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To evaluate the impact of frailty on postoperative complications following cytoreductive surgery (CRS) with hyperthermic intra-peritoneal chemotherapy (HIPEC) in women with advanced or recurrent gynecologic cancer.An IRB-approved single-institution prospective registry was queried for women who underwent CRS with HIPEC for advanced or recurrent gynecologic cancer from 1/1/2014-12/31/2020. Frailty was defined as a modified Frailty Index (mFI) score of ≥2. Logistic regression was used to assess the impact of mFI upon the rate of moderate or higher (≥ grade 2) Accordion postoperative complications.Of 141 women, 81.6% (n = 115) were non-frail with mFI of 0-1 and 18.4% (n = 26) were frail with mFI ≥2. The incidence of ≥ grade 2 complications was 21.2% (n = 14) for mFI = 0, 26.5% (n = 13) for mFI = 1, 64.7% (n = 11) for mFI = 2 and 100.0% (n = 9) for patients with mFI ≥3. The incidence of re-operation (1.7% vs. 11.5%, p = 0.044), ICU admission (13.2% vs. 34.6%, p = 0.018), acute kidney injury (6.3% vs. 30.8%, p = 0.001), and respiratory failure (0.9% vs. 19.2%, p0.001) were significantly lower amongst non-frail vs. frail women. On multivariable analysis, mFI ≥2 was associated with significantly increased ≥ grade 2 complications versus mFI of 0-1 (OR 9.4, 95% CI 3.3, 26.4, p0.001). Age (OR 1.04, 95% CI 1.00, 1.09, p = 0.07), surgical indication (recurrent vs. primary) (OR 0.71, 95% CI 0.30, 1.7, p = 0.44) and Surgical Complexity Score of Intermediate or High vs. Low (OR 1.5, 95% CI 0.67, 3.5, p = 0.31) were not associated with ≥grade 2 complications.Frailty, defined by the modified frailty index, is predictive of ≥grade 2 postoperative complications following CRS with HIPEC in women with gynecologic cancer. Frailty screening before CRS with HIPEC may assist patient selection and improve postoperative outcomes.

Objective(s) To identify recurrence patterns and outcomes in women with advanced or recurrent epithelial ovarian cancer (EOC) after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Methods This is an IRB-approved single-institution cohort study of women who underwent CRS+HIPEC for advanced or recurrent EOC followed in a prospective registry from 1/12/2014–3/1/2020. Recurrence locations were defined as pelvic, upper abdominal (UA) and/or extra-peritoneal (EP). Univariate analysis assessed associations between recurrence location, progression-free survival (PFS), and overall survival (OS). Results In total, 92 women with EOC underwent interval (56.5%; n=52) or recurrent CRS+HIPEC (43.5%; n=40). For interval CRS+HIPEC, recurrence locations were pelvic in 50.0% (n=15), UA in 23.3% (n=7) and EP in 56.7% (n=17); 40.0% (n=12) were EP alone. Similarly, for recurrent CRS+HIPEC, recurrence locations were pelvic (22.5%, n=9), UA (5.0%, n=2) and EP (60.0%, n=24); 66.7% (n=20) were EP alone. For both interval and recurrent CRS+HIPEC, median PFS was 10.5 vs. 13.0 months for pelvic and UA vs. EP only recurrences (p=0.02). Similarly, median OS was 29.2 months for pelvic and UA and not reached for EP only (p=0.05). For interval CRS+HIPEC, there was no difference in median PFS (10.6 vs. 11.7 months, p=0.68) and OS (27.1 vs. 24.8 months, p=0.96) for pelvic and UA vs EP alone. However, for recurrent CRS+HIPEC, pelvic and UA sites of recurrence were associated with reduced PFS (10.0 vs. 18.1 months, p=0.03) and OS (33.6 months vs. not reached, p=0.02) vs. EP only. Conclusions In women with advanced or recurrent EOC undergoing CRS+HIPEC, one-half of patients experience their first recurrence outside of the peritoneal cavity. Providers must be aware of the risk of EP failure in patients treated with CRS+HIPEC.

Das neuroendokrine Karzinom der Cervix uteri ist eine seltene und aggressive Form von Gebärmutterhalskrebs, die durch häufige Metastasierung schon bei Diagnosestellung und durch hohe Rezidivraten gekennzeichnet ist. Die Primärtherapie ist multimodal und beinhaltet oft eine Chemotherapie, zum Teil in Verbindung mit einer Strahlentherapie. Es liegen keine Daten vor, die Orientierung für das Vorgehen bei Rezidiven geben; Zweitlinientherapien werden aus Daten zum kleinzelligen Bronchialkarzinom abgeleitet. Die engmaschige Überwachung dieser Patientinnen im Hinblick auf Rezidive ist von größter Bedeutung. Dafür stellt die Bestimmung der zirkulierenden Tumor-DNA (ctDNA) im peripheren Blut eine attraktive, weil nicht-invasive Option dar. Mit dem ULP-WGS-Verfahren (ultra-low-pass whole-genome sequencing) lassen sich die Tumorlast und das Tumoransprechen beurteilen und Prognosen zur Rezidivierung abgeben; allerdings mangelt es bisher noch an Daten zur Rolle der ULP-WGS beim kleinzelligen Zervixkarzinom. Die vorliegende Arbeit stellt eine Patientin vor, deren Chemotherapie-Ansprechen und Tumor-Rezidivierung durch die ctDNA-Analyse korrekt überwacht wurden, wie radiologische Befunde bestätigten.

To determine whether antibiotic treatment (ABX) during platinum chemotherapy (PC) for epithelial ovarian cancer (EOC) impacts progression-free survival (PFS) and overall survival (OS).Retrospective single institution cohort study in women with newly diagnosed stage III/IV EOC (n = 424) who underwent cytoreductive surgery (CRS) and PC from 2009 to 2015. ABX for48 h, including ABX against gram-positive (anti-G + ABX) bacteria were recorded. The impact of ABX on PFS and OS was assessed using univariate and multivariable Cox regression models.Of 424 eligible women, 34.7% (n = 147) received ABX, with 11.3% (n = 48) treated with anti-G + ABX. ABX decreased PFS (17.4 vs. 23.1 months, HR 1.50, 95% CI 1.20-1.88, p 0.001) and OS (45.6 vs. 62.4 months, HR 1.63, 95% CI 1.27-2.08, p 0.001) compared to no ABX. Similarly, anti-G + ABX worsened PFS (16.5 vs. 23.1 months; HR 1.85, 95% CI 1.33-2.55) and OS (35.0 vs. 62.4 months; HR 2.12, 95% CI 1.50-3.0, p 0.001). On multivariable analysis, all ABX and anti-G + ABX significantly worsened PFS (HR 1.31, 95% CI 1.04-1.65, p = 0.02), (HR 1.50, 95% CI 1.07-2.10, p = 0.02) and OS (HR 1.52, 95% CI 1.18-1.96, p = 0.001), (HR 1.83, 95% CI 1.27-2.62, p = 0.001) respectively. Increased Clavien Dindo score was associated with worsened PFS (1-2 - HR 1.52, 95% CI 1.14-2.03, p = 0.004; 3-4 - HR 1.86, 95% CI 1.27-2.72, p = 0.001) but not OS (1/2 - HR 1.35, 95% CI 0.97-1.88, p = 0.08; 3/4 - HR 1.53, 95% CI 1.00-2.34, p = 0.05); residual disease (p 0.05) and neoadjuvant chemotherapy (p 0.001) were associated with worse PFS and OS.In this retrospective cohort study of women with advanced EOC undergoing PC, ABX treatment was associated with decreased PFS and OS. Mechanistic studies are needed to investigate the negative impact of ABX upon PC response in EOC.

Purpose After definitive surgery, women with early-stage, low-risk endometrial cancer are observed. However, some will require salvage radiation therapy for recurrence. The purpose of this study was to evaluate our experience using salvage radiation for recurrent endometrial cancer in patients who did not receive upfront adjuvant therapy. Methods and Materials Twenty-eight women with endometrial cancer who had undergone initial definitive hysterectomy without adjuvant therapy developed isolated local or regional recurrence and were treated with salvage radiation in our department from 2004 to 2018. Salvage radiation included whole pelvic radiation, vaginal brachytherapy, or both. Patient and tumor characteristics, treatment details, and toxicities were recorded and analyzed. Results The median time to first recurrence was 1.7 years. First recurrences consisted of local recurrence in 23 patients, regional recurrence in 4, and both in 1. The median times from hysterectomy to first recurrence, local and regional, were 1.2 and 4.0 years, respectively. All patients underwent salvage radiation for management of their first recurrence. The median total equivalent dose in 2 Gy fractions for this treatment was 67.6 Gy (37.5–81.8 Gy). Two second recurrences occurred following salvage treatment, both local recurrence, at 6.5 and 13.5 months after radiation. The 2-year rates of local control, disease-free survival, and overall survival were 93%, 80%, and 88%, respectively. Treatment was well-tolerated, with low rates of gastrointestinal and genitourinary toxicity. Conclusions In this group of patients, salvage radiation therapy for local or regional recurrence of endometrial cancer resulted in excellent control with low rates of acute and chronic toxicities.

To assess incidence and oncologic outcomes in women with advanced epithelial ovarian cancer (EOC) with inguinal lymph node metastasis (ILNM) at diagnosis.An IRB-approved, retrospective single-institution cohort study was performed in women with stage III/IV EOC from 2009 to 2017. Patients with inguinal lymphadenopathy (defined as1 cm in short axis) clinically or radiographically were identified. The impact of ILNM on progression-free survival (PFS) and overall survival (OS) were assessed.Of the 562 women with advanced EOC, 18 (3.2%) had ILNM at diagnosis, accounting for 25.7% of all patients with stage IVB disease (n = 70). Five patients (27.7%) had a known genetic predisposition for EOC, including BRCA1 (11.1%, n = 2), BRCA2 (11.1%, n = 2) and BRIP1 (5.6%, n = 1). The majority of patients underwent optimal primary cytoreductive surgery (CRS), including debulking of inguinal nodal metastasis (83.3%, n = 15), with 50% (n = 9) having no gross residual disease after surgery. There was no difference in PFS (19.9 vs. 19.9 vs. 17.2 months, p = 0.84) or OS (137.2 vs. 52.9 vs. 67.6 months, p = 0.29) in women with stage III/IV with ILNM, stage III/IV without ILNM, and stage IVB disease without ILNM, respectively. Progression-free survival was improved in women with ILNM who underwent an optimal resection to no macroscopic disease vs. non-optimal resection (27.4 vs. 14.3 months, p = 0.019). Median overall survival at the time of analysis did not reach statistical significance (137.2 vs. 57.3 months, p = 0.24).In this retrospective cohort study, 3.2% of women with advanced EOC presented with ILNM at diagnosis. Although ILNM did not portend worse clinical outcomes compared to all Stage III/IV and Stage IVB patients, respectively, resection to no gross residual disease was associated with improved PFS.

Objective(s) To evaluate the incidence and associated risk factors for anastomotic failure following interval debulking surgery (IDS) with or without hyperthermic intraperitoneal chemotherapy (HIPEC) in women with advanced ovarian cancer. Methods We performed a retrospective cohort study in women with stage III/IV high-grade ovarian cancer treated with neoadjuvant chemotherapy followed by IDS with colorectal resection and HIPEC from 2017 to 2020. These patients were compared to a historical control cohort who underwent IDS with colorectal resection without HIPEC from 2009 to 2016. Data was collected for demographics, surgical variables, and perioperative outcomes. The univariate analysis compared progression-free survival and overall survival. Results 61 women were identified; 21 (34.4%) underwent IDS with HIPEC from 2017 to 2020, and 40 underwent IDS alone from 2009 to 2016. None of the patients who had IDS with HIPEC had protective ileostomy, compared to 10.0% of those who received had IDS alone (n = 4)(p = 0.29). The cumulative incidence of anastomotic leak rate was 8.2% (n = 5). There was no significant difference in anastomotic leak rate for women who underwent IDS with HIPEC (9.5%, n = 2) versus without HIPEC (7.5%, n = 3) (p = 0.99). While there was no difference in PFS (12.2 vs. 13.3 months, log-rank p = 0.31), OS (9.4 vs. 40.6 months, log-rank p = 0.013) was significantly decreased following postoperative anastomotic leak. Conclusions In this retrospective series of women with advanced ovarian cancer, HIPEC was not associated with increased risk for anastomotic leak at the time of IDS with colorectal resection and reanastomosis. While further study is needed, HIPEC alone should not preclude colorectal resection or dictate practices for colonic diversion in IDS.

ObjectiveTo evaluate perioperative outcomes in elderly versus non-elderly women with advanced or recurrent epithelial ovarian cancer undergoing surgery with hyperthermic intraperitoneal chemotherapy (HIPEC).MethodsA single-institution prospective registry was analyzed for women with ovarian cancer who underwent surgery with HIPEC from January 2014 to December 2020. Elderly age was defined as ≥65 years at surgery. Complications were defined according to the Accordion scale. Univariate and multivariable analysis was used to compare progression-free survival and overall survival.ResultsOf 127 women who underwent surgery with HIPEC, 33.1% (n=42) were ≥65 and 17.3% (n=22) were ≥70 years old. The median age for non-elderly and elderly patients were 55.7±8.3 versus 72.0±5.4 years, respectively (pConclusionsIn this prospective registry of women with ovarian cancer, perioperative morbidity is not increased for non-elderly versus elderly patients following surgery with HIPEC. While age should not exclude patients from surgery with HIPEC, additional research is needed regarding oncologic benefits in elderly women.

Objectives: To investigate progression-free survival (PFS) and peri-operative outcomes in women with EOC undergoing interval debulking surgery (IDS) with hyperthermic intraperitoneal chemotherapy (HIPEC) with paclitaxel/cisplatin (PC) vs single-agent cisplatin (C). Methods: This study was an Institutional Review Board approved, a single-institution cohort study of women with stage III or IV high-grade EOC treated from 1/1/2017-3/1/2020, followed in a prospective HIPEC registry with at least six months of follow-up. HIPEC regimen was administered at primary surgeon's discretion: C alone (80-100mg/m2 for 90 minutes) or P (135-175mg/m2 for 90 minutes) with C (80-100mg/m2 for 45 minutes) in a perfusate of normal saline at 41-43C degrees for 90 minutes, as previously described.3 PFS was defined as months from HIPEC date to recurrence. A Log-rank test was performed for PFS between PC vs. C. A p-value of Results: In total, 54 eligible patients underwent IDS with HIPEC following 3-4 cycles of NACT with carboplatin and paclitaxel were identified from a prospectively maintained HIPEC registry. Patients underwent HIPEC with C (51.9%, n=28) or PC (n=26; 48.1%). All patients underwent optimal cytoreduction to less than 1cm of residual disease. There were no differences in patient demographics, including age (67.4 vs 63.3 years, p=0.10), race (p=0.99), medical co-morbidities (p > 0.05), and pre-operative American Society of Anesthesiologists (ASA) score (III or IV - 64.3% vs 80.8%, p=0.18) for those who received C vs. PC. Additionally, the majority of patients had stage III disease (77.8% vs 76.9%, p=0.87) and serous histology (100.0% vs 92.3%, p=0.23). There were no differences in operative time (6.0 hours vs 5.3 hours, p=0.11) or surgical procedures performed, including small bowel (3.6% vs 3.8%, p=0.99) and large bowel resection (17.9% vs 23.1%, p=0.63). Notably, no differences in the Accordion postoperative adverse events were appreciated (None – 42.9% vs 42.3%; Mild – 25.0% vs 38.5%; Moderate – 21.4% vs 7.7%; Severe – 7.1% vs 11.5%; Death – 3.6% vs 0.0%; p=0.46). Additionally, there was no difference in need for blood transfusion (50.0% vs 57.7%, p=0.57), intra-operative vasopressor use (75.0% vs 92.3%, p=0.14) or ICU admission (7.1% vs 26.9%, p=0.07) The median PFS for the entire cohort was 15.7 months. However, when stratified by treatment regimen, PFS was 10.9 vs 22.2 months for C vs PC, respectively (HR 0.38, 95% CI 0.18, 0.81, p=0.009) (Figure). Conclusions: In this analysis of a prospective HIPEC registry, we demonstrate that PC is associated with a significantly improved PFS compared to C, without increased postoperative morbidity in patients with optimally cytoreduced stage III/IV EOC undergoing IDS with HIPEC. While further study is ongoing regarding overall survival benefit, consideration should be given for incorporation of P with C at the time of IDS with HIPEC. Download : Download high-res image (145KB) Download : Download full-size image

Neuroendocrine carcinoma of the cervix is a rare and aggressive form of cervical cancer that presents with frequent metastasis at diagnosis and high recurrence rates. Primary treatment is multimodal, which often includes chemotherapy with or without radiation therapy. There is no data available to guide treatment for recurrence, and second-line therapies are extrapolated from small cell lung carcinoma data. Close monitoring of these patients for recurrence is paramount. Evaluation of circulating tumor DNA (ctDNA) in the peripheral blood is an attractive approach due to its noninvasive nature. Ultra-low pass whole genome sequencing (ULP-WGS) can assess tumor burden, response to therapy, and predict recurrence; however, data are lacking regarding the role of ULP-WGS in small cell carcinoma of the cervix. This study demonstrates a patient whose response to chemotherapy and cancer recurrence was accurately monitored by ctDNA using ULP-WGS testing and confirmed with radiologic imaging findings.

Objective To determine peri-operative outcomes in women with advanced epithelial ovarian cancer (EOC) undergoing interval debulking surgery (IDS) with hyperthermic intraperitoneal chemotherapy (HIPEC) via minimally invasive interval debulking surgery (MIS) or laparotomy (LAP). Methods A single institution, retrospective cohort study was performed in women with EOC who underwent IDS with HIPEC from 2017 to 2019 via MIS or LAP. Peri-operative outcomes were compared using univariate analysis. Results In total, 50 eligible women were identified; ten (20.0%) underwent MIS + HIPEC and 40 (80.0%) LAP + HIPEC. The median age of patients in the MIS group was 71.1 vs. 64.2 years in LAP (p = 0.031). There was no significant difference in pre-operative complete radiographic response following NACT (p = 0.18). Notably, there was no difference in the rate of R0 resection (70.0% vs. 77.5%; p = 0.39). There was no significant difference in ICU admission, estimated blood loss, operative time, or use of vasopressors between the cohorts. Similarly, there was no difference in 30-day adverse events for MIS vs. LAP, but length of stay was decreased for those who underwent minimally invasive procedures (3 vs. 4 days, p = 0.016). Time to initiation of chemotherapy following surgery was not significantly different between groups (26.2 days vs 32.0 days, p = 0.090). With median follow-up of 15.1 months, there was no difference in recurrence free survival (median 15.0 vs 17.2 months log-rank, p = 0.30) for MIS vs. LAP. Conclusions In this retrospective cohort study, we demonstrate that in women with advanced EOC, HIPEC with MIS at the time of IDS following NACT is feasible. Our institutional experience demonstrates similar rates of R0 cytoreduction, compared to LAP. An MIS approach should not prevent surgeons from utilizing HIPEC where indicated for management of advanced EOC., Highlights • When comparing MIS and LAP at time of HIPEC, no differences are observed in adverse perioperative outcomes. • MIS was associated with shorter hospitalization and with no significant difference in the rate of R0 resections. • Patient candidacy for an MIS IDS should not prevent surgeons from utilizing HIPEC in appropriate candidates.

To evaluate additional treatments, symptoms, satisfaction and quality of life 1 year after vaginal and abdominal pelvic organ prolapse (POP) repair. Adult women enrolled in a prospective POP database were reviewed. Baseline and outcomes data 1 year after surgery were collected including the Pelvic Floor Distress Inventory (PFDI) and mailed surveys. Data were analyzed with descriptive statistics, Fisher’s exact tests and t tests. Of 222 women, 147 (66%) had vaginal and 75 (34%) had abdominal repair. Vaginal group patients were older (64.1 vs. 59.7 years; p = 0.003), but other demographic characteristics did not differ. Vaginal group patients had lower baseline anterior and apical prolapse grades (anterior 2.7 vs. 3.1, p = 0.003; apical 2.1 vs. 3.1, p

The compound [Pt(Et2dien)Cl]Cl, where Et2dien = N,N-diethyldiethylenetriamine, has been synthesized and reacted with N-acetylmethionine (N-AcMet) and guanosine 5′-monophosphate (5′-GMP). Reaction with 5′-GMP at pH 4 leads to formation of [Pt(Et2dien)(5′-GMP)]+, as expected. Reaction with N-AcMet occurs more rapidly than with 5′-GMP; when the reaction with N-AcMet occurs at low pH values (∼2), one set of resonances is observed initially but a second set of resonances appears over several days as the initial set decreases. The initial set of resonances disappears slowly (several days) at pH 2 but disappears much faster (minutes to hours) if the pH is 4 or higher; the initial resonances do not re-appear even if the pH is lowered. Reaction of the [Pt(Et2dien)Cl]+ with a mixture of N-AcMet and 5′-GMP at pH 4 leads to formation of a unique set of NMR resonances that does not correspond to the resonances of either the 5′-GMP or the N-AcMet products; mass spectrometry identifies a new product corresponding to [Pt(Et2dien)(N-AcMet)(5′-GMP)], in which the Et2dien ligand is bidentate. Such a complex is also observed if 5′-GMP is added to a sample of [Pt(Et2dien)(N-AcMet)]+ that has been kept at low pH, but it is not observed when N-AcMet is added to a sample of [Pt(Et2dien)(5′-GMP)]+. We propose that the additional set of resonances observed for [Pt(Et2dien)(N-AcMet)]+ at low pH is due to a less stable conformation of the complex and the addition of 5′-GMP when this less stable conformation exists leads to displacement of one of the nitrogen atoms.

Objectives The aim of this study was to conduct a systematic review and meta-analysis on the performance of the WHO's Fracture Risk Assessment (FRAX) instrument in predicting 10-year risk of Major Osteoporotic Fractures (MOF) and Hip Fractures (HF), using the USA treatment thresholds, in populations other than their derivation cohorts. Design EMBASE and MEDLINE database were searched with search engine PubMed and OVID as well as Google Scholar for the English-language literature from July 2008 to July 2016. Limiting our search to articles that analyzed only MOF and/or HF as an outcome, 7 longitudinal cohorts from 5 countries (USA, Poland, France, Canada, New Zealand) were identified and included in the meta-analysis. SAS NLMIXED procedure (SAS v 9.3) was applied to fit the Hierarchical Summary Receiver Operating Characteristics (HSROC) model for meta-analysis. Forest plot and HSROC plot was generated by Review Manager (RevMan v 5.3). Results Seven studies (n = 57,027) were analyzed to assess diagnostic accuracy of FRAX in predicting MOF, using 20% as the 10-year fracture risk threshold for intervention, the mean sensitivity, specificity, and diagnostic odds ratio (DOR) along with their 95% confidence intervals (CI) were 10.25% (3.76%–25.06%), 97.02% (91.17%–99.03%) and 3.71 (2.73–5.05), respectively. For HF prediction, using 3% as the 10-year fracture risk threshold, six studies (n = 50,944) were analyzed. The mean sensitivity, specificity, and DOR along with their 95% confidence intervals (CI) were 45.70% (24.88%–68.13%), 84.70% (76.41%–90.44%) and 4.66 (2.39–9.08), respectively. Conclusions Overall, using the 10 year intervention thresholds of 20% for MOF and 3% for HF, FRAX performed better in identifying patients who will not have a MOF or HF within 10 years, than those who will. A substantial number of patients who developed fractures, especially MOF within 10 years of follow up, were missed by the baseline FRAX assessment.

Introduction: Heterotopic pregnancy is the coexistence of intrauterine pregnancy (IUP) and extrauterine gestation. It is a rare and dangerous life-threatening situation that is difficult to diagnose and easily missed. The incidence in the general population is estimated to be 1 in 30,000. Risk factors for ectopic pregnancy are pelvic inflammatory disease (PID), tubo-ovarian abscess (TOA), previous ectopic pregnancies, or previous surgery. Case: A 22 year old gravida 2 para 1-0-0-1 presented to the emergency department (ED) and was diagnosed with heterotopic pregnancy despite lack of any notable risk factors. Transvaginal ultrasound showed live IUP and right ovarian/adnexal ectopic pregnancy with heartbeat, along with moderate hemoperitoneum. She underwent operative laparoscopy and right salpingectomy, being discharged home on post-operative day 1 with a stable hemoglobin concentration. She delivered the IUP at 38 weeks 5 days gestation via spontaneous vaginal delivery. Discussion: This case represents a spontaneous heterotopic pregnancy in a 22-year-old patient with no previous risk factors identified and demonstrates laparoscopy as a successful treatment modality for heterotopic pregnancy.