Value of the 68Ga-DOTATATE PET-CT in the diagnosis of endometriosis. A pilot study.

OBJECTIVE: The non-invasive diagnosis of endometriosis remains challenging. Recent data suggested that somatostatin might be involved in its pathogenesis. High sensitive visualization of somatostatin receptors expression is possible using PET-CT imaging after the administration of a 68Ga-labeled somatostatin analog (DOTATATE) that will bind to the somatostatin receptor sub-types 2 and 5. The aim of the present study was to assess the usefulness of 68Ga-DOTATATE PET-CT in the diagnosis of endometriosis. STUDY DESIGN: This is a prospective, single center pilot study. A pre operative 68Ga-DOTATATE PET-CT was performed in all of the patients who presented with suspected endometriosis and who were scheduled for a laparoscopy. Surgical endometriosis staging and histopathological analysis, including somatostatin receptors SST1, 2 and 5 immunohistochemistry (IHC) of removed specimens, were confronted to the results of the 68Ga-DOTATATE PET-CT. RESULTS: 12 patients were included in this study. 68Ga-DOTATATE PET-CT performed pre operatively showed increased pathologic uptake in four patients with a deep infiltrating endometriosis (DIE) recto-vaginal lesion and in another patient with an adenomyoma. Expression of SST1, 2 and 5 receptors in surgical specimens was confirmed by IHC in these five lesions. Neither superficial peritoneal endometriosis, nor ovarian endometrioma were found to show an increased pathologic uptake on 68Ga-DOTATATE PET-CT. IHC analysis confirmed that SST1, 2, and 5 receptors were not present in these lesions. CONCLUSION: The results observed in this small size series of patients seem to confirm expression of somatostatin receptors only in recto-vaginal DIE and focal adenomyosis lesions. The usefulness of 68Ga-DOTATATE PET-CT in the diagnosis of this entity is uncertain. Future research should concentrate on studying the role of somatostatin in the pathogenesis of DIE.

Fertility-sparing management of gynecological cancers.

Fifteen to 21% of women diagnosed with genital tract tumors are younger than 40. Adequate counseling of these patients must be conducted to decide whether fertility-sparing treatment is allowed and what would be the oncological, fertility and obstetrical outcomes. We performed a comprehensive PubMed literature search using the terms "Uterine Cervical Neoplasms"[Mesh], "Trachelectomy", "Endometrial Neoplasms"[Mesh], "Ovarian Neoplasms"[Mesh] and "Fertility"[Mesh]. The following review reports available evidence for the conservative management of cervical, endometrial and ovarian cancer. Data regarding the selection of patients, surgical techniques, obstetrical issues and cancer prognosis are summarized. The level of evidence is low in most of the available reports. The therapeutic options presented in this paper should not therefore be considered as a standard of care. Nevertheless, fertility-sparing treatments of gynecological malignancies should be discussed in a multidisciplinary team and suggested to eligible patients who are younger than 40 and wish to become pregnant further.

Should we abstain from treating women with endometriosis using menopausal hormone therapy, for fear of an increased ovarian cancer risk?

Women suffering from endometriosis often have an early menopause, resulting in severe menopausal symptoms and an increased risk of osteoporosis. They are therefore candidates for menopausal hormone therapy (MHT). Unfortunately, MHT may increase the risk of endometriosis recurrence. Moreover, endometriosis patients are at increased risk of ovarian cancer, which may be further enhanced by MHT use. It is unknown, however, whether MHT more frequently increases type I (low-grade serous tumors), which seem to be increased when endometriosis is present, or type II (the more aggressive high-grade serous) tumors. We propose the following decision-making algorithm for endometriosis patients considering MHT. Those who have been treated with bilateral salpingo-oophorectomy, and in whom there is no residual endometriotic disease, can probably be treated using MHT without risk of endometriosis recurrence or fear of ovarian cancer. For women with significant, residual endometriosis lesions, the benefit may outweigh the risks, when menopause is reached before the age of 45 years or when severe symptoms are present.

Safety and usefulness of cryopreservation of ovarian tissue to preserve fertility: a 12-year retrospective analysis.

STUDY QUESTION: Do the benefits of ovarian tissue cryopreservation outweigh the risks for patients seeking to preserve fertility before gonadotoxic treatment in various indications? SUMMARY ANSWER: In >90% of the patients undergoing cryopreservation of ovarian tissue, oncological treatment was associated with a reduced ovarian reserve and in 30% of patients, premature ovarian failure (POF) occurred within 5 years. WHAT IS KNOWN ALREADY: Ovarian tissue cryopreservation is an effective fertility preservation option, especially for pre-pubertal patients and patients who have a short time between diagnosis of a disease and gonadotoxic treatment. STUDY DESIGN, SETTING, DURATION: This study retrospectively analysed ovarian function and fertility recovery rates, as well as ovarian tissue characteristics, of patients who underwent ovarian tissue cryopreservation at Erasme Hospital between 1999 and 2011. PARTICIPANTS/MATERIALS, SETTINGS, METHODS: A total of 225 patients referred from 15 Belgian oncological units underwent cryopreservation of ovarian tissue before gonadotoxic therapy for malignant or benign diseases. There were 28 patients (12.4%) who died during follow-up due to recurrence of disease. One severe adverse event occurred during anaesthesia for ovarian tissue collection, leading to the death of the patient. Ovarian function and fertility outcomes were available for 114 patients including 13 girls who were pre-pubertal at the time of the procedure. Eight patients had undergone ovarian tissue transplantation in order to restore their fertility after remission of the disease. MAIN RESULTS AND THE ROLE OF CHANCE: Breast cancer and haematological disease were the most frequent indications for ovarian tissue cryopreservation. Overall, 90% of post-pubertal patients were diagnosed with poor ovarian reserve (AMH < 0.5 ng/ml) after a mean of 50 months of follow-up (11-125 months), including 30% with POF (FSH > 40 IU/ml). Breast cancer patients had a lower rate of POF than did post-pubertal patients with haematological diseases (11 versus 34.5%, respectively), despite the older age (mean 31 versus 23.5 years old, respectively) of the breast cancer patients. Ovarian function returned in 71 post-pubertal patients without the need for grafts of cryopreserved tissue. Spontaneous pregnancies were reported for 33 of them, leading to 34 live births. Among the 13 pre-pubertal patients who reached pubertal age during the follow-up, 10 had POF. Eight patients received cryopreserved ovarian grafts to reverse POF and three of them have already become pregnant. LIMITATIONS, REASONS FOR CAUTION: This study is a retrospective analysis. The cohort was not compared with a control group of patients who did not undergo the procedure. WIDER IMPLICATIONS OF THE FINDINGS: After careful evaluation of the surgical risks, ovarian tissue cryopreservation can be proposed as an efficient option to preserve the fertility of children and young adults facing gonadotoxic therapies. However, alternative procedures such as oocyte or embryo cryopreservation should be considered as first options especially for older patients or if there is high risk of neoplastic cells within the ovaries. STUDY FUNDING/COMPETING INTEREST: This study was supported by the Télévie, FNRS-FRSM and Fondation Belge contre le cancer. There are no competing interests to report.

A survey among breast cancer survivors: treatment of the climacteric after breast cancer.

AIM: To evaluate the prevalence and type of menopausal treatments used by breast cancer survivors. To assess factors that impaired the quality of life of these patients. MATERIAL AND METHODS: A questionnaire assessing quality of life was sent to 325 breast cancer patients. A 66% valid response rate was obtained. Among these responses, 169 women were postmenopausal. The following results concern these patients only. RESULTS: Forty-five women were using some treatment to alleviate certain menopausal symptoms (26.6%). More than half of the patients used no therapy to alleviate menopausal symptoms, either because they had no symptoms (n = 43; 25.4%), they feared breast cancer recurrence (n = 24; 14.2%), they were advised not to use a treatment (n = 27; 16%), it had been shown to be inefficient (n = 5; 3%), or because of contraindication (n = 3; 1.8%). In this survey, 62.3% of postmenopausal women affected by breast cancer suffered from hot flushes (n = 94), of which half were severe (n = 46). Among women suffering from hot flushes, a third used various products to alleviate their symptoms (n = 30). Younger women suffered more often from vasomotor symptoms than did older women (p < 0.000). Current users of aromatase inhibitors suffered more from sexual disorders than did non-users (p < 0.001). They had more often an unsatisfactory sexual life (p < 0.01), more vaginal dryness (p = 0.01) and a decreased libido (p < 0.02) compared to non-users. CONCLUSION: More than 50% of postmenopausal women suffered from climacteric symptoms such as hot flushes, but few were taking a treatment to alleviate these symptoms.

Desire for a child and breast cancer.

About 10% of breast cancers occur in women who are younger than 40 years of age. For many of them, the breast cancer diagnosis will occur when they are still planning pregnancy. Most breast cancers are diagnosed at an early stage of the disease, i.e. stage I or II, which is associated with a high survival rate (5 years-survival ranging between 97% and 79% respectively) (1). Many of these patients will use adjuvant endocrine therapy. This treatment has no direct impact on their fertility, but postpones a possible pregnancy, since pregnancy is contra-indicated during Tamoxifen treatment. On the other hand, chemotherapy increases the risk of premature ovarian failure, of early menopause, and of definitive sterility. This may result in an increased risk of depression and impaired quality of life. Furthermore, those women who remain fertile will often be advised to avoid pregnancy in the near future, in order to ensure the absence of breast cancer recurrence. Nevertheless, fertility decreases with age. Possible strategies, which permit optimal treatment of breast cancer and maintain the possibility of pregnancy, should be systematically discussed with the patient as soon as possible during treatment planning (2). Gynecologists and surgeons should encourage such patients to participate in multi-center studies evaluating strategies to preserve their fertility. Life continues after cancer; the prospect of pregnancy and child birth are part of a positive project.

Differential expression of S100 calcium-binding proteins characterizes distinct clinical entities in both WHO grade II and III astrocytic tumours.

The computer-assisted microscopic analysis of Feulgen-stained nuclei enabled us to identify two subgroups of astrocytomas (WHO grade II) and two subgroups of anaplastic astrocytomas (WHO grade III) with significantly distinct clinical outcomes (Decaestecker et al. Brain Pathol 1998; 8: 29-38). The astrocytomas labelled in the present study as typical (TYP-ASTs) behaved clinically like real astrocytomas while atypical astrocytomas (ATYP-ASTs) behaved similarly to anaplastic astrocytomas. The anaplastic astrocytomas that we labelled as typical (TYP-ANAs) behaved clinically like anaplastic astrocytomas while atypical ones (ATYP-ANAs) behaved like glioblastomas. In the present study, we investigate whether some biological characteristics could be evidenced across these four groups of TYP- and ATYP-ASTs and TYP- and ATYP-ANAs. The data show that the levels of expression (immunohistochemically assayed and quantitatively determined by means of computer-assisted microscopy) of vimentin, the glial fibrillary acidic protein and the platelet-derived growth factor-alpha did not differ significantly across these four groups of astrocytic tumours. The level of cell proliferation (determined by means of both the anti-proliferating cell nuclear antigen and the anti-MIB-1 antibodies; P < 0.001 to P < 0.0001) differed very significantly between the astrocytomas and anaplastic astrocytomas, but not between the typical and atypical variants identified in each group. In sharp contrast, the levels of expression of the S100A3 and S100A5 proteins differed markedly in the solid tumour tissue in relation to the astrocytic tumour types and grades. In addition, while the levels of expression of S100A6 did not change in the astrocytic tumour tissue in relation to histopathological grade, the levels of expression of this S100 protein (but not those of S100A3 and S100A5) differed markedly in the blood vessel walls according to whether these vessels originated from low- or high-grade astrocytic tumours.

Long-term follow-up of elderly patients with severe aortic stenosis treated by balloon aortic valvuloplasty. Importance of haemodynamic parameters before and after dilatation.

Early and late prognosis after percutaneous balloon aortic valvuloplasty (PBAV) was assessed in 38 consecutive elderly patients (mean age, 78.5 +/- 6.1 years). Significant valve opening was achieved in 35 patients. The hospital mortality was 8% (three patients); two other patients died within the first month and three underwent aortic valve replacement. At 2 years follow-up, there were 10 additional deaths (seven cardiac deaths) and five patients had symptom recurrence managed by aortic valve replacement (3) or repeat PBAV (2). Overall, six patients underwent surgery without untoward events and six had repeat PBAV. Only two out of six patients with repeat PBAV had sustained improvement; one was referred to surgery and the remaining three died soon after the second PBAV. One- and 2-year survival were respectively 72 and 62% and percentage of survivors with persistent improvement 68 and 41%. Although aortic valve area after PBAV was associated with outcome, predictors of poor long-term prognosis were primarily related to the pre-operative haemodynamic status. Patients with pulmonary resistances greater than 400 dynes cm-1 s-5 had the poorest outcome (chi 2 = 18.4-P less than 0.0001). Overall, signs of heart failure were predictors of poor long term follow-up. These data indicate that long-term success of PBAV is mainly related to the left ventricular dysfunction noted prior to intervention.