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Biomedical subjects

J P Rodrigo

Publications and source records attributed to J P Rodrigo.

At least 19 recordsLinked to original sources

[Orthotopic murine model of head and neck squamous cell carcinoma].

PURPOSE: To develop a reliable animal model able to reproduce the behavior of head and neck squamous cell carcinomas (HNSCC). This model should facilitate our understanding of the molecular mechanisms of tumorigenicity and progression of these tumors, as well as the evaluation of novel therapies. MATERIAL AND METHODS: 20 nude mice nu/nu were injected intraorally and submucosally with a cell line derived from a human squamous cell carcinoma of the glottis. RESULTS: 90% of the mice developed locally agressive squamous cell carcinomas, invading the surrounding muscle fibers and into loose connective tissue structures. All the tumors showed perineural growth. Four (22%) of the 18 mice showed bone destruction, and 22% vascular invasion. Tumor cells invaded lymphatic vessels in all the specimens, and 100% of the mice developed regional lymph node metastases. None of the animals developed haematogenous metastases. CONCLUSIONS: We present a metastasing model of HNSCC that resembles its human counterpart in many aspects.

Animals↗

[Functional outcomes of transoral laser surgery of supraglottic carcinoma].

OBJECTIVES: To analyse the functional outcome of patients with supraglottic carcinomas treated by transoral laser surgery. METHODS: The clinical records of 55 patients who underwent transoral laser surgery were reviewed. Swallowing capacity, surgical complications, requirements for tracheotomies, percentage of decannulations, laryngeal paralysis, stenosis, aspiration associated pneumonia, time to remove the nasogastric tube and postsurgical stay in hospital were the studied variables. RESULTS: 52% of the patients had a normal or within functional limits swallowing performance. 18% suffered aspiration pneumonia. 13% developed a laryngeal stenosis. 7% suffered of laryngeal palsy. 18 tracheostomies were performed, of them 10 could be reverted. The mean time to remove the nasogastric tube was 9 days. The mean hospital stay was 23 days. CONCLUSIONS: The main functional advantages of transoral laser surgery for supraglottic carcinoma, when compared with the conventional approach, are a lower incidence of temporary tracheotomies, a faster removal of the nasogastric feeding tube, and a lower incidence of pharyngocutaneous fistulas (0%).

Adult↗

[Efficacy of postoperative radiation therapy for squamous cell carcinoma of the head and neck: results of a prospective randomised clinical trial].

INTRODUCTION: A prospective randomised clinical trial was designed to assess the usefulness of postoperative radiotherapy (RT) in terms of loco-regional control and survival in patients with surgically treated advanced (stages III to IV) head and neck squamous cell carcinoma with negative margins and without extracapsular extension in positive neck nodes. MATERIALS AND METHODS: Between 1994 and 1995, 51 patients were included in the study and 42 were considered evaluables (from which 21 received postoperative RT). A minimum follow-up of 3 years was required. RESULTS: The loco-regional recurrence rates were identical in irradiated and non-irradiated patients (15/21 cases--70%--in each group), as was the 5-year disease-specific survival (35% for both groups). The only parameter that was associated with a reduced disease-specific survival was the presence of regional lymph node metastases. CONCLUSION: Our results suggest that postoperative RT does not increase loco-regional control or survival in patients with completely resected advanced head and neck squamous cell carcinoma.

Carcinoma, Squamous Cell↗

[Nasal polyposis: postoperative long term results (5 years) after endoscopic sinus surgery].

The purpose of this study is to evaluate the results after endoscopic sinus surgery in cases of nasal polyposis. We include 54 patients with diffuse nasal polyposis suffering from nasal obstruction. An endoscopic sinus surgery under general anesthesia with excision of the polyposis was performed. There were no complications. The patients were followed closely and treated with local and systemic steroids. After 5 years, the 75% of these patients were free of nasal symptoms and in the 67% the mucosa appeared normal. We also review the influence of some factors (ASA triad, anosmia, allergy...) in the recurrence of the disease.

Adult↗

Expression of E-cadherin in squamous cell carcinomas of the supraglottic larynx with correlations to clinicopathological features.

The aim of this study was to investigate the prognostic significance of E-cadherin expression in squamous cell carcinomas of the supraglottic larynx. 101 primary carcinomas were retrospectively studied. The level of E-cadherin expression was determined by immunohistochemistry. There was a significant correlation between decreased E-cadherin expression and the presence of nodal metastases (P=0.007). T-stage (P=0.025) and histological grade (P=0.043) were also associated with nodal metastases. Multivariate analysis confirmed that these three parameters were independent predictors of nodal metastases. Decreased E-cadherin expression also correlated with an increase in recurrence rates (P=0.019). However, in multivariate analysis only pathological N-stage was significantly associated with disease-specific survival. We conclude that E-cadherin is an independent predictor of nodal metastases in supraglottic squamous cell carcinomas. Determination of E-cadherin expression levels might be useful in identifying patients with clinically negative lymph nodes who are at risk of occult metastases, allowing more effective treatment strategies to be implemented.

Biomarkers, Tumor↗

P53 allelic loss and outcome in patients with squamous cell carcinoma of the head and neck.

Although loss of heterozygosity (LOH) on the p53 locus is frequent in squamous cell carcinomas of the head and neck (SCCHN), controversy still remains regarding the prognostic significance of such an event. Eighty consecutive SCCHN were studied. DNA was extracted from matched sets of normal and tumour tissue and used for polymerase chain reaction amplification of microsatellite markers located in the p53 locus. LOH at the p53 locus was found in 39 (70%) of the 56 informative cases. No relationship was found between p53 LOH and age, site, T stage, N stage, disease stage, and histological differentiation. Recurrence occurred in 53% of the cases with LOH and in 58% of the cases without it (P = 0.28). Moreover, no statistically significant association was found between p53 LOH and disease-specific survival (log-rank P = 0.98). These data suggest that although LOH at the p53 locus is common in SCCHN, this finding is of little clinical significance.

Carcinoma, Squamous Cell↗

Variability of genetic alterations in different sites of head and neck cancer.

OBJECTIVE: Tumors arising from different sites of the head and neck area have different clinical behavior. However, most of the studies on genetic alterations in head and neck squamous cell carcinomas do not make a distinction between the sites within this area. The objective of this study is to compare the genetic alterations in three different sites of the head and neck (larynx, oropharynx, and hypopharynx). STUDY DESIGN: Prospective study. METHODS: Thirty-eight laryngeal, 29 oropharyngeal, and 37 hypopharyngeal carcinomas were studied. DNA from tumor and healthy tissue was evaluated for amplification of the oncogenes at 11q13 region (CCND1, FGF3, FGF4 and EMS1) and of the oncogenes MYC and ERBB1; for integration of the human papillomavirus (HPV) types 6b and 16; for loss of heterozygosity (LOH) at p53 and NAT2; and for the cellular DNA content. RESULTS: FGF3 and FGF4 showed a significantly higher frequency of amplification in hypopharyngeal tumors (P =.006 and P =.0002, respectively). CCND1 amplification had a nearly statistically significant (P =.072) higher frequency of amplification in hypopharyngeal tumors. Aneuploid tumors were found in a significantly lower proportion in the larynx (P =.03) compared with the other sites. For the other genetic alterations, no significant differences among the three sites were found. CONCLUSIONS: These results suggest that cancers originating from different sites in the head and neck may have different tumor biology. Therefore, they should be considered as different entities.

Aneuploidy↗

EMS1 gene amplification correlates with poor prognosis in squamous cell carcinomas of the head and neck.

The relationship between CCND1 and/or EMS1 amplification and disease outcome was studied in a prospective series of 104 head and neck squamous cell carcinomas treated by surgical resection. The CCND1 and EMS1 copy number in tumor samples was estimated by differential PCR. The presence or absence of amplification was analyzed in relation to clinicopathological variables, tumor recurrence, and patient survival. CCND1 amplification occurred in 32 cases (31%) and was associated with increased lymph node stage (P = 0.005) and advanced disease stage (P = 0.003). EMS1 amplification was identified in 21 cases (20%) and was related with advanced T stages (P = 0.001), increased lymph node stage (P = 0.02), advanced disease stage (P = 0.041), poor histological differentiation (P = 0.018), recurrent disease (P = 0.0004), and reduced disease-specific survival (P < 0.0001). Coamplification of both genes occurred in 11 cases (11.5%). Multivariate analysis confirmed that in addition to regional lymph node status, EMS1 amplification is an independent predictor of death from the tumor (P = 0.0027). CCND1 amplification was not prognostic. These data indicate that EMS1 amplification, but not CCND1 amplification, predicts early recurrence and reduced survival in squamous cell carcinoma of the head and neck. The prognostic significance previously attributed to CCND1 amplification may be attributable to its frequent coamplification with EMS1.

Carcinoma, Squamous Cell↗

Relationship of human papillomavirus to ploidy in squamous cell carcinomas of the head and neck.

To establish the relationship between the presence of human papillomavirus (HPV) gene sequences and the development of genetic abnormalities, 31 squamous cell carcinomas of the head and neck were studied for the presence of HPV types 6b and 16 and the DNA content by flow cytometry. Eighteen (58%) cases were aneuploid. HPV DNA was present in seven (22.5%) tumors. Five of them were positive for the HPV type 6b and two for the HPV type 16. Aneuploidy was correlated with poorly differentiated tumors. No correlation was found between the presence of HPV, DNA content, or tumor differentiation. Consequently, the presence of HPV gene sequences does not seem to be related to a higher incidence of genetic abnormalities in squamous cell carcinomas of the head and neck.

Adult↗

Prognostic significance of postoperative wound infection on head and neck cancer.

The prognostic significance of wound infections after surgery for squamous cell carcinoma of the head and neck is controversial. We retrospectively studied the relationship between wound infection, tumor recurrence, and survival rates in 158 patients operated on for supraglottic cancer. All patients had 3-year follow-up. Wound infection developed in 14 patients (8.8%). The overall recurrence rate was 29.7%. For those in whom a wound infection developed the recurrence rate was 57%, compared with 27% for those in whom no such infection developed (p = 0.041). Disease-free survival was also adversely affected in the group of patients with infections, although because of the limited number of patients the differences did not reach statistical significance. We conclude that postoperative wound infection may have an adverse effect on prognosis in squamous cell carcinomas of the head and neck.

Adult↗

Metastatic squamous cell carcinoma in cervical lymph nodes from an unknown primary tumour: prognostic factors.

The aim of this retrospective review is the study of the prognostic factors related to cervical metastases of squamous cell carcinoma from an unknown primary tumour. Sixty-seven patients were selected and surgery and postoperative radiotherapy was the treatment used. Nineteen tumours were subsequently found (27%). The 5-year actuarial survival rate of all patients was 22%. Survival rates were significantly related to lymph node stages and to the histological degree of differentiation. Nevertheless, actuarial survival rates were not related to the appearance of the primary tumour (P = 0.07). In our series, the single most important prognostic factor was the neck stage. The value close to statistical significance observed when the primary tumour subsequently appeared (P = 0.07), suggests that this could worsen the prognosis.

Actuarial Analysis↗

Comparison of three prophylactic antibiotic regimens in clean-contaminated head and neck surgery.

BACKGROUND: Although appropriate perioperative antibiotic prophylaxis has significantly reduced wound infection rates in clean-contaminated head and neck surgical procedures, controversy still remains regarding the optimal antibiotic regimen. METHODS: In this prospective, double-blind clinical trial, 159 patients were randomized to receive amoxicillin-clavulanate, clindamycin plus gentamicin, or cefazolin intravenously up to 1/2 hour before surgery and at 6-hour intervals for an additional three doses. RESULTS: An overall wound infection rate of 23% was observed. Thirteen (22.8%) infections occurred in the amoxicillin-clavulanate-treated group, 11 (21.2%) in the clindamycin plus gentamicin-treated group, and 13 (26%) in the cefazolin-treated group, which was not statistically significant. Only prior medical illnesses, such as chronic obstructive pulmonary disease and diabetes mellitus, correlated with an increased wound infection rate (p = 0.018). CONCLUSIONS: Amoxicillin-clavulanate, clindamycin plus gentamicin, and cefazolin seem to have similar efficacy when administered prophylactically in clean-contaminated head and neck surgical procedures.

Adult↗

Infratemporal approaches to nasopharyngeal tumors.

Twenty patients with neoplasms originating in the nasopharynx were operated using the infratemporal fossa approach with facial translocation (15 cases), the subtemporal-preauricular infratemporal approach (2 cases), and the transmandibular approach (3 cases). A craniectomy was also required in 14 cases. Fifteen tumors were malignant, while 5 were juvenile angiofibromas with infratemporal and intracranial extensions. Most of the lesions were large and involved multiple areas of the skull base. Tumor excision was total in all but 3 patients. Local flaps were utilized in all patients to seal the operative cavity and consisted of temporalis muscle flaps. The most frequent postoperative complications were wound infections and cerebrospinal leaks. Two patients died as a result of postoperative complications. To date, 1 patient has died from disease and 3 are alive with local or distant disease.

Adolescent↗

Expression of the AMPA-selective receptor subunits in the vestibular nuclei of the chinchilla.

The distribution of the AMPA type glutamate receptor has been investigated throughout the central nervous system; however, no detailed description of its distribution is available in the vestibular nuclei. In the present study, in situ hybridization histochemistry and immunohistochemistry were used to localize the messenger RNAs and proteins of the AMPA-selective receptor subunits GluR1, GluR2, GluR3 and GluR4 in the vestibular nuclei of the chinchilla. Immunohistochemistry with subunits specific antisera showed differential distribution of the subunits in the vestibular nuclei. GluR2/3 antiserum labeled the most neurons, suggesting that many if not all vestibular neurons receive glutamatergic input. GluR1-positive neurons were fewer than GluR2/3 immunoreactive neurons and GluR4 immunoreactivity was found in the fewest number of neurons. GluR1 and GluR4 immunoreactivity was also found in astrocyte-like structures. In situ hybridization with 35S-labeled complementary RNA probes confirmed the distribution of the AMPA receptor subunits obtained by immunohistochemistry. Quantitative analysis of the levels of hybridization showed a high degree of diversity in the levels of expression of the GluR2 subunit mRNA, with the highest levels of expression in the giant Deiter's cells of the lateral vestibular nuclei and the lowest levels in the small neurons throughout the vestibular nuclei. The subunit compositions of the AMPA receptors determine their physiological properties. Differential distribution and levels of expression of the receptor subunits in the vestibular nuclei may be related to the characteristics of information processing through the vestibular system.

Animals↗

Tumours of the posterior pharyngeal wall: the use of the platysma flap.

Posterior pharyngeal will tumours are infrequent neoplasms with a very poor prognosis. The 5 year survival rate range from 3% to 32%. Most authors agree that the treatment of choice is surgery with post-operative radiotherapy. The results of treatment of 36 patients (tumour excision plus bilateral neck dissection and post-operative radiotherapy) in which the posterior pharyngeal wall defect was closed with a platysma myocutaneous flap were compared with other forms of repair (13 patients). The 5 year survival rate was 17.2% in the whole group. Laryngeal voice was achieved in 79% of patients having a platysma flap reconstruction. The platysma myocutaneous flap is very satisfactory for the repair of the posterior pharyngeal wall as it is easy to perform, it is oncologically safe and its functional results match well with other forms of reconstruction, with the advantage of laryngeal preservation.

Actuarial Analysis↗

MYC amplification in squamous cell carcinomas of the head and neck.

OBJECTIVES: To establish the frequency of MYC amplification in squamous cell carcinoma (SCC) of the head and neck to evaluate its correlation with clinicopathologic variables that are used in clinical practice. DESIGN: Cohort analytic study. SETTING: University Hospital. PATIENTS: Fifty-nine consecutive patients with SCC of the head and neck. INTERVENTION: Oncologic surgery. MAIN OUTCOME MEASURES: The MYC copy number in tumor samples was estimated with the polymerase chain reaction. The presence or absence of amplification was correlated with the anatomic site, T stage, nodal involvement, pathologic grade, recurrence, distant metastases, and survival. RESULTS: Six SCC specimens (11%) showed MYC amplification. A highly statistical correlation between MYC amplification and T stage was noted (P < .005). Amplification was also significantly correlated with a hypopharyngeal primary site (P < .05). No correlation among amplification status, nodal involvement, pathologic grade, relapse, metastases, and survival was observed. CONCLUSIONS: Amplification of MYC is associated with advanced primary tumors, and it appears to be a late event in the tumorigenesis of SCCS of the head and neck. However, there is no correlation between MYC amplification and prognosis.

Adult↗

Amplification of ERBB oncogenes in squamous cell carcinomas of the head and neck.

The activation of ERBB oncogenes has been described in various human tumours, including squamous cell carcinomas of the head and neck (SCCHN), and, in some of them, it has been correlated with a poor prognosis. Tissue samples from 59 patients with SCCHN were studied. After DNA extraction, the ERBB1, ERBB2 and ERBB3 copy number in tumour samples was estimated with the polymerase chain reaction (PCR) method. The PCR products were analysed by agarose gel electrophoresis and quantified by image analysis techniques. 9 (15%) cases presented with ERBB1 amplification, which was correlated with lymph node involvement (P = 0.04), poorly differentiated tumours (P = 0.03) and a hypopharyngeal primary site (P = 0.035). No correlation among amplification status, recurrence, metastases and survival was observed, although this may be due to the small number of patients in the amplified group. None of the 59 cases presented amplification of ERBB2 and ERBB3 oncogenes.

Adult↗