The impact of tamoxifen treatment on voice parameters in premenopausal women with breast cancer.

OBJECTIVE: The study aims to investigate the estrogen-agonistic effects of tamoxifen on voice parameters in premenopausal women diagnosed with breast cancer. METHODS: A total of 108 premenopausal women were included, segmented into distinct treatment groups and a control group. Objective sound analysis was conducted using robust statistical methods, employing SPSS 25.0 for data analysis. RESULTS: The study identified a statistically significant reduction in Jitter values across all treatment groups compared to the control group. No significant changes were observed in other voice quality parameters such as F0, Shimmer, NHR, and HNR. CONCLUSIONS: The findings suggest that tamoxifen may have an estrogen-agonistic effect on voice quality, thereby potentially influencing future treatment protocols. This research fills a critical void in existing literature and sets the stage for more comprehensive studies that consider affects of hormonal therapies to voice.

Brigatinib-associated autoimmune hepatitis: A case report.

INTRODUCTION: Brigatinib is a next-generation anaplastic lymphoma kinase (ALK) inhibitor that targets a wide variety of ALK mutations and ROS1 rearrangements. While pancreatic enzyme elevations due to brigatinib are well known, we wanted to present a case that caused liver toxicity. CASE REPORT: ALK and ROS1 translocations were detected in a 58-year-old patient diagnosed with metastatic lung adenocarcinoma. In the patient who had a good response with brigatinib, more than 5-fold elevation was detected in liver enzymes at the fifth month of treatment. MANAGEMENT & OUTCOME: After excluding other hepatitis factors, the patient was thought to have autoimmune hepatitis, and methylprednisolone was started and liver enzymes were decreased. DISCUSSION: Increased creatine kinase and lipase levels are common side effects associated with brigatinib, while liver toxicity is rare. Autoimmune hepatitis due to brigatinib was considered because of hepatic toxicity that developed in the fifth month of treatment and responded well to steroids.

Proton pump inhibitors may reduce the efficacy of ribociclib and palbociclib in metastatic breast cancer patients based on an observational study.

INTRODUCTION: Approximately 20-33% of all cancer patients are treated with acid-reducing agents (ARAs), most commonly proton pump inhibitors (PPIs), to reduce gastroesophageal reflux disease symptoms. Palbociclib and ribociclib are weak bases so their solubility depends on different pH. The solubility of palbociclib dramatically decreases to < 0.5 mg/ml when pH is above 4,5 but ribociclibs' solubility decreases when pH increases above 6,5. In the current study, we aimed to investigate the effects of concurrent PPIs on palbociclib and ribociclib efficacy in terms of progression-free survival in metastatic breast cancer (mBC) patients. PATIENTS AND METHODS: We enrolled hormone receptor-positive, HER2-negative mBC patients treated with endocrine treatment (letrozole or fulvestrant) combined palbociclib or ribociclib alone or with PPI accompanying our observational study. During palbociclib/ribociclib therapy, patients should be treated with "concurrent PPIs" defined as all or more than half of treatment with palbociclib/ribociclib, If no PPI was applied, it was defined as 'no concurrent PPI', those who used PPI but less than half were excluded from the study. All data was collected from real-life retrospectively. RESULTS: Our study included 217 patients, 105 of whom received palbociclib and 112 received ribociclib treatment. In the study population CDK inhibitor treatment was added to fulvestrant 102 patients ( 47%), to letrozole 115 patients (53%). In the Palbociclib arm fulvestrant/letrozole ratio was 53.3/46.7%, in the ribociclib arm it was 41.07/58.93%. Of 105 patients who received palbociclib, 65 were on concomitant PPI therapy, 40 were not. Of the 112 patients who received ribociclib, 61 were on concomitant PPI therapy, 51 were not. In the palbociclib group, the PFS of the patients using PPIs was shorter than the PFS of the patients not using (13.04 months vs. unreachable, p < 0.001). It was determined that taking PPIs was an independent predictor of shortening PFS (p < 0.001) in the multivariate analysis, In the ribociclib group, the PFS of the patients using PPIs was shorter than the PFS of the patients not using (12.64 months vs. unreachable, p = 0.003). It was determined that taking PPIs was single statistically independent predictor of shortening PFS (p = 0.003, univariate analysis). CONCLUSIONS: Our study demonstrated that concomitant usage of PPIs was associated with shorter PFS in mBC treated with both ribociclib and especially palbociclib. If it needs to be used, PPI selection should be made carefully and low-strength PPI or other ARAs (eg H2 antagonists, antacids) should be preferred.

Prognostic Importance of Inflammatory Indexes in Patients Treated by Pazopanib for Soft Tissue Sarcoma.

BACKGROUND: The goal of this study was to evaluate the predictive and prognostic importance of the lymphocyte to monocyte ratio (LMR), neutrophil to lymphocyte ratio (NLR), derived neutrophil to lymphocyte ratio (DNLR), and systemic immune inflammation index (SSI) in STS cases treated with pazopanib. METHODS: Thirty STS patients treated with pazopanib were included in this study. SSI, DNLR, LMR, and NLR values were calculated at baseline and in the first month. Median values of these predictors in these patients (SSI (944), DNLR (1.8), LMR (2.7), and NLR (3.0)) were taken as cutoff values. The associations between the survival time (both overall survival (OS) and progression-free survival (PFS)) and cutoff values were evaluated using Kaplan Meier curves and Cox regression models. RESULTS: Patients with low SSI, NLR, and DNLR values at pretreatment and after the initial response had longer OS (for OS - p = 0.024, p = 0.015, and p = 0.041, respectively). Longer OS was also found in patients who showed increasing LMR and decreasing NLR after one month of therapy (for ΔLMR, p = 0.016; for ΔNLR, p = 0.016). Pa-tients with low SSI and NLR values at pretreatment and after the initial response had longer PFS (for PFS, p = 0.014, p = 0.04, p ˂ 0.001, respectively). In terms of initial responses to treatment, SSI, NLR, DNLR, and increased LMR were detected as independent risk factors in univariate analysis, but initial response was found to be the only independent risk factor for PFS in multivariate analysis. CONCLUSIONS: Low values of SSI, NLR, and DNLR at pretreatment and at initial response may predict long-term survival rates. After one month of treatment with pazopanib, decreased NLR and increased LMR are predictive of favorable outcomes in these cases.

Evaluation of antibody response after two doses of the Sinovac vaccine and the potential need for booster doses in cancer patients.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is more severe in some specific patient groups, such as cancer patients with a mortality rate of 26.5%. The main way of protection is vaccination. In this study, we aimed to evaluate the antibody responses of our cancer patients who received two doses of the inactivated COVID-19 vaccine manufactured by Sinovac Life Sciences. Patients over the age of 18, who had not been suspected or polymerase chain reaction-confirmed COVID-19 positive, who received two doses of the vaccine, and at least 28 days passed after the second dose, and who received at least one dose of cancer treatment before the vaccination-were included in the study. Immunoglobulin class G antibodies against the receptor binding region (S-RBD) of the spike protein S1 subunit of SARS-CoV-2 were studied. A total of 200 patients with a diagnosis of cancer were included in the study. The median time between the second dose of the Sinovac vaccine and the time of blood collection was 3.44 (3.20-3.84) months. SARS-CoV-2 antibody positivity was detected in 110 (55%) patients. The two subgroups with the highest antibody levels were gynecological cancers and breast cancers, with median 158.5 AU/ml (38.4-764.5) and 106.3 AU/ml (61.9-162.9) levels, respectively. Antibody positivity rate was 46.8% in patients who received chemotherapy at any time between the first dose of the vaccine and the date of blood collection; and it was 73.8% in the group that did not receive chemotherapy (p < 0.001). As a result, the expected antibody response was not obtained with two doses of the Sinovac vaccine. Therefore, if the Sinovac vaccine is to be preferred for these patients, the appropriate booster time for the third dose should be determined or other vaccines, such as messenger RNA vaccines, with reported higher antibody responses should be considered.

Panitumumab Associated Acute Pancreatitis.

INTRODUCTION: The addition of panitumumab to chemotherapy in wild-type metastatic colon cancer contributes to survival. While the skin related side effects of panitumumab are well known, we wanted to present a case where it was a possible cause of acute pancreatitis. CASE REPORT: The FOLFOX regimen was started in a 67-year-old patient with sigmoid colon cancer and multiple liver metastases. After 2 cycles, genetic tests were concluded and panitumumab 6 mg/kg was added to the treatment. The patient who presented with abdominal pain 2 days after the treatment was hospitalized with acute pancreaatitis. MANAGEMENT & OUTCOME: Abdominal tomography of the patient was compatible with acute pancreatitis. Oral intake was stopped, IV hydration was started. The patient, whose complaints regressed, was discharged on the 3rd day of hospitalization. DISCUSSION: Skin side effects related to panitumumab are observed quite frequently. Although panitumumab related gastrointestinal side effects have been reported, there is no data on acute pancreatitis. Panitumumab was added to the chemotherapy regimen he received, and it was thought that panitumumab might be the etiological factor in the case who developed pancreatitis.

Inhaled corticosteroids' effects on biomarkers in exhaled breath condensate and blood in patients newly diagnosed with asthma who smoke.

OBJECTIVE: Exposure to cigarette smoke complicates the treatment and management of asthma through a variety of inflammatory effects. This study aimed to investigate the differences between newly diagnosed cases of asthma in smokers and nonsmokers in terms of localized and systemic biomarkers following treatment with inhaled corticosteroids (ICS) or ICS in combination with a long-acting ß2 agonist (LABA). METHODS: Specimens of exhaled breath condensate (EBC) from newly diagnosed patients with asthma were used to quantify inflammation in the airways, while blood samples were used to assess systemic inflammation. In both samples, the levels of IL-6, LTB4, LTD4, and 8-isoprostane were measured and these were repeated after 3 months of treatment with ICS or ICS + LABA. RESULTS: Of the 20 patients, 10 (50%) were nonsmokers with asthma (NSA) and 10 (50%) smokers with asthma (SA). There was no statistically significant difference in the blood or EBC levels of IL-6, LTB4, LTD4, or 8-isoprostane between the groups prior to treatment. Only the decrease in 8-isoprostane level in the EBC samples was found to be significantly greater in the NSA group after treatment (for smokers, the change was 2.91 ± 23.22, while for nonsmokers it was -22.72 ± 33.12, p = 0.022). Post-treatment asthma control was significantly better in the NSA group (p = 0.033). CONCLUSION: Monitoring the alterations in 8-isoprostane levels in EBC in patients with asthma who smoke may be helpful in deciding on therapeutic management and switching treatments. Asthma control was better in nonsmokers than in smokers.

Efficacy of US, MRI, and F-18 FDG-PET/CT for Detecting Axillary Lymph Node Metastasis after Neoadjuvant Chemotherapy in Breast Cancer Patients.

BACKGROUND: The aim of this study was to investigate the efficacy of post-neoadjuvant chemotherapy (NAC) ultrasound (US), magnetic resonance imaging (MRI), and F-18fluorodeoxyglucose positron emission tomography (F-18 FDG-PET/CT) for detecting post-NAC axillary lymph node(ALN) metastasis in patients who had ALN metastasis at the time of diagnosis. METHODS: This study included all breast cancer patients who received NAC for ALN metastasis; underwent axillary assessment with US, MRI, or F18FDG-PET/CT; and then were operated on in the General Surgery Clinic, Adana City Research and Training Hospital, Turkey. Patients' data were recorded, including demographic data, clinicopathological parameters, NAC regimens, and operation types. The axillary response to chemotherapy on post-NAC US, MRI, and F-18 FDG-PET/CT was compared with the postoperative histopathological result of the ALN. RESULTS: The study included a total of 171 female patients. The mean age of the patients was 53.28 ± 10.62 years. The post-NAC assessment revealed that the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of US for detecting ALN metastasis were 59.42%, 82.35%, 82.00%, and 60.00%, respectively, while the same measures regarding MRI for detecting ALN metastasis were 36.67%, 77.78%, 73.33%, and 42.42%, respectively. The sensitivity, specificity, PPV, and NPV of F-18FDG-PET/CT were 47.50%, 76.67%, 73.08%, and 52.27%, respectively. The evaluation of dual combinations of these three imaging techniques showed that the specificity and PPV of the combined use of US and F-18FDG-PET/CT was 100%. CONCLUSIONS: The results showed that US has the highest sensitivity and specificity for detecting ALN metastasis after NAC. Furthermore, ALND may be preferred for these patients instead of SLNB if both examinations simultaneously indicate lymph node metastasis in the post-NAC assessment with US and F-18 FDG-PET/CT. SLNB may be preferred if these two examinations simultaneously show a complete response.

Male Breast Cancer: Clinical, Demographical, and Pathological Features in a Cohort of 41 Patients.

Background and objective Male breast cancer (MBC) is a rare malignancy, and it accounts for less than 1% of all cancers in men. The pathogenesis of MBC remains unclear, with most available data obtained from single-center studies and retrospective series. The aim of this study was to share our experiences of MBC cases and to describe the characteristics of MBC patients. Materials and methods We retrospectively reviewed the records of 41 MBC cases and recorded the pathological, clinical, and demographic features of the patients. Data on progression-free survival (PFS) and overall survival (OS) were also recorded. Results The mean age of the patients was 64.1 ± 10.0 years. The most common histopathological subtype was invasive ductal carcinoma. Hormone receptor positivity was detected in 39 (95.1%) patients. Human epidermal growth factor receptor 2 (HER2) positivity was present in five (12.2%) patients. Most of the patients had early-stage disease. Surgery was the treatment of choice for most primary tumors. Thirty-nine (95.1%) patients received hormonotherapy, and 21 (51.2%) received systemic chemotherapy. OS was found to be 126.4 months and PFS was 83.2 months. The OS and PFS time in patients with a Nottingham Prognostic Index (NPI) score of <5.4 were longer than those with an NPI score of >5.4. Conclusion The hormone receptor status of most of the MBC patients was positive, and their HER2 status was negative. A multimodality approach was associated with longer survival, which has been reported in female patients with breast cancer as well. The NPI score is a useful tool for predicting survival time in MBC patients.

Predictors of Survival in Turkish Patients with Primary Glioblastoma.

AIM: An increasing number of biomarkers of primary glioblastoma (GBM) have recently been described. We aimed to investigate the biological and clinical factors that affect survival in Turkish patients with primary GBM. MATERIAL AND METHODS: The clinical and demographic data of all patients with primary GBM diagnosed between 2007 and 2016 were evaluated. In all the patients? pathological specimens, O6 methylguanine-DNA methyltransferase (MGMT) methylation and isocitrate dehydrogenase (IDH) 1 mutation were detected retrospectively by immunohistochemistry. Kaplan-Meier survival analysis, log-rank test, and multivariate analyses of the Cox hazard proportional model for all the variables were performed using the SPSS statistical package. The treatment details and other patient-related factors were identified, and their correlations were analyzed. RESULTS: We enrolled 137 primary GBM patients to the study. Median progression free survival (PFS) was 8.57 months (95% CI:6.8-9.5) and median overall survival (OS) was 12 months (95% CI:10.8-13.3). IDH-1 mutations were detected in 21 primary GBMs (15.3%). PFS was 15.43 ± 1.95 months. Survival rates were higher, but no statistically significant difference (p=0.074). MGMT methylation was detected in 40 primary GBMs (29.2%). OS and PFS of MGMT (+) cases were higher than MGMT(-) cases (p=0.001; p=0.001 respectively). Ki67 (%) measurement (10%-90%) average is 32.64 ± 16.56. No statistically significant between higher and lower ki67 levels (p=0.510, p=0.505 respectively). KPS (%) more than 70 at the time of diagnosis statistically significant longer median OS and PFS (p=0.001). PFS and OS were higher in all treatment modalities. CONCLUSION: The most important factors that affected survival were performance score, MGMT methylation status, systemic oncologic therapy, and IDH mutation in the Turkish population with primary GBM. We demonstrated that MGMT methylation and higher KPS levels were associated with significiantly longer OS and PFS.

Evaluation of Oxidative Stress Biomarkers in Brain Metastatic and Non-Metastatic Lung Cancer Patients with Different Cell Types.

BACKGROUND: Oxidative stress that leads to an imbalanced prooxidant/antioxidant status can be a critical factor affecting lung cancer etiopathology. The antioxidant system provides primary protection under oxidative stress. OBJECTIVE: The purpose of the study was to investigate the serum antioxidant system status in brain metastatic and non-metastatic lung cancer patients with different cell types. METHODS: In this prospective study, 33 patients with lung cancer metastasis (metastatic patient group), 36 lung cancer patients (non-metastatic patient group), and 25 healthy control groups were included. Enzymatic (Superoxide Dismutase, SOD; Glutathione Peroxidase, GPX; and Glutathione Reductase, GR) and non-enzymatic (Glutathione, GSH) antioxidant system biomarkers with Thiobarbituric Acid Reactive Substances (TBARS) levels were studied in the serum samples of the control and patient groups. The oxidative stress biomarkers were measured spectrophotometrically. RESULTS: SOD activity increased though TBARS levels and GR activity decreased in both patient groups compared to the control. GPX activity increased only in the non-metastatic group. Antioxidant biomarkers varied between small cell and non-small cell group patients. GR activity and GSH levels were significantly higher in the non-metastatic group compared to the metastatic group. Correlations were also found between antioxidant parameters in the non-metastatic group. CONCLUSION: It was emphasized the imbalanced antioxidant system in the duration of the disease is related to not only cell type but also the metastatic structure. This is the preliminary study exhibiting the contribution of antioxidant imbalance in different subtypes with varied prognosis and behavior of lung cancer in the presence of brain metastasis. Therefore, oxidative stress biomarkers can serve as a useful tool to get information about the progression of lung cancer. Thus, it may provide fundamental data for further cancer research when considering the diagnosis of the disease.

Extracranial Metastasis of IDH-1 Wild Type Glioblastomas.

AIM: To identify the effects of different immunohistochemical features of glioblastomas with spinal metastases based on the metastatic spread and survival rate. MATERIAL AND METHODS: A total of 214 patients who were diagnosed with and operated for brain tumor in our clinic between 2007 and 2018, and pathologically diagnosed with glioblastoma were retrospectively evaluated. Among them, 141 medical records were reviewed, and 23 of them underwent spinal magnetic resonance imaging postoperatively due to various complaints. RESULTS: All patients with glioblastoma with spinal metastases had negative isocitrate dehydrogenase 1 (IDH-1) in the immunohistochemical examination. The incidence of spinal metastasis is 1.91%. The median Ki-67 index is 30 (range, 4-90; median Ki-67 index: 30+/-18.5). IDH mutation is wild in 55%, mutant in 33%, and not otherwise specified in 12%. Four patients with spinal metastasis has wild-type IDH with mean Ki-67 index of 60, and one of them was a woman (25%) and the remaining three were men (%75), with mean age of 32 years. CONCLUSION: Gliomas with high immunohistochemical proliferation indexes and wild-type IDH with poor prognostic features based on the new classification tended to metastasize to the spine in the early disease stage; therefore, early spinal scanning and radiation therapy might extend the life expectancy. High Ki-67 index and the presence of wild-type isocitrate dehydrogenase may be the predictive factors for spinal screening.

Malignant Melanoma Metastasis to the Thyroid Gland Causing Severe Central Airway Obstruction.

Metastasis of malignant melanoma to the thyroid gland causing airway obstruction is an extremely rare condition. In an 80-year-old woman who presented with painless swelling of the neck, a diagnosis of malignant melanoma metastasis to the thyroid gland with an unknown source was established. She received multiple radiotherapy sessions that resulted in occasional regression but not complete resolution. She was then referred for tracheal stenting owing to progressed dysphagia and dyspnea. Rigid bronchoscopy was performed, and a fully covered metal stent was placed to secure the open airway. Dyspnea improved immediately after stent insertion. The patient died at her residence because of a cerebrovascular event 2 weeks after the procedure. To the best of our knowledge, central airway obstruction due to malignant melanoma metastasis to the thyroid gland has been not reported in the literature. The approach for palliation of obstruction is similar to that of other malignant central airway obstructions.

Steatohepatitis due to FOLFIRINOX regimen in adjuvant pancreas cancer treatment mimicking liver metastasis.

INTRODUCTION: The combination of fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) is more toxic than gemcitabine, but it is a safe regimen with manageable toxicities. CASE REPORT: We report a case with steatohepatitis mimicking liver metastasis as toxicity that was not seen in study patient population.Management and outcome: In the adjuvant statement with FOLFIRINOX due to biopsy, we give the same regimen by excluding metastasis. DISCUSSION: The adverse events of drugs are important predictive factor for treatment management, as important as efficacy. Especially the new lesion and metastasis is the most important factor for changing treatment. The clinicians must be careful about adverse events of regimens. CONCLUSION: FOLFIRINOX regimen is the most important combination in pancreas cancer adjuvant setting. This case shows us the different presentation of usual adverse event.

Risk factors for developing cardiotoxicity of trastuzumab in breast cancer patients: An observational single-centre study.

BACKGROUND: Trastuzumab is a recombinant humanized monoclonal antibody used to treat human epidermal growth factor receptor 2 positive breast cancer, with recognized associated cardiotoxicity. In this retrospective observational study, we investigated associated cardiotoxicity on clinical outcomes using trastuzumab in women referred to our clinic. MATERIALS AND METHODS: The study was made up of 111 women with human epidermal growth factor receptor 2-overexpressing breast cancer who received trastuzumab in the Medical Oncology Department, between 2010 and 2013. RESULTS: A > 10% reduction of the baseline fraction of the left ventricular ejection fraction was observed in 18 (16.21%) women. Two individuals (1.8%) suffered from symptomatic heart failure, seven women showed cardiac symptoms and nine women showed asymptomatic decline of left ventricular ejection fraction. Risk factors for cardiotoxicity in the group included: postmenopausal status (p = 0.01), hypertension (p = 0.002), obesity (p = 0.0001), previously diagnosed coronary artery disease (p = 0.0001) and smoking (p = 0.03). CONCLUSION: The aforementioned factors pose a risk for cardiotoxicity. We found postmenopausal status, hypertension, obesity, previous coronary artery disease and smoking to be associated with an increased risk of cardiac dysfunction in women using trastuzumab. While administering trastuzumab to women who have these conditions, one must be aware of the risk of cardiotoxicity of trastuzumab.

ERCC1 and RRM1 as a predictive parameter for non-small cell lung, ovarian or pancreas cancer treated with cisplatin and/or gemcitabine.

BACKGROUND: We aimed to investigate the impact of RRM1 and ERCC1 expression on response to cisplatin and/or gemcitabine chemotherapy in patients with lung, ovarian or pancreatic cancer. MATERIAL AND METHODS: Patients with lung, ovarian or pancreatic cancer, who used cisplatin and/or gemcitabine therapy were included; hospital files were examined and RRM1 and ERCC1 expression were evaluated with an immunohistochemical method on tissue cross sections from paraffin blocks of the tumour. RESULTS: Out of 89 patients, 51%, 30% and 19% had lung, ovarian and pancreatic cancer, respectively. The response rates to the therapy in patients with lung and ovarian cancer having low ERCC1 expression were 62% and 90%, respectively (p = 0.028 and p = 0.044, respectively). No significant association was found between ERCC1 expression and response to therapy in patients with pancreatic cancer (p = 0.354). Therapeutic response rates in patients with lung and pancreatic cancer with low RRM1 expression were 60% and 82%, respectively. Survival rates were higher in patients with lung cancer in which ERCC1 and RRM1 expressions were low. Median survival duration in patients with ovarian cancer showing low ERCC1 and RRM1 expressions was longer than that seen in patients with high expressions. Although no significant correlation was found between ERCC1 and the survival in ovarian cancer (p = 0.183), there was a significant correlation between RRM1 expression and survival in patients with pancreatic cancer (p = 0.005). CONCLUSIONS: Our results suggest a predictive value of ERCC1 in lung and ovarian cancers, and also RRM1 in lung and pancreatic cancers.

Factors affecting the tuberculosis risk in patients receiving anti-tumor necrosis factor-α treatment.

BACKGROUND: Tumor necrosis factor (TNF)-α inhibitors are known to increase the risk of tuberculosis (TB). OBJECTIVES: To examine the factors associated with an increased risk of TB in patients receiving anti-TNF-α treatment (aTNF-α-T). METHOD: Of 3,094 patients who received aTNF-α-T between 2003 and 2013, a total of 1,964 subjects with a follow-up time longer than 6 months were identified and included in this retrospective analysis. Potential risk factors for the development of TB in patients receiving aTNF-α-T were evaluated. RESULTS: Of the 1,964 patients, 1,009 (51%) were male and 955 (49%) were female, with a mean age of 39.7 ± 13.9 years. The primary conditions requiring aTNF-α-T included ankylosing spondylitis (n = 875), rheumatoid arthritis (n = 711), Behçet's disease (n = 83), and others (n = 295). Sixteen patients [8 (50%) males and 8 (50%) females; 5 (31.2%) with pulmonary TB and 11 (68.8%) with extrapulmonary TB] developed TB, with a corresponding TB incidence of 466/100,000. No significant associations were found between age, gender, smoking history, pack-years of smoking, isoniazid (INH) chemoprophylaxis, type of anti-TNF-α agent, use of other immunosuppressive drugs, and the risk of TB (p > 0.05). Multivariate logistic regression analysis showed a significantly higher risk of TB in patients diagnosed with Behçet's disease, and a significantly lower risk of TB in patients with a tuberculin skin test wheal ≥10 mm in diameter (p < 0.05). CONCLUSION: aTNF-α-T is associated with an increased risk of pulmonary or extrapulmonary TB, even when follow-up protocols and INH chemoprophylaxis are implemented, and TB often develops in the later stages of treatment. The risk of TB was higher in patients with Behçet's disease and lower in patients who had a strong tuberculin skin test reaction.

Effect of the cumulative dose of zoledronic acid on the pathogenesis of osteonecrosis of the jaws.

Bisphosphonate-related osteonecrosis of the jaws (BRONJ) is a severe bone disease for which the pathogenetic mechanisms and risk factors are not fully understood. The present study evaluated the data of 652 patients with bone metastasis that had undergone treatment with biphosphonates. Subsequently, 24 patients with BRONJ and 20 control patients without BRONJ that were treated with zoledronic acid were enrolled. It was found that BRONJ occurred in 3.6% of patients. The mean age and the administration of dental treatment were found to be significantly associated with BRONJ development (P=0.049 and P=0.013, respectively). The cumulative dose median in the BRONJ group was found to be significantly higher compared with the cumulative dose average in the control group (P=0.037). In addition, at the time of BRONJ development, improvement in the disease was determined to be better in the BRONJ group than in the control group (P=0.031). The present study determined that age, the existence of dental extraction and the cumulative dose of zoledronate were all important risk factors in BRONJ development.

PRAME Expression and Its Clinical Relevance in Hodgkin's Lymphoma.

OBJECTIVES: Although Hodgkin's lymphoma (HL) is one of the most curable cancers in adult patients, new targets have to be defined in cases resistant to traditional chemotherapy. The preferentially expressed antigen of melanoma (PRAME) is a cancer testis antigen and its expression is very scarce or absent in normal tissues. For this reason PRAME is a promising candidate for tumor immunotherapy. The aim of this study is to understand the correlation of PRAME expression with prognostic factors in HL, to determine the utility of PRAME as a targeted molecule for immunotherapy and to compare real-time polymerase chain reaction (real-time PCR) and immunohistochemistry (IHC) for the detection of PRAME. METHODS: In 82 patients, PRAME was studied using real-time PCR and IHC. Data analyses were performed using statistical methods such as t test, Mann-Whitney U test, χ 2 test, Kaplan-Meier method, log-rank test and Cox regression analysis. RESULTS: PRAME was detected in 15 (18.3%) patients using IHC and in 8 (9.8%) patients using real-time PCR. A correlation was found between PRAME positivity and higher International Prognostic Score (p = 0.039). PRAME positivity detected using real-time PCR was found to be correlated with shorter disease-free survival (DFS) and overall survival (OS, p = 0.0005). DISCUSSION: The demonstration of PRAME especially in histiocytes and Reed-Sternberg cells may provide guidance for immunotherapy. Although PRAME positivity increases the risk for death (3.56), independent risk factors that affected DFS and OS occurred in advanced age and high-risk groups. CONCLUSION: Although real-time PCR is sensitive in the detection of PRAME, IHC can be another useful method. Despite the need for studies conducted on larger patient samples, PRAME expression is considered as a poor prognostic parameter in HL.