Effect of Glut-1 and HIF-1α double knockout by CRISPR/CAS9 on radiosensitivity in laryngeal carcinoma via the PI3K/Akt/mTOR pathway.

Hypoxic resistance is the main obstacle to radiotherapy for laryngeal carcinoma. Our previous study indicated that hypoxia-inducible factor 1α (HIF-1α) and glucose transporter 1 (Glut-1) double knockout reduced tumour biological behaviour in laryngeal carcinoma cells. However, their radioresistance mechanism remains unclear. In this study, cell viability was determined by CCK8 assay. Glucose uptake capability was evaluated by measurement of 18 F-fluorodeoxyglucose radioactivity. A tumour xenograft model was established by subcutaneous injection of Tu212 cells. Tumour histopathology was determined by haematoxylin and eosin staining, immunohistochemical staining, and TUNEL assays. Signalling transduction was evaluated by Western blotting. We found that hypoxia induced radioresistance in Tu212 cells accompanied by increased glucose uptake capability and activation of the PI3K/Akt/mTOR pathway. Inhibition of PI3K/Akt/mTOR activity abolished hypoxia-induced radioresistance and glucose absorption. Mechanistic analysis revealed that hypoxia promoted higher expressions of HIF-1α and Glut-1. Moreover, the PI3K/Akt/mTOR pathway was a positive mediator of HIF-1α and/or Glut-1 in the presence of irradiation. HIF-1α and/or Glut-1 knockout significantly reduced cell viability, glucose uptake and PI3K/Akt/mTOR activity, all of which were induced by hypoxia in the presence of irradiation. In vivo analysis showed that knockout of HIF-1α and/or Glut-1 also inhibited tumour growth by promoting cell apoptosis, more robustly compared with the PI3K inhibitor wortmannin, particularly in tumours with knockout of both HIF-1α and Glut-1. HIF-1α and/or Glut-1 knockout also abrogated PI3K/Akt/mTOR signalling transduction in tumour tissues, in a manner similar to wortmannin. HIF-1α and/or Glut-1 knockout facilitated radiosensitivity in laryngeal carcinoma Tu212 cells by regulation of the PI3K/Akt/mTOR pathway.

Clinical features and hypoxic marker expression of primary sinonasal and laryngeal small-cell neuroendocrine carcinoma: a small case series.

BACKGROUND: Small-cell neuroendocrine carcinoma (SCNEC) of the head and neck is rare. The prognosis of SCNEC in the nasal cavity and larynx is poor. The aim of this study was to investigate the clinicopathological features of nasal and laryngeal SCNEC and to determine the expression of HIF-1α, GLUT-1, PI3K, and p-Akt in SCNEC. METHODS: Between 2003 and 2012, 10 consecutive patients with histologically demonstrated nasal and laryngeal SCNEC were enrolled. Clinicopathological materials and follow-up data were analyzed retrospectively. Immunohistochemistry was used to detect GLUT-1, HIF-1α, PI3K, and p-Akt expression in paraffin wax-embedded tumor specimens. RESULTS: The subjects were eight males and two females with a mean age of 60.8 (range: 53 to 71) years. Tumors were located in the maxillary sinus (n = 3) and larynx (n = 7). At last follow-up, four patients (40.0%) had local recurrence and five patients (50.0%) had developed distant metastases. Six patients died. The mean overall survival was 19.3 ± 2.1 months. Expression of GLUT-1, HIF-1α, PI3K, and p-Akt was seen in sinonasal and laryngeal SCNEC in 80 (8 out of 10), 50 (5 out of 10), 40 (4 out of 10), and 40% (4 out of 10) of cases, respectively. Expression of GLUT-1, HIF-1α, PI3K, and p-Akt was higher in sinonasal and laryngeal SCNEC than in precancerous lesions. CONCLUSIONS: Primary sinonasal and laryngeal SCNEC is rare. This paper presents 10 cases of sinonasal and laryngeal SCNEC with more common local recurrence and distant metastasis. HIF-1α, GLUT-1, PI3K, and p-Akt expression was higher in sinonasal and laryngeal SCNEC than in precancerous lesions.

Expression of hypoxia-related markers in inflammatory myofibroblastic tumors of the head and neck.

BACKGROUND: The etiology of inflammatory myofibroblastic tumors (IMTs) is controversial and the prognosis is unpredictable. Previous studies have not investigated the expression of hypoxia-related markers in IMTs. METHODS: Between 2002 and 2012, 12 consecutive patients with histologically proven IMTs were enrolled in the study. Immunohistochemistry was used to detect GLUT-1, HIF-1α, PI3K, and p-Akt expression in paraffin-embedded tumor specimens. Associations among GLUT-1, HIF-1α, PI3K, and p-Akt protein expression and clinical parameters were investigated. RESULTS: The mean duration of follow-up was 52.1 months (range, 11 to 132 months). Six patients had local recurrence. GLUT-1, HIF-1α, PI3K, and p-Akt expression were detected in 41.7%, 50.0%, 33.3%, and 41.7% of patients, respectively. Fisher's exact test revealed significant correlations between recurrence of IMT and PI3K expression (P = 0.01) and p-Akt expression (P = 0.015). Univariate analyses revealed significant correlations between survival and GLUT-1 expression (P = 0.028), PI3K expression (P = 0.006), and p-Akt expression (P = 0.028). Multivariate analysis did not show a significant relationship between survival and GLUT-1, HIF-1α, PI3K, or p-Akt. Spearman rank correlation analysis showed significant correlations between HIF-1α and PI3K expression (r = 0.707, P = 0.01) and between p-Akt and PI3K expression (r = 0.837, P = 0.001). CONCLUSIONS: Although our results are inconclusive owing to the small sample size, they suggest that PI3K and p-Akt expression may play a role in the recurrence of IMTs of the head and neck.

Upregulation of caveolin-1 and SR-B1 in mice with non-alcoholic fatty liver disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is one of the most frequent causes of liver diseases, with markedly increased prevalence. However, its mechanisms are not clear. The present study was undertaken to illustrate the role of caveolin-1 (cav1) and the scavenger receptor class B type 1 (SR-B1) in NAFLD. METHODS: Adult male C57BL/6 mice were fed with a normal diet or high fat and cholesterol (HFC) diet for 14 weeks. The mice were sacrificed to collect plasma and harvest the liver; their plasma lipid concentration was measured. Hepatic cav1 and SR-B1 mRNA and protein expression were determined by real-time quantitative polymerase chain reaction (qPCR) and Western blotting, respectively. In order to study cav1 and SR-B1 distribution and change in hepatocytes, immunohistochemical analysis was performed. RESULTS: HFC diet increased plasma lipids, induced NAFLD and increased the liver/body weight ratio. Compared to the control mice (n=6), the mRNA and protein levels of cav1 and SR-B1 in liver tissue of the NAFLD mice (n=12) increased significantly (cav1 mRNA: 1.536+/-0.226 vs 0.980+/-0.272, P<0.05; protein: 0.643+/-0.240 vs 0.100+/-0.130, P<0.01; SR-B1 mRNA: 1.377+/-0.125 vs 0.956+/-0.151, P<0.01; protein: 2.156+/-0.507 vs 0.211+/-0.211, P<0.01). Furthermore, both cav1 and SR-B1 immunoreactivity increased and their distribution was also changed, mainly in the plasma membrane of hepatocytes, cytoplasm and membrane of lipid droplets and around. CONCLUSION: NAFLD is associated with increased concentration of plasma lipids and upregulation of hepatic cav1 and SR-B1 gene and protein expressions, which indicate that cav1 and SR-B1 might play crucial roles in the pathogenesis of NAFLD.

Poor outcome of comprehensive therapy in a case of laryngeal synovial sarcoma.

BACKGROUND: Synovial sarcoma is common in the extremities. Our search revealed only 17 cases of synovial sarcoma of the larynx in the English-language literature. CASE REPORT: We report an additional case of a 37-year-old man with primary laryngeal synovial sarcoma who underwent positron emission tomography/computed tomography (PET/CT) following the treatment. Although the patient received comprehensive therapy including surgery, radiotherapy, repeated chemotherapies, and targeted therapies, he had an unfavourable outcome and died of distant metastases. CONCLUSIONS: In synovial sarcoma of the larynx, PET/CT can detect recurrence and metastasis. PET/CT can also predict the treatment effect in patients with synovial sarcoma.

Pepsin Increases the Proliferation of Vocal Cord Leukoplakia Epithelial Cells by Inducing Autophagy.

OBJECTIVE: To investigate the role of H+ /K+ ATPase in the proliferation of pepsin-induced vocal cord leukoplakia (VCL) cells. STUDY DESIGN: Translation research. SETTING: Affiliated Hospital of University. METHODS: Immunohistochemistry was used to detect pepsin, H+ /K+ ATPase (ATP4A and ATP4B subunits) in VCL cells with varying degrees of dysplasia. After primary cultures of VCL cells had been established, the effects of acidified pepsin on the proliferation, autophagy, and H+ /K+ -ATPase distribution of VCL cells were investigated. RESULTS: The levels of pepsin, ATP4A, and ATP4B were significantly higher in VCL tissue with moderate-to-severe dysplasia than in normal tissue (p < .05); these levels gradually increased according to dysplasia severity. The expression levels of ATP4A and ATP4B were significantly correlated with the amount of pepsin in VCL cells (p < .01). Acidified pepsin enhanced the levels of proliferation and autophagy in human VCL epithelial cells. The cloning- and autophagy-promoting effects of acidified pepsin on VCL cells were partially reversed by pantoprazole; these effects were completely blocked by the autophagy inhibitor chloroquine. Finally, acidified pepsin promoted the colocalization of H+ /K+ -ATPase and lysosomes in VCL cells; it also mediated lysosome acidification. CONCLUSION: Pepsin and H+ /K+ -ATPase may contribute to the progression of VCL. Specifically, acidified pepsin may regulate lysosome acidification by promoting lysosomal localization of H+ /K+ -ATPase.

Angioleiomyoma of the Epiglottis Mimicking Epiglottic Hemangioma: Clinical Experience and Literature Review.

We describe a case of laryngeal angioleiomyoma, discuss its characteristic features and management, and provide a review of the literature, to improve clinical diagnosis and treatment. We report the oldest patient with a laryngeal angioleiomyoma to date and analyze the clinicopathological features reported in the literature. To the best of our knowledge, a total of 36 cases have been described in the English and Chinese medical literature (including our case). The male-to-female ratio was 5:1 and the mean age was 53.89 years. The most common laryngeal site was the supraglottic region (23 cases; 63.89%), followed by the subglottic region (8 cases; 22.22%), and glottis (5 cases; 13.89%). The most common and serious intra- and postoperative complication was massive bleeding. Angioleiomyoma is a benign tumor that rarely occurs in the larynx. Biopsy of this lesion should not be performed; complete surgical resection is the best treatment. Recurrence and malignant transformation are extremely rare.

Epstein-Barr virus-associated leiomyosarcoma of the larynx in an adult patient with human immunodeficiency virus infection: Case report and review of the literature.

We investigated the clinical features, treatment, and prognosis of laryngeal leiomyosarcoma (LLMS) and Epstein-Barr virus-associated (EBV-associated) LMS. We report a case of EBV-associated LLMS in an adult patient with HIV infection. We also conducted a review of the English-language literature on LLMS and EBV-associated leiomyosarcoma. To the best of our knowledge, 62 cases of LLMS and EBV-associated leiomyosarcoma have been reported to date. Of patients with LLS, 18.9% had distant metastases and 17.0% had local recurrence. The overall 5-year survival rate was 64.0%. Distant metastases affected the survival of patients with LLMS (p = 0.04). EBV-positive patients had a low survival rate (p = 0.01). Among patients with EBV-associated LMS, 8.2% had distant metastases and recurrence and the overall 5-year survival rate was 50.0%. EBV-associated LLMS is rare. The EBV infection might be a poor prognostic factor of LLMS.

Roles of sulfonylurea receptor 1 and multidrug resistance protein 1 in modulating insulin secretion in human insulinoma.

BACKGROUND: Sulfonylurea receptor 1 (SUR1) and multidrug resistance protein 1 (MRP1) are two prominent members of multidrug resistance proteins associated with insulin secretion. The aims of this study were to investigate their expression in insulinomas and their sole and synergistic effects in modulating abnormal insulin secretion. METHODS: Fasting glucose, insulin and C-peptide were measured in 11 insulinoma patients and 11 healthy controls. Prolonged oral glucose tolerance tests were performed in 6 insulinoma patients. Insulin content, SUR1 and MRP1 were detected in 11 insulinoma patients by immunohistochemistry. SUR1 and MRP1 were also detected in 6 insulinoma patients by immunofluorescence. RESULTS: Insulinoma patients presented the typical demonstrations of Whipple's triad. Fasting glucose of each insulinoma patient was lower than 2.8 mmol/L, and simultaneous insulin and C-peptide were increased in insulinoma patients. Prolonged oral glucose tolerance tests showed that insulin secretion in insulinoma patients were also stimulated by high glucose. Immunohistochemistry and immunofluorescence staining showed that SUR1 increased, but MRP1 decreased in insulinoma compared with the adjacent islets. CONCLUSIONS: The hypersecretion of insulin in insulinomas might be, at least partially, due to the enrichment of SUR1. In contrast, MRP1, which is down-regulated in insulinomas, might reflect a negative feedback in insulin secretion.

[Expression of GADD153 in follicular tumors of thyroid and comparison with CK19, Galectin-3 and HBME-1].

OBJECTIVE: To study immunohistochemical expression of GADD153 and assess its usefulness as markers in the differential diagnoses in follicular tumors of the thyroid. METHODS: Immunohistochemical staining was performed on formalin-fixed paraffin-embedded tissue of 34 cases of follicular thyroid adenomas (FTA), 46 cases of follicular thyroid carcinomas (FTC), 29 cases of follicular variant papillary carcinomas (FVPC). RESULTS: (1) GADD153 was expressed in cell nucleus with positive or strong positive expression in FTC, and no or weak expression in FTA and FVPC. The positive expressions of GADD153 were present in 38 of 46(82.6%) in FTC, 11 of 34(32.4%) in FTA and three of 29(10.3%) in FVPC, the positive expression rate in FTC was obviously higher than that in FTA and in FVPC, the differences were statistically significant (χ² = 20.80 and 37.48; P < 0.01). (2) CK19, Galectin-3 (Gal-3) and HBME-1 were all expressed in the cytoplasm, the positive expressions of CK19, Gal-3 and HBME-1 were present in 54.3% (25/46), 67.4% (31/46) and 58.7% (27/46) in FTC; 50.0% (17/34), 29.4% (10/34) and 32.4% (11/34) in FTA; 100% (29/29), 93.1% (27/29) and 89.7% (26/29) in FVPC, the differences were statistically significant as well (χ² = 21.20 and 8.22; P < 0.01). (3) According to the expressions of CK19, Gal-3, HBME-1 and GADD153, we divided the results into low expression group (0 or 1+) and high expression group (2+ or 3+), the sensitivity and the specificity were calculated. in FTA, the sensitivity were 26.5%, 8.8%, 2.9% and 11.8%; the specificity were 50.7%, 52.0%, 54.7% and 58.7%. in FTC, the sensitivity were 19.6%, 26.1%, 23.9% and 65.2%; the specificity were 41.3%, 57.1%, 62.0% and 92.1%. in FVPC, the sensitivity were 96.6%, 82.8%, 79.3% and 3.4%; the specificity were 77.5%, 81.3%, 85.0% and 57.5%. CONCLUSIONS: The sensitivity and the specificity of GADD153 expression are well for diagnosing FTC, and CK19, Gal-3, HBME-1 are well for FVPC. The four markers when used in combination, are better to identify the follicular tumors of the thyroid.

Relationship Between Pepsin Expression and Dysplasia Grade in Patients With Vocal Cord Leukoplakia.

OBJECTIVE: To measure pepsin expression in patients with vocal fold leukoplakia and elucidate its clinical significance. STUDY DESIGN: Retrospective analysis of pathologic archive specimens. SETTING: Affiliated university hospital. SUBJECTS AND METHODS: The study included 45 patients with vocal fold leukoplakia and 19 with vocal fold polyps who underwent surgical treatment between December 2013 and July 2016. Masses were detected on both vocal cords in 5 patients with vocal fold leukoplakia and in 1 patient with vocal fold polyps. Immunohistochemistry was used to assess pepsin expression. In addition, the relationship of pepsin expression level with clinical characteristics of vocal fold leukoplakia was assessed. RESULTS: The rate of pepsin expression was high in the polyp group (75%) and the leukoplakia group (68%); however, the difference between groups was not significant (P > .05). Pepsin expression significantly increased according to grade of dysplasia (mild, 57.1%; moderate, 88.9%; severe, 100.0%; P = .034). Similarly, the percentage of lesions that exhibited strongly positive pepsin expression increased with the grade of dysplasia (mild, 37.1%; moderate, 66.7%; severe, 100.0%; P = .005). The leukoplakia recurrence rate was higher in patients with positive pepsin expression than in patients with negative pepsin expression but without a significant difference (P > .05). CONCLUSION: Our study suggests that pepsin was associated with the grade of dysplasia of vocal cord leukoplakia. Further investigation with appropriate control groups and controlling for other risk factors, such as smoking or alcohol consumption, is needed.

Epstein-Barr Virus-Positive Langerhans Cell Sarcoma: Is There a Link? A Case Report.

Langerhans cell sarcoma (LCS) is an extremely rare, malignant neoplasm that originates from Langerhans cells (LCs). Fewer than 70 cases have been reported in the English-language literature. LCS typically involves multiple organs, including the skin, lymph nodes, lungs, bone, bone marrow, liver, spleen, and soft tissues. Several etiological factors for LCS have been proposed, including immunosuppression, virus infection, and prior hematological disease. We report a rare case of LCS with Epstein-Barr virus (EBV) infection; bilateral cervical giant cysts were the initial manifestation. To our knowledge, this is the first report of LCS with EBV infection. The case information was complete, and the relevant literature was reviewed to gain insight into LCS. The case raises new questions on the oncogenic character of EBV.

Gastric H+/K+-ATPase Expression in Normal Laryngeal Tissue and Laryngeal Carcinoma.

BACKGROUND: Several studies have suggested that laryngopharyngeal reflux disease (LPRD) or gastroesophageal reflux disease (GERD) is an independent risk factor for laryngeal carcinoma. However, it remains unclear whether either condition affects the level of H+/K+-ATPase expression in laryngeal carcinoma. MATERIALS AND METHODS: Immunohistochemistry, real-time RT-PCR, and Western blotting were used to explore the distributions of proton pump (H+/K+-ATPase) α- and ß-subunits in normal laryngeal tissue and laryngeal carcinoma. RESULTS: Messenger RNAs encoding both the α- and ß-subunits were found in the normal epiglottic, ventricular fold, vocal fold, and arytenoid mucosae, as well as epiglottic cartilage. The distributions and expression levels of H+/K+-ATPase α-subunits in various laryngeal subregions did not significantly differ in IHC, RT-PCR, or Western blotting. However, Western blotting revealed a significant difference between the expression level of the ß-subunit protein in the epiglottic cartilage and the levels in other sites. The expression levels of both subunits were significantly higher in carcinomatous than in paracarcinomatous tissue and normal laryngeal tissue. The mean follow-up duration was 66.2 months (range, 17-162 months). In all, 4 patients died during follow-up, 4 were lost to follow-up, and 22 were alive and free of disease at the end of follow-up. Two patients developed lung metastases and six developed disease recurrences (at 2, 8, 14, 16, 36, and 41 months). The 3- and 5-year overall survival (OS) rates were 93.0% and 77.0%, respectively. Univariate analyses showed that the 5-year OSs were significantly associated with the T, N, and clinical stages but not with age, alcohol use, pathological differentiation, or the expression levels of the α- or ß-subunits (as revealed by IHC, RT-PCR, or Western blotting). However, in multivariate regression analyses, the 5-year OSs were not significantly associated with any clinicopathological factor or the expression levels of either subunit. CONCLUSION: H+/K+-ATPase is expressed in the normal larynx, including in the epiglottic cartilage and the mucosae of the epiglottis, ventricular fold, and arytenoid vocal fold. The expression levels of the H+/K+-ATPase α- and ß-subunits in laryngeal carcinomas were higher than in normal laryngeal tissues.

Collision carcinoma of squamous cell carcinoma and small cell neuroendocrine carcinoma of the larynx: A case report and review of the literature.

BACKGROUND: Collision carcinoma is rare in clinical practice, especially in the head and neck region. In this paper, we report a case of squamous cell carcinoma (SCC) and neuroendocrine carcinoma (NEC) colliding in the larynx and review 12 cases of collision carcinoma in the head and neck to further understand collision carcinoma, including its definition, diagnosis, and treatment. CASE SUMMARY: A 61-year-old man presented with a 1-year history of hoarseness. Contrast-enhanced magnetic resonance imaging of the larynx revealed that the right vocal cord had a nodule-like thickening with obvious enhancement. Laryngoscopy revealed a neoplasm on the right vocal cord, and a malignant tumor was initially considered. A frozen section of right vocal cord was performed under general anesthesia. The pathological result showed a malignant tumor in the right vocal cord. The tumor was excised with a CO2 laser (Vc type). Routine postoperative pathology showed moderately differentiated SCC with small cell NEC in the right vocal cord. No metastatic lymph nodes or distant metastases were found on postoperative positron emission tomography/computed tomography. Because of the coexistence of SCC and NEC, the patient received adjuvant chemotherapy and radiotherapy. The patient was followed for 8 mo, and no recurrence or distant metastasis was found. CONCLUSION: The treatment of collision carcinoma in the head and neck region is uncertain due to the small number of cases.

True hypopharyngeal carcinosarcoma: a case report and literature review.

Objective Carcinosarcoma consists of carcinomatous and sarcomatous tissues and is an aggressive malignant tumor. It is rarely reported in the hypopharynx. Methods A 72-year-old man presented with dysphagia and dyspnea. Laryngoscopy, computed tomography (CT), and 18F-fluorodeoxyglucose positron emission tomography/CT (18F-FDG PET/CT) showed a neoplasm on the left posterior hypopharyngeal wall. The patient underwent bilateral neck dissection and excision of the hypopharyngeal cancer followed by postoperative radiation therapy. Results Immunohistochemistry revealed carcinomatous cells with membrane positivity for cytokeratin, glucose transporter-1 (GLUT-1), phosphoinositide-3 kinase (PI3K), hypoxia-inducible factor-1α (HIF-1α), and hexokinase-II as well as sarcomatous cells with membrane positivity for smooth muscle actin, GLUT-1, HIF-1α, and PI3K. Histopathology and immunohistochemistry revealed a true carcinosarcoma of the hypopharynx (pT3N0M0, Stage III). Conclusions Thorough immunohistochemistry is required for a correct diagnosis of hypopharyngeal carcinosarcoma. 18F-FDG PET/CT may help to distinguish hypopharyngeal carcinosarcoma from benign tumors.

[Inflammatory myofibroblastic tumor of bladder: a clinicopathologic study of five cases].

OBJECTIVE: To study the clinicopathologic features, diagnosis and differential diagnosis of inflammatory myofibroblastic tumor of the urinary bladder. METHODS: Excisional specimens from 5 cases of vesical inflammatory myofibroblastic tumor were studied by light microscopy and immunohistochemistry (EnVision). The clinical data were also analyzed. RESULTS: Among the 5 patients studied, 3 were males and 2 were females. The age of the patients ranged from 10 to 53 years (mean age = 35 years). The most common clinical presentation was micturition pain and hematuria. Three cases were located at the dome of the urinary bladder and the remaining 2 cases were found in the left lateral wall. Histologically, the tumor varied from myxoid to highly cellular. The tumor cells were spindle to stellate in shape, widely separated or showed a compact fascicular pattern. There were often associated with mixed inflammatory infiltrates and an irregular meshwork of small dilated vessels. Immunohistochemical study showed that the tumor cells expressed AE1/AE3 (5/5), vimentin (5/5), smooth muscle actin (5/5), calponin (5/5), caldesmon (3/5), desmin (4/5) and anaplastic lymphoma kinase protein (4/5). Follow-up data were available in 4 patients and none had local recurrence or died of this disease. CONCLUSION: Inflammatory myofibroblastic tumour of urinary bladder is a rarely encountered but distinctive neoplasm with intermediate malignant potential.

Cutaneous and Subcutaneous Metastases From Atypical Laryngeal Carcinoids: Case Report and Review of the Literature.

The incidence of cutaneous and subcutaneous metastases from atypical laryngeal carcinoids is approximately 20%. However, the pathogenesis and natural history of, and prognostic factors for, the condition remain poorly understood. We reported a 54-year-old female presented with cutaneous and subcutaneous metastases from atypical laryngeal carcinoid. Laryngoscopy revealed a 0.5 × 1.5-cm reddish mass on the laryngeal surface of the epiglottis. Under general anesthesia, a biopsy sample was obtained via suspension laryngoscopy. Routine pathology revealed atypical laryngeal carcinoid. Immunohistochemical staining of the sections of primary tumor was positive for cytokeratin, chromogranin A, synaptophysin, hypoxia-inducible factor-1α, P53, and CD56. GLUT-1, p-Akt, and PI3K were negative. The Ki-67 index was 15%. Supraglottic laryngectomy and selective right-neck dissection were performed. After 6 months, the patient complained of pain in the right wall of the chest; multiple cutaneous and subcutaneous nodules were evident at that site and in the abdomen. An abdominal nodule was biopsied and pathology revealed that the atypical metastatic carcinoid had metastasized to both cutaneous and subcutaneous areas of the abdomen. Chemotherapy was then prescribed. Currently, the intrathecal drug delivery system remains in place. No local recurrence has been detected. Furthermore, we systematically reviewed clinical manifestations of the disease, pathogenesis, prognostic factors, and treatment. The metastasis rate (cutaneous and subcutaneous) was approximately 12.2%. Thirty patients (62.5%) with cutaneous and subcutaneous metastases exhibited contemporaneous lymph node invasion. The 3-, 5-, and 10-year survival rates were 44.0%, 22.0%, and 13.0%, respectively. The prognosis of patients with atypical laryngeal carcinoids was poor. Relevant prognostic factors included the level of p53, human papilloma virus status, certain hypoxic markers, and distant metastasis. No optimal treatment for such metastases has yet been defined.

Increased expression of aquaporin-4 in human traumatic brain injury and brain tumors.

OBJECTIVE: To characterize the expression of aquaporin-4 (AQP4), one of the aquaporins (AQPs), in human brain specimens from patients with traumatic brain injury or brain tumors. METHODS: Nineteen human brain specimens were obtained from the patients with traumatic brain injury, brain tumors, benign meningioma or early stage hemorrhagic stroke. MRI or CT imaging was used to assess brain edema. Hematoxylin and eosin staining were used to evaluate cell damage. Immunohistochemistry was used to detect the AQP4 expression. RESULTS: AQP4 expression was increased from 15 h to at least 8 d after injury. AQP4 immunoreactivity was strong around astrocytomas, ganglioglioma and metastatic adenocarcinoma. However, AQP4 immunoreactivity was only found in the centers of astrocytomas and ganglioglioma, but not in metastatic adenocarcinoma derived from lung. CONCLUSION: AQP4 expression increases in human brains after traumatic brain injury, within brain-derived tumors, and around brain tumors.