The effects of body ıron stores on metabolic control, ınsulin resistance and microalbuminuria in patients with type 2 diabetes mellitus

Objective: Free iron is involved in processes including oxidative stress, inflammation and insulin resistance which play key roles in the development of type 2 diabetes. The aim of this study is to investigate the role of body iron stores in metabolic control, insulin resistance and microalbuminuria. Materials and Methods: Our study included 50 patients with newly diagnosed type 2 diabetes mellitus and 50 healthy subjects as controls. Groups were compared for sex, age, body mass index, various biochemical and metabolic parameters. Correlation between these parameters with mean ferritin levels of patients was also calculated. Diabetic patients were grouped according to metabolic control, insulin resistance and microalbuminuria and the correlation between these paremeters and ferritin level was analyzed. Results: There was no difference in mean ferritin levels between two groups In the patient group, significant correlation was determined between mean ferritin level and fasting blood glucose, hemoglobin A1c, C-peptide, insulin andHOMAscore. There was no difference in mean ferritin levels between diabetic patients with good or bad metabolic control. The mean ferritin level was significantly higher in diabetic patients with insulin resistance than non-insulin resistant diabetics. Mean ferritin level was significantly higher in microalbuminuric patients. Conclusion: Our findings support that body iron stores are involved in the pathogenesis of type 2 diabetes

Pleomorphic Carcinoma of the Lung with High Serum Beta-human Chorionic Gonadotropin Level and Gynecomastia

Although gynecomastia is a well-defined paraneoplastic syndrome in patients with non-small cell lung cancer, the association with pleomorphic carcinoma has not been reported. A 50-yr-old man presented with bilateral gynecomastia and elevated serum beta-human chorionic gonadotropin (βhCG) level. Chest tomography showed a mass in the right middle lobe. Right middle lobectomy and mediastinal lymph node dissection were performed. βhCG levels decreased rapidly after surgery. Histological examination revealed pleomorphic carcinoma with positive immunostaining for βhCG. Serum βhCG levels began to increase gradually on postoperatively 4th month. Computed tomography detected recurrence and chemotherapy was started. After second cycle of chemotherapy, βhCG levels decreased dramatically again and tomography showed regression in mass. Patient died 6 months later due to brain metastasis. βhCG expression may be associated with aggressive clinical course and increased risk of recurrence, also βhCG levels may be used to evaluate therapy response in patients with pleomorphic carcinoma

Predictive and prognostic importance of PTEN, p27 and PI3K expression in HER2 positive metastatic breast cancer

İstanbul Bilim Üniversitesi, Tıp Fakültesi, İç Hastalıkları Anabilim DalıGİRİŞ: PTEN, HER2 aşırı ekspresyonu olan meme kanserinde trastuzumab duyarlılığını etkileyen en önemli düzenleyicidir. PI3K/Akt yolu aktivasyonunun HER2 pozitif metastatik meme kanserinde trastuzumab tedavisine direnç ve kötü prognozla ilişkili olduğuna dair bulgular mevcuttur. Bu çalışmada HER2 pozitif metastatik meme kanserinde PTEN ve PI3K/Akt yolunun diğer komponentlerinden PI3K ve p27 ekspresyonunun prediktif ve prognostik önemi araştırıldı. GEREÇ VE YÖNTEM: Çalışmamıza İstanbul Bilim Üniversitesi Tıbbi Onkoloji Bilimdalı’ nda takip edilen ve meme dokusu örnekleri Patoloji Anabilimdalı tarafından incelenerek histolojik olarak tanısı konmuş, HER2 pozitif metastatik meme kanseri olan ve birinci basamakta trastuzumab içeren tedavi alan 25 hasta dahil edildi. Hastaların mevcut meme dokusu bloklarında bulunan invaziv tümör, in situ tümör ve çevre normal meme dokusu komponentlerinde IHK yöntemi kullanılarak saptanan PTEN, PI3K ve p27 ekspresyonu ile tümör karakteristikleri, tedavi yanıtı, ilk meme kanseri tanısı tarihinden (OS1), metastatik hastalık tanısı tarihinden (OS2) ve trastuzumab içeren tedavinin başlandığı tarihten itibaren değerlendirilen genel sağkalım, progresyona kadar geçen süre (TTP) ve rekürrense kadar geçen süre (TTR) arasındaki ilişki araştırıldı. BULGULAR: Hastaların %76’ sında (n=19) PTEN ekspresyonu negatif ve %80’ inde (n=20) p27 ekspresyonu negatif saptandı, 24 hastada (%96) PI3K ekspresyonu pozitif bulundu. İn situ PTEN ile çevre meme dokusu PTEN ekspresyonu arasında pozitif, invaziv PTEN ile çevre meme dokusu PTEN ekspresyonu arasında ise negatif korelasyon tespit edildi (p değerleri sırasıyla 0.036 ve 0.042). İnvaziv tümör komponentindeki PTEN, p27 ve PI3K ekspresyonunun kendi aralarındaki ilişkisi incelendiğinde; PTEN ile p27 arasında istatistiksel olarak anlamlı pozitif korelasyon bulundu (p=0.036). Trastuzumaba yanıtlı ve yanıtsız hastalar PTEN, p27 ve PI3K ekspresyonu açısından karşılaştırıldığında anlamlı ilişki bulunmadı. Tümör karakteristikleri açısından incelendiğinde PTEN, p27 ve PI3K ekspresyonu ile tümör çapı arasında anlamlı ilişki bulundu (p değerleri sırasıyla 0.009, 0.003 ve <0.001); tümör gradı, lenfatik invazyon, vasküler invazyon, lenf bezi metastazı ve uzak metastaz durumu ile ilişki saptanmadı. OS1 ve TTP, trastuzumab içeren tedaviye yanıtlı hastalarda yanıt vermeyen hastalarla karşılaştırıldığında anlamlı olarak uzundu (p değerleri sırasıyla 0.016 ve 0.006). İnvaziv tümör komponentindeki PTEN, p27 ve PI3K ekspresyonu pozitifliği ve negatifliği arasında trastuzumab yanıtı açısından istatistiksel olarak anlamlı bir farklılık saptanmadı. PTEN kaybı olan hastalarda daha kısa OS1, OS2, OS3, TTP ve TTR olduğuna dair bir trend izleniyordu, ancak aradaki fark istatistiksel olarak anlamlı bulunmadı.. Benzer trend p27 negatif olan hastalarda OS1, OS2, OS3 ve TTR açısından saptandı. PI3K ekspresyonu ve tümör karakteristikleri ile OS, TTP ve TTR arasında ilişki saptanmadı. SONUÇ: Çalışmamızda PTEN kaybı, düşük p27 ekspresyonu ve pozitif PI3K ekspresyonu HER2 meme kanserinde sık görülen bulgular olarak göze çarpmaktadır ve literatürde sporadik meme kanserinde bildirilenden daha yüksek sıklıkta bulunmuştur. Vaka sayımızın az olması çalışmanın sonuçlarının istatistiksel yorumunu güçleştirse de, çalışmamız PTEN ve p27 ekspresyonunun HER2 pozitif metastatik meme kanserinde trastuzumab yanıtını ve kısalmış sağkalımı predikte ettiğini destekler niteliktedir. Sonuçlarımız PI3K/Akt yolunun HER2 pozitif meme kanserinde aktif olduğunu göstermektedir.INTRODUCTION: PTEN is the key regulator for sensitivity to trastuzumab therapy in HER2 overexpressing breast cancer. There are data indicating the activation of PI3K/Akt pathway is associated with poor prognosis and resistance to trastuzumab therapy in HER2 positive metastatic breast cancer. In this study the predictive and prognostic significance of PTEN and expression of PI3K and p27 which are components of the PI3K/Akt signaling pathway in HER2 positive metastatic breast cancer was assessed. MATERIAL AND METHODS: 25 patients who carried a diagnosis of metastatic HER2 positive breast carcinoma and who have attended Istanbul Bilim University Medical Oncology Clinic were recruited for the study group. All of the patients breast tissue samples were examined by the institution’s pathology department. All patients in the study group received trastuzumab based therapies as their first line treatment. Invasive tumor, in situ tumor and surrounding normal mammary tissue components from all of the patients breast tissue blocks were evaluated for PTEN, PI3K and p27 expression by immunohistochemistry and their correlations with tumor characteristics, response to treatment, overall survival from the date of diagnosis of breast cancer (OS1), from the date of recognition of metastatic disease (OS2) and from the starting date of trastuzumab containing therapy (OS3), time to progression (TTP) and time to recurrence (TTR) were analyzed . RESULTS : In 76 % (n=19) of the patient group PTEN expression and in 80% (n=20) p27 expression was found to be negative. In 24 subjects (96%) PI3K expression was reported as positive. A positive correlation between in situ cancer and surrounding normal mammary tissue PTEN expression was found while the correlation between invasive cancer and surrounding normal mammary tissue PTEN expression was negative (p values 0.036 and 0.042, respectively ). When the correlation between PTEN, p27 and PI3K expression in invasive cancer tissue with each other was analyzed it was found that there was a positive statistically significant correlation between PTEN and p27 expression (p=0.036). When the group of patients who respond to trastuzumab treatment was compared to the group who did not respond to treatment with trastuzumab, there was no statistically significant association found for expression of PTEN, p27 and PI3K. When the same comparison was made for tumor characteristics a significant relation was found between tumor size and PTEN, p27 and PI3K expression (p values 0.009, 0.003 and <0.001, respectively ); but a statistically significant relation between expression of the above stated expression of the genes and tumor grade, lymphatic invasion, vascular invasion, and presence of distant metastasis was not found to be present. OS1 and TTP was significantly longer in the patient group who responded to trastuzumab based treatment compared to the group who was unresponsive to the treatment (p values 0.016 and 0.006, respectively). Although the status of PTEN, p27 and PI3K expression in the invasive tumor tissue was not found to be significantly correlated with response to trastuzumab treatment a trend towards lower OS1, OS2, OS3, TTP and TTR in patients with loss of PTEN expression which did not reach a statistical significance was observed. A similar trend for lower OS1, OS2, OS3 and TTR in patients whose invasive breast tissues did not express p27 was also found. A relation between PI3K expression and tumor characteristics with OS, TTP and TTR was not found . CONCLUSION: Loss of expression of PTEN, low expression of p27 and positive PI3K expression was found to be frequent in HER2 positive breast cancer. Their frequency was higher when compared to frequency of expression in sporadic breast cancer reported in the literature. Although the small number of our study group has made statistical interpretation of the results difficult, we propose the results of our study support the view that the presence of PTEN and p27 expression in HER2 positive metastatic breast cancer predicts response to trastuzumab treatment and shortened overall survival. Our results indicate that PI3K/Akt signaling pathway is active in HER2 overexpressing breast cancer

Concept of paraneoplasia

İstanbul Bilim Üniversitesi, Tıp Fakültesi.Birçok kanser hastasında tümörün ya da metastazlarının invazyonu ya da kompresyonundan kaynaklanmayan belirti ve bulgular görülmektedir. Tümörün varlığı ile ilişkili olarak çeşitli organ ve sistemlere ait olabilen bu “uzak” etkiler “paraneoplazi” veya “Paraneoplastik sendrom” başlığı altında incelenmektedir. Paraneoplaziler sıklıkla tümör hücrelerince üretilen bazı hormonlar, peptidler ve uzun veya kısa etkili sinyal moleküllerine bağlı olarak ya da tümör-ilişkili antijenlerle immun reaksiyonlar sonucu gelişmektedir. Bu makalede paraneoplastik sendromların oluşum mekanizmaları ve sık görülen paraneoplaziler tartışılmıştır.In many cancer patients, various symptoms and signs not due to invasion or compression of tumor and its metastases are observed. These “remote” effects which can perta into various organs or systems are associated with the presence of tumor and examined under the title of “paraneoplasia” or “paraneoplastic syndrome”. Paraneoplasias are usually developed through hormones, peptides and long- and short-acting signal molecules produced by the tumoror immunereactions against tumor-associated antigens. Inthisarticle, mechanisms of paraneoplastic syndromes and commonly seen paraneoplasias were discussed

Metastasis of Gastric Signet-Ring Cell Carcinoma to the Urinary Bladder: A Case Report and Review of the Literature

Although signet-ring cell (SRC) adenocarcinoma is commonly seen in the stomach, it is a very rarely seen histologic entity in the bladder. It is difficult to distinguish primary SRC adenocarcinoma of the bladder from bladder metastasis of SRC carcinoma of the stomach only based on histological findings. In such cases, clinical findings and immunohistochemical studies may be helpful. We present here a 48-year-old male patient presenting with hematuria and abdominal pain. Computerised tomography of the patient revealed a gastric mass, peritoneal involvement, and thickening of the bladder wall, and histopathological analysis revealed SRC adenocarcinoma in both of the endoscopic biopsies taken from the stomach and bladder. Immunohistochemical analyses confirmed the diagnosis of SRC adenocarcinoma of the bladder secondary to gastric cancer

EMPHYSEMATOUS PYELONEPHRITIS CAUSED BY KLEBSIELLA OXYTOCA IN A PATIENT WITH DIABETIC NEPHROPATHY

WOS: 000281404900020A 50-year-old woman with a 30 years history of diabetes mellitus and has been diagnosed with diabetic nephropathy for the last 4 years presented with abdominal pain, nausea and vomiting. Abdominal ultrasonography revealed a hyperechogenic air image at right kidney and with the aid of subsequently performed abdominal tomography type 2 emphysematous pyelonephritis diagnosis was made. Klebsiella oxytoca was isolated in blood culture and with appropriate antibiotic therapy and subsequent percutenous drainage the patient made a full recover

Interstitial lung disease caused by everolimus treatment

Altmış yedi yaşında kadın hasta bir aydır halsizlik, nefes darlığı ve öksürük yakınması ile başvurdu. Hasta 2007 yılında sağ memede invaziv duktal karsinom nedeniyle cerrahi ve radyoterapi tedavisi gördüğünü ve dört ay önce de akciğerde multipl metastatik lezyonların saptanması üzerine everolimus tedavisine (10 mg/gün) başlanmış. Tedaviden sonra hastada everolimusa bağlı intersitisyel akciğer hastalığı saptandı.. Everolimus nispeten güvenli bir oral anti-kanser ajanıdır ancak interstisyel akciğer hastalığı ciddi bir yan etki olarak bildirilmiştir. Bu olgu Everolimusa bağlı ciddi akciğer toksisitesini göstermek için sunulmuşturSixty seven years old female patient was admitted with complaints of fatigue, shortness of breath and cough, for one month. In 2007, the patient was treated with surgery and radiotherapy because of invasive ductal carcinoma in the right breast. Four months ago, after the identification of multiple metastatic lesions in lung, a treatment of everolimus 10mg/day began. After treatment the patient was diagnosed as everolimus-induced interstitial lung disease. Everolimus is a relatively safe oral anti-cancer agent, but as a serious side effect of interstitial lung disease have been reported. This case was presented to show the serious pulmonary toxicity related to Everolimu

Akut batının nadir bir nedeni: Rüptüre adrenal feokromositoma

İstanbul Bilim Üniversitesi, Tıp Fakültesi.Pheochromocytoma is a tumor of the chromaffin cells which secretes catecholamines and 90% of it originates from adrenal medulla. The main symptoms and signs are hypertension, tachycardia, sweating and headache. Rarely, acute abdomen may occur as a result of the rupture of tumoral mass or bleeding inside the mass. Here we present a 43 year old male patient who applied with acute abdominal syndrome and severe hypertension. Abdominal MRI showed a large mass hemorrhagic in natüre above the right kidney. At laparotomy, ruptured adrenal mass was seen and excised successfully. The histological evaluation confirmed the diagnosis as pheochromocytoma. Ruptured adrenal pheochromocytoma is a mortal situation potentially and it should be considered in patients who present with an acute obdominal syndrome and hypertension or shock. It should be known that early diagnosis and surgey with proper preoperative treatment is a life saver.Feokromositoma katekolamin sentezleyen kromaffin hücrelerden orjin alan, %90’ı adrenal medulla kaynaklı bir tümördür. Başlıca belirti ve bulguları hipertansiyon, taşikardi, terleme ve başağrısıdır. Nadiren tümör içine kanama veya kitlenin rüptürü sonucu akut batın gelişebilmektedir. 43 yaşında erkek hasta akut batın sendromu ve ciddi hipertansiyon ile başvurdu. Abdomen magnetik rezonans görüntülemesinde sağ böbreğin prosimalinde hemorajik kitle saptandı. Laparotomide sağ adrenal kitle görüldü ve başarıyla eksize edildi. Histolojik incelemede feokromositoma tanısı doğrulandı. Rüptüre adrenal feokromositoma potansiyel olarak mortal bir durumdur ve akut batın sendromuna eşlik eden hipertansiyon veya şok kliniğiyle başvuran hastalarda düşünülmelidir. Erken tanı ve uygun preoperatif tedaviyle beraber uygulanan cerrahinin hayat kurtarıcı olduğu bilinmelidir