Explore the vast range of titles available.

Produced by senescent cells, the senescence-associated secretory phenotype (SASP) is a potential driver of age-related dysfunction. We tested whether circulating concentrations of SASP proteins reflect age and medical risk in humans. We first screened senescent endothelial cells, fibroblasts, preadipocytes, epithelial cells, and myoblasts to identify candidates for human profiling. We then tested associations between circulating SASP proteins and clinical data from individuals throughout the life span and older adults undergoing surgery for prevalent but distinct age-related diseases. A community-based sample of people aged 20-90 years (retrospective cross-sectional) was studied to test associations between circulating SASP factors and chronological age. A subset of this cohort aged 60-90 years and separate cohorts of older adults undergoing surgery for severe aortic stenosis (prospective longitudinal) or ovarian cancer (prospective case-control) were studied to assess relationships between circulating concentrations of SASP proteins and biological age (determined by the accumulation of age-related health deficits) and/or postsurgical outcomes. We showed that SASP proteins were positively associated with age, frailty, and adverse postsurgery outcomes. A panel of 7 SASP factors composed of growth differentiation factor 15 (GDF15), TNF receptor superfamily member 6 (FAS), osteopontin (OPN), TNF receptor 1 (TNFR1), ACTIVIN A, chemokine (C-C motif) ligand 3 (CCL3), and IL-15 predicted adverse events markedly better than a single SASP protein or age. Our findings suggest that the circulating SASP may serve as a clinically useful candidate biomarker of age-related health and a powerful tool for interventional human studies.

In ovarian cancer (OC), IL-17-producing T cells (Th17s) predict improved survival, whereas regulatory T cells predict poorer survival. We previously developed a vaccine whereby patient-derived dendritic cells (DCs) are programmed to induce Th17 responses to the OC antigen folate receptor alpha (FRα). Here we report the results of a single-arm open-label phase I clinical trial designed to determine vaccine safety and tolerability (primary outcomes) and recurrence-free survival (secondary outcome). Immunogenicity is also evaluated. Recruitment is complete with a total of 19 Stage IIIC-IV OC patients in first remission after conventional therapy. DCs are generated using our Th17-inducing protocol and are pulsed with HLA class II epitopes from FRα. Mature antigen-loaded DCs are injected intradermally. All patients have completed study-related interventions. No grade 3 or higher adverse events are seen. Vaccination results in the development of Th1, Th17, and antibody responses to FRα in the majority of patients. Th1 and antibody responses are associated with prolonged recurrence-free survival. Antibody-dependent cell-mediated cytotoxic activity against FRα is also associated with prolonged RFS. Of 18 patients evaluable for efficacy, 39% (7/18) remain recurrence-free at the time of data censoring, with a median follow-up of 49.2 months. Thus, vaccination with Th17-inducing FRα-loaded DCs is safe, induces antigen-specific immunity, and is associated with prolonged remission. The folate receptor alpha (FRα) is overexpressed in the majority of high-grade serous ovarian cancers and has been proposed as a candidate vaccine antigen. Here the authors report the safety and immunogenicity of Th17-inducing dendritic cells pulsed with FRα-derived epitopes in an early phase I clinical trial with ovarian cancer patients.

Objective: We aimed to analyze the current literature for IORT in gynecological cancers and summarized clinical outcomes regarding patient selection. Methods: A systematic search was conducted utilizing PUBMED, Embase, and CINAHL to identify studies following PRISMA-ScR guidelines. A PICOS structure was utilized: population: patients with epithelial gynecological cancers; intervention: IORT; C: a comparator was not required, as we aimed to analyze patient selection; outcome: clinical outcomes and overall survival; and S: experimental and quasi-experimental analytical observational studies and descriptive observational studies, excluding case series published in English and limited to the last 10 years. Data extraction was conducted for patient selection, IORT, oncological outcomes, and morbidity. Results: A total of 707 results were identified, and 509 studies were uploaded to Covidence for screening after removing duplications. Of the 21 eligible studies, 9 were included in the final review. The total number of patients included was 348. The studies were retrospective single-institution studies, except for one. There was significant heterogeneity in their design and protocols. IORT was exclusively used for recurrent and advanced stage gynecological cancers adjunct to pelvic exenteration or laterally extended endopelvic resections with variable indications across institutions. The mean number of IORT patients per study was 2.8 per year. Survival rates were variable and dependent on the surgical margin. Endometrial cancer had a favorable outcome compared to vulvar and cervical cancers. Conclusions: Current clinical practice, as demonstrated by the research, is consistent with NCCN guidelines that endorse the application of IORT in instances of recurrent cervical, vaginal, and vulvar malignancies; however, there are no established recommendations for primary tumors. The analysis shows that there are gaps in our knowledge, mainly regarding the status of the margins, the criteria used to choose patients, and the outcomes that are specific to each histology. The standardization of protocols and prospectively powered studies are needed to refine patient selection criteria.

We would like to thank Maccio and Madeddu for their thoughtful and interesting Letter to the Editor.1 We agree that advanced ovarian cancer represents an excellent model for evaluating the mechanisms of sarcopenia because of the catabolic state created by the disease. Sarcopenia is associated with increased age and with poorer outcomes in patients with advanced cancer, as reinforced by our study2 and others. Maccio and Madeddu3 highlight the need to investigate the interplay of patient fixed factors (age and stage), tumor biology, and energetics. We do not really know how much control over body composition there is by our tumor-directed and energetics-directed interventions. On this point, among our patient cohort no one who was sarcopenic at baseline recovered following treatment, even those with excellent tumor response to chemotherapy (data unpublished).

A detailed transabdominal and transvaginal ultrasound examination, performed by an expert examiner, could render a similar diagnostic performance to computed tomography for assessing pelvic/abdominal tumor spread disease in women with epithelial ovarian cancer (EOC). This study aimed to describe and assess the feasibility of lung and intercostal upper abdomen ultrasonography as pretreatment imaging of EOC metastases of supradiaphragmatic and subdiaphragmatic areas. A preoperative ultrasound examination of consecutive patients suspected of having EOC was prospectively performed using transvaginal, transabdominal, and intercostal lung and upper abdomen ultrasonography. A surgical-pathological examination was the reference standard to ultrasonography. Among 77 patients with histologically proven EOC, supradiaphragmatic disease was detected in 13 cases: pleural effusions on the right (n = 12) and left (n = 8) sides, nodular lesions on diaphragmatic pleura (n = 9), focal lesion in lung parenchyma (n = 1), and enlarged cardiophrenic lymph nodes (n = 1). Performance (described with area under the curve) of combined transabdominal and intercostal upper abdomen ultrasonography for subdiaphragmatic areas (n = 77) included the right and left diaphragm peritoneum (0.754 and 0.575 respectively), spleen hilum (0.924), hepatic hilum (0.701), and liver and spleen parenchyma (0.993 and 1.0 respectively). It was not possible to evaluate the performance of lung ultrasonography for supradiaphragmatic disease because only some patients had this region surgically explored. Preoperative lung and intercostal upper abdomen ultrasonography performed in patients with EOC can add valuable information for supradiaphragmatic and subdiaphragmatic regions. A reliable reference standard to test method performance is an area of future research. A multidisciplinary approach to ovarian cancer utilizing lung ultrasonography may assist in clinical decision-making.

ObjectivePrevious studies have investigated the impact of preoperative hysteroscopy on the staging and survival of predominantly grade 1 endometrial cancers. We sought to evaluate the effect of hysteroscopy on the peritoneal spread of tumor cells and disease course in a large series of patients with high-risk endometrial cancer.MethodsPatients who underwent hysterectomy for grade 3 endometrial carcinoma on final surgical pathology at the Mayo Clinic in Rochester, MN between January 2009 to June 2016 were included, noting hysteroscopy within 6 months from surgery. Intra-peritoneal disease was defined as any positive cytology OR adnexal invasion OR stage IV. The presence of intra-peritoneal disease OR peritoneal recurrence within 2 years from surgery was defined as peritoneal dissemination. Cox proportional hazards models were fit to evaluate associations between hysteroscopy exposure and progression within 5 years following surgery.ResultsAmong 831 patients, 133 underwent hysteroscopy. There was no difference in age, body mass index, ASA ≥3, or serous histology between patients who did or did not undergo hysteroscopy. Advanced stage disease (III/IV) was less common among patients who underwent hysteroscopy (30.1% vs 43.8%, P=0.003). No difference was observed between those with vs without hysteroscopy in the rate of positive cytology (22.0% vs 29.7%, P=0.09), stage IV (16.5% vs 21.9%, P=0.16), intra-peritoneal disease (28.6% vs 36.1%, P=0.09), or peritoneal dissemination (30.8% vs 39.3%, P=0.06). On stratifying by stage, hysteroscopy did not increase the risk of progression (HR 1.06, 95% CI 0.59 to 1.92 for stage I/II; HR 0.96, 95% CI 0.62 to 1.48 for stage III/IV).ConclusionIn this retrospective study of grade 3 endometrial cancer, we did not observe any significant association between pre-operative hysteroscopy and the incidence of positive cytology, peritoneal disease, peritoneal dissemination, or cancer progression.

Background: International patients seeking medical care in the United States represent a diverse population with unique needs. Clinicians caring for international patients face ethical dilemmas due to differences in culture, religion, expectations for medical care, clinical practice norms and healthcare financing. Objective: We conducted a retrospective review of all ethics consultations on international patients at a global destination medical center over 18-years (2006-2023). We aimed to examine patient characteristics and describe the most common clinical ethics questions arising in this setting. Methods: Patients were identified by from an existing prospectively-maintained database established by the Office of Clinical Ethics at Mayo Clinic. Inclusion criteria included having a home address from an international location. Demographic, medical, psychosocial, and ethics consultation data was abstracted from the medical record. Data was summarized with descriptive statistics. Results: Amongst all ethics consults, 42 international patients were identified. The majority of ethics consults were placed on adult patients 88% with n = 34/42 (81%) from Middle Eastern countries and n = 29/42 (69%) speaking Arabic as a primary language. The majority of patients identified as Muslim n = 33/42 (79%). The embassy of Saudi Arabia or UAE provided funding for n = 21/42 (50%) of patients. The most common primary diagnoses were malignancy n = 20/42 (48%) and neurologic n = 7/42 (17%). The most common primary reasons for Ethics Consultation were religious or cultural issue n = 15/42 (36%), goals of care or 'futility\" n = 13/42 (31%), and financial issues affecting allocation of resources and/or access to healthcare n = 8/42 (19%). Palliative care was involved in 57% of cases. In 33% cases, the patient died in the U.S. and in 48% of cases, the patient returned to their home country alive. Conclusion: The most common ethical dilemmas for international patients were religious or cultural issues, goals of care or 'futility\" issues, and financial issues affecting allocation of resources and/or access to healthcare. Preventive ethics activities to address these dilemmas may include improved cross cultural ethics education, greater investment in spiritual care resources for Muslim patients, earlier involvement of palliative care, and improved transparency and policies regarding fiduciary responsibility for international patients.

Gynecologic cancers can lead to gynecologic tract destruction with extension into both the gastrointestinal and urinary tracts. Recurrent disease can also affect the surrounding bony pelvis and pelvic musculature. As opposed to advanced ovarian cancer, where cytoreduction is the goal, in these scenarios, an oncologic approach to achieve negative margins is critical for benefit. Surgeries aimed at achieving a R0 resection in gynecologic oncology can have a significant impact on pelvic anatomy, and require reconstruction. Overall, it appears that these types of radical surgery are less frequently performed; however, when required, multidisciplinary teams at high-volume centers can potentially improve short-term morbidity. There are few data to examine the long-term, quality-of-life outcomes after reconstruction following oncologic resection in advanced and recurrent gynecologic cancers. In this review we outline considerations and approaches for reconstruction after surgery for gynecologic cancers. We also discuss areas of innovation, including minimally invasive surgery and the use of 3D surgical anatomy models for improved surgical planning.In the era of ‘less is more’, pelvic exenteration in gynecologic oncology is still indicated when there are no other curative-intent alternatives in persistent or recurrent gynecological malignancies confined to the pelvis or with otherwise unmanageable symptoms from fistula or radiation necrosis. Pelvic exenteration is one of the most destructive procedures performed on an elective basis, which inevitably carries a significant psychologic, sexual, physical, and emotional burden for the patient and caregivers. Such complex ultraradical surgery, which requires removal of the vagina, vulva, urinary tract, and/or gastrointestinal tract, subsequently needs creative and complex reconstructive procedures. The additional removal of sidewall or perineal structures, like pelvic floor muscles/vulva, or portions of the musculoskeletal pelvis, and the inclusion of intra-operative radiation further complicates reconstruction. This review paper will focus on the reconstruction aspects following pelvic exenteration, including options for urinary tract restoration, reconstruction of the vulva and vagina, as well as how to fill large empty spaces in the pelvis. While the predominant gastrointestinal outcome after exenteration in gynecologic oncology is an end colostomy, we also present some novel new options for gastrointestinal tract reconstruction at the end.

ObjectivesTo assess predictors of extensive lymph node dissemination and non-vaginal recurrence in patients with endometrial cancer with positive sentinel lymph nodes (SLNs).MethodsPatients with endometrial cancer who underwent primary surgery with SLN mapping and had at least one positive node between October 2013 and May 2019 were included. Positive SLNs were reviewed, and cases were classified according to the location of the metastasis (extracapsular vs intracapsular), and the size of the largest SLN metastasis (isolated tumor cells, micrometastasis, macrometastasis). Associations were assessed based on fitting logistic regression models and Cox proportional hazards models.ResultsA total of 103 patients met the inclusion criteria: including 36 (34.9%) with isolated tumor cells, 27 (26.2%) with micrometastasis, and 40 (38.8%) with macrometastasis. Notably, 71.4% of patients exhibiting extracapsular SLN metastases had multiple positive SLNs (p=0.008). Extracapsular invasion (adjusted odds ratio (aOR) 5.81, 95% CI 1.4 to 23.6) and age (aOR=1.8, 95% CI 1.1 to 3.0) emerged as independent predictors of multiple positive SLNs. Among the 38 patients who underwent a backup pelvic lymphadenectomy, 18 (47.4%) presented with positive pelvic non-SLNs, a phenomenon more prevalent in patients with macrometastasis (p=0.004).Independent predictors of non-vaginal recurrence included SLN macrometastasis (adjusted hazard ratio (aHR) 3.3, 95% CI 1.3 to 8.3), non-endometrioid histology (aHR=3.7, 95% CI 1.5 to 9.3), and cervical stromal invasion (aHR=5.5, 95% CI 2.0 to 14.9). Among the 34 patients with isolated tumor cells and endometrioid histology, 3 (9%) experienced a recurrence, all of whom had not received any adjuvant chemotherapy or external beam radiotherapy.ConclusionPatients with positive SLN macrometastasis are independently associated with extensive lymphatic dissemination and distant recurrences. The risk of multiple positive SLNs increases with the extracapsular location of the SLN metastasis and with age. Independent uterine pathologic predictors of non-vaginal recurrence are non-endometrioid histology and cervical stromal invasion.