A phase I/II study of paclitaxel plus cisplatin as first-line therapy for head and neck cancers: preliminary results.

Improved outcomes among patients with head and neck carcinomas require investigations of new drugs for induction therapy. Preliminary results of an Eastern Cooperative Oncology Group study of single-agent paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) reported a 37% response rate in patients with head and neck cancer, and the paclitaxel/cisplatin combination has been used successfully and has significantly improved median response duration in ovarian cancer patients. We initiated a phase I/II trial to determine the response and toxicity of escalating paclitaxel doses combined with fixed-dose cisplatin with granulocyte colony-stimulating factor support in patients with untreated locally advanced inoperable head and neck carcinoma. To date, 23 men with a median age of 50 years and good performance status have entered the trial. Primary tumor sites were oropharynx, 10 patients; hypopharynx, four; larynx, two; oral cavity, three; unknown primary, two; and nasal cavity and parotid gland, one each. Of 20 patients evaluable for toxicity, four had stage III and 16 had stage IV disease. Treatment, given every 21 days for a maximum of three cycles, consisted of paclitaxel by 3-hour infusion followed the next day by a fixed dose of cisplatin (75 mg/m2). The dose levels incorporate escalating paclitaxel doses, and intrapatient escalations within a given dose level are permitted if toxicity permits. At the time of this writing, dose level 4 (260, 270, and 280 mg/m2) is being evaluated; three patients from this level are evaluable. With paclitaxel doses of 200 mg/m2 and higher, granulocyte colony-stimulating factor 5 micrograms/kg/d is given (days 4 through 12). Of 18 patients evaluable for response, seven (39%) achieved a complete response and six (33%) achieved a partial response. Three patients had no change and disease progressed in two. The overall response rate is 72%. Eleven responding patients had subsequent surgery/radiotherapy or radical radiotherapy. Two pathologic complete responses were observed in patients who had achieved clinical complete responses. Alopecia, paresthesias, and arthralgias/myalgias have occurred frequently, but with one exception (a grade 3 myalgia) they have been grade 1 or 2. No dose-limiting hematologic toxicity has been seen. Paclitaxel/cisplatin is an effective first-line regimen for locoregionally advanced head and neck cancer and continued study is warranted. Results thus far suggest no dose-response effect for paclitaxel doses above 200 mg/m2.

Phase I/II study of paclitaxel/cisplatin as first-line therapy for locally advanced head and neck cancer.

A phase I/II study was conducted to determine the response rate and the toxicity of escalating doses of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) plus cisplatin with granulocyte colony-stimulating factor support in patients with untreated advanced head and neck carcinoma. Twenty-eight patients with locally advanced inoperable squamous cell head and neck carcinoma were included. Median age was 51 years. Karnofsky performance status was > or =90% in all patients. Primary tumor sites were oropharynx, hypopharynx, larynx, oral cavity, parotid gland, nasal cavity, and unknown primary. We observed 13 complete responses, eight partial responses, four patients with stable disease, and two patients with progressive disease for an overall response rate of 78%. Toxicity was paresthesia grade 1/2 in 27 patients, and myalgias were grade 1/2 in 23 patients and grade 3 in four patients. One patient died 5 days after the first cycle due to acute renal failure, respiratory distress, and pancytopenia. No dose-limiting hematologic toxicity has been observed, and intrapatient escalations were performed in all patients when planned. Calculated dose intensity for the two drugs was 100% in all evaluable patients. The combination of escalating doses of paclitaxel 175 to 300 mg/m2 and cisplatin 75 mg/m2 was active in untreated head and neck carcinoma, with an overall response rate of 78%. No dose-limiting toxicity has been encountered at paclitaxel doses up to 300 mg/m2 given with granulocyte colony-stimulating factor.

Nitric oxide synthase activity in human squamous cell carcinoma of the head and neck.

OBJECTIVES: To test whether nitric oxide synthase (NOS) is expressed in primary otolaryngologic tumors and whether this expression is associated with the degree of malignancy. STUDY DESIGN: Twenty-six samples from the primary localization of human pharyngolaryngeal squamous cell carcinoma. MATERIALS AND METHODS: the activity of calcium-dependent and calcium-independent NOS was analyzed by the conversion of L-[14C]-arginine into L-[14C]-citrulline. RESULTS: NOS activity is below detectable levels in pharyngolaryngeal mucosa from noncancer patients. In the primary localization of the tumor, calcium-independent NOS activity is maximal at early stages of tumor growth, whereas calcium-dependent activity increases from early to advanced stages. CONCLUSIONS: These data suggest that tumor growth and malignancy is associated with a change in the enzymatic source of NO from calcium-independent NOS to calcium-dependent NOS isoform in primary localization. These data suggest that the inhibition of calcium-independent NOS activity in early stages and/or inhibition of calcium-dependent NOS activity in later stages could delay growth of solid tumors.

p53 expression in locally advanced pharyngeal squamous cell carcinoma.

BACKGROUND: Prognosis for advanced head and neck squamous cell carcinoma remains poor despite advances in treatment, although a small number of patients may benefit from induction therapy leading to increased local control. Mutations of the p53 gene, which are present in a considerable percentage of head and neck squamous cell carcinomas, have been associated with poor response to chemotherapy. The role of p53 protein overexpression (which is associated with p53 gene mutations) in predicting the response to chemotherapeutic agents and survival rates is not clear. OBJECTIVE: To determine the association of p53 expression with chemotherapy response rates and disease-free survival rates in 62 patients with locally advanced pharyngeal cancer treated with induction cisplatin-5-fluorouracil chemotherapy between 1983 and 1995. DESIGN: Historical cohort. Archival tissue from biopsies done before chemotherapy was immunohistochemically stained for the p53 tumor suppressor gene (clone D0-7; DAKO Corp, Glostrup, Denmark). RESULTS: Positive staining for p53 occurred in 45 (73%) of 62 cases, with the percentage of reactive cells ranging from 35% to 98%. Chemotherapy response rates were higher in the p53-negative group (15/17 [88%]) compared with the p53-positive group (27/45 [60%]) (P =.07). The risk of recurrence was lower in the p53-negative group compared with the p53-positive group at 2, 3, and 5 years after treatment (P = .03, P = .01, and P = .007, respectively). The median relapse-free survival rates of patients in the p53-negative group was 16 months, whereas those with p53 protein expression demonstrated a median relapse-free survival time of 9 months (P = .07). In multivariate analyses, the only independent factor of relapse-free survival rates was age older than 70 years. CONCLUSION: The present study shows a trend favoring p53 overexpression as a predictive and prognostic factor in locally advanced pharyngeal cancer treated with induction chemotherapy.

Pediatric tonsillectomy: post-operative morbidity comparing microsurgical bipolar dissection versus cold sharp dissection.

A prospective single-blinded study was conducted to compare pediatric tonsillectomy using the traditional cold sharp dissection with ligation for securing hemostasis (CSDL) versus microsurgical bipolar dissection technique (MBCT). Sixty children aged between 2 and 14 years were sequentially assigned to each group. Blood loss and postoperative pain in the first hour were markedly decreased in the MBCT group (P < 0.0001 and P < 0.05, respectively). Average surgical time was slightly decreased in diathermy tonsillectomy (15'30") compared with the cold technique (16'30"). Return to normal diet was significantly earlier in the CSDL group (P < 0.05). Late postoperative pain measured on the tenth day showed a moderate increase in children who underwent MBCT. There was no difference between the two techniques in the incidence of postoperative hemorrhage. No major complications occurred. We believe MBCT is a fast and safe technique which may be useful in children with known bleeding disorders. However, it increases late postoperative pain and, therefore, delay in patients' return to normal activities. Consequently, it does not represent a significant advantage over the traditional CSDL procedure.

Ultrastructural diagnosis of facial nerve schwannoma using fine needle aspiration.

In a 14-year-old boy presenting with left facial nerve paralysis, physical examination revealed a soft, round mass in the floor of the left external auditory canal. A fine needle aspiration biopsy was performed to obtain material for light and electron microscopy. Several small groups of uniform, spindle-shaped neoplastic cells were present on the slides; a malignant mesenchymal tumor was considered, but a definite diagnosis could not be established under light microscopy. The ultrastructural examination revealed spindle-shaped and stellate cells with multiple parallel cytoplasmic processes lined with a well-developed basal lamina; these features are highly characteristic of a benign schwannoma.

Salivary gland heterotopia in the lower neck: a report of five cases.

Heterotopic salivary gland tissue (HSGT) represents an uncommon lesion, usually presenting as a discharging sinus in the base of the neck. Diagnostic criteria and embryogenesis of this entity still remain unclear. For the purpose of clarifying both subjects, all lateral cervical anomalies undergoing surgery during a 12-year period were examined. Histological study showed salivary tissue in 10 out of 119 patients. However, only 5 of them accomplished HSGT criteria. This study presents the second largest series to date of undisputed HSGT in the lower neck. Both accessory glands and branchial cleft anomalies should be distinguished from this lesion. Neoplastic transformation in HSGT, although extremely rare, should also be considered.

Immunoreactivity in granular cell tumours of the larynx.

OBJECTIVE: To elucidate histogenesis and behaviour of laryngeal granular cell tumours (GCT) and to determine the role of p53 protein expression in these lesions. METHODS: The clinical, pathological and immunohistochemical findings of three cases of laryngeal GCTs are described. RESULTS: All tumours were surgically excised and appeared histologically benign. Pseudoepitheliomatous hyperplasia, mitosis and nuclear pleomorphism were not found in any of the three cases. All lesions were negative for keratin 8, desmin and actin. Only one case stained for collagen IV. Positive staining was found for S-100 protein and CD68 in all tumours. Ki-67 and Bcl-2 staining was confined to occasional cells. p53 reactivity was seen in all tumours; positivity ranged from 35 to 42%. The three patients have remained free of disease without complications up to 10 years after treatment. CONCLUSION: Immunohistochemical findings support benign behaviour and a Schwann cell origin for laryngeal GCT. The expression of p53 by granular cells is unclear but appears to be unrelated to behaviour.

[Functional laryngectomy using a technic of subperichondrial laryngeal curettage]. / Laryngectomie fonctionnelle selon la technique de l'évidement sous-périchondral du larynx

A new technique of functional laryngectomy using sub-perichondral curettage of some or all of the soft parts of the larynx is described. This method has an embryological and anatomical basis. It is supported by a score of cases which have had a satisfactory outcome, all the patients operated on having been decannulated. Histopathological research was continued with a view to confirming the function of the perichondrium and the cartilage as a barrier to neoplastic invasion.

[Adenosquamous carcinoma of minor salivary glands. Reporting a case in the tongue]. / Carcinoma adenoescamoso de glándulas salivares menores. Exposición de un caso de localización lingual.

Adenosquamous carcinoma of the salivary glands is an unusual neoplasm not unanimously included in many classifications of salivary gland malignancies. A case sited in the oral cavity, within the tongue is reported. Clinical and histopathologic features are described together with a discussion about treatment and behaviour. We also include an updated of literature relating to this entity.

[Adjuvant chemotherapy in the treatment of pharyngolaryngeal cancers in advanced stages]. / Tratamiento quimioterápico adyuvante en carcinomas laringo-faríngeos en estadios avanzados.

Since 1980 we use adjuvant chemotherapy in advanced laryngopharyngeal carcinomas. These cases were resectable and unresectable lesions with tumoral extent to the pharynx as a common characteristic. We analyze the survival of the first 50 cases treated with chemotherapy followed by: A) surgery and radiotherapy (36 cases) and B) radiotherapy alone (14 cases). Results of this not randomized study are compared with a historic group of advanced laryngopharyngeal carcinomas (T4/N+) treated with conventional therapy (surgery +/- radiotherapy). Response to chemotherapy was complete or partial (> 50% reduction) in 56 percent of the patients. There was improvement in overall survival and five-years disease-free survival in the latter group compared with those who did show any response (p < 0.01). We would point out that disease-free survival of the group A was better than historic group (60% vs 36%, p < 0.05), although these result should be carefully interpreted. Laryngeal preservation was achieved in 47 percent in the group A by modification of the initially scheduled radical surgery, in selected cases.

[Follow-up and evaluation using brain-stem evoked potentials of a pediatric population diagnosed as premature]. / Seguimiento y valoración mediante potenciales evocados de tronco cerebral de una población pediátrica diagnosticada de prematuridad.

We study 65 patients coming from neonatology service with a diagnostic of prematurity and we test of audiometric level with brain stem response audiometry during three years, giving importance to the clinics characteristics that have affected during the story in the hospital. We diagnose hearing loss in a 41% of the patients, and in one case (5.88%) is retrocochlear (17.6%) as with no valuable. After three years only one patient presents persistent hearing loss; while in the first exploration 17 are considered pathologics. The prematurity by itself and without others clinic factors doesn't involve an important risk in the generation of hypoacusy.

[Modifications of the technic of endolaryngeal extirpation. The author's own functional technic of laryngectomy]. / Modificaciones a la técnica del vaciado endolaríngeo. Técnica personal funcional de laringuectomía.

A brief summary of the original technique will be made incorporating the following modifications and additions: glottis substituted by neoglottis muscles, sternohyoid or external perichondrium. Supraglottis substituted by remaining tissues of the epiglottis or neoepiglottis. Hypopharynx, section medium line of the pharynx constrictor. Suturing of cartilage with homologous donor cartilage. An evaluation will be made of the functional results.

[Follow-up and evaluation by means of brain stem evoked potentials of a pediatric population diagnosed as having had fetal distress]. / Seguimiento y valoración mediante potenciales evocados de tronco cerebral de una población pediátrica diagnosticada de sufrimiento fetal.

A population of 80 patients affected with foetal distress is analyzed classifying it according to a qualitative variable (Apgar test) to which we assigned three category levels: normal/low/very low; and a quantitative variable, the pH from the umbilical artery being more or less than 7.15. We also studied all the clinical variables and complications derived from the base illness and their relationship. Four subpopulations were established which were studied by means of brain stem potential audiometry over 3 years, establishing that in those patients whose pH is less than 7.15 and their Apgar test is low/very low there exists a very high incidence of hypoacusis, characterized as sensorineural in 13.3%, conductive in 13.3%, not classifiable in 60%, and retrocochlear in 13.3%. There was a tendency to improve in 26.6%. Four of the 24 patients that are in this group wear an auditory prosthesis as an indication of the important damage suffered. There is no relationship in our study between the hypoacusis and the tests of the clinical variables which confirms the foetal distress.

[Branchial cysts with heterotopic salivary tissue in the upper third of the neck]. / Quistes branquiales con tejido salival heterotópico en el tercio superior del cuello.

The presence of heterotopic salivary gland tissue (HSGT) in rather uncommon in the neck. Usually it has been located in its lower third. HSGT in the upper neck is believed to be a rare entity. Two cases of HSGT in the upper neck are presented, with a review of their clinical and histopathological characteristics. The embryologic derivation of salivary tissue and close association with the branchial apparatus are discussed. The possibility of neoplastic transformation must always be considered in these uncommon lesions.

[Extra-naso-pharyngeal angiofibroma: report of a new case and review of literature]. / Angiofibroma extranasofaríngeo: aportación de un nuevo caso y revisión bibliográfica.

Juvenile nasopharyngeal angiofibromas are vascular neoplasms, which originate characteristically in the posterior lateral wall of the nasopharynx. Although angiofibromas extend beyond the nasopharynx commonly, sometimes they can have their origin outside nasopharynx. We present an unusual case of extranasopharyngeal angiofibroma. A high level of suspicion is essential for an adequate diagnosis and treatment of these neoplasms.

[Detection of p53 protein in advanced head and neck cancer]. / Detección de proteína p53 en tumores avanzados de cabeza y cuello.

P53 protein expression, synonymous to p53 gene mutation, is a common event in head and neck squamous cell carcinoma (HNSCC). However, the correlation between p53 expression and clinico-pathologic parameters remains unclear. Primary tumors for analysis were obtained from 99 patients with HNSCC. The expression of p53 was analyzed with monoclonal D07 antibody (Dako Corp., Glostrup, Denmark). Seventy five percent of 79 valid cases expressed the protein. A correlation was found between alcohol intake and p53 expression. None of the other clinico-pathologic factors were associated to p53 expression. Our results suggest that p53 may be involved in the development of HNSCC. However its clinical significance is still not completely understood.

[An unusual complication of esophageal foreign body]. / Complicación inusual de un cuerpo extraño esofágico.

Esophageal foreign bodies must be carefully managed because they carry a high risk of potentially severe complications. A case of a sharp foreign body located in a previously unsymptomatic pharyngoesophageal diverticulum is described. The management protocol for esophageal foreign bodies is reviewed. Fiberesophagoscopy is the therapeutic technique of choice, but it may be dangerous if patients are not selected properly.

[Incidence and treatment of otitis with effusion in patients with cleft palate]. / Incidencia y tratamiento de la otitis seromucosa en pacientes con fisura palatina.

We evaluated 40 children with cleft palate repaired, between 1990 and 1995. Treatment was myringotomy and insertion of a tympanostomy tube, followed by monitoring. In this retrospective study of 40 children aged 8 to 48 months, the prevalence of otitis media with effusion was 84.8%. The condition was persistent in 17.6% of children up to 3 years of age after treatment. Audiological thresholds were evaluated with BERA one or more times. Hearing acuity improved after so, therefore we propose it as the best strategy for ensuring adequate hearing for language development while minimizing morbidity (incidence of complications = 14.7%).

[The inverted ipsilateral reflex: is it an artefact?]. / El reflejo invertido ipsilateral: es un artefacto?

We have studied the characteristics of the inverted reflex obtained by ipsilateral stimulation in nineteen patients. Six of them were affected by perceptual hypoacusis, eleven of those patients had an otosclerosis and two a facial paralysis. The conclusion about our investigation is that in all the cases, it was produced by an artefact and it was not a response from the muscles of the middle ear.