Conrad Timon

p16INK4A genetic and epigenetic profiles differ in relation to age and site in head and neck squamous cell carcinomas

Head and neck squamous cell carcinoma (HNSCC) typically affects male smokers older than 55 years. Recently, an increase in the incidence of HNSCC in young adults has been recognized, many of them nonsmokers and females. Functional inactivation of p16 is known to be a common event in HNSCC, mainly by either deletion or methylation. A previous study by this group has shown that p16 deletions in HNSCC are significantly associated with age. The primary objective of this study was to evaluate additional molecular alterations of p16 in HNSCC, specifically in relation to age, site, and human papillomavirus (HPV) status. Patients ranging in age from 22 to 76 years with HNSCC were prospectively identified (n = 24). Methylation-specific polymerase chain reaction and immunohistochemistry were used to evaluate p16 gene inactivation and p16 protein expression, respectively. HPV 16 status was determined for each case. Overall, p16 inactivation was a frequent event detected in 46% of cases. Methylation of p16 was more often detected in females than males (P = .05). All cases showing p16 methylation were from the anterior tongue, and 75% of them were young patients. The results indicate that p16 methylation is a more common event in those younger than 40 years in contrast to p16 deletions, which are more common in those older than 40 years. Consequently, it appears that specific modes of inactivation of p16 in HNSCC are related to specific patient risk profiles. Interestingly, HPV 16 messenger RNA was detected exclusively in HNSCC from the base of tongue lesions and was only found in males. This differs from the patient profile of HNSCC in the young, which affects the anterior tongue and commonly females, thus, making it highly unlikely that this virus is a primary causative agent of HNSCC in these young adults.

Paratracheal lymph node involvement in advanced cancer of the larynx, hypopharynx, and cervical esophagus.

Objectives/Hypothesis The presence of nodal metastatic disease in head and neck cancer is the foremost prognostic factor. Although neck dissection is the surgical gold standard for the treatment of cervical lymphatic spread, the paratracheal nodal group is not routinely included in the dissection. The study determined the nodal yield, presence of metastases, and prognostic importance of paratracheal nodes in patients with advanced carcinoma of the upper aerodigestive tract.

Globus pharyngeus: long-term follow-up and prognostic factors.

A prospective trial of 80 patients with globus pharyngeus is reported. An in-depth analysis of the typical history at presentation is given. The average follow-up period was 27 months (range, 21 to 42 months). The asymptomatic rate at this interval was 25%, with a further 35% reporting a significant improvement in symptoms. Three independent factors were found to influence prognosis (p < .05). These were sex, length of history at consultation, and the presence or absence of associated throat symptoms. Male patients having a history of the globus symptom for less than 3 months and not complaining of any associated throat symptoms had the best chance of becoming asymptomatic or symptomatically improved. The presence or absence of heartburn or its treatment had no bearing on outcome.

DISTINCT ARRAY COMPARATIVE GENOMIC HYBRIDIZATION PROFILES IN ORAL SQUAMOUS CELL CARCINOMA OCCURRING IN YOUNG PATIENTS

Oral cancer typically affects smokers older than 50 years of age. Recently, however, a marked increase in the number of patients 40 years old and younger, many with no history of tobacco smoking, has been noted. Studies in this age group have so far been restricted to genomic areas well recognized as abnormal in typical patients with oral cancer. The aim of this study was to assess genomic aberrations in oral cancer, using comparative genomic hybridization (CGH) microarray technology, and to compare the genomic aberration profile of patients older than 40 years old with those 40 years old and younger.

Minimal incision for open thyroidectomy

Objectives To establish the incision length for thyroid surgery that optimizes access and cosmesis. Study Design and Setting Prospective study from January 2003 to June 2004. All thyroidectomies were included. Exclusion criteria were concomitant neck dissections, previous surgery, and those performed endoscopically. The first 40 cases were attempted through a 5 cm incision and the second 40 through a 4 cm incision. Methods In both groups, the size of the incision was compared with the thyroids weight and histology. Results Two subtotal, 22 total, and 56 hemithyroidectomies were performed. In the first group, median gland weight was 39.5 gm and 62.5% of these were removed through a 5 cm incision. In the second group, median gland weight was 34 gm and 75% were removed through a 4 cm incision. Conclusion A 4 cm incision provides adequate access for the majority of thyroidectomies in our cohort. Significance The minimal incision thyroidectomy is a useful addition to the thyroid surgeons armamentarium. EBM rating: B-3b

Evaluation of the impact of addition of PET to CT and MR scanning in the staging of patients with head and neck carcinomas

The addition of whole body positron emission tomography (PET) to the investigation of patients with newly diagnosed head and neck squamous cell carcinoma (HNSCC) was assessed over a 6-month period. Staging investigations included laryngoscopy, oesophagoscopy, CXR, CT and MRI. In addition, all patients had an extended-field (whole body) FDG-PET scan and were restaged. Standardised Uptake Values (SUV) were used to measure FDG uptake. SUV levels above 5 were considered indicative of the presence of tumour, values below 3 indicative of benign aetiology and values equal to and between 3 and 5 were considered equivocal. Forty-eight consecutive patients with biopsy proven HNSCC were included for study. Three patients presenting with neck disease had unknown primary tumours. Of the remaining 45 patients, CT scan correctly identified 40 of the primary tumours (89%). MRI and PET both identified 41 primary tumours (91%). Thirty-two patients underwent neck dissection. Of these patients 12 had pathologically N0 necks and 20 had positive nodal disease. CT scan and MRI each correctly staged pN0 necks in 10 of 12 patients (83%) whereas PET alone had a lower true negative rate of 8 out of 12 patients (67%). PET correctly staged the N+ necks in 14/20 patients (70%) versus 12/20 (60%) for MRI, and 8/20 (40%) for CT alone. All four patients who were judged to have distant metastases by PET had these metastases deemed negative by other investigation. None of the three imaging modalities was able to identify the tumour site in the three patients with unknown primaries. In conclusion, although PET has got a higher sensitivity in detecting nodal disease, it has only slightly improved the classification of N+ necks. The findings of this study cast doubt on the merit of routine addition of PET to the current investigative protocols for HNSCC patients.

Prospective trial of the ultrasonic dissector in thyroid surgery.

Use of the ultrasonic dissector in thyroid surgery is becoming more prevalent, with reduced operative time and incision size reported. We assessed the value of the harmonic scalpel in routine thyroid lobectomy.

Role of CO2 laser in the management of obstructive ectopic lingual thyroids

Ectopic lingual thyroid glands may occasionally undergo massive hypertrophy and be a source of airway obstruction. Securing the airway prior to surgery in such cases may be difficult. In the present paper, we report on two cases of obstructive ectopic lingual thyroids which were successfully managed endoscopically using CO(2) laser. The use of CO(2) laser for removal of ectopic lingual thyroid tissue offers advantages over traditional surgical techniques. In our opinion, removal of an appropriate amount of gland to secure an adequate airway is all that is required in most cases.

Acute food bolus impaction: aetiology and management.

A prospective study into the aetiology of acute food bolus obstruction (AFBO) was carried out on 17 consecutive patients who presented with this complaint. There were nine males and eight females. Twelve patients (71 per cent) had symptoms of oesophageal disease and 10 patients (59 per cent) had prior food bolus obstruction. Investigations included endoscopy, barium swallow, oesophageal pH and manometry studies. Evidence of oesophageal pathology was found in 12/14 (86 per cent) of patients investigated. No patients had malignancy and the most common abnormality, gastroesophageal reflux (GOR) was found in eight out of 14 (57 per cent) of cases. Oesophageal dysmotility was seen in five out of 12 (42 per cent) patients who had manometric studies. With such a high incidence of recurrence of AFBO, we suggest that patients with this condition be investigated to exclude malignancy and to identify benign oesophageal pathology using techniques such as oesophageal pH and manometry. Appropriate treatment of oesophageal disease may help prevent recurrence of this distressing condition.

Surgical management of drooling in the neurologically damaged child

Continuous drooling after infancy is rarely seen in normal children. Neurologically damaged children are more likely to continue to drool, and it may be so severe in some cases as to require surgical correction. Submandibular duct relocation is a procedure with minimal morbidity and excellent results. This procedure has been carried out on 16 children at the Eye and Ear Hospital and Temple Street Childrens Hospital, Dublin, between the years 1982 to 1987. An overall improvement occurred in 13 cases with only one post-operative complication. Such surgery has transformed the lives of these children as well as being a great source of relief for the parents.