Correlation of Radiologic with Surgical Peritoneal Cancer Index Scores in Patients with Pseudomyxoma Peritonei and Peritoneal Carcinomatosis: How Well Can We Predict Resectability?

Introduction

Pseudomyxoma peritonei (PMP) and peritoneal carcinomatosis (PC) arises from primary or secondary peritoneal cancer and can be treated with complete surgical removal of disease. Suitability for surgery is based on a peritoneal cancer index (PCI), with a PCI?≥?20 representing unresectable disease.

Aims

Compare preoperative imaging with surgical findings based on PCI.

Methods

All cases of patients with PMP and PC undergoing cytoreductive surgery ± hyperthermic intraperitoneal chemotherapy (HIPEC) between 2010 and 2014 were included. Two staff radiologists blinded to surgical PCI scores retrospectively reviewed imaging studies to calculate corresponding radiologic PCI scores for each patient. Correlation between radiologic PCI and surgical PCI, as obtained from operative reports, was assessed using Spearman’s rho correlation coefficients. Preoperative assessment of a PCI cutoff of 20 on imaging was compared with actual surgical PCI using sensitivity, specificity, and positive and negative predictive values.

Results

Forty-two patients had a mean surgical PCI?±?SEM score of 15.1?±?1.3 and mean radiologic PCI of 15.5?±?1.5. The most common tumor histologies were appendiceal (60 %) and colon (33 %) adenocarcinoma and were of low tumor grade (67 %). Correlation between individual radiologists and surgical PCI was 0.59 and 0.62, respectively (all p?<?0.001). When mean radiologic PCI was used, this correlation with surgical PCI improved to 0.64 and to 0.65 when good quality studies only were considered (all p?<?0.001). Radiologic PCI score had a sensitivity of 76 %, a specificity of 69 %, positive predictive value of 85 %, and a negative predictive value of 56 % when compared with the surgical PCI. In patients with a radiologic PCI score?≥?20, 6/13 (46 %) still achieved adequate cytoreduction.

Conclusions

Good quality cross-sectional imaging, combined with overreading and formal assessment of all components of the PCI score yields the best correlation with actual surgical findings. Although preoperative assessment of PCI?≥?20 was reasonably accurate, using this cutoff to assess resectability is problematic as almost half of these patients were still able to undergo adequate cytoreduction. Better assessment of resectability is needed preop, either by refinement of the PCI criteria or routine staging laparoscopy.

     

Dynamic development of the pancreas from birth to adulthood

After birth the endocrine pancreas continues its development, a complex process that involves both the maturation of islet cells and a marked expansion of their numbers. New beta cells are formed both by duplication of pre-existing cells and by new differentiation (neogenesis) across the first postnatal weeks, with the result of beta cells of different stages of maturation even after weaning. Improving our understanding of this period of beta cell expansion could provide valuable therapeutic insights.     

Mucosal challenge with cell-associated or cell-free feline immunodeficiency virus induces rapid and distinctly different patterns of phenotypic change in the mucosal and systemic immune systems

The majority of human immunodeficiency virus type 1 (HIV-1) infections occur via mucosal transmission through contact with genital secretions containing cell-associated and cell-free virus. However, few studies have assessed whether exposure to cells, HIV-1 infected or uninfected, plays a role in the sexual transmission of HIV-1. This study examined phenotypic changes in mucosal and systemic lymphoid tissue 24 hr after vaginal exposure to in vitro equilibrated infectious doses of cell-associated or cell-free feline immunodeficiency virus, uninfected heterologous cells, or medium alone. We found that even at this early time-point, mucosal exposure to virus induced substantial alterations in the phenotype and distribution of leucocytes, particularly in the tissues of the mucosal immune system. Second, we found that the type of virus inoculum directly influenced the phenotypic changes seen. Vaginal exposure to cell-free virus tended to induce more generalized phenotypic changes, typically in the peripheral immune system (blood and systemic lymph nodes). In contrast, exposure to cell-associated virus was primarily associated with phenotypic shifts in the mucosal immune system (gut and mucosal/draining lymph nodes). In addition, we found that exposure to uninfected heterologous cells also induced alterations in the mucosal immune system. These data suggest that significant immune changes occur within the first 24 hr of virus exposure, well before substantial replication would be anticipated. As the mucosal immune system, and particularly the gut, is an early and persistent target for lentiviral replication, these findings have substantial implications for HIV-1 pathogenesis and vaccine development.     

Medial temporal lobe abnormalities in pediatric unipolar depression

In vivo anatomical magnetic resonance imaging (MRI) studies in adults with major depressive disorder (MDD) have implicated neurocircuitries involved in mood regulation in the pathophysiology of mood disorders. Specifically, abnormalities in the medial temporal lobe structures have been reported. This study examined a sample of children and adolescents with major depressive disorder to investigate anatomical abnormalities in these key medial temporal brain regions. Nineteen children and adolescents with DSM-IV major depression (mean age +/- S.D.=13.0 +/- 2.4 years; 10 unmedicated) and 24 healthy comparison subjects (mean age +/- S.D.=13.9 +/- 2.9 years) were studied using a 1.5T Philips MRI scanner. We measured hippocampus and amygdala gray matter volumes. MRI structural volumes were compared using analysis of covariance with age and total brain volumes as covariates. Pediatric depressed patients had significantly smaller left hippocampal gray matter volumes compared to healthy controls (1.89 +/- 0.16 cm(3) versus 1.99 +/- 0.18 cm(3), respectively; F=5.0, d.f.=1/39, p=0.03; effect size: eta2(p) =0.11). Unmedicated depressed patients showed a trend towards smaller left hippocampal volumes compared to medicated patients and healthy subjects (F=2.8, d.f.=2/38, p=0.07; effect size: eta2(p) =0.13). There were no statistically significant differences in mean volumes for left or right amygdala. Smaller left hippocampal volumes in children and adolescents with MDD are in agreement with findings from adult studies and suggest that such abnormalities are present early in the course of the illness. Amygdala volumes are not abnormal in this age group. Smaller hippocampal volumes may be related to an abnormal developmental process or HPA axis dysfunction.     

Moderate aging does not modulate morphological responsiveness of the neuromuscular system to chronic overload in Fischer 344 rats

The purpose of this investigation was to determine the effect of aging on neuromuscular adaptations to chronic overload. Eight young adult (8 months old) and eight aged (22 months old) Fischer 344 rats underwent unilateral synergist ablation to overload the plantaris and soleus muscles of that hindlimb and to provide control muscles from the contralateral hindlimb. Cytofluorescent staining and confocal microscopy were used to quantify pre- and post-synaptic features of neuromuscular junctions (NMJs). Histochemical staining and light microscopy were used to assess adaptations of myofibers to chronic overload. Results demonstrate that NMJs of young adult and aged muscles did not undergo morphological remodeling as a result of 4 weeks of chronic overload. In contrast, myofibers of young and aged rats displayed significant (P<0.05), but similar hypertrophy ( approximately 18%) following that 4 week intervention. In both age groups, however, this hypertrophy was detected in the plantaris, but not the soleus. These data indicate that moderate aging (the equivalent of 65 years in human lifetime) does not modify the sensitivity of the neuromuscular system to chronic overload.     

Temporal profile of subventricular zone progenitor cell migration following quinolinic acid-induced striatal cell loss

A number of studies have demonstrated directed migration of neural progenitor cells to sites of brain injury and disease, however a detailed examination of when a cell is "born" in relation to injury induction and the migratory response of that cell has not previously been determined. This study therefore examined the temporal correlation between progenitor cell proliferation ("birth") and neuroblast migratory response into the damaged striatum following quinolinic acid (QA) lesioning of the adult rat striatum. Retroviral labeling of subventricular zone (SVZ)-derived progenitor cells demonstrated that cell loss in the QA-lesioned striatum increased progenitor cell migration through the rostral migratory stream (RMS) for up to 30 days. In addition, a population of dividing cells originating from the SVZ generated doublecortin positive neuroblasts that migrated into the damaged striatum in response to cell loss invoked by the QA lesion. Quantification of bromodeoxyuridine (BrdU)-labeled cells co-expressing doublecortin revealed that the majority of cells present in the damaged striatum were generated from progenitor cells dividing within 2 days either prior to or following the QA lesion. In contrast, cells dividing 2 or more days following QA lesioning, migrated into the striatum and exhibited a glial phenotype. These results demonstrate that directed migration of SVZ-derived cells and neuroblast differentiation in response to QA lesioning of the striatum is acute and transient. We propose this is predominantly due to a reduced capacity over time for newly generated neuroblasts to respond to the lesioned environment due to a loss or inhibition of migratory cues.     

Genotrim, a DNA-customized nutrigenomic product, targets genetic factors of obesity: hypothesizing a dopamine-glucose correlation demonstrating reward deficiency syndrome (RDS)

Obesity is the second largest cause of preventable death in the United States. Historically, obesity was considered a behavioral problem that could be simply addressed with behavioral modifications in diet and exercise. As scientific advancements have demonstrated in other neurological healthcare conditions such as alcoholism, there are important biological and genetic components that limit the efficacy of behavioral adjustments alone. In light of data suggesting frequent co-morbidities to obesity, including diabetes mellitus, atherosclerosis, osteoporosis, and potentially others, we hypothesize that the biologic and genetic factors, synergistically with behavioral modifications, must be addressed to adequately treat this disease. We hypothesize that one such genetic factor that influences behavior and thus obesity is a predisposition to glucose craving and the overall effect of dopaminergic activity in the reward center of the brain. This defect drives individuals to engage in activities of behavioral excess, which will increase brain dopamine function, for which we have created the term reward deficiency syndrome (RDS) to categorize such biological influences on behavior. Consuming large quantities of alcohol or carbohydrates (carbohydrate bingeing) stimulates the brain's production of and utilization of dopamine. So too does the intake of crack/cocaine and the abuse of nicotine. We are proposing that a novel approach to nutritional supplementation may be required to target the RDS role in obesity. In this regard, Genotrim, a DNA based customized nutraceutical has been designed and is currently under investigation in several clinical studies. This is the first hypothesis paper whereby this new paradigm shift in thinking about obesity is presented.     

The LDLR locus in Alzheimer's disease: a family-based study and meta-analysis of case-control data

Genetic linkage studies suggest the presence of an Alzheimer's disease (AD) risk gene on chromosome 19, acting independently of apolipoprotein E (apoE), a known AD risk factor on 19q13. The low density lipoprotein receptor (LDLR) is an interesting candidate because it maps within the linked interval, and is intimately involved in cholesterol homeostasis and the function of apoE. We tested three previously reported single nucleotide polymorphisms (SNPs) within LDLR in a large sample of discordant sibships from multiplex AD families, and failed to find evidence for genetic association with disease risk. In addition, we performed meta-analyses for SNP rs5925 on published data from five independent case control samples, but did not detect any significant summary odds ratios. Based on our data, it seems unlikely that these genetic variants in LDLR make a significant contribution to AD risk in the general population.