Peritoneal dialysis catheter function and survival are not adversely affected by obesity regardless of the operative technique used.

BACKGROUND: Obesity has been considered a relative contraindication to peritoneal dialysis (PD). Surprisingly, PD catheter dysfunction rates and longevity have not been studied in the growing obese ESRD population. The aim of this study was to determine the effect of patient weight on PD catheter survival in the three insertion technique categories of advanced laparoscopy (AL), basic laparoscopy (BL), and open. METHODS: We examine retrospectively collected data on 231 consecutive PD catheter insertions at the NorthShore University HealthSystem between 2004 and 2014. Three cohorts were created based on the catheter insertion technique: open, BL using selective adhesiolysis, and AL using rectus sheath tunnel, selective omentopexy, and adhesiolysis. Primary outcomes included catheter dysfunction and catheter dysfunction-free survival for each cohort by BMI: normal weight (18.5-24.9), overweight (25-29.9), obese (≥30). Nominal variables were compared using Chi-square test, continuous variables using ANOVA or Kruskal-Wallis tests, and catheter survival was assessed using the Kaplan-Meier method with log-rank test. Statistical significance was established at 0.05. RESULTS: For the three BMI categories, there were no statistically significant differences in patient demographics. There were no statistically significant differences in catheter dysfunction or peri-operative complications by BMI category among all patients. This was also true in the AL cohort. Among all patients, similar 2-year dysfunction-free catheter survival was noted for normal weight, overweight, and obese patients (log-rank p = 0.79). This was also true across all insertion techniques: open (log-rank p = 0.87), BL (log-rank p = 0.41), AL (log-rank p = 0.43). In the obese cohort, the 2-year dysfunction-free catheter survival was 91.1% in AL, 83.5% in BL, and 65.7% in open (log-rank p = 0.58). CONCLUSION: Obesity does not increase complications or shorten dysfunction-free PD catheter survival regardless of the operative technique used. Obesity should not be considered as a relative contraindication to PD catheter placement as it confers similar technique success to normal- and overweight individuals.

FABP7 is a key metabolic regulator in HER2+ breast cancer brain metastasis.

Overexpression of human epidermal growth factor receptor 2 (HER2) in breast cancer patients is associated with increased incidence of breast cancer brain metastases (BCBM), but the mechanisms underlying this phenomenon remain unclear. Here, to identify brain-predominant genes critical for the establishment of BCBM, we conducted an in silico screening analysis and identified that increased levels of fatty acid-binding protein 7 (FABP7) correlate with a lower survival and higher incidence of brain metastases in breast cancer patients. We validated these findings using HER2+ BCBM cells compared with parental breast cancer cells. Importantly, through knockdown and overexpression assays, we characterized the role of FABP7 in the BCBM process in vitro and in vivo. Our results uncover a key role of FABP7 in metabolic reprogramming of HER2 + breast cancer cells, supporting a glycolytic phenotype and storage of lipid droplets that enable their adaptation and survival in the brain microenvironment. In addition, FABP7 is shown to be required for upregulation of key metastatic genes and pathways, such as integrins-Src and VEGFA, and for the growth of HER2+ breast cancer cells in the brain microenvironment in vivo. Together, our results support FABP7 as a potential target for the treatment of HER2+ BCBM.

Intranasal delivery of stem cell-based therapies for the treatment of brain malignancies.

INTRODUCTION: Glioblastoma (GBM) is the most aggressive malignant brain cancer in adults, and its poor prognosis and resistance to the existing standard of care require the development of innovative therapeutic modalities. The local delivery of stem cells as therapeutic carriers against glioma has produced encouraging results, but encounters obstacles with regards to the repeatability and invasiveness of administration. Intranasal delivery of therapeutic stem cells could overcome these obstacles, among others, as a noninvasive and easily repeatable mode of administration. AREAS COVERED: This review describes nasal anatomy, routes of stem cell migration, and factors affecting stem cell delivery to hard-to-reach tumors. Furthermore, this review discusses the molecular mechanisms underlying stem cell migration following delivery, as well as possible stem cell effector functions to be considered in combination with intranasal delivery. EXPERT OPINION: Further research is necessary to elucidate the dynamics of stem cell effector functions in the context of intranasal delivery and optimize their therapeutic potency. Nonetheless, the technique represents a promising tool against brain cancer and has the potential to be expanded for use against other brain pathologies.

Laparoscopic peritoneal dialysis catheter insertion using rectus sheath tunnel and selective omentopexy significantly reduces catheter dysfunction and increases peritoneal dialysis longevity.

BACKGROUND: Success of peritoneal dialysis depends on the durability of the peritoneal dialysis catheter, which in turn depends on insertion technique. Catheter-related complications are among the main reasons for peritoneal dialysis failure. Techniques showing evidence of improved catheter function include rectus sheath tunnel, selective omentopexy, and adhesiolysis. METHODS: Single-institution retrospective review of consecutive peritoneal dialysis catheter insertions was performed between 2004 and 2014. Of 235 procedures, the open technique was utilized in 63, basic laparoscopy with selective adhesiolysis in 80, and advanced laparoscopy utilizing rectus sheath tunnel, selective omentopexy, and adhesiolysis in 92. Primary outcomes included catheter dysfunction, catheter dysfunction-free, and overall survival. RESULTS: Mechanical catheter dysfunction occurred in 4 patients (4.4%) in the advanced laparoscopy group, 14 (17.5%) in the basic laparoscopy group, and 20 (31.8%) in the open group (P < .01). The advanced laparoscopy group had the highest rate of dysfunction-free and overall catheter survival. The rectus sheath tunnel was protective independently of dysfunction free catheter survival. The rate of switch to hemodialysis also was significantly lower in the advanced laparoscopic group (P = .031). CONCLUSION: Advanced laparoscopic peritoneal dialysis catheter insertion using rectus sheath tunnel, selective omentopexy, and adhesiolysis is associated with decreased catheter dysfunction rates, improved dysfunction-free and overall catheter survival, and lowest rate of switch to hemodialysis.

Efficacy of a Required Preoperative Weight Loss Program for Patients Undergoing Bariatric Surgery.

The efficacy of mandatory medically supervised preoperative weight loss (MPWL) prior to bariatric surgery continues to be a controversial topic. The purpose of this observational study was to assess the efficacy of a MPWL program in a single institution, which mandated at least 10% excess body weight loss before surgery, by comparing outcomes of patients undergoing primary bariatric surgery with and without a compulsory preoperative weight loss regimen. We analyzed our database of 757 patients who underwent primary bariatric surgery between March 2008 and January 2015. Patients were placed into two cohorts based on their participation in a MPWL program requiring at least 10% excess weight loss (EWL) prior to surgery. Patients were evaluated at 3, 6, 12, and 24 months after surgery for weight loss, comorbidity resolution, and the occurrences of hospital readmissions. A total of 717 patients met the inclusion criteria of whom 465 underwent surgery without a preoperative weight loss requirement and 252 participated in the MPWL program. One year after surgery, 67.1% of non-participants and 62.5% of MPWL participants showed a resolution of at least one of five associated comorbidities (p = 0.45). Non-participants showed an average of 58.6% EWL, while MPWL participants showed 59.1% EWL at 1 year postoperatively (p = 0.84). Readmission rates, excluding those which were ulcer-related, at 30 days (3.4 vs. 6.40%, p = 0.11) and 90 days (9.9 vs. 7.5%, p = 0.29) postoperatively were not significantly different between the non-participants and MPWL patients, respectively. A mandatory preoperative weight loss program prior to bariatric surgery did not result in significantly greater %EWL or comorbidity resolution 1 year after surgery compared to patients not required to lose weight preoperatively. Additionally, the program did not result in significantly lower 30- or 90-day readmission rates for these patients. The value of a MPWL program must be weighed against the potential loss of bariatric surgery candidates. Patients who fail to lose 10% excess weight preoperatively are thus ineligible for a procedure from which they would otherwise benefit. Our data suggest these patients will have similar positive outcomes.