MicroRNA-125b Interacts with Foxp3 to Induce Autophagy in Thyroid Cancer.

Thyroid cancer is rapidly increasing in incidence worldwide. Although most thyroid cancer can be cured with surgery, radioactive iodine, and/or chemotherapy, thyroid cancers still recur and may become chemoresistant. Autophagy is a complex self-degradative process that plays a dual role in cancer development and progression. In this study, we found that miR-125b was downregulated in tissue samples of thyroid cancer as well as in thyroid cancer cell lines, and the expression of Foxp3 was upregulated. Further, we demonstrated that miR-125b could directly act on Foxp3 by binding to its 3' UTR and inhibit the expression of Foxp3. A negative relationship between miR-125b and Foxp3 was thus revealed. Overexpression of miR-125b markedly sensitized thyroid cancer cells to cisplatin treatment by inducing autophagy through an Atg7 pathway in vitro and in vivo. Taken together, our findings demonstrate a novel mechanism by which miR-125b has the potential to negatively regulate Foxp3 to promote autophagy and enhance the efficacy of cisplatin in thyroid cancer. miR-125 may be of therapeutic significance in thyroid cancer.

Expression of Antioxidant Molecules and Heat Shock Protein 27 in Thyroid Tumors.

Oxidative stress-induced DNA damage is a known causing factor for many types of tumors, but information on the role of oxidants and antioxidants in thyroid tumors is limited. The aim of this study was to determine antioxidant levels in thyroid tumors. In this study, tumor and its matched non-tumor thyroid tissue samples were obtained from 53 patients with thyroid tumors. The levels of manganese superoxide dismutase (MnSOD), thioredoxin reductase 2 (TXNRD2), glutathione (GSH), glutathione peroxidase (Gpx), catalase (CAT), and 27 kd heat-shock protein (hsp27) were determined in both thyroid tissue samples and cultured thyroid cells by immunohistochemical staining and western blot. Hydrogen peroxide (H2 O2 ) was used to generate oxidant stress in the cell culture experiments. We found that the levels of MnSOD, TXNRD2, GSH, Gpx, and Hsp27 were increased in both malignant and benign tumors, while the level of CAT was decreased. To verify the results of the tissue study, we treated cultured thyroid cells with H2 O2 and found the same pattern of antioxidant changes. Hsp27 was also increased after H2 O2 treatment. The expression of hsp27 was upregulated by 8.24-, 6.96-, and 3.09-fold in thyroid cancer, follicular adenoma, multinodular goiter, respectively. Collectively, our study demonstrated that the levels of hsp27 together with MnSOD, TXNRD2, GSH, and Gpx were significantly upregulated by H2 O2 in thyroid tumors. The increase of these antioxidants is observed in both malignant and benign tumors, particularly in the former. The upregulation of antioxidants is likely a protective mechanism of tumor cells to maintain their survival and growth. J. Cell. Biochem. 117: 2473-2481, 2016. © 2016 Wiley Periodicals, Inc.

Narrow band imaging endoscopy of the nasopharynx is not more useful than white light endoscopy for suspected nasopharyngeal carcinoma.

Endoscopy is often used to screen for nasopharyngeal carcinoma. A normal nasopharynx on white light endoscopy may yet harbor subclinical or occult malignancy. This study assessed whether the vascular pattern seen on narrow band imaging endoscopy could indicate this and thus be useful for detecting suspected nasopharyngeal carcinoma. The nasopharynx of 156 patients who failed serological screening for or presented with symptoms of nasopharyngeal carcinoma was graded under white light and narrow band imaging endoscopy and a biopsy taken. The accuracy of assessing the nasopharynx as being probably or definitely malignant on white light endoscopy was high (area under the curve = 0.924), as it was of being normal on narrow band imaging endoscopy (=0.799). The sensitivity and specificity of white light and narrow band imaging endoscopy for nasopharyngeal carcinoma was 93 and 22 %, and 92 and 98 %, respectively. Significantly associated with nasopharyngeal carcinoma was a high index of suspicion or definitely malignant grade on white light endoscopy (p < 0.0005, odds 58.978) and vascular tufts on narrow band imaging endoscopy (p = 0.020, odds 41.210). Narrow band imaging endoscopy of vasculature alone for suspected nasopharyngeal carcinoma is not more useful than white light endoscopy of nasopharyngeal morphology, nor does it add to or surpass the diagnostic accuracy of white light endoscopy in this regard.

Sodium-iodide symporter and its related solute carriers in thyroid cancer.

The solute carrier (SLC) family is a large group of membrane transport proteins. Their dysfunction plays an important role in the pathogenesis of thyroid cancer. The most well-known SLC is the sodium-iodide symporter (NIS), also known as sodium/iodide co-transporter or solute carrier family 5 member 5 (SLC5A5) in thyroid cancer. The dysregulation of NIS in thyroid cancer is well documented. The role of NIS in the uptake of iodide is critical in the treatment of thyroid cancer, radioactive iodide (RAI) therapy in particular. In addition to NIS, other SLC members may affect the autophagy, proliferation, and apoptosis of thyroid cancer cells, indicating that an alteration in SLC members may affect different cellular events in the evolution of thyroid cancer. The expression of the SLC members may impact the uptake of chemicals by the thyroid, suggesting that targeting SLC members may be a promising therapeutic strategy in thyroid cancer.

The Isoforms of Estrogen Receptor Alpha and Beta in Thyroid Cancer.

The incidence of thyroid cancer was predominant in women, indicating that the sex hormone may have a role in thyroid cancer development. Generally, the sex hormone exerts its function by binding to the correspondent nuclear receptors. Therefore, aberrant of these receptors may be involved in the development of thyroid cancer. Estrogen receptor alpha (ERα) and beta (ERß), two main estrogen receptors, have been reported to have an important role in the pathogenesis of thyroid cancer. When the ERα and ERß genes undergo the alternative RNA splicing, some ERα and ERß isoforms with incomplete functional domains may be formed. To date, several isoforms of ERα and ERß have been identified. However, their expression and roles in thyroid cancer are far from clear. In this review, we summarized the expressions and roles of ERα and ERß isoforms in thyroid cancer, aiming to provide the perspective of modulating the alternative RNA splicing of ERα and ERß against thyroid cancer.

Otitis media with effusion and hearing loss in Chinese children with cleft lip and palate.

OBJECTIVE: To determine the incidence of otitis media with effusion and the associated hearing loss, the rate of ventilation tube insertion, and complications of ventilation tube insertion in Chinese cleft palate patients. DESIGN: Retrospective review in a tertiary care hospital in Hong Kong. PATIENTS: A total of 104 consecutive patients with cleft lip and/or cleft palate who were born between January 1996 and January 2006. RESULTS: The incidence of otitis media with effusion in Chinese cleft palate patients for the first 2 years after birth was 76.1%. Of these patients, 16.9% had otitis media with effusion associated with a moderate hearing loss (>40 decibels hearing level [dBHL]). Approximately half (53.2%) of our patients had ventilation tube insertion. Complications including retraction, tympanosclerosis, and perforation of the tympanic membrane were found in 15.7% of all ears with otitis media with effusion and ventilation tube insertion. CONCLUSIONS: The high incidence of otitis media with effusion in cleft palate infants found in this study is consistent with that reported in the Western literature. A small but significant proportion of otitis media with effusion was associated with moderate hearing loss that truly required surgical treatment. Cleft palate children are much more likely to develop otitis media with effusion than normal children, and they develop the condition at an earlier age. A protocol for the treatment of otitis media with effusion in cleft palate patients and further prospective studies are warranted.

The Knockdown of Nrf2 Suppressed Tumor Growth and Increased the Sensitivity to Lenvatinib in Anaplastic Thyroid Cancer.

Papillary thyroid cancer can dedifferentiate into a much more aggressive form of thyroid cancer, namely into anaplastic thyroid cancer. Nrf2 is commonly activated in papillary thyroid cancer, whereas its role in anaplastic thyroid cancer has not been fully explored. In this study, we used two cell lines and an animal model to examine the function of Nrf2 in anaplastic thyroid cancer. The role of Nrf2 in anaplastic thyroid cancer was investigated by a series of functional studies in two anaplastic thyroid cancer cell lines, FRO and KAT-18, and further confirmed with an in vivo study. The impact of Nrf2 on the sensitivity of anaplastic thyroid cancer cells to lenvatinib was also investigated to evaluate its potential clinical implication. We found that the expression of Nrf2 was significantly higher in anaplastic thyroid cancer cell line cells than in papillary thyroid cancer cells or normal control cells. Knockdown of Nrf2 in anaplastic thyroid cancer cells inhibited their viability and clonogenicity, reduced their migration and invasion ability in vitro, and suppressed their tumorigenicity in vivo. Mechanistically, knockdown of Nrf2 decreased the expression of Notch1. Lastly, knockdown of Nrf2 increased the sensitivity of anaplastic thyroid cancer cells to lenvatinib. As knockdown of Nrf2 reduced the metastatic and invasive ability of anaplastic thyroid cancer cells by inhibiting the Notch 1 signaling pathway and increased the cancer cell sensitivity to lenvatinib, Nrf2 could be a promising therapeutic target for patients with anaplastic thyroid cancer.

Differential Effects of Estrogen Receptor Alpha and Beta on Endogenous Ligands of Peroxisome Proliferator-Activated Receptor Gamma in Papillary Thyroid Cancer.

Purpose: The inhibition of estrogen receptor alpha (ERα) or the activation of ERß can inhibit papillary thyroid cancer (PTC), but the precise mechanism is not known. We aimed to explore the role of ERα and ERß on the production of endogenous peroxisome proliferator-activated receptor gamma (PPARγ) ligands in PTC. Methods: 2 PTC cell lines, 32 pairs of PTC tissues and matched normal thyroid tissues were used in this study. The levels of endogenous PPARγ ligands 15(S)-hydroxyeicosatetraenoic acid (15(S)-HETE), 13-S-hydroxyoctadecadienoic acid (13(S)-HODE), and15-deoxy-Δ12,14-prostaglandin J2 (PGJ2) were measured by ELISA. Results: The levels of PGJ2 and 15(S)-HETE were significantly reduced in PTC, but 13(S)-HODE was not changed. Activation of ERα or inhibition of ERß significantly downregulated the production of PGJ2, 15(S)-HETE and 13(S)-HODE, whereas inhibition of ERα or activation of ERß markedly upregulated the production of these three ligands. Application of endogenous PPARγ ligands inhibited growth, induced apoptosis of cancer cells, and promoted the efficacy of chemotherapy. Conclusion: The levels of endogenous PPARγ ligands PGJ2 and 15(S)-HETE are significantly decreased in PTC. The inhibition of ERα or activation of ERß can inhibit PTC by stimulating the production of endogenous PPARγ ligands to induce apoptosis in cancer cells.

Whole-genome profiling of nasopharyngeal carcinoma reveals viral-host co-operation in inflammatory NF-κB activation and immune escape.

Interplay between EBV infection and acquired genetic alterations during nasopharyngeal carcinoma (NPC) development remains vague. Here we report a comprehensive genomic analysis of 70 NPCs, combining whole-genome sequencing (WGS) of microdissected tumor cells with EBV oncogene expression to reveal multiple aspects of cellular-viral co-operation in tumorigenesis. Genomic aberrations along with EBV-encoded LMP1 expression underpin constitutive NF-κB activation in 90% of NPCs. A similar spectrum of somatic aberrations and viral gene expression undermine innate immunity in 79% of cases and adaptive immunity in 47% of cases; mechanisms by which NPC may evade immune surveillance despite its pro-inflammatory phenotype. Additionally, genomic changes impairing TGFBR2 promote oncogenesis and stabilize EBV infection in tumor cells. Fine-mapping of CDKN2A/CDKN2B deletion breakpoints reveals homozygous MTAP deletions in 32-34% of NPCs that confer marked sensitivity to MAT2A inhibition. Our work concludes that NPC is a homogeneously NF-κB-driven and immune-protected, yet potentially druggable, cancer.

Endoscopic assessment of the nasopharynx: an objective score of abnormality to predict the likelihood of malignancy.

OBJECTIVES: We developed an objective endoscopic score of abnormality of the nasopharynx to predict the likelihood of malignancy. METHODS: A score sheet with 44 variables was developed to objectively quantify the bilateral endoscopic assessment of the nasopharynx. Patients scheduled to undergo nasopharyngeal biopsies were recruited. The nasopharynx was assessed endoscopically, photographed, and scored on 44 variables. The scores were compared to the biopsy results, and predictors of malignancy were modeled with regression analysis. The sensitivity and specificity of the novel scoring system were examined. RESULTS: Seventeen patients had carcinoma, and 60 had a benign lesion or no disease. Patients with a nasopharyngeal malignancy scored significantly higher than did patients with a benign lesion or no disease. No patient with a malignant lesion had a score of less than 12. With a receiver operating characteristic curve area of 0.917, the score demonstrated an excellent ability to discriminate between nasopharynges that were likely or unlikely to contain malignant disease. Independent predictors for both malignant disease and a score greater than 12 were modeled. CONCLUSIONS: A cutoff score above 12 on the novel objective endoscopic assessment of the nasopharynx measure was highly predictive of possible malignancy.

Reversal of pale-to-dark nasopharyngeal follicle ratio on narrow-band imaging.

Normal nasopharyngeal mucosa contains varying amounts of lymphoid tissue, which in adults may be minimal or absent. Nasopharyngeal mucosa with minimal lymphoid tissue has a regular follicular pattern on narrow-band imaging; pale follicles have thin, dark borders and the ratio of the pale follicle to the dark border (pale-to-dark ratio) is roughly 90%. In some patients undergoing routine nasopharyngeal endoscopy, the pale-to-dark ratio is reversed on narrow-band imaging, with dark centres surrounded by pale borders and a pale-to-dark ratio of roughly 50%. These dark follicles may represent abnormal capillary loops, as they have the same appearance as microvascular changes seen on narrow-band imaging of the oesophageal mucosa which indicate dysplasia or malignancy. While this observed change in the follicular pattern may be an early event in the evolution of nasopharyngeal carcinoma, the significance of this finding remains to be confirmed by a larger-scale study.

Frontal inverted papillomas: A 25-year study.

OBJECTIVES/HYPOTHESIS: This study analyzes the treatment outcomes of frontal inverted papillomas (FIPs) in an attempt to provide guidelines for surgery selection. STUDY DESIGN: Retrospective case series. METHODS: The treatment results of 29 FIPs classified into five categories were retrospectively analyzed. The five categories are F1, tumor prolapsed into frontal sinus, tumor origin outside frontal sinus; F2, tumor origin inside frontal sinus, medial to the plane of lamina papyracea; F3, tumor origin inside frontal sinus, lateral to the plane of lamina papyracea; F4, bilateral; and F5, extrasinonasal. RESULTS: Of the 11 F1 cases, 73% had Draf I and 27% had Draf IIA procedures. There was one (9%) frontal recurrence and one (9%) frontal stenosis. Of the 10 F2 cases, 10% had Draf I, 40% had Draf IIA, 40% had Draf IIB, and 10% had Draf III surgery with a trephination. One patient (10%) had a frontal recurrence. Of the five F3 cases, 40% had Draf IIA surgery, 20% had external frontoethmoidectomy, and 40% had external frontal sinusotomy. The recurrence rate was 60%, and frontal stenosis rate was 60%. The two F4 cases had external frontal sinusotomies and Draf III surgery with no frontal recurrence or stenosis. The patient with the F5 had a frontal recurrence after Draf IIA surgery and external frontoethmoidectomy. CONCLUSIONS: Draf I or IIA surgery is adequate for most F1 tumors, and Draf II surgery is adequate for most F2 tumors. F3 and F4 tumors can be managed initially by Draf III surgery with external frontal sinusotomy added when required. F5 tumors probably require combined surgical approaches. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:1622-1628, 2020.

The role of microRNA in cisplatin resistance or sensitivity.

INTRODUCTION: Cisplatin is a chemotherapy drug that has been used to treat a number of cancers for decades, and is still one of the most commonly used anti-cancer agents. However, some patients do not respond to cisplatin while other patients who were originally sensitive to cisplatin eventually develop chemoresistance, leading to treatment failure or/and tumor recurrence. AREAS COVERED: Different mechanisms contribute to cisplatin resistance or sensitivity, involving multiple pathways or/and processes such as DNA repair, DNA damage response, drug transport, and apoptosis. Among the various mechanisms, it appears that microRNAs play an important role in determining the resistance or sensitivity. In this article, we analyzed and summarized recent findings in this area, with the aim that these data can aid further research and understanding, leading to the eventual reduction of cisplatin resistance. EXPERT COMMENTARY: microRNAs can positively or negatively regulate cisplatin resistance by acting on molecules or/and pathways related to apoptosis, autophagy, hypoxia, cancer stem cells, NF-κB, and Notch1. It appears that the modulation of relevant microRNAs can effectively re-sensitize cancer cells to cisplatin regimen in certain types of cancers including breast, colorectal, gastric, liver, lung, ovarian, prostate, testicular, and thyroid cancers.

Iodine mediated mechanisms and thyroid carcinoma.

Iodine is a key element in the synthesis of thyroid hormones and the process of iodine transport by thyroid cells is active. Iodine deficiency, which is a known risk factor for thyroid cancer, may result from inadequate dietary iodine or from defects in iodine transportation. In contrast, a sufficient supply of iodine can induce cell-cycle arrest and apoptosis in thyroid cancer cells and may prevent the transformation of a differentiated thyroid cancer into a less differentiated or anaplastic form. However, the functions of iodine are complex, and the mechanisms of its action in thyroid cancer are unclear. This review focuses on the role of iodine in the carcinogenesis, proliferation, and apoptosis of thyroid cancers as well as on iodine transporters, most of which are impaired in thyroid cancer. Elucidating the roles of iodine may generate novel diagnostic and therapeutic approaches to thyroid cancer and improve current strategies for its treatment and prevention.

Inhibition of apoptosis in human laryngeal cancer cells by E6 and E7 oncoproteins of human papillomavirus 16.

The carcinogenesis of human papillomaviruses type 16 (HPV-16) is mainly due to its two oncoproteins, E6 and E7. Their carcinogenic features in term of their relationship with Bcl-2 family are still unclear. We thus aimed to analyze the expression of Bcl-2 family members, Bcl-2, Bax, and Bak in laryngeal cancer cells transfected with the E6 or E7 and to determine the sensitivity of these cells to apoptotic stimuli. We employed two human laryngeal cancer cell lines, UMSCC12 and UMSCC11A in this study. These two cell lines were stably transfected with HPV16 E6, E7 or empty vector, pcDNA3.1. We found that E6 and E7 inhibited apoptosis induced by TNF-alpha/CHX in both UMSCC11A and UMSCC12 cells, enhanced the stability of Bcl-2 protein and increased the degradation of Bak protein. Furthermore, it was found that HPV-16 E7 statistically enhanced the expression of Bcl-2 in laryngeal cancer. The alteration of Bak by E6 and E7 was not through the influence on the Bak promoter, as the luciferase assay showed that neither E6 nor E7 changed the Bak promoter activity. We conclude that the evasion of apoptosis mediated by HPV-16 E6 and E7 is associated with increased Bcl-2 and decreased Bak in laryngeal carcinogenesis and that the decreased level of Bak by E6 and E7 is not caused by the regulation of the Bak promoter but by reducing its protein stability.

Nasopharyngectomy: does the approach to the nasopharynx influence survival?

OBJECTIVE: To investigate whether the approach used to the nasopharynx to perform a salvage nasopharyngectomy for recurrent or residual nasopharyngeal carcinoma influences survival. STUDY DESIGN: A retrospective case series. SUBJECTS AND METHODS: Eighty patients underwent a nasopharyngectomy via a transpalatal, maxillary swing, or midfacial degloving approach. Local progression-free, locoregional progression-free, and overall survival rates were calculated for each approach. RESULTS: For the whole group (N = 80), there were no significant differences in the survival rates between the three approaches. For the subgroup of patients with recurrent T1 and T2 tumors (n = 68), the local progression-free and locoregional progression-free survival rates were significantly better when a maxillary swing approach was used than when a midfacial degloving approach was used. CONCLUSION: The maxillary swing approach is associated with significantly better survival rates than the midfacial degloving approach when used to perform a salvage nasopharyngectomy for residual or recurrent T1 and T2 nasopharyngeal carcinoma.

An audit of risk factors for wound infection in patients undergoing coronary artery bypass grafting or valve replacement.

OBJECTIVES: To investigate the epidemiology of surgical site infection in cardiac surgery patients operated on in 2006. DESIGN: Retrospective study of a case-control sample. SETTING: Cardiac surgery unit of a university teaching hospital in Hong Kong. PATIENTS: Cardiac surgery patients with surgical site infection were matched by procedure type, sex, and year of surgery with non-infected patients. MAIN OUTCOME MEASURES: Identification of risk factors for surgical site infection. RESULTS: The infected and non-infected cardiac surgery patients did not differ in age, sex, or smoking history; however, patients with surgical site infection were significantly heavier (mean body mass index, 26.6 vs 23.9 kg/m2, P < 0.046). Almost 41% of the subjects had a history of diabetes mellitus, there being a significantly greater proportion among infected than non-infected patients (53.1% vs 28.1%, P < 0.042). All 37 of the patients without a diagnosis of diabetes had normal (ie < 8 mmol/L) preoperative glucose levels, but 99% of them yielded evidence of subsequent glycaemic dysfunction during or after surgery. Overall, 50% of the patients had a blood transfusion during the operation, with infected patients significantly more likely to have been transfused than the non-infected ones (65.6% vs 34.4%, P < 0.008). CONCLUSIONS: There appears to be a relationship between surgical site infection in cardiac surgery patients and pre-existing (diagnosed and covert) diabetes mellitus and blood transfusion. Future studies should consider these factors in relation to surgical site infections, both in the wider surgical population and from a risk-minimisation perspective.

Induction of functional MT1 and MT2 isoforms by calcium in anaplastic thyroid carcinoma cells.

Metallothionein (MT) expression in carcinogenesis of thyrocytes is unknown. We demonstrated that cadmium induced transcription of all functional MT-1 and MT-2 isoforms and promoted the cell cycle from the G1 to the S phase in thyroid cancer cells, which can be suppressed by the ERK inhibitor. Cadmium exposure stimulated intracellular calcium and the phosphorylation of ERK1/2. Therefore, a common pathway initiated by a rapid rise in calcium and followed by calcium-mediated activation of ERK is involved in the transcriptional induction of functional MT1 and MT2 isoforms and in the progression of the cell cycle in thyroid cancer cells exposed to cadmium.

Long-term outcome of the Hong Kong vascularized, pedicled temporalis fascia flap in reconstruction of mastoid cavity.

OBJECTIVES: The vascularized, pedicled temporalis fascia flap (Hong Kong flap) is an established procedure in the reconstruction of the mastoid cavity. The long-term outcome and complications have not been studied. We set out to appraise this procedure in our study. STUDY DESIGN: The clinical records of 302 ears that had the Hong Kong flap procedure from 1987 to 2006 were retrospectively studied. The study reviewed the otologic complaints leading to Hong Kong flap, the number and findings of the second or more looks, analysis of procedures year by year, time to achieve a dry ear, and the complications. RESULTS: The main otologic complaint leading to use of the Hong Kong flap is otorrhoea. The number of Hong Kong flap procedures has decreased in recent years. Twenty-one percent had second or more looks after the procedure. Forty percent of the mastoid cavities at the second look were found to have residual or recurrent cholesteatoma. It takes a median of 2 months to achieve a dry ear after the procedure. CONCLUSIONS: We conclude that the Hong Kong flap procedure is simple and desirable for mastoid reconstruction to achieve a safe and dry cavity with few complications.

Nasopharyngectomy and surgical margin status: a survival analysis.

OBJECTIVE: To explore whether the margin status at surgical salvage nasopharyngectomy for local residual or recurrent nasopharyngeal carcinoma affects patient survival. DESIGN: Retrospective case series review. SETTING: Academic tertiary referral center. PATIENTS: Seventy-nine consecutive patients with operable local residual or recurrent nasopharyngeal carcinoma after failure of primary treatment with radiotherapy with or without chemotherapy underwent surgical salvage nasopharyngectomy with curative intent between November 28, 1987, and November 17, 2003. Sixty-one patients were men and 18 were women. Their mean age was 48 years (age range, 26-70 years). INTERVENTION: Surgical salvage nasopharyngectomy. MAIN OUTCOME MEASURES: The status of the closest margin at surgery was assessed as clear, close, or positive. Survival time was measured from the date of surgery to the date of the last follow-up, to the date of an event occurrence, or to the date of death. The Kaplan-Meier method was used to estimate the probability of local progression-free survival and overall survival at 5 years. Differences in survival rates between surgical margin statuses were assessed using the log-rank test. RESULTS: Five-year overall survival for patients with clear margins was 77%, for patients with close margins was 46% (P = .05), and for patients with positive margins was 23% (P < .001). CONCLUSION: Clear surgical margins at the time of surgical salvage nasopharyngectomy for residual or recurrent nasopharyngeal carcinoma positively affect patient survival.