Endometriosis and perceived stress: impact of surgical and medical treatment.

BACKGROUND: The aim of the study was to investigate the levels of perceived stress in a group of women with a long-term history of endometriosis in conjunction with surgical and/or medical treatments. METHODS: A clinical trial was conducted at the Department of Molecular and Developmental Medicine, University of Siena, in collaboration with a non-profit association of women with endometriosis, A.P.E. Onlus. Patients (n = 204) with a previous diagnosis of endometriosis (for at least 3 years) were included in this study. Each patient completed a semi-structured questionnaire and a validated scale to assess perceived stress, the Perceived Stress Scale (PSS) by e-mail. RESULTS: The study showed that in women with a long-term history of endometriosis, the level of perceived stress was increased by repeated surgical treatments and reduced by some medical treatments. The median PSS value was 23 (range 9-36) and 30.6% of the study population were included in the highest stress category (>26). The highest levels were found in patients who had undergone the most surgery. The use of progestins was associated with a lower perceived stress (p = 0.004) than in the patients treated with gonadotropin-releasing hormones. CONCLUSIONS: Long-term endometriosis has a relevant impact on perceived stress, in particular in those undergoing repeated surgery.

Cytochrome 450 1B1 (CYP1B1) polymorphisms associated with response to docetaxel in Castration-Resistant Prostate Cancer (CRPC) patients.

BACKGROUND: The selection of patients according to key genetic characteristics may help to tailor chemotherapy and optimize the treatment in Castration-Resistant Prostate Cancer (CRPC) patients. Functional polymorphisms within the cytochrome P450 1B1 (CYP1B1) gene have been associated with alterations in enzymatic expression and activity and may change sensitivity to the widely used docetaxel regimen. METHODS: CYP1B1 genotyping was performed on blood samples of 60 CRPC patients treated with docetaxel, using TaqMan probes-based assays. Association between CYP1B1-142C>G (leading to the 48ArgGly transition), 4326C>G (432LeuVal), and 4390A>G (453AsnSer) polymorphisms and treatment response, progression-free-survival (PFS) and overall-survival (OS) was estimated using Pearson χ2 test, Kaplan-Meier curves and Log-rank test. RESULTS: Patients carrying the CYP1B1-432ValVal genotype experienced a significantly lower response-rate (P = 0.014), shorter progression-free-survival (P = 0.032) and overall-survival (P < 0.001). Multivariate analyses and correction for multiple comparisons confirmed its prognostic significance for OS. No significant associations were found among other polymorphisms and both response and clinical outcome. CONCLUSIONS: CYP1B1-4326C>G (432LeuVal) polymorphism emerged as possible predictive marker of response and clinical outcome to docetaxel in CRPC patients and may represent a potential new tool for treatment optimization. Larger prospective trials are warranted to validate these findings, which might be applied to the future practice of CRPC treatment.

Epirubicin plus low-dose trastuzumab in HER2 positive metastatic breast cancer.

PURPOSE: This phase II study, evaluated the activity and cardiotoxicity of first-line epirubicin plus low-dose trastuzumab (LD-T) in patients with HER2 positive MBC. METHODS: Patients received epirubicin 90 mg/sqm every 3 weeks plus weekly LD-T (2 mg/kg loading dose, then 1 mg/kg). After 6/8 cycles of epirubicin, single agent trastuzumab was continued. Cardiotoxicity was defined as signs or symptoms of congestive heart failure (CHF), or >or=15% decline in LVEF without symptoms, or <15% LVEF decline to less than 50%, without symptoms. RESULTS: Forty-five patients were enrolled. Twenty-three received prior adjuvant anthracyclines. Overall response rate was 61.4%. The median time to progression was 7.4 months and the median survival was 32.8 months. Two (4.5%) patients developed CHF. CONCLUSIONS: Epirubicin plus LD-T is an active regimen, however, the relatively high rate of cardiotoxicity together with the availability of less cardiotoxic and active trastuzumab-containing combinations precludes further evaluation of this regimen.

5-fluorouracil pharmacokinetics predicts disease-free survival in patients administered adjuvant chemotherapy for colorectal cancer.

PURPOSE: To evaluate 5-fluorouracil (5-FU) and 5-fluoro-5,6-dihydrouracil (5-FDHU) pharmacokinetics and disease-free survival (DFS) in colorectal cancer patients given 5-FU-based adjuvant chemotherapy within a nonrandomized, retrospective, pharmacokinetic study. EXPERIMENTAL DESIGN: One hundred fifteen patients including 72 men (median age, 63 years; range, 36-79 years) and 43 women (median age, 60 years; range, 36-73 years) received 6 cycles of l-leucovorin 100 mg/m(2)/day and 5-FU 370 mg/m(2)/day i.v. boluses (5 days every 4 weeks). Individual plasma concentrations of 5-FU and 5-FDHU were determined on day 1 of the first cycle with a validated high performance liquid chromatography method, and the main pharmacokinetic variables were determined. Follow-up of all patients was extended up to 5 years after the end of adjuvant chemotherapy, and DFS was recorded. Univariate and multivariate analyses were conducted to evaluate any correlation among 5-FU pharmacokinetics, clinical and pathologic variables, and DFS. RESULTS: The area under the time/concentration curve (AUC) of 5-FU was significantly lower in 58 subjects who recurred (7.5 +/- 2.9 h x mg/L) with respect to other patients (9.3 +/- 4.1 h x mg/L). Furthermore, AUC values lower than 8.4 h x mg/L together with lymph node involvement and the interruption of treatment or reduction of doses were identified as risk factors at univariate analysis. The completion of 6 cycles of adjuvant treatment without dosage modifications was the only independent risk factor at multivariate analysis, despite a trend toward significance for 5-FU AUC values (cutoff value, 8.4 hxmg/L) was observed (P = 0.06). CONCLUSIONS: Pharmacokinetics of 5-FU should be regarded as an important factor for predicting disease recurrence in colorectal cancers.

Correlation of CDA, ERCC1, and XPD polymorphisms with response and survival in gemcitabine/cisplatin-treated advanced non-small cell lung cancer patients.

PURPOSE: Selecting patients according to key genetic characteristics may help to tailor chemotherapy and optimize the treatment in non-small cell lung cancer (NSCLC). Polymorphisms at the xeroderma pigmentosum group D (XPD), excision repair cross-complementing 1 (ERCC1), and cytidine deaminase (CDA) genes have been associated with alterations in enzymatic activity and may change sensitivity to the widely used cisplatin-gemcitabine regimen. EXPERIMENTAL DESIGN: Analyses of CDA, XPD, and ERCC1 polymorphisms were done on blood samples of 65 chemotherapy-naïve, advanced NSCLC patients treated with cisplatin-gemcitabine. Furthermore, CDA enzymatic activity was evaluated by high-performance liquid chromatography analysis. Association between XPD Asp(312)Asn and Lys(751)Gln, ERCC1 C118T, and CDA Lys(27)Gln polymorphisms and response, clinical benefit, toxicity, time to progression (TTP), and overall survival (OS) was estimated using Pearson's chi(2) tests, the Kaplan-Meier method, the log-rank test, and the Cox proportional hazards model. RESULTS: The CDA Lys(27)Lys polymorphism significantly correlated with better clinical benefit (P = 0.04) and grade > or =3 neutropenia and thrombocytopenia, as well as with longer TTP and OS (P = 0.006 and P = 0.002, respectively), whereas no significant associations were found among ERCC1 and XPD polymorphisms and both response and clinical outcome. Finally, the enzymatic activity assay showed a significant lower mean in subjects harboring the CDA Lys(27)Lys polymorphism. CONCLUSIONS: Our data suggested the role of CDA Lys(27)Lys polymorphism as a possible predictive marker of activity, toxicity, TTP, and OS in advanced NSCLC patients treated with cisplatin and gemcitabine. These results may be explained by the lower enzymatic activity associated with the Lys(27)Lys CDA and offer a potential new tool for treatment optimization.

Plasma and urine aldosterone to plasma renin activity ratio in the diagnosis of primary aldosteronism.

OBJECTIVE: To establish the best cut-off value of the aldosterone (ALD)/plasma renin activity (PRA) ratio when screening patients for primary aldosteronism. One hundred and six patients with primary aldosteronism and 100 essential hypertensive patients were investigated in rigorous standardized conditions. METHODS: The ALD/PRA cut-off values were calculated from both the plasma and urine ALD/PRA ratio and analyzed by receiver operating characteristic (ROC) curve. In patients with PRA below 0.2 ng/ml/h [our radioimmunoassay detection limit], values were calculated both with PRA levels set at 0.2 ng/ml/h ('adjusted') and with PRA levels detected ('unadjusted') in the assay. RESULTS: ROC analysis on the ALD/PRA ratio indicated that the best performance was obtained when the plasma ALD (ng/dl)/PRA ratio was used in comparison with that observed in the urine ALD (microg/day)/PRA ratio. In patients with primary aldosteronism, as a whole group, the cut-off value of 69 corresponded to the best compromise value between sensitivity (96%) and specificity (85%), with and without PRA adjustment. In patients with aldosterone-producing adenoma, the cut-off to obtain 100% sensitivity with high specificity (85%) proved to be 69, with and without PRA adjustment. In patients with bilateral adrenal hyperplasia, both with and without PRA adjustment, the best compromise between sensitivity (94%) and specificity (86%) was a cut-off value of 71. CONCLUSION: The best cut-off to identify patients with primary aldosteronism, corresponding to 69, was obtained by using the plasma ALD/PRA ratio. Adjustment of PRA to 0.2 ng/ml/h does not interfere with calculation of the plasma ALD/PRA ratio cut-off.

Optimal detection of sentinel lymph node metastases by intraoperative radioactive threshold and molecular analysis in patients with melanoma.

UNLABELLED: The aim of this study was to optimize a protocol for radioguided biopsy of the sentinel lymph node (SLN) in patients with melanoma. The protocol was based on a combination of ex vivo counting of the nodes detected intraoperatively and analysis of the harvested nodes by hematoxylin and eosin staining plus immunohistochemistry (conventional histopathology [PATH]) and by molecular biology (reverse-transcriptase polymerase chain reaction [RT-PCR]). METHODS: A total of 124 patients with primary clinical stage I-II (according to the American Joint Committee on Cancer) cutaneous melanoma underwent successful radioguided SLN biopsy. SLNs harvested for analysis included any additional nodes whose ex vivo counting rate exceeded 20% of the hottest node. All removed SLNs were examined by conventional PATH and with RT-PCR analysis for the expression of messenger RNA for tyrosinase and the melanoma antigens recognized by T cells. Complete lymph node dissection (CLND) was performed only in the case of SLN metastasis detected by PATH. Different combinations of the intraoperative parameters (only the hottest node and all nodes harvested) and of analysis (PATH and RT-PCR) were tested as predictors of clinical outcome on the basis of long-term follow-up (12-81 mo; median, 55 mo). RESULTS: A total of 197 SLNs were harvested, 41 of which harbored metastasis as detected by RT-PCR analysis; PATH detected metastasis in only 24 of 41 metastatic SLNs. In 5 of 41 instances, metastasis was not in the hottest SLN. The main factor determining correct classification of the SLN status was RT-PCR, which significantly improved detection of metastasis, even if applied only to the hottest node (P < 0.0001 vs. PATH analysis of either the hottest SLN or all nodes above the 20% threshold). Metastatic disease recurred locally in 5 patients who had not undergone CLND; RT-PCR analysis showed metastasis in 4 of these patients. The false-negative rate of SLN biopsy progressively decreased when applying PATH only to the hottest node (32.1%), additional RT-PCR to the hottest node (21.4%), PATH to all nodes (17.9%), and RT-PCR to all nodes (3.6%, P = 0.015 vs. PATH analysis of only the hottest SLN). CONCLUSION: On the basis of long-term follow-up (the gold standard for final clinical outcome of SLN biopsy), both 20% threshold and RT-PCR analysis should be applied for optimal detection of nodal metastases in patients with melanoma.

Transcription analysis of human equilibrative nucleoside transporter-1 predicts survival in pancreas cancer patients treated with gemcitabine.

Gene expression analysis may help the management of cancer patients, allowing the selection of subjects responding to treatment. The aim of this study was the characterization of expression pattern of genes involved in gemcitabine activity in pancreas tumor specimens and its correlation with treatment outcome. The role of drug transport and metabolism on gemcitabine cytotoxicity was examined with specific inhibitors, whereas transcription analysis of human equilibrative nucleoside transporter-1 (hENT1), deoxycytidine kinase (dCK), 5'-nucleotidase (5'-NT), cytidine deaminase (CDA), and ribonucleotide reductase subunits M1 and M2 (RRM1 and RRM2) was done by quantitative reverse transcription-PCR in tumor tissue isolated by laser microdissection from surgical or biopsy samples of 102 patients. Association between clinical outcome and gene expression levels was estimated using Kaplan-Meier method and Cox's proportional hazards model. Transport and metabolism had a key role on gemcitabine sensitivity in vitro; moreover, hENT1, dCK, 5'-NT, CDA, RRM1, and RRM2 were detectable in most tumor specimens. hENT1 expression was significantly correlated with clinical outcome. Patients with high levels of hENT1 had a significantly longer overall survival [median, 25.7; 95% confidence interval (95% CI), 17.6-33.7 months in the higher expression tertile versus median, 8.5; 95% CI, 7.0-9.9 months in the lower expression tertile]. Similar results were obtained with disease-free survival and time to disease progression, and the multivariate analysis confirmed the prognostic significance of hENT1. This study suggests that the expression levels of hENT1 may allow the stratification of patients based on their likelihood of survival, thus offering a potential new tool for treatment optimization.

Mental health, pain symptoms and systemic comorbidities in women with endometriosis: a cross-sectional study.

INTRODUCTION: Endometriosis is a gynecological disease with a severe impact on quality of life. The aim of this study is to assess mental health status in a group of women with endometriosis, investigating their clinical history, pain symptoms and systemic comorbidities. METHODS: An observational cross-sectional study was performed on a group of Italian Caucasian women with endometriosis (n = 134). All patients filled the 'Patient Health Questionnaire' (PHQ), a self-administered screening tool for mental health disorders. The characteristics of endometriosis, pain symptoms and their severity, the presence and types of comorbid systemic disorders were added into the same survey. RESULTS: According to PHQ algorithms, 59% of patients were affected by at least one psychiatric disorder, with a significant correlation with pain symptoms (p = 0.0026). Patients with severe pain showed a higher incidence of multiple psychiatric disorders (p = 0.026) and somatoform disorder than those with mild pain (p = 0.0009). There was no correlation between the presence of psychiatric disorders and age, BMI, parity, infertility, need for surgery, number of intervention, localization of endometriotic lesions and systemic comorbidities. DISCUSSION: Women with endometriosis showed a high frequency of PHQ results positive for psychiatric disorders, with a significant association with pain severity.

Abnormal uterine bleeding unrelated to structural uterine abnormalities: management in the perimenopausal period.

Abnormal uterine bleeding (AUB) is one of the commonest health problems encountered by women and a frequent phenomenon during menopausal transition. The clinical management of AUB must follow a standardized classification system to obtain the better diagnostic pathway and the optimal therapy. The PALM-COEIN classification system has been approved by the International Federation of Gynecology and Obstetrics (FIGO); it recognizes structural causes of AUB, which can be measured visually with imaging techniques or histopathology, and non-structural entities such as coagulopathies, ovulatory dysfunctions, endometrial and iatrogenic causes and disorders not yet classified. In this review we aim to evaluate the management of nonstructural causes of AUB during the menopausal transition, when commonly women experience changes in menstrual bleeding patterns and unexpected bleedings which affect their quality of life.

Sexual pain in women: quality of sex life and marital relations.

Common gynecological and dermatological conditions resulting in sexual pain are often observed in gynecological practice and are easily diagnosed with visual observation and laboratory tests. The lower genital tract diseases we are referring to are vaginitis, vaginoses, dermatoses, hypoestrogenism and endometriosis. All of them affect the vaginal mucosa with diverse mechanisms, their effects lasting for only few days or many months. Furthermore, they change the women's sense of wellbeing sometimes significantly and for a long period. The conditions we mentioned above are recognized promptly with basic gynecological interventions but when burning or sharp pain occurs with light pressure (as in case of penetration attempts) without physical signs we must suspect the genitopelvic pain penetration disorder. This condition was defined for the first time in the Diagnostic and Statistical Manual of Mental Disorders-5 and its dimensions include difficulty or pain at penetration associated with fear, anxiety, and pelvic floor hypertonus. Pain is most often localized at the vulvar vestibule and described as burning, pressure, and itching. These dimensions are iconic of sexual pain associated with vulvodyina and vaginismus but are common also in fibromyalgia, a syndrome of widespread chronic pain of unknown origin; sexual pain in fibromyalgia is mostly attributed both to the joint pathology and to the lower sensitive threshold that are the pathognomonic signs of this condition. In our study we analyzed the characteristics of pain as reported for each disease to evaluate its influence on sexuality and marital relations.

Maternal anemia effects during pregnancy on male and female fetuses: are there any differences?

OBJECTIVE: Sideropenic anemia is a common pregnancy disorder. The relationship between anemia and adverse pregnancy outcome are contradictory, and it is related to the severity of the hemoglobin deficit. The aim of the study was to evaluate the relationship between maternal mild anemia at third trimester of pregnancy, fetal birth weight and fetal gender. STUDY DESIGN: A retrospective study including 1131 single physiological term pregnancies was conducted. According to maternal Hb levels during the third trimester, pregnant women enrolled were divided in two groups: Group A (n = 156) with Hb ≤ 11 g/dl and Group B (n = 975) with Hb ≥ 11,1 g/dl. RESULTS: Maternal characteristics, gestational age at delivery, Apgar score and post-partum hemorrhage were similar between groups. However, when neonatal sex was considerate, female newborns of anemic women had a higher birth weight (p = 0.01). Moreover, anemic women showed a significantly higher rate of emergency cesarean section (p = 0.006), in particular when the newborn was a male (p= 0.03). CONCLUSION: Maternal mild anemia in third trimester of pregnancy correlates with fetal birth weight, influencing fetal growth and delivery outcome on the basis of fetal gender. Even though the reason of this phenomenon is still unknown, these new data may represent a novel parameter to add significant prognostic information in relation to maternal mild anemia and neonatal outcome.

The Detection of Androgen Receptor Splice Variant 7 in Plasma-derived Exosomal RNA Strongly Predicts Resistance to Hormonal Therapy in Metastatic Prostate Cancer Patients.

BACKGROUND: The androgen receptor splice variant 7 (AR-V7) is associated with resistance to hormonal therapy in castration-resistant prostate cancer (CRPC). Due to limitations of the methods available for AR-V7 analysis, the identification of a reliable detection method may facilitate the use of this biomarker in clinical practice. OBJECTIVE: To confirm AR-V7 as a predictor of resistance to hormonal therapy and develop a new approach to assess AR-V7 by highly sensitive digital droplet polymerase chain reaction (ddPCR) in plasma-derived exosomal RNA. DESIGN, SETTING, AND PARTICIPANTS: Plasma samples were collected from 36 CRPC patients before they began second-line hormonal treatment. Exosomes were isolated and RNA extracted for analysis of AR-V7 by ddPCR. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The absolute target gene concentration as copies per milliliter (copies/ml) was determined by ddPCR. Statistical analyses were performed with SPSS software (IBM Corp., Armonk, NY, USA). RESULTS AND LIMITATIONS: A total of 26 patients received abiraterone and 10 enzalutamide; 39% of patients were found to be AR-V7 positive (AR-V7+). Median progression-free survival was significantly longer in AR-V7 negative (AR-V7-) versus AR-V7+ patients (20 vs 3 mo; p<0.001). Overall survival was significantly shorter in AR-V7+ participants at baseline compared with AR-V7- participants (8 mo vs not reached; p<0.001). CONCLUSIONS: This study demonstrates that plasma-derived exosomal RNA is a reliable source of AR-V7 that can be detected sensitively by ddPCR assay. We also showed that resistance to hormonal therapy may be predicted by AR-V7, making it a clinically relevant biomarker. PATIENT SUMMARY: We report a first study on a method for androgen receptor splice variant 7 (AR-V7) detection in RNA extracted from cancer cell vesicles released in blood. Results confirmed the role of AR-V7 as a predictive biomarker of resistance to hormonal therapy. Our assay showed that vesicles are a reliable source of AR-V7 RNA and that the method is fast, highly sensitive, and affordable.

Ultrasonography estimated thyroid volume: a prospective study about its reliability.

Ultrasonography is supposed to provide a reliable preoperative estimate of thyroid volume. This prospective study compares the estimated thyroid volume (EV) to real volume (MV), obtained by measuring the excised gland after surgery. One hundred one patients undergoing total thyroidectomy were selected for the study. Indications for surgery were: multinodular goiter, diffuse toxic goiter (DTG), uninodular disease. In all cases, ultrasound was repeated 1 month after surgery to verify complete thyroid removal. EV was underestimated in 89 cases; it perfectly matched the MV in 5 and was overestimated in 7. Mean EV was 28.3 mL (range, 7-50) and mean MV 36.2 mL (range, 7-76); this difference was statistically significant (p < 0.0001). Patients were then divided in groups according to EV (< or > than 25 mL) and thyroid morphology. Highly significant differences were found between all groups (p < 0.0001) except the DTG population, where the difference was less significant (p < 0.042). The study demonstrates that a correct preoperative measurement of the thyroid gland is not achievable because the volume estimated by ultrasound is largely underestimated in comparison to the real volume of the excised gland. Nevertheless ultrasound is more reliable in DTG than in other thyroid diseases. Increasing the number of cases may help to verify a new mathematical model.

Cyclin A and E2F1 overexpression correlate with reduced disease-free survival in node-negative breast cancer patients.

BACKGROUND: Available prognostic factors do not accurately identify node-negative breast cancer patients at high risk of disease recurrence and progression. PATIENTS AND METHODS: Cyclin A and E2F1 expression levels were evaluated in 75 consecutive node-negative breast cancer patients with a median follow-up of 10 years. Both parameters were tested for correlation with all the available clinicopathological parameters and with the clinical evolution of the disease. RESULTS: Cyclin A was overexprNed in 45.3% of patients and significantly related to large tumor size, high Ki67 and high E2F1 expression levels. No relationship was observed between cyclin A and tumor estrogen receptor (ER) status, grading or patient age. Seventeen patients relapsed within 5 years from diagnosis. Twelve (71%) of them showed cyclin A overexpression in comparison with 22 (38%) out of the 58 who did not relapse (p = 0.02). Disease-free survival (DFS) was significantly shorter in patients with cyclin A-overexpressing tumors compared to non-overexpressing ones (p = 0.01). DFS was also significantly longer in low vs. high Ki67 expression (p = 0.003) and in low vs. high E2F1 expression (p = 0.02). On multivariate analysis, the simultaneous high expression of all three parameters (cyclin A, Ki67 and E2Fl) was a strong independent prognostic factor for shorter DFS (HR 13.4). CONCLUSION: These findings suggest that assessment of cyclin A and/or E2F1 expression levels, associated with Ki67, might be useful for a better prognostic evaluation of node-negative breast cancer patients and support the need for further studies to evaluate their suitability for use in the routine clinical management of these patients.

Randomized controlled trial of harmonic scalpel use during thyroidectomy.

OBJECTIVE: To compare operative factors, postoperative outcomes, and surgical complications of thyroidectomy when using the harmonic scalpel (HS) vs conventional hemostasis (CH). DESIGN: Single-blind, randomized controlled trial. SETTING: Department of Surgery, S. Chiara Hospital, University of Pisa, Pisa, Italy. PATIENTS: One hundred patients undergoing thyroidectomy. MAIN OUTCOME MEASURES: Postoperative pain, drainage volume, hypocalcemia, nerve injury, and operative time. INTERVENTION: Patients underwent total thyroidectomy in which either the HS or CH was used. RESULTS: We found no significant differences between the HS and CH groups at baseline. Postoperative pain was reduced in the HS group at 24 hours (mean visual analog scale score, 3.90 vs 5.30; P<.001) and 36 hours (2.27 vs 3.95; P<.001). Drainage volume was significantly lower in the HS group (40.1 mL vs 75.4 mL; P<.001). Transient hypocalcemia was significantly lower in the HS group (5 patients [10%] vs 16 [32%]; P=.01). No patients experienced nerve injury or permanent hypocalcemia. Mean operative times were shorter in the HS group (40.0 vs 46.7 minutes, P<.001). CONCLUSIONS: Use of the HS may reduce postoperative pain, drainage volume, and transient hypocalcemia in patients undergoing thyroidectomy. Shorter operative times and improved outcomes might justify the cost of the HS compared with that of CH.

Potential influence of in utero and early neonatal exposures on the later development of endometriosis.

OBJECTIVE: To investigate the possible correlation between maternal characteristics, in utero and early neonatal life exposures, and the development of endometriosis in adult life. DESIGN: Case-control study. SETTING: University hospital. PATIENT(S): A group of 161 patients with endometriosis and a control group of 230 women undergoing laparoscopy for benign adnexal diseases and free of endometriosis. INTERVENTION(S): All women included in the study were requested to answer a series of questions about their mothers' gestational data and on their own perinatal and early postnatal lives. MAIN OUTCOME MEASURE(S): Odds ratio, adjusted odds ratios, and 95% confidence intervals for the associations between maternal characteristics during the patient's pregnancy, in utero exposure to obstetrical and perinatal complications, and the type of feeding received during the neonatal period with the development of endometriosis in adult life. RESULT(S): Mothers of women with endometriosis were significantly more likely to be affected by endometriosis or uterine fibroids, with a higher incidence of smoking during pregnancy. Women with endometriosis were more frequently born prematurely, with a significantly lower birth weight, and their mothers experienced preeclampsia during their pregnancies more often than control subjects. They were also more frequently formula fed than breast fed in early life. However, only prematurity and formula feeding were retained in the multivariate analysis model. CONCLUSION(S): Among intrauterine and early neonatal exposures, prematurity and formula feeding were risk factors for the development of endometriosis in adult life. Further studies should evaluate the underlying biologic mechanisms.

Surgical treatment affects perceived stress differently in women with endometriosis: correlation with severity of pain.

OBJECTIVE: To investigate the amount of perceived stress in a group of women with different forms of endometriosis-related pain before and after surgical treatment. DESIGN: Prospective clinical trial. SETTING: University hospital. PATIENT(S): A group of women (n = 98) referred to our center for chronic pain and suspected of having endometriosis. INTERVENTION(S): All women suspected of having endometriosis with ultrasonography underwent to a clinical evaluation including assessment of perception of stress. Endometriosis was confirmed histologically by laparoscopy. Painful symptoms and perception of stress were recorded 1 month after surgery. MAIN OUTCOME MEASURE(S): Perceived stress scale (PSS) and visual analog scale for painful symptoms before and 1 month after surgery for endometriosis. RESULT(S): The PSS score before surgery was perceived as "very high" in patients with deep endometriosis (n = 20) or deep endometriosis associated with endometrioma (n = 21); "high" or "medium" PSS was perceived in patients with endometrioma (n = 34) or endometrioma associated with peritoneal endometriosis (n = 23). After the surgical treatment a significant decrease of the "very high" PSS score was shown, as well as when the entire group of patients was considered. When evaluated before and after surgery, according to the severity of pain (dysmenorrhea, dyspareunia, and pelvic pain), a direct correlation was found with the level of PSS. CONCLUSION(S): Patients with deep endometriosis-related pain (dysmenorrhea, pelvic pain, dyspareunia) showed the highest level of perceived stress, which significantly decreased after surgical treatment.

Akt1 rs2498801 is related to survival in head and neck squamous cell cancer treated with radiotherapy.

BACKGROUND: Radiotherapy (RT) with or without chemotherapy (CT) plays an important role as exclusive treatment in patients with head and neck squamous cell cancer (HNSCC). Unfortunately, in some cases, benefit for patients is not recorded and only treatment-related complications are registered. MATERIALS AND METHODS: Data relating to Akt1 single nucleotide polymorphism (SNP) and response to treatment of 46 patients treated with exclusive RT or RT-CT for HNSCC were evaluated. RESULTS: For heterozygous patients median overall survival was 28.5 months, while for the wild-type group median overall survival was 10.9 (p=0.019). Three-year survival was 85% for mutated Akt1 homozygosis and 40% for patients with a heterozygous status (p=0.019, hazard ratio (HR)=7.960). CONCLUSION: SNP of rs2498804 can recognize patients resistant to RT-CT. Further studies are needed to confirm our data and to investigate the role of Akt SNPs in HNSCC patients.