What Is Your Choice for Androgen Deprivation Therapy in Metastatic Prostate Carcinoma: Surgical or Medical?

OBJECTIVE: At the time of diagnosis, approximately 16.5% of prostate cancer patients are metastatic. The main framework of metastatic prostate cancer treatment is androgen deprivation therapy, which is performed surgically or medically. The aim of this study is to evaluate the attitudes of medical oncologists and urologists about orchiectomy as androgen deprivation therapy. MATERIAL AND METHODS: A total of 387 physicians working in the Departments of Urology (n=217) and Medical Oncology (n=170) were included in this descriptive study. Data were collected through an electronic survey. RESULTS: Only 7.5% of participants indicated that they offered surgical castration to their patients. Urologists preferred surgical castration more than oncologists for the treatment of metastatic castration-sensitive prostate carcinoma (P=.003). The reasons why medical oncologists preferred surgical castration less are that it is an invasive procedure, has risk of morbidity and mortality, high cost of hospitalization, and may cause deterioration of the patient's body image (P < .05). CONCLUSION: This study showed that physicians were less likely to perform orchiectomy as an androgen deprivation therapy. Although the most important reason for this is the patient preference, the biased presentation of treatment options to patients, the lack of knowledge of physicians about orchiectomy, and the effect of the pharmaceutical industry should also be kept in mind.

CD47 (don't eat me signal) expression levels and its relationship with clinicopathologic features in early-stage prostate carcinoma.

BACKGROUND: Prostate cancer is a cancer with poor host immune response and could be defined as a non-T-cell inflamed tumor. Therefore, immunotherapy treatments could not be included in the treatment of prostate cancer until recently. Inadequate antitumoral response is one of the main reasons why tumor cells multiply rapidly and cause lethal results. It was shown that CD47 molecule, which is secreted at high levels by leukemia cells, reduces macrophage-mediated phagocytosis and thus facilitates escape from the antitumoral immune response. The aim of this study was to show don't eat me signaling in prostate carcinoma tissues and its relationship with macrophage polarization. MATERIALS AND METHODS: A total of 263 patients with a diagnosis of prostatic adenocarcinoma after radical prostatectomy between 2015 and 2020 at our institute were included in the study. CD47, CD68, and CD163 expression levels were examined immunohistochemically (IHC) in these tissues. The relationship of these expression levels with unfavorable prognostic factors and survival for prostate carcinoma was investigated. RESULTS: In this study, all the operated prostate carcinoma cases had CD47 expression in tumor tissue, but only 52.5% had a high level of expression. Of 263 prostate cancer tissues, 135 (51.3%) showed high expression of CD68 protein and 189 (71.9%) showed high expression of CD163 protein. There was a statistically strong relationship between CD47, CD68, and CD163. CONCLUSIONS: The CD47 molecule is basically a molecule that inhibits macrophage activation. CD68 is mostly used for macrophage classification, while CD163 is used for tumor-associated macrophage classification. Unlike others, we IHC examined CD47, CD68, and CD163 expressions in the surgical materials of patients who were operated for prostate carcinoma. In addition, we concluded that strong CD47 expression was closely associated with strong CD68 and CD163 expression in all tumor samples. However, a significant relationship between these expression levels and survival could not be demonstrated.

Evaluation of hereditary/familial breast cancer patients with multigene targeted next generation sequencing panel and MLPA analysis in Turkey.

Breast cancer, a worldwide leading cause of cancer in women, may occur in familial cases. Germline mutations in BRCA1/2 genes are responsible for 15% of the familial cases. With the power of next generation sequencing (NGS) analysis, it is possible to analyze genes related to hereditary susceptibility to breast cancer and investigate the genetic etiology more thoroughly. In this study, we investigated 30 genes identified frequent pathogenic alleles in Turkish population. The study includes 495 unrelated individuals diagnosed with breast cancer who are selected for genetic testing according to NCCN criteria for hereditary breast cancer. All patients were analyzed by NGS for BRCA1/2 genes. Deletion/duplication investigation by Multiplex ligation-dependent probe amplification (MLPA) and massive sequencing of 30 breast cancer-related genes (Oncorisk Gene Panel) were performed in a stepwise manner. BRCA1/2 variants are the most frequent pathogenic variants which are found in 45 of 495 (9.1%) patients. Four previously unreported, novel, pathogenic variants of BRCA2 gene are identified. In four cases, exonic deletions of BRCA1/2 genes are determined and there is no duplication of these genes. NGS panel investigation involving other moderate-high risk genes contributed genetic diagnosis in an extra 39 out of 419 (9.3%) cases. Our study presents the cost effectiveness of the gene panel approach. We suggest that gene panels should be the first-tier genetic testing for hereditary breast cancer and MLPA analysis of BRCA1/2 genes should be investigated as a complementary method of NGS analysis.

GLASS: Global Lorlatinib for ALK(+) and ROS1(+) retrospective Study: real world data of 123 NSCLC patients.

Lorlatinib is a third-generation tyrosine-kinases inhibitor (TKI) targeting ALK/ROS1 fusions. The FDA has approved lorlatinib for TKI-pretreated ALK(+) NSCLC, while its approval for ROS1(+) is still pending. Here we present the largest real-world data of NSCLC patients harboring ALK/ROS1 rearrangements treated with lorlatinib. METHODS: 123 patients were enrolled retrospectively (data cut-off 1/1/2019). Lorlatinib was administered through an early access program for patients with no other available therapy. Outcome and response were defined by each investigator upon RECIST 1.1 criteria. RESULTS: 106 ALK(+) and 17 ROS1(+) patients recruited from 8 different countries. The ALK(+) cohort included 50 % males, 73 % never-smokers and 68 % with brain metastases. Extracranial (EC) and intracranial (IC) response rates (RR) were 60 % and 62 %, with disease control rates (DCR) of 91 % and 88 % respectively. Mean duration of therapy (DoT) was 23.9 ±â€¯1.6 months and median overall survival (mOS) was 89.1 ±â€¯19.6 months. ROS1 cohort enrolled 53 % males, 65 % never-smokers and 65 % had brain metastases. EC and IC RR were 62 % and 67 % with DCR of 92 % and 78 % respectively. Median DoT was 18.1 ±â€¯2.5 months and mOS of 90.3 ±â€¯24.4 months. OS and DoT in both cohorts were not significantly correlated with line of therapy nor other parameters. The most common adverse events of any grade were peripheral edema (48 %), hyperlipidemia (47 %), weight gain (25 %) and fatigue (30 %). CNS adverse events such as cognitive effect of grade 1-2 were reported in 18 % of patients. CONCLUSION: Lorlatinib shows outstanding EC/IC efficacy in ALK/ROS1(+) NSCLC. The observed mOS of 89 ±â€¯19 months in ALK(+) NSCLC supports previous reports, while mOS from of 90 ±â€¯24 months is unprecedented for ROS1(+) NSCLC.

Prevalence of depressive symptoms in elderly cancer patients receiving chemotherapy and influencing factors.

BACKGROUND: Depression is one of the most prevalent causes of distress in the geriatric population. The purpose of this study was to examine the prevalence of depressive symptoms in elderly cancer patients and to determine the possible associated factors. METHODS: Cancer patients 65 years or older and on active chemotherapy completed the Yesavage Geriatric Depression Scale. We examined the relationship of depressive symptoms with age, gender, marital status, educational background, type of cancer, stage of disease, comorbidities, types of treatment for cancer, the duration after diagnosis of cancer, social support, and pain status. RESULTS: The study included 170 patients with a mean age of 71 years, and 47.1% were women. The prevalence of a high depressive symptom score was 19.4%. Of the patients who had a high depressive symptom score based on the Yesavage Geriatric Depression Scale, 18.2% had already been diagnosed with depression and used antidepressants. The mean pain score was significantly higher in patients who had a high depressive symptom score compared to others (P = 0.012). CONCLUSION: The prevalence of depressive symptoms in elderly cancer patients receiving chemotherapy was similar to that in the geriatric population without cancer. It was also consistent with previous studies on elderly cancer population. Pain was found to be a factor related to depressive symptoms. The prevalence of depression may be reduced by pain control. The treatment of depression may both improve the patient's quality of life and enhance their compliance with treatment.

A national, multicenter, non-interventional, observational study on treatment patterns in patients with metastatic renal cell carcinoma in Turkey - NOTES study.

INTRODUCTION: The introduction of targeted therapies in renal cell carcinoma has significantly improved its prognosis and treatment outcomes in recent years. Such treatment options are targeted therapies of the vascular endothelial growth factor (VEGF) pathway and the mammalian target of the rapamycin pathway. With the use of tyrosine kinase inhibitors (TKIs) and mammalian target of the rapamycin inhibitors, overall survival has increased up to 2 years. In Turkey, due to applicable reimbursement conditions for patients with metastatic renal cell carcinoma (mRCC), interferon use is mandated as a first-line treatment, thus providing information on the use of everolimus only after initial interferon and second-line VEGF-targeted treatments such as VEGF-TKI. PATIENTS AND METHODS: To provide a first real-life data set in Turkey, we conducted a prospective, non-interventional, observational study and assessed the efficacy and safety of everolimus after two lines of treatment including interferon. A total of 100 patients with histologically confirmed mRCC were enrolled in the study from 11 centers between June 2012 and March 2014 (70 males and 30 females). Efficacy was assessed on the basis of progression-free survival and overall survival; safety of everolimus was assessed on the basis of adverse event occurrence. RESULTS: The study results showed that the median progression-free survival with everolimus treatment was 8.1 months (95% CI: 5.1-11.1) and the median overall survival was 17.6 months (95% CI: 10.1-25.1), thus indicating a better overall response based on survival durations than those from the randomized Phase III REnal Cell cancer treatment with Oral RAD001 given Daily study results (4.9 and 14.8 months, respectively). CONCLUSION: The study showed that everolimus treatment is a safe and effective treatment option in the treatment of mRCC after VEGF-TKI, with an acceptable safety and tolerability profile in real-life settings.

Effectiveness and Safety of LMWH Treatment in Patients With Cancer Diagnosed With Non-High-Risk Venous Thromboembolism: Turkish Observational Study (TREBECA).

We compared the efficacy and safety of low-molecular-weight heparins (LMWHs) in patients with cancer who are at low risk of venous thromboembolism (VTE). Patients were treated by medical oncologists in Turkey at 15 sites, where they were enrolled and followed up for a period of 12 months. Due to the study design, there was no specific treatment protocol for LMWH. Primary end points were efficacy and the time to change in VTE status. Of the included 250 patients, 239 (95.6%), 176 (70.4%), 130 (52.0%), and 91 (36.4%) completed their day 15, month 3, month 6, and month 12 visits, respectively. Number of patients treated with enoxaparin, bemiparin, and tinzaparin were 133, 112, and 5, respectively. Anticoagulant therapy provoked thrombus resolution in 1.2% and 12.7% of patients using enoxaparin and bemiparin, respectively ( P = .004). Thrombus resolution was observed in 81 more patients at month 3 visit. This ratio was 35 (40.2%) of 87 and 46 (54.1%) of 85 patients administered enoxaparin and bemiparin at the third visit, respectively ( P = .038). Thrombus resolution was observed in 21 more patients during month 6 visit. This ratio was 5 (7.7%) of 65 and 15 (23.4%) of 64 patients administered enoxaparin and bemiparin at the fourth visit, respectively ( P = .022). The LMWH was discontinued in only 2 patients due to gastrointestinal bleeding. This pioneering study shows bemiparin is more effective than enoxaparin in thrombosis resolution and has a similar tolerability profile.

Is advanced age a hesitation for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in colorectal cancer?

PURPOSE: The purpose of this study was to assess the feasibility and safety of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in elderly patients with peritoneal carcinomatosis of colorectal cancer. METHODS: Patients who underwent curative complete CRS and HIPEC for peritoneal carcinomatosis of colorectal cancer with minimum follow-up of 24 months were included in the analysis. Charlson comorbidity index and ECOG performance status were used to evaluate preoperative condition. Patients were tiered into two groups according to age (<65 and ≥65 years). Postoperative morbidity, mortality, recurrence, and overall survival were compared between groups. RESULTS: One-hundred patients were meeting the inclusion criteria. Median age was 56 years (ranging, 20-86). The origin of peritoneal carcinomatosis (PC) was colon in 77 and rectum in 23 patients. There were 31 patients in the elderly group. Mean hospital stay was 1711.8 and 16.814.3 days in young and elderly groups (p=0.937). In young patients, postoperative morbidity was seen in 26 (37.6%) patients versus 9 (29%) patients in elderly group (p=0.272). Mortality was higher in elderly group (n=4, 12.9%) than in the younger group (n=5, 7.2%), but the difference was not statistically significant (p=0.287). Median follow-up was 25 months (ranging, 2-112). Local and/or distant recurrence occurred in 30 (43.4%) patients in the young group and 9 (29%) patients in elderly group (p=0.169). Two-years disease-free survival was similar: 67.1% in the young and 74% in the elderly groups (p=0.713). CONCLUSIONS: CRS and HIPEC offer comparable oncologic outcome in meticulously selected medically-fit elderly patients without increased postoperative morbidity and mortality.

Response to Cabazitaxel Beyond 20 Cycles in A Patient with Penile Metastasis of Prostate Cancer: A Case Report.

Penile metastases are extremely rare events and generally occurs at a late stage of primary disease. They mostlyoriginate from prostate and bladder in the genitourinary tract. Penile metastases have a dismal prognosis and verylow survival rates. We report a case of penile metastasis in 70-year-old geriatric male patient with prostatic adenocarcinomawho was treated with cabazitaxel chemotherapy beyond 20 cycles with a good response and acceptableminimal toxicity.

The Rate of Neoadjuvant Chemotherapy Use in Muscle Invasive Bladder Cancer and The Approach of Urologists in Turkey.

PURPOSE: To investigate the proportion of neoadjuvant chemotherapy (NAC) use in patients with muscle invasive bladder cancer before radical cystectomy and the approach of urologists to this subject. MATERIALS AND METHODS: We invited 242 urologists during the 12th International Urooncology Congress in Turkey to answer a self-administered questionnaire. The questionnaire included questions related to radical cystectomy, lymph node dissection and neoadjuvant chemotherapy that had been performed in patients with muscle invasive bladder cancer by the urologist. RESULTS: The median number of radical cystectomy operations was 20 per year. 122 (50.5 %) of 242 urologists had used neoadjuvant chemotherapy for the treatment of muscle invasive bladder cancer before radical cystectomy. The mean rate of neoadjuvant chemotherapy use by these urologists (n=122) was 28.46 %. The most common reasons for not using neoadjuvant chemotherapy by urologists in Turkey were as follows: (i) neoadjuvant chemotherapy might lead to a decrease in the cure rate of radical cystectomy due to delayed surgery (ii) complication rate of radical cystectomy might be elevated and the surgery might be complicated by NAC use. CONCLUSION: Although the European Association of Urology (EAU) guidelines panel on muscle invasive bladder cancer recommends using NAC in T2-T4a bladder, the rate of neoadjuvant chemotherapy use was still found to be low in our country because urologists have concerns about adverse effects NAC on radical cystectomy. .

Protective Role of Selenium and High Dose Vitamin E against Cisplatin - Induced Nephrotoxicty in Rats.

BACKGROUND: Cisplatin (CDDP) is one of the most active cytotoxic agents in the treatment of cancer. We investigated the effect of selenium (Se) with high dose vitamin E (VE) administration to prevent CDDP-induced nephrotoxicity in rats. MATERIALS AND METHODS: In this study, 40 female Wistar rats were randomly divided into five equal groups. The first group, which served as the control, was administered physiological saline (2.5 cc/day, 5 days) intraperitoneally (IP), while group A was administered cisplatin (6 mg/kg BW/ single dose) plus physiological saline IP. Groups B, C, D received IP five doses of Se (1.5 mg/kg BW), and a high dose of VE (1000 mg/kg BW) (Se-VE) in combination before, simultaneously, and after CDDP, respectively. The rats were sacrificed five days after CDDP administration. Plasma malondialdehide (MDA), glutathione peroxidase (GSH-Px), reduced glutathione (GSH), catalase, urea, creatinine levels, renal histopathological changes were measured. RESULTS: The histopathological injury score, plasma levels of MDA, urea, creatinine were found to increase in group A compared to the control (p<0.05), while plasma levels of GSH-Px, GSH and catalase decreased (p<0.05). In contrast, plasma levels of MDA decreased (p<0.05) in groups B, C, D, which were treated with Se- VE, whereas levels of GSH-Px, GSH were found to increase only for group D (p<0.05). Plasma urea, creatinine levels improved in the treatment groups compared to group A (p<0.001). Histopathological changes caused by CDDP were also significantly improved after Se-VE treatment (p<0.05). CONCLUSIONS: Oxidative stress increases with CDDP-induced nephrotoxicity in rats. Se-VE supplementation might thus play a role in the prevention of CDDP-induced nephrotoxicity in patients.

The effect of octreotide, an analog of somatostatin, on bleomycin-induced interstitial pulmonary fibrosis in rats.

In this study, octreotide (OCT), a synthetic somatostatin analog, was tested for its beneficial effects in the prevention of interstitial pulmonary fibrosis (IPF) induced by bleomycin (BLM) in rats by histological examination and by evaluating tissue OH-proline levels. Thirty male Wistar rats were divided randomly into three groups: group I: intratracheal (i.t.) BLM (7.5 mg/kg, single dose) + saline solution [0.9% NaCl, subcutaneously (s.c.), once-daily for 7 days]; group II: i.t. BLM (7.5 mg/kg, single dose) + OCT acetate (82.5 µg/kg, s.c., once-daily for 7 days); and the control group. At the end of the 7 days, lung tissues were excised and examined by histopathological methods. Levels of tissue hydroxyproline (OH-proline) were determined. BLM administration resulted in prominent histopathologic findings, such as diffuse alveolar damage and interstitial pulmonary fibrosis, as well as a significant increase in OH-proline level, as compared to controls. OCT application explicitly attenuated the histopathologic changes to a significant extent. OCT decreased paranchymal fibrosis and structural deformities in BLM-induced lung fibrosis. These results suggest that OCT administration to rats with BLM-induced IPF has a protective effect. Further studies are necessary to reveal the molecular mechanism(s) of OCT-induced protective effect.

Human telomerase reverse transcriptase expression in colorectal tumors: correlations with immunohistochemical expression and clinicopathologic features.

Human telomerase reverse transcriptase (hTERT) proteins in colorectal cancer investigated in several studies, but to our knowledge, hTERT expression has not been evaluated in all of colorectal tumors, including hyperplastic polyps (HPs), adenomas, and carcinomas, on paraffin-embedded tissue sections. The aim of the present study is to investigate immunohistochemical hTERT expression and its relationship with the clinicopathologic features in a spectrum of colorectal tumors. In this study, hTERT expression was determined in HP (n = 20), adenomatous polyp (AP) (n = 20), colorectal adenocarcinomas (n = 20), and normal mucosa (n = 20) by immunohistochemical method. The findings were correlated with the clinicopathologic features. The staining level of hTERT in adenomas and carcinomas was significantly higher than in normal tissues (P < .05). There was also significant difference between HP and AP (P < .05). Level of hTERT in carcinomas was higher than in adenomas, but the difference was of no statistical significance (P > .05). There was no significant association of hTERT expression in cancerous, precancerous, or normal mucosa related to clinicopathologic parameters including age, sex, and size of lesion, (P > .05), but only association with histologic grade for carcinoma was found (P < .05). Levels of hTERT by immunohistochemistry demonstrated that the expression of hTERT was very little in normal mucosa and HP, moderate in AP, and highest in carcinoma. Thereby, hTERT expression may use the aggressiveness of the colorectal tumors as a marker, but it is not related to clinicopathologic data.

Malignancies diagnosed during pregnancy and treated with chemotherapy or other modalities (review of 27 cases): multicenter experiences.

BACKGROUND: Cancer is the second leading cause of death in women of reproductive age. The most common tumors diagnosed during pregnancy are breast and cervix cancer, Hodgkin lymphoma and non-Hodgkin lymphoma, leukemias, and malignant melanoma. The aim of therapy in pregnancy is to give optimal treatment to the mother without harm to the fetus. In the first trimester, organogenesis continues, so chemotherapy should not be given because of increasing risk of spontaneous abortion, fetal malformation, and mortality. We evaluated mostly seen tumors during pregnancy and assessed treatment type and outcome of pregnancy after chemotherapy in our population. METHODS: We retrospectively analyzed 27 patients who have been treated during pregnancy or after the delivery because of several malignancies. RESULTS: The tumors associated with pregnancy were breast cancer, hematologic malignancies,gynecologic malignancies, sarcomas, and others. The chemotherapy regimens were given in 17 of 27 patients in the second or third trimester of pregnancy. Four of the patients were diagnosed with cervical cancer, hemangiopericytoma, chronic myeloid leukemia,and breast cancer during the first trimester, so their pregnancies were ended by therapeutic abortion. Although 1 of the 3 fetuses who were exposed to chemotherapy in utero at the second or third trimester was born prematurely and low birth weight was diagnosed in the other 2 fetuses, fetal malformation was not seen in any of them. There were 7 normal and 9 cesarean deliveries. Twenty-three healthy babies survived from 27 pregnancies, of whom 17 babies were exposed to chemotherapeutic agents. CONCLUSIONS: We reported herein 27 patients with malignancies diagnosed during pregnancy; 17 patients received chemotherapy during the gestational period without any fetal or maternal abnormalities. Because of the low incidence of malignancy during pregnancy, our report is noteworthy.

Ghrelin and obestatin expression in oral squamous cell carcinoma: an immunohistochemical and biochemical study.

The underlying molecular mechanism of carcinogenesis in oral squamous cell carcinoma (OSCC) is poorly understood and appears to be controlled on many genetic, environmental, and hormonal factors. Obestatin and ghrelin, two recently discovered hormones, are co-expressed in endocrine cells. The purpose of this investigation was to examine the immunohistochemical features of OSCCs in relation to the tissue concentration of ghrelin and obestatin. The association between OSCC and Epstein Barr Virus (EBV) status was also explored. The expression of ghrelin and obestatin was examined by immunohistochemistry and immunoassay in oral biopsy specimens: 10 benign squamous epithelial cell samples, 10 microinvasive squamous cell carcinomas, and seven well-differentiated and seven poorly differentiated OSCCs. The presence of EBV was evaluated in these samples using immunohistochemistry. The concentrations of ghrelin and obestatin in tissue homogenates were measured by RIA and ELISA, respectively. Squamous cell carcinomas and benign tissue samples were positive for anti-EBV antibody, and obestatin and ghrelin were shown to be co-expressed in all stratified squamous epithelium samples. Expression of ghrelin and obestatin was decreased or absent in OSCCs in relation to the invasiveness of the carcinoma; ghrelin and obestatin levels in cancerous tissue homogenates were lower than in benign tissue homogenates. These results indicate that the concentrations and distribution of immunoreactive obestatin and ghrelin might be helpful in distinguishing OSCC from benign tumors. Maintaining normal levels of these hormones might be required for regulation of normal cell division. However, detailed studies will be required for better understanding of the complex mechanism of carcinogenesis relating to OSCCs.

Protective effect of octreotide on intra-tracheal bleomycin-induced oxidative damage in rats.

The present study is aimed at determining the effect of parenteral octreotide against oxidative damage caused by intra-tracheal bleomycin (BLM) administration. A total of 30 male Wistar rats randomly divided into three groups (control, bleomycin alone, and bleomycin and octreotide) were used in the study. A group of animals received a single dose of intra-tracheal bleomycin (7.5mg/kg). Animals in another group, which also received intra-tracheal bleomycin, were given 82.5 microg/kg octreotide via i.m. injection for a week. Animals in the control group received neither bleomycin nor octreotide. All animals were sacrificed at the end of the experiment. Serum levels of malondialdehyde, vitamins A, E, and C, selenium levels were determined. In addition, glutathion peroxidase activity levels in erythrocytes were also determined. Malondialdehyde levels and glutathion peroxidase activity were increased whereas antioxidant vitamin levels were decreased significantly in animals that received only bleomycin compared to control animals (p<0.05). The values in rats that received bleomycin and octreotide were found to be closer to the control group (p<0.05). Selenium levels in animals that received only bleomycin were determined to be reduced compared to controls (p<0.05). On the other hand, selenium levels in bleomycin and octreotide groups were similar to control values in (p<0.05). In conclusion, bleomycin induces a severe stress and more importantly increases the amount of free radicals whereas octreotide administration reduces this oxidative damage significantly.

Efficacy and toxicity of gemcitabine and pegylated liposomal Doxorubicin in recurrent platinum-resistant/refractory epithelial ovarian cancer.

BACKGROUND: Treatment of patients with platinum resistant/refractory ovarian cancer is a significant problem. In this study, we evaluated the efficacy and tolerability of the combination of gemcitabine and pegylated liposomal doxorubicin (PLD) in patients with platinum resistant/refractory ovarian cancer. PATIENTS AND METHODS: We retrospectively evaluated the activity and toxicity of gemcitabine and PLD combination in 35 patients with recurrent platinum resistant/refractory ovarian cancer who had been treated and followed up in 7 centers in Turkey between December 2005 and June 2008. The patients received gemcitabine 1.000 mg/m(2) on day 1 and 8, and PLD 25 mg/m(2) on day 1 every 28 days. RESULTS: A total of 187 cycles (median, 6 cycles) were delivered. An objective response rate of 28,6 % (1 complete, 9 partial response) was achieved. Additionally, 16 patients (45.7 %) had disease stabilization. The median time-to-progression was 6 months (95 % confidence interval, 4-8) and the median overall survival was 17 months (95 % confidence interval, 12-22). Grade 3-4 hematologic toxicities were as follows: leucopenia (14.3%), neutropenia (8.6%), and anemia (2.9%). One febrile neutropenic episode (2.9%) was observed. Non-hematologic toxicity was well tolerated and easily managed and no grade 3-4 palmoplantar erytrodysestesia (PPE) was observed. CONCLUSION: The combination of gemcitabine and PLD is an effective and tolerable treatment option, with 74.3 % disease control rate for patients with platinum resistant/refractory ovarian cancer.

Expression of obestatin and ghrelin in papillary thyroid carcinoma.

Ghrelin and obestatin are two peptide hormones with opposing roles in the control of appetite: orexigenic and anorexigenic, respectively. Loss of appetite is a common, serious complication of many forms of malignancy. The goals of this study were to investigate: (i) whether there are differences in ghrelin and obestatin peptide expression in thyroid tissues from a series of papillary carcinoma cases and normal controls, and (ii) whether there are correlations between tissue ghrelin and obestatin levels in series of papillary carcinoma cases and normal controls. Immunohistochemical analysis showed that in sections of benign human thyroid tissue, anti-ghrelin antibody reacted with intense staining in colloid-filled follicles. In benign thyroid tissues, colloids displayed plentiful dispersion in comparison with papillary microcarcinomas, whereas colloids in malignant thyroid tissues were uncommon. We found markedly lower tissue ghrelin levels in thyroid tissue of patients with papillary carcinomas, compared with normal thyroid tissues (P = 0.001). Immunohistochemical analysis also showed that obestatin in papillary carcinoma stained positively to various degrees. Obestatin tissue levels in papillary carcinomas tended to be slightly higher than those in normal thyroid tissue, but this was not statistically significant (P = 0.29). We also report that thyroid tissue of patients with Hashimoto's thyroiditis produced ghrelin and obestatin at similar levels as in normal thyroid tissue, even though colloid in Hashimoto's disease is scarce. We conclude that depressed expression of ghrelin, but not obestatin, is specific to papillary carcinoma, and this difference might constitute a diagnostic tool to differentiate papillary carcinoma from normal thyroid tissue. We currently do not know how these peptides are regulated and what factors are involved in papillary carcinoma, which inhibit the expression of ghrelin but not obestatin. This issue warrants further studies.

Uterine primitive neuroectodermal tumor: a case report.

BACKGROUND: Primitive neuroectodermal tumors of uterus (PNET) are extremely rare in tumors of the female genital system and therefore there is no sufficient information about their diagnosis, treatment, and follow-up. CASE: The case is a 32-year-old, operated in emergency conditions due to intra-abdominal hemorrhage, and discusses our diagnosis and treatment approaches in the light of literature data. CONCLUSION: To the best of our knowledge, this is first report of uterine PNET that presented with intraabdominal hemorrhage due to uterine rupture. Despite advances in therapy, the prognosis is poor. The low number of these cases precludes accurate standardization of therapy.