Use of Single Chimeric Free Flaps or Double Free Flaps for Complex Head and Neck Reconstruction.

BACKGROUND: Free flaps have become the preferred reconstructive approach to restore form and function for patients presenting with complex head and neck defects. For composite, complex defects for which a regular free flap might not meet all reconstructive demands, adequate coverage can be achieved with either a single chimeric free flap or a double free flap. METHODS: We performed a single-center retrospective chart review of patients who underwent either single chimeric free flap or double free flap reconstruction. Indications for reconstruction included defects resultant from head and neck tumor or osteoradionecrosis resections. We extracted the following variables: tumor location, defect, flap(s) performed, and postoperative complications. Unpaired t-tests were performed to evaluate for statistically significant differences in complications encountered between the single chimeric versus the double free flap patient groups. RESULTS: In our series of 44 patients, a total of 55 single chimeric and double free flaps were performed. We found no significant difference in overall complications (p = 0.41) or flap/skin paddle loss (p = 0.45) between the groups. There were three total flap losses; two patients underwent successful salvage procedures and one patient died. The anterolateral thigh (ALT) was the most common free flap (70%) used in our series, and 98% of our patients completed successful reconstruction. CONCLUSION: As the initial reconstructive effort is critical for achieving favorable long-term outcomes in complex head and neck cases, effective and safe techniques should be employed to ensure optimal delivery of care. We believe that single chimeric and double free flap techniques should be appropriately utilized as part of the armamentarium of head and neck reconstructive microsurgeons.

HMGA2, but not HMGA1, is overexpressed in human larynx carcinomas.

AIMS: Malignant tumours from the upper aerodigestive tract are grouped collectively in the class of head and neck squamous cell carcinoma (HNSCC). The head and neck tumours were responsible for more than 500 000 cancer cases in 2012, accounting for the sixth highest incidence rate and mortality worldwide among all tumour types. Laryngeal squamous cell carcinoma (LSCC) possesses the second highest incidence rate among all HNSCC. Despite significant advances in surgery and radiotherapy during the last few decades, no treatment has been shown to achieve a satisfactory therapeutic outcome and the mortality rate of LSCC is still high, with a 5-year survival rate of 64%. Therefore, further investigations are required to identify the pathogenesis of LSCC. METHODS AND RESULTS: In order to search for new LSCC biomarkers, we have analysed the expression of the HMGA family members, HMGA1 and HMGA2, by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and immunohistochemistry. HMGA proteins are usually absent in the healthy adult tissues. In contrast, their constitutive expression is a feature of several neoplasias, being associated with a highly malignant phenotype and reduced survival. Here, we report HMGA2 overexpression in larynx carcinomas. Conversely, HMGA1 does not show any differences in its expression between normal and carcinoma tissues. Interestingly, HMGA2 overexpression appears associated with that of two HMGA1-pseudogenes, HMGA1P6 and HMGA1P7, acting as a sponge for HMGA1- and HMGA2-targeting microRNAs and involved in several human cancers. CONCLUSIONS: Therefore, HMGA2 overexpression appears to be a strong feature of larynx carcinoma, supporting its detection as a valid tool for the diagnosis of these malignancies.

cDNA microarray analysis of human keratinocytes cells of patients submitted to chemoradiotherapy and oral photobiomodulation therapy: pilot study.

Oral mucositis is an acute toxicity that occurs in patients submitted to chemoradiotherapy to treat head and neck squamous cell carcinoma. In this study, we evaluated differences in gene expression in the keratinocytes of the oral mucosa of patients treated with photobiomodulation therapy and tried to associate the molecular mechanisms with clinical findings. From June 2009 to December 2010, 27 patients were included in a randomized double-blind pilot study. Buccal smears from 13 patients were obtained at days 1 and 10 of chemoradiotherapy, and overall gene expression of samples from both dates were analyzed by complementary DNA (cDNA) microarray. In addition, samples from other 14 patients were also collected at D1 and D10 of chemoradiotherapy for subsequent validation of cDNA microarray findings by qPCR. The expression array analysis identified 105 upregulated and 60 downregulated genes in our post-treatment samples when compared with controls. Among the upregulated genes with the highest fold change, it was interesting to observe the presence of genes related to keratinocyte differentiation. Among downregulated genes were observed genes related to cytotoxicity and immune response. The results indicate that genes known to be induced during differentiation of human epidermal keratinocytes were upregulated while genes associated with cytotoxicity and immune response were downregulated in the laser group. These results support previous clinical findings indicating that the lower incidence of oral mucositis associated with photobiomodulation therapy might be correlated to the activation of genes involved in keratinocyte differentiation.

The role of transoral robotic surgery in the management of oropharyngeal cancer.

PURPOSE OF REVIEW: The rising incidence of oropharyngeal squamous cell carcinoma (OPSCC), in large part as a result of the human papillomavirus (HPV), has driven a movement for the change in the management strategies. Renewed interest in minimally invasive approaches of endoscopic head and neck surgery led to introduction of transoral surgery, including transoral robotic surgery (TORS). RECENT FINDINGS: Several recent studies, based on large multi-institutional studies and systematic reviews of the literature, have shown excellent oncologic and functional outcomes with TORS for OPSCC. Also, a growing amount of clinical evidence supports the use of TORS in the management of carcinoma of unknown primary site and in selected patients with recurrent OPSCC with acceptable oncologic and better functional outcomes in comparison with traditional surgical approaches. Comparative studies with other therapeutic modalities (conventional surgical and nonsurgical) showed that TORS can be used to treat OPSCC, reducing morbidity and treatment costs, while providing equivalent oncologic results. SUMMARY: Large and robust data available in the literature supports the role of TORS within the multidisciplinary treatment paradigm for the management of OPSCC. Information from ongoing randomized clinical trials comparing TORS with and without dose-reduced radiotherapy or with and without intensified adjuvant treatment for high-risk OPSCC patients is necessary to determine the role of de-escalation of therapy in the era of HPV and OPSCC.

Ameloblastic carcinoma: a Brazilian collaborative study of 17 cases.

AIMS: Ameloblastic carcinoma (AMECA) is an odontogenic malignancy that combines the histological features of ameloblastoma and cytological atypia. Because of its rarity, it poses difficulties in diagnosis. The aim of this study was to investigate the socio-demographic data, histopathology, immunohistochemical features, treatment and outcomes of 17 cases. METHODS AND RESULTS: Descriptive statistical analyses were used to portray the clinicopathological data collected, retrospectively. Log-rank tests were performed to determine new prognostic factors. Lesions were immunostained for Ki67, p16, p53, and cytokeratins (CKs), and compared with solid/multicystic ameloblastomas (n = 15). AMECA was mostly diagnosed at a late stage, affecting the posterior mandible of male patients in their fifth decade of life. Recurrence was diagnosed in nearly 90% of treated patients, and metastasis occurred in four patients. The mean number of Ki67-positive cells was 86.4 ± 66 per field. Tumours were focally positive for CK7, CK8, CK14, and CK18, and diffusely positive for CK19, p53, and p16. AMECA showed increased immunoexpression of CK18, CK19, p16, p53 and Ki67 as compared with benign cases. CONCLUSIONS: Our study has contributed to the improved characterization of the epidemiology, prognostic markers, treatment options and outcomes of AMECA. Current criteria must be reviewed to simplify the diagnostic process for these neoplasms.

Metallothionein gene expression is altered in oral cancer and may predict metastasis and patient outcomes.

AIMS: Metallothioneins (MTs) are proteins associated with the carcinogenesis and prognosis of various tumours. Previous studies have shown their potential as biomarkers in oral squamous cell carcinoma (OSCC). Aiming to understand more clearly the function of MTs in OSCC we evaluated, for the first time, the gene expression profile of MTs in this neoplasm. MATERIALS AND RESULTS: Tissue samples from 35 cases of tongue and/or floor of mouth OSCC, paired with their corresponding non-neoplastic oral mucosa (NNOM), were retrieved (2007-09). All tissues were analysed for the following genes using TaqMan(®) reverse transcription-quantitative polymerase chain reaction (RT-qPCR) assays: MT1A, MT1B, MT1E, MT1F, MT1G, MT1H, MT1X, MT2A, MT3 and MT4. The expression of MT1B and MT1H was seldom detected in both OSCC and NNOM. A significant loss of MT1A, MT1X, MT3 and MT4 expression and gain of MT1F expression was observed in OSCC, compared to NNOM. Cases with MT1G down-regulation exhibited the worst prognoses. The up-regulation of MT1X was restricted to non-metastatic cases, whereas up-regulation of MT3 was related to cases with lymph node metastasis. CONCLUSIONS: Metallothionein mRNA expression is altered significantly in oral squamous cell carcinomas. The expression of MT1G, MT1X and MT3 may aid in the prognostic discrimination of OSCC cases.

ALCAM is a biomarker of tumor aggressiveness and worse prognosis in glottic laryngeal squamous cell carcinoma.

BACKGROUND: Laryngeal squamous cell carcinoma (LSCC) is the second most frequent head and neck tumor. Prognosis of patients with LSCC has not improved in recent decades, showing a need for the identification of prognostic biomarkers and new therapeutic targets. Recently, we showed that ALCAM overexpression was associated with glottic LSCC prognosis. OBJECTIVES AND METHODS: Aiming to validate the prognostic value of ALCAM, we evaluate the ALCAM protein levels by immunohistochemistry in 263 glottic LSCC surgically treated with neck dissection. RESULTS: ALCAM was expressed in 48.7% and overexpressed in 36.5% of glottic LSCC samples. ALCAM overexpression was associated with lymph node metastasis (p = 0.030), lymphovascular involvement (p = 0.0002), high-grade tumors (p = 0.025), and tumor relapse (p = 0.043). Multivariate survival analyses showed an overfitting between ALCAM overexpression and lymph node metastasis as a prognostic variable. CONCLUSIONS: High ALCAM expression was associated with an aggressive glottic LSCC profile.

Advances in anatomical visualization on the head and neck through robotic surgery: A Brazilian perspective.

Trans Oral Robotic Surgery (TORS) is an emerging technique that provides several benefits over existing treatment regimens for head and neck cancer, including smaller incisions, less bleeding, shorter term inpatient hospitalization, and reduced intensive care unit (ICU) length of stay. TORS allows a high resolution, magnified, three-dimensional wide view of the surgical field through an endoscope, avoiding large external cervical incisions and split-lip mandibulotomy, usually required in cancer surgeries of the oropharynx. The anatomy of the Oropharynx viewed from the perspective of the robotic surgeon is different from the anatomy taught in medical schools and residence/fellowship programs, which is more directly related to emergency procedures, open field surgery, and imaging exams. Developing an understanding of the anatomic relationships and landmarks from the "inside out" perspective is critical for any surgeon willing to perform surgical procedures through a transoral robotic approach. Here we address the major anatomic landmarks and structures in head and neck robotic surgeries and advantages and disadvantages of this approach. We emphasize the importance of imaging for successful outcomes, pointing out important anatomic landmarks considered as blind spots for surgeons in clinical and endoscopic evaluations. We also describe the Brazilian current scenario and future perspectives of Robotic Surgery in terms of training and access to this technique, including institutions that currently offer this service in the different regions of Brazil.

Supratracheal laryngectomy: a multi-institutional study.

INTRODUCTION: Supratracheal laryngectomy has been described as a surgical procedure for glottic or supraglottic cancer extending to the subglottic region and/or involving the cricoarytenoid joint, aiming to preserve laryngeal function (breathing, phonation and swallowing), without diminishing locoregional cancer control. The choice of supracricoid laryngectomy in these cases could result in a high risk of compromised resection margins. OBJECTIVE: To determine the safety, viability, adequacy of surgical margins and the supratracheal laryngectomy results for intermediate and advanced laryngeal cancer by reviewing the results at three different institutions in Brazil. METHODS: This is a retrospective study that analyzed the charts of 29 patients submitted to supratracheal laryngectomy from October 1997 to June 2017. The type of laryngectomy performed was classified according to the European Laryngological Society classification for horizontal laryngectomies. Early and late results were evaluated. Survival rates (overall, specific, disease-free and total laryngectomy-free survival) were calculated. The mean follow-up time was 44 months. RESULTS: Of the 29 patients submitted to supratracheal laryngectomy, 25 had no previous treatment. One patient (3.4%) had compromised margins. Four patients (13.8%) had recurrence. Of these, three had local recurrence and one had regional recurrence. Five patients (17.2%) required a total laryngectomy, two due to ruptured pexy and three due to local recurrence. Four of these patients (80%) achieved a successful total procedure. Four patients (13.8%) died, two due to postoperative complications and two due to recurrence. Overall, specific, disease-free and total laryngectomy-free survival at 5 years were, respectively, 82.1%; 88.2%; 83.0% and 80.2%. CONCLUSION: Selected patients with intermediate and advanced laryngeal cancer may benefit from supratracheal laryngectomy, that resulted in total laryngectomy-free survival and specific survival of 80.2% and 88.2%, respectively.

Assessment of angiogenesis by CD105 antigen in epithelial salivary gland neoplasms with diverse metastatic behavior.

BACKGROUND: Information on the biology of metastasis development in salivary gland tumors is scarce. Since angiogenesis seems associated with this phenomenon in other tumors, we sought to compare salivary gland tumors with diverse metastatic behavior in order to improve the knowledge and management of these lesions. METHODS: Samples from the most important salivary gland tumors were segregated according to its metastatic behavior and submitted to routine immunohistochemistry to identify vessels positive for CD105 expression. Frequency of positive cases and intratumoral microvessel density (IMD) was compared among the group of lesions. RESULTS: CD105 positive vessels were absent in normal salivary gland tissue, were rare in pleomorphic adenomas and adenoid cystic carcinomas (ACC), more common in polymorphous low-grade adenocarcinomas and highest in mucoepidermoid carcinomas. Only ACC with such feature were metastatic. IMD was higher in malignant rather than benign tumors. CONCLUSION: Immunostaining of CD105 in salivary gland tumors implies participation of angiogenesis in the development of malignant lesions, as well as some role for myoepithelial cells in the control of new vessel formation. In addition, suggest that ACC with positive CD105 vessels are at higher risk for metastasis.

Management of the N0 neck in moderately advanced squamous carcinoma of the larynx.

OBJECTIVE: To assess the oncological efficacy of selective neck dissection (SND) in patients with T3-4 N0 laryngeal squamous carcinoma. SUBJECTS AND METHODS: A total of 327 patients underwent 654 neck dissections; each side of the neck was individually evaluated. RESULTS: Three percent of patients who had SND developed regional recurrence (RR) in comparison with 11.7 percent of patients who underwent modified radical neck dissection (MRND) (P=0.005). Only 3 (0.9%) patients developed RR outside the field of SND. The presence of extracapsular extension (P=0.002) in node-positive (pN+) group and of microvascular invasion (P=0.007), together with the type of neck dissection (ND) (P=0.0003) in node-negative (pN0) group had statistical impact on RR. The development of RR significantly affected disease-specific survival (P=0.0001). Equivalent rates of RR were found in pN+ (2.6%) or pN0 (3.2%) patients treated with SND (P=0.98) as well as in pN+ patients who underwent SND (2.6%) or MRND (4.7%) (P=0.85). CONCLUSION: This study confirmed the adequacy of SND as a satisfactory staging and therapeutic procedure, and suggests its use in the treatment of limited node-positive (N+) neck.

Impact of previous tracheotomy as a prognostic factor in patients with locally advanced squamous cell carcinoma of the larynx submitted to concomitant chemotherapy and radiation.

HYPOTHESIS: The combination of chemotherapy and radiotherapy is a standard nonsurgical treatment for locally advanced laryngeal cancer. Nevertheless, there are no validated markers to predict the outcome of nonsurgical therapies. The impact of previous tracheotomy is not clear in patients submitted to concomitant chemoradiotherapy. STUDY DESIGN: A non-randomized prospective study. Prognostic factors such as stage, age, performance status, number of chemotherapy cycles, radiotherapy dose, stage VIb disease, and previous tracheotomy were analyzed using the Cox's proportional hazard model. The Kaplan-Meier and log rank tests were used to evaluate the progression-free and overall survival. PATIENTS AND METHODS: Patients with stage III/IV laryngeal carcinoma were prospectively selected. Treatment consisted of cisplatin 100 mg/m(2) every 3 weeks for 3 cycles, radiotherapy to a total dose of 70.2 Gy and salvage surgery. RESULTS: Forty-nine patients were analyzed; tracheotomy was performed in 12 patients (24.5%) before therapy. Patients who had previous tracheotomy had a lower rate of complete response (41.7 vs. 75%, p = 0.034, HR 0.55, CI 95% 0.27-1.11), shorter progression free-survival (HR 2.83, CI 95% 1.60-4.88, p < 0.001), and median overall survival (12 vs. 56 months, HR 2.37, CI 95% 1.43-3.93, p < 0.001), in comparison to those without a tracheotomy. Moreover a significant difference was observed in 3-year survival rates (6 vs. 61%, p = 0.001), in favor of the group without tracheotomy. Interestingly, the impact of previous tracheotomy was not altered when adjusted by other prognostic factors (HR 8.7, CI 95% 3.1-24.0, p < 0.001). CONCLUSIONS: Previous tracheotomy is a negative prognostic factor for patients submitted to chemotherapy combined with radiotherapy and should be considered as a negative clinical prognostic factor in the selection of patients for more aggressive treatment strategies.

Postoperative adjuvant radiation therapy in the treatment of primary head and neck mucosal melanomas.

BACKGROUND/AIMS: The role of postoperative radiotherapy (PORT) in head and neck mucosal melanomas (HNMM) is not yet clearly defined. The aim of this study is to report the 21-year experience of the Brazilian National Cancer Institute in such treatment. METHODS: From January 1983 to December 2003, 31 patients with confirmed histological diagnosis of HNMM underwent treatment at the Brazilian National Cancer Institute. Of these, 20 received radical treatment with surgery alone (8 patients--group 1) or surgery and PORT (12 patients--group 2). RESULTS: Local control and the median time to local failure at 5 years were 75% and 14 months for group 1 and 83.5% and 40 months for group 2 (p = 0.06). The overall survival rates at 3 years were 37.5% for group 1 and 58% for group 2. At 5 years the survival rates were 25% for both groups (p = NS). When PORT was initiated within 60 days after surgery, there was a trend towards improvement in overall survival (p = 0.08). After univariate analysis, distant metastasis, location of primary disease and tobacco smoking were important prognostic factors. CONCLUSION: Early (<60 days) PORT for HNMM provides better local control with a longer disease-free survival.

Criteria for eligibility to cisplatin in the curative treatment of head and neck cancer: Consensus opinion from a panel of experts.

Squamous-cell carcinoma of the head and neck (SCCHN) is an important problem in Brazil, where epidemiological and socioeconomic features often create barriers to the implementation of combined modalities with curative potential. Cisplatin improves the efficacy of radiotherapy in the adjuvant treatment of localized SCCHN and in the definitive therapy of locally advanced disease. However, the addition of high-dose cisplatin to radiotherapy increases treatment toxicity and is not always warranted. A panel of experts convened in Sao Paulo, Brazil, for discussions and recommendations regarding the use of high-dose cisplatin in combination with radiotherapy in SCCHN. In addition to discussing their professional experience, panel members used the current literature to provide evidence-based, practical recommendations regarding sociodemographic or medical criteria that may preclude safe administration of cisplatin. It is hoped that the application of these recommendations in clinical practice may improve therapeutic results in Brazil and other countries with similar health-care environments.

Outcomes and prognostic factors in patients with head and neck cancer and severe acute illnesses.

OBJECTIVES: To evaluate the outcomes of patients with head and neck cancer and severe acute illnesses, and to identify characteristics associated with hospital mortality. DESIGN: Cohort study. SETTING: Ten-bed medical-surgical oncologic intensive care unit (ICU). PATIENTS: Consecutive patients admitted to the ICU over a 68-month period. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Demographic, clinical and cancer-related data were collected. Multivariate logistic regression analysis was performed to identify predictive factors of hospital mortality. One hundred and twenty-one patients aged 63.3+/-14.7 years were enrolled in the study. The main sites of primary tumor were oral cavity (30%), larynx (25%), pharynx (14%) and thyroid (9%). The main reasons for ICU admission were sepsis (37%) and acute respiratory failure (20%). The mean SAPS II score was 49.6+/-17.8 points, and during ICU stay 100 (83%) patients received mechanical ventilation, 70 (58%), vasopressors, and 12 (10%), dialysis. The ICU, hospital and 6-month mortality rates were 39%, 56% and 72%, respectively. A performance status >or=2 [odds ratio (OR)=5.17 (95% confidence interval, CI=1.84-14.53)], advanced cancer (TNM stage IV) [OR=3.80 (95% CI=1.28-11.28)], and the number of organ failures [OR=2.87 (95% CI=1.83-4.50)] were associated with increased mortality in multivariate analysis. CONCLUSIONS: In conjunction with clinical judgment and taking into consideration the patient's preferences and values, the knowledge of these outcome predictors may be useful in helping physicians to identify patients who might benefit from the intensive care and to improve discussions on patients' prognosis.

Atypical facial access: an unusually high prevalence of use among patients with skull base tumors treated at 2 centers.

OBJECTIVE: To analyze the influence of the unique percentage of skin carcinomas with skull base invasion on the choice of the facial surgical approach. DESIGN: Multi-institutional retrospective analysis of the medical charts of all patients who had undergone oncological craniofacial operations from 1981 to 2005. Data were collected on demographic distribution, location of the primary tumor, histologic type, type of operation, reconstruction, complications, and outcome. Special attention was directed toward the choice of facial approach. SETTING: Two major tertiary care centers. PATIENTS: A total of 484 patients who had undergone major skull base operations. INTERVENTION: Frequency of atypical facial approaches. MAIN OUTCOME MEASURES: Impact on the need for more sophisticated reconstructions and on surgical morbidity. RESULTS: During this 25-year period, 484 patients underwent major skull base operations in the 2 centers; data concerning 467 cases were available for analysis. The median age of the patients was 52.8 years (range, 4-88 years), and the male-female ratio was 1.9:1.0. The initial location of the tumor was the craniofacial skin in 63.5% of cases, ethmoid in 10.8%, maxilla in 2.3%, orbit in 1.9%, and other origins, including endocranial, in 19.4%. The histologic type of the lesions was basal cell carcinoma in 42.0% of cases, squamous cell carcinoma in 29.5%, esthesioneuroblastoma in 5.3%, adenocarcinoma in 3.9%, adenoid cystic carcinoma in 2.8%, and other types in 16.5%. Owing to this high prevalence of advanced skin carcinomas, the most commonly employed facial approach was atypical, tailored to encompass all compromised skin and underlying tissues, in 55.5% of cases, followed by the Weber-Ferguson approach, with all its variations (eg, nasal swing) in 17.8%, lateral rhinotomy in 12.2%, facial translocation in 3.8%, and other facial techniques in 7.7%. No facial approach was required in 1.5% of cases. CONCLUSION: In most situations, head and neck surgeons chose an atypical surgical approach to properly resect all facial structures invaded by very advanced skin cancers.

Long-term survival of a randomized phase III trial of head and neck cancer patients receiving concurrent chemoradiation therapy with or without low-level laser therapy (LLLT) to prevent oral mucositis.

BACKGROUND: The impact of low-level laser therapy (LLLT) to prevent oral mucositis in patients treated with exclusive chemoradiation therapy remains unknown. This study evaluated the overall, disease-free and progression-free survival of these patients. METHODS: Overall, disease-free and progression-free survival of 94 patients diagnosed with oropharynx, nasopharynx, and hypopharynx cancer, who participated on a phase III study, was evaluated from 2007 to 2015. The patients were subjected to conventional radiotherapy plus cisplatin every 3weeks. LLLT was applied with an InGaAlP diode (660nm-100mW-1J-4J/cm2). RESULTS: With a median follow-up of 41.3months (range 0.7-101.9), patients receiving LLLT had a statistically significant better complete response to treatment than those in the placebo group (LG=89.1%; PG=67.4%; p=0.013). Patients subjected to LLLT also displayed increase in progression-free survival than those in the placebo group (61.7% vs. 40.4%; p=0.030; HR:1:93; CI 95%: 1.07-3.5) and had a tendency for better overall survival (57.4% vs. 40.4%; p=0.90; HR:1.64; CI 95%: 0.92-2.91). CONCLUSION: This is the first study to suggest that LLLT may improve survival of head and neck cancer patients treated with chemoradiotherapy. Further studies, with a larger sample, are necessary to confirm our findings.

Relevance of skip metastases for squamous cell carcinoma of the oral tongue and the floor of the mouth.

OBJECTIVE: To analyze the therapeutic implications of the distribution of neck metastases (NM) in patients with squamous cell carcinoma (SCC) of the tongue and the floor of the mouth (FOM). PATIENTS AND METHODS: From January 1987 through December 1997, 339 previously untreated patients with T1-2 N0 M0 SCC of the tongue and the FOM underwent primary surgical treatment in our institution. A retrospective review of the pathology reports and outcome of these patients was made to ascertain the prevalence and distribution of NM. Patients were grouped by clinical neck status at the time of neck dissection: elective neck dissection (END) in the NO neck and subsequent therapeutic dissection (STD) in the neck observed which converted clinically to N+ or regional recurrences after END. All patients were classified according to the American Joint Committee on Cancer (AJCC)/UICC 2002 TNM classification. RESULTS: All patients underwent surgical treatment of the primary cancer and had negative margins at frozen section. Overall incidence of NM was 41.3%. Twenty-seven point eight percent of T1 N0 M0 and 48.2% of T2 N0 M0 patients developed NM (P = .0004). Occult neck metastases occurred in 24.1% of patients. Clinically, N+ metastases occurred in 23.6% of patients. The overall incidence of NM in levels IV and V was 8.5%. Neck level IV nodes were involved in only 1.5% of patients in the END group versus 23.7% in the STD group (P < 0.001). Level V was always associated to nodal metastases in other neck levels. Only 2% of patients in our study presented "skip metastases" in the neck. CONCLUSIONS: Neck levels I and II were at great risk for the development of NM (46.9% and 75.3% respectively). Levels IV (6.5%) and V (2%) were rarely involved in our group of patients. The results found in this study support the indication of supraomohyoid neck dissection for N0 and a more comprehensive neck dissection (levels I-V) for N+ patients in Stage I-II SCC of the tongue and FOM. EBM RATING: C-4.

Cost-effectiveness of low-level laser therapy (LLLT) in head and neck cancer patients receiving concurrent chemoradiation.

BACKGROUND: Oral mucositis is a major event increasing treatment costs of head and neck squamous cell carcinoma (HNSCC) patients treated with chemoradiation (CRT). This study was designed to estimate the cost-effectiveness of low-level laser therapy (LLLT) to prevent oral mucositis in HNSCC patients receiving CRT. METHODS: From June 2007 to December 2010, 94 patients with HNSCC of nasopharynx, oropharynx, and hypopharynx entered a prospective, randomized, double blind, placebo-controlled, phase III trial. CRT consisted of conventional radiotherapy (RT: 70.2 Gy, 1.8 Gy/d, 5 times/wk)+concurrent cisplatin (100mg/m2) every 3 weeks. An InGaAlP (660 nm-100 mW-4J/cm2) laser diode was used for LLLT. RESULTS: From the perspective of Brazil's public health care system (SUS), total costs were higher in Placebo Group (PG) than Laser Group (LG) for opioid use (LG=US$ 9.08, PG=US$ 44.28), gastrostomy feeding (LG=US$ 50.50, PG=US$ 129.86), and hospitalization (PG=US$ 77.03). In LG, the cost was higher for laser therapy only (US$ 1880.57). The total incremental cost associated with the use of LLLT was US$ 1689.00 per patient. The incremental cost-effectiveness ratio (ICER) was US$ 4961.37 per grade 3-4 OM case prevented compared to no treatment. CONCLUSIONS: Our results indicate that morbidity was lower in the Laser Group and that LLLT was more cost-effective than placebo up to a threshold of at least US$ 5000 per mucositis case prevented. CLINICAL TRIAL INFORMATION: NCT01439724.

Clinical prognostic factors in malignant parotid gland tumors.

OBJECTIVE: To analyze the factors in parotid malignant epithelial tumors influencing recurrences and disease-specific survival. METHODS: We retrospectively reviewed the files of 150 patients treated at our institution, from 1974 to 1998. Twenty-four patients were not treated by surgery and were excluded from this study. The remaining 126 patients were treated with surgery and 74 patients had postoperative radiotherapy. Thirty-three patients were treated with parotidectomy plus neck dissection. Neck lymph node metastasis was found in 22 patients, 5 patients had occult neck metastasis, and 4 periparotid lymph nodes metastasis. The mean age was 49 years old. According to the UICC/1997 TNM Classification, 49 patients were stage I, 27 stage II, 22 stage III, and 28 stage IV. The influence of selected factors on the 10 year disease-specific survival was analyzed using the Kaplan-Meier actuarial method and the log-rank test. RESULTS: Forty patients had mucoepidermoid carcinoma, 18 patients adenocarcinoma NOS, 18 patients acinic cell carcinoma, 15 patients adenoid cystic carcinoma, 11 patients malignant mixed tumor, 11 patients salivary duct carcinoma, and 13 patients other pathology. Twenty-five patients had recurrences: 17 had local recurrences, 4 patients had neck recurrences, and 4 were loco-regional recurrences. Five factors influenced negatively the prognosis: 1) T stage (p.00001), 2) grade (p.00001), 3) + lymph nodes (p.0007), 4) facial nerve dysfunction (p.0001), and 5) age (p.004). Patients with high-grade tumors and high-stage tumors had the worst prognosis according to the multivariate analysis. The 10-year disease-specific survival was 97% for stage I, 81% for stage II, 56% for stage III, and 20% for stage IV. CONCLUSION: The grade of the tumor and stage were the most important prognostic factor. EBM RATING: C.