Complex Obstetrical Surgery: Building a Team and Defining Roles.

As the number of placenta accreta spectrum (PAS) cases continues to rise, the gap in surgical skills in labor and delivery units becomes more apparent. Recent scholarly work has highlighted the diminishing advanced surgical skills among obstetricians-gynecologists, particularly among new graduates. Therefore, it has become a practice in many institutions to refer complex cesarean deliveries (CD) and obstetrical hysterectomies to subspecialists, specifically gynecologic oncologists. Hence, in this commentary, we propose a process whereby key personnel within departments of obstetrics and gynecology are identified, and their appropriate level of involvement in cases of complex obstetrical surgery is delineated. In doing so, we describe the surgical skills expected from each provider level so that the CD complexity level can be matched to specific surgical expertise. Through this process, an obstetrician-led complex obstetrical surgery team is formed. Ultimately, the goal of this process is twofold: first, to return cases with higher levels of surgical complexity back to obstetricians, and second, to reduce the surgical back-up burden from gynecology subspecialists such as gynecologic oncologists.

Trends in Early-Stage Cervical Cancer Management in the US: A National Cancer Database Analysis.

The Laparoscopic Approach to Cervical Cancer (LACC) trial was published in 2018 and demonstrated that minimally invasive surgery (MIS) yields inferior survival outcomes in early-stage cervical cancer compared to open surgery. This study investigates how the results of the LACC trial have impacted the selection of the primary treatment modality and adjuvant radiation utilization in early-stage cervical cancer. Using the National Cancer Database (NCDB), we compared patients with stage IA2-IB1 cervical cancer before (1/2016-12/2017) and after (1/2019-12/2020) the LACC trial. A total of 7930 patients were included: 4609 before and 3321 after the LACC trial. There was a decline in MIS usage from 67% pre-LACC to 35% thereafter (p < 0.001). In both the pre- and post-LACC periods, patients undergoing radical MIS more frequently had small volume disease (pre-LACC tumors ≤ 2 cm, 48% MIS vs. 41% open, p = 0.023; post-LACC stage IA2, 22% vs. 15%, p = 0.002). Pre-LACC, MIS radical hysterectomy was associated with White race (82% vs. 77%, p = 0.001) and private insurance (63% vs. 54%, p = 0.004), while there was no difference in socioeconomic factors in the post-LACC period. Although the proportion of patients treated with primary chemoradiation remained stable, the post-LACC cohort had a younger median age (52.47 vs. 56.37, p = 0.005) and more microscopic disease cases (13% vs. 5.4%, p = 0.002). There was no difference in the rate of radiation after radical hysterectomy before and after the trial (26% vs. 24%, p = 0.3). Conclusions: Post-LACC, patients were less likely to undergo MIS but received adjuvant radiation at similar rates, and primary chemoradiation patients were younger and more likely to have microscopic disease.

Case report: Minimally invasive primary debulking surgery for advanced stage epithelial ovarian cancer.

The surgical management of advanced ovarian cancer has historically emphasized an open technique, but advances in minimally invasive surgery (MIS) have led to its increasing use in ovarian cancer. Most research has focused on the utility of MIS in the interval debulking setting. Here, we present a case of a 38-year-old patient with incidentally diagnosed advanced stage ovarian cancer. We describe the robotic surgery techniques used to achieve complete primary cytoreduction, including resection of disease on the diaphragm. The patient has completed standard adjuvant chemotherapy and maintenance treatment and remains without evidence of disease for more than 2 years. This case details the techniques utilized to achieve complete cytoreduction including trocar placement, robotic instrument preference, and rotation of the robotic boom. This patient has had successful perioperative and oncologic outcomes, and her case highlights the role for minimally invasive primary debulking surgery for select patients with advanced ovarian cancer.

Comparison of Minimally Invasive Surgery with Open Surgery for Type II Endometrial Cancer: An Analysis of the National Cancer Database.

OBJECTIVE: Prior studies comparing minimally invasive surgery with open surgery among patients with endometrial cancer have reported similar survival outcomes and improved perioperative outcomes with minimally invasive surgery (MIS). However, patients with Type II endometrial cancer were underrepresented in these studies. We sought to compare the overall survival and surgical outcomes between open surgery and MIS in a large cohort of women with Type II endometrial cancer. METHODS: Using data from the National Cancer Database, we identified a cohort of women who underwent hysterectomy for type II endometrial cancer (serous, clear cell, and carcinosarcoma) between January 2010 and December 2014. The primary outcome was a comparison of the overall survival for MIS with that for the open approach. The secondary outcomes included a comparison of the length of hospital stay, readmission within 30 days of discharge, and 30- and 90-day mortality. Outcomes were compared between the cohorts using the Mann-Whitney U test, Pearson's chi-square test, or Fisher's exact test. Multivariable logistic regression with inverse propensity weighting was used to determine clinical characteristics that were statistically significant predictors of outcomes. p values < 0.05 were considered significant. RESULTS: We identified 12,905 patients with Type II, Stage I-III endometrial cancer that underwent a hysterectomy. In total, 7123 of these women (55.2%) underwent MIS. The rate of MIS increased from 39% to 64% over four years. Women who underwent MIS were more often White, privately insured, older, and had a higher income. The laparotomy group had a higher rate of carcinosarcoma histology (30.9% vs. 23.6%, p < 0.001), stage III disease (38.4% vs. 27.4%, p < 0.001), and larger primary tumors (59 vs. 45 mm, p < 0.001). Lymph node dissection was more commonly performed in the MIS group (89.6% vs. 85.4%, p < 0.001). With regard to adjuvant therapy, subjection to postoperative radiation was more common in the MIS group (37% vs. 40.1%, p < 0.001), while chemotherapy was more common in the laparotomy group (37.6% vs. 33.9%, p < 0.001). The time interval between surgery and the initiation of chemotherapy was shorter in the MIS group (39 vs. 42 days, p < 0.001). According to the results of propensity-score-weighted analysis, MIS was associated with superior overall survival (101.7 vs. 86.7 months, p = 0.0003 determined using the long-rank test), which corresponded to a 10% decreased risk of all-cause mortality (HR 0.9; CI 0.857-0.954, p = 0.0002). The survival benefit was uniform across all three histology types and stages. MIS was associated with superior perioperative outcomes, including shorter length of stay (1 vs. 4 days, p < 0.001), lower 30-day readmission rates (2.5% vs. 5%), and lower 30- and 90-day postoperative mortality (0.5% vs. 1.3% and 1.5% vs. 3.6%, respectively; p < 0.001 for both). The increased adoption of MIS from 2010 to 2014 corresponds to a decrease in 90-day postoperative mortality (2.8% to 2.2%, r = -0.89; p = 0.04) and overall mortality (51% to 38%, r = -0.95; p = 0.006). CONCLUSIONS: In a large cohort of patients from the National Cancer Database, MIS was associated with improved overall survival and superior perioperative outcomes compared to open surgery among women with Type II endometrial cancer. A decrease in postoperative mortality and a shorter interval between surgery and the initiation of chemotherapy may contribute to the survival benefit of MIS. A racial and economic disparity in the surgical management of Type II endometrial cancer was identified, and further investigation is warranted to narrow this gap and improve patient outcomes.

Minimally invasive versus open surgery for women with stage 1A1 and stage 1A2 cervical cancer: A retrospective database cohort study.

Background: Recent studies comparing minimally invasive versus open radical hysterectomy in patients with early-stage cervical cancer have reported a worse overall survival with minimally invasive surgery (MIS). However, in the patients with microscopic disease, there was no survival difference and the optimal surgical approach for microscopic cervical cancer remains unclear. Methods: Using the National Cancer Database, we identified a cohort of women who underwent hysterectomy as the primary treatment for stage IA1/IA2 cervical cancer between January 2010 and December 2016. Using multivariable logistic regression, our primary outcome was to compare overall survival between the open and MIS groups. The data was stratified for simple and radical hysterectomies. Secondary endpoint was comparison of readmission rates and length of stay (LOS). Results: We identified 6230 patients with stage IA1 and IA2 cervical cancer that underwent hysterectomy as primary treatment. 4054 of these women (65%) underwent MIS. There was no difference in age, lympho-vascular invasion, number of lymph nodes retrieved and histology between the two groups. In the overall cohort, there was no difference in survival between the open and the MIS group (Hazard ratio for the open group 1.23; CI 0.92-1.63). Post-operative radiation therapy was more common in the open group (5.24% vs 4.09%, p value < 0.02). The mean LOS (1.35 days vs 3.08 days) was shorter in MIS group (p value < 0.0001). No difference was found in the readmission rates (60% for the MIS group vs 55% for the open group; p value 0.14). Conclusions: Our data suggest that MIS is associated with similar overall survival and shorter length of hospital stay compared to the open hysterectomy in women with stage IA cervical cancer. Based on this large data set, MIS appears to be a safe and effective surgical approach for women with stage IA1/IA2 cervical cancer.

Endometrial cancer recurrence in the sacrum and the Psoas: A case report and literature review.

Musculoskeletal metastasis of endometrial carcinoma is rare. Data regarding the management of metastatic disease to these sites is limited. We report a case of a 73-year-old woman who had surgery for endometrial adenocarcinoma (FIGO stage IB, Grade II) followed by vaginal cuff brachytherapy and one year later developed an isolated recurrence in the sacrum and iliopsoas muscle. She was treated with chemotherapy followed by whole pelvis radiation and a complete clinical response was achieved. At her last follow up, 12 months after the completion of the radiation, she had no clinical or radiologic evidence of disease.

Elective robotic hysterectomy for placenta accreta spectrum in the second trimester: Case report.

BACKGROUND: A scheduled pre-viable hysterectomy is a treatment option for women with early diagnosed placenta accreta spectrum who do not wish future fertility. A minimally invasive hysterectomy with pregnancy in situ for placenta accreta spectrum has not been previously reported. CASE: A patient with evidence of placenta accreta spectrum on prenatal imaging underwent an elective robot-assisted laparoscopic hysterectomy at 16 weeks of gestation. The procedure was uncomplicated and she was discharged on postoperative day 1. Pathology was consistent with placenta percreta. CONCLUSION: Robot-assisted laparoscopic hysterectomy with pregnancy in situ is feasible in a patient with placenta accreta spectrum in the second trimester. TEACHING POINTS: 1. Early diagnosis of placenta accreta spectrum is important for surgical planning and management. 2. We present a technique for minimally invasive hysterectomy in a patient with placenta accreta spectrum diagnosed before viability.

Synergy between Paclitaxel and Anti-Cancer Peptide PNC-27 in the Treatment of Ovarian Cancer.

OBJECTIVES: Paclitaxel is widely used in the treatment of gynecologic malignancies. It targets tumor cells in the M phase of the cell cycle. Cells in other phases survive the insult and repopulate the tumor. PNC-27 is a peptide synthesized of amino acids of the p53-MDM-2 binding domain. It kills various cancer cell lines in a dose-dependent manner. The goal of this study is to assess ovarian cancer cells' sensitivity to PNC-27 after surviving exposure to paclitaxel and to investigate the potential for synergy between PNC-27 and paclitaxel in the treatment of ovarian cancer. METHODS: The impact of exposure to paclitaxel on the surface expression of MDM-2 was assessed with the use of flow cytometry. For measurement of cytotoxicity in vitro, ID8 cells were exposed to paclitaxel for 12 hours in various concentrations. At 12 hours, the drug containing media was removed and the cells were cultured in media containing various concentrations of PNC-27 for 24 hours. Viability was assessed with the use of an MTT assay. Survival fractions were plotted against drug concentrations and the data were fit to logistic dose-response curves. Isoeffective combinations were used to create isobolograms. The combined treatment with weekly paclitaxel and PNC-27 was tested in an intraperitoneal mouse model of ovarian cancer (ID8). RESULTS: Exposure to paclitaxel rendered incomplete time-dependent killing, while PNC-27 mediated comprehensive, dose-dependent killing of ID8 cells. The cytotoxic effect of PNC-27 was dependent on its binding to MDM-2. Blocking MDM-2 inhibited the killing by PNC-27. ID8 cells surviving paclitaxel demonstrated increased expression of MDM-2 and increased susceptibility to PNC-27. Isobologram for dose combinations that were isoeffective indicates synergistic effect between the 2 agents (Combination index <1). In an in vivo model of ovarian cancer (ID8), the addition of PNC-27 to weekly paclitaxel administration significantly reduces tumor growth. CONCLUSIONS: These data demonstrate synergism between PNC-27 and paclitaxel. PNC-27 could target cells surviving paclitaxel and improve its antitumor effect.

Extent of lymph node dissection and overall survival in patients with uterine carcinosarcoma, papillary serous and endometrioid adenocarcinoma: A retrospective cohort study.

OBJECTIVE: To evaluate the interaction between extent of lymph node dissection (LND) and overall survival (OS) in patients with various histologic types of uterine cancer. METHODS: We retrospectively identified 834 patients who had primary surgery in our institution for uterine carcinosarcoma (CS), papillary serous (UPSC) and endometrioid adenocarcinoma between 1984 and 2009. Stage, grade, total lymph node count (LNC), positive LNC, adjuvant therapy, age, race and OS were collected. OS was calculated using the Kaplan-Meier method. Predictive factors were compared with the log rank test and Cox regression analysis. RESULTS: Our cohort included 158 patients with CS, 115 patients with UPSC and 561 patients with endometrioid adenocarcinoma. Of the cohort, 38% of the patients had Stage III or IV disease. LND was performed in 73% of patients with CS, 68% of patients with UPSC and 79% of patients with endometrioid adenocarcinoma. LND was performed in 82% of Stage I-II and in 68% of Stage III-IV cases. The median total LNC was 13 (range 1-75) and there was no significant difference in the total LNC between the different histologies. Median OS was 21 months for CS, 18 months for UPSC and 200 months for patients with endometrioid adenocarcinoma. A positive association between the total and positive LNC was present in all three histologic types (Spearman coefficient, p < 0.001). The cohort was divided in quartiles based on the total LNC and a Kaplan-Meier survival analysis was performed. A continuum of improved OS was noted in correlation with increased LNC. OS was 27 months for the group with 0 nodes, 112 months for the group with 1-8 nodes, 117 months for the group with 9-16 nodes and 196 months for the group with >17 nodes. Doubling the total LNC was associated with 28% risk of death reduction (HR 0.724, CI 0.66-0.794, p < 0.001) for the first year and 14% risk reduction (HR 0.858, CI 0.761-0.967, p = 0.012) for the second year. CONCLUSIONS: In our cohort, the performance of LND is associated with improved OS. This effect appears to be uniform across pathology types. The extent of the LND is inversely correlated with the risk of death for the first 2 years.

Metronomic cyclophosphamide with bevacizumab provides disease stabilization in patients with advanced uterine cancer.

•We present two cases of advanced uterine cancer that were treated with the combination of metronomic cyclophosphamide and bevacizumab.•Targeting angiogenesis can provide disease control in patients with advanced uterine cancer.•Randomized controlled trials comparing metronomic and conventional regimens in advanced uterine cancer are required.

Survival impact of cytoreduction to microscopic disease for advanced stage cancer of the uterine corpus: a retrospective cohort study.

OBJECTIVE: To assess the impact of cytoreduction to no gross residual disease (R0) on overall survival (OS) in patients with stage III-IV uterine carcinosarcoma (CS), papillary serous/clear cell (UPSC/CC) and endometrioid carcinoma (EC). METHODS: We retrospectively identified 168 patients who underwent primary surgery for advanced uterine cancer between 1984 and 2009 in two teaching hospitals in Brooklyn, New York. Histology, stage, grade, residual disease (RD), adjuvant therapy, age, race and OS were collected. OS was calculated using the Kaplan-Meier method. Predictive factors were compared using the log-rank test and Cox regression analysis. RESULTS: Our cohort included 54 patients with CS (stage III, n = 32; stage IV, n = 22), 54 patients with UPSC/CC (stage III, n = 20; stage IV, n = 34) and 60 patients with EC (stage III, n = 45; stage IV, n = 15). R0 was achieved in 64% of patients with CS, in 53% of patients with UPSC/CC and in 68% of patients with EC. There was no interaction between histologic subtype and feasibility of complete cytoreduction (p = 0.39). R0 was associated with a median OS of 25 months (95% CI [18, 33]) versus 13 months (95% CI [8, 18]) in patients with gross RD (p = 0.03). This effect was uniform among histologic subtypes. On multivariate analysis, predictors of increased mortality were gross residual disease (HR = 2.0, 95% CI [1.1, 3.7], p = 0.01), stage IV (HR = 1.8, 95% CI [1.1, 3.1], p = 0.02) and age (HR = 1.04 per year of age, 95% CI [1.02, 1.07], p = 0.002). CONCLUSION: Cytoreductive surgery to R0 is associated with improved OS in advanced uterine cancer. This effect is uniform among histologies. There is no interaction between histologic subtype and feasibility of complete cytoreduction.

Glassy cell carcinoma of the cervix: a systematic review and meta-analysis.

OBJECTIVE: The purpose of this study is to summarize the data on the incidence, clinical behavior and overall survival of patients with glassy cell cervical carcinoma (GCCC). METHODS: Twenty-four case series and fifteen case reports identified by searching PubMed database qualified for inclusion in this study. The published cases were combined with data from a retrospective chart review of patients with GCCC in two major teaching hospitals in Brooklyn, NY. RESULTS: A total of 292 cases were collected through our literature and chart review. Median age at diagnosis was 45 years old (range 12-87 years of age). GCCC incidence ranges from 0.2 to 9.3% of all cervical cancers and 2 to 30.2% of cervical adenocarcinomas. The stage distribution is similar to squamous cell carcinoma with 79% of the patients being diagnosed with Stage I or II disease. Most common sites of recurrence for Stage I patients are the vagina and pelvis. In Stage II patients locoregional and distant metastases are equally common. Recurrence rate was higher among patients treated only with surgery (32.7%), as compared to patients treated with surgery followed by radiation (11%) or patients treated with radiation only (10%). Median overall survival (OS) was 25 months (95% CI 8.4-41.6). Overall 5-year survival for all stages is lower when compared to all cervical cancers (54.8% vs 75%). There was no interaction between race and OS (p=0.66). CONCLUSION: GCCC is a rare histologic type of cervical cancer that presents at a younger age, is associated with high risk for distant failure and carries worse prognosis as compared to the squamous cell type. Radiation therapy is associated with decreased risk of recurrence.

External validation of a nomogram for predicting survival of women with uterine cancer in a cohort of African American patients.

OBJECTIVE: This study aimed to externally validate a nomogram for predicting overall survival of women with uterine cancer in an African American population. METHODS: After the institutional review board approval, data from the uterine cancer database from 2 major teaching hospitals in Brooklyn, NY, were analyzed. The predicted survival for each patient was calculated with the use of the nonogram; the data were clustered in deciles and compared with the observed survival data. RESULTS: High incidence of aggressive histologic types (22% carcinosarcoma, 16% serous/clear cell), poorly differentiated (53% grade 3), and advanced stage (38% stage III or IV) tumors was found in our study population. The median follow-up for survivors was 52 months (range, 1-274 months). The observed and predicted 3-year overall survival probabilities were significantly different (62.5% vs 72.6%, P < 0.001). Similarly, the observed 5-year overall survival probability was significantly lower than the predicted by the nomogram (55.5% vs 63.4%, P < 0.001). The discrepancy between predicted and observed survival was more pronounced in the midrisk groups. CONCLUSIONS: The nomogram is not an adequate tool to predict survival in the African American population with cancer of the uterine corpus. Race seems to be a significant, independent factor that affects survival and should be included in predictive models.

Port-site recurrence in a patient undergoing robotic hysterectomy and lymph node dissection for endometrioid adenocarcinoma of the uterus.

•We present a case of port-site recurrence of endometrioid adenocarcinoma after robotic hysterectomy and staging.•Port-site recurrence is commonly an indicator of multifocal disease with poor prognosis.•Surgical techniques that decrease the risk of this complication should be implemented.

Invasive recurrence of serous borderline ovarian tumor as multifocal lymphadenopathy 25 years after initial diagnosis.

► We present the case with the latest reported recurrence of low malignant potential ovarian tumor. ► Borderline ovarian tumors have the potential for delayed recurrence that is not always salvageable surgically. ► Optimization of surveillance strategies and lifelong follow up is required for these patients.

Time-dependent cytotoxic drugs selectively cooperate with IL-18 for cancer chemo-immunotherapy.

BACKGROUND: Time-dependent chemotherapeutic agents can selectively target tumor cells in susceptible phases of the cell cycle however a fraction of tumor cells in non-vulnerable cell cycle phases remain drug-resistant. Immunotherapy represents a promising approach to overcome the limitation of phase-specific drugs and improve their clinical efficacy. Here, we investigated the potential use of anticancer chemotherapeutic drugs in combination with IL-18, a cytokine with strong immunostimulatory properties. METHODS: Four chemotherapeutic drugs commonly used in ovarian cancer were first tested for the ability to increase the immunogenicity and killing of the murine ovarian cancer cell line ID8 in vitro. Chemotherapeutric agents with measured time-dependent immune-enhancing effects were then tested for antitumor effectiveness in vivo in combination with IL-18 immunotherapy using the ID8-Vegf ovarian cancer model. RESULTS: Paclitaxel or topotecan exposure alone mediated incomplete, time-dependent killing against the murine ovarian cancer cell line ID8 in vitro, whereas carboplatin or gemcitabine mediated comprehensive, dose-dependent killing. In the plateau phase of the time-dependent killing by topotecan or paclitaxel, drug-resistant ID8 cells were more immunogenic with elevated expression of MHC-I and Fas, and increased sensitivity to CTL and Fas agonistic antibody in vitro. Moreover, the antitumor effectiveness of time-dependent agents in vivo was significantly improved with the addition of IL-18 through a T cell-dependent mechanism, while the effectiveness of drugs without significant phase specificity were not. CONCLUSIONS: Tumor immunotherapy with IL-18 can significantly augment the killing fraction of phase-specific chemotherapeutic drugs and provide survival benefit. The safety profile of IL-18 and its positive interactions with select anticancer chemotherapeutic agents strongly supports the clinical investigation of this combinatorial approach.

Factors complicating surgical management of the vulvar abscess.

OBJECTIVE: To delineate risk factors and demographics in those patients with vulvar abscess that required surgical intervention, identify the most common bacterial isolate present at the time of surgery and comment on the progression to necrotizing fasciitis and the need for reoperation. STUDY DESIGN: Retrospective chart review. RESULTS: A total of 47 vulvar abscesses with cellulitis were managed surgically. The most common isolate was methicillin-resistant Staphylococcus aureus (MRSA), which comprised 43% of the total. The median length of stay was 4 days (1-66), and 17% had stays >7 days. Diabetes was significantly related to hospitalization >7 days (38% vs. 6%, p<0.01), reoperation (25% vs. 3%, p=0.02) and progression to necrotizing fasciitis (19% vs. 0%, p=0.01). CONCLUSION: When treating abscess of the vulva with cellulitis, antibiotic coverage of MRSA should be undertaken. Inpatient management with aggressive treatment for abscess of the vulva in those patients with concomitant diabetes is recommended.