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Mikrosatellit instabilite (MSI), DNA tamir genlerindeki hatalardan kaynaklanan ve kolorektal kanserin (KRK) oluşmasına neden olan genetik bir durumdur. Sporadik KRK’larda MSI görülme sıklığı, prognoza olan etkisi literatürde çelişkilidir. Bununla birlikte MSI’ya sahip KRK’larda standart kemoterapi yetersiz kaldığı için yeni tedavi seçeneklerine ihtiyaç duyulmaktadır. micoRNA’lar (miRNA) kanserleşme sürecinde görev alan ve tanıda, prognozda ve tedavide belirteç olarak kullanılan küçük RNA molekülleridir. Mevcut çalışmada, Türk popülasyonuna ait sporadik gelişen KRK’larda MSI’nın görülme sıklığının tanımlanması ve bu tümörlerde miRNA’ların ekspresyon farklılıklarının belirlenmesi amaçlanmıştır. Çalışmada, sporadik KRK tanısı almış 63 hasta değerlendirildi. Hastalara ait arşiv tümör ve normal dokula-rından DNA ve RNA izolasyonları yapıldı. DNA örneklerinden fragment analizine dayalı MSI testi gerçekleştirildi. qRT-PCR kullanılarak 38 farklı miRNA’nın ekspresyon profili incelendi. 63 hastada MSI görülme oranı %23.8 olarak belirlendi. MSI ve mikrosatellit stabil (MSS) tümörler karşılaştırıldığında, MSI tümörlerde, miR-124 ve miR-106a’nın yüksek ve miR-145’in ise düşük ekspresyon gösterdiği belirlendi (p, Microsatellite instability (MSI) is a genetic condition that results from errors in DNA repair genes and causes colorectal cancer (CRC). The incidence of MSI in sporadic CRCs and its effect on prognosis are contradictory in the literature. However, since standard chemotherapy is insufficient in CRCs with MSI, new treatment options are needed. micoRNAs (miRNAs) are small RNA molecules that take part in the cancer process and are used as markers in diagnosis, prognosis and treatment. In the study, it is aimed to define the prevalence of MSI in sporadically developing CRCs belonging to the Turkish population and to determine the expression differences of miRNAs in these tumors. 63 patients diagnosed with sporadic CRC were evaluated in the study. DNA and RNA isolations were made from archive tumor and normal tissues of the patients. MSI test was performed based on fragment analysis from DNA samples. The expression profiles of 38 different miRNAs were examined using qRT-PCR. In 63 patients, the incidence of MSI was determined as 23.8%. When MSI and microsatellite stable (MSS) tumors were compared, it was determined that miR-124 and miR-106a showed high expression and miR-145 low expression in MSI tumors (p

Patients with advanced pancreatic cancer have a dismal prognosis, and their management is still an important problem in medical oncology practice. So,in this study, we aimed to investigate the clinical features and survival outcomes in patients with locally advanced or metastatic pancreatic cancer. A total of 183 pancreatic cancer patients treated between January 1995 and May 2012 at Medical Oncology Department of Uludag University Faculty of Medicine were retrospectively analyzed. Demographics, clinical features, treatments and outcome were detect-ed There were 123 male and 60 female patients. The median age of patients was 60 years (range 33-84). One hundred five patients had metastatic disease at the time of diagnosis, and the most common metastatic site was liver (90%). Seventy-five patients received gemcita-bine+5-fluorouracil, 42 received gemcitabine, 24 received gemcitabine+cisplatin, and 3 received UFT+cisplatin. Eleven (%6) patients had complete response, 16 (%8.7) had partial response and 18(%9.8) had stable disease. Weight gain was observed in 34 of 145 (%18.6) patients. The median overall survival was 7 months (5-8 months), and there was a positive correlation between weight gain and overall survival (p, İleri evre pankreas kanserli hastalar kötü bir prognoza sahiptir ve tedavileri medikal onkoloji pratiğinde önemli bir problem olmaya devam etmektedir. Bu nedenle bu çalışmada metastatik veya lokal ileri pankreas kanseri tanısıyla tedavi edilen hastalarımızın klinik özelliklerini ve tedavi sonuçlarını retrospektif olarak değerlendirmeyi amaçladık. Bu çalışma için, Ocak 1995-Mayıs 2012 tarihleri arasında tedavi edilen ve klinik bilgileri elde edilebilen toplam 183 olgunun dosyasını retrospektif olarak inceledik. Hastaların demografik özelliklerini, almış oldukları tedavileri ve sağkalım sonuçlarını belirledik. Olguların 123'ü erkek, 60'ı kadın olup ortanca yaş 60 (33-84) idi. Tanı anında 105 olgu metastatikti ve en sık metastaz yeri karaciğerdi. Yetmiş beş hasta gemsitabin + 5-Fluorourasil, 42 hasta gemsitabin, 24 hasta gemsita-bin+sisplatin ve 3 hasta UFT+sisplatin ile tedavi edilmişti. Kemoterapi ile olguların %6'sında tam yanıt, %8.7'de kısmi yanıt ve %9.8'de stabil hastalık elde edilmişti. Tedavi ile olguların ancak 34'ünde kilo artışı mevcut olup, kilo artışı ile sağ kalım arasında pozitif bir ilişki (p

Oxaliplatin (OXA), gastrointestinal sistem kanserlerinin tedavisinde yaygın olarak kullanılan üçüncü kuşak, platin bileşiği bir kemoterapötik ilaçdır ve ağrılı periferik nöropati OXA?nın en önemli yan etkilerinden birisidir. CDP-kolin, vücutta endojen olarak sentezlenen bir nükleotiddir ve akut, nöropatik ve inflamatuvar ağrı modellerinde ekzojen (intraserebroventriküler [i.s.v.] veya lokal yolla) uygulanan CDP-kolin?in analjezik ve antihiperaljezik etki meydana getirdiği bilinmektedir. Bu çalışmada OXA?nın neden olduğu nöropatik ağrıda CDP-kolin?in antihiperaljezik etkisi ve etki mekanizmasının araştırılması amaçlandı. Deney hayvanı olarak sıçanlar kullanıldı ve ağrı eşiği Randall-Selitto cihazı ile pençe çekme eşiği olarak değerlendirildi. Sıçanlara tek doz (6 mg/kg) intraperitoneal yolla uygulanan OXA, uygulamadan bir gün sonra başlayan ve 14 gün süreyle devam eden mekanik hiperaljeziye neden oldu. OXA uygulamasından 48 saat sonra i.s.v. yolla uygulanan CDP-kolin (0.5, 1.0 ve 2.0 µmol), OXA?nın neden olduğu mekanik hiperaljeziyi doza ve zamana bağlı olarak azalttı. Eşmolar dozlarda (1 µmol;i.s.v.) uygulanan CDP-kolin?in hidroliz ürünü kolin ve sitidin de CDP-kolin?e benzer şekilde antihiperaljezik etki gösterdi. CDP-kolin?in antihiperaljezik etkisi, yüksek afiniteli nöronal kolin geri alım inhibitörü hemikolinyum-3 (1 µg; i.s.v.), selektif olmayan nikotinik kolinerjik reseptör antagonisti mekamilamin (50 µg; i.s.v.), selektif ?7 nikotinik asetilkolin reseptör (nAChR) antagonisti ?-bungarotoxin (2 µg; i.s.v.) ve spesifik GABAB reseptör antagonisti CGP-35348 (20 µg; i.s.v.) ön tedavileri ile önlendi. Bununla birlikte, selektif olmayan opioid reseptör antagonisti nalokson (10 µg; i.s.v.) ve selektif olmayan muskarinik reseptör antagonisti atropin (10 µg; i.s.v.) ön tedavileri, CDP-kolin?in antihiperaljezik etkisini değiştirmedi. Bu çalışmadan elde elde edilen sonuçlara göre, merkezi yolla uygulanan CDP-kolin?in OXA tedavisinin neden olduğu nöropatik hiperaljeziyi azalttığı ve CDP-kolin?in bu etkisine presinaptik kolinerjik mekanizmalarla birlikte supraspinal ?7 nAChR ve GABAB reseptörlerinin aracılık ettiği ilk defa gösterildi. Oxaliplatin (OXA) is a third-generation platinum compound that is commonly used for the treatment gastrointestinal cancer, and painful peripheral neuropathy is one of the most important side effects of OXA. CDP-choline is synthesized endogenously in the body, and it is known that exogenously administered (intracerebroventricularly [i.c.v.] or locally) CDP-choline produces analgesic and anti-hyperalgesic effects in acute, neuropathic and inflammatory pain models. In this study, we aimed to investigate the anti-hyperalgesic effect of CDP-choline and the mechanisms of its anti-hyperalgesic action in OXA-induced neuropathic pain. Rats were used in the experiment, and paw withdrawal pain threshold was assessed using the Randall-Selitto instrument. Intraperitoneal administration of a single dose (6 mg/kg) OXA to the rats caused mechanical hyperalgesia beginning on day 1 and continuing through 14 days after the injection. CDP-choline (0.5, 1.0 and 2.0 µmol), which was given i.c.v. 48 hours after OXA injection, significantly reduced OXA-induced mechanical hyperalgesia, in a dose- and time-dependent manner. Equimolar doses (1 µmol; i.c.v.) of choline and cytidine (hydrolysis products of CDP-choline) also showed significant antihiperalgesic effect. The antihyperalgesic effect of CDP-choline was blocked by the pretreatment with neuronal high affinity choline uptake inhibitor hemicholinium-3 (1 µg; i.c.v.), nonselective nicotinic receptor antagonist mecamylamine (50 µg; i.c.v.), ?7 selective nicotinic acetylcholine receptor antagonist ?-bungarotoxin (2 µg; i.c.v.), and gamma-amino butyric acid (GABA)-B receptor antagonist CGP-35348 (20 µg; i.c.v.). However, it was not changed by the pretreatment with nonselective opioid receptor antagonist naloxone (10 µg; icv) and nonselective muscarinic receptor antagonist atropine (10 µg; icv). The results of the present study demonstrated that for the first time centrally administered CDP-choline attenuates hyperalgesia caused by OXA treatment, and antihyperalgesic effect of CDP-choline is mediated by a presynaptic cholinergic mechanisms and activation supraspinal ?7 nAChR and GABAB receptors. 55

In this study, patients who received adjuvant chemotherapy for locally advanced bladder cancer were retrospectively analyzed. A total of 32 patients received gemcitabine (%18.8), cisplatin plus gemcitabine (%50), carboplatin plus gemcitabine (%15,6) or MVAC (Methotrexate, vinblastine, doxorubicin, and cisplatin). The most common adverse effect was myelosuppression during chemotherapy administration. Treatment-related died was not observed. The median overall and disease-free survival was 23 months (range, 18.7-27.4) and 17.8 months (range, 12.7-22.9), respectively. We concluded that our results were comparable to those in the literature., Bu çalışmada, lokal ileri mesane kanseri nedeniyle adjuvant kemoterapi alan hastalar retrospektif olarak analiz edildi. Toplam 32 hasta gemsitabin (%18.8), sisplatin+gemsitabin (%50), carboplatin+gemsitabin (%15.6) veya MVAC (Metotreksat, vinblastin, doksorubisin ve sisplatin) (%15.6) tedavisi aldı. Tedaviler sırasında en sık görülen yan etki kemik iliği toksisitesi idi. Tedaviye bağlı ölüm gözlenmedi. Medyan genel ve hastalıksız sağkalım süreleri sırasıyla 23 ay (18.7-27.4) ve 17.8 ay (12.7-22.9) idi. Verilerimizin literatür ile uyumlu olduğu sonucuna varıldı.

Primary mediastinal B-cell lymphoma (PMBL) is a rare neoplasm that develops from thymic medullary B cells in the mediastinum. It covers about 2-3% of all non-hodgin lymphomas. Despite its identification in 1980s, the optimal treatment is controversial. Although late relapse is rare, it usually develops within the first year of treatment. A 33 year-old woman had an anterior mediastinal mass was diagnosed with lymphoma, which was confirmed with biopsy. Despite not having lympoadenopathy and hepatosplenomegaly, PET was consistent with PMBL. The patient was treated with 6 cycles of R-CHOP and then with radiotherapy to mediastinum. After treatment, we observed a complete response. With close follow up, we did not see any relapse at the end of first year., Primer mediastinal B hücreli lenfoma (PMBL), mediastende timik meduller B hücrelerinden gelişen nadir görülen bir neoplazmdır. Tüm nonhodgin lenfomaların %2-3'ünü oluşturur. 1980'li yıllarda tanımlanmasına rağmen optimal tedavi tartışmalıdır. PMBL'da geç relaps nadir olup çoğunlukla tedavi sonrası ilk bir yılda gelişir. Ön mediastende kitle saptanan 33 yaşındaki kadın olguda çekilen positron emission tomografi sonucu ve yapılan biyopsi ile birlikte PMBL tanısı konuldu. Hasta 6 kür R-CHOP ve sonrasında mediastene radyoterapi ile tedavi edildi. Düzenli aralıklarla takip edilen olguda ilk bir yılın sonunda relaps gözlenmedi.

Adrenocortical carcinoma (ACC) is a rare and aggressive tumor with a poor prognosis. In this study, we retrospectively evaluated clinical features and treatment results of our ACC patients. A total of eight patients with ACC were treated in our department. All patients had metastatic disease. Patients received etoposide, doxorubicin and cisplatin (EAP) or etoposide and cisplatin regimen (EP). Stabile disease was observed in four patients and progressive disease in four. At a mean follow up 7.7 months (range, 3-15 months) 5 patients died from progressive disease. Our findings reflect the aggressive nature of ACC., Adrenokortikal karsinom (AKK) nadir ve agresif bir tümor olup prognozu kötüdür. Bu çalışmada, AKK hastalarımızın klinik özellikleri ve tedavi sonuçları retrospektif olarak değerlendirildi. Departmanımızda, toplam sekiz AKK'lu hasta tedavi edildi. Hastaların tamamında metastaz mevcuttu. Hastalara etoposid, doksorubisin ve sisplatin (EAP) veya etoposid ve sisplatin (EP) rejimi uygulandı. Dört hastada stabil hastalık, diğer dört hastada ise progresyon olduğu gözlendi. Ortalama 7.7 aylık (3-15 ay) takipte 5 hasta progresif hastalık nedeniyle öldü. Bulgularımız AKK'un agresif doğasını yansıtmaktadır.

Small cell carcinoma (SCC) of the prostate is a rare and extremely aggressive malignant disease. It constitutes less than 1% of all prostatic neoplasms. Frequently it presents at advanced stage with nodal or visceral metastasis and has a poor prognosis. From the existing data it is difficult to define an optimum treatment strategy for SCC of the prostate. Here, we present a case of SCC of the prostate with a brief review of the literature., Prostatın küçük hücreli karsinomu (KHK) nadir ve son derece saldırgan bir tümördür. Tüm prostat kanserlerinin %1'den daha azını oluşturur. Sıklıkla nodal veya visseral metastazlarla birlikte ileri evrede prezente olur ve kötü bir prognoza sahiptir. Mevcut verilerden yola çıkılarak prostat KHK için optimal bir tedavi şeklinin belirlenmesi zordur. Biz burada bir prostat KHK olgusunu literatür bilgileri ile birlikte sunuyoruz.

The aims of the present study were to test activity and tolerability of cisplatin and etoposide in advanced non-small cell lung cancer (NSCLC) patients aged 70 years or higher. Twenty-four patients were enrolled. Cisplatin was given at a dose of 60 mg/m2 on day 1 and etoposide at a dose of 120 mg/m2 on days 1-3. Total 116 courses were administered. Twelve patients (50%) completed all six cycles of treatment. Three patients (12.5%) obtained a partial response, as well as 12 (50%) stable disease and 9 (37.5%) progressive disease. The median survival was 48.5 ± 6.06 weeks, and the 1 year survival rate was 38%. Grade 3-4 neutropenia occurred in 16.6% of patients, grade 4 thrombocytopenia in %4.1, and grade 1-2 neuropathy in 25%. One patient discontinued treatment due to grade 3 nephrotoxicity. In conclusion, cisplatin and etoposide regimen is active and relatively well-tolerated in the treatment of elderly NSCLC patients. New, active and well-tolerated combination regimens could improve present results., Bu çalışmanın amaçları 70 yaş ve üzeri ileri evre küçük hücreli dışı akciğer kanseri (KHDAK) hastalarında sisplatin ve etoposid tedavisinin aktivitesini ve tolerabilitesini araştırmaktı. Yirmi dört hasta çalışmaya alındı. Sisplatin 60 mg/m2 dozunda 1. günde ve etoposid 120 mg/m2 dozunda 1-3. günlerde verildi. Toplam 116 siklus uygulandı. On iki (%50) hasta altı siklus tedaviyi tamamladı. Üç hastada (%12.5) kısmi yanıt elde edilirken, 12 hastada (%50) stabil hastalık ve 9 hastada (%37.5) progresyon mevcuttu. Ortalama sağ kalım 48.5 ± 6.06 hafta ve 1 yıllık sağ kalım oranı %38'di. Grade 3-4 nötropeni hastaların %16.6'ında, grade 4 trombositopeni %4.1'nde ve grade 1-2 nöropati %25'inde görüldü. Bir hastada grade 3 nefrotoksisite nedeniyle tedavi sonlandırıldı. Sonuç olarak sisplatin ve etoposid yaşlı KHDAK hastalarının tedavisinde aktiftir ve nisbeten iyi tolere edilmektedir. Yeni, aktif ve iyi tolere edilen rejimler mevcut sonuçları iyileştirebilir.

Despite the demonstration of the protective effects of misoprostol, an oral prostaglandin E1 analogue, on the nephrotoxicity of non-steroidal antiinflammatory drugs (NSAID) and cyclosporine, its role in cisplatin nephrotoxicity has not been investigated. In our study, we planned to investigate cisplatin-induced acute renal failure and the efficacy of misoprostol on acute cisplatin nephrotoxicity. For this purpose, 28 lung cancer patients who had been planned to receive the cisplatin+etoposide chemotherapy regimen were included in the study. Patients then were divided into two groups. In addition to chemotherapy, Misoprostol group received misoprostol at the dose of 100 μg qid during the study. Control group received only chemotherapy. Renal functions were evaluated in both groups before the onset of chemotherapy and 2nd and 6th days of chemotherapy. In conclusion, it was demonstrated that misoprostol could not produce any protective effect on the functional disturbances due to cisplatin administration., Bir oral prostaglandin E1 analoğu olan misoprostolün steroid olmayan antienflamatuar ilaçlar (NSAID) ve siklosporin nefrotoksisitesinde protektif etkisi olduğu gösterilmesine karşın, cisplatin nefrotoksisitesindeki rolü incelenmemiştir. Çalışmamızda cisplatine bağlı gelişen akut böbrek yetmezliğinin ve misoprostolün akut cisplatin nefrotoksisitesindeki etkinliğinin incelenmesi amaçlanmıştır. Bu amaçla cisplatin+etoposid kemoterapi rejimi alması planlanan 28 akciğer kanserli hasta çalışmaya dahil edildi. Hastalar iki gruba ayrıldı. Misoprostol grubu kemoterapinin yanısıra çalışma süresince günde 4 kez 100 μg dozda misoprostol aldı. Kontrol grubu sadece kemoterapi aldı. Her iki grupta renal fonksiyonlar kemoterapi başlamasından önce ve kemoterapinin 2. ve 6. günlerinde değerlendirildi. Sonuç olarak, cisplatin kullanımına bağlı gelişen fonksiyonel bozukluklarda misoprostolün koruyucu etkinlik gösteremediği saptandı.

Continuous inhibition of angiogenesis beyond progression is an emerging treatment concept in the management of metastatic colorectal cancer patients with prior bevacizumab exposure. Treatment options include the continuation or reintroduction of bevacizumab during the second-line chemotherapy or switching to a different antiangiogenic monoclonal antibody such as aflibercept or ramucirumab. In the selection of treatment, patient-based factors such as performance status, age, tumor burden, and tolerance and sensitivity to the first-line bevacizumab-based therapy, as well as treatment-related factors such as toxicity, efficacy, and cost, should be taken into consideration.

Despite the availability of potent chemotherapy regimens, such as 5-fluorouracil, folinic acid, irinotecan, and oxaliplatin (FOLFIRINOX) and nab-paclitaxel plus gemcitabine, treatment outcomes in metastatic pancreatic cancer (PC) remain unsatisfactory. The presence of an abundant fibrous stroma in PC is considered a crucial factor for its unfavorable condition. Apparently, stroma acts as a physical barrier to restrict intratumoral cytotoxic drug penetration and creates a hypoxic environment that reduces the efficacy of radiotherapy. In addition, stroma plays a vital supportive role in the development and progression of PC, which has prompted researchers to assess the potential benefits of agents targeting several cellular (e.g., stellate cells) and acellular (e.g., hyaluronan) elements of the stroma. This study aims to briefly review the primary structural properties of PC stroma and its interaction with cancer cells and summarize the current status of anti-stromal therapies in the management of metastatic PC.

Aim The aim was to compare the pathological complete response (pCR) rate at 8 compared to 12 weeks' interval between completion of neoadjuvant chemoradiotherapy (CRT) and surgery in patients with locally advanced rectal cancer. Method This was a randomized trial which included a total of 330 patients from two institutions. Patients with locally advanced (T3-4N0M0, TxN+M0) rectal cancer were randomized into 8- and 12-week interval groups. All the patients received long-course CRT (45 Gy in 1.8 Gy fractions and concomitant oral capecitabine or 5-fluorouracil infusion). Surgery was performed at either 8 or 12 weeks after CRT. The primary end-point was pCR. Secondary end-points were sphincter preservation, postoperative morbidity and mortality. Results Two-hundred and fifty-two patients (n = 125 in the 8-week group, n = 127 in the 12-week group) were included. Demographic and clinical characteristics were similar between groups. The overall pCR rate was 17.9% (n = 45): 12% (n = 15) in the 8-week group and 23.6% (n = 30) in the 12-week group (P = 0.021). Sphincter-preserving surgery was performed in 107 (85.6%) patients which was significantly higher than the 94 (74%) patients in the 12-week group (P = 0.016). Postoperative mortality was seen in three (1.2%) patients overall and was not different between groups (1.6% in 8 weeks vs 0.8% in 12 weeks, P = 0.494). Groups were similar in anastomotic leak (10.8% in 8 weeks vs 4.5% in 12 weeks, P = 0.088) and morbidity (30.4% in 8 weeks and 20.1% in 12 weeks, P = 0.083). Conclusion Extending the interval between CRT and surgery from 8 to 12 weeks resulted in a 2-fold increase in pCR rate without any difference in mortality and morbidity.

Renal Hücreli Karsinom (RHK) tüm kanserlerin %2-3'lük kısmını oluşturmaktadır. En yüksek insidans, gelişmiş ülkelerde görülür. Tüm dünyada ve Avrupa'da hastalığın insidansında yıllık yaklaşık %2 oranında artış gözlenmektedir. RHK, böbrek içinde en sık gelişen kitlesel lezyondur. Klinik olarak sessiz ilerleyen ve yüksek oranda metastatik seviyede tespit edilen renal hücreli kanserlerde tedavi seçeneklerinin sırası ve etkisi yapılan araştırmalarla önem kazanmaktadır. Lokalize RHK için cerrahi genellikle tedavi edicidir. Cerrahi prosedür, hastanın yaş, komorbiditesi, hastalığın yayılımına bağlı olarak radikal veya parsiyel nefrektomiyi içerebilir. Rezektabl tümör ve eşlik eden tek metastazı olan seçilmiş hastalarda metastaz rezeksiyonu ile birlikte olan radikal nefrektomi küratif olabilir. Cerrahi adayı olmayan göreceli küçük renal kitleli olan hastalarda diğer ablatif tedaviler seçenek olabilir (kriyoterapi, radyofrekans ablasyon) .Tanı anında %20-30, takiplerinde %20-40 oranında metastaz saptanan RHK'larının ülkemizde ilk basamak tedavisi interferon alfa olarak uygulansa da genellikle sonrasında progresyon gözlenen hastalarda, tirozin kinaz inhibitörleri (TKI) , vasküler endotelyal growth faktör (VEGF) yolu ve rapamisin protein kompleksinin mekanistik hedefi (m TOR) inhibisyonuyla geliştirilen tedavilerin daha etkin olduğu gösterilmiştir. Fakat ülkemizde halen 1. basamak tedavide TKI ve VEGF reseptör inhibitörlerinin ödemesi devlet tarafından yapılmamaktadır.VEGF yolunun blokajı iki yolaktan gerçekleşmektedir, bu yolları kullanan ajanlar; VEGF reseptörünün intrasellüler parçasını bloke eden küçük molekül TKI'lar (sunitinib, pazopanib, cabozantinib, axitinib, sorafenib), VEGF reseptörüne bağlanmayı engelleyen, dolaşan VEGF'ye bağlanan monoklonal antikorlardır (bevacizumab). Bu çalışmanın amacı; merkezimizdeki 01.01.1998 - 31.12.2016 arasında RHK tanısı almış 98 hastada, hastaların tedavisinde uygulanan tirozin kinaz inhibitörü, m TOR inhibitörü ve VEGF inhibitörü gruplarının yanıtlarının değerlendirilmesidir. Renal cell carcinoma (RCC) accounts for 2-3% of all cancers. The highest incidence is seen in developed countries. The incidence of the disease is increasing by about 2% annually in the whole world and in Europe. RCC is the most common massive leuconium in the kidney. In renal cell carcinomas with clinically silent progression and at high metastatic levels, the order and effect of the treatment options gain importance.Surgery for localized RCC is usually curative. The surgical procedure may involve radical or partial nephrectomy depending on the age, comorbidity, and extent of disease in the patient. In selected patients with resectable tumor and concomitant single metastasis, radical nephrectomy with metastatic resection may be curative. Other ablative therapies may be an option in patients with relatively small renal masses without surgical candidates (cryotherapy, radiofrequency ablation).In patients with RCC who have metastasized 20-30% at the time of diagnosis and 20-40% of follow-up, they are treated with interferon alpha as the first line therapy in our country, and in patients with progression usually followed by tyrosine kinase inhibitors (TKIs), vascular endothelial growth factor (VEGF) pathway and rapamycin (mTOR) of the protein complex has been shown to be more effective. However, in our country, payment of TKI and VEGF receptor inhibitors is not done by the state at the first step treatment.Blockage of the VEGF pathway occurs in two ways; Small molecule TKIs (sunitinib, pazopanib, cabozantinib, axitinib, sorafenib) that block the intracellular part of the VEGF receptor are monoclonal antibodies (bevacizumab) that bind to circulating VEGF, which prevents binding to the VEGF receptor.The purpose of this study is; to evaluate the response of tyrosine kinase inhibitor, mTOR inhibitor and vascular endothelial growth factor inhibitor groups in 98 patients who were diagnosed with RCC between 01.01.1998 and 31.12.2016 in our center. 68

Akciğer kanseri dünyada kanserden ölümün en sık nedenidir. En sık küçük hücreli olmayan akciğer kanserleri (KHOAK) görülür. Tedavi planı; tümörün tipi, evrelemesi, KHOAK ise EGFR (Epidermal büyüme faktörü reseptörü), ALK (Anaplastik lenfoma kinaz), ROS1 gibi driver mutasyonların olup olmaması ve hastanın fonksiyonel kapasitesine göre yapılır. Dünyada standart tedavide birinci seçimde pemetrexed ve taksan bazlı tedaviler kullanılırken, ülkemizde bu kemoterapötik ajanlar ikinci seçimde kullanılmaktadır. Üçüncü seçimde optimal tedavi seçeneği belli değildir.Retrospektif olarak gerçekleştirdiğimiz bu çalışmanın amacı, 17.10.2010 – 17.10.2017 tarihleri arasında merkezimizde takip ettiğimiz 96 adet KHOAK'li hastada ikinci seçim pemetreksed sonrası üçüncü seçimde verdiğimiz tedavileri ve bu tedavilerin progresyonsuz sağkalım ile genel sağkalım oranlarını güncel literatür bilgileri ile karşılaştırmaktır. Beraberinde hastalarımızda yaş, cinsiyet, Eastern Cooperative Oncology Group (ECOG) performans skoru, metastaz varlığı bakılmış ve bu durumların da progresyonsuz sağkalım ile genel sağkalım etkileri incelenmiştir.Çalışmamızdaki hastaların büyük çoğunluğunun erkekler olduğu (%84,4) ve genel sağkalımın kadınlara göre daha yüksek olduğu görüldü (ortalama 53,4 hafta, p=0,04). Kranial metastazı olan ve ECOG performans skoru düşük olan hastaların genel sağkalımı üzerine etkisi anlamlı saptandı (p=0,023 ve p=0,003).Driver mutasyon taşımasalar bile üçüncü seçimde en sık verilen grup tirozin kinaz inhibitörleriydi (TKIs) (52 hasta). 48 hastaya erlotinib verildi. Üçüncü seçim tedavinin sağkalımı (p=0,015) ve progresyonsuz sağkalımı (p=0,022) arttırdığı görüldü. Tedavilerin birbirlerine üstünlükleri saptanmadı. TKIs alan hastaların sağkalımları ortalama 37,2 hafta, progresyonsuz sağkalımları da ortalama 18,1 hafta olarak belirlendi ve genel literatür bilgisine benzer olarak sonuçlandı.Sonuç olarak; çalışmamızda Erlotinib, diğer TKIs'lara ve sitotoksik ajanlara göre üstün bulunmasa da literatürde, üçüncü seçimde hasta eğer daha önce almadıysa Erlotinib tedavisini önerilmektedir.Anahtar kelimeler: Küçük hücreli olmayan akciğer kanseri, üçüncüseçim, pemetrexed, erlotinib. Lung cancer is the most common cause of cancer death worldwide. Non–small cell lung cancer (NSCLC) is the most common of them. Treatment plan is based on factors as tumor type, stage, patient's functional capacity and whether there is a driving mutation such as EGFR (Epidermal growth factor receptor), ALK (Anaplastic lymphoma kinase), ROS1 if it is NSCLC. Pemetrexed and taksan based treatments are the first-line worldwide, whereas in our country these chemotherapeutic agents are used in second-line treatment. Optimal treatment is unclear in third-line. In this retrospective study that enrolled 96 patients with NSCLC who received pemetrexed as second-line treatment between 17.10.2010 and 17.10.2017, we aimed to compare the third-line treatment options and total survival rates and progression-free survival rates with literature. We studied patient's age, sex, Eastern Cooperative Oncology Group (ECOG) performance score, presence of metastasis and examined how these factors affecting total survival rates and progression-free survival rates. In our study, majority of patiens were males (%84.4) and in men total survival rate was higher than women (mean 53.4 weeks, p = 0.04). There was a statistically significant effect of lower ECOG performance and presence of cranial metastasis (p = 0.023 and p = 0.003). Tyrosine kinase inhibitors (TKIs) are the most common treatment option as third-line, even there was no driver mutation (52 patients). Erlotinib was received to 48 patients. Third-line treatment was found to increase total survival rates (p = 0.015) and progression-free survival rates (p= 0.022). No superiority was found between treatments. Survival was 37.2 weeks and progression-free survival was 18.1 weeks in patients recieved TKIs and these results are consistent with literature. In conclusion, although in our study results erlotinib is not superior than other TKIs and cytotoxic agents, erlotinib treatment is recommended as third-line if patient did not use it before.Keywords: non small cell lung cancer, third line, pemetrexed,erlotinib 50

Kolorektal kanserler en sık görülen kanserlerden biri olup tüm dünyada halen önemli bir mortalite nedenidir. Kolorektal kanser biyolojisindeki gelişmeler ile kemoterapötik ilaçlardaki son dönem gelişmeler sağkalımda uzama sağlamıştır. Çalışmamızda 2000-2016 tarihleri arasında Uludağ Üniversitesi Tıp Fakültesi Hastanesi Onkoloji Polikliniğinden takipli tanı anında ya da takip sırasında metastatik olan kolorektal kanser hasta grubunda birinci ve ikinci seri tedavide epidermal büyüme faktörü reseptör (EGFR) inhibitörü kullanan hastaların sağkalım analizleri ve sağkalım üzerinde etkili prognostik faktörleri belirlemeyi amaçladık.Çalışmaya Ocak 2000- Ağustos 2016 tarihleri arasında Uludağ Üniversitesi Tıp Fakültesi Hastanesinde kolorektal kanser tanısı almış ve Tıbbi Onkoloji Bilim Dalı'nda tedavi almış toplam 84 hasta alındı. Tüm hastalarda yaş, komorbid hastalık varlığı, tanı tarihi, evre, tümör lokalizasyonu, tümöre yönelik operasyon öyküsü, operasyon tarihi, neoadjuvant kemoterapi durumu, adjuvant kemoterapi rejimleri, adjuvant kemoterapide EGFR inhibitörü kullanımı ile ortaya çıkan yan etkiler, karaciğer ve akciğer metastazına yönelik metastazektomi durumu, karaciğer metastazı olması durumunda transarteriyel kemoemboliazasyon/ radyofrekans ablasyon işleminin yapılması, radyoterapi durumu, progresyonsuz sağkalım ve genel sağkalım süreleri gibi parametreler ve bu parametrelerin sağkalım ve nüks üzerine olan etkileri değerlendirildi. Hastaların son kontrol tarihleri ya da exitus tarihleri kaydedilerek median progresyonsuz ve genel sağkalımları hesaplandı.Hastaların tanı anında yaşları 23 ile 82 arasında değişmekte olup yaş ortalması 55,16, standart sapması ise 12,37'dir. Hastaların 29'u (%31,9) kadın, 55'i (%60,4) erkekti. Hastaların 26'sı (%28,6) tanı anında evre 1-3 iken takipleri sırasında progrese olan hasta grubudur. Hastaların 58'i (%63,7) tanı anında evre 4'tü. EGFR inhibitörü alan hastaların median progresyonsuz sağkalım (PFS) 11 ay; median genel sağkalım (OS) ise 30 ay olarak saptandı. Primer hastalık lokalizasyonuna göre sağkalım analizi yapıldığında sol kolon yerleşimli hastalarda PFS (12 ay) ve OS (32 ay); sağ kolon yerleşimli hastalara göre ( median PFS 7 ay ve OS 18 ay) anlamlı olarak yüksek bulundu (p=0,029; p

INTRODUCTION The identification of novel prognostic markers may help to better assess survival probability in different subgroups of patients with non-small-cell lung cancer (NSCLC) and to tailor treatment according to the molecular profile of the tumour. AIM We sought to examine whether the immunohistochemical expression of excision repair cross-complementing 1 (ERCC1), an essential component of the nucleotide excision repair pathway, may predict prognosis in NSCLC. MATERIAL AND METHOD Formalin-fixed paraffin-embedded tumour samples from 44 Turkish patients with NSCLC treated by adjuvant platinum-based chemotherapy were included in the study. Immunohistochemical expression levels of ERCC1 were correlated with clinical outcomes by Kaplan-Meier curves and multivariable Cox proportional hazards regression analysis. RESULTS A total of 29 patients had ERCC1-negative tumours while 15 had ERCC1-positive tumours. The mean progression- free survival (PFS) was significantly lower in patients with ERCC1-positive tumours (13±2 months) than in those with ERCC1-negative tumours (27±5 months, p0.05). Similarly, the mean overall survival (OS) was significantly lower in patients with ERCC1-positive tumours (20±3 months) than in those with ERCC1-negative tumours (33±5 months, p0.05). After allowance for potential confounders, Cox regression analysis demonstrated that ERCC1 expression was significantly associated with both PFS and OS (both p0.05). CONCLUSION This study provides support for the prognostic value of ERCC1 immunohistochemical expression in patients with NSCLC treated by adjuvant platinum-based chemotherapy. If independently confirmed, these findings may improve prognostic stratification in this group of patients.

In the West in particular, the vast majority of gastric cancer (GC) patients present with advanced-stage disease. Although combination chemotherapy is still the most important component of treatment for these patients, it confers a modest survival advantage. Recently, increased knowledge of the key molecular signaling pathways involved in gastric carcinogenesis has led to the discovery of specific molecular-targeted thera-peutic agents. Some of these agents such as trastuzumab and ramucirumab have changed the treatment paradigm for this disease. In this paper, we will summarize the current clinical status of targeted drug therapy in the management of GC.

Aims and background To evaluate the efficacy and tolerability of a new treatment approach including induction chemotherapy (CT) and concurrent chemoradiotherapy (CRT) in unresectable, locally advanced pancreatic cancer (LAPC). Patients and methods Twenty-four patients with LAPC were enrolled in the study. They first received induction CT consisting of 5-fluorouracil (5FU) (500 mg/m2) and gemcitabine (1000 mg/m2), which were given weekly for 3 weeks of every 4. Patients showing a response or disease stabilization after 2 cycles of induction CT received CRT consisting of external beam radiotherapy (50.4-54 Gy in fractions of 1.8 Gy/day) and gemcitabine (350 mg/m2, weekly for 6 weeks). Patients without disease progression received 2 additional cycles of CT consisting of 5FU plus gemcitabine with the same doses and schedule as given in the induction CT. Results After the end of the study, 2 (8%) and 5 (21%) patients showed complete and partial responses, respectively. Five patients (21%) had disease stabilization. The grade 3 and 4 toxicities associated with CT were neutropenia (21%) and thrombocytopenia (4%). The grade 3 and 4 toxicities occurring in patients who received CRT were neutropenia (24%), thrombocytopenia (24%), diarrhea (18%), and nausea (12%). The median progression-free survival for all patients was 6 months (95% CI, 3.6-8.4), and the median overall survival was 11 months (95% CI, 8.16-13.84). Conclusions The CRT approach of this study is moderately active and has an acceptable toxicity profile. However, the incor-poration of combination CT into CRT at the present schedule could not produce any additional benefit over CRT alone. Newer agents with more systemic activity are clearly warranted.

AimTo determine the activity and toxicity of a combination of weekly gemcitabine and 5-fluorouracil bolus intravenously in patients with metastatic pancreatic cancer.Patients and methodsTwenty-one patients with previously untreated metastatic pancreatic cancer were included in this phase II study. The schedule was gemcitabine (1000 mg/m2iv) and 5-fluorouracil (500 mg/m2bolus iv) weekly for 3 weeks every month.ResultsFour patients (19%) achieved a partial response and three stable disease. A clinical benefit was obtained in 7 patients (33%). Median survival for all the patients was 6 months. The treatment was well tolerated and toxicity was mild. WHO grade 3 leukopenia occurred in 2 (9.5%) patients, grade 3 anemia in 4 (19%) patients, grade 3-4 thrombocytopenia in 4 (19%) patients, grade 1 diarrhea in 1 (4.7%) patient and grade 1 mucositis in 3 (14.2%) patients.ConclusionThe weekly administration of gemcitabine combined with 5-fluorouracil bolus iv is an active and well-tolerated regimen in metastatic pancreatic cancer. However, its efficacy is relatively limited.

Kaşeksi kanser hastalarının %50-80'ini etkileyen çok faktörlü ve çoğunlukla geri dönüşümsüz bir sendromdur. Kaşeksi kanserin sık görülen bir komplikasyonu olup kanserden ölümlerin önemli bir sebebi olarak karşımıza çıkmaktadır. Günümüzde kanser ile ilişkili kaşeksinin tedavisi için etkili bir tedavi şekli mevcut değildir. Bu çalışmada oral yoldan kullanılan beta hidroksi bütirik asitten (BHBA) zengin beslenme sıvılarının yaşlı ve kaşektik kanser hastalarındaki etkinliği araştırıldı. Çalışmaya farklı kanser tipleri nedeniyle takip edilen ve 3 aydan fazla yaşam beklentisi olan 65 yaş ve üzeri toplam 26 hasta alındı. Bu hastalara 1.3 gram BHBA içeren beslenme sıvısından günde iki kez (toplam 2.6 gram) verildi. Tedavi öncesi ve tedavi sonrası 3. ayda hastaların kilo, vücut kitle indeksi, yağ kütlesi, yağsız vücut kitlesi, serum albümin, total protein ve hemoglobin değerleri üzerine olan etkileri ölçüldü. Üç aylık BHBA tedavisi sonunda hastaların kilo, vücut kitle indeksi, yağ kitlesi ve yağsız vücut kitlesi değerlerinde istatistiksel olarak anlamlı olmayan bir artış tespit edildi. Serum albümin (3.72 vs 3.51 g/dL, p=0.005), total protein (6.95 vs 6.69 g/dL, p=0.035) ve hemoglobin (12.38 vs 10.64 g/dL, p=0.001) değerlerinde ise tedaviye rağmen azalma saptanmıştır. Sonuç olarak, bu hasta grubunda BHBA içeren beslenme sıvılarının belirlenen kaşeksi parametreleri üzerinde anlamlı bir etkisinin olmadığı görülmüştür. Cachexia is a multifactorial and often irreversible syndrome, affecting 50-80% of patients with cancer. Cachexia is a common complication of cancer and as a major cause of death from cancer. An effective treatment modality for the treatment of cancer cachexia is not available for today. In this study,the effect of oral nutritional supports containing beta-hydroxy butyric acid (BHBA) was investigated in the elderly cachectic cancer patients.A total of 26 patients over 65 years of age who were followed with the diagnosis of different types of cancer with a life expectancy of more than 3 months were included to the study. Oral nutritional supports containing 1.3 grams of BHBAwere given to the patients twice daily (2.6 g in total). Treatment effects on the weight, body mass index, fat mass, lean body mass, serum albumin, total protein andhemoglobin levels were evaluated before and 3 months after treatment. Although an increase was observed on weight, body mass index, fat mass and lean body mass values, it was not statistically significant. And a decrease was noted in serum albumin (3.72 vs. 3.51 g/dL, p=0.005), total protein (6.95 vs. 6.69 g/dL, p=0.035) and hemoglobin (12.38 vs 10.64 g/dL, p=0.001) values despite treatment.As a result, we observed that the nutritional support containing HBA showed no significant effect on cachexia parameters in this group of patients. 45

Tüm dünyada mortalitesi yüksek kanser türleri içinde mide kanseri ön sıralarda yer almaktadır. Son yıllarda mide kanseri insidansında öncelikle gelişmiş ülkelerde bir azalma olmasına rağmen halen dünya genelinde kanser mortalitesinde önemli bir yer tutmaktadır. Mide kanserlerinin çoğunluğu tanı anında uzak metastaz göstermektedir. İleri evre mide kanserlerinde cerrahi tedavi yöntemleri başarısız olmakla birlikte ilk tercih kemoterapidir. Mide kanseri için standart bir kemoterapi protokolü yoktur. Bu çalışmada sisplatin-kapesitabin kombine kemoterapi tedavisinin sağ kalım, tedavi yan etkileri gibi parametreler üzerinden hastalar üzerindeki etkisi klinik olarak araştırıldı.Bu çalışmada, lokal ileri (unrezektaabl) veya metastatik mide kanseri nedeniyle Uludağ Üniversitesi Tıp Fakültesi Tıbbi Onkoloji bölümünde sisplatin-kapesitabin tedavisi almış hastalar retrospektif olarak değerlendirildi. Toplam 45 hastaya (15 kadın ve 30 erkek) intravenöz sisplatin 75 mg/m2 (1. gün) ve kapesitabin 2000 mg/m2 (1-14 günler) verildi. Tedavi 3 haftada bir tekrarlandı. Ortalama olarak 3,4 siklus uygulandı. Hastalarda, tedavi sonrası genel sağ kalım, progresyona kadar geçen süre ve çeşitli yan etkiler takip edildi.Çalışma sonunda 5 (%11,1) hastada tam yanıt, 11 (%24,4) hastada parsiyel yanıt olduğu gözlendi. 7 (%15,6) hasta stabil hastalık olarak kabul edildi. Araştırma sonucunda genel sağ süresi 12 ay olarak saptandı. Progresyona kadar geçen süre 7 ay olarak saptandı.Tedaviye bağlı en sık yan etki bulantı kusma oldu ( 33 hasta, %73,3). Hematolojik yan etkilerde anemi %42,2, febril nötropeni %33,3 ve trombositopeni %22,2 olarak saptandı. Bunların dışında %33,3 vakada nefrotoksisite, %26,7 vakada diyare gözlendi. Sonuç olarak tedavi genel olarak iyi tolere edildi. Tedavinin lokal ileri veya metastatik mide kanserinde orta derece etkinliğe sahip olduğu gözlendi.Anahtar kelimeler: Mide kanseri, ileri evre, sisplatin, kapasitabin Gastric cancer is one of the leading cancers with high mortality in worldwide. Although there is a decrease in gastric cancer incidence especially in developed countries; it still has an important place in cancer mortality around worldwide. Most of the gastric cancers have distant metastasis on diagnosis. First treatment choice in advanced level gastric cancers is chemotherapy as surgical treatment methods fail. There is no standart chemotherapy protocol for gastric cancer. In this study, effects of cisplatin-capecitabine combine chemotherapy treatment in terms of parameters such as survival and side effects of treatment on patients were clinically evaluated.In this study, patients received cisplatin-capecitabine treatment in Uludağ University Faculty of Medicine, Department of Medical Oncology due to local advanced (unresectable) or metastatic gastric cancer were retrospectively evaluated. A total of 45 patient (15 women and 30 men) received 75 mg/m2 of cisplatin (1st day) and 2000 mg/m2 of capecitabine (1-14th days) intravenously. Treatment replaced in every three weeks. Averagely 3-4 cyclus administered. Post-treatment survival, time elapsed until progression and various advers effects were followed in patients.In the end of study; 5 (%11,1), 11 (%24,4) and 7 (%15,6) patients were considered as complete response, partial response and stable disease; respectively. General duration of survival was 12 months. Time elapsed until progression was 7 months.Most common advers effect of treatment was nausea-vomiting (33 patients, %73.3). Hematologic side effects were identified as anemia (%42.2), febrile neutropenia (%33,3) and thrombocytopenia (%22,2). In addition, %33,3 of cases experienced nephrotoxicity whereas %26,7 of cases suffered from diarrhea.In conclusion, treatment was generally well-tolerated. It was observed that treatment had intermediate effectiveness on local advanced or metastatic gastric cancers.Key words: Gastric cancer, advanced stage, cisplatin, capecitabine 49

Recent studies have demonstrated that arginine vasopressin (AVP) plays a crucial role in pain modulation. In addition, our previous studies have proven that centrally administered cytidine-5-diphosphate-choline (CDP-choline; citicoline) elicits an analgesic effect in different pain models in rats. Given that CDP-choline enhances central and peripheral vasopressin levels, the present study was designed to investigate the role of central AVP receptors in the analgesic effect of CDP-choline in acute and chronic constriction injury-induced neuropathic pain models. For this purpose, rats were pretreated intracerebroventricularly with the AVP V-1 or AVP V-2 receptor antagonist 15 min before intracerebroventricular injection of CDP-choline or saline, and pain threshold was determined using the Randall-Selitto test. AVP V-1 and AVP V-2 receptor antagonist blocked the CDP-choline-induced analgesic effect either in acute or neuropathic models of pain in rats. These results suggest, for the first time, that central AVP receptors are involved in the CDP-choline-elicited analgesic effect.

İleri evre pankreas kanserli hastalar kötü bir prognoza sahiptir ve tedavileri medikal onkoloji pratiğinde önemli bir problem olmaya devam etmektedir. Bu nedenle bu çalışmada metastatik veya lokal ileri pankreas kanseri tanısıyla tedavi edilen hastalarımızın klinik özelliklerini ve tedavi sonuçlarını retrospektif olarak değerlendirmeyi amaçladık. Bu çalışma için, Ocak 1995-Mayıs 2012 tarihleri arasında tedavi edilen ve klinik bilgileri elde edilebilen toplam 183 olgunun dosyasını retrospektif olarak inceledik. Hastaların demografik özelliklerini, almış oldukları tedavileri ve sağkalım sonuçlarını belirledik. Olguların 123’ü erkek, 60’ı kadın olup ortanca yaş 60 (33-84) idi. Tanı anında 105 olgu metastatikti ve en sık metastaz yeri karaciğerdi. Yetmiş beş hasta gemsitabin + 5-Fluorourasil, 42 hasta gemsitabin, 24 hasta gemsitabin+sisplatin ve 3 hasta UFT+sisplatin ile tedavi edilmişti. Kemoterapi ile olguların %6’sında tam yanıt, %8.7’de kısmi yanıt ve %9.8’de stabil hastalık elde edilmişti. Tedavi ile olguların ancak 34’ünde kilo artışı mevcut olup, kilo artışı ile sağ kalım arasında pozitif bir ilişki (p

Overexpression of the gene c-erbB2, which encodes a receptor tyrosine kinase, has been associated with prognosis and response to therapy in several solid tumors. This study was designed to test whether c-erb-B2 overexpression can be related to prognosis of patients with metastatic gastric cancer. Between 2005 and 2010, 46 cases of metastatic gastric cancer were evaluated immunohistochemically for c-erb-B2 overexpression. Overall survival (OS) and time-to-progression (TTP) served as the main outcome measures. c-erbB2 was overexpressed in 19 (41.3 %) cases and 8 patients (17.4 %) had a c-erbB2 score of 3+ (a strong complete membrane staining observed in > 10 % of the tumor cells). c-erbB2 expression was not associated with the clinicohistological characteristics of the study participants. The mean OS was 11.48 +/- A 1.03 months, whereas the mean TTP was 8.28 +/- A 0.8 months. Compared with patients with a score of 2+ or less (n = 38), those with a c-erbB2 score of 3+ (n = 8) had both a significantly lower OS (15.55 +/- A 1.63 vs. 8.22 +/- A 0.88 months, respectively, p < 0.05) and TTP (10.72 +/- A 1.81 vs. 6.11 +/- A 0.61 months, respectively, p < 0.05). After allowance for potential confounders, Cox regression analysis identified a c-erbB2 score of 3+ as an independent predictor of both OS (hazard ratio = 1.9; 95 % confidence interval = 1.1-3.7, p < 0.05) and TTP (hazard ratio = 1.8; 95 % confidence interval = 1.1-4.1, p < 0.05). Our results suggest that c-erbB-2 overexpression may have a prognostic significance in patients with metastatic gastric cancer.

Metastatic gastric cancer is incurable and remains one of the leading causes of cancer-related deaths around the world. Despite the significant progress in its systemic treatment, metastatic gastric cancer is still a major therapeutic challenge for oncologists. Newer chemotherapy regimens and the addition of molecularly targeted agents to chemotherapy seem to provide better clinical outcomes for patients with metastatic gastric cancer. The objective of this article is to review the current treatment approach for this formidable disease.

Purpose: This study was designed to evaluate the antihyperalgesic effect of CDP-choline (cytidine-5'-diphosphate-choline; citicoline) in a rat model of neuropathic pain produced by oxaliplatin (OXA). Methods: A single administration of OXA (6 mg/kg intraperitoneally/ip) was used for induction of neuropathy. We assessed the antihyperalgesic effect of intracerebroventricularly (icv) administered CDP-choline (0.5, 1.0 and 2.0 mu mol) using the rat paw pressure test (Randall-Selitto). Results: CDP-choline significantly reduced OXA-induced mechanical hyperalgesia, in a dose- and time-dependent manner. The antihyperalgesic effect of CDP-choline was blocked by the neuronal high affinity choline uptake inhibitor hemicholinium-3 (1 mu g; icv), the nonselective nicotinic receptor antagonist mecamylamine (50 mu g; icv), the a7 selective nicotinic acetylcholine receptor antagonist a-bungarotoxin (2 mu g; icv), and the gamma-amino butyric acid (GABA)-B receptor antagonist CGP-35348 (20 mu g; icv), but not by the nonselective opioid receptor antagonist naloxone (10 mu g; icv) and the nonselective muscarinic receptor antagonist atropine (10 mu g; icv). Conclusion: These findings indicate that CDP-choline exerts an antihyperalgesic effect in OXA-induced neuropatic pain and it can be tested in clinical trials.

Akciğer kanseri, günümüzde kansere bağlı ölümlerin tüm dünyadaki en yaygın nedenidir. Akciğer kanseri olgularının yaklaşık %80?ini küçük hücreli dışı akciğer kanseri (KHDAK) oluşturmaktadır ve bu olguların yaklaşık %55-60?ı tanı anında ileri evrede (metastatik) yakalanmaktadır. Metastatik KHDAK?de tedavinin amacı semptomatik iyileşme sağlamak ve sağkalım süresini uzatmaktır. Bu çalışmada, kemoterapiye dirençli KHDAK?li hastaların 2. veya daha sonraki tedavi basamağında oral tirozin kinaz inhibitörü erlotinibin etkisi ve toleribilitesi araştırıldı. Erlotinib tedavisini alan toplam 39 hasta retrospektif olarak değerlendirildi. Altı hastada (%15.8) kısmı yanıt elde edilirken, 16 hastada (%42.1) stabil hastalık ve 16 hastada (%42.1) progresyon tespit edildi. Bir hasta veri eksikliğinden dolayı değerlendirmeye alınmadı. Hastaların ortalama genel sağ kalımı 377 (291-462) gün saptanırken progresyona kadar geçen süre 242 (151-334) gün saptandı. Hastalar tedaviyi genel olarak iyi tolere etmiş olup tedavinin kesilmesini gerektirir yan etki gelişmedi. Sonuç olarak kemoterapiye dirençli KHDAK?li hastaların tedavisinde erlotinib iyi bir seçenek olabilir.Anahtar kelimeler: Küçük hücreli dışı akciğer kanseri, tirozin kinaz inhibitörü , erlotinib Lung cancer is now the most common cause of cancer-related deaths worldwide. Non-small Cell Lung Cancer (NSCLC) accounts for approximately 80% of all lung cancer and 55?60% of NSCLC patients have advanced stage at diagnosis. The main aim of treatment in this patients to provide symptomatic relief and survival benefit. In this study, the efficacy and tolerability of erlotinib, an oral tyrosine kinase inhibitor, as second line or later lines of chemotherapy in patients with advanced stage NSCLC. Thirty-nine patients treated with erlotinib were evaluated retrospectively. Partial response was achieved in 6 (15.8%) patients, disease remained stable in 16 (42.1%) patients and progression in 16 (42.1%) patients. The median over all survival and progression free survival was 377 (291-462) days and 242 (151-334) days respectively. Erlotinib treatment was generally well tolerated and no significant adverse effect was observed. In conclusion, erlotinib may be a good option in the treatment of patients with chemotherapy-refractory NSCLC.Key words: non-small cell lung cancer, tyrosine kinase inhibitor, erlotinib 37

Kanser hastalarında istem dışı olarak % 10?dan fazla kilo kaybı kaşeksi olarak tanımlanmaktadır. Kaşeksi sağ kalım üzerine olan olumsuz etkilerinin yanı sıra radyoterapi ve kemoterapi komplikasyonlarının sıklığını da arttırmaktadır. Kaşeksinin belirleyici faktörleri azalmış kas kitlesi, azalmış vücut kitle indeksi, iştahsızlık, performans durumunda bozulma ve CRP, albumin, hemoglobin, sedimentasyon gibi biyomedikal parametrelerdir. Bu çalışmada farklı maligniteler nedeniyle takip edilen, 3 aydan fazla yaşam beklentisi olan kanser hastalarında oral yoldan alınan Eicosapentaenoic asitten zengin beslenme desteğinin kilo, yaş, vücut kitle indeksi, yağsız vücut kitlesi, crp, albumin, hemoglobin ve sedimentasyon parametreleri üzerindeki etkileri karşılaştırıldı. Bu parametreler tedavi verilmeden önce, 1. ay ve 3. ayda değerlendirildi. Çalışmamızda Onkoloji Bilim Dalımıza başvuran 25 (4 kadın, 21 erkek) hastaya günde 2 kez toplam 2 kutu (700 gr prosure) ve günde 2 kez toplam 2 kutu (48 gr abound) Eicosapentaenoic asitten zenginleştirilmiş oral beslenme solüsyonu verildi. Etkinlik parametreleri olarak kas kitlesi, azalmış vücut kitle indeksi, iştahsızlık, performans durumunda bozulma ve CRP, albumin, hemoglobin, sedimentasyon karşılaştırıldı. Çalışmamızda 3 aylık oral nutrisyonel destek tedavisi sonrası hemoglobin, albumin düzeyleri, yağ kitlesi, yağ yüzdesi arasında anlamlı fark saptandı. Ancak hastaların kilo ve kas kitleleri arasında anlamlı fark saptanmadı. Kaşeksi kanser hastalarında önemli bir sorundur ve patofizyolojinin iyi tanınması gerekmektedir. Sonuç olarak kanserin başlangıcından itibaren hastaların nutrisyonel durumlarının da göz önünde bulundurulması hastaların yaşam standartlarının iyileştirilmesinde ve tedaviye yanıt oranlarında olumlu katkı sağlayabilir.Anahtar kelimeler: kaşeksi, nutrisyon, albumin, hemoglobin, yağ ve kas kitlesi. Cachexia is defined to be the unintentional weight loss of more than 10% in cancer patients. Besides its negative effects on mortality, Cachexia also increases the complication frequencies of radiotherapy and chemotherapy. The defining factors of cachexia are biomedical parameters such as reduced muscle mass, reduced body mass index, loss of appetite, disruption in performance and c-reactive protein (CRP), albumin, hemoglobin, sedimentation.In this study the effects of orally consumed Eicosapentaenoic acid rich nutrition support on weight, age, body mass index, fat-less body mass, CRP, albumin,hemoglobin and sedimentation parameters are compared on cancer patients that are monitored for different malignancies and have more than 3 months of life expectancy. The parameters are evaluated before, in the 1st and 3rd months of the treatment.In our study, an eicosapentaenoic acid rich nutrition solution made of 700gr prosure (2 times per day, 2 boxes in total) and 48gr abound (2 times per day, 2 boxes in total) are given to 25 patients (4 female, 21 male) who applied to our Oncology Department. Muscle mass reduced body mass index, loss of appetite, disruption in performance and CRP, albumin, hemoglobin, sedimentation are compared as activity parameters.After a 3 months long nutrition support treatment, a meaningful difference is detected between the hemoglobin, albumin levels, fat mass, fat percentage. However meaningful differences between patients' weight and muscle masses are not detected.Cachexia is a crucial problem for cancer patients and the acknowledgement of the physiopathology is needed. As a conclusion, considering the nutritional conditions from the beginning of cancer, plays an important role for improving the patients' life standards and their response to the treatment.Key words: Cachexia, nutrition, albumin, hemoglobin, fat and muscle mass. 36

Aims and background The optimal treatment of cancer cachexia remains unknown. In this study, we compared the efficacy of three different treatment modalities in the management of cancer cachexia. Methods Sixty-two assessable cachectic cancer patients were randomized to one of the following three arms: 1) megesterol acetate (MA) plus meloxicam (n = 23); 2) MA plus meloxicam plus oral eicosapentaenoic acid (EPA)-enriched nutritional supplement (n = 21); or 3) meloxicam plus oral EPA-enriched nutritional supplement (n = 18). Treatment duration was 3 months. Results The treatment arms were well balanced at baseline. The primary efficacy (body weight and lean body mass) and secondary efficacy (body mass index, quality of life, and serum levels of IL-6 and TNF-α) parameters improved after treatment in all three arms. There were no statistically significant differences between treatment groups in the mean percentage changes in all efficacy parameters from baseline to end of study. Conclusions MA plus meloxicam or EPA supplement plus meloxicam may be effective treatment options in the management of cancer cachexia. The combined use of these agents does not provide further advantages.

Aims and Background Small cell carcinoma of the bladder (SCCB) is a rare entity characterized clinically by an aggressive behavior with a high incidence of systemic metastases. We report the clinicopathologic findings of five cases. Methods We reviewed five consecutive patients with SCCB treated at our institute. In each case the following clinical data were recorded: age, sex, presenting symptoms, endoscopically determined location of the tumor, clinical staging, node involvement (if any), site of metastases (if any), treatment, follow-up and outcome. Results There were four male and one female patients, age range 42 to 68 years, mean 57.6 years. The clinical presentation was not different from conventional transitional cell carcinoma, with hematuria being the most frequent complaint (four cases). Microscopic examination revealed oat cells in three cases and an intermediate variant in one. At the time of diagnosis the tumors were staged as T3bN2M0, T2N2M0, T4N0M0, T3aN0M0, and T2N0M0. Primary therapy consisted of radical cystectomy alone (one case), transurethral resection (TUR) alone (one case), TUR with chemotherapy (two cases), or TUR with chemotherapy and radiotherapy (one case). Four patients died of progressive disease, with survival from the time of diagnosis ranging from 7 to 16 months (mean, 12.2 months). One patient died of myocardial infarction (unrelated to the primary disease) one month after diagnosis. Conclusion Our study indicates that primary small cell carcinoma of the urinary bladder is as aggressive as its pulmonary counterpart and the overall prognosis of this tumor is very poor.

Background: Pulmonary actinomycosis may create a diagnostic and therapeutic dilemma especially in cancer patients. Case Report: A 64-year-old male patient presented with a productive cough, bloody sputum, and weight loss. Thoracic computed tomography (CT) showed a 5-cm mass in the upper lobe of the right lung, and a 2-cm mass in the lower lobe of the left lung. Bronchoscopic examination did not show any endobronchial lesions. CT-guided needle biopsy of the right pulmonary lesion showed lung adenocarcinoma. Whole-body positron emission tomography/CT revealed an increase in fluorodeoxyglucose accumulation in the upper lobe of the right lung, in the lower lobe of the left lung, and in the right hilar and paratracheal lymph nodes. Before chemotherapy was initiated, the patient had to be admitted to the hospital because of massive hemoptysis. Bronchoscopic examination indicated persistent bleeding in the left lower lobe bronchus. The patient underwent diagnostic left thoracotomy, and wedge resection of the lower lobe mass. The diagnosis was pulmonary actinomycosis, and the patient received oral amoxicillin. He underwent successful surgery for the primary disease following 6 cycles of chemotherapy. Conclusion: Oncologists should be aware of rare diseases that may affect management approaches in the treatment of cancer.

Polymorphisms in the X-ray repair cross complementing 1 (XRCC1) gene have been found to be associated with susceptibility to various types of cancers. We investigated the association between the XRCC1 gene Arg399Gln polymorphism and the susceptibility to lung cancer in Turkish patients. To determine the association of this polymorphism with the risk of lung cancer in Turkish patients, a hospital-based case-control study was designed, involving 67 patients with lung cancer and 60 control subjects with no cancer history who were matched for age and gender. XRCC1 genotypes (Arg/Arg, Arg/Gln, and Gln/Gln) were determined using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) analysis on genomic DNA. No statistically significant relationship was determined between the lung cancer and control groups (p>0.05). Among the patients, 61% were Arg/Arg, 28% were Arg/Gln, and 11% were Gln/Gln. Among the controls, 50% were Arg/Arg, 38% were Arg/Gln, and 12% were Gln/Gln. There was no difference in the distribution of XRCC1 genotypes or the frequencies of the Arg (75% versus 69%) and Gln (25% versus 31%) alleles between the lung cancer patients and controls. Our results suggest that the XRCC1 gene Arg399Gln polymorphism is not associated with an increased risk for the development of lung cancer in Turkish patients.

Bu çalışmada metastatik mide kanserli hastalarda taksan içerentedaviler ile taksan içermeyen tedavilerin etkinliklerinin karşılaştırılması amaçlanmıştır.Çalışmaya Uludağ Üniversitesi Tıp Fakültesi Onkoloji Bölümü'ndeOcak 2012-Haziran 2012 tarihleri arasında metastatik mide kanseri nedeniyle takip edilen 146 hasta dahil edildi (E:106, K:40). Çalışmaya dahil edilen hastaların dosyaları retrospektif olarak analiz edildi. Bu hastaların 86'sı taksan içeren 60'ı taksan içermeyen kemoterapi rejimi alan hastalardı. İkigrup kendi arasında progresyona kadar geçen süre, genel sağkalım süresi ve tedaviye yanıt bakımından karşılaştırıldı.Genel sağkalım süresi; taksan alan hastalar için 9,2 ay, taksanalmayan hastalar için 9,9 ay bulundu (p=0,62). Progresyona kadar geçen süre taksan alan hastalar için 9,1 ay, taksan almayan hastalarda 8,7 ay bulundu (p=0,46). Tedaviye yanıt oranları (kısmi yanıt+tam yanıt) taksan alan hastalarda %6 iken taksan almayan hastalarda %7 idi (p=0,14).Bu retrospektif analiz, metastatik mide kanseri tedavisinde taksan içermeyen rejimlerin, taksan içeren rejimler kadar etkili olduğunu göstermiştir.Anahtar kelimeler: Taksan, metastatik mide kanseri. The aim of our study was comparison of the effects of taxane andnon taxane containing regimens in patients with metastatic gastric cancer.One hundred and forty six patients (106 male and 40 female) withmetastatic gastric cancer who were followed in Uludağ University, School of Medicine, Department of Oncology between January 2002 and June 2012 were included in this study. Patient data were retrospectively analyzed. 86 of 146 patients were treated with taxane-containing chemotherapy regimens, 60patients were treated with non-taxane containing chemotherapy regimens. Two groups were compared in terms of time to progression, overall survival and response (complete and partial) to therapy. Patients treated with taxane containing regimens and non-taxane containing regimens had similar overall survival (9.2 months and 9.9 months respectively, p=0.62), time to progression (9.1 months and 8.7 months respectively, p=0.46), and response rate (6% and 7% respectively, p=0.14).Our study showed that non-taxane based regimens are as efficientas taxane-based regimens.Key words: Taxane, metastatic gastric cancer. 49

Meme kanseri, kadınlarda en sık teşhis edilen kanser çeşididir ve mortalitenin önde gelen sebeplerindendir. Meme kanseri olan bireylerin çoğunluğunu yaşlı popülasyon oluşturur. Erken tanı aldığı takdirde gelişmiş cerrahi seçenekler, kemoterapi, radyoterapi ve hormonoterapi gibi tedavilerin yanı sıra hedefe yönelik tedavi seçenekleri ile başarı oranının yüksek olduğu malignite çeşididir.Bu çalışmada meme kanseri olan ileri yaş hastaların tedavi seçenekleri, aldıkları kemoterapi ajanları ve yan etkileri, operasyon tipleri, tümör evresi, komorbid hastalıkları ve bunların sağkalıma olan etkileri karşılaştırıldı.Retrospektif çalışmamıza Onkoloji Bilim Dalı'na başvuran 70 yaş üzeri 99 hasta dahil edildi. Hastaların aldıkları tedavilerin ve cerrahi yöntemlerin yanı sıra komorbid hastalıklarda kullandıkları tedaviler, patolojik incelemelerde tümörün lenfatik, vasküler invazyon varlığı ve ekstrakapsüler yayılımı, östrojen, progesteron ve cerb-B2 reseptör pozitifliği, tümörün evresi ve histolojik alt grupları ele alınarak bu faktörlerin hastalıklı sağkalıma olan etkileri istatistiksel olarak ortaya kondu.Çalışmada sağkalıma olumlu etkileri olan 2 faktör saptandı. Bunlar hormonoterapi ve radyoterapi idi. Radyoterapi ve hormonoterapi almayan hastaların yaşam sürelerinin, bu tedavileri alanlara göre daha kısa olduğu görüldü. Düşünülenin aksine kemoterapinin hastalıklı sağ kalıma olumlu etkisinin olmadığı gözlendi.İleri yaş meme kanserli hastalarda sağ kalım ve tedavi başarısında radyoterapi ve hormonoterapinin üstünlüğü ilgili literatürlerle benzerdir.Anahtar kelimeler: Meme kanseri, tedavi, yaşlı hasta. Breast cancer is the most commonly diagnosed cancer and the leading cause of cancer mortality in women worldwide. Elderly individuals make up a large part of the breast cancer population. If the advanced surgical options for early diagnosis, chemotherapy, radiotherapy and hormonotherapies, such as treatment options, as well as the success rate is high, targeted type of malignancy.In this study, elderly patients with breast cancer treatment options, their agents and the side effects of chemotherapy, type of operation, tumor stage, the effect of comorbid diseases and their survival are compered.Retrospective study of 99 patients over the age of 70 who consulted to Oncology Science were included. Patients with comorbid disorders, as well as the methods used in their treatments and surgical treatments, lymphatic pathological examination of the tumor, presence of vascular invasion and spread of extracapsuler, estrogen, progesterone and c-erb B2 reseptor positivity, tumor stage and histological subgroups statistically by considering the effects of these factors, disease free survival as was put forward.The study was survival of the positive effects of the two factors. They were hormonal and radiotherapy. Survival of patients without radiotherapy and hormonotherapy, according to the people who recieved these treatments were found to be shorter. Contrary to the positive impact of chemotherapy on survival was observed morbid.Advanced age, radiation therapy and patients with breast cancer survival and the success of treatment is similar to the literature related to the rule of hormonotherapy.Key words: Breast cancer, treatment, elderly patient. 58