Impact of adjuvant therapy on oncologic outcomes in uterine-confined clear cell carcinoma of the endometrium.

OBJECTIVES: To determine the impact of adjuvant therapy on oncologic outcomes in patients with 2009 International Federation of Gynecology and Obstetrics (FIGO) stage IA, IB, or II endometrial clear cell carcinoma (ECCC). METHODS: We conducted a retrospective review at 4 international institutions. Patients with newly diagnosed clinical stage I or II disease of either clear cell or mixed histology with a clear cell component treated between 01/01/2000-12/31/2015 were included. Oncologic outcomes were assessed for patients based on adjuvant treatment received, including chemotherapy, radiation, or chemotherapy with radiation. RESULTS: Of 125 patients identified and analyzed, 77 (61.6%) had clear cell histology and 118 (94.4%) had stage I disease. Median age at diagnosis was 65 years (range, 33-91). All patients underwent hysterectomy, bilateral salpingo-oophorectomy, and lymph node assessment. Twenty-five patients (20.0%) underwent surgical management alone and 100 (80.0%) received adjuvant therapy: 20 (16.0%) received postoperative chemotherapy, 47 (37.6%) received postoperative radiation, and 33 (26.4%) received postoperative chemotherapy with radiation. Median follow-up was 88.4 months (range, <1-234). Progression-free survival (PFS) or overall survival (OS) did not significantly differ between surgery alone and type of adjuvant therapy (P = 0.18 and P = 0.56, respectively). Patients with mixed ECCC did not have a survival advantage over those with pure ECCC (5-year PFS rate, 85.0% vs 82.7%, P = 0.77; 5-year OS rate, 88.3% vs 91.2%, P = 0.94). CONCLUSIONS: Receipt of adjuvant therapy in surgically staged I/II ECCC did not appear to offer a survival advantage over observation alone. Adjuvant therapy in early-stage ECCC with consideration of molecular classification should be evaluated.

Laparoscopy with or without robotic assistance does not negatively impact long-term oncologic outcomes in patients with uterine serous carcinoma.

OBJECTIVES: We sought to compare outcomes between minimally invasive surgery (MIS) and laparotomy in patients with clinical stage I uterine serous carcinoma (USC). METHODS: Patients who underwent surgery for newly diagnosed USC between 11/1/1993 and 12/31/2017 were retrospectively identified and assigned to either the MIS cohort or the laparotomy cohort. Patients with conversion to laparotomy were analyzed with the MIS cohort. Chi-square and Mann-Whitney tests were used to compare categorical and continuous variables, respectively. Kaplan-Meier curves were used to estimate survival and compared using the log-rank test. RESULTS: In total, 391 patients met inclusion criteria; 242 underwent MIS (35% non-robotic and 65% robotic-assisted laparoscopies) and 149 underwent laparotomy. Age, BMI, stage, and washings status did not differ between cohorts. Patients who underwent MIS were less likely to have lymphovascular space invasion (LVSI; 35.1% vs 48.3%), had fewer nodes removed (median, 9 vs 15), and lower rates of paraaortic nodal dissection (44.6% vs 65.1%). Rates of adjuvant therapy did not differ between cohorts. Median follow-up times were 63.0 months (MIS cohort) vs 71.0 months (laparotomy cohort; P = .04). Five-year PFS rates were 58.7% (MIS) vs 59.8% (laparotomy; P = .1). Five-year OS rates were 65.2% (MIS) compared to 63.5% (laparotomy; P = .2). On multivariable analysis, higher stage, deep myometrial invasion, and positive washings were associated with decreased PFS. Age ≥ 65 years, higher stage, LVSI, and positive washings were associated with shorter OS. CONCLUSIONS: MIS does not compromise outcomes in patients with newly diagnosed USC and should be offered to these patients to minimize surgical morbidity.

Clear Cell Ovarian Carcinoma With C1 Lateral Mass Metastasis and Pathologic Fracture: A Case Report.

Osseous metastasis (OM) in ovarian cancer (OC) are rare, with an incidence ranging from 0.8% to 2.6%, and are associated with poor prognosis. The available literature on their management and associated complications is scarce. We report a case of International Federation of Gynecology and Obstetrics (FIGO) stage IVB clear cell epithelial OC (EOC) who presented with neck pain. Imaging revealed multiple cervical spine metastases with left vertebral artery encasement and concurrent C1 lateral mass compression fracture, without neurological deficit, requiring occiput to C2 posterior instrumentation and fusion. Early OM may be associated with shorter overall survival, and survival after OM diagnosis is on the order of months. Management of OM should include a multidisciplinary team and may require surgical stabilization in addition to systemic chemotherapy, local radiotherapy, and osteoclast inhibitors.

Assessing the need for venous thromboembolism prophylaxis at the time of neoadjuvant chemotherapy for ovarian cancer: A literature review.

OBJECTIVE: Gynecologic cancers, especially ovarian cancer, are associated with a high incidence of venous thromboembolism (VTE). Recent data have shown the risk of VTE development is not only limited to the postoperative period; there also appears to be an increased risk during neoadjuvant chemotherapy (NACT) administration, prompting the need for better risk stratification in this setting. We sought to assess the risk of VTE development in patients with ovarian cancer undergoing NACT. METHODS: We performed a PubMed literature review using the following medical terms: advanced ovarian cancer, advanced peritoneal cancer, advanced fallopian tube cancer, thrombosis, thromboembolic events, and neoadjuvant chemotherapy. Eligible studies included patients with advanced ovarian, fallopian tube, or peritoneal cancer who underwent NACT and had VTE. VTE was defined as either a deep venous thrombosis or a pulmonary embolism. RESULTS: Seven relevant studies were identified; all 7 were published between 2017 and 2021. Across these studies, we identified 1427 patients who underwent NACT and either had VTE at presentation or developed VTE during their treatment course. Of these patients, 1171 underwent NACT and were at risk for VTE development and were included in our pooled analysis. Of these patients, 144 (12.3%) developed VTE. CONCLUSIONS: VTE prophylaxis may be considered in patients with ovarian cancer undergoing NACT.

Gastric-type adenocarcinoma of the cervix: Clinical outcomes and genomic drivers.

OBJECTIVES: Gastric-type endocervical adenocarcinoma (GEA) is a rare form of cervical cancer not associated with human papilloma virus (HPV) infection. We summarize our experience with GEA at a large cancer center. METHODS: Clinical and demographic information on all patients diagnosed with GEA between June 1, 2002 and July 1, 2019 was obtained retrospectively from clinical charts. Kaplan-Meier survival analysis was performed to describe progression-free survival (PFS) and overall survival (OS). Tumors from a subset of patients underwent next generation sequencing (NGS) analysis. RESULTS: A total of 70 women with GEA were identified, including 43 who received initial treatment at our institution: of these 4 (9%) underwent surgery alone, 15 (35%) underwent surgery followed by adjuvant therapy, 10 (23%) were treated with definitive concurrent chemoradiation (CCRT), 7 (16%) with chemotherapy alone, and 3 (7%) with neoadjuvant CCRT and hysterectomy with or without chemotherapy. One-third (n = 14) of patients experienced disease progression, of whom 86% (n = 12) had prior CCRT. The median PFS and OS for patients with stage I GEA were 107 months (95% CI 14.8-199.2 months) and 111 months (95% CI 17-205.1 months) respectively, compared to 17 months (95% CI 5.6-28.4 months) and 33 months (95% CI 28.2-37.8 months) for patients with stages II-IV, respectively. On NGS, 4 patients (14%) had ERBB2 alterations, including 2 patients who received trastuzumab. CONCLUSIONS: GEA is an aggressive form of cervical cancer with poor PFS and OS when diagnosed at stage II or later. Further investigation is needed to identify the optimal management approach for this rare subtype.

Safety and Efficacy of Supradiaphragmatic Lymph Node Dissection in Advanced Ovarian Cancer.

Objective: Postoperative gross residual disease after cytoreductive surgery for advanced ovarian cancer impacts patient survival negatively. Specifically, unresected enlarged, metastatic supradiaphragmatic lymph nodes (SDLNs) may worsen progression-free survival (PFS) and overall survival (OS). Multiple studies have shown that upper abdominal debulking during primary cytoreductive surgery improves survival outcomes, but the evidence for resection of SDLN metastasis is less definitive. This review focuses on the feasibility, safety, and efficacy of SDLN resection for metastatic disease in advanced-stage ovarian cancer and explores emerging data on survival outcomes. Materials and Methods: A literature review from January 2004 to December 2021 identified 4 relevant studies, all published after 2016. Eligible studies included patients with advanced ovarian, tubal, or peritoneal cancer who had undergone SDLN resection using a transdiaphragmatic approach or video-assisted thorascopy, and had evaluated SDLN dissection for diagnoses and treatment or assessed the benefits of SDLN resection as it relates to prognosis. Results: All 4 studies demonstrated the feasibility and safety of SDLN resection. Three of the studies reported a low intrathoracic recurrence rate after intrathoracic debulking. Cowan et al. described an impressive median PFS and OS of 17.2 months and 70.1 months, respectively, in patients who had undergone SDLN resection. Conclusions: Resection of enlarged SDLNs in carefully selected patients has the potential to confirm intrathoracic disease spread, help achieve maximal cytoreduction without delaying adjuvant treatment, and improve survival. More studies are needed to quantify the survival benefit of SDLN resection. (J GYNECOL SURG 38:202).

The accuracy and clinical impact of intraoperative frozen section in determining the extent of surgical intervention in patients with early stage endometrial cancer.

The aim of this study was to compare intraoperative frozen section (FS) with the final pathology (FP), and determine its clinical impact in clinically apparent early stage endometrial cancer (EC) at the American University of Beirut Medical Center (AUBMC). Data for patients 18 years or older, with clinically apparent early stage, grade 1 or 2, endometrioid EC, who underwent hysterectomy ± lymph node dissection (LND) at AUBMC between January 1st 1996 and June 30th 2016 were retrospectively reviewed. 70 patients were included. The overall concordance between FS and FP was 92.3% for histological subtype, 77% for tumour grade, 82% for Myometrial invasion (MI) and 100% for tumour size. At a median follow up of 30 months, 8 recurrences (11.4%) were noted, with a 5-year PFS and OS of 76 and 84% respectively, with a trend towards lower recurrence and improved survival in patients who underwent FS or LND.Impact statementWhat is already known on this subject? Hysterectomy and bilateral salpingo-oophorectomy is the standard surgery for stage I endometrial cancer (EC). Intraoperative frozen section (FS) facilitates the decision on performing lymph node dissection (LND). However, its accuracy and clinical impact have been questioned.What do the results of this study add? Our objective is to compare FS with the final pathology (FP), and determine its clinical impact in clinically apparent early stage EC at the American University of Beirut Medical Center (AUBMC). There is a lack of standardisation regarding FS use and reporting at AUBMC.What are the implications of these findings for clinical practice and/or further research? The strong correlation between FS and FP can serve as a tool to guide decision to perform LND in patients with apparent early stage disease, where use of sentinel LN biopsy technique is not available.

Gastric-type adenocarcinoma of the cervix in patients with Peutz-Jeghers syndrome: a systematic review of the literature with proposed screening guidelines.

OBJECTIVES: To perform a systematic review of gastric-type adenocarcinoma of the cervix and lobular endocervical glandular hyperplasia (a possible precursor lesion) in Peutz-Jeghers syndrome, and to analyze data from the literature, along with our institutional experience, to determine recommendations for screening and detection. METHODS: A comprehensive literature searc and retrospective search of pathology records at our institutio were conducted. Articles were screened by two independent reviewers. Case reports/series on lobular endocervical glandular hyperplasia/gastric-type adenocarcinoma of the cervix in Peutz-Jeghers syndrome were included. Demographic, clinical, and radiologic information was collected. RESULTS: A total of 1564 publications were reviewed; 38 met the inclusion criteria. Forty-nine were included in the analysis (43 from the literature, 6 from our institution). Forty-three reported on gastric-type adenocarcinoma alone, 4 on lobular endocervical glandular hyperplasia alone, and 2 on concurrent lobular endocervical glandular hyperplasia/gastric-type adenocarcinoma. Median age at diagnosis was 17 (range, 4-52) for patients with lobular endocervical glandular hyperplasia alone and 35 (range, 15-72) for those with gastric-type adenocarcinoma. The most common presenting symptoms were abdominal/pelvic pain and vaginal bleeding/discharge. Imaging was reported for 27 patients; 24 (89%) had abnormal cervical features. Papanicolaou (Pap) smear prior to diagnosis was reported for 12 patients; 6 (50%) had normal cytology, 4 (33%) atypical glandular cells, and 2 (17%) atypical cells not otherwise specified. Patients with gastric-type adenocarcinoma (n=45) were treated with surgery alone (n=16), surgery/chemotherapy/radiation (n=11), surgery/chemotherapy (n=9), surgery/radiation (n=5), or radiation/chemotherapy (n=4). Twelve (27%) of 45 patients recurred; median progression-free survival was 10 months (range, 1-148). Twenty patients (44%) died; median overall survival was 26 months (range, 2-156). Thirteen patients (27%) were alive with no evidence of disease. CONCLUSIONS: Gastric-type adenocarcinoma in Peutz-Jeghers syndrome is associated with poor outcomes and short progression-free and overall survival. Screening recommendations, including pathognomonic symptom review and physical examination, with a low threshold for imaging and biopsy, may detect precursor lesions and early-stage gastric-type adenocarcinoma, leading to better outcomes in this high-risk population. PROSPERO REGISTRATION NUMBER: CRD42019118151.

Risk of venous thromboembolism in ovarian cancer patients receiving neoadjuvant chemotherapy.

PURPOSE: To determine the incidence of venous thromboembolism (VTE) and define clinical risk factors associated with the development of new-onset VTE in patients receiving neoadjuvant chemotherapy (NACT) for ovarian cancer (OC). METHODS: An institutional ovarian cancer database was used to identify all OC patients receiving NACT from 04/2015-09/2018. VTE events were recorded and included clinically diagnosed deep venous thrombosis (DVT) and/or pulmonary embolism (PE). The incidence of VTE events was categorized according to treatment phases (P): P0) First visit/prior to induction of NACT; P1) during NACT before interval debulking surgery (IDS); P2) intraoperative through day 28 post-IDS; P3) during adjuvant chemotherapy. RESULTS: A total of 290 patients were identified during the study period. Seventy-five (25.9%) developed a VTE at some point from time of presentation through the peri-operative period. Forty (13.8%) presented with VTE prior to initiation of NACT. An additional 27 (11.6%) developed a VTE during NACT (P1); 6 (3.9%) during the intraoperative and 28-day post-operative period (P2); and 2 (1.3%) during the adjuvant period (P3). The overall VTE rate was 25.9% (n = 75). FIGO stage IV disease was the only factor associated with increased risk for a new-onset VTE [Odds Ratio (OR): 3.9 (95% Confidence Interval [CI] = 1.2-13.6; p = 0.03]. CONCLUSIONS: Patients receiving NACT for advanced OC are at extremely high risk for developing thromboembolic events, either at initial presentation or during induction of NACT, a treatment phase that is traditionally without use of prophylactic anticoagulation. Since Khorana scoring is not predictive in this population, clinicians might need to consider increased screening or use of prophylactic anticoagulation in patients receiving NACT for OC, particularly in advanced metastatic disease.

Case report: Sentinel lymph node mapping of endometrial carcinoma occurring in uterine didelphys.

•In a bleeding postmenopausal woman with didelphys uterus, endometrial biopsy should be taken from both uterine cavities.•Sentinel lymph node mapping has not been previously described in the setting of endometrial cancer and uterine didelphys.•Routine sentinel lymph node mapping was successfully performed in a patient with endometrial cancer and uterine didelphys.

Diaphragm hernia after debulking surgery in patients with ovarian cancer.

Over 80% of patients with epithelial ovarian cancer present with advanced disease, FIGO stage III or IV at the time of diagnosis. The majority require extensive upper abdominal surgery to obtain complete gross resection. This may include splenectomy, distal pancreatectomy, partial hepatectomy, cholecystectomy, and usually diaphragmatic peritonectomy or resection. Following surgery, diaphragmatic hernia-a very rare but serious complication-may occur. We describe four cases of left-sided diaphragmatic hernia resulting after debulking surgery, which included left diaphragm peritonectomy and splenectomy, in patients with advanced ovarian cancer. In association with the current shift towards more extensive debulking surgery for ovarian cancer, more patients may present with postoperative left-sided diaphragm hernia, making the prevention, diagnosis, and management of this complication important to practicing gynecologic oncologists. Intraoperatively the diaphragm should be checked thoroughly to rule out any defects, which should be closed. A diaphragmatic hernia may be easily misdiagnosed because the patient can present with various symptoms. While rare, these hernias require prompt identification, intervention and surgical correction to avoid serious complications.

Acute pericarditis after transabdominal cardiophrenic lymph node dissection and pericardotomy during ovarian cancer debulking surgery: A case report.

•Complete gross resection as part of debulking surgery is crucial in advanced ovarian cancer.•Supradiaphragmatic lymph node resection may prolong survival in patients with ovarian cancer.•We report acute pericarditis after supradiaphragmatic lymph node resection and pericardotomy.

Accuracy of Pelvic Ultrasound in Diagnosing Adnexal Torsion.

Ovarian/adnexal torsion is a rather frequent occurrence in women of reproductive age group worldwide. Etiologies are quite diverse with ovarian lesions and corpus luteal cysts being the most two common. Pelvic or intravaginal ultrasound remains the first-line imaging modality used for diagnosis and evaluation of suspected ovarian/adnexal torsion. In this study, we have adopted a case-based statistical analysis to identify important sonographic markers and further evaluated their contribution in identifying ovarian torsion. Our study successfully determined the important sonographic markers. Our observation and analysis suggest that ovarian enlargement is the most sensitive marker. Ovarian edema was found to be the most specific marker to identify the ovarian torsion with higher level of accuracy and confidence. This pioneer study will provide valuable information and direction to the medical practitioners and radiologists for better diagnosis. Further studies with large sample size will help in establishing our findings universally.