatum (C. complanatum) after morphological observation. C. complanatum is a digenetic trematode which usually infects fish-eating birds. Human infection by C. complanatum is very rare, and if a human eats infected raw fish, the worm can be on the pharyngeal or laryngeal mucosa. Human cases of parasitic C. complanatum infection have been reported twice in Korea, with the present report being the first case in the otolaryngology field.

Outcomes of Ultra-Early Decompressive Craniectomy after Severe Traumatic Brain Injury-Treatment Outcomes after Severe TBI / 대한신경손상학회지

OBJECTIVE: The beneficial effect of decompressive craniectomy in the treatment of severe traumatic brain injury (TBI) is controversial, but there is no debate that decompression should be performed before irreversible neurological deficit occurs. The aim of our study was to assess the value of ultra-early decompressive craniectomy in patients with severe TBI. METHODS: Total of 127 patients who underwent decompressive craniectomy from January 2007 to December 2013 was included in this study. Among them, 60 patients had underwent ultra-early (within 4 hours from injury) emergent operation for relief of increased intracranial pressure. Initial Glasgow coma scale, brain computed tomography (CT) scan features by Marshall CT classification, and time interval between injury and craniectomy were evaluated retrospectively. Clinical outcome was evaluated, using the modified Rankin score. RESULTS: The outcomes of ultra-early decompressive craniectomy group were not better than those in the comparison group (p=0.809). The overall mortality rate was 68.5% (87 patients). Six of all patients (4.7%) showed good outcomes, and 34 patients (26.8%) remained in a severely disabled or vegetative state. Forty of sixty patients (66.7%) had died, and two patients (3.3%) showed good outcomes at last follow-up. CONCLUSION: Ultra-early decompressive craniectomy for intracranial hypertension did not improve patient outcome when compared with "early or late" decompressive craniectomy for managing severe TBI.

A Case of Giant Carcinosarcoma of the Parotid Gland / 대한이비인후과학회지

Carcinosarcoma, or true malignant mixed tumor of the salivary gland, is a very rare malignant tumor comprised of both carcinomatous and sarcomatous elements and accounts for only 0.04-0.16% of all salivary gland tumors. Carcinosarcoma usually occurs in the parotid gland. Other locations including submandibular gland, minor salivary gland, uterus, bladder or lung have been reported. We report a rare case of carcinosarcoma of the parotid gland in an 85-year-old female. The tumor was large, about 19x17 cm in size, and was successfully excised.

Clinical Outcomes of Treatment for Intracranial Aneurysm in Elderly Patients

OBJECTIVE: The aim of this study is to evaluate the clinical course of intracranial aneurysm in patients aged 65 years and older and the immediate outcome after its aggressive management. MATERIALS AND METHODS: We performed a retrospective analysis using the medical records of 159 elderly patients managed at our institute from September 2008 to December 2013. Obtained clinical information included age, sex, Hunt and Hess grade (HHG), aneurysm location, Fisher grade (FG) and the treatment modality. Concomitant clinical data aside from cerebrovascular condition (hypertension, diabetes, previous medication) were evaluated to determine risk factors that might affect the functional outcomes. RESULTS: A total of 108 patients (67.9%) presented with subarachnoid hemorrhage (SAH), and 51 (32.1%) with unruptured intracranial aneurysms (UIAs). Coiling was performed in 101 patients and 58 patients underwent clipping. In the SAH population, 62 patients (57.4%) showed favorable outcomes, with a mortality rate of 11.3% (n = 18). In the UIAs population, 50 (98%) patients achieved 'excellent' and one (2%) achieved 'good' outcome. Factors including high-grade HHG (p < 0.001), advanced age (p = 0.014), and the presence of intraventricular hematoma (IVH) (p = 0.017) were significant predictors of poor outcome. CONCLUSION: SAH patients with high grade HHG and IVH are associated with poor outcome with statistical significance, all the more prominent the older the patient is. Therefore, the indication for aggressive therapy should be considered more carefully in these patients. However, as the outcomes for elderly patients with UIAs were excellent regardless of the treatment modality, aggressive treatment could always be considered in UIAs cases.

Clinical Outcomes of Posterior C2-C3 Fixation for Unstable Hangman's Fracture Compared with Posterior C1-C3 Fusion

OBJECTIVE: To verify the clinical outcomes of posterior C2-C3 fixation for unstable Hangman's fracture compared with posterior C1-C3 fixation. METHODS: Twenty four patients for unstable Hangman's fracture were enrolled between July 2007 and June 2010 in this study. Thirteen patients underwent posterior C2-C3 fusion and 11 patients underwent posterior C1-C3 fusion. Clinical outcomes were evaluated using Neck Disability Index (NDI) scores and Visual Analogue Scale (VAS) scores during preoperative and postoperative follow up period. Plain radiographs were obtained on postoperative 1 day, 1 week, and then at 1, 2, 6, and 12 months. CT was done at postoperative 12 months in all patients for evaluation of bone fusion. The mean period of clinical follow-up was 15 months. RESULTS: The mean ages were 43.3 years in C2-C3 group and 50.0 years in C1-C3 group. Mean follow-up period was 17.2 months in C2-C3 group and 16.3 months in C1-C3 group. VAS scores and NDI scores in C2-C3 group were much less than those in C1-C3 group at each follow-up period. The differences of VAS score and NDI scores between C2-C3 and C1-C3 groups at each follow-up period were statistically significant (p<0.001) by paired T-test. Solid Bone fusion was confirmed in all cases at the final follow-up. CONCLUSION: C2-C3 group showed better clinical and biomechanical results than C1-C3 group in terms of axial pain and disability of neck.

Large Perforation of Hypopharynx Secondary to Anterior Cervical Approach : A Complicated Case

Perforation of the hypopharynx, which can occur after anterior cervical approach, is a very rare type of complication. If diagnosed late, it can lead to very fatal course, such as mediastinitis and hematosepsis. Therefore, a precise and prompt diagnosis is crucial. When conservative treatment alone is not expected to heal the perforated site or is likely to lead to serious complications, surgical treatment becomes necessary. This report demonstrates that surgical intervention performed immediately after an early diagnosis can lead to the successful treatment of a large perforation in the hypopharynx on a 58-year-old male patient.

Survival of hypoxic human mesenchymal stem cells is enhanced by a positive feedback loop involving miR-210 and hypoxia-inducible factor 1

The use of mesenchymal stem cells (MSCs) has emerged as a potential new treatment for myocardial infarction. However, the poor viability of MSCs after transplantation critically limits the efficacy of this new strategy. The expression of microRNA-210 (miR-210) is induced by hypoxia and is important for cell survival under hypoxic conditions. Hypoxia increases the levels of hypoxia inducible factor-1 (HIF-1) protein and miR-210 in human MSCs (hMSCs). miR-210 positively regulates HIF-1alpha activity. Furthermore, miR-210 expression is also induced by hypoxia through the regulation of HIF-1alpha. To investigate the effect of miR-210 on hMSC survival under hypoxic conditions, survival rates along with signaling related to cell survival were evaluated in hMSCs over-expressing miR-210 or ones that lacked HIF-1alpha expression. Elevated miR-210 expression increased survival rates along with Akt and ERK activity in hMSCs with hypoxia. These data demonstrated that a positive feedback loop involving miR-210 and HIF-1alpha was important for MSC survival under hypoxic conditions.

Gunshot Injury to the Anterior Arch of Atlas

Penetrating injuries to the upper cervical spine resulting from gunshots are rare in South Korea due to restrictions of gun use. Moreover, gunshot wounds to the upper cervical spine without neurological deficits occur infrequently because of the anatomic location and surrounding essential structures. We present an uncommon case involving the surgical removal of a bullet located in the anterior arch of first cervical vertebra (C1) via a transoral approach without neurological complications or subsequent mechanical instability.

Sequential bipolar radiofrequency lumbar sympathectomy in Raynaud's disease: A case report / 대한마취과학회지

A 39-year-old female was suffering from cold-induced Raynaud's attacks in both hands and feet, with symptoms being most severe in her left foot. The patient did not respond to medical treatments and was referred to our department of pain medicine. We performed sequential bipolar radiofrequency lumbar sympathectomy to the patient, which offered a long duration of symptom relief. Sequential bipolar radiofrequency lesions could create continuous strip lesion, and thus, could achieve better results, while the potential risk of liquid neurolytic agents could be avoided.

Granular Cell Tumor on Larynx

Granular cell tumors (GCTs) are uncommon neoplasm. They can originate in any part of the body. The most common sites of origin are in the head and neck, while the larynx is a relatively uncommon location. Patients affected with a laryngeal GCT typically present with persistent hoarseness, stridor, hemoptysis, dysphagia, and otalgia but, the tumor may be asymptomatic. Care must be taken to differentiate this lesion from others due to the presence of pseudo-epitheliomatous hyperplasia which overlies the GCT and may occasionally mimic squamous cell carcinoma. Therefore, a confirmative diagnosis should be made histopathologically and should be supported by immunohistochemical staining. These tumors are treated by complete surgical resection. Examining the complete removal of the tumor through securing a negative free margin is considered to be a consequential procedure. We experienced a 64-yr-old man with a laryngeal granular cell tumor involving the right true vocal cord. He was treated by surgical resection under a fine dissection laryngomicroscope. Here we present this case and a review of literature.

Galectin-8 Expression in Laryngeal Squamous Cell Carcinoma

OBJECTIVES: Despite the ongoing development of treatment protocols for laryngeal squamous cell carcinoma (LSCC), the patients suffering with this malady have shown only a modestly improved outcome. This poor outcome has been attributed to the lack of therapy that's individualized to the tumor's biological properties. Various studies have showed that galectin-8 is widely expressed in tumor tissues as well as in normal tissues, and the level of the galectin-8 expression may correlate with the malignancy of human squamous cell carcinoma. The purpose of this study is to evaluate the expression of galectin-8 and to investigate its correlations with the primary stage, the nodal involvement, the clinical stage and the histologic grade of squamous cell carcinoma of the larynx. METHODS: The paraffin-embedded tissue specimens from 77 patients who were diagnosed as LSCC between 1993 and 2007 were immunohistochemically stained for galectin-8. RESULTS: Immunohistochemical analysis showed that a strong positive expression of galectin-8 was correlated with the T-stages, the nodal stages and the clinical stages. However, the histopathologic grades were not correlated with the galectin-8 expression in LSCC. CONCLUSION: The expression of galectin-8 protein can be used as a prognostic factor for patients with LSCC.

Unilateral phrenic nerve block guided by ultrasonography and nerve stimulator for the treatment of hiccup developed after tongue cancer operation: A case report / 대한마취과학회지

Hiccups are common benign and usually transient phenomenon that occur in nearly everyone. However, persistent or intractable hiccups can cause multiple problems including malnutrition, weight loss, fatigue, dehydration, insomnia, and wound dehiscence. We have experienced a case of postoperative persistent hiccup. The patient was formerly diagnosed tongue cancer and developed persistent hiccup after partial glossectomy with modified radical neck dissection and a radial forearm free-flap operation. He was unsuccessfully managed using pharmacologic methods, and then we tried phrenic nerve block guided by ultrasonography and a nerve stimulator because the surface anatomy of neck was deformed by the previous operation. Thirty minutes after the block, the hiccups disappeared.

Cavernous Lymphangioma in the Nasal Cavity / 대한이비인후과학회지

Cavernous lymphangioma is a benign congenital malformation that usually appears in the early childhood. It may arise in any anatomical location, including the head and neck, but is rarely found in the nasal cavity. Recently, we experienced a case of a cavernous lymphangioma originating from the nasal cavity, which was successfully treated by endoscopic approach without recurrence. Cavernous lymphangioma can occur in the nasal cavity, and therefore, it should be included in the differential diagnosis of mass on the nasal cavity and paranasal sinuses. In this paper, we present and discuss this rare case with a review of the literature.

Distinct Linkage Disequilibrium (LD) Runs of Single Nucleotide Polymorphisms and Microsatellite Markers; Implications for Use of Mixed Marker Haplotypes in LD-based Mapping

It has been suggested that the haplotypic relationship between microsatellite markers and single nucleotide polymorphisms (SNPs) is of considerable importance, as microsatellite markers can potentially be incorporated into haplotypes containing SNPs to increase marker density across a region of interest. However, SNPs and microsatellite markers have different mutation rates and durations, and it is conceivable that the linkage disequilibrium (LD) patterns between the genetic markers may considerably differ. We assessed the LD patterns using 1,661 SNPs and 65 microsatellite markers along chromosome 22 and investigated whether common patterns of LD between the two genetic markers are deduced from the results. The results demonstrated that the patterns of LD among microsatellite markers varied considerably and the LD runs of SNPs and microsatellite markers showed distinct patterns. Microsatellite markers have a much higher mutation rate and the evolution of microsatellite markers is a more complex process which has distinct mutation properties from those of SNPs. We consider that these might contribute to the different LD patterns between the two genetic markers. Therefore, it would seem inadvisable to make assumptions about persistence of LD across even a relatively small genetic distance among microsatellite markers and to construct mixed marker haplotypes/LD maps employing microsatellite markers.

Hemoptysis after Left Subclavian Central Venous Catheterization during Anesthesia Induction for Open Heart Surgery : Two cases report / 대한마취과학회지

Central venous catheters allow a measurement of the hemodynamic variables that cannot be measured accurately by noninvasive means, and allow the delivery of medications and nutritional support that cannot be administered safely through peripheral venous catheters. Unfortunately, the use of central venous catheters is associated with adverse events that are hazardous to patients. Hemoptysis is a significant clinical presentation in respiratory medicine. Often a life threatening emergency, it mandates a prompt assessment and intervention. Fiberoptic bronchoscope is useful and essential for investigating the cause of hemoptysis as well as for managing airway hygiene. We report two cases of hemoptysis after left subclavian central venous catheterization along with the use of a fiberoptic bronchoscope for hemoptysis.