Humans ; Herpesvirus 4, Human ; Epstein-Barr Virus Infections ; Carcinoma, Small Cell ; Nasopharynx/pathology* ; Carcinoma, Neuroendocrine/pathology* ; Nasopharyngeal Neoplasms/pathology*

Objective:To compare the clinical effects and complications of surgery + chemotherapy and radiotherapy + chemotherapy in patients with nasopharyngeal carcinoma recurrence, so as to compare the safety and efficacy of two different therapeutic methods. Methods:A retrospective analysis was performed on 40 patients with recurrent nasopharyngeal carcinoma after radiotherapy and chemotherapy admitted to our hospital from January 2016 to June 2020. Among them, 26 patients were treated with surgery. The recurrent tumor was removed under nasal endoscope, and the frozen resection margin was negative during the operation. Chemotherapy was continued for stage Ⅲ and Ⅳ patients from 3 to 5 weeks after surgery. Fourteen patients received secondary radiotherapy and chemotherapy. Postoperative complications and survival rate were observed. Results:There were 14 patients in the secondary chemoradiotherapy group（control group） and 26 patients in the nasal endoscopic surgery group（observation group）. Among the 26 patients, 19 patients underwent nasal septal mucosal repair, 5 patients underwent temporal muscle flap repair, 2 patients underwent submental flap repair, 2 patients had nasal septal mucosal flap necrosis and cerebrospinal fluid leakage, and the temporal muscle flap was used for secondary repair in the second stage operation, and 8 patients needed cervical lymph node dissection. The patients recovered well after surgery, and the patients in stage Ⅲ and Ⅳ were treated with chemotherapy after 3 weeks to 5 weeks according to the patient's wound condition. There were significant differences in the incidence of complications and 1-, 2-, and 3-year survival rates between the two groups（P<0.05）. Conclusion:Patients with recurrent nasopharyngeal carcinoma can be treated by nasal endoscopic surgery to remove the tumor, and the use of pedicled nasal septal mucosal flap or temporal muscle flap for skull base reconstruction, The operation can effectively prevent major complications such as internal carotid artery rupture and hemorrhage, and improve the survival rate and quality of life of patients. It provides a safe and effective treatment for patients with recurrent nasopharyngeal carcinoma.
Humans ; Plastic Surgery Procedures ; Nasopharyngeal Carcinoma/surgery* ; Retrospective Studies ; Quality of Life ; Skull Base/surgery* ; Nose Diseases/pathology* ; Nasopharyngeal Neoplasms/pathology*

Nasopharyngeal carcinoma (NPC) is a malignant tumor that mainly occurs in East and Southeast Asia. Although patients benefit from the main NPC treatments (e.g., radiotherapy and concurrent chemotherapy), persistent and recurrent diseases still occur in some NPC patients. Therefore, investigating the pathogenesis of NPC is of great clinical significance. In the present study, replication factor c subunit 4 (RFC4) is a key potential target involved in NPC progression via bioinformatics analysis. Furthermore, the expression and mechanism of RFC4 in NPC were investigated in vitro and in vivo. Our results revealed that RFC4 was more elevated in NPC tumor tissues than in normal tissues. RFC4 knockdown induced G2/M cell cycle arrest and inhibited NPC cell proliferation in vitro and in vivo. Interestingly, HOXA10 was confirmed as a downstream target of RFC4, and the overexpression of HOXA10 attenuated the silencing of RFC4-induced cell proliferation, colony formation inhibition, and cell cycle arrest. For the first time, this study reveals that RFC4 is required for NPC cell proliferation and may play a pivotal role in NPC tumorigenesis.
Humans ; Nasopharyngeal Carcinoma/pathology* ; Carcinoma/pathology* ; Replication Protein C/metabolism* ; Nasopharyngeal Neoplasms/pathology* ; Cell Line, Tumor ; Cell Proliferation ; Gene Expression Regulation, Neoplastic ; Cell Movement

Nasopharyngeal carcinoma (NPC) is the third most common malignancy with a high recurrence and metastasis rate in South China. Natural compounds extracted from traditional Chinese herbal medicines have been developed and utilized for the treatment of a variety of cancers with modest properties and slight side effects. Maackiain (MA) is a type of flavonoid that was first isolated from leguminous plants, and it has been reported to relieve various nervous system disorders and exert anti-allergic as well as anti-inflammatory effects. In this study, we demonstrated that MA inhibited proliferation, arrested cell cycle and induced apoptosis in nasopharyngeal carcinoma CNE1 and CNE2 cells in vitro and in vivo. The expression of the related proteins associated with these processes were consistent with the above effects. Moreover, transcriptome sequencing and subsequent Western blot experiments revealed that inhibition of the MAPK/Ras pathway may be responsible to the anti-tumor effect of MA on NPC cells. Therefore, the effects of MA and an activator of this pathway, tertiary butylhydroquinone (TBHQ), alone or combination, were investigated. The results showed TBHQ neutralized the inhibitory effects of MA. These data suggest that MA exerts its anti-tumor effect by inhibiting the MAPK/Ras signaling pathway and it has the potential to become a treatment for patients with NPC.
Humans ; Nasopharyngeal Carcinoma/pathology* ; Cell Line, Tumor ; Cell Proliferation ; Apoptosis ; Signal Transduction ; Nasopharyngeal Neoplasms/pathology*

The abnormal activation of HER family kinase activity is closely related to the development of human malignancies. In this study, we used HER kinases as targets for the treatment of nasopharyngeal carcinoma (NPC) and explored the anti-tumor effects of the novel pan-HER inhibitor HM781-36B, alone or in combination with cisplatin. We found that HER family proteins were positively expressed in tumor tissues of some NPC patients, and the high levels of those proteins were significantly related to poor prognosis. HM781-36B inhibited NPC in vitro and in vivo. HM781-36B exerted synergistic effects with cisplatin on inhibiting proliferation and promoting apoptosis of NPC cells. In NPC xenograft models in nude mice, HM781-36B and cisplatin synergistically inhibited tumor growth. Downregulating the activity of HER family proteins and their downstream signaling pathways and regulating tumor microenvironment may explain the synergistic anti-tumor effects of HM781-36B and cisplatin. In conclusion, our study provides evidence for HER family proteins as prognostic biomarkers and potential therapeutic targets for NPC. The pan-HER inhibitor HM781-36B alone or in combination with cisplatin represents promising therapeutic effects for the treatment of NPC patients, which provides a new idea for the comprehensive treatment of NPC.
Humans ; Animals ; Mice ; Cisplatin/therapeutic use* ; Antineoplastic Agents/therapeutic use* ; Nasopharyngeal Carcinoma/drug therapy* ; Mice, Nude ; Nasopharyngeal Neoplasms/pathology* ; Tumor Microenvironment

Humans ; Nasopharyngeal Carcinoma ; Nasopharyngeal Neoplasms/pathology* ; Carcinoma/surgery* ; Neoplasm Recurrence, Local/therapy* ; Treatment Outcome

Objective:To investigate the surgical approach for the resection of juvenile nasopharyngeal angiofibroma（JNA） under nasal endoscopy. Methods:The clinical data of 87 patients undergoing endoscopic resection of nasopharyngeal fibroangioma were retrospectively analyzed. We classified JNA according to tumor site, size, invasion scope and anatomic position relationship between tumor and midline of pupil. Three endoscopic surgical approaches were selected according to the classification, and the postoperative symptoms, complications and recurrence were investigated and analyzed. Results:The tumor resection rate of 87 cases by nasal endoscopic surgery was 100%. Thirty-five cases were approached through the middle nasal passage（small tumors located in the nasal sinuses and pterygopalatine fossa）, forty-five cases were approached through the lateral wall of the nasal cavity（tumor invaded the pterygopalatine fossa but did not exceed the midline of the pupil） , and seven cases were approached via the lateral wall of nasal cavity + ipsilateral anterior wall of maxillary sinus（tumor invaded the infratemporal fossa beyond the midline of pupil or invaded the cavernous sinus and the middle cranial fossa epidural）, Postoperative patients with nasal congestion, nasal bleeding, headache, dizziness, vision loss and other symptoms showed varying degrees of improvement. No surgical death or intracranial infection occurred. The postoperative follow-up was 6-78 months, and the recurrence rate was 3.44%. Conclusion:Endoscopic resection of nasopharyngeal fibroangioma is the main treatment method for JNA. Selecting suitable endoscopic approach to resect JNA, To maximize the advantage of nasal endoscopic equipment according to the inherent anatomical space of the human nasal cavity, In order to achieve the purpose of JNA resection, reduce intraoperative and postoperative complications, reduce the recurrence rate and improve the prognosis.
Humans ; Angiofibroma/pathology* ; Retrospective Studies ; Nasopharyngeal Neoplasms/pathology* ; Endoscopy/methods* ; Prognosis

Humans ; Nasal Cavity ; Nasopharyngeal Carcinoma/pathology* ; Neoplasm Recurrence, Local/therapy* ; Paranasal Sinuses ; Nose Neoplasms/therapy* ; Nasopharyngeal Neoplasms/pathology* ; Paranasal Sinus Neoplasms/pathology*

Objective: To investigate the clinicopathological features, immunophenotype and gene alterations of thyroid-like low-grade nasopharyngeal papillary adenocarcinoma (TL-LGNPPA). Methods: Fifteen case of TL-LGNPPA diagnosed at Zhejiang Cancer Hospital (5 cases) and the First Affiliated Hospital, Zhejiang University School of Medicine (10 cases) from November 2011 to August 2020 were collected. Clinical and pathological examinations, immunohistochemical staining and next-generation sequencing were performed. The clinicopathological and molecular characteristics were summarized, and relevant literature was reviewed. Results: Fifteen patients were identified and included. Their median age was 36 years (range, 20-60 years). The male-female ratio was 1.0∶1.1. The most common symptoms were epistaxis and nasal obstruction. The neoplasms were located on the roof of the nasopharynx or the posterior margin of the nasal septum. The pathological features included complex papillary and glandular structures mainly composed of single or pseudostratified cubic and columnar cells, with mild to moderate cytological atypia. In some cases, spindle cell features, nuclear grooves, ground glass nuclei, squamous metaplasia, or scattered psammoma bodies were identified. In addition, nuclear polar reversal cells, hobnail cells and micropapillary structures were found, but have not been reported in previous literature. Immunohistochemistry showed that the tumor cells were diffusely positive for TTF1, CK7, vimentin and CKpan; focally positive for p40, CK5/6 and p16; and negative for Tg, NapsinA, CK20, CDX2, S-100 and PAX8. The Ki-67 positive rates ranged from 1% to 20% and were≤10% in thirteen cases (13/15). EBER in situ hybridization was negative in all cases. DNA sequencing of 6 specimens was performed and all specimens were found harboring gene mutations (EWSR1, SMAD2, ROS1, JAK3, GRIN2A, ERRCC5, STAT3, and TET2), but no hot spot gene alterations were found. No MSI-H and MMR related gene changes were detected. All tumors showed low tumor mutation burden. All 15 patients underwent endoscopic surgery, and only 1 of them underwent radiotherapy postoperatively. All patients were recurrence free and alive at the end of follow-up periods (range: 23 to 129 months). Conclusions: TL-LGNPPA is a rare indolent tumor of the nasopharynx and exhibits a unique morphology and immunophenotype. Endoscopic resection is an effective treatment for TL-LGNPPA with excellent overall prognosis.
Humans ; Male ; Female ; Adult ; Thyroid Gland/pathology* ; Adenocarcinoma, Papillary/pathology* ; Nasopharyngeal Neoplasms/pathology* ; Protein-Tyrosine Kinases ; Proto-Oncogene Proteins ; Nasopharynx/pathology* ; Biomarkers, Tumor

Objective: To investigate the safety, efficacy, locally control and survival results of transoral Da Vinci robotic surgery for salvage treatment of locally recurrent nasopharyngeal carcinoma. Methods: This retrospective study included 33 patients with locally recurrent nasopharyngeal carcinoma (stage rT1-2, partial rT3) underwent transoral Da Vinci robotic surgery between October 2017 and January 2020. There were 20 males and 11 females, with an average age of (47.9±10.5) years. The lesions were localized in nasopharyngeal cavity in 14 cases, with extending to parapharyngeal space in 6 cases and the floor of sphenoid sinus in 13 cases. Transnasal endoscopy was used to assist surgery if necessary. SPSS 25.0 statistical software was used for statistical analysis. Results: Transoral robotic nasopharyngectomy was successfully performed in all cases without conversion to open surgery, of which 13 cases were combined with transnasal endoscopic surgery. The average operation time was (126.2±30.0) min, ranging from 90 to 180 min. The postoperative pathological margin was R0 (31 cases) and R1 (2 cases), with no tumor residue. Complications of surgery mainly included symptoms of headache, nasal dryness and velopharyngeal insufficiency without nasopharyngeal hemorrhage. Follow-up time was from 3 to 54 months. One case had tumor recurrence 11 months after operation, 1 case had ipsilateral cervical lymph node metastasis 27 months after operation, 2 cases had distant metastasis and 1 case died of nasopharyngeal hemorrhage 3 months after operation. The 1-year, 2-year and 3-year overall survival rates were 97.0%, 96.0% and 92.9%, respectively and the local recurrence free rates were 97.0%, 95.7% and 91.7%, respectively. Conclusion: Transoral robotic nasopharyngectomy is safe and feasible for local recurrent nasopharyngeal carcinoma in selected patients, with higher local control rate and quality of life.
Adult ; Female ; Humans ; Male ; Middle Aged ; Nasopharyngeal Carcinoma/surgery* ; Nasopharyngeal Neoplasms/pathology* ; Neoplasm Recurrence, Local/surgery* ; Quality of Life ; Retrospective Studies ; Robotic Surgical Procedures