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.

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.

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.

Patterns of failure and outcome in esthesioneuroblastoma.

OBJECTIVES: To evaluate the results of standardized treatment of esthesioneuroblastoma (ENB) during a 17-year period and to identify pertinent factors for clinical outcome. DESIGN: Review of clinical and radiographic data and retrospectively staging ENB according to 3 staging systems: Kadish, Biller, and Dulguerov and Calcaterra. SETTING: Hospital do Cancer I-Instituto Nacional de Cancer, Rio de Janeiro, Brazil. PATIENTS: Thirty-six patients with histologically confirmed ENB treated between January 1, 1983, and December 31, 2000; 35 fulfilled study inclusion criteria. INTERVENTIONS: Treatment included gross tumor resection through a transfacial approach with postoperative radiotherapy (RT) in 11 patients, craniofacial resection (CFR) and postoperative RT in 7, exclusive RT in 14, CFR alone in 1, and a combination of chemotherapy and RT in 2. Histopathological slides were reviewed and graded using the Hyams staging system. Analysis of prognostic factors was performed. MAIN OUTCOME MEASURES: Evaluation of survival rates using the Kaplan-Meier method. Analysis of prognostic factors carried out with the Fisher exact test and the log-rank test. RESULTS: Analysis of survival showed that the Kadish classification best predicted disease-free survival (P =.046). The presence of regional and distant metastases adversely affected prognosis (P<.001 and P =.01, respectively). Craniofacial resection plus postoperative RT provided a better 5-year disease-free survival rate (86%) compared with the other therapeutic options used (P =.05). The 5-year disease-specific survival rate was 64% and 43% for the low- and high-grade tumors, respectively (P =.20). Disease-free survival for this cohort of 35 patient was 46% and 24% at 5 and 10 years, respectively. Overall survival was 55% and 46% at 5 and 10 years of follow-up, respectively. CONCLUSIONS: The development of cervical nodal metastases and distant metastases had a significant adverse impact on prognosis. The value of the Kadish staging system was confirmed in our study, significantly correlating with prognosis. Tumor grade according to the Hyams staging system also seems to be an important factor in determining prognosis for tumor recurrence and survival. Aggressive multimodality therapeutic strategies, particularly CFR and adjuvant RT, yielded the best treatment outcome.

Prognostic factors and outcome for nasopharyngeal carcinoma.

BACKGROUND: Nasopharyngeal cancer (NPC) is a distinct form of cancer of the upper respiratory or digestive tract in which the epidemiologic features, origin, histopathologic types, treatment, and prognosis are different from those associated with other malignant neoplasms of this anatomical area. Recent publications have demonstrated the advantage of aggressive multimodality treatment for advanced NPC. OBJECTIVES: To evaluate the results of standardized treatment of NPC during 11 years and to identify pertinent factors for clinical outcome. METHODS: Between January 1, 1989, and December 31, 2000, 173 patients with newly diagnosed NPC were treated at Instituto Nacional de Cancer. Clinical records and radiographic studies of the patients were retrospectively reviewed. Documented data of the initial presenting symptoms, head and neck examination, radiotherapy protocols, chemotherapy regimens, and surgical technique were analyzed. To determine important prognostic factors, we correlated survival rates with age, clinical stage, tumor extent, histopathological type, and therapeutic approach. The major end point used for assessment was relapse-free survival. Survival curves were estimated by the Kaplan-Meier product-limit method. Multivariate analysis was performed using the Wilcoxon signed rank and Cox proportional hazards regression tests. RESULTS: Most patients (88.5%) had locoregional advanced disease, mostly (53.4%) of the nonkeratinizing subtype. Forty-seven percent of patients had clinical cervical nodal metastases at first consultation. Gross extension of the primary tumor involving the facial bones and skull base was observed in 39.3% and 20.8%, respectively. Just under 75% of patients were treated with radiotherapy (median dose, 6600 cGy), and 25.4% underwent concomitant chemoradiotherapy with adjuvant chemotherapy (cisplatin plus 5-fluorouracil) (median dose, 6800 cGy). The 5-year disease-specific survival for the 173 patients was 32.3%. The disease-specific survival for the radiotherapy group was 22.5%, compared with 61.4% for the chemoradiotherapy plus adjuvant chemotherapy group (P =.004). Factors associated with adverse outcomes were age older than 40 years at treatment (P =.001), advanced TNM stage (P =.002), skull base invasion (P =.004), and facial bone invasion (P<.001). CONCLUSIONS: Compared with radiotherapy alone, concomitant chemoradiotherapy with adjuvant chemotherapy improved the treatment outcome of patients with NPC treated in our institution. Advanced age, local extension, and stage of the disease adversely affected the prognosis in our patients. Compared with reirradiation, salvage brachytherapy and radical neck dissection for local and regional residual or recurrent NPC were associated with increased rates of locoregional control and survival.

Clarithromycin-resistant Helicobacter pylori in Recife, Brazil, directly identified from gastric biopsies by polymerase chain reaction.

CONTEXT: Clarithromycin is the most effective drug used in the eradication of infection by Helicobacter pylori. Due to worldwide increase in resistance, pre-treatment susceptibility testing for clarithromycin is recommended. OBJECTIVES: To evaluate the prevalence of clarithromycin resistance of H. pylori in Recife, a city in Northeast Brazil. METHODS: From January 2006 to December 2007, 114 gastric biopsy samples positive for H. pylori at culture were directly assayed by polymerase chain reaction (PCR) to detect the most frequent point mutations involved in clarithromycin resistance. Results were compared with those obtained by Etests. RESULT: Molecular and phenotypic methods showed 111 (97.4%) susceptible or resistant concordant results. PCR detected 3 (2.6%) biopsy specimens with H. pylori-resistant genotypes, which were misdiagnosed as susceptible by Etests. In Recife, based on PCR results, primary clarithromycin resistance was found in 15 (16.5%) patients, prevalence close to that observed in Southeast Brazil. Resistance increased to 52% among previously treated patients. The point mutation A2143G was present in 20 (71.4%) of specimens and A2142G, in 8 (28.6%) of specimens. A2142C was not found. CONCLUSION: In Recife, the prevalence of primary clarithromycin resistance, 16.5%, showed the need for pretreatment susceptibility testing in H. pylori infections.

How to minimize complications in thyroid surgery?

BACKGROUND: In ancient times, operations on the thyroid gland caused unacceptable morbidity and mortality. Only after the landmark work of Kocher, the technical principles of thyroidectomy were solidly established, and are still valid nowadays. METHODS: Revision article on practical suggestions to decrease morbidity associated with thyroidectomy, as well as warning against common pitfalls that the surgeon may encounter. RESULTS: The following subjects are objectively addressed: how to manage upper airway obstruction, how to avoid non-esthetic scars and how to recognize the most prevalent anatomic variations concerning the recurrent nerve, the external branch of the superior laryngeal nerve and the parathyroid glands, in order to decrease operative morbidity. CONCLUSION: The Head and Neck Surgeon must be fully aware of the complex anatomy of the central visceral compartment of the neck, as well as must be prepared to handle some complications of thyroidectomy that can be life-threatening.

Supracricoid laryngectomy with cricohyoidoepiglottopexy for advanced glottic cancer.

BACKGROUND: Supracricoid laryngectomy with cri-cohyoidoepiglottopexy (CHEP) is a conservative surgical procedure indicated in selected cases of advanced glottic carcinoma. METHODS: This study is a review of our experience with 43 patients with T3/T4 glottic squamous cell carcinoma who underwent CHEP in our institution. All but two patients underwent selective neck dissections. All patients were staged on the basis of the 2002 TNM classification. Rates of recurrence and death were estimated by the Kaplan-Meier method. RESULTS: The 5-year disease-specific survival and 5-year relapse-free survival rates were 78% and 83%, respectively. Neck metastases were found in three patients. Cartilage invasion occurred in 11 cases. The average length of hospital stay was 5.7 days. The mean time of enteral feeding tube was 33.8 days, and the mean time for tracheotomy was 29.6 days. Overall, normal swallowing was achieved in 74.4% of patients. Eleven patients had mild and major complications. Laryngeal stenosis emerged as the most frequent major complication. Three patients (6.9%) had local recurrences. Two patients (4.6%) had neck metastases. CONCLUSIONS: On the basis of this study, over a 7-year period with 43 patients with advanced glottic cancer, a successful on-cologic outcome is confirmed.

Clarithromycin-resistant Helicobacter pylori in Recife, Brazil, directly identified from gastric biopsies by polymerase chain reaction / Helicobacter pylori resistente à claritromicina no Recife, Brasil, identificada diretamente de biopsias gástricas pela reação em cadeia de polimerase

CONTEXT: Clarithromycin is the most effective drug used in the eradication of infection by Helicobacter pylori. Due to worldwide increase in resistance, pre-treatment susceptibility testing for clarithromycin is recommended. OBJECTIVES: To evaluate the prevalence of clarithromycin resistance of H. pylori in Recife, a city in Northeast Brazil. METHODS: From January 2006 to December 2007, 114 gastric biopsy samples positive for H. pylori at culture were directly assayed by polymerase chain reaction (PCR) to detect the most frequent point mutations involved in clarithromycin resistance. Results were compared with those obtained by Etests. RESULT: Molecular and phenotypic methods showed 111 (97.4 percent) susceptible or resistant concordant results. PCR detected 3 (2.6 percent) biopsy specimens with H. pylori-resistant genotypes, which were misdiagnosed as susceptible by Etests. In Recife, based on PCR results, primary clarithromycin resistance was found in 15 (16.5 percent) patients, prevalence close to that observed in Southeast Brazil. Resistance increased to 52 percent among previously treated patients. The point mutation A2143G was present in 20 (71.4 percent) of specimens and A2142G, in 8 (28.6 percent) of specimens. A2142C was not found. CONCLUSION: In Recife, the prevalence of primary clarithromycin resistance, 16.5 percent, showed the need for pretreatment susceptibility testing in H. pylori infections.

CONTEXTO: Claritromicina é a droga mais eficaz usada na erradicação da infecção pelo H. pylori. Devido ao aumento mundial da resistência, o teste de susceptibilidade à claritromicina pré-tratamento é recomendado. OBJETIVO: Determinar a prevalência de H. pyloriclaritromicina resistente em Recife, PE, Brasil. MÉTODO: De janeiro de 2006 a dezembro de 2007, 114 biopsias gástricas positivas à cultura para H. pylori foram diretamente analisadas pela reação em cadeia da polimerase (PCR), para detectar a frequência das mutações em ponto que envolvem a resistência à claritromicina. Os resultados foram comparados com os obtidos pelos E-testes. RESULTADO: Os métodos molecular e fenótipo fenotípico mostraram 111 (97.4 por cento) resultados concordantes, sensíveis ou resistentes. A PCR detectou três (2.6 por cento) espécimes de H. pyloricom genótipo resistente, diagnosticados erroneamente como sensíveis pelo E-teste. No Recife, baseando-se nos resultados da PCR, a resistência primária à claritromicina foi encontrada em 15 (16.5 por cento) pacientes, esta prevalência também foi observada no sudeste do Brasil. Entre os pacientes previamente tratados, a resistência elevou-se para 52 por cento. A mutação em ponto A2143G foi observada em 20 (71.4 por cento) dos espécimes e a A2142G, em 8 (28.6 por cento). A mutação A2142C não foi encontrada. CONCLUSÃO: No Recife, a prevalência da resistência a claritromicina, 16.5 por cento, mostrou a necessidade de realização dos testes de susceptibilidade prétratamento nas infecções por H. pylori.

Therapeutic options in advanced laryngeal cancer: an overview.

Historically, patients with advanced laryngeal cancer have been treated with radical surgery and adjuvant radiation therapy. Intensive surgical research has allowed surgeons to deal with almost any local extension and to propose an appropriate surgical procedure for each case. Several function-sparing surgical options are available to treat moderately advanced/advanced laryngeal cancer. Better understanding of the anatomy and biology of cancer in this anatomical site has enabled us to devise effective oncological strategies associated with a great effort to preserve laryngeal function. Numerous efforts have been made to augment the therapeutic armamentarium with the addition of chemotherapeutic agents combined with radiation therapy. For advanced laryngeal cancer, the debate is still open between partial/subtotal surgical procedures, which are more efficient but sacrifice parts of the larynx, and radiotherapy/chemoradiation protocols which can preserve the larynx and its function even though it requires radical surgery for salvage. Efforts should be made to select patients properly, in an individual basis, based on tumor characteristics, clinical aspects, patient's expectations, and the expertise of the head and neck oncologic team for the various therapeutic strategies in order to get better oncological results in association with the preservation of the laryngeal form and function, when possible.

Chemical constituents of Simarouba versicolor.

From the roots, stems and fruits of Simarouba versicolor (Simaroubaceae) were isolated quassinoids (3, 5-7), triterpenoids (8-14), a mixture of steroids (15-17), the flavonoid kaempferol (18) and the squalene derivative 11,14-diacetoxy-7,10; 15,18-diepoxy-6,19-dihidroxy-6,7,10,11,14,15,18,19-octahydrosqualene (19). Spectral data were used for structural characterization.

Víbrios não coléricos na rotina enterobacteriológica / Non-cholera vibrios in enterobacteriologic routine

Of 3250 diarrheal stools received for microbiologic diagnosis at a private clinical laboratory in Recife, Brazil, strains of Vibrio were isolated from 55 (1.7). The study was carried out from May 1989 through May 1991. For recovering Vibrio, fecal samples were enriched in alkaline peptone water supplemented with 2 NaCl and subcultured on thiosulfate-citrate-bile salts-sucrose agar (TCBS). Of the recovered species, V. parahaemolyticus was most commonly found (24 strains), followed by V. furnissii (15 strains), V. cholerae non-01 (6 strains), V. alginolyticus (4 strains), V. fluvialis (2 strains), and Vibrio sp. (1 strain). The low isolation rate of Vibrio raises doubts about the cost-effectiveness of the use of TCBS in the routine enterobacteriologic workup of clinical laboratories.

Chemical constituents of Simarouba versicolor

From the roots, stems and fruits of Simarouba versicolor (Simaroubaceae) were isolated quassinoids (3, 5-7), triterpenoids (8-14), a mixture of steroids (15-17), the flavonoid kaempferol (18) and the squalene derivative 11,14-diacetoxy-7,10; 15,18-diepoxy-6,19-dihidroxy-6,7,10,11,14,15,18,19-octahydrosqualene (19). Spectral data were used for structural characterization

Atividade comparativa do trimetoprim e trimetoprim associado ao sulfametoxanol sobre 130 linhagens bacterianas obtidas de urinoculturas / Comparative antibacterial activity of trimethoprim and trimethoprim combined with sulfamethoxazole on 130 bacterial strains from urinary cultures

Estudou-se a atividade antimicrobiana do trimetoprim e do sulfametoxazol isoladamente e em combinaçäo, contra 130 linhagens bacterianas obtidas de urinoculturas. Independentemente da espécie bacteriana, observou-se significativa sinergia na maioria dos casos, inclusive naqueles em que houve resistência a uma das drogas. Esses resultados sugerem que o trimetoprim deva ser usado em associaçäo com o sulfametoxazol no tratamento das infecçöes das vias urinárias