Fernando Luiz Dias

Supraomohyoid neck dissection in the treatment of T1/T2 squamous cell carcinoma of oral cavity*

BACKGROUND Recent studies in patients with previously untreated T1 and T2 squamous cell carcinoma (SCC) of the tongue and floor of the mouth have shown a relationship between tumor thickness, neck metastasis, and survival. Our study was conducted to determine the indication of elective neck dissection in patients with early oral cavity SCC. PATIENTS AND METHODS Sixty-seven patients were stratified by stage (T1 and T2 NO), and those in each stage were randomized to receive one of two types of treatment; resection alone (RA) or resection plus elective supraomohyoid neck dissection (RSOND). Fifty-two patients (78%) were men and 15 (22%) were women. The median age was 57 years old (range 34 to 95). RESULTS Twenty-six (39%) patients had tumor in the floor of the mouth and 41 (61%), in the tongue. Using the criteria of the Union Internationale Contre le Cancer (UICC), 1987, we classified 31 tumors (46%) as T1 lesions and 36 (54%) as T2 lesions. Thirty patients had a tumor thickness < or = 4 mm and 37 had a tumor thickness > 4 mm. Thirty-three (49%) patients were treated with RA, and 34 patients (51%) were treated with RSOND. Seven (21%) patients of the RSOND group had occult cervical metastasis. There were recurrences in 14 (42%) patients of the RA group and 8 (24%) patients of the RSOND group. The disease-free survival rates at 3.5 years for RA and RSOND patients were 49%, and 72%, respectively. The impact of sex, age, site, cancer stage, and tumor thickness was assessed by the Mantel-Haenszel chi-square procedure. Later stage (P = 0.05) and increased tumor thickness (P = 0.005) were significantly associated with treatment failures. CONCLUSION Neck dissection remains mandatory in the early stage of oral SCC, because of better survival rates compared to RA and the poor salvage rate. In particular, patients with tumor thickness > 4 mm treated with RSOND had significant benefit on disease-free survival.

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.

Elective neck dissection versus observation in stage I squamous cell carcinomas of the tongue and floor of the mouth.

A retrospective study was undertaken of patients with T1N0M0 squamous cell carcinoma of the oral tongue and floor of the mouth who underwent surgical treatment between 1985 and 1995. Evaluation of two groups of patients (neck dissection versus observation) was made according to the management of the neck. Results were obtained regarding the presence of occult metastases, recurrence in the neck, treatment failure, results of salvage treatment, and disease-free survival. Forty-nine patients underwent surgical treatment: 25 resection of primary and 24 resection plus neck dissection. Overall incidence of regional metastases was 24.5%. Eight patients (16%) developed recurrence of the disease. Seven (14%) had regional recurrences (including 1 with distant metastases) and 1(2%) had local recurrence. Twenty-four percent of patients from the resection of primary group developed neck recurrences in comparison with 4% of the resection plus neck dissection group (P = 0.05). Overall salvage rate was 37.5%. Second primary tumors developed in 16% of patients. Patients who underwent elective neck dissection had a 23% higher disease-free survival rate compared with those who underwent resection of the tumor alone (P = 0.03). The findings of this study stress the importance of control of the neck in early oral cancer. Elective neck dissection significantly improved regional control of the disease.

Spontaneous remission in thyroid cancer patients after biochemical incomplete response to initial therapy

To validate the American Thyroid Association (ATA) initial risk of recurrence scheme and the Memorial Sloan Kettering Cancer Center (MSKCC) response to therapy re‐stratification approach in a large cohort of patients with differentiated thyroid cancer (DTC) treated outside of the United States.

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

Elective neck dissection in the treatment of T3/T4 N0 squamous cell carcinoma of the larynx

BACKGROUND This study analyzed pathologic findings of clinically occult cervical lymph nodes of T3/T4 N0 squamous cell laryngeal carcinoma and their impact on locoregional failures and overall survival. PATIENTS AND METHODS A retrospective analysis of 76 patients with T3/T4 N0 laryngeal carcinoma was carried out between 1981 and 1989. Sixty-seven patients had transglottic tumor, 31 patients had extralaryngeal spread, 56 patients were T3 N0, and 20 patients were T4 N0. Seventy-five patients had total laryngectomy and 1 had near total laryngectomy. All patients had bilateral elective neck dissection. The chi-square test was applied to factors related to neck metastasis and locoregional failure. Survival was analyzed using the Kaplan-Meier actuarial method; differences were tested using the Wilcoxon signed-rank test. RESULTS Eighteen patients had positive surgical margins. Occult neck metastasis was observed in 30%. Univariate analysis showed that cancer stage and cartilage status were not significant to predict neck metastasis. Locoregional recurrence was observed in 28% of patients. Surgical margins, cervical metastasis, lesion extension, and cartilage invasion had significant impact on disease-free survival. The 5-year overall survival was 52%; disease-free survival was 57%. CONCLUSION The elective bilateral neck dissection performed in T3/T4 N0 patients yielded a 30% incidence of occult neck metastasis. Classification of transglottic carcinomas into endolaryngeal and exolaryngeal provides a better parameter for predicting neck metastasis than does T status. Disease-free and overall survival were significantly affected by neck metastasis, T stage, exolaryngeal tumor, cartilage infiltration, and surgical margins.

Expression of Bcl-2 family proteins and associated clinicopathologic factors predict survival outcome in patients with oral squamous cell carcinoma.

The aims of this study were to assess the expression levels of three proteins involved in apoptosis--Bcl-2, Bcl-X, and Bax--and evaluate their relationship with clinicopathologic features and survival in oral squamous cell carcinoma (OSCC). Immunohistochemistry was used to evaluate protein expression in 53 primary OSCCs treated by radical surgery with free margins at a single institution in 1999. Histologic specimens were graded and analyzed for perineural invasion, lymphocytic infiltrate, and pattern of invasion. Digital image analysis was performed to quantify immunostaining. Survival was analyzed using the Kaplan-Meier method and Coxs proportional hazard model. Cancer-specific 5-year survival (CSS) was 61% (56% overall survival (OS), and 51% disease-free interval (DFI)). Kaplan-Meier analysis identified pathologic stage (p=0.0007, log-rank test, OS), negative nodes status (pN) (p<0.0001, log-rank test, OS), presence of lymphocytic infiltrate (p=0.0084, log-rank test, OS), and high Bax expression (p=0.025, log-rank test, OS) to each be associated with both better OS and CSS. Tongue tumors (p=0.0179, log-rank test), worst pattern of invasion (p=0.0293, log-rank test), lack of lymphocytic infiltrate (p=0.0328, log-rank test), perineural invasion (p=0.0448, log-rank test), poorly differentiated tumors (p=0.0318, log-rank test), and low Bcl-X expression (p=0.044, log-rank test) were all associated with a low DFI. Cox regression found pN, lymphocytic infiltrate, and Bax expression to be independent prognostic factors for OS and CSS, whereas lymphocytic response and tongue tumors were predictors of DFI. Bcl-2 expression emerged as an independent marker of favorable CSS. Lymphocytic infiltrate was the most meaningful histopathologic parameter in survival analysis, whereas expression of Bcl-2 family members seems to be an important marker of a favorable prognosis in OSCC.

Supracricoid laryngectomy with cricohyoidoepiglottopexy for advanced glottic cancer

Supracricoid laryngectomy with cri‐cohyoidoepiglottopexy (CHEP) is a conservative surgical procedure indicated in selected cases of advanced glottic carcinoma.

Phase III trial of low-level laser therapy to prevent oral mucositis in head and neck cancer patients treated with concurrent chemoradiation☆

BACKGROUND Oral mucositis (OM) is a complication of chemoradiotherapy treatment of head and neck squamous cell carcinoma (HNSCC) patients with no effective therapy. This study was designed to assess the efficacy of preventive low-level laser therapy (LLLT) in reducing the incidence of grade 3-4 OM. MATERIAL AND METHODS From June 2007 to December 2010, 94 HNSCC patients entered a prospective, randomized, double-blind, placebo-controlled phase III trial. Chemoradiotherapy consisted of conventional radiotherapy plus concurrent cisplatin every 3weeks. A diode InGaAlP (660nm-100mW-1J-4J/cm(2)) was used. OM evaluation was performed by WHO and OMAS scales and quality of life by EORTC questionnaires (QLQ). RESULTS A six-fold decrease in the incidence of grades 3-4 OM was detected in the LLLT group compared to the placebo; (6.4% versus 40.5%). LLLT impacted the incidence of grades 3-4 OM to a relative risk ratio of 0.158 (CI 95% 0.050-0.498). After treatment QLQ-C30 showed, differences favoring LLLT in physical, emotional functioning, fatigue, and pain; while the QLQ-H&N35 showed improvements in LLLT arm for pain, swallowing, and trouble with social eating. CONCLUSION Preventive LLLT in HNSCC patients receiving chemoradiotherapy is an effective tool for reducing the incidence of grade 3-4 OM. Efficacy data were corroborated by improvements seen in quality of life.

Supracricoid Laryngectomy with CHEP: Functional Results and Outcome:

OBJECTIVES: To assess whether supracricoid laryngectomy with cricohiodoepiglottopexy could successfully reach the cure and preserve the voice in glottic laryngeal cancer, we studied 27 patients with T2/T3 squamous cell carcinoma of the larynx treated in our institution with cricohiodoepiglottopexy. STUDY DESIGN: A retrospective analysis has been carried out between 1995 through 1997. We classified 11 patients as T2N0M0 and 16 patients as T3N0M0. Nineteen patients had bilateral selective lateral neck dissection, 3 patients had unilateral lateral neck dissection, and 5 patients had undissected neck. Survival was analyzed under the Kaplan-Meyer method. RESULTS: Five patients had postoperative complications, 2 were treated with a total laryngectomy. The remaining 25 patients kept the normal airway, swallowing, and speech. None of the patients in the neck dissection group had neck metastasis. Two patients had recurrences, 1 with local recurrence was treated with a total laryngectomy and is alive without disease; the other patient had neck recurrence, was treated with radical neck dissection plus radiotherapy, and is dead of the disease. One patient had a second tumor in oropharynx treated with palliative radiotherapy and is dead of the disease. Three years disease-free survival was 75% for T2 and 79% for T3. CONCLUSIONS: This technique is useful in the treatment of selected cases of T3/T2 glottic cancer regarding the extent of disease. The incidence of complications in need of a complete laryngectomy does not compromise the functionality of this technique. The survival is comparable to patients who submitted to total laryngectomy and near-total laryngectomy, regarding the extent of the lesion.