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Background Based on our cadaveric study findings and the clinical practice, the improved submental island flaps (SIF) used on a case series to reconstruct postoperative defects were reviewed and analyzed, to summarize the technical operation of flap cutting and propose the anterograde anatomical technique of point-line-plane alignment. Methods The cadaveric study was carried out first and a case series of about 23 head and neck tumor cases that underwent one-stage SIF repair were reviewed and followed up. The intraoperative anatomy, the technical essentials for vascular pedicle protection and submandibular lymph nodes treatment, and the rational design of flap incisions were analyzed and described. Results Most patients (21/23, 91.3%), comprising 19 males and 4 females with a mean age of 59 years, recovered completely from the application of SIFs in the repair and reconstruction of head and neck tumors; Only 2 patients experienced partial flap necrosis, which resolved following a local dressing change. The predominant donor site complication was transitory paralysis of the mandibular marginal branch of the facial nerve (MMBFN) (3/23, 13.0%), and the donor site was closed in one stage without skin grafting. The hair growth on skin flaps was not an issue for male patients requiring postoperative radiotherapy. Conclusions SIF is a viable choice for correcting abnormalities of the head and neck tumor with the convenience of flap cutting and the effectiveness of the repair. In addition, it permits simultaneous treatment of the lymph nodes in the region I.

OBJECTIVE/HYPOTHESIS To examine the clinical features of benign intratracheal thyroid (ITT) and their management strategies and outcomes. STUDY DESIGN Case series study. METHODS This systemic review was conducted in two international academic centers. This review includes 43 patients: one new case from the Massachusetts Eye and Ear Infirmary, four new cases from Beijing Tongren Hospital, and 38 previously published cases. We analyzed these 43 cases and summarized the patients' epidemiological data, clinical features, and treatment regimens. RESULTS ITTs were less common in men than in women (male:female ratio of 3:10). ITT was observed in patients as young as neonates and as old as 85 years. Orthotopic thyroid nodules were present in 55.8% of the patients with ITT. Malignancy was incidentally found in 4.6% of all ITTs. Imaging examinations showed that the ITTs were typically attached to the posterolateral/lateral tracheal wall of the first, second, or third tracheal rings. Tissue attachment between the ITT and normal thyroid lobes was seen in 59.5% of the patients. Thirty-seven patients underwent surgery: 30 underwent open surgery, and seven underwent endoscopic debulking resections. One neonate received thyroid suppression therapy. One patient with ITT and papillary thyroid cancer was treated with radiotherapy and ultimately died after recurrence. CONCLUSIONS Surgical resection is an effective treatment for benign ITT. We hypothesized that abnormalities during the embryonic development of Berry's ligament might play a role in ITT pathogenesis. LEVEL OF EVIDENCE NA Laryngoscope, 131:E2609-E2617, 2021.

Objective Structural anomalies of the jugular foramen (JF) and adjacent structures may contribute to development of pulsatile tinnitus (PT). The goal of this study was to assess anatomical variants in the ipsilateral JF region in patients with PT and to explore possible predisposing factors for PT. Methods One hundred ninety-five patients with PT who underwent CT angiography and venography of the temporal bone were retrospectively analyzed. Anatomic variants including dominance of the ipsilateral JF, bony deficiency of the sigmoid sinus and internal carotid artery canal, high riding or dehiscent jugular bulb, dehiscence of the superior semicircular canal, tumors in the JF region, or cerebellopontine angle were assessed. Results Of 195 patients with PT, the prevalence of a dominant JF on the ipsilateral side of patients with PT was 67.2%. Furthermore, the dominant JF demonstrated a significant correlation with the presence of ipsilateral PT (p Conclusion Structural abnormalities of the JF and adjacent structures may predispose to the development of PT. Knowledge of these anatomical variants in the JF region may help establish a clinical strategy for addressing PT.

The aims of this study were to examine the symptom severity and interference among patients with lung cancer treated with PD-1 immunotherapy, explore whether those symptoms were clustered together, and identify factors associated with symptom clusters.A cross-sectional study was conducted. Data were collected by demographic and clinical characteristic questionnaires and the M.D. Anderson Symptom Inventory Lung Cancer Module. Symptom clusters were identified using exploratory factor analysis, and stepwise linear regression was applied to analyze the factors affecting the symptom clusters.A total of 148 patients with lung cancer treated with PD-1 immunotherapy participated in this study. The overall symptom burdens of these patients were mainly at a mild level. The patient symptom clusters identified in this study were a general cluster, a treatment-related cluster, a pulmonary cluster, a gastrointestinal cluster, and a neural cluster. The patients' Karnofsky performance status (KPS) score (The symptom burdens of patients with lung cancer and treated with PD-1 immunotherapy were at a mild level and appeared to be clustered. In addition, because the symptoms that comprise a cluster are interrelated, the diagnosis and management of each symptom in a cluster should not be performed in isolation, and each symptom in a cluster should be treated either simultaneously or in an orderly manner.

Background To investigate the outcomes of using the residual thyroid cartilage for laryngeal function reconstruction in early glottic laryngeal carcinoma. Methods From March 2017 to June 2022, 21 patients with glottic carcinoma who underwent laryngeal function reconstruction were analyzed retrospectively. The operation was performed under general anesthesia. Reconstruction of ipsilateral hemilarynx defect by downward movement of ipsilateral residual thyroid cartilage plate. During the follow-up period, the laryngeal function and tumor recurrence were evaluated. Results otally 20 male patients and 1 female patient were enrolled in this study. Of the 20 initial primary tumors, there were 6 patients with T1N0M0 stage, 12 ones with T2N0M0 stage, 1 with T1N1M0 stage, 1 with T3N0M0 stage, and 1 with T2N1M0 stage. The patient with recurrent tumor was T3N1M0 stage. The follow-up time ranged from 9 to 63 months. All patients were healed by first intention after surgery. All patients without laryngeal stenosis were removed from tracheotomy tube. So far, all patients have good laryngeal function. One patient relapsed at the last follow-up. Conclusion It is safe to repair hemilarynx defect with residual thyroid cartilage plate on the affected side, and it is an important choice for laryngeal function reconstruction after vertical partial laryngectomy.

Background: Organic mulching is an important management practice in agricultural production to improve soil quality, control crop pests and diseases and increase the biodiversity of soil microecosystem. However, the information about soil microbial diversity and composition in litchi plantation response to organic mulching and its attribution to litchi downy blight severity was limited. This study aimed to investigate the effect of organic mulching on litchi downy blight, and evaluate the biodiversity and antimicrobial potential of soil microbial community of litchi plantation soils under organic mulching. Results: Organic mulching could decrease the disease incidence in the litchi plantation. As a result of high-throughput 16S rRNA and ITS rDNA gene illumine sequencing, higher bacterial and fungal community diversity indexes were found in organic mulching soils, the relative abundance of norank f norank o Vicinamibacterales, norank f Vicinamibacteraceae, norank f Xanthobacteraceae, Unclassified c sordariomycetes, Aspergillus and Thermomyces were significant more than that in control soils. Isolation and analysis of antagonistic microorganism showed that 29 antagonistic bacteria strains and 37 antagonistic fungi strains were unique for mulching soils.Conclusions: Thus, we believe that organic mulching has a positive regulatory effect on the litchi downy blight and the soil microbial communities, and so, is more suitable for litchi plantation.

Primary laryngeal carcinosarcoma is a rare type of malignancies, and the standard therapeutic protocol for its treatment has yet to be established. This retrospective study analyzed the clinical and pathological characteristics, risk factors, treatment options, and prognosis of 13 patients with primary laryngeal carcinosarcomas. This case series included 11 males and 2 females with an age range from 32 to 78 years at diagnosis. The initial clinical symptoms included hoarseness, dyspnea, and foreign body sensation in the throat. The primary tumor sites were at the glottis, supraglottis, and larynx. All these patients were active or passive smokers, and more than half of them were alcohol addictive. The surgical treatment for laryngeal carcinosarcomas included CO2 laser surgery in seven cases, partial laryngectomy and neck dissection in three cases, and total laryngectomy and neck dissection in three cases. Among them, seven cases received postoperative radiotherapy. After follow-up with a mean of 31.15-month, four cases died. Primary laryngeal carcinosarcoma is a rare but more aggressive malignancy. Contralateral lymph node metastasis can occur at the early stage of this disease. A treatment combining surgery and postoperative radiotherapy is strongly recommended.

Objectives To investigate the prognosis and quality of life for primary malignant maxillary sinus tumors. Methods This was a retrospective analysis. 164 patients diagnosed with primary malignant maxillary sinus tumors between 2005 and 2018 were recruited. Patients were treated according to the pathological type and the lesion range. Prognostic differences of different pathological types, surgical resection methods, repair methods, treatment methods, and different local recurrence sites were analyzed. Survival analysis and prognostic factors analysis were performed. Results Overall survival (OS) rate was 74.7% at 3 years, 60.5% at 5 years, and 45.8% at 10 years. Disease-free survival (DFS) rate was 67.2% at 3 years, 45.6% at 5 years, and 30.8% at 10 years. There was significant difference in OS rate among different pathological types (χ2 = 14.18, P < 0.05). The order of 5-year OS rate was as follows: malignant transformation of inverted Papilloma (77.7%) > adenoid cystic carcinoma (74.1%) > squamous cell carcinoma (48.4%) > sarcoma (22.1%). The order of disease-free survival was as follows: total maxillary resection > subtotal maxillary resection > endoscopic nasal tumor resection ≥enlarged maxillary resection, the 5-year DFS rate were 68.6%, 53.5%, 46.2%, and 42.9%, respectively. The OS of postoperative radiotherapy was significantly better than that of preoperative radiotherapy (χ2 = 7.16, P < 0.05). There was significant difference in OS between recurrent and non-recurrent patients (χ2 = 68.57, P < 0.05). Conclusions The pathological type and the timing of radiotherapy are independent prognostic factors for primary malignant tumor of maxillary sinus. In addition, different local surgical resection methods are independent factors affecting the recurrence rate.

Background The diagnosis of microinvasive laryngeal squamous cell carcinoma (LSCC) is not always straightforward and sometimes can be very challenge in daily clinical practice. The focus lies in the confirmation of microinvasion. Cancer-associated fibroblasts (CAFs), as the major element of reactive tumor stroma, are believed to participate actively in the growth and invasion of tumor cells. Objectives To evaluate the diagnostic role of α-smooth muscle actin (α-SMA) labelling CAFs in microinvasive LSCC. Methods A total of 81 laryngeal biopsy specimens were retrieved, including 41 cases of microinvasive LSCC with depth of invasion no more than 3 mm, 20 laryngeal squamous intraepithelial lesion (SIL), and 20 benign pseudoepitheliomatous hyperplasia (PEH). All cases were stained for immunohistochemistry, using antibody against the α-SMA antigen. The correlation between the presence of CAFs in microinvasive LSCC and tumor histological characteristics was investigated. Results Immunoreactivity of α-SMA was detected in twenty-nine microinvasive LSCC (29/41, 71%), while no reactivity was observed in laryngeal SIL (0/20, 0%), and rarely in PEH (2/20, 10%). The α-SMA expression pattern in stroma of microinvasive LSCC was significantly different from that of SIL (χ2 = 26.966, p = 0.000) and PEH (χ2 = 19.838, p = 0.000). In addition, there seemed to be a certain correlation between the histological characteristics of microinvasive LSCC and the presence of interstitial CAFs. Conclusions This study highlights the practical role of utilizing α-SMA in the pathological diagnosis of microinvasive LSCC, with emphasis on variable histomorphologic features of microinvasive LSCC.

Aim To comprehensively assess the current level and identify associated factors of intention to response and emergency preparedness of clinical nurses during COVID‐19 outbreak. Design A cross‐sectional study was designed. Methods Demographic and characteristic questionnaire, intention to response scale, emergency preparedness scale and a self‐designed questionnaire related to effects of events and intention to leave were used in this study. Results The mean scores of intention to response and emergency preparedness were 82.00 (SD = 18.17) and 64.99 (SD = 12.94), respectively. Moral consideration, engaged in COVID‐19 protection training, had working experience in SARS, and the other eight factors were explained 34.6% of the total model variance in intention to response model (F = 80.05, p

Background The prognostic factors and survival difference between inverted papilloma (IP)-associated sinonasal squamous cell carcinoma (SCC) and de novo SCC are unclear. Objective This study aimed to compare the clinical features and oncologic outcomes in patients with IP-associated SCC and de novo SCC; and additionally, to analyze the prognostic factors of the two types of SCCs. Methods Data from 173 SCC patients treated for IP-associated SCC (n = 89) and de novo SCC (n = 84), were reviewed retrospectively for demographic features, tumor characteristics, treatment modality, and clinical outcomes. 5-year overall survival (OS) and disease free survival (DFS) was analyzed using the Kaplan-Meier method, and Cox proportional hazards model was used to analyze factors influencing prognosis. Results A higher proportion of IP-associated SCC occurred in frontal and sphenoid sinus compared to de novo SCC. The two groups demonstrated similar 5-year OS and DFS (5-year OS: 63.3% and 55.4%, DFS: 45.4% and 50.1%, respectively). The metachronous tumor had a relatively better prognosis outcome than synchronous tumor and de novo SCC (5-year OS: 73.1%, 54.5% and 55.4%, respectively). Both groups showed similar loco-regional recurrence rates ( p > 0.05); however, de novo SCC tumors demonstrated an increased incidence of distant metastasis. Multivariate analysis indicated that age >70 years, advanced tumor stage and surgical margin were independent predictive factors for the risk of mortality (HR 2.047, 1.581 and 1.931, respectively). Conclusion IP-associated SCCs have an aggressive loco-regional tendency, whereas de novo SCCs have a higher aggressive distant metastatic propensity. Age, tumor stage and surgical positive margin are key factors for poor prognosis and should be routinely taken into consideration during treatment planning and subsequent surveillance.

Background This study aimed to evaluate the potential of induction chemotherapy as an indicator of the management of advanced hypopharyngeal carcinoma with cervical oesophageal invasion. Methods Sixty-eight patients admitted to our hospital between February 2003 and November 2016 with stage IVB hypopharyngeal carcinoma with cervical oesophageal invasion were retrospectively analysed. Patients were divided into two groups according to the treatment they selected following an explanation of the different treatments available. Patients in group A received induction chemotherapy and had (1) complete/partial remission following chemotherapy and radiotherapy/concurrent chemoradiotherapy or (2) stable disease following chemotherapy and surgery. Patients in group B underwent surgery followed by adjuvant radiotherapy/concurrent chemoradiotherapy. Survival analyses were performed using the Kaplan–Meier method, and differences between the groups were evaluated using the log-rank test. Laryngeal and oesophageal retention rates were compared using the cross-tabulation test. Results The 3- and 5-year overall survival rates were 22.86% and 11.43% in group A and 24.25% and 6.06% in group B, respectively (all P > 0.05). The laryngeal and oesophageal retention rates were 40.0% and 74.3% in group A and 0.0% and 27.3% in group B, respectively (all P < 0.01). There was no statistically significant difference in the incidence of post-operative complications between the two groups (group A 8.6%, group B 12.1%; P > 0.05). Conclusions Induction chemotherapy may be an appropriate first choice to ensure laryngeal and oesophageal preservation in the individualised treatment of advanced hypopharyngeal carcinoma with cervical oesophageal invasion.

Backgroud: Induction chemotherapy, as a larynx preservation treatment, has been available for over 20 years. We conducted a retrospective study to evaluate the efficacy of this protocol with taxene, cisplatin and 5-fluorouracil in Chinese patients with hypopharyngeal cancer that chose preservation strategy.170 patients with locally advanced hypopharyngeal cancer were assigned to receive induction chemotherapy. 107 patients (63%) with complete response or partial response received larynx preservation treatment and 63 non-responders (37%) received radical surgery.Median survival time was 30 months (range: 3-59 months). 63 patients (37%) had local-regional failure and 15 (9%) had distant metastasis. Three-year LFS was 27.8% (95% CI: 23.6-32.0%). The estimated three-year overall survival rate was 44.5% (95% CI: 39.5-49.5%). There was no significant difference in the three-year survival rate between responders (44.8%) and non-responders (43.9%) (p = .237), however patients with a partial response had a significant decrease in survival (32.2%) (p .001).In patients with hypopharyngeal cancer, ICT with TPF regimen followed by RT, as a larynx preservation treatment, may be suitable for complete responders, but not partial responders.

Tumor resection causes damage in the head and neck which creates problems in swallowing, chewing, articulation, and vision, all of which seriously affect patients’ quality of life. In this work, we evaluated the application of a free medial tibial flap in reconstruction of head and neck defects after tumor resection. We discussed the anatomy, surgical technique, and the advantages and disadvantages of the flap. We found several benefits for the flap, such as, it is especially effective for the defects that require thin-layer epithelium to cover or the separated soft tissue defect; a two-team approach can be used because the donor site is far away from the head and neck; and the flap is easy to integrate because of the subcutaneous fat layer of the free medial tibial flap is thin and the flap is soft. Thus, the medial tibial flap could replace the forearm flap for certain applications.

Background Oncolytic viral efficacy may be limited by the penetration of the virus into tumors. This may be enhanced by intraoperative application of virus immediately after surgical resection. Methods Oncolytic vaccinia virus GLV-1h68 was delivered in silk-elastin-like protein polymer (SELP) in vitro and in vivo in anaplastic thyroid carcinoma cell line 8505c in nude mice. Results GLV-1h68 in SELP infected and lysed anaplastic thyroid cancer cells in vitro equally as effectively as in phosphate-buffered saline (PBS), and at 1 week retains a thousand fold greater infectious plaque-forming units. In surgical resection models of residual tumor, GLV-1h68 in SELP improves tumor control and shows increased viral β-galactosidase expression as compared to PBS. Conclusion The use of SELP matrix for intraoperative oncolytic viral delivery protects infectious viral particles from degradation, facilitates sustained viral delivery and transgene expression, and improves tumor control. Such optimization of methods of oncolytic viral delivery may enhance therapeutic outcomes. © 2014 Wiley Periodicals, Inc. Head Neck, 2015

Metastases to the supraclavicular region usually originate from the head and neck or from infraclavicular tumors. Ovarian primaries of supraclavicular metastases are extremely rare. The present study reports the case of a 60-year-old patient with a bilateral supraclavicular mass that was diagnosed as a poorly-differentiated squamous cell carcinoma of unknown primary, following a fine-needle aspiration biopsy (FNAB) and comprehensive clinical investigation. The analysis of a peripheral blood sample using the CellSearch system revealed the presence of circulating tumor cells (CTCs) that were positive for epithelial cell adhesion molecule (EpCAM) and cytokeratin (CK) expression. Since EpCAM is usually expressed in adenocarcinoma, an excisional biopsy of the right supraclavicular lymph node was performed. The patient was diagnosed with occult ovarian low-grade serous carcinoma by immunohistochemistry. To the best of our knowledge, this is the first report to demonstrate that CTCs may be detected in the peripheral blood of a patient with cancer of unknown primary (CUP) by using the CellSearch system. A literature review was performed to analyze the diagnostic procedures of CUP metastatic to the cervical lymph nodes and the clinical features of CTCs.

Purpose This study was to investigate clinicopathologic characteristics and prognostic factors in adenoid cystic carcinoma of head and neck minor salivary glands. Materials and methods We conducted a retrospective review of 130 patients with adenoid cystic carcinoma of head and neck minor salivary glands that were evaluated between 2000 and 2013 in Beijng Tongren Hospital. Results Five-year overall survival and disease-free survival rates were 80.8% and 55.6%. Local recurrence rate was 40%, regional recurrence 3.8%, and distant metastasis was 28.5%. On univariate analysis, solid histological subtype, perineural invasion, positive surgical margins and advanced stages were found to be poor prognostic indicators. On multivariate analysis, solid histological subtype and positive surgical margins were significant prognostic factors of worse overall survival. Conclusions Solid histological subtype and positive surgical margins were the most important predictors of poor outcome in adenoid cystic carcinoma of minor salivary glands. Surgery with postoperative radiation were recommended treatment and offered durable local control.

Objective To evaluate the expression of mismatch repair gene PMS2 in human nasopharyngeal carcinoma (NPC) tissues and evaluate the effect of glycogen synthase kinase (GSK)-3β on PMS2 production in vivo and in vitro. Methods The expression of PMS2 and inactivated phosphorylated GSK-3β( s 9) was examined by immunohistochemical staining in 25 NPC tissues and the relation was determined by correlation analysis. The effect of GSK-3β transfection in CNE-2 cells on PMS2 production as well as cell apoptosis and chemosensitization were evaluated using small interference RNA (siRNA), immunoblotting and flow cytometric analysis in vitro. Results The expression of inactivated phosphorylated GSK-3β( s 9) was found to negative correlated with PMS2 in vivo. And transfected GSK-3β was found to be able to enhance PMS2 production, and increase cell apoptosis in CNE-2 cells in combination with cisplatin administration in vitro. Conclusion Inactivation of GSK-3β might be important for NPC tumorgenesis through negatively regulating PMS2 production, and enhanced PMS2 production by GSK-3β is beneficial for understanding the NPC tumorgenesis and developing potential strategy for future therapy.

To explore the feasibility and effect of CO2 laser surgery for early glottic carcinoma with anterior commissure involvement.Twenty-seven patients with T1b glottic squamous cell carcinoma who underwent transoral CO2 laser surgery as the primary modality of treatment from January 2008 to August 2013 were reviewed. All patients were males and the age ranged from 46 to 81 years old. The patients did not receive any other treatments. Preoperative enhanced CT scan was performed to assess the status of the tumors and the lamina of thyroid cartilage. All the patients without the lamina of thyroid cartilage involved underwent transoral CO2 laser surgery.Among 27 cases, aside from 1 patient converted to open operation due to inadequate exposure, 26 patients were successfully implemented operation. All the patients were followed-up for 12 to 60 months (median 26 months) and no recurrence. Granulation occurred four to six weeks after operation in all patients. Among them, granulation disappeared automatically three to six months in 22 patients and was resected with local anesthesia in other 4 patients, which the pathological results were inflammatory lesion. All patients did not undergo tracheotomy and nasogastric feeding, with an average stay of three days in hospital after surgery, and had different degree of vocal cord adhesion 6 months later.Transoral CO2 laser surgery is an ideal procedure for early glottic carcinoma with anterior commissure involvement. Better preoperative evaluation, endoscopic technique and satisfied exposure are keys to the success of operation.

RATIONALE Infantile desmoid fibromatosis of the postcricoid area is a rare disease and is characterized by a proliferation of fibrous tissue with non-metastasis, local infiltration, and a high rate of recurrence after surgical resection. Currently, ultrasound is scarcely used in the hypopharynx and larynx area. PATIENT CONCERNS A 4-year-old boy presented with hoarseness, deep voice and snoring for 2∼4 years without any surgical history. On sonography, the lesion was found in the postcricoid area, and the left larynx showed impaired mobility in real time observation. Complete excision with a negative margin in this pivotal anatomic area is impossible, and necessitates a long-time surveillance. DIAGNOSES Infantile desmoid fibromatosis of the postcricoid area was diagnosed according to surgery and histopathology. INTERVENTIONS Local excision was carried out to relieve the upper airway narrowing. OUTCOMES Relieved hoarseness and snoring were reported on the latest follow-up. A residual lesion was seen in the surgical bed and maintained a stable extent on ultrasound and MR imaging after a year. LESSONS Considering the non-radiation merit and diagnostic ability, ultrasonography is advocated as a valuable supplementary imaging method to CT, MR and laryngoscopy in the juvenile larynx and hypopharynx.

To study the definition, etiology, diagnosis, treatment and prognosis in patients with multiple primary malignant tumor of upper aerodigestive tract cancer and thyroid cancer.Retrospectively analyze the events of 7 cases with multiple primary malignant tumors of upper aerodigestive tract cancer and thyroid cancer.Lesions of upper aerodigestive tract cancer and thyroid cancer located on the same side. After 4 to 8 years of follow-up, 2 cases of hypopharyngeal cancer and thyroid cancer got poor prognosis, prognosis of other patients with early stage laryngeal cancer and thyroid cancer is better.The prognosis of multiple primary malignant tumors in patients with upper aerodigestive tract cancer and thyroid cancer depends on the biological behavior of aerodigestive tract cancer.

Cervical lymph node metastatic rates tend to increase by T stage in cN0 glottic laryngeal carcinoma (GLC). Moreover, cervical lymph node metastasis (LNM) shows a sequential pattern according to the regions involved and LNM affects the prognosis.To investigate factors that contribute to LNM of N0 (cN0) T2-T4 GLC and their effect on prognosis.A total of 212 GLC patients who had been admitted between December 2002 and January 2013 were retrospectively analyzed. They included 202 men and 10 women, median age 58.6 years (range 29-85 years), whose identified tumor stages included T2 (n = 81), T3 (n = 67), and T4 (n = 64). Relevant factors of cervical LNM were analyzed; multivariate analyses and receiver operating characteristic (ROC) curve were carried out to predict the metastasis and prognosis.The overall metastatic rate of N0 GLC was 14.6%. T staging and pathological classification were the risk factors for LNM. Metastatic rates for levels II, III, and IV were 10.2%, 14.6%, and 2.5%, respectively. Approximate 4.2% of patients experienced LNM with no recurrence of laryngeal cancer. Overall 3- and 5-year survival rates were 85% and 80%, respectively, compared with 66% and 57%, respectively, among patients with LNM. The inter-group survival curve comparison was statistically significant (p = 0.012).

To investigate factors that contribute to lymph node metastasis (LNM) from clinical cT2-T4 N0M0 (cN0) supraglottic laryngeal carcinoma (SLC), and to predict the risk of occult metastasis before surgery.A total of 121 patients who received surgery were retrospectively analyzed. Relevant factors regarding cervical LNM were analyzed. Multivariate analyses were conducted to predict the region where the metastasis occurred and prognosis.The overall metastatic rate of cN0 SLC was 28.1%. Metastatic rates were 15.4%, 32.5% and 35.7% for T2, T3 and T4, respectively. Metastatic rates for SLC levels II, III and IV were 19.6%, 17.2% and 3.6%, respectively. A regression equation was formulated to predict the probability of metastasis in cN0 SLC as follows: Pn=e((-3.874+0.749T3+1.154T4+1.935P1+1.750P2))/[1+e((-3.874+0.749T3+1.154T4+1.935P1+1.750P2))]. Approximately 0.2% of patients experienced LNM with no recurrence of laryngeal cancer. Comparison of the intergroup survival curves between patients with and without LNM indicated a statistically significant difference (P=0.029).Cervical lymph node metastatic rates tended to increase in tandem with T stage in patients with LNM in cN0 SLC, and neck dissection is advised for these patients. Moreover, cervical LNM in cN0 SLC showed a sequential pattern and may be predicted.

Salivary gland carcinomas are relatively rare malignant tumors, accounting for less than 5% of all cancers of the head and neck.1 They encompass a wide spectrum of histologic abnormalities with varied biologic behavior. Initial therapy of localized disease consists of complete surgical excision. The risk of recurrence and metastasis is significantly higher in patients with locally advanced salivary carcinomas. Individuals with high-grade salivary carcinomas have a 5-year survival of roughly 40%; those with low-and intermediate-grade tumors have a 5-year survival of 85% to 90%.2,3 For these patients, complete surgical resection followed by postoperative radiation therapy is recommended.4 Unfortunately, patients with recurrent and/or unresectable disease have few effective treatment options. Clinical trials exploring the role of chemotherapy in the management of salivary gland carcinomas failed to show survival benefit.1 Chemotherapy, therefore, is generally reserved as a palliative measure for patients with symptoms and/or rapid disease progression. Clearly, novel therapies are needed to improve outcomes for patients with salivary carcinomas. Oncolytic viruses have emerged as versatile therapeutic agents that can selectively infect, replicate within, and ultimately lyse a host cancer cell. A variety of viruses have been reported5–7 to possess on-colytic antitumoral activity, including herpes simplex type 1, adenovirus, reovirus, vesicular stomatitis virus, measles virus, poliovirus, West Nile virus, and New-castle disease virus. Vaccinia virus, which is a double-stranded DNA member of the genus Orthopoxvirus, has many unique characteristics that make it an excellent tool in cancer treatment. In addition to its natural tropism for tumor tissues and its abilities for efficient entry, replication, and lysis, vaccinia virus has a remarkable safety record in its historical widespread human application as a vaccine for smallpox. The vaccinia replication cycle occurs exclusively in the cytoplasm, which eliminates the possibility of chromosomal integration.7 Furthermore, there are many Food and Drug Administration–approved antiviral agents available to limit viral spread and control the unlikely possibility of viral toxicity.8 Consequently, several recombinant vaccinia viruses have been constructed and studied in preclinical and clinical phase 1 settings.8,9 Recombinant, replication-competent vaccinia virus (GLV-1h68) has been reported10–16 as effective in breast cancer, thyroid cancer, mesothelioma, pancreatic cancer, prostate cancer, human hepatocellular carcinoma, and head and neck cancer models. The aim of this study was to assess the usefulness of GLV-1h68 as a therapeutic agent against salivary gland carcinoma in vitro and in vivo. Murine flank and orthotopic parotid tumor models were used.

Background Approximately one fourth of bone and soft-tissue sarcomas recur after prior treatment. GLV-1h68 is a recombinant, replication-competent vaccinia virus that has been shown to have oncolytic effects against many human cancer types. We sought to determine whether GLV-1h68 could selectively target and lyse a panel of human bone and soft-tissue sarcoma cell lines in vitro and in vivo . Methods GLV-1h68 was tested in a panel of four cell lines including: fibrosarcoma HT-1080, osteosarcoma U-2OS, fibrohistiocytoma M-805, and rhabdomyosarcoma HTB-82. Gene expression, infectivity, viral proliferation, and cytotoxicity were characterized in vitro . HT-1080 xenograft flank tumors grown in vivo were injected intratumorally with a single dose of GLV-1h68. Results All four cell lines supported robust viral transgene expression in vitro . At a multiplicity of infection (MOI) of five, GLV-1h68 was cytotoxic to three cell lines, resulting in >80% cytotoxicity over 7 d. In vivo , a single injection of GLV-1h68 into HT-1080 xenografts exhibited localized intratumoral luciferase activity peaking at d 2–4, with gradual resolution over 8 d and no evidence of spread to normal tissues. Treated animals exhibited near-complete tumor regression over a 28-d period without observed toxicity. Conclusion GLV-1h68 has potent direct oncolytic effects against human sarcoma in vitro and in vivo . Recombinant vaccinia oncolytic virotherapy could provide a new platform for the treatment of patients with bone and soft tissue sarcomas. Future clinical trials investigating oncolytic vaccinia as a therapy for sarcomas are warranted.

Replication-competent oncolytic viruses have shown great promise as a potential cancer treatment. This study aimed to determine whether a novel vaccinia virus, GLV-1h151, with genetic modifications enhancing cancer specificity and enabling virus detection, is effective against a range of human cancers and is safe when administered in preclinical models. GLV-1h151 was modified with deletion of thymidine kinase enhancing specificity and insertion of the green fluorescent protein (GFP) gene. The virus was tested in several human cancer cell lines for cytotoxicity including breast, lung, pancreatic, and colorectal. Virus replication was assessed via visualization of GFP expression and bioluminescence, and viral plaque assays. Finally, GLV-1h151 was administered systemically or intratumorally in mice with pancreatic cancer xenografts (PANC-1) to assess virus biodistribution, toxicity, and effect on tumor growth. GLV-1h151 effectively infected, replicated in, and killed several cancer cell types. Detection and visualization of virus replication was successful via fluorescence imaging of GFP expression, which was dose dependent. When administered intravenously or intratumorally in vivo, GLV-1h151 regressed tumor growth (P

Background. Newcastle disease virus (NDV) is a paramyxovirus that is pathogenic in birds but causes only mild flu- like symptoms in human beings. NDV(F3aa)-GFP is a genetically modified, fusogenic NDV. We assessed the utility of NDV(F3aa)- GFP in treating head and neck squamous cell carcinoma. Methods and Results. At a multiplicity of infection (MOI) of 1, NDV(F3aa)-GFP infection of 3 cell lines supported strong GFP expression by 36 hours. Four cell lines were highly sensitivite to vi- ral cytotoxicity, with >75% of cells lysed by day 6 at MOI 0.1, and 2 other cell lines were partially susceptible. Murine SCC25 flank tumors exhibited robust GFP expression after a single intratumoral viral injection and showed near-complete tumor regression over 34 days. There were no adverse effects attributable to therapy. Conclusions. We demonstrate that a fusogenic NDV exerts potent oncolytic effects against human head and neck cancer and support its continued investigation for clinical application. V C 2010 Wiley Periodicals, Inc. Head Neck 33: 1394-1399

Background Sinonasal squamous cell carcinoma (SSCC) and nasal inverted papilloma (NIP) represent the predominant type of malignant and benign tumors in sinonasal tract, respectively. CD4+CD25+Foxp3+ natural regulatory T (Treg) cells might play critical role(s) in the suppression of anti-tumor immune response and thus shed light on tumor progression from benign to malignant. Objective This study aimed to evaluate the frequency and suppressive capacity of Treg cells in SSCC compared to NIP and further to explore the underlying mechanisms. Patients and Methods Frequencies of Treg, Th1 and Th2 cells were evaluated by flow cytometry in tissue homogenate and peripheral blood from 31 SSCC patients, 32 NIP patients and 35 normal controls. Treg cells were tested for regulatory function by co-culture with effector T cells. CCR4 and its ligands, CCL22 and CCL17, were analyzed by flow cytometry and Luminex, respectively. The chemoattractant properties of CCR4/CCL22 and CCR4/CCL17 for Treg cells were assessed using the Boyden chamber technique, to elucidate the potential mechanisms of Treg recruitment in tumor microenvironment. Treg cells induction via TGF-β was assessed with transwells after local CD4+Foxp3+ T cells were assessed by immunohistochemistry and TGF-β concentration was measured by Luminex. Results Tumor-infiltrating Treg cells increased significantly from normal to NIP to SSCC (P ≤ 0.001 for normal vs. NIP and P = 0.004 for NIP vs. SSCC). Significantly elevated frequency and enhanced suppression capacity of circulating Treg cells in SSCC were detected compared to NIP and healthy controls, concomitant with Th1 decrease and Th2 increase. Apparently increased CCL22 attracted CCR4-expressing Treg cells to tumor microenvironment in SSCC, compared to NIP. SSCC produced significantly more TGF-β than NIP and thus possessed greater potential for Treg cell induction. Conclusion Frequency and suppressive capacity of Treg cells enhanced with progression of malignancy from NIP to SSCC. Circulating Treg cells were recruited to tumor tissue via CCR4/CCL22 signalling, whereas tumor-synthesised TGF-β contributed to induction of peripheral Treg cells.