T Atula

Helsinki University Central Hospital, Helsinki, Province of Southern Finland, Finland

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Publications (17)30.53 Total impact

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    Article: High CIP2A immunoreactivity is an independent prognostic indicator in early-stage tongue cancer.
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    ABSTRACT: 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. 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. 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. 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.
    British Journal of Cancer 06/2011; 104(12):1890-5. · 5.04 Impact Factor
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    Article: Bmi-1 expression predicts prognosis in squamous cell carcinoma of the tongue.
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    ABSTRACT: 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. 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. 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). Negative Bmi-1 immunoexpression might serve as a marker of poor prognosis in oral tongue carcinoma patients.
    British Journal of Cancer 02/2010; 102(5):892-7. · 5.04 Impact Factor
  • Article: Micrometastases and isolated tumour cells in sentinel lymph nodes in oral and oropharyngeal squamous cell carcinoma.
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    ABSTRACT: 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. 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. 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%). 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.
    European journal of surgical oncology: the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 02/2009; 35(5):532-8. · 2.56 Impact Factor
  • Article: The MDM2 promoter polymorphism SNP309T-->G and the risk of uterine leiomyosarcoma, colorectal cancer, and squamous cell carcinoma of the head and neck.
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    ABSTRACT: 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. 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. 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. 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.
    Journal of Medical Genetics 10/2005; 42(9):694-8. · 6.36 Impact Factor
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    Article: Sentinel lymph node biopsy in oral cavity squamous cell carcinoma without clinically evident metastasis.
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    ABSTRACT: 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. 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. 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. Our results show that SLN biopsy is a promising tool for use in patients with oral SCC. However, further studies are necessary.
    Head & Neck 02/2004; 26(1):16-21. · 2.40 Impact Factor
  • Article: Cartilage invasion of laryngeal cancer detected by magnetic resonance imaging.
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    ABSTRACT: 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.
    Archiv für Klinische und Experimentelle Ohren- Nasen- und Kehlkopfheilkunde 09/2001; 258(6):272-5. · 1.29 Impact Factor
  • Article: Unilateral blindness in a child with acute sinusitis.
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    ABSTRACT: 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.
    Rhinology 04/2000; 38(1):43-4. · 1.32 Impact Factor
  • Article: Otitis media as a sign of Wegener's granulomatosis in childhood.
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    ABSTRACT: 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.
    Acta oto-laryngologica. Supplementum 02/2000; 543:48-50.
  • Article: Complications of acute sinusitis in children.
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    ABSTRACT: 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.
    Acta oto-laryngologica. Supplementum 02/2000; 543:154-7.
  • Article: [Serious complications following sinusitis in children].
    Duodecim; lääketieteellinen aikakauskirja 02/1999; 115(12):1306-10.
  • Article: Human papillomavirus, Epstein-Barr virus, human herpesvirus 8 and human cytomegalovirus involvement in salivary gland tumours.
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    ABSTRACT: 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.
    Oral Oncology 10/1998; 34(5):391-5. · 2.86 Impact Factor
  • Article: The evaluation and treatment of the neck in carcinoma of the oral cavity.
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    ABSTRACT: 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.
    Acta oto-laryngologica. Supplementum 02/1997; 529:223-5.
  • Article: Fine-needle aspiration biopsy in the diagnosis of parotid gland lesions: evaluation of 438 biopsies.
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    ABSTRACT: 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.
    Diagnostic Cytopathology 10/1996; 15(3):185-90. · 1.16 Impact Factor
  • Article: Fine-needle aspiration cytology of submandibular gland lesions.
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    ABSTRACT: The usefulness of fine-needle aspiration cytology (FNAC) in the diagnosis and treatment of submandibular gland lesions is not well known. The 210 FNACs taken from submandibular gland lesions at Turku University Central Hospital between 1984 and 1991 were reviewed. Of these FNACs, 78 samples from primary lesions were confirmed histologically. Within this subset 10 FNACs were taken from benign neoplasms, all of which were correctly classified (sensitivity 100 per cent; specificity 88 per cent). Only four of the 14 FNACs from malignant lesions were cytologically considered malignant (sensitivity 29 per cent). On the other hand, four FNACs raised a false suspicion of malignancy (specificity 6 per cent). Out of 54 FNACs from non-neoplastic lesions 43 were correct (sensitivity 80 per cent; specificity 63 per cent). There were 104 patients (123 FNACs), who had not been operated on: the follow-up of these patients shows that in this subset of FNACs there were no false malignant but probably one false benign finding (1 per cent). We conclude that FNAC can offer valuable information about the type of the submandibular gland lesion, but the decision of operative and other treatment should not be based solely on the result of FNAC.
    The Journal of Laryngology & Otology 10/1995; 109(9):853-8. · 0.60 Impact Factor
  • Article: Aneuploidy in salivary gland adenomas.
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    ABSTRACT: The occurrence of abnormal nuclear DNA content in major salivary gland adenomas is not well known and its correlation with tumor recurrence has not been documented previously. From 1987 to 1991, 119 consecutive major salivary gland adenomas were operated on at Turku University Central Hospital. These tumors were analyzed by flow cytometry and 100 (84%) were found to be diploid, 12 (10%) near-diploid and 7 (6%) aneuploid with DNA indexes > 1.15. The mean proliferation rate measured as a percentage of cells in the S-phase fraction was 2.5 +/- 1.6%. The histological slides were then blindly reclassified according to current World Health Organization classification. As a result histological classification was changed in 3 tumors: malignant cells were found in 2 aneuploid tumors and 1 diploid neoplasm. Preoperative cytological fine-needle aspiration biopsy had been considered as possibly malignant in 2 of these cases. Among all case material 10 specimens were recurrent tumors; although the tendency to recur depended on the extent and adequacy of the surgery performed, multiple recurrences were associated with non-diploid tumors.
    Archiv für Klinische und Experimentelle Ohren- Nasen- und Kehlkopfheilkunde 01/1995; 252(7):395-400. · 1.29 Impact Factor
  • Article: Basal cell adenocarcinoma of the parotid gland: a case report and review of the literature.
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    ABSTRACT: Basal cell adenocarcinoma is a rare salivary gland tumour. A DNA diploid parotid gland basal cell adenocarcinoma, with a low mitotic rate, in a 78-year-old female patient is described. Total removal of the affected salivary gland without sacrificing the facial nerve gave a good therapeutic result.
    The Journal of Laryngology & Otology 10/1993; 107(9):862-4. · 0.60 Impact Factor
  • Article: Micrometastases and isolated tumour cells in sentinel lymph nodes in oral and oropharyngeal squamous cell carcinoma