Abstract Evaluation of endometrial thickness by transvaginal ultrasonography (TVUS) in postmenopausal estrogen receptor positive breast cancer patients treated with anastrozole after tamoxifen ...therapy. This study included 70 postmenopausal estrogen receptor positive breast cancer patients who switched to anastrozole after tamoxifen; patients had endometrial thickness >4 mm and no endometrial malignancy. Endometrial thickness was measured after anastrozole treatment. Endometrial thickness during anastrozole therapy was lower than after tamoxifen therapy ( p < 0.001); the mean reduction in endometrial thickness was 4.5 mm (±3.0). Cystic endometrial appearance was more frequent in patients under tamoxifen than in those under anastrozole ( p < 0.001). Duration of tamoxifen therapy was not correlated to the endometrial thickness at the time of its suspension. Duration of tamoxifen therapy and endometrial thickness at the time of tamoxifen suspension was correlated to the relative reduction of endometrial thickness during anastrozole therapy. Anastrozole reverses tamoxifen-induced increased endometrial thickness and sonographic endometrial cystic appearance.
Asthma in women with endometriosis Ferrero, S.; Petrera, P.; Colombo, B.M. ...
Human reproduction (Oxford),
12/2005, Letnik:
20, Številka:
12
Journal Article
Recenzirano
Odprti dostop
INTRODUCTION: This study aimed to investigate asthma prevalence and severity in women with and without endometriosis. METHODS: Before laparoscopy, asthma prevalence was evaluated in 879 women of ...reproductive age, undergoing surgery because of benign gynaecological conditions. Diagnosis of bronchial asthma was based on the American Thoracic Society criteria; asthma severity was classified in four categories according to the 2002 Global Initiative for Asthma guidelines. Asthmatic patients completed the Living with Asthma Questionnaire (LWAQ). Endometriosis was confirmed histologically and classified according to the revised American Fertility Society criteria. RESULTS: There were no significant differences in age, smoking status, and other demographic and health characteristics between patients with endometriosis (n = 467) and controls (n = 412). Asthma prevalence was similar in women with (23/467, 4.9%; 95% CI, 3.1–7.3) and without (22/412, 5.3%; 95% CI, 3.4–8.0; P = 0.781) endometriosis. Asthma severity was similar in women with and without endometriosis, with 12 (52.2%) women with endometriosis and 13 (59.1%) controls being in the intermittent (mildest) degree of severity. No significant difference was observed between women with and without endometriosis in the LWAQ total score. CONCLUSIONS: Women with endometriosis do not have an increased risk of having asthma.
Images in clinical medicine. Endometriosis Ferrero, Simone; Remorgida, Valentino
The New England journal of medicine,
2007-Aug-16, 20070816, Letnik:
357, Številka:
7
Journal Article
Abstract 3375
Telomere are effective sensors of cell integrity and their accelerated shortening is a marker of genetic and/or proliferative stress in several tissues including the hematopoietic ...compartment. Severe telomere attrition has been indeed observed in aplastic anemia and post-transplant setting. Little is currently known on the genetic integrity of Ph-negative hematopoietic cells (HCs) repopulating the bone marrow (BM) after successful chronic myeloid leukemia (CML) treatment. We thus decided to verify whether severe telomere shortening might occur in this setting and to assess whether its presence might correlate to genetic and functional impairment of Ph-negative hematopoiesis.
We investigated 81 CML patients with persistent (≥12 months) complete cytogenetic remission (CCyR). Median age was 62 years (23-88), M/F ratio was 1.5. Median time from diagnosis and CCyR were 4 years (1-18) and 3 years (1-12) respectively. 15 patients had acquired cytogenetic abnormalities (CA) (del7: 4 patients, +8: 5 patients, del5q: 2 patients, del or +Y: 2 patients, other CA: 2 patients). Telomere length (TL) analysis was performed by Southern Blotting on polymorphonucleates (PMN) and on monocyte-depleted PBMC (MD-PBMC) to monitor both the myeloid and lymphoid compartments. As control group we analyzed 76 age-matched healthy donors. Prospective follow-up monitoring of TL was performed on 56 CML patients with a median time of 22 months from the first determination (range 12–20).
PMN (but not MD-PBMC) from CML patients showed a major erosion of their telomeric DNA (median loss 1294 bp p<0.001). Correlations were sought by using a multivariate general linear model on the whole population (CML patients and controls) and then exclusively on the CML population. In the whole population a previous history of CML was a predictor of TL attrition together with age (both p <0.001). In the CML-only population we found no association between TL and sex, Sokal score, or treatment schedule. Most notably we found a correlation between TL attrition and presence of acquired CA (p=0.02, figure 1A), particularly in case of del7 and +8. Somehow more surprisingly we found an increased TL shortening among patients lacking complete molecular remission (CMolR) (p=0.001). The physiological correlation between age and TL persisted also among CML patients (p=0.003). Moreover we found an association between the presence of short telomeres and G≥2 hematological toxicity of any kind (p=0,005), anemia (p=0,007) and a trend with the presence of neutropenia (p=0,080). The association persisted also when G1-4 toxicities were considered (hematological toxicity of any kind p=0.030, anemia p=0.010). We than made a prospective assessment of the telomere dynamics over time performing a second TL determination after at least 12 months on 56 patients. The overall population showed further significant ongoing telomere shortening that was superior to the expected yearly loss for healthy subjects (median annual telomeric loss of 261 bp). We then performed a patient by patient analysis of TL dynamics over time. None of the patients had evidence of telomere recovery. Moreover even considering the maximal recorded interassay variability of 300 bp and the maximal physiological annual telomeric loss (50 bp), a non-physiological telomeric loss was observed in 17 patients (30% of CML population, median loss of 534 bp, range 1290-357 bp, figure 1C).
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i) Ph-negative HCs display severe telomeric loss, compared to healthy controls; ii) telomere erosion is more pronounced in patients with CA and without CMolR; iii) a strong association between shorter telomeres and hematological toxicity (particularly anemia) was observed; iv) telomere loss is persistent over time in the whole population. Moreover one third of them has a clear evidence of ongoing telomere erosion during the remission phase. Our results indicate that Ph-negative hematopoiesis emerging after successful CML treatment suffers from severe and ongoing telomeric stress whose biological and clinical consequences need to be carefully investigated.
No relevant conflicts of interest to declare.
Ectopic endometrial tissue is found in 1.5% to 6.2% of women of reproductive age, in up to 60% of those with dysmenorrhoea, and in up to 30% of women with subfertility, with a peak incidence at ...around 40 years of age. However, symptoms may not correlate with laparoscopic findings.
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of hormonal treatments given at diagnosis of endometriosis? What are the effects of hormonal treatments before surgery for endometriosis? What are the effects of non-hormonal medical treatments for endometriosis? What are the effects of surgical treatments for endometriosis? What are the effects of hormonal treatment after conservative surgery for endometriosis? What are the effects of hormonal treatment after oophorectomy (with or without hysterectomy) for endometriosis? What are the effects of treatments for ovarian endometrioma? We searched: Medline, Embase, The Cochrane Library, and other important databases up to December 2009 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
We found 40 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
In this systematic review we present information relating to the effectiveness and safety of the following interventions: combined oral contraceptives, danazol, dydrogesterone, gestrinone, gonadorelin analogues, aromatase inhibitors, hormonal treatment before surgery, hormonal treatment, laparoscopic cystectomy, laparoscopic removal of endometriotic deposits (alone or with uterine nerve ablation), laparoscopic removal plus presacral neurectomy, laparoscopic uterine nerve ablation, non-steroidal anti-inflammatory drugs, presacral neurectomy alone, and progestogens other than dydrogesterone.
Abstract 827
We have recently shown that a consolidation therapy with bortezomib/thalidomide/dexamethasone (VTD) in multiple myeloma (MM) patients responding to autologous transplantation (ASCT) ...induces major tumor shrinking assessed by real time-quantitative (RQ)-PCR. Moreover we found that low levels of minimal residual disease (MRD) associated to a better progression-free survival (PFS) GIMEMA VEL-03-096 trial, EudraCT Number 2004-000531-28: Ladetto et al, J Clin Oncol 2010. We here present the updated results of this study at a median follow-up of 65 months. In the present analysis the following additional issues have been addressed: a) impact of MRD on PFS over time, with special interest to the role of MRD kinetics on outcome; b) impact of MRD on overall survival (OS).
Inclusion criteria and treatment schedule for this study have been already reported Ladetto et al., J Clin Oncol 2010 and included: 1) a documented complete or very good partial remission following ASCT delivered as first line treatment; 2) no previous therapy with thalidomide or bortezomib; 3) presence of a molecular marker based on the immunoglobulin heavy chain rearrangement (IGH). MRD was assessed on bone marrow samples at diagnosis, study entry, after two VTD courses, at the end of treatment and then at six months intervals, up to clinical relapse. Patients underwent MRD detection using either qualitative nested PCR and RQ-PCR, employing IGH-derived patient specific primers as already described Voena et al., Leukemia 1997; Ladetto et al., Biol Bone Marrow Transpl 2000. For outcome analysis patients were grouped according to following definitions: a) MRD negativity on two consecutive samples by the most sensitive PCR method (nested PCR): full molecular remission (FMR); b) MRD negativity on two consecutive samples by RQ-PCR (less sensitive but currently better standardized, according to European Study Group on MRD detection guidelines van der Vendel et al., Leukemia 2007): standard molecular remission (SMR); c) post-treatment tumor load above the median by RQ-PCR: high tumor burden (HTB); d) post-treatment tumor load below the median by RQ-PCR: low tumor burden (LTB); e) recurrence of detectable MRD after FMR/SMR: molecular relapse (M-rel); f) increase of MRD levels of at least one log: active disease (AD).
Feasibility, toxicity and clinical outcome of the trial have been already reported Ladetto et al., J Clin Oncol 2010. Thirty-nine patients were enrolled and median clinical follow-up from start of first line treatment is 65 months. 270 of the planned samples for MRD monitoring (86%) were actually received by the centralized lab. So far 17 relapses and six deaths have been reported. Following VTD consolidation, 7/38 evaluable patients achieved FMR (18%) and 15/38 achieved SMR (39%). Three M-rel were observed, two of them followed by clinical relapse within six months. Achievement of SMR proved highly predictive for PFS (5-years (y) PFS 82% vs 44%, p=0.009, figure 1A), as well as the presence of HTB and AD (5-y PFS 35% vs 87%, p<0.001, figure 2). Interestingly, patients with LTB and no evidence of M-rel or AD had an excellent outcome with a 5-y PFS of 87%, (even considering that molecular follow-up was incomplete due to lack of samples in the two events observed in the low risk group, figure 2). Most notably, none of the patients achieving FMR or SMR has so far died and both SMR and AD proved to be significant predictors for OS (respectively, 5y-OS 100% vs 74%, p=0.012, figure 1B, and 5y-OS 86% vs 100%, p=0.037, data not shown). Display omitted Display omitted
Our long-term results indicate that: 1) the achievement of SMR following VTD consolidation in MM patients is associated with a better outcome in terms of PFS and OS; 2) a dynamic increase in molecular tumor burden (AD), detectable by RQ-PCR, predicts late disease relapses several months before clinical recurrence. Taken together these results suggest the importance of developing tailored treatment for patients with high residual burden or showing increasing levels of MRD during follow-up, as already pursued for example in mantle cell lymphoma Andersen et al., J Clin Oncol 2009.
Ladetto:Celgene: Honoraria, Research Funding; Roche: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Bayer: Honoraria; Mundipharma: Honoraria; Janssen-Cilag: Research Funding; Italfarmaco: Research Funding. Cavallo:celgene: Honoraria. Guglielmelli:celgene: Honoraria; Janssen-Cilag: Honoraria. Boccadoro:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen-Cilag: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Palumbo:Merck: Honoraria; Janssen-Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees; celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria.
Endometriosis is a gynecological disorder defined by the presence of endometrial-like tissue outside the uterus. Several studies have found an epidemiological correlation between endometriosis and ...migraine, probably due to the association of both diseases with female hormones. Progestins or combined oral contraceptives are the first-line medical therapy in women with endometriosis; however, it is well known that in some women the use of combined oral contraceptives could exacerbate migraine. This observation poses a challenge to clinicians who must concomitantly treat endometriosis-related symptoms and migraine. This review summarizes the available literature on the medical treatment of endometriosis in women suffering concomitant migraine without aura until March 2012. Due to the lack of available studies on this topic, it is difficult to draw definitive conclusions. Further studies evaluating hormonal therapies are needed; in particular, progestin therapy should be reconsidered in women with migraine and concomitant endometriosis.
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