Prognostic value of isolated tumor cells in sentinel lymph nodes in low risk endometrial cancer: results from an international multi-institutional study.

OBJECTIVE: The prognostic significance of isolated tumor cells (≤0.2 mm) in sentinel lymph nodes (SLNs) of endometrial cancer patients is still unclear. Our aim was to assess the prognostic value of isolated tumor cells in patients with low risk endometrial cancer who underwent SLN biopsy and did not receive adjuvant therapy. Outcomes were compared with node negative patients. METHODS: Patients with SLNs-isolated tumor cells between 2013 and 2019 were identified from 15 centers worldwide, while SLN negative patients were identified from Mayo Clinic, Rochester, between 2013 and 2018. Only low risk patients (stage IA, endometrioid histology, grade 1 or 2) who did not receive any adjuvant therapy were included. Primary outcomes were recurrence free, non-vaginal recurrence free, and overall survival, evaluated with Kaplan-Meier methods. RESULTS: 494 patients (42 isolated tumor cells and 452 node negative) were included. There were 21 (4.3%) recurrences (5 SLNs-isolated tumor cells, 16 node negative); recurrence was vaginal in six patients (1 isolated tumor cells, 5 node negative), and non-vaginal in 15 (4 isolated tumor cells, 11 node negative). Median follow-up among those without recurrence was 2.3 years (interquartile range (IQR) 1.1-3.0) and 2.6 years (IQR 0.6-4.2) in the SLN-isolated tumor cell and node negative patients, respectively. The presence of SLNs-isolated tumor cells, lymphovascular space invasion, and International Federation of Obstetrics and Gynecology (FIGO) grade 2 were significant risk factors for recurrence on univariate analysis. SLN-isolated tumor cell patients had worse recurrence free survival (p<0.01) and non-vaginal recurrence free survival (p<0.01) compared with node negative patients. Similar results were observed in the subgroup of patients without lymphovascular space invasion (n=480). There was no difference in overall survival between the two cohorts in the full sample and the subset excluding patients with lymphovascular space invasion. CONCLUSIONS: Patients with SLNs-isolated tumor cells and low risk profile, without adjuvant therapy, had a significantly worse recurrence free survival compared with node negative patients with similar risk factors, after adjusting for grade and excluding patients with lymphovascular space invasion. However, the presence of SLNs-isolated tumor cells was not associated with worse overall survival.

Immunohistochemical Markers in Endometrial Cancer: Latest Updates.

Ten years ago, The Cancer Genome Atlas (TGCA) Research Network classified endometrial cancer into four molecular categories with prognostic significance, suggesting sensitivity to postsurgical treatments [...].

Effective Surgical Management of a Large Serous Ovarian Cyst in a Morbidly Obese Middle-Aged Woman: A Case Study and Literature Review.

BACKGROUND In contemporary gynecological practice, encountering giant ovarian tumors is a rarity. While most are benign and of the mucinous subtype, the borderline variant only accounts for approximately 10% of these cases. This paper addresses the paucity of information about this specific subtype, emphasizing critical elements of managing borderline tumors that can pose life-threatening complications. Additionally, a review of other documented cases of the borderline variant in the literature is also included to foster a deeper understanding of this uncommon condition. CASE REPORT We present the multidisciplinary management of a 52-year-old symptomatic woman with a giant serous borderline ovarian tumor. Preoperative assessment showed a multiloculated pelvic-abdominal cyst responsible for compression of the bowel and retroperitoneal organs, and dyspnea. All tumor markers were negative. Together with anesthesiologists and interventional cardiologists, we decided to perform a controlled drainage of the cyst of the tumor, to prevent hemodynamic instability. Subsequent total extrafascial hysterectomy, contralateral salpingo-oophorectomy, and abdominal wall reconstruction, followed by admission to the intensive care unit, were also conducted by the multidisciplinary team. During the postoperative period, the patient experienced a cardiopulmonary arrest and acute renal failure, which were managed by dialysis. After discharge, the patient underwent oncologic followup, and after 2 years, she was found to be completely recovered and disease free. CONCLUSIONS Intraoperative controlled drainage of Giant ovarian tumor fluid, planned by a multidisciplinary management team, constitutes a valid and safe alternative to the popular choice of "en bloc" tumor resection. This approach avoids rapid changes in body circulation, which are responsible for intraoperative and postoperative severe complications.

HE4 Tissue Expression as A Putative Prognostic Marker in Low-Risk/Low-Grade Endometrioid Endometrial Cancer: A Review.

Low-grade stage I endometrioid endometrial carcinomas should have an excellent prognosis, but a small subset of these cancers can relapse. The search for putative immunohistochemical prognostic markers for relapse in low-risk/low-grade endometrioid endometrial cancers remains open. Among the candidate molecules that may implicate the roles of immunohistochemical risk markers, we focused our attention on human epididymis protein 4 (HE4) after a review of the literature. Few authors have devoted themselves to this topic, and none have found a correlation between the tissue expression of HE4 and the molecular classification of endometrial cancer. Five different variants of HE4 mRNA and multiple protein isoforms of HE4 were identified many years ago, but current HE4 assays only measure the total HE4 expression and do not distinguish the different proteins encoded by different mRNA variants. It is important to have an approach to distinguish specific variants in the future.

Same-day discharge protocol for laparoscopic treatment of adnexal disease: management and acceptance.

OBJECTIVE: Develop a 'same-day discharge' setting for laparoscopic treatment of adnexal disease. SETTING: Preventive Gynecology, European Institute of Oncology, Milan, Italy. POPULATION: Two hundred patients undergoing laparoscopic procedures. MATERIAL AND METHODS: Data were retrospectively collected through clinical, surgical and laboratory reports. After discharge patients were contacted by phone and e-mail. MAIN OUTCOME MEASURES: The rate of discharge, adverse events and readmission was measured. The need for adjunctive care provided by our on-call service or by a primary care physician and the acceptability of the same-day discharge protocol were also investigated. RESULTS: One hundred and sixty-five patients out of 200 were discharged on the same day. Of the 35 patients hospitalized, the most frequent causes for overnight admission were: uncontrolled pain, surgical length or complexity of the procedure in nine patients, nausea/vomit in four patients. One hundred and one out of 200 patients answered the mailed questionnaire. None of the discharged patients were readmitted. Eighty-five percent of the answering patients evaluated the length of their hospital stay as adequate or moderately adequate. Ninety-two percent of the patients would recommend the day surgery to other patients. CONCLUSIONS: our experience demonstrates that the same-day discharge protocol for laparoscopic treatment of adnexal disease is safe and acceptable.

PAX8 Positivity, Abnormal p53 Expression, and p16 Negativity in a Primary Endometrial Squamous Cell Carcinoma: A Case Report and Review of the Literature.

Primary endometrial squamous cell carcinoma (PESCC) is a rare entity. As the clinicopathologic features and the immunophenotype have not been completely defined yet, here we report our experience and review of the literature on this topic. A 73-yr-old nulliparous woman presented with pelvic pain and vaginal bleeding. Endometrial biopsy showed a carcinoma with squamous differentiation infiltrating the myometrium. Total hysterectomy with bilateral salpingo-oophorectomy and selective pelvic lymphadenectomy was performed. Definitive diagnosis was squamous carcinoma of the endometrium, with one lymph node metastasis (stage IIIC1). Immunohistochemistry evidenced immunoreactivity of the tumor cells for cytokeratin 5, p63, cytokeratin 7, PAX8, PTEN, and cyclin D1, aberrant p53 overexpression, and Ki-67 reactivity in ~70% of the tumor cells. Estrogen and progesterone receptor, PAX2, WT1, and p16 were negative. Our case was the first PAX8-positive PESCC in the literature, underlining the Mullerian system origin of this neoplasm. Abnormal p53 expression of this case confirmed its role in the pathogenesis of PESCC. Further studies on a large number of cases are needed to better understand the pathologic features and the immunophenotype of PESCC.

Laparoscopic treatment of deep endometriosis with a diode laser: our experience.

PURPOSE: To evaluate whether laparoscopic treatment with a diode laser is feasible, safe, and effective in symptomatic patients affected by deep endometriosis (DE). METHODS: This retrospective study was performed using medical record data. The surgical reports, chronic pain scores, and quality of life (QoL) data were evaluated for 50 patients who had undergone laparoscopic surgery between November 2017 and March 2019 at two university hospitals (Monserrato (CA) and Foggia, Italy). Indications for surgery were chronic pelvic pain and/or infertility in patients who wished to conceive spontaneously. Endometriosis lesions/nodules were excised using a diode laser (Leonardo®, Biolitec® DUAL 45) that can combine 980 and 1470 nm wavelengths transmitted through a 1000 µm conical optical fibre. RESULTS: The median patient age was 32 years (range 21-44), with a body mass index (BMI) mean of 21.7  ±  2.9 kg/m2. The mean operation time was 147 min (range 106-190). No intraoperative or early complications (< 30 days) were reported. All patients left the hospital, on average, within 3 days (range 2-9 days) after surgery. A significant improvement in pain was observed at the 3-, 6-, and 12-month follow-up (p < 0.01) in all patients. Moreover, patients reported a significant QoL improvement at the 12-month follow-up. CONCLUSION: The diode laser confirmed its feasibility and safety for treating endometriosis. During the shaving surgical procedure, the diode laser system ensures a safe and effective laparoscopic dissection of deep endometriotic lesions. Further comprehensive randomized trials are necessary to confirm these preliminary data in terms of efficacy, recurrence rates, and pregnancy outcomes.

Oncologic outcomes of endometrial cancer in patients with low-volume metastasis in the sentinel lymph nodes: An international multi-institutional study.

OBJECTIVE: To assess oncologic outcomes in endometrial cancer patients with low-volume metastasis (LVM) in the sentinel lymph nodes (SLNs). METHODS: Patients with endometrial cancer and SLN-LVM (≤2 mm) from December 3, 2009, to December 31, 2018, were retrospectively identified from 22 centers worldwide. Patients with International Federation of Gynecology and Obstetrics (FIGO) stage IV, adnexal involvement, or unknown adjuvant therapy (ATx) were excluded. RESULTS: Of 247 patients included, 132 had isolated tumor cell (ITC) and 115 had micrometastasis (MM). Overall 4-year recurrence-free survival (RFS) was 77.6% (95% CI, 70.2%-85.9%); median follow-up for patients without recurrence was 29.6 (interquartile range, 19.2-41.5) months. At multivariate analysis, Non-endometrioid (NE) (HR, 5.00; 95% CI, 2.50-9.99; P < .001), lymphovascular space invasion (LVSI) (HR, 3.26; 95% CI, 1.45-7.31; P = .004), and uterine serosal invasion (USI) (HR, 3.70; 95% CI, 1.44-9.54; P = .007) were independent predictors of recurrence. Among 47 endometrioid ITC patients without ATx, 4-year RFS was 82.6% (95% CI, 70.1%-97.2). Considering 18 ITC patients with endometrioid grade 1 disease, without LVSI, USI, or ATx, only 1 had recurrence (median follow-up, 24.8 months). CONCLUSIONS: In patients with SLN-LVM, NE, LVSI, and USI were independent risk factors for recurrence. Patients with any risk factor had poor prognosis, even when receiving ATx. Patients with ITC and grade 1 endometrioid disease (no LVSI/USI) had favorable prognosis, even without ATx. Further analysis (with more patients and longer follow-up) is needed to assess whether ATx can be withheld in this low-risk subgroup.

Immunohistochemical Markers in Endometrial Cancer.

In 2018, 382,069 new cases of uterine cancer were registered worldwide and 89,929 deaths from this cancer were reported [...].

Feasibility of hand-assisted laparoscopic sentinel node biopsy in open endometrial cancer surgery.

Background: The aim of this preliminary retrospective study was to assess the feasibility and accuracy of Indocyanine Green (ICG) sentinel node (SLN) sampling using a laparoscopic camera during open endometrial cancer surgery.Material and methods: Retrospective study. Fourteen women with endometrial cancer, not fit for a complete laparoscopic staging, underwent SLN mapping using the IMAGE1 camera during open surgery.Results: The median age of patients was 67 (range 33-86) years. Median BMI was 31 (range 23-58). Mean operative time 157.5 minutes and hospital stay three days. The overall detection rate of SLN mapping was 93%. Bilateral detection was 86%. No post-operative short or long-term complications were observed.Conclusions: Real-time NIR technology supported by the IMAGE1 S is a reliable system and represents a promising method for SLN mapping in selected cases with EC and severe surgical risks, during 48 traditional open approaches. The use of laparoscopy ICG in open surgery seems to be a feasible and useful tool for the detection of SLN in endometrial cancer patients with intraoperative and/or postoperative high morbidity risk. It represents a valid alternative to robotic surgery, particularly in countries and centers where the robotic platform or SPY system for open surgery are not available.

What women want: Fertility sparing surgery in Borderline ovarian tumours patients and pregnancy outcome.

OBJECTIVE: Borderline ovarian tumours (BOTs) are characterized by the presence of cellular proliferation and nuclear atypia without stromal invasion. Compared to malignant ovarian tumours, BOTs have better prognoses. The most important treatment of BOT is surgery. Considering the good prognosis of BOT, fertility-sparing surgery (FSS) can be considered for young women who desire to preserve fertility. Our study evaluated the pregnancy rate in patients with childbearing desire, the efficacy and risk of recurrence of women affected by BOTs who have undergone FSS. MATERIALS AND METHODS: Patients characteristics have been restrospectively retrieved for diagnosis made from June 2000 to December 2017 from San Raffaele Hospital and Policlinico Cagliari. Patients underwent FSS for BOT were interviewed about child wishing and pregnancy outcomes. RESULTS: 85 patients were recruited for the study. Median age at diagnosis was 33 years. Unilateral salpingo-oophorectomy was performed in 33 patients (38%), unilateral cystectomy in 40 (47%) and 12 underwent both procedures (14%). 40 women (50%) tried to conceive after surgery. The pregnancy rate was 73% and live birth rate was 67%. Childbearing desire and age at diagnosis were significantly associated with the pregnancy rate. CONCLUSIONS: Conservative surgical treatment seems to be a reasonable therapeutic option for women with BOTs who wish to preserve fertility. Our results suggest that the obstetric outcomes after FSS are promising. Maternal desire and the age of diagnosis are the most important factors affecting PR after surgery. Fertility counselling should be an integral part of the clinical management of women with BOT.

New Keystone flap application in vulvo-perineal reconstructive surgery: A case series.

OBJECTIVE: This study aimed to evaluate the application of the Keystone flap technique and the long-term results of vulvovaginal reconstruction after vulvar surgery. METHODS: This is the first case series describing the application of the Keystone perforator island flaps (KPIF) technique to close a wide defect after radical vulvectomy. We prospectively collected patient demographics, operative times, complications, pathologic results, and length of stay on all patients. The benefits, cosmetic results and satisfaction of patients were analyzed in the follow up. RESULTS: Five patients were selected for the study: four underwent radical vulvectomy for squamous cell vulvar cancer, and one underwent vulvar wide excision for Paget disease followed by reconstruction with the Keystone flap technique. The defects were successfully covered by the Keystone flap technique in all patients. CONCLUSIONS: Keystone flaps seem to be easy to design and elevate, and it offers rapid fasciocutaneous closure in wide vulvo-perineal defects with excellent long-term results.

Systemic therapy for the treatment of endometrial cancer.

Introduction: Endometrial cancer (EC) is one of the most frequent gynecological cancers worldwide. The gold standard treatment of EC is most certainly surgery and may very well be the only therapy in the early stages of disease. To improve outcomes in non-early EC, adjuvant therapy is often employed but this is not standardized. Adjuvant options can include radiotherapy, chemotherapy or a combination of both. Adjuvant chemotherapy could be indicated in high-risk stage I and II or advanced stage EC. Several clinical trials are ongoing in an attempt to define the optimal adjuvant treatment. Furthermore, chemotherapy is the front-line therapy in advanced unresectable, metastatic or recurrent endometrial cancer. Areas covered: Herein, the authors review the first-line chemotherapy for the treatment of endometrial cancer and provide their expert perspectives on these therapies. Expert opinion: Chemotherapy is fundamental in advanced/recurrent EC. Further evidence is needed to characterize the role of adjuvant chemotherapy. Future studies should consider genomic and molecular heterogeneities to identify even more efficient tailored therapies.

Conservative treatment for well-differentiated endometrial cancer: when and why it should be considered in young women.

The aim of this review was to update current knowledge on the conservative treatment of endometrial cancer (EC) based on a literature review. A web-based search in the MEDLINE database was carried out on EC management and treatment. All relevant information has been collected and analysed. Case series were mainly found in the literature search. Conservative treatments were offered to young patients with stage I low-grade endometrioid carcinomas of the endometrium. Different options included high/low dose progestin treatments, hysteroscopic resection of the disease, a levonorgestrel intrauterine device or a combination of various strategies. The overall complete response rate was near 76.5% with a recurrence rate of up to 33.8%. Pregnancy outcomes reached rates of 64.8% for live births. The current clinical outcomes show that conservative treatment aimed at preserving fertility is feasible for stage I endometrial well-differentiated adenocarcinomas in motivated patients under close monitoring.

Complete remission of cerebral endometriosis with dienogest: a case report.

The most recent evidences suggest the use of progesterone mimicking drugs for the treatment of endometriosis. Particularly, dienogest has been largely tested. However, the standard treatment of extra-pelvic endometriosis is debated. Particularly, cerebral localization of endometriosis is a very rare clinical condition. The surgical approach for such a particular disorder would consist in difficult procedures, thus leading to prefer the medical treatment. We hereby report the clinical case of a cerebral localization of endometriosis treated with dienogest who experienced a complete remission of the disease.

Laparoscopy for primary cytoreduction with multivisceral resections in advanced ovarian cancer: prospective validation. "The times they are a-changin"?

BACKGROUND: Primary cytoreduction is the mainstay of treatment for advanced ovarian cancer (AOC). We developed and prospectively evaluated an algorithm to investigate the possible role of laparoscopic primary cytoreduction (LPC) in carefully selected patients, with AOC. METHODS: From June 2007 to July 2015, all patients with stage III-IV ovarian cancer and clinical conditions allowing aggressive surgery were candidate to primary cytoreduction with the aim of achieving residual tumor (RT) = 0. The possibility of attempting laparoscopic cytoreduction was carefully evaluated using strict selection criteria. The other patients were approached by abdominal primary cytoreduction (APC). At the end of LPC, an ultra-low pubic mini-laparotomy was performed to extract surgical specimens and to accomplish a laparoscopic hand-assisted exploration of the abdominal organs, in order to confirm complete excision of the disease. RESULTS: Of the included 66 patients, 21 were considered eligible for LPC; the remaining 45 underwent APC. Optimal cytoreduction (i.e., RT = 0) was obtained in 95 and 88.4% in the LPC and APC groups, respectively. No intra-operative complication and 4 (19%) early post-operative complications were observed among patients who received LPC. Patients who underwent APC had 17.8 and 46.7% intra- and early post-operative complications, respectively. Median time to initiation of chemotherapy was 15 (range, 10-30) days in the LPC group and 28 (20-35) days in the APC group. After a median follow-up of 51 months, 2-year disease-free survival was 76.2% in the LPC group and 73.4% in the APC group. CONCLUSIONS: After strict selection, a group of patients with AOC may undergo LPC with extremely high rates of optimal cytoreduction, satisfactory perioperative morbidity, a short interval to chemotherapy, and encouraging survival outcomes. Clinical trial registration NCT02980185.

Quality control in ovarian cancer surgery.

The optimal surgical management of patients with ovarian cancer includes a thorough staging with peritoneal and retroperitoneal assessment for early disease stages and a complete debulking with the removal of all macroscopic tumor for advanced disease stages. Disparities across different institutions in terms of optimal surgical management have been described. Surgical quality control programs constitute a real possibility to ensure and improve the quality of the surgery performed. Guidelines for surgery in early and advanced disease stages have been recently reviewed by the National Comprehensive Cancer Network (NCCN), and several quality indicators (QIs) have been proposed. These QIs can be used as a powerful tool to monitor, compare, and improve the quality of surgery across different centers and institutions. Furthermore, a transparent report of surgical outcomes through the creation of National and International Networks, adherence to the NCCN guidelines, and the establishment of quality control programs with a strong training and education component are key factors in enhancing the quality of surgery for patients with ovarian cancer.

The Improvement of Laparoscopic Surgical Skills Obtained by Gynecologists after Ten Years of Clinical Training Can Reduce Peritoneal Adhesion Formation during Laparoscopic Myomectomy: A Retrospective Cohort Study.

OBJECTIVE: To evaluate if improvement of laparoscopic skills can reduce postoperative peritoneal adhesion formation in a clinical setting. STUDY DESIGN: We retrospectively evaluated 25 women who underwent laparoscopic myomectomy from January 1993 to June 1994 and 22 women who underwent laparoscopic myomectomy from March 2002 to November 2004. Women had one to four subserous/intramural myomas and received surgery without antiadhesive agents or barriers. Women underwent second-look laparoscopy for assessment of peritoneal adhesion formation 12 to 14 weeks after myomectomy. Adhesions were graded according to the Operative Laparoscopy Study Group scoring system. The main variable to be compared between the two cohorts was the proportion that showed no adhesions at second-look laparoscopy. RESULTS: Demographic and surgical characteristics were similar between the two cohorts. No complications were observed during surgery. No adverse events were recorded during postoperative course. At second-look laparoscopy, a higher proportion of adhesion-free patients was observed in women who underwent laparoscopic myomectomy from March 2002 to November 2004 (9 out of 22) compared with women who underwent the same surgery from January 1993 to June 1994 (3 out of 25). CONCLUSION: The improvement of surgeons' skills obtained after ten years of surgery can reduce postoperative adhesion formation.