Effect of physical exercise on the hippocampus and global grey matter volume in breast cancer patients: A randomized controlled trial (PAM study).

BACKGROUND: Physical exercise in cancer patients is a promising intervention to improve cognition and increase brain volume, including hippocampal volume. We investigated whether a 6-month exercise intervention primarily impacts total hippocampal volume and additionally hippocampal subfield volumes, cortical thickness and grey matter volume in previously physically inactive breast cancer patients. Furthermore, we evaluated associations with verbal memory. METHODS: Chemotherapy-exposed breast cancer patients (stage I-III, 2-4 years post diagnosis) with cognitive problems were included and randomized in an exercise intervention (n = 70, age = 52.5 ± 9.0 years) or control group (n = 72, age = 53.2 ± 8.6 years). The intervention consisted of 2x1 hours/week of supervised aerobic and strength training and 2x1 hours/week Nordic or power walking. At baseline and at 6-month follow-up, volumetric brain measures were derived from 3D T1-weighted 3T magnetic resonance imaging scans, including hippocampal (subfield) volume (FreeSurfer), cortical thickness (CAT12), and grey matter volume (voxel-based morphometry CAT12). Physical fitness was measured with a cardiopulmonary exercise test. Memory functioning was measured with the Hopkins Verbal Learning Test-Revised (HVLT-R total recall) and Wordlist Learning of an online cognitive test battery, the Amsterdam Cognition Scan (ACS Wordlist Learning). An explorative analysis was conducted in highly fatigued patients (score of ≥ 39 on the symptom scale 'fatigue' of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire), as previous research in this dataset has shown that the intervention improved cognition only in these patients. RESULTS: Multiple regression analyses and voxel-based morphometry revealed no significant intervention effects on brain volume, although at baseline increased physical fitness was significantly related to larger brain volume (e.g., total hippocampal volume: R = 0.32, B = 21.7 mm3, 95 % CI = 3.0 - 40.4). Subgroup analyses showed an intervention effect in highly fatigued patients. Unexpectedly, these patients had significant reductions in hippocampal volume, compared to the control group (e.g., total hippocampal volume: B = -52.3 mm3, 95 % CI = -100.3 - -4.4)), which was related to improved memory functioning (HVLT-R total recall: B = -0.022, 95 % CI = -0.039 - -0.005; ACS Wordlist Learning: B = -0.039, 95 % CI = -0.062 - -0.015). CONCLUSIONS: No exercise intervention effects were found on hippocampal volume, hippocampal subfield volumes, cortical thickness or grey matter volume for the entire intervention group. Contrary to what we expected, in highly fatigued patients a reduction in hippocampal volume was found after the intervention, which was related to improved memory functioning. These results suggest that physical fitness may benefit cognition in specific groups and stress the importance of further research into the biological basis of this finding.

Effect of physical exercise on cognitive function after chemotherapy in patients with breast cancer: a randomized controlled trial (PAM study).

BACKGROUND: Up to 60% of breast cancer patients treated with chemotherapy is confronted with cognitive problems, which can have a significant impact on daily activities and quality of life (QoL). We investigated whether exercise training improves cognition in chemotherapy-exposed breast cancer patients 2-4 years after diagnosis. METHODS: Chemotherapy-exposed breast cancer patients, with both self-reported cognitive problems and lower than expected performance on neuropsychological tests, were randomized to an exercise or control group. The 6-month exercise intervention consisted of supervised aerobic and strength training (2 h/week), and Nordic/power walking (2 h/week). Our primary outcome was memory functioning (Hopkins Verbal Learning Test-Revised; HVLT-R). Secondary outcomes included online neuropsychological tests (Amsterdam Cognition Scan; ACS), self-reported cognition (MD Anderson Symptom Inventory for multiple myeloma; MDASI-MM), physical fitness (relative maximum oxygen uptake; VO2peak), fatigue (Multidimensional Fatigue Inventory), QoL (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire; EORTC QLQ C-30), depression (Patient Health Questionnaire-9, Hospital Anxiety and Depression Scale; HADS), and anxiety (HADS). HVLT-R total recall was analyzed with a Fisher exact test for clinically relevant improvement (≥ 5 words). Other outcomes were analyzed using multiple regression analyses adjusted for baseline and stratification factors. RESULTS: We randomized 181 patients to the exercise (n = 91) or control group (n = 90). Two-third of the patients attended ≥ 80% of the exercise sessions, and physical fitness significantly improved compared to control patients (B VO2peak 1.4 ml/min/kg, 95%CI:0.6;2.2). No difference in favor of the intervention group was seen on the primary outcome. Significant beneficial intervention effects were found for self-reported cognitive functioning [MDASI-MM severity (B-0.7, 95% CI - 1.2; - 0.1)], fatigue, QoL, and depression. A hypothesis-driven analysis in highly fatigued patients showed positive exercise effects on tested cognitive functioning [ACS Reaction Time (B-26.8, 95% CI - 52.9; - 0.6) and ACS Wordlist Learning (B4.4, 95% CI 0.5; 8.3)]. CONCLUSIONS: A 6-month exercise intervention improved self-reported cognitive functioning, physical fitness, fatigue, QoL, and depression in chemotherapy-exposed breast cancer patients with cognitive problems. Tested cognitive functioning was not affected. However, subgroup analysis indicated a positive effect of exercise on tested cognitive functioning in highly fatigued patients. Trial Registration Netherlands Trial Registry: Trial NL5924 (NTR6104). Registered 24 October 2016, https://www.trialregister.nl/trial/5924 .

The effect of chemotherapy on subjective cognitive function in younger early-stage breast cancer survivors treated with chemotherapy compared to older patients.

PURPOSE: To evaluate the impact of chemotherapy on subjective cognitive functioning according to age in a large cohort of breast cancer patients. METHODS: Within the UMBRELLA cohort, 715 patients with early-stage primary invasive breast cancer (T1-3N0-1M0) were selected. Subjective cognitive function was assessed by means of the EORTC QLQ-C30 up to 24 months and compared between patients treated with and without chemotherapy, for three different age strata (355 patients < 55 years, 240 patients aged 55-65 years, and 120 patients > 65 years). Differences between chemotherapy and non-chemotherapy patients by age at different time points were assessed by linear mixed-effect models correcting for age, tumor stage, educational level, endocrine therapy, anxiety, and depression. RESULTS: In total, 979 patients from the UMBRELLA cohort were included, of which 715 (73%) responded to baseline and at least one follow-up questionnaire. Questionnaire response rates ranged between 92 and 70%. The proportion of patients treated with chemotherapy decreased with age: 64% (n = 277) in patients < 55 years, 45% (n = 107) in patients 55-65 years, and 23% (n = 27) in patients > 65 years. Chemotherapy was associated with reduced subjective cognitive functioning. The impact of chemotherapy on subjective cognitive function was most pronounced in patients < 55 years, followed by those between 55 and 65 years. In the youngest age groups, patients treated with chemotherapy had significantly lower cognitive functioning up to 24 months. In women over 65 years, subjective cognitive functioning was comparable between patients treated with and without chemotherapy. CONCLUSION: This study confirms that chemotherapy is associated with impaired subjective self-reported cognitive functioning in breast cancer patients, and the effect persists at least up to 2 years after diagnosis. The impact of chemotherapy on self-reported cognitive functioning in the first 24 months is most pronounced in younger patients, especially those under 55 years of age.

Gemcitabine combined with the monoclonal antibody nimotuzumab is an active first-line regimen in KRAS wildtype patients with locally advanced or metastatic pancreatic cancer: a multicenter, randomized phase IIb study.

BACKGROUND: This randomized study was designed to investigate the superiority of gemcitabine (gem) plus nimotuzumab (nimo), an anti-epidermal growth factor receptor monoclonal antibody, compared with gem plus placebo as first-line therapy in patients with advanced pancreatic cancer. PATIENTS AND METHODS: Patients with previously untreated, unresectable, locally advanced or metastatic pancreatic cancer were randomly assigned to receive gem: 1000 mg/m2, 30-min i.v. once weekly (d1, 8, 15; q29) and nimo: fixed dose of 400 mg once weekly as a 30-min infusion, or gem plus placebo, until progression or unacceptable toxicity. The primary end point was overall survival (OS), secondary end points included time to progression, overall response rate, safety and quality of life. RESULTS: A total of 192 patients were randomized, with 186 of them being assessable for efficacy and safety (average age 63.6 years). One-year OS/progression-free survival (PFS) was 34%/22% for gem plus nimo compared with 19%/10% for gem plus placebo (HR = 0.69; P = 0.03/HR = 0.68; P = 0.02). Median OS/PFS was 8.6/5.1 months for gem plus nimo versus 6.0/3.4 mo in the gem plus placebo group (HR = 0.69; P = 0.0341/HR = 0.68; P = 0.0163), with very few grade 3/4 toxicities. KRAS wildtype patients experienced a significantly better OS than those with KRAS mutations (11.6 versus 5.6 months, P = 0.03). CONCLUSION: This randomized study showed that nimo in combination with gem is safe and well tolerated. The 1-year OS and PFS rates for the entire population were significantly improved. Especially, those patients with KRAS wildtype seem to benefit. The study was registered as protocol ID OSAG101-PCS07, NCT00561990 and EudraCT 2007-000338-38.

EVALUATION OF PREIMPLANTATION GENETIC ANEUPLOIDY SCREENING CASES AT A REFERENCE GENETICS CENTER: 10 YEARS' EXPERIENCE.

The aim of this study is to review and evaluate our preimplantation genetic screening (PGS) records in terms of their demographic data, indications, cytogenetic results, pregnancy outcomes and discuss these findings in different aspects. PGS was performed in a total of 84 couples (87 cycles) between the period 2005 to 2015. Biopsied blastomeres from embryos on day 3 were fixed and fluorescence in situ hybridization was carried out for chromosomes 13, 16, 18, 21, 22, X and Y depending on the indication. The diagnostic and clinical data were retrospectively evaluated. A total of 450 blastomeres were biopsied. Ninety-eight of them were found to be suitable for transfer. They were transferred to 72 patients in 75 cycles resulting in 23 pregnancies and 20 healthy births. The most common indication was unexplained infertility. The implantation rate was calculated as 23.4% whereas the take-home baby rate was 26.6% per transfer. The highest rate of healthy living births is achieved in patients having low grade maternal mosaic sex chromosomal aneuploidy. All living births achieved by PGS had normal chromosomal structure which we can propose it as an alternative test for couples at risk to select normal embryos to improve the outcomes of assisted reproductive procedures and to avoid the transfer of chromosomally unbalanced and multiple embryos.

Altered Stem Cell Receptor Activity in the Ovarian Surface Epithelium by Exogenous Zinc and/or Progesterone.

BACKGROUND: Ovarian surface epithelium (OSE) has the characteristics of a stem cell and the potential for differentiation. Previous studies on this subject have succeeded in deriving oocytes from OSE stem cells, leading to the belief that OSE could be used for infertility treatment. METHODS: Each rat (n = 10) was subjected to zinc and/or progesterone injection for 5 days after conception. After a 6-day implantation period, ovarian tissues were removed and comprehensive immunohistochemical analysis of stem cell markers was conducted: Sox2, Klf4, Oct3/4, c-Myc, CD117, CD90, SSEA-1 and Notch pathway analysis; Notch1, Jagged1, and Delta1 in the OSE and ovarian stromal cells were evaluated after treatment with zinc, progesterone, or both. RESULTS: Progesterone moderately affected Sox2 expression (p < 0.001), while zinc application strongly affected Klf4 and Oct3/4 and immunoreactivity (p < 0.001). CD90 immunoreactivity was decreased in the OSE and stroma of the progesterone group (p = 0.006) compared with the zinc (p = 0.244) and zinc/progesterone groups (p = 0.910). On the other hand, SSEA-1 showed moderate staining in the OSE and weak staining in stromal cells in animals treated with zinc (p = 0.727), progesterone (p = 0.626), and zinc/progesterone (p = 0.371), with no differences compared with control. Zinc application affected Notch pathway immunoreactivity, with a significant increase in Notch1 (p = 0.0015) and Jagged1 (p < 0.001). CONCLUSIONS: The expression of putative stem cell markers in the OSE was verified and stem cell receptor activity was raised in the OSE and ovarian stromal cells by zinc and progesterone. Thus, this increased expression allows the therapeutic use of zinc and progesterone in ovary-related infertility and brings a different perspective to reproductive medicine.

What constitutes best supportive care in the treatment of advanced non-small cell lung cancer patients?--Results from the lung cancer economics and outcomes research (LUCEOR) study.

BACKGROUND: A significant proportion of advanced non-small cell lung cancer (NSCLC) patients receive supportive treatments to manage disease-related symptoms either separately or combined with systemic anti-cancer therapy (SACT). This supportive treatment is commonly referred to as best supportive care (BSC). Definition of BSC in clinical trials and its description in published comparative and real-life NSCLC studies is limited. The lack of a consensus BSC definition makes detailed evaluations of clinical trials and comparisons between clinical trials problematic. METHODS: Data were collected as part of the lung cancer economics and outcomes research (LUCEOR) study. Information on treatment and treatment outcomes from deceased stage IIIb/IV NSCLC patients across ten countries was retrospectively collected from medical records. BSC was defined as the best care available as judged by the attending physicians. RESULTS: A total of 1327 patients' data were analyzed. Of those, 774/1327 (58%), 316/631 (50%), 123/259 (47%), 25/56 (45%) and 15/26 (58%) were administered treatment defined as BSC with first, second, third, fourth and fifth-line SACT respectively. In total, 346/678 (51%), 149/335 (45%), 86/176 (49%), 11/28 (39%) and 13/25 (52%) of patients were administered treatment defined as BSC in the end-of-life setting after finishing first, second, third, fourth and fifth-line SACT respectively. BSC therapies could be grouped into 24 different categories. The most common elements did not vary substantially whether given with SACT (irrespective of treatment line), in the end-of-life setting, or between countries. The commonest categories of BSC were narcotic and non-narcotic analgesics, corticosteroids and gastrointestinal medication. CONCLUSION: There were no major differences in what constituted BSC. BSC included in all instances narcotic and non-narcotic analgesics, corticosteroids and gastrointestinal medication. To our knowledge this is the first study attempting to describe BSC in routine clinical practice. This study's results could help define a practical, up to date, evidence-based definition of BSC.

Alveolar rhabdomyosarcoma originating from the uterine cervix.

Cervical alveolar rhabdomyosarcoma is a rare condition associated with poor prognosis. An 18-year-old patient presented with vaginal bleeding and a protruding mass from the vagina. Biopsy of the mass revealed alveoler rhabdomyosarcoma (ARMS), and radiological evaluation demonstrated that it originated from the uterine cervix. First, Wertheim's operation was carried out followed by four cycles of vincristine, actinomycine-D, ifosfamide (VAI) chemotherapy. However, the disease relapsed within three months, and the patient died of disease progression. Despite combination treatment, we could not achieve a desirable survival advantage in ARMS. Future studies may unveil the genomic profile of this rare condition, leading to invention of targeted therapies, which is the emerging trend in the treatment of sarcomas.

Randomized phase III study comparing irinotecan combined with 5-fluorouracil and folinic acid to cisplatin combined with 5-fluorouracil in chemotherapy naive patients with advanced adenocarcinoma of the stomach or esophagogastric junction.

BACKGROUND: We aimed to establish the superiority (or noninferiority if superiority was not achieved) in terms of time to progression (TTP) of irinotecan/5-fluorouracil (IF) over cisplatin/5-fluorouracil (CF) in chemonaive patients with adenocarcinoma of the stomach/esophagogastric junction. PATIENTS AND METHODS: Patients received either IF: i.v. irinotecan 80 mg/m(2) 30 min, folinic acid 500 mg/m(2) 2 h, 5-fluorouracil (5-FU) 2000 mg/m(2) 22 h, for 6/7 weeks or CF: cisplatin 100 mg/m(2) 1-3 h, with 5-FU 1000 mg/m(2)/day 24 h, days 1-5, every 4 weeks. RESULTS: In all, 333 patients were randomized and treated (IF 170, CF 163). Patient characteristics were balanced except more IF patients had Karnofsky performance status 100%. TTP for IF was 5.0 months [95% confidence interval (CI) 3.8-5.8] and 4.2 months (95% CI 3.7-5.5) for CF (P = 0.088). Overall survival (OS) was 9.0 versus 8.7 months, response rate 31.8% versus 25.8%, time to treatment failure (TTF) 4.0 versus 3.4 months for IF and CF, respectively. The difference in TTF was statistically significant (P = 0.018). IF was better in terms of toxic deaths (0.6% versus 3%), discontinuation for toxicity (10.0% versus 21.5%), severe neutropenia, thrombocytopenia and stomatitis, but not diarrhea. CONCLUSION: IF did not yield a significant TTP or OS superiority over CF, and the results of noninferiority of IF were borderline. However, IF may provide a viable, platinum-free front-line treatment alternative for metastatic gastric cancer.

Docetaxel and platinum combination chemotherapy in locally advanced or metastatic head and neck cancer.

PURPOSE: To assess the efficacy and toxicity of the docetaxel and platinum combination in patients with locoregionally advanced or metastatic squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS: A total of 24 patients with metastatic or locoregionally advanced SCCHN treated with docetaxel and platinum combination chemotherapy were retrospectively reviewed. All of them had histologically proven SCCHN, measurable disease and ECOG performance status of 2 or less, and were treated with docetaxel 75 mg/m(2) as a 60 min i.v. infusion on day 1, followed by cisplatin 75 mg/m(2) or carboplatin AUC 6 as a 60 min i.v. infusion on day 1 every 3 weeks, until disease progression or unacceptable toxicity. Patients were evaluated for response, survival and toxicity. RESULTS: Seven (29%) patients showed partial response (PR) and 1 (4%) complete response (CR) for an overall response rate of 33%. Twelve (50%) patients had stable disease (SD). Disease control rate was 83%. The median follow-up time was 26.4 months (range 2-127), the median time to progression 16 months (range 2-20), and the median overall survival 19 months (range 2-22). Grade 3-4 hematologic toxicity occurred in 13 (54%) patients. Febrile neutropenia was seen in 5 (21%) patients. CONCLUSION: Docetaxel plus cisplatin or carboplatin is an effective regimen with acceptable safety profile for palliation of locally advanced or metastatic SCCHN.

Laparoscopic resection or sonography-guided vaginal aspiration of endometriomas prior to ICSI-ET does not worsen treatment outcomes.

OBJECTIVE: To evaluate the effect of the management modality of ovarian endometriomas on ovarian response to COH (controlled ovarian hyperstimulation) and ART (assisted reproductive technology) treatment outcome. DESIGN: Retrospective case control study. SETTING: Ege University Infertility-Family Planning Research and Treatment Center. PATIENTS: 115 cycles of 84 patients who underwent ICSI-ET (intracytoplasmic sperm injection-embryo transfer) with ejaculated sperm were enrolled in the study. The endometrioma resection group (Group I) was comprised of 36 cycles in 29 patients who were treated with laparoscopic endometrioma cyst resection prior to treatment; endometrioma aspiration (Group II) was comprised of 26 cycles in 15 patients whose endometriomas were aspirated prior to treatment; and the control group (Group III) was comprised of 53 cycles in 40 patients for whom the only infertility cause was the tubal factor. INTERVENTIONS: ICSI-ET treatment, laparascopic ovarian endometrioma cyst resection, transvaginal ultrasonography-guided endometrioma cyst aspiration. MAIN OUTCOMES MEASURES: COH results and ICSI-ET treatment outcomes. RESULTS: The groups were similar in all characteristics except for the mean age of the patients in group II being older than those in group I. Gonadotropin consumption was higher, peak estradiol level lower, and the number of oocytes less in the laparascopic resection group (Group I) with respect to the control group. The number of follicles was lower in the cyst aspiration group (Group II) with respect to the control group. The number of follicles larger than 15 mm, number of metaphase II oocytes, the fertilization, pregnancy and implantation rates were similar in all three groups. CONCLUSION: Interventions (laparascopic endometrioma resection, transvaginal ultrasound-guided endometrioma cyst aspiration) performed on endometriomas prior to ART treatment do not worsen the treatment outcome.

Arsenic trioxide exposure to ovarian carcinoma cells leads to decreased level of topoisomerase II and cytotoxicity.

The objective of this study was to investigate the effect of arsenic trioxide (As(2)O(3)) on topoisomerase II levels using western blotting method on MDAH 2774 ovarian carcinoma cell culture. Experimental designs were established to determine the cytotoxic effects of As(2)O(3) on MDAH 2774 cells and the IC50 (fatal dose for the 50% of cells) value. Cytotoxicity experiments were carried out using various concentrations of As(2)O(3). The 2,3-bis[2-methyloxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxanilide (XTT) and trypan blue dye-exclusion tests were used to evaluate cytotoxicity. Topoisomerase II expressions were investigated using western blotting method with various concentrations of As(2)O(3). Densitometric analysis of topoisomerase 2 bands was carried out using Quantity One 1-D analysis software (Bio-Rad USA, Life Science Research, Hercules, CA). IC50 value of As(2)O(3) was found to be 5 x 10(-6) M for MDAH 2774 cells. When the bands were evaluated, it was observed that there was a decrease in topoisomerase II levels in MDAH 2774 cells with increasing concentrations of As(2)O(3). It was also observed by the densitometric analysis that topoisomerase II expression ratios of MDAH 2774 cells were decreased by approximately 50% at this concentration. Topoisomerase II levels were significantly decreased with the increasing concentrations of As(2)O(3). Inhibition of topoisomerase II enzyme was one of the antiproliferative influence mechanisms of As(2)O(3).

Successful treatment of liver transplant-associated Kaposi's sarcoma with long-term vincristine.

Kaposi's sarcoma has a higher incidence in organ transplant recipients. We report on a 41-year-old Turkish man with liver transplantation-associated Kaposi's sarcoma that involved the skin and the gut. Immediately after discontinuation of immunosuppressive medication, there was an acute rejection episode. After controlling the acute rejection with steroids, the immunosuppressive treatment was continued together with vincristine, which resulted in disease remission. After 6 months, withdrawal of vincristine lead to relapse of the disease, prompting commencement of vincristine again, which has maintained the patient in remission for more than 3 years without any significant side effects. In conclusion, long-term vincristine may be an effective, safe treatment option for Kaposi's sarcoma.

Predictive value of serum interleukin-8 levels in ovarian cancer patients treated with paclitaxel-containing regimens.

Previous findings showed that paclitaxel induces interleukin-8 (IL-8) transcription and secretion in ovarian cancer cells in vitro. We hypothesized that paclitaxel treatment, which is a standard care for ovarian cancer patients, may increase the secretion of IL-8, resulting in the elevated serum IL-8 levels. In this study, we investigated the relationship between paclitaxel exposure and IL-8 levels of an ovarian and a breast carcinoma cell line in vitro and serums of patients with ovarian carcinoma. Both MDAH 2774 ovarian and MCF-7 breast carcinoma cell lines were sensitive to paclitaxel-mediated cytotoxicity. However, supernatant levels of IL-8 assessed by enzyme-linked immunosorbent assay before and after treatment with different concentrations of paclitaxel were significantly lower in MCF-7 than in MDAH 2774. Serum IL-8 levels were measured in serum samples from patients with ovarian carcinoma before and after paclitaxel-containing treatment regimens. Forty-eight patients were included in the study. The basal level of IL-8 after paclitaxel-containing treatment was found to be significantly higher in the serums of patients who had high tumor burden than in patients who had optimal debulking surgery and low tumor burden. These data strongly suggest that IL-8 may be an important predictive marker for tumor volume as well as sensitivity to paclitaxel.

Potential predictive factors for response to weekly paclitaxel treatment in patients with metastatic breast cancer.

The authors compare results obtained from weekly paclitaxel treatment in advanced breast cancer patients with biological and clinical prognostic factors. Expression of c-erbB-2, Ki-67, p53 and hormone receptors (HR) was examined by immunohistochemistry in samples of breast tissue from 30 patients. Univariate analysis showed that Ki-67 positivity and low performance status (PS) were associated with poor outcome (P <0.05). We observed that expression of p53 and c-erbB-2 did not have any negative effect on response to chemotherapy and survival. HR-negative patients had better response and slightly statistically significant overall survival (OS) rates compared to HR-positive patients (P >0.05). In a multivariate analysis low PS was the only significant predictor of shorter survival (P <0.05). In conclusion, while the expression of p53 and c-erbB-2 did not have any effect on treatment results, negative Ki-67 expression and negative HR status were associated with better OS in this patient population. PS was the only significant predictor for OS.

Therapy, outcome and analysis of c-kit expression in patients with extrapulmonary small cell carcinoma.

In this study, we aimed to investigate the clinicopathological characteristics with special emphasis on c-kit expression and the treatment results of patients with extrapulmonary small cell carcinoma (EPSCC). The medical records of the patients with EPSCC were reviewed, and the data regarding patient and tumour characteristics, treatment and clinical outcome were retrieved and analysed. A total of 28 patients with the diagnosis of EPSCC were identified. There were 19 males and 9 females, with a mean age of 56.5 years. Patients with limited disease (LD) (n = 13) were treated with surgery, chemotherapy (CT) and radiotherapy with different sequences. Patients with extensive disease (ED) (n = 15) were mainly treated with combination CT. The median overall survival was 14.5 months in patients with LD compared to 11 months in those with ED (p = 0.029). Ten patients (36%) showed c-kit overexpression. There was no significant difference between the survival of c-kit-positive and c-kit-negative patients (p = 0.367). In conclusion, our study demonstrates that the prognosis of EPSCC is poor despite currently available treatments. C-kit may be considered as a potential target for novel therapeutical approaches.

Bioembolisation for unresectable hepatocellular carcinoma: preliminary results of a translational research study.

Lack of effective treatment for surgically unresectable hepatocellular carcinoma has made this disease dismal. Although, systemic and/or locoregional chemotherapy and chemo-embolization are among the established treatment options, the results of these modalities are still far from being satisfactory. Systemic interferon administration is also used for the treatment of this disease however it has high toxicity rates. We conducted a pharmacology guided phase I/II study with the aim to explore the effect of hypoxy and interferon alpha-2a in vitro using the HepG2 Hepatoma cell line. We then translated the in-vitro results to the clinical setting and designed a treatment protocol. This schema consisted of lipiodol embolisation via a hepatic artery port in between two sets of seven loco-regional injections of IFNalpha-2a, 3 MU every other day. The in-vitro study revealed the best sequence of hypoxy and IFN as IFN-Hypoxy-IFN. Based on this finding, ten patients with HCC were treated with loco-regional IFN and lipiodolisation. Seven of them achieved partial response and the mean duration of response was 10 months. There was no Grade 4 toxicity. In conclusion, our preliminary clinical results suggest that the combined use of IFN and lipiodolisation in the optimal sequence may provide a new therapeutic option for patients with HCC.

Screening of Y chromosome microdeletion which contains AZF regions in 71 Turkish azoospermic men.

Screening of Y chromosome microdeletion which contains AZF regions in 71 turkish azoospermic men: In 71 Turkish men Y chromosome microdeletions have been studied before intracytoplasmic sperm injection (ICSI). DNA samples were amplified with 18 STS primers of the azoospermia factor (AZF) region on the Y chromosome by using multiplex polymerase chain reaction (PCR). Microdeletions were detected in 4 azoospermic men (5.6 %); one with a deletion in the AZFb region, while the 3 others had a large deletion extending over multiple chromosomal regions (AZFb+c+d and AZFa+b+c+d). In the patients with microdeletion, no spermatogenetic activity could be detected in testis biopsies. This result confirms the idea that Y chromosome microdeletion analysis is important in investigating the possibility of finding sperm in testicular sperm extraction (TESE). Therefore, we point out the importance of genetic testing and counselling regarding Y chromosome microdeletion for couples requesting ICSI.

Complete down-regulation is not mandatory for good assisted reproductive treatment cycle outcomes.

OBJECTIVE: To determine the implications and predictive value of estradiol concentrations following pituitary down-regulation with gonadotrophin releasing hormone agonists in women undergoing controlled ovarian hyperstimulation for assisted reproductive technology. STUDY DESIGN: A total of 277 patients undergoing ovarian hyperstimulation for intracytoplasmic sperm injection (ICSI) were enrolled into the study and the patients were divided into four groups according to estradiol levels on the initial day of stimulation of which group-A consisted of the patients who had < or =25 pg/ml (n=90), group-B with levels between 26 and 50 pg/ml (n=104), group-C with levels between 51 and 75 pg/ml (n=67) and group-D with levels > or =76-90 pg/ml (n=16) and the results were compared. The primary outcome measures included ovarian response and the clinical pregnancy rates. RESULTS: The clinical pregnancy rates in groups-A, B, C and D were 33.3% (30/90), 26.0% (27/104), 35.8% (24/67), and 25.0% (4/16), respectively, and there was no statistically significant difference (P=0.482). The mean number of oocytes retrieved in groups were (9.7+/-5.8, 10.3+/-6.5, 11.0+/-6.8, and 12.1+/-6.6), respectively (P=0.453) and the fertilization rates in groups-A, B, C and D were found to be similar (75, 80, 73 and 79%, respectively; P=0.658). CONCLUSION: Complete and deep desensitization obviously seems not to be mandatory for successful stimulation in assisted reproductive technology cycles.

Relationship of follicle number, serum estradiol level, and other factors to clinical pregnancy rate in gonadotropin-induced intrauterine insemination cycles.

OBJECTIVE: To determine the characteristics associated with clinical pregnancy rate after gonadotropin-induced intrauterine insemination cycles in patients without male or tubal factor infertility. MATERIALS AND METHODS: One hundred and eighty patients undergoing controlled ovarian hyperstimulation followed by intrauterine insemination were included in the study retrospectively. The patients' files were retrospectively evaluated with respect to age, number of follicles, endometrial thickness and serum hormone levels at baseline and at the day of human chorionic gonadotropin (hCG) administration. The patients with male or unilateral tubal factor infertility were excluded from the study. RESULTS: The serum estradiol level at the day of hCG administration was not correlated with the clinical pregnancy rate (r=-0.05, p=0.481). The number of follicles was not correlated with the clinical pregnancy rate (r=-0.09, p=0.209). There was no significant difference between the clinically pregnants (n=32) and not pregnants (n=148) regarding the mean age, baseline serum levels of luteinizing hormone (LH) and estradiol, serum estradiol and LH levels at the day of hCG administration and endometrial thickness (p>0.05). Although not statistically significant, a pregnancy rate of 14.2% with less than 3 follicles > or = 18 mm is present compared to a pregnancy rate of 27.5% with at least 3 follicles > or = 18 mm and 24% with > or = 4 follicles > or = 18 mm. CONCLUSION: The clinical pregnancy rate does not seem to be affected with the number of follicles present at the time of intrauterine insemination or the serum estradiol level at the day of hCG administration in a controlled ovarian hyperstimulation cycle in non-andrologic and non-peritubal factor infertility; however, there is a clear trend towards higher pregnancy rates with higher number of follicles.