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Inflammatory pseudotumor-like follicular dendritic cell sarcoma (IPT-like FDCS) is a rare malignancy with fewer than 150 cases in the literature. IPT-like FDCS follows an indolent course with most cases definitively managed with surgical resection. We present a case of IPT-like FDCS with multiple recurrences with a trial of immunotherapy. The patient initially presented with splenic involvement requiring splenectomy, subsequently recurring in the liver requiring hepatic resections. Afterwards, there was recurrence with pelvic/small bowel involvement for which treatment was trialed with ipilimumab and nivolumab. The patient progressed despite dual immune checkpoint inhibitor therapy requiring a small bowel resection. To date, this is the first case of immunotherapy use in IPT-like FDCS. Therefore, more evidence is needed to support additional treatments in recurrent IPT-like FDCS after resection. [ABSTRACT FROM AUTHOR]

Philadelphia chromosome (Ph)-like acute lymphoblastic leukaemia (ALL) is a high-risk subtype with a gene expression profile similar to Ph-positive ALL, due to activation of tyrosine kinase signalling. To understand the clinical implications of Ph-like ALL, this single-centre retrospective study evaluates outcomes in 268 adults, largely Hispanic ALL patients treated between 2013 and 2024, with a subgroup analysis of 139 haematopoietic stem cell transplantation (HSCT) patients. ALL subtypes included 68 (25.4%) Ph-like, 89 (33.2%) Ph-positive, and 111 (41.4%) Ph-negative. Ph-like patients were the youngest age at diagnosis (p = 0.007), most likely to have refractory disease (p < 0.001), and least likely to achieve minimal residual disease (MRD) negativity after induction (p = 0.031). Relative to Ph-negative ALL, Ph-like achieved worse event-free survival (EFS) (HR = 1.66; 95% CI 1.12-2.46; p = 0.012), whereas Ph-positive had improved EFS (HR = 0.60; 95% CI 0.38-0.93; p = 0.024) and cumulative incidence of relapse (CIR) (HR = 0.59; 95% CI 0.35-0.99; p = 0.046). Within the transplant subgroup, Ph status did not impact disease-free survival (DFS), CIR, or overall survival (OS). However, patients who received blinatumomab within 1-year pre-HSCT had improved DFS (HR = 0.43; 95% CI 0.20-0.94; p = 0.034) and CIR (HR = 0.26; 95% CI 0.09-0.75; p = 0.13). In conclusion, our data suggest that Ph-like is less likely to respond to standard induction therapy and HSCT may result in similar survival outcomes to Ph-negative ALL., (© 2024 British Society for Haematology and John Wiley & Sons Ltd.)

Background: Lung cancer screening with low-dose computed tomography (CT) scans (LDCT) has reduced mortality for patients with high-risk smoking histories, but it has significant limitations: LDCT screening implementation remains low, high rates of false-positive scans, and current guidelines exclude those without smoking histories. We sought to explore the utility of liquid biopsy (LBx) in early cancer screening and diagnosis of lung cancer., Methods: Using the high-definition single-cell assay workflow, we analyzed 99 peripheral blood samples from three cohorts: normal donors (NDs) with no known pathology (n = 50), screening CT patients (n = 25) with Lung-RADS score of 1-2, and biopsy (BX) patients (n = 24) with abnormal CT scans requiring tissue biopsy., Results: For CT and BX patients, demographic information was roughly equivalent; however, average pack-years smoked differed. A total of 14 (58%) BX patients were diagnosed with primary lung cancer (BX+). The comparison of the rare event enumerations among the cohorts revealed a greater incidence of total events, rare cells, and oncosomes, as well as specific cellular phenotypes in the CT and BX cohorts compared with the ND cohort. LBx analytes were also significantly elevated in the BX compared with the CT samples, but there was no difference between BX+ and BX- samples., Conclusions: The data support the utility of the LBx in distinguishing patients with an alveolar lesion from those without, providing a potential avenue for prescreening before LDCT., (© 2024 The Author(s). Thoracic Cancer published by John Wiley & Sons Australia, Ltd.)

Background: Hematopoietic stem cell transplantation (HSCT) is a pivotal treatment for high-risk acute lymphocytic leukemia (ALL), although limited by suitable human leukocyte antigen (HLA)-matched sibling donors (MSD). This study evaluates the impact of donor selection on outcomes in post-HSCT Hispanic B-cell ALL patients., Methodology: This single-center retrospective study evaluates outcomes in 88 adult Hispanic B-cell ALL patients who underwent haploidentical, MSD, or MUD myeloablative HSCT between 2013 and 2023., Results: Compared to Haploidentical transplants, MSD exhibited worse cumulative incidence of relapse (CIR) (HR = 3.39; P = 0.014) and disease-free survival (DFS) (HR = 2.44; P = 0.048) whereas MUD outcomes did not differ. This effect persisted even when controlling for pre-HSCT stage and Minimal residual disease (MRD) status. In addition, Ph-like was a significant predictor of worse DFS (HR = 3.60; P=0.014) and CIR (HR = 2.97; P=0.035) on multivariate analysis. Older donor age correlated with worse GVHD-free, relapse-free survival (GRFS) in haploidentical transplants (HR = 1.05; P=0.036)., Conclusion: Our data highlights improved outcomes with younger, haploidentical donors among Hispanic B-cell ALL patients undergoing myeloablative HSCT. This underscores the importance of donor selection in optimizing outcomes for ALL patients., Competing Interests: Declaration of Competing Interest None, (Copyright © 2024 Elsevier Ltd. All rights reserved.)

High-grade serous carcinoma (HGSC) is the most common and lethal ovarian cancer subtype. PARP inhibitors (PARPi) have become the mainstay of HGSC-targeted therapy, given that these tumors are driven by a high degree of genomic instability (GI) and homologous recombination (HR) defects. Nonetheless, approximately 30% of patients initially respond to treatment, ultimately relapsing with resistant disease. Thus, despite recent advances in drug development and an increased understanding of genetic alterations driving HGSC progression, mortality has not declined, highlighting the need for novel therapies. Using a small-molecule activator of protein phosphatase 2A (PP2A; SMAP-061), we investigated the mechanism by which PP2A stabilization induces apoptosis in patient-derived HGSC cells and xenograft (PDX) models alone or in combination with PARPi. We uncovered that PP2A genes essential for cellular transformation (B56α, B56γ, and PR72) and basal phosphatase activity (PP2A-A and -C) are heterozygously lost in the majority of HGSC. Moreover, loss of these PP2A genes correlates with worse overall patient survival. We show that SMAP-061-induced stabilization of PP2A inhibits the HR output by targeting RAD51, leading to chronic accumulation of DNA damage and ultimately apoptosis. Furthermore, combination of SMAP-061 and PARPi leads to enhanced apoptosis in both HR-proficient and HR-deficient HGSC cells and PDX models. Our studies identify PP2A as a novel regulator of HR and indicate PP2A modulators as a therapeutic therapy for HGSC. In summary, our findings further emphasize the potential of PP2A modulators to overcome PARPi insensitivity, given that targeting RAD51 presents benefits in overcoming PARPi resistance driven by BRCA1/2 mutation reversions., (©2023 The Authors; Published by the American Association for Cancer Research.)

Purpose: Clinical utility of up-front multigene panel testing (MGPT) is directly related to the frequency of pathogenic variants (PVs) in the population screened and how genetic findings can be used to guide treatment decision making and cancer prevention efforts. The benefit of MGPT for many common malignancies remains to be determined. In this study, we evaluated up-front MGPT in unselected patients with endometrial cancer (EC) to determine the frequency of PVs in cancer susceptibility genes., Methods: Patients with EC were prospectively enrolled at nine Ohio institutions from October 1, 2017, to December 31, 2020. Nine hundred and sixty-one patients with newly diagnosed EC underwent clinical germline MGPT for 47 cancer susceptibility genes. In addition to estimating the prevalence of germline PVs, the number of individuals identified with Lynch syndrome (LS) was compared between MGPT and tumor-based screening., Results: Likely pathogenic variants or PVs were identified in 97 of 961 women (10.1%). LS was diagnosed in 29 of 961 patients (3%; 95% CI, 2.1 to 4.3), with PVs in PMS2 most frequent. MGPT revealed nine patients with LS in addition to the 20 identified through routine tumor-based screening. BRCA1 and BRCA2 PVs were found in 1% (10 of 961; 95% CI, 0.6 to 1.9) of patients and that group was significantly enriched for type II ECs., Conclusion: This prospective, multicenter study revealed potentially actionable germline variants in 10% of unselected women with newly diagnosed EC, supporting the use of up-front MGPT for all EC patients. The discovery that BRCA1 or BRCA2 heterozygotes frequently had type II cancers points to therapeutic opportunities for women with aggressive histologic EC subtypes., Competing Interests: Heather HampelThis author is a member of the JCO Precision Oncology Editorial Board. Journal policy recused the author from having any role in the peer review of this manuscript.Stock and Other Ownership Interests: Genome MedicalConsulting or Advisory Role: Invitae, Genome Medical, Promega, 23andMe David CohnConsulting or Advisory Role: Oncology AnalyticsResearch Funding: NRG Oncology, Advaxis, Agenus, Ajinomoto, Array BioPharma, AstraZeneca, Bristol Myers Squibb, Clovis Oncology, Exelixis, Genentech, GlaxoSmithKline, Gynecologic Oncology Group, ImmunoGen, INC Research, inVentiv Health, Janssen Research & Development, Ludwig Institute for Cancer Research, EMD Serono, Stemcentrx, Tesaro, AbbVie, Henry Jackson Foundation, PharmaMar, Sanofi, Eisai, Pfizer, Novartis, Regeneron, Tricon PharmaceuticalsOther Relationship: Elsevier, UpToDate Joseph P. McElroyEmployment: Pfizer (I) Steven WaggonerConsulting or Advisory Role: Regeneron John NakayamaHonoraria: ZoomRx, Medscape, M3, Curio ScienceConsulting or Advisory Role: AstraZeneca, Clovis OncologySpeakers' Bureau: Merck, EisaiResearch Funding: Xodus Kim ResnickHonoraria: Clovis Oncology Sareena SinghSpeakers' Bureau: AstraZeneca, Merck Aine ClementsConsulting or Advisory Role: AstraZeneca, Tesaro/GSK Paul J. GoodfellowResearch Funding: PromegaNo other potential conflicts of interest were reported.

Objectives: To determine whether a specific estimated fetal weight (EFW) or abdominal circumference (AC) measurement percentile at the 18-to 24-week ultrasound (US) examination is associated with a small-for-gestational-age (SGA) neonate., Methods: A retrospective case-control study was conducted including women with uncomplicated singleton gestations who delivered a term SGA neonate identified as having a birth weight (BW) below the 10th percentile on the Olsen growth curve and had an 18- to 24-week US examination in our database. The study period was October 2011 to January 2018. A similar number of control charts were requested randomly over the same time with BW in the 10th to 90th percentiles, all which had an 18-to 24-week US examination in our database. After all neonates meeting BW criteria were identified, a chart review was performed to specifically evaluate biometric parameters from the US at 18 to 24 weeks to determine a potential correlation with the EFW percentile and AC percentile. Pregnancy, neonatal outcomes, and maternal demographic characteristics were collected., Results: A total of 549 term neonates with a BW below the 10th percentile, and 593 control term neonates with BW in the of 10th to 90th percentiles were reviewed. Our analyses revealed that the AC and EFW percentiles were poor predictors of BW (<10th percentile; areas under the receiver operating characteristic curves, 0.68 and 0.69, respectively). A similar low ability of AC and EFW to predict BW below the 5th percentile was noted., Conclusions: (1) No tipping point or cutoff for the EFW or AC percentile at the 18- to 24-week US examination was identified to predict a term SGA neonate. (2) These data are helpful when counseling women in midgestation about specific parameters, their importance, and the potential need for follow up imaging., (© 2020 by the American Institute of Ultrasound in Medicine.)

Objectives: Improving chronic obstructive pulmonary disease (COPD) care and reducing hospital readmissions is an urgent healthcare system priority. However, little is known about the organizational factors that underlie intersite variation in readmission rates. Evidence from other chronic diseases points to care coordination as one such factor., Study Design: To understand whether intersite differences in care coordination may be one of the organizational factors contributing to the variation in readmission rates, we examined provider perspectives on COPD care at Veterans Affairs (VA) sites., Methods: In this mixed-methods positive deviance study, we selected 3 VA sites in the lowest quartile and 3 in the highest quartile for 2016 risk-adjusted COPD readmission rates. During June to October 2017, we conducted semistructured interviews with primary and specialty care providers involved in COPD care at VA sites with low (n = 14) and high (n = 11) readmission rates., Results: Although providers at all sites referenced ongoing readmission reduction initiatives, only providers at low-readmission sites described practice environments characterized by high relational coordination (ie, high-quality work relationships and high-quality communication). They also reported fewer significant structural barriers to collaboration in areas like patient volume., Conclusions: The most notable differences between high- and low-readmission sites were related to the quality of relational coordination and the presence of structural barriers to coordination, rather than specific readmission reduction initiatives. Implementing organizational reforms aimed at enhancing relational coordination and removing structural barriers would enhance care for COPD and may improve quality of care for other chronic conditions.

Psychotic disorders are not uncommon in late life. These disorders often have varied etiologies, different clinical presentations, and are associated with significant morbidity and mortality among the older adult population. Psychotic disorders in late life develop due to the complex interaction between various biological, psychological, social, and environmental factors. Given the significant morbidity and mortality associated with psychotic disorders in late life, a comprehensive work-up should be conducted when they are encountered. The assessment should not only identify the potential etiologies for the psychotic disorders, but also recognize factors that predicts possible outcomes for these disorders. Treatment approaches for psychotic disorders in late life should include a combination of nonpharmacological management strategies with the judicious use of psychotropic medications. When antipsychotic medications are necessary, they should be used cautiously with the goal of optimizing outcomes with regular monitoring of their efficacy and adverse effects., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest., (© The Author(s), 2019.)

Somatic mutation of the protein phosphatase 2A (PP2A) Aα-subunit gene PPP2R1A is highly prevalent in high-grade endometrial carcinoma. The structural, molecular, and biological basis by which the most recurrent endometrial carcinoma-specific mutation site P179 facilitates features of endometrial carcinoma malignancy has yet to be fully determined. Here, we used a series of structural, biochemical, and biological approaches to investigate the impact of the P179R missense mutation on PP2A function. Enhanced sampling molecular dynamics simulations showed that arginine-to-proline substitution at the P179 residue changes the protein's stable conformation profile. A crystal structure of the tumor-derived PP2A mutant revealed marked changes in A-subunit conformation. Binding to the PP2A catalytic subunit was significantly impaired, disrupting holoenzyme formation and enzymatic activity. Cancer cells were dependent on PP2A disruption for sustained tumorigenic potential, and restoration of wild-type Aα in a patient-derived P179R-mutant cell line restored enzyme function and significantly attenuated tumorigenesis and metastasis in vivo . Furthermore, small molecule-mediated therapeutic reactivation of PP2A significantly inhibited tumorigenicity in vivo . These outcomes implicate PP2A functional inactivation as a critical component of high-grade endometrial carcinoma disease pathogenesis. Moreover, they highlight PP2A reactivation as a potential therapeutic strategy for patients who harbor P179R PPP2R1A mutations. SIGNIFICANCE: This study characterizes a highly recurrent, disease-specific PP2A PPP2R1A mutation as a driver of endometrial carcinoma and a target for novel therapeutic development. See related commentary by Haines and Huang, p. 4009 ., (©2019 American Association for Cancer Research.)

Background: More and more Veterans are receiving care from community providers, increasing the need for effective coordination across health systems. For Veterans with chronic obstructive pulmonary disease (COPD), this need is intensified by complex comorbidity patterns that often include multiple providers co-managing patient care., Objectives: We sought to understand how VA providers perceive coordination with community providers for Veterans with COPD., Design: Qualitative study of VA providers., Methods: We selected six geographically diverse VA sites and conducted semi-structured telephone interviews with providers practicing in inpatient and/or outpatient settings who care for Veterans with COPD., Main Measures: Interviews focused on communication with community providers about discharge information and clinic management. We analyzed responses according to the principles of conventional content analysis, allowing inductive themes to emerge., Key Results: We interviewed 25 providers during the period of June to October 2017. Qualitative data analysis yielded five themes: (1) VA providers perceive communication challenges between VA and community providers, including difficult, inadequate, and delayed communication; (2) communication is facilitated by personal relationships across health systems; (3) the lack of electronic health record (EHR) interoperability impairs communication, resulting in transmission of unstructured data; (4) poor communication leads to duplicative efforts and wasted resources; and (5) providers frequently rely on patients to communicate about care taking place in the community., Conclusions: VA providers described major challenges in coordinating with community providers, leading to perceptions of delayed, missed, or duplicative care and jeopardizing the overall quality, safety, and efficiency of Veteran care. Our study highlights the need for system-level solutions to support coordination across health systems for Veterans with COPD and may have implications for other conditions that lead to recurrent hospitalization and/or care in the community.

Objective: To explore the pregnancy and childbirth experiences and preferences of women with a history of sexual trauma in order to identify trauma-informed care practices that health care providers may use to improve obstetric care., Methods: We conducted a qualitative study consisting of semistructured interviews with women who either self-identified as having a history of sexual trauma or did not. Participants were recruited from a tertiary care ambulatory clinic and had at least one birth experience within the past 3 years. Interviews were audio-recorded and transcribed verbatim. Grounded theory was used to derive themes using the participants' own words., Results: From 2015 to 2017, we interviewed 20 women with a history of sexual trauma and 10 without. Women with a history of sexual trauma desired clear communication about their history between prenatal care providers and the labor and delivery team. In the intrapartum period, they desired control over who was present in the labor room at the time of cervical examinations and for health care providers to avoid language that served as a stressing reminder of prior sexual trauma. They wanted control over the exposure of their bodies during labor and to be asked about their preference for a male health care provider. In the postpartum period, some women with a history of sexual trauma found breastfeeding healing and empowering., Conclusion: Women with a history of sexual trauma have clear needs, preferences, and recommendations for obstetric care providers regarding disclosure, cervical examinations, health care provider language, body exposure, and male health care providers. They offer insight into unique breastfeeding challenges and benefits.

Objective: Our objective was to examine the association of the modified frailty index (mFI) and non-home discharge in patients undergoing surgery for endometrial cancer (EMCA)., Methods: Patients who underwent surgery for EMCA from 2011 to 2012 were identified from the American College of Surgeons - Nastional Surigical Quality Improvement Project (ACS-NSQIP) database. Current Procedural Terminology (CPT) codes were used to identify surgical characteristics. We excluded patients who were already living in a non-home facility. To determine frailty, we used the NSQIP frailty index. For analysis purposes, patients with an mFI score ≥0.18 were defined as frail. Patients were divided into groups based on discharge destination. Logistic regression were used to identify predictors of post-operative non-home discharge., Results: 1216 patients were identified. 26 (2.1%) were discharged to a non-home facility. On multivariate analysis, patients who were discharged to a non-home facility were older (OR 1.09, 95% CI 1.04-1.14, p < 0.001), had a higher Body Mass Index (BMI) (OR 1.08, 95% CI 1.04-1.12, p < 0.001), were more likely to have disseminated cancer (OR 10.02, 95% CI 2.28-44.1, p = 0.002), and were frail (OR 1.95, 95% CI 1.91-5.01, p = 0.008). Undergoing minimally-invasive surgery was independently associated with discharge to home (OR 0.165, 95% CI 0.059-0.458, p = 0.001)., Conclusion: Frailty is associated with increased risk of non-home discharge in patients undergoing surgery for EMCA. The mFI can be easily calculated using patient characteristics that are readily available pre-operatively. This information can be used for pre-op counseling and to facilitate appropriate and timely discharge planning., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: To examine the impact of operative time on the development of post-operative medical and surgical complications in patients undergoing minimally-invasive surgery for endometrial cancer., Methods: Patients who underwent laparoscopic surgery for endometrial cancer from 2005 to 2014 were identified from the ACS-NSQIP database. Operative times were initially divided into hour-long intervals and complication rates were determined. Outcomes included development of any complication, medical complication, or surgical complication. Subsequent analysis were based on dividing patients into 2 groups based on operative times <240min and operative times ≥240min. Associations between categorical variables were determined using Chi-Squared and Fisher's exact tests. Differences between means of continuous variables were determined using Student's t-tests. Univariate and multivariate analysis using logistic regression were used to identify predictors of post-operative complications., Results: 9145 patients were included, of which 639 (7%) experienced a complication. As operative time increased, rates of complications also increased. Operative time ≥240min was associated with increased overall complication rate (11.7% vs. 6%, p<0.001), medical complication rate (9.3% vs. 4.2%, p<0.001), and surgical complication rate (3.9% vs. 2.4%, p=0.001). When performing multi-variate logistic regression of factors associated with increased complication rates, increased operative time, COPD, hypertension, diabetes, ASA class ≥3, dependent functional status, and chronic steroid use were found to be independently associated with increased complications. Lymphadenectomy was not associated with increased operative time or increase in complications., Conclusion: Increased operative time is independently associated with increased risk of developing complications after laparoscopic surgery for endometrial cancer., (Copyright © 2017. Published by Elsevier Inc.)

Background: Little is known about the feasibility of providing massage or music therapy to medical inpatients at urban safety-net hospitals or the impact these treatments may have on patient experience., Objective: To determine the feasibility of providing massage and music therapy to medical inpatients and to assess the impact of these interventions on patient experience., Design: Single-center 3-arm feasibility randomized controlled trial., Setting: Urban academic safety-net hospital., Patients: Adult inpatients on the Family Medicine ward., Interventions: Massage therapy consisted of a standardized protocol adapted from a previous perioperative study. Music therapy involved a preference assessment, personalized compact disc, music-facilitated coping, singing/playing music, and/or songwriting. Credentialed therapists provided the interventions., Measurements: Patient experience was measured with the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) within 7 days of discharge. We compared the proportion of patients in each study arm reporting "top box" scores for the following a priori HCAHPS domains: pain management, recommendation of hospital, and overall hospital rating. Responses to additional open-ended postdischarge questions were transcribed, coded independently, and analyzed for common themes., Results: From July to December 2014, 90 medical inpatients were enrolled; postdischarge data were collected on 68 (76%) medical inpatients. Participants were 70% females, 43% non-Hispanic black, and 23% Hispanic. No differences between groups were observed on HCAHPS. The qualitative analysis found that massage and music therapy were associated with improved overall hospital experience, pain management, and connectedness to the massage or music therapist., Conclusions: Providing music and massage therapy in an urban safety-net inpatient setting was feasible. There was no quantitative impact on HCAHPS. Qualitative findings suggest benefits related to an improved hospital experience, pain management, and connectedness to the massage or music therapist.

Background: Malignant ovarian germ cell tumors are rare, and often treatable with surgery and chemotherapy. Few data are available for treatment of platinum-resistant tumors., Case: A 31 year old gravida 0 with a 20 cm pelvic mass was found to have a malignant ovarian germ cell tumor after she underwent debulking surgery. She initially responded to chemotherapy; however her AFP began to rise before all cycles were completed. She underwent additional debulking surgery that was again suboptimal. She was then referred for salvage therapy with high-dose chemotherapy with stem cell transplant, which was successful and she has had no evidence of disease for over two years., Conclusion: High-dose chemotherapy with stem cell transplant is a viable salvage therapy for patients with platinum-resistant germ cell tumors.

Background . To determine the prognostic significance of pretreatment levels of circulating lymphocyte (CLC), neutrophil (CNC), and monocyte (CMC) counts in patients with locally advanced cervical carcinoma (CC) treated with definitive radiation. Methods . A retrospective, dual-institution review of patients with Stage IB2-IVA CC from 2005 to 2015. Progression-free (PFS) and Overall Survival (OS) were determined for high and low CLC, CNC, and CMC groups. Multivariate analysis was used to confirm prognostic value of baseline leukocyte counts. Results . 181 patients were included. Median follow-up time was 26 (3-89) months. CNC had no effect on PFS or OS. PFS was similar between CMC groups; however, OS was significantly improved for patients with low CMC (62.5 versus 45.3 months, p = 0.016). High CLC was associated with improved PFS (48.5 versus 27.8 months, p = 0.048) and OS (58.4 versus 34.9 months, p = 0.048). On multivariate analysis, high CNC was associated with increased relapse risk (HR 1.12, p = 0.006) and low CLC was associated with increased mortality risk (HR 0.67, p = 0.027). Conclusion . This study demonstrates that leukocyte values can provide prognostic information in CC. These hypothesis-generating findings warrant further prospective investigations., Competing Interests: The authors declare that there is no conflict of interests regarding the publication of this paper.

Objective: The objective of this study was to identify preoperative characteristics of patients that experience a delay in initiation of adjuvant chemotherapy after primary debulking surgery for ovarian cancer., Materials/methods: We performed a retrospective review of patients with Stage II to IV high-grade epithelial ovarian, tubal, and peritoneal carcinoma who underwent primary debulking surgery followed by adjuvant chemotherapy from 2005 to 2013. Patients were divided into 2 groups: Control (those who received their first cycle of chemotherapy within 6weeks of debulking surgery) vs. chemotherapy delay (those who received their first cycle of chemotherapy at an interval >6weeks from primary debulking surgery). Relevant clinical variables and survival outcomes were compared between the 2 groups using standard statistical methods., Results: A total of 221 patients were included in the analyses - 169 (76.5%) were in the control group and 52 (23.5%) were in the chemo delay group. On multi-variate analysis, risk factors that were significantly associated with a delay in initiation in chemotherapy included: age >65, albumin <3.5, and high age-adjusted Charlson Comorbidity Index score. Delay in chemotherapy initiation was associated with a shorter progression-free (p=0.014) but not overall survival (p=0.19)., Conclusions: Delay in initiation of chemotherapy affected 23.5% of patients in our study population. Easily identifiable risk factors for chemotherapy delay exist that can help us pre-operatively identify patients for which neoadjuvant chemotherapy may be a better treatment option. Further study into prospective modeling with these identified risk factors is warranted., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: Integrative Medicine Group Visits (IMGVs) are an 8-week outpatient medical group visit program for chronic pain patients combining mindfulness-based stress reduction (MBSR), integrative medicine, and patient education. The authors conducted a qualitative study with IMGV participants to better understand the effects of IMGVs on patients' health., Design: This qualitative study enrolled a convenience sample of 19 participants from the parent prospective observational cohort study of IMGVs (n = 65). All participants in the parent study were invited to participate., Setting: Boston Medical Center (BMC) is a private, not-for-profit, 496-bed, academic medical center and the largest safety net hospital in New England., Subjects: Individuals in this study had a diagnosis of chronic pain and/or one or more chronic conditions (e.g., diabetes, depression, or metabolic syndrome), had attended ≥1 group visit, and their 8-week session had ended before completing the interview., Methods: The authors conducted individual semi-structured interviews. Interviews were audio-taped, transcribed, and analyzed., Results: Participants cite gains from IMGVs including improved self-monitoring, self-regulation, and increased mindfulness. The group setting leads patients to feel "not alone" in their health conditions, gain a sense of perspective on their health, and share coping strategies in a supportive network. These improvements in physical and mental health improved clinical outcomes for participants including reductions in pain., Conclusions: Group visits and integrative medicine both offer some potential solutions in the treatment of chronic pain. Models such as IMGVs can help individuals living with chronic conditions, addressing their emotional and physical health needs., (© 2016 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background/aims: The aim of this study is to compare the distribution of anatomic sites of first recurrence in African American (AA) patients with ovarian carcinoma compared to Caucasians., Methods: Patients diagnosed with high-grade epithelial ovarian, fallopian tube or peritoneal carcinoma from 2007 to 2013 were identified. Patterns of recurrence were compared for AA and Caucasian patients. Progression-free survival (PFS) and overall survival (OS) were compared., Results: A total of 238 patients were included - 210 Caucasians and 28 AAs. At a follow-up time of 28 months, AAs were more likely to have multiple anatomic sites of recurrence rather than a single site when compared to Caucasians (63.6 vs. 35.5%, p = 0.01). Time to first recurrence was shorter for AA patients (12 vs. 18 months, p < 0.01). PFS and OS did not differ. AA patients with multiple sites of first recurrence had a significantly shorter OS than Caucasian patients with multiple sites of first recurrence (24 vs. 30 months, p = 0.022)., Conclusion: Patterns of first recurrence differ between AAs and Caucasians. AAs have shorter times to first recurrence and are more likely to have multiple anatomic sites involved. AA patients with multiple sites of recurrence have a shorter OS than Caucasian patients with multiple sites., (© 2015 S. Karger AG, Basel.)

Resistance to platinum-based chemotherapy is the major barrier to treating epithelial ovarian cancer. To improve patient outcomes, it is critical to identify the underlying mechanisms that promote platinum resistance. Emerging evidence supports the concept that platinum-based therapies are able to eliminate the bulk of differentiated cancer cells, but are unable to eliminate cancer initiating cells (CIC). To date, the relevant pathways that regulate ovarian CICs remain elusive. Several correlative studies have shown that Wnt/β-catenin pathway activation is associated with poor outcomes in patients with high-grade serous ovarian cancer (HGSOC). However, the functional relevance of these findings remain to be delineated. We have uncovered that Wnt/β-catenin pathway activation is a critical driver of HGSOC chemotherapy resistance, and targeted inhibition of this pathway, which eliminates CICs, represents a novel and effective treatment for chemoresistant HGSOC. Here we show that Wnt/β-catenin signaling is activated in ovarian CICs, and targeted inhibition of β-catenin potently sensitized cells to cisplatin and decreased CIC tumor sphere formation. Furthermore, the Wnt/β-catenin specific inhibitor iCG-001 potently sensitized cells to cisplatin and decreased stem-cell frequency in platinum resistant cells. Taken together, our data is the first report providing evidence that the Wnt/β-catenin signaling pathway maintains stem-like properties and drug resistance of primary HGSOC PDX derived platinum resistant models, and therapeutic targeting of this pathway with iCG-001/PRI-724, which has been shown to be well tolerated in Phase I trials, may be an effective treatment option.

Background: Wandering spleen is a rare and potentially devastating condition that can present in a variety of ways. Here we present a case that led to acute abdomen and hemoperitoneum in a young woman., Case: A 27-year-old woman with a history of human immunodeficiency virus (HIV), pelvic inflammatory disease, and tuboovarian abscess was readmitted to the hospital for intravenous antibiotic treatment. When her clinical picture did not improve, she underwent placement of a pelvic drain for abscess drainage. Overnight she developed an acute abdomen and hemorrhagic shock. She was taken to the operating room for an exploratory laparotomy, which revealed a ruptured spleen with a single, elongated vascular pedicle., Conclusion: Wandering spleen is a rare diagnosis, more common in reproductive-aged women, with potentially fatal complications. It is a necessary component of a differential diagnosis for acute abdomen in reproductive-aged women.

Objective: Cervical and vaginal cancers have virally-mediated or mutated defects in DNA damage repair responses, making these cancers sensible targets for ribonucleotide reductase inhibition during radiochemotherapy., Methods: We conducted a phase II study evaluating 3× weekly 2-hour intravenous 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, 25 mg/m(2)) co-administered with 1× weekly intravenous cisplatin (40 mg/m(2)) and daily pelvic radiation (45 Gy) in women with stage I(B2)-IV(B) cervical (n=22) or stage II-IV vaginal (n=3) cancers. Brachytherapy followed (40 Gy). Toxicity was monitored by common terminology criteria for adverse events (version 3.0). The primary end point of response was assessed by 3-month posttherapy 2-[(18)F] fluoro-2-deoxy-d-glucose positron emission tomography (PET/CT) and clinical examination., Results: 3-AP radiochemotherapy achieved clinical responses in 24 (96% [95% confidence interval: 80-99%]) of 25 patients (median follow-up 20 months, range 2-35 months). 23 (96% [95% confidence interval: 80-99%]) of 24 patients had 3-month posttherapy PET/CT scans that recorded metabolic activity in the cervix or vagina equal or less than that of the cardiac blood pool, suggesting complete metabolic responses. The most frequent 3-AP radiochemotherapy-related adverse events included fatigue, nausea, diarrhea, and reversible hematological and electrolyte abnormalities., Conclusions: The addition of 3-AP to cisplatin radiochemotherapy was tolerable and produced high rates of clinical and metabolic responses in women with cervical and vaginal cancers. Future randomized phase II and III clinical trials of 3-AP radiochemotherapy are warranted., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Introduction: The diagnosis of urethral diverticulum can be challenging given the vague or absent presenting symptoms. In addition, vaginal cancer can present with elusive symptoms--some parallel to urethral diverticula. A case of a bleeding ulcerated mass anticipated to be a vaginal cancer was instead identified as a benign urethral diverticulum. To the best of our knowledge, this is the first case report of a benign urethral diverticulum presenting as a bleeding, necrotic ulcerated mass., Case Presentation: A 52 year-old multiparous African-American woman presented with a 2-day history of heavy vaginal bleeding passing large clots and suprapubic pain. A pelvic examination revealed blood clots in the vagina along with a friable, fibrous ulcerated lesion on the anterior suburethral vagina, just left of the midline measuring 4 × 2cm. Initially, this mass was considered to be a vaginal cancer. Intraoperative diagnosis of a benign urethral diverticulum was made., Conclusions: The diagnosis of urethral diverticula based on the vast array of presenting symptoms, is difficult. This original case report may benefit both gynecologic oncologists and female pelvic surgeons and reconstructive surgeons to keep urethral diverticulum in the differential diagnosis when faced with a bleeding midline anterior vaginal mass. This unusual presentation of a urethral diverticulum demonstrates how similarly it may present to a vaginal cancerous mass.

A major mechanism of DNA repair related to homologous recombination is the Fanconi anemia (FA) pathway. FA genes collaborate with BRCA genes to form foci of DNA repair on chromatin after DNA damage or during the S phase of the cell cycle. Our goal was to develop a method capable of evaluating the functional status of the pathway in patients' tumor tissue, which could also be practically incorporated into large-scale screening. To develop this method, we first used Western immunoblot to detect FANCD2 protein monoubiquitination in fresh tumor specimens of patients with ovarian cancer undergoing surgery and stained formalin-fixed paraffin-embedded tumor tissue simultaneously with 4',6-diamidino-2-phenylindole, FANCD2, and Ki67 antibodies, eventually extending this method to other solid tumors. This triple stain permitted evaluation of the presence, or lack thereof, of FANCD2 subnuclear repair foci in proliferating cells by immunofluorescence microscopy. Overall, we evaluated 156 formalin-fixed paraffin-embedded tumor samples using the FA triple-staining immunofluorescence method. The ratios of FANCD2 foci-negative tumors in ovarian, lung, and breast tumor samples were 21%, 20%, and 29.4%, respectively. Our studies have led to the development of a suitable method for screening, capable of identifying tumors with somatic functional defects in the FA pathway. The use of paraffin-embedded tissues renders the reported method suitable for large-scale screening to select patients for treatment with DNA interstrand crosslinking agents, poly ADP-ribose polymerase inhibitors, or their combination., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Background: Recurrent gynecologic cancers are often difficult to manage without significant morbidity. We conducted a phase II study to assess the safety and the efficacy of ablative robotic stereotactic body radiosurgery (SBRT) in women with metastatic gynecologic cancers., Methods: A total of 50 patients with recurrent gynecologic cancer who had single or multiple (≤4) metastases underwent robotic-armed Cyberknife SBRT (24Gy/3 daily doses). Toxicities were graded prospectively by common toxicity criteria for adverse events (version 4.0). SBRT target responses were recorded following RECIST criteria (version 1.0). Rates of clinical benefit for SBRT and non-radiosurgical disease relapse were calculated. Disease-free and overall survivals were estimated by the Kaplan-Meier method and the Cox proportional hazards model was used to control for prognostic variables., Findings: SBRT was safely delivered, with 49 (98%) of 50 patients completing three prescribed fractions. The most frequent grade 2 or higher adverse events attributed to SBRT included fatigue (16%), nausea (8%), and diarrhea (4%). One (2%) grade four hyperbilirubinemia occurred. SBRT target response was 96% (48 of 50 patients). A 6-month clinical benefit was recorded in 34 [68% (95% CI, 53.2, 80.1)] patients. No SBRT targeted disease progressed. Non-radiosurgical disease relapse occurred in 31 (62%) patients. Median disease-free survival was 7.8 months (95% CI, 4.0, 11.6). Median overall survival was 20.2 months (95% CI, 10.9, 29.5)., Interpretation: SBRT safely controlled metastatic gynecologic cancer targets. Given an observed high rate of non-radiosurgical disease relapse, a phase I trial assessing co-administration of SBRT and cytotoxic chemotherapy is underway., Funding: Case Comprehensive Cancer Center.

Objective: To estimate the cost-effectiveness of screening strategies for Lynch syndrome among newly diagnosed endometrial cancer patients., Methods: A decision analysis compared four strategies to screen women with newly diagnosed endometrial cancer for Lynch syndrome: 1) Amsterdam criteria strategy, where full gene sequencing was performed for women who meet Amsterdam criteria; 2) Sequence-all strategy, where full gene sequencing was performed for all women with endometrial cancer; 3) Sequence aged younger than 60 years strategy, where full gene sequencing was performed for women aged younger than 60 years with endometrial cancer; and 4) immunohistochemistry/single gene strategy, where immunohistochemistry was performed for the DNA mismatch repair genes for all women after single gene sequencing for specific women lacking protein expression. Prevalence rates, probabilities of immunohistochemistry staining loss, and gene mutation rates were calculated from published data. Costs were estimated from Medicare reimbursement rates. Cost-effectiveness ratios and incremental cost-effectiveness ratios were estimated for each strategy., Results: For the estimated 40,000 women diagnosed annually with endometrial cancer, the sequence-all strategy detects 920 patients with Lynch syndrome at a cost of $105 million. The Amsterdam criteria give the least-expensive strategy ($7 million), but detect the fewest patients (n=83) with Lynch syndrome. The immunohistochemistry/single gene sequencing strategy detects 858 patients at a cost of $17 million; this strategy has an incremental cost-effectiveness ratio of $13,812. The sequence aged younger than 60 years strategy was less effective and more costly than other strategies., Conclusion: Of the strategies studied, immunohistochemical evaluation of tumor specimens for mismatch repair protein expression after single gene sequencing for patients with endometrial cancer is a cost-effective strategy for detecting Lynch syndrome., Level of Evidence: : III.

Purpose: The use of a temporary keratoprosthesis has allowed earlier surgical intervention in eyes with coexisting vitreoretinal and corneal disease. We analyzed our experience with this type of surgery., Methods: We retrospectively reviewed charts of patients in whom a temporary keratoprosthesis was used between 1987 and 1998. Analysis was focused on ocular history, indications for surgery, visual acuity (VA), intraocular pressure, anatomic results, and complications., Results: A temporary keratoprosthesis was used in 31 eyes, 22 (71.0%) of which were for trauma-related indications. In 6 (19.4%) of the operated eyes, the fellow eye also had severely reduced VA. Retinal detachments were present in 30 (96.8%) eyes; most had evident proliferative vitreoretinopathy. Twelve (38.7%) eyes had vitreous hemorrhage, and 20 (64.5%) had corneal scars. Improvement in VA was seen initially in 45.1% of patients, and 51.6% maintained equal or better VA at their final visit as compared with before surgery. The common documented reasons for poor final VA were recurrent retinal detachments deemed inoperable (32.3%), phthisis (22.6%), and optic atrophy or macular scar (16.1%). Corneal grafts remained clear in 41.9%. Nine patients had further surgery. The most significant complication was one case of sympathetic ophthalmia., Conclusions: Combined vitreoretinal and corneal surgery using temporary keratoprostheses has been used in our institution to treat eyes with extreme abnormalities. Outcomes were less favorable than some reported in the literature, probably because of the severity of disease for which temporary keratoprostheses were reserved. Although results are probably better than the natural course of the disease, patients should be informed of realistic expectations for improvement and potential complications when offered this option.

Purpose: To evaluate the safety and efficacy of transscleral diode laser for retinopexy in rhegmatogenous retinal detachment surgery in a multicenter trial., Methods: Seventy-two patients with primary rhegmatogenous retinal detachments were enrolled. No patient with chronic detachment, a retinal break greater than 90 degrees, history of uveitis or infectious retinopathy, or proliferative vitreoretinopathy was enrolled., Results: Information from follow-up of 6 months or longer was available on 65 eyes. Retinas were attached at 6 months with a single operation in 58 (89%) of these eyes. Complications included apparent pinpoint breaks in Bruch's membrane in 15 eyes, scleral-thermal effect in 14 eyes, and limited hemorrhage, which was intraretinal in 10 eyes and extended into the vitreous in 3 eyes. In one case, hemorrhage was judged perhaps to have contributed to initial surgical failure. The other complications had no known adverse effects. Complications were significantly associated with the physician's experience in using transscleral laser retinopexy., Conclusions: In this multicenter study, transscleral diode laser retinopexy served as a safe and effective means of creating chorioretinal adhesion during retinal reattachment surgery. Minor complications were minimized by increasing experience with the technique.