Deep Learning Application for Vocal Fold Disease Prediction Through Voice Recognition: Preliminary Development Study.

BACKGROUND: Dysphonia influences the quality of life by interfering with communication. However, a laryngoscopic examination is expensive and not readily accessible in primary care units. Experienced laryngologists are required to achieve an accurate diagnosis. OBJECTIVE: This study sought to detect various vocal fold diseases through pathological voice recognition using artificial intelligence. METHODS: We collected 189 normal voice samples and 552 samples of individuals with voice disorders, including vocal atrophy (n=224), unilateral vocal paralysis (n=50), organic vocal fold lesions (n=248), and adductor spasmodic dysphonia (n=30). The 741 samples were divided into 2 sets: 593 samples as the training set and 148 samples as the testing set. A convolutional neural network approach was applied to train the model, and findings were compared with those of human specialists. RESULTS: The convolutional neural network model achieved a sensitivity of 0.66, a specificity of 0.91, and an overall accuracy of 66.9% for distinguishing normal voice, vocal atrophy, unilateral vocal paralysis, organic vocal fold lesions, and adductor spasmodic dysphonia. Compared with the accuracy of human specialists, the overall accuracy rates were 60.1% and 56.1% for the 2 laryngologists and 51.4% and 43.2% for the 2 general ear, nose, and throat doctors. CONCLUSIONS: Voice alone could be used for common vocal fold disease recognition through a deep learning approach after training with our Mandarin pathological voice database. This approach involving artificial intelligence could be clinically useful for screening general vocal fold disease using the voice. The approach includes a quick survey and a general health examination. It can be applied during telemedicine in areas with primary care units lacking laryngoscopic abilities. It could support physicians when prescreening cases by allowing for invasive examinations to be performed only for cases involving problems with automatic recognition or listening and for professional analyses of other clinical examination results that reveal doubts about the presence of pathologies.

Interplay between HDAC3 and WDR5 is essential for hypoxia-induced epithelial-mesenchymal transition.

Epithelial-mesenchymal transition (EMT) is important for organ development, metastasis, cancer stemness, and organ fibrosis. Molecular mechanisms to coordinately regulate hypoxia-induced EMT remain elusive. Here, we show that HIF-1α-induced histone deacetylase 3 (hdac3) is essential for hypoxia-induced EMT and metastatic phenotypes. Change of specific chromatin states is associated with hypoxia-induced EMT. Under hypoxia, HDAC3 interacts with hypoxia-induced WDR5, recruits the histone methyltransferase (HMT) complex to increase histone H3 lysine 4 (H3K4)-specific HMT activity, and activates mesenchymal gene expression. HDAC3 also serves as an essential corepressor to repress epithelial gene expression. Knockdown of WDR5 abolishes mesenchymal gene activation but not epithelial gene repression during hypoxia. These results indicate that hypoxia induces different chromatin modifiers to coordinately regulate EMT through distinct mechanisms.

Treatment for T1-2 oral squamous cell carcinoma with or without perineural invasion: neck dissection and postoperative adjuvant therapy.

BACKGROUND: Although perineural invasion (PNI) has been a poor prognostic factor for head and neck cancers, few studies have focused on oral squamous cell carcinoma (OSCC). The independent significance of PNI in early T1-2 OSCC and the benefit of treatment modification based on PNI status have not been assessed. This study investigated the role of PNI in T1-2 OSCC patients, with focus on the controversial issues of neck management and postoperative adjuvant therapy. METHODS: PNI status was re-reviewed under hematoxylin and eosin staining in tumors of 307 consecutive T1-2 OSCC patients. Oncologic and survival outcomes were analyzed by univariate and multivariate analyses. RESULTS: PNI was identified in 84 (27.4%) patients, correlating with several established poor prognostic factors. In multivariate analysis, PNI remained an independent predictor for neck metastasis, neck recurrence, and a worse 5-year disease-specific survival. Elective neck dissection contributed to a significantly better 5-year disease-specific survival only in cN0 patients with PNI-positive tumors (P = 0.0071) but not in those with PNI-negative tumors (P = 0.3566). In low-risk patients who were treated by surgery alone, including neck dissection, the 5-year disease-specific survival rates were almost the same in those with PNI-positive tumors and those with PNI-negative tumors (92.0 vs. 92.9%; P = 0.9104). CONCLUSIONS: Elective neck dissection is indicated for cN0 patients with PNI-positive tumors for the efficacy of improving disease-specific survival as well as neck control. However, low-risk PNI-positive patients who undergo neck dissection do not need postoperative adjuvant therapy, because the residual risk from PNI is minimal.

Office-Based Structural Autologous Fat Injection Laryngoplasty for Unilateral Vocal Fold Paralysis.

Unilateral vocal fold paralysis (UVFP) is a common cause of incomplete glottic closure, leading to significant somatic and social disabilities. Office-based autologous fat injection laryngoplasty (AFIL) has been proposed as an effective treatment for glottic insufficiency but has not been well-studied for UVFP. We enrolled 23 patients who underwent office-based structural AFIL due to unilateral vocal paralysis at our institution between February 2021 and January 2022. In the procedure, autologous fat was harvested and injected into the vocal fold under the guidance of flexible digital endoscopy for structural fat grafting. The voice handicap index-10 (VHI-10) score and perceptual voice measurements were collected before the operation, 2 weeks postoperatively, and 3 months postoperatively. Twenty-two patients were followed-up for at least 3 months. The VHI-10 score improved significantly from 29.65 ± 8.52 preoperatively to 11.74 ± 7.42 at 2 weeks (p < 0.0001) and 5.36 ± 6.67 at 3 months (p < 0.0001). Significant improvements in grades of dysphonia (p < 0.0001), breathiness (p < 0.0001), and asthenia (p = 0.004) were also noted at 3 months postoperatively when perceptual measurements were investigated. Office-based structural AFIL is an effective treatment for improving voice-related disability for UVFP patients.

Persistent Krüppel-like factor 4 expression predicts progression and poor prognosis of head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is one prevalent human cancer worldwide. No molecular markers are presently used for predicting prognosis in HNSCC. Krüppel-like factor 4 (KLF4) is a transcription factor with diverse physiological functions, and possesses opposing roles in different human cancers. The expression and roles of KLF4 in HNSCC remain to be elucidated. In this study, immunohistochemical (IHC) analysis of KLF4 in 62 HNSCC was firstly performed. IHC results demonstrated that 42 (67.7%) had decreased KLF4 expression compared with surrounding normal epithelium, while persistent KLF4 expression was demonstrated in 20 (32.3%). The IHC results were further verified by Western blot and real-time PCR analyses to confirm the robustness of staining and interpretation. Interestingly, persistent KLF4 expression independently correlated with a worse disease-specific survival (P = 0.005), especially in patients with advanced disease. In consistent with clinical observation, all five HNSCC cell lines tested revealed a low level of baseline KLF4 expression. Moreover, enforced KLF4 expression in cell line SAS significantly increased in vitro migration/invasion abilities, multi-drug resistance, and in vivo tumorigenicity. These results clearly illustrate that persistent KLF4 expression predicts poor prognosis and confers aggressiveness in HNSCC. Our data therefore provides valuable information that HNSCC with persistent KLF4 expression might require intensified combination treatment in future practice.

A study using ifosfamide and etoposide in patients with cisplatin-refractory recurrent or metastatic head and neck squamous cell carcinoma.

OBJECTIVE: To investigate the efficacy and safety of combination therapy with ifosfamide and etoposide in cisplatin-refractory recurrent/metastatic squamous cell carcinoma of the head and neck. METHODS: Thirty patients with cisplatin-refractory recurrent/metastatic squamous cell carcinoma of the head and neck were treated with ifosfamide (1000 mg/m(2)/day) as a continuous 24 h infusion for 3 days and etoposide (100 mg/m(2)/day) as a bolus 1 h infusion on the same 3 days. The treatment was repeated every 4 weeks until disease progression. RESULTS: The overall rate of response was 27% (8/30), and 20% (6/30) of the patients achieved stable disease status. Median overall survival was 7.7 months. Subgroup analysis demonstrated significant improvement in overall survival in the group that achieved control of disease. Thirteen (43.3%) patients developed grade 3-4 neutropenia, and five (16.6%) developed grade 3-4 non-hematologic mucositis. CONCLUSIONS: This combination chemotherapy had an effective and safe profile and improved survival in patients with cisplatin-refractory recurrent/metastatic squamous cell carcinoma of the head and neck who achieved disease control.

Promising long-term results with attenuated adverse effects by methotrexate-containing sequential chemoradiation therapy in locally advanced head and neck squamous cell carcinoma.

OBJECTIVE: To reduce severe acute and late toxicities without compromising organ preservation survival in patients with locoregionally advanced head and neck squamous cell carcinoma, we performed three-drug induction methotrexate-cisplatin-fluorouracil with weekly cisplatin-fluorouracil concurrent chemoradiation. METHODS: Two induction courses of methotrexate (40 mg/m(2)/day, days 1, 8 and 15), cisplatin and 5-fluorouracil (25 and 750 mg/m(2)/day, days 1-4) were given in new diagnoses of patients with non-nasopharyngeal locoregionally advanced head and neck squamous cell carcinoma. Responders received concurrent chemoradiation with weekly cisplatin (20 mg/m(2)/day) and 5-fluorouracil (400 mg/m(2)/day) on day 1. RESULTS: Among 57 patients (58% with Stage IV and hypopharyngeal cancer), the rates of Grade 3-4 toxicity were 30 and 74% during induction and CCRT, respectively. A total of 49 patients completed induction and began concurrent chemoradiation; 47 (96%) completed all planned treatment. With a median follow-up of 62 months (range 19-83 months) for the current survivors, the 3-year overall and disease-specific survival estimates were 50 and 58%, respectively. The 3-year organ preservation survival was 74% in patients who achieved complete remission after concurrent chemoradiation, and 96% of current survivors are tracheotomy and feeding tube-free. No patient without local/regional failure suffered from distant metastasis. CONCLUSIONS: Methotrexate-cisplatin-fluorouracil induction chemotherapy followed by weekly cisplatin-fluorouracil concurrent chemoradiation is an acute and late toxicity-acceptable protocol without attenuating organ preservation survival in patients with locoregionally advanced head and neck squamous cell carcinoma. In this patient cohort with advanced head and neck squamous cell carcinoma, overall and organ preservation survivals were encouraging, and provided promising long-term benefits of this approach.

Extra-major salivary gland pleomorphic adenoma of the head and neck: a 10-year experience and review of the literature.

Pleomorphic adenomas, or benign mixed tumors, make up 65% of all salivary gland tumors. They also can be found as solid tumors in other parts of the head and neck region, such as the auditory canal, the eyelids, and the orbital area. In this study, we investigated extra-major salivary gland pleomorphic adenomas of the head and neck region retrospectively at a tertiary care center. Between March 1998 and June 2009, 37 patients underwent primary surgery for extra-major salivary gland pleomorphic adenoma of the head and neck. The duration of symptoms, radiographic findings, operative procedures, and pathologic findings were documented. Of the 37 patients enrolled, 22 were male and 15 were female, with a median age of 57 years. Tumors were found in the soft palate, hard palate, nasopharynx, orbital area, trachea, buccal mucosa, cheek, nasal septum, upper lip, lower eyelid, and external auditory canal. Cellular variant of the pleomorphic adenoma was found in four patients, while the remaining patients presented with the classic variant. No myxoid subgroup was noted in our study. Carcinoma ex pleomorphic adenoma was observed only in one patient for whom radical surgery was performed. Twenty-eight patients (76%) had long-term follow-ups, with the average follow-up period being 4.5 years. Local recurrence was observed in three patients, and they underwent revision surgery during the follow-up period. Our results indicate that extra-major salivary gland pleomorphic adenomas are most commonly found in the soft palate. Wide excision was the treatment of choice, although its efficacy might be compromised with cosmetics and functional structures of the head and neck. Therefore, long-term follow-up of patients is necessary.

Identification of increased NBS1 expression as a prognostic marker of squamous cell carcinoma of the oral cavity.

Oral squamous cell carcinoma (OSCC) is one of the most prevalent cancers worldwide; however, accurate molecular markers to predict its prognosis are still limited. We previously demonstrated that overexpression of the DNA double-strand break repair protein NBS1 is a prognostic marker of advanced head and neck squamous cell carcinoma (HNSCC). Therefore, we aimed to investigate the feasibility of using NBS1 as a biomarker in OSCC. In this study, we enrolled 148 OSCC for immunohistochemical (IHC) and clinical analysis. Data from 58 advanced non-oral-cavity HNSCC (NO-HNSCC) cases were also included for comparison due to the biological and clinical discrepancy between OSCC and HNSCC originated from the other sites (e.g. pharynx or larynx). First, we validated the NBS1 IHC results by real-time RT-PCR analysis, and an excellent correlation between the results of these two assays confirmed the reliability and robustness of IHC procedures and interpretation. NBS1 overexpression was an independent prognostic marker in both OSCC and NO-HNSCC cases. In OSCC, the prognostic significance of NBS1 was shown regardless of T stage and lymph node status. Increased NBS1 expression correlated with advanced T stage and recurrence/metastasis. NBS1 overexpression correlated with the phosphorylation levels of Akt and its downstream target mammalian target of rapamycin (mTOR). These results clearly illustrate the expression profile of NBS1 in OSCC and NO-HNSCC, and highlight the role of NBS1 in HNSCC irrespective of the primary sites. It also indicates the practicability of application of NBS1 as a marker in OSCC.

Prolonged facial edema is an indicator of poor prognosis in patients with head and neck squamous cell carcinoma.

OBJECTIVE: The purpose of this study was to identify the causes of prolonged facial edema and its associations with other clinical factors. Facial edema sometimes is observed in patients with head and neck squamous cell carcinoma (HNSCC), but its prevalence and association with other factors is unclear. METHODS: Between July 2003 and July 2007, the medical records from 264 patients with HNSCC were reviewed. Prolonged facial edema is defined as persistence of edematous status (largest thickness >5 mm by CT scan) for more than 100 days. Clinical data including age, gender, tumor stage, and tumor primary sites were recorded. Statistical analyses were performed to determine the prognostic effect of prolonged facial edema, as well as its relationship to other clinical variables. The etiology of prolonged facial edema was also analyzed. RESULTS: Prolonged facial edema occurred in 32 (12.1%) patients. The etiologies included internal jugular vein thrombosis, local infection, neck lymph nodes dissection, flap reconstruction, and direct vessel compression by tumors or metastatic lymph nodes. There was no significant difference in the incidence of prolonged facial edema in patients receiving different treatment modalities; however, patients receiving neck dissection correlated with the occurrence of late-onset facial edema. In addition to previously demonstrated prognostic factors (T status, nodal involvement and distant metastasis), prolonged facial edema was also identified as independent prognostic indicators for HNSCC patients (P = 0.001). CONCLUSIONS: Prolonged facial edema may reflect the underlying disease status, and it can be applied as a prognostic marker in patients with HNSCC.

Different patterns of second primary malignancy in patients with squamous cell carcinoma of larynx and hypopharynx.

PURPOSE: The aim of the present study was to compare the incidence, patterns, and survival of second primary malignancy (SPM) in patients with squamous cell carcinoma of the larynx (LSCC) and hypopharynx (HPSCC). METHODS: We retrospectively review the medical record of 581 previously untreated patients with LSCC (392 cases) and HPSCC (189 cases) who received primary surgery with or without postoperative radiotherapy from 1990 to 2000. Data including age, sex, risk factors, subsites and TNM stage of primary tumor, treatment, site and incidence of SPM, and prognosis were collected from medical charts. RESULTS: Groups with HPSCC had a higher incidence (4.2% vs 2.9% annual rate) and shorter median time (30 vs 59 months) developing SPM rather than LSCC. Fifty-five percent of the SPM occurred in the respiratory axis in LSCC, and 66% developed in the digestive axis in HPSCC. The factors influencing the appearance of SPM included early T stage, tobacco use, and less tumor recurrence. Long-term survival was poorer in those with than without SPM (38% vs 49% at 10 years). CONCLUSIONS: There is a tendency for SPM to occur in the respiratory axis (lung and larynx) in LSCC and in the digestive axis (oral cavity, pharynx, and esophagus) in HPSCC. This information is important for posttreatment follow-up.

Interaction between HSP60 and beta-catenin promotes metastasis.

Heat shock protein 60 (HSP60) plays an essential role in assisting many newly synthesized proteins to reach their native forms. Increased HSP60 expression is observed in different types of human cancers with metastasis (e.g. pancreatic cancer and large bowel carcinoma). However, the role of HSP60 in metastasis remains little known. Aberrant activation of beta-catenin plays a key role in tumorigenesis and metastasis. Here, we show that overexpression of HSP60 induces metastatic phenotypes in vitro and in vivo. HSP60 interacts with beta-catenin, increases beta-catenin protein levels through the apical domain and enhances its transcriptional activity. Short-interference RNA-mediated repression of beta-catenin reverts metastatic activity caused by HSP60 overexpression. Proteosomal activity is not required for the induction of beta-catenin by HSP60. Coexpression of HSP60 and nuclear beta-catenin predicts a worse prognosis of metastatic head and neck cancer patients. These results implicate a novel role of HSP60 in metastasis.

Role of ATP in the ROS-mediated laryngeal airway hyperreactivity induced by laryngeal acid-pepsin insult in anesthetized rats.

The pathogenetic mechanisms of laryngeal airway hyperreactivity (LAH) in patients with extraesophageal reflux are unclear. We recently reported that a laryngeal acid-pepsin insult produces LAH that is mediated through sensitization of the capsaicin-sensitive laryngeal afferent fibers by reactive oxygen species (ROS) in rats. Since ROS may promote the release of ATP from cells, we hypothesized that activation of P2X purinoceptors by ATP subsequent to an increase in ROS induces LAH in an inflamed larynx that has been insulted by acid-pepsin or H(2)O(2) (a major type of ROS). The larynxes of 208 anesthetized rats were functionally isolated while the animals breathed spontaneously. Ammonia vapor was delivered into the larynx to measure laryngeal reflex reactivity. Laryngeal insult with acid-pepsin or H(2)O(2) produced LAH with similar characteristics. The H(2)O(2)-induced LAH was prevented by laryngeal pretreatment with dimethylthiourea (a hydroxyl radical scavenger), suggesting a critical role for ROS. The LAH induced by both insults were completely prevented by ATP scavengers (a combination of apyrase and adenosine deaminase) or a P2X receptor antagonist (iso-pyridoxalphosphate-6-azophenyl-2',5'-disulfonate). Laryngeal application of a P2X receptor agonist (alpha,beta-methylene-ATP) also produced LAH. An insult with either acid-pepsin or H(2)O(2) similarly promoted an increase in the levels of ATP, lipid peroxidation, and inflammation in the larynx. Our findings suggest that laryngeal insult with acid-pepsin or H(2)O(2) induces inflammation and produces excess ROS in the rat's larynx. The latter may in turn promote the release of ATP to activate P2X receptors, resulting in sensitization of capsaicin-sensitive laryngeal afferent fibers and LAH.

Activation of phosphoinositide 3-kinase by the NBS1 DNA repair protein through a novel activation motif.

Class IA phosphoinositide 3-kinases (PI 3-kinases) are key signaling components downstream of tyrosine kinases and Ras, regulating many different cellular functions and contributing to tumorigenesis. Class IA PI 3-kinases are heterodimers comprised of a p85 regulatory and a p110 catalytic subunit. Nijmegen breakage syndrome (NBS) is a chromosomal instability syndrome associated with cancer predisposition, radiosensitivity, microcephaly, and growth retardation. The NBS gene product p95 (also known as NBS1) is part of the Mre11-Rad50-Nbs1 complex, a central player associated with double-strand break repair. We previously demonstrated that NBS1 overexpression induces transformation through activation of PI 3-kinase/Akt. In this study, we show that NBS1 directly interacts, through a highly conserved C-terminal motif (aa 653-669) of NBS1, with the N-terminal domain (aa 1-108) of the p110alpha catalytic subunit of PI 3-kinase, and stimulates PI 3-kinase activity. Mutations of different regions of the conserved motif abolish the ability of NBS1 to activate PI 3-kinase in vitro and in vivo. Co-expression of NBS1/p110alpha/p-Akt is observed in certain percentage of head and neck cancer patient samples. These results demonstrate that NBS1 can function as an adaptor/activator of p110alpha PI 3-kinase through a novel activation motif, consistent with its possible role in cell transformation and tumorigenesis.

Reconstruction of the hypopharynx after surgical treatment of squamous cell carcinoma.

Squamous cell carcinoma of the hypopharynx (HPSCC) tends to present with an advanced stage. Surgery with postoperative radiation or chemoradiation therapy has been the standard treatment for HPSCC. Radical surgery may result in a large surgical defect of the hypopharyngeal and cervical esophageal regions. Reconstruction of the surgical defect is also important after ablation procedures. Many reconstructive methods have been developed. However, each method has its own advantages and disadvantages. The ideal method for hypopharyngeal reconstruction should have the following attributes if possible: single-stage procedure, high success rate of tissue transfer, low donor-site morbidity, low fistula and stenosis rates, restoration of the ability to speak and swallow, able to achieve successful reconstruction in a heavily radiated area and tolerance of postoperative radiotherapy. In this review article, we discuss the indications and drawbacks of several reconstructive methods that have been frequently used in our clinical practice. Finally, we will introduce the technique of laryngotracheal flap reconstruction, which was developed in our institution and has proved to be a simple and reliable method for hypopharyngeal reconstruction.

Office-Based Autologous Fat Injection Laryngoplasty for Glottic Insufficiency in Patients Under 50 Years Old.

OBJECTIVE: We sought to determine the outcomes of office-based autologous fat injection laryngoplasty in the treatment of patients under 50 years old with glottic insufficiency but without neurological problems or acquired organic lesions in the vocal fold. METHODS: We conducted a retrospective chart review of consecutive patients under 50 years of age who underwent office-based autologous fat injection laryngoplasty for glottic insufficiency. None of the patients presented neurological problems or acquired organic lesions in the vocal fold. Videolaryngostroboscopic data, objective voice assessment, perceptual measurements of vocal quality, and subjective ratings of voice quality were evaluated before and after treatment. RESULTS: The 23 patients (7 men and 16 women) in this study presented significant improvements in phonatory function in terms of maximum phonation time, jitter, grade, asthenia, and Voice Handicap Index-10 (VHI-10) values at 3 months. Significant improvements in terms of jitter, noise-to-harmonic ratio, grade, roughness, breathiness, asthenia, and the VHI-10 values were also observed at 6 months. CONCLUSIONS: Glottic insufficiency in younger patients without neurological problems or acquired organic lesions in the vocal fold can be treated effectively using office-based autologous fat injection laryngoplasty. Significant improvements in phonatory function were observed even 6 months after surgery.

Author Correction: Bmi1 is essential in Twist1-induced epithelial-mesenchymal transition.

In the version of Supplementary Fig. 3c originally published with this Article, the authors mistakenly duplicated a blot from Supplementary Fig. 3b. The correct versions of these figures are shown below. In addition, two independent repeats of the experiments presented in Supplementary Figs. 3b and 3c, showing results consistent with those originally reported, have been deposited in Figshare ( 10.6084/m9.figshare.7545263 ).

Nm23-H1 expression of metastatic tumors in the lymph nodes is a prognostic indicator of oral squamous cell carcinoma.

We recently reported that low Nm23-H1 expression of primary oral squamous cell carcinoma (OSCC) was correlated with the occurrence of lymphatic metastasis. However, little is known about whether Nm23-H1 level of metastatic tumors in the cervical lymph nodes is reduced in comparison with primary oral cancers and its significance for patients' prognosis. By immunohistochemistry, we analyzed the Nm23-H1 expression in 52 pairs of OSCC specimens from primary oral cancers and their metastatic lymph nodes. Western blot analysis further confirmed the immunohistochemical interpretation. To verify the effects of Nm23-H1 on cell migration and invasion, we established several stable clones derived from a human OSCC cell line (SAS) by knockdown and overexpression. Wound-healing closure, transwell migration and invasion assays were performed to determine cell motility, migratory and invasive activities. Western blot analysis was carried out to evaluate cyclin A expression of OSCC cells with the altered Nm23-H1 levels following knockdown and overexpression. By immunohistochemistry, Nm23-H1 expression of metastatic lymph nodes was significantly lower than that of their primary oral cancers, supporting a role of Nm23-H1 in metastasis suppression. Negative Nm23-H1 interpretation of OSCC specimens, in either primary oral cancers or metastatic lymph nodes, indicated a poor survival outcome of patients. On the basis of in vitro studies of Nm23-H1 knockdown and overexpression, we demonstrated an inverse correlation between Nm23-H1 expression and the invasiveness of OSCC cells. Moreover, we observed the concomitant reduction in Nm23-H1 and cyclin A levels of metastatic tumors in both results of in vitro OSCC cells and ex vivo tumor specimens.

Chemoradiotherapy laryngeal preservation for advanced hypopharyngeal cancer.

OBJECTIVE: Laryngeal preservation is a challenge for the treatment of advanced hypopharyngeal cancer. The objective of this study is to evaluate the results of chemoradiotherapy laryngeal preservation for advanced hypopharyngeal cancer at a single institute and the impact of treatment factors on prognosis. METHODS: The study population consisted of 42 consecutive patients with resectable stage III-IV hypopharyngeal cancer. Patients with T4b tumor, synchronous primary cancer or those treated palliatively were excluded. Induction chemotherapy followed by concurrent chemoradiotherapy (CCRT) was performed in 32 (76.2%) patients, whereas primary CCRT was done in the other 10 (23.8%). Patients were grouped according to the dose intensity of chemotherapy and total dose of radiotherapy (RT). RESULTS: Grade 3-4 toxicities occurred mostly during CCRT. Thirty-five (83.3%) patients received an optimum dose of cisplatin (CT-optimum), 27 (64.3%) received an optimum dose of RT-optimum and 26 (61.9%) received optimum doses of both (CRT-optimum). CT- and RT-optimum both correlated significantly with better disease-free survival (DFS) (P < 0.001 and = 0.003), overall survival (OS) (P < 0.001 and = 0.004) and laryngeal preservation survival (LPS) (P = 0.01 and 0.04). The 3-year DFS, OS and LPS for CRT-optimum patients were 48.1, 50.0 and 45.6%, respectively. CONCLUSIONS: Achievement of optimum treatment dose remains challenging in chemoradiotherapy laryngeal preservation for advanced hypopharyngeal cancer. Intensive patient care and monitoring by experienced multi-disciplinary teamwork are mandatory. The criteria for selecting patients who will respond to and complete the treatment remain key issues for future investigation.

Clinical and pathologic predictors of survival in patients with squamous cell carcinoma of the hypopharynx after surgical treatment.

OBJECTIVES: Hypopharyngeal squamous cell carcinoma (HPSCC) usually presents at an advanced stage. Although chemoradiotherapy has become more popular in treating HPSCC in recent years, surgery with postoperative adjuvant therapy still plays an important role. The purpose of this study was to identify the clinicopathologic factors that predict survival in patients with HPSCC who underwent surgical treatment. METHODS: Between 1986 and 1995, 94 previously untreated HPSCC patients who underwent surgery with or without postoperative radiotherapy were enrolled. The surgical specimens were reexamined by a single pathologist. The clinicopathologic parameters and prognostic data were analyzed. RESULTS: With a median follow-up of 50 months, the 5-year overall survival (OS), disease-specific survival (DSS), and relapse-free survival (RFS) were 47%, 60%, and 58%, respectively. Thirty-seven patients (39%) had tumor recurrence. The level of lymph node metastasis was an independent factor in OS, DSS, and RFS. Neck biopsy before surgery, tumor involvement of more than 1 subsite, and extracapsular spread were independent factors in DSS, as was lymphovascular permeation in RFS. CONCLUSIONS: The level of cervical lymph node metastasis is the only independent prognostic factor in OS, DSS, and RFS. The addition of postoperative chemoradiotherapy may benefit high-risk cases.