Assessing Attitudes and Understanding After Ovarian Tissue Cryopreservation: A Follow-Up Telephone Interview Survey.

Purpose: Assessing patient and guardian experiences regarding their history of ovarian tissue cryopreservation (OTC) years after initial procedure. Methods: Cross-sectional follow-up telephone survey. A questionnaire developed by The Pediatric Initiative Network of the Oncofertility Consortium, modified to assess intent and attitudes regarding OTC, tissue access knowledge, financial burden of tissue storage, and intent to use tissue, was utilized. Interviews were conducted for those who underwent OTC at a metropolitan children's hospital between 2013 and 2022. Results: Of 60 eligible patients, 39 interviews were completed. Contacted patients were 3-28 years old, with minors accompanied by guardians. Average age at OTC was 8.5 years old, and 5.1% (2/39) were deceased at the time of contact. All interviewees underwent OTC for fertility preservation before gonadotoxic treatment. Seventy percent of patients (7/10) and 48.1% (13/27) of guardians stated they would use frozen tissue for pregnancy, with 50% (5/10) of patients and 59.3% (16/27) of guardians not understanding tissue access. Regret occurred in 10% (1/10) of patients and 3.4% (1/29) of guardians. It was associated with 10.8% (4/37) of tissue discard due to failed storage payments. Financial concerns occurred in 29.7% (11/37) of interviewees. Overall, 92.3% (36/39) would recommend OTC, and 94.9% (37/39) would repeat their choice to undergo OTC. Conclusion: Follow-up after OTC is essential to patient understanding of tissue status, access, and payments. Most do not regret OTC, except in cases of financial burden leading to tissue discard. Follow-up should be sequentially scheduled and include counseling on financial assistance programs.

Gastric carcinoma's primary presentation as multiple cutaneous nodules throughout the body.

Cutaneous metastasis resulting from internal primary tumors remains a rare phenomenon. The prompt recognition of these metastases is important, as they are an indicator of advanced disease and poor prognosis. We report the case of a 44-year-old Caucasian man presenting with a four-month history of multiple cutaneous nodules on the face, trunk, and upper extremities. Results from skin biopsy revealed strands and cords of atypical cells concerning for poorly differentiated metastatic carcinoma. An esophagogastroduodenoscopy was performed and a poorly differentiated signet-ring type invasive adenocarcinoma at the lesser curvature of the stomach was found. As the cancer had already metastasized to the skin and bones, the patient was started on chemotherapy with an oxaliplatin-based regimen and denosumab for the bone metastases, with resultant objective response and diagnostic control for greater than one year to the present date.

Acid Loading Unmasks Glucose Homeostatic Instability in Proximal-Tubule-Targeted Insulin/Insulin-Like-Growth-Factor-1 Receptor Dual Knockout Mice.

BACKGROUND/AIMS: Metabolic syndrome and type 2 diabetes are associated with some degree of acidosis. Acidosis has also been shown to upregulate renal gluconeogenesis. Whether impaired insulin or insulin-like-growth factor 1 receptor (IGF1) signaling alter this relationship is not known. Our aim was to determine the effects of deletion of insulin and IGF1 receptors (Insr and Igf1r) from renal proximal tubule (PT) on the gluconeogenic response to acidosis. METHODS: We developed a mouse model with PT-targeted dual knockout (KO) of the Insr/Igf1r by driving Cre-recombinase with the gamma-glutamyl transferase (gGT) promoter. Male and female mice were maintained as control or acidotic by treatment with NH4Cl in the drinking water for 1-week. RESULTS: Acidosis in both genotypes increased renal expression of phosphoenolpyruvate carboxykinase (PEPCK) and fructose-1-bisphosphatase (FBP1), but not glucose-6-phosphatase catalytic subunit (G6PC), which showed significantly lower expression in the KO regardless of treatment. Several differences between KO and WT suggested a protective role for insulin/IGF1 receptor signaling in maintaining relative euglycemia in the face of acidosis. First, the increase in FBP1 with acid was greater in the KO (significant interactive term). Secondly, proximal-tubule-associated FOXO1 and AKT overall protein levels were suppressed by acid loading in the KO, but not in the WT. Robust intact insulin signaling would be needed to reduce gluconeogenesis in PT. Third, phosphorylated FOXO1 (pS256) levels were markedly reduced by acid loading in the KO PT, but not in the WT. This reduction would support greater gluconeogenesis. Fourth, the sodium-glucose cotransporter (SGLT1) was increased by acid loading in the KO kidney, but not the WT. While this would not necessarily affect gluconeogenesis, it could result in increased circulatory glucose via renal reabsorption. Reduced susceptibility to glucose-homeostatic dysregulation in the WT could potentially relate to the sharp (over 50%) reduction in renal levels of sirtuin-1 (SIRT1), which deacetylates and regulates transcription of a number of genes. This reduction was absent in the KO. CONCLUSION: Insulin resistance of the kidney may increase whole-body glucose instability a major risk factor for morbidity in diabetes. High dietary acid loads provide a dilemma for the kidney, as ammoniagenesis liberates α-ketoglutarate, which is a substrate for gluconeogenesis. We demonstrate an important role for insulin and/or IGF1 receptor signaling in the PT to facilitate this process and reduce excursions in blood glucose. Thus, medications and lifestyle changes that improve renal insulin sensitivity may also provide added benefit in type 2 diabetes especially when coupled with metabolic acidosis.