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Gateshead, United Kingdom

Galaal K.,Northern Gynaecological Oncology Center
Cochrane database of systematic reviews (Online) | Year: 2011

Uterine carcinosarcomas are uncommon with about 35% not confined to the uterus at diagnosis. The survival of patients with advanced uterine carcinosarcoma is poor with pattern of failure indicating greater likelihood of upper abdominal and distant metastatic recurrence. To evaluate the effectiveness and safety of radiotherapy and/or systemic chemotherapy in the management of stage III-IV persistent or recurrent uterine carcinosarcoma. We searched the Cochrane Gynaecological Cancer Group Trials Register, CENTRAL, The Cochrane Library 2010, Issue 2, MEDLINE and EMBASE to May 2010. We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. Randomised controlled trials comparing adjuvant radiotherapy and/or chemotherapy in women with uterine carcinosarcoma. We independently abstracted data and assessed risk of bias. We pooled hazard ratios (HRs) for overall and progression-free survival and risk ratios (RRs) comparing adverse events in women who received radiotherapy and/or chemotherapy in meta-analyses. Three trials (579 women, of whom all were assessed at the end of the trials) met the inclusion criteria. Two trials (373 women with stage III-IV persistent or recurrent disease) found that women who received combination therapy had a significantly lower risk of death and disease progression than women who received single agent ifosfamide. There was no statistically significant difference in all reported adverse events, with the exception of nausea and vomiting, which affected significantly more women in the combination therapy group than in the ifosamide group.One trial found no statistically significant difference in the risk of death and disease progression in women who received whole abdominal irradiation and chemotherapy, after adjustment for age and FIGO stage (HR = 0.71, 95% CI 0.48 to 1.05 and HR = 0.79, 95% CI 0.53 to 1.18 for overall survival and progression-free survival respectively). There was no statistically significant difference in all reported adverse events, with the exception of haematological and neuropathy morbidities, which affected significantly fewer women in the whole body irradiation group than in the chemotherapy group (RR = 0.02, 95% CI 0.00 to 0.16). The results of this review are limited to two trials. In the primary treatment/ first line therapy of advanced stage metastatic uterine carcinosarcoma, as well as in recurrent disease, adjuvant combination chemotherapy with ifosfamide and paclitaxel should be considered. None of the included studies reported on quality of life.


Kucukmetin A.,Northern Gynaecological Oncology Center
The Cochrane database of systematic reviews | Year: 2013

Cervical cancer is the second most common cancer among women and is the most frequent cause of death from gynaecological cancers worldwide. Standard surgical management for selected early-stage cervical cancer is radical hysterectomy. Traditionally, radical hysterectomy has been carried out via the abdominal route and this remains the gold standard surgical management of early cervical cancer. In recent years, advances in minimal access surgery have made it possible to perform radical hysterectomy with the use of laparoscopy with the aim of reducing the surgical morbidity and promoting a faster recovery. To compare the effectiveness and safety of laparoscopically assisted radical vaginal hysterectomy (LARVH) and radical abdominal hysterectomy (RAH) in women with early-stage (1 to 2A) cervical cancer. We searched the Cochrane Gynaecological Cancer Group Trials Register, and Cochrane Register of Controlled Trials (CENTRAL) Issue 7, 2013, MEDLINE, and EMBASE up to July 2013. We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. Randomised controlled trials (RCTs) that compared laparoscopically assisted radical hysterectomy and radical abdominal hysterectomy, in adult women diagnosed with early (stage 1 to 2A) cervical cancer. Two review authors independently abstracted data and assessed risk of bias. We found one RCT, which included 13 women, that met our inclusion criteria and this trial reported data on LARVH versus RAH.Women who underwent LARVH for treatment of early-stage cervical cancer appeared to have less blood loss compared with those who underwent RAH. The trial reported a borderline significant difference between the two types of surgery (median blood loss 400 mL (interquartile range (IQR): 325 to 1050) and 1000 mL (IQR: 800 to 1025) for LARVH and RAH, respectively, P value = 0.05). RAH was associated with significantly shorter operation time compared with LARVH (median: 180 minutes with LARVH versus 138 minutes with RAH, P value = 0.05).There was no statistically significant difference in the risk of perioperative complications in women who underwent LARVH and RAH. The trial reported two (29%) and four (57%) cases of intraoperative and postoperative complications, respectively, in the LARVH group and no (0%) reported cases of intraoperative complications and five (83%) cases of postoperative complications in the RAH group. There were no reported cases of severe perioperative complications.Bladder and bowel dysfunction of either a transient or chronic nature remain major morbidities after radical hysterectomy, and the one included study showed that there may be significantly less after LARVH. The included trial lacked statistical power due to the small number of women in each group and the low number of observed events. Therefore, the absence of reliable evidence, regarding the effectiveness and safety of the two surgical techniques for the management of early-stage cervical cancer, precludes any definitive guidance or recommendations for clinical practice. The trial did not report data on long-term outcomes, but was at moderate risk of bias due to very low numbers of included women.


Kucukmetin A.,Northern Gynaecological Oncology Center
Cochrane database of systematic reviews (Online) | Year: 2010

BACKGROUND: Ovarian cancer is the sixth most common cancer among women and is usually diagnosed at an advanced stage. Bowel obstruction is a common feature of advanced or recurrent ovarian cancer. Patients with bowel obstruction are generally in poor physical condition with a limited life expectancy. Therefore, maintaining their QoL with effective symptom control is the main purpose of the management of bowel obstruction. OBJECTIVES: To compare the effectiveness and safety of palliative surgery (surgery performed to control the cancer, reduce symptoms and improve quality of life for those whose cancer is not able to be entirely removed) and medical management for bowel obstruction in women with ovarian cancer. SEARCH STRATEGY: We searched the Cochrane Gynaecological Cancer Group Trials Register, The Cochrane Central Register of Controlled trials (CENTRAL), Issue 1 2009, MEDLINE and EMBASE up to February 2009. We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. SELECTION CRITERIA: Studies that compared palliative surgery and medical interventions, in adult women diagnosed with ovarian cancer who had either full or partial obstruction of the bowel. Randomised controlled trials (RCTs) and non-RCTs that used multivariable statistical adjustment for baseline case mix were eligible. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed whether potentially relevant studies met the inclusion criteria, abstracted data and assessed risk of bias. One non-randomised study was identified so no meta-analyses were performed. MAIN RESULTS: The search strategy identified 183 unique references of which 22 were identified as being potentially eligible on the basis of title and abstract. Only one study met our inclusion criteria and was included in the review. It analysed retrospective data for 47 women who received either palliative surgery (n = 27) or medical management with Octreotide (n = 20) and reported overall survival and perioperative mortality and morbidity. Women with poor performance status were excluded from surgery. Although six (22%) women who received surgery had serious complications of the operation and three (11%) died of complications, multivariable analysis found that women who received surgery had significantly (p < 0.001) better survival than women who received Octreotide, after adjustment for important prognostic factors. However, the magnitude of this effect was not reported. Quality of life (QoL) was not reported and adverse events were incompletely documented. AUTHORS' CONCLUSIONS: We found only low quality evidence comparing palliative surgery and medical management for bowel obstruction in ovarian cancer. Therefore we are unable to reach definite conclusions about the relative benefits and harms of the two forms of treatment, or to identify sub-groups of women who are likely to benefit from one treatment or the other. However, there is weak evidence in support of surgical management to prolong survival.


Galaal K.,Northern Gynaecological Oncology Center
Cochrane database of systematic reviews (Online) | Year: 2010

BACKGROUND: Most women with advanced epithelial ovarian cancer will ultimately develop recurrent disease after completion of initial treatment with primary surgery and adjuvant chemotherapy. Secondary cytoreductive surgery may have survival benefits in selected patients. However, a number of chemotherapeutic agents are active in recurrent ovarian cancer and the standard treatment of patients with recurrent ovarian cancer remains poorly defined. OBJECTIVES: To evaluate the effectiveness and safety of secondary surgical cytoreduction and chemotherapy compared to chemotherapy alone for women with recurrent epithelial ovarian cancer. SEARCH STRATEGY: We searched the Cochrane Gynaecological Cancer Group Trials Register, The Cochrane Register of Controlled Trials, (CENTRAL) Issue 1 2009, MEDLINE and EMBASE up to February 2009. We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of review articles and contacted experts in the field. SELECTION CRITERIA: We searched for RCTs, quasi-randomised trials and non-randomised studies that compared secondary cytoreductive surgery and chemotherapy to chemotherapy alonein women with recurrent epithelial ovarian cancer. DATA COLLECTION AND ANALYSIS: Three reviewers independently assessed whether potentially relevant studies met the inclusion criteria. No trials were found and therefore no data were analysed. MAIN RESULTS: The search strategy identified 1431 unique references of which all were excluded on the basis of title and abstract. AUTHORS' CONCLUSIONS: We found no evidence from RCTs to inform decisions about secondary surgical cytoreduction and chemotherapy compared to chemotherapy alone for women with recurrent epithelial ovarian cancer. Ideally, a large randomised controlled trial or, at the very least, well designed non-randomised studies that use multivariate analysis to adjust for baseline imbalances are needed to compare these treatment modalities.


The use of cell lines or animal models has significant disadvantages when dealing with a set of heterogeneous diseases such as epithelial ovarian cancer. This has clinical relevance in that biomarkers developed using cell line or animal models are often not transferable to the clinical setting. In this study, we describe the development of a robust protocol for developing primary cultures of ovarian cancer which will overcome some of these difficulties. Women undergoing surgery for ovarian cancer were recruited and samples of ascites and solid tumour deposits were used to develop primary cultures. Cells were characterised using a panel of immunofluorescent antibodies prior to use in a variety of assays including functional assessment of DNA repair pathways. During the four year study period, viable cultures, confirmed to be epithelial in origin were generated from 156 of 172 (91%) cases recruited. Characterisation was carried out using a panel of antibodies including pancytokeratin, CA125, EpCAM, MOC-31, D2-40 and vimentin. Senescence occurred between the 2nd and 8th passages in all cultures except one in which spontaneous immortalization occurred. Cells could be successfully cultured even after a period of storage at 4°C and cultured cells were capable of being used for a variety of applications including functional assays. Upon functional assessment there was minimal intra-tumour heterogeneity. It is therefore possible to derive viable ovarian cancer cell cultures in the majority of patients undergoing surgery. Cells cultured directly from patient cancers provide an accurate and highly diverse model.

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