Mutations in cancer-relevant genes are ubiquitous in histologically normal endometrial tissue.

OBJECTIVE: Endometrial cancer (EndoCA) is the most common gynecologic cancer and incidence and mortality rate continue to increase. Despite well-characterized knowledge of EndoCA-defining mutations, no effective diagnostic or screening tests exist. To lay the foundation for testing development, our study focused on defining the prevalence of somatic mutations present in non-cancerous uterine tissue. METHODS: We obtained ≥8 uterine samplings, including separate endometrial and myometrial layers, from each of 22 women undergoing hysterectomy for non-cancer conditions. We ultra-deep sequenced (>2000× coverage) samples using a 125 cancer-relevant gene panel. RESULTS: All women harbored complex mutation patterns. In total, 308 somatic mutations were identified with mutant allele frequencies ranging up to 96.0%. These encompassed 56 unique mutations from 24 genes. The majority of samples possessed predicted functional cancer mutations but curiously no growth advantage over non-functional mutations was detected. Functional mutations were enriched with increasing patient age (p = 0.045) and BMI (p = 0.0007) and in endometrial versus myometrial layers (68% vs 39%, p = 0.0002). Finally, while the somatic mutation landscape shared similar mutation prevalence in key TCGA-defined EndoCA genes, notably PIK3CA, significant differences were identified, including NOTCH1 (77% vs 10%), PTEN (9% vs 61%), TP53 (0% vs 37%) and CTNNB1 (0% vs 26%). CONCLUSIONS: An important caveat for future liquid biopsy/DNA-based cancer diagnostics is the repertoire of shared and distinct mutation profiles between histologically unremarkable and EndoCA tissues. The lack of selection pressure between functional and non-functional mutations in histologically unremarkable uterine tissue may offer a glimpse into an unrecognized EndoCA protective mechanism.

vNOTES retroperitoneal sentinel lymph node dissection for endometrial cancer staging: First multicenter, prospective case series.

INTRODUCTION: The current standard treatment for endometrial cancer is a laparoscopic hysterectomy with adnexectomies and bilateral sentinel node resection. A retroperitoneal vNOTES sentinel node resection has several theoretical potential advantages. These include being less invasive, leaving no visible scars, operating without Trendelenburg, and therefore offering the anesthetic advantage of easier ventilation in obese patients and following the natural lymph node trajectory from caudally to cranially and therefore a lower risk of missing the sentinel node. The aim of this study is to determine the feasibility of a retroperitoneal vNOTES approach to sentinel lymph node dissection for staging of endometrial cancer. MATERIAL AND METHODS: A prospective multicenter case series was performed in four hospitals. A total of 64 women with early-stage endometrial carcinoma suitable for surgical staging with sentinel lymph node removal were operated via a transvaginal retroperitoneal vNOTES approach. The paravesical space was entered through a vaginal incision after injecting the cervix with indocyanine green. A vNOTES port was placed into this space and insufflation of the retroperitoneum was performed. Sentinel lymph nodes were identified bilaterally using near-infrared light followed by endoscopic removal of these nodes. RESULTS: A total of 64 women with early-stage endometrial cancer underwent sentinel lymph node removal by retroperitoneal vNOTES technique. All patients also underwent subsequent vNOTES hysterectomy and bilateral salpingo-oophorectomy. The median age was 69.5 years, median total operative time was 126 min and the median estimated blood loss was 80 mL. In 97% of the cases bilateral sentinel nodes could be identified. A total of 60 patients had negative sentinel nodes, three had isolated tumor cells and one had macroscopically positive sentinel nodes. No complications with sequel occurred. CONCLUSIONS: This prospective multicenter case series demonstrates the feasibility of the vNOTES approach for identifying and removing sentinel lymph nodes in women with endometrial carcinoma successfully and safely. vNOTES allows sole transvaginal access with exposure of the entire retroperitoneal space, following the natural lymph trajectory caudally to cranially, and without the need for a Trendelenburg position.

High-intensity focused ultrasound treatment for large and small solitary uterine fibroids.

This retrospective study used data from patients treated for uterine fibroids with ultrasound-guided high-intensity focused ultrasound (USgHIFU) from April 2015 to April 2019. One hundred and seven patients with solitary fibroids were divided into two groups: (1) the L group with larger fibroids (≥10 cm) and (2) the S group with smaller fibroids (<10 cm). Using magnetic resonance imaging (MRI), we examined the efficacy of high-intensity focused ultrasound (HIFU) ablation by comparing uterine and fibroid volumes before and three months after the procedure. The three-month follow-up clinical visit used a visual analog scale and a uterine fibroid symptom health-related quality of life questionnaire to evaluate clinical symptoms. Both the L and S groups had significant reduction in uterine and fibroid volumes, but the rate was significantly higher in the S group (p < 0.05). Both groups also had improvements in clinical symptoms, but there was no statistical difference. USgHIFU reduced the size of both large and small fibroids but was most effective on fibroids smaller than 10 cm. Both the L and S groups had improved dysmenorrhea symptoms and quality of life.

Copenhagen Index versus ROMA in preoperative ovarian malignancy risk stratification: Result from the first Vietnamese prospective cohort study.

OBJECTIVES: This study aimed to evaluate the diagnostic performances of the Copenhagen Index (CPH-I) and Risk of Ovarian Malignancy Algorithm (ROMA) in the preoperative prediction of ovarian cancer. METHODS: In a prospective cohort study, data were collected from 475 patients with ovarian masses diagnosed by gynecologic examination / ultrasound who were hospitalized at the Departments of Obstetrics and Gynecology, Hue University of Medicine and Pharmacy Hospital and Hue Central Hospital, Vietnam, between January 2018 and June 2020. ROMA and CPH-I were calculated based on measurements of serum carbohydrate antigen (CA-125) and human epididymis protein (HE4). The final diagnosis was based on clinical features, radiologic and histologic findings, and the International Federation of Gynecology and Obstetrics (FIGO) 2014 stages of ovarian cancer were recorded. Matching the values of ROMA and CPH-I to postoperative histopathology reports resulted in the preoperative prediction values. RESULTS: Among the 475 women, 408 had benign tumors, 5 had borderline tumors and 62 had malignant tumors. The two indices showed similar discriminatory performances with no significant differences (p > 0.05). At an optimal cut-off, the sensitivities/specificities of ROMA and CPH-I for ovarian cancer diagnosis were 74.2% and 91.8%, 87.1% and 78.5%, respectively. The optimal cut-off for CPH-I was 1.89%. The areas under the ROC curves (AUCs) of ROMA and CPH-I were 0.882 (95% CI: 0.849-0.909) and 0.898 (95% CI: 0.867-0.924), respectively. CONCLUSIONS: The introduction of the Copenhagen Index to help stratify the malignancy risk of ovarian tumors, irrespective of menopausal status, might be applied as a simple alternative with a similar efficacy to ROMA in clinical practice.

Initial review of pregnancy and neonatal outcomes of pregnant women with COVID-19 infection.

OBJECTIVES: Data regarding the pathogenesis and clinical manifestations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue to emerge, however, there's limited data in regard to maternal and neonatal outcomes. Therefore, we conducted a retrospective analysis of all pregnant women who tested positive for SARS-CoV-2 within Nuvance Health system. METHODS: Data were abstracted from the medical records of each patient and descriptive analysis was performed. Variables included demographics, COVID testing results, symptoms, management, labor course, neonatal information, and complications. RESULTS: Total of 40 patients were identified. Average age was 29.6 years old, 35% were Hispanic, and approximately one in three patients had comorbidities. Of the patients who had repeated testing, the average number of days between first positive test and negative test was 36.8 days (± 19.9 days). Three out of four women reported symptoms. Of the 40 pregnant women who were positive for SARS-CoV-2, 25 of them delivered. About 84% of the women delivered after 37 weeks. Twelve percent of the women delivered under 33 and 6/7 weeks. Most patients had vaginal deliveries (68%) and the remaining had cesarean deliveries. Neonatal outcomes included: mean 1 and 5 min Apgar scores of 8 and 8.8, respectively and the mean birth weight was 3212 g. Twenty neonates were tested for SARS-CoV-2 and were all found to be negative. CONCLUSIONS: Overall, with routine prenatal care and preventive measures, pregnant patients and neonates in our study had good outcomes. At this time, there appears to be no evidence of vertical transmission.

Monolithically integrated L-band PICs and transceiver modules with 6λ x 200 Gbps (1.2 Tbps) for C + L band communication systems.

We present monolithically integrated multi-channel coherent L-band transmitter (Tx) and receiver (Rx) photonic integrated circuits (PICs) on InP substrates. The L-band PICs are able to provide post-forward error correction (FEC), error-free operation for dual-polarization (DP) 16-QAM coherent transmission at 33 Gbaud. These transceivers operate at 200 Gbps per channel and support 1.2 Tbps aggregate capacity per 6 channel PIC. We also demonstrate in this work a C + L band communication system with two C-band superchannels (2 x 6λ) and three L-band superchannels (3 x 6λ) over a 600 km link. The received signals all have Q > 7.7 dB, which is well above the error-free threshold of the FEC used in this work.

Cervical cancer: A global health crisis.

Cervical cancer is the fourth most common malignancy diagnosed in women worldwide. Nearly all cases of cervical cancer result from infection with the human papillomavirus, and the prevention of cervical cancer includes screening and vaccination. Primary treatment options for patients with cervical cancer may include surgery or a concurrent chemoradiotherapy regimen consisting of cisplatin-based chemotherapy with external beam radiotherapy and brachytherapy. Cervical cancer causes more than one quarter of a million deaths per year as a result of grossly deficient treatments in many developing countries. This warrants a concerted global effort to counter the shocking loss of life and suffering that largely goes unreported. This article provides a review of the biology, prevention, and treatment of cervical cancer, and discusses the global cervical cancer crisis and efforts to improve the prevention and treatment of the disease in underdeveloped countries. Cancer 2017;123:2404-12. © 2017 American Cancer Society.

Cancer and the world's poor: What's a gynecologic cancer specialist to do?

Women in low- and middle-income countries (LMICs) face a drastically increased burden of cervical cancer and the same burden of other gynecologic cancers as do women in high-income countries, yet there are few resources or specialists to meet their needs. 85% of deaths from cervical cancer occur in LMICs. As the population of these regions age, and as death from infectious diseases decrease, this burden will increase further without strong intervention. There are few cancer specialists in LMICs and training in gynecologic cancer care is rare. Gynecologic cancer specialists are uniquely positioned to meet this challenge as advocates, educators and experts. On behalf of the SGO International Committee, we call on our colleagues to meet this historic challenge.

Sister Society Meeting on Global Education Development and Collaboration: Meeting Report.

OBJECTIVES: To identify common barriers to teaching and training and to identify strategies that would be useful in developing future training programs in gynecologic oncology in low- and middle- income countries. METHODS: There is a lack of overall strategy to meet the needs of education and training in gynecologic oncology in low- and middle- income countries, the leaderships of sister societies and global health volunteers met at the European Society of Gynecologic Oncology in October 23, 2015. The challenges of the training programs supported by gynecologic oncology societies, major universities and individual efforts were presented and discussed. Strategies to improve education and training were identified. RESULTS: Major challenges include language barriers, limited surgical equipment, inadequate internet access, lack of local support for sustainability in training programs, inadequate pathology and radiation oncology, finance and a global deficiency in identifying sites and personnel in partnering or developing training programs. The leaderships identified various key components including consultation with the local Ministry of Health, local educational institutions; inclusion of the program into existing local programs, a needs assessment, and the development of curriculum and regional centers of excellence. CONCLUSIONS: Proper preparation of training sites and trainers, the development of global curriculum, the establishment of centers of excellence, and the ability to measure outcomes are important to improve education and training in gynecologic oncology in low- and middle- income countries.

Laparoscopic Removal of Streak Gonads in Turner Syndrome.

STUDY OBJECTIVE: To demonstrate the skills necessary for complete resection of bilateral streak gonads in Turner syndrome. DESIGN: Video case presentation with narration highlighting the key techniques used. The video was deemed exempt from formal review by our institutional review board. SETTING: Turner syndrome is a form of gonadal dysgenesis that affects 1 in 2500 live births. Patients often have streak gonads and may present with primary amenorrhea or premature ovarian failure. Patients with a mosaic karyotype that includes a Y chromosome are at increased risk for gonadoblastoma and subsequent transformation into malignancy. Gonadectomy is recommended for these patients, typically at adolescence. Streak gonads can be difficult to identify, and tissue margins are often in close proximity to critical retroperitoneal structures. Resection can be technically challenging and requires a thorough understanding of retroperitoneal anatomy and precise dissection techniques to ensure complete removal. INTERVENTIONS: Laparoscopic approach to bilateral salpingo-oophorectomy of streak gonads. Retroperitoneal dissection and ureterolysis are performed, with the aid of the Ethicon Harmonic Ace, to ensure complete gonadectomy. CONCLUSION: Careful and complete resection of gonadal tissue in the hands of a skilled laparoscopic surgeon is key for effective cancer risk reduction surgery in Turner syndrome mosaics.

Use of TachoSil® to Prevent Symptomatic Lymphocele after an Aggressive Tumor Debulking with Lymphadenectomy for Advanced Stage Ovarian Cancer. A Pilot Study.

OBJECTIVE: To describe the incidence of symptomatic lymphocele (SLC) after an aggressive tumor debulking surgery and lymphadenectomy in patients with ovarian cancer and peritoneal carcinomatosis with or without TachoSil®. MATERIAL AND METHODS: A pilot retrospective comparative observational study was performed between patients with advanced ovarian cancer International Federation of Gynecology and Obstetrics stages III-IV who underwent complete debulking surgery and radical retroperitoneal lymphadenectomy. In 18 patients, 4 TachoSil® patches were placed in the retroperitoneal area, since January 2014-October 2014. This group was compared with other 18 consecutive patients matched by age, International Federation of Gynecology and Obstetrics stage, surgical complexity, American Society of Anesthesiologists score, comorbidity, and BMI without the use of TachoSil®. RESULTS: Baseline characteristics were similar between groups. There were no statistically significant differences in terms of surgical complexity, surgical time, estimated blood loss, node removed, length of hospital stay, and complications between groups. SLC was diagnosed in 7 patients (38.8%) without TachoSil®, and in 2 patients (11.1%) with TachoSil® (p = 0.121). The use of TachoSil® was associated with a statistically significant lower re-admission rate (p = 0.041) and with a significantly shorter time to adjuvant chemotherapy (p = 0.02). CONCLUSIONS: Using TachoSil® in women with advanced stage ovarian cancer who underwent radical debulking with retroperitoneal lymph node dissection is associated with a non-statistically significant reduction in the incidence of SLC. A larger-scale randomized controlled study should be conducted to confirm our preliminary results.

Surgical outcomes and complications of prophylactic salpingectomy at the time of benign hysterectomy in premenopausal women.

STUDY OBJECTIVE: To compare the surgical outcome and short-term postoperative complications in premenopausal women who had undergone hysterectomies for benign indication with or without prophylactic bilateral salpingectomy. DESIGN: A cohort of consecutive women who had undergone hysterectomy plus bilateral salpingectomy between May 2012 and July 2014 (group A) were compared with the same number of consecutive premenopausal patients who had undergone simple hysterectomy operated on before May 2012 (group B). Inclusion criteria included premenopausal women and benign indication for surgery (Canadian Task Force classification III). SETTING: tertiary care hospital. INTERVENTION: Salpingectomy versus no salpingectomy at the time of benign hysterectomy. MEASUREMENTS AND MAIN RESULTS: A total of 97 and 71 patients were included in groups A and B, respectively. No differences between the 2 groups were observed regarding patient characteristics. The average operative time, estimated blood loss, uterine size, and intraoperative complications were similar between groups. The mean (standard deviation) length of hospitalization time was 43.7 (22.4) hours in group A and 53.9 (83.5) hours in group B (p = .008). There were no significant differences in terms of the incidence of postoperative complications, emergency visits after readmission, and hospital readmission between both groups of patients. CONCLUSION: Prophylactic salpingectomy at the time of benign hysterectomy in premenopausal women is safe and feasible and does not worsen surgical outcomes or the incidence of intraoperative and postoperative complications.

Survival analysis of robotic versus traditional laparoscopic surgical staging for endometrial cancer.

OBJECTIVE: The purpose of this study was to compare the survival of women with endometrial cancer managed by robotic- and laparoscopic-assisted surgery. STUDY DESIGN: This was a retrospective study conducted at 2 academic centers. Primary outcomes were overall survival, disease-free survival (DFS), and disease recurrence. RESULTS: From 2003 through 2010, 415 women met the study criteria. A total of 183 women had robotic and 232 women had laparoscopic-assisted surgery. Both groups were comparable in age, body mass index, comorbid conditions, histology, surgical stage, tumor grade, total nodes retrieved, and adjuvant therapy. With a median follow-up of 38 months (range, 4-61 months) for the robotic and 58 months (range, 4-118 months) for the traditional laparoscopic group, there were no significant differences in survival (3-year survival 93.3% and 93.6%), DFS (3-year DFS 83.3% and 88.4%), and tumor recurrence (14.8% and 12.1%) for robotic and laparoscopic groups, respectively. Univariate and multivariate analysis showed that surgery is not an independent prognostic factor of survival. CONCLUSION: Robotic-assisted surgery yields equivalent oncologic outcomes when compared to traditional laparoscopic surgery for endometrial adenocarcinoma.

Quality of life and sexual function of patients following radical hysterectomy and vaginal extension.

INTRODUCTION: Radical hysterectomy (RH) has negative consequences on sexual function due to a shortened vagina, vaginal dryness, and dyspareunia. Peritoneovaginoplasty aims to extend vagina by vesical peritoneum and anterior rectal wall to improve postoperative sexual function. AIM: The aim of this study was to investigate whether vaginal extension can improve sexual function and quality of life and the problem of sexual dysfunction in early-stage cervical cancer survivors (CCSs) in China. METHODS: Case-control and questionnaire-based methods were employed. Thirty-one patients who had undergone vaginal extension following RH and 28 patients with matching factors after RH alone were enrolled in the study. MAIN OUTCOME MEASURES: Both groups were assessed retrospectively by questionnaires at least 6 months after treatment. The European Organization for Research and Treatment of Cancer Quality-of-Life questionnaire cervical cancer module and the Sexual Function Vaginal Changes Questionnaire are validated measurements for disease- and treatment-specific issues. RESULTS: Vaginal length was 10.03 ± 1.26 cm and 5.92 ± 1.05 cm in study and control group, respectively (P < 0.05). In the study group, 67.7% patients and 64.3% of control group resumed sexual activity at the time of interview, averaging 6 months between treatment and sexual activity. While difficulty emptying bladder, incomplete emptying, and constipation were the most commonly reported symptoms, no significant difference was observed regarding pelvic floor symptoms. Reduced vagina size and shortened vagina was significantly more prominent in the control group, whereas both group presented with hypoactive sexual desire (88.1%), orgasm dysfunction (71.8%), and low enjoyment or relaxation after sex (51.3%). CONCLUSION: Shortened vagina was significantly less reported in study group, while no difference was observed in other sex-related dimensions. Vaginal extension does not worsen pelvic floor symptoms. Sexual rehabilitation interventions are of significance and should be paid more attention to the CCSs in China.

Primary malignant melanoma of the vagina: a retrospective clinicopathologic study of 44 cases.

OBJECTIVE: This study aimed to identify prognostic factors of survival and improve treatment strategies in women diagnosed with primary malignant melanoma of the vagina. METHODS: Between December 2002 and August 2011, 44 patients with lesions confined to the vagina and diagnosed with melanoma at Fudan University Shanghai Cancer Center were evaluated retrospectively. Prognostic factors were analyzed by Kaplan-Meier method. RESULTS: With a median follow-up time of 18.9 months (range, 6.0-94.3 months), 30 (68.2%) patients developed recurrences, whereas 21 (47.7%) died of disease. Median progression-free survival (PFS) was 14.4 months and median overall survival (OS) was 39.5 months. Depth of invasion (DOI) was significantly associated with OS (P = 0.023), and there was an obvious tendency toward improved OS with a negative lymph node status (P = 0.063). The DOI was significantly associated with lymph node status (P = 0.047). The extent of surgery (wide local excision vs radical excision) was not associated with differences in PFS or OS (P = 0.573 and P = 0.842, respectively). Longer PFS was observed in patients who received adjuvant chemotherapy and radiotherapy (P = 0.038). CONCLUSIONS: The prognosis of primary vaginal melanoma is dependent on the DOI and lymph node status in our study. Surgical resection of disease, especially wide local excision, should be considered as the optimal treatment when complete removal of tumor with a negative margin is possible. Adjuvant therapy may be associated with a longer PFS.

The role of liver resection at the time of secondary cytoreduction in patients with recurrent ovarian cancer.

OBJECTIVE: The aim of this study is to determine the role of liver metastatectomy in the morbidity and survival of patients with recurrent ovarian carcinoma. METHODS: We retrospectively reviewed the records of all patients who had undergone hepatic resection for liver metastases from ovarian carcinoma at the time of cytoreductive surgery at our institution from 1988 to 2012. The Kaplan-Meier method was used for survival analysis. A total of 76 patients met the inclusion criteria and had undergone liver resection as part of cytoreductive surgery for ovarian carcinoma during the study period. Of these 76 patients, 27 underwent liver resection at the time of secondary cytoreduction, and these patients that are the focus of this analysis. RESULTS: Median overall survival for the study group from the time of diagnosis to the last follow-up or death was 56 months (range, 12-249 months). Twenty died of the disease with an overall median survival of 12 months from the time of the liver resection (2-190 months), and 7 patients were alive with the disease at the time of the last follow-up. Based on Kaplan-Meier survival analysis, the factors associated with the longest survival after the liver resection (2-190 months) were the interval from the primary surgery of less than 24 months versus more than 24 months (P = 0.044) and secondary cytoreduction to residual disease of less than 1 cm (P = 0.014). CONCLUSIONS: Based on our analysis of a single institution's series of ovarian cancer patients with hepatic metastasis, liver resection is feasible and safe and should be considered as an option in selected patients at the time of secondary cytoreduction.

ACR Appropriateness Criteria® Pretreatment Evaluation and Follow-Up of Invasive Cancer of the Cervix: 2023 Update.

Cervical cancer is a common gynecological malignancy worldwide. Cervical cancer is staged based on the International Federation of Gynecology and Obstetrics (FIGO) classification system, which was revised in 2018 to incorporate radiologic and pathologic data. Imaging plays an important role in pretreatment assessment including initial staging and treatment response assessment of cervical cancer. Accurate determination of tumor size, local extension, and nodal and distant metastases is important for treatment selection and for prognostication. Although local recurrence can be diagnosed by physical examination, imaging plays a critical role in detection and follow-up of local and distant recurrence and subsequent treatment selection. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.