Same-day Discharge after Robotic Hysterectomy for Benign Conditions: Feasibility and Safety.

STUDY OBJECTIVE: To investigate the feasibility and predictive factors for same-day discharge (SDD) after robotic hysterectomy (RH) for benign indications to optimize patient selection by incorporating preoperative, intraoperative, and postoperative variables. DESIGN: A single-center retrospective cohort study. SETTING: Tertiary academic hospital. PATIENTS: Patients undergoing RH for benign indications. INTERVENTIONS: Patients were designated for SDD by implementing enhanced recovery after surgery protocol. MEASUREMENTS AND MAIN RESULTS: The study included 890 patients who underwent RH for benign indications between the years 2016 and 2021. Of these, 618 (69.4%) were discharged the same day and 272 (30.5%) were admitted for overnight stay. Both groups had similar age (46.4 vs 46.2 years), body mass index (28.3 vs 28.9), and indications for surgery. In multivariable logistic regression, factors that were significant for overnight stay were American Society of Anesthesiologists score 3, Charlson comorbidity index, previous laparotomy, and operative time. Other factors such as surgery start time and preoperative hemoglobin levels were not statistically significant. Postoperative outcomes were comparable for both groups with similar readmission and reoperation rates. CONCLUSION: The likelihood of SDD after RH in this cohort after implementing enhanced recovery after surgery protocol was almost 70%, and most of the predictive factors for overnight stay were nonmodifiable. Importantly, both groups had similar outcomes after surgery.

Does a Uterine Manipulator Increase the Distance of the Ureter to the Cervix and/or Vagina? An Anatomical Cadaver Study.

STUDY OBJECTIVE: To determine whether advancing a manipulator increased the distance of the ureter to the cervix and/or vagina. DESIGN: Prospective. SETTING: Academic institution. PATIENTS: A total of 22 intact fresh-frozen female pelvises. INTERVENTIONS: A total of 6 ureteral distances were measured per pelvis. Included were the following measurements on each side: (1) from the lateral cervical wall to the ureter at the intersection with the uterine artery; (2) from the lateral cervical wall to the parametrial ureter; and (3) from the vagina to the ureter at the intersection with the uterine artery. All measurements were obtained with and without advancement of a uterine manipulator. MEASUREMENTS AND MAIN RESULTS: The average distance from the ureter to the cervix and vagina without advancing the manipulator was 2.8 and 3.1 cm, respectively, and the distance from the parametrial ureter to the cervix was 3.3 cm. When the manipulator was advanced, all ureteral distances increased by 0.8, 0.6, and 0.6 cm, respectively, in 12 of the 22 pelvises (55%). Advancing the manipulator did not increase at least 1 of the distances in 10 of the 22 pelvises (45%). The advancement of the manipulator lengthened the 2 shortest ureteral distances of 1 cm noted in 1 pelvis (4.5%) by 0.9 and 0.4 cm. CONCLUSION: The uterine manipulator increased the distance of the ureter to the cervix and vagina for all measurements in 55.5% of the pelvises. The greatest increase was 0.9 cm. The manipulator did not increase at least 1 of the distances in 10 of the 22 pelvises (45.4%).

The shift from inpatient to outpatient hysterectomy for endometrial cancer in the United States: trends, enabling factors, cost, and safety.

OBJECTIVE: To evaluate trends in outpatient versus inpatient hysterectomy for endometrial cancer and assess enabling factors, cost and safety. METHODS: In this retrospective cohort study, patients aged 18 years or older who underwent hysterectomy for endometrial cancer between January 2008 and September 2015 were identified in the Premier Healthcare Database. The surgical approach for hysterectomy was classified as open/abdominal, vaginal, laparoscopic or robotic assisted. We described trends in surgical setting, perioperative costs and safety. The impact of patient, provider and hospital characteristics on outpatient migration was assessed using multivariate logistic regression. RESULTS: We identified 41 246 patients who met inclusion criteria. During the time period studied, we observed a 41.3% shift from inpatient to outpatient hysterectomy (p<0.0001), an increase in robotic hysterectomy, and a decrease in abdominal hysterectomy. The robotic hysterectomy approach, more recent procedure (year), and mid-sized hospital were factors that enabled outpatient hysterectomies; while abdominal hysterectomy, older age, Medicare insurance, black ethnicity, higher number of comorbidities, and concomitant procedures were associated with an inpatient setting. The shift towards outpatient hysterectomy led to a $2500 savings per case during the study period, in parallel to the increased robotic hysterectomy rates (p<0.001). The post-discharge 30-day readmission and complications rate after outpatient hysterectomy remained stable at around 2%. CONCLUSIONS: A significant shift from inpatient to outpatient setting was observed for hysterectomies performed for endometrial cancer over time. Minimally invasive surgery, particularly the robotic approach, facilitated this migration, preserving clinical outcomes and leading to reduction in costs.

Tumor-free margins and local recurrence in squamous cell carcinoma of the vulva.

OBJECTIVE: To investigate the relation of pathologic tumor-free margins and local recurrence in patients who underwent primary surgery for vulvar squamous cell carcinoma. METHODS: In this retrospective analysis, patients with stage I-III vulvar squamous cell carcinoma who underwent primary surgery between 2000 and 2018 were identified from the Mayo Clinic Cancer Registry. RESULTS: A total of 335 patients were included and divided into three groups according to tumor-free margins: group 1 (<3 mm, n = 32); group 2 (≥3 to <8 mm, n = 151); group 3 (≥8 mm, n = 152). The median follow-up time was 73 months (range 2-240). A total of 78 (23.3%) patients developed local recurrence. With the inverse propensity score weighing method adjusting baseline characters, margins <8 mm had inferior local control (HR 1.98, 95% CI 1.13-3.41). The 5-year local disease-free survival (DFS) was 48.2%, 81.5% and 84.6% for group 1, 2 and 3 respectively (p < 0.001). There were no differences in groin lymph nodes relapse (p = 0.850), distant metastases (p = 0.253), or disease-specific survival (DSS) (p = 0.289) among the three groups. Margins <8 mm, midline involvement, multifocal disease, precancerous lesions on margins and depth of invasion >1 mm were found to be poor prognosticators for local DFS in univariate analysis. Multifocal disease was the strongest predictor for local recurrence in multivariate analysis (HR 4.32, 95% CI 2.67-6.99). CONCLUSION: Patients undergoing primary surgery for vulvar squamous cell carcinoma with tumor free-margins <8 mm have a higher local recurrence rate.

Management and outcomes of primary vaginal Cancer.

OBJECTIVE: To analyze clinical characteristics and survival of patients with primary vaginal cancer. METHODS: Retrospective analysis of patients with primary squamous, adenocarcinoma and adenosquamous cell carcinoma of the vagina identified from the Mayo Clinic Cancer Registry between 1998 and 2018. RESULTS: A total of 124 patients were identified: stage I, 39 patients; stage II, 44, stage III, 20 and stage IV, 21. Patients with stage III and IV were older as compared to stage I and II. (mean ages 61 vs 67) (p = 0.024). Squamous cell carcinoma made up 71% of tumors. History of other malignancy was present in 24% patients. Median follow-up time was 60 months (range 1-240). Five-year PFS in stage I, II, III and IV was 58.7%, 59.4%, 67.3% and 31.8%, respectively (p = 0.039). Five-year DSS was 84.3%, 73.7%, 78.7% and 26.5% respectively (p < 0.001). Advanced stage, tumor size >4 cm, entire vaginal involvement, and lymph node (LN) metastasis were poor prognosticators in univariate analysis. Primary surgery in stage I/II patients had similar survival outcomes as compared to primary radiation, but post-operative RT rate was 55%. Brachytherapy alone was associated with a high local recurrence (80%) in stage I/II patients. The addition of brachytherapy had improved 5-year PFS and DSS than EBRT alone in patients with stage III/IVA. (p < 0.001). CONCLUSION: Surgery or radiation is effective treatment for vaginal cancer stage I and II. The addition of brachytherapy to external pelvic radiation increases survival in stages III-IV.

Comparing survival outcomes between surgical and radiographic lymph node assessment in locally advanced cervical cancer: A propensity score-matched analysis.

OBJECTIVE: To investigate progression-free survival (PFS) and overall survival (OS) between women who underwent surgical versus radiographic assessment of pelvic lymph nodes (PLN) and para-aortic lymph nodes (PALN) prior to chemoradiation therapy for cervical cancer. METHODS: In this retrospective cohort analysis, patients with stage IB2 - IIIB squamous cell, adenocarcinoma and adenosquamous carcinoma of the cervix who completed concurrent chemoradiation therapy (CCRT) between 2000 and 2017 from the Mayo Clinic Cancer Registry were identified. A 1:2 propensity score matching between surgical and imaging groups was performed and PFS and OS were compared between groups. RESULTS: 148 patients were identified and after propensity score matching, 35 from the surgical group and 70 from the imaging group were included in the analysis. There were no statistical differences in baseline characteristics between the 2 groups. The median follow-up time was 41 months (range 7-218) for the surgical group and 51.5 months (range 7-198) for the imaging group. Five-year PFS was 62.6% for the surgical group and 72.4% in imaging group (HR 1.11, 95% CI 0.54-2.30, p = 0.77). Five-year OS was 70.2% for the surgical group and 70.5% for the imaging group (HR 1.02, 95% CI 0.46-2.29, p = 0.96). FIGO stage, PALN metastasis, and parametrial involvement were found to be poor prognosticators for PFS and OS in univariate analysis. Only PALN metastasis significantly predicted unfavorable PFS (HR 2.76, 95% CI 1.23-6.18, p = 0.01) and OS (HR 3.46, 95% CI 1.40-8.55, p = 0.01) in multivariate analysis. There were no differences in locoregional recurrence and distant metastasis between the two groups (p = 0.33 and 0.59 respectively). CONCLUSION: Patients with cervical cancer who underwent radiographic assessment of PLN and PALN had comparable survival outcomes to surgical assessment.

Survival outcomes in patients with cervical cancer treated with open versus robotic radical hysterectomy: Our surgical pathology interrogation.

OBJECTIVE: To compare the survival outcomes and surgical radicality between women who underwent open versus robotic radical hysterectomy (RH) for early cervical cancer. METHODS: In this institutional retrospective study, patients with clinical stage IA2- IIA (FIGO 2009) squamous cell, adenocarcinoma and adenosquamous carcinoma of the cervix who underwent either open or robotic RH between 2000 and 2017 were identified. Parametrial width and vaginal length were re-measured from pathology slides. An inverse propensity score weighting model was used to adjust selection bias. RESULTS: A total of 333 patients were included (181 open, 152 robotic). The median follow-up time was 130 months for the open group and 53 months for the robotic group. There were 31 (17.1%) recurrences in the open and 21 (13.8%) in the robotic group. The 5-year progression-free survival (PFS) for the robotic and open group were 79.0% and 90.5%, respectively (HR 2.37, 95% CI 1.40-4.02). Five-year overall survival (OS) were 85.8% and 95.3%, respectively (HR 3.17, 95% CI 1.76-5.70). The mean parametrial width was similar between the open and robotic groups (2.5 vs 2.4 cm, p = 0.99). Unique recurrences (38.1%, 8/21) were noted in the robotic group: 2 port-site, 4 peritoneal, and 2 carcinomatosis. The time to vaginal recurrence was shorter in the robotic group than the open group (p = 0.001). CONCLUSION: Patients who underwent robotic RH had inferior PFS and OS compared to open surgery. Surgical radicality according to pathology measurements was similar between the two approaches.

Implementing robotic surgery for uterine cancer in the United States: Better outcomes without increased costs.

OBJECTIVE: To examine the effect of robotic-assisted surgery implementation for treatment of endometrial cancer in the United States on 30-day clinical outcomes and costs. METHODS: We retrospectively reviewed data of adult patients who underwent total hysterectomy for endometrial cancer in the US hospitals in Premier Healthcare Database between January 1, 2008 and September 30, 2015. We conducted trend analyses comparing the proportions of surgical approaches with the associated clinical outcomes and costs over the study period using Mann-Kendall tests. Clinical outcomes and costs of robotic-assisted surgery, laparoscopic and open surgery have been compared after propensity score 1:1 matching in the most recent 3 years (January 1, 2013-September 30, 2015). RESULTS: Of a total of 35,224 patients, use of robotic-assisted surgery increased from 9.48% to 56.82% while open surgery decreased from 70.4% to 28.1% over the study period. A 2.5% decrease in major complications (P < .001), a 2.9% decrease in minor complications (P = .001), and a 2.0% decrease 30-day readmissions (P = .001) was observed across all surgical approaches. Perioperative 30-day total cost slightly decreased from US $11,048 to US $10,322 (P = .08). Among propensity-score matched patients, robotic-assisted surgery was associated with shorter hospitalization than open surgery (median [interquartile range], 2.0 [2.0-3.0] vs 4.0 [3.0-6.0] days) and laparoscopic surgery (2.0 [2.0-3.0] vs 3.0 [2.0-4.0] days), fewer 30-day complications (20.1% vs 33.7%) (all P < .001), and comparable perioperative 30-day total costs (median [interquartile range], US $12,200 [US $9,509-US $16,341] vs US $12,018 [US $8,996-US $17,162]; P = .34) with open surgery. CONCLUSION: Robotic-assisted surgery facilitated the widespread diffusion of a minimally invasive approach nationally for endometrial cancer, with reduction of perioperative morbidity and no increase in overall treatment-related 30-day costs at national level.

The relation between social support, anxiety and distress symptoms and maternal fetal attachment.

OBJECTIVE: The aims of this study were to: (1) examine the relation between social support, trait anxiety, symptoms of maternal distress (including stress, depression and anxiety) and maternal-fetal attachment; and (2) to determine if social support buffers the relation between trait anxiety, symptoms of distress and maternal-fetal attachment. DESIGN: Ninety-four pregnant women completed five self-report questions. Two hierarchical regression analyses were conducted to examine the influence of trait anxiety, symptoms of distress, and social support on two factors of maternal-fetal attachment, quality and intensity/frequency. RESULTS: In the first model with the dependent measure as the maternal-fetal attachment quality score, trait anxiety (ß = -.24, p < .05) and social support (ß = .30, p < .01) were significant predictors, accounting for 18% of the variance. In the second model with the dependent measure as the maternal-fetal attachment intensity/frequency score, trait anxiety (ß = -.23, p < .05) and social support (ß = .32, p < .01) were significant predictors, accounting for 23% of the variance. In addition, the interaction term contributed a significant 4% of the variance, indicating that when social support is high, the relation between anxiety and maternal-fetal attachment intensity/frequency is attenuated. CONCLUSIONS: This study demonstrates that prenatal attachment is related to trait anxiety and social support. These findings suggest that interventions to decrease anxiety and increase social support could enhance maternal-fetal attachment.

Outcomes of Concurrent Breast and Gynecologic Risk Reduction Surgery.

BACKGROUND: Women considering risk reduction surgery after a diagnosis of breast/ovarian cancer and/or inherited cancer gene mutation face difficult decisions. The safety of combined breast and gynecologic surgery has not been well studied; therefore, we evaluated the outcomes for patients who have undergone coordinated multispecialty surgery. METHODS: We conducted a retrospective review of patients undergoing simultaneous breast and gynecologic surgery for newly or previously diagnosed breast cancer and/or an inherited cancer gene mutation during the same anesthetic at a single institution from 1999 to 2013. RESULTS: Seventy-three patients with a mean age of 50 years (range 27-88) were identified. Most patients had newly diagnosed breast cancer or ductal carcinoma in situ (62 %) and 28 patients (38 %) had an identified BRCA mutation. Almost all gynecologic procedures were for risk reduction or benign gynecologic conditions (97 %). Mastectomy was performed in 39 patients (53 %), the majority of whom (79 %) underwent immediate reconstruction. The most common gynecologic procedure involved bilateral salpingo-oophorectomy, which was performed alone in 18 patients (25 %) and combined with hysterectomy in 40 patients (55 %). A total of 32 patients (44 %) developed postoperative complications, most of which were minor and did not require surgical intervention or hospitalization. Two of the 19 patients who underwent implant reconstruction (11 %; 3 % of the entire cohort) had major infectious complications requiring explantation. CONCLUSION: Combined breast and gynecologic procedures for a breast cancer diagnosis and/or risk reduction in patients can be accomplished with acceptable morbidity. Concurrent operations, including reconstruction, can be offered to patients without negatively impacting their outcome.

Randomized controlled trial of postoperative belladonna and opium rectal suppositories in vaginal surgery.

BACKGROUND: After vaginal surgery, oral and parenteral narcotics are used commonly for pain relief, and their use may exacerbate the incidence of sedation, nausea, and vomiting, which ultimately delays convalescence. Previous studies have demonstrated that rectal analgesia after surgery results in lower pain scores and less intravenous morphine consumption. Belladonna and opium rectal suppositories may be used to relieve pain and minimize side effects; however, their efficacy has not been confirmed. OBJECTIVE: We aimed to evaluate the use of belladonna and opium suppositories for pain reduction in vaginal surgery. MATERIALS AND METHODS: A prospective, randomized, double-blind, placebo-controlled trial that used belladonna and opium suppositories after inpatient or outpatient vaginal surgery was conducted. Vaginal surgery was defined as (1) vaginal hysterectomy with uterosacral ligament suspension or (2) posthysterectomy prolapse repair that included uterosacral ligament suspension and/or colporrhaphy. Belladonna and opium 16A (16.2/60 mg) or placebo suppositories were administered rectally immediately after surgery and every 8 hours for a total of 3 doses. Patient-reported pain data were collected with the use of a visual analog scale (at 2, 4, 12, and 20 hours postoperatively. Opiate use was measured and converted into parenteral morphine equivalents. The primary outcome was pain, and secondary outcomes included pain medication, antiemetic medication, and a quality of recovery questionnaire. Adverse effects were surveyed at 24 hours and 7 days. Concomitant procedures for urinary incontinence or pelvic organ prolapse did not preclude enrollment. RESULTS: Ninety women were randomly assigned consecutively at a single institution under the care of a fellowship-trained surgeon group. Demographics did not differ among the groups with mean age of 55 years, procedure time of 97 minutes, and prolapse at 51%. Postoperative pain scores were equivalent among both groups at each time interval. The belladonna and opium group used a mean of 57 mg morphine compared with 66 mg for placebo (P=.43) in 24 hours. Patient satisfaction with recovery was similar (P=.59). Antiemetic and ketorolac use were comparable among groups. Subgroup analyses of patients with prolapse and patients <50 years old did not reveal differences in pain scores. The use of belladonna and opium suppositories was uncomplicated, and adverse effects, which included constipation and urinary retention, were similar among groups. CONCLUSION: Belladonna and opium suppositories are safe for use after vaginal surgery. Belladonna and opium suppositories did not reveal lower pain or substantially lower narcotic use. Further investigation may be warranted to identify a population that may benefit optimally from belladonna and opium use.

The role of sexuality symptoms in myeloproliferative neoplasm symptom burden and quality of life: An analysis by the MPN QOL International Study Group.

BACKGROUND: Patients with myeloproliferative neoplasms (MPNs) including polycythemia vera, essential thrombocythemia, and myelofibrosis, are faced with oppressive symptom profiles that compromise daily functioning and quality of life. Among these symptoms, sexuality-related symptoms have emerged as particularly prominent and largely unaddressed. In the current study, the authors evaluated how sexuality symptoms from MPN relate to other patient characteristics, disease features, treatments, and symptoms. METHODS: A total of 1971 patients with MPN (827 with essential thrombocythemia, 682 with polycythemia vera, 456 with myelofibrosis, and 6 classified as other) were prospectively evaluated and patient responses to the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ C30) were collected, along with information regarding individual disease characteristics and laboratory data. Sexuality scores were compared with an age-matched, healthy control population. RESULTS: Overall, patients with MPN were found to have greater sexual dysfunction compared with the healthy population (MPN-SAF score of 3.6 vs 2.0; P<.001), with 64% of patients with MPN describing some degree of sexual dysfunction and 43% experiencing severe symptoms. The presence of sexual symptoms correlated closely with all domains of patient functionality (physical, social, cognitive, emotional, and role functioning) and were associated with a reduced quality of life. Sexual problems also were found to be associated with other MPN symptoms, particularly depression and nocturnal and microvascular-related symptoms. Sexual dysfunction was more severe in patients aged >65 years and in those with cytopenias and transfusion requirements, and those receiving certain therapies such as immunomodulators or steroids. CONCLUSIONS: The results of the current study identify the topic of sexuality as a prominent issue for the MPN population, and this area would appear to benefit from additional investigation and management. Cancer 2016;122:1888-96. © 2016 American Cancer Society.

Human papillomavirus and occupational exposure: The need for vaccine provision for healthcare providers.

To probe the understanding of healthcare providers regarding occupational exposure to human papillomavirus and their knowledge about human papillomavirus vaccination in relation to the American Society for Colposcopy and Cervical Pathology (ASCCP) recommendations. In this cross-sectional study, the healthcare providers at Mayo Clinic Arizona, Florida, and Minnesota were delivered an electronic survey. The survey was completed by 349 healthcare providers, with one respondent excluded for inconsistent entry. The mean age of respondents was 42.7 ± 10.9, and of those, 68% were female and 32% were male. Of the unvaccinated respondents, 43.3% were ≤ 45 y of age (eligible for vaccination), while those vaccinated formed 41% of the respondents. Healthcare providers are highly concerned about their cancer safety, as shown by their awareness of occupational human papillomavirus hazards and broad knowledge about vaccine efficacy. The use of personal protective equipment varied widely, including eyewear, double gloving, procedural face mask, N95 face mask, and/or nothing. Human papillomavirus and cancer risk was clearly perceived by healthcare providers. For professions, pairwise comparisons revealed that nurse practitioners, physician assistants, certified registered nurse anesthetists, and allied healthcare providers had lower scores than medical doctors. Despite the high level of understanding among healthcare providers of occupational human papillomavirus exposure, only a few of them knew of the recommendations of the ASCPP for vaccination of healthcare providers treating human papillomavirus-related diseases. In such cases, most of those surveyed embraced vaccination, which was considered 100% safe by medical doctors and allied health professionals.

Same-day dismissal for endometrial cancer robotic surgery: feasibility factors.

The aim of this study was to investigate the factors in feasibility and safety of same-day dismissal (SDD) of endometrial cancer patients undergoing robotic hysterectomy and staging. A single-institution retrospective chart review of endometrial cancer patients who underwent robotic hysterectomy and staging between 2012 and 2021 was performed. Patient demographics, medical and surgical history, intra- and postoperative events were examined as possible factors related to non-SDD. These factors were analyzed using univariate (chi-square test) and multivariate logistic regression analysis. Of the 292 patients, 117 (40%) had SDD, and 175 (60%) had non-SDD. The SDD rate increased from 13.8% to 88% over the 10-year study period. The factors significantly associated with non-SDD (p < 0.05) were surgery in the first 5 years after the introduction of the SDD and ERAS protocols (2012-2016), age > 75 years, and comorbidities such as cardiovascular diseases, anemia (Hb < 11 g/dl), and anticoagulant therapy. Extensive adhesiolysis, the performance of complete pelvic and/or aortic lymphadenectomy, operating time > 180 min, and PACU discharge after 2:00 p.m. were significant factors for non-SDD. Sentinel lymph node sampling was significantly associated with SDD (OR 0.050; CI 0.273-0.934, p = 0.029). We reported no significant difference in the number, setting and timing of any unscheduled postoperative contacts, complications, and readmissions between SDD and non-SDD groups. SDD after robotic hysterectomy and staging for endometrial cancer is feasible and safe. There are patient and surgery factors for the failure of SDD. The sentinel lymph node sampling was significantly associated with achieving SDD. Trial registration: Institutional Review Board approved the study protocol (#: 1764-05).

A Phase III Study of Pafolacianine Injection (OTL38) for Intraoperative Imaging of Folate Receptor-Positive Ovarian Cancer (Study 006).

PURPOSE: The adjunctive use of intraoperative molecular imaging (IMI) is gaining acceptance as a potential means to improve outcomes for surgical resection of targetable tumors. This confirmatory study examined the use of pafolacianine for real-time detection of folate receptor-positive ovarian cancer. METHODS: This phase III, open-label, 11-center study included subjects with known or suspected ovarian cancer, scheduled to undergo cytoreductive surgery. The objectives were to confirm safety and efficacy of pafolacianine (0.025 mg/kg IV), given ≥ 1 hour before intraoperative near-infrared imaging to detect macroscopic lesions not detected by palpation and normal white light. RESULTS: From March 2018 through April 2020, 150 patients received a single infusion of pafolacianine (safety analysis set); 109 patients with folate receptor-positive ovarian cancer comprised the full analysis set for efficacy. In 33.0% of patients (95% CI, 24.3 to 42.7; P < .001), pafolacianine with near-infrared imaging identified additional cancer on tissue not planned for resection and not detected by white light assessment and palpation, exceeding the prespecified threshold of 10%. Among patients who underwent interval debulking surgery, the rate was 39.7% (95% CI, 27.0 to 53.4; P < .001). The sensitivity to detect ovarian cancer was 83%, and the patient false-positive rate was 24.8%. Investigators reported achieving complete R0 resection in 62.4% (68 of 109) of patients. Drug-related adverse events were reported by 30% of patients (45 of 150) and most commonly included nausea, vomiting, and abdominal pain. No drug-related serious adverse events or deaths were reported. CONCLUSION: This phase III study of pafolacianine met its primary efficacy end point, identifying additional cancers not otherwise identified or planned for resection. Pafolacianine may offer an important real-time adjunct to current surgical approaches for ovarian cancer.

PP4 inhibition sensitizes ovarian cancer to NK cell-mediated cytotoxicity via STAT1 activation and inflammatory signaling.

BACKGROUND: Increased infiltration of T cells into ovarian tumors has been repeatedly shown to be predictive of enhanced patient survival. However, despite the evidence of an active immune response in ovarian cancer (OC), the frequency of responses to immune checkpoint blockade (ICB) therapy in OC is much lower than other cancer types. Recent studies have highlighted that deficiencies in the DNA damage response (DDR) can drive increased genomic instability and tumor immunogenicity, which leads to enhanced responses to ICB. Protein phosphatase 4 (PP4) is a critical regulator of the DDR; however, its potential role in antitumor immunity is currently unknown. RESULTS: Our results show that the PP4 inhibitor, fostriecin, combined with carboplatin leads to increased carboplatin sensitivity, DNA damage, and micronuclei formation. Using multiple OC cell lines, we show that PP4 inhibition or PPP4C knockdown combined with carboplatin triggers inflammatory signaling via Nuclear factor kappa B (NF-κB) and signal transducer and activator of transcription 1 (STAT1) activation. This resulted in increased expression of the pro-inflammatory cytokines and chemokines: CCL5, CXCL10, and IL-6. In addition, IFNB1 expression was increased suggesting activation of the type I interferon response. Conditioned media from OC cells treated with the combination of PP4 inhibitor and carboplatin significantly increased migration of both CD8 T cell and natural killer (NK) cells over carboplatin treatment alone. Knockdown of stimulator of interferon genes (STING) in OC cells significantly abrogated the increase in CD8 T-cell migration induced by PP4 inhibition. Co-culture of NK-92 cells and OC cells with PPP4C or PPP4R3B knockdown resulted in strong induction of NK cell interferon-γ, increased degranulation, and increased NK cell-mediated cytotoxicity against OC cells. Stable knockdown of PP4C in a syngeneic, immunocompetent mouse model of OC resulted in significantly reduced tumor growth in vivo. Tumors with PP4C knockdown had increased infiltration of NK cells, NK T cells, and CD4+ T cells. Addition of low dose carboplatin treatment led to increased CD8+ T-cell infiltration in PP4C knockdown tumors as compared with the untreated PP4C knockdown tumors. CONCLUSIONS: Our work has identified a role for PP4 inhibition in promoting inflammatory signaling and enhanced immune cell effector function. These findings support the further investigation of PP4 inhibitors to enhance chemo-immunotherapy for OC treatment.

Radical Extirpation With Intraoperative Radiotherapy for Locally Recurrent Gynecologic Cancer: An Institutional Review.

OBJECTIVE: To report survival outcomes in patients with locally recurrent gynecologic cancers managed with curative-intent radical extirpation, perioperative external beam radiotherapy, and intraoperative radiotherapy (IORT). PATIENTS AND METHODS: We conducted a retrospective cohort analysis of 44 patients with locally recurrent gynecologic cancer treated at a single tertiary-care center (Mayo Clinic in Arizona) over a 15-year period (January 1, 2004, to July 31, 2019). This cohort included patients with uterine (n=21, 47.7%), ovarian (n=3, 6.8%), cervical (n=11, 25.0%), vaginal (n=2, 4.5%), vulvar (n=1, 2.3%), and unknown primary (n=6, 13.6%) cancer. Curative-intent radical extirpation included pelvic exenteration (n=13, 29.5%), laterally extended endopelvic resection (n=22, 50.0%), excision of para-aortic lymph node metastasis (n=8, 18.2%), and radical vaginectomy (n=1, 2.3%). Of the 44 patients in our cohort, 37 (84.1%) received IORT and 7 (15.9%) had intended to receive IORT but did not receive it. RESULTS: The median follow-up for the 44 patients was 12 months (range, 1 to 161 months). For patients who received IORT, the median progression-free survival (PFS) and overall survival (OS) were 13 and 21 months, respectively, and the 3-year cumulative incidence of central, locoregional, and distant recurrence was 27.0% (10 of 37), 40.5% (15 of 37), and 37.8% (14 of 37), respectively. Surgical margins were classified as negative (28 of 44, 63.6%), microscopic (11 of 44, 25.0%), or macroscopic (5 of 44, 11.4%). Negative, microscopic, and macroscopic surgical margins resulted in 3-year PFS of 51.8%, 20.5%, and 0%, respectively (P=.01) and 3-year OS of 62.9%, 20.0%, and 0%, respectively (P=.035). Progression-free survival (P=.69) and OS (P=.88) were not different between patients with negative surgical margins who received (n=21) and did not receive (n=7) IORT. Ten of 37 patients (27.0%) had development of grade 3 or higher toxicities, with 1 death due to sepsis. CONCLUSION: Complete tumor resection at the time of curative-intent radical extirpation achieved higher rates of PFS and OS regardless of IORT administration.

Instruction of Immunometabolism by Adipose Tissue: Implications for Cancer Progression.

Disruption of metabolic homeostasis at the organismal level can cause metabolic syndrome associated with obesity. The role of adipose tissue in cancer has been investigated over the last several decades with many studies implicating obesity as a risk factor for the development of cancer. Adipose tissue contains a diverse array of immune cell populations that promote metabolic homeostasis through a tightly controlled balance of pro- and anti-inflammatory signals. During obesity, pro-inflammatory cell types infiltrate and expand within the adipose tissue, exacerbating metabolic dysfunction. Some studies have now shown that the intracellular metabolism of immune cells is also deregulated by the lipid-rich environment in obesity. What is not fully understood, is how this may influence cancer progression, metastasis, and anti-tumor immunity. This review seeks to highlight our current understanding of the effect of adipose tissue on immune cell function and discuss how recent results offer new insight into the role that adipose tissue plays in cancer progression and anti-tumor immunity.

Current update on malignant epithelial ovarian tumors.

Epithelial ovarian cancer (EOC) represents the most frequently occurring gynecological malignancy, accounting for more than 70% of ovarian cancer deaths. Preoperative imaging plays an important role in assessing the extent of disease and guides the next step in surgical decision-making and operative planning. In this article, we will review the multimodality imaging features of various subtypes of EOC. We will also discuss the role of imaging in the staging, management, and surveillance of EOC.