Transvaginal Sonography for the Preoperative Assessment of Parametrial Deep Infiltrating Endometriosis: A Diagnostic Accuracy Study.

OBJECTIVE: The aim of the study was to evaluate the diagnostic accuracy for parametria endometriosis (PE) of transvaginal sonography (TVS) performed following a systematic approach for the assessment of the lateral parametria. DESIGN: A diagnostic accuracy study was employed based on a prospective observational design. PARTICIPANTS: All consecutive patients who underwent laparoscopic surgery for endometriosis between January 2016 and December 2020 were considered. SETTING: The study was conducted at endometriosis referral hospitals. METHODS: We prospectively collected clinical, imaging, and surgical data of all consecutive patients who underwent laparoscopic surgery for endometriosis between January 2016 and December 2020. A standardized technique with a systematic approach for the assessment of the lateral parametria following specific anatomic landmarks was used for the TVS. The diagnostic accuracy for PE in TVS was assessed using the intraoperative and pathologic diagnosis of PE as the gold standard. RESULTS: In 476 patients who underwent surgery, PE was identified in 114 out of 476 patients (23.95%): 91 left and 54 right PE out of 476 surgical procedures were identified (19.12% vs. 11.34%; p = 0.001); bilateral involvement in 27.19% (31/114 patients) cases. The sensitivity of TVS for PE was 90.74% (79.70-96.92%, 95% CI) for the right side and 87.91% (79.40-93.81%, 95% CI) for the left side. The specificity was almost identical for both sides (98.58% vs. 98.18%). For the right parametrium, the positive likelihood ratio (PLR) and negative likelihood ratio (NLR) were 63.82 (28.70-141.90, 95% CI) and 0.09 (0.04-0.22, 95% CI), respectively. On the left parametrium, the PLR and NLR were 48.35 (23.12-101.4, 95% CI) and 0.12 (0.07-0.21, 95% CI), respectively. The diagnostic accuracy for right and left PE was 97.69% (95.90-98.84%, 95% CI) and 96.22% (94.04-97.74%, 95% CI), respectively. LIMITATIONS: The principal limit is the high dependence of TVS on the operator experience. Therefore, although a standardized approach following precise definitions of anatomical landmarks was used, we cannot conclude that the observed accuracy of TVS for PE is the same for all sonographers. In this regard, the learning curve was not assessed. In the case of negative TVS for parametrial involvement with an absent intraoperative suspect, a complete dissection of the parametrium was not performed to avoid surgical complications; therefore, cases of minor PE may be missed, underestimating false negatives. CONCLUSIONS: TVS performed following a systematic approach for assessing the lateral parametria seems to have good diagnostic accuracy for PE with large changes in the posttest probability of parametrial involvement based on the TVS evaluation. Considering the clinical and surgical implications of PE, further studies implementing a standardized approach for assessing the parametrium by TVS are recommended to confirm our observations and implement a standardized protocol in clinical practice.

"Things Have Changed"-Laparoscopic Cytoreduction for Advanced and Recurrent Ovarian Cancer: The Experience of a Referral Center on 108 Patients.

OBJECTIVE: To report the feasibility of laparoscopic cytoreduction surgery for primary and recurrent ovarian cancer in a select group of patients. METHODS: A retrospective analysis was conducted on a cohort of patients with FIGO stage IIIA-IV advanced ovarian cancer who underwent laparoscopic primary debulking surgery (PDS), interval debulking surgery (IDS), or secondary debulking surgery (SDS) between June 2008 and January 2020. The primary endpoint was achieving optimal cytoreduction, defined as residual tumor less than 1 cm. Secondary endpoints included evaluating surgical complications and long-term survival, assessed at three-month intervals during the initial two years and then every six months. RESULTS: This study included a total of 108 patients, among whom, 40 underwent PDS, 44 underwent IDS, and 24 underwent SDS. Optimal cytoreduction rates were found to be 95.0%, 97.7%, and 95.8% for the PDS, ISD, and SDS groups, respectively. Early postoperative complications (<30 days from surgery) occurred in 19.2% of cases, with 7.4% of these cases requiring reintervention. One patient died following postoperative respiratory failure. Late postoperative complications (<30 days from surgery) occurred in 9.3% of cases, and they required surgical reintervention only in one case. After laparoscopic optimal cytoreduction with a median follow-up time of 25 months, the overall recurrence rates were 45.7%, 38.5%, and 39.3% for PDS, ISD, and SDS, respectively. The three-year overall survival rates were 84%, 66%, and 63%, respectively, while the three-year disease-free survival rates were 48%, 51%, and 71%, respectively. CONCLUSIONS: Laparoscopic cytoreduction surgery is feasible for advanced ovarian cancer in carefully selected patients, resulting in high rates of optimal cytoreduction, satisfactory peri-operative morbidity, and encouraging survival outcomes. Future studies should focus on establishing standardized selection criteria and conducting well-designed investigations to further refine patient selection and evaluate long-term outcomes.

Conservative Management of Atypical Endometrial Hyperplasia and Early Endometrial Cancer in Childbearing Age Women.

Total hysterectomy and bilateral adnexectomy is the standard treatment for atypical endometrial hyperplasia and early-stage endometrial cancer. However, the recommended surgical treatment precludes future pregnancy when these conditions are diagnosed in women in their fertile age. In these patients, fertility-sparing treatment may be feasible if the desire for childbearing is consistent and specific conditions are present. This review summarizes the available evidence on fertility-sparing management for atypical endometrial hyperplasia and early-stage endometrial cancer. Historically, oral progestins have been the mainstay of conservative management for atypical endometrial hyperplasia and stage IA endometrioid endometrial cancer with no myometrial invasion, although there is no consensus on dosage and treatment length. Intrauterine progestin therapy has proved a valid alternative option when oral progestins are not tolerated. GnRH analogs, metformin, and hysteroscopic resection in combination with progestins appear to increase the overall efficacy of the treatment. After a complete response, conception is recommended; alternatively, maintenance therapy with strict follow-up has been proposed to decrease recurrence. The risk of disease progression is not negligible, and clinicians should not overlook the risk of hereditary forms of the disease in young patients, in particular, Lynch syndrome. Hysterectomy is performed once the desire for childbearing desire has been established. The conservative management of atypical endometrial hyperplasia and early-stage endometrial cancer is feasible, provided a strong desire for childbearing and permitting clinical-pathological conditions. However, patients must be aware of the need for a strict follow-up and the risk of progression with a possible consequent worsening of the prognosis. More homogenous and well-designed studies are necessary to standardize and identify the best treatment and follow-up protocols.

Prevalence of Intrauterine Adhesions after Myomectomy: A Prospective Multicenter Observational Study.

OBJECTIVES: The aim of this study was to evaluate intrauterine adhesion formation after laparoscopic and laparotomic myomectomy. DESIGN: This is a prospective, multicenter, observational study (ClinicalTrials.gov ID: NCT04030273). METHODS: We included patients after laparotomic and laparoscopic myomectomy. All patients underwent postsurgical diagnostic hysteroscopy, after 3 months. The intrauterine adhesion rate and associated factors were investigated. RESULTS: Between January 2020 and December 2020, 38 and 24 consecutive patients underwent laparoscopic and laparotomic myomectomy, respectively. All diagnostic hysteroscopies were performed in the office setting without complications. Intrauterine adhesions were identified in 19.4% of women (95% CI: of 9-29%). Factors univariately associated (p < 0.2) with the presence of intrauterine adhesions after myomectomy were previous uterine surgery, the surgical approach (laparoscopic or laparotomic), the number of removed fibroids, the type and diameter of the largest myoma, and the opening of the uterine cavity. In the multivariable analysis, only the opening of the uterine cavity (odds ratio [OR] 51.99; 95% confidence interval [CI]: 4.53-596.28) and the laparotomic approach (OR, 16.19; 95% CI: 1.66-158.35) were independently associated with the identification of intrauterine adhesions after myomectomy. LIMITATIONS: One of the main limitations of our study is that we used uterine manipulator only in the laparoscopic group; in addition, we did not perform a preoperative hysteroscopy to evaluate the rate of intrauterine adhesions potentially present even before the myomectomy. CONCLUSIONS: The prevalence of intrauterine adhesions after 3 months from surgery was significantly associated with the opening of the uterine cavity and the laparotomic approach.

Linzagolix: a new GnRH-antagonist under investigation for the treatment of endometriosis and uterine myomas.

INTRODUCTION: Uterine myomas and endometriosis are benign hormone-dependent diseases affecting women of reproductive age. Substantial efforts have been made to develop innovative medical options for treating these gynecologic diseases. Elagolix and relugolix have been approved in some countries for treating endometriosis and myomas, respectively; however, linzagolix (OBE 2109, KLH 2109) is a new oral gonadotropin-releasing hormone (GnRH) antagonist in phase II-III trials. Treatment options for women with contraindications for hormonal therapies or who refuse particular options, are the driving force behind the development of new drugs in this area. AREA COVERED: This drug evaluation highlights definitive and preliminary results from previous and ongoing studies of linzagolix for the treatment of endometriosis and myomas. EXPERT OPINION: Linzagolix showed a dose-dependent and rapidly reversible action on the pituitary-gonadal axis. In a recent phase II trial (EDELWEISS), linzagolix significantly reduced pain related to endometriosis and improved quality of life at single daily doses of 75-200 mg. The preliminary results of international, double-blind phase III trials (PRIMROSE 1 and 2) reported its efficacy in treating heavy menstrual bleeding related to myomas with a good safety profile. Further studies will determine the necessity of add-back therapy during long-term use of linzagolix.

Are fibroid and bony pelvis characteristics associated with urinary and pelvic symptom severity?

BACKGROUND: Urinary and pelvic floor symptoms often are attributed to size and location of uterine fibroid tumors. However, direct supporting evidence that links increased size to worsening symptoms is scant and limited to ultrasound evaluation of fibroid tumors. Because management of fibroid tumors is targeted towards symptomatic relief, the identification of fibroid and pelvic characteristics that are associated with worse symptoms is vital to the optimization of therapies and prevention needless interventions. OBJECTIVE: We examined the correlation between urinary, pelvic floor and fibroid symptoms, and fibroid size and location using precise uterine fibroid and bony pelvis characteristics that were obtained from magnetic resonance imaging. STUDY DESIGN: A retrospective review (2013-2017) of a multidisciplinary fibroid clinic identified 338 women who had been examined via pelvic magnetic resonance imaging, Pelvic Floor Distress Inventory questionnaire (score 0-300), and a Uterine Fibroid Symptoms questionnaire (score 1-100). Multiple linear regression analysis was used to assess the influence of clinical factors and magnetic resonance imaging findings on scaled Pelvic Floor Distress Inventory and Uterine Fibroid Symptoms scores. Data were analyzed with statistical software. RESULTS: Our cohort of 338 women had a median Pelvic Floor Distress Inventory of 72.7 (interquartile range, 41-112.3). Increased Pelvic Floor Distress Inventory score was associated with clinical factors of higher body mass index (P<.001), noncommercial insurance (P<.001), increased parity (P=.001), and a history of incontinence surgery (P=.003). Uterine volume, dominant fibroid volume, dimension and location, and fibroid tumor location relative to the bony pelvis structure did not reach significance when compared with pelvic floor symptom severity. The mean Uterine Fibroid Symptoms score was 52.0 (standard deviation, 23.5). An increased Uterine Fibroid Symptoms score was associated with dominant submucosal fibroid tumors (P=.011), body mass index (P<.0016), and a clinical history of anemia (P<.001) or any hormonal treatment for fibroid tumors (P=.009). CONCLUSION: Contrary to common belief, in this cohort of women who sought fibroid care, size and position of fibroid tumors or uterus were not associated with pelvic floor symptom severity. Whereas, bleeding symptom severity was associated with dominant submucosal fibroid tumor and previous hormonal treatment. Careful attention to clinical factors such as body mass index and medical history is recommended when pelvic floor symptoms are evaluated in women with uterine fibroid tumors.

Evaluation of the routine use of pelvic MRI in women presenting with symptomatic uterine fibroids: When is pelvic MRI useful?

BACKGROUND: Pelvic ultrasound (US) diagnosis of uterine fibroids may overlook coexisting gynecological conditions that contribute to women's symptoms. PURPOSE: To determine the added value of pelvic MRI for women diagnosed with symptomatic fibroids by US, and to identify clinical factors associated with additional MRI findings. STUDY TYPE: Retrospective observational study. POPULATION: In all, 367 consecutive women with fibroids diagnosed by US and referred to our multidisciplinary fibroid center between 2013-2017. FIELD STRENGTH/SEQUENCE: All patients had both pelvic US and MRI prior to their consultations. MRIs were performed at 1.5 T or 3 T and included multiplanar T2 -weighted sequences, and precontrast and postcontrast T1 -weighted imaging. ASSESSMENT: Demographics, symptoms, uterine fibroid symptom severity scores, and health-related quality of life scores, as well as imaging findings were evaluated. STATISTICAL TESTS: Patients were separated into two subgroups according to whether MRI provided additional findings to the initial US. Univariate and multivariate regression analyses were performed. RESULTS: Pelvic MRI provided additional information in 162 patients (44%; 95% confidence interval [CI] 39-49%). The most common significant findings were adenomyosis (22%), endometriosis (17%), and partially endocavitary fibroids (15%). Women with pelvic pain, health-related quality of life scores less than 30 out of 100, or multiple fibroids visualized on US had greater odds of additional MRI findings (odds ratio [OR] 1.68, 2.26, 1.63; P = 0.02, 0.004, 0.03, respectively), while nulliparous women had reduced odds (OR 0.55, P = 0.01). Patients with additional MRI findings were treated less often with uterine fibroid embolization (14% vs. 36%, P < 0.001) or MR-guided focused US (1% vs. 5%, P = 0.04), and more often with medical management (17% vs. 8%, P = 0.01). DATA CONCLUSION: Pelvic MRI revealed additional findings in more than 40% of women presenting with symptoms initially ascribed to fibroids by US. Further evaluation using MRI is particularly useful for parous women with pelvic pain, poor quality of life scores, and/or multiple fibroids. LEVEL OF EVIDENCE: 4 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2019.

High-Intensity Focused Ultrasound for Pain Management in Patients with Cancer.

Cancer-related pain affects up to 80% of patients with malignancies. Pain is an important distressing symptom that diminishes the quality of life and negatively affects the survival of patients. Opioid analgesics are generally the primary therapy for cancer-related pain, with surgery, radiation therapy, chemotherapy, and other interventions used in cases of treatment-resistant pain. These treatments, which can be associated with substantial side effects and systemic toxicity, may not be effective. High-intensity focused ultrasound is an entirely noninvasive technique that is approved for treatment of uterine fibroids, bone metastases, and essential tremors. With magnetic resonance imaging or ultrasonographic guidance, high-intensity ultrasound waves are focused on a small well-demarcated region to result in precise localized ablation. This treatment may represent a multimodality approach to treating patients with malignant diseases-facilitating pain palliation, enhanced local drug delivery and radiation therapy effects, and stimulation of anticancer specific immune responses, and potentially facilitating local tumor control. Focused ultrasound can be used to achieve pain palliation by producing several effects, including tissue denervation, tumor mass reduction, and neuromodulation, that can influence different pathways at the origin of the pain. This technology has several key advantages compared with other analgesic therapies: It is completely noninvasive, might be used to achieve rapid pain control, can be safely repeated, and can be used in combination with chemotherapy and radiation therapy to enhance their effects. Online supplemental material is available for this article. ©RSNA, 2018.

Nonoperative Ablation of Pancreatic Neoplasms.

Pancreatic cancer is a poor prognostic tumor and about 20% of patients are eligible for surgical resection at the time of diagnosis. Recently, minimally invasive procedures have provided promising results as a therapeutic option for locally advanced unresectable pancreatic cancer. In particular, high-intensity focused ultrasound is an emerging noninvasive thermally ablative procedure that may have a dominant role in the future. Although the clinical applications of minimally invasive therapies to pancreatic cancers are still in their infancy, the results at present are promising.

A meta-analysis of palliative treatment of pancreatic cancer with high intensity focused ultrasound.

BACKGROUND: Pancreatic adenocarcinoma is currently the fourth-leading cause of cancer-related death. Up to 60-90% of patients with advanced disease suffer cancer-related pain, severely impacting their quality of life. Current management involves primarily pharmacotherapy with opioid narcotics and celiac plexus neurolysis; unfortunately, both approaches offer transient relief and cause undesired side-effects. High intensity focused ultrasound (HIFU) is a non-invasive thermal ablation technique that has been used to treat pancreatic cancer. This meta-analysis aims to evaluate the role of HIFU in pain palliation of advanced unresectable pancreatic adenocarcinoma. METHODS: An electronic search was performed in PubMed Medline database up to the end of July 2016, for unresectable pancreatic cancer pain palliation with HIFU. Pertinent studies were identified through the PubMed search engine using the following keywords: HIFU, pancreas, pancreatic cancer, pain and palliation. Additional studies were included after manual search of the selected bibliographies. Pain palliation results reported in each study were analyzed using a logit-transformed random-effects model using the inverse variance method, with the DerSimonian-Laird estimator for τ2, and Cochran's Q test for heterogeneity among studies. The I2 was calculated to assess the percentage of the total variability in the different effect size estimates that can be attributed to heterogeneity among the true effects. A rank correlation test of funnel plot asymmetry was done to assess possible publication bias. RESULTS: The meta-analysis includes a total number of 23 studies with 865 patients, 729 with pancreatic cancer. The population enrolled ranges from 3 patients in the smallest series, up to 61 in the largest study. τ2 (variance among studies) was 0.195, and I2 (percentage of variation among studies) was 40% (95% CI: 1-64%); the Q test p-value was 0.026, indicating significant heterogeneity among studies. Among 639 patients treated with HIFU, 567 complained of pancreatic pain before the treatment and 459 patients experienced partial or complete pain relief after treatment. The random effects estimate of the proportion of patients with pain reduction was 0.81 (95% CI: 0.76-86). CONCLUSIONS: HIFU appears to be an effective tool for pain palliation in advanced pancreatic cancer. Studies assessing treatment in patients with pancreatic adenocarcinoma are limited by factors such as small sample sizes and heterogeneity in clinical definitions and assessments. Prospective randomized and standardized studies are necessary to confirm the effectiveness of HIFU in relieving pain, and to evaluate for any potential impact on tumor control and patient survival.