Strengths and limitations of diagnostic tools for endometriosis and relevance in diagnostic test accuracy research.

Endometriosis is a chronic systemic disease that can cause pain, infertility and reduced quality of life. Diagnosing endometriosis remains challenging, which yields diagnostic delays for patients. Research on diagnostic test accuracy in endometriosis can be difficult due to verification bias, as not all patients with endometriosis undergo definitive diagnostic testing. The purpose of this State-of-the-Art Review is to provide a comprehensive update on the strengths and limitations of the diagnostic modalities used in endometriosis and discuss the relevance of diagnostic test accuracy research pertaining to each. We performed a comprehensive literature review of the following methods: clinical assessment including history and physical examination, biomarkers, diagnostic imaging, surgical diagnosis and histopathology. Our review suggests that, although non-invasive diagnostic methods, such as clinical assessment, ultrasound and magnetic resonance imaging, do not yet qualify formally as replacement tests for surgery in diagnosing all subtypes of endometriosis, they are likely to be appropriate for advanced stages of endometriosis. We also demonstrate in our review that all methods have strengths and limitations, leading to our conclusion that there should not be a single gold-standard diagnostic method for endometriosis, but rather, multiple accepted diagnostic methods appropriate for different circumstances. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Ultrasound features of highly vascularized uterine myomas (uterine smooth muscle tumors) and correlation with histopathology.

OBJECTIVE: To correlate the ultrasound appearance of highly vascularized uterine myomas with their histopathological diagnosis. METHODS: This was a prospective observational study of patients with a preoperative ultrasound diagnosis of a highly vascularized uterine myoma (color score of 3 or 4, according to the Morphological Uterus Sonographic Assessment (MUSA) criteria), characterized by circumferential and intralesional vascular pattern, who underwent myomectomy or hysterectomy. For each patient, ultrasound characteristics were recorded at baseline, including the number of lesions, the size, echogenicity and border regularity of the lesion, presence of cystic areas and shadowing within the myoma, and visualization of the endometrium. Ultrasound features were correlated with the definitive histological diagnosis. Ultrasound features were then compared between malignant and benign lesions. RESULTS: We included 70 patients with highly vascularized uterine myomas on power/color Doppler. Their mean age was 46.5 ± 11.4 years and 13 (18.6%) were postmenopausal. At histological examination, 65 (92.9%) uterine myomas were benign lesions, comprising 32 typical leiomyomas, 29 leiomyoma variants and four adenomyomas. The remaining five (7.1%) uterine myomas were malignant masses, comprising two uterine sarcomas, one leiomyosarcoma, one neuroendocrine tumor and one uterine smooth muscle tumor of uncertain malignant potential (STUMP). The mean age of patients with a malignant lesion was significantly higher than the age of those with a benign lesion (64.8 ± 16.0 vs 42.4 ± 5.1; P < 0.001). Four out of five patients with a malignant lesion were over 45 years old. Ultrasound demonstrated cystic areas within the lesion in 10/32 (31.3%) typical leiomyomas, 16/29 (55.2%) leiomyoma variants, all four adenomyomas and in the cases of STUMP and leiomyosarcoma. Lesion borders were regular in 64/65 (98.5%) benign lesions and 2/5 (40%) malignant lesions (P < 0.05). No significant differences were observed between benign and malignant lesions with respect to echogenicity, presence of shadowing and size. The endometrium was visible in 55/65 women with benign lesions and in 2/5 with malignant lesions (P = 0.03). CONCLUSIONS: Our results showed that ultrasound features of uterine myomas, such as circumferential and intralesional vascularity, cystic areas and lesion borders, are important parameters for differential diagnosis, especially when combined with the patient's age. Such features could be useful to differentiate typical myomas from benign variants and malignant lesions in a preoperative setting and to select patients that may benefit from conservative management rather than surgery. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Accuracy of sonography for non-invasive detection of ovarian and deep endometriosis using #Enzian classification: prospective multicenter diagnostic accuracy study.

OBJECTIVE: To compare the preoperative detection of endometriosis using transvaginal sonography (TVS) supplemented by transabdominal sonography (TAS) with surgical assessment of disease, using the #Enzian classification for endometriosis. METHODS: This was a prospective multicenter diagnostic accuracy study of women undergoing TVS/TAS and radical surgery for deep endometriosis (DE) at different tertiary referral centers. The localization and grade of severity of the endometriotic lesions and adhesions were described according to the criteria of the #Enzian classification, both at preoperative ultrasound examination and during surgery. According to the #Enzian classification, the small pelvis is divided into three compartments for DE: A (rectovaginal septum and vagina); B (uterosacral and cardinal ligaments, parametrium and pelvic sidewalls); and C (rectum). In addition, further locations (F) are classified as adenomyosis (FA), urinary bladder involvement (FB) and ureteric involvement with signs of obstruction (FU). Other intestinal locations (FI) and other extragenital locations (FO) are also included. Ovarian endometriosis and adhesions at the level of the tubo-ovarian unit are listed as O and T, respectively. The #Enzian grade of severity (Grade 1-3) was determined for #Enzian compartments O, T, A, B and C based on the size of the lesion or the severity of the adhesions. Concordance between preoperative assessment using TVS/TAS and evaluation at surgery was assessed. The sensitivity, specificity, positive and negative predictive values and accuracy of TVS/TAS in the detection of endometriotic lesions/adhesions in the different #Enzian compartments were calculated. RESULTS: In total, 745 women were included in the analysis. Preoperative TVS/TAS and surgical findings showed a concordance rate ranging between 86% and 99% for the presence or absence of endometriotic lesions/adhesions, depending on the evaluated #Enzian compartment. The concordance rate between TVS and surgery ranged between 71% and 92% for different severity grades, in #Enzian compartments O, T, A, B and C. Determining the presence or absence of adhesions at the level of the tubo-ovarian unit and classifying them accurately as Grade 1, 2 or 3 on TVS was more difficult than determining the presence and severity of endometriotic lesions in #Enzian compartments O, A, B and C. The sensitivity of TVS/TAS for the detection of endometriotic lesions ranged from 50% (#Enzian compartment FI) to 95% (#Enzian compartment A), specificity from 86% (#Enzian compartment Tleft ) to 99% (#Enzian compartment FI) and 100% (#Enzian compartments FB, FU and FO), positive predictive value from 90% (#Enzian compartment Tright ) to 100% (#Enzian compartment FO), negative predictive value from 74% (#Enzian compartment Bleft ) to 99% (#Enzian compartments FB and FU) and accuracy from 88% (#Enzian compartment Bright ) to 99% (#Enzian compartment FB). CONCLUSIONS: The localization and severity of endometriotic lesions/adhesions, as described and classified according to the #Enzian classification, can be diagnosed accurately and non-invasively using TVS/TAS. The #Enzian classification provides a uniform classification system for describing endometriotic lesions, which can be used both at TVS/TAS and during surgical evaluation. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

What to choose and why to use - a critical review on the clinical relevance of rASRM, EFI and Enzian classifications of endometriosis.

BACKGROUND: Endometriosis is a common benign gynaecological disease that affects pelvic structures and causes adhesions. Endometriosis outside the pelvis exists but is rarer. Deep endometriosis may affect organs such as the urinary bladder, ureters, bowel and sacral roots. Adenomyosis (growth of endometrium in the myometrium, sometimes explained by disruption of the uterine junctional zone) frequently co-exists with deep endometriosis. Over the past decades, multiple attempts have been made to describe the anatomical extent of endometriosis. Out of approximately 20 classification systems suggested and published so far, three have gained widespread acceptance. These are the rASRM (American Society of Reproductive Medicine) classification, the Endometriosis Fertility Index (EFI) and the Enzian classification. Ideally, a classification system should be useful both for describing disease extent based on surgical findings and results of imaging methods (ultrasound, magnetic resonance imaging). OBJECTIVES: To highlight the advantages and disadvantages of the three classification systems. METHODS: This is a narrative review based on selected publications and experience of the authors. We discuss the current literature on the use of the rASRM, EFI and Enzian classification systems for describing disease extent with imaging methods and for prediction of fertility, surgical complexity, and risk of surgical complications. We underline the need for one universally acceptable terminology to describe the extent of endometriosis. CONCLUSIONS: A useful classification system for endometriosis should describe the sites and extent of the disease, be related to surgical complexity and to disease-associated symptoms, including subfertility and should satisfy needs of both, imaging specialists for pre-operative classification and surgeons. The need for such a system is obvious and is provided by the #Enzian classification. Future research is necessary to test its validity.

Predictors of recurrence following laparoscopic radical hysterectomy for early-stage cervical cancer: A multi-institutional study.

OBJECTIVE: To assess predictors of recurrence following laparoscopic radical hysterectomy (LRH) for apparent early stage cervical cancer (CC). METHODS: This is a retrospective multi-institutional study reviewing data of consecutive patients who underwent LRH for FIGO 2009 stage IA1 (with lymphovascular space invasion (LVSI)), IA2 and IB1(≤4 cm) CC, between January 2006 and December 2017. The following histotypes were included: squamous, adenosquamous, and adenocarcinoma. Multivariable models were used to estimate adjusted odds ratio (OR) and corresponding 95% CI. Factors influencing disease-free survival (DFS) and disease-specific survival (DSS) were also explored. RESULTS: 428 patients were included in the analysis. With a median follow-up of 56 months (1-162) 54 patients recurred (12.6%). At multivariable analysis, tumor size (OR:1.04, 95%CI:1.01-1.09, p = .02), and presence of cervical residual tumor at final pathology (OR: 5.29, 95%CI:1.34-20.76, p = .02) were found as predictors of recurrence; conversely preoperative conization reduced the risk (OR:0.32, 95%CI:0.11-0.90, p = .03). These predictors remained significant also in the IB1 subgroup: tumor size: OR:1.05, 95%CI:1.01-1.09, p = .01; residual tumor at final pathology: OR: 6.26, 95%CI:1.58-24.83, p = .01; preoperative conization: OR:0.33, 95%CI:0.12-0.95, p = .04. Preoperative conization (HR: 0.29, 95%CI: 0.13-0.91; p = .03) and the presence of residual tumor on the cervix at the time of surgery (HR: 8.89; 95%CI: 1.39-17.23; p = .01) independently correlated with DFS. No independent factors were associated with DSS. CONCLUSIONS: In women with early stage CC the presence of high-volume disease at time of surgery represent an independent predictor of recurrence after LRH. Conversely, preoperative conization and the absence of residual disease at the time of surgery might play a protective role.

Minilaparoscopic radical hysterectomy for cervical cancer: multi-institutional experience in comparison with conventional laparoscopy.

OBJECTIVE: To analyze the preliminary experience of three gynecologic oncology services with minilaparoscopic radical hysterectomy (mLRH) for the treatment of cervical cancer and to compare perioperative outcomes with those of conventional laparoscopic surgery (LRH). METHODS: Prospectively collected data on consecutive cervical cancer patients undergoing radical hysterectomy with a laparoscopic approach were analyzed retrospectively. Perioperative outcomes of women undergoing mLRH were compared to data from control patients who had undergone LRH with 5-mm instruments. Adjustment for potential selection bias in surgical approach was made with propensity score (PS) matching. RESULTS: The study cohort consisted of 257 patients, 35 undergoing mLRH and 222 undergoing LRH. The two groups were comparable in terms of demographic and tumor characteristics. No significant differences were observed between groups in terms of operative time, blood loss, lymph node yield, amount of parametrial or vaginal cuff tissue removed, and percentage of intra- or postoperative complications, both in the entire cohort and in the PS matched group. No conversions were needed from mLRH to standard laparoscopy or from minilaparoscopy to open surgery. Conversion from standard laparoscopy to open surgery was necessary in 2 patients. A shorter hospital stay was observed among women who had mLRH than in those undergoing LRH [2 (1-10) vs 4 (1-14) days, p = 0.005]. This difference remained significant after PS matching. CONCLUSION: Our preliminary study suggests that in experienced hands minilaparoscopy is a feasible and safe technique for radical hysterectomy and yields results that are equivalent to those of LRH.

[A case of double ectopic pregnancy dealed with a laparoscopic management]. / Un caso di duplice gravidanza ectopica trattato per via laparoscopica.

UNLABELLED: Uterine horn pregnancy is a very rare condition and is associate with a high rate of maternal morbidity and mortality. The standard treatment is laparotomy. CASE: A 40-year-old woman, previosly undegone laparotomy surgery for extrauterine pregnancy, was admitted to hospital "Casa di Cura Malzoni" because ectopic pregnancy was diagnosed. The patient was treated with laparoscopic surgery.

Total laparoscopic radical hysterectomy (type III) and pelvic lymphadenectomy.

A case of Stage IIA, G2 carcinoma of the cervix treated by total laparoscopic radical hysterectomy and pelvic lymphadenectomy is reported. To our knowledge, a total laparoscopic radical hysterectomy with laparoscopic lymphadenectomy has not been previously described in Italy.

[A review of 445 cases of laparoscopic hysterectomy: benefits and outcome]. / Review di 445 casi di isterectomia laparoscopica: vantaggi e outcome.

Hysterectomy is a major procedure indicated for women with gynaecologic pathologies. After reporting the first laparoscopic hysterectomy (Reich 1989), this technique has recently been considered as a safe and efficient alternative to traditional abdominal hysterectomy in the management of benign uterine pathologies when vaginal route is contraindicated. The laparoscopic approach should not be held to compete with vaginal hysterectomy. From 1995 to 2001 in our institute, the proportion of laparoscopic hysterectomy has increased and laparotomic hysterectomy has decreased. Between January 1999 and January 2001 we carried out 445 total laparoscopic hysterectomies. There were 5 laparotomy conversions for large uterus. The average haemoglobin drop was 1,36 g/dl. Median operative time was 95 +/- 27 min. The mean in postoperative stay was 2.7 +/- 0.8 gg. The postoperative complications were minimal. Laparoscopic approach is less painful, is associated to less blood loss, shorter hospital stay, more rapid recovery and a better assumption by affected women. Some disadvantages are reported too, such as larger operating time, high rate of complication and experience required for performing laparoscopy including a learning curve. A training period is necessary to standardize the operating procedure, to put in place methods of avoiding complication and to reach a plateau of surgical skill. The purpose of this study was to show the role of total laparoscopic hysterectomy and how it can be performed safely with a minimal morbidity after a period of training in which we worked out shrewdness to get a standardized technique with the most effective outcome.

Laparoscopic surgery in treatment of stage IIb cervical cancer after neoadjuvant chemotherapy. A case report and review of the literature.

BACKGROUND: A detailed operative procedure of laparoscopic radical hysterectomy (type III) with pelvic and aortic lymphadenectomy after neoadjuvant chemoterapy in treatment of Stage IIb cervical cancer is described. CASE REPORT: A 50-year-old patient with Stage IIb squamous cell carcinoma of the uterine cervix, who initially was not surgically resectable, received three courses of neoadjuvant chemotherapy that included ifosfamide 5 g/m2, cisplatin 50 mg/m2 and paclitaxel 175 mg/m2 (TIP). Following a partial clinical response to chemotherapy, the patient underwent laparoscopic type III radical hysterectomy with bilateral salpingo-oophorectomy and pelvic and paraaortic lymphadenectomy. The surgical procedure lasted 250 minutes. Blood loss was 310 ml. The patient was discharged on postoperative day 4. The mean length of the resected parametria and paracolpia was 4.1 cm and 2.0 cm, respectively. The number of dissected lymph nodes was 48:29 pelvic and 19 paraaortic nodes. No major intraoperative or postoperative complications occurred. The patient also underwent adjuvant radiation therapy. Follow-up was performed at six months so far. CONCLUSIONS: This experience suggests that such a surgical procedure is safe. Laparoscopic radical hysterectomy potentially allows for decreased perioperative morbidity and blood loss, faster recovery and better cosmetic results. Large studies with long term follow-up are needed to confirm that this approach may be proposed as an alternative to conventional surgery.

Fertility after laparoscopic myomectomy of large uterine myomas: operative technique and preliminary results.

OBJECTIVE: The purpose of this study was to evaluate indications and complications of laparoscopic myomectomy with regard to the reproductive outcome of infertile women with a large leiomyomatous uterus. METHODS: From January 1997 to July 1999, 144 patients underwent laparoscopic myomectomy for a myoma measuring > or = 5 cm in diameter. Indications for surgery were increase in size of myoma in infertile patients (70.8%), pain (44.4%) or abnormal bleeding (68%). Average size of myomas were 7.8 cm with a range of 5 cm to 18 cm. The myomas were intramural/submucosal (n = 108), subserosal (n = 15), intraligamentous (n = 14) and peduncolated (n = 7). The laparotomy conversion rate was 1.39% (n = 2); one case required a blood transfusion. Operating time ranged from 58 to 180 minutes with an average of 95 minutes. Average hospital stay was 2.6 days and the overall complication rate was 2.08%. Eighteen patients (12.5%) underwent second-look laparoscopy. The rate of postoperative adhesion was 33.3%; there were no adnexal adhesions. In all cases ultrasonography was done one day after the operation and five weeks postoperatively to compare wound healing, the last control showed an irregular hypodense area in only 14 patients (9.7%). RESULTS: Twenty-six patients operated on in 1997 went on to conceive: nine vaginal deliveries, 12 Caesarean sections, four miscarriages and one ectopic pregnancy. No uterine rupture was observed. The pregnancy rate for patients submitted to laparoscopic myomectomy in 1997 (n = 38) was 34.21% at six months (n = 13) and 55.26% (n = 21) at 12 months after the procedures. CONCLUSIONS: Our preliminary results confirm that conception occurs in the majority of infertile women with a large leiomyomatous uterus who undergo myomectomy and second-look laparoscopy leads to a low complication rate.

Radiofrequency bipolar coagulation for radical hysterectomy: technique, feasibility and complications.

This study describes the surgical technique and intra- and postoperative complications associated with the use of a radiofrequency bipolar coagulator in a series of 18 Piver type III-IV radical hysterectomies performed in cervical cancer patients. Preliminary vessel-by-vessel dissection of the lateral parametria was possible in 17 out of 18 (94%) cases, and a direct application of a radiofrequency bipolar coagulation instrument was performed to coagulate the posterior and anterior parametrial tissues in all cases. We were able to easily coagulate isolated vessels up to 5 mm of maximal diameter. In no case were clamps or hemoclips necessary to complete hemostasis. We did not observe any parametrial vessel damage or heat-related injury of the surrounding normal tissue. The median size of the parametria removed was 44 mm (range 31-58) and nodes were detected in 15 cases (83%). Median operative time and estimated blood loss for the whole procedure including systematic pelvic and aortic lymphadenectomy was 250 min (range 200-410) and 550 ml (range 400-2500), respectively. Median follow-up time was 9 months (range 5-13). No complications specifically related to the use of radiofrequency coagulation were found. In conclusion the radio-frequency coagulation with this instrument appears to be a safe technique that is particularly useful in reducing blood loss and operative time without affecting radicality in patients undergoing radical hysterectomy.