Disparities in refusal of surgery for gynecologic cancer.

OBJECTIVE: To identify sociodemographic and clinical factors associated with refusal of gynecologic cancer surgery and to estimate its effect on overall survival. METHODS: The National Cancer Database was surveyed for patients with uterine, cervical or ovarian/fallopian tube/primary peritoneal cancer treated between 2004 and 2017. Univariate and multivariate logistic regression were used to assess associations between clinico-demographic variables and refusal of surgery. Overall survival was estimated using the Kaplan-Meier method. Trends in refusal over time were evaluated using joinpoint regression. RESULTS: Of 788,164 women included in our analysis, 5875 (0.75%) patients refused surgery recommended by their treating oncologist. Patients who refused surgery were older at diagnosis (72.4 vs 60.3 years, p < 0.001) and more likely Black (OR 1.77 95% CI 1.62-1.92). Refusal of surgery was associated with uninsured status (OR 2.94 95% CI 2.49-3.46), Medicaid coverage (OR 2.79 95% CI 2.46-3.18), low regional high school graduation (OR 1.18 95% CI 1.05-1.33) and treatment at a community hospital (OR 1.59 95% CI 1.42-1.78). Patients who refused surgery had lower median overall survival (1.0 vs 14.0 years, p < 0.01) and this difference persisted across disease sites. Between 2008 and 2017, there was a significant increase in refusal of surgery annually (annual percent change +1.41%, p < 0.05). CONCLUSIONS: Multiple social determinants of health are independently associated with refusal of surgery for gynecologic cancer. Given that patients who refuse surgery are more likely from vulnerable, underserved populations and have inferior survival, refusal of surgery should be considered a surgical healthcare disparity and tackled as such.

Factors contributing to delays in initiation of front-line cervical cancer therapy: disparities in a diverse south Florida population.

OBJECTIVE: Delay in initiating cervical cancer treatment may impact outcomes. In a cohort of patients initially treated by surgery, chemoradiation, chemotherapy, or in a clinical trial, we aim to define factors contributing to prolonged time to treatment initiation. METHODS: Data from patients initiating treatment for cervical cancer at a single institution was abstracted. Time to treatment initiation was defined as the interval from the date of cancer diagnosis to the date of treatment initiation. Poisson regression model was used for analysis. RESULTS: Of 274 patients studied, the median time to treatment initiation was 60 days (range 0-551). The median times to initiate surgery (54 days, range 3-96) and chemoradiation (58 days, range 4-187) were not significantly different (relative risk (RR) 1.01, 95% CI 0.98 to 1.04, p=0.54). The shortest median initiation time was for chemotherapy (47 days; RR 1.13, 95% CI 1.08 to 1.19, p<0.0001) and the longest was for clinical trial (62 days; RR 1.18, 95% CI 1.12 to 1.24, p<0.0001). Charity care (RR 1.09, 95% CI 1.05 to 1.14, p<0.0001), Medicare or Medicaid (RR 1.10, 95% CI 1.06 to 1.14, p<0.0001), and self-pay (RR 1.38, 95% CI 1.32 to 1.45, p<0.0001) delayed treatment initiation more than private insurance. Hispanic White women (RR 0.69, 95% CI 0.66 to 0.73, p<0.0001) had a shorter treatment initiation time compared with non-Hispanic White patients, while Afro-Caribbean/Afro-Latina women (RR 0.86, 95% CI 0.81 to 0.90, p<0.0001) and African-American patients (RR 1.13, 95% CI 1.07 to 1.19, p<0.0001) had longer initiation times. Spanish speaking patients did not have a prolonged treatment initiation (RR 0.68, 95% CI 0.66 to 0.71, p<0.0001), though Haitian-Creole speaking patients did (RR 1.07, 95% CI 1.01 to 1.13, p<0.002). Diagnosis at an outside institution delayed treatment initiation time (RR 1.24, 95% CI 1.18 to 1.30, p<0.0001) compared with diagnosis at the cancer center. CONCLUSION: Factors associated with prolonged time to treatment initiation include treatment modality, insurance status, language spoken, and institution of diagnosis. By closely examining each of these factors, barriers to treatment can be identified and modified to shorten treatment initiation time.

Uterine Sarcomas: How to Navigate an Ever-Growing List of Subtypes.

Uterine sarcomas are rare mesenchymal tumors that are aggressive cancers. The rarity of these tumors, and consequently limited prospective data, has made surgical management of uterine sarcomas challenging. One major obstacle in the management of uterine sarcomas is establishing the diagnosis prior to surgery, which is crucial for appropriate intraoperative management. This paper serves to review aspects of surgical management of uterine sarcomas that remain unanswered. Distinguishing common benign myomas from rare uterine sarcomas is important for operative planning and subspecialty care because benign myomas are frequently managed with minimally invasive hysterectomy or myomectomy, whereas the mainstay of management of uterine sarcomas is hysterectomy without specimen fragmentation. Preoperative clinical presentation, serum studies, imaging, and histologic examination all have limitations in establishing a preoperative diagnosis. In addition, patients are often of reproductive age and desire fertility preservation. Although surgery remains the cornerstone for management, high-quality data guiding best practices are sparse. Morcellation should be avoided. Expert pathologic review, imaging to assess for metastatic disease, and consideration of hormone receptor testing are advisable. Recent data have further informed surgical approach and fertility preservation in early-stage disease, but controversy remains. Despite substantial advancement in the medical management of uterine sarcomas, surgical management of uterine sarcomas remain challenging. Larger studies with long-term follow-up are needed to guide fertility preservation surgery options, both local resection and ovarian preservation, further in young women. Development of novel methods to differentiate between benign and malignant uterine masses is needed.

Understanding the Role and Clinical Applications of Exosomes in Gynecologic Malignancies: A Review of the Current Literature.

BACKGROUND: Gynecologic malignancies are those which arise in the female reproductive organs of the ovaries, cervix, and uterus. They carry a great deal of morbidity and mortality for patients, largely due to challenges in diagnosis and treatment of these cancers. Although advances in technology and understanding of these diseases have greatly improved diagnosis, treatment, and ultimately survival for patients with gynecologic malignancies over the last few decades, there is still room for improvements in diagnosis and treatment, for which exosomes may be the key. This paper reviews the current knowledge regarding gynecologic tumor derived-exosomal genetic material and proteins, their role in cancer progression, and their potential for advancing the clinical care of patients with gynecologic cancers through novel diagnostics and therapeutics. LITERATURE REVIEW: Ovarian tumor derived exosome specific proteins are reviewed in detail, discussing their role in ovarian cancer metastasis. The key microRNAs in cervical cancer and their implications in future clinical use are discussed. Additionally, uterine cancer-associated fibroblast (CAF)-derived exosomes which may promote endometrial cancer cell migration and invasion through a specific miR-148b are reviewed. The various laboratory techniques and commercial kits for the isolation of exosomes to allow for their clinical utilization are described as well. CONCLUSION: Exosomes may be the key to solving many unanswered questions, and closing the gaps so as to improve the outcomes of patients with gynecologic cancers around the world. The potential utilization of the current knowledge of exosomes, as they relate to gynecologic cancers, to advance the field and bridge the gaps in diagnostics and therapeutics highlight the promising future of exosomes in gynecologic malignancies.

Tissue specific reactions to positional discontinuities in the regenerating axolotl limb.

We investigated cellular contributions to intercalary regenerates and 180° supernumerary limbs during axolotl limb regeneration using the cell autonomous GFP marker and exchanged blastemas between white and GFP animals. After distal blastemas were grafted to proximal levels tissues of the intercalary regenerate behaved independently with regard to the law of distal transformation; graft epidermis was replaced by stump epidermis, muscle-derived cells, blood vessels and Schwann cells of the distal blastema moved proximally to the stylopodium and cartilage and dermal cells conformed to the law. After 180° rotation, blastemas showed contributions from stump tissues which failed to alter patterning of the blastema. Supernumerary limbs were composed of stump and graft tissues and extensive contributions of stump tissues generated inversions or duplications of polarity to produce limbs of mixed handedness. Tail skeletal muscle and cardiac muscle broke the law with cells derived from these tissues exhibiting an apparent anteroposterior polarity as they migrated to the anterior side of the blastema. We attribute this behavior to the possible presence of a chemotactic factor from the wound epidermis.

Radiological diagnosis and follow-up of pulmonary tuberculosis.

Mycobacterium tuberculosis, the causal organism of tuberculosis (TB), is one of the oldest and still one of the deadliest pathogens known to man. Approximately 1 in 10 people with primary pulmonary tuberculosis (PTB) present clinically; of untreated cases, approximately 1 in 10 reactivate usually at a time of relative immunodeficiency. The spectrum of radiologic manifestations of PTB can pose a variety of diagnostic and management challenges. PTB infection often leaves long term sequelae of infection, particularly granulomatous nodules, cavitation, and fibrosis; distinguishing dormant disease from reactivation is not always clear-cut. The radiologic presentation of primary PTB infection tends to differ from that of post-primary PTB, but there is significant overlap in the appearances. Primary PTB typically presents with consolidation and regional lymphadenopathy, whereas post-primary PTB more often results in cavitation. The pathology and therefore the radiology of TB infection will be altered based on the efficacy of the immune response and will therefore vary depending on the immune competency. Clinically, in the presence of infection, the main questions are whether M tuberculosis is the infecting organism and, if treated, does the radiology indicate response to treatment. In order to interpret the radiology of TB one needs to be aware of the spectrum of presentation, the expected reaction to treatment, and the myriad of non-pulmonary sites of infection that may prove to be more clinically significant than the pulmonary infection.