CA19-9 Normalization During Pre-operative Treatment Predicts Longer Survival for Patients with Locally Progressed Pancreatic Cancer

Background

Compared to the widely adopted 2–4 months of pre-operative therapy for patients with borderline resectable (BR) or locally advanced (LA) pancreatic ductal adenocarcinoma (PDAC), our institution tends to administer a longer duration before considering surgical resection. Using this unique approach, the aim of this study was to determine pre-operative variables associated with survival.

Methods

Records from patients with BR/LA PDAC who underwent attempt at surgical resection from 1992–2014 were reviewed.

Results

After a median duration of 6 months of pre-operative treatment, 109 patients with BR/LA PDAC (BR 63, LA 46) were explored; 93 (85.3 %) underwent pancreatectomy. Those who received at least 6 months of pre-operative treatment had longer median overall survival (OS) than those who received less (52.8 vs. 32.1 months, P?=?0.044). On multivariate analysis, pre-operative treatment duration was the strongest predictor of survival (hazard ratio (HR) 4.79, P?=?0.043). However, OS was similar in those whose CA19-9 normalized regardless of whether they received more or less than 6 months of chemotherapy (71.4 vs. 101.8 months, P?=?0.930).

Conclusions

Pre-operative CA19-9 decline can guide treatment duration in patients with BR/LA PDAC. We endorse 6 months of therapy except in those patients whose values normalize, where surgery can be considered after a shorter course.

     

Impulse oscillometry measurement of distal airways obstruction in depleted uranium‐exposed Gulf War veterans

Introduction

A cohort of Gulf War I veterans who sustained exposure to depleted uranium undergoes biennial surveillance for potential uranium‐related health effects. We performed impulse oscillometry and hypothesized that veterans with higher uranium body burdens would have more obstructive abnormalities than those with lower burdens.

Methods

We compared pulmonary function of veterans in high versus low urine uranium groups by evaluating spirometry and oscillometry values.

Results

Overall mean spirometry and oscillometry resistance values fell within the normal ranges. There were no significant differences between the high and low uranium groups for any parameters. However, more veterans were classified as having obstruction by oscillometry (42%) than spirometry (8%).

Conclusions

While oscillometry identified more veterans as obstructed, obstruction was not uranium‐related. However, the added sensitivity of this method implies a benefit in wider surveillance of exposed cohorts and holds promise in identifying abnormalities in areas of the lung historically described as silent.

     

Relationship of muscle sympathetic nerve activity to insulin sensitivity

Purpose

An association between insulin resistance and activation of the sympathetic nervous system has been reported in previous studies. However, potential interactions between insulin sensitivity and sympathetic neural mechanisms in healthy people remain poorly understood. We conducted a study to determine the relationship between sympathetic activity and insulin resistance in young, healthy humans.

Methods

Thirty-seven healthy adults (18–35 years, BMI <28 kg m^?2) were studied. Resting muscle sympathetic nerve activity (MSNA) was measured with microneurography and insulin sensitivity of glucose and free fatty acid metabolism was measured during a hyperinsulinemic-euglycemic clamp with two levels of insulin.

Results

During lower doses of insulin, we found a small association between lower insulin sensitivity and higher MSNA (P < 0.05) but age was a cofactor in this relationship. Overall, we found no difference in insulin sensitivity between groups of low and high MSNA, but when women were analyzed separately, insulin sensitivity was lower in the high MSNA group compared with the low MSNA group of women.

Conclusions

These data suggest that MSNA and insulin sensitivity are only weakly associated with young healthy individuals and that age and sex may be important modifiers of this relationship.     

Higher temporal variability of forest breeding bird communities in fragmented landscapes

Understanding the relationship between animal community dynamics and landscape structure has become a priority for biodiversity conservation. In particular, predicting the effects of habitat destruction that confine species to networks of small patches is an important prerequisite to conservation plan development. Theoretical models that predict the occurrence of species in fragmented landscapes, and relationships between stability and diversity do exist. However, reliable empirical investigations of the dynamics of biodiversity have been prevented by differences in species detection probabilities among landscapes. Using long-term data sampled at a large spatial scale in conjunction with a capture-recapture approach, we developed estimates of parameters of community changes over a 22-year period for forest breeding birds in selected areas of the eastern United States. We show that forest fragmentation was associated not only with a reduced number of forest bird species, but also with increased temporal variability in the number of species. This higher temporal variability was associated with higher local extinction and turnover rates. These results have major conservation implications. Moreover, the approach used provides a practical tool for the study of the dynamics of biodiversity.     

Interleukin-3 treatment of rhesus monkeys leads to increased production of histamine-releasing cells that express interleukin-3 receptors at high levels

To understand the hematopoietic and nonhematopoietic responses to interleukin-3 (IL-3), expression of cell-surface IL-3 receptors (IL-3R) was examined on bone marrow (BM) cells and peripheral blood (PB) cells of rhesus monkeys during the course of in vivo IL-3 treatment. Whereas IL-3R expression is low in untreated monkeys, IL-3 administration led to a gradual increase in both low- and high-affinity binding sites for IL-3. This increase reflected the total number of cells expressing IL- 3Rs, as detected by flow cytometry using biotinylated IL-3. Most of these IL-3R+ cells in both BM and PB could be characterized as basophilic granulocytes that contained high levels of histamine. In contrast to the effect on these differentiated cells, IL-3 administration did not significantly alter the low level IL-3R expression on immature, CD34+ cells. Further flow cytometric analysis using biotinylated growth factors showed that the IL-3R+ basophils also expressed receptors for granulocyte-macrophage colony-stimulating factor (GM-CSF), but not for IL-6 or Kit ligand. These findings indicated that the IL-3R+ cells included neither monocytes, which express GM-CSFRs and IL-6Rs abundantly, nor mast cells, which express c- kit. By combining flow cytometric and Scatchard data, it was calculated that the basophils contain as many as 1 to 2 x 10(3) high-affinity IL- 3Rs and 15 to 30 x 10(3) low-affinity sites. The finding that in vivo IL-3 treatment leads to the production of large numbers of cells that express high levels of IL-3R and are capable of producing histamine provides an explanation for the often severe allergic reactions that occur during prolonged IL-3 administration. It also indicates that IL- 3, in addition to its direct effects on hematopoietic cells, may also stimulate hematopoiesis through the release of secondary mediators such as histamine by IL-3-responsive mature cells.     

Na+/H+ exchange mediates postprandial ileal water and electrolyte transport

Feeding stimulates fluid and electrolyte absorption in the small intestine. Previous studies have suggested that Na⁺/glucose cotransport is important in initiating this response in the jejunum. The purpose of this study was to determine whether Na⁺/H⁺ exchange plays a role in meal-induced absorption. Exteriorized, neurovascularly intact jejunal and ileal loops (25 cm) were constructed in dogs. Following a two-week period of postoperative recovery, the loops of awake dogs were perfused with standard buffer alone or with increasing concentrations of amiloride, a Na⁺/H⁺ exchange inhibitor. Water, sodium, and chloride fluxes were calculated following a meal using [¹⁴C]PEG as a volume marker. The meal significantly increased absorption in both the jejunum (P<0.001) and ileum (P<0.01) in those animals perfused with buffer alone. More significantly, amiloride suppressed the increased absorption seen following a meal in the ileum (P<0.001) but not the jejunum. The response in the ileum was dose dependent. These findings suggest that a major mediator of postprandial sodium and water absorption in the ileum is the Na⁺/H⁺ exchanger.Supported by NIH R29-DK-47326 (S.W.A.), R01-DK-39879 (M.J.Z.), and a VA Merit Review (D.W.M.).Portions of this work were presented at the Annual Meeting of the American Gastroenterological Association, May 1993, Boston, Massachusetts.     

Geographic Residency Status and Census Tract Socioeconomic Status as Determinants of Colorectal Cancer Outcomes

Objectives. We examined the impact of geographic residency status and census tract (CT)-level socioeconomic status (SES) on colorectal cancer (CRC) outcomes.Methods. This was a retrospective cohort study of patients diagnosed with CRC in Georgia for the years 2000 through 2007. Study outcomes were late-stage disease at diagnosis, receipt of treatment, and survival.Results. For colon cancer, residents of lower-middle-SES and low-SES census tracts had decreased odds of receiving surgery. Rural, lower-middle-SES, and low-SES residents had decreased odds of receiving chemotherapy. For patients with rectal cancer, suburban residents had increased odds of receiving radiotherapy, but low SES resulted in decreased odds of surgery. For survival, rural residents experienced a partially adjusted 14% (hazard ratio [HR] = 1.14; 95% confidence interval [CI] = 1.07, 1.22) increased risk of death following diagnosis of CRC that was somewhat explained by treatment differences and completely explained by CT-level SES. Lower-middle- and low-SES participants had an adjusted increased risk of death following diagnosis for CRC (lower-middle: HR = 1.16; 95% CI = 1.10, 1.22; low: HR = 1.24; 95% CI = 1.16, 1.32).Conclusions. Future efforts should focus on developing interventions and policies that target rural residents and lower SES areas to eliminate disparities in CRC-related outcomes.For men and women in the United States, colorectal cancer (CRC) ranks third in incidence and mortality among cancers, with an estimated 142 820 new cases and 50 830 deaths in 2013.1 Reflecting the US population distribution according to geography2 and evidence of similar incidence rates3,4 for rural residents, approximately 20% of incident CRC cases are expected to occur in rural populations. Although CRC incidence is equivalent for rural and urban residents, CRC mortality is higher in rural populations,5 and the causes of rural versus urban disparities in CRC mortality are not well understood. Compared with their suburban and urban counterparts, rural citizens are more likely to be older, live in poverty, have less education, lack health insurance, and have no regular health care provider.6–9 These facets of rural living pose challenges to accessing health promotional messages and high-quality primary care, not to mention treatment of cancer.10,11Those of lower socioeconomic status (SES) have worse health-related outcomes than their more affluent counterparts, and SES often has a gradient effect on health.12 A challenge in studying the association between rurality and health is being able to disentangle the confounding effect of SES associated with geographic residency.13 As we previously demonstrated for a sample of urban and rural residents of Georgia with CRC, rural residence was associated with an increased risk of death following diagnosis.14 A limitation of that study was an inability to account for SES differences between urban and rural populations. If adjustment for SES explains the poorer survival that is associated with rural residence, this explanation provides an opportunity to investigate mediators of the SES effect as potential avenues for intervention.15 Identification of these mediating factors will facilitate the development of focused interventions with the goal of eliminating rural CRC-related disparities.16,17Building on our previous work,14 we evaluated the independent and combined effects of rurality and area-level SES on CRC outcomes. In our previous study, (1) we were unable to evaluate the independent and potential confounding effect of SES on rurality,2 (2) our study population was a sample of the Georgia CRC population, and (3) residents were classified as urban or rural at the county level, which may have resulted in misclassification. In the present study, the exposures of interest were geographic residency status (rural, suburban, or urban) and area-level SES, both at the census tract (CT) level. In addition, the study population represents the entire state of Georgia rather than a sample. The primary study outcome was overall survival. Secondarily, we wanted to evaluate the effect of SES and geography adjusted for SES on the odds of late-stage disease at diagnosis and receipt of first-course treatment.The findings of this study are meant to bring importance to a highly relevant area of public health research: disparities related to rural versus urban cancer outcomes, and specifically to rural CRC outcomes. As a result, interventions may be designed and policies developed to address the difficulties of accessing and providing high-quality cancer care in rural areas of the United States.11 It is through the combination of applying what is learned from epidemiological findings to community-level interventions and policymaking that the elimination of health disparities will occur.18