Can Atalay

Multidrug Resistance in Locally Advanced Breast Cancer

Background: Advanced breast cancer cases can still be encountered resulting in poor prognosis. The primary treatment for these patients is chemotherapy, and multidrug resistance (MDR) is a serious obstacle in the treatment. Detecting drug resistance before first-line chemotherapy may increase the patient’s survival. In this study, the role of MDR is evaluated in locally advanced breast cancer patients. Methods: Reverse transcriptase polymerase chain reaction was used for the detection of MDR genes, ABCB1 and ABCC1. Immunohistochemistry was used for the detection of MDR proteins, P-glycoprotein (Pgp) and MDR-associated protein 1. Results: Breast tissues from 25 patients both before and after chemotherapy were examined. Five patients were unresponsive to chemotherapy. Four had ABCB1 gene expression induced by chemotherapy, and Pgp positivity was detected in 9 patients after chemotherapy. Both the induction of ABCB1 gene expression (p < 0.001) and Pgp positivity (p < 0.001) during chemotherapy were significantly related with clinical response. Although 80% of the clinically unresponsive patients had ABCC1 gene expression, the relation between ABCC1 expression and clinical drug response was not significant. Conclusion: In locally advanced breast cancer, ABCB1 gene expression during chemotherapy contributes to clinical unresponsiveness. However, ABCC1 gene expression did not correlate strongly with the clinical response.

Predictive Factors for Residual Disease in Re-Excision Specimens After Breast-Conserving Surgery

Abstract:  Local recurrence is an issue of concern after breast‐conserving therapy and removing the primary tumor with negative surgical margins is the most important determinant of local recurrence. However, some patients with positive margins after initial surgery will have no residual tumor in the re‐excision specimen. To avoid unnecessary re‐excisions, factors predicting residual disease in re‐excision material should be determined. This study aimed to determine the predictive factors for residual disease in the re‐excision material in a homogeneous group of patients with positive margins and only invasive ductal carcinoma. Breast cancer patients treated between 2005 and 2008 with breast‐conserving surgery and subsequent re‐excisions due to positive surgical margins after initial surgery were included in the study. Patients were divided into two groups as those with and without residual disease in the re‐excision material. One hundred and four breast cancer patients were included in the study. Forty‐seven patients (45.2%) had residual tumor in re‐excision specimen. Patient characteristics such as age (p = 0.42) and physical findings (p = 1.0) and specimen volume (p = 0.24), tumor grade (p = 0.33), estrogen (p = 1.0), and progesterone (p = 0.37) receptor status, axillary lymph node metastases (p = 0.16), extensive intraductal component (p = 0.8), and lymphovascular invasion (p = 0.064) were found as insignificant factors for predicting residual tumor. Large tumor size (>3 cm) (p = 0.026), human epidermal growth factor receptor2 (HER2) positivity (p = 0.013), and tumor to specimen volume ratio of >70% (p = 0.002) significantly increased the probability of finding residual disease after re‐excision. In multivariate analysis, HER2 positivity (p = 0.046) and tumor to specimen volume ratio of >70% (p = 0.006) independently predicted the presence of residual disease. As a result, in patients with HER2 positive tumors larger than 3 cm, larger volume of breast tissue around the tumor should be removed to decrease the number of re‐excisions due to positive surgical margins.

Multidrug Resistance Mediated by MRP1 Gene Overexpression in Breast Cancer Patients

Multidrug resistance (MDR) is a serious handicap towards the effective treatment of breast cancer patients. One of the most prevalent MDR mechanisms is through the overexpression of genes coding the proteins called Multidrug Resistance-associated Proteins (MRPs). The aim of this study was to investigate the expression of MRP1 in tumor tissues from breast cancer patients. In this study, a semi-quantitative RT-PCR approach was utilized. Our results suggest that MRP1 overexpression can mediate MDR in patients. Pre-evaluation of the level of such MDR mediators before chemotherapy can increase the efficacy of the treatment.

Role of ABCB1 and ABCC1 gene induction on survival in locally advanced breast cancer.

Abstract Drug resistance to chemotherapy in patients with locally advanced breast cancer results in a decrease in treatment efficacy and in patient survival. This study aimed to evaluate the impact of ABCB1 and ABCC1 gene induction during chemotherapy on disease-free and overall survival of breast cancer patients. Patients with locally advanced breast cancer were prospectively included. All patients were preoperatively treated with chemotherapy and underwent mastectomy. ABCB1 and ABCC1 gene and protein expressions were evaluated both before and after chemotherapy and investigated as molecular predictive parameters affecting disease free and overall survival. ABCB1 and ABCC1 gene expressions were evaluated with RTPCR following RNA isolation from tissue samples. P-glycoprotein and MRP1 in tissues were detected using immunohistochemistry. Twenty-five female patients treated with either doxorubicin or epirubicin were included. Median follow-up time was 36 months during which 11 patients (44%) had recurrence, all of whom died. Mean disease-free survival for patients with and without ABCB1 gene induction was 13 and 55 months (p=0.0004), respectively, whereas overall survival was 21 and 57 months (p=0.0025), respectively. Mean disease-free survival for patients with and without ABCC1 gene induction was 32 and 48 months (p=0.97), respectively, and overall survival was 43 and 49 months (p=0.36), respectively. ABCB1 gene induction decreases disease-free and overall survival in patients with locally advanced breast cancer due to anthracycline resistance. Detecting ABCB1 gene expression during chemotherapy helps to increase the efficacy of drug treatment by choosing the appropriate drugs resulting in prolonged survival.

Angiosarcoma of the Thyroid and Regional Lymph Node Metastasis

DOI: 10.4328/JCAM.828 Received: 14.10.2011 Accepted: 07.12.2011 Printed: 01.09.2014 J Clin Anal Med 2014;5(5): 426-8 Corresponding Author: Niyazi Karaman, Angora Evleri Ressamlar Caddesi F6 Blok No 8 Beysukent Ankara, Turkey. T.:+90 3122251869 F.: +90 3122251871 E-Mail: niyazikaraman@hotmail.com Ozet Tiroid anjiosarkomlari tipik olarak infiltratif ve buyuk tumorlerdir ve klinik bulgulari anaplastik tiroid kanserine cok benzer. Erken hematojen yayilim cok sik iken, bolgesel lenf nodu metastazi oldukca nadirdir. Bu yazida 68 yasinda bir erkek hastada bolgesel lenf bezi metastazi olan tiroid anjiosarkom olgusu bildirilmistir. Hastaya total tiroidektomi ile birlikte sag modifiye radikal boyun diseksiyonu uygulandi. Disseke edilen 19 lenf nodunun dordunde metastaz saptandi. Metastatik tumor cok sayida kan dolu yariklari iceren sarkomatoz alanlardan olusmaktaydi. Ameliyattan sonra PET-CT cekilen hastada multipl metastazlar saptandi. Tiroid anjiosarkomlari anjiomatoid anaplastik karsinomlardan tamamen farkli tumorlerdir. Bu tumorlerde uzun sag kalim sadece agresif cerrahi ile mumkundur ve bolgesel lenf bezi metastazi varliginda boyun diseksiyonu yapilmalidir.

A prospective evaluation of the risk factors for development of wound dehiscence and incisional hernia

OBJECTIVE Post-laparotomy wound dehiscence, evantration and evisceration are important complications leading to an increase in both morbidity and mortality. Incisional hernias are frequently observed following abdominal surgeries and their occurrence is related to various local and systemic factors. This study aims to analyze the factors affecting wound healing by investigating the parameters that may cause wound dehiscence, incisional hernia, sinus formation and chronic incisional pain. MATERIAL AND METHODS The records of 265 patients who underwent major abdominal surgery were analyzed. The data on patient characteristics, medication, surgical procedure type, type of suture and surgical instruments used and complications were recorded. The patients were followed up with respect to sinus formation, incisional hernia occurrence and presence of chronic incision pain. Statistical analysis was performed using SPSS 10.00 program. The groups were compared via chi-square tests. Significance was determined as p<0.05. Multi-variate analysis was done by forward logistic regression analysis. RESULTS 115 (43.4%) patients were female and 150 (56.6%) were male. Ninety-four (35.5%) patients were under 50 years old and 171 (64.5%) were older than 50 years. The median follow-up period was 28 months (0-48). Factors affecting wound dehiscence were found to be; creation of an ostomy (p=0.002), postoperative pulmonary problems (p=0.001) and wound infection (p=0.001). Factors leading to incisional hernia were; incision type (p=0.002), formation of an ostomy (p=0.002), postoperative bowel obstruction (p=0.027), postoperative pulmonary problems (p=0.017) and wound infection (p=0.011). CONCLUSION Awareness of the factors causing wound dehiscence and incisional hernia in abdominal surgery, means of intervention to the risk factors and taking relevant measures may prevent complications. Surgical complications that occur in the postoperative period are especially related to wound healing problems.

Impact of cyclooxygenase-2 over-expression on the prognosis of breast cancer patients

Establishing new predictive and prognostic factors in various cancers is an ongoing challenge for many decades. Biomarkers detected in preclinical studies as predictive and prognostic factors could be potential targets for new drug development. Cyclooxygenase enzyme plays a key role in inflammation and has two isozymes synthesized by cyclooxygenase-1 and cyclooxygenase-2 genes. Cyclooxygenase enzyme was first evaluated in colorectal cancer since its increased synthesis is a known driver for carcinogenesis. Induction of cyclooxygenase-2 gene causes cancer formation by increasing prostaglandin E2 synthesis which results in estrogen production in adipose tissue (1). Besides, prostaglandin E2 shows immunosuppressive effect in the tumor microenvironment promoting tumor progression. Thus, potential role of cyclooxygenase-2 in breast cancer development became the topic of recent studies. Cyclooxygenase-2 gene overexpression was reported in 40–84% of the breast cancer patients depending on the stage of cancer (2). Similarly, cyclooxygenase-2 gene expression increases as the disease progresses from atypical hyperplasia to invasive breast cancer.

Re: Predictive value of fine needle aspiration biopsy of axillary lymph nodes in preoperative breast cancer staging

Axillary management in breast cancer has evolved tremendously in the last decades. Sentinel lymph node biopsy (SLNB) has replaced axillary dissection in patients without any clinical and radiological involvement in the axilla. Although the complication rate of SLNB is lower than axillary dissection, the search for an accurate method to determine the axillary status in breast cancer with even lower complication rate is continuing. Fine needle aspiration biopsy (FNAB) is performed under ultrasonography guidance in case of suspicious lymph nodes in the axilla, especially in those with cortical thickening or decreased echogenecity in the hilum in addition to changes in size and shape of the lymph node. The accuracy of FNAB in predicting the status of the axilla is investigated in recent studies. Fine needle aspiration biopsy of the axilla helps the clinician in determining surgical approach and neoadjuvant chemotherapy. Nowadays, extent of axillary surgery has almost no definitive role in deciding the mode of adjuvant treatment. Obtaining information about the presence of metastatic disease in the axilla is enough to determine the prognosis of the patient. However, 30% of axillary metastases were detected with FNAB under ultrasonography guidance and additional 30% with SLNB whereas the axillary status of the remaining patients were determined by histopathologic examination (1). In addition to the information about the axilla, FNAB enables us to place clips into the metastatic lymph nodes to follow the results of neoadjuvant treatment. Akinci et al. investigated this topic in the article entitled “Predictive value of fine needle aspiration biopsy of axillary lymph nodes in preoperative breast cancer staging” (2). This study aimed to determine the role of ultrasound-guided FNAB in axillary staging. Sensitivity, specificity, positive and negative predictive value, and accuracy of FNAB were studied. Sensitivity and negative predictive value showed moderate values (60%) whereas specificity and positive predictive values were 100%. Overall accuracy of axillary FNAB was reported as 76.1%. These results are in accordance with the results of the previous studies. Sensitivity of FNAB under ultrasound guidance changes between 45-95% and the specific ity is almost 100% (3, 4). Microbiopsies using larger needles and addition of immunohistochemical examination increase the sensitivity and presence of micrometastases in the lymph node contributes to the false negative results (5). Small number of patients included in the study may be its limitation, however, prospective design of the study supports the results with higher reliability. Finally, this study encourages the clinicians to utilize ultrasound-guided FNAB more frequently to avoid unnecessary SLNB in breast cancer. As a conclusion, randomized controlled trials including large enough number of patients are required to establish the value of FNAB in axillary staging of breast cancer. Sentinel node vs. observation after axillary ultrasound (SOUND) trial is an ongoing prospective randomized trial comparing SLNB and no axillary surgery in patients with normal axillary ultrasound (6). If a high predictive power of FNAB for axillary lymph node metastases could be proven, SLNB might be replaced by this method in the future. Detection of axillary metastases with FNAB might avoid performing SLNB and frozen section study decreasing time spent during surgery and total expenses in treatment.