Jakub Pazdrowski

Oral cavity and oropharyngeal squamous cell carcinoma in young adults: a review of the literature

Abstract Background. Head and neck squamous cell carcinoma (HNSCC) is a disease of middle-aged to elderly adults. However, an increased incidence of HNSCC in young people under 45 years of age has been reported recently. In the present review, we focused on the epidemiology and aetiology of HNSCC in adults under 45 years of age. Methods. We reviewed literature related to HNSCC in adult patients less than 45 years of age and discussed current treatment options and prognosis. Results. HNSCC in young adults is associated with a higher incidence rate in nonsmokers, lower female-to-male ratio, a higher percentage of oral cavity and oropharynx tumours, and fewer second primary tumours. However, aside from traditional risk factors of tobacco and alcohol exposure, the causes of these cancers in young adults remain unclear. Agents that might contribute to risk include infection with high-risk human papillomavirus subtypes as well as genetic factors or immunodeficiency status. The expected increase in incidence and mortality of the young with HNSCC may become a major public health concern if current trends persist, particularly lifestyle habits that may contribute to this disease. Conclusions. Given the younger age and potential long-term adverse sequelae of traditional HNSCC treatments, young adults should be treated on a case-by-case basis and post-therapy quality of life must be considered in any treatment-decision making process.

Analiza występowania mutacji w obrębie genu TP53 u chorych na raka płaskonabłonkowego głowy i szyi

Head and neck cancer is the sixth most common type of cancer. Tobacco and alcohol consumption are implicated in 75% of all SCCHN and have a multiplicative combined effect. It is considered to be the main risk factor for the cancer development. The identification of a number of these genetic alterations, for example mutations in the p53 tumour suppressor gene, paved the way for their use as molecular markers. Mutations in the TP53 gene frequently occur in many cancers and are present in 50-60% of head and neck cancers, p53 plays a sentinel role in the pathways that prevent development of cancer by inducing apoptosis, DNA repair and cell cycle arrest in response to different types of cellular stress The aim of the study, was the assessment of the TP53 mutations prevalence in the head and neck cancer patients and its relation with the clinical data and course of the disease. The material comprised of peripheral blood and tumour tissue obtained from 50 HNSCC patients with a primary tumour in the oral cavity, oropharynx or larynx, who were scheduled for surgical treatment. The mutations in TP53, were detected with use of PCR-SSCP technique. In total 8 patients (16%), showed TP53 mutation in primary tumour. The significant correlation between tobacco and alcohol consumption and the mutation incidence has been observed. The site of the tumour and histopathological grading were also related to the prevalence of mutations, however without reaching the level of statistical significance. There was no correlation between mutations and the T and N stage of the disease.Summary Head and neck cancer is the six most common type of cancer. Tobacco and alcohol consumption are implicated in 75% of all SCCHN and have a multiplicative combined effect. It is considered to be the main risk factor for the cancer development. The identification of a number of these genetic alterations, for example mutations in the p53 tumour suppressor gene, paved the way for their use as molecular markers. Mutations in the TP53 gene frequently occur in many cancers and are present in 50–60% of head and neck cancers. p53 plays a sentinel role in the pathways that prevent development of cancer by inducing apoptosis, DNA repair and cell cycle arrest in response to different types of cellular stress The aim of the study, was the assessment of the TP53 mutations prevalence in the head and neck cancer patients and its relation with the clinical data and course of the disease. The material comprised of peripheral blood and tumour tissue obtained from 50 HNSCC patients with a primary tumour in the oral cavity, oropharynx or larynx, who were scheduled for surgical treatment. The mutations in TP53, were detected with use of PCR-SSCP technique. In total 8 patients (16%), showed TP53 mutation in primary tumour. The significant correlation between tobacco and alcohol consumption and the mutation incidence has been observed. The site of the tumour and histopathological grading were also related to the prevalence of mutations, however without reaching the level of statistical significance. There was no correlation between mutations and the T and N stage of the disease.

Transforming growth factor-β1 in plaque morphea

Introduction Morphea (localized scleroderma) is a rare cutaneous disease characterized by skin fibrosis of unknown pathogenesis. Transforming growth factor-β (TGF-β) is a potent profibrotic factor. The role of TGF-β in morphea remains unclear. Aim The goal of this study was to estimate the expression level of TGF-β1 in skin and peripheral blood mononuclear cells as well as the plasma levels of TGF-β1 in plaque morphea (MEP). Material and methods The study involved 20 MEP patients. Three control groups were involved: 1 – plasma: 36 healthy volunteers; 2 – PBMC: 47 healthy volunteers; 3 – skin biopsies: 13 samples collected during mastectomy (breast cancer was not skin involved). The analysis of TGF-β1 plasma levels was performed with the use an adequate ELISA kit, while real-time polymerase chain reaction was employed for the expression of TGF-β1 in peripheral blood mononuclear cells (PBMC) and skin. Results In our study we have not detected differences in TGF-β 1 expression in PBMC, skin, nor in plasma levels of TGF-β1 between MEP patients and healthy controls, regardless of disease activity and its duration. Conclusions The results of our study contradict the claim of the substantial role of TGF-β1 in the most common morphea subtype – MEP.

Analysis of selected recurrence risk factors after treatment of head and neck basal cell carcinoma

Introduction Basal cell carcinoma (BCC) is the most common type of non-melanoma malignant skin tumors. Eighty-five percent of all cases are located on the skin of the head and neck. The risk of recurrence after surgery is estimated at 5–15%. Aim To evaluate the selected risk factors for recurrence after surgical treatment of head and neck BCC at the Department of Head and Neck Surgery in the Greater Poland Cancer Centre of the Poznan University of Medical Sciences. Material and methods A retrospective analysis was made of patients treated at the Department of Head and Neck Surgery in the Greater Poland Cancer Centre of the Poznan University of Medical Sciences in 2007–2012 for BCC of the head and neck region. The study covered 312 patients: 198 males (63%) and 114 females (37%), aged 32–96 years. Results In the study group of 312 tumors, recurrence after initial treatment in this Centre was diagnosed in 18 patients (9%), whereas in patients who were previously operated elsewhere, recurrence was found in 22 cases (17%). The nodular type was the most common BCC type in the study group and concerned 175 patients (56%). The most numerous group (114; 37%) in this study group comprised patients with external nose and cheek tumors. Conclusions The importance of preoperative biopsy to assess the histological type as a routine treatment of patients with BCC is essential. Ultrasound evaluation to assess the exact size and depth of tumor invasion should also be implemented.

Wznowy raka podstawnokomórkowego (BCC) twarzy w materiale Oddziału Chirurgii Głowy i Szyi i Onkologii Laryngologicznej Wielkopolskiego Centrum Onkologii w latach 2007–2010

Abstract Introduction The incidence of basal-cell carcinomas (BCC) in Europe is estimated at 10 cases per 100,000 people and is continuously increasing. Recurrent cases of BCC tend to have a more aggressive progression. The treatment methods include: conventional surgery, Mohs surgery, laser therapy, cryosurgery, curettage and radiotherapy. The recurrence of basalcell carcinoma depends on the method of treatment and ranges between 4% and 18%. In the case of recurrent BCC the treatment method of choice is margin control surgery. Aim of the study The purpose of this paper is to conduct a retrospective analysis of patients with facial BCC treated with classic surgery and laser therapy as well as to present a strategy for action in the case of recurrence. Material and Methods The retrospective analysis was conducted on patients with diagnosed facial BCC, treated at the Head and Neck Surgery Ward and Laryngological Oncology Clinic of the Greater Poland Cancer Centre in the years 2007–2010. The research included 58 patients aged 56–80; 34 women and 24 men. Results Out of 58 patients 8 had recurrent BCC – 4 cases after laser therapy (Group A), and 4 cases after classic surgery (Group B). In 2 cases from Group A and all cases from Group B further treatment involved removal of the recurrent tumour by margin control surgery and skin flap plastic surgery. In 2 remaining cases from Group A further CO2 laser therapy was performed under local anaesthesia and analgosedation. This type of treatment was chosen due to general medical and cardiological concerns which disqualified the use of general anaesthesia and conventional surgery. So far no further local recurrent cases of BCC have been diagnosed, and the folow-up periods range from 4 to 26 months. Conclusion Recurrent cases of BCC are 10% more frequent in patients treated with cryosurgery or laser therapy without margin control than in patients who had the tumour removed by margin control surgery. Margin control surgery remains the method of choice in cases involving large tumours, recurrence or spread by invasion.

Rola zespołu interdyscyplinarnego w diagnostyce i leczeniu chorych z nowotworami krtani i gardła dolnego

INTRODUCTION In Poland the annual incidence of cancer of the larynx is about 3,000 cases which accounts 2% of all malignant tumors. Results of treatment of head and neck cancers are still unsatisfactory (five-year survival - 50%). In order to improve the outcome in Greater Poland Cancer Centre in 2010 a multidisciplinary team was created which is involved in the individual qualification of each patient to the best form of therapy. AIM The aim of the publication is to evaluate the work of the multidisciplinary team in the diagnostic, therapeutic, and post-operative follow-up of patients with larynx and hypopharynx cancer treated in Greater Poland Cancer Centre in 2007-2012. MATERIALS AND METHODS The analysis included 558 patients (84% men, 16% women) aged 38-82 years who were treated in the Department of Head and Neck Surgery Greater Poland Cancer Centre in the years 2007 to 2012 because of cancer of larynx and hypopharynx. Patients were divided into two groups - the first consisted of patients qualified without the cooperation of the multidisciplinary team - 312 patients (56%), the second - patients qualified with help of the multidisciplinary team - 246 patients (44%). In the two groups of patients evaluated were: mean time required for the implementation of additional tests and specialist consultations before treatment, the average time from the appearance of the patient to the start of treatment, the distribution of qualifications to specific forms of therapy. RESULTS Evaluating type of treatment administered after the establishment of the team noticed were an increase by 11% the number of patients treated with surgery. There has been a reduction in the time between the appearance of the patient at the clinic and the start of treatment and reduce the waiting time for diagnostic imaging and specialist consultations. It was also an increase in the number of regular check-ups and a decrease in the number of patients who stopped visits. CONCLUSION The work of the multidisciplinary team improves the effectiveness of treatment by optimizing the process of preparation and organization, and finally by contributing knowledge and experience in decision-making. His creation results in benefits for the patient, his family and the medical staff. Qualification for the most optimal treatment within the multidisciplinary team should be used in all patients with cancer of the head and neck.

Występowanie i rola aktywnej infekcji wirusem brodawczaka ludzkiego (HPV) w rakach płaskonabłonkowych głowy i szyi

Summary HPV, mainly HPV type 16 and to a lesser extent type 18, is a newly identified causal factor for SCCHN. The association between HPV and SCCHN is strongest for cancers of the tonsil, intermediate for the rest of the oropharynx, and weakest for the oral cavity and larynx. However, The prevalence of HPV in SCCHN in Poland reported in the literature varies from 0–72% One of the reasons of such a different results may be in our opinion method-related false positive results. The aim of the study, was the assessment of HPV prevalence in the head and neck cancer patients in polish population of SCCHN patients. The material comprised of tumor tissue obtained from 50 HNSCC patients with a primary tumor in the oral cavity, oropharynx or larynx, who were scheduled for surgical treatment. For all cases algorithm was performed: First p16 immunostaining was conducted and secondly the HPV DNA has been detected with the use of HPV DNA general primer (GP)5+/6+ PCR, followed by RLB hybridization. In 8% of cases the staining was observed in 50% of cancer cells or more. There was no HPV DNA detected in any case. There was no HPV DNA detected in any case, which may indicate the lower HPV prevalence in polish population than in Western Europe and US and smoking and drinking associated carcinogenesis. The p16 expression has been found in 8% of the patients and supplementary (GP)5+/6+ PCR did not detect the presence of HPV DNA. Thus, the p16 immunostaining is of limited use as a sole method of HPV detection and needs to be complemented by other techniques.

Positive fresh frozen section margins as an adverse independent prognostic factor for local recurrence in oral cancer patients: Positive Fresh Frozen as an Adverse Factor

To access 1) the value of further surgical resection (completion surgery) in cases with a positive intraoperative margin analysis, and 2) whether cancers that undergo completion surgery following positive intraoperative margin analysis with subsequent negative margins should be considered true margin‐negative (R0) resections in terms of adjuvant treatment planning.

Blood Serum From Head and Neck Squamous Cell Carcinoma Patients Induces Altered MicroRNA and Target Gene Expression Profile in Treated Cells

The head and neck squamous cell carcinoma (HNSCC) represents one of the most common cancers in humans. Close to 600,000 new diagnoses are made every year worldwide and over half of diagnosed patients will not survive. In view of this low survival rate, the development of novel cell-based assays for HNSCC will allow more mechanistic approaches for specific diagnostics for each individual patient. The cell-based assays will provide more informative data predicting cellular processes in treated patient, which in effect would improve patient follow up. More importantly, it will increase the specificity and effectiveness of therapeutic approaches. In this study, we investigated the role of serum from HNSCC patients on the regulation of microRNA (miRNA) expression in exposed cells in vitro. Next-generation sequencing of miRNA revealed that serum from HNSCC patients induced a different miRNA expression profile than the serum from healthy individuals. Out of 377 miRNA detected, we found that 16 miRNAs were differentially expressed when comparing cells exposed to serum from HNSCC or healthy individuals. The analysis of gene ontologies and pathway analysis revealed that these miRNA target genes were involved in biological cancer-related processes, including cell cycle and apoptosis. The real-time PCR analysis revealed that serum from HNSCC patients downregulate the expression level of five genes involved in carcinogenesis and two of these genes—P53 and SLC2A1—are direct targets of detected miRNAs. These novel findings provide new insight into how cancer-associated factors in circulation regulate the expression of genes and regulatory elements in distal cells in favor of tumorigenesis. This has the potential for new therapeutic approaches and more specific diagnostics with tumor-specific cell lines or single-cell in vitro assays for personalized treatment and early detection of primary tumors or metastasis.

The role of selectins in alopecia areata.

Introduction One of the main histopathological features of alopecia areata (AA) is a lymphocytic infiltration that surrounds hair follicles. Soluble forms of E, L, P-selectins are known indicators of ongoing inflammation. There are no studies regarding the assessment of their contribution in AA. Aim To assess serum concentrations of selectins (E-selectin, L-selectin and P-selectin) in patients with AA in relation to selected clinical parameters, including disease severity and activity. Material and methods Sixty-four patients with AA were involved in the study. The diagnosis was based on physical examination and photodermoscopy. The control group consisted of 40 healthy subjects. The serum concentrations of soluble E-selectin, L-selectin and P-selectin were detected with ELISA method. Results Statistically significantly higher levels of E, P, L-selectins were found in AA patients as compared with the healthy group. Serum concentrations of soluble forms of E- and L-selectins correlated with the severity of the disease, while E-selectin with activity of AA. Conclusions This study shows that selectins may play an important role in the pathogenesis of AA and may be a target of future therapies in this disease.