PubMed Health⌕ Search

Biomedical subjects

J Irish

Publications and source records attributed to J Irish.

At least 19 recordsLinked to original sources

Reconstructive options in the treatment of osteoradionecrosis of the craniomaxillofacial skeleton.

Osteoradionecrosis (ORN) of the craniomaxillofacial skeleton is a serious and debilitating complication that can occur following radiation therapy in the head and neck. Patients require effective treatment, which eradicates diseased tissue and restores function with minimal additional morbidity in a single stage, a requirement fulfilled in many cases by free tissue transfer. In a 6-year period from 1994 to 1999, 21 patients with ORN were treated by wide resection and free-flap reconstruction. The median interval between radiation therapy and ORN was 4 years (range: 1-33 years). The median radiation dose was 6000cGy. The affected areas were the mandible (15 patients), the temporal bone (three patients), the maxilla (one patient), the cervical vertebrae (one patient) and the frontal bone (one patient). Clinical symptoms included pain, ulceration, a persistent draining fistula, exposure of bone or hardware, and pathological fracture or non-union of bone. Six patients had had previous unsuccessful attempts at conservative surgical resection. Ten patients had preoperative hyperbaric oxygen (HBO) therapy. A number of different flaps were used for reconstruction in these patients. These included free fibula flaps (13 patients), iliac crest flaps (two patients), scapula flaps (three patients) and rectus abdominis flaps (three patients). All patients achieved relief from their presenting symptoms and primary bone or wound healing. One flap (4.8%) was lost. This was successfully reconstructed in a subsequent procedure. There were three flap re-explorations, two for arterial thrombosis and one for venous thrombosis. Conservative measures, such as limited debridement and HBO therapy, may be effective in preventing the progression of ORN. However, they fail to eradicate established ORN, which requires radical surgical resection followed by functional reconstruction with well-vascularised tissue.

Aged↗

The benefits and pitfalls of ipsilateral radiotherapy in carcinoma of the tonsillar region.

PURPOSE: Ipsilateral techniques designed to restrict treatment to the primary tumor and neck on the same side have been used in selected cases of cases of carcinoma of the tonsillar region at our institution for many years. The primary purpose of this study is to evaluate the risk of failure in the opposite neck in cases selected for unilateral radiotherapy over a 21-year period. METHODS AND MATERIALS: Ipsilateral radiotherapy techniques were used in 228 of 642 patients with carcinoma of the tonsillar region from 1970 to 1991. Local control, regional lymph-node control (including contralateral failure), and survival were calculated for different degrees of tumor extent treated with these techniques. RESULTS: Mean follow-up was 7 years. Cases tended to be T1 and T2, with N0 disease. The 3-year actuarial local control rate was 77% and cause-specific survival was 76%. Opposite neck failure was seen in 8 patients (crude rate of 3.5%). In the earlier period of the study, primary coverage was problematic in a proportion of cases and resulted in higher rates of local failure. CONCLUSION: Appropriately selected cases of carcinoma of the tonsil show minimal risk of failure in the opposite neck with ipsilateral techniques. Patients should undergo computed tomography planning to ensure adequate target coverage.

Adult↗

High frequency of microsatellite instability in young patients with head-and-neck squamous-cell carcinoma: lack of involvement of the mismatch repair genes hMLH1 AND hMSH2.

The most prevalent risk factors in the development of head-and-neck squamous-cell carcinoma (HNSCC) are excessive tobacco and alcohol consumption. In young patients with HNSCC, these risk factors are often absent. Our purpose was to investigate the risk factors, microsatellite instability (MSI) changes and status of the mismatch repair genes hMLH1 and hMSH2 in a cohort of young patients with HNSCC. Fifty-seven HNSCC tumors were examined for the presence of MSI at 16 microsatellite sites using PCR. In the young patient group (24 cases, < or = 44 years old), 100% of tumors had MSI at 1 site at least and 88% had MSI at 2 or more loci. In older patients (33 cases, > or = 45 years), MSI at 1 or more sites was found in 61% of tumors (young vs. old, p = 0.0003) and instability at 2 or more sites was found in 36% of tumors (young vs. old, p = 0.0001). The involvement of the mismatch repair genes was investigated by examining promoter methylation, exon mutation and gene expression of hMLH1 and hMSH2. All results were negative, indicating that inactivation of these 2 genes does not play a role in the development of MSI in tumors from this patient group. Furthermore, the young patient group had a significantly lower incidence of smoking (46% young, 88% old; p = 0.001) and alcohol consumption (33% young, 67% old; p = 0.0169), emphasizing the probable importance of other environmental and/or genetic factors in the development of their disease.

Adaptor Proteins, Signal Transducing↗

Abnormalities of the ARF-p53 pathway in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is associated with heavy smoking and drinking, but the molecular pathway of tumorigenesis is not understood. Inactivation of the p53 tumor suppressor gene is likely to play an important role since p53 mutation is frequently found. The p14ARF tumor suppressor gene is functionally linked to p53, because it is activated by oncogenes and causes p53-dependent growth arrest and apoptosis. The relationship between p14ARF and p53 inactivation has not been described for OSCC. We studied 25 cases of OSCC to determine if there is an inverse correlation between p53 mutation and p14ARF inactivation by homozygous deletion or mutation. p53 mutation was found in 16 of 25 cases (64%), including nine missense and seven truncating mutations. While all cases with missense mutations showed abnormal accumulation of p53 protein, there were also five carcinomas which showed increased p53 staining in the absence of mutation. p14ARF deletion or mutation was found in eight cases (32%), six of which also demonstrated p53 mutation. Our findings indicate that OSCC often involves loss of both p14ARF and p53 function and suggest that inactivation of these two tumor suppressor genes are not functionally equivalent during tumorigenesis.

Adult↗

Brush biopsy for detection of nasopharyngeal cancer.

The technique described above for sampling the nasopharynx requires minimal equipment, instruction, and expertise and causes minimal morbidity. Hence, it may be a valuable tool in a widespread screening program for a far too common and debilitating cancer in certain parts of the world.

Biopsy↗

Role of the sternocleidomastoid muscle flap preventing Frey's syndrome and maintaining facial contour following superficial parotidectomy.

The sternocleidomastoid muscle flap may play a significant role in reducing the incidence of Frey's syndrome and maintaining facial contour after parotidectomy. Patients who underwent superficial parotidectomy from August 1992 to March 1999 were divided into two groups (N = 26). One group had sternocleidomastoid muscle flap reconstruction. A historical cohort study was designed with the two groups being matched for sex, age, pathology, postoperative radiation, date of surgery, and extent of dissection. The starch iodine test was used to evaluate for gustatory sweating, and the Observer Rated Disfigurement Scale was used to assess facial contour and aesthetics. The results of our study suggest that the sternocleidomastoid flap reconstruction following parotidectomy surgery does not alter the incidence of Frey's syndrome and does not significantly improve facial contour and aesthetics.

Cohort Studies↗

Multicentricity in papillary thyroid carcinoma: analysis of predictive factors.

OBJECTIVES: Multicentricity has been cited as a rationale for total thyroidectomy in patients with papillary thyroid carcinoma (PTC) confined to one lobe. The purpose of this study was to examine the incidence of multicentricity of PTC in a cohort of 165 patients with PTC confined to one lobe and to examine clinical and pathologic features that may help predict for the presence of contralateral disease. DESIGN: Retrospective review. SETTING: Tertiary care hospital. METHOD: A retrospective review of 165 patients with PTC confined to one lobe treated at the Toronto General Hospital from 1992 to 1997 was performed. MAIN OUTCOME MEASURE: The predictive factors affecting the presence of multicentricity of PTC were analyzed. RESULTS: The incidence of PTC present in the contralateral lobe was 56.3%. We were unable to find any correlation of multicentricity with age, sex, tumour size, extrathyroidal spread, thyroiditis, or tall cell variant of PTC. There were trends toward higher incidence of contralateral disease in those patients with a prior history of irradiation and those with lymphatic metastases, but these trends did not reach statistical significance. CONCLUSIONS: The incidence of contralateral disease in papillary thyroid cancer treated at the Toronto Hospital was 56.3%. There was a higher incidence of contralaterality in those patients with a previous history of irradiation and in those with lymphatogenous metastases, but this did not reach statistical significance.

Adult↗

Pectoralis major myocutaneous pedicled flap in head and neck reconstruction: retrospective review of indications and results in 244 consecutive cases at the Toronto General Hospital.

The pectoralis major myocutaneous pedicled flap (PMMPF) has been considered to be the "workhorse" of pedicled flaps for head and neck reconstruction, and several series of PMMPF procedures have been reported in the literature. Between 1983 and 1997, 244 reconstruction procedures using the PMMPF were carried out on 229 patients by the Otolaryngology-Head and Neck Surgery Department at the Toronto General Hospital. Pectoralis major myocutaneous pedicled flap reconstructions were completed after ablation of cancer in the following sites: oral cavity, 113; oropharynx/hypopharynx, 50; larynx, 59; and other, 21. The locations of reconstruction were oral cavity, 121; pharynx, 74; and neck or face, 50. Of the 244 cases, 202 were carried out as primary reconstructive procedures, whereas 42 flaps were "salvage" procedures (reconstruction after fistula, flap failure, osteoradionecrosis, and internal jugular vein rupture). Eighty-five cases (35%) were affected by complications such as dehiscence, infection, hematoma, seroma, partial flap failure, total flap failure, fistula, and donor site complications. The duration of admission for cases with complications was longer, and higher complication rates were associated with salvage procedures, number of comorbidities, number of pack-years of cigarettes smoked, and oral cavity reconstructions. This series of consecutive PMMPF procedures is the largest reported to date.

Canada↗

The role of panendoscopy in the management of mucosal head and neck malignancy-a prospective evaluation.

BACKGROUND: It is common practice for a panendoscopy to be included in the evaluation of patients with mucosal head and neck malignancies. Whether this intervention is efficient or cost-effective has not been established in our patient population. METHODS: Two hundred twenty-four patients with squamous cell carcinoma involving the oral cavity, pharynx, larynx, or neck were evaluated prospectively with panendoscopy and chest x-ray with or without barium swallow. One hundred fifty-four patients had newly diagnosed tumors and 70 were previously diagnosed and currently undergoing symptom-directed investigations. RESULTS: The incidence of synchronous primary tumors was 2.6% (4 of 154); pulmonary, 1.3%; head and neck mucosa, 1.3%; and esophageal, 0%. There was no associated morbidity. CONCLUSIONS: Although there was no associated morbidity, our head and neck oncology group is of the opinion that routine panendoscopy is not warranted. Specific indications for this investigation are discussed.

Barium Sulfate↗

The treatment of essential voice tremor with botulinum toxin A: a longitudinal case report.

The purpose of this study was to evaluate the effects of bilateral botulinum toxin injection into the thyroarytenoid (TA) muscles of a patient with essential voice tremor. Acoustic and aerodynamic data were collected weekly over a 16-week period. Flexible nasolaryngoscopy was performed prior to injection and 2, 6, 10, and 16 weeks postinjection. Perceptual analyses of the acoustic and nasolaryngoscopic data were performed. A reduction in frequency tremor and, to a lesser extent, amplitude tremor was observed during the 1-10 week period. Estimated laryngeal resistance decreased after injection and was accompanied in perceptual measures by a reduction in vocal effort, laryngeal tremor, and supraglottic hyperfunction. Essential voice tremor can be successfully attenuated with bilateral percutaneous injection of botulinum toxin A into the vocalis muscle.

Aged↗

Telomerase activity is upregulated in laryngeal squamous cell carcinoma.

OBJECTIVE/HYPOTHESIS: The immortalizing enzyme telomerase has been linked to carcinogenesis and is being targeted as a novel molecular marker. This study investigated telomerase expression in patients with laryngeal squamous cell carcinoma and correlated telomerase activity with conventional prognostic parameters. STUDY DESIGN: A consecutive series of patients with laryngeal squamous cell carcinoma undergoing surgical salvage for persistent or progressive disease after failed radiation therapy. METHODS: Twenty patient samples of laryngeal squamous cell carcinoma and 20 adjacent histologically normal mucosal samples were assayed using the telomeric repeat amplification protocol (TRAP) method for detection of telomerase activity. The leukemic cell line, K562, acted as a positive control and the human fibroblast line, Hs21Fs, as a negative control. A sample was classified as telomerase positive when an RNase-sensitive hexameric repeat ladder was observed. Absence of laddering was considered a negative result. RESULTS: Seventeen of 20 (85%) tumor samples and 4 of 20 (20%) adjacent histologically normal samples were telomerase positive. No statistically significant difference was observed when densitometric readings were compared by T category, tumor grade, or site (by ANOVA). CONCLUSIONS: Although telomerase activity is present in laryngeal cancer, levels of activation do not correlate with conventional parameters used for prognostication. Our study indicates that the marker may be a useful adjunctive method in the diagnosis of malignancy after radiation failure.

Adult↗

Does nasal nitric oxide come from the sinuses?

OBJECTIVE: The purpose of this study was to assess nitric oxide (NO) output by the nose and sinuses. METHOD: In one volunteer, the osteomeatal complex and sphenoethmoidal recess were occluded to isolate the nose from the sinuses. The antrum and frontal sinus were each punctured by two catheters and irrigated with air at constant flow. Nitric oxide output and its rate of accumulation in the absence of air flow were measured in each sinus and in the adjacent nasal cavity. RESULTS: Prior to ostial occlusion, NO output in the nose was 96 nL/min. It decreased by 12% after blockage of all of the ostia. In the isolated sinuses, it was 190 nL/min (antrum) and 68 nL/min (frontal). After 5 minutes stagnation; NO concentration [NO] rose in the occluded sinuses to 24,700 nL/L in the antrum and 22,300 nL/L in the frontal sinus. In the nose, it increased to 29,000 nL/L. When the period of stagnation was prolonged in the frontal sinus, the [NO] reached a plateau. NO output and accumulation were not altered in the nose or either sinus by opening their ostia. In the antrum and frontal sinus, lidocaine reduced NO output and the rate of NO accumulation, but not in the nose. CONCLUSIONS: In this volunteer, 88% of nasal NO was derived from the nose itself. Nitric oxide exchange between the frontal sinus, antrum, and nose was negligible. In the absence of air flow, [NO] rose to a plateau in the nose and frontal sinus. Lidocaine inhibited NO output in the sinuses but not the nose.

Humans↗

Telomerase activity in oral squamous cell carcinoma.

BACKGROUND: The riboprotein telomerase has been linked to cellular immortality and is believed to play a key role in tumorigenesis. OBJECTIVE: To determine if telomerase is expressed in patients with oral squamous cell carcinoma. DESIGN: Twenty patient samples of oral squamous cell carcinoma and 20 adjacent histologically normal mucosal samples were assayed using the telomeric repeat amplification protocol (TRAP) method for detection of telomerase activity. The leukemic cell line, K562, was used as a positive control and the human fibroblast line, Hs21Fs, as a negative control. PATIENTS: Consecutive series of patients with oral squamous cell carcinoma presenting to a tertiary referral center. MAIN OUTCOME MEASURE: A sample was classified as telomerase positive when an RNase-sensitive hexameric repeat ladder was observed. Absence of laddering was considered a negative result. RESULTS: Eighteen (90%) of 20 tumor samples and 7 (35%) of 20 adjacent histologically normal samples were telomerase positive. A statistically significant difference was observed in telomerase activity for T1 and T2 cancers compared with T4 cancers (P<.05 by analysis of variance). No statistically significant difference was observed in activity for T1 and T2 cancers vs T3 cancers. CONCLUSIONS: The finding of telomerase activity in 90% of tumor samples is consistent with the concept of telomerase playing a key role in tumorigenesis. Further study is needed to determine the usefulness of this enzyme as a molecular marker.

Adult↗

Reoperative parathyroidectomy in the era of localization technology.

BACKGROUND: Recurrent and/or persistent hyperparathyroidism (HPT) is an uncommon disease. Relatively few cases are seen by any one center or surgeon. Most of the prior reviews of this problem were done in the era prior to potentially accurate magnetic resonsance imaging (MRI) and sestimibi scan localization and do not reflect current preoperative localization technology. METHODS: All cases of recurrent or persistent parathyroidectomy seen in our institution between 1992 and 1996 were reviewed retrospectively to assess the predictive value of preoperative MRI, selective venous sampling, sestimibi scanning, ultrasound examination, and computerized tomography (CT) scanning. The preoperative localization studies were compared with the findings at operation, the pathology report, and the patient's long-term calcium status. RESULTS: Twenty-eight patients were operated upon at our institution for recurrent or persistent HPT during this time interval. The final pathology turned out to be: adenoma, 24; hyperplasia, 2; carcinoma, 2. The site at which the reoperative pathology was found was in the neck in 22 patients and intrathoracic requiring sternotomy in 6. The long-term outcome, i.e., serum calcium level at > 6 months postoperatively, was normocalcemia in 22 of 28 (85%), persistent hypocalcemia in 2 of 28, and persistent hypercalcemia in 2 of 28. Some combination of MRI, sestimibi, selective venous sampling, ultrasound, and CT scan was performed on all patients preoperatively. Preoperative MRI scans were performed on 26 of 28 patients. They correctly localized the side and site of the pathology in only 12, yielding a sensitivity of 66%. There were, however, no false positives; therefore, the positive predictive value of this test was 100%. Selective venous sampling was carried out on 26 of 28 patients and correctly localized in only 8 (sensitivity, 50%). Again, there were no false positives, yielding a positive predictive value of 100%. Sestimibi scanning was performed in 16 of 28, localizing in 8 (sensitivity, 50%). The positive predictive value of this test was 80%. Ultrasound was performed in 26 of 28 patients and localized in only 3, yielding a sensitivity of 17%, with a positive predictive value of 75%. Computerized tomographic scan was performed preoperatively only when all other investigations turned out to have been nonlocalizing and was therefore done in only four patients, one of whom had a positive CT scan showing an intrathoracic, intrapericardial adenoma. CONCLUSIONS: These data demonstrate that despite the availability of what are putatively accurate preoperative localizing tests for previously unoperated cases, no one localizing test is particularly sensitive in reoperative parathyroid surgery. Magnetic resonance imaging and selective venous sampling, however, are complementary and when positive do accurately predict the site of the persistent/recurrent parathyroid pathology. Use of these preoperative localizing studies resulted in a successful outcome, i.e., normocalcemia or hypocalcemia in 93% of patients operated on.

Adult↗

Surgical salvage after failed radiation for paranasal sinus malignancy.

OBJECTIVE: To comment on the role of surgical salvage following failed initial treatment for paranasal sinus malignancy. DESIGN: A retrospective analysis of one hundred eighty patients treated at The Princess Margaret Hospital, Toronto, from 1976 to 1993. MATERIALS AND METHODS: Thirty-four of 95 patients (36%) who failed initial treatment underwent surgical salvage. Initial therapy in this group was radiation only (n = 27) and combined therapy (n = 7). Patient, tumor, and surgical data were recorded. There were 23 T4, three T3, six T2, and two T1 carcinomas. Survival, recurrence rates, and the influence of a variety of variables on outcome were analyzed. RESULTS: Two- and 5-year overall actuarial survival calculated from the date of diagnosis was 54% and 35%, respectively. Two- and 5-year overall actuarial survival calculated from the date of salvage surgery was 44% and 22%, respectively. Advanced age (P < .004), patients with T4 category disease (P < .04), and squamous cell carcinomas (P < .049) correlated with poorer outcome on univariate analysis. Local failure was the most common cause of death (n = 13; 65%). CONCLUSION: Salvage surgery has a limited role in the management of persistent or progressive disease following failure of initial treatment. Careful postradiation surveillance with endoscopic biopsy under general anesthesia and immediate surgical resection when appropriate may improve the salvage rate.

Actuarial Analysis↗

Surgical salvage after radiotherapy for advanced laryngopharyngeal carcinoma.

OBJECTIVE: To comment on the use of surgery after the failure of radiotherapy in patients with advanced laryngeal, oropharyngeal, and hypopharyngeal carcinomas. DESIGN: Randomized, controlled, clinical trial, with a mean follow-up period of 3.1 years. SETTING: The Princess Margaret Hospital, Toronto, Ontario. PATIENTS: Patients with advanced laryngopharyngeal carcinoma (T3 or T4 or N+). INTERVENTION: Three hundred thirty-six patients who met the eligibility criteria were enrolled in a randomized, controlled, clinical trial and treated with primary radiotherapy using either the standard fractionation regimen or the hyperfractionation regimen. One hundred eight patients with recurrent disease underwent salvage surgery and were observed prospectively, with careful documentation of surgical and tumor data, complications, recurrences, and survival. MAIN OUTCOME MEASURES: Surgical complication rate and survival. RESULTS: Of the 108 patients who underwent surgery, 29 (27%) had complications. One third of these had multiple complications. There was no statistical difference between the surgical complication rates of the 2 radiotherapy groups (16 patients [28%] in the standard fractionation radiotherapy group and 13 [25%] in the hyperfractionation radiotherapy group). Survival after surgery was statistically correlated with the TNM system for the stage of the recurrent tumor, the pathologic nodal status, and the surgical margin status. The overall 3-year survival rate, which was calculated from the date of surgery, for the group of patients who underwent surgery was 22%. CONCLUSIONS: In this patient population, the hyperfractionation regimen was not associated with a higher surgical complication rate. Using the policy of primary radiotherapy and reserving surgery for the management of failures of radiotherapy, 140 patients (71%) at highest risk (laryngeal and hypopharyngeal primary tumor sites) retained an intact larynx until the end of the study or death. Since it is the stage of the recurrent tumor that correlates with survival rather than the stage of the tumor at initial presentation, we suggest that tumors be restaged at the time of recurrence.

Adult↗

Outcome and analysis of the surgical management of esthesioneuroblastoma.

OBJECTIVE: The aim of this study was to evaluate the effectiveness of combined radical surgical resection and radiotherapy for the treatment of esthesioneuroblastoma, a rare malignant neoplasm accounting for 1 to 5% of malignant neoplasms of the nasal cavity. METHOD: A 10-year review of 12 patients treated at our institution suggests that primary treatment consisting of a combined otolaryngologic/neurosurgical craniofacial approach results in good local control with relatively low morbidity and complication. Patients tend to present with advanced stage disease because of the nonspecific presenting signs and symptoms. Eighty-three percent of the patients were treated with combined surgery and radiation. RESULTS: Seventy-five percent of the patients are free of disease with an average follow-up time of 54 months. Based on our experience in anterior skull base surgery (zone I), we strongly advocate the pericranial flap for dural reconstruction. Postoperative complications occurred in 25% of the cases with no postoperative deaths. CONCLUSION: Failure analysis suggests that radical surgical resection combined with radiotherapy provides the best chance of disease control.

Adolescent↗