Jiajia Liu

Diagnosis and treatment of nine cases with carotid artery rupture due to hypopharyngeal and cervical esophageal foreign body ingestion

The aim of our study is to present our experience in the diagnosis and treatment of patients with carotid artery rupture (CAR) due to foreign body ingestion. A total of nine admissions with CAR due to foreign body ingestion were recorded in Second Xiangya Hospital between 1969 and 2011. The carotid artery was sutured with muscle flap coverage in six cases, ligated in three cases. We retrospectively compared different surgical procedures of the patients and their clinical outcomes. Results show that CAR was found in all of these nine cases in imaging examinations or surgery. Among these six patients treated by suture of the carotid artery, five patients had a complete recovery without any complications, one patient underwent common carotid artery (CCA) ligation after suture surgery, but finally died of massive hemorrhage due to uncontrollable infection with carotid artery erosion. Among these three patients treated only by CCA ligation, one patient had no complications, one patient had hemiplegia, and one patient died of severe cerebral edema. Hence, timely diagnosis and open surgery are important for the patients of CAR due to foreign body ingestion. Suture of the carotid artery with muscle flap coverage is a better method compared with ligation of the carotid artery in the treatment of CAR.

Elevated expression of T-lymphoma invasion and metastasis inducing factor 1 in squamous-cell carcinoma of the head and neck and its clinical significance.

PURPOSEnT-lymphoma invasion and metastasis inducing factor 1 (Tiam1) overexpression has been reported in a variety of human cancers. However, the investigation of Tiam1 in squamous-cell carcinoma of the head and neck (SCCHN) is extremely rare. The aim of the present study is to assess Tiam1 expression and to explore its role in SCCHN.nnnMETHODSnTiam1 expression in 119 primary SCCHN tissue specimens was analysed by immunohistochemistry and correlated with clinicopathological parameters and patients survival. Additionally, 12 paired SCCHN tissues were evaluated for Tiam1 expression by Western blotting.nnnRESULTSnWestern blotting indicated that Tiam1 expression levels in SCCHN carcinomas were significantly higher than those in the corresponding paraneoplastic tissues (P<0.001). Immmunohistochemistry staining revealed that Tiam1 was detected in all primary tumour samples, moreover, Tiam1 overexpression was significantly correlated with lymph node metastasis (P<0.001), clinical stage (P<0.001), histological grade (P=0.001) and recurrence (P<0.001). Survival analysis demonstrated that high Tiam1 expression was significantly correlated with shorter disease-free survival and overall survival (both P<0.001). When combining the Tiam1 expression and lymph node status, Kaplan-Meier survival showed that patients with Tiam1 overexpression/lymph node metastasis (+) had both shorter disease-free and overall survival than others (both P<0.001). Multivariate Cox proportional hazards model analysis confirmed that lymph node metastasis, histological grade and Tiam1 overexpression were statistically significant, independent predictor of prognosis for patients with SCCHN.nnnCONCLUSIONnTiam1 may contribute to SCCHN progression, and represent as a novel prognostic indicator as well as a potential therapeutic target for SCCHN.

Inhibition of HAX-1 by miR-125a reverses cisplatin resistance in laryngeal cancer stem cells

Chemoresistance is a major obstacle in chemotherapy of laryngeal carcinoma. Recently, studies indicate that cancer stem cells are responsible for chemotherapy failure. In addition, microRNAs play important roles in tumor initiation, development and multidrug resistance. In the present study, we found that the expression of microRNA-125a was decreased in laryngeal carcinoma tissues and Hep-2 laryngeal cancer stem cells (Hep-2-CSCs). MicroRNA-125a gain-of-function significantly increased the sensitivity of Hep-2-CSCs to cisplatin in vitro and in vivo. Combination with microRNA-125a mimics can decrease the half maximal inhibitory concentration of Hep-2-CSCs to cisplatin. Mechanically, we found that microRNA-125a reverses cisplatin resistance in Hep-2-CSCs by targeting Hematopoietic cell-specific protein 1-associated protein X-1 (HAX-1). Inhibition of HAX-1 by microRNA-125a significantly promotes the cisplatin-induced apoptosis in Hep-2-CSCs through mitochondrial pathway. In addition, multidrug resistance of Hep-2-CSCs to vincristine, etoposide and doxorubicin was greatly improved after the cells were transfected with microRNA-125a mimics. These dates strongly suggested the promotion of microRNA-125a/HAX-1 axis on chemotherapy of laryngeal carcinoma.

Value of fused positron emission tomography CT in detecting primaries in patients with primary unknown cervical lymph node metastasis

Objective: Identification of the primary tumour can prolong the life expectancy of patients with primary unknown cervical lymph node metastasis (PUCLNM) through targeted therapy. This study investigated the value of 18F‐fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET‐CT) at identifying primaries in patients with PUCLNM.

Xenogeneic acellular dermal matrix in combination with pectoralis major myocutaneous flap reconstructs hypopharynx and cervical esophagus.

The aim of this study was to explore xenogeneic acellular dermal matrix (ADM) in combination with pectoralis major myocutaneous flap in hypopharynx and cervical esophagus reconstruction. A total of five patients were treated with this surgical method to reconstruct hypopharynx and cervical esophagus in Second Xiangya Hospital between January 2012 and April 2013. Four of them had hypopharyngeal carcinoma with laryngeal and cervical esophageal invasion, while the fifth patient with hypopharyngeal cancer had developed scars and atresia after postoperative radiotherapy. The defect length after hypopharyngeal and cervical esophageal resection was 6–8xa0cm, and was repaired by a combination of ADM and pectoralis major myocutaneous flap by our team. Interestingly, the four patients had primary healing and regained their eating function about 2–3xa0weeks after surgery, the fifth individual suffered from pharyngeal fistula, but recovered after dressing change about 2xa0months. Postoperative esophageal barium meals revealed that the pharynx and esophagus were unobstructed in all five patients. Xenogeneic ADM in combination with pectoralis major myocutaneous flap for hypopharynx and cervical esophagus reconstruction is a simple, safe and effective method with fewer complications. Nevertheless, according to the defect length of the cervical esophagus, the patients need to strictly follow the medical advice.

Simultaneously targeting Bcl-2 and Akt pathways reverses resistance of nasopharyngeal carcinoma to TRAIL synergistically.

AIMS AND BACKGROUNDnDespite progress in treatment techniques, the five-year survival rate of nasopharyngeal carcinoma (NPC) is disappointing. Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) can selectively induce apoptosis in most tumor cells while sparing normal cells. Given the antiapoptotic functions of Bcl-2 and Akt, we examined the effects of targeting these pathways alone or simultaneously on TRAIL apoptosis in NPC cell lines.nnnMETHODS AND STUDY DESIGNnWe first tested the cytotoxic effect of TRAIL and the expression of death receptors, Bcl-2, Akt, and p-Akt on four NPC cell lines by MTT and Western blotting, respectively. Small interfering RNAs (siRNAs) targeting Bcl-2 and PI3-K inhibitor (LY294002) were used alone or combined with TRAIL in the cell lines and cytotoxicity was examined by MTT. Apoptosis rates, mitochondrial transmembrane potential, and apoptotic pathway signals were detected by flow cytometric analysis, DiOC6(3) assays, and Western blotting after the various combination treatments on CNE-2, the cell line that was most resistant to TRAIL.nnnRESULTSnAlthough no direct correlation between the sensitivity to TRAIL and the relative expression levels of Bcl-2 and activated Akt was found in the NPC cell lines examined, siRNA mediated the downregulation of Bcl-2 and LY294002-induced inactivation of Akt, increasing the sensitivity of all examined NPC cell lines to TRAIL. Synergistic enhancement of TRAIL-mediated cytotoxicity was observed in combination treatment of Bcl-2 siRNA and LY294002 compared to cells treated with each treatment alone. The synergistic effects were mediated through increased apoptotic signaling of the mitochondrial pathway, as was evident from the more increased mitochondrial depolarization, activation of caspase-9 and caspase-3, and suppression of XIAP.nnnCONCLUSIONSnThis study provides proof of principle that TRAIL combined with simultaneously targeting the Bcl-2 and Akt signaling pathways may have potential as a novel future treatment strategy for NPC.

Bisphenol A triggers proliferation and migration of laryngeal squamous cell carcinoma via GPER mediated upregulation of IL-6

Bisphenol A (BPA) can be accumulated into the human body via food intake and inhalation. Numerous studies indicated that BPA can trigger the tumorigenesis and progression of cancer cells. Laryngeal cancer cells can be exposed to BPA directly via food digestion, while there were very limited data concerning the effect of BPA on the development of laryngeal squamous cell carcinoma (LSCC). Our present study revealed that nanomolar BPA can trigger the proliferation of LSCC cells. Bisphenol A also increased the in vitro migration and invasion of LSCC cells and upregulated the expression of matrix metallopeptidase 2. Among various chemokines tested, the expression of IL‐6 was significantly increased in LSCC cells treated with BPA for 24 hours. Neutralization antibody of IL‐6 or si–IL‐6 can attenuate BPA‐induced proliferation and migration of LSCC cells. Targeted inhibition of G protein–coupled estrogen receptor, while not estrogen receptor (ERα), abolished BPA‐induced IL‐6 expression, proliferation, and migration of LSCC cells. The increased IL‐6 can further activate its downstream signal molecule STAT3, which was evidenced by the results of increased phosphorylation and nuclear translocation of STAT3, while si–IL‐6 and si‐GPER can both reverse BPA‐induced activation of STAT3. Collectively, our present study revealed that BPA can trigger the progression of LSCC via GPER‐mediated upregulation of IL‐6. Therefore, more attention should be paid for the BPA exposure on the development of laryngeal cancer.

Pharyngoesophageal perforation 3 years after anterior cervical spine surgery: a rare case report and literature review

Pharyngoesophageal perforation after anterior cervical spine surgery is rare and the delayed cases were more rarely reported but potentially life-threatening. We report a case of pharyngoesophageal perforation 3xa0years after anterior cervical spine surgery. The patient presented with dysphagia, fever, left cervical mass and developing dyspnea 3xa0years after cervical spine surgery for trauma. After careful examinations, he underwent an emergency tracheostomy, neck exploration, hardware removal, abscess drainage and infected tissue debridement. 14xa0days after surgery, CT of the neck with oral contrast demonstrated no contrast extravasation from the esophagus. Upon review of literature, only 14 cases of pharyngoesophageal perforation more than 1xa0year after anterior cervical spine surgery were found. We discussed possible etiology, diagnosis and management and concluded that in cases of dysphagia, dyspnea, cervical pain, swelling and edema of the cervical area even long time after anterior cervical spine surgery, potential pharyngoesophageal damage should be considered.

lncRNA-NKILA/NF-κB feedback loop modulates laryngeal cancer cell proliferation, invasion, and radioresistance

Laryngeal cancer is one of the most common head and neck malignant tumors and is commonly resistant to X‐ray‐based radiotherapy. NF‐κB interacting lncRNA (NKILA) has been reported to serve as a tumor suppressor in several cancers through combining with NF‐κB: IκB complex thereby inhibiting NF‐κB activation. Herein, we demonstrated a low NKILA expression in laryngeal cancer and its correlation with shorter overall survival in patients with laryngeal cancer. NKILA serves as a tumor suppressor in laryngeal cancer by suppressing laryngeal cancer cell viability and migration, whereas promoting cell apoptosis; NKILA knockdown reverses the cytotoxicity of X‐ray radiation on laryngeal cancer cells through combining with NF‐κB: IκB complex to inhibit IκB phosphorylation, inhibit p65 nuclear translocation, and finally inhibit NF‐κB activation. NF‐κB binds to the promoter region of NKILA to activate its transcriptional activity, upregulated NKILA then inhibits IκB phosphorylation and NF‐κB activation, thus forming a negative feedback loop to sensitize laryngeal cancer cell to X‐ray radiation. In conclusion, NKILA can serve as a promising agent of enhancing the cytotoxicity of X‐ray radiation on laryngeal cancer and addressing the radioresistance of laryngeal cancer.

Clinical significance of TrkB expression in nasopharyngeal carcinoma.

Recent research has demonstrated that tropomyosin‑related kinase B (TrkB) plays an important role in neuronal survival, differentiation and migration; yet, its specific role in human nasopharyngeal carcinoma (NPC) is unclear. To elucidate its role in NPC, we examined TrkB expression in NPC tissues and cell lines, and investigated the correlation between TrkB expression and prognosis in patients with NPC. Immunohistochemical analysis was performed on NPC specimens from 108 patients with follow-up information. Additionally, reverse transcriptase-polymerase chain reaction (RT-PCR) and western blot analyses were used to determine TrkB expression levels in NPC and noncancerous nasopharyngeal tissues. RT-PCR and western blot analyses were also used to determine TrkB expression levels in 7 NPC cell lines and a nasopharyngeal epithelium cell line. High TrkB expression was significantly correlated with T classification, lymph node metastasis and clinical stage, respectively. Patients with NPC who had high TrkB expression had reduced disease-free survival and overall survival when compared with patients who had low TrkB expression. Multivariate Cox regression analysis revealed that TrkB overexpression was an independent prognostic factor for patients with NPC. Furthermore, TrkB was overexpressed in NPC specimens and cell lines. TrkB expression levels were significantly increased in NPC specimens, and enhanced levels were correlated with a poor prognosis in patients with NPC. These findings suggest that TrkB may contribute to NPC progression and represent a novel prognostic indicator for patients with NPC.