Tehran University Medical Journal

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Background: Wilm’s tumor is the most frequent primary renal neoplasma in pediatric age group. Classically it is composed of three histologic parts: Blastemal, Epithelial and stromal. Different factors are implicated as prognostic determinants. Nowadays special attention is paid to proliferation markers for determining the biologic behavior of tumors. In this study we tried to ascertain the proliferative index of 22 cases of Wilm’s tumor in our center who have had rather good follow up (at least two years).

Materials and Methods: After reviewing the H and E slides, we stained sections with PCNA and ki67 and scanned them by image cytomertry. Then the proliferative indices for each histological part was determined.

Results: We resuted that proliferative indices of blastemal and epithelial parts have significant (P< 0.0002) difference (increment) from that of stromal part. Also the patients were divided into those with recurrence (within two ys of primary surgery) and recurrence. The profileration indices of PCNA for those recurring tumors was significantly higher (PCNA= 22.3%) (P= 0.0015).

Conclusion: Finally we concluded that using proliferative markers in Wilm’s tumor is useful as an effective prognostic factor.

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Background: Studies of the association between post operative AF and Plasma level of NT- Pro BNP have reported conflicting findings. The aim of the present study was evaluation of the association between post coronary bypass graft- Atrial Fibrillation (AF) and Plasma level of NT- ProBNP as an independent risk factor of AF development in patients undergoing coronary artery bypass graft.

Methods: In a cohort study, 79 patients with sinus rhythm who admitted in Imam Khomeini Hospital in Tehran, Iran, during February 2009 and February 2010 for CABG are included the study and followed for developing post operative AF rhythm.

Results: Post operative AF was found in 17.7% of patients. The peak time from the operation to the first AF episode was in second post op day in ten patients (71.4%). The serum level of ProBNP in patients with AF was significantly higher (1624± 647 versus 221± 238 pg/ml, p< 0/0001). Increased age, Increased LA size and high plasma level of ProBNP were associated with increased risk for post op AF. After adjustment of risk factors, plasma level of ProBNP was the most important risk factor with odds ratio of 15.34 with CI 95% 1.77-132.95 and then LA diameter with odds ratio of 6.11 with CI 95% 0.99-37.42 was independently correlated with post op AF. Correlation between plasma level of ProBNP with age and LA size was seen too (LA size r = 0.0281, p= 0.012). Between age and ProBNP (r= 0.337, p= 0.002). The best cut off point for plasma ProBNP as a predictor of post op AF was 854 pg/ml.

Conclusion: Increased level of preoperative ProBNP levels could be an independent predictor of post operative Atrial Fibrillation.

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Background: The incidence rate of gastric cancer in Western countries has shown a remarkable decline in recent years although it is still the almost common cancer between men in Iran. The proto-oncogene MYC, located at 8q24.1, regulates almost 15% of human genes and is activated in 20% of all tumors. MYC amplification and overexpression of its protein product are observed in 15-30% of gastric neoplasia. The objective of this study was to find the preference of CISH or IHC in the diagnosis and prognosis of gastric cancer. Methods: In this cross-sectional investigation, 102 paraffin blocks samples of Iranian patients with gastric cancers were studied. All the patients had undergone primary surgical resection at the Cancer Institute Hospital, Tehran University of Medical Sciences from 1987 to 1993. CISH and IHC techniques were applied to the samples. CISH was carried out on 3-µm-thick tissue sections and with a ZytoDot CISH Implementation Kit (ZytoVision GmbH, Germany). IHC was down using the HRP method with the monoclonal antibody. A universal peroxidase-conjugated secondary antibody kit was used for the detection system. All samples were gastric adenocarcinoma and were selected randomly. Results: Our data revealed that both diffuse and intestinal types of gastric cancer occurred significantly in men more than women. Our results showed an indication of some correlation between grades and CISH results, although the difference was not significant. Our data also showed that CISH+ patients (43.1%) were more frequent in comparison with IHC+ patients (14.7%). There was a correlation between CISH and IHC. This result revealed that there was a significant difference between grades and IHC. There was also no statistically significant difference between CISH amplification in diffuse and intestinal types. Conclusion: Our conclusion is that for the treatment, management of stomach cancer, and monitoring of progress and prognosis of the tumor that is almost important for patients and clinicians, CISH test is a better and feasible to IHC test, with regards to sensitivity and specificity.

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Background: Breast cancer is the most common cancer in women around the world. It has been known for over a century that androgens and androgen receptor (AR) play a role in normal and neoplastic breast cells. The aim of this study was to determined the AR expression on tumor cells and its correlation with other prognostic and predictive factors as well as contribution of AR in patients overall survival (OS) and disease- free survival (DFS). Methods: This retrospective cross-sectional study performed on 189 patients who referred to Medical Oncology Ward of Cancer Institute, Tehran University of Medical Sciences, from April 2007 to February 2010. We performed an immunohistochemistry study for AR (AR441 clone, Dako, Germany) (10% cut-off point) and Ki-67 MIB-1 clone, Dako, Germany) on paraffin embedded blocks. Other data were extracted from patients’ documents. Results: Overall, AR expression was 49.1%. Mean age of the patients with and without AR was 47.86 and 48.49 years, respectively. AR positive tumors presented more in stage I/II than III/IV (P=0.02) and AR were more positive for estrogen receptor positive, lower grade of tumor (grade I/II versus III) and lower Ki-67 (P=0.01). AR positivity had neither correlation with progesterone receptor, HER2/neu, P53 expression or menopausal status. OS and DFS were higher in AR positive patients but did not reach statistical significance. In triple-negative breast cancer (TNBC) group, 25% of tumors showed AR expression. AR had non-significant positive correlation with OS in TNBC cancer patients. OS and DFS had significant statistic positive correlation with ER, PR and stage regardless of AR status. Conclusion: Based on this study, although androgen receptor expression showed correlation with other prognostic factors for survival in patients, we didn’t find statistically significant independent relationship between AR and overall survival in patients. As far as there isn’t any targeted therapy for triple-negative breast cancer (TNBC), prospective basic and clinical studies regarding AR inhibitors in the treatment of TNBC seems to be logical and valuable.

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Background: Metformin has been suggested as anti-cancer in retrospective studies. We design a prospective controlled study about metformin efficacy in the window time between biopsy and definite surgery with changes of Ki-67 as the primary endpoint.

Methods: The primary cohort had composed of 50 pathologically diagnosed invasive breast cancers, accrued in Medical Oncology Department of Iran Cancer Institute from February to November 2014. Patients neither had indication of neoadjuvant chemotherapy, nor involved with diabetes mellitus. They followed during the time period of biopsy and definitive surgery with taking tests on pathology specimens for ER, PgR, HER-2/neu and Ki-67 index. We checked fasting insulin and glucose level as well as quality of life and adverse effects in both times in the intervention group. Metformin (1500 mg/day) was prescribed to intervention group from pathology report to the night before surgery.

Results: From 45 patients, 25 had been received metformin for median time of 2.8 weeks. Controlled group included 20 patients who followed in the window time. There were no statistically significant differences between two groups regarding baseline clinical and tumor characteristics such as age, stage, grade, ER, PgR, HER2 status, time and type of surgery. However, immunohistochemistry study showed decrease of median Ki-67 from 35.14 to 29.6% in the intervention group and increase from 24.5 to 30.6 in the control group. Both of these results were statistically significant. Patients tolerated metformin very well, but mild gastrointestinal symptoms were seen in 30% of cases. There was a correlation between metabolic factor of HOMA score (fasting insulin level fasting blood sugar/405) and changes in Ki-67.

Conclusion: In the present study metformin prescription in the short period of time between Biopsy and definite surgery had shown inhibition of breast cancer cell growth. We found relationship between metformin anti-proliferative effect and glucose and insulin metabolism. To find direct apoptotic stimulation of metformin and long-term results of this drug further studies in the adjuvant settings with cooperation of pharmacokinetic groups are recommended.