Small access postaural parotidectomy: an analysis of techniques, feasibility and safety.

For cosmetic consideration of parotidectomy, the surgical approaches have evolved from Blair incision through modified facelift incision to postaural-hairline incision. The present study aims at evaluating the feasibility and safety of the new technique of postaural approach. Parotidectomy was performed with a 4-5 cm incision in the postaural sulcus. There were 69 patients who were assessed pre-operatively feasible for consideration of the postaural parotidectomy. There were 56 (81 %) patients who could have the postaural parotidectomy successfully without complications. The minimally invasive postaural approach is a further step in cosmetic consideration of parotidectomy. It is a feasible and safe approach for most small to medium size benign parotid tumors located in the mid and lower pole regions of the parotid gland.

Efficient immortalization of primary nasopharyngeal epithelial cells for EBV infection study.

Nasopharyngeal carcinoma (NPC) is common among southern Chinese including the ethnic Cantonese population living in Hong Kong. Epstein-Barr virus (EBV) infection is detected in all undifferentiated type of NPC in this endemic region. Establishment of stable and latent EBV infection in premalignant nasopharyngeal epithelial cells is an early event in NPC development and may contribute to its pathogenesis. Immortalized primary nasopharyngeal epithelial cells represent an important tool for investigation of EBV infection and its tumorigenic potential in this special type of epithelial cells. However, the limited availability and small sizes of nasopharyngeal biopsies have seriously restricted the establishment of primary nasopharyngeal epithelial cells for immortalization. A reliable and effective method to immortalize primary nasopharyngeal epithelial cells will provide unrestricted materials for EBV infection studies. An earlier study has reported that Bmi-1 expression could immortalize primary nasopharyngeal epithelial cells. However, its efficiency and actions in immortalization have not been fully characterized. Our studies showed that Bmi-1 expression alone has limited ability to immortalize primary nasopharyngeal epithelial cells and additional events are often required for its immortalization action. We have identified some of the key events associated with the immortalization of primary nasopharyngeal epithelial cells. Efficient immortalization of nasopharyngeal epithelial cells could be reproducibly and efficiently achieved by the combined actions of Bmi-1 expression, activation of telomerase and silencing of p16 gene. Activation of MAPK signaling and gene expression downstream of Bmi-1 were detected in the immortalized nasopharyngeal epithelial cells and may play a role in immortalization. Furthermore, these newly immortalized nasopharyngeal epithelial cells are susceptible to EBV infection and supported a type II latent EBV infection program characteristic of EBV-infected nasopharyngeal carcinoma. The establishment of an efficient method to immortalize primary nasopharyngeal epithelial cells will facilitate the investigation into the role of EBV infection in pathogenesis of nasopharyngeal carcinoma.

Ultrasonographic screening for occult thyroid cancer.

BACKGROUND: It has been shown that occult thyroid carcinoma can be identified in about 10% of thyroid glands in autopsy. The purpose of this study was to evaluate the prevalence of asymptomatic thyroid carcinoma in the Hong Kong Chinese population by ultrasonographic screening. METHODS: Volunteer subjects without symptoms of thyroid disease were recruited for ultrasonographic screening for thyroid cancer. A total of 1140 subjects were recruited in this study. RESULTS: Thyroid nodules were found in 45% subjects (511 of 1140); the mean age was 48 years. Ultrasonographic-guided aspiration cytology was performed in 258 subjects. Twenty-six subjects (2.3%) had cytologic findings suspicious of malignancy. Fourteen subjects (1.2%) had pathologic diagnosis of thyroid cancer, including 13 papillary carcinomas and 1 follicular carcinoma. CONCLUSION: A high incidence of occult thyroid cancer could be identified on ultrasonographic screening. Subjects could benefit with early diagnosis with either early intervention or close monitoring.

Early resection and reconstruction of head and neck masses in infants with upper airway obstruction.

OBJECTIVE: Congenital airway obstruction can be caused by tumors or lesions arising from the neck, tongue and oral cavity. Neonates may require prolonged intubation or tracheostomy before curative resection and reconstruction. The aim of the study was to carry out surgical resection and reconstruction with locoregional flap and free bone graft in the neonatal and early infantile period for definitive management of head and neck masses and treatment of potential airway obstruction. METHODS: Newborns with obstructive head and neck masses in Queen Mary Hospital, University of Hong Kong Medical Centre between 2006 and 2009 were operated on in the neonatal period. RESULTS: There were one obstructive neck teratoma, two intraoral teratomas and one neuroglial heterotopia. All tumors were resected within the first 3 months of life without major complication. A local cervical cutaneous flap was first used to reconstruct the lateral pharyngeal wall defect in a neonate with a huge neck teratoma, followed by another infant with a neuroglial heterotopia. A piece of cranial bone was used for reconstruction of the skull base defect. None of them required tracheostomy or prolonged intubation. Oral feeding was resumed in the early postoperative period. CONCLUSION: Surgical resection and reconstruction with locoregional flap and bone graft can be performed safely in neonatal and early infantile period as management of head and neck masses and treatment of upper airway obstruction.

Prospective randomized study of selective neck dissection versus observation for N0 neck of early tongue carcinoma.

BACKGROUND: There are controversies on the benefits of elective neck dissection (END) for oral tongue carcinoma. METHOD: This is a prospective randomized study of elective selective I, II, III neck dissection versus observation for N0 neck of stage I to II oral tongue carcinoma. There were 35 patients on the observation arm and 36 patients on the END arm. The main outcome assessment parameters are node-related mortality and disease-specific survival rate. RESULTS: There were 11 patients in the observed arm and 2 patients in the END arm who developed nodal recurrence alone without associated local or distant recurrence. All 13 patients were salvaged, and no patient died of nodal recurrence. The 5-year disease-specific survival rate was 87% for the observation arm and was 89% for the END arm; the 2% difference was not significant. CONCLUSION: Observation may be an acceptable alternative to END if strict adherence to a cancer surveillance protocol is followed.

Lateral thoracic flap for donor site repair of pectoralis major myocutaneous flap.

OBJECTIVE: To study the use of the lateral thoracic flap to repair a pectoralis major flap donor site defect when primary closure is not possible. STUDY DESIGN: Prospective study. SUBJECTS AND METHODS: All patients requiring pectoralis major flap reconstruction after tumour extirpation in the head and neck region, whose chest wall donor defects could not be closed primarily, were recruited to the study; lateral thoracic flaps were performed to close the wounds. RESULTS: Ten patients were recruited between July 2005 and November 2007. The patients were between 48 and 76 years of age. The lateral thoracic flap size ranged from 5 x 8 cm to 9 x 12 cm. All secondary donor sites in the lateral chest wall were closed primarily. There was no flap necrosis and the secondary donor sites healed without complications. CONCLUSION: The lateral thoracic flap is safe and reliable technique for reconstructing the chest wall donor defect from the pectoralis major flap when primary closure is not possible.

Mature miR-184 as Potential Oncogenic microRNA of Squamous Cell Carcinoma of Tongue.

PURPOSE: The aim of this study was to evaluate the microRNA expression patterns in squamous cell carcinoma (SCC) of the tongue. EXPERIMENTAL DESIGN: Expression levels of 156 human mature microRNAs were examined using real-time quantitative PCR (Taq Man MicroRNA Assays; Human Panel) on laser microdissected cells of 4 tongue carcinomas and paired normal tissues. Expression of mature miR-184 was further validated in 20 paired tongue SCC and the normal tissues. Potential oncogenic functions of miR-184 were evaluated in tongue SCC cell lines (Cal27, HN21B, and HN96) with miR-184 inhibitor. Plasma miR-184 levels were evaluated using real-time quantitative PCR. RESULTS: Using 3-fold expression difference as a cutoff level, we identified 24 up-regulated mature miRNAs including miR-184, miR-34c, miR-137, miR-372, miR-124a, miR-21, miR-124b, miR-31, miR-128a, miR-34b, miR-154, miR-197, miR-132, miR-147, miR-325, miR-181c, miR-198, miR-155, miR-30a-3p, miR-338, miR-17-5p, miR-104, miR-134, and miR-213; and 13 down-regulated mature miRNAs including miR-133a, miR-99a, miR-194, miR-133b, miR-219, miR-100, miR-125b, miR-26b, miR-138, miR-149, miR-195, miR-107, and miR-139. Overexpression of miR-184 was further validated in 20 paired tongue SCC and normal tissues (P = 0.002). Inhibition of miR-184 in tongue SCC cell lines could reduce cell proliferation rate. Down-regulation of c-Myc was observed in two cell lines in response to miR-184 inhibitor. Suppressing miR-184 could induce apoptosis in all three cell lines. Plasma miR-184 levels were significantly higher in tongue SCC patients in comparison with normal individuals, and the levels were significantly reduced after surgical removal of the primary tumors. CONCLUSIONS: Overexpression of miR-184 might play an oncogenic role in the antiapoptotic and proliferative processes of tongue SCC. In addition, plasma miR-184 levels were associated with the presence of primary tumor. Further studies on the aberrantly expressed miRNAs in tongue SCC as well as using plasma miRNAs as novel tumor markers are warranted.

Thyroid dysfunction in laryngectomees-10 years after treatment.

BACKGROUND: Hypothyroidism is 1 of the complications that follow treatment of various head and neck cancers. In the literature, reviews using different primary sites and differences in treatment modalities make comparison of post-treatment hypothyroidism not possible. The objective of this study was to evaluate the incidence of hypothyroidism in a homogenous group of patients who were treated with total laryngectomy and irradiation for laryngeal carcinoma and to assess the importance of different variables in the occurrence of hypothyroidism. METHODS: A retrospective review of 147 total laryngectomy patients between 1993 and 2003 was carried out. Serum thyroxine level and free T4 levels were assessed in all patients. Hypothyroidism was classified as subclinical (increased thyroid-stimulating hormone and normal free T4 levels) and clinical (increased thyroid-stimulating hormone and decreased free T4 levels). RESULTS: The results showed that the overall incidence of hypothyroidism was 49% (44% subclinical and 5% clinical). Hemithyroidectomy and advanced tumor staging were risk factors for the development of hypothyroidism in these patients (p < .05) with a relative risk of 2.1 (CI 95%, 1.4-3.1) and 1.3 (CI 95%, 1.1-1.6), respectively. During follow-up, 19.9% of patients developed hypothyroidism at 3 years, 38.6% at 6 years; at 10 year follow-up, 93.3% of them had hypothyroidism. CONCLUSIONS: In conclusion, hypothyroidism is a frequent complication in patients treated with radiotherapy and total laryngectomy for laryngeal cancer, especially when treatment includes hemithyroidectomy. These patients should have their thyroid function evaluated periodically even 10 years after treatment.

Preoperative measurement of tumor thickness of oral tongue carcinoma with intraoral ultrasonography.

BACKGROUND: Tumor thickness of oral tongue carcinoma is an important independent prognostic factor for local recurrence, subclinical nodal metastasis, and survival. An accurate preoperative assessment of tumor thickness is therefore essential in optimizing treatment algorithm. The present study aims at evaluating the accuracy of intraoral ultrasonography in preoperative measurement of tumor thickness. METHODS: Forty-five patients with oral tongue carcinoma had intraoral ultrasonography to document tumor thickness using a 7.5 MHz right angle probe. The ultrasonic tumor thickness was correlated with the fresh unpreserved surgical specimen pathologic tumor thickness. RESULTS: Ultrasonic tumor thickness had significant correlation with pathologic tumor thickness. The accuracies of ultrasonic measurement of tumor thickness in staging of tumor thickness at cutoff values between 3 and 15 mm were above 91%. CONCLUSION: Intraoral ultrasonography had satisfactory accuracy in the measurement of tumor thickness and is a useful adjunct in assisting pretreatment staging and prognosis evaluation of oral tongue carcinoma.

Surgical techniques and results of lateral thoracic cutaneous, myocutaneous, and conjoint flaps for head and neck reconstruction.

BACKGROUND: This paper aims at presentation of our surgical techniques and results of the lateral thoracic (LT) flaps for head and neck reconstructions. METHOD: There were seven LT cutaneous, seven LT myocutaneous, and two LT conjoint myocutaneous flaps for reconstruction of head and neck mucosal or cutaneous defects. RESULTS: The largest flap size was 22 cm x 13 cm. All donor sites were closed primarily. The highest point of reconstruction was in the nasopharynx internally and zygoma externally. All flaps survived without major complication. CONCLUSIONS: The LT flap has the versatility of cutaneous, myocutaneous, and conjoint flaps with pectoralis major or latissimus dorsi myocutaneous flaps to reconstruct large surgical defects. It has a large, reliable surface area, a long pedicle to reach nasopharynx and zygoma, and has less bulky muscle to facilitate tubular reconstruction of circumferential pharyngeal defect, one-stage operation, esthetic hidden donor site scar in axillary region, and minimal donor site morbidity. It is an additional reliable pedicle flap in our armamentarium for reconstruction of both cutaneous and mucosal defects in the head and neck region.

Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry serum protein profiling to identify nasopharyngeal carcinoma.

BACKGROUND: Diagnosis of nasopharyngeal carcinoma (NPC) at an early disease stage is important for successful treatment and improving the outcome of patients. The use of serum protein profiles and a classification tree algorithm were explored to distinguish NPC from noncancer. METHODS: Serum samples were applied to metal affinity protein chips to generate mass spectra by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS). Protein peak identification and clustering were performed using the Biomarker Wizard software. Proteomic spectra of serum samples from 50 NPC patients and 54 noncancer controls were used as a training set and a classification tree with 6 distinct protein masses was generated by using Biomarker Pattern software. The validity of the classification tree was then challenged with a blind test set including another 20 NPC patients and 25 noncancer controls. RESULTS: The software identified an average of 93 mass peaks/spectrum and 6 of the identified peaks were used to construct the classification tree. The classification tree correctly determined 83% (123 of 149) of the test samples with 83% (58 of 70) of the NPC samples and 82% (65 of 79) of the noncancer samples. In a combination of the serum protein profiles with Epstein-Barr (EBV) nuclear antigen 1 (EBNA1 IgA) test, the diagnostic sensitivity and specificity were increased to 99% and 96%, respectively. CONCLUSIONS: The results suggest that SELDI-TOF-MS serum protein profiles could discriminate NPC from noncancer. The combination of serum protein profiles with an EBV antibody serology test could further improve the accuracy of NPC screening.

Long-term performance of indwelling tracheoesophageal speaking valves in Chinese patients undergoing laryngectomy.

OBJECTIVES: To assess the use of indwelling tracheoesophageal speaking valves in Chinese patients undergoing laryngectomy, to identify the clinicopathologic factors for favorable outcome, and to evaluate the factors that determine prosthesis lifetime. DESIGN: Retrospective review. SETTING: Tertiary care institution. PATIENTS: Sixty consecutive patients with total laryngectomy were included. All had indwelling tracheoesophageal speaking valves for voice restoration. INTERVENTION: Anterograde replacement of voice prosthesis in case of failure of functional speech production or leakage of saliva. MAIN OUTCOME MEASURES: Incidence of successful tracheoesophageal speech rehabilitation for daily communication, influence of different clinicopathologic factors on the outcome, and prosthesis lifetime and its relationship to different clinicopathologic factors. RESULTS: The success rate of speech rehabilitation was 78%. Age younger than 60 years was the only clinicopathologic factor associated with successful speech rehabilitation (P = .04, Fisher exact test). The median device lifetime was 8.2 months. Both age of 60 years or older and the use of subsequent prosthetic valves were identified as risk factors for valve failure on univariate analysis (n = 192; log-rank test; P = .02 and P = .03, respectively), with age of 60 years or older as the only risk factor that reduced the device lifetime in the Cox proportional hazards model (P = .03; relative hazard ratio, 1.5; 95% confidence interval, 1.1-2.4). CONCLUSIONS: Our success rate in using indwelling tracheoesophageal speaking valves was comparable to that reported in the Western literature. The median device lifetime of 8.2 months was satisfactory. Patient age was found to be a significant predictor of successful tracheoesophageal speech rehabilitation, with age of 60 years or more adversely affecting device lifetime.

Ultrasonic glossectomy--simple and bloodless.

BACKGROUND: The aim of the study was the evaluation of the feasibility of glossectomy using an ultrasonic-activated surgical instrument. METHODS: This was a prospective study of 13 consecutive patients who underwent glossectomy (12 partial and one total) for carcinoma of tongue with the use of ultrasonic scissors. RESULTS: All 13 patients had glossectomy, with median blood loss of 0 mL. The glossectomies were done with an ultrasonic dissector alone. None of the glossectomies required diathermy, ligature, plication, or other methods for hemostasis. The lingual artery and veins of all 13 patients were controlled by use of the ultrasonic scissors alone. No operative complications occurred, including bleeding or wound healing problems. CONCLUSIONS: The excellent combination of coagulation and the cutting effect of ultrasonic scissors has made glossectomy a simple and bloodless procedure. It is a recommended surgical technique in our surgical armamentarium.

Endoscopic-assisted cranionasal resection of olfactory neuroblastoma.

BACKGROUND: Cranionasal resection was first described in 1997 for the surgical resection of olfactory neuroblastoma. The endoscopic transnasal approach is used in cranionasal resection to replace the more invasive craniofacial resection. It has the advantages of avoiding the facial wound and its associated pain, swelling, and scar. The authors have routinely practiced cranionasal resection since 1996 for resection of all anterior skull base tumors in which the resultant skull base bony defect is limited to the nasal and sinus roof. The aim of this study was to review the results of cranionasal resection for olfactory neuroblastoma. METHODS: The results of cranionasal resection for olfactory neuroblastoma in six patients from 1996 to 2003 were reviewed. RESULTS: The Kadesh stages were 3A, 2B, and 1C. None of the patients had postoperative complications. Postoperative radiotherapy was given only to the patient with Kadesh stage C disease. There were no local recurrences. Two patients died of lung metastasis. CONCLUSIONS: Cranionasal resection is a safe and adequate procedure. Postoperative radiotherapy is not necessary after clear resection of Kadesh A and B tumors.

Proteomics of buccal squamous cell carcinoma: the involvement of multiple pathways in tumorigenesis.

Squamous cell carcinoma (SCC) of the buccal mucosa is an aggressive oral cancer. It mainly occurs in Central and Southeast Asia, and is closely related to the practice of tobacco smoking and betel squid chewing. The high recurrence and low survival rates of buccal SCC require our continued efforts to understand the pathogenesis of the disease for designing better therapeutic strategies. We used proteomic technology to analyze buccal SCC tissues aiming at identifying tumor-associated proteins for the utilization as biomarkers or molecular targets. With the exception of alpha B-crystallin being substantially reduced, a number of proteins were found to be significantly over-expressed in cancer tissues. These increased proteins included glycolytic enzymes, heat-shock proteins, tumor antigens, cytoskeleton proteins, enzymes involved in detoxification and anti-oxidation systems, and proteins involved in mitochondrial and intracellular signaling pathways. These extensive protein variations indicate that multiple cellular pathways were involved in the process of tumorigenesis, and suggest that multiple protein molecules should be simultaneously targeted as an effective strategy to counter the disease. At least, SCC antigen, G protein, glutathione S-transferase, manganese superoxide dismutase, annexins, voltage-dependent anion channel, cyclophilin A, stratifin and galectin 7 are candidates for targeted proteins. The present findings also demonstrated that rich protein information can be produced by means of proteomic analysis for a better understanding of the oncogenesis and pathogenesis in a global way, which in turn is a basis for the rational designs of diagnostic and therapeutic methods.

Smoking and drinking can induce p15 methylation in the upper aerodigestive tract of healthy individuals and patients with head and neck squamous cell carcinoma.

BACKGROUND: The consumption of tobacco and alcohol has been implicated in the development of head and neck squamous cell carcinoma (HNSCC). Promoter methylation of tumor suppressor genes is common in HNSCC. In this study, the authors evaluated the effects of tobacco and alcohol on p15 gene methylation of cells in cells from the mouth and throat of physically healthy individuals and patients with HNSCC. METHODS: The study participants were divided into 3 groups, including a group of 37 healthy nonsmokers and nondrinkers, a group of 22 healthy smokers and/or drinkers and a group of 31 patients with HNSCC. RESULTS: Methylation of p15 was detected in cells obtained from mouth and throat (M&T) rinsing fluid samples from 3 of 37 healthy individuals (8%) who did not drink or smoke, from 15 of 22 healthy smokers and/or drinkers (68%), and from 15 of 31 patients (48%) with HNSCC. Among 31 patients with HNSCC, 20 patients (65%) had methylated p15 gene in their tumor biopsies. With the use of beta-actin as a reference, the ratio of methylated p15 to beta-actin was calculated as an index of the percentage of cells with p15 methylation. The percentage of exfoliated cells from M&T rinsing fluid samples that had p15 methylation ranged from 0% to 11% for patients with HNSCC and from 0% to 21% for healthy smokers/drinkers, respectively. The methylation index of tumor cells with p15 methylation ranged from 0% to 65%. CONCLUSIONS: The results suggest that p15 gene methylation can be induced by chronic smoking and drinking and may play a role in the very early stages of carcinogenesis in HNSCC.

Quantitative plasma hypermethylated DNA markers of undifferentiated nasopharyngeal carcinoma.

PURPOSE: Gene-specific methylation is common in primary undifferentiated nasopharyngeal carcinoma (NPC). DNA released from apoptotic or necrotic cell death including those aberrantly methylated promoter DNA of cancer cells is absorbed into the circulation as cell-free plasma DNA of the patient. This study aims at evaluation of the potential use of methylated gene promoter DNA as a serological tumor marker of primary and potentially salvageable local or nodal recurrent NPC. EXPERIMENTAL DESIGN: The quantity of plasma hypermethylated gene promoters of CDH1, DAPK1, p15, p16, RASSF1A, and MLH1 of 41 NPC patients before treatment and 43 normal individuals were studied using real-time quantitative PCR. The post-treatment plasma hypermethylated CDH1, DAPK1,and p16 were also measured in 13 NPC patients with locoregional recurrence and 17 patients in remission. RESULTS: Concentrations of cell-free circulating DNA were significantly higher in NPC patients than normal controls (28.79 ng/ml versus 16.57 ng/ml, respectively). There was no significant difference in plasma DNA concentration of EBV-positive and -negative normal individuals. Methylated DNA was detectable in plasma of NPC patients before treatment including 46% for CDH1,42% for p16,20% for DAPK1,20% for p15,and 5% for RASSF1A. Hypermethylated MLH1 was not detected in plasma of all of the NPC patients and normal individuals. Aberrantly hypermethylated promoter DNA of at least one of the five genes was detectable in 29 of 41 (71%) plasma of NPC patients before treatment. Hypermethylated promoter DNA of at least one of the three genes (CDH1, DAPK1, and p16) was detectable in post-treatment plasma of 5 of 13 (38%) recurrent NPC patients and none of the patients in remission. CONCLUSIONS: Our results suggested that cell-free circulating methylated gene promoter DNA is a possibly useful serological marker in assisting in screening of primary and potentially salvageable local or regional recurrent NPC.

Correlating MRI and histologic tumor thickness in the assessment of oral tongue cancer.

OBJECTIVE: Tumor thickness in oral tongue cancer is an important independent prognostic factor for local recurrence, nodal metastasis, and patient survival. An accurate preoperative assessment of tumor thickness is therefore essential for optimal treatment planning. The aim of our study was to evaluate the accuracy of MRI findings for the preoperative measurement of tumor thickness. SUBJECTS AND METHODS. Eighteen patients with oral tongue cancer underwent preoperative MRI of the tongue. After surgery, the glossectomy specimens were serially sectioned. The radiologic tumor thickness of contrast-enhanced T1-weighted and T2-weighted images was compared with the histologic tumor thickness using our proposed tumor thickness staging classifications. These included stage I (tumor < or = 3 mm), stage II (> 3 mm but < or = 9 mm) and stage III (> 9 mm). RESULTS: The overall accuracy in assessment of proposed tumor thickness staging using contrast-enhanced T1-weighted and T2-weighted images was 83% and 56%, respectively. The radiologic tumor thickness as measured on contrast-enhanced T1-weighted and T2-weighted images had significant correlation with histologic tumor thickness (R = 0.938 and 0.941, respectively). CONCLUSION: MR images provide satisfactory accuracy for the measurement of tumor thickness and staging of oral tongue cancer. Preoperative MRI is recommended to assist in treatment planning for patients with this disease.