Extended-duration antibiotics are not associated with a reduction in surgical site infection in patients with ovarian cancer undergoing cytoreductive surgery with large bowel resection.

OBJECTIVE(S): To evaluate whether extended dosing of antibiotics (ABX) after cytoreductive surgery (CRS) with large bowel resection for advanced ovarian cancer is associated with reduced incidence of surgical site infection (SSI) compared to standard intra-operative dosing and evaluate predictors of SSI. METHODS: A retrospective single-institution cohort study was performed in patients with stage III/IV ovarian cancer who underwent CRS from 2009 to 2017. Patients were divided into two cohorts: 1) standard intra-operative dosing ABX and 2) extended post-operative ABX. All ABX dosing was at the surgeon's discretion. The impact of antibiotic duration on SSI and other postoperative outcomes was assessed using univariate and multivariable Cox regression models. RESULTS: In total, 277 patients underwent cytoreductive surgery (CRS) with large bowel resection between 2009 and 2017. Forty-nine percent (n = 137) received standard intra-operative ABX and 50.5% (n = 140) received extended post-operative ABX. Rectosigmoid resection was the most common large bowel resection in the standard ABX (89.9%, n = 124) and extended ABX groups (90.0%, n = 126), respectively. No significant differences existed between age, BMI, hereditary predisposition, or medical comorbidities (p > 0.05). No difference was appreciated in the development of superficial incisional SSI between the standard ABX and extended ABX cohorts (10.9% vs. 12.9%, p = 0.62). Of patients who underwent a transverse colectomy, a larger percentage of patients developed a superficial SSI versus no SSI (21% vs. 6%, p = 0.004). CONCLUSION(S): In this retrospective study of patients with advanced ovarian cancer undergoing CRS with LBR, extended post-operative ABX was not associated with reduced SSI, and prolonged administration of antibiotics should be avoided unless clinically indicated.

Bridging the Gap from Bench to Bedside: A Call for In Vivo Preclinical Models to Advance Endometrial Cancer and Cervical Cancer Immuno-Oncology Research.

Advanced-stage endometrial and cervical cancers are associated with poor outcomes despite contemporary advances in surgical techniques and therapeutics. Recent clinical trial results have led to a shift in the treatment paradigm for both malignancies, where immunotherapy is now incorporated in the upfront setting for most patients with advanced endometrial and cervical cancers as the standard of care. Impressive response rates have been observed, but unfortunately, a subset of patients do not benefit from immunotherapy, and survival remains poor. Continued pre-clinical research and clinical trial development are crucial for our understanding of resistance mechanisms to immunotherapy and maximization of therapeutic efficacy. In this setting, syngeneic models are preferred over xenograft models as they allow for evaluation of the tumor-immune interaction in an immunocompetent host, most closely mimicking the tumor-immune interaction in human cancer patients. Unfortunately, significant disparities exist regarding syngeneic models in gynecologic malignancy, where queries from multiple large bioscience companies confirm no commercial availability of endometrial or cervical cancer syngeneic cell lines. Few published data exist regarding the recent development of several endometrial and cervical cancer syngeneic cell lines, warranting further investigation. Closing the disparity gap for pre-clinical models in endometrial and cervical cancer will support physician-scientists, basic and translational researchers, and clinical trialists who are dedicated to improving outcomes for our patients with advanced disease and poor prognosis.

Mobilizing faith-based COVID-19 health ambassadors to address COVID-19 health disparities among African American older adults in under-resourced communities: A hybrid, community-based participatory intervention.

INTRODUCTION: The COVID-19 pandemic disproportionately affected older adults, particularly those with pre-existing chronic health conditions. To address the health disparity and challenges faced by under-resourced African American older adults in South Los Angeles during this period, we implemented a hybrid (virtual/in-person), pre-post, community-based participatory intervention research project utilizing a faith-based lay health advisor model (COVID-19 Health Ambassador Program (CHAP)). We recruited COVID-19 Health Ambassadors (CHAs) and African American older adults (participants) from faith-based organizations who partook in CHA-led meetings and follow-ups that educated and supported the participants. This paper seeks to evaluate this intervention's implementation using the Consolidated Framework for Implementation Research (CFIR) as a reporting tool with an emphasis on fidelity, challenges, and adaptations based on data collected via stakeholder interviews and surveys. RESULTS: CHAP was delivered to 152 participants by 19 CHAs from 17 faith-based organizations. CHAs assisted with chronic disease management, resolved medication-related challenges, encouraged COVID-19 vaccination, reduced psychological stress and addressed healthcare avoidance behaviors such as COVID-19 vaccine hesitancy among the participants. Challenges encountered include ensuring participant engagement and retention in the virtual format and addressing technological barriers for CHAs and participants. Adaptations made to better suit the needs of participants included providing communication tools and additional training to CHAs to improve their proficiency in using virtual platforms in addition to adapting scientific/educational materials to suit our participants' diverse cultural and linguistic needs. CONCLUSION: The community-centered hybrid approach in addition to our partnership with faith-based organizations and their respective COVID-19 health ambassadors proved to be essential in assisting underserved African American older adults manage chronic health conditions and address community-wide health disparities during the COVID-19 pandemic. Adaptability, cultural sensitivity, and teamwork are key to implementing health interventions especially in underserved populations.

Activity of pembrolizumab and lenvatinib in mismatch repair deficient (dMMR) endometrial cancer patients who have failed pembrolizumab monotherapy: A case series.

To evaluate the efficacy of the combination of pembrolizumab and lenvatinib in MMR deficient (dMMR) endometrial cancer (EC) patients who previously failed to respond to single-agent pembrolizumab. A retrospective review of MMR deficient endometrial cancer patients was performed. Patients who failed to respond to pembrolizumab as a single-agent and subsequently received a combination of pembrolizumab and lenvatinib were analyzed. RECIST 1.1 criteria was used to establish clinical response (complete response, partial response, stable disease, and progression) based on CT and/or PET, comparing imaging before and after the addition of lenvatinib. Radiologic review was conducted by an independent radiologist. Eight patients with dMMR EC meeting treatment criteria were identified. The patients' ages ranged from 54 to 80 and all tumors identified were of endometrioid histology. Initial pathologic stage ranged from FIGO stage IB to IVB and recurrence confirmed via imaging or tissue biopsy. Patients received a median of 14 cycles of therapy with pembrolizumab and lenvatinib (range 1-39). All patients had decrease in measurable disease with an objective response of 75 % (PR 62.5 %, CR 12.5 %). Both patients who received the initial recommended dose of 20 mg daily required a dose reduction. Based on this retrospective study, patients with dMMR EC without significant benefit from pembrolizumab monotherapy have a significant clinical response after the addition of lenvatinib. Combination therapy should be considered for dMMR EC patients who fail pembrolizumab monotherapy.

Brainstem and Spinal Arachnoiditis Ossificans Associated With Neurocysticercosis: A Case Report.

Arachnoiditis ossificans (AO), a very rare entity that can cause severe neurological deficit, is associated with an inflammatory response and compressive effect on the spinal cord. A 65-year-old woman with diagnosis of arachnoiditis ossificans, who had a past medical history of neurocysticercosis diagnosed eight years before the actual onset that was accompanied by obstructive hydrocephalus and required bilateral ventriculoperitoneal shunts, presented with lower limb paresis. The spinal CT reported large calcified subdural spinal plaques. She was treated with high-dose steroids with subsequent improvement of the clinical manifestations. Spinal neurocysticercosis is a rare manifestation of this disease, although the Mexican population is especially prone to it, due to the endemic presence of this entity, it can provoke spinal arachnoiditis. We conclude that the chronic inflammation of the spinal meninges induced by the cysticercosis could encourage the arachnoid cells to go through osteoblastic metaplasia with consequent production of thick calcium deposits, such as those found in AO. Thus it may be associated with AO. We present, to our knowledge, the first patient with AO-associated neurocysticercosis.

Association of Clinical Trial Participation With Improved Overall Survival for Recurrent, Platinum-Resistant Ovarian Cancer.

OBJECTIVE: To investigate whether clinical trial participation is associated with overall survival in patients with platinum-resistant ovarian cancer. METHODS: An IRB-approved, retrospective, single-institution cohort study was performed in patients with platinum-resistant ovarian cancer from January 1, 2009, to December 31, 2017. Platinum resistance was defined as progression within 6 months after completion of platinum chemotherapy. Patients were divided into two cohorts: 1) clinical trial participants for platinum-resistant ovarian cancer or 2) standard of care. The association of trial participation with overall survival from the date of platinum resistance was assessed with univariate and multivariable models. RESULTS: Of 305 eligible patients with recurrent platinum-resistant ovarian cancer, 46 (15.1%) were clinical trial participants. There were no significant differences in age (61.2 years vs 63.3 years, P =.21), body mass index (27.5 vs 27.6, P =.90), race ( P =.61), medical comorbidities ( P >.05), or performance status ( P =.07) for clinical trial participants compared with those receiving standard of care. The majority underwent primary cytoreduction (76.1% vs 69.1%, P =.34) with no differences in residual disease ( P =.43) for clinical trial participants compared with those receiving standard of care. There was no difference in poly-ADP-ribose polymerase inhibitor (21.7% vs 15.1%, P =.26) or bevacizumab (22.2% vs 32.1%, P =.31) use for clinical trial participants compared with those receiving standard of care. On multivariable analysis controlling for comorbidities, stage, and germline mutational status, clinical trial participation was associated with significantly improved overall survival from the date of platinum resistance compared with standard of care (13.8 months vs 10.5 months, adjusted hazard ratio 1.46, 95% CI 1.04-2.05, P =.028). CONCLUSIONS: In this retrospective cohort of patients with platinum-resistant ovarian cancer, clinical trial participation was associated with improved overall survival compared with standard of care therapies. Availability and participation in clinical trials should be prioritized in patients with recurrent, platinum-resistant ovarian cancer.

Drink Tap: A Multisector Program to Promote Water Access and Intake in San Francisco Parks.

Taxes on sugar-sweetened beverages (SSBs), or drinks with added sugars, show promise in decreasing purchases and consumption of SSBs. Some have called for coupling such taxes with improvements in access to safe drinking water as a strategy for reducing inequities in SSB intake, yet no studies have examined such an approach. Drink Tap is a San Francisco-based program in which public tap water stations were installed in parks and public spaces (winter 2017) and promotional efforts (fall and winter 2018) encouraged water intake. At the same time, San Francisco and surrounding communities were also implementing SSB taxes. We conducted a quasi-experimental study to examine whether water access and promotion combined with SSB taxes affected beverage intake habits more than SSB taxes alone. We conducted 1-hour observations (N = 960) at 10 intervention parks (Drink Tap plus SSB taxes) and 20 comparison parks (SSB taxes only) in San Francisco Bay Area cities before (July-September 2016) and after (June-August 2019) implementation of Drink Tap. We found significant adjusted percentage increases in drinking water among visitors to intervention parks, compared with comparison parks: water from park water sources (+80%, P < .001) and water from reusable bottles (+40%, P = .02). We found no significant reductions in visitors observed drinking bottled water, juices, or SSBs. The Drink Tap intervention led to increases in water intake from park sources and reusable bottles across parks that surpassed increases achieved through SSB taxes alone. Jurisdictions should consider coupling tap water access and promotion with policies for reducing intake of SSBs.

Efficacy and toxicity of carboplatin and gemcitabine administered on day 1 and day 8 (day1&8) versus day 1-only for platinum-sensitive recurrent epithelial ovarian cancer.

OBJECTIVE: To compare response rate, progression-free survival, overall survival, and toxicity of carboplatin and gemcitabine administered on day 1 and day 8 (day1&8) versus a modified day 1-only regimen in recurrent platinum-sensitive ovarian cancer. METHODS: A retrospective single-institution cohort study was performed in women with recurrent platinum-sensitive ovarian cancer between January 2009 and December 2020 treated with carboplatin and gemcitabine on a 21-day cycle. The impact of dosing schedule on response rate, progression-free survival, overall survival, and toxicities was assessed with univariate and multivariate models. RESULTS: Of 200 patients, 26% (n=52) completed day 1&8, 21.5% (n=43) started day 1&8 but dropped day 8, and 52.5% (n=105) received day 1-only. There were no differences in demographics. Median starting carboplatin and gemcitabine doses were area under curve (AUC) 5 and 600 mg/m2 for day 1-only versus AUC4 and 750 mg/m2 among day 1&8, respectively (p<0.001). A total of 43 patients (45.3%) dropped day 8 primarily due to neutropenia (51.2%) or thrombocytopenia (30.2%). The response rates were 69.3% for day 1&8-completed, 67.5% for day 1&8-dropped, and 67.6% for day 1-only (p=0.92). Median progression-free survival was 13.1, 12.1, and 12.4 months for day 1&8-completed, day 1&8-dropped, and day 1-only, respectively (p=0.29). Median overall survival was 28.2, 33.5, and 34.3 months for the above groups (p=0.42). The rate of grade 3/4 hematologic toxicity (48.9% vs 31.4%, p=0.002), dose reductions (58.9% vs 33.7%, p<0.001), blood transfusions (22.1% vs 10.5%, p=0.025), and treatment with pegfilgrastim (64.2% vs 51%, p=0.059) were higher among day 1&8 versus day 1-only, respectively. CONCLUSIONS: There was no difference in response rate, progression-free survival, or overall survival for day 1&8 versus day 1-only, regardless of whether day 8 was dropped. Day 1&8 was associated with greater hematologic toxicity. A modified day 1-only regimen may represent an alternative to day 1&8 and warrants prospective study.

Factors Associated with Telehealth Utilization among Older African Americans in South Los Angeles during the COVID-19 Pandemic.

BACKGROUND: The COVID-19 pandemic transformed healthcare delivery with the expansive use of telemedicine. However, health disparities may result from lower adoption of telehealth among African Americans. This study examined how under-resourced, older African Americans with chronic illnesses use telehealth, including related sociodemographic and COVID-19 factors. METHODS: Using a cross-sectional design, 150 middle-aged and older African Americans were recruited from faith-based centers from March 2021 to August 2022. Data collected included sociodemographics, comorbidities, technological device ownership, internet usage, and attitudes toward COVID-19 disease and vaccination. Descriptive statistics and multivariable regression models were conducted to identify factors associated with telehealth use. RESULTS: Of the 150 participants, 32% had not used telehealth since the COVID-19 pandemic, with 75% reporting no home internet access and 38% having no cellular/internet network on their mobile device. Age, access to a cellular network on a mobile device, and wireless internet at home were significantly associated with the utilization of telehealth care. Higher anxiety and stress with an increased perceived threat of COVID-19 and positive attitudes toward COVID-19 vaccination were associated with telehealth utilization. DISCUSSION: Access and integration of telehealth services were highlighted as challenges for this population of African Americans. To reduce disparities, expansion of subsidized wireless internet access in marginalized communities is necessitated. Education outreach and training by healthcare systems and community health workers to improve uptake of telehealth currently and post-COVID-19 should be considered.

Environmental assessment of casual dining restaurants in urban and suburban areas of peninsular Malaysia during the COVID-19 pandemic.

Food waste has been considered a global problem due to its adverse impacts on food security, the environment, and the economy; hence needs urgent attention and action. Its generation is expected to increase as the world population grows rapidly, leading to more global waste. This study sought the impacts of the COVID-19 outbreak on the 1-week operation of selected casual dining restaurants in urban (Ampang, Kuala Lumpur) and suburban areas (Kota Bharu, Kelantan and Jasin, Melaka) of Peninsular Malaysia, as the local community adjusted to life with COVID-19. The food waste in this study was classified into three categories: preparation loss, serving loss, and customer's plate waste. Our material flow analysis revealed that the highest food loss at these locations came from preparation loss (51.37%), followed by serving loss (30.95%), and preparation loss (17.8%). Meanwhile, the total average electricity consumption and its carbon footprint for Ampang were 127 kWh and 13.87 kgCO2e, Kota Bharu 269.8 kWh and 29.47 kgCO2e, and Jasin 142.2 kWh and 15.54 kgCO2e, respectively. As for water, Ampang exhibited 22.93 m3 total average consumption and 7.91 kgCO2e greenhouse emissions from this source, Jasin consuming 17.11 m3 of water and releasing 5.88 kgCO2e of carbon footprint, while Kota Bharu emitted 20.21 kgCO2e of greenhouse gases from its 58.71 m3 water consumption. Our findings indicate a major 'food leak' at the preparation stage, from which the waste could be utilised as livestock feed, and that electricity consumption is a greater carbon emitter than water consumption, suggesting a need for improvement to the kitchen practices and equipment.

Persistence of Trypanosoma cruzi vector-borne transmission among school-age children in the Bolivian Chaco documented by 24-month longitudinal serosurveillance.

BACKGROUND: Chagas disease represents a major public health concern in several Latin American countries, including Bolivia. METHODS: We present a longitudinal serosurvey for Trypanosoma cruzi antibodies among a cohort of 120 school-age children from rural communities in the Bolivian Chaco at three time points between 2017 and 2019. Serum samples extracted from dry blood spots collected on filter paper were tested for T. cruzi antibodies by enzyme-linked immunosorbent assay and rapid diagnostic test. RESULTS: T. cruzi antibodies were detected in 7/120 (5.8%), 8/120 (6.7%) and 11/120 (9.2%) samples in 2017, 2018 and 2019, respectively. An average incidence of 1.76 per 100 person-years was observed. CONCLUSIONS: Our findings support the persistence of vector-borne T. cruzi transmission in this area, highlighting the need for strengthening multidisciplinary efforts against Chagas disease.

Mitigating COVID-19 Risk and Vaccine Hesitancy Among Underserved African American and Latinx Individuals with Mental Illness Through Mental Health Therapist-Facilitated Discussions.

BACKGROUND: Underserved ethnic minorities with psychiatric disorders are at an increased risk of COVID-19. This study aims to examine the effectiveness of one-to-one counseling on COVID-19 vaccination and vaccination readiness among underserved African American and Latinx individuals with mental illnesses and adult caregivers of children with mental illness. METHODS: Through an academic-community partnered collaboration, a multidisciplinary and culturally sensitive training on COVID-19 was co-developed and delivered to 68 therapists from January to March 2021. Mental health clients and their caregivers were recruited to participate in pre- and post-intervention surveys to evaluate the impact of the intervention on their perceptions of COVID-19 public health guidelines, testing, and vaccination. Mental health therapists delivered four lessons of the COVID-19 educational intervention with 254 clients from March to June 2021, when vaccine availability was widely available. Of those clients, we collected 180 baseline and 115 follow-up surveys. The main outcome was the uptake in COVID-19 vaccine. RESULTS: There was a positive shift in participant vaccine acceptance and receptivity. Pre-intervention survey shows that only 56% of adult clients and 48% of caregivers had indicated a likelihood of getting the vaccine for themselves at baseline. Post-intervention documented that more than 57% of each group had been vaccinated, with another 11-15% of the unvaccinated individuals reporting that they were somewhat or very likely to get the vaccine. CONCLUSION: This study demonstrated that multidisciplinary academic-community and theoretical-based educational intervention delivered by mental health therapists is an effective strategy in increasing COVID-19 vaccine acceptance and reducing the negative impact and disruption that COVID-19 caused in the daily life of mental health patients and caregivers.

Addressing racial/ethnic inequities in vaccine hesitancy and uptake: lessons learned from the California alliance against COVID-19.

Lack of trust in biomedical research, government, and health care systems, especially among racial/ethnic minorities and under-resourced communities, is a longstanding issue rooted in social injustice. The COVID-19 pandemic has further highlighted existing health and socioeconomic inequities and increased the urgency for solutions to provide access to timely, culturally, and linguistically appropriate evidence-based information about COVID-19; and ultimately to promote vaccine uptake. California's statewide alliance STOP COVID-19 CA (comprising eleven sites), leverages long standing community partnerships to better understand concerns, misinformation, and address racial/ethnic inequities in vaccine hesitancy and uptake. Using data from the California CEAL Communication Working Group, we demonstrate the wide range of strategies, communication methods, languages, and trusted messengers that have been effective in reaching diverse communities across the state. We also showcase challenges and lessons learned, such as the importance of including trusted community partners to share information or provide vaccines. These approaches, rooted in community engagement, are crucial for addressing inequities and responding to future public health emergencies.

Predictors of hospital readmissions in adult patients with sickle cell disease.

BACKGROUND: Sickle cell disease (SCD) is the most common inherited blood disorder, affecting primarily Black and Hispanic individuals. In 2016, 30-day readmissions incurred 95,445 extra days of hospitalization, $152 million in total hospitalization costs, and $609 million in total hospitalization charges. OBJECTIVES: 1) To estimate hospital readmissions within 30 days among patients with SCD in the State of California. 2) Identify the factors associated with readmission within 30 days for SCD patients in California. METHODS: We conducted a retrospective observational study of adult SCD patients hospitalized in California between 2005 and 2014. Descriptive statistics and logistic regression models were used to examine significant differences in patient characteristics and their association with hospital readmissions. RESULTS: From 2,728 individual index admissions, 70% presented with single admission, 10% experienced one readmission, and 20% experienced ≥ two readmissions within 30 days. Significant predictors associated with zero vs. one readmission were male gender (OR=1.37, CI: 1.06-1.77), Black ethnicity (OR=3.27, CI: 1.71-6.27) and having Medicare coverage (OR=1.89, CI: 1.30-2.75). Lower likelihood of readmission was found in those with a Charlson Comorbidity index of three or more (OR=0.53, CI: 0.29-0.97). For zero vs. ≥ two readmissions, significant predictors were male gender (OR=1.43, CI: 1.17-1.74), Black ethnicity (OR=6.90, CI: 3.41-13.97), Hispanic ethnicity (OR=2.33, CI: 1.05-5.17), Medicare coverage (OR=3.58, CI: 2.68-4.81) and Medi-Cal coverage (OR=1.70, CI: 1.31-2.20). Lower likelihood for having two or more readmissions were associated with individuals aged 65+ (OR=0.97, CI: 0.96-0.98) and those with self-payment status (OR=0.32, CI: 0.12-0.54). CONCLUSIONS: In California, male, Black, and Hispanic patients, as well as those covered by Medicare or Medi-Cal, were found to have an increased risk of hospital readmissions. Redirecting outpatient goals to address these patient populations and risk factors is crucial for reducing readmission rates.

COVID-19 Vaccination Perceptions Among Young Adults of Color in the San Francisco Bay Area.

Background: COVID-19 vaccination rates among U.S. young adults, particularly in communities of color, remain lower than other age groups. We conducted a qualitative, community-based participatory study to explore beliefs and attitudes about COVID-19 vaccines among young adults in Black/African American, Latinx, and Asian American or Pacific Islander (AAPI) communities in the San Francisco Bay Area. Methods: We conducted six focus groups between June and August 2021. Participants were recruited by partnering with community-based organizations in the San Francisco Bay Area. Focus groups included Black/African American (N=13), Latinx (N=20), and AAPI (N=12) participants between 18 and 30 years of age. Emerging themes were identified using a modified Grounded Theory approach. Results: Prominent themes among all three racial-ethnic groups included mistrust in medical and government institutions, strong conviction about self-agency in health decision-making, and exposure to a thicket of contradictory information and misinformation in social media. Social benefit and a sense of familial and societal responsibility were often mentioned as reasons to get vaccinated. Young adult mistrust had a generational flavor fueled by anger about increasing inequity, the profit-orientation of pharmaceutical companies and health institutions, society's failure to rectify injustice, and pessimism about life prospects. Conclusion: Factors influencing vaccine readiness among Black/African American, Latinx, and AAPI young adults have a distinct generational and life-course texture. Outreach efforts should appeal to young adults' interest in family and social responsibility and the social benefits of vaccination, while being cognizant of the friction mandates pose for young adults' sense of self-agency. Efforts will be most effective coming from trusted messengers with a proven commitment to communities of color and health equity.

The impact of obesity and adipokines on breast and gynecologic malignancies.

The link between obesity and multiple disease comorbidities is well established. In 2003, Calle and colleagues presented the relationship between obesity and several cancer types, including breast, ovarian, and endometrial malignancies. Nearly, 20% of cancer-related deaths in females can be accounted for by obesity. Identifying obesity as a risk factor for cancer led to a focus on the role of fat-secreted cytokines, known as adipokines, on carcinogenesis and tumor progression. Early studies indicated that the adipokine leptin increases cell proliferation, invasion, and inhibition of apoptosis in multiple cancer types. As a greater appreciation of the obesity-cancer link has amassed, we now know that additional adipokines can impact tumorigenesis. A deeper understanding of the adipokine-activated signaling in cancer may identify new treatment strategies irrespective of obesity. Moreover, adipokines may serve as disease biomarkers, harnessing the potential of obesity-associated factors to serve as indicators of treatment response and disease prognosis. As studies investigating obesity and women's cancers continue to expand, it has become evident that breast, ovarian, and uterine cancers are distinctly impacted by adipokines. While complex, these distinct interactions may provide insight into cancer progression in these organs and new opportunities for targeted therapies. This review aims to organize and present the literature from the last 5 years investigating the mechanisms and implications of adipokine signaling in breast, endometrial, and ovarian cancers with a special focus on leptin and adiponectin.

Disruption of the Gut Microbiota Confers Cisplatin Resistance in Epithelial Ovarian Cancer.

Epithelial ovarian cancer (EOC) is the leading cause of gynecologic cancer death. Despite initial responses to intervention, up to 80% of patient tumors recur and require additional treatment. Retrospective clinical analysis of patients with ovarian cancer indicates antibiotic use during chemotherapy treatment is associated with poor overall survival. Here, we assessed whether antibiotic (ABX) treatment would impact growth of EOC and sensitivity to cisplatin. Immunocompetent or immunocompromised mice were given untreated control or ABX-containing (metronidazole, ampicillin, vancomycin, and neomycin) water prior to intraperitoneal injection with EOC cells, and cisplatin therapy was administered biweekly until endpoint. Tumor-bearing ABX-treated mice exhibited accelerated tumor growth and resistance to cisplatin therapy compared with control treatment. ABX treatment led to reduced apoptosis, increased DNA damage repair, and enhanced angiogenesis in cisplatin-treated tumors, and tumors from ABX-treated mice contained a higher frequency of cisplatin-augmented cancer stem cells than control mice. Stool analysis indicated nonresistant gut microbial species were disrupted by ABX treatment. Cecal transplants of microbiota derived from control-treated mice was sufficient to ameliorate chemoresistance and prolong survival of ABX-treated mice, indicative of a gut-derived tumor suppressor. Metabolomics analyses identified circulating gut-derived metabolites that were altered by ABX treatment and restored by recolonization, providing candidate metabolites that mediate the cross-talk between the gut microbiome and ovarian cancer. Collectively, these findings indicate that an intact microbiome functions as a tumor suppressor in EOC, and perturbation of the gut microbiota with ABX treatment promotes tumor growth and suppresses cisplatin sensitivity. SIGNIFICANCE: Restoration of the gut microbiome, which is disrupted following antibiotic treatment, may help overcome platinum resistance in patients with epithelial ovarian cancer. See related commentary by Hawkins and Nephew, p. 4511.

Metastatic primary brain rhabdomyosarcoma in a pediatric patient: illustrative case.

BACKGROUND: Primary intracranial rhabdomyosarcoma is an extraordinarily rare malignant tumor, with even fewer presenting with distant metastasis. To date, only five cases, including the one presented here, have been reported to present metastatic activity. OBSERVATIONS: A 12-year-old boy presented with a few days of headache, nausea, vomiting, but no neurological deficit. Brain computed tomography and magnetic resonance imaging demonstrated hydrocephalus and a cystic lesion with left parieto-occipital extension. After resection, pathology reported primary rhabdomyosarcoma, with positive desmin and myogenin on immunohistochemistry. The patient presented with pulmonary metastasis. The patient had an overall survival of 21 months after diagnosis with optimal treatment. LESSONS: Rhabdomyosarcoma is a malignant neoplasm arising from undifferentiated skeletal muscle cells, with morphological, immunohistochemical, ultrastructural, or molecular genetic evidence of primary skeletal muscle differentiation. It presents with a rapidly worsening clinical course and the final outcome is poor. Treatment is widely based on protocols that have been proven to be effective in extracranial versions of these tumors, although repeatedly ineffective. Primary brain rhabdomyosarcoma poses a diagnostic challenge because of its infrequent presentation, grade of undifferentiation and tumor heterogeneity. Immunohistochemical and genetic testing have proven to be useful tools for diagnosis.

NCCN Guidelines® Insights: Ovarian Cancer, Version 3.2022.

Epithelial ovarian cancer is the leading cause of death from gynecologic cancer in the United States, with less than half of patients living >5 years following diagnosis. The NCCN Guidelines for Ovarian Cancer provide recommendations for the diagnosis, evaluation, treatment, and follow-up for patients with ovarian, fallopian tube, and primary peritoneal cancers. These NCCN Guidelines Insights summarize the panel discussion behind recent important updates to the guidelines, including revised guidance on alternative chemotherapy regimens for patients with advanced age and/or comorbidities, a new algorithm for recurrent low-grade serous carcinoma based on developing research and novel therapeutic agents, and updated language regarding tumor molecular analysis applications in ovarian cancer.

Association Between Adrenal-Restrictive HSD3B1 Inheritance and Hormone-Independent Subtypes of Endometrial and Breast Cancer.

BACKGROUND: The germline variant rs1047303 (HSD3B1[1245A/C]), restricting or enabling production of potent androgens and estrogens from adrenal precursors, affects outcomes of castration-resistant prostate cancer and is associated with estrogen receptor positivity in postmenopausal breast cancer. Like breast cancer, endometrial cancer is another malignancy with hormone-dependent and hormone-independent subtypes. We hypothesized that adrenal-restrictive HSD3B1 genotype would associate with hormone-independent cancer subtypes. METHODS: We employed a previously described classification of tumors in The Cancer Genome Atlas into genomic clusters. We determined HSD3B1 genotype frequencies by endometrial cancer genomic cluster and calculated the odds per adrenal-restrictive A allele for the largely hormone-independent copy-number (CN) high subtype vs other subtypes. An equivalent analysis was performed for the genomically similar, hormone-independent basal breast cancer subtype. Last, we performed survival analyses for UK Biobank participants with endometrial cancer by HSD3B1 genotype. All statistical tests were 2-sided. RESULTS: The adrenal-restrictive HSD3B1(1245A) allele was associated with the CN-high endometrial cancer subtype (odds ratio [OR] = 1.63, 95% confidence interval [CI] = 1.14 to 2.32; P = .007). Similarly, HSD3B1(1245A) was associated with the basal breast cancer subtype (OR = 1.54, 95% CI = 1.13 to 2.08; P = .006). In the UK Biobank, endometrial cancer patients homozygous for HSD3B1(1245A) had worse overall (hazard ratio [HR] = 1.39, 95% CI = 1.16 to 1.68; P < .001) and cancer-specific (HR = 1.39, 95% CI = 1.14 to 1.70; P = .001) survival, consistent with the A allele being enriched in the more aggressive CN-high subtype. CONCLUSIONS: These findings suggest roles for adrenal-restrictive vs adrenal-permissive steroidogenesis, by way of rs1047303 genotype, in the development of and/or outcomes from at least 3 commonly hormone-associated types of cancer: prostate, breast, and endometrial.