An Unusual Presentation: High-Grade Serous Carcinoma of the Fallopian Tube Manifesting With Altered Mental Status Secondary to a Single Brain Metastasis-A Case Report and Review of the Literature.

Epithelial ovarian and fallopian cancers are aggressive lesions that rarely metastasize to the central nervous system. Brain metastases usually occur in the setting of known primary disease or widespread metastatic disease. However, in extremely rare cases, an isolated intracranial neoplasm may be the first presentation of fallopian cancer. To the best of our knowledge, only one such case has been reported previously. We present an illustrative case with multimodality imaging and histopathologic correlation of a fallopian tube carcinoma first presenting with altered mental status secondary to an isolated brain metastasis. A 64-year-old female with no pertinent medical history presented with altered mentation. Initial workup identified a 1.6 cm avidly enhancing, solitary brain lesion at the gray-white junction with associated vasogenic edema concerning for either central nervous system lymphoma or metastatic disease. Additional imaging identified a 7.5 × 3 cm left adnexal lesion, initially thought to be a hydrosalpinx with hemorrhage, but magnetic resonance imaging suggested gynecologic malignancy. No lesions elsewhere in the body were identified. Given the lack of locoregional or systemic disease, the intracranial and pelvic lesions were assumed to represent synchronous but distinct processes. The intracranial lesion was biopsied. Preliminary results were suggestive of lymphoma, but further analysis was consistent with high-grade serous carcinoma of müllerian origin. Positron emission tomography/computed tomography was performed to evaluate for other neoplastic lesions, only highlighting the intracranial and pelvic lesions. At this point, a diagnosis of metastatic fallopian cancer was made. The patient was taken for robot-assisted laparoscopy with surgical debulking of the pelvic neoplasm, pathology demonstrating high-grade serous carcinoma of the fallopian tube, matching that of the intracranial lesion. Even though rare, metastatic fallopian cancer should be considered in patients with isolated brain lesions and adnexal lesions, even in the absence of locoregional or systemic disease.

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).

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.

Does MIS Play a Role in the Treatment of Advanced Ovarian Cancer?

Neoadjuvant chemotherapy allows a minimally invasive approach for interval debulking in patients with ovarian cancer considered unresectable to no residual disease by laparotomy at diagnosis. The aim of the study was to evaluate the type of surgical approach at interval debulking (ID) after three courses of carboplatin and taxol in patients with unresectable ovarian cancer at diagnosis compared with the type of surgical approach at primary debulking (PD). A secondary objective was to compare the perioperative outcomes of MIS vs. laparotomy at ID. A retrospective review of the type of surgical approach at ID following three courses of carboplatin and taxol was compared with the surgical approach at PD, and a review of the perioperative outcomes of MIS vs. open at ID was performed during the period from 21 January 2012, through 21 February 2013, for stage IIIC > 2 cm or IV epithelial ovarian cancer (EOC) unresectable at diagnosis and the surgical approach at PD. During the study period, 127 patients with stage IIIC or IV EOC met the inclusion criteria. Minimally invasive surgery (MIS), laparoscopic or robotic, was used in 21.6% of patients at ID and in 23.3% of patients at PD. At ID, MIS patients had a shorter hospital stay as compared to laparotomy (2 vs. 8 days; p < 0.001). At 5 year follow-up, 31.5% of EOC patients were alive (ID MIS: 47.5% vs. ID open: 30%; PD MIS: 41% vs. PD open: 28%), while 24.4% had no evidence of disease (ID MIS: 39% vs. ID open: 19.5%; PD MIS: 32% vs. PD open: 22%). Among living patients, 22% had evidence of disease. Neoadjuvant chemotherapy is a form of chemo-debulking and allows a minimally invasive approach at interval debulking in about one-fifth of the patients, with initial disease deemed unresectable to no residual tumor at initial diagnosis.

Granulomatosis with Polyangiitis-Mimicking Advanced Gynecological Cancer: A Case Report and Systematic Review of the Literature.

(1) Background: Granulomatosis with polyangiitis (GPA) is a necrotizing vasculitis that mimics gynecologic cancer. In GPA patients, the genitourinary system is affected in <1%. The objective of the study was to provide a systematic review of the literature of GPA patients with gynecological involvement. (2) Methods: PubMed and Embase were searched from inception to July 2021 for GPA patients with gynecological involvement Medical Subject Headings (MeSH) and free-text terms. Exclusion criteria were other language, review articles, pregnancy, fertility, or male patients. Data were extracted on clinical evolution, symptoms, examinations findings, diagnosis delay, treatment, outcome, patient status, and follow-up. (3) Results: Seventeen studies included data from patients with GPA and primary or relapsed gynecological involvement. 68% of the authors of this review thought the patient had cancer. The main gynecological symptom is bleeding, but exclusive gynecologic symptomatology is rare (ENT: 63%, lungs: 44%, kidneys-urinary tract: 53%). GPA could affect all areas of the genital tract, but the most frequent location is the uterine cervix. Medical treatment for GPA is effective. (4) Conclusions: GPA of the female genital tract must be considered when biopsies of an ulcerated malignant-appearing cervical or vaginal mass are negative for malignancy even when they are unspecific. Rheumatology consultation is indicated.

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.

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.

Robotic LESS and Reduced-Port Hysterectomy Using the da Vinci SP Surgical System: A Single-Institution Case Series.

STUDY OBJECTIVE: To present a series of robotic laparoendoscopic single-site surgery (LESS) and reduced-port hysterectomy cases and discuss the surgical technique required for successful use on this new platform. DESIGN: Retrospective case series. SETTING: Academic medical center. PATIENTS: All patients undergoing robotic LESS or reduced-port hysterectomy with the SP1098 da Vinci SP Surgical System (Intuitive Surgical, Sunnyvale, CA) from December 2019 to March 2020. INTERVENTIONS: Robotic LESS or reduced-port hysterectomy. MEASUREMENTS AND MAIN RESULTS: A total of 8 cases of hysterectomy were performed successfully. Four cases included concomitant resection of endometriosis. Five cases required placement of an additional port. The average uterine weight was 136.1 g ± 61.5 g (range 87-246). The average estimated blood loss was 37.5 mL ± 27 mL (range 20-100). The average operative time was 86.5 minutes ± 27.1 minutes (range 60-132). The time required for vaginal cuff closure was available for patients 5 to 8, and ranged from 10 minutes to 13 minutes. All patients had same-day discharge. There were no conversions to alternative surgical modality, complications, or readmissions. CONCLUSION: Our preliminary experience with the SP1098 da Vinci SP Surgical System demonstrated the technical feasibility and safety of this surgical modality for gynecologic surgery. Additional studies examining postoperative outcomes and prospective studies comparing this modality with traditional robotic surgery are indicated.

Surgical or imaging lymph node assessment in locally advanced cervical cancer: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the survival impact of imaging vs surgical nodal assessment in patients with cervical cancer stage IB2-IVA prior to definitive chemoradiotherapy (CRT). METHODS: PubMed, MEDLINE, Cochrane Library, and ClinicalTrials.gov were used to search for publications in English and Chinese over a 50-year period. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols was used to conduct this review. Inclusion criteria were studies that compared survival outcomes in International Federation of Gynecology and Obstetrics 2009 stage IB2-IVA cervical cancer patients with pre-therapy pelvic and/or aortic lymphadenectomy (LND) or imaging. One or more of the following modalities were used for nodal assessment: computed tomography (CT), magnetic resonance imaging, or positron emission tomography-CT. The National Institutes of Health Quality Assessment Tool was utilized to assess study quality. RESULTS: The initial search identified 65 studies, and five met the inclusion criteria. There were a total of 1,112 patients. Seven hundred and fifty-four underwent pelvic and/or aortic LND and 358 had imaging. When compared to LND, imaging had a sensitivity and specificity of 88.9% and 22.2% for pelvic lymph node (LN), and 33%-62.5% and 92%-95.5% for para-aortic LN. There were no differences in progression-free survival (PFS) (hazard ratio [HR]=1.13; 95% confidence interval [CI]=0.73-1.74; I²=75%; p<0.01) and overall survival (OS) (HR=1.06; 95% CI=0.66-1.69; I²=75%; p<0.01) between surgical and imaging nodal assessment. CONCLUSIONS: Imaging and surgical nodal assessment has comparable PFS and OS in patients with cervical cancer stage IB2-IVA. TRIAL REGISTRATION: PROSPERO Identifier: CRD42020155486.

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.

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.

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.

Robotic Resection of Diaphragm Metastases in Ovarian Cancer: Technical Aspects.

Diaphragm metastases in ovarian cancer can be safely resected robotically in selected patients. The technique is similar to laparotomy, whether it is a peritoneal or full-thickness excision. Trocar placement is very important for successful resection and is dependent on the location of the disease. Metastases involving the left diaphragm and the ventral aspect of the right diaphragm are accessed with trocars placed slightly cranial to the umbilicus. Metastases in the dorsal aspect of the right diaphragm are removed with trocars in the upper quadrants. Metastases located in the lateral portion of the right diaphragm are excised using an infrahepatic approach, and those in the medial aspect are removed using a suprahepatic approach. In peritoneal resection, monopolar instruments must be kept at 10 W to 15 W to prevent contraction of the diaphragm and pleural perforation. Intraoperative pleural decompression is performed via an aspirating catheter. A video of the technique described in this report is available online (Supplementary Video 1).