Critical Analysis of Stage IV Epithelial Ovarian Cancer Patients after Treatment with Neoadjuvant Chemotherapy followed by Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (CRS/HIPEC).

BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) after neoadjuvant chemotherapy (NACT) showed promise as initial treatment for stage IIIC (SIII) epithelial ovarian cancer (EOC); however, stage IV (SIV) outcomes are rarely reported. We assessed our experience and outcomes treating newly diagnosed SIV EOC with NACT plus CRS/HIPEC compared to SIII patients. METHODS: Advanced EOC from 2015-2018 managed with NACT (carboplatin/paclitaxel) due to unresectable disease or poor performance status followed by interval CRS/HIPEC were reviewed. Perioperative factors were assessed. Overall survival (OS) and progression-free survival (PFS) were analyzed by stage. RESULTS: Twenty-seven FIGO stage IIIC (n = 12) and IV (n = 15) patients were reviewed. Median NACT cycles were 3 and 4, respectively. Post-NACT omental caking, ascites, and pleural effusions decreased/resolved in 91%, 91%, and 100% of SIII and 85%, 92%, and 71% of SIV. SIII/SIV median PCI was 21 and 20 obtaining 92% and 100% complete cytoreduction (≤0.25 cm), respectively. Median organ resections were 6 and 7, respectively. Grade III/IV surgical complications were 0% SIII and 23% SIV, without hospital mortality. Median time to adjuvant chemotherapy was 53 and 74 days, respectively (p=0.007). SIII OS at 1 and 2 years was 100% and 83% and 87% and 76% in SIV (p=0.269). SIII 1-year PFS was 54%; median PFS: 12 months. SIV 1- and 2- year PFS was 47% and 23%; median PFS: 12 months (p=0.944). CONCLUSION: Outcomes in select initially diagnosed and unresectable SIV EOC are similar to SIII after NACT plus CRS/HIPEC. SIV EOC may benefit from CRS/HIPEC, and further studies should explore this treatment approach.

Efficacy of Hyperthermic Intraperitoneal Chemotherapy and Cytoreductive Surgery in the Treatment of Recurrent Uterine Sarcoma.

OBJECTIVE: Uterine sarcomas (USs) are characterized by poor response to systemic chemotherapy and high recurrence rates. This study evaluates whether the use of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) confers survival benefit in comparison with conventional treatment modalities in patients with recurrent US. METHODS/MATERIALS: A retrospective analysis of patients with recurrent US at a single institution for an 11-year study period was performed. All women with a pathologic diagnosis of leiomyosarcoma, adenosarcoma, endometrial stromal sarcoma, or undifferentiated US were identified. Overall and disease-free survival was estimated using Kaplan-Meier method. Comparisons between the study groups were performed with the log-rank test and Cox regression. RESULTS: A total of 26 patients were identified. Five patients received chemotherapy and/or radiotherapy without surgical intervention, 14 patients underwent surgery alone or a combination of surgery and adjuvant systemic chemotherapy, and 7 patients received cytoreductive surgery with HIPEC. There was no treatment-related mortality in any group, and only 1 patient had grade III-IV surgical complications. Median disease-free survival was 2.4 months for patients with nonsurgical treatments, 5.3 months for patients treated with conventional surgery, and 11.3 months for patients treated with HIPEC. Median overall survival was 35.9 months for patients treated with conventional surgery and 43.8 months for patients treated with HIPEC. CONCLUSIONS: Our study is the first to compare survival outcomes of HIPEC versus conventional therapies for recurrent US and is suggestive of treatment benefit. Further studies with more patients and longer follow-up to evaluate the role of HIPEC in management of this disease are warranted.

Multi-institutional study of peritoneal sarcomatosis from uterine sarcoma treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

OBJECTIVE: Uterine sarcoma (US) is a rare tumor representing 1% of female genital tract malignancies. Peritoneal sarcomatosis (PS) after US, diminishes median overall survival (OS) and progression-free survival (PFS) with cytoreductive surgery (CRS) alone, with or without systemic chemotherapy is <1 year and 6 months, respectively. A multi-institutional review of PS from US was conducted to evaluate CRS and hyperthermic intraperitoneal chemotherapy (HIPEC) and effects on survival outcomes. METHODS: A retrospective review of 36 patients from 7 specialized international centers was performed. Selection criteria included PS of uterine origin with CRS/HIPEC treatment. Clinical data were analyzed. OS and PFS were estimated with Kaplan-Meier method. RESULTS: Thirty-six patients underwent a total 38 HIPEC procedures performed from 2005 to 2014; 35 previous treatment and 1 primary treatment. Twenty-nine (81%) LMS patients, 3 (8%) endometrial stromal sarcoma (ESS), 3 (8%) adeneosarcoma (AS), and 1 (3%) categorized as other. Median PCI was 16 (range: 2-39), 10 patients had PCI ≥20. Thirty-four patients (94%) had complete cytoreduction (CC 0-1), 19 patients recurred. CRS/HIPEC OS at 1, 3, and 5-years was 75%, 53%, and 32% respectively, with median OS of 37 months (CI 95%: 20-54). PFS in 32 patients with CC at 1, 3, and 5-years was 67%, 32% and 32%, respectively with median PFS of 18.9 months (CI 95%: 6.7-31). CONCLUSIONS: CRS/HIPEC is a promising treatment modality for patients with PS. Histological subtype may influence survival. A global prospective registry of patients to further assess the efficacy of CRS/HIPEC is needed.

The importance of social support for women with elevated anxiety undergoing care for gynecologic malignancies.

OBJECTIVES: The aim of this study was to screen for depression and anxiety and to assess well-being among women diagnosed with gynecologic malignancies, identify factors associated with elevated depressive or anxiety symptoms, and further characterize the needs of those with elevated anxiety or depressive symptoms. METHODS/MATERIALS: Women presenting for gynecologic cancer at an academic center during the course of 10 months were offered screening for depressive and anxiety symptoms. Patients were screened with the Primary Care Evaluation of Mental Disorders' Patient Health Questionnaire-9 and the Generalized Anxiety Disorder-7. The Functional Assessment of Cancer Therapy-General assessed well-being. Demographics, psychiatric history, and components about the cancer and treatment were collected. Those who screened positive with scores of 10 or higher on the Patient Health Questionnaire-9 or the Generalized Anxiety Disorder-7 were offered a meeting with the study psychiatrist for further evaluation both with the Structured Clinical Interview for Diagnosis as well as with an interview to discuss their experiences and to assess their desired needs. RESULTS: When family and social well-being was added to the logistic regression model, higher family and social well-being was the strongest factor associated with lower amounts of anxiety (odds ratio, 0.10; P = 0.001 for a cutoff of 10; odds ratio, 0.21; P = 0.012 for a cutoff of 8). Less than 30% who screened positive met with the study psychiatrist and were not receiving optimal treatment. CONCLUSIONS: Given that low family and social well-being and elevated anxiety symptoms were so highly correlated, those with anxiety symptoms would most benefit from social interventions. However, this study also found that patients with elevated depressive or anxiety symptoms were difficult to engage with a psychiatric provider. We need partnership between psychiatry and gynecology oncology to identify those with elevated depressive and anxiety symptoms and develop better ways to provide psychosocial supports.

Pathologic features associated with resolution of complex atypical hyperplasia and grade 1 endometrial adenocarcinoma after progestin therapy.

OBJECTIVE: To determine the response of complex atypical hyperplasia (CAH) and well differentiated endometrioid adenocarcinoma of the uterus (WDC) to progestin therapy and whether pre-treatment estrogen and progesterone receptor status predicts outcome. METHODS: We performed a retrospective review encompassing women treated with progestin therapy for CAH or WDC at two institutions. Clinicopathologic, treatment, and recurrence data were recorded. Pre/post-treatment pathologic evaluation was performed. SAS 9.2 was used for statistical analyses. RESULTS: Forty-six patients were included. The median age was 35, and median BMI was 36.9. Thirty-seven percent were diagnosed with CAH and 63% had WDC. Megestrol acetate was the most commonly used agent (89%); 24% received multiple progestin therapies. Median treatment length was 6 months (range, 1-84); 36% of the patients underwent eventual hysterectomy, and 17.4% had carcinoma in their uterine specimens (8 primary endometrial, 1 primary ovarian). After a median follow-up of 35 months (range, 2-162), 65% experienced a complete response (CR), 28% had persistent or progressive disease, and 23% had a CR followed by recurrence. On univariate analysis, decreased post-treatment glandular cellularity (p = 0.0006), absence of post-treatment mitotic figures (p = 0.0008), and use of multiple progestin agents (p = 0.025) were associated with CR; however, only decreased glandular cellularity was significant on multivariate analysis (p = 0.007). Estrogen and progesterone receptor expression was not associated with treatment response. CONCLUSION: In women with CAH or WDC, the overall response rate to progestin therapy was 65%; pre-treatment estrogen/progesterone receptor status did not predict response to treatment.

Dedifferentiated endometrioid adenocarcinoma: An under-recognized but aggressive tumor?

•Dedifferentiated endometrioid adenocarcinoma is characterized by the coexistence of an undifferentiated carcinoma and a low-grade endometrioid adenocarcinoma.•Given its histological appearance, this tumor can be mistaken for other less aggressive tumors.•The possibility of undifferentiated carcinoma should be considered in endometrioid carcinoma with patterns of solid growth without appreciable glandular differentiation.

Primary uterine cancer in Maryland: impact of distance on access to surgical care at high-volume hospitals.

OBJECTIVE: To evaluate the influence of distance on access to high-volume surgical treatment for patients with uterine cancer in Maryland. METHODS: The Maryland Health Services Cost Review Commission database was retrospectively searched to identify primary uterine cancer surgical cases from 1994 to 2010. Race, type of insurance, year of surgery, community setting, and both surgeon and hospital volume were collected. Geographical coordinates of hospital and patient's zip code were used to calculate primary independent outcomes of distance traveled and distance from nearest high-volume hospital (HVH). Logistic regression was used to calculate odds ratios and confidence intervals. RESULTS: From 1994 to 2010, 8529 women underwent primary surgical management of uterine cancer in Maryland. Multivariable analysis demonstrated white race, rural residence, surgery by a high-volume surgeon and surgery from 2003 to 2010 to be associated with both travel 50 miles or more to the treating hospital and residence 50 miles or more from the nearest HVH (all P < 0.05). Patients who travel 50 miles or more to the treating hospital are more likely to have surgery at a HVH (odds ratio, 6.03; 95% confidence interval, 4.67-7.79) In contrast, patients, who reside ≥50 miles from a HVH, are less likely to have their surgery at an HVH. (odds ratio, 0.37; 95% confidence interval, 0.32-0.42). CONCLUSION: In Maryland, 50 miles or more from residence to the nearest HVH is a barrier to high-volume care. However, patients who travel 50 miles or more seem to do so to receive care by a high-volume surgeon at an HVH. In Maryland, Nonwhites are more likely to live closer to an HVH and more likely to use these services.

Outcomes in Ovarian Cancer among Hispanic Women Living in the United States: A Population-Based Analysis.

Introduction. Ovarian cancer is the deadliest gynecologic cancer in the United States. There is limited data on presentation and outcomes among Hispanic women with ovarian cancer. Objective. To investigate how ovarian cancer presents among Hispanic women in the USA and to analyze differences in presentation, staging, and survival between Hispanic and non-Hispanic women with ovarian cancer. Methods. Data from January 1, 2000 to December 31, 2004 were extracted from the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) database. Results. The study sample comprised 1215 Hispanics (10%), 10 652 non-Hispanic whites (83%), and 905 non-Hispanic blacks (7%). Hispanic women were diagnosed with ovarian cancer at a younger age and earlier stage when compared to non-Hispanic whites, non-Hispanic blacks; P < 0.001. Similar proportion of Hispanics (33%), non-Hispanic whites (32%), and non-Hispanic blacks (24%) underwent lymphadenectomy; P < 0.001. Hispanics with epithelial ovarian cancer histology had longer five-year survival of 30.6 months compared to non-Hispanic whites (22.8 months) and non-Hispanic blacks (23.3 months); P = 0.001. Conclusion. Hispanic women with ovarian cancer have a statistically significantly longer median survival compared to whites and blacks. This survival difference was most apparent in patients with epithelial cancers and patients with stage IV disease.

Perioperative care in gynecologic oncology.

PURPOSE OF REVIEW: To review perioperative care in gynecologic oncology with special emphasis on areas of controversy. RECENT FINDINGS: Major gynecologic surgery still represents the cornerstone of management among women diagnosed with gynecologic malignancies. The implementation of clinical guidelines can significantly impact perioperative morbidity and mortality. Preoperative evaluation and preparation allows the surgeon to identify patient risks and develop risk factor modification strategies decreasing delays in preparation and cost and improving patient safety. Preoperative areas of controversy include preoperative testing and evaluation, use of mechanical bowel preparation, prophylactic antibiotics, and use of anticoagulants, and the timing of postoperative feeding. SUMMARY: In healthy women undergoing gynecologic cancer surgery preoperative evaluation requirements will be minimal. For women with extensive comorbid conditions a more detailed evaluation will be required to decrease perioperative morbidity and mortality. Mechanical bowel preparations should not be required preoperatively. Preoperative administration of antibiotics and anticoagulants should be provided to all patients undergoing major gynecologic cancer surgery.

Importance and timing of end-of-life care discussions among gynecologic oncology patients.

OBJECTIVES: To assess the importance and desired timing of end-of-life care (EOLC) discussions among women with gynecologic cancer. METHODS: A questionnaire related to EOLC issues was distributed to patients with gynecologic cancer. Answers were analyzed via SPSS using descriptive statistics. Contingency analysis was done to evaluate for differences among disease status and age regarding preferences for timing of discussions. RESULTS: Patients expressed that addressing EOLC is an important part of their treatment. Most patients were familiar with advanced directives (73.0%), do not resuscitate/do not intubate (88.5%), and hospice (97.5%). Designating someone to make decisions was significantly related to disease status (P = .03) and age (P = 0.02). CONCLUSIONS: Patients are familiar with basic EOLC with optimal timing for discussions at disease progression or when treatment is no longer available.

Introduction of checklists at daily progress notes improves patient care among the gynecological oncology service.

OBJECTIVES: To evaluate the impact of the introduction of checklists at the daily progress note to improve patient care among gynecologic oncology patients. METHODS: A progress note incorporating checklists that were pertinent for our patient population was developed with input obtained from all staff involved on patients care. The form was approved by the hospital. The average length of stay, compliance with prophylactic guidelines (anticoagulation, peptic ulcer disease), reason for admission, and readmission rate were compared among the preimplementation and postimplementation periods. RESULTS: A total of 492 discharge summaries were evaluated through the study period (267 for the preimplementation period and 225 for the postimplementation period). The mean length of stay was of 4.46 days for the preimplementation and 3.46 days for the postimplementation period (P = 0.007). TEDs/SCDs were not used in 9.3% of the patients in the pre group versus 0.6% in the post group (P < 0.001). DVT prophylaxis was given to 30.1% of the pre group versus 34.8% of the post group (P = 0.0013). The administration of PUD prophylaxis also increased from 28.3% in the pre group to 40.2% of the post group (P < 0.001). There was a decrease in the nonsurgical admissions from 22.2% in the pre group versus 14.6% in the post group (P = 0.049). CONCLUSIONS: The use of checklists in daily progress notes enhances patient care by improving the delivery of routine care that is often overlooked in the light of major medical issues.

Stage I noninvasive and minimally invasive uterine serous carcinoma: comprehensive staging associated with improved survival.

OBJECTIVE: The aim of this study was to determine if comprehensive surgical staging is a better predictor of outcome than incomplete staging for women with stage I noninvasive or minimally invasive (≤3 mm) uterine serous carcinoma (USC). METHODS: Retrospective chart review was used to identify patients undergoing hysterectomy at the Johns Hopkins Hospital from 1989 to 2010. Relevant clinical and pathologic data were extracted. Patients with noninvasive and minimally invasive (≤3-mm myometrial invasion) USC were identified. Stage was assigned based on the 2009 International Federation of Gynecology and Obstetrics endometrial cancer criteria. Survival curves were generated using the Kaplan-Meier method. RESULTS: We identified 63 patients with noninvasive or minimally invasive (≤3 mm) USC. Stages I, II, III, and IV disease were noted in 65% (41/63), 6% (4/63), 14% (9/63), and 14% (9/63) of the patients, respectively. Lower stage was associated with a significantly improved disease-specific survival (P = 0.001). Comprehensive staging, including total hysterectomy, bilateral salpingo-oophorectomy, pelvic and para-aortic lymphadenectomy, omentectomy, and peritoneal biopsies, was completed in 29% (12/41) of the patients with stage I disease. There were no disease-specific deaths in the comprehensive staging group. Compared with incomplete staging, comprehensive staging was associated with a significantly improved disease-specific survival (P = 0.039). CONCLUSIONS: Patients with stage I noninvasive and minimally invasive USC on comprehensive staging have an excellent prognosis. Adjuvant therapy may not benefit this patient population.

Volume-Based Care among Young Women Diagnosed with Uterine Cancer.

Purpose. To characterize volume-based care of uterine cancer among women aged ≤50 years. Methods. The Maryland Health Service Cost Review Commission database was accessed for uterine cancer surgical cases from 1994 to 2005. Cross-tabulations and logistic regression models were used to evaluate for significant associations among volume-based care and other variables comparing women ≤50 years with those aged >50 years. Results. Women ≤50 years comprised 13.6% of the cases. Women ≤50 years were less likely to be managed by high-volume surgeons (31.6% versus 35.1%, P = 0.02). For women ≤50 years, there was a trend toward management at low-volume hospitals (52.0% versus 54.0%, P = 0.22). No deaths were reported among the group of women ≤50 years treated by high-volume providers or at high-volume centers. Women ≤50 years managed by high-volume surgeons had longer length of stay (P < 0.001) and higher adjusted cost of hospital-related care (P < 0.00). Women ≤50 years managed at high-volume centers had higher adjusted cost of hospital-related care (P = 0.01). Conclusion. Primary surgical care of young women with uterine cancer is often performed by low-volume providers.

The role of liver-directed surgery in patients with hepatic metastasis from a gynecologic primary carcinoma.

BACKGROUND: The management of patients with liver metastasis from a gynecologic carcinoma remains controversial, as there is currently little data available. We sought to determine the safety and efficacy of liver-directed surgery for hepatic metastasis from gynecologic primaries. METHODS: Between 1990 and 2010, 87 patients with biopsy-proven liver metastasis from a gynecologic carcinoma were identified from an institutional hepatobiliary database. Fifty-two (60%) patients who underwent hepatic surgery for their liver disease and 35 (40%) patients who underwent biopsy only were matched for age, primary tumor characteristics, and hepatic tumor burden. Clinicopathologic, operative, and outcome data were collected and analyzed. RESULTS: Of the 87 patients, 30 (34%) presented with synchronous metastasis. The majority of patients had multiple hepatic tumors (63%), with a median size of the largest lesion being 2.5 cm. Of those patients who underwent liver surgery (n=52), most underwent a minor hepatic resection (n=44; 85%), while 29 (56%) patients underwent concurrent lymphadenectomy and 45 (87%) patients underwent simultaneous peritoneal debulking. Postoperative morbidity and mortality were 37% and 0%, respectively. Median survival from time of diagnosis was 53 months for patients who underwent liver-directed surgery compared with 21 months for patients who underwent biopsy alone (n=35) (p=0.01). Among those patients who underwent liver-directed surgery, 5-year survival following hepatic resection was 41%. CONCLUSIONS: Hepatic surgery for liver metastasis from gynecologic cancer can be performed safely. Liver surgery may be associated with prolonged survival in a subset of patients with hepatic metastasis from gynecologic primaries and therefore should be considered in carefully selected patients.

Late onset hemorrhage caused by ruptured uterine artery pseudoaneurysm after robotic-assisted total hysterectomy.

Robotic surgery has been used increasingly for the management of benign or malignant gynecologic conditions. Vaginal hemorrhage after hysterectomy is fairly uncommon. Uterine artery pseudoaneurysm is a rare phenomenon causing late onset hemorrhage that could be potentially life-threatening. This case describes the management of vaginal bleeding due to ruptured uterine artery pseudoaneurysm after robotic-assisted total hysterectomy. This is the first known reported case of a ruptured uterine artery pseudoaneurysm after a robotic-assisted hysterectomy.

Computed tomographic peritoneography prior to intraperitoneal chemotherapy in advanced Müllerian cancer: a pilot study.

OBJECTIVE: The objective of this study was to utilize computed tomographic peritoneography (CTP) to assess distribution prior to intraperitoneal chemotherapy for advanced müllerian cancer. METHODS: Nineteen patients were submitted to CTP. A novel 6-point peritoneal distribution index was developed and applied to the patients prospectively. RESULTS: The median peritoneal distribution index was 6 (range, 4-6). The most common region for incomplete peritoneal distribution correlated to the right subphrenic space. CONCLUSION: Further studies are needed to determine the impact of inadequate distribution on recurrence and survival.

Surveillance for the detection of recurrent ovarian cancer: survival impact or lead-time bias?

OBJECTIVE: To compare the survival impact of diagnosing recurrent disease by routine surveillance testing versus clinical symptomatology in patients with recurrent epithelial ovarian cancer (EOC) who have achieved a complete response following primary therapy. METHODS: We identified all patients who underwent primary surgery for EOC at two institutions between 1/1997 and 12/2004 and were diagnosed with recurrent disease following a complete clinical response to primary chemotherapy. Survival and post-recurrence management were compared between asymptomatic patients in which recurrent disease was diagnosed at a scheduled visit by routine surveillance testing and symptomatic patients in which recurrent disease was diagnosed based on clinical symptomatology at an unscheduled office visit or hospitalization. RESULTS: Of the 121 patients that met inclusion criteria, 22 (18.2%) were diagnosed with a symptomatic recurrence. Median primary PFS was similar for asymptomatic and symptomatic patients (24.8 versus 22.6 months, P = 0.36); however, post-recurrence survival was significantly greater in asymptomatic patients (45.0 versus 29.4 months, P = 0.006). Secondary cytoreductive surgery (SCRS) was attempted equally in both groups (41% versus 32%, P = NS); however, optimal residual disease (

Impact of surgeon and hospital ovarian cancer surgical case volume on in-hospital mortality and related short-term outcomes.

OBJECTIVE: To evaluate the impact of surgeon and hospital case volume, and other related variables, on short-term outcomes after surgery for ovarian cancer. METHODS: The Maryland Health Service Cost Review Commission database was accessed for ovarian cancer surgical cases including both oophorectomy and any staging/cytoreductive surgical procedure from 2001 to 2008. Multivariate logistic regression analyses and multiple linear regression models were used to evaluate for significant associations between surgeon and hospital case volume, as well as other independent variables, and the risk of in-hospital death, extent of surgery, length of hospital stay, and hospital-related cost of care. RESULTS: Overall, 1894 primary ovarian cancer operations were performed by 352 surgeons at 43 hospitals. After controlling for the effects of all variables, the only independently significant factors associated with the risk of in-hospital death were surgery by a high-volume surgeon and an APR-DRG mortality risk score of 4. Ovarian cancer surgery performed by a high-volume surgeon was associated with a 69% reduction in the risk of in-hospital death. Surgery at a high-volume hospital was an independent positive predictor of a cytoreductive procedure. A statistically significant negative correlation was observed between surgery at a high-volume hospital and both length of hospital stay and hospital-related cost. CONCLUSIONS: After controlling for other factors, ovarian cancer surgery performed by a high-volume surgeon is associated with a 69% reduction in the risk of in-hospital death, while high-volume hospital care is associated with increased likelihood of cytoreduction, shorter length of stay, and lower hospital-related cost of care.