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Introduction High-grade serous ovarian cancer (HGSOC) is characterized by high mortality and prevalent recurrences. This study investigates the prognostic value of phosphoglycerate dehydrogenase (PHGDH) in HGSOC which has been linked to metabolic reprogramming and recurrences in other cancers. Methods Data from 306 patients with advanced-stage HGSOC treated between 2008 and 2015 were analyzed. PHGDH expression levels were determined using immunohistochemistry and categorized as "low" or "high." Results PHGDH-high was associated with higher FIGO stage and increased use of neoadjuvant chemotherapy. Patients with PHGDH-high tumors had significantly worse survival than PHDH-low, even after adjusting for confounding factors. [ABSTRACT FROM AUTHOR]

Motivation Circulating-cell free DNA (cfDNA) is widely explored as a noninvasive biomarker for cancer screening and diagnosis. The ability to decode the cells of origin in cfDNA would provide biological insights into pathophysiological mechanisms, aiding in cancer characterization and directing clinical management and follow-up. Results We developed a DNA methylation signature-based deconvolution algorithm, MetDecode, for cancer tissue origin identification. We built a reference atlas exploiting de novo and published whole-genome methylation sequencing data for colorectal, breast, ovarian, and cervical cancer, and blood-cell-derived entities. MetDecode models the contributors absent in the atlas with methylation patterns learnt on-the-fly from the input cfDNA methylation profiles. In addition, our model accounts for the coverage of each marker region to alleviate potential sources of noise. In-silico experiments showed a limit of detection down to 2.88% of tumor tissue contribution in cfDNA. MetDecode produced Pearson correlation coefficients above 0.95 and outperformed other methods in simulations (P  < 0.001; T -test; one-sided). In plasma cfDNA profiles from cancer patients, MetDecode assigned the correct tissue-of-origin in 84.2% of cases. In conclusion, MetDecode can unravel alterations in the cfDNA pool components by accurately estimating the contribution of multiple tissues, while supplied with an imperfect reference atlas. Availability and implementation MetDecode is available at https://github.com/JorisVermeeschLab/MetDecode. [ABSTRACT FROM AUTHOR]

Known risk loci for endometrial cancer explain approximately one third of familial endometrial cancer. However, the association of germline copy number variants (CNVs) with endometrial cancer risk remains relatively unknown. We conducted a genome-wide analysis of rare CNVs overlapping gene regions in 4115 endometrial cancer cases and 17,818 controls to identify functionally relevant variants associated with disease. We identified a 1.22-fold greater number of CNVs in DNA samples from cases compared to DNA samples from controls (p = 4.4 × 10–63). Under three models of putative CNV impact (deletion, duplication, and loss of function), genome-wide association studies identified 141 candidate gene loci associated (p < 0.01) with endometrial cancer risk. Pathway analysis of the candidate loci revealed an enrichment of genes involved in the 16p11.2 proximal deletion syndrome, driven by a large recurrent deletion (chr16:29,595,483-30,159,693) identified in 0.15% of endometrial cancer cases and 0.02% of control participants. Together, these data provide evidence that rare copy number variants have a role in endometrial cancer susceptibility and that the proximal 16p11.2 BP4-BP5 region contains 25 candidate risk gene(s) that warrant further analysis to better understand their role in human disease. [ABSTRACT FROM AUTHOR]

The incidence of antenatal cancer is increasing, prompting a medical‐ethical evaluation. The International Network on Cancer, Infertility, and Pregnancy (INCIP) was established to study cancer treatment safety during pregnancy and its impact on maternal and child health. Pivotal research has led to a paradigm shift in clinical management, demonstrating the feasibility and safety of most antenatal oncological treatments. Short‐term outcomes reveal normal growth and cardiac function in the exposed offspring, but caution is advised against first‐trimester chemotherapy. Psychological impact studies highlight the elevated levels of distress in pregnant cancer patients, underscoring the need for personalized information and ongoing psychological support. Long‐term follow‐up studies address gaps in postnatal impacts, while research into specific chemotherapeutic agents continues. Despite generally reassuring outcomes, continued monitoring is crucial, especially in families, such as those where the child was born premature after cancer (treatment) during pregnancy or where mothers are frequently absent due to continued illness or have died from. The ongoing INCIP child follow‐up initiative aims to further elucidate knowledge gaps, emphasizing the importance of large‐scale studies and personalized patient care. [ABSTRACT FROM AUTHOR]

During pregnancy, the use of radiation therapy for cancer treatment is often considered impossible due to the assumed associated fetal risks. However, suboptimal treatment of pregnant cancer patients and unjustifiable delay in radiation therapy until after delivery can be harmful for both patient and child. In non‐pregnant patients, proton‐radiation therapy is increasingly administered because of its favorable dosimetric properties compared with photon‐radiation therapy. Although data on the use of pencil beam scanning proton‐radiation therapy during pregnancy are scarce, different case reports and dosimetric studies have indicated a more than 10‐fold reduction in fetal radiation exposure compared with photon‐radiation therapy. Nonetheless, the implementation of proton‐radiation therapy during pregnancy requires complex fetal dosimetry for the neutron‐dominated out‐of‐field radiation dose and faces a lack of clinical guidelines. Further exploration and standardization of proton‐radiation therapy during pregnancy will be necessary to improve radiotherapeutic management of pregnant women with cancer and further reduce risks for their offspring. [ABSTRACT FROM AUTHOR]

Endometriosis, polycystic ovary syndrome (PCOS) and uterine fibroids have been proposed as endometrial cancer risk factors; however, disentangling their relationships with endometrial cancer is complicated due to shared risk factors and comorbidities. Using genome-wide association study (GWAS) data, we explored the relationships between these non-cancerous gynecological diseases and endometrial cancer risk by assessing genetic correlation, causal relationships and shared risk loci. We found significant genetic correlation between endometrial cancer and PCOS, and uterine fibroids. Adjustment for genetically predicted body mass index (a risk factor for PCOS, uterine fibroids and endometrial cancer) substantially attenuated the genetic correlation between endometrial cancer and PCOS but did not affect the correlation with uterine fibroids. Mendelian randomization analyses suggested a causal relationship between only uterine fibroids and endometrial cancer. Gene-based analyses revealed risk regions shared between endometrial cancer and endometriosis, and uterine fibroids. Multi-trait GWAS analysis of endometrial cancer and the genetically correlated gynecological diseases identified a novel genome-wide significant endometrial cancer risk locus at 1p36.12, which replicated in an independent endometrial cancer dataset. Interrogation of functional genomic data at 1p36.12 revealed biologically relevant genes, including WNT4 which is necessary for the development of the female reproductive system. In summary, our study provides genetic evidence for a causal relationship between uterine fibroids and endometrial cancer. It further provides evidence that the comorbidity of endometrial cancer, PCOS and uterine fibroids may partly be due to shared genetic architecture. Notably, this shared architecture has revealed a novel genome-wide risk locus for endometrial cancer. [ABSTRACT FROM AUTHOR]

Blood lipids have been associated with the development of a range of cancers, including breast, lung and colorectal cancer. For endometrial cancer, observational studies have reported inconsistent associations between blood lipids and cancer risk. To reduce biases from unmeasured confounding, we performed a bidirectional, two‐sample Mendelian randomization analysis to investigate the relationship between levels of three blood lipids (low‐density lipoprotein [LDL] and high‐density lipoprotein [HDL] cholesterol, and triglycerides) and endometrial cancer risk. Genetic variants associated with each of these blood lipid levels (P < 5 × 10−8) were identified as instrumental variables, and assessed using genome‐wide association study data from the Endometrial Cancer Association Consortium (12 906 cases and 108 979 controls) and the Global Lipids Genetic Consortium (n = 188 578). Mendelian randomization analyses found genetically raised LDL cholesterol levels to be associated with lower risks of endometrial cancer of all histologies combined, and of endometrioid and non‐endometrioid subtypes. Conversely, higher genetically predicted HDL cholesterol levels were associated with increased risk of non‐endometrioid endometrial cancer. After accounting for the potential confounding role of obesity (as measured by genetic variants associated with body mass index), the association between genetically predicted increased LDL cholesterol levels and lower endometrial cancer risk remained significant, especially for non‐endometrioid endometrial cancer. There was no evidence to support a role for triglycerides in endometrial cancer development. Our study supports a role for LDL and HDL cholesterol in the development of non‐endometrioid endometrial cancer. Further studies are required to understand the mechanisms underlying these findings. What's new? Some studies have suggested that serum lipids may correlate with endometrial cancer (EC) risk, but results have been inconsistent. In our study, the authors used genetic markers to predict LDL and HDL cholesterol levels and analyze EC risk. They found that when lower LDL or higher HDL levels were predicted, EC risk was increased. These results support a role for LDL and HDL cholesterol in the development of EC, and lipid levels may represent a risk factor for EC. Further studies are required to assess the biological and clinical significance of these associations. [ABSTRACT FROM AUTHOR]

Objective: Approach to precancerous and high-risk breast lesions occurring in pregnancy has received little attention in the literature. We carried out a study to investigate the practice of surgeons in the management of these cases. Materials and Methods: A short survey was sent to surgeons, including a multiple-choice questionnaire about their practice for atypical hyperplasia or lobular carcinoma in situ presenting in each trimester of pregnancy or at time of breastfeeding. Answer options included observation, immediate vacuum biopsy, immediate surgery, surgery in next trimester, surgery after delivery, and surgery after end of breastfeeding; based on the time of presentation. Results: Out of the 671 practitioners invited, 97(14.5 %) responded to the survey. Participants were from 23 countries. Answers showed that management of gestational Atypical Ductal Hyperplasia (ADH) and Lobular Neoplasia (LN) was readily postponed by surgeons in favor of fetus safety while being cautious about risks of conservative management alone. Conclusion: Various methods of treatment are selected by surgeons for managing high-risk breast lesions during pregnancy. In the absence of relevant literature, decision making in a multidisciplinary team would be the best approach in these cases. [ABSTRACT FROM AUTHOR]

Objective: A subset of patients with recurrent ovarian cancer (ROC) may benefit from antiestrogen therapy with higher response rates reported in tumors that are strongly estrogen receptor (ER)-positive (ER+). PARAGON is a basket trial that incorporates 7 phase 2 trials investigating the activity of anastrozole in patients with ER+ and/or progesterone receptor (PR)-positive (PR+) recurrent/metastatic gynecological cancers. Methods: Postmenopausal women with ER+ and/or PR+ ROC, who were asymptomatic and had cancer antigen 125 (CA125) progression after response to first line chemotherapy, where chemotherapy was not clinically indicated. Patients received anastrozole 1 mg daily until progression or unacceptable toxicity. Results: Fifty-four patients were enrolled (52 evaluable). Clinical benefit at three months (primary endpoint) was observed in 18 patients (34.6%; 95% confidence interval [CI]=23%-48%). Median progression-free survival (PFS) was 2.7 months (95% CI=2.1-3.1). The median duration of clinical benefit was 6.5 months (95% CI=2.8-11.7). Most patients progressed within 6 months of starting anastrozole but 12 (22%) continued treatment for longer than 6 months. Anastrozole was well tolerated. In the exploratory analysis, ER histoscores and the intensity of ER staining did not correlate with clinical benefit rate or PFS. Conclusion: A subset of asymptomatic patients with ER+ and/or PR+ ROC and CA125 progression had durable clinical benefit on anastrozole, with acceptable toxicity. Anastrozole may delay symptomatic progression and the time to subsequent chemotherapy. The future challenge is to identify the subset of patients most likely to benefit from an aromatase inhibitor and whether the clinical benefit could be increased by the addition of other agents. [ABSTRACT FROM AUTHOR]

Objective: A pilot study was conducted to establish a human placental xenograft, which could serve as a model to evaluate the effect of toxic exposures during pregnancy. Study Design: The protocol consisted of engraftment of third-trimester human placental tissue in immunocompromised mice, after induction of a pseudo-pregnancy state by ovariectomy and progesterone supplementation. To validate the model, the placental tissue before and after engraftment was examined by immunohistochemistry, fluorescence-activated cell sorting (FACS), single-nucleotide polymorphism (SNP) genotyping, and whole transcriptome sequencing (WTSS). The human chorion gonadotropin (hCG) production in serum and urine was examined by enzyme-linked immunosorbent assay. Results: Microscopic evaluation of the placental tissue before and after engraftment revealed a stable morphology and preserved histological structure of the human tissue. Viable trophoblast was present after engraftment and remained stable over time. Vascularization and hormonal secretion (hCG) were present till 3 weeks after engraftment. Thirty-one SNPs were equally present, and there was a stable expression level for 56 451 genes evaluated by whole transcriptome sequencing. Conclusion: Although this human placental xenograft model cannot copy the unique uterine environment in which the placenta develops and interacts between the mother and the fetus, it could be a suitable tool to evaluate the acute impact and adaptive processes of the placental tissue to environmental changes. [ABSTRACT FROM AUTHOR]

Background: Fertility preservation before or during cancer treatment in young women has become an important health issue because of delayed motherhood and improved survival rates. This study evaluates the necessity and the efficacy of fertility preservation, with a focus on actual pregnancy wish and outcome after fertility preservation and cancer treatment.Patients and Methods: All consecutive patients who received fertility preservation in 2 university referral centers before or during cancer treatment were included. After a minimal follow-up of 3 years, pregnancy wish, pregnancy attempts and fertility outcome were assessed during a dedicated consultation or during a telephone interview.Results: A total of 159 patients received fertility preservation including hormonal protection with gonadotropin-releasing hormone agonist (n = 93, 58.5%), ovarian tissue cryopreservation (n = 44, 27.7%), and combined hormonal protection and ovarian tissue cryopreservation (n = 22, 13.8%). Among the 91 (57.2%) patients in remission after a mean follow-up of 61.5 months, 29 (31.9%) women actively attempted pregnancy. Patients who had received ovarian cryopreservation were more likely to attempt pregnancy (18/66) than those who only received hormonal protection (11/93, p = 0.02). Out of the 29 women who attempted pregnancy, 16 (55.2%) became pregnant, and most of them conceived spontaneously (87.5%, 14/16). Out of the 13 women who did not become pregnant, 1 patient adopted a child and 12 patients still wanted to become pregnant, including 1 patient who underwent a transplantation of her cryopreserved ovarian tissue without success.Conclusion: In one of the first studies reporting real-life experience in centers for fertility preservation, we found that, within 5 years following the end of cancer treatment, only one third of patients in remission attempted to become pregnant, with a pregnancy rate of 55%, mostly after spontaneous conception. [ABSTRACT FROM AUTHOR]

In a previous longitudinal diffusion tensor imaging (DTI) study, we observed cerebral white matter (WM) alterations (reduced fractional anisotropy (FA)) related to decreased cognitive performance 3-5 months after chemotherapy-treatment (t2) when compared to baseline (t1) (Deprez et al. in Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology, 30(3), 274-281. doi:10.1200/JCO.2011.36.8571, 2012). The current study investigates the evolution and the nature of these previously observed microstructural changes. Twenty-five young women with early-stage breast cancer who received chemotherapy treatment (C+), 14 who did not receive chemotherapy (C-) and 15 healthy controls (HC) previously studied, underwent reassessment 3-4 years after treatment (t3). We assessed (1) longitudinal changes of cognitive performance and FA and (2) cross-sectional group differences in myelin-water-imaging and multishell diffusion MRI metrics at t3. MRI metrics were assessed on a voxel-by-voxel basis and in regions-of-interest (ROI) in which previous WM injury was detected. Longitudinal results: Mixed-effects modeling revealed significant group-time interactions for verbal memory and processing speed (p < 0.05) reflecting regained performance in the C+ group at t3. Furthermore, in chemotherapy-treated patients, FA returned to baseline levels at t3 in all ROIs (p < 0.002), whereas no FA changes were seen in controls. Additionally, FA increase from t2 to t3 correlated with time since treatment in two of the four regions (r = 0.40, p < 0.05). Cross-sectional results: Advanced diffusion MRI and myelin-water imaging metrics in the ROIs did not differ between groups. Similarly, no whole-brain voxelwise differences were detected. Initial WM alterations and reduced cognitive performance following chemotherapy-treatment were found to recover in a group of young breast cancer survivors three to four years after treatment. [ABSTRACT FROM AUTHOR]

Objective: Recent studies suggest that mucinous borderline ovarian tumors (MBOTs) belong to a high-risk group that is more likely to develop an invasive recurrence. The objective is to determine these risk factors.Methods: A monocentric retrospective review of all consecutive patients with intestinal-type MBOT diagnosed between 1993 and 2013. All tumors were evaluated by one pathologist without knowledge of clinical outcome. Extensive surgical staging and pathological tumor sampling (1 block/cm diameter in tumors <10 cm and 2 blocks/cm diameter in tumors >10 cm) were performed in all cases.Results: A total of 81 patients were included. Patients with micro-invasion were also included. None of the patients recurred. No bilateral tumors, nor tumors with International Federation of Gynecology and Obstetrics stage II or higher, were diagnosed. Median follow-up was 87 months.Conclusions: In our series of pure intestinal-type MBOT, including micro-invasion, no recurrences were observed. Given the heterogeneity of these tumors staging with at least unilateral salpingo-oophorectomy, extensive pathological sampling, and expert pathological review are of paramount importance to be able to diagnose a pure intestinal-type MBOT and excluding gastrointestinal mucinous tumors and more important, excluding an invasive focus, defining a mucinous ovarian carcinoma. When these conditions are fulfilled, the prognosis of pure intestinal-type MBOT is excellent. [ABSTRACT FROM AUTHOR]

Introduction Currently used tools for breast cancer prognostication and prediction may not adequately reflect a young patient's prognosis or likely treatment benefit because they were not adequately validated in young patients. Since breast cancers diagnosed at a young age are considered prognostically unfavourable, many treatment guidelines recommend adjuvant systemic treatment for all young patients. Patients cured by locoregional treatment alone are, therefore, overtreated. Lack of prognosticators for young breast cancer patients represents an unmet medical need and has led to the initiation of the PAtients with bReAst cancer DIaGnosed preMenopausally (PARADIGM) initiative. Our aim is to reduce overtreatment of women diagnosed with breast cancer aged =40 years. Methods and analysis All young, adjuvant systemic treatment naive breast cancer patients, who had no prior malignancy and were diagnosed between 1989 and 2000, were identified using the population based Netherlands Cancer Registry (n=3525). Archival tumour tissues were retrieved through linkage with the Dutch nationwide pathology registry. Tissue slides will be digitalised and placed on an online image database platform for clinicopathological revision by an international team of breast pathologists. Immunohistochemical subtype will be assessed using tissue microarrays. Tumour RNA will be isolated and subjected to next-generation sequencing. Differences in gene expression found between patients with a favourable and those with a less favourable prognosis will be used to establish a prognostic classifier, using the triple negative patients as proof of principle. Ethics and dissemination Observational data from the Netherlands Cancer Registry and left over archival patient material are used. Therefore, the Dutch law on Research Involving Human Subjects Act (WMO) is not applicable. The PARADIGM study received a 'non-WMO' declaration from the Medical Ethics Committee of the Netherlands Cancer Institute - Antoni van Leeuwenhoek hospital, waiving individual patient consent. All data and material used are stored in a coded way. Study results will be presented at international (breast cancer) conferences and published in peer-reviewed, open-access journals. [ABSTRACT FROM AUTHOR]

Surgery is the cornerstone in primary endometrial cancer treatment, and with curative intent it constitutes total hysterectomy and bilateral salpingo-oopherectomy. In addition, lymphadenectomy is performed in selected patients dependent on a preoperative risk assessment. Recent reports from the surgical approach to esophageal cancer reveal worse outcome when esophagectomy is performed later in the week. On this basis, we set out to explore weekday of surgery in relation to long-term outcome in 1302 endometrial cancer patients prospectively included in the MoMaTEC multicenter study. Day of surgery was dichotomized as early-week (Monday-Tuesday) or late-week (Wednesday-Friday), and evaluated as a discrete variable. Adjusted for patient age, Body Mass Index (BMI), FIGO stage, and histology, surgery performed later in the week was associated with 50.9% increased risk of all-cause death (p = 0.029). Among high-stage patients (FIGO stage III and IV), 5-year disease-specific survival proportions were 53.0% for early-week operated vs. 40.2% for late-week operated (p = 0.005 for difference). In multivariate survival analysis of high-stage patients, late-week surgery correlated with an increased risk of disease-specific death by 88.7% and all-cause death by 76.4% (p<0.017). Evaluating only patients who underwent lymphadenectomy, the adverse prognostic effect of being operated late-week remained for both disease-specific and all-cause death (HR 2.151 and HR 1.912, p = 0.004). Whether surgery was performed early- or late-week was not influenced by patient age, BMI, preoperative histology risk classification, FIGO stage or postoperative histology (all p>0.05). In conclusion, endometrial cancer surgery conducted late-week is associated with worse long-term outcome. Our findings are most evident among patients with higher FIGO stages, and patients who underwent more extensive surgical procedure (lymphadenectomy). With support from other studies, our results suggest that high-risk patients may benefit from surgery earlier in the week. [ABSTRACT FROM AUTHOR]

Although p53 protein aggregates have been observed in cancer cell lines and tumour tissue, their impact in cancer remains largely unknown. Here, we extensively screened for p53 aggregation phenotypes in tumour biopsies, and identified nuclear inclusion bodies ( nIBs) of transcriptionally inactive mutant or wild-type p53 as the most frequent aggregation-like phenotype across six different cancer types. p53-positive nIBs co-stained with nuclear aggregation markers, and shared molecular hallmarks of nIBs commonly found in neurodegenerative disorders. In cell culture, tumour-associated stress was a strong inducer of p53 aggregation and nIB formation. This was most prominent for mutant p53, but could also be observed in wild-type p53 cell lines, for which nIB formation correlated with the loss of p53's transcriptional activity. Importantly, protein aggregation also fuelled the dysregulation of the proteostasis network in the tumour cell by inducing a hyperactivated, oncogenic heat-shock response, to which tumours are commonly addicted, and by overloading the proteasomal degradation system, an observation that was most pronounced for structurally destabilized mutant p53. Patients showing tumours with p53-positive nIBs suffered from a poor clinical outcome, similar to those with loss of p53 expression, and tumour biopsies showed a differential proteostatic expression profile associated with p53-positive nIBs. p53-positive nIBs therefore highlight a malignant state of the tumour that results from the interplay between (1) the functional inactivation of p53 through mutation and/or aggregation, and (2) microenvironmental stress, a combination that catalyses proteostatic dysregulation. This study highlights several unexpected clinical, biological and therapeutically unexplored parallels between cancer and neurodegeneration. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

This article describes the case of a 70-year-old woman with an adnexal cystadenocarcinoma located in the right broad ligament and displaying a striking resemblance to a well-differentiated endometrioid adenocarcinoma. The uniqueness of this pseudoendometrioid carcinoma lies in the fact that its mesonephric nature is revealed by the origin from a papillary cystadenoma of the broad ligament, where remnants of the mesonephric duct are seated, and the immunohistochemical profile, particularly a uniform negativity for estrogen and progesterone receptors, apical-luminal positivity for CD10, and strong nuclear positivity for GATA3. [ABSTRACT FROM AUTHOR]

Background: While immunotherapy moved to the forefront of treatment of various cancers, it remains underexplored for uterine cancer. This might be due to the small patient population with advanced endometrial carcinoma and uterine sarcoma. Data about immunotherapeutic targets are scarce in endometrial carcinoma and lacking in uterine sarcoma. Methods: Expression of five tumor-associated antigens (TAA) (BORIS, MUC1, hTERT, MAGE-A3 and Sp17) was validated in uterine tumor samples by immunohistochemistry (IHC) and/or quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR). TAA immunogenicity was analyzed by determining spontaneous T cell responses towards overlapping peptide pools covering the whole TAA in patient blood. Results: At mRNA level, MAGE-A3 and Sp17 were overexpressed in a minority of patients and BORIS was moderately overexpressed (26% in endometrial carcinoma and 62% in uterine sarcoma). hTERT was overexpressed in the vast majority of tumors. On protein level, MUC1 was upregulated in primary, recurrent and metastatic EMCAR and in metastatic US tumors. hTERT protein was highly expressed in both normal and malignant tissue. Spontaneous TAA-specific T cell responses were detected in a minority of patients, except for hTERT to which T cell responses occurred more frequently. Conclusions: These data point to MUC1 and hTERT as most suitable targets based on expression levels and T cell immunogenicity for use in immunotherapeutic regimens. [ABSTRACT FROM AUTHOR]

The article describes a case of low-grade bronchial mucoepidermoid carcinoma diagnosed during midpregnancy in a 30-year-old woman. The patient presented with symptoms of a recurrent pneumonia affecting the right upper lobe. Laboratory tests revealed an acute inflammatory condition with elevated C-reactive protein (CRP) and leukocytosis. A sleeve right upper lobectomy was performed to treat the mucoepidermoid carcinoma.

Several studies have reported associations between multiple cancer types and single-nucleotide polymorphisms (SNPs) on chromosome 5p15, which harbours TERT and CLPTM1L, but no such association has been reported with endometrial cancer. To evaluate the role of genetic variants at the TERT- CLPTM1L region in endometrial cancer risk, we carried out comprehensive fine-mapping analyses of genotyped and imputed SNPs using a custom Illumina iSelect array which includes dense SNP coverage of this region. We examined 396 SNPs (113 genotyped, 283 imputed) in 4,401 endometrial cancer cases and 28,758 controls. Single-SNP and forward/backward logistic regression models suggested evidence for three variants independently associated with endometrial cancer risk ( P = 4.9 × 10 to P = 7.7 × 10). Only one falls into a haplotype previously associated with other cancer types (rs7705526, in TERT intron 1), and this SNP has been shown to alter TERT promoter activity. One of the novel associations (rs13174814) maps to a second region in the TERT promoter and the other (rs62329728) is in the promoter region of CLPTM1L; neither are correlated with previously reported cancer-associated SNPs. Using TCGA RNASeq data, we found significantly increased expression of both TERT and CLPTM1L in endometrial cancer tissue compared with normal tissue ( TERT P = 1.5 × 10, CLPTM1L P = 1.5 × 10). Our study thus reports a novel endometrial cancer risk locus and expands the spectrum of cancer types associated with genetic variation at 5p15, further highlighting the importance of this region for cancer susceptibility. [ABSTRACT FROM AUTHOR]

The management of patients with breast cancer during pregnancy is very demanding and it should be better performed in highly qualified and experienced centers. Referral to institutes and physicians trained in this special clinical scenario allows reducing the risk of both overtreating and undertreating the patients. Moreover, patients can receive appropriate information regarding safety of treatments without old-fashioned taboo. The purpose of the current paper is to discuss the main issues concerning surgical management and in general locoregional treatment of patients diagnosed with breast cancer and treated during gestation, focusing on those women who chose to continue their pregnancy. We cover the issues regarding type of breast surgery, radiation therapy, immediate reconstruction during mastectomy, and management of the axilla. [ABSTRACT FROM AUTHOR]

Aims To check the usefulness of a standardized protocol of PTEN FISH in 31 endometrial carcinomas ( ECs) in comparison with SNP array ( SNPA), multiplex ligation-dependent probe amplification ( MLPA), and immunohistochemistry. Methods and results Fluorescence in-situ hybridization analysis showed two PTEN copies in 17 cases, three copies in nine cases, hemizygous deletion in two cases, and diverse cell populations with different PTEN copy number in three cases. A good correlation was seen between FISH and SNPA, particularly in cases with three copies. FISH identified two cases with entire deletion of chromosome 10, but did not identify a focal deletion of PTEN. Five cases with PTEN deletion and duplication of the second allele by SNPA were interpreted as normal by FISH. Concordance between FISH and MLPA was seen in 15 cases with two copies, and in two cases with PTEN deletion. Six cases were interpreted as amplified by MLPA, but showed polyploidy by FISH. FISH was superior to SNPA and MLPA in assessing the tumours with diverse cell populations with different PTEN copies. Conclusions The results show good concordance between FISH, SNPA and MLPA. SNPA was superior in tumours with deletion of one copy and duplication of the second allele. FISH was superior in assessing tumour heterogeneity. [ABSTRACT FROM AUTHOR]

Background The inflammatory marker, C reactive protein has been proposed to also be a biomarker for adaptive immune responses in cancer patients with a possible application in time based chemotherapy. Fluxes in serum CRP levels were suggested to be indicative of a cyclical process in which, immune activation is followed by auto-regulating immune suppression. The applicability of CRP as a biomarker for regulatory or effector T cells was therefore investigated in a cohort of patients with gynaecological malignancies. Methods Peripheral blood samples were obtained from a cohort of patients at 7 time points over a period of 12 days. Serum and mononuclear cells were isolated and CRP levels in serum were detected using ELISA while regulatory and effector T cell frequencies were assessed using flow cytometry. To test periodicity, periodogram analysis of data was employed while Pearson correlation and the Wilcoxon signed rank test were used to determine correlations. Results The statistical analysis used showed no evidence of periodic oscillation in either serum CRP concentrations or Teff and Treg frequencies. Furthermore, there was no apparent correlation between serum CRP concentrations and the corresponding frequencies of Tregs or Teffs. Relative to healthy individuals, the disease state in the patients neither significantly affected the mean frequency of Tregs nor the mean coefficient of variation within the Treg population over time. However, both Teff mean frequency and mean coefficient of variation were significantly reduced in patients. Conclusion Using our methods we were unable to detect CRP oscillations that could be used as a consistent serial biomarker for time based chemotherapy. [ABSTRACT FROM AUTHOR]

Purpose: The addition of 4 % O and 10 % NO to the CO pneumoperitoneum (PP), together with slight cooling and humidification (conditioning), contributes to reducing adhesions by preventing mesothelial damage. We investigated the effect of peritoneal damage during laparoscopy on tumor implantation. Methods: In Experiment 1, different tumor cell concentrations were injected into control mice without PP and into mice with 60-min dry COPP (mesothelial damage). In Experiment 2, tumor cells were injected into control mice (group I) and in mice with mesothelial damage (group II). In groups III to VI, mesothelial damage was decreased by adding humidification, humidification + 10 % NO, humidification + 10 % NO + 4 % O, and conditioning, respectively. Results: In Experiment 1, the tumors increased with the number of cells injected and with mesothelial damage in the abdominal cavity ( p = 0.018) and abdominal wall ( p < 0.0001). Experiment 2 confirmed that 60 min of dry COPP increased the number of tumors in the abdominal cavity and wall ( p = 0.026 and p = 0.003, respectively). The number of tumors was decreased in the abdominal cavity by conditioning ( p = 0.030) and in the abdominal wall using humidified CO ( p = 0.032) or conditioning ( p = 0.026). Conclusions: Tumor implantation was enhanced by peritoneal damage (60 min of dry COPP and desiccation), but this was prevented by conditioning. If confirmed in humans, conditioning would become important for oncologic surgery. [ABSTRACT FROM AUTHOR]

The major hurdle for cancer vaccines to be effective is posed by tumor immune evasion. Several common immune mechanisms and mediators are exploited by tumors to avoid immune destruction. In an attempt to shed more light on the immunosuppressive environment in uterine tumors, we analyzed the presence of PD-L1, PD-L2, B7-H4, indoleamine 2,3-dioxygenase (IDO), galectin-1, galectin-3, arginase-1 activity and myeloid-derived suppressor cell (MDSC) infiltration. IDO, PD-L1, PD-L2 and B7-H4 were analyzed by immunohistochemistry. PD-L2 was mostly expressed at low levels in these tumors. We found high IDO expression in 21 % of endometrial carcinoma samples and in 14 % of uterine sarcoma samples. For PD-L1 and B7-H4, we found high expression in 92 and 90 % of endometrial cancers, respectively, and in 100 and 92 % of the sarcomas. Galectin-1 and 3 were analyzed in tissue lysates by ELISA, but we did not find an increase in both molecules in tumor lysates compared with benign tissues. We detected expression of galectin-3 by fibroblasts, immune cells and tumor cells in single-cell tumor suspensions. In addition, we noted a highly significant increase in arginase-1 activity in endometrial carcinomas compared with normal endometria, which was not the case for uterine sarcomas. Finally, we could demonstrate MDSC infiltration in fresh tumor suspensions from uterine tumors. These results indicate that the PD-1/PD-L1 interaction and B7-H4 could be possible targets for immune intervention in uterine cancer patients as well as mediation of MDSC function. These observations are another step toward the implementation of inhibitors of immunosuppression in the treatment of uterine cancer patients. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate whole-body MRI with diffusion-weighted sequence (WB-DWI/MRI) for staging and assessing operability compared with CT and FDG-PET/CT in patients with suspected ovarian cancer. Methods: Thirty-two patients underwent 3-T WB-DWI/MRI, F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) and CT before diagnostic open laparoscopy (DOL). Imaging findings for tumour characterisation, peritoneal and retroperitoneal staging were correlated with histopathology after DOL and/or open surgery. For distant metastases, FDG-PET/CT or image-guided biopsies were the reference standards. For tumour characterisation and peritoneal staging, WB-DWI/MRI was compared with CT and FDG-PET/CT. Interobserver agreement for WB-DWI/MRI was determined. Results: WB-DWI/MRI showed 94 % accuracy for primary tumour characterisation compared with 88 % for CT and 94 % for FDG-PET/CT. WB-DWI/MRI showed higher accuracy of 91 % for peritoneal staging compared with CT (75 %) and FDG-PET/CT (71 %). WB-DWI/MRI and FDG-PET/CT showed higher accuracy of 87 % for detecting retroperitoneal lymphadenopathies compared with CT (71 %). WB-DWI/MRI showed excellent correlation with FDG-PET/CT (κ = 1.00) for detecting distant metastases compared with CT (κ = 0.34). Interobserver agreement was moderate to almost perfect (κ = 0.58-0.91). Conclusions: WB-DWI/MRI shows high accuracy for characterising primary tumours, peritoneal and distant staging compared with CT and FDG-PET/CT and may be valuable for assessing operability in ovarian cancer patients. Key Points: • Whole- body MRI with diffusion weighting ( WB- DWI/ MRI) helps to assess the operability of suspected ovarian cancer. • Interobserver agreement is good for primary tumour characterisation, peritoneal and distant staging. • WB- DWI/ MRI improves mesenteric/ serosal metastatic spread assessment compared with CT and FDG- PET/ CT. • Retroperitoneal/ cervical- thoracic nodal staging using qualitative DWI criteria was reasonably accurate. • WB- DWI/ MRI and FDG- PET/ CT showed the highest diagnostic impact for detecting thoracic metastases. [ABSTRACT FROM AUTHOR]

Endometrial stromal sarcomas (ESSs) are a genetically heterogeneous group of rare uterine neoplasms that are commonly driven by recurrent gene rearrangements. In conventional low-grade ESS, JAZF1-SUZ12, PHF1-JAZF1, EPC1-PHF1 and MEAF6-PHF1, and recently described ZC3H7- BCOR chimeric fusions have been reported in > 50% of cases. Conversely, oncogenic t(10;17)(q22;p13) translocation yields YWHAE-FAM22A/B chimeric proteins that are associated with histologically high-grade and clinically more aggressive ESS. Integrating whole-transcriptome paired-end RNA sequencing with fluorescence in situ hybridization (FISH) and banding cytogenetics, we identified MBTD1 (malignant brain tumor domain-containing 1) and CXorf67 (chromosome X open reading frame 67) as the genes involved in the novel reciprocal t(X;17)(p11.2;q21.33) translocation in two independent low-grade ESS of classical histology. The presence of the MBTD1-CXorf67 fusion transcript was validated in both cases using reverse-transcription polymerase chain reaction followed by Sanger sequencing. A specific FISH assay was developed to detect the novel t(X;17) translocation in formalin-fixed paraffin-embedded material, and resulted in identification of an additional low-grade ESS case positive for the MBTD1-CXorf67 fusion among 25 uterine stromal tumors [14 ESS and 11 undifferentiated endometrial sarcomas (UESs)] that were negative for JAZF1 and YWHAE rearrangements. Gene expression profiles of seven ESS (including three with YWHAE and two with JAZF1 rearrangements) and four UES without specific chromosomal aberrations indicated clustering of tumors with MBTD1-CXorf67 fusion together with low-grade JAZF1-associated ESS. The chimeric MBTD1-CXorf67 fusion identifies yet another cytogenetically distinct subgroup of low-grade ESS and offers the opportunity to shed light on the functions of two poorly characterized genes. [ABSTRACT FROM AUTHOR]

Breast cancer during pregnancy (BCP) is an important subgroup within the young and very young breast cancer patients. It accounts for about 1% of all breast cancers. Due to an increased awareness, the attitude towards breast cancer during pregnancy has changed and, today, women with BCP are more likely to receive standard chemotherapy and have a term delivery instead of being advised to interrupt the pregnancy or undergo an early preterm delivery. This increased knowledge is based on small cohort studies and international collaborations such as the registry by the German Breast Group for BCP and the initiative of the European Society of Gynaecological Oncology (ESGO). Guidelines and recommendations such as the German guidelines by the AGO (Arbeitsgemeinschaft Gynäkologische Onkologie, www.ago-online.org) and the National Comprehensive Cancer Network (NCCN) guidelines include recommendations for BCP. In general, surgery and chemotherapy (beyond the 13th week of gestation) can be safely performed during pregnancy. Chemotherapy should follow the treatment recommendations for breast cancer in young women. Trastuzumab, endocrine treatment, and radiotherapy are not indicated during pregnancy. Preterm delivery should be avoided as far as possible because it bears a higher risk of infant morbidity and mortality. The treatment of BCP should be planned within a multidisciplinary team including perinatologists, obstetricians and neonatologists. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Every year approximately 74,000 women die of endometrial cancer, mainly due to recurrent or metastatic disease. The presence of tumor infiltrating lymphocytes (TILs) as well as progesterone receptor (PR) positivity has been correlated with improved prognosis. This study describes two mechanisms by which progesterone inhibits metastatic spread of endometrial cancer: by stimulating T-cell infiltration and by inhibiting epithelial-to-mesenchymal cell transition (EMT). Methodology and Principal Findings: Paraffin sections from patients with (n = 9) or without (n = 9) progressive endometrial cancer (recurrent or metastatic disease) were assessed for the presence of CD4+ (helper), CD8+ (cytotoxic) and Foxp3+ (regulatory) T-lymphocytes and PR expression. Progressive disease was observed to be associated with significant loss of TILs and loss of PR expression. Frozen tumor samples, used for genome-wide expression analysis, showed significant regulation of pathways involved in immunesurveillance, EMT and metastasis. For a number of genes, such as CXCL14, DKK1, DKK4, PEG10 and WIF1, quantitive RT-PCR was performed to verify up- or downregulation in progressive disease. To corroborate the role of progesterone in regulating invasion, Ishikawa(IK) endometrial cancer cell lines stably transfected with PRA (IKPRA), PRB(IKPRB) and PRA+PRB (IKPRAB) were cultured in presence/absence of progesterone (MPA) and used for genome-wide expression analysis, Boyden- and wound healing migration assays, and IHC for known EMT markers. IKPRB and IKPRAB cell lines showed MPA induced inhibition of migration and loss of the mesenchymal marker vimentin at the invasive front of the wound healing assay. Furthermore, pathway analysis of significantly MPA regulated genes showed significant down regulation of important pathways involved in EMT, immunesuppression and metastasis: such as IL6-, TGF-b and Wnt/b-catenin signaling. Conclusion: Intact progesterone signaling in non-progressive endometrial cancer seems to be an important factor stimulating immunosurveilance and inhibiting transition from an epithelial to a more mesenchymal, more invasive phenotype. [ABSTRACT FROM AUTHOR]

Recent large--scale association studies, both of genome-wide and candidate gene design, have revealed several single-nucleotide polymorphisms (SNPs) which are significantly associated with risk of developing breast cancer. As both breast and endometrial cancers are considered to be hormonally driven and share multiple risk factors, we investigated whether breast cancer risk alleles are also associated with endometrial cancer risk. We genotyped nine breast cancer risk SNPs in up to 4188 endometrial cases and 11 928 controls, from between three and seven Caucasian populations. None of the tested SNPs showed significant evidence of association with risk of endometrial cancer. [ABSTRACT FROM AUTHOR]

Alterations in stromal tissue components can inhibit or promote epithelial tumorigenesis. Decorin (DCN) and lumican (LUM) show reduced stromal expression in serous epithelial ovarian cancer (sEOC). We hypothesized that common variants in these genes associate with risk. Associations with sEOC among Caucasians were estimated with odds ratios (OR) among 397 cases and 920 controls in two U.S.-based studies (discovery set), 436 cases and 1,098 controls in Australia (replication set 1) and a consortium of 15 studies comprising 1,668 cases and 4,249 controls (replication set 2). The discovery set and replication set 1 (833 cases and 2,013 controls) showed statistically homogeneous (Pheterogeneity≥0.48) decreased risks of sEOC at four variants: DCN rs3138165, rs13312816 and rs516115, and LUM rs17018765 (OR = 0.6 to 0.9; Ptrend, = 0.001 to 0.03). Results from replication set 2 were statistically homogeneous (Pheterogeneity≤0.13) and associated with increased risks at DCN rs3138165 and rs13312816, and LUM rs17018765: all ORs = 1.2; Ptrend≥0.02. The ORs at the four variants were statistically heterogeneous across all 18 studies (Pheterogeneity≤0.03), which precluded combining. In post-hoc analyses, interactions were observed between each variant and recruitment period (Pinteraction≤0.003), age at diagnosis (Pinteraction = 0.04), and year of diagnosis (Pinteraction = 0.05) in the five studies with available information (1,044 cases, 2,469 controls). We conclude that variants in DCN and LUM are not directly associated with sEOC, and that confirmation of possible effect modification of the variants by non-genetic factors is required. [ABSTRACT FROM AUTHOR]

Endometrial cancer is the most common malignancy of the female genital tract in developed countries. To identify genetic variants associated with endometrial cancer risk, we performed a genome-wide association study involving 1,265 individuals with endometrial cancer (cases) from Australia and the UK and 5,190 controls from the Wellcome Trust Case Control Consortium. We compared genotype frequencies in cases and controls for 519,655 SNPs. Forty seven SNPs that showed evidence of association with endometrial cancer in stage 1 were genotyped in 3,957 additional cases and 6,886 controls. We identified an endometrial cancer susceptibility locus close to HNF1B at 17q12 (rs4430796, P = 7.1 × 10−10) that is also associated with risk of prostate cancer and is inversely associated with risk of type 2 diabetes. [ABSTRACT FROM AUTHOR]

The article presents a study which examined how the cognitive defects experienced by some breast cancer survivors are related to chemotherapy-induced structural changes in cerebral white matter (WM). It also provides neuropsychological, fractional anisotropy (FA) and magnetic resonance (MR) image assessment of the subjects. It suggests that WM integrity is lower in chemotherapy-treated breast cancer patients when compared with healthy controls or with nonchemotherapy-treated patients.

Prolonged excessive estrogen exposure unopposed by progesterone is widely accepted to be a risk factor for endometrial cancer development. The physiological function of progesterone is dependent upon the presence of its receptor [progesterone receptor (PGR)] and several studies have reported single nucleotide polymorphisms (SNPs) in the PGR gene to be associated with endometrial cancer risk. We sought to confirm the associations with endometrial cancer risk previously reported for four different PGR polymorphisms. A maximum of 2888 endometrial cancer cases and 4483 female control subjects from up to three studies were genotyped for four PGR polymorphisms (rs1042838, rs10895068, rs11224561 and rs471767). Logistic regression with adjustment for age, study, ethnicity and body mass index was performed to calculate odds ratios (ORs) and associated 95% confidence intervals (CIs) and P-values. Of the four SNPs investigated, only rs11224561 in the 3′ region of the PGR gene was found to be significantly associated with endometrial cancer risk. The A allele of the rs11224561 SNP was associated with increased risk of endometrial cancer (OR per allele 1.31; 95% CI 1.12–1.53, P = 0.001, adjusted for age and study), an effect of the same magnitude and direction as reported previously. We have validated the endometrial cancer risk association with a tagSNP in the 3′ untranslated region of PGR previously reported in an Asian population. Replication studies will be required to refine the risk estimate and to establish if this, or a correlated SNP, is the underlying causative variant. [ABSTRACT FROM AUTHOR]

Aim: To evaluate safety and fertility outcome after assisted conception in patients who were treated conservatively for a borderline ovarian tumor (BOT). Methods: A systematic literature review using Medline was conducted. From all the relevant case series the following information was obtained for each reported patient: primary diagnosis; disease stage; surgical treatment; duration of follow-up; incidence of recurrence; current disease status; the number of controlled ovarian stimulation cycles and/or oocyte retrievals, and successful pregnancies. Results: Overall 588 articles were screened, of which finally 15 reports including 62 patients met the inclusion criteria. Within a median follow-up duration of 52 months in this small group of patients, overall 12 patients (19.4%) had recurrences, and those recurrences were again successfully treated by surgery in 11 patients. In terms of assisted reproductive outcome, in our series overall 152 ovarian stimulation cycles as well as 135 oocyte retrievals were performed with a baby-take-home rate of 28.3% per stimulated cycle. Conclusion: It is mandatory to counsel all patients with a history of BOT who are seeking treatment for infertility that, due to the limited data, it is unclear whether assisted reproductive techniques are associated with an increased risk of recurrence. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Aims To examine the frequency of axillary lymph node (ALN) invasion of operable breast cancers by their combined oestrogen receptor (ER), progesterone receptor (PR) and HER-2 status. Methods 2227 recently operated cases in one centre were retrieved from the Multidisciplinary Breast Centre database and stratified according to their combined immunohistochemical (IHC) expression of ER/PR/HER-2 status. An equivocal HER-2 status was further analysed by Fluorescence in situ Hybridisation (FISH). The following 6 groups were considered: ER−PR−HER-2− (NNN; triple negative), ER−PR−HER-2+ (NNP), ER+PR−HER-2− (PNN), ER+PR−HER-2+ (PNP), ER+PR+HER-2− (PPN), ER+PR+HER-2+ (PPP; triple positive). For ALN, the following variables were tested in uni- and multivariate models: age at diagnosis (years), tumour size (mm), tumour grade, ER, PR, HER-2 and the combined steroid receptor and HER-2 status. Likelihood ratio χ2-tests were used for univariate analysis and logistic regression for multivariate analysis. Results Triple positive tumours had a higher likelihood of being ALN positive than others (56.2% versus 35.7%; P < 0.0001). Univariate logistic regression also withheld age, size, grade and HER-2 as predictors of ALN involvement. Final multivariate logistic regression revealed age, size, grade and PPP versus non-PPP to be independent predictors of ALN involvement; the odds ratio (OR) and 95% CI for PPP versus non-PPP tumours was 2.169 (1.490–3.156). Conclusion Our data provide insight into the natural history of triple positive breast carcinomas. Such tumours are more likely ALN positive than those with another steroid receptor and HER-2 status. How these findings correlate with breast cancer prognosis remains to be investigated. [ABSTRACT FROM AUTHOR]

Objective. Retroperitoneal para-aortic laparoscopic lymphadenectomy is a technically challenging operation. The robotic Da Vinci system might be valuable in this operation due to a steady three-dimensional visualization, instrumentation with articulating tips, and an adaptive downscaling of the surgeons movements (without tremor). To the best of our knowledge, this is the first report on robotic retroperitoneal para-aortic lymphadenectomy in patients with gynecologic cancer. Method and results. We report on the technique and operative results of the robotic retroperitoneal lower para-aortic lymphadenectomy using the Da Vinci Surgical System. Five patients with cervical carcinoma stage IIb-IIb were included. Technically the procedure was easier to perform than with the classical retroperitoneal laparoscopic approach. However using the Da Vinci Surgical System it is important to tilt the patient slightly to the left to avoid collision between the left arm of the patient and the robotic arms, and to place the endoscopic robotic arm between the 2 arms used for dissection. Finally, we experienced that using a 30° scope is advantageous for the dissection of the paracaval nodes. None of the patients had evidence of para-aortic metastases on preoperatively staging, including Positron Emission Tomography - Computed Tomography (PET-CT). One of the patients had positive para-aortic lymph nodes. Conclusion. Here we report on the surgical technique used in our first 5 patients undergoing retroperitoneal para-aortic lymphadenectomy using the robotic Da Vinci system. It is important to adapt the surgical technique using the Da Vinci Surgical System compared with the classical laparoscopic technique. [ABSTRACT FROM AUTHOR]

Background: Mammary tuberculosis is rare in the Western world. It has no defined clinical or imaging features, and has to be differentiated from breast cancer and an abscess. Case Report: We present a case of mammary tuberculosis combined with borderline ovarian cancer. The bilateral breast tuberculosis was the first and only symptom of underlying tuberculosis with Ziehl-Neelsenpositive para-aortic lymph nodes. During further exploration, an asymptomatic pelvic mass was discovered, which appeared later to be a borderline ovarian tumor. The patient was treated with tuberculostatic therapy for 6 months, resulting in a complete regression of the breast lesions. She also underwent hysterectomy with bilateral salpingo-oophorectomy and lymph node dissection for her ovarian cancer. Conclusions: This case report emphasizes that breast tuberculosis should be included in the differential diagnosis of any atypical breast mass. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objectives. In this paper we wish to present the reasons why i.p. chemotherapy cannot be accepted as standard of care for first-line systemic treatment of advanced ovarian carcinoma. Methods. The recent literature on i.p. chemotherapy is critically reviewed. All possible arguments against i.p. chemotherapy are reviewed. Conclusions. Intraperitoneal chemotherapy is associated with a higher toxicity rate than i.v. chemotherapy. For this reason, none of the regimens investigated in the three Gynecologic Oncology Group (GOG) studies can be used as standard treatment outside clinical protocols. The trials on i.p. chemotherapy have suggested a survival difference. However, in the two most recent trials, i.p. chemotherapy or not was not the only research question because different schedules and dosages were used. In addition, the significance of the most recent GOG 172 study was only weak (p = .03), and the result was non-significant for progression-free survival. Intraperitoneal chemotherapy should be used only in the context of properly designed clinical trials. These trials must either assess i.p. therapy in comparison with the standard treatment or address the issue of route of administration for equivalent dosages and schedules of the same drugs, and not a mosaic of these questions. In addition, these trials should investigate i.p. regimens that are less toxic than the regimens used in the three GOG trials, and which can be combined with molecular targeted therapies. [ABSTRACT FROM AUTHOR]

Traditionally when cervical cancer is diagnosed during the first trimester of pregnancy, oncological treatment is given priority despite the pregnant state. A 32-year-old primigravida was diagnosed with invasive endocervical adenocarcinoma stage Ib1 at 8 weeks' gestation. As the patient wanted to preserve the pregnancy, an amputation of the anterior cervix and retroperitoneal pelvic lymphadenectomy were performed. Based on favourable prognostic markers, we decided to maintain the pregnancy with careful cytological and histological follow-up. The patient gave birth at term to a healthy boy, and 18 months after the delivery there is no evidence of recurrent disease. In the absence of poor prognostic markers, we decided to adopt a conservative approach for cervical adenocarcinoma in a pregnant patient at 8 weeks' gestation. [ABSTRACT FROM AUTHOR]

Background: In a previously published pilot study we explored the performance of microarrays in predicting clinical behaviour of ovarian tumours. For this purpose we performed microarray analysis on 20 patients and estimated that we could predict advanced stage disease with 100% accuracy and the response to platin-based chemotherapy with 76.92% accuracy using leave-one-out cross validation techniques in combination with Least Squares Support Vector Machines (LS-SVMs). Methods: In the current study we evaluate whether tumour characteristics in an independent set of 49 patients can be predicted using the pilot data set with principal component analysis or LS-SVMs. Results: The results of the principal component analysis suggest that the gene expression data from stage I, platin-sensitive advanced stage and platin-resistant advanced stage tumours in the independent data set did not correspond to their respective classes in the pilot study. Additionally, LS-SVM models built using the data from the pilot study -- although they only misclassified one of four stage I tumours and correctly classified all 45 advanced stage tumours -- were not able to predict resistance to platin-based chemotherapy. Furthermore, models based on the pilot data and on previously published gene sets related to ovarian cancer outcomes, did not perform significantly better than our models. Conclusion: We discuss possible reasons for failure of the model for predicting response to platin-based chemotherapy and conclude that existing results based on gene expression patterns of ovarian tumours need to be thoroughly scrutinized before these results can be accepted to reflect the true performance of microarray technology. [ABSTRACT FROM AUTHOR]

Therapeutic options for cervical cancer have improved extensively over the last decade with the introduction of neoadjuvant chemotherapy prior to surgery for stage IB2–IIB and chemoradiation (radiation with concomitant weekly cisplatinum). Both regimens showed an improvement in overall survival of 14 and 12%, respectively, in comparison with radiotherapy alone. As for metastatic or recurrent cervical cancer, chemotherapy regimens are changing from cisplatin only to combination chemotherapy. Cisplatin with topotecan is the first combination regimen that showed an improvement in overall survival. However, further randomized trials will be necessary to confirm the superiority of this combination. [ABSTRACT FROM AUTHOR]

Primary debulking surgery by a gynecologic oncologist remains the standard of care in advanced ovarian cancer. Optimal debulking surgery should be defined as no residual tumor bail. In retrospective analye ses, neoadjuvant chemotherapy followed by interval debulking surgery does not seem to worsen prognosis compared to primary debulking surgery followed by chemotherapy. However, we will have to wait for the results of future randomized trials to know whether neoadjuvant chemotherapy followed by intend debulking surgery is as good as primary debulking surgery in stage HIC and IV patients. Interval debulking is defined as an operation performed after a short course of induction citemotherapy. Based on the randomized European Organization for Research and Treatment of Cancer-Gynecological Cancer Group (EORTC-GCG) trial, intend debulking by an experienced surgeon improves survival in some patients who did not undergo optimal primary debulking surgery. Based on Gynecobogic Oncology Group (GOG) 152 data, interval debulking surgery does not seem to be indicated in patients who underwent primarily a maximal surgical effort by a gynecologic oncologist Open laparoscopy is probably the most valuable tool for evaluating the operability primarily or at the time of interval debulking surgery. [ABSTRACT FROM AUTHOR]

Background: To investigate the role of the CYP17 gene promoter polymorphism in the pathobiology of uterine leiomyomas in African and Caucasian women.Methods: During a 6-month period, 145 Caucasian and black South African women undergoing hysterectomy were included prospectively. Blood samples were obtained for DNA analysis. Factors modifying the risk for uterine leiomyoma growth such as age, parity, age at last birth, weight, body mass index, menopausal status, cigarette smoking and oral contraceptive use were determined.Results: The risk for leiomyoma development among black South African homozygous carriers of the CYP17 A2 allele was shown to be significantly increased when compared to women homozygous for the CYP17 A1 allele or to heterozygous women. Logistic regression analysis disclosed age, parity and CYP17 polymorphism to have an impact on the presence of uterine leiomyomas (p-values are, respectively, 0.0006, 0.0001 and 0.03) in black South African women. However, among Caucasian women, logistic regression analysis showed only intake of oral contraceptives to influence the formation of uterine leiomyomas (p = 0.03).Conclusion: This exploratory trial suggests that among African women, homozygous carriers of the CYP17 A2 allele expose their myometrium to a stronger estrogenic stimulation contributing to the pathobiology of uterine leiomyomas. [ABSTRACT FROM AUTHOR]