Continuity of Care, Follow-Up Care, and Outcomes among Breast Cancer Survivors.

This retrospective cohort study examined the effects of care continuity on the utilization of follow-up services and outcome of breast cancer patients (stages I-III) in the post-treatment phase of care. Propensity score matching and generalized estimation equations were used in the analysis of data obtained from national longitudinal databases. The continuity of care index (COCI) was calculated separately for primary care physicians (PCP) and oncologists. Our results revealed that breast cancer survivors with a higher oncology COCI were more likely than those with a lower oncology COCI to use mammography or breast ultrasound during the follow-up period (OR = 1.26, 95% CI: 1.19-1.32; OR = 1.12, 95% CI: 1.06-1.18; respectively). In terms of health outcomes, a higher oncology COCI was associated with a lower likelihood of hospitalization (OR = 0.78, 95% CI: 0.71-0.85) and emergency department use (OR = 0.88, 95% CI: 0.82-0.95). A higher PCP COCI was also associated with a lower likelihood of hospitalization (OR = 0.77, 95% CI: 0.70-0.85) and emergency department use (OR = 0.75, 95% CI: 0.68-0.82). Overall, this study determined that ambulatory care continuity is positively associated with the likelihood of using recommended follow-up care services and negatively associated with adverse health events among breast cancer survivors.

Differences in the outcomes of adjuvant chemotherapy for colon cancer prescribed by physicians in different disciplines: a population-based study in Taiwan.

OBJECTIVES: One feature unique to the Taiwanese healthcare system is the ability of physicians other than oncologists to prescribe systemic chemotherapy. This study investigated whether the care paths implemented by oncologists and non-oncologists differ with regard to patient outcomes. SETTING: Data from the Taiwan Cancer Registry and National Health Insurance Database were linked to identify patients with colon cancer who underwent colectomy as first treatment within 3 months of diagnosis and adjuvant chemotherapy between 2005 and 2009. PARTICIPANTS AND METHODS: Postoperative patients who underwent adjuvant chemotherapy were included in this study. The exclusion criteria included patients with stage IV disease, a positive surgical margin and early disease recurrence. Among the patients presenting with multiple primary cancers, we also excluded patients who were diagnosed with colon cancer but for whom this was not the first primary cancer. The variables included sex, age, comorbidities, disease stage, chemotherapy cycle and changes in treatment regimen as well as the specialty of treatment providers and their case volume. Cox regression models and Kaplan-Meier analysis were used to examine differences in outcomes in the matched cohorts. RESULTS: We examined 3534 patients who were prescribed adjuvant chemotherapy by physicians from different disciplines. In terms of 5-year disease-free survival, no significant difference was observed between the groups of oncologists or surgeons among patients with stage II (90.02%vs88.99%) or stage III (77.64%vs79.99%) diseases. Patients who were subjected to changes in their chemotherapy regimens presented recurrence rates higher than those who were not. CONCLUSIONS: The discipline of practitioners is seldom taken into account in most series. This is the first study to provide empirical evidence demonstrating that the outcomes of patients with colon cancer do not depend on the treatment path, as long as the selection criteria for adjuvant chemotherapy is appropriate. Further study will be required before making any further conclusions.

The Impact of Prenatal Exposure to Power Plant Emissions on Birth Weight: Evidence from a Pennsylvania Power Plant Located Upwind of New Jersey.

To examine the infant health impact of prenatal exposure to power plant emissions, we draw scientific evidence on the impacted region downwind of a large polluter, a coal-fired power plant located on the border of two states and proven to be the sole contributor to the violation of air quality standards of the impacted region. Our results show that among all live singleton births that occurred during 1990 through 2006, those born to mothers living as far as 20 to 30 miles away downwind from the power plant (which is also an affluent region) during pregnancy are at greater risks of low birth weight (LBW) and very low birth weight (VLBW): the likelihoods of LBW and VLBW could increase approximately by 6.50 and 17.12 percent, respectively. In light of the continual efforts of The U.S. Environmental Protection Agency in reducing cross-state air pollution caused by transboundary power plant emissions, our study is aimed at broadening the scope of cross-border pollution impact analysis by taking into account adverse infant health effects of upwind polluters, which can impose disproportionate burdens of health risks on downwind states due to air pollutants transported by wind.

Combination of Two Targeted Medications (Bevacizumab Plus Cetuximab) Improve the Therapeutic Response of Pancreatic Carcinoma.

The objective of this study is to evaluate the efficacy and safety profiles of the targeted medications, bevacizumab and cetuximab, in combination with cytostatic drugs in patients with locally advanced or metastatic pancreatic cancer. In this retrospective phase 2 study, a total of 59 patients with pancreatic cancer were recruited and received conventional (gemcitabine, cisplatin, and fluorouracil) or targeted regimen (conventional plus bevacizumab and cetuximab for the first cycle) in 2-week intervals for four cycles. The primary end-point for this study was the overall response rate. Secondary end-points were progression-free survival and the safety profiles of the combined therapy. The median time-to-progression and overall survival were 3 and 7 months, respectively, in the conventional treatment group as well as 11 and 13 months, respectively, in the targeted medications treatment group. The most common adverse events in both treatment groups were nausea and vomiting. Moderate (Grade 2) nausea and vomiting were more common in the conventional group than the targeted group but severe (Grade 3) nausea and vomiting were more common in the targeted group. Bevacizumab and cetuximab in combination with gemcitabine, cisplatin, and fluorouracil may help lengthen overall survival up to six months for patients with pancreatic cancer.

Evaluation of Safety and Efficacy of Salvage Therapy With Sunitinib, Docetaxel (Tyxan) and Cisplatinum Followed by Maintenance Vinorelbine for Unresectable/Metastatic Nonsmall Cell Lung Cancer: Stage 1 of a Simon 2 Stage Clinical Trial. [Corrected].

Current chemotherapeutic regimens for nonsmall cell lung cancer (NSCLC) have reached a plateau over the last few years. Targeted therapy makes use of tyrosine kinase inhibitors (TKIs) to suppress a number of signaling pathways including epidermal growth factor receptor and vascular endothelial growth factor which are active in NSCLC biology. In this study, we used sunitinib, a multi-target receptor TKI, combined with chemotherapy for unresectable/metastatic NSCLC.This open label Simon's 2 stage clinical trial enrolled a total of 6 NSCLC patients who received docetaxel (40 mg) and cisplatin (50 mg) on day 1 of each cycle (14 day interval between cycles) and sunitinib (25 mg qd for 10 days between cycles) for a total of 12 cycles (24 weeks), after which patients received maintenance therapy with vinorelbine (30 mg TIW) until disease progression. The sample size was based on a Simon's Optimal Two-Stage Designs for Phase II clinical trials. The expected response rate was set as 35% for P0 and as 60% for P1. The study was designed for a minimum of 6 patients for first stage and 15 patients until second stage with a significance level alpha = 0.10 and power = 70%. Diagnosis of a poor response in the second of 6 patients in Stage I or seventh of the 15 patients in Stage II would lead to early termination of the trial.The overall response rate was 66.7%. Four patients had an overall survival >60 months. The time to PFS ranged from 3 to 42 months. The combination therapy was well-tolerated.Sunitinib combined with chemotherapy shows promise and warrants further investigation.

A Decade of Changes in Preferences for Life-Sustaining Treatments Among Terminally Ill Patients With Cancer.

BACKGROUND: Changes over time in preferences for life-sustaining treatments (LSTs) at end of life (EOL) in different patient cohorts are not well established, nor is the concept that LST preferences represent more than 2 groups (uniformly prefer/not prefer). PURPOSE: The purpose of this study was to explore heterogeneity and changes in patterns of LST preferences among 2 independent cohorts of terminally ill patients with cancer recruited a decade apart. METHODS: Preferences for cardiopulmonary resuscitation, intensive care unit care, cardiac massage, intubation with mechanical ventilation, intravenous nutritional support, nasogastric tube feeding, and dialysis were surveyed among 2,187 and 2,166 patients in 2003-2004 and 2011-2012, respectively. Patterns and changes in LST preferences were examined by multigroup latent class analysis. RESULTS: We identified 7 preference classes: uniformly preferring, uniformly rejecting, uniformly uncertain, favoring nutritional support but rejecting other treatments, favoring nutritional support but uncertain about other treatments, favoring intravenous nutritional support with mixed rejection of or uncertainty about other treatments, and preferring LSTs except intubation with mechanical ventilation. Probability of class membership decreased significantly over time for the uniformly preferring class (15.26%-8.71%); remained largely unchanged for the classes of uniformly rejecting (41.71%-40.54%) and uniformly uncertain (9.10%-10.47%), and favoring nutritional support but rejecting (20.68%-21.91%) or uncertain about (7.02%-5.47%) other treatments, and increased significantly for the other 2 classes. The LST preferences of Taiwanese terminally ill patients with cancer are not a homogeneous construct and shifted toward less-aggressive treatments over the past decade. CONCLUSIONS: Identifying LST preference patterns and tailoring interventions to the unique needs of patients in each LST preference class may lead to the provision of less-aggressive EOL care.

Association of treatment and outcomes of doctor-shopping behavior in patients with hepatocellular carcinoma.

BACKGROUND: A variety of unfulfilled needs may trigger doctor-shopping behavior (DSB) in patients. In oncology, treatment results usually cause patients the most concern. This study investigated the association of DSB with active treatments received by patients with hepatocellular carcinoma (HCC) and outcomes. METHODS: With approval from the institutional review board, all patients registered in the cancer database of a teaching hospital and diagnosed as having HCC by self-referral from outside hospitals or by in-house diagnosis were retrospectively identified. Patient data were then reviewed and analyzed via electronic medical records. RESULTS: Hepatitis B carriers were significantly more likely than noncarriers to show first-time DSB. Recurrent disease was less likely to result in DSB than predicted. Patients from outside hospitals not receiving upfront first treatment after diagnosis were significantly more likely to show more frequent DSB than those receiving it. Male patients eligible for salvage treatment were less likely to have frequent occurrences of DSB than their female counterparts. Receiving first salvage treatment was not associated with more frequent DSB. Treatment recommendations offered in the study hospital did not influence patients' decisions to leave or stay. Only elderly patients (>70 years) were less likely to show DSB. CONCLUSION: DSB can occur throughout the entire course of treatment for HCC for a variety of reasons. Active treatments, disease status, and patient characteristics all exerted an influence on DSB.

Differential distributions of CSE1L/CAS and E-cadherin in the polarized and non-polarized epithelial glands of neoplastic colorectal epithelium.

Colorectal glands are important functional organs in colorectal tissue and are also the origin of colorectal carcinomas. Epithelial cell polarization of colorectal glands is related to structural integrity and physiological functions of colorectal glands as well as colorectal carcinoma formation. The cellular apoptosis susceptibility (CSE1L/CAS) protein has been shown to induce polarity formation of human colorectal cells in cell culture. E-cadherin expression in epithelial cells is crucial for the establishment and maintenance of epithelial cell polarity. In this study we examined the distributions of CSE1L and E-cadherin in the epithelial glands of normal and neoplastic colorectal epithelium and correlated these to polarity formation in the colorectal glands. Our results showed that CSE1L was differentially stained in the epithelial glands of neoplastic colorectal epithelium, and the staining was related to gland epithelial cell polarization and E-cadherin distribution. CSE1L was associated E-cadherin in GST pull-down experiments and immunoprecipitation assays. Basolateral staining of CSE1L and E-cadherin were seen in the polarized glands of normal and neoplastic colorectal epithelium. Absence of basolateral CSE1L staining in neoplastic epithelium glands was associated with loss of gland epithelial cell polarity, and this was parallel with E-cadherin staining. The non-polarized areas in epithelium glands showed a patchy staining for CSE1L and E-cadherin. These results indicate that examination of CSE1L and E-cadherin distribution in colorectal epithelium glands may be valuable for evaluating the malignance of colorectal disease.

Increased cellular apoptosis susceptibility (CSE1L/CAS) protein expression promotes protrusion extension and enhances migration of MCF-7 breast cancer cells.

Microtubules are part of cell structures that play a role in regulating the migration of cancer cells. The cellular apoptosis susceptibility (CSE1L/CAS) protein is a microtubule-associated protein that is highly expressed in cancer. We report here that CSE1L regulates the association of α-tubulin with ß-tubulin and promotes the migration of MCF-7 breast cancer cells. CSE1L was associated with α-tubulin and ß-tubulin in GST (glutathione S-transferase) pull-down and immunoprecipitation assays. CSE1L-GFP (green fluorescence protein) fusion protein experiments showed that the N-terminal of CSE1L interacted with microtubules. Increased CSE1L expression resulted in decreased tyrosine phosphorylation of α-tubulin and ß-tubulin, increased α-tubulin and ß-tubulin association, and enhanced assembly of microtubules. Cell protrusions or pseudopodia are temporary extensions of the plasma membrane and are implicated in cancer cell migration and invasion. Increased CSE1L expression increased the extension of MCF-7 cell protrusions. In vitro migration assay showed that enhanced CSE1L expression increased the migration of MCF-7 cells. Our results indicate that CSE1L plays a role in regulating the extension of cell protrusions and promotes the migration of cancer cells.

Transient response of sap flow to wind speed.

Transient responses of sap flow to step changes in wind speed were experimentally investigated in a wind tunnel. A Granier-type sap flow sensor was calibrated and tested in a cylindrical tube for analysis of its transient time response. Then the sensor was used to measure the transient response of a well-watered Pachira macrocarpa plant to wind speed variations. The transient response of sap flow was described using the resistance-capacitance model. The steady sap flow rate increased as the wind speed increased at low wind speeds. Once the wind speed exceeded 8.0 m s(-1), the steady sap flow rate did not increase further. The transpiration rate, measured gravimetrically, showed a similar trend. The response of nocturnal sap flow to wind speed variation was also measured and compared with the results in the daytime. Under the same wind speed, the steady sap flow rate was smaller than that in the daytime, indicating differences between diurnal and nocturnal hydraulic function, and incomplete stomatal closure at night. In addition, it was found that the temporal response of the Granier sensor is fast enough to resolve the transient behaviour of water flux in plant tissue.

Use of combined molecular biomarkers for prediction of clinical outcomes in locally advanced tonsillar cancers treated with chemoradiotherapy alone.

BACKGROUND: Environmental exposures to tobacco, alcohol, human papillomavirus (HPV) and/or Epstein-Barr virus (EBV), all of which can perturb multiple cell cycle proteins or tumor suppressors, have been implicated in the pathogenesis of different subsets of head and neck cancers. The aim of this study was to investigate to which extent the virus infection by itself, and/or the altered cell cycle proteins, contributes to prognosis in locally advanced tonsillar squamous cell carcinomas (TSCCs) treated with concurrent chemoradiotherapy (CCRT) alone. METHODS: Serial tumor tissue arrays from archival samples were tested for the presence of HPV genome integration or EBV episome by means of DNA sequencing, real-time polymerase chain reaction (PCR), and in situ hybridization. Alterations of cell cycle proteins (p53, pRb, and p21) were evaluated by immunohistochemical staining. The association of viral presence with altered cell cycle proteins was correlated to clinical outcomes. RESULTS: Of the 46 patients with the same T2N2bM0 stage IVA among consecutive patients with TSCC, 23 (50%) had integrated HPV DNA and only 1 (2%) had EBV episome. The HPV types detected were almost all HPV-16. A reduced expression pattern of p53, pRb, and p21 was noted in HPV-positive tumors, and the incremental number of alterations in the 3 proteins was significantly associated with HPV-negative tumors. The presence or absence of HPV together with the number of altered expression of the 3 cell cycle markers resulted in further identification of 4 biologically and clinically distinct subgroups with different outcomes after CCRT. CONCLUSIONS: Use of combined biomarkers of oncogenic HPV and tumor suppressors of p53, pRb, and p21 in advanced TSCC provides prognostic molecular classification superior to the TNM stage system and identifies low-risk patients for organ preservation by CCRT alone and high-risk patients who might benefit from planned tonsillectomy and neck dissection before or after CCRT.

The Lagrangian stochastic model for estimating footprint and water vapor fluxes over inhomogeneous surfaces.

This study investigated a two-dimensional Lagrangian stochastic dispersion model for estimating water vapor fluxes and footprint over homogeneous and inhomogeneous surfaces. Over the homogeneous surface, particle trajectories were computed from a 2-D Lagrangian model forced by Eulerian velocity statistics determined by Monin-Obukhov similarity theory (MOST). For an inhomogeneous surface, the velocity and atmospheric stability profiles were computed using a second-order Eulerian closure model, and these local profiles were then used to drive the Lagrangian model. The model simulations were compared with water vapor flux measurements carried out above an irrigated bare soil site and an irrigated potato site. The inhomogeneity involved a step change in surface roughness, humidity, and temperature. Good agreement between eddy-correlation-measured and Lagrangian-model-predicted water vapor fluxes was found for both sites. Hence, this analysis demonstrates the practical utility of second-order closure models in conjunction with Lagrangian analysis to estimate the scalar footprint in planar inhomogeneous flows.

Long-term estimation of soil heat flux by single layer soil temperature.

Soil heat flux is one of the important components of surface energy balance. In this study, long-term estimation of soil heat flux from single layer soil temperature was carried out by the traditional sinusoidal analytical method and the half-order time derivative method of Wang and Bras [Wang and Bras (1999) J Hydrol 216:214-226]. In order to understand the characteristics of soil heat flux and to examine the performances of the two methods, a field experiment was conducted at a temperate and humid grassland in Cork, Ireland. Our results show that the soil heat flux had the same magnitude as the sensible heat flux at this grassland site. It was also demonstrated that the analytical method did not predict the soil heat flux well because the sinusoidal assumption for the temporal variation in soil heat flux was invalid. In contrast, good agreement was found between the soil heat flux measurements and predictions made by the half-order time derivative method. This success suggests that this method could be used to estimate soil heat flux from long-term remotely sensed surface temperature.

Estimation of sensible heat, water vapor, and CO2 fluxes using the flux-variance method.

This study investigated the flux-variance relationships of temperature, humidity, and CO(2), and examined the performance of using this method for predicting sensible heat (H), water vapor (LE), and CO(2) fluxes (F(CO2)) with eddy-covariance measured flux data at three different ecosystems: grassland, paddy rice field, and forest. The H and LE estimations were found to be in good agreement with the measurements over the three fields. The prediction accuracy of LE could be improved by around 15% if the predictions were obtained by the flux-variance method in conjunction with measured sensible heat fluxes. Moreover, the paddy rice field was found to be a special case where water vapor follows flux-variance relation better than heat does. However, the CO(2) flux predictions were found to vary from poor to fair among the three sites. This is attributed to the complicated CO(2) sources and sinks distribution. Our results also showed that heat and water vapor were transported with the same efficiency above the grassland and rice paddy. For the forest, heat was transported 20% more efficiently than evapotranspiration.

Solid-state P-31 NMR study of the formation of hydroxyapatite in the presence of glutaric acid.

We demonstrate that glutaric acid can be used to prepare nanorods of hydroxyapatite under hydrothermal condition at 100 degrees C with a Ca(2+):glutaric acid molar ratio of 1:4. Frequency-switched Lee-Goldburg irradiation is employed to obtain high-resolution (31)P{(1)H} correlation spectra of the reaction mixture at two different reaction periods, from which it is shown that octacalcium phosphate is the precursor phase of the final hydroxyapatite product. In addition, the spectra show that a substantial amount of water molecules is trapped between the glutaric acid and the hydroxyapatite surface, indicating that water molecules may play a prominent role in the noncovalent interaction of the glutaric acid and the HAp surface.

A prognostic scoring system for locoregional control in nasopharyngeal carcinoma following conformal radiotherapy.

PURPOSE: This study established a prognostic scoring system for nasopharyngeal carcinoma (NPC), which estimates the probability of locoregional (LR) control following definitive conformal radiotherapy. METHODS AND MATERIALS: Patients with nondisseminated NPC at initial presentation (n = 630) were enrolled in this study. All patients had magnetic resonance imaging of the head and neck and were treated with conformal radiotherapy. Among them, 93% had concurrent chemotherapy, and 76% had postradiation chemotherapy. The extent of the primary tumor, age at diagnosis, primary tumor size, tumor and nodal classification, histology, and serum lactate dehydrogenase (LDH) level before treatment were included in the analysis for building a prognostic scoring system. The end point for this study was LR control. RESULTS: The prognostic score was defined as the number of adverse prognostic factors present at diagnosis. Four factors had similarly independent prognostic effects (hazard ratio, 2.0-2.6): age >40 years, histologic WHO type I-II, serum LDH level > or =410 U/L, and involvement of two or more sites of the following anatomic structures, i.e., sphenoid floor, clivus marrow, clivus cortex, prevertebral muscles, and petrous bone. The score predicted the 5-year probability of LR control as follows: 0 (15% of the patients), 100%; 1 (42% of the patients), 93%; 2 (29% of the patients), 83%; 3 or higher (13% of the patients), 71%. CONCLUSION: This scoring system is useful in the decision-making for individual patients and the design of clinical trials to improve LR control for advanced-stage NPC.

Extended-field radiotherapy and high-dose-rate brachytherapy with concurrent and adjuvant cisplatin-based chemotherapy for locally advanced cervical cancer: a phase I/II study.

OBJECTIVE: The purpose of this prospective study was to investigate the toxicity and efficacy of integrating extended-field para-aortic and pelvic external radiation, high-dose-rate intracavity brachytherapy, and concurrent and adjuvant cisplatin-based chemotherapy for locally advanced cervical cancer. METHOD: A phase I/II study was performed from 1998 to 2003 including sixty-three patients with both clinical FIGO and MRI/CT-based TNM stage IIB-IVA cervical cancer. Patients were treated with extended-field external radiation to the para-aortic and pelvic regions with 45 Gy in 25 fractions, and an additional boost to the gross nodes to 50.4 Gy and the parametrium to 59.4 Gy. Patients also received a high-dose-rate (HDR) intracavity brachytherapy with doses of 22-31 Gy to point A in 4-6 fractions. Concurrently, two cycles of cisplatin (50-80 mg/m(2)) were administered in weeks 1 and 5 during radiotherapy, as well as two cycles of cisplatin (60-80 mg/m(2)) for 1 day and 5-fluorouracil (600-800 mg/m(2)) for 4 days at 1 and 2 months after completion of radiotherapy. The treatment-related acute and late side effects were evaluated using RTOG criteria, and the disease control and survival rate were calculated using the Kaplan-Meier method. The median follow-up interval was 36 months. RESULTS: All sixty-three patients completed the planned extended-field radiotherapy and high-dose-rate brachytherapy with 2 concurrent cycles of cisplatin. Fifty-eight (92%) patients received 2 cycles of the post-radiation adjuvant chemotherapy of cisplatin and 5-fluorouracil. RTOG grade III acute toxicity was gastrointestinal (2%) and hematological (10%). No patient had grade IV acute toxicity. Late grades III-IV morbidity actuarial risk of 6% at 6.5 years primarily involved the injuries to the bowels requiring surgical intervention for intestinal obstruction or fistula formation. Initial sites of recurrence were locoregional failure alone (pelvic and para-aortic regions within the radiation field), 3%; distant metastases only, 8%; and locoregional failure plus distant metastases, 8%. The observed rates at 3-year and 5-year of locoregional control, freedom from distant metastasis, and overall survival were 86% and 86%, 81% and 81%, and 81% and 77%, respectively. CONCLUSION: Incorporating HDR brachytherapy into a regimen including concurrent chemotherapy and extended radiation appears safe and effective.

Removal of copper (II) by manganese-coated sand in a liquid fluidized-bed reactor.

This study was performed in a fluidized-bed reactor (FBR) filled with manganese-coated sand (MCS) to treat copper-contaminated wastewater. The adsorption characteristics of MCS, the adsorption equilibrium of MCS, and the copper removal capacity by MCS in FBR were investigated. In terms of the adsorption characteristics of MCS, the surface of MCS was evaluated using a scanning electron microscope (SEM). Energy dispersive analysis (EDS) of X-rays indicated the composition of MCS, and the quantity of manganese on MCS was determined by means of acid digestion analysis. The experimental results indicated that copper was removed by both sorption (ion exchange and adsorption) and coprecipitation on the surface of MCS in FBR. Copper removal efficiency was highly dependent on the pH and increased with increasing pH from pH 2 to 8. After the copper adsorption by MCS, the pH in solution was decreased. When the MCS concentration was greater than 10 g/l, the copper adsorptivities obtained by FBR were almost the same as that from the shaker and when the MCS concentration reached 40 g/l, the copper adsorptivity in FBR was greater than that from the shaker. The adsorption sites of MCS could be used efficiently by the FBR. A Langmuir adsorption isotherm equation fit the measured adsorption data from the batch equilibrium adsorption test better than the Freundlich adsorption isotherm equation did. In addition, the adsorption rate increased when the influent wastewater was aerated.