Glucose has been omitted from hemodialysates in the recent past. Currently, there is a tendency to include glucose in dialysates at physiological concentrations between 100 and 200 mg/dl (5.56-11.12 mmol/l). In adult patients, this induces, over the dialysis session, a significant uptake of glucose, with some benefits, i.e., avoidance of caloric loss, but also with some metabolic risks, i.e. decreased dialytic potassium removal secondary to an insulin-dependent intracellular potassium shift. We have performed a crossover study in five stable children (mean age 11.7 years) with normal fasting glucose on chronic bicarbonate hemodialysis. The dialysis prescription of 3-h sessions was changed only in terms of the glucose dialysate concentration, being either glucose free or containing 9.17 mmol/l (165 mg/dl) glucose; dialysates were potassium free. Twenty sessions were analyzed for each group by whole dialysate collection (glucose, potassium, phosphate) and serum concentration analysis during and post dialysis (glucose, potassium, phosphate, insulin). Glucose-free dialysis was associated with a patient net glucose loss of 113 +/- 12 mmol/session (nearly 20 g). Conversely, with the glucose-charged dialysate a small uptake of glucose was noted [13.8 +/- 2.1 mmol/session (nearly 2 g)]. At the end of the session, serum glucose was lower with the glucose-free dialysate (4.64 +/- 0.52 mmol/l) than the glucose-charged dialysate (6.11 +/- 0.92 mmol/l). Conversely, serum insulin was higher with the glucose-charged dialysate (38 +/- 17 mU/l) than the glucose-free dialysate (19 +/- 9 mU/l). There were no significant differences either for dialytic removal of potassium (70 vs. 73 mmol/session) or phosphate (20 vs. 22 mmol/session), with and without glucose dialysates. Our study, contrary to previously published data in adults, demonstrated that in children the use of a physiological concentration of glucose in the dialysate (165 mg/dl) avoids dialytic glucose loss without a significant decrease in dialytic potassium removal.

Ovarian cancer is the leading cause of death by gynecological malignancy in the Western world, the fourth most deadly cancer in women. Typically originating from the layer of epithelial cells surrounding the ovary, cancer cells exfoliate to disseminate throughout the peritoneal cavity. The omental fat band (OFB) has been described as a secondary lymphoid organ composed of heavily vascularized fatty tissue interspersed with immune cell aggregates, or “milky spots”. It is also the site of preferential tumor cell adhesion and invasion within the peritoneal cavity, and is removed at the time of surgical debulking in ovarian cancer patients as a preventative measure. Several studies have suggested that obesity is a risk factor for ovarian cancer, but it is unclear whether the obese state directly influences peritoneal dissemination of ovarian cancer. Here, we set out to elucidate the obesity-related changes in the immune microenvironment of the OFB in the homeostatic state as well as following cancer cell adhesion and outgrowth. Our lab has developed a spontaneously transformed murine ovarian surface epithelial (MOSE) cell model that mimics the progressive stages of ovarian cancer following long-term passaging. Importantly, these cells can be used to study the immune microenvironment of tumor cells in an immunocompetent host. EGFP-expressing MOSE-L (late) cells that had been selected in vivo for an aggressive phenotype were injected i.p. into 6 month-old C57Bl/6 mice and changes to the OFB immune microenvironment were evaluated after 6, 24 hrs and 4 weeks. Furthermore, mice fed a high- or low-fat diet (40 or 5% calories as fat, respectively) were used to determine the effects of diet-induced obesity on cancer cell seeding and outgrowth. Immunofluorescence microscopy, real-time PCR and flow cytometry were used to determine tumor cell attachment and growth and identify changes in OFB immune cell populations. Early seeding (24 hrs post-injection) of EGFP-MOSE-L cells at the OFB was increased in high-fat fed mice. Preliminary data from mRNA expression profiling identified genes in the OFB that were i) obesity-associated, ii) a direct response to tumor cell seeding or iii) were exacerbated in the obese microenvironment following tumor cell seeding. This suggests that obesity-associated signaling events could be polarizing the OFB towards a pro-tumorigenic microenvironment. There were also distinct differences in the immune cell populations within the OFB as function of both obesity and time post-tumor cell seeding. These results indicate that ovarian cancer cells preferentially populate the OFB early during peritoneal dissemination and are capable of escaping immune surveillance mechanisms. This study sheds light on the obesity-induced changes in immunomodulatory events associated with tumor seeding and outgrowth in the peritoneal cavity. Supported by NIH CA118846 to EMS and PCR Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 799. doi:10.1158/1538-7445.AM2011-799