Eszter Szabó

Cetuximab, gemcitabine and capecitabine in patients with inoperable biliary tract cancer: A phase 2 study

PURPOSE Biliary tract cancer is rare and has dismal prognosis. Chemotherapy has its role in inoperable disease but the role of targeted agents like cetuximab remains to be defined. On the basis of high epidermal growth factor receptor expression of biliary tract cancers this study aims to investigate the efficacy of cetuximab, gemcitabine and capecitabine in an exploratory phase 2 trial. PATIENTS AND METHODS Inoperable biliary tract cancer patients were treated with the combination of gemcitabine (1000 mg/m(2) on day 1 and 8), capecitabine (1300 mg/m(2)/d on day 1-14) and weekly cetuximab (400mg/m(2) loading and 250 mg/m(2) maintenance dose) in 21-d cycles until progression or the appearance of intolerable side-effects. RESULTS Out of 34 patients (mean age 59.7 years) accrued in this study 16 had intrahepatic, eight extrahepatic cholangiocarcinoma and 10 gall bladder cancer. The best overall response rate was 17.6% (two complete responses and four partial responses) and the clinical benefit rate was 76.5%. After a median of 15.4 months follow-up the median progression free survival was 34.3 weeks and the median overall survival was 62.8 weeks. The performance status and chemotherapy efficacy were independent and significant markers of survival. Only moderate side-effects were registered in this study. KRAS mutation was evaluable in 24 tumours, all of these were of wild type. CONCLUSION The efficacy of cetuximab, gemcitabine and capecitabine combination is encouraging and a well tolerated treatment of inoperable biliary tract cancers.

Subitizing is sensitive to the arrangement of objects.

Subitizing is a fast and accurate enumeration process of small sets of usually less than four objects. Several models were proposed in the literature. Critically, only pattern recognition theory suggests that subitizing performance is sensitive to the arrangement of the array. In our study, arrays of dots in random or canonical arrangements were enumerated. The subitizing range was larger and the reaction time slope was less steep in the canonical arrangements. When noise was added to the canonical pattern, the reaction time slope was proportional to the amount of noise. Moreover, arrangement has a stronger effect on sets with more than four objects. These results support the pattern recognition model of subitizing.

The Role of Number Notation: Sign-Value Notation Number Processing is Easier than Place-Value

Number notations can influence the way numbers are handled in computations; however, the role of notation itself in mental processing has not been examined directly. From a mathematical point of view, it is believed that place-value number notation systems, such as the Indo-Arabic numbers, are superior to sign-value systems, such as the Roman numbers. However, sign-value notation might have sufficient efficiency; for example, sign-value notations were common in flourishing cultures, such as in ancient Egypt. Herein we compared artificial sign-value and place-value notations in simple numerical tasks. We found that, contrary to the dominant view, sign-value notation can be applied more easily than place-value notation for multi-power comparison and addition tasks. Our results are consistent with the popularity of sign-value notations that prevailed for centuries. To explain the notation effect, we propose a natural multi-power number representation based on the numerical representation of objects.

A Comparative Analysis on the Efficacy and Safety of Intaxel® and Taxol® in Advanced Metastatic Breast Cancer

BACKGROUND Among the presently available cytotoxic drugs, paclitaxel, in combination with doxorubicin and carboplatin, come under the highly active therapy for metastatic breast cancer. Between the two brands of paclitaxel (Intaxel, which is marketed by Fresenius Kabi and Taxol, the original paclitaxel which is manufactured by BMS) the similarity has not been evaluated in clinical trial settings till date. This prospective, controlled, randomized, multicentre, open-label phase IV study was planned to compare the safety and efficacy of Intaxel with Taxol, when they were used in combination with carboplatin or doxorubicin, as a second line treatment for metastatic breast cancer. METHODS Fourty nine eligible patients were randomized to receive Intaxel or Taxol with either doxorubicin or carboplatin. The patients who had received a prior anthracycline based chemotherapy were randomized to the paclitaxel/carboplatin arm. The patients were evaluated in three phases i.e. at baseline, during the treatment and at follow up for the tumour response, the time period till the disease progression and the toxicity. The time till the disease progression was assessed by the Kaplan-Meier method. The continuous and categorical variables were assessed by using the ANOVA test and Fishers exact test, respectively. RESULTS After 3 cycles, an objective response rate of 55.56% (CR = 3, PR = 7) was noted in the Intaxel group and that of 59.09% (CR = 1, PR = 12) was noted in the Taxol group. After 6 cycles, an objective response rate of 50% was noted in both the groups. No significant difference was observed in the response rate of the two groups after 3 cycles (p > 0.05) and at the end of the treatment (p > 0.05). The patients who received Intaxel had a lower incidence of thrombocytopaenia (p = 0.0146) and neurosensory loss (p = 0.008) as compared to those who received Taxol. CONCLUSION The results of this study demonstrated that the safety and efficacy of Intaxel and Taxol are equivalent when they are used in combination with other cytotoxic agents as the second line of treatment for metastatic stage IV breast cancer.

Prevalence of Anal Human Papillomavirus Infection in Hungarian Men Who Have Sex with Men

Anal cancer is one of the leading causes of death in non-AIDS defining cancers. Most of these cancers are associated with high risk HPV infection. So far, the prevalence and the significance of anal HPV infection have not been studied in the Hungarian MSM population. The main objective of our study was to determine the prevalence and associated risk factors of HPV-infection in the Hungarian MSM community, particularly in HIV-infected MSM. Out of 109 examinations 92 samples (80 HIV-infected and 12 HIV-negative MSM) were evaluated for both cytological abnormalities and HPV genotyping PCR. Using a questionnaire all enrolled individuals were interviewed about their sexual behavior, socioeconomic factors, drug use and other known or suspected risk factors. In the HIV-infected cohort 97.5% of the examined individuals were positive for any HPV type. In this group we detected high risk (HR) HPV in 88.8%, low risk (LR) HPV in 75.0% and probably high risk (PHR) HPV in 47.5% and multiple HPV infection was absolutely common (82.5%). In the HIV-negative MSM group the incidence of HPV-infection was 58.3%. The respective rate of HR-HPV, LR-HPV and PHR-HPV genotypes were 33.3%, 58.4%, and 16.7%. In the HIV-negative group both HPV infection frequency and the prevalence of the pertinent genotypes were much lower. The Hungarian MSM population is severely infected with HPV and HR-HPV. High-risk sexual behaviors are strong predictors for acquiring HR-HPV co-infections. Our results underline the necessity of anal cancer screening and the introduction of the vaccination program in the high-risk population.

Prevalence and Type Diversity of Human Papillomaviruses in Penile Cancers in Hungary

To the editor Penile cancers are one of the rare forms of oncological diseases as in developed countries their prevalence is less than 1 %. Epidemiological studies suggested the role of oncogenic HPV-types as a causative agent of penile tumors [1, 2]. Around 40 % of patients with penile cancer had also been affected by HPV with type 16 being the most prevalent [3]. Currently available literature data explain HPV-induced tumors with the integration of virus into the epithelial cells’ genome, and its genetic manipulation of the host DNA. Another interesting fact is that HPV infection is much more frequently associated with certain types of penile cancers, than other malignant manifestations [3]. Clinical course and prognosis of patients with penile cancer is unequivocally determined by the lymphatic node status. Five year survival rate of pathologically negative lymph nodes (pN0) is 85–100 %, whereas the involvement of pathologically verified metastatic lymph nodes in the inguinal region dramatically reduces this rate [4]. A retrospective study including 145 male patients describes: tumor thickness and lymphatic or vascular invasion as prognostic factors for lymph node involvement. Interestingly, no statistical correlations can be indicated in lymphatic involvement in connection with T status and the grade of cancer [5]. The aims of the present study were i) to identify and estimate the prevalence of high-risk HPV (hrHPV) genotypes in both primary penile tumors and metastatic lymph nodes, ii) to analyse the potential correlation between the hrHPV positivity and the severity and progression of the cancer. Tissue samples were taken from both the primary tumor and the regional lymph nodes, in over the course of operations of penile cancers in the Department of Urology, University of Pécs, Hungary, between 2002 and 2012. Samples were forwarded to histopathological processing where tissues were fixed in formalin and embedded into paraffin for histological processing. For retrospective molecular studies, 10 μm sections of the paraffin blocks were deparaffinated. Subsequently, DNAwas extracted for the purpose of HPV-identification. Cells were disintegrated using TissueLyser (Qiagen), and subcellular structures were digested enzymatically using Proteinase-K. DNA was purified from tissues using QIAmp DNA FFPE Tissue Kit (Qiagen), according to the manufacturer’s recommendations. HPV DNA was detected by virus-specific TaqMan PCR (DIAGON Ltd., Hungay). In case of HPV positive samples Linear Array HPV Genotyping Test (Roche) was further used for genotyping. A total of 35 patients were involved in the current clinical study. High-risk HPV was identified from primary tumors in 17 cases (48.5 %), regional (inguinal) lymph nodes were positive in 3 cases. The average age of hrHPV positive males was 55 years (range: 44–87 years) while HPV negative patients were slightly older, averaging 66 years of age (range: 50– 82 years). Genotyping using high-sensitivity molecular assays was available for 14 cases out of the 17 hrHPV-positive patients. HPV 16 was identified in 11 of 14 samples (78.5 %), HPV 59 and 82 were detected in two separate cases, while * Ferenc Jakab jakabf@gamma.ttk.pte.hu

Changes in renal function during bisphosphonate treatment of breast cancer patients

Renal function aberrations during bisphosphonate treatment is a well-known phenomenon. In our retrospective study we examined renal functions of 97 breast cancer patients with bone metastasis during their first year of bisphosphonate treatment i.e. (1) frequency of initial renal function alterations; (2) frequency of decreasing renal function during bisphosphonate treatment; (3) the connection between the laboratory findings and the renal function parameters measured at the beginning of bisphosphonate treatment. At the beginning of bisphosphonate treatment we found a surprisingly high rate (26.80%) of decreased creatinine clearance calculated by the Cockcroft-Gault formula. Decreased creatinine clearance at least once during bisphosphonate treatment has been found in 32.99% of the patients, and in 13.4% of the patients with decreased renal function parameters before bisphosphonates it remained decreased during the one-year period. Expected normal renal function is prognosticated by the renal function parameters and serum calcium level measured before starting bisphosphonate treatment. However, we could not demonstrate any connection between decreasing renal function and either the route of administration or the generation or type of bisphosphonates or the previous use of platinum compounds. Our analysis confirms the necessity of monitoring renal function before and during bisphosphonate treatment, and it is advisable to calculate the creatinine clearance in the upper quarter of the normal range of creatinine levels. In case of decreased renal function, change to a less nephrotoxic bisphosphonate or discontinuing the treatment is suggested. While our results are at variance with the published literature, the above-mentioned questions should be examined in a prospective trial.

A biszfoszfonát-kezelés során észlelhető vesefunkció-változás vizsgálata emlőrákos betegeinknél@@@Changes in renal function during bisphosphonate treatment of breast cancer patients

Renal function aberrations during bisphosphonate treatment is a well-known phenomenon. In our retrospective study we examined renal functions of 97 breast cancer patients with bone metastasis during their first year of bisphosphonate treatment i.e. (1) frequency of initial renal function alterations; (2) frequency of decreasing renal function during bisphosphonate treatment; (3) the connection between the laboratory findings and the renal function parameters measured at the beginning of bisphosphonate treatment. At the beginning of bisphosphonate treatment we found a surprisingly high rate (26.80%) of decreased creatinine clearance calculated by the Cockcroft-Gault formula. Decreased creatinine clearance at least once during bisphosphonate treatment has been found in 32.99% of the patients, and in 13.4% of the patients with decreased renal function parameters before bisphosphonates it remained decreased during the one-year period. Expected normal renal function is prognosticated by the renal function parameters and serum calcium level measured before starting bisphosphonate treatment. However, we could not demonstrate any connection between decreasing renal function and either the route of administration or the generation or type of bisphosphonates or the previous use of platinum compounds. Our analysis confirms the necessity of monitoring renal function before and during bisphosphonate treatment, and it is advisable to calculate the creatinine clearance in the upper quarter of the normal range of creatinine levels. In case of decreased renal function, change to a less nephrotoxic bisphosphonate or discontinuing the treatment is suggested. While our results are at variance with the published literature, the above-mentioned questions should be examined in a prospective trial.

A biszfo szfo nát-keze lés során és zlelhet o vese funkci ó-válto zás vizsg álata emlorákos betege inknél

Renal function aberrations during bisphosphonate treatment is a well-known phenomenon. In our retrospective study we examined renal functions of 97 breast cancer patients with bone metastasis during their first year of bisphosphonate treatment i.e. (1) frequency of initial renal function alterations; (2) frequency of decreasing renal function during bisphosphonate treatment; (3) the connection between the laboratory findings and the renal function parameters measured at the beginning of bisphosphonate treatment. At the beginning of bisphosphonate treatment we found a surprisingly high rate (26.80%) of decreased creatinine clearance calculated by the Cockcroft-Gault formula. Decreased creatinine clearance at least once during bisphosphonate treatment has been found in 32.99% of the patients, and in 13.4% of the patients with decreased renal function parameters before bisphosphonates it remained decreased during the one-year period. Expected normal renal function is prognosticated by the renal function parameters and serum calcium level measured before starting bisphosphonate treatment. However, we could not demonstrate any connection between decreasing renal function and either the route of administration or the generation or type of bisphosphonates or the previous use of platinum compounds. Our analysis confirms the necessity of monitoring renal function before and during bisphosphonate treatment, and it is advisable to calculate the creatinine clearance in the upper quarter of the normal range of creatinine levels. In case of decreased renal function, change to a less nephrotoxic bisphosphonate or discontinuing the treatment is suggested. While our results are at variance with the published literature, the above-mentioned questions should be examined in a prospective trial.