How to Manage Endometriosis in Adolescence: The Endometriosis Treatment Italian Club Approach.

The evaluation of endometriosis in an adolescent girl is a challenging topic. The initial stage of the disease and the limited diagnostic instrument appropriate for the youth age and for its typical features can reduce the ability of the gynecologist. At the same time, missing a prompt diagnosis can delay the beginning of specific and punctual management of endometriosis, which could avoid a postponed diagnosis from 6 to 12 years, typical of adolescent girls complaining of dysmenorrhea. This article aimed to answer all the potential questions around the diagnosis and management of endometriosis in adolescents starting from a clinical case looking at the possible solution that is easily reproducible in the clinical practice.

"Better late than never but never late is better", especially in young women. A multicenter Italian study on diagnostic delay for symptomatic endometriosis.

PURPOSE: The aim of the study was to assess the length of diagnostic delay of symptomatic endometriosis in Italy and analyse the presence of correlations between the socio-demographic status of patients and the clinical characteristics/type of diagnosis. MATERIALS AND METHODS: This multicenter cross-sectional questionnaire-based study was conducted in 10 tertiary Italian referral centres for diagnosis and treatment endometriosis. A total of 689 respondents with histologically proven endometriosis and onset of the disease with pain symptoms completed an on-line self-reported questionnaire written in their own language (World Endometriosis Research Foundation-Endometriosis Phenome and Biobanking Harmonisation Project-Endometriosis Patient Questionnaire-Minimum) evaluating endometriosis related symptoms, family history of endometriosis and chronic pelvic pain, demographic data, as well as medical, reproductive, and obstetric history. RESULTS: The mean diagnostic delay found was of 11.4 years. The mean time (14.8 years) from symptoms onset to diagnosis was significantly longer among patients aged 9-19 vs patients aged 20-30 (mean 6.9 years, p < 0.001) and patients aged 31-45 (mean 2.9, p < 0.001). No significant association were found between a delayed diagnosis and any of the clinically relevant factors such as the number or severity of the reported symptoms, familiarity, hormonal therapy intake or methodology of diagnosis. CONCLUSIONS: The mean diagnostic delay of endometriosis in Italy is about 11 years. The delay can be up to 4 years longer in patients with pain symptoms onset under 20 years. Educating clinicians and patients on pathologic nature of endometriosis related pelvic pain is advisable to reduce waiting time to diagnosis, especially for young women.

Approaching ovarian endometrioma with medical therapy.

Endometriosis is a chronic inflammatory gynecological disorder associated with pelvic pain symptoms and infertility. Ovarian cysts (endometriomas) are the most common localization of endometriosis in the pelvis. Considering non-invasive methods, transvaginal ultrasound has high sensitivity and specificity for endometrioma diagnosis. Laparoscopic removal of endometrioma is related to a damage to the ovarian reserve and should be limited to patients with suspicious cysts or unresponsive to medical treatment. The main goal of medical therapy of symptomatic endometrioma is the control of pain symptoms, while no benefits have been demonstrated in terms of improving fertility rates of women seeking pregnancy. The aim of medical treatment is the inhibition of ovulation, stop of menstruation and achievement of a stable hypo-hormonal milieu. Estroprogestins and progestins are indicated by guidelines as first line medications for symptomatic patients. Several hormonal treatments have been proposed for the treatment of symptomatic endometriomas. In particular, dienogest, a relatively new progestin, has shown promising results. Medical treatment should be conceived as a long-term treatment. Safety, tolerability, a low percentage of side effects and an easy route of administration are essential for patient acceptance and adherence to therapy.

Transvaginal Ultrasound Findings After Laparoscopic Rectosigmoid Segmental Resection for Deep Infiltrating Endometriosis.

OBJECTIVES: To evaluate transvaginal ultrasound (TVUS) findings in patients who underwent segmental rectosigmoid resection for deep infiltrating endometriosis (DIE) and to correlate postsurgical ultrasound findings with symptoms. METHODS: A retrospective study including 50 premenopausal women with bowel endometriosis who underwent segmental rectosigmoid resection was conducted. Within 12 months after surgery, a TVUS examination was conducted in all patients to evaluate the presence of postsurgical endometriosis locations and symptoms, including dysmenorrhea, dyspareunia, dysuria, dyschezia, and chronic pelvic pain. Pelvic pain was assessed in all women by a visual analog scale. RESULTS: At the follow-up 32 of 50 patients were receiving medical treatment, whereas 18 women declined postsurgical medical therapy and tried to conceive. A high percentage of adhesions (90%) was found. A negative sliding sign (a simple diagnostic sign that can be performed during a TVUS examination, consisting of gentle pressure applied by both the vaginal transducer and the examiner's hand on the abdomen; if the uterus does not glide freely along with the rectum and posterior fornix, the sign is considered negative, and adhesions can be suspected) was found in 29 (58%) women and was associated with bowel symptoms. Recurrence of posterior DIE was found in 9 cases (18%) and endometriomas in 8 cases (16%). Adenomyosis was observed in 80% of women and was present in all symptomatic patients. CONCLUSIONS: After rectosigmoid segmental resection patients with DIE may continue to be symptomatic, and postoperative TVUS may reveal foci of disease or pelvic adhesions. Moreover, adenomyosis could be linked to symptoms experienced during follow up. Women should be aware that painful symptoms and alterations of pelvic organs could still be present after surgery and be detectable by TVUS.

Hormonal therapy potentiates the effect of surgery on gene expression profile of peripheral blood mononuclear cells in patients affected by endometriosis.

BACKGROUND: Combined oral contraceptives (COCs) represent a common pharmacological approach for endometriosis. They have been demonstrated to mitigate painful symptoms in patients and are considered the first line therapy for symptomatic disease. The goal of this study was to evaluate whether the presence of pelvic endometriotic lesions can exert a systemic effect on PBMC gene expression and to investigate whether hormonal treatment may restore a normal gene expression profile. METHODS: Forty women, with endometriosis at stage III-IV, were enrolled in the study. After surgery, 20, randomly chosen, were treated with COC for six months and 20 did not receive hormonal therapy. Blood samples were obtained few days before surgery and six months after surgery. Gene expression profile of PBMC was studied by microarray. Gene expression levels before surgery and post-surgery, in presence and absence of COC, were compared. RESULTS: Nine genes previously reported to be overexpressed by endometriosis, were confirmed to be significantly downregulated after surgery. COC treatment lead to a greater down-regulation of these genes and to a significant down-regulation of 3 additional genes. 145 genes resulted downregulated and 28 upregulated by comparing gene expression before surgery with that 6 months after surgery in the presence of COC therapy. CONCLUSIONS: Results support the concept that a systemic chronic inflammatory status is among the mechanisms underlying endometriosis. Moreover, they shed light into the mechanisms of action of COCs and strength the rationale for their use to improve quality of life of women affected by the disease.

Pudendal Neurolysis: 6-Step Laparoscopic Approach.

OBJECTIVE: To demonstrate the safety and feasibility of the laparoscopic approach to perform pudendal neurolysis in a case of pudendal nerve entrapment syndrome [1-3]. DESIGN: A video tutorial that highlights the laparoscopic steps to performing pudendal neurolysis, with a focus on the main anatomic landmarks [4,5]. SETTING: A tertiary care regional hospital. INTERVENTIONS: This video shows a 6-step approach to laparoscopic pudendal neurolysis for the treatment of pudendal nerve entrapment between the sacrospinous and sacrotuberous ligaments [2,6-8]. Step 1: Identification of the umbilical artery. Step 2: Dissection and development of the lateral paravesical space until the pelvic floor. Step 3: Identification of the arcus tendineus of the endopelvic fascia. Step 4: Identification of the ischial spine and the sacrospinous ligament covered by the coccygeus muscle. Step 5: Coagulation and section of the coccygeus muscle and the sacrospinous ligament. Step 6: Medialization of the pudendal nerve until its entrance into the Alcock canal. CONCLUSION: This video demonstrates the safety, feasibility, and reproducibility of laparoscopic pudendal neurolysis in 6 steps. A minimally invasive approach is adequate to treat the pudendal compression until the Alcock canal [2].

Adolescence and endometriosis: symptoms, ultrasound signs and early diagnosis.

OBJECTIVE: To evaluate the ultrasonographic presence of different forms of endometriosis and the associated clinical symptoms in adolescent women. DESIGN: Retrospective observational study. SETTING: University hospital. PATIENT(S): Two hundred and seventy women aged 12-20 years referred to the gynecologic ultrasound unit from January 2014 to June 2019. INTERVENTION(S): Two-dimensional, three-dimensional, and power Doppler ultrasound (US) pelvic examination (transvaginal or transrectal in pre-sexually active adolescents) were performed in all included adolescents. Medical history was collected for each patient before the scan. MAIN OUTCOME MEASURE(S): All possible locations of endometriosis evaluated and recorded using a dedicated ultrasound mapping sheet and severity of painful symptoms evaluated through a visual analogue scale (VAS). RESULT(S): Dysmenorrhea was detected in 147 (54.4%) of 270 patients and heavy menstrual bleeding in 76 (28.1%) of 270. At least one ultrasound feature of endometriosis was identified in 36 (13.3%) of 270 cases. Ovarian endometriomas were found in 22 (11%) patients, adenomyosis in 16 (5.2%), and deep infiltrating endometriosis (DIE) in 10 (3.7%). Ultrasound signs of endometriosis were found in 21% of adolescents who reported dysmenorrhea and 33% with dyspareunia. The presence of DIE at ultrasound was associated with bowel symptoms in 33% of patients and associated with dyspareunia in 25% of patients. CONCLUSION(S): The detection rate of pelvic endometriotic lesions at ultrasound was 13%. The rates of dysmenorrhea, dyspareunia and heavy menstrual bleeding in adolescents with endometriosis ultrasound signs were statistically significantly higher compared with those without. In patients with dysmenorrhea, the detection rate of pelvic endometriosis at ultrasound increased to 20%. Professionals involved with teens should be aware of the clinical presentation of endometriosis to reduce the delay between the onset of symptoms and the diagnosis, referring these young women to dedicated centers.

Recurrent atypical polypoid adenomyoma and pregnancy: A new conservative approach with levonorgestrel-releasing intrauterine system.

•Levonorgestrel IUD was effective in treatment of recurrent APA.•No side effects were reported.•No impairments on a subsequent pregnancy were reported.

Adenomyosis: What the Patient Needs.

A panel of experts in the field of endometriosis expressed their opinions on management options in a 28-year-old patient, attempting pregnancy for 1 year, with severe cyclic pelvic pain and with clinical examination and imaging techniques suggestive of adenomyosis. Many questions this paradigmatic patient may pose to the clinician are addressed, and all clinical scenarios are discussed. A decision algorithm derived from this discussion is also proposed.

Vaginal Uterine Morcellation Within a Specimen Containment System: A Study of Bag Integrity.

STUDY OBJECTIVE: To evaluate the integrity of the endoscopic bag after transvaginal in-bag morcellation of uteri that need to be removed by vaginal morcellation during total laparoscopic hysterectomy (TLH). DESIGN: Prospective pilot study (Canadian Task Force classification II-2). SETTING: University hospital. PATIENTS: Twelve patients with uteri that needed to be removed and who required vaginal morcellation underwent TLH from September 2014 to February 2015, without suspected or confirmed malignancy. INTERVENTIONS: After transvaginal in-bag morcellation of uteri at the end of TLH, careful visual inspection of the endoscopic pouch, using diluted methylene blue, was carried out, highlighting any minimal bag damage. MEASUREMENTS AND MAIN RESULTS: No gross rupture was encountered after morcellation; however, 4 minimal ruptures were recognized (33%) after filling up the bag with diluted methylene blue. CONCLUSIONS: Minimal lesions of the bag may occur after transvaginal morcellation of uteri that need to be removed by vaginal morcellation; this may potentially affect the spread of cancer cells into the abdominal cavity.

Embryonal rhabdomyosarcoma of the uterine cervix in adults: a case report and literature review.

OBJECTIVE: We report a case of cervical rhabdomyosarcoma in an adult and review of literature. MATERIALS AND METHODS: A 44-year-old, premenopausal, white woman, complained of vaginal bleeding for 2 months. The gynecological examination showed a cervical polyp protruding from the vagina. The polyp was partially removed by polypectomy. Pathological examination was diagnostic for embryonal rhabdomyosarcoma-botryoid type-of the cervix. Radical class II hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and pelvic lymphadenectomy were performed. Adjuvant multidrug chemotherapy (vincristine, doxorubicin, ifosfamide, and etoposide) plus external beam radiotherapy were administered. Forty-six months after diagnosis, the patient is disease free. RESULTS: Here, we report a new case and a literature review of a fairly rare cancer, rhabdomyosarcoma of the cervix in an adult. Pathological features and treatment with an aggressive multimodal approach (radical surgery followed by multidrug adjuvant chemotherapy and radiotherapy) are reported. Good treatment-tolerance and optimal results were achieved. CONCLUSIONS: Every effort should be done during both the diagnostic and therapeutic phase to offer these patients the best chance of survival. Further studies on best approach, chemotherapeutic protocols, and outcome in adults are warranted.

The role of lymphadenectomy in cervical cancer patients: the significance of the number and the status of lymph nodes removed in 526 cases treated in a single institution.

PURPOSE: To investigate whether the total number of removed lymph nodes (LNs) and the number of metastatic LNs would prove to be independent prognostic factors for survival in patients with cervical cancer (CC). METHODS: Data from patients with CC who underwent radical surgery between March 1980 and September 2009 were reviewed. A total of 526 patients were included in the statistical analysis. Full pathologic evaluation was performed. The total number of examined LNs and their histopathological status were analyzed for their prognostic effect on survival by means of multivariable Cox proportional hazard regression models. RESULTS: The median number (interquartile range) of total, pelvic, and para-aortic nodes removed was 37 (29-47), 34 (27-42), and 19 (14-24), respectively. Positive pelvic nodes were found in 102 of 526 (19%) patients. All 8 patients with para-aortic metastases had also pelvic node metastases. At multivariable analysis, vaginal involvement, type of lymphadenectomy and LN status all significantly negatively affected disease-free survival and overall survival, whereas the number of total LNs removed did not affect survival. CONCLUSIONS: LN metastasis and number of LN metastases confer an independent risk for worse survival in patients with CC. Pelvic lymphadenectomy is important for staging and regional disease control when LNs are involved. If a standardized complete lymphadenectomy is performed, the number of LNs is not a significant factor per se.

Photodynamic therapy with M-ALA as non surgical treatment option in patients with primary extramammary Paget's disease.

INTRODUCTION: Extramammary Paget disease (EMPD) is a rare neoplasm of the skin that presents with erythematous or leukoplacic plaques causing pruritus and pain. Standard treatment is surgical but local failures and recurrences are frequent, leading to multiple mutilating surgeries. Aim of the study is to evaluate the effectiveness of photodynamic therapy (PDT) to obtain a clinical response and symptom control with a non surgical approach in these patients. MATERIALS AND METHODS: After disease extension evaluation and symptoms assessment women with EMPD were prospectively treated with aminolevulinic-acid methyl-esther (M-ALA) PDT. Clinical and symptoms response were evaluated after 3 cycles and after any further PDT. RESULTS: Thirty-two patients with vulvar EMPD underwent M-ALA PDT. In sixteen (50%) patients the lesion extended to the perineal and/or perianal area. After three courses of treatment, three patients (9.4%) had a complete resolution of the symptoms; 25 patients (78.1%) a partial resolution and a stable disease was recorded in four patients (12.5%). None of the patients had progression of disease. Both size of the lesion and EMPD associated symptoms decreased significantly after three courses of treatment. Eighteen patients (56.2%) recurred and 16 (88.9%) were treated with further PDT. Among the 26 patients who underwent a further PDT, 16 patients (61.5%) achieved at least a partial response. CONCLUSION: M-ALA PDT even if not curative is a reliable strategy to control EMPD and its associated symptoms even in an outpatient setting. M-ALA PDT is able to control large and multiple lesions regardless of the area involved, preserving cosmetic and/or functional anatomy.

Diagnostic accuracy of sentinel node in endometrial cancer by using hysteroscopic injection of radiolabeled tracer.

OBJECTIVE: Retrospective and perspective series have shown the feasibility of sentinel lymph-node (SLN) identification of pelvic nodes in endometrial cancer using a cervical injection of tracers. We designed a perspective study to assess the detection rate and diagnostic accuracy of the SLN procedure by means of hysteroscopic injection of a radiolabeled tracer in endometrial cancer patients. METHODS: Patients with endometrial cancer underwent hysteroscopic technetium injection. SLN assessment was performed intraoperatively. A systematic pelvic and paraaortic dissection was carried out thereafter. SLNs were examined by standard and immunochemistry methods. The primary endpoint was estimation of sensitivity and negative predictive value (NPV) of sentinel-node biopsy. RESULTS: From 2005 to 2010, 80 consecutive patients entered the study. No severe complications occurred during or after the injection or during surgical SLN biopsy. At least one SLN was detected in 76 of the 80 eligible patients. Fifty nine patients were evaluable according to the study protocol. Ten of these patients (17%) had node metastases. Thirty-three patients (56%) had SLN in the para-aortic area. NPV was 98% (95% CI 89.4-100) and sensitivity 90% (55.5-99.8). CONCLUSIONS: SLN detection for endometrial cancer patients has a high sensitivity and NPV when injection is carried out by hysteroscopy. The occurrence of a 56% of sentinel node in paraaortic area may suggest a better sensitivity in this area using hysteroscopic injection compared to cervical injection.

Systematic para-aortic and pelvic lymphadenectomy in early stage epithelial ovarian cancer: a prospective study.

BACKGROUND: Lymphadenectomy is important in the surgical treatment of apparent early epithelial ovarian cancers (eEOC); however, its extent is not well defined. We evaluated the role of systematic lymphadenectomy, the risk factors related with lymph node metastases, the implications, and the morbidity of comprehensive surgical staging. METHODS: We prospectively recruited 124 patients diagnosed with apparent eEOC [International Federation of Gynecology and Obstetrics (FIGO) stage I and II] between January 2003 and January 2011. Demographics, surgical procedures, morbidities, pathologic findings, and correlations with lymph node metastases were assessed. RESULTS: A total of 111 patients underwent complete surgical staging, including lymphadenectomy, and were therefore analyzed. A median of 23 pelvic and 20 para-aortic nodes were removed. Node metastases were found in 15 patients (13.5 %). The para-aortic region was involved in 13 (86.6 %) of 15 cases. At univariate analysis, age, menopause, FIGO stage, grading, and laterality were found to be significant factors for lymph node metastases, while CA125 of >35 U/ml and positive cytology were not. No lymph node metastases were found in mucinous histotypes. At multivariate analysis, only bilaterality (p = 0.018) and menopause (p = 0.032) maintained a statistically significant association with lymph node metastases. Lymphadenectomy-related complications (lymphocyst formation and lymphorrhea) were found in 14.4 % patients. CONCLUSIONS: The data of this prospective study demonstrate the prognostic value of lymphadenectomy in eEOC. Menopause, age, bilaterality, histology, and tumor grade are identifiable factors that can help the surgeon decide whether to perform comprehensive surgical staging with lymph node dissection. These parameters may be used in planning subsequent treatment.

What is the role of lymphadenectomy in surgical management of patients with endometrial carcinoma?

The role of lymphadenectomy in the management of endometrial carcinoma remains controversial in gynecologic oncology. Comprehensive pelvic and paraaortic lymphadenectomy should be performed in patients with intermediate- and high-risk endometrial cancer.

Class III nerve-sparing radical hysterectomy versus standard class III radical hysterectomy: an observational study.

BACKGROUND: The purpose of this observational study was to evaluate disease-free survival, overall survival, local recurrence rate, and morbidities in patients submitted to class III nerve-sparing radical hysterectomy (NSRH) compared with standard radical hysterectomy (RH) in cervical cancer (CC). This was a comparative study in the context of multimodal therapies. MATERIALS AND METHODS: We investigated patients with CC admitted to the National Cancer Institute of Milan between January 4, 2001, and September 29, 2009, treated with NSRH. We compared patients operated with RH between March 20, 1980, and December 28, 1995. A total of 496 patients were enrolled. The median follow-up was 93 months (42 and 159 months for the NSRH and RH groups, respectively). RESULTS: The overall number of relapses was 30 out of 185 and 60 out of 311 for NSRH and RH, respectively. Five-year disease-free survival estimate was 78.9% (95% confidence interval [CI] 72.0-85.7) in NSRH and 79.8% (95% CI 75.3-84.3) in RH (P=0.519). Five-year overall survival estimate was 90.8% (95% CI 85.9-95.6) in NSRH and 84.1% (95% CI 8.0-88.3) in RH (P=0.192). Rates of postoperative serious complications were 9.7% and 19.6% for NSRH and RH, respectively (P=0.004). Positive pelvic lymph node and vagina status were significant (P<0.01) independent predictors by multivariable analyses. CONCLUSIONS: The oncologic results were comparable between NSRH and conventional class III RH in the context of two multimodal treatments. Bladder function and postoperative complications rate are improved by nerve-sparing technique. The nerve-sparing technique should be considered in all CC patients addressed to surgery because it improves functional outcome and preserves radicality without compromising overall survival.