A Prospective Intervention Trial on Tailored Radiofrequency Ablation of Uterine Myomas.

Background and Objective: Investigating the use of radiofrequency myolysis (RFM) for the treatment of fibroids through less invasive access by combining transvaginal ultrasound, hysteroscopy and laparoscopy. Materials and Methods: Fifty-four premenopausal women with 106 symptomatic uterine myomas. Patients underwent RFM in three ways: Vaginal Ultrasound-guided RFM (VU-RFM), Laparoscopic RFM (L-RFM) and Hysteroscopic-RFM (H-RFM). The mean patient age was 43 years; 52 symptomatic uterine myomas were subserosal, 44 intramural and 10 submucosal. The outcomes evaluated at 1 and 12 months after RFM were myoma size (volume-diameter), "Uterine Fibroid Symptom and Quality of Life (UFS-QOL)" questionnaire and a 10-point Visual Analogue Scale (VAS). The therapy was completed with a single ablation in all patients, no complication was registered. The average number of fibroids treated per intervention was two with the use of different accesses: 64/106 VU-RFMs (60.4%), 32/106 L-RFMs (30.2%) and 10/106 H-RFMs (9.4%). Results: Volume and diameter of fibroids were significantly reduced by, respectively, 51.3% and 20.1% in the first 30 days post-intervention (p < 0.001) up to a maximum of 73.5% and 37.1% after the second follow-up visit at 12 months (p < 0.001). A similar trend was shown in terms of disability with a progressive and significant reduction of symptoms (menorrhagia, dysmenorrhea, dyspareunia and pollakiuria) demonstrated by percentage variation of UFS-QOL Symptom Severity and VAS scores to -74.3% and -45.3% as well as -84.9% and -74.3%, respectively, at 1 and 12 months after RFM (p < 0.001). An overall improvement in the quality of life was also demonstrated by a significant increase in the UFS-QOL total score of +38.2% in the first 30 days post-intervention up to +44.9% after the second follow-up visit at 12 months (p < 0.001). The overall average surgery time of the RFM for each patient was 48 minutes, and the time to treat each fibroid by Vaginal Ultrasound-guided RFM (23 min) was found to be significantly less than those of laparoscopy or hysteroscopy (respectively 35 and 34 min) (p < 0.05). An electromagnetic virtual needle tracking system (VNTS) was successfully tested during the RFM procedures, and real-time contrast-enhanced ultrasound (CEUS) has proven to be effective in determining the duration of myolysis through the identification of eventual residual areas of enhancement within the fibroids. Conclusion: Radiofrequency can be considered a minimally invasive and safe procedure for the treatment of uterine myomas through the customization and possible combination of transvaginal, laparoscopic or hysteroscopic accesses. The standardization of the ablation technique with pre-intervention biopsy and new technologies such as VNTS and CEUS spares healthy uterine tissue and may change the future management of symptomatic uterine fibroids.

Ultrasound-guided transvaginal radiofrequency ablation of uterine fibroids assisted by virtual needle tracking system: a preliminary study.

PURPOSE: The purpose of this study was to assess the feasibility and outcome of transvaginal ultrasound (US)-guided radiofrequency ablation of uterine fibroids assisted by a real-time virtual needle tracking (VT) system. METHODS: Between January 2017 and February 2018, 19 patients (age 45 ± 8 y, range 36-53 y) with 25 symptomatic uterine fibroids underwent transvaginal radiofrequency ablation (RFA) at a single center. Mean number of fibroids for patient was 1.7 (min, max: 1-3). Patients with more than one fibroid were 10 (52.6%). Uterine fibroids (mean volume: 13.6 mL; range: 5.3-41.9 mL) were treated with a dedicated internally cooled 17 G 35 cm RF needle with 1 cm or variable active tip and the moving shot technique. An electromagnetic system was used for showing a virtual needle during the procedure. Contrast-enhanced ultrasound evaluation was performed before and immediately at the end of procedure. Feasibility of the procedure, technical success rate, volume percentage reduction at 1, 3 and 6 months, clinical outcome (QOL score) and complications were analyzed. RESULTS: Procedure was feasible in 19/19 patients (100%). Technical success was achieved in 100% of 25 treated fibroids. Mean fibroids volume decreased from 13.6 ml at baseline to 5.9 ml at 6 month (reduction rate 62.7%, range 48.5-76.9; p < .05). No major immediate or late complications occurred. Minor complications occurred in two patients. QOL score significantly improved from 68 ± 36 at baseline to 97 ± 16 at six-months follow-up (p < .05). CONCLUSION: Transvaginal US-guided RFA assisted by a real-time VT system is a feasible, safe and effective technique for the treatment of uterine fibroids.

Uterine Myoma Position-based Radiofrequency Ablation (UMP-b RFA): 36 months follow-up clinical outcomes.

OBJECTIVE: To assess the efficacy of Uterine Myoma Position-based Radiofrequency Ablation (UMP-b RFA) at 36 months. An analysis of a new uterine fibroid ablation technique that allows personalized access of delivering radiofrequency energy (transvaginal, hysteroscopic or laparoscopic) based on myoma localization. STUDY DESIGN: Prospective observational cohort study in a community-based secondary care medical center enrolled 61 premenopausal women with 112 symptomatic uterine myomas. 112 fibroids were ablated in 5 ways with single or combined accesses: 82 Vaginal Ultrasound (VU)-guided RFA, 19 Laparoscopic (L)-RFA, 5 Hysteroscopic (H)-RFA, 5 VU+H-RFA, and 1 VU+L-RFA. The primary endpoint of this study was to evaluate the 3-year clinical outcome of UMP-b RFA. The secondary endpoint was the possible identification of predictors of its success. The outcomes evaluated at 12, 24, and 36 months after UMP-b RFA were myoma size, type of symptomatology suffered, quality of life based on the "Uterine Fibroid Symptom and Quality of Life" questionnaire, and interviews on the degree of satisfaction with this surgery. The reintervention and complication rates were also recorded and analyzed. RESULTS: Fibroids volume and diameter were significantly reduced by -90.2 % / -55.7 % at 36 months post-intervention (p < 0.001) and the reduction of Symptom Severity scores was -71.8 % three years after UMP-b RA (p < 0.001). The overall improvement in the quality of life was demonstrated by an increase in the Quality-of-Life score of + 26.0 % at the third follow-up (p < 0.001). 88.5 % of the patients interviewed would have the surgery done again if they went back in time. The reintervention rate was 10/61 (16.4 %): 3 hysterectomies, 3 myomectomies, 3 operative hysteroscopies and 1 VU-RFA reoperation. In this group of unsuccessful surgeries, the mean diameter of the dominant myomas was found to be greater than that of the successes (5.3 vs 4.4 cm.). Out of the 61 cases, no major complications occurred, and the 2 minor complications observed were self-limiting. CONCLUSION: Uterine Myoma Position-based Radiofrequency Ablation is a safe, effective, and minimally invasive solution for the treatment of symptomatic fibroids. Indeed, these clinical outcome data at 36 months shows how UMP-b RFA can treat the symptomatology of uterine fibromatosis. Hysterectomies or myomectomies were successfully avoided in more than 80 % of women bearing myomas with an average diameter of less than 5 cm.

Antiangiogenic versus cytotoxic therapeutic approaches to human pancreas cancer: an experimental study with a vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor and gemcitabine.

Pancreatic adenocarcinoma is a leading cause of cancer death in the United States and represents a challenging chemotherapeutic problem. The pharmacological control of angiogenesis might represent a novel approach to the management of pancreas cancer, since the pathological development of vascular supply is a critical step for tumor growth and may affect its prognosis. In order to test this hypothesis, SU5416 ([3-(3,5-dimethyl-1H-pyrrol-2-ylmethylene)-1,3-dihydro-indol-2-one]) a selective inhibitor of the vascular endothelial growth factor receptor-2 tyrosine kinase, and gemcitabine (2', 2'-difluorodeoxycytidine) were tested on endothelial (HUVEC) and pancreatic tumor cells (MIA PaCa-2) in vitro and in vivo alone and in simultaneous association. SU5416 inhibited HUVEC cells stimulated to proliferate by vascular endothelial growth factor but not MIA PaCa-2 cells; the drug concentration that decreased cell growth by 50% (IC50) was 0.14 microM. Furthermore, SU5416 reduced the development of microvessels from placental explants (IC50, 0.23 microM). Gemcitabine inhibited the growth of both HUVEC and MIA PaCa-2 cells with an IC50 of 0.08 and 0.1 microM, respectively. A synergistic effect (combination index <1 and dose reduction index >1) on anti-proliferative and pro-apoptotic activity was calculated with the simultaneous combination of the two drugs on endothelial cells. A marked in vivo antitumor effect on MIA PaCa-2 xenografts was observed with SU5416 at a protracted schedules, as well as with gemcitabine; furthermore, the combination between the two drugs resulted in an almost complete suppression of tumor growth and relapse. In conclusion, the present results provide the evidence of an effective anti-endothelial/antitumor activity of protracted administration of SU5416 on human pancreas cancer xenografts, which is comparable with the one obtained by gemcitabine; moreover, the synergistic combination between these drugs on endothelial cells and the promising association in pancreatic cancer xenografts could be used in future studies and translated into the clinical setting.

Three-dimensional in vitro culture of endometrial explants mimics the early stages of endometriosis.

OBJECTIVE: To reproduce the earliest phases of endometriosis using a new in vitro model in which cells from a cultured endometrial fragment can proliferate, invade, reconstitute new endometrial-like tissue, and generate blood vessels. DESIGN: Experimental in vitro study. SETTING: A hospital-based academic research institute. PATIENT(S): Five normal ovulating women undergoing surgery for various benign gynecological indications. INTERVENTION(S): Endometrial samples obtained from the fundus of the uterine cavity were placed in a three-dimensional fibrin matrix culture system. MAIN OUTCOME MEASURE(S): Degree of proliferation of stromal cells and invasion of the fibrin matrix, gland, and stroma formation, vessel sprouting, and immunohistochemical characterization of various cellular components. RESULT(S): During the first week of culture, an endometrial cell outgrowth was observed from the original fragments in 120 of 144 wells (83.3%). Subsequently, cell outgrowths could be quantified in 132 (91.6%), 129 (89.5%), and 127 (88.1%) of the wells after 15, 60, and 90 days, respectively. An invasion of the matrix by the human endometrial cells led to the formation of tubular structures that coalesced into tissue, architecturally resembling endometrium and in which the glands were immunohistochemically positive for cytokeratin. New capillaries, immunohistochemically positive for CD31 and vimentin, sprouted from the endometrial outgrowths at the beginning of the fifth week of culture. CONCLUSION(S): These data show that cells from endometrial explants can proliferate and invade a fibrin matrix in vitro generating new glands, stroma, and vessels consistent with endometriosis. The three-dimensional fibrin matrix used in the present study provides an opportunity to observe the earliest biological events of endometriosis in a quantifiable way.

Overexpression and functional relevance of somatostatin receptor-1, -2, and -5 in endometrium and endometriotic lesions.

CONTEXT: Somatostatin plays a role in physiological and pathological cell proliferation and angiogenesis. Five subtypes of somatostatin receptors have been identified, and the therapeutic use of somatostatin receptor-selective agonists has been reported in several diseases. OBJECTIVES: The aim was to describe the expression and the functional relevance of three human somatostatin receptors (sst1, sst2, and sst5) in tissues of women with and without endometriosis. PATIENTS AND METHODS: This pilot study analyzed endometrium, ovarian endometriomata, and peritoneal lesions in 15 patients affected by endometriosis and the endometrium of five women without endometriosis. 111In-pentetreotide scintigraphy was used to detect endometriotic lesions; real-time RT-PCR and immunohistochemistry for sst1, sst2, and sst5 were performed. Migration and proliferation assays were performed on human endometrial stromal cells (ESC) treated with somatostatin and octreotide for 48 h. RESULTS: 111In-pentetreotide scintigraphy was able to correctly identify and locate pelvic endometriotic lesions as confirmed by computed tomography scans. The endometrium of women with endometriosis expressed significantly more sst1, sst2, and sst5 in comparison to that of control women. Moreover, sst1, sst2, and sst5 were highly expressed in ovarian endometriomata and peritoneal lesions. The sst receptor ligand octreotide significantly inhibited ESC migration and proliferation with a maximum effect at 10(-6) m, whereas somatostatin was effective only on ESC growth. CONCLUSIONS: This is the first report characterizing the overexpression and functional relevance of somatostatin receptors in eutopic endometrium and lesions of patients affected by endometriosis. Thus, the use of these receptors may provide new strategies for the diagnosis and treatment of endometriosis.