Intrahepatic cholangiocarcinoma: risk factors affecting survival of operated patients.

INTRODUCTION: The aim of this study was to evaluate the results of surgical treatment of intrahepatic cholangiocarcinoma (IHCHCA) in terms of overall survival and disease-free survival, and to analyse and find potential prognostic factors affecting overall survival and disease-free survival. METHODS: Retrospective evaluation was performed of consecutively enrolled patients operated for IHCHCA from January 2005 to January 2022 (17 years) had undergone surgery. During the monitored period, 38 surgical procedures were performed, of which liver resection was done in 25 cases (65.8%). RESULTS: The 5-year survival in the radically resected group was 44%, and the 5-year disease-free survival was 32%. Based on univariate and multivariate analysis, radicality of surgery (p=0.01116) and lymph node involvement (p=0.00576) were assessed as negative prognostic factors for overall survival. Radicality of surgery (p=0.018) and administration of adjuvant chemotherapy (p=0.044) were significant negative prognostic factors affecting disease-free survival. However, they lost their significance in the multivariate analysis. CONCLUSION: Radical surgical resection of the liver remains an essential treatment option for intrahepatic cholangiocarcinoma aimed at achieving a radical procedure with microscopically negative margins. KEY WORDS: cholangiocarcinoma, resection, recurrence, survival.

Association of triple positivity with prognostic parameters and overall survival in a population-based study of 6,122 HER2-positive breast cancer patients: analysis of real-world clinical practice based on a research database.

Triple-positive breast cancer (TPBC), i.e. HER2-positive (HER2+) and hormone receptors-positive breast cancer, is a specific subgroup of breast cancers. TPBC biology is characterized by strong mutual interactions between signaling pathways stimulated by estrogens and HER2 amplification. The present study aims to carry out a population-based analysis of treatment outcomes in a cohort of hormone receptor (HR) positive and negative breast cancer patients who were treated with anti-HER2 therapy in the Czech Republic. The BREAST research database was used as the data source for this retrospective analysis. The database covers approximately 95% of breast cancer patients treated with targeted therapies in the Czech Republic. The analysis included 6,122 HER2-positive patients. The patients were divided into two groups, based on estrogen receptor (ER) or progesterone receptor (PR) positivity: hormone receptor negative (HR-) patients had both ER- and PR-negative tumors (n=2,518), unlike positive (HR+) patients (n=3,604). HR+ patients were more often diagnosed premenopausal at the time of diagnosis, presented more often at stage I or II and their tumors were less commonly poorly differentiated. The overall survival (OS) was significantly higher in subgroups of HR+ patients according to treatment setting. When evaluated by stages, significantly higher OS was observed in HR+ patients diagnosed at stages II, III, and IV and regardless of tumor grade.

Deregulation of Selected MicroRNAs in Sinonasal Squamous Cell Carcinoma: Searching for Potential Prognostic Biomarkers.

Sinonasal carcinomas are head and neck tumours arising from the nasal cavity and paranasal sinuses characterized by unfavourable outcome, difficult treatment, diagnosis and prognosis. MicroRNAs are key molecules in the regulation of development and progression of cancer and their expression profiles could be used as prognostic biomarkers, to predict the patients' survival and response to treatment. In this study, we used quantitative real­time PCR with TaqMan® Advanced miRNA Assays to investigate the relative expression values of selected micro- RNAs in a unique set of formalin-fixed paraffin-embedded tissue samples obtained from 46 patients with sinonasal squamous cell carcinoma. Our results showed statistically significant up-regulation of three mature microRNAs: miR-9-5p (fold change: 6.80), miR-9-3p (fold change: 3.07) and let-7d (fold change: 3.93) in sinonasal carcinoma patients. Kaplan-Meier survival analysis and logrank test identified association between higher expression of miR-9-5p and longer survival of the patients (P = 0.0264). Lower expression of let-7d was detected in the patients with impaired survival, and higher expression of miR-137 was linked to shorter survival of the patients. We also identified several correlations between expression of the studied microRNAs and recorded clinicopathological data. Higher expression of miR-137 and lower expression of let-7d correlated with local recurrence (P = 0.045 and P = 0.025); lower expression of miR-9-5p and higher expression of miR-155-5p correlated with regional recurrence (P = 0.045 and P = 0.036). Higher expression of miR-9-3p correlated with occupational risk (P = 0.031), presence of vascular invasion (P = 0.013) and perineural invasion (P = 0.031). Higher expression of miR-155-5p was present in the samples originating from maxillary sinus (P = 0.011), cN1-3 classified tumours (P = 0.009) and G2-3 classified tumours (P = 0.017). In conclusion, our study supports the hypothesis of future prospect to use expression of miRNAs as prognostic biomarkers of squamous cell sinonasal carcinoma. In particular, miR-9-5p and miR-9-3p seem to be important members of the sinonasal cancer pathogenesis.

Laparoscopic versus open liver resections for colorectal cancer liver metastases: short term results.

INTRODUCTION: Analysis and comparison of short-term results of laparoscopic liver resections (LLR) and open liver resections (OLR) for colorectal cancer liver metastases (CRCLM). METHODS: Retrospective analysis of patients operated for CRCLM in the time period from May 2007 to May 2019 (12 years) at the department of surgery, University Hospital Hradec Králové and University Hospital Královské Vinohrady. RESULTS: 206 liver resections were performed; 167 (81.1%) OLR and 39 (18.9%) LLR procedures. Conversion to open surgery was necessary in 6 cases (15.4%). LLR was associated with a longer operation time (194±107 min) vs (129±58 min) for OLR. The ICU stay, 3.5±4.3 days for OLR and 4.1±8.1 days for LLR, and the hospital stay, 11.9±8.3 days (OLR) vs 12.1±11.3 days (LLR), were comparable. Perioperative blood loss was lower in the LLR group, 189±166 ml vs 360±410 ml. Total transfusion rate was similar, 10.8% (OLR) vs 12.8% (LLR). Oncologic radicality was also comparable in both groups; negative resection margin was achieved in 78% (OLR) and 80% (LLR). Postoperative morbidity and mortality was comparable in both groups; morbidity was 33% (OLR) vs 31% (LLR), while mortality was 1.8% (OLR) vs 2.6% (LLR). CONCLUSION: LLR for CRCLM provided comparable short-term results compared to OLR in our group of patients even in the learning curve period. However, it should be noted that the study group is a highly selected group of patients.

HPV Status and Mutation Analysis Using Multiparallel Sequencing in Distal Oesophageal and Gastro-oesophageal Junction Adenocarcinomas.

The incidence of adenocarcinoma of oesophagus or gastro-oesophageal junction is increasing in Europe and other regions of the Western world. Research of possible causes has shifted to the molecular level. This study evaluated human papillomavirus (HPV) using real-time PCR and mutational status of selected genes using the multiparallel sequencing method (NGS) in DNA extracted from paraffin-embedded tumour tissue of 56 patients with oesophageal or gastro-oesophageal junction adenocarcinoma. The genetic material was in sufficient quality for the analysis in 37 cases (66 %). No HPV-positive sample was found. NGS revealed higher frequency of mutations in TP53, ARID1A, PIK3CA, SMAD4, ERBB2, MSH6, BRCA2, and RET genes. Association between gene mutations and histological grade, subtype according to Lauren, or primary tumour site was not statistically significant. In conclusion, the study did not confirm any HPV-positive sample of oesophageal and gastro-oesophageal junction adenocarcinoma. The study confirmed the usefulness of NGS analysis of paraffin-embedded tissue of these tumours, and it could be used in clinical studies to evaluate the prognostic and/or predictive value of the tested mutations. The association between gene mutations and histological features should be tested in larger patient cohorts.

Analysis of DNA methylation and microRNA expression in NUT (nuclear protein in testis) midline carcinoma of the sinonasal tract: a clinicopathological, immunohistochemical and molecular genetic study.

The aim of this study was a detailed clinicopathological investigation of sinonasal NUT midline carcinoma (NMC), including analysis of DNA methylation and microRNA (miRNA) expression. Three (5%) cases of NMC were detected among 56 sinonasal carcinomas using immunohistochemical screening and confirmed by fluorescence in situ hybridization. The series comprised 2 males and 1 female, aged 46, 60, and 65 years. Two tumors arose in the nasal cavity and one in the maxillary sinus. The neoplasms were staged pT1, pT3, and pT4a (all cN0M0). All patients were treated by radical resection with adjuvant radiotherapy. Two patients died 3 and 8 months after operation, but one patient (pT1 stage; R0 resection) experienced no evidence of disease at 108 months. Microscopically, all tumors consisted of infiltrating nests of polygonal cells with vesicular nuclei, prominent nucleoli and basophilic cytoplasm. Abrupt keratinization was present in only one case. Immunohistochemically, there was a diffuse expression of cytokeratin (CK) cocktail, CK7, p40, p63, and SMARCB1/INI1. All NMCs tested negative for EBV and HPV infection. Two NMCs showed methylation of RASSF1 gene. All other genes (APC, ATM, BRCA1, BRCA2, CADM1, CASP8, CD44, CDH13, CDKN1B, CDKN2A, CDKN2B, CHFR, DAPK1, ESR1, FHIT, GSTP1, HIC1, KLLN, MLH1a, MLH1b, RARB, TIMP3, and VHL) were unmethylated. All NMCs showed upregulation of miR-9 and downregulation of miR-99a and miR-145 and two cases featured also upregulation of miR-21, miR-143, and miR-484. In summary, we described three cases of sinonasal NMCs with novel findings on DNA methylation and miRNA expression, which might be important for new therapeutic strategies in the future.

Importance of Tumour Suppressor Gene Methylation in Sinonasal Carcinomas.

Epigenetic changes are considered to be a frequent event during tumour development. Hypermethylation of promoter CpG islands represents an alternative mechanism for inactivation of tumour suppressor genes, DNA repair genes, cell cycle regulators and transcription factors. The aim of this study was to investigate promoter methylation of specific genes in samples of sinonasal carcinoma by comparison with normal sinonasal tissue. To search for epigenetic events we used methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) to compare the methylation status of 64 tissue samples of sinonasal carcinomas with 19 control samples. We also compared the human papilloma virus (HPV) status with DNA methylation. Using a 20% cut-off for methylation, we observed significantly higher methylation in RASSF1, CDH13, ESR1 and TP73 genes in the sinonasal cancer group compared with the control group. HPV positivity was found in 15/64 (23.4 %) of all samples in the carcinoma group and in no sample in the control group. No correlation was found between DNA methylation and HPV status. In conclusion, our study showed that there are significant differences in promoter methylation in the RASSF1, ESR 1, TP73 and CDH13 genes between sinonasal carcinoma and normal sinonasal tissue, suggesting the importance of epigenetic changes in these genes in carcinogenesis of the sinonasal area. These findings could be used as prognostic factors and may have implications for future individualised therapies based on epigenetic changes.

[Discordance between Clinical and Pathological TNM Classifications in Patients with Oropharyngeal Cancer - Influence on Treatment and Prognosis]. / Shoda a neshoda klinické a patologické TNM klasifikace u karcinomu orofaryngu - vliv na prognózu a výsledky lécby.

BACKGROUND: The aim of this study was to determine the percentage of discordance between clinical (c) and pathological (p) TNM classifications in cases of oropharyngeal carcinoma and whether it influences recurrence rate and prognosis of primary disease. MATERIALS AND METHODS: Fifty-one patients with oropharyngeal carcinoma who underwent primary surgical treatment were included in this retrospective study. Clinical TNM was determined on the basis of clinical examinations and imaging (US, CT, or MRI), and pathological TNM was determined by a histopathologist (analysis of the primary tumor and neck lymph nodes). Concordance and discordance were statistically evaluated. As potential prognostic factors, we statistically analyzed tumor recurrence, specific and nonspecific patient survival, patient age, extent of primary tumor, lymph node positivity, number of removed lymph nodes, and positive tumor margins. RESULTS: Discordance in the TNM classification was found in 27 cases. Disease-free survival was shorter in patients with discordance in T, and this was statistically significant (p = 0.034). Six patients died due to primary disease (11.8%). Disease-specific survival was at the limit of statistical significance (p = 0.069). CONCLUSIONS: Discordance between clinical and pathological TNM classifications was 52.9% patients with oropharyngeal carcinoma. Discordance in T is a potential prognostic factor. Improvement in cancer treatment to some extent relies on preoperative staging and should influence the decision about whether or not to administer adjuvant oncological treatment.

[Survival Analysis Three-year Follow-up of Pacients with Head and Neck Cancer]. / Analýza prezití tríletého sledování nemocných s rakovinou hlavy a krku.

BACKGROUND: Patients with head and neck cancer are predominantnly at the risk for malnutrition. Monitoring of nutritional status and pre-treatment variables can favorably observe many prognostic indicators for overall survival in head and neck cancer before and during oncological treatment up to three years in head and neck cancer pacients. MATERIALS AND METHODS: In 726 patients diagnosed head and neck cancer patients with curative intent, were collected data according to the monitoring scheme of observation. As a clinical important of uninteded weight loss was defined weight loss 10% in input (T0). Differences in groups were analysed by Coxs regression with adjustments for important demografic and tumor-related data. RESULTS: The acceptance of the percutaneous endoscopic gastrostomy was a key factor for less complications and to improve tolerance of anticancer treatment. Men-smokers have the highest risk of cardiovascular mortality. Men-stop-smokers have the most significant life extension of 11 to 22 months; p < 0.007. Men-non-smokers have a life extension of 15 to 23 months (p < 0.005) and having its lowest cardiovascular mortality (11%). Women tolerate cancer better, have minor subjective complaints and a lower number of complications but significantly higher consumption of antidepressants (p < 0.003). While men have higher analgesic consumption (p < 0.001). Weight loss > 10% significantly correlates with the clinical manifestations of malnutrition and is associated with an increase in complications and mortality dependent cancer (p < 0.008). CONCLUSION: Consistent assessment of nutritional status with early intervention is considered as an essential part of comprehensive anticancer treatment. An independent risk factor for cancer-dependent mortality is considered weight loss of > 5% with a BMI < 21 at time T0 or weight loss > 10% weight T0 in BMI 21- 29 and continuing weight loss to T12 and also BMI 30. The highest-risk profile has a male sex-smoker, age > 63, hypopharyngeal carcinoma, stage III- IV, weight loss of > 10% and non-acceptance of percutaneous endoscopic gastrostomy. Another long-term observation of monitored nutritional status with intervention, clinical status and quality of life are needed.

[Current status in the treatment of rectal cancer in the Czech Republic regarding the rate of complete pathological response after neoadjuvant therapy--PATOD C20 study 2011-2012]. / Soucasný stav strategie lécby karcinomu rekta v Ceské republice s ohledem na výskyt kompletní patologické odpovedi pri neoadjuvantní lécbe--studie PATOD C20 2011-2012.

INTRODUCTION: Deciding on the strategy in rectal cancer´s treatment requires a complex and multidisciplinary approach. The primary rectal resection is indicated in early stages, while locally advanced tumors should be pretreated by one of the modes of neoadjuvant (chemo) radiotherapy. The main goal of this study was to explore the therapeutic strategy in patients with rectal cancer in the Czech Republic. The second aim was to determine the incidence of the pathological complete response after neoadjuvant therapy. METHODS: This is a retrospective multicenter clinical study, which includes data from all patients with rectal cancer who were treated at participating centers in the period from 01/01/2011 to 31/12/2012. The required data has been passed into the online registry PATOD C20.Three issues have been set up: 1. Characteristics of the center and cooperation with the oncological department; 2. Characteristics of the treatment of patients with rectal cancer; and 3. Detailed analysis of the group of patients with complete pathological response. The analysis was performed with regard to the nature of individual departments, i.e. departments of surgery in university hospitals with complex oncological centres, departments of surgery within complex oncologic centers, and departments of surgery outside complex oncologic centers. RESULTS: In total, 21 departments of surgery in the Czech Republic provided data about 1860 patients with rectal cancer for the study. The treatment strategy for rectal cancer was determined at multidisciplinary seminars at 19 centers (90.5%). Statistically significant differences between the centers were found in the indication for neoadjuvant treatment (p<0.001), rectal resection with anastomosis (p=0.048), and resection without anastomosis (p=0.022). Complete pathological response was found in 61 (8.7%) patients. Positivity of mesorectal lymph nodes (ypN+) was found in the case of ypT0 stage in 7 (9.7%) patients. CONCLUSION: PATOD study showed that therapy of rectal cancer is highly heterogeneous in the Czech Republic. Despite the best conditions provided, university hospitals and large departments within complex oncologic centers do not fully utilize this benefit.

[Long Term Monitoring of Nutritional, Clinical Status and Quality of Life in Head and Neck Cancer Patients]. / Dlouhodobé sledování nutricního, klinického stavu a kvality zivota u nemocných s rakovinou hlavy a krku.

BACKGROUND: Malnutrition in head and neck cancer (HNC) patients decreases survival, quality of life (QOL) and oncological outcomes. The aim of the prospective three-year study was to compare QOL, clinical symptoms and variables (complications, survival and mortality rates in HNC patients). PATIENTS AND METHODS: A total of 726 patients aged 55 to 72 years with treatable HNC were included from January 2004 to December 2009; these patients were randomized to either group with PEG and enteral nutrition and nonPEG group with nutritional counselling according to nutritional care. We used EORTC questionnaires QOL C-30 and Head and neck module (HN-35) for measuring of QOL. The following variables due to expectable influence on QOL (demographic data, oncological data, nutritional screening, Clinical symptom score, Karnofsky performance status score, Charlson comorbidity index) were included. Monitoring was done five times in three years. RESULTS: In the first six months, we found decrease of weight and body mass index (BMI). After this critical time point and finish of oncological treatment, a marked difference in the development of patients treated with PEG. Negative factors influencing patients survival, QOL, clinical status were males aged > 63 years, hypopharyngeal cancer (stage III- IV), smoking, weight loss > 10%, BMI < 21 and disallowance of PEG. CONCLUSIONS: QOL is an essential factor for cancer patients. Our study showed that nutritional intervention with early enteral nutrition may improve QOL and survival in HNC patients. The PEG group better tolerated oncological treatment, had lower incidence of complications, shorter time to re-entry of permanent increase in weight, lower rate of rehospitalization and its shorter length. We found QOL questionnaires to be very important for better understanding and communication and a key instrument for improving solution of patients difficulties during their therapy in multidisciplinary approach.

ATM and TGFB1 genes polymorphisms in prediction of late complications of chemoradiotherapy in patients with locally advanced cervical cancer.

The purpose of our study was to evaluate a possible correlation between genetic polymorphisms in ATM and TGFB1 genes and late toxicity of chemoradiotherapy for locally advanced cervical cancer. Fifty five patients with FIGO stage IIB and higher without a disease recurrence with a mean follow up of 6 years were included. Late toxicity was assessed by EORTC/RTOG late toxicity criteria. Univariate and multivariate logistic regression model was used for statistical analysis. Degree of association between polymorphisms and late toxicity of chemotherapy was assessed on the basis of phi-coefficient (φ) as well. We did not find any association between 5557G>A polymorphism in the ATM gene or single TGFB1 polymorphisms and late toxicity. TGFB1 compound homozygosity (-1552delAGG, -509C>T, L10P) was a significant predictive factor of grade III-IV and any grade of complications in both univariate and multivariate logistic regression analyses and statistical significance of association between polymorphisms and late toxicity of chemoradiotherapy was confirmed also by the evaluation of phi-coefficient (φ). We conclude that haplotypes instead of single nucleotide polymorphic sites in the genes may better characterize the individual radiosensitivity.

[Five-year results of IMRT for prostate cancer - tumor control]. / Petileté výsledky IMRT karcinomu prostaty - kontrola nádoru.

BACKGROUND: Intensity-modulated radiation therapy (IMRT) is the method of choice in external-beam radiotherapy tolocalized prostate cancer. This work analyses five year results of IMRT with a dose of 78/82 Gy. PATIENTS AND METHODS: From June 2003 to December 2007, the IMRT technique was employed to treat 233 patients with T1-3 N0 M0 prostate cancer. It was supplemented by hormone therapy especially in high-risk patients. Two IMRT techniques were applied - IMRT with a dose of 78 Gy in 39 fractions to prostate and seminal vesicles (SV) (IMRT 78) and IMRT with simultaneous integrated 82 Gy boost to prostate concurrently with 73,8 Gy in 41 fractions to SV (IMRT SIB 82). The IMRT 78 technique was used in 160 patients (69%). Seventy-three (31%) patients with intermediate (IR) or high-risk (HR) prostate cancer without SV involvement were treated with IMRT SIB 82 technique. The PSA relapse was defined as an increase in PSA of at least 2.0 ng/mL above the nadir or in comparison to the value at the initiation of hormone therapy. Clinical relapse was defined as an occurence of distant metastases and/or local recurrence. RESULTS: The median follow-up of our patients´ population was 4.3 years (range 0.6-8.9 years). The estimated 5-year PSA relapse-free survival in low-risk (LR), IR and HR patients was 86%, 89% and 83%, respectively (p = NS). In a multivariate analysis, Gleason score (GS) 8-10 was associated with significantly higher risk of PSA relapse (RR 2.76), while higher age at the time of diagnosis significantly decreased the PSA relapse risk (RR 0.94). The estimated 5-year clinical relapse-free survival in LR, IR and HR patients was 100%, 99% and 95%, respectively (p = NS). In a univariate analysis, both GS and PSA had a significant impact on the 5-year clinical relapse-free survival - GS 2-7 97 % vs GS 8-10 88 % (p = 0.03), PSA 20 98 % vs PSA > 20 85 % (p < 0.01). CONCLUSION: Treatment of localized prostate cancer using IMRT with a dose 78/82 Gy yielded an excellent 5-year tumour control with a risk of clinical relapse being less than 5%.

[The radicality of surgical resection in rectal cancer. Analysis of factors associated with incomplete mesorectal excision]. / Radikalita resekcní lécby pro karcinom rekta Analýza prediktivních faktoru spojených s nekompletní mezorektální excizí

INTRODUCTION: Circumferential resection margin (pCRM) and the completeness of mesorectal excision (ME) are two independent prognostic factors significantly associated with the radicality of surgical treatment. Positive pCRM and incomplete mesorectal excision are associated with a significantly higher incidence of local recurrence and worse patient prognosis. The aim of this article is to analyze the risk factors associated with incomplete mesorectal excision. MATERIAL AND METHODS: Patients operated on at the Department of Surgery, University Hospital Hradec Kralove between January 2011 and February 2013 were included in the study. The patients data were prospectively collected and entered in the Dg C20 registry. The following factors were analyzed: sex, age, BMI, cN, pT, clinical stage, the involved segment of the rectum, neoadjuvant therapy, circumferential tumour location, the type of surgical approach and the type of surgery. RESULTS: 168 patients were operated on during the above period. 9 (5.3%) palliative stomas and 159 (94.6%) resection procedures were performed in this group of 168 patients. 7 (4.4%) patients were excluded because the quality of excision was not assessed in them. 114 (75%) resections, including 5 intersphincteric resections, were performed in the group of the remaining 152 patients. 10 (7%) were Hartmanns procedures a 28 (18%) were amputation procedures. Out of 152 procedures, 69 (45%) were performed laparoscopically. Positive (y)pCRO was recorded in 26 (17%) patients, predominantly after abdominoperineal resection (APR) - 11 out of 27 (41%), and Hartmanns operation - 6 out of 10 (60%). Incomplete ME was observed in 45 patients (30%), complete ME in 81 patients (53%) and partially complete in 26 patients (17%). Univariate analysis confirmed statistically significant factors associated with incomplete mesorectal excision: (y)pT (P = 0.00027), type of surgery (P = 0.00001) and tumour location (P = 0.00001). Multivariate analysis then confirmed two independent prognostic factors associated with incomplete mesorectal excision. It was the location of the tumour in the distal third of the rectum and the (y)pT stage of the tumour. CONCLUSION: Distal rectum tumor location and higher (y)pT are associated with a higher risk of incomplete mesorectal excision with worse patient prognosis.

[Radiotherapy in vulvar cancer treatment]. / Radioterapie v lécbe karcinomu vulvy.

OBJECTIVE: To provide an actual review of radiotherapy in the treatment of vulvar carcinoma. DESIGN: A review article. SETTING: Department of Oncology and Radiotherapy, University Hospital in Hradec Králové. METHODS: A review article evaluating the application of ionizing radiation in the treatment of early and advanced vulvar carcinoma, based on the most significant previously published studies. CONCLUSION: Postoperative groin irradiation in patients with positive groin lymph-nodes improves local control, time to progression, and overall survival; especially in 2 positive nodes and in N2/3 initial findings. In case of positive inguinal nodes, radiotherapy of both groins and at least lower pelvic iliac node-chains should follow. Adjuvant irradiation of the primary remains controversial, except for positive resection margins where radiotherapy improves overall survival. Concurrent chemoradiotherapy seems to be appropriate primary treatment of advanced vulvar carcinomas, in attempt to avoid mutilating intervention or exenteration. Chemoradiation should be followed by subsequent surgery, including potential groin dissection in case of lymph-node involvement. Definitive chemoradiotherapy is of limited evidence, and radical dose escalation to the gross tumor is essential for its implementation. Modern radiotherapy techniques, especially with intensity modulation, are convenient for dose escalation.

[The role of radiotherapy in the treatment of malignant lymphomas - recommendations of the Czech Lymphoma Study Group]. / Postavení radioterapie v lécbe maligních lymfomu - doporucení Kooperativní lymfomové skupiny.

BACKGROUND: Indication of radiotherapy in lymphoma treatment is an important strategic decision requiring comprehensive expertise. It also calls for a better definition of the position of radiotherapy in clinical practice. DESIGN: This position paper represents a consensus between hematooncologists and radiation oncologists on the role of RT in treatment of different histological types and stages of malignant lymphomas. The discussion was underway within professional societies of both specializations (Czech Lymphoma Study Group for the hematooncologists and the Society of Radiation Oncology, Biology and Physics for the radiation oncologists). RESULTS: The consensus presented here was reached in early 2012 and draws on evidence-based medicine and clinical practice. Besides defining the role of radiotherapy in lymphoma treatment, this paper also gives specific recommendations on total doses of radiotherapy in lymphoma treatment. CONCLUSION: These recommendations will supplement 7th edition of "Diagnostic and treatment guidelines in patients with malignant lymphoma" scheduled for publication in 2013.

Biologic importance and prognostic significance of selected clinicopathological parameters in patients with oral and oropharyngeal squamous cell carcinoma, with emphasis on smoking, protein p16(INK4a) expression, and HPV status.

The aim of this study is to evaluate the biologic importance and prognostic significance of selected clinicopathological parameters in patients with oral (OSCC) and oropharyngeal (OPSCC) squamous cell carcinoma, with emphasis on smoking, protein p16(INK4a) (p16) expression, and human papillomavirus (HPV) status.The study sample consisted of 48 patients with OSCC and 44 patients with OPSCC. Half of the patients were nonsmokers and the other half were gender-, age- and tumor localization-matched smokers. p16 expression was detected in 17/48 (35 %) OSCCs and in 36/44 (82 %) OPSCCs and HPV DNA was present in 7/48 (15 %) OSCCs and in 35/44 (80 %) OPSCCs. The sensitivity and specificity of p16 expression for HPV DNA presence were 0.74 and 0.88, respectively. The OPSCCs were more frequently basaloid (p < 0.001) while the OSCCs were more frequently conventional (p < 0.000001). The OSCCs were more likely to recur locally and to be the cause of death (p = 0.009 in both parameters).The HPV-positive tumors were more frequently localized in oropharynx, were basaloid SCCs and were p16- and HPV-positive (p < 0.000001 in all 4 parameters). The HPV-negative tumors were more frequently localized in oral cavity (p < 0.000001), more frequently asociated with local, regional and locoregional recurence (p = 0.011, p = 0.019 and p = 0.030, respectively) and with tumor-related death (p = 0.003). There was no significant difference with regard to smoking history (p > 0.05). The survival of patients with HPV-positive tumors was significantly longer (median 112 months; 95% CI 54 - 112 months) than that of patients with HPV-negative tumors (median 17 months; 95% CI 12 - 39 months) (p < 0.001). The HPV status of OSCC/OPSCC is an important biological and prognostic parameter and should be examined in all cases, using PCR or immunohistochemical detection of surrogate marker p16. Smoking itself does not seem to be an important prognostic factor.

[Good's syndrome (thymoma associated hypogammalobulinaemia) - 2 case reports]. / Gooduv syndrom (s thymomem spojená hypogamaglobulinemie) - 2 kazuistiky.

Although tumours of the thymus are rare, they are common among neoplasms of the anterior superior mediastinum. They usually exhibit indolent behavior, but do have the capacity to invade surrouding structures. Their metastatic potential is low. Paraneoplastic complications including autoimmune disorders (frequently myastenia, cytopenia) or combined immunodeficiency are of clinical significance. Here we report two case reports of thymoma patients associated with secondary immunodeficiency known as Goods syndrom. The first case exhibited as symptomatic combinated immunodeficiency with oral lichen planus. Thymoma findings was accidental. Severity of immunodeficiency required long-term intravenous immunoglobulins supplementations, even after complete surgical resection. On the other hand, the second case manifested by signs of advanced local tumour growth. Antibiotic prophylaxis was selected as immunodeficiency treatment.

Molecular predictive factors of outcome of radiotherapy in cervical cancer.

Radical radiotherapy with concurrent cisplatin-based chemotherapy is an established treatment for cervical cancer patients with stage FIGO IIB and higher. The tumor control can be achieved in 40-80% of patients, the treatment is associated with the risk of late postiradiation complications in 10 - 15% of cases. Detection of the factors predictive for tumor control and late morbidity is a possible direction how to individualize radiotherapy dose and technique. The aim of our review is to summarize results of studies inquiring various molecular markers predicting tumor response to radiotherapy and a risk of late complications. A lot of candidate molecules were evaluated in histochemical studies: membrane receptors (EGFR, HER-2), cell cycle regulators (p53, p21), proliferative markers (Ki-67), hypoxia and angiogenetic factors (HIF, VEGF), HPV status, and others (COX-2), with promising results in some of them (HPV, HIF-1α, Ku80, ATM polymorphism). Microarray studies identified decades of genes with different expression in radiosensitive/radioresistant cervical tumors and sets of genes are able to comletely separate responding and nonresponding tumors, but these sets differ across studies. Further well designed studies will be necessary to achieve results matured for use in clinical practice.