Magnetic tweezers optimized to exert high forces over extended distances from the magnet in multicellular systems.

Magnetic tweezers are mainly divided into two classes depending on the ability of applying torque or forces to the magnetic probe. We focused on the second category and designed a device composed by a single electromagnet equipped with a core having a special asymmetric profile to exert forces as large as 230 pN-2.8 µm Dynabeads at distances in excess of 100 µm from the magnetic tip. Compared to existing solutions our magnetic tweezers overcome important limitations, opening new experimental paths for the study of a wide range of materials in a variety of biophysical research settings. We discuss the benefits and drawbacks of different magnet core characteristics, which led us to design the current core profile. To demonstrate the usefulness of our magnetic tweezers, we determined the microrheological properties inside embryos of Drosophila melanogaster during the syncytial stage. Measurements in different locations along the dorsal-ventral axis of the embryos showed little variation, with a slight increase in cytoplasm viscosity at the periphery of the embryos. The mean cytoplasm viscosity we obtain by active force exertion inside the embryos is comparable to that determined passively using high-speed video microrheology.

Expectant management may reduce overtreatment in women affected by unexplained infertility confirmed by diagnostic laparoscopy.

PURPOSE: To determine whether the mini-invasive surgery still play a role in the diagnostic workup and in the management of the couples affected by unexplained infertility. METHODS: 170 infertile women (age range 25-38 years) with documented normal ovarian, tubal and uterine function underwent combined hysteroscopic and laparoscopic surgery; 100 women refused surgery or ART treatment (control group) choosing expectant management. A retrospective assessment questionnaire was proposed to enrolled women to collect the rate of spontaneous or ART-induced pregnancies. RESULTS: The combined surgery revealed pelvic pathologies in 49.4% of patients, confirming the diagnosis of unexplained infertility only in 86 of studied patients. In this group of 86 selected women, 28 of them achieved a spontaneous pregnancy and 23 women obtained pregnancy after ART. The Chi-square analysis shows that the pregnancy rate was not influenced by the employment of ART. In the group of 100 control women, only 14 (14%) achieved a spontaneous pregnancy after 18 months of expectant management. CONCLUSIONS: Combined laparoscopy and hysteroscopy in women with unexplained infertility may reveal previously undiagnosed pathologies that could require ART, and in those without abnormal surgical finding, ART does not improve pregnancy rate.

Bowel dysfunction following nerve-sparing radical hysterectomy for cervical cancer: a prospective study.

OBJECTIVE: To objectively assess anorectal dysfunction following nerve-sparing radical hysterectomy in stage I-II cervical carcinoma patients. MATERIAL AND METHODS: Between 2008 and 2012, 21 patients with primary cervical cancer stage FIGO I-II were enrolled in this prospective study. All women underwent nerve-sparing radical hysterectomy. Anorectal manometry was performed preoperatively and 6 months after surgery. A paired Student t test was used to assess the statistical difference between the manometric evaluations. A p value <0.05 was considered statistically significant. RESULTS: Twenty-one patients were available for follow-up. Maximal and mean anal resting and squeezing pressures were unaffected by the surgical procedure, rectoanal inhibitory reflex and length of the high anal pressure zone did not change after the operation. The minimal volume to elicit rectal sensation, urge to defecate and maximal tolerable volume did not change significantly in the postoperative period, although they decreased in 2 and increased in 3 patients. In addition, rectal compliance did not change after surgery. Furthermore, no significant differences were found between patients who were or were not treated with adjuvant radiotherapy. CONCLUSIONS: Our findings suggest that nerve-sparing radical hysterectomy for cervical cancer does not seem to be associated with long-term anorectal dysfunction. © 2014 S. Karger AG, Basel.

Association between follicular fluid leptin and serum insulin levels in nonoverweight women with polycystic ovary syndrome.

AIMS: We evaluated the links between leptin and visfatin levels and fertilization rates in nonoverweight (NOW) women with PCOS (NOW-PCOS) from Apulia undergoing in vitro fertilization/embryo transfer (IVF). MATERIALS AND METHODOLOGY: We recruited 16 NOW women with PCOS (NOW-PCOS) and 10 normally ovulating NOW women (control-NOW). All women underwent IVF. Androgens, 17- ß -estradiol (17 ß -E2), and insulin levels were measured in plasma and/or serum and leptin and visfatin levels were assayed in both serum and follicular fluid (FF-leptin, FF-visfatin). RESULTS: In NOW-PCOS, both serum and FF-leptin were significantly lower than in control-NOW. In NOW-PCOS, significant correlations were found between BMI and serum leptin and insulinemia and FF-leptin. By contrast, in control-NOW, FF-leptin levels were not correlated with insulinemia. Serum visfatin levels were not significantly different in NOW-PCOS and control-NOW, but FF-visfatin levels were 1.6-fold higher, although not significantly, in NOW-PCOS than in control-NOW. CONCLUSIONS: Both serum leptin levels and FF-leptin are BMI- and insulin-related in Southern Italian NOW-PCOS from Apulia. In line with other reports showing that FF-leptin levels are predictive of fertilization rates, lower than normal FF-leptin levels in NOW-PCOS may explain their lower fertilization rate and this may be related to the level of insulin and/or insulin resistance.

The impact of lymph vascular space invasion on recurrence and survival in patients with early stage endometrial cancer.

The aim of this study was to determine impact of lymph vascular space involvement (LVSI) on recurrence and survival in early stage of endometrial cancer. From 1991 through 2010, all endometrial cancer patients at University Hospital of Bari, Italy were identified. The Log-rank test and Kaplan-Meyer methods were used for time-to-event analysis to evaluate the effects of on lymph vascular space involvement recurrence rate and survival time. Of the 560 endometrial cancer patients, 525 underwent primary surgery. Of those, 399 had early stage disease. Three hundred and forty women were not found to have LVSI, whereas 59 were found to have lymph vascular space involvement. Forty-nine (12%) patients developed a recurrence and 20 of them showed lymph vascular space involvement. The statistical analysis demonstrated that LVSI was strongly associated with a poor survival (P < 0.0001). Lymph vascular space involvement is associated with a high risk of recurrence and poor overall survival in early stage of endometrial cancer; therefore, the clinical decision to decide whether or not a patient with early stage endometrial cancer should receive adjuvant therapy should be included the evaluation of lymph vascular space involvement.

"Intestinal-type" mucinous adenocarcinoma of the vulva: a report of two cases.

BACKGROUND: "Intestinal-type" mucinous carcinoma of the vulva is extremely rare with very few cases reported in the literature. CASE REPORT: The authors report two patients who had diagnosis of intestinal-type mucinous adenocarcinoma of the vulva after excisional biopsy. In both cases, restaging was perfomed with total body computed tomography (CT) scan, gastroscopy, and colonoscopy that showed no other site of disease. A radical vulvectomy with bilateral systematic inguinal lymphadenectomy was performed, and in both cases no residual disease was found. A patient developed metastatic (liver, bone marrow) colonic cancer 36 months after primary surgery, received multiple lines of chemotherapy, and died of disseminated disease 18 months after diagnosis. The other patient was found to have dysplastic polyp in the sigmoid colon, and is alive without disease at 39 months after primary diagnosis. CONCLUSION: Intestinal-type mucinous carcinoma of the vulva has a poor prognosis. Strict endoscopic follow-up of the colon is mandatory in such cases, considering the high propensity of associated gastrointestinal (GI) tumors.

Accuracy of transvaginal sonography and contrast-enhanced magnetic resonance-colonography for the presurgical staging of deep infiltrating endometriosis.

OBJECTIVE: To investigate the accuracy of transvaginal sonography (TVS) and contrast-enhanced magnetic resonance-colonography (CE-MR-C) for the presurgical assessment of deep infiltrating endometriosis (DIE). METHODS: Ninety women were enrolled prospectively for suspicion of DIE. All patients underwent TVS and CE-MR-C, with each operator blinded to the results of the other exam, before laparoscopy. The sites of DIE examined by both imaging techniques were: rectovaginal septum, pouch of Douglas, uterosacral ligaments, vesicouterine pouch, bowel, bladder and vagina. The presence of adhesions and the involvement of adnexa and of a previous abdominal scar, when there was clinical suspicion, were also evaluated. TVS and CE-MR-C findings were compared with laparoscopic and histological results. RESULTS: Endometriosis was confirmed by laparoscopy in 95.6% (86/90) of cases. In 82.2% (74/90) of patients there was DIE. The global accuracy for TVS in the detection of DIE was 89.2%, sensitivity was 81.1%, specificity was 94.2%, positive predictive value was 89.6%, negative predictive value was 89.0%, the positive likelihood ratio was 13.9 and the negative likelihood ratio was 0.2. For CE-MR-C, these values were 87.2%, 71.1%, 97.1%, 93.7%, 84.6%, 24.4 and 0.3, respectively. CE-MR-C allowed diagnosis of all cases of bowel involvement; the accuracy for infiltration and stenosis was 100%. The accuracy of TVS for rectosigmoid nodules was 91.1% and that for infiltration was 88.9%. CONCLUSIONS: Both TVS and CE-MR-C showed satisfactory results for the presurgical assessment of DIE. TVS appears to be a powerful, simple, feasible, cost-effective tool for preoperative staging of DIE. CE-MR-C is an 'X-ray free' technique, which could be reserved for cases with deep infiltrating rectosigmoid lesions and for the prediction of stenosis and involvement of the upper part of the colon and small intestine.

Could antispasmodic drug reduce pain during hysterosalpingo-contrast sonography (HyCoSy) in infertile patients? A randomized double-blind clinical trial.

OBJECTIVE: To assess the effectiveness of an antispasmodic drug, hyoscine-N-butylbromide, in reducing pain during hysterosalpingo-contrast sonography (HyCoSy). METHODS: Eight hundred and sixteen patients undergoing HyCoSy were randomized to receive 10 mg hyoscine-N-butylbromide (n = 408) or placebo (n = 408) per os, 30 min before the procedure, in a double-blind randomized controlled trial. Immediately after the procedure, the patient was asked to describe any pain experienced in comparison with pain usually suffered during the menstrual cycle, and the operator assigned a pain score between 0 and 4 as follows: 0 (no reaction or discomfort), 1 (slight pain, less than menstrual pain), 2 (moderate pain, exceeding menstrual cramps but no vasovagal reaction), 3 (vasovagal reaction or pain requiring observation in a hospital) and 4 (vasovagal reaction or pain requiring resuscitation). The primary aim was to estimate the difference in pain score, considered as a categorical value, between the active arm of the trial and the control group. The secondary aim was to evaluate if pain is related to tubal patency. RESULTS: There was no difference in pain score between the hyoscine-N-butylbromide group and the placebo group (P = 0.807). There was a negative correlation between pain and tubal patency, regardless of treatment group (P < 0.0001). CONCLUSIONS: Administration of 10 mg antispasmodic drug hyoscine-N-butylbromide does not reduce pain in patients undergoing HyCoSy.

Prognostic factors and outcomes in 28 cases of uterine leiomyosarcoma.

OBJECTIVES: It was the aim of this study to evaluate clinicopathological characteristics and prognostic factors of uterine leiomyosarcomas (LMS). METHODS: Twenty-eight patients with uterine LMS were evaluated in this retrospective study. Their features and survival were analyzed by Kaplan-Meier and log-rank tests. RESULTS: The median age of the patients was 52 years (range 25-74). Nine patients had a disease with a mitotic count <10/10 high-power fields. Twenty-one patients presented with stage I disease, 1 with stage II and 6 with stage IV. Twelve patients underwent total hysterectomy and bilateral salpingo-oophorectomy, 2 simple hysterectomy, 5 myomectomy and 9 more comprehensive surgical treatments. Adjuvant chemotherapy was administered to 16 patients, whereas chemoradiation was given only to 2 patients. Fifty percent presented with recurrence of the disease. The median overall survival was 46 months. Age, mitotic count, type of surgery, adjuvant therapy, recurrence and clinical response to chemotherapy were not found to affect survival, while the menopausal status and FIGO (International Federation of Gynecology and Obstetrics) stage were found to be prognostic factors. CONCLUSION: In our series, the menopausal state and FIGO stage were found to be prognostic factors related to survival.

Anti-laminin-1 antibodies in sera and follicular fluid of women with endometriosis undergoing in vitro fertilization.

There is increasing evidence that autoimmune phenomena, including auto-antibody production, may affect fertility in women with endometriosis. The aims of this study are to evaluate anti-laminin-1 antibody (aLN-1) presence in sera and in follicular fluids (FF) of women with endometriosis undergoing IVF and its impact on oocyte maturation and IVF outcome. aLN-1 were measured by a home-made enzyme linked immunosorbent assay in sera and FF obtained from 35 infertile women with endometriosis and in sera from 50 fertile controls and 27 infertile women without endometriosis (IWWE). aLN-1 serum levels were significantly higher in women with endometriosis in comparison with both fertile controls and IWWE (P<0.001 and P<0.05, respectively) and a positive correlation was found between serum- and FF-aLN-1 (r=0.47, P=0.004). According to the cut-off (mean+3 SD of fertile controls), 31% of women with endometriosis were aLN-1 positive. Metaphase II oocyte counts showed inverse correlation with FF-aLN-1 levels (r=-0.549, P=0.0006). Ongoing pregnancy (i.e pregnancy progressing beyond the 12th week of gestation) occurred in 4/11 aLN-1 positive patients and in 7/24 aLN-1 negative with no significant difference (P=0.7). In conclusion, our results highlight that aLN-1 are increased in women with endometriosis and their presence in FF may affect oocyte maturation leading to a reduced fertility. However, aLN-1 seem to have no effect on IVF outcome.

Long-term topotecan therapy in recurrent or persistent ovarian cancer.

BACKGROUND: The objective of this study was to evaluate feasibility, safety and clinical outcome of long-term therapy with topotecan (Hycamtin) in recurrent or persistent ovarian cancer. PATIENTS AND METHODS: A retrospective chart review was conducted on all patients treated with topotecan (TPT) at the Department of Obstetrics and Gynecology, University of Bari, Italy between 1999 and 2007. Pertinent clinicopathologic information, response and toxicity following treatment with TPT were collected. TPT was given at a dosage ranging between 1.5 and 1.0 mg/m2 every three to four weeks. All patients were evaluated for toxicity acording to the CTC and response according to the RECIST response criteria. Time to progression (TTP) was calculated from initiation of TPT treatment and start of the next chemotherapy regimen. RESULTS: A total of 30 patients received TPT for at least eight cycles for recurrent ovarian (22), fallopian tube (3) or primary peritoneal carcinoma (5). A total of 432 cycles of chemotherapy were given, with an average of 14.4 cycles per patient (range 8-22). Dose reduction was necessary in 20 patients (66%). About half of the patients required blood transfusions and growth factors. Non hematologic toxicity was mild and manageable. Responses were observed in 16/30 patients (53%), the remaining having SD. Median time to treatment progression was 28 months (range 9-88). CONCLUSION: Long-term treatment with topotecan in recurrent/persistent ovarian cancer is feasible with limited evidence of cumulative toxicity. The results of this retrospective analysis suggest a potential role for late response and survival benefit for those patients without disease progression who continue topotecan therapy beyond six cycles of treatment.

Locally advanced cervical cancer associated with complete uterine prolapse.

Although uterine prolapse and carcinoma of the uterine cervix are not rare event, their association is very uncommon. An 86-year-old patient gravida 8, para 5 was admitted for vaginal bleeding from a uterine prolapse of 20 years of duration. On physical examination, a complete third-degree prolapsed uterus with an ulcerated lesion of 12 cm in maximum diameter involving both the anterior and posterior lips of the cervix was observed. Because of the poor performance status and high American Society of Anesthesiology scoring, the patient was admitted for a vaginal hysterectomy with upper vaginectomy in spinal anesthesia. However, she died of pulmonary embolism 20 days after surgery. A case of a cervical cancer with a complete uterine prolapse of 20 years of duration is reported. We believe that this case typically rare to see in a developed country might be a useful addition to the few published reports.

Groin recurrence in carcinoma of the vulva: management and outcome.

The aim of the study was to investigate the management and outcome of inguinal recurrence in vulvar carcinoma patients. A retrospective chart review was conducted on 140 patients with squamous cell carcinoma of the vulva treated between 1994 and 2006. Twenty-one patients were found to have groin recurrence. Median interval between primary treatment of vulvar cancer and groin recurrence was 7 months. Three patients refused any treatment, 3 received chemotherapy, 2 inguino-pelvic radiotherapy and 13 had resection of the groin recurrence. After surgery seven patients received irradiation of the groin and pelvis, and three patients received chemotherapy. One patient died following surgery; 19 patients died of disease with the median survival after diagnosis of inguinal recurrence of 9 months. Only one patient is alive without evidence of disease at 60 months following surgery. In univariate analysis, stage and grade at diagnosis, age and performance status at the recurrent disease, and the extent of residual tumour after resection of groin recurrence were predictors for survival. Groin recurrences from vulvar carcinoma carry a poor prognosis. Multi-modal treatment may result in a palliation of the disease, and a very limited number of patients have long-term survival.

Spleen involvement in women with ovarian cancer.

The aim of this study was to determine the prognostic factors of spleen metastases in ovarian cancer. A retrospective chart review was conducted and ten patients with spleen metastases were evaluated. Eight were Stage III, one Stage I and one Stage IV. One patient had a spleen metastasis at the time of ovarian cancer diagnosis, whereas, the remaining patients 23.4+12 months after ovarian cancer diagnosis. Spleen involvement is a late complication that rarely occurs in ovarian cancer and confers a poor prognosis. The interval time between ovarian cancer diagnosis and appereance of spleen involvement is the most important prognostic factor.

Is there a role for neoadjuvant chemotherapy in early invasive cervical carcinoma?

OBJECTIVE: The purpose of this study was to determine if a survival advantage may exist from neoadjuvant chemotherapy (NACT) followed by radical surgery in early invasive (Stage IB1 and IIA) cervical carcinoma. METHODS: Using information from studies published on the topic of NACT in cervical carcinoma along with baseline control rates of standard treatment and patterns of failure, an estimate of how many patients with early invasive cervical cancer would benefit from this procedure was calculated. RESULTS: NACT followed by tailored radical surgery could result in a significant decrease (about 40%) in recurrence rate (13 vs 22%) and ultimately in survival compared to conventional treatment in early invasive cervical cancer. Moreover the introduction of NACT in all patients should result in a 75% decrease of adjuvant radiotherapy (10 vs 40%), and probably in a decrease in surgical and radiation related complications. CONCLUSION: A fraction of patients with early invasive cervical cancer (high-risk Stage IB-IIA cervical cancer) could benefit from NACT followed by tailored radical surgery. A randomized controlled trial to test this research question is very difficult due to the large population required. A subset population is identified which may benefit from NACT.

Conservative management of uterine leiomyosarcoma: report of a failure.

BACKGROUND: Conservative management of uterine leiomyosarcoma has rarely been reported in the literature. CASE REPORT: A 26-year-old woman was diagnosed with uterine leiomyosarcoma after resection of a 11 cm uterine mass. Conservative management was proposed, demolitive surgery was not performed and the patient received four courses of chemotherapy. Four months after completion of chemotherapy the patient developed a local recurrence and died of disease 48 months after the primary diagnosis. CONCLUSION: Reporting a failure after conservative management of uterine leiomyosarcoma is important in order to try to evaluate correct indications for fertility-sparing surgery.

Metformin improves endothelial function in normoinsulinemic PCOS patients: a new prospective.

BACKGROUND: Metformin was reported to improve the alterations of endothelial reactivity in normal-weight subjects with polycystic ovary syndrome (PCOS). The aim of the present study was to investigate the mechanisms of action of this drug on the vascular function of this population. METHODS: Thirteen normal-weight, normoinsulinemic and normolipemic PCOS women were studied before and after 6 months of metformin treatment (1000 mg/day). The endothelial function was assessed by evaluating the flow-mediated dilatation (FMD) of the brachial artery. We correlated this parameter with the endocrine-metabolic features of the patients. RESULTS: Metformin significantly reduced testosterone (1.56 +/- 0.52 after 6 months versus 2.98 +/- 1.00 at baseline) and 17-hydroxyprogesterone (0.03 +/- 0.01 versus 0.06 +/- 0.02 nmol/ml) levels, without affecting gluco-insulinemic parameters. Concomitantly, the basal vessel diameter and the FMD significantly increased (4.12 +/- 0.68 versus 3.2 +/- 0.41 and 5.2 +/- 0.6 versus 3.76 +/- 0.5 mm, respectively), thus documenting an improved endothelial function. CONCLUSIONS: Our data confirm the positive effects of metformin on the altered vascular reactivity, a precocious marker of cardiovascular risk, in normoinsulinemic PCOS subjects. This improvement seems to be mediated through hormonal changes, thus highlighting the detrimental role of hyperandrogenemia on the endothelial function, even beyond the metabolic factors. However, a direct effect of metformin on the endothelium should not be excluded.