Feasibility and safety of planned early discharge following laparotomy in gynecologic oncology with enhanced recovery protocol including opioid-sparing anesthesia.

Objective: This study aims to evaluate the feasibility and safety of planned postoperative day 1 discharge (PPOD1) among patients who undergo laparotomy (XL) in the department of gynecology oncology utilizing a modified enhanced recovery after surgery (ERAS) protocol including opioid-sparing anesthesia (OSA) and defined discharge criteria. Methods: Patients undergoing XL and minimally invasive surgery (MIS) were enrolled in this prospective, observational cohort study after the departmental implementation of a modified ERAS protocol. The primary outcome was quality of life (QoL) using SF36, PROMIS GI, and ICIQ-FLUTS at baseline and 2- and 6-week postoperative visits. Statistical significance was assessed using the two-tailed Student's t-test and non-parametric Mann-Whitney two-sample test. Results: Of the 141 subjects, no significant demographic differences were observed between the XL group and the MIS group. The majority of subjects, 84.7% (61), in the XL group had gynecologic malignancy [vs. MIS group; 21 (29.2%), p < 0.001]. All patients tolerated OSA. The XL group required higher intraoperative opioids [7.1 ± 9.2 morphine milligram equivalents (MME) vs. 3.9 ± 6.9 MME, p = 0.02] and longer surgical time (114.2 ± 41 min vs. 96.8 ± 32.1 min, p = 0.006). No significant difference was noted in the opioid requirements at the immediate postoperative phase and the rest of the postoperative day (POD) 0 or POD 1. In the XL group, 69 patients (73.6%) were successfully discharged home on POD1. There was no increase in the PROMIS score at 2 and 6 weeks compared to the preoperative phase. The readmission rates within 30 days after surgery (XL 4.2% vs. MIS 1.4%, p = 0.62), rates of surgical site infection (XL 0% vs. MIS 2.8%, p = 0.24), and mean number of post-discharge phone calls (0 vs. 0, p = 0.41) were comparable between the two groups. Although QoL scores were significantly lower than baseline in four of the nine QoL domains at 2 weeks post-laparotomy, all except physical health recovered by the 6-week time point. Conclusions: PPOD1 is a safe and feasible strategy for XL performed in the gynecologic oncology department. PPOD1 did not increase opioid requirements, readmission rates compared to MIS, and patient-reported constipation and nausea/vomiting compared to the preoperative phase.

Increasing trends of cervical conization with lymph node evaluation for fertility-sparing surgery in early cervical cancer.

OBJECTIVE: To examine uptake, characteristics, and survival outcome of less-radical fertility-sparing surgery with cervical conization and lymph node evaluation (Cone-LN) in reproductive age patients with early cervical cancer. METHODS: This retrospective cohort study examined the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. The study population included 407 patients aged <50 years with stage IA-IB2 (≤4 cm) cervical cancer who received fertility-sparing surgery from 2004 to 2019. The exposure was fertility-sparing surgery type: Cone-LN (n = 196) or trachelectomy with lymph node evaluation (Trach-LN, n = 211). The main co-outcomes were (i) temporal trends of surgery type, assessed with Cochran-Armitage test, and (ii) clinical and tumor characteristics, assessed with multivariable binary logistic regression model. The secondary outcome was overall survival, assessed with inverse probability of treatment weighting propensity score. RESULTS: The number of patients receiving Cone-LN increased from 43.5% in 2004-2007 to 58.4% in 2016-2019 (P-trend = 0.005). Patients receiving conization and sentinel lymph node (SLN) biopsy alone increased from 0% to 14.4% (P-trend < 0.001). In a multivariable analysis, patients in the Cone-LN group were more likely to undergo SLN biopsy (aOR 6.04) compared to those in the Trach-LN group whereas those with adenocarcinoma (aOR 0.49) and T1b tumors (aOR for ≤2 cm 0.21, and aOR for 2.1-4.0 cm 0.10) were less likely to receive Cone-LN. In a propensity score-weighted model, the Cone-LN and Trach-LN groups had comparable overall survival (7-year rates, 98.9% vs 97.8%). Similar associations were observed for patients with squamous, adenocarcinoma / adenosquamous, T1a classification, and T1b(≤2 cm) classification. CONCLUSION: The current population-based analysis suggests that the performance of cervical conization with lymph node evaluation, particularly with SLN biopsy, is gradually increasing for early cervical cancer patients desiring future fertility.

Prognostic features of endometrial cancer metastasis to the central nervous system.

OBJECTIVES: Central nervous system metastases (CNSm) secondary to endometrial cancer (EC) are rare. As a result, prognostic factors for this patient population are not well described. METHODS: EC patients with CNSm were identified retrospectively from two academic centers. EC patients without CNSm (non-CNSm) were used as controls. Chi-square and Fisher's exact tests were used for analysis of categorial variables. Wilcoxon tests were used for quantitative measures. Overall survival (OS) was compared with Log-rank test. Cox proportional hazard models were used to estimate hazard ratios for OS. RESULTS: 22 EC patients with CNSm and 354 non-CNSm patients were included. Compared to non-CNSm EC, the CNSm cohort was younger (58.5 vs 62.0 years, p = 0.018) with lower BMI (27.7 vs. 33.7 kg/m2, p = 0.005), and had more advanced stages (p = ≤ 0.001), grade 3 tumors (81.8% CNSm vs 25.1% non CNSm, p≤0.001) and serous histology (22.7% vs 8.5%, p = 0.010). Median survival after CNSm diagnosis was 9 months (95% CI 4, NA). CNSm was a strong poor prognostic factor (HR death 4.96, p = 0.022). Improved OS was seen with CNS as the only disease site (83m CNSm only vs 30m additional sites, p = 0.007) and less than five CNSm (49m <5 vs. 23m ≥5, p = 0.004). Surgical resection of CNSm (OS 83m surgery vs 33m no surgery, p = 0.003) or multimodal therapy (83m multimodal vs 33m single therapy, p = 0.027) resulted in longer OS. CONCLUSIONS: CNSm is a poor prognostic factor in EC, however, low volume disease with aggressive treatment may result in more favorable survival outcomes.

Fertility-Sparing Surgery for Early-Stage Cervical Cancer: A Systematic Review of the Literature.

OBJECTIVE: This systematic review aimed to evaluate oncologic and reproductive outcomes after fertility-sparing surgery (FSS) for early-stage cervical cancer (early CC). DATA SOURCES: Ovid MEDLINE, Ovid EMBASE, and Cochrane CENTRAL were searched from 1980 to the present using Medical Subject Headings terms; other controlled vocabulary terms; and keywords related to fertility, cervical cancer, and surgical techniques. METHODS OF STUDY SELECTION: A total of 2415 studies were screened, with 53 studies included. Studies reporting recurrences with a median follow-up of 12 months in early CC (International Federation of Gynecology and Obstetrics 2009 stages IA with lymphovascular space invasion, IB, or IIA) of traditional histologic type undergoing FSS were included. TABULATION, INTEGRATION, AND RESULTS: The studies were grouped by intervention, including vaginal radical trachelectomy (VRT), abdominal radical trachelectomy (ART), minimally invasive radical trachelectomy (MIS-RT), and conization or simple trachelectomy (ST), and studies involving neoadjuvant chemotherapy (NACT). Combined rates of recurrence (RR), cancer death (CDR), pregnancy (PR), and live birth (LBR) were calculated per procedure on the basis of all included studies that reported outcomes on that procedure. The results were as follows: VRT: RR 4%, CDR 1.7%, PR 49.4%, and LBR 65.0% ART: RR 3.9%, CDR 1.4%, PR 43.2%, and LBR 44.0% MIS-RT: RR 4.2%, CDR 0.7%, PR 36.2%, and LBR 57.1% Cone or ST: RR 4.2%, CDR 0.8%, PR 55.1%, and LBR 71.9% NACT: RR 7.5% and CDR 2.0% CONCLUSION: FSS of early CC with VRT, ART, or MIS-RT have comparable oncologic outcomes in carefully selected patients, with reproductive outcomes favoring VRT. Data on nonradical FSS with cone or ST are less robust but support similar oncologic outcomes to radical trachelectomy with fewer reproductive complications. NACT in this setting requires more investigation before routine implementation into practice.

Predictors of response to immune checkpoint inhibition in a real world gynecologic cancer population.

Prognostic factors for immune checkpoint inhibitor (CPI) response in gynecologic cancer are limited. This retrospective study aimed to identify prognostic factors associated with improved overall response rate (ORR) and progression free survival (PFS) in gynecologic cancer patients receiving at least two cycles of CPI. PFS was compared by univariate cox regressions. Univariate and multivariable analyses were used for prognostic factors of PFS and ORR. 72 patients were identified (20 ovarian, 36 endometrial, 13 cervix, 1 vaginal, 2 others). Immune related adverse events (IRAE) occurred in 40.3% of patients (29/72). IRAE was associated with higher ORR (44.8% IRAE vs 20.9% no IRAE, OR 3.1, p = 0.024), improved PFS (12.9 m IRAE vs 4.7 m no IRAE, HR 0.43, p = 0.004) and improved OS (22.9 m IRAE vs 12.2 m no IRAE, HR 0.47, p = 0.021). Additionally, Clear cell histology had superior ORR compared to MSI stable endometrial and ovarian cancers (ORR 57.1% vs 11.8%, OR 10.0, p = 0.032). Responders more often had ARIDIA mutation, PI3K/PTEN alteration and less often had a P53 mutation. In a subset of six MSI-H, recurrent, chemo-naive endometrial cancer ORR was 83.3%. Overall, we found favorable outcomes after CPI for clear cell tumors and patients who developed IRAE. Additionally, first-line systemic therapy with CPI in recurrent MSI-H endometrial cancer had encouraging ORR with durable responses.

Recurrence, death, and secondary malignancy after ovarian conservation for young women with early-stage low-grade endometrial cancer.

OBJECTIVE: To examine the association between ovarian conservation and oncologic outcome in surgically-treated young women with early-stage, low-grade endometrial cancer. METHODS: This multicenter retrospective study examined women aged <50 with stage I grade 1-2 endometrioid endometrial cancer who underwent primary surgery with hysterectomy from 2000 to 2014 (US cohort n = 1196, and Japan cohort n = 495). Recurrence patterns, survival, and the presence of a metachronous secondary malignancy were assessed based on ovarian conservation versus oophorectomy. RESULTS: During the study period, the ovarian conservation rate significantly increased in the US cohort from 5.4% to 16.4% (P = 0.020) whereas the rate was unchanged in the Japan cohort (6.3-8.7%, P = 0.787). In the US cohort, ovarian conservation was not associated with disease-free survival (hazard ratio [HR] 0.829, 95% confidence interval [CI] 0.188-3.663, P = 0.805), overall survival (HR not estimated, P = 0.981), or metachronous secondary malignancy (HR 1.787, 95% CI 0.603-5.295, P = 0.295). In the Japan cohort, ovarian conservation was associated with decreased disease-free survival (HR 5.214, 95% CI 1.557-17.464, P = 0.007) and an increased risk of a metachronous secondary malignancy, particularly ovarian cancer (HR 7.119, 95% CI 1.349-37.554, P = 0.021), but was not associated with overall survival (HR not estimated, P = 0.987). Ovarian recurrence or metachronous secondary ovarian cancer occurred after a median time of 5.9 years, and all cases were salvaged. CONCLUSION: Our study suggests that adoption of ovarian conservation in young women with early-stage low-grade endometrial cancer varies by population. Ovarian conservation for young women with early-stage, low-grade endometrial cancer may be potentially associated with increased risks of ovarian recurrence or metachronous secondary ovarian cancer in certain populations; nevertheless, ovarian conservation did not negatively impact overall survival.

Metastatic uterine tumor resembling ovarian sex cord tumor: A case report and review of the literature.

Uterine tumors resembling ovarian sex cord tumors (UTROSCTs) are rare and commonly characterized as benign tumors, with infrequent reports of metastasis and recurrence. Treatment recommendations have not been well established, particularly for more advanced cases. We present the first reported death from a metastatic UTROSCT, summarize the available literature, and describe characteristics common to UTROSCTs with aggressive features. In this case, a 49-year-old woman presented with abdominal distension and pain; initial imaging and diagnostic workup suggested metastatic epithelial ovarian cancer to be the cause. The patient subsequently underwent neoadjuvant chemotherapy followed by optimal cytoreductive surgery and adjuvant chemotherapy. Final pathology revealed UTROSCT with omental and peritoneal metastases. She then underwent adjuvant chemotherapy with subsequent recurrence and died 15 months after her initial diagnosis. Our analysis of this case and the available literature led us to identify pathologic risk factors that may help predict aggressive UTROSCT behavior.

Organically modified silica nanoparticles are biocompatible and can be targeted to neurons in vivo.

The application of nanotechnology in biological research is beginning to have a major impact leading to the development of new types of tools for human health. One focus of nanobiotechnology is the development of nanoparticle-based formulations for use in drug or gene delivery systems. However most of the nano probes currently in use have varying levels of toxicity in cells or whole organisms and therefore are not suitable for in vivo application or long-term use. Here we test the potential of a novel silica based nanoparticle (organically modified silica, ORMOSIL) in living neurons within a whole organism. We show that feeding ORMOSIL nanoparticles to Drosophila has no effect on viability. ORMOSIL nanoparticles penetrate into living brains, neuronal cell bodies and axonal projections. In the neuronal cell body, nanoparticles are present in the cytoplasm, but not in the nucleus. Strikingly, incorporation of ORMOSIL nanoparticles into the brain did not induce aberrant neuronal death or interfered with normal neuronal processes. Our results in Drosophila indicate that these novel silica based nanoparticles are biocompatible and not toxic to whole organisms, and has potential for the development of long-term applications.

In vivo visualization of synaptic vesicles within Drosophila larval segmental axons.

Elucidating the mechanisms of axonal transport has shown to be very important in determining how defects in long distance transport affect different neurological diseases. Defects in this essential process can have detrimental effects on neuronal functioning and development. We have developed a dissection protocol that is designed to expose the Drosophila larval segmental nerves to view axonal transport in real time. We have adapted this protocol for live imaging from the one published by Hurd and Saxton (1996) used for immunolocalization of larval segmental nerves. Careful dissection and proper buffer conditions are critical for maximizing the lifespan of the dissected larvae. When properly done, dissected larvae have shown robust vesicle transport for 2-3 hours under physiological conditions. We use the UAS-GAL4 method to express GFP-tagged APP or synaptotagmin vesicles within a single axon or many axons in larval segmental nerves by using different neuronal GAL4 drivers. Other fluorescently tagged markers, for example mitochondria (MitoTracker) or lysosomes (LysoTracker), can be also applied to the larvae before viewing. GFP-vesicle movement and particle movement can be viewed simultaneously using separate wavelengths.