Phase I trial of DNA-hsp65 immunotherapy for advanced squamous cell carcinoma of the head and neck.

Considering that mycobacterial heat-shock protein 65 (hsp65) gene transfer can elicit a profound antitumoral effect, this study aimed to establish the safety, maximum-tolerated dose (MTD) and preliminary efficacy of DNA-hsp65 immunotherapy in patients with advanced head and neck squamous cell carcinoma (HNSCC). For this purpose, 21 patients with unresectable and recurrent HNSCC were studied. Each patient received three ultrasound-guided injections at 21-day intervals of: 150, 600 or 400 microg of DNA-hsp65. Toxicity was graded according to CTCAE directions. Tumor volume was measured before and after treatment using computed tomography scan. The evaluation included tumor mass variation, delayed-type hypersensitivity response and spontaneous peripheral blood mononuclear cell proliferation before and after treatment. The MTD was 400 microg per dose. DNA-hsp65 immunotherapy was well tolerated with moderate pain, edema and infections as the most frequent adverse effects. None of the patients showed clinical or laboratory alterations compatible with autoimmune reactions. Partial response was observed in 4 out of 14 patients who completed treatment, 2 of which are still alive more than 3 years after the completion of the trial. Therefore, DNA-hsp65 immunotherapy is a feasible and safe approach at the dose of 400 microg per injection in patients with HNSCC refractory to standard treatment. Further studies in a larger number of patients are needed to confirm the efficacy of this novel strategy.

[Applied anatomy of the superior laryngeal nerve and surgical prophylactics of its lesions].

The article gives a brief historical reference on the discovery and investigation of the superior laryngeal nerve, the anatomical and clinical exploration of its topography, physiology and pathophysiology, as well as main variants of the correlations of the external branch of the nerve and the superior thyroid artery. The importance of superior laryngeal nerve is shown in the voice-forming function of the larynx. The incidence and main methods of prevention of intraoperative lesions of the nerve are described. The authors consider the potentials of clinical and instrumental diagnostics, as well as the effectiveness of treatment of traumas of the exterior branch of the superior laryngeal nerve during surgery for diseases of the thyroid gland.

The importance of the ligation of the inferior thyroid artery in parathyroid function after subtotal thyroidectomy.

UNLABELLED: We prospectively studied the effects of the ligation of the inferior thyroid artery (ITA) on postoperative hypoparathyroidism in 48 patients who underwent functional subtotal thyroidectomy. Patients were randomized into two groups: A, with bilateral ligation of the ITA and B, without ligation of the ITA. Parathyroid function was checked preoperatively and after surgery by clinical examination and measurement of total calcium, intact PTH, urinary calcium, and AMPc. RESULTS: A significant incidence of postoperative hypocalcemia occurred: 17% in group A and 13% in B on the 4th postoperative day. Six months later, the incidence was 5% in Group A and 0% in Group B. These differences were not statistically significant between the two groups, and neither were any of the other clinical and laboratory observations. CONCLUSION: The ligation of the ITA was not an important causal factor for the occurrence of postoperative hypocalcemia after subtotal thyroidectomy.

[Cervical perforating foreign body: case report]. / Corpo estranho perfurante cervical: relato de caso.

BACKGROUND: Neck perforations by foreign bodies are uncommon. The surgical approach depends on the extension of visceral wounds and the development of cervical or mediastinal infection. PURPOSE: The objective of this paper is to report a neck perforation trauma by a piece of wire, with associated laryngeal and hypopharyngeal wounds and extensive cervico-mediastinal emphysema. Anatomic and clinical correlations are discussed, as well as the management of the case. MATERIAL AND METHODS: A 28-year-old male patient suffered a perforating trauma in his neck by a piece of wire. This foreign body was laid in the retropharyngeal space, at the level of the sixth cervical vertebra, after perforating the larynx and hypopharynx. There are no similar cases previously reported. The imaging tests are presented. Despite the potential severity of the lesions, the patient had a favorable outcome, and no surgical approach was necessary. CONCLUSIONS: This case illustrates, by the imaging tests, the complex anatomy of the cervical fasciae and deep neck spaces, and confirms the possibility of conservative management in a great number of laryngeal and hypopharyngeal traumatic lesions.

Corpo estranho perfurante cervical: relato de caso / Cervical perforating foreign body: case report

As perfurações cervicais por corpos estranhos são incomuns. Sua abordagem cirúrgica depende do grau de lesão das vísceras cervicais e do desenvolvimento de sinais e sintomas de infecção cérvico-mediastinal. OBJETIVO: O presente artigo objetiva registrar a ocorrência de trauma perfurante cervical por fragmento de arame com lesão de laringe e hipofaringe dando origem a extenso enfisema cérvico-mediastinal. Correlações anátomo-clínicas e a conduta adotada são discutidas MATERIAL E MÉTODOS: O caso relatado é o de um indivíduo de 28 anos, do sexo masculino, vítima de ferimento perfurante na região cervical anterior por fragmento de arame. O corpo estranho assestou-se no espaço retrofaríngeo do doente, ao nível da 6a vértebra cervical, após perfurar a laringe e a hipofaringe. Não há caso semelhante relatado na literatura. A documentação radiológica do caso é apresentada. Apesar da potencial gravidade das lesões, o doente evoluiu bem e não necessitou de tratamento cirúrgico. CONCLUSÕES: O caso em questão, além de ilustrar, através dos exames de imagem, a complexa anatomia das fáscias e dos espaços cervicais profundos, demonstra a possibilidade da aplicação do tratamento conservador em grande parte das lesões traumáticas de laringe e hipofaringe.

Study of immunohistochemical expression of insulin-like growth factor I and proliferating cell nuclear antigen in thyroid gland papillary carcinoma and its metastasis.

BACKGROUND: Several tumor factors are associated with papillary thyroid cancer. Most studies do not compare the expressions of these factors in the primary tumors and in their associated cervical metastasis. METHODS: Paraffin sections of 20 patients with papillary carcinoma of the thyroid gland with lymph node metastasis were studied. The presence and distribution of insulin-like growth factor I (IGF-I) and proliferating cell nuclear antigen (PCNA) was analyzed, through immunohistochemical technique, in both primaries and lymph node metastasis. The results were correlated with clinical-pathologic data (sex, age, size of primary, multicentricity, thyroid capsule invasion, lymphatic and blood vessels invasion, development of distant metastasis, and associated thyroid diseases). RESULTS: The qualitative analysis showed the reaction for IGF-I was present in more than 90% of the neoplastic cells in both primaries and lymph node metastasis. No correlation with the clinical-pathological features was observed. Regarding the PCNA, the mean percentage of nuclei stained showed no statistical difference between primaries and metastasis (p = 0.598). Except for age, clinicopathologic data had no influence on the mean percentage of nuclei stained. A correlation was verified between the percentage of cells stained by PCNA in primary tumors and the patients' age (p < 0. 01). CONCLUSIONS: The expressions of these tumor factors are equally intense for both primary and metastatic tissue in papillary thyroid cancer. Despite the small size of the sample, the expressions of IGF-I and PCNA could not be associated to clinical-pathologic features, except for the age. As patients over 40 years old had higher expression of PCNA, this marker may have prognostic significance for patients with papillary thyroid cancer.

Galeal pedicle flap of the occipital region for pharynx reconstruction: anatomic and clinical considerations.

Surgeons are still searching for the ideal method for pharynx reconstruction after tumor ablation. The objective of this study was to prove the anatomic and clinical viability of an occipital galeal pedicle flap for hypopharynx reconstruction. We studied anatomic details in 50 fresh adult cadavers. The dissections were performed after posterior galea exposure, silicone injection in occipital vessels, and mobilization of the galeal flap with an 8 x 8 cm square of galea. We also used the proposed flap in three clinical cases after laryngopharyngectomy. The surgical technique and its problems are described. Some of the anatomic data obtained are as follows: occipital artery diameter, 2.69 mm (mean); occipital artery length, 134.25 mm; area of occipital vessels network on galea, 148.77 cm2; pedicle length, 116.63 mm; and success in rotation to pharynx region (100 percent). The flap showed good functional and cosmetic results when used in three patients. A partial necrosis occurred in one case. The pedicled galeal occipital flap has favorable anatomic characteristics for use in head and neck reconstruction. Additional studies are necessary to provide more substantial information about its clinical viability.

[Parathyroid cyst: case report]. / Cisto de paratireóide: relato de caso.

Parathyroid cysts are very uncommon lesions, with about 200 cases in the literature. Differential diagnosis is difficult, particularly with thyroid mass and symptoms of cervical compression and hyperparathyroidism are described. We present a case in which the diagnosis was intraoperative and discuss the treatment of this unusual disease.

Osteogaleal pedicle flap of the occipital region for head and neck reconstruction--anatomic study.

OBJECTIVE: This study was conducted to assess the anatomic viability of an occipital osteogaleal pedicle flap for head and neck reconstruction. DESIGN: Anatomic study in cadavers. METHOD: We studied anatomic details in 50 fresh adult cadavers (100 sides). The dissections were realized after total posterior galea exposition, silicone injection of occipital vessels, and mobilization of the osteogaleal flap, with a 8 x 8-cm square of galea and a 2.5 x 7-cm rectangle of outer-table calvarial bone. RESULTS: Occipital artery obstruction = 4%; artery diameter = 2.69 mm (mean); occipital artery length = 134.25 mm (mean); occipital vein running close to the artery = 93%; area of occipital vessel network on galea = 148.77 cm2 (mean); thickness of outer-table bone graft = 6.07 mm (mean); pedicle length = 116.63 mm; and success in rotation to nose (82%), mandible (70%) and cricoid region (100%). CONCLUSIONS: We concluded that the pedicle osteogaleal occipital flap has favourable anatomic characteristics for its use in head and neck reconstruction.

Parathyroid carcinoma.

BACKGROUND: Parathyroid carcinoma is rare and represents 0.1% to 5% of the cases of hyperparathyroidism. New accounts are important to the understanding of these tumors. Experience in 9 cases is reported. METHODS: From 1970 to 1995, 10 patients with parathyroid carcinoma demonstrated by clinical course or pathologic features of malignancy were treated. The patient's clinical data, laboratory and imaging examinations, surgical findings, pathology, recurrences, and survival were analyzed. RESULTS: One male patient was excluded because of insufficient data. Average age was 51 years, with female:male ratio of 2:1. Average calcium level was 14,3 mg/dL. Palpable mass was found in 55%, bone disease in 89%, and renal disease in 78%. Four patients were reoperations. Five were operated on for hyperparathyroidism (1/tertiary). Capsular invasion was the most incident pathologic feature. Local recurrence occurred in 55%; neck node and bone metastasis in 11%, and lung in 33%. Two patients are alive and 5 died of disease. CONCLUSIONS: Parathyroid carcinoma has clinical and laboratory features that can help diagnosis at the first surgery. It seems to have variable malignancy.

[Incidence of oral cancer profile at a general hospital in Säo Paulo]. / Perfil de incidência do câncer oral em um hospital geral em São Paulo.

Cancer of the oral cavity are 4% of all cancers, being in 8th place in males and 11th in females. The world incidence in male sex is 7.9:100,000 and 2.2:100,000 in females. Squamous cell carcinoma is the most frequent, corresponding to 90-95% of the cases and tongue, lips and floor of the mouth are the most common sites. Fifty-four patients were surgically treated for cancer of the oral cavity in a General Hospital in São Paulo, during last ten years. It occurs more in males (81.5%), the age ranges of 35-97, with mean age of 58.1 years. Smoking was associated in 88.9%, at the time of treatment 50% of the patients had history of disease inferior of 6 months and 42% were T2 and 38% T4. These results agree with international literature and emphasize the importance of preventive aspects of this cancer.

Os espaços cervicais profundos e seu interesse nas infecçoes da regiäo / Deep neck spaces and their interest in cervical infections

As infecçoes dos espaços cervicais profundos, embora raras, associam-se a alta morbi-mortalidade. A abordagem cirúrgica faz-se necessaria na maioria dos casos e se baseia no conhecimento da complexa anatomia das fascias cervicais e dos espaços cervicais profundos. Objetivo. Apresentar consideraçoes anatomicas de interese pratico sobre fascias e espaços do pescoço, sua conceituaçao e nomenclatura, relatando, a título de exemplo, quatro casos de infecçoes dos espaços cervicais profundos. Material e Método. Sao apresentados um caso de angina de Ludwig complicada com mediastinite, pericardite, pneumonia, empiema pleural, fístula esofagica e choque séptico, um caso de abscesso cervical espontâneo em paciente diabético, um caso de abscesso de loja submandibular e um caso de abscesso parafaríngeo iniciado após manipulaçao dentaria. Nos quatro casos, a documentaçao imagenológica é rica e, em dois deles, evidencia o comprometimento de mais e um espaço profundo do pescoço. Conclusoes. A literatura enfatiza morbidade e mortalidade elevadas, etiologia diversificada (infecçoes dentarias, uso de drogas endovenosas, infecçoes do trato aerodigestivo alto e outras), a necessidade de traqueostomia em cerca de 50 por cento dos casos e o emprego da terapêutica combinada (antibioticoterapia e abordagem cirúrgica do pescoço). Os métodos imagenológicos, como a tomografia computadorizada, sao imprescindíveis no estudo de infecçoes dos espaços profundos do pescoço, tanto para a avaliaçao do sítio e extensao da afecçao, como para o planejamento terapêutico.

[Deep neck spaces and their significance in cervical infections]. / Os espaços cervicais profundos e seu interesse nas infecções da região.

BACKGROUND: Although rare, deep neck space infections are associated with high morbidity and mortality rates. The surgical approach is necessary in the majority of the cases, and the surgeon must know the complex anatomy of the cervical fasciae and deep neck spaces. PURPOSE: The anatomy of the cervical fasciae and deep neck spaces in reviewed. As an illustration, a series of deep neck space infections is presented. MATERIAL AND METHOD: Four clinical cases are reported: 1) a case of Ludwig's angina with several complications (mediastinitis, pericarditis, pneumonia, pleural effusion and empyema, esophageal fistula and septic shock), 2) a case of cervical abscess that appeared without apparent cause, in a young diabetic patient, 3) a case of abscess of the submandibular triangle, and 4) a case of parapharyngeal abscess that came forth after a dental treatment. Data from history taking, physical examination, X-rays, echography, CT scan and treatment and the follow-up are presented. The image tests were valuable and, in two of the cases, they demonstrated that more than one deep neck space were affected. CONCLUSIONS: The literature reinforces the high mortality and morbidity rates, the diversified etiology (dental infection, intravenous drug abuse, infections of the upper aerodigestive tract and others), and the tracheostomy indication made in about half of the cases. It stresses also the need for combined therapy (antibiotics and surgery). Evaluation with CT scan and other radiologic methods is indispensable to determine the site and extent of the process and to plan properly the treatment.

[Brain metastases from papillary thyroid carcinoma: a case report and review of the literature]. / Metástase cerebral de carcinoma papilífero de tireóide como apresentação inicial da doença: relato de caso e revisão da literatura.

Papillary carcinoma, the commonest thyroid malignancy, has a good prognosis and low incidence of distant metastases. Brain metastasis is extremely rare with a frequency of about 1% in reported series. In this paper we present the clinical details of one case of histologically proven brain metastasis from papillary thyroid cancer, first presented with neurological symptoms, initially treated with excisional biopsy and radiotherapy in other hospital, without clinical response. The patient was then referred to our service, where he underwent a total thyroidectomy and modified radical neck dissection, with the aim of posterior radioactive iodine treatment for the brain lesion. Unfortunately, he died of neurological complications, two months after the neck treatment. Also presented is a review of the literature of this unusual clinical presentation.

Squamous-cell carcinoma of the lower lip: a retrospective study of 58 patients.

The charts of 58 patients with squamous-cell carcinomas of the lower lip, treated at the General Hospital of the University of São Paulo Medical School from January 1980 to December 1989, were retrospectively analyzed. In addition to regular demographic data, all available information was collected regarding: smoking and drinking habits; sun exposure; clinical stage; macroscopic features of the primary lesions; type of treatment; and follow-up. A meticulous pathological analysis, comprising the histologic differentiation grade, maximal tumor thickness, sun elastosis, perineural spread, vascular and muscular invasion, surgical margins, peritumoral inflammatory infiltrate, and positive lymph nodes, with or without extracapsular spread, was undertaken as well. The evaluation of the overall 5-year survival showed significant statistical differences, with prognostic implications, for the following variables: maximal tumor thickness, T-stage and positive nodes.

Prospective study using skin staplers in head and neck surgery.

BACKGROUND: A prospective trial was undertaken to investigate the advantages and disadvantages of stapled skin closure versus conventional nylon sutures in head and neck surgery. PATIENTS AND METHODS: The study included 20 consecutive patients who underwent extensive surgery in which their skin was closed with staples. Another group of 20 matched patients receiving a noncontinuous nylon suture closure was followed in parallel. RESULTS: The complications recorded occurred in 5 patients in the stapled group and 3 in the sutured group. Analysis of cosmetic results showed 16 patients (80%) in the stapled group with good wound appearance and 17 (85%) in the sutured group. The mean closure time was 5 minutes for the stapled group and 25 minutes for the sutured group. Cost was $19.75 for conventional closure and $22.00 for mechanical suture. CONCLUSION: The use of skin staples speeds up closure time by 80%, yields similar cosmetic results with no increase in complications, although at a slightly higher cost.

Posterior trapezius myocutaneous flap.

Since last decade, myocutaneous flaps have appeared among the most versatile and safest options for the reconstruction of defects caused by large oncological resections, in the head and neck area. Undoubtedly, the myocutaneous flap of the pectoralis major muscle is the most widespread and accepted, due to the long experience obtained through its use. Nevertheless, it presents some restrictions related not only to its rotation arch, but also to the esthetic consequences for the donor site in females. Over the last years, there has been a growing interest in the posterior trapezius myocutaneous flap (PTMF), which proved to be a valuable alternative for reconstruction in selected cases. The experience of the Department of Head and Neck Surgery, at the University of São Paulo Medical School-Hospital das Clínicas, using this technique, is reported here in a detailed description.

Identification of the external branch of the superior laryngeal nerve during thyroidectomy.

Seventy-six patients underwent preoperative vocal evaluation and were randomized into 3 groups: (1) those with the superior thyroid pole dissected by the first author, with the external branch of the superior laryngeal nerve (EBSLN) identified by means of a nerve stimulator; (2) those patients whose dissection was executed by a resident, with no nerve search; and (3) those whose dissection was undertaken by the first author, without any nerve search. Postoperative analysis consisted of voice evaluation and electromyography of the cricothyroid muscle. No lesion occurred in patients in group 1. Twenty-eight percent of patients in group 2 and 12% in group 3 experienced a complete lesion of the EBSLN (p = 0.0123). When the patients in group 1 were compared with the patients with 62 nerves corresponding to nonoperated thyroid lobes, patients in group 1 exhibited no increased risk, whereas a significantly increased hazard was evident in both groups 2 (p = 0.0002776) and 3 (p = 0.0346393). In this study, effective prevention of iatrogenic EBSLN lesions during thyroidectomies was achieved only by the intraoperative identification of the nerve with the nerve stimulator.