Publications by authors named "Matti Pukkila"

24 Publications

  • Page 1 of 1

Long-term Quality of Life After Treatment of Oropharyngeal Squamous Cell Carcinoma.

Laryngoscope 2020 Aug 25. Epub 2020 Aug 25.

Department of Otorhinolaryngology-Head and Neck Surgery, Turku University and Turku University Hospital, Turku, Finland.

Objectives: To analyze the long-term quality of life (QOL) among oropharyngeal squamous cell carcinoma (OPSCC) survivors.

Study Design: Retrospective chart analysis and patient response to European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, Core Module (EORTC QLQ-C30), Head and Neck Module (EORTC QLQ-H&N35), and M.D. Anderson Dysphagia Inventory (MDADI) survey questionnaires.

Methods: All survivors of OPSCC diagnosed and treated between 2000 and 2009 in Finland were included. There were 263 survivors (44.2% of all curatively treated patients), of which a total of 164 participated in this study (62.4%). Median follow-up was 11.79 years (range = 8.59-18.53 years, interquartile range [IQR] = 4.64 years). The mean age of the participants was 67.9 years (standard deviation = 8.0 years) at QOL follow-up.

Results: Most survivors reported a good QOL. The EORTC QLQ-C30 global health status median was 75.00 (IQR = 31.25). The single modality treatment group had significantly better QOL outcomes than the combined treatment group. Nonsmokers and previous smokers had significantly better QOL outcomes than patients who smoked at the time of diagnosis. A history of heavy alcohol use resulted in significantly worse QOL outcomes. The p16-positive cancer patients had significantly better QOL outcomes than p16-negative patients. Percutaneous endoscopic gastrostomy (PEG) tube-dependent patients reported a significantly worse QOL than patients without a PEG tube.

Conclusions: Long-term QOL in OPSCC survivors is generally good. In line with previous literature, single modality treatment was superior to combined treatment in long-term QOL outcomes, and it should be pursued whenever possible.

Level Of Evidence: 4 Laryngoscope, 2020.
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http://dx.doi.org/10.1002/lary.29042DOI Listing
August 2020

Small oral tongue cancers (≤ 4 cm in diameter) with clinically negative neck: from the 7th to the 8th edition of the American Joint Committee on Cancer.

Virchows Arch 2018 Oct 23;473(4):481-487. Epub 2018 Jul 23.

Department of Pathology, University of Turku, Turku, Finland.

One of the main changes in the 8th edition of the American Joint Committee on Cancer (AJCC) for staging of oral cancer is the inclusion of depth of invasion (DOI) in the T category. However, cancers in different oral subsites have variable behavior, with oral tongue squamous cell carcinoma (OTSCC) being the most aggressive one even at early stage. Thus, it is necessary to evaluate the performance of this new T category in homogenous cohort of early OTSCC. Therefore, we analyzed a large cohort of patients with a small (≤ 4 cm) OTSCC to demonstrate the differences in T stage between the AJCC 7th and 8th editions. A total of 311 early-stage cases (AJCC 7th) of OTSCC were analyzed. We used 5 mm and 10 mm DOI for upstaging from T1 to T2 and from T2 to T3 respectively, as in the AJCC 8th. We further reclassified the cases according to our own proposal suggesting 2 mm to upstage to T2 and 4 mm to upstage to T3. According to AJCC 7th, there were no significant differences in the survival analysis. When we applied the 8th edition, many cases were upstaged to T3 and thus associated with worse disease-specific survival (HR 2.37, 95% CI 1.12-4.99) and disease-free survival (HR 2.12, 95% CI 1.09-4.08). Based on our proposal, T3 cases were associated with even worse disease-specific survival (HR 4.19, 95% CI 2.27-7.74). The 8th edition provides better survival prediction for OTSCC than the 7th and can be further optimized by lowering the DOI cutoffs.
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http://dx.doi.org/10.1007/s00428-018-2417-yDOI Listing
October 2018

Prognostic impact of tumour-stroma ratio in early-stage oral tongue cancers.

Histopathology 2018 Jun 23;72(7):1128-1135. Epub 2018 Mar 23.

Department of Pathology, University of Helsinki, Helsinki, Finland.

Aims: Oral tongue squamous cell carcinoma (OTSCC) has a relatively poor outcome, and there is a need to identify better prognostic factors. Recently, tumour-stroma ratio (TSR) has been associated with prognosis in several cancers. The aim of this multi-institutional study was to evaluate the prognostic value of TSR from original haematoxylin and eosin (HE)-stained tumour-resection slides in a series of early-stage (cT1-2N0) OTSCC patients.

Methods And Results: A TSR cutoff value of 50% was used to divide the patients into stroma-rich (≥50%) and stroma-poor (<50%) groups. The relationships between TSR and clinicopathological characteristics of 311 early-stage OTSCC cases were analysed. The prognostic value of TSR in OTSCC was calculated separately and in combination with a previously published cancer cell budding and depth of invasion (BD) prognostic model. A total of 89 cases (28.6%) belonged to the stroma-rich group. In a multivariate analysis, the stroma-rich group had worse disease-free survival, with a hazard ratio (HR) of 1.81 [95% confidence interval (CI) 1.17-2.79, P = 0.008], and higher cancer-related mortality (HR 1.71, 95% CI 1.02-2.86, P = 0.03). The combination of the highest-risk parameter scores of TSR and the BD model showed significant correlations with recurrence rate (HR 3.42, 95% CI 1.71-6.82, P = 0.004) and cancer-related mortality (HR 11.63, 95% CI 3.83-35.31, P < 0.001).

Conclusions: We conclude that TSR is a simple histopathological feature that is useful for prognostication of early-stage OTSCC, and suggest that TSR analyses in association with BD score could be included in routine clinical pathology reports for HE-stained slides.
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http://dx.doi.org/10.1111/his.13481DOI Listing
June 2018

Epidemiological and treatment-related factors contribute to improved outcome of oropharyngeal squamous cell carcinoma in Finland.

Acta Oncol 2018 Apr 17;57(4):541-551. Epub 2017 Nov 17.

a Department of Otorhinolaryngology-Head and Neck Surgery , University of Helsinki, Helsinki University Hospital , Helsinki , Finland.

Background: Treatment for oropharyngeal squamous cell carcinoma (OPSCC) has changed, as the proportion of human papilloma virus (HPV)-related disease has increased. We evaluated nationwide information on its management and outcome during the treatment paradigm change period.

Methods: We included all patients diagnosed and treated for OPSCC at the five Finnish university hospitals from 2000 to 2009. Patient records and pathology registries provided the clinicopathological data. p16 staining was performed on primary tumor samples of patients who had received treatment with curative intent.

Results: A total of 674 patients were diagnosed and treated for OPSCC and the incidence increased along the study period. Of the evaluable tumors 58.5% were p16-positive and the number of p16-positive tumors increased along the years. The treatment was given with curative intent for 600 patients and it was completed in 564. Of them, 47.9% underwent primary surgery and 52.1% received definitive oncological treatment. Also, the treatment protocol changed towards a more oncological approach. Among patients treated with curative intent the five-year overall, disease-specific and disease-free survival rates were 60.1, 71.5 and 57.0%. In multivariate analysis, p16-positivity seemed to relate to reduced disease mortality in lateral and anterior-wall disease. Depending on primary tumor localization, also sex, classes T3-4, presence of regional metastasis and radiotherapy modality had an association with disease mortality.

Conclusion: The incidence of p16-positive OPSCC and delivery of definitive oncological treatment increased in Finland during the study period. An improved survival outcome compared with the previous nationwide investigation was observed in this subset of patients.
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http://dx.doi.org/10.1080/0284186X.2017.1400688DOI Listing
April 2018

Improved outcomes with oral tongue squamous cell carcinoma in Finland.

Head Neck 2017 07 8;39(7):1306-1312. Epub 2017 May 8.

Department of Otorhinolaryngology - Head and Neck Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Background: Incidence rates for oral tongue squamous cell carcinoma (SCC) are steadily rising worldwide.

Methods: All patients diagnosed with primary oral tongue SCC at the 5 university hospitals in Finland from 2005 to 2009 were studied. The mean follow-up time was 43 months (median, 54 months; range, 0-111 months).

Results: Three hundred sixty patients with primary oral tongue SCC were identified. Treatment with curative intent was provided for 328 patients (91%). The 5-year disease-specific survival (DSS) rates were as follows: stage I 87%; stage II 73%; stage III 69%; and stage IV 51%. The 5-year recurrence-free survival in general has improved from 47% in our previous published series (1995-1999) to 65% in the current series (p < .001).

Conclusion: The outcome of oral tongue SCC has significantly improved in Finland. However, the relatively high number of disease recurrences in patients with stage I and II disease, when compared with patients with stage III and IV disease, calls for an investigation of new treatment approaches. © 2017 Wiley Periodicals, Inc. Head Neck 39: 1306-1312, 2017.
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http://dx.doi.org/10.1002/hed.24744DOI Listing
July 2017

For early-stage oral tongue cancer, depth of invasion and worst pattern of invasion are the strongest pathological predictors for locoregional recurrence and mortality.

Virchows Arch 2015 Jul 3;467(1):39-46. Epub 2015 Apr 3.

Department of Pathology, Haartman Institute, University of Helsinki, Helsinki, Finland.

Despite early diagnosis and treatment, almost 20% of patients with early-stage (cT1-cT2N0) oral tongue squamous cell carcinoma (OTSCC) still die of their disease. The prognosis of OTSCC patients is influenced by several demographic, clinical, and histopathologic factors. The aim of this multicenter international study was to find which of the factors age, gender, stage, grade, lymphocytic host response, perineural invasion, worst pattern of invasion, or depth of invasion has the strongest prognostic power in early-stage OTSCC. Patient data of 479 patients with early-stage (cT1-2N0) OTSCC in Finland, Brazil, and the USA were retrieved and analyzed using Cox proportional hazards regression models. Our results indicate that depth of invasion (DOI) and worst pattern of invasion (WPOI) are the strongest pathological predictors for locoregional recurrence, with a hazard ratio (HR) for 4 mm DOI of 1.67 (95% confidence interval (CI) 1.07-2.60) and HR for WPOI of 1.46 (95% CI 0.95-2.25). In addition, mortality from early OTSCC was also predicted by DOI (HR 2.44, 95% CI 1.34-4.47) and by WPOI (HR 2.34, 95% CI 1.26-4.32). We suggest that clinically early-stage oral tongue carcinomas 4 mm or deeper, or with a growth pattern of small cell islands or satellites, should be considered as high-risk tumors which require multimodality treatment.
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http://dx.doi.org/10.1007/s00428-015-1758-zDOI Listing
July 2015

SIP1 predicts progression and poor prognosis in pharyngeal squamous cell carcinoma.

Histol Histopathol 2015 May 21;30(5):569-79. Epub 2014 Nov 21.

Department of Otorhinolaryngology- Head and Neck Surgery, Kuopio University Hospital, and Institute of Clinical Medicine, Otorhinolaryngology- Head and Neck Surgery, University of Eastern Finland, Kuopio, Finland.

Objectives: The epithelial-mesenchymal transition (EMT) is a crucial process in tumorigenesis that enables tumor cells to invade and metastasize. The transcription factors SIP1, SLUG, ZEB1, SNAI1, and TWIST are fundamental in regulating EMT. We investigated the relationships between several clinicopathological variables, prognosis, and SIP1, SLUG, or ZEB1 in a retrospective pharyngeal squamous cell carcinoma (PSCC) cohort.

Study Design: Immunohistochemistry was used to evaluate the expression of SIP1, SLUG, and ZEB1 in 108 tumor samples from a retrospective cohort of patients with PSCC.

Results: Tumors with positive epithelial SIP1 immunostaining were more advanced (SIII-IV, p=0.02) and had more lymph node metastases (p=0.04) than SIP1-negative tumors. Tumors with positive stromal staining of SIP1 relapsed more often than SIP1-negative tumors (p=0.007). Negative SIP1 immunoreactivity correlated significantly with better disease-specific survival (DSS) and better overall survival (OS) (p=0.012 and p=0.003 for epithelial reactivity, p=0.018 and p=0.003 for stromal reactivity, respectively). Lack of epithelial SIP1 expression remained an independent and favorable prognostic factor in a Cox proportional hazards model (p=0.046), together with high Karnofsky performance status score and low T class (p<0.001 for both). Co-expression of SNAI1, TWIST, and SIP1 in tumor epithelium predicted even shorter DSS than SIP1 expression alone (p<0.001) in the present study cohort.

Conclusions: SIP1 is related to cancer progression and appears to be an independent prognostic factor in PSCC.
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http://dx.doi.org/10.14670/HH-30.569DOI Listing
May 2015

Characteristics and medical-care-seeking of head and neck cancer patients: a population-based cross-sectional survey.

Oral Oncol 2014 Aug 21;50(8):740-5. Epub 2014 May 21.

Medical Research Center Oulu, Oulu University Hospital, Oulu, Finland.

Objectives: Well-known risk factors, such as smoking and alcohol consumption, easily denounce head and neck cancer patients as smokers, alcohol abusers, and persons who are socially excluded and have low socioeconomic status. To diagnose these patients as early as possible, we should not have a prejudiced assumption of their characteristics.

Materials And Methods: We collected detailed data on patient characteristics and health behavior and explored whether these traits had any effect on seeking medical advice in a population-based cross-sectional study involving 85 patients with head and neck cancer diagnosed between January 2003 and December 2007, residing in two health care districts (population 1,600,000) in Finland. The data were gathered from patient charts and questionnaires. The questionnaire data were compared with the general population in Finland.

Results: We found these patients to be ordinary elderly people whose demographic and social features resembled those of the general population. They smoked more often, but otherwise had a rather healthy lifestyle. Only half were aware that smoking and alcohol consumption were risk factors of head and neck cancer. In a multivariate analysis, fear of physicians (adjusted odds ratio 11.0; 95% confidence interval 1.2-103), medical-care-seeking for symptoms other than pain (18.5; 2.2-156), and not suspecting cancer (11.2; 1.7-75.1) were independent risk factors for delayed consultation (combined appraisal and help-seeking interval over 3 months).

Conclusion: Head and neck cancer patients deviated from the same-aged general population only in excessive smoking. Fear of doctors, having no pain, and no suspicion of cancer resulted in delayed medical-care-seeking.
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http://dx.doi.org/10.1016/j.oraloncology.2014.04.009DOI Listing
August 2014

The impact of weight reduction in the prevention of the progression of obstructive sleep apnea: an explanatory analysis of a 5-year observational follow-up trial.

Sleep Med 2014 Mar 31;15(3):329-35. Epub 2014 Jan 31.

Clinical Research Center, Kuopio University Hospital, Kuopio, Finland; Department of Medicine, Division of Internal Medicine, University of Helsinki, Helsinki, Finland.

Background: Obstructive sleep apnea (OSA) is a chronic progressive disease, and it is well-documented that severe OSA is associated with an increased cardiovascular morbidity and mortality. Weight reduction has been shown to improve OSA; however, we need further evidence to determine if it may prevent the progression of OSA in the long term. The aim of our study was to assess the impact of weight change during a 5-year observational follow-up of an original 1-year randomized controlled trial.

Methods: The participants were divided into the two groups according to the weight change at 5-year follow-up using the 5% weight loss as a cutoff point, which was later referred to as the successful (n = 20) or unsuccessful groups (n = 27). The change in apnea-hypopnea index (AHI) was the main objective outcome variable.

Results: Fifty-seven patients participated in the 5-year follow-up. At 5 years from the baseline, the change in AHI between the groups was significant in the successful group (-3.5 [95% confidence interval {CI}, -6.1 to -0.9]) compared with the unsuccessful group (5.0 [95% CI, 2.0-8.5]) (P = .002). Successful weight reduction achieved an 80% reduction in the incidence of progression of OSA compared to the unsuccessful group (log-rank test, P = .016).

Conclusions: A moderate but sustained weight reduction can prevent the progression of the disease or even cure mild OSA in obese patients.
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http://dx.doi.org/10.1016/j.sleep.2013.11.786DOI Listing
March 2014

Depth of invasion, tumor budding, and worst pattern of invasion: prognostic indicators in early-stage oral tongue cancer.

Head Neck 2014 Jun 2;36(6):811-8. Epub 2013 Sep 2.

Department of Pathology, Haartman Institute, University of Helsinki, Helsinki, Finland.

Background: Oral (mobile) tongue squamous cell carcinoma (SCC) is characterized by a highly variable prognosis in early-stage disease (T1/T2 N0M0). The ability to classify early oral tongue SCCs into low-risk and high-risk categories would represent a major advancement in their management.

Methods: Depth of invasion, tumor budding, histologic risk-assessment score (HRS), and cancer-associated fibroblast (CAF) density were studied in 233 cases of T1/T2 N0M0 oral tongue SCC managed in 5 university hospitals in Finland.

Results: Tumor budding (≥5 clusters at the invasive front of the tumor) and depth of invasion (≥4 mm) were associated with poor prognosis in patients with early oral tongue SCC (hazard ratio [HR], 2.04; 95% confidence interval [CI], 1.17-3.55; HR, 2.55; 95% CI, 1.25-5.20, respectively) after multivariate analysis. The HRS and CAF density did not predict survival. However, high-risk worst pattern of invasion (WPOI), a component of HRS, was also an independent prognostic factor (HR, 4.47; 95% CI, 1.59-12.51).

Conclusion: Analyzing the depth of invasion, tumor budding, and/or WPOI in prognostication and treatment planning of T1/T2 N0M0 oral tongue SCC is recommended.
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http://dx.doi.org/10.1002/hed.23380DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4229066PMC
June 2014

Accuracy of the current TNM classification in predicting survival in patients with sinonasal mucosal melanoma.

Laryngoscope 2012 Aug 1;122(8):1734-8. Epub 2012 May 1.

Department of Otorhinolaryngology-Head and Neck Surgery Oulu University Hospital, Oulu, Finland.

Objectives/hypothesis: The first International Union Against Cancer (UICC) TNM classification for aerodigestive malignant mucosal melanoma was not published until 2009, and since then, only a few studies have evaluated the accuracy of this staging system. Our aim was to evaluate the accuracy of this UICC staging system for sinonasal malignant mucosal melanoma (SMMM) in a nationwide survey.

Study Design: Retrospective, population-based, multicenter study.

Methods: The hospital surgical and discharge registries were used to identify the patients. A database including demographic and clinicopathologic variable was created.

Results: Altogether, 50 SMMM patients diagnosed in Finland from 1990 to 2004 were evaluated. Three- and 5-year overall survival rates were 44% and 27%, respectively. Significant differences in overall survival according to T classification (P = .028, log rank) and stage (P = .02, log rank) were found. Tumor extension to the sphenoid sinus had a significant negative impact on survival (n = 11, P = .03, log rank).

Conclusions: The current UICC staging system for mucosal melanoma provides a useful format for staging SMMMs in clinical settings.
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http://dx.doi.org/10.1002/lary.23343DOI Listing
August 2012

[Current issues in the treatment of pharyngeal cancer].

Duodecim 2011 ;127(18):1971-7

TAYS:n korva-, nenä- ja kurkkutautien klinikka.

In Finland over the past few years approximately 100 new cases of oro- and hypopharyngeal cancer have been diagnosed annually. Most of these are squamous cell carcinomas. The incidence of these diseases increases after age 45. Minor and nonspecific local symptoms caused by the primary tumor are common to pharyngeal cancers at the initial stage of the disease. Often the diagnosis is delayed and the search for the primary tumor is begun only after detection of neck metastases. They occur in 60 to 80% at the time of diagnosis. Among the risk factors, smoking and heavy drinking are most important.
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December 2011

Twist and snai1 expression in pharyngeal squamous cell carcinoma stroma is related to cancer progression.

BMC Cancer 2011 Aug 11;11:350. Epub 2011 Aug 11.

Department of Otorhinolaryngology - Head and Neck Surgery, Kuopio University Hospital, FI-70211 Kuopio, Finland.

Background: Epithelial-mesenchymal transition (EMT) is a crucial process in tumorigenesis since tumor cells attain fibroblast-like features enabling them to invade to surrounding tissue. Two transcription factors, TWIST and SNAI1, are fundamental in regulating EMT.

Methods: Immunohistochemistry was used to study the expression of TWIST and SNAI1 in 109 pharyngeal squamous cell carcinomas.

Results: Tumors with intense stromal staining of TWIST relapsed more frequently (p = 0.04). Tumors with both positive TWIST and SNAI1 immunoreactivity in the stroma were at least Stage II (p = 0.05) and located more often in hypopharynx (p = 0.035). Tumors with negative immunostaining of TWIST and SNAI1 in the stromal compartment were smaller (T1-2) (p = 0.008), less advanced (SI-II) (p = 0.031) and located more often in the oropharynx (p = 0.007). Patients with negative SNAI1 and TWIST immunostaining in tumor stroma had a better 5-year disease-specific and overall survival (p = 0.037 and p = 0.014 respectively).

Conclusion: TWIST and SNAI1 expression in stromal cells is associated with clinical and histopathological characteristics that indicate progressive disease. Negative expression of these EMT-promoting transcription factors predicts a better outcome.
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http://dx.doi.org/10.1186/1471-2407-11-350DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3173446PMC
August 2011

A national series of 244 sinonasal cancers in Finland in 1990-2004.

Eur Arch Otorhinolaryngol 2012 Feb 18;269(2):615-21. Epub 2011 May 18.

Department of Otorhinolaryngology-Head and Neck Surgery, Oulu University Hospital, Oulu, Finland.

Sinonasal cancer is still a somewhat controversial entity because most series are single-center studies. The aim of this study was to give more accurate and generalisable information about treatment of the neck and prognosis of sinonasal cancer. Retrospective, population-based, multicentre study. Altogether 244 patients diagnosed in 1990-2004 were evaluated. The 3- and 5-year disease-specific survival (DSS) rates after treatment with curative intent were 68 and 57%, respectively. Regional status at the time of the diagnosis (P < 0.001, log rank) and local recurrence (P = 0.02, log rank) during the follow-up had a statistically significant effect on DSS. Initially 13% of the patients were diagnosed with neck metastasis. The proportion of regional recurrences during the follow-up was 9%, but it did not have a statistically significant impact on DSS (P = 0.68, log rank). Histopathology had no statistically significant impact on survival in this material of 244 patients. In conclusion, routine elective neck treatment of all sinonasal cancer patients is not recommended, but the importance of the treatment of the primary location is emphasised.
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http://dx.doi.org/10.1007/s00405-011-1615-xDOI Listing
February 2012

Transcription factor snail1 expression and poor survival in pharyngeal squamous cell carcinoma.

Histol Histopathol 2011 04;26(4):443-9

Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, Kuopio, Finland.

Snail1, a key regulator of epithelial-mesenchymal transition (EMT), plays an important role in tumour progression. Previous studies of snail1 have mainly focused on the epithelial tumour cells. The objective of this study was to evaluate the expression of snail1 protein in endothelial cells, stromal myofibroblasts and malignant epithelial cells of pharyngeal squamous cell carcinomas (PSCC), as well as its relation to clinicopathological features and survival. One hundred and ten tissue microarray samples were analyzed for snail1 expression using immunohistochemistry. In endothelial cells snail1 expression was observed in 51 (48%) of 107 cases and it predicted reduced disease specific survival (DSS) (p=0.009). In 49 (46%) tumour samples snail1 immunostaining was detected in stromal myofibroblasts and there was a tendency to poorer DSS in that group (p=0.067). Snail1 expression in endothelial cells and stromal myofibroblasts is also associated with hypopharyngeal tumours (p=0.01 and p=0.038 respectively), increasing T category (T3-4) (p=0.005, p=0.037 respectively) and poorer general condition of the patient (Karnofsky performance status score <70; p=0.029, p=0.039 respectively). Moreover endothelial expression correlated with advanced stage (III-IV) (p=0.005) and poorer differentiation (grade 2-3; p=0.012). In malignant epithelial cells snail1 immunostaining was detected in 75 of 110 cases (68%). Expression of the protein was more common in hypopharyngeal tumours (p=0.044). Snail1 positive tumours associated with a lower Karnofsky performance status score (p=0.039) and regional failure (p=0.042). Our findings indicate that snail1 protein expression in endothelial cells and to some extent also in tumour stromal myofibroblasts seems to be a predictor of poor survival in PSCC. The presence of snail1 protein in tumour microenvironment rather than in malignant epithelial tumour cells may induce tissue remodelling and tumour progression.
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http://dx.doi.org/10.14670/HH-26.443DOI Listing
April 2011

Surgical intervention represents a feasible option for patients with mild obstructive sleep apnoea.

Acta Otolaryngol 2009 Nov;129(11):1266-73

Institute of Clinical Medicine, Department of Otorhinolaryngology, University Hospital and University of Kuopio, Kuopio, Finland.

Conclusions: Patients with mild obstructive sleep apnoea (OSA) depict the disease as being detrimental to their health, causing significant symptoms. These patients were found to achieve significant improvements in OSA-related symptoms after surgical intervention.

Objectives: Although the effects of surgical treatment on OSA have been encouraging in many previous studies, little is known about its effects in patients with mild OSA. The aim of our study was to assess the evolution of symptoms experienced by mild OSA patients after surgical intervention.

Subjects And Methods: This was an observational follow-up study in a university hospital in Finland. The change in daytime and night-time symptoms was assessed by a standardized questionnaire before treatment and after a mean follow-up time of 3 years in both operative and control groups in 81 adult patients with mild OSA.

Results: At the follow-up, the control group experienced significantly more daytime sleepiness (p<0.001) compared with the operative group. Adjusted odds ratio (OR) for daytime sleepiness was 0.05 (95% CI 0.01-0.25, p<0.001) in operatively treated patients as compared with control patients, with improvement of witnessed apnoeas (p<0.001) and sleep quality (p=0.033). The OR for intensive snoring was 0.06 (95% CI 0.02-0.22) in the operative group as compared with the control group.
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http://dx.doi.org/10.3109/00016480802595724DOI Listing
November 2009

Reduced gamma-catenin expression and poor survival in oral squamous cell carcinoma.

Arch Otolaryngol Head Neck Surg 2009 Oct;135(10):1035-40

Department of Otorhinolaryngology-Head and Neck Surgery, Kuopio University Hospital and University of Kuopio, 70211 Kuopio, Finland.

Objective: To investigate whether reduced expression of alpha-, beta-, or gamma-catenin predicts poor survival in oral squamous cell carcinoma (OSCC).

Design: Immunohistochemical analyses of a retrospective cohort.

Setting: University-affiliated hospital.

Patients: One hundred twenty-four patients with OSCC.

Main Outcome Measure: The prognostic value of gamma-catenin expression on disease-specific survival in different T and N category groups in patients with OSCC.

Results: Reduced expression of gamma-catenin correlated with poor tumor differentiation of OSCC (P = .04). Patients with reduced gamma-catenin expression in the primary tumor had significantly more frequent lymph node metastasis than did patients with normal gamma-catenin expression (P = . 03). Reduced expression of gamma-catenin (004) but not of alpha-catenin (P = .25) or beta-catenin (P = .48) correlated with poor clinical outcome. Reduced gamma-catenin expression predicted poor disease-specific survival also in the 92 patients with T1 or T2 tumors (P = . 02). In multivariate analysis, advanced T category (P = . 04), neck lymph node metastases (P = . 01), and reduced gamma-catenin expression (P = . 05) were independently related to poor survival.

Conclusions: Reduced expression of gamma-catenin was associated with poor differentiation of OSCC, with neck lymph node metastases, and, more importantly, with poor disease-specific survival. Loss of gamma-catenin expression seems to contribute to metastatic properties of OSCC. Evaluation of the expression pattern of gamma-catenin may be useful for predicting outcome in patients with OSCC.
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http://dx.doi.org/10.1001/archoto.2009.132DOI Listing
October 2009

Evolution of mild obstructive sleep apnea after different treatments.

Laryngoscope 2007 Jun;117(6):1107-11

Department of Otorhinolaryngology, Kuopio University Hospital and University of Kuopio, Kuopio, Finland.

Study Objectives: To evaluate the prognosis of mild obstructive sleep apnea in relation to different treatment modalities.

Study Design: An open, retrospective, longitudinal follow-up study.

Methods: Fifty adult patients diagnosed and treated for mild obstructive sleep apnea at the Department of Otorhinolaryngology at Kuopio University Hospital between 1998 and 2004 had a control polysomnography in 2005. The changes in apnea-hypopnea index (AHI) were observed in untreated (n = 28), operative (n = 11), and continuous positive airway pressure (n = 11) treatment groups at a long-term follow-up visit.

Results: The mean follow-up period was 4 (range, 1.3-9.0; SD, 1.9) years. The untreated patients had a statistically significant increase in AHI (13.3, SD 18.3) at the follow-up. Half of these patients developed a moderate or severe degree of sleep apnea, and only 11% were cured. In patients who were treated with continuous positive airway pressure, the degree of obstructive sleep apnea became worse in 64% of cases, and in 27% of patients, the AHI returned to normal (<5). The degree of obstructive sleep apnea in operated patients deteriorated only in 18%, and in 27% of the patients, the AHI returned to normal (<5).

Conclusions: Mild obstructive sleep apnea has a natural tendency to worsen with time. Active treatment of mild obstructive sleep apnea appears, therefore, to be advisable.
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http://dx.doi.org/10.1097/MLG.0b013e3180514d08DOI Listing
June 2007

Oral tongue carcinoma and its treatment in Finland.

Eur Arch Otorhinolaryngol 2007 Mar 21;264(3):263-7. Epub 2006 Sep 21.

Department of Otorhinolaryngology, Head and Neck Surgery, Helsinki University Central Hospital, Helsinki, Finland.

Management of oral tongue squamous cell cancer (OTSCC) remains a challenge. This nationwide study reports the used treatment approach and the outcome of OTSCC in Finland. Retrospective study of OTSCC patients in 1995-1999 with a 5-year follow-up. The corresponding data from 1980 to 1989 is also included. About 235 patients (125 M, 110 F; mean age 61.6 years; range 24-90 years) were included, 77% had SCC of lateral border of the tongue and 25% were N+. Treatment with curative intent was given to 224 (95%) patients. Surgery of the primary tumour was performed in 218 (97%) patients and with a reconstruction in 69 (31%) patients. A neck dissection was performed ipsilaterally in 114 (51%) and bilaterally in 9 (4%) cases. Irradiation was given to 131 (58%) patients. The rate for locoregional recurrence was 28%. The 3- and 5-year overall survival (OS) rates were 66 and 47%, respectively. The corresponding disease specific survival (DSS) rates were 74 and 64%, respectively. The mean DSS for patients younger than 40 years and older than 40 years was 111 and 88 months, respectively (P < 0.02). The 3- and 5-year DSS rates were: Stage I, 88 and 74%; Stage II, 74 and 62%; Stage III, 79 and 71% and Stage IV, 36 and 33%, respectively. In the present study the surgical treatment approach seems effective in controlling early stage OTSCC but the modest survival, in spite of combination of radiotherapy and surgery, points out the need to consider new strategies in the management of advanced stage disease.
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http://dx.doi.org/10.1007/s00405-006-0158-zDOI Listing
March 2007

High stromal versican expression predicts unfavourable outcome in oral squamous cell carcinoma.

J Clin Pathol 2007 Mar 26;60(3):267-72. Epub 2006 May 26.

Otorhinolaryngology-Head and Neck Surgery, Institute of Clinical Medicine, University of Kuopio and Kuopio University Hospital, Kuopio, Finland.

Background: Versican, an extracellular matrix proteoglycan, has been noted to be expressed in several malignant tumours and has been suggested to play an important role in cancer development and tumour growth.

Aims: To investigate whether the versican expression level in the peritumoural stromal tissue of primary oral squamous cell carcinoma (OSCC) predicts relapse-free or disease-specific survival. Also, to study the associations between versican expression and several other clinicopathological variables, as well as tumour cell proliferation.

Methods: Immunohistochemistry was used to study the expression of versican and tumour cell proliferative activity in 139 OSCCs. All pertinent clinical data were collected retrospectively from the hospital records.

Results: In this cohort, versican expression did not correlate with the clinicopathological factors or tumour cell proliferation. In univariate analyses, higher risk for disease recurrence was associated with higher stromal versican expression score (p = 0.02), positive neck node status (p = 0.02), lower Karnofsky performance status (p = 0.03) and higher tumour cell proliferation index (p = 0.04). Increased disease-specific risk of death was associated with high stromal versican expression score (p = 0.005) higher T class (p = 0.002), positive neck node status (p<0.001), higher stage (p<0.001), poorer histological differentiation (p = 0.005), worse general condition of the patient (p = 0.049) and increased tumour cell proliferative index (p = 0.02). In multivariate disease-specific survival analysis, high stromal versican expression score (p = 0.048), poorer histological differentiation (p = 0.047) and higher stage (p = 0.002) independently predicted poorer disease outcome.

Conclusions: In this cohort, increased stromal versican expression correlated with both increased risk for disease recurrence and shortened survival. High stromal versican expression may thus be considered an independent and adverse prognostic marker in OSCC.
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http://dx.doi.org/10.1136/jcp.2005.034181DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1860561PMC
March 2007

Oropharyngeal carcinoma and its treatment in Finland between 1995-1999: a nationwide study.

Eur Arch Otorhinolaryngol 2006 Feb 8;263(2):139-43. Epub 2005 Jul 8.

Department of Otorhinolaryngology and Head and Neck Surgery, Helsinki University Central Hospital, Helsinki, Finland.

The survival figures for advanced stage oropharyngeal carcinoma (OPC) have remained moderate in spite of radical combined modality treatments. The purpose of this study was to investigate the used treatment approach and the outcome of OPC in a nationwide study. Retrospective clinicopathological data of all patients diagnosed with OPC between 1995 and 1999 at the five university hospitals in Finland were reviewed. All patients had a minimum 4-year follow-up. A total of 168 patients (145 men and 23 women, mean age 59 years; range 28 - 89 years) were included. The T categories were as follows: T1, n =34; T2, n =55; T3, n =40; T4, n =39. One hundred and seventeen (69.6%) patients presented with neck node metastases and three (1.8%) patients with distant metastases. In the majority (61.3%) of the patients the tumor was located in the lateral wall of the oropharynx. In 144 (85.7%) patients the treatment was performed with curative intent. Of these, surgery of the primary tumor was performed in 123 (85.4%) patients, and the defect was reconstructed with a pedicled flap or free tissue transfer in 66 (53.7%) of these patients. A neck dissection (ND) was performed in 86 (69.9%) out of these 123 cases. Surgery was the only treatment modality in 10 (6.9%) patients. Radiation therapy (RT) only (with or without chemotherapy) was given to 21 (14.6%), combined treatment with surgery + radiation therapy (S + RT) to 110 (76.4%) and surgery + chemoradiotherapy (S + CRT) to 3 (2.1%) patients. Overall (OS) 3- and 5-year survival rates were 58 and 45%, respectively. Disease-specific (DSS) 5-year survival rates by T-class for the patients treated with curative intent were as follows: T1, 77%; T2, 70%; T3, 66%; T4, 53%. The variable treatment approach, the frequent locoregional recurrences and the moderate survival point out the need to consider new strategies in the management of OPC.
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http://dx.doi.org/10.1007/s00405-005-0975-5DOI Listing
February 2006

Hypopharyngeal carcinoma in Finland from 1990-1999.

Eur Arch Otorhinolaryngol 2005 May 22;262(5):374-8. Epub 2004 Oct 22.

Department of Otorhinolaryngology and Head and Neck Surgery, Tampere University Medical School Hospital, P.O. Box 2000, 33521 Tampere, Finland.

Data concerning the diagnosis, treatment and clinical course of patients with hypopharyngeal carcinoma (HPC) in all five university hospitals in Finland between 1 January 1990-31 December 1999 were retrospectively analysed. During the study period, 149 HPC cases were diagnosed in 111 men and 38 women (74%/26%), with a mean age of 64.5 years. At the time of diagnosis, 6 patients (4%) had stage I, 11 (7%) stage II, 32 (22%) stage III and 100 (67%) stage IV disease. In 74 (49%) cases, the primary treatment was surgery. Pre- or postoperative radiation therapy was given to 67 patients. Radiation therapy was the primary treatment in 47 (32%) patients, and 12 patients (8%) received concomitant chemoradiation. The overall 5- and 10-year disease specific survival (DSS) was 22 and 13%, respectively. The 5-year DSS was 66% for stage I, 59% for stage II, 31% for stage III and 12% for stage IV disease. In the three major treatment groups, i.e., surgery and radiation therapy, radiation therapy alone and concomitant chemoradiation, the 5-year DSS were 32% for surgery and radiation therapy, 7% for radiation therapy alone and 38% for concomitant chemoradiation. Prognosis of HPC remains poor, especially in the more advanced stages of the disease. In addition to traditional surgery and radiation therapy, concomitant chemoradiotherapy seems to give equal results in tumor control, thus making organ preservation possible in the primary treatment of HPC.
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http://dx.doi.org/10.1007/s00405-004-0847-4DOI Listing
May 2005

Nuclear and cytoplasmic p53 expression in pharyngeal squamous cell carcinoma: prognostic implications.

Head Neck 2002 Aug;24(8):784-91

Department of Otorhinolaryngology, Head and Neck Surgery, University of Kuopio, Kuopio University Hospital, PO Box 1777, FIN-70211 Kuopio, Finland.

Background: The role of p53 expression in human neoplasms is still controversial, and it has been associated with both favorable and unfavorable outcome of the patients. Also cytoplasmic expression of p53 protein has been reported to affect survival in some cancers. Furthermore, an association between p53 and beta-catenin expression has been demonstrated. We studied the expression of p53 in a large group of oropharyngeal and hypopharyngeal squamous cell carcinomas and its relation to catenin expression, histologic differentiation, clinical data, and prognosis.

Methods: Primary tumors for analyses were obtained from 123 patients diagnosed with squamous cell carcinoma of the oropharynx or hypopharynx between 1975 and 1998 in Eastern Finland. Immunohistochemistry was used to evaluate the expression of p53 as well as alpha-, beta-, and gamma-catenins.

Results: In the primary tumors (n = 123), the nuclear p53 expression index was low in 42 (34%), intermediate in 38 (31%), and high in 43 (35%) cases. Cytoplasmic p53 expression was present in 56 (46%) and absent in 67 (54%) tumors. In univariate analyses (Kaplan-Meier), hypopharyngeal primary site (p =.02), high T class (p <.0005), presence of distant metastases (p =.02), low Karnofsky performance index (p <.0005), high nuclear p53 expression index (p =.01), and positive cytoplasmic p53 expression (p =.04) predicted poorer overall survival (OS). In Cox proportional hazards model, only T class (p =.0005), Karnofsky performance index (p =.005), and nuclear beta-catenin expression (p =.038) predicted poorer OS.

Conclusion: Positive cytoplasmic p53 expression and nuclear p53 overexpression seem to relate to more aggressive features and unfavorable outcome in pharyngeal squamous cell carcinoma (PSCC). However, unlike more traditional variables, p53 expression is not an independent predictor of disease outcome in PSCC.
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http://dx.doi.org/10.1002/hed.10124DOI Listing
August 2002

Inducible nitric oxide synthase expression in pharyngeal squamous cell carcinoma: relation to p53 expression, clinicopathological data, and survival.

Laryngoscope 2002 Jun;112(6):1084-8

Department of Otolaryngology-Head and Neck Surgery, University of Kuopio and Kuopio University Hospital, Finland.

Objective: To investigate the expression of inducible nitric oxide synthase (iNOS) in oropharyngeal and hypopharyngeal squamous cell carcinoma (SCC) and its relation to p53 expression, histologic differentiation, clinical data, and prognosis.

Study Design: A retrospective survey.

Methods: Primary tumors for analyses were obtained from 118 patients diagnosed with SCC of the oropharynx or hypopharynx between 1975 and 1998 in eastern Finland. Immunohistochemical analysis was used to evaluate the expression of iNOS and p53. The expression pattern of iNOS was related to p53 expression, clinical data, and survival.

Results: High iNOS score was associated significantly with high nuclear p53 expression index (P = .006) and positive cytoplasmic p53 expression (P = .025). The score for iNOS expression was significantly lower in the largest (T4) tumors (P = .043). No association was seen between iNOS score and N or M class, tumor stage, or histologic differentiation. The score for iNOS expression was not related to overall survival.

Conclusions: The expressions of iNOS and p53 seem to be inter-related in pharyngeal SCC, although the causality remains to be clarified. The expression of iNOS shows no prognostic value in pharyngeal SCC.
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http://dx.doi.org/10.1097/00005537-200206000-00027DOI Listing
June 2002