The Pretreatment Neutrophil-to-Lymphocyte Ratio is a Prognostic Determinant of T3-4 Hypopharyngeal Squamous Cell Carcinoma.

OBJECTIVE: This study aimed to investigate the clinicopathological factors that influence recurrence and survival in patients who undergo operations for T3-4 hypopharyngeal squamous cell carcinomas (SCCs). MATERIALS AND METHODS: One hundred and five patients who underwent surgery between 2001 and 2008 for advanced hypopharyngeal SCCs were consecutively enrolled and reviewed. RESULTS: The pretreatment neutrophil-to-lymphocyte ratio (NLR; median 3.22, range 0.62-46.50) was associated with disease recurrence and patient survival. A difference in the 5-year cumulative disease recurrence rate between patients with high (≥3.22) and low (<3.22) NLRs was significant (60.4 and 36.5%, respectively; p = 0.004). A multivariate analysis confirmed that an NLR ≥3.22 was an independent indicator of a poor prognosis for advanced hypopharyngeal SCC, as per the following parameters: overall survival (hazard ratio [HR] 2.53, 95% confidence interval [CI] 1.48-4.30, p = 0.001), disease-specific survival (HR 2.45, 95% CI 1.38-4.34, p = 0.002), and disease-free survival (HR 2.18, 95% CI 1.24-3.83, p = 0.007). Additional prognostic factors per the survival analyses included lymph node density, surgical margin, lymphovascular invasion, and perineural invasion. CONCLUSIONS: An NLR ≥3.22 is associated with a higher risk of disease recurrence and poor survival in patients with T3-4 hypopharyngeal SCCs. We propose the use of the NLR to broaden the current TNM staging system; the development of a more effective treatment protocol for patients with high NLRs will be essential.

Lymph Node Ratio Predicts Recurrence and Survival for Patients with Resectable Stage 4 Hypopharyngeal Cancer.

BACKGROUND: This study aimed to investigate the clinicopathologic prognostic predictors of stage 4 hypopharyngeal cancer and to extend the traditional tumor-node-metastasis classification system to advance its predictive ability. METHODS: The study enrolled 120 patients with pathologically stage 4 hypopharyngeal cancer treated with pharyngolaryngectomy and neck dissection between 2001 and 2007. RESULTS: The study showed a 5-year overall survival (OS) of 44.6%, a disease-specific survival (DSS) of 51.6%, and a disease-free survival (DFS) of 48% for all the patients. In the multivariate analysis, a lymph node (LN) ratio of 0.113 or higher was a significant poor prognostic factor for OS (hazard ratio [HR] 1.89; 95% confidence interval [CI] 1.17-3.05; p = 0.009), DSS (HR 2.17; 95% CI 1.29-3.64; p = 0.003), and DFS (HR, 2.24; 95% CI 1.12-4.52; p = 0.024) in stage 4 hypopharyngeal cancer. In addition, pretreatment neutrophil-lymphocyte ratio, lymphovascular invasion, and margin status also were predictors of survival outcomes. Furthermore, the study found that disease recurrence differed significantly between the patients with a LN ratio of 0.113 or higher (68.2%) and those with a LN ratio lower than 0.113 (39.5%) (p = 0.002). CONCLUSIONS: A LN ratio of 0.113 or higher is a strong predictor of disease recurrence and survival for patients with stage 4 hypopharyngeal cancer.

Evaluation of swallowing disorders by use of transnasal esophagoscopy in patients treated for head and neck cancer.

BACKGROUND: The purposes of this study were to identify an index of symptoms and signs of swallowing disorders that indicate the occurrence of local recurrence or second primary malignancy and to evaluate the application of transnasal esophagoscopy in patients treated for head and neck squamous cell carcinoma (HNSCC). METHODS: Patients treated for HNSCC with swallowing disorders who received transnasal esophagoscopy examinations between January 2010 and June 2014 were included in this study. Local recurrence and second primary malignancy were pathologically diagnosed. RESULTS: In total, 136 patients were examined and one-third of them had local recurrence or second primary malignancy. Thirty-two patients had local recurrence and 14 patients had second primary malignancy. Common swallowing disorders and objective transnasal esophagoscopy findings were similar between the patients with and without local recurrence or second primary malignancy. CONCLUSION: No definite index of symptoms and signs was an indicator of local recurrence or second primary malignancy in the patients treated for HNSCC. Routine transnasal esophagoscopy examination of patients treated for HNSCC with swallowing disorders is strongly recommended. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1137-E1143, 2016.

The impact of perineural invasion and/or lymphovascular invasion on the survival of early-stage oral squamous cell carcinoma patients.

BACKGROUND: For early-stage oral squamous cell carcinoma (OSCC) patients, the impact of perineural invasion (PNI) and lymphovascular invasion (LVI) on disease control and survival has not been clarified. METHODS: The medical records of all early-stage OSCC patients who underwent curative surgery between 2004 and 2009 were reviewed. RESULTS: A total of 442 early stage patients were included in this study. There were 360 patients in group A (without PNI or LVI) and 82 patients in group B (with PNI and/or LVI). Between groups A and B patients, there were no significant differences in the 5-year disease-free survival (73.8 vs 68.7 %, p = 0.48) and overall survival (90.9 vs 86.1 %, p = 0.25). Between groups A and B patients without postoperative radiotherapy (PORT), there were no significant differences in the 5-year disease-free survival (73.8 vs 70.2 %, p = 0.51) and overall survival (90.9 vs 85.2 %, p = 0.18). Between group B patients with and without PORT, there was no significant difference in either the disease-free survival (61.1 vs 70.2 %, p = 0.98) and overall survival (88.9 vs 85.2 %, p = 0.64). Multivariate analyses revealed that PNI, LVI, and PORT could not provide significant effect on treatment outcome. CONCLUSIONS: PNI and LVI were not significant risk factors for the disease control and overall survival for early stage OSCC patients. Furthermore, PORT could not provide an additional benefit for the disease control and overall survival for stages I and II OSCC patients with PNI and/or LVI.

The clinical predictive factors for subsequent distant metastasis in patients with locoregionally advanced oral squamous cell carcinoma.

OBJECTIVES: Only a small portion of the patients with locoregionally advanced oral squamous cell carcinoma (OSCC) experience subsequent distant metastasis. This study is to evaluate the occurrence of distant metastasis after curative treatment and to explore the predictive factors for subsequent distant metastasis in patients with locoregionally advanced OSCC. MATERIALS AND METHODS: The medical records of all patients with locoregionally advanced OSCC without distant metastasis at the time of diagnosis (AJCC stage III, IV but not IVC) who underwent curative surgery with or without adjuvant radiation between 2004 and 2009 were retrospectively reviewed. RESULTS: A total of 628 patients were enrolled, including 562 male and 66 female patients. The 5-year distant metastasis rate was 13.2%. The 5-year disease-free and overall survival rates were 57.0% and 60.3%, respectively. Multivariate analyses revealed that poorly differentiated tumors (HR=2.3 (1.16-4.53), p=0.02) and contralateral neck metastasis (HR=7.55 (3.20-17.83), p<0.001) were independent adverse factors for distant metastasis-free survival. The 5-year distant metastasis rates of 447 patients with well-differentiated tumors, 140 patients with moderately differentiated tumors and 41 patients with poorly differentiated tumors were 12.1%, 18.2%, and 34.1%, respectively. The 5-year distant metastasis rates of 227 patients without neck metastasis, 350 patients with ipsilateral neck metastasis and 51 patients with contralateral neck metastasis were 6.7%, 15.1%, and 55.3%, respectively. CONCLUSIONS: Poorly differentiated tumors and contralateral neck metastasis were independent factors for subsequent distant metastasis in patients with locoregionally advanced OSCC.

Clinicopathological features of salivary and non-salivary adenoid cystic carcinomas.

Adenoid cystic carcinoma (ACC), commonly from salivary glands, is known for its insidious local growth and usually protracted clinical course. ACC developing from non-salivary glands (i.e., non-salivary ACC) is heterogeneous, and its clinicopathological features remain poorly defined. Patients treated for ACC in a single institution between 1995 and 2007 were included in this study. Immunohistochemical evaluation of Ki-67, E-cadherin, p16, and cyclinD1 was performed. The prognostic significance of clinical and immunophenotypic markers was evaluated. 83 cases of salivary ACC and 24 cases of non-salivary ACC were included. The expression levels of Ki-67 (54.8%), E-cadherin (90.4%), p16 (32.9%), and cyclinD1 (19.2%) between ACCs present at various sites were not different. Sinonasal, lacrimal, and tracheobronchial ACCs had significantly worse outcomes than those of ACC of the major salivary glands. Postoperative radiotherapy reduced the recurrence rate of patients with a negative resection margin (P=0.028). Older age (age >60 years), advanced stage, positive resection margin, high histological grade, and high expression of Ki-67 were significantly correlated with poor prognosis. In conclusion, the site of origin plays a role in the prognosis of ACC, in which positive resection margin and advanced stage are possible factors underlying the differences in outcomes.

The determining risk factors for treatment outcomes in patients with squamous cell carcinoma of the hard palate.

BACKGROUND: The determining risk factors for patients with squamous cell carcinoma of the hard palate are not well verified. METHODS: Medical records from our facility of all patients with squamous cell carcinoma of the hard palate receiving curative surgery between March 2003 and May 2009 were reviewed. RESULTS: Seventy-eight patients were enrolled in the study. The 5 year disease-free and overall survival rates were 49.8 and 49.7%, respectively. The 5 year disease-free and overall survival rates were statistically different between positive/close margins and negative margins (24.6% vs. 65.4%, P = 0.02; 20.1% vs. 63.1%, P = 0.001, respectively), with and without soft palate invasion (38.8% vs. 68.9%, P = 0.02; 27.4% vs. 77.5%, P = 0.001, respectively), and soft palate invasion patients with and without perineural invasion (10.4% vs. 52.8%, P = 0.02; 0% vs. 38.1%, P = 0.008, respectively). The rate of positive nodal metastasis for T3 and T4 tumors was 44%. For the tumor with soft palate invasion, the rate of positive nodal metastasis was 29%. After multivariate analyses, soft palate invasion and positive/close margins were the determining risk factors for disease-free and overall survival. CONCLUSIONS: Soft palate invasion and positive/close margins were the determining risk factors for disease-free and overall survival in patients with squamous cell carcinoma of the hard palate. Elective neck dissection is suggested for advanced primary tumors (T3 or T4) or tumors with soft palate invasion.

Salvage treatment for isolated regional failure of nasopharyngeal carcinoma after primary radiotherapy.

BACKGROUND: Isolated regional failure of nasopharyngeal carcinoma (NPC) after primary treatment is traditionally treated with radical neck dissection (RND). The roles of modified radical neck dissection (MRND) and postoperative radiotherapy after salvage surgery currently remain unclear. METHODS: Medical records from our facility of all NPC patients with isolated regional failure after complete primary radiotherapy and receipt of radical surgery as a part of salvage treatment between January 1985 and December 2004 were retrospectively reviewed. RESULTS: Forty-five patients were enrolled onto the study. On univariate analyses, the 5-year regional-free, disease-free, and overall survival rates were 67.7%, 47.8%, and 65.7% for patients who underwent salvage surgery alone and were 66.0%, 34.7%, and 61.3% for patients who received salvage surgery plus postoperative radiotherapy (P = 0.74, P = 0.39 and P = 0.7, respectively). The 5-year regional-free, disease-free, and overall survival rates were 87.4%, 53.5%, and 87.1% for patients undergoing RND and were 54.3%, 34.2%, and 50.5% for patients undergoing MRND (P = 0.01, P = 0.02 and P = 0.05, respectively). On multivariate analyses, recurrent N3 disease was the only adverse prognostic factor for disease-free and overall survival (P = 0.05 and P = 0.03, respectively). CONCLUSIONS: RND or MRND alone may be the superior treatment for NPC patients with isolated regional failure after primary radiotherapy. Compared to MRND, radical neck dissection could provide better regional control. Postoperative radiotherapy seems to have no benefit on disease-free or overall survival. Distant metastasis is the major cause of death in these patients.

Prognostic factors of unknown primary head and neck squamous cell carcinoma.

OBJECTIVE: To evaluate the prognostic factors of unknown primary head and neck squamous cell carcinoma (HNSCC). STUDY DESIGN: Retrospective study. SUBJECTS: Patients with unknown primary HNSCC from 1980 to 2000 were included. RESULTS: Forty-eight patients, predominantly male and with a mean age of 63.3+/-11.6 years, were recruited. The median survival time (MST) was 44 months. The overall survival rate was 60.4 percent at three years and 39.6 percent at five years. Forty-two patients receiving intervention regimens had a MST of 45 months, while six patients receiving palliative therapy had a MST of 8.5 months (log rank test, P=0.016). With multivariate Cox regression analysis, age (per year), higher nodal stage (N3 vs N1 or N2), and treatment (operation vs nonoperation) had a hazard ratio of 1.081 (P<0.0001), 5.852 (P=0.010), and 0.4 (P=0.042), respectively. CONCLUSION: Older age, higher nodal stage, and palliative treatment indicated poor prognosis. Survival time might be prolonged if surgical treatment is tolerable.

Malignant parotid tumor and facial palsy.

OBJECTIVE: To evaluate risk factors for postoperative facial palsy in patients with parotid carcinoma. STUDY DESIGN AND SETTING: We conducted a retrospective chart review of patients with parotid carcinoma who underwent parotidectomy at National Taiwan University Hospital from 1980 to 2000. RESULTS: Eighty-eight patients with a mean age of 53 +/- 17 y were recruited. Sixty patients (68.2%) experienced postoperative facial palsy. Tumor size of larger than 4 cm was associated with an increased incidence of facial palsy (P = 0.0422). Facial palsy was noted in 95.5 percent of patients with facial nerve involvement and 51.3 percent of patients without facial nerve involvement (P = 0.0004). Of 42 patients with tumor over the deep lobe, 37 (88.1%) had facial palsy but only 50 percent (23 of 46) of those with tumor over the superficial lobe had facial palsy (P = 0.0001). CONCLUSION: There were no significant associations between histopathology and facial palsy. Increasing tumor size, deep lobe tumor location, and tumor invasion of facial nerve increased the incidence of postparotidectomy facial palsy. SIGNIFICANCE: By paying attention to these risk factors a reduction of postoperative facial nerve palsy my be achieved.

Specific induction of the high-molecular-weight microtubule-associated protein 2 (hmw-MAP2) by betel quid extract in cultured oral keratinocytes: clinical implications in betel quid-associated oral squamous cell carcinoma (OSCC).

Betel quid (BQ) chewing, a popular habit in numerous Asian countries including India and Taiwan, has a strong correlation with an increased risk of oral squamous cell carcinoma (OSCC). While substantial efforts have been made to test the cytotoxic, genotoxic and mutagenic effects of BQ extract and its components, the disease mechanisms underlying BQ-induced oral carcinogenesis remain obscure. Here, we show that a neuronal protein, microtubule-associated protein 2 (MAP2), was induced by BQ extract in cultured normal human oral keratinocytes (NHOKs). Subsequent analyses demonstrated that such induction was more eminent and consistent in the high-molecular-weight isoform of MAP2 (hmw-MAP2) than that in its low-molecular-weight counterpart (lmw-MAP2). Furthermore, we analyzed expression of hmw-MAP2 protein in 88 oral specimens consisting of clinicopathologically pre-malignant (leukoplakia) and malignant (OSCC) lesions, along with their adjacent normal mucosa. Immunohistochemistry revealed that, with the exposure to BQ, the hmw-MAP2 was over-expressed in 41.2% (7/17) of OSCC, 11.2% (1/9) of leukoplakia and none (0/19) of normal mucosa. In contrast, expression of the hmw-MAP2 was barely detected in BQ-free OSCC. These results suggest a significant correlation between expression of the hmw-MAP2 and BQ-associated progression of oral carcinogenesis (P=0.0046). Interestingly, the hmw-MAP2 was found to preferentially express in histopathologically less differentiated OSCC (P=0.014); the percentages of positive staining in poorly, moderately and well differentiated OSCC were 62.5, 21.4 and 7.1%, respectively. However, BQ chewing appeared to have marginal correlation with such propensity. Finally, we show that the majority of hmw-MAP2-positive poorly differentiated lesions were also histopathologically invasive. Taken together, these findings suggest the possibility that the hmw-MAP2 may be a diagnostic marker for BQ-chewing lesions and a potential therapeutic target. To our knowledge, this study has provided the first clinical implication that closely links a cytoskeletal protein to BQ-associated oral cancer.