Causes for delay before specialist consultation in head and neck cancer.

BACKGROUND: Head and neck cancers are often diagnosed at a late stage, thus resulting in a generally poor prognosis. This is partly attributable to patients' hesitancy in seeking treatment. However, the length and causes of these patient delays remain relatively unknown. MATERIAL AND METHODS: We included all new head and neck cancer patients treated at our tertiary care center between 2016 and 2017. Using a patient questionnaire, we collected data on patients' symptoms and other factors related to seeking medical care, and recorded both patient- and primary health care-related delays. We then compared the data collected from these patients to patient and tumor characteristics collected from hospital records, and analyzed various causes for delay before a specialist consultation to the Department of Otorhinolaryngology - Head and Neck Surgery. RESULTS: Among the patients (n = 142) in our study, the median patient delay was 35 d with 73% of patients seeking medical care within 3 months. In comparison, the median primary health-care delay was 20 d. Certain symptoms influenced patient delay. Hoarseness and breathing difficulties correlated with longer patient delay while patients with a lump on the neck had a shorter delay. Patient delay was associated with certain tumor-related factors such as the tumor site and the presence of regional metastases, which resulted in shorter patient delay. None of the patient-related factors appeared to impact delay. Important factors influencing primary health-care delay included the initial location visited and whether any follow-up visit was scheduled or not. CONCLUSIONS: Although most patients sought medical advice without a major delay and were adequately referred, we found that long delays existed. Raising awareness of the symptoms of head and neck cancer among general population and health-care providers is probably the best way to get patients to curative treatment without delay.

Intracranial Suppurative Complications of Sinusitis.

BACKGROUND: Intracranial complications of paranasal sinusitis have become rare due to widespread and early use of antibiotics. Potentially life-threatening intracranial complications of sinusitis include subdural empyema, epidural and intracerebral abscess, meningitis, and sinus thrombosis. Patients with intracranial complication of sinusitis can present without neurological signs, which may delay diagnosis and correct treatment. AIMS: Our aim was to evaluate the diagnostics, treatment, and outcome of sinusitis-related intracranial infections at our tertiary referral hospital with a catchment area of 1.9 million people. MATERIALS AND METHODS: We retrospectively collected data on all patients diagnosed and treated with an intracranial infection at the Helsinki University Hospital, Helsinki, Finland, during a 10-year period between 2003 and 2013. RESULTS: Six patients were diagnosed to have a sinusitis-related intracranial infection. Four patients had an epidural abscess, one both an epidural abscess and a subdural empyema and one a subdural empyema. The most common presenting complaint was headache (100%) followed by fever (83%), vomiting (50%), nasal congestion (50%), forehead lump (34%), and neck stiffness (17%). All patients were managed surgically. Most (83%) patients recovered to premorbid state without neurological sequelae. One patient died intraoperatively. CONCLUSION: Patients with a sinusitis-related intracranial suppuration typically present with signs of raised intracranial pressure rather than signs of sinusitis. Most are likely to need neurosurgical intervention and evacuation of the abscess without delay.

Association of multiple sclerosis and sudden sensorineural hearing loss.

BACKGROUND: Multiple sclerosis (MS) may affect other cranial nerves besides the optic nerve. Sudden sensorineural hearing loss (SSHL), possibly caused by a deficit in the auditory tract, including the vestibulocochlear nerve, is sometimes associated with MS. OBJECTIVES: We aimed to assess the incidence of SSHL among MS patients, its frequency as an initial symptom of MS, and magnetic resonance imaging (MRI) findings associated with SSHL in MS. METHODS: We collected retrospectively all patients diagnosed with MS and SSHL at the Helsinki University Hospital between 2004 and 2014. Patients with both diagnoses were re-evaluated using hospital medical records, audiograms and head MRI scans. RESULTS: A total of 2736 patients were diagnosed with MS, 1581 patients with SSHL, and 18 patients (0.7% of all MS patients) with both; two patients presented with SSHL as an initial symptom of MS. The annual incidence of SSHL was 59.8/100 000 (95% confidence interval (CI) 37.7-94.9) in MS patients, and 12.4/100 000 (95% CI 11.8-13.0) in the normal population. CONCLUSION: SSHL is a rare symptom of MS and is even less frequent as an initial symptom. Its incidence in MS patients, however, markedly exceeds that in the normal population.

High CIP2A immunoreactivity is an independent prognostic indicator in early-stage tongue cancer.

BACKGROUND: No reliable prognostic markers exist for squamous cell carcinoma of the tongue, and its prognosis can even in early stages be unpredictable and survival poor despite treatment. A potential marker is oncoprotein cancerous inhibitor of PP2A (CIP2A), which acts as a prognostic marker in gastric and non-small cell lung cancers. METHODS: We collected specimens of 73 stage T1N0M0 and T2N0M0 oral squamous cell carcinomas of the tongue, as well as samples from normal oral mucosa, dysplastic lesions, and invasive carcinomas (n=39). All samples were stained for CIP2A by immunohistochemistry. Survival curves were constructed according to the Kaplan-Meier method. The Cox proportional hazard model served for univariate and multivariate survival analysis. RESULTS: High CIP2A immunoreactivity predicted poor survival in tongue cancer patients (P=0.027, logrank test). In multivariate survival analysis, CIP2A was an independent prognostic factor (HR 2.02, 95% confidence interval 1.07-3.82, P=0.030). Cytoplasmic CIP2A expression was higher in severe dysplasia than in mild dysplasia. CONCLUSION: Our results suggest that high CIP2A expression characterises aggressive disease. Acting as a prognostic marker it might be of help when choosing patients for adjuvant treatment in tongue cancer patients.

Bmi-1 expression predicts prognosis in squamous cell carcinoma of the tongue.

BACKGROUND: The prognosis of squamous cell carcinoma of the oral tongue is poor and it would be beneficial to find prognostic markers to better adjust treatment. Bmi-1 controls cell cycle and self-renewal of tissue stem cells, transcription factor c-myc affects cell proliferation and apoptosis, and Snail regulates epithelial-mesenchymal transition. The expression of these markers has been connected to prognosis in many cancer types. METHODS: Bmi-1, c-myc, and Snail expressions were studied in our material consisting of 73 primarily T1N0M0 oral tongue carcinoma patients. We compared the immunoexpressions of Bmi-1, c-myc, and Snail with clinical parameters including the degree of histological differentiation, tumour size, TNM classification, depth of invasion, and resection margins. In addition, survival analyses were performed, comparing disease-free survival time with the registered protein expression of the markers mentioned above. RESULTS: A significant correlation between Bmi-1 protein expression and recurrence (log-rank test, P=0.005) was detected. Snail and c-myc expression did not correlate with prognosis. Snail expression correlated with histopathological grade (Fisher's exact test, P=0.007) and with the invasion depth of tumours (chi(2)-test, P=0.037). CONCLUSION: Negative Bmi-1 immunoexpression might serve as a marker of poor prognosis in oral tongue carcinoma patients.

Micrometastases and isolated tumour cells in sentinel lymph nodes in oral and oropharyngeal squamous cell carcinoma.

BACKGROUND: The occurrence of micrometastases (MMs) and isolated tumour cells (ITCs) in oral sentinel lymph node (SLN) biopsy is poorly known, and the definitions and clinical significance of MMs and ITCs in SLN biopsy are controversial. We compared the UICC/TNM definitions of MMs and ITCs with our previously published sentinel node protocol to assess how the adoption of the UICC/TNM criteria would affect the staging of nodal micrometastatic disease. METHODS: Of 107 patients who had a SLN biopsy and pathology at 150 microm intervals, 35 with metastatic tumour were included. Eighty-six SLNs were reassessed using the UICC/TNM definitions for MMs and ITCs. Findings were linked to the final pathology in the subsequent neck dissection. RESULTS: Initial H&E sections showed metastases in 24 patients (in 34 out of 61 SLN), 8 of whom (9 SLNs) had MMs. Additional step serial sections revealed metastatic deposits in a further 11 patients (15 out of 25 SLNs were positive) which were reassessed as MMs (6 patients) or ITCs (5 patients). Subsequent neck dissection revealed additional metastases in 46% of patients with MM, whilst one of the ITC patients had subsequent neck metastases (20%). CONCLUSION: Despite some limitations, the UICC/TNM classification provides an objective, uniform method of detecting MMs and ITC's. Unlike in cases with ITC, metastases in other non-SLNs were common when a micrometastasis was detected in a SLN, indicating need for further treatment of the neck.

The MDM2 promoter polymorphism SNP309T-->G and the risk of uterine leiomyosarcoma, colorectal cancer, and squamous cell carcinoma of the head and neck.

BACKGROUND: MDM2 acts as a principal regulator of the tumour suppressor p53 by targeting its destruction through the ubiquitin pathway. A polymorphism in the MDM2 promoter (SNP309) was recently identified. SNP309 was shown to result, via Sp1, in higher levels of MDM2 RNA and protein, and subsequent attenuation of the p53 pathway. Furthermore, SNP309 was proposed to be associated with accelerated soft tissue sarcoma formation in both hereditary (Li-Fraumeni) and sporadic cases in humans. METHODS: We evaluated the possible contribution of SNP309 to three tumour types known to be linked with the MDM2/p53 pathway, using genomic sequencing or restriction fragment length polymorphism as screening methods. Three separate Finnish tumour materials (population based sets of 68 patients with early onset uterine leiomyosarcomas and 1042 patients with colorectal cancer, and a series of 162 patients with squamous cell carcinoma of the head and neck) and a set of 185 healthy Finnish controls were analysed for SNP309. RESULTS: Frequencies of SNP309 were similar in all four cohorts. In the colorectal cancer series, SNP309 was somewhat more frequent in women and in patients with microsatellite stable tumours. Female SNP309 carriers were diagnosed with colorectal cancer approximately 2.7 years earlier than those carrying the wild type gene. However, no statistically significant association of SNP309 with patients' age at disease onset or to any other clinicopathological parameter was found in these three tumour materials. CONCLUSION: SNP309 had no significant contribution to tumour formation in our materials. Possible associations of SNP309 with microsatellite stable colorectal cancer and with earlier disease onset in female carriers need to be examined in subsequent studies.

Sentinel lymph node biopsy in oral cavity squamous cell carcinoma without clinically evident metastasis.

BACKGROUND: The clinically N0 neck in patients with oral SCC is commonly treated by neck dissection because the existence of metastases cannot be excluded. To determine whether unnecessary treatment could be avoided, we evaluated the feasibility of sentinel lymph node (SLN) biopsy. METHODS: Fifteen previously untreated patients with T1 or T2 oral SCC without clinically or radiologically detectable metastasis were included. A blue dye and gamma probe were used to identify SLNs. SLNs were stained with cytokeratins. All nodes in neck dissection specimens were stained using H and E. RESULTS: SLNs were identified in 14 patients by lymphoscintigraphy and in all patients when probe and dye were combined. Four neck dissection specimens contained four metastatic lymph nodes. Three of the four lymph nodes were SLN. One SLN was found to be metastatic after immunostaining. However, although there was one blue sentinel node in one neck, a metastatic non-SLN was present. CONCLUSIONS: Our results show that SLN biopsy is a promising tool for use in patients with oral SCC. However, further studies are necessary.

Cartilage invasion of laryngeal cancer detected by magnetic resonance imaging.

Cartilage invasion of laryngeal cancer has a significant impact on the choice of treatment modality and on the outcome for the patients. Cartilage invasion was evaluated radiologically and histopathologically in 18 patients who underwent total laryngectomy. The histopathological examination showed intracartilaginous tumor spread in nine specimens, whereas in the other nine no cartilage invasion was found. Magnetic resonance imaging (MRI) detected the cartilage invasion in six patients and excluded it in six. There were three false negative and three false positive findings from the MRI examination. The relatively common false findings of MRI should be kept in mind in the choice of treatment.

Otitis media as a sign of Wegener's granulomatosis in childhood.

Wegener's granulomatosis (WG) is a rare disease among paediatric patients. Chronic otitis media with or without facial nerve dysfunction is a known manifestation of the disease among adults. A case of a 15-year-old boy with WG, whose initial symptoms were acute otitis media and facial nerve paralysis, is presented. The otorhinolaryngological manifestations, as well as diagnostic and current treatment modalities in paediatric patients with WG, are discussed.

Complications of acute sinusitis in children.

Acute sinusitis is often a mild, self-limiting disease. However, in some cases, especially among children, sinusitis may become a severe, even life-threatening, disease. To examine the nature of complications of acute sinusitis, we studied the cases of children treated at the Helsinki University ENT Hospital, because of a complication caused by acute sinusitis from January 1997 to September 1998. There were 12 children (4 girls, 8 boys), whose ages ranged from 16 months to 16 years. One child had an epidural abscess, one got meningitis and cavernous sinus thrombosis, five had orbital cellulitis, one of whom lost her vision permanently in one eye, and five had preseptal cellulitis. All the children were treated with intravenous antibiotics and all, except the youngest, were treated with a direct sinus puncture. An operation (intranasal antrostomy, orbital drainage, functional endoscopic sinus surgery or adenoidectomy) was performed on six patients. In the majority of children, acute sinusitis is a mild self-limiting disease. However, severe complications still exist. When a complication of sinusitis is suspected, it is of utmost importance that the child be sent immediately to a hospital for proper diagnosis and treatment.

Unilateral blindness in a child with acute sinusitis.

Orbital infection in association with sinusitis is an emergency. It may cause visual disturbances, and in rare cases even permanent blindness by affecting the optic nerve. We report an unusual case of acute sinusitis that was complicated by irreversible visual loss in a young patient. As there is increasing evidence that respiratory viruses play an important role in the pathogenesis of acute community acquired sinusitis and spontaneous healing with only symptomatic treatment is common, the use of antibiotics in the treatment of acute sinusitis may not be needed in all cases. If the general policy to use antibiotics in acute sinusitis will be changed to more restrained and expectant, we have to be even more aware of these nowadays rare complications.

Human papillomavirus, Epstein-Barr virus, human herpesvirus 8 and human cytomegalovirus involvement in salivary gland tumours.

Human papillomaviruses (HPV) are involved in the etiology of both benign and malignant epithelial lesions. The occurrence of HPV types 16 and 18 in gynecological squamous cell carcinomas is also well known. Of the herpesviruses, Epstein-Barr virus (EBV) is associated with, for example, undifferentiated nasopharyngeal carcinoma, endemic Burkitt's lymphoma and immunoblastic lymphoma, and human herpesvirus 8 (HHV-8) with Kaposi's sarcoma. As little is known about the etiological factors of salivary gland tumours, the presence of HPV, EBV, HHV-8 and human cytomegalovirus (CMV) in these tumours were examined. Fresh tissue samples obtained from 19 consecutive pleomorphic adenomas and 19 malignant salivary gland tumours were analyzed with polymerase chain reaction. Two samples showed EBV DNA positivity, a lymphoma of the parotid gland and a pleomorphic adenoma arising in the nasal cavity. HPV, HHV-8 and CMV DNA were not detected in any of the tumour samples. The results indicate that HPV, HHV-8 and CMV do not seem to have any role in the etiology of salivary gland neoplasms.

Assessment of cervical lymph node status in head and neck cancer patients: palpation, computed tomography and low field magnetic resonance imaging compared with ultrasound-guided fine-needle aspiration cytology.

OBJECTIVE: Since the assessment of lymph node metastases in head and neck cancer patients remains a major problem, the findings of different imaging methods and the role of these methods in the clinical management are compared. MATERIAL AND METHODS: Palpation, computed tomography (CT) and low field magnetic resonance imaging (MRI; 0.1 T) are evaluated and compared with ultrasound-guided fine-needle aspiration cytology (US-guided FNAC) prospectively in 105 consecutive patients with a primary cancer in the head and neck region. RESULTS: In the subgroup of 86 patients with palpable normal necks, CT showed lymph nodes fulfilling the radiologic criteria for malignancy in 27% (23/86), MRI in 17% (10/60) and US in 14% (12/86) of the patients US guided FNAC usually showed malignancy in necks containing lymph nodes with central necrosis on CT, but the enlarged lymph nodes that were also common on the contralateral side were often benign on cytology. In 5 patients, FNAC under US-guidance showed malignancy although none of them had lymph nodes fulfilling the radiologic criteria for malignancy. In the other subgroup of 19 patients with palpable metastatic necks, 2 patients had bilateral metastases detected by all imaging methods but not by palpation. CONCLUSION: CT is superior to low field MRI in depicting small pathologic lymph nodes. Unlike lymph node structure, lymph node size is not a highly reliable criterion for malignancy. The findings must be correlated in relation to the primary disease. Since FNAC under US-guidance offers additional information about enlarged lymph nodes and since it can show malignancy in small lymph nodes not found by other methods, it can be recommended for most head and neck cancer patients irrespective of the use of CT or MRI.

The evaluation and treatment of the neck in carcinoma of the oral cavity.

Locoregional recurrence is the most common cause of failure in the treatment of carcinoma in the oral cavity. The extent of the disease can be evaluated by inspection, endoscopy, palpation, computed tomography (CT), magnetic resonance imaging (MRI), and ultrasound (US). The treatment consists of surgery, radiation, and their combination. The purpose of this study was to evaluate the effect of imaging and active treatment of the neck in patients with oral cancer. Altogether 31 consecutive patients with 32 squamous cell carcinomas in the oral cavity were included. Of the tumors, 5 were T1, 18 were T2, 5 were T3 and 4 were T4. According to CT and US findings, 19 of the patients had a normal lymph node status, whereas 12 patients had enlarged or rim-like enhanced lymph nodes in the neck. Preoperative radiotherapy to the primary site and the neck was given to all except 3 patients. Surgery was carried out in all except 4 patients. A neck dissection was performed in N-positive cases (n = 9) and electively in patients with a high risk of metastases (n = 10). The median follow-up time was 31 months, with the minimum of 11 months, or until death. Seventeen (55%) of the patients experienced a recurrence. In only 1 patient the recurrence appeared initially in the neck, whereas all others had a local recurrence. Later, a distant metastasis was found in 3 patients. The meticulous imaging and active treatment of the neck were successful since only one patient's disease recurred primarily in the neck. The high number of recurrencies at the primary site show the need for intensified therapy.

Palpation, ultrasound, and ultrasound-guided fine-needle aspiration cytology in the assessment of cervical lymph node status in head and neck cancer patients.

BACKGROUND: Lymph node status of the neck is the most important prognostic factor in head and neck cancer patients. Assessment of the lymph nodes status is still often based on palpation only, although the low accuracy of palpation is known. METHODS: Altogether 105 consecutive head and neck cancer patients were examined using ultrasound (US) and ultrasound-guided fine-needle aspiration cytology (FNAC) to evaluate the additional information obtained by these methods. RESULTS: Of the 86 patients with palpable normal necks, FNAC taken under US-guidance showed malignancy in 13. The US size criteria for malignancy were fulfilled in 7 of these patients, whereas the lymph nodes were of normal size in 6 of them. In the whole patient material, US-guided FNAC showed bilateral metastasis in 3 patients although only unilateral or no metastasis was found by palpation. CONCLUSION: US combined with US-guided FNAC can be recommended as a method for evaluating for regional metastases in head and neck cancer patients, both for those with and those without palpable metastasis.

Fine-needle aspiration biopsy in the diagnosis of parotid gland lesions: evaluation of 438 biopsies.

The usefulness of fine-needle aspiration biopsy (FNAB) in the diagnosis and treatment of salivary gland lesions is still controversial. The 438 FNABs taken at the Turku University Central Hospital between 1984-1991 were reviewed. Of these FNABs, 218 had been confirmed histologically. Within this subset, 136 FNABs were taken from benign neoplasms, and of these, 103 were correct (sensitivity 76%, specificity 83%). Only 26 of the 47 FNABs from malignant lesions were cytologically considered to be malignant (sensitivity 55%) and 11 samples raised a false suspicion of malignancy (specificity 92%). Out of 35 FNABs from non-neoplastic lesions, 27 were correct (sensitivity 77%, specificity 80%). There were 175 patients (217 FNABs), who had not been operated on: the follow-up of these patients showed that false malignant and false benign findings were rare. FNAB was safe and no serious complications occurred. However, there was a delay in the treatment of six patients probably because of the physicians' limited understanding of the diagnostic role of FNAB. FNAB offers valuable information about the type of parotid lesion, but the clinician must know how to interpret the cytologic statement, and the decision to use operative and other treatment should not be based solely on the result of FNAB. Diagn Cytopathol 1996; 15:185-190.