Analysis of the prognostic significance of lymph node related characteristics in papillary thyroid carcinoma patients presenting with pre- or intra-operative evidence of cervical lymph node metastases.

OBJECTIVE: To identify the prognostic significance of specific lymph node related characteristics for disease persistence and recurrence in patients with pre- or intra-operative evidence of neck metastases and no other risk factors. METHOD AND RESULTS: Sixty-eight patients were identified; 50 per cent had persistent or recurrent disease. All underwent the same treatment strategy. There were no statistically significant differences in any of the patient- or tumour-related parameters when patients with and without persistence or recurrence were compared. Patients with recurrent or persistent disease had significantly larger (>3 cm) metastatic lymph nodes, but there were no differences regarding other lymph node related parameters (i.e. number, extracapsular extension, number of lymph nodes with extracapsular extension, and central vs lateral neck location). On multivariate analysis, however, none of the parameters were predictive of persistent or recurrent disease. CONCLUSION: In papillary thyroid carcinoma patients with no other risk factors, pre- or intra-operative evidence of cervical metastases was associated with a very high rate of disease persistence or recurrence. Specific lymph node characteristics were not shown to have prognostic significance.

EZH2 promotes a bi-lineage identity in basal-like breast cancer cells.

The mechanisms regulating breast cancer differentiation state are poorly understood. Of particular interest are molecular regulators controlling the highly aggressive and poorly differentiated traits of basal-like breast carcinomas. Here we show that the Polycomb factor EZH2 maintains the differentiation state of basal-like breast cancer cells, and promotes the expression of progenitor associated and basal-lineage genes. Specifically, EZH2 regulates the composition of basal-like breast cancer cell populations by promoting a 'bi-lineage' differentiation state, in which cells co-express basal- and luminal-lineage markers. We show that human basal-like breast cancers contain a subpopulation of bi-lineage cells, and that EZH2-deficient cells give rise to tumors with a decreased proportion of such cells. Bi-lineage cells express genes that are active in normal luminal progenitors, and possess increased colony-formation capacity, consistent with a primitive differentiation state. We found that GATA3, a driver of luminal differentiation, performs a function opposite to EZH2, acting to suppress bi-lineage identity and luminal-progenitor gene expression. GATA3 levels increase upon EZH2 silencing, mediating a decrease in bi-lineage cell numbers. Our findings reveal a novel role for EZH2 in controlling basal-like breast cancer differentiation state and intra-tumoral cell composition.

Anti-estrogen therapy for hereditary hemorrhagic telangiectasia - a long-term clinical trial.

STATEMENT OF PROBLEM: Hereditary hemorrhagic telangiectasia (HHT) is associated with recurrent epistaxis in 90% of the cases. Good response to hormone treatment has been documented, although its use remains controversial. The aim of this study was to examine the efficacy of an anti-estrogenic agent, tamoxifen, in the treatment of HHT-associated epistaxis. METHOD OF STUDY: Out of 46 patients with diagnosis of epistaxis due to HHT who started treatment with tamoxifen 20 mg/d, 38 patients completed a mean of 23.4 months of treatment. All patients filled out a self-assessment questionnaire of rhinologic Quality of Life and epistaxis grading scale. MAIN RESULTS: The bleeding score and the Quality of Life score improved. Hemoglobin concentration also improved. None of the patients needed blood transfusions during the treatment period. Only one patient had minor side effects of the drug. PRINCIPAL CONCLUSIONS: Tamoxifen appears to be an effective agent for the treatment of epistaxis due to HHT.

Outcome of oral tongue squamous cell carcinoma in patients with and without known risk factors.

BACKGROUND: Tobacco smoking and high alcohol consumption are considered major risk factors of oral tongue squamous cell carcinoma. This study compared disease outcome between patients with and without known risk factors. METHODS: Patients with oral tongue squamous cell carcinoma treated at two major medical centers from 1994 to 2008 were identified by cancer registry search. The medical files were reviewed for background-and-disease-related data, risk factors, and outcome. RESULTS: The study sample consisted of 291 patients: 175 had a history of heavy tobacco smoking and alcohol abuse and 116 did not. Comparison of the patients without risk factors between the two centers yielded no differences in background features. Men accounted for 74% of the total patients with risk factors and comprised 77% of the risk-factor group. The risk-factor group was characterized by a significantly higher mean tumor grade (p=0.0001) and greater tumor depth of invasion (p=0.022) than the non-risk-factor group. The 5-year local and regional control rates were 85.3% and 74%, respectively, with no significant difference between the groups. The 5-year overall survival rate was 68% in the risk-factor group and 64% in the non-risk-factor group (p=NS). Separate analysis of patients aged <40 years at diagnosis revealed a worse overall (p=0.015) and disease-free survival (p=0.038) in those without risk factors. CONCLUSIONS: The outcome of oral tongue carcinoma is similar in patients with and without risk factors. The worse prognosis in younger patients (<40 years) without risk factors suggests that the pathogenesis in these cases involves factors other than smoking and alcohol.

The impact of positive resection margins in partial laryngectomy for advanced laryngeal carcinomas and radiation failures.

OBJECTIVES: To investigate the prognostic significance of positive margin and disease course in partial laryngectomy for advanced laryngeal carcinoma and radiation failure. DESIGN: Retrospective case control study. SETTING: A major tertiary referral centre. PARTICIPANTS: Patients who underwent partial laryngectomy for advanced laryngeal carcinoma or for radiation failure with at least 2 years of follow-up. MAIN OUTCOME MEASURES: Margin status versus primary treatment and salvage treatment versus disease-free survival and overall survival. RESULTS: Twenty nine patients with sufficient follow-up data were found. Twelve patients had histological positive margin. Five of the 12 patients with a histological positive margin failed surgery as did four patients with clear margins. A positive margin had no effect on disease-free survival (P = 0.287) but was associated with poorer overall survival (P = 0.051). Of 11 patients treated primarily with surgery, recurrence was documented in one of eight with a positive margin and none of three with clear margins. Of 18 patients who underwent surgery secondary to radiation failure, recurrence was documented in all four with a positive margin and 4 of 14 with negative margins. Extended frontolateral resection, performed only in radiation failures, was associated with worse disease-free survival. CONCLUSIONS: Non-irradiated patients with involvement of a single margin after partial laryngectomy may be spared total laryngectomy if adjuvant radiation is administered. Patients who fail radiation should undergo radical partial laryngectomy, with conversion to total laryngectomy in those with a positive margin.

Squamous cell carcinoma of the oral tongue in patients younger than 30 years: clinicopathologic features and outcome.

OBJECTIVE: To assess the possible effect of young age on clinical behaviour and survival outcome of squamous cell carcinoma of the oral tongue. DESIGN: Retrospective, case control study. SETTING: A major tertiary referral centre. PARTICIPANTS: Eighty-five patients with oral tongue squamous cell carcinoma with at least 2 years of follow-up. MAIN OUTCOME MEASUREMENTS: Clinical and histopathological staging, disease-free survival, disease-specific survival and overall survival. RESULTS: Eleven patients (13%) were younger than 30 years. Compared to the older patients, they had a significantly worse N stage (P = 0.041), more perineural invasion (P = 0.012), and higher rates, though not significant, of treatment failure (46%, including 60% with distant metastases, versus 35%, nearly all locoregional) and mortality (100% of treatment failures versus 73%). There were no significant between-group differences in 5-year disease-free, disease-specific, and overall survival. CONCLUSION: In this study, patients younger than 30 years of age presented with advanced tumour stages and with a different failure pattern compared to the older age group. This may be attributable to age-related biologic behaviour or delayed cancer diagnosis. Differences in disease free survival and overall survival could not be established.

Laser posterior ventriculocordectomy with partial arytenoidectomy for the treatment of bilateral vocal fold immobility.

Bilateral vocal fold immobility in adduction usually creates severe dyspnoea. Many surgical procedures have been established to improve the airway insufficiency in affected patients. Over the last six years 22 patients with bilateral vocal fold immobility in our department have undergone CO(2) laser posterior ventriculocordectomy with partial arytenoidectomy (PVCPA). None had dyspnoea or a disturbance in the immediate post-operative period or during follow up, which ranged from five months to six years. Only one patient required a second procedure. Laser PVCPA appears to be an effective and reliable method for the treatment of bilateral vocal fold immobility in selected patients.

The effects of passive smoking on olfaction in children.

The effect of passive smoking on odor identification was studied in 10 children exposed to passive smoke at home. All had at least one parent who smoked at least one pack of cigarettes a day. The control group consisted of 10 children of nonsmoking parents. Ten odorants were tested: vinegar, ammonia, peppermint, roses, bleach, vanilla, cough drops, turpentine, licorice and mothballs. Each child was presented with five test trays containing all 10 odorants in random order. Of the total of 500 odors presented, the control group correctly identified 396 (79%) and the study group, 356 (71%) (p < 0.005). This work demonstrates that children exposed to passive smoke have difficulty identifying odors in comparison to children raised in relatively smoke-free environments. Since the study group tend to misidentify four of the 10 odorants tested--vanilla, roses, mothballs and cough drops--we suggest that these four odorants should suffice in testing odor identification in children.

[The endoscopic approach to isolated sphenoid sinus disease].

UNLABELLED: We reviewed the records of 38 patients aged 16 to 76 years with isolated sphenoid sinus disease who were treated by intranasal endoscopic sphenoidotomy at our hospital during the period 1992-1997. Diagnosis was made on the basis of history rigid nasal endoscopy and computed tomography (CT) scan of the sinuses. Headache was the main symptom in 29 (76%) patients. Other complaints were rhinitis, cough, nasal obstruction and nasal bleeding. Sphenoidotomy was performed endoscopically, directly through the area of the natural ostium. Acute or chronic sinusitis was found in 57% of the patients, cysts in 13%, polyps in 10%, mucocele in 8%, and fungal infection, pituitary adenoma, inverted papilloma and adenocarcinoma, in 3% each. Surgical results were excellent. The endoscopic approach proved to be both safe and effective. CONCLUSION: Sphenoid sinus disease is mostly inflammatory in origin. The endoscopic approach to the sphenoid sinus is currently the most appropriate method of surgery for an isolated sphenoid lesion.

Histological changes in the cervical lymph nodes after radiotherapy.

Radiotherapy to the neck is frequently employed in the treatment of malignancies, sometimes alone and sometimes before or after surgery or with or without chemotherapy. We checked the histopathological changes in the neck after radiotherapy, dividing the changes into two groups. One with short-term changes between six months to one year, and the second group with long-term changes after more than six years. We compared these two groups with a control group without radiotherapy. The changes in the long-term group were more pronounced than in the short-term group, with more stromal fibrosis, vascular changes, and specially lymph nodes smaller than one centimeter. Thus, bigger lymph nodes (more then one centimeter) are more radiosensitive and become smaller after six years.

Effects of passive smoking on odour identification in children.

BACKGROUND AND OBJECTIVE: The effect of passive smoking on odour identification in children has rarely been reported. This study assessed the ability of such young subjects to identify a variety of odours. METHODS: The study population consisted of 20 children, 10 who were exposed to passive smoke at home and 10 with nonsmoking parents. Ten odourants were tested: vinegar, ammonia, peppermint, roses, bleach, vanilla, cough drops, turpentine, licorice, and mothballs. Each child was presented with five test trays containing all 10 odourants in random order. RESULTS: Of the total of 500 odours presented, the control group correctly identified 396 (79%) and the study group identified 356 (71%) (p < .005). The study group tended to misidentify 4 of the 10 odourants tested, namely, vanilla, roses, mothballs, and cough drops-56 of 200 (28%), compared with 96 of 200 (48%) in the control group. This was a highly significant finding (p < .0005). CONCLUSION: This work demonstrated that children exposed to passive smoke have difficulty identifying odours in comparison with children raised in relatively smoke-free environments. The identification of four odourants, vanilla, roses, mothballs, and cough drops, was particularly diminished in this study group.

Mucus retention cyst of the maxillary sinus: the endoscopic approach.

OBJECTIVE: To present our experience of endoscopic surgery for symptomatic mucus retention cyst of the maxillary sinus. DESIGN: Retrospective study. SETTING: Teaching hospital, Israel. PATIENTS: 60 patients with 65 symptomatic cysts of the maxillary sinus who were operated on endoscopically. Only patients with large cysts that filled at least 50% of the sinus space were included. INTERVENTION: A rigid nasal endoscope was used in all cases; most of the cysts were removed through the natural sinus ostium. RESULTS: Cysts recurred in only two patients during the first postoperative year. There were no complications from the procedure. CONCLUSION: The endoscopic approach to the treatment of maxillary sinus cyst is associated with a low rate of recurrence (3% in this study) and no complications, and we recommend it as the surgical procedure of choice.

Clinicopathologic study and classification of vocal cord cysts.

Cysts of the true vocal cords are less common than other laryngeal cysts. They are usually easily recognized and managed. Patients present with complaints of hoarseness and/or dyspnea. We report our experience with 41 cases of cysts located in the true vocal cords. Clinical and histological aspects are reviewed and discussed. A new histological classification is proposed: A: cysts lined by columnar epithelium with mucous content; B: lined by columnar epithelium with cilia; C: lined b squamous epithelium without keratinization; D: lined by squamous epithelium with keratinization.

Endoscopic transnasal transsphenoidal microsurgery versus the sublabial approach for the treatment of pituitary tumors: endonasal complications.

OBJECTIVE: To evaluate the nasal complications after transnasal transsphenoidal operations for pituitary tumors, comparing two surgical techniques: traditional sublabial transseptal and endoscopic transseptal techniques. STUDY DESIGN: We retrospectively evaluated by self-reported questionnaire and endoscopic examination the nasal condition of 40 consecutive patients with pituitary tumors: 20 patients had endoscopic surgery and 20 had surgery with the traditional sublabial technique. RESULTS: Compared with the traditional technique, the endoscopic approach was associated with a shorter operative time (about 40 min), shorter hospitalization time (about half), absence of recurrent epistaxis snoring and denture problems, and lower incidence of septal perforation, synechia, and crust formation. Furthermore, loss of nasal tip projection was found only in the group that had surgery with the sublabial technique. CONCLUSIONS: Endoscopically guided transseptal transsphenoidal surgery is simple to perform and time-saving, and it results in fewer nasal and denture complications than the sublabial technique. At the same time, it allows the surgeon all the benefits of the binocular microscopic surgical field that are associated with the traditional approach.

Cochlear histopathologic analysis in diabetic rats.

HYPOTHESIS: This study aimed to show whether sensorineural hearing loss in diabetes mellitus is secondary to changes in the organ of Corti and stria vascularis. BACKGROUND: The high rate of sensorineural hearing loss in diabetes mellitus has led to much speculation as to whether there is an association between the two. METHODS: A well-established diabetic animal model was used to examine the inner ear histopathologically. RESULTS: No statistical difference in the inner and outer hair cells or in the stria vascularis was shown between the genetic-diabetic rats and control subjects. CONCLUSIONS: If there is hearing loss with diabetes, its pathogenesis does not involve damage to the hair cells or stria vascularis.

Supraglottic carcinoma: a retrospective study of 114 patients.

We retrospectively evaluated the management of supraglottic carcinoma at our centre during the last 35 years to determine the preferred mode of treatment. A review of the medical records yielded 114 patients with supraglottic T1 and T2 carcinoma who were diagnosed and treated in the Departments of Otolaryngology, Head and Neck Surgery, and Oncology between 1959 and 1993. Of these, 47 (41.2%) had T1 carcinoma (stage I) and 67 (58.8%) T2 (stage II). Treatment varied among radiotherapy, surgery, or combined radiotherapy and surgery. Twelve patients underwent elective neck dissection, one of whom (8.3%) was found to have occult metastases. Local failures were noted in 22 patients (11 T1: 11 T2), three of whom also had neck metastases. All except one T2 patient received radiotherapy. Radiotherapy yielded the best survival rates for T1 disease as combined therapy did for T2. Five-year recurrence rates for T1 patients were 35% for those treated by radiotherapy and 42% for those treated with combined therapy; corresponding figures for T2 patients were 39% and 28%. We suggest that patients with T1 supraglottic carcinoma be managed with radiotherapy and patients with T2 with combined therapy. We believe there is no need for elective neck dissection, especially in T1.

Objective and subjective nasal airflow.

PURPOSE: This study was designed to assess whether a correlation exists between the rhinomanometric measurement of nasal resistance, nasal airflow, and the subjective sensation of airflow. MATERIALS AND METHODS: Sixteen patients with recurrent maxillary sinusitis were examined before and after uncinectomy during functional endoscopic sinus surgery. Subjective nasal sensation of airflow was assessed by means of a visual scale before and after uncinectomy. Rhinomanometry was performed three times for every patient: before anesthesia, and before and after uncinectomy. The subjective nasal sensation of airflow was compared with the nasal airflow and resistance to flow as measured by rhinomanometry. RESULTS: Rhinomanometric measurements were almost the same before and after uncinectomy, with no significant difference, whereas patients reported a significant improvement in nasal airflow. CONCLUSION: Rhinomanometric measurements of nasal airflow and resistance often have no correlation to the patients's sensation of airflow. However, because it is the patients' ultimate concern to breathe more comfortably, the rhinomanometer has little clinical value.

Isolated sphenoid sinus changes--history, CT and endoscopic finding.

This study reviews the records of 21 patients with isolated sphenoid sinus disease who were treated by rigid endoscopic sphenoidotomy at the Nose and Sinus Unit, Department of Otolaryngology of Beilinson Medical Center, Israel. Diagnosis was made on the basis of history, rigid nasal endoscopy and computed tomography (CT) scan. The most frequent symptom was headache; no instances of 'pathognomonic' headache were found. Sphenoidotomy was performed through the area of the natural ostium. The pathological finding was infection in 11 patients, cyst in four patients, polyps in three patients, mucocoele in two, and inverted papilloma in one patient. Surgical results were very good. Endoscopic sphenoidotomy proved to be safe, with minimal blood loss, reduced operating time, decreased morbidity, and short post-operative hospitalization.

The significance of serum IgM IgA and IgG antibodies specific for Epstein-Barr virus as determined by immunoperoxidase assay in the rapid diagnosis of infectious mononucleosis.

The feasibility of using serum IgM, IgA and IgG antibodies specific to Epstein-Barr virus (EBV) viral capsid antigen (VCA), as determined by immunoperoxidase assay (IPA), for the early diagnosis of mononucleosis was evaluated in 65 patients with infectious mononucleosis (IMN). Control groups consisted of 104 healthy students and 15 cytomegalovirus-infected patients. In the first serum sample obtained upon admission, IgM antibodies (titer > or = 64) to EBV VCA were found in 64 of the 65 IMN patients (98%), while EBV-VCA IgA antibodies (titer > or = 32) were found in 32 patients (49%). In those particular titers, no EBV-VCA IgM or IgA antibodies were found in any of the control sera. EBV-VCA-specific IgM antibodies were also not detected in any of the 15 patients with cytomegalovirus infection. In sera obtained from IMN patients within 10 days of the onset of symptoms, 18 of 19 (95%) were IgM seropositive. This study demonstrates that serum EBV-VCA IgM antibodies (titer > or = 64) as determined by IPA are highly specific (100%) and highly sensitive (98%) and can be of value for the early and rapid diagnosis of EBV-IMN infection.

Follicular carcinoma of the thyroid.

BACKGROUND: Follicular carcinomas of the thyroid are less common than papillary carcinomas of the thyroid, and the available data on prognostic factors are relatively scant. A retrospective study covering four decades was undertaken to evaluate clinical and pathologic findings with regard to their effect on prognosis. METHODS: In 195 cases of follicular carcinoma treated from 1954 to 1991 age, sex, histologic type (minimally invasive vs. widely invasive), tumor size, and local, regional, and distant spread as well as the contribution of treatment to survival were evaluated in relation to prognosis. RESULTS: Age was a significant prognostic factor: there was 100% survival of patients younger than 20 years of age at diagnosis and only one death in the 20-39 year age group. Sex was not a significant prognostic factor, although there was a tendency to a better prognosis in females. Tumor size was significant, more than 6 cm having a poor prognosis. Blood vessel invasion influenced prognosis for the first 10 years. The presence of distant metastases was significant regarding survival. Lymph node involvement had a negative effect on the outcome. CONCLUSIONS: The factors of age, tumor size, invasion of blood vessels, and distant metastases are significant predictors of survival for patients with follicular carcinoma, whereas sex is not; regional spread needs to be evaluated further.