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ObjectiveTo evaluate oncologic outcomes in patients with stage I endometrioid ovarian cancer treated with fertility-sparing compared with conventional surgery and to describe reproductive outcomes.MethodsA retrospective cohort study was carried out of patients aged 18–45 with stage I, grade 1 and 2 (low-grade) endometrioid ovarian cancer treated at two cancer centers between July 2001 and December 2019. Clinical and pathologic characteristics were compared using Fisher’s exact test for categorical and the Mann–Whitney U test for continuous variables. Recurrence-free and overall survival were calculated from Kaplan–Meier curves and compared for fertility-sparing and conventional surgery using the log rank test. Pregnancy outcomes are described.ResultsThere were 230 patients with endometrioid ovarian cancer. After exclusion of patients with stage greater than I and those older than 45 years, there were 31 patients with stage I cancer aged 18–45. Of these patients, 11 (35.5%) underwent fertility-sparing surgery and 20 (64.5%) underwent conventional surgery. The median follow-up was 6.0 years (range 1.8–17.3). The median age was 36 years (range 26–42) in the fertility-sparing group and 42 years (range 35–45) in the conventional surgery group (p=0.001), with no difference in other clinical and pathologic characteristics. The 5-year recurrence-free survival was 90.9% (95% CI 73.9% to 100%) for the fertility-sparing group and 84.0% (95% CI 67.3% to 100%) for the conventional surgery group (p=0.65). The 5-year overall survival was 100% for patients in the fertility-sparing group and 92.6% (95% CI 78.7% to 100%) for patients treated with conventional surgery (p=0.49). Four (12.9%) patients had disease recurrence: three (15%) after conventional surgery and one (9.1%) in the contralateral ovary after fertility-sparing surgery and embryo cryopreservation. After fertility-sparing surgery, seven (63.6%) patients attempted pregnancy, of which five (71.4%) conceived with four (57.1%) usingin vitrofertilization. Of the five patients who conceived, there were three spontaneous abortions and five live births.ConclusionFertility-sparing surgery appears safe and may be considered in young women with stage I, low-grade endometrioid ovarian cancer when fertility preservation is desired.

Roughly 10% of the world’s population has chronic kidney disease (CKD). In its advanced stages, CKD greatly increases the risk of hospitalization and death. Although kidney transplantation has revolutionized the care of advanced CKD, clinicians have limited ways of assessing donor kidney quality. Thus, optimal donor kidney–recipient matching cannot be performed, meaning that some patients receive damaged kidneys that function poorly. Fibrosis is a form of chronic damage often present in donor kidneys, and it is an important predictor of future renal function. Currently, no safe, easy-to-perform technique exists that accurately quantifies renal fibrosis. We describe a potentially novel photoacoustic (PA) imaging technique that directly images collagen, the principal component of fibrotic tissue. PA imaging noninvasively quantifies whole kidney fibrotic burden in mice, and cortical fibrosis in pig and human kidneys, with outstanding accuracy and speed. Remarkably, 3-dimensional PA imaging exhibited sufficiently high resolution to capture intrarenal variations in collagen content. We further show that PA imaging can be performed in a setting that mimics human kidney transplantation, suggesting the potential for rapid clinical translation. Taken together, our data suggest that PA collagen imaging is a major advance in fibrosis quantification that could have widespread preclinical and clinical impact.

ObjectivesTo assess the effect of complete surgical staging and adjuvant chemotherapy on survival in stage I, low grade endometrioid ovarian cancer.MethodsThis retrospective study was conducted at two cancer centers from July 2001 to December 2019. Inclusion criteria were all stage I, grade 1 and 2 endometrioid ovarian cancer patients. Patients with mixed histology, concurrent endometrial cancer, neoadjuvant chemotherapy, and patients who did not undergo follow-up at our centers were excluded. Clinical, pathologic, recurrence, and follow-up data were collected. Cox proportional hazard model evaluated predictive factors. Recurrence-free survival and overall survival were calculated using the Kaplan-Meier method.ResultsThere were 131 eligible stage I patients: 83 patients (63.4%) were stage IA, 5 (3.8%) were stage IB, and 43 (32.8%) were stage IC, with 80 patients (61.1%) having grade 1 and 51 (38.9%) patients having grade 2 disease. Complete lymphadenectomy was performed in 34 patients (26.0%), whereas 97 patients (74.0%) had either partial (n=22, 16.8%) or no (n=75, 57.2%) lymphadenectomy. Thirty patients (22.9%) received adjuvant chemotherapy. Median follow-up was 51.5 (95% CI 44.3 to 57.2) months. Five-year recurrence-free survival was 88.0% (95% CI 81.6% to 94.9%) and 5 year overall survival was 95.1% (95% CI 90.5% to 99.9%). In a multivariable analysis, only grade 2 histology had a significantly higher recurrence rate (HR 3.42, 95% CI 1.03 to 11.38; p=0.04). There was no difference in recurrence-free survival (p=0.57) and overall survival (p=0.30) in patients with complete lymphadenectomy. In stage IA/IB, grade 2 there was no benefit of adjuvant chemotherapy (p=0.19), and in stage IA/IB, low grade without complete surgical staging there was no benefit of adjuvant chemotherapy (p=0.16). Twelve patients (9.2%) had recurrence; 3 (25%) were salvageable at recurrence and are alive with no disease.ConclusionsPatients with stage I, low grade endometrioid ovarian cancer have a favorable prognosis, and adjuvant chemotherapy and staging lymphadenectomy did not improve survival.

In healthy blood vessels, albumin crosses the endothelium to leave the circulation by transcytosis. However, little is known about the regulation of albumin transcytosis or how it differs in different tissues; its physiological purpose is also unclear. Using total internal reflection fluorescence microscopy, we quantified transcytosis of albumin across primary human microvascular endothelial cells from both lung and skin. We then validated our in vitro findings using a tissue-specific knockout mouse model. We observed that albumin transcytosis was saturable in the skin but not the lung microvascular endothelial cells, implicating a receptor-mediated process. We identified the scavenger receptor CD36 as being both necessary and sufficient for albumin transcytosis across dermal microvascular endothelium, in contrast to the lung where macropinocytosis dominated. Mutations in the apical helical bundle of CD36 prevented albumin internalization by cells. Mice deficient in CD36 specifically in endothelial cells exhibited lower basal permeability to albumin and less basal tissue edema in the skin but not in the lung. Finally, these mice also exhibited a smaller subcutaneous fat layer despite having identical total body weights and circulating fatty acid levels as wild-type animals. In conclusion, CD36 mediates albumin transcytosis in the skin but not the lung. Albumin transcytosis may serve to regulate fatty acid delivery from the circulation to tissues.

Upon repeated exposure to endotoxin or lipopolysaccharide (LPS), myeloid cells enter a refractory state called endotoxin tolerance as a homeostatic mechanism. In innate immune cells, LPS is recognized by co-receptors Toll-like receptor 4 (TLR4) and CD-14 to initiate an inflammatory response for subsequent cytokine production. One such cytokine, interleukin (IL)-27, is produced by myeloid cells in response to bacterial infection. In monocytes, IL-27 has proinflammatory functions such as up-regulating TLR4 expression for enhanced LPS-mediated cytokine production; alternatively, IL-27 induces inhibitory functions in activated macrophages. This study investigated the effects of IL-27 on the induction of endotoxin tolerance in models of human monocytes compared with macrophages. Our data demonstrate that IL-27 inhibits endotoxin tolerance by up-regulating cell surface TLR4 expression and soluble CD14 production to mediate stability of the surface LPS-TLR4-CD14 complex in THP-1 cells. In contrast, elevated basal expression of membrane-bound CD14 in phorbol 12-myristate 13-acetate (PMA)-THP-1 cells, primary monocytes, and primary macrophages may promote CD14-mediated endocytosis and be responsible for the preservation of an endotoxin-tolerized state in the presence of IL-27. Overall, the efficacy of IL-27 in inhibiting endotoxin tolerance in human THP-1 monocytes and PMA-THP-1 macrophages is affected by membrane-bound and soluble CD14 expression.