Neoadjuvant chemotherapy with bevacizumab for locally advanced vulvar cancer.

OBJECTIVES: External beam radiation with sensitizing platinum is the recommended therapy for locally advanced vulvar cancers not amenable to curative surgery and is associated with considerable acute and chronic side effects. Radical vulvectomy post-radiation for persistent disease is often compromised with poor wound healing. We describe clinical outcomes for patients who received neoadjuvant chemotherapy plus bevacizumab followed by radical vulvectomy for locally advanced vulvar cancer. METHODS: We performed retrospective analyses of all patients at our institution who underwent radical vulvectomy from January 2015 to November 2023. Of 113 patients, 13 patients underwent neoadjuvant chemotherapy. Demographics and clinicopathologic data were extracted, and descriptive statistical analyses were performed. Cases with neoadjuvant chemotherapy plus bevacizumab were further evaluated for response, adverse effects, and survival. RESULTS: Neoadjuvant chemotherapy was administered to 13 patients with stage II-IV disease that involved the urethra, vagina, or anus. Lesion sizes ranged from 4 to 20 cm (median 7 cm). Patients received 2-6 cycles of carboplatin or cisplatin, paclitaxel, and bevacizumab. Nine (69.2%) patients had partial pathologic responses, and four patients had complete responses. All patients had negative surgical margins. Ten (76.9%) patients had radiographic evidence of inguinal lymph node metastasis prior to neoadjuvant chemotherapy, and four had residual nodal disease. Only one patient developed a superficial groin seroma. Three patients developed recurrence, two locally and one distant, and there was one death. The median follow-up was 23 months (range 6-84 months). CONCLUSIONS: Neoadjuvant chemotherapy using combination platinum/paclitaxel/bevacizumab was efficacious for locally advanced vulvar cancer, resulting in complete resections, negative margins, and excellent wound healing. A multi-institutional phase II trial is warranted to validate these findings.

Prognostic features of the tumor microenvironment in high-grade serous ovarian cancer and dietary immunomodulation.

High-grade serous ovarian cancer (HGSOC) is a particularly lethal malignancy that is prognostically influenced by the immune profile of the tumor microenvironment (TME). TME immune profiles have been sub-categorized according to features associated with both survival outcomes as well as response to systemic therapies. Five suggested immune phenotypes have been described and correlated with overall survival outcomes. Phenotypes associated with shorter overall survival rates appear to have prominent immunosuppressive features within their TME. The opportunity to triage patients according to their prognostic TME profile might allow selection of individual patients with poor prognostic features who could most benefit from innovative immunomodulatory treatment strategies. Two potential strategies to indirectly manipulate the TME (and oncologic outcomes) are alteration of the gut microbiome composition and alteration of TME metabolism through dietary interventions. Experimental dietary modifications in humans designed for influencing cancer outcomes are only beginning to be studied in a prospective fashion. Herein we summarize prognostic TME features in HGSOC and potential opportunities for immunomodulation via dietary and gut microbial interventions.

An Overview of Endometrial Cancer with Novel Therapeutic Strategies.

Endometrial cancer (EC) stands as the most prevalent gynecologic malignancy. In the past, it was classified based on its hormone sensitivity. However, The Cancer Genome Atlas has categorized EC into four groups, which offers a more objective and reproducible classification and has been shown to have prognostic and therapeutic implications. Hormonally driven EC arises from a precursor lesion known as endometrial hyperplasia, resulting from unopposed estrogen. EC is usually diagnosed through biopsy, followed by surgical staging unless advanced disease is expected. The typical staging consists of a hysterectomy with bilateral salpingo-oophorectomy and sentinel lymph node biopsies, with a preference placed on a minimally invasive approach. The stage of the disease is the most significant prognostic marker. However, factors such as age, histology, grade, myometrial invasion, lymphovascular space invasion, tumor size, peritoneal cytology, hormone receptor status, ploidy and markers, body mass index, and the therapy received all contribute to the prognosis. Treatment is tailored based on the stage and the risk of recurrence. Radiotherapy is primarily used in the early stages, and chemotherapy can be added if high-grade histology or advanced-stage disease is present. The risk of EC recurrence increases with advances in stage. Among the recurrences, vaginal cases exhibit the most favorable response to treatment, typically for radiotherapy. Conversely, the treatment of widespread recurrence is currently palliative and is best managed with chemotherapy or hormonal agents. Most recently, immunotherapy has emerged as a promising treatment for advanced and recurrent EC.

Malignant peritoneal cytologic contamination with robotic hysterectomy for endometrial cancer.

BACKGROUND: Malignant peritoneal cytology in endometrial cancer (EC) is not considered an independent adverse prognostic factor for uterine-confined disease and is not a determinant factor in the International Federation of Gynecology and Obstetrics (FIGO) staging system. NCCN Guidelines still recommend obtaining cytologies. The aim of this study was to determine the prevalence of peritoneal cytologic contamination following robotic hysterectomy for EC. METHODS: Peritoneal cytology from the pelvis and diaphragm were obtained at the initiation of surgery, and from the pelvis only at the completion of robotic hysterectomy with sentinel lymph node mapping (SLNM). Cytology specimens were evaluated for the presence of malignant cells. Pre- and post-hysterectomy cytology results were compared, and pelvic contamination was defined as conversion from negative to positive cytology following surgery. RESULTS: 244 patients underwent robotic hysterectomy with SLNM for EC. Pelvic contamination was identified in 32 (13.1%) cases. In multivariate analysis, pelvic contamination was associated with >50% myometrial invasion, tumor size >2 cm, lymphovascular space invasion (LVSI), and lymph node metastasis. There was no association with FIGO stage or histology subtypes. CONCLUSIONS: Malignant peritoneal contamination occurred during robotic surgery for EC. Large lesions (>2 cm), deep invasion (>50%), LVSI, and lymph node metastasis were each independently associated with peritoneal contamination. Whether or not peritoneal contamination increases risk for disease recurrence should be studied in larger series, including an evaluation of patterns of recurrence and the potential impact of adjuvant therapies. Until the clinical impact of peritoneal contamination during hysterectomy for EC is better understood, methods to reduce peritoneal contamination are warranted.

Thirty-day Postoperative Adverse Events in Minimally Invasive versus Open Abdominal Radical Hysterectomy for Early-stage Cervical Cancer.

STUDY OBJECTIVE: To identify the incidence, type, and grade of postoperative adverse events in minimally invasive radical hysterectomy vs abdominal radical hysterectomy (ARH) for patients with early-stage cervical cancer and determine risk factors associated with these adverse events. DESIGN: The American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) was queried to identify patients with early-stage cervical cancer undergoing radical hysterectomy. Multivariable logistic regression was used to assess risk factors associated with adverse postoperative outcomes among patients undergoing radical hysterectomy. SETTING: ACS NSQIP participating institutions within the United States. PATIENTS: Patients were collected from the ACS NSQIP databases (2014-2017) undergoing radical hysterectomy for early-stage cervical cancer. INTERVENTIONS: N/A MEASUREMENTS AND MAIN RESULTS: ARH had a significantly increased incidence of any 30-day postoperative adverse event compared with minimally invasive radical hysterectomy (31.2% vs 19.9%, p <.001). There was a higher incidence of surgical site infection, both deep and superficial, and blood transfusions in ARH. On multivariable logistic regression, the abdominal surgical approach was the only risk factor significantly associated with any postoperative adverse event (odds ratio, 1.4; confidence interval, 1.1-1.9; p = .018; 95% CIs). CONCLUSIONS: In this study, the abdominal surgical approach for radical hysterectomy in early-stage cervical cancer was associated with a higher incidence of postoperative adverse events than the minimally invasive approach.

Criminal Justice Involvement and Abnormal Cervical Cancer Screening Results Among Women in an Urban Safety Net Hospital.

OBJECTIVE: The aim of the study was to elucidate the risk factors underlying abnormal cytology-based cervical cancer screening (Pap testing) in justice-involved women (JIW) compared with non-JIW in an urban safety net hospital. METHODS: Retrospective chart review of women with a history of correctional involvement who received care at Grady Health System between 2010 and 2018 and had a Pap test was performed (n = 191). An age-matched cohort of women with no correctional involvement and had a Pap test at Grady served as the control (n = 394). Variables of interest were age, HIV, smoking, race, mental health history, and history of incarceration. Outcomes of interests were rate of abnormal Pap tests and follow-up. χ2 and logistic regression models evaluated associations between the variables of interest and outcomes. RESULTS: Rates of abnormal Pap tests were significantly higher in JIW (35.6%) than controls (18.5%, p < .0001). Compared with controls, JIW were significantly more likely to have high-grade cervical cytology (odds ratio [OR] = 3.89, p < .0005) and be lost to gynecologic follow-up (OR = 8.75, p < .0001) and a history of severe mental illness (29.5% vs 4.3%, p < .0001). Those with abnormal Pap tests were likely to be HIV-positive (OR = 20.7, p < .001) and have a history of incarceration (OR = 2.33, p < .001). Predictors of high-grade Pap test were smoking history (OR = 0.16, p = .014), HIV-positive (OR = 3.66, p = .025), and history of incarceration (OR = 3.96, p < .0005). CONCLUSIONS: Justice-involved women represent a high-risk subpopulation with significantly increased rates of high-grade cytology and lost to follow-up. This underscores the need for attention to screening programs and follow-up interventions for JIW.

Do High Rates of Atypical Glandular Cells Correlate With Higher Incidence of Disease in a Large Safety Net Hospital.

OBJECTIVE: The aim of the study was to describe the incidence and correlates of atypical glandular cell (AGC) Pap tests in a low socioeconomic status, underserved population. MATERIALS AND METHODS: Medical records of patients with AGC Pap tests at a single institution were reviewed from January 2013 to August 2019. Baseline characteristics were extracted including age, body mass index, birth control, abnormal uterine bleeding, and human papillomavirus (HPV). All colposcopy and endometrial biopsies were classified into negative/low-risk (polyps, tubular metaplasia, microglandular hyperplasia, cervical intraepithelial neoplasia 1) and high-risk (HR) lesions (cervical intraepithelial neoplasia 2/3, adenocarcinoma in situ, endometrial hyperplasia, cervical cancer, endometrial cancer). Logistic regression identified significant associations. Sixty-eight randomly selected AGC cytology slides from the cohort and 32 non-AGC slides outside the cohort were blindly reviewed by 6 pathologists. Fleiss κ interrater agreement was assessed. RESULTS: Seven hundred forty patients with AGC Pap tests were identified (0.8% of all Pap tests performed during this time). After excluding for incomplete data, 478 patients were included. Sixty-three patients had HR lesions (13.3%). Patients with HR lesions had increased odds of abnormal uterine bleeding (odds ratio = 4.32, p < .001) and HPV positivity (odds ratio = 10.89, p < .001) when compared with patients with low-risk lesions. The κ agreement was 0.21 for all cases and 0.18 for AGC alone. CONCLUSIONS: This population falls within the national averages for AGC Pap tests. There was an increased risk of HR lesions in patients with abnormal uterine bleeding and HPV positivity. The rate of HR lesions among AGC Pap tests was at the lower end of values in the literature. After blinded pathologist review, interobserver κ agreement was low for AGC Pap tests.

Primary colonic extrauterine endometrial stromal sarcoma: A case and review of the literature.

•Primary colonic extrauterine endometrial stromal sarcoma is a rare entity and diagnosis of this tumor can be challenging.•There is a common gene translocation specific to the tumors, our case was confirmed by identifying it.•Classifying these tumors correctly is important for treatment.

Robotic Surgery in the Frail Elderly: Analysis of Perioperative Outcomes.

PURPOSE: The frail are considered at higher risk for unfavorable surgical outcomes (major complications/mortality). We assessed the safety of and outcomes associated with robotic surgery in the frail elderly undergoing gynecologic procedures. METHODS: We identified patients aged ≥ 65 years who underwent a robotic procedure between May 2007 and December 2016. Frailty was defined as the presence of at least three of five frailty factors-more than five comorbidities, low physical activity, weight loss, exhaustion, and fatigue. Perioperative outcomes were recorded. We compared variables among frail and non-frail patients and performed a multivariate logistic regression to detect variables associated with major complications (≥ grade 3) or 90-day mortality. RESULTS: We identified 982 patients: 71 frail and 911 non-frail patients. Median age was 71 years. Median BMI was 29.8 kg/m2. Thirty-four patients (3.5%) had a 30-day readmission. Seventy-seven (7.8%) had a postoperative complication, of which 23 (2.3%) were major. Ninety-day mortality was 0.5%. There were significant differences with regard to age (P < 0.001), body mass index (BMI) (P < 0.001) and performance status (P < 0.001); the frail were more likely to have had surgery for oncologic reasons (P = 0.047). There were differences in hospital stay (P < 0.001), postoperative (P = 0.042) and major complications (P = 0.007), and 90-day mortality (P = 0.05). At multivariable logistic regression, age ≥ 85 was associated with major complications. BMI, performance status, and major complications were associated with 90-day mortality. CONCLUSIONS: The frail elderly have longer hospital stays and more complications after surgery than the general population, consistent with the reported literature. Careful selection of surgical candidates is required.

The Effect of Forced Cough to Minimize Pain and Discomfort at the Time of Colposcopy-Guided Cervical Biopsy.

OBJECTIVE: The aim of the study was to determine whether forced cough during colposcopy-guided cervical biopsy affected pain and anxiety levels. MATERIALS AND METHODS: The study was conducted at the University Hospital (Newark, NJ) Ambulatory Care Center from December 2016 to June 2018 and evaluated 110 patients at the time of a colposcopy-guided cervical biopsy. Study patients were randomized to either cough or no cough group during the biopsy procedure. Pain level was assessed using a visual analog pain scale before, during, and immediately after a colposcopy-guided cervical biopsy. Study patients also completed a standardized anxiety survey before and after the procedure. T tests, Pearson χ, or Cochran-Mantel-Haenszel were used to compare baseline characteristics between the cough and no cough groups. Multivariate linear regression analysis was used to identify potential confounders and then compare pain levels across both groups. RESULTS: There was no statistically significant difference in pain scores between the cough and no cough group when analyzed for each demographic variable even when confounders were accounted for. The anxiety scores for both study groups before and after the procedure were similar and not significantly reduced. CONCLUSIONS: We observed a trend that cough reduced pain associated with the colposcopy-guided cervical biopsy but did not reach statistical significance. A similar outcome was observed in anxiety level, where anxiety was reduced in the cough group but was not statistically significant as compared with the no cough group. Further studies are necessary to assess various modalities in reducing pain and anxiety associated with colposcopy-guided cervical biopsy.

Minimally invasive surgery versus laparotomy for radical hysterectomy in the management of early-stage cervical cancer: Survival outcomes.

OBJECTIVE: To compare oncologic and perioperative outcomes in patients who underwent minimally invasive surgery (MIS) compared to laparotomy for newly diagnosed early-stage cervical carcinoma. METHODS: We retrospectively identified patients who underwent radical hysterectomy for stage IA1 with lymphovascular invasion (LVI), IA2, or IB1 cervical carcinoma at our institution from 1/2007-12/2017. Clinicopathologic characteristics and surgical and oncologic survival outcomes were compared using appropriate statistical testing. Multivariable Cox regression analysis was used to control for potential confounders. RESULTS: We identified 196 evaluable cases-117 MIS (106 robotic [90.6%]) and 79 laparotomy cases. Cohorts had similar age, BMI, substage, histologic subtype, clinical and pathologic tumor size, positive margins, and presence of LVI. The MIS group had more cases with no residual tumor in the hysterectomy (24.8% vs. 10.1%, P = 0.01). The laparotomy group had more cases with positive nodes (29.1% vs. 17.1%, P = 0.046) and more patients who received adjuvant therapy (53.2% vs. 33.3%, P = 0.006). Median follow-up was ~4 years. Five-year disease-free survival (DFS) rates were 87.0% in the MIS group and 86.6% in the laparotomy group (P = 0.92); 5-year disease-specific survival (DSS) rates were 96.5% and 93.9%, respectively (P = 0.93); and 5-year overall survival (OS) rates were 96.5% and 87.4%, respectively (P = 0.15). MIS was not associated with DFS, DSS, or OS on multivariable regression analysis. The rate of postoperative complications was significantly lower in the MIS cohort (11.1% vs. 20.3%; P = 0.04). CONCLUSIONS: MIS radical hysterectomy for cervical carcinoma did not confer worse oncologic outcomes in our single-center and concurrent series of patients with early-stage cervical carcinoma.

Interpregnancy interval and abnormally invasive placentation.

INTRODUCTION: The presence of a previous uterine scar is a strong risk factor for developing abnormally invasive placentation (AIP). We sought to determine whether a short interpregnancy interval predisposes to AIP. We hypothesized that a short interpregnancy interval after a previous cesarean delivery increases the risk of AIP in comparison with a longer interpregnancy interval. MATERIAL AND METHODS: We performed a retrospective cohort study of women with a histological diagnosis of AIP and a history of a previous cesarean section. Women were included in the control group if they had a previous cesarean section with a placenta underlying the previous uterine scar or an anterior previa. The time interval between pregnancy and AIP data was analyzed using the chi-square test and two-tailed Fisher's exact test. RESULTS: There was no statistical difference in the interpregnancy interval between women who had AIP vs the control group. Gravidity and parity were found to be significantly higher in the women with AIP vs the controls. CONCLUSIONS: These results suggest that a short interpregnancy interval may not increase the risk of developing AIP.

Is Robotic-Assisted Surgery Safe in the Elderly Population? An Analysis of Gynecologic Procedures in Patients ≥ 65 Years Old.

BACKGROUND: The elderly population is expanding worldwide but is underrepresented in clinical trials. We sought to assess the safety of robotic gynecologic surgery in an elderly cohort and to identify factors associated with unfavorable outcomes. METHODS: All patients ≥ 65 years who underwent a robotically assisted procedure at a single institution between May 2007 to December 2016 were divided into three age groups: 65-74 (Group 1); 75-84 (Group 2); ≥ 85 (Group 3). Perioperative outcomes were recorded in patients who did not require conversion to laparotomy. We compared clinical variables among groups and performed multivariate logistic regression to detect variables associated with major complications (≥ Grade 3) or 90-day mortality. RESULTS: We retrospectively identified 982 cases: 685 in Group 1; 249 in Group 2; 48 in Group 3. Median age = 71 years. Median BMI = 28.9. Malignancy was documented in 72.8% of cases; the majority were endometrial cancer (61.8%). Thirty-four patients (3.5%) were readmitted within 30 days. Seventy-seven (7.8%) had a postoperative complication, and 23 (2.3%) had a major complication. Ninety-day mortality was 0.5%. There was significant difference between groups with respect to body mass index (P = 0.026), ECOG PS (P ≤ 0.001), > 5 comorbidities (P = 0.005), hospital stay (P < 0.001), major complications (P = 0.001), and 90-day mortality (P < 0.001). On multivariable logistic regression, age ≥ 85 years was associated with major complications. Body mass index, age ≥ 85 years, and major complications were significantly associated with 90-day mortality. CONCLUSIONS: Robotic-assisted surgery appears to be safe in an elderly cohort. The incidence of overall and major complications is consistent with those reported in the literature. Patients ≥ 85 years old appear to be at higher risk of unfavorable outcomes.

Prophylactic Hypogastric Artery Ligation during Placenta Percreta Surgery: A Retrospective Cohort Study.

Objective To evaluate if prophylactic hypogastric artery ligation (HAL) decreases surgical blood loss and blood products transfused. Study Design This is a retrospective cohort study comparing patients with placenta percreta undergoing prophylactic HAL at the time of cesarean hysterectomy versus those who did not. Data were presented as means ± standard deviations, proportions, or medians with interquartile ranges. Demographic and clinical data were compared in the groups using Student's t -test for normally distributed data or the Mann-Whitney U test for nonnormally distributed data. Fisher's exact test was used for proportions and categorical variables. Data are reported as significant where p was <0.05. Results There were 26 patients included in the control group with no HAL and 11 patients included in the study group. Estimated blood loss for the study group was 1,000 mL versus 800 mL in the control. Units of PRCBs transfused were 4.5 units in the study group versus 2 units for the control group. None of these measures were found to be statistically significant. Conclusion Our data suggest there was no benefit in the use of prophylactic HAL in decreasing surgical blood loss or amount of blood products transfused in patients who had a cesarean hysterectomy performed for placenta percreta. Précis Prophylactic HAL does not decrease blood loss during surgery for placenta percreta.

Use of the Tei Index in the Conservative Management of TRAP Sequence Pregnancies Diagnosed during the Periviable Period: A Case Series.

Twin Reverse Arterial Perfusion (TRAP) Sequence is a rare complication of monochorionic pregnancies. Without intervention, the viable pump twin in a case of TRAP Sequence may develop high output cardiac failure leading to an intrauterine fetal demise. We present 3 cases of TRAP Sequence pregnancy diagnosed during the second or third trimesters of pregnancy. There are minimal sonographic tools for the guidance of a fetal therapeutic interventional procedure during the second trimester or timing of delivery during the third trimester to reduce morbidity and mortality of a viable fetus. Tei index may be a useful sonographic tool in the management of TRAP Sequence during the second or third trimester of pregnancy.

Primary signet ring cell adenocarcinoma of the uterine cervix - A rare neoplasm that raises the question of metastasis to the cervix.

Primary signet ring cell adenocarcinoma is extremely rare. Signet ring cell carcinoma is more commonly primary in the stomach or breast, and the more likely metastatic disease to the cervix needs to be ruled out. We present a case of primary signet ring cell carcinoma of the cervix and review the literature.