Population-based study of the impact of surgical and adjuvant therapy at the same or a different institution on survival of patients with pancreatic adenocarcinoma.

Background: Pancreatic cancer surgery is increasingly regionalized in high-volume centres. Provision of adjuvant chemotherapy in the same institution can place a burden on patients, whereas receiving adjuvant chemotherapy at a different institution closer to home may create disparities in care. This study compared long-term outcomes of patients with pancreatic adenocarcinoma receiving adjuvant chemotherapy at the institution where they had undergone surgery with outcomes for those receiving chemotherapy at a different institution. Methods: This was a population-based study of patients receiving adjuvant chemotherapy after resection of pancreatic adenocarcinoma performed at ten designated hepatopancreatobiliary centres in Ontario, Canada, between 2004 and 2014. Patients were divided into those receiving chemotherapy at the same institution as surgery or a different institution from where surgery was performed. The primary outcome was overall survival (OS). Multivariable Cox regression assessed the association between OS and each chemotherapy group, adjusted for potential confounders. Results: Of 589 patients, 374 (63·5 per cent) received adjuvant chemotherapy at the same institution as surgery. After adjusting for age, sex, co-morbidity, socioeconomic status, rural living, tumour stage, margin positivity and year of surgery, the location of adjuvant chemotherapy was not independently associated with OS (hazard ratio 1·03, 95 per cent c.i. 0·85 to 1·24). For patients who underwent chemotherapy at a different institution, mean travel distance to receive chemotherapy was less (22·9 km) than that needed for surgery (106·7 km). Conclusion: After pancreatectomy for pancreatic adenocarcinoma at specialized hepatopancreatobiliary surgery centres, OS was not affected by the location of the centre delivering adjuvant chemotherapy. Receiving this treatment in a local centre reduced patients' travel burden.

Geographic variation in surgical practice patterns and outcomes for resected nonmetastatic gastric cancer in Ontario.

Background: Gastrectomy with negative resection margins and adequate lymph node dissection is the cornerstone of curative treatment for gastric cancer (gc). However, gastrectomy is a complex and invasive operation with significant morbidity and mortality. Little is known about surgical practice patterns or short- and long-term outcomes in early-stage gc in Canada. Methods: We undertook a population-based retrospective cohort study of patients with gc diagnosed between 1 April 2005 and 31 March 2008. Chart review provided clinical and operative details such as disease stage, primary tumour location, surgical approach, operation, lymph nodes, and resection margins. Administrative data provided patient demographics, geography, and vital status. Variations in treatment and outcomes were compared for 14 local health integration networks. Descriptive statistics and log-rank tests were used to examine geographic variation. Results: We identified 722 patients with nonmetastatic resected gc. We documented significant provincial variation in case mix, including primary tumour location, stage at diagnosis, and tumour grade. Short-term surgical outcomes varied across the province. The percentage of patients with 15 or fewer lymph nodes removed and examined varied from 41.8% to 73.8% (p = 0.02), and the rate of positive surgical margins ranged from 15.2% to 50.0% (p = 0.002). The 30-day surgical mortality rates did not vary statistically significantly across the province (p = 0.13); however, rates ranged from 0% to 16.7%. Overall 5-year survival was 44% and ranged from 31% to 55% across the province. Conclusions: This cohort of patients with resected stages i-iii gc is the largest analyzed in Canada, providing important historical information about treatment outcomes. Understanding the causes of regional variation will support interventions aiming to improve gc operative outcomes in the cancer system.

"Low platelet usage" haematology laboratories: To store or not to store?

In the UK, hospitals with annual platelet use of less than 500 pools, like our institution, usually do not store platelets on-site and these are only ordered from the national blood service (NBS) when a transfusion is required. In 2016, we piloted routine on-site storage of one pool of A RhD negative PLT. Data were collected retrospectively on units of PLTs ordered from NBS, units transfused to patients, wastage, requirements for emergency deliveries from NBS and overall cost. These were compared to corresponding data from the four preceding years (2012-2015). There was a 39% reduction in the PLT ordered from NBS in 2016 compared to previous years and a 50% reduction in transfused PLT. Annual wastage for 2016 increased by 23% even though the absolute number of wasted PLT did not alter significantly. Annual cost reduced by 36% in 2016 resulting from reduction in the total amount of PLTs ordered as well as reduction in emergency deliveries.

Budget impact analysis of a breast rapid diagnostic unit.

BACKGROUND: The Odette Cancer Centre's recent implementation of a rapid diagnostic unit (rdu) for breast lesions has significantly decreased wait times to diagnosis. However, the economic impact of the unit remains unknown. This project defined the development and implementation costs and the operational costs of a breast rdu in a tertiary care facility. METHODS: From an institutional perspective, a budget impact analysis identified the direct costs associated with the breast rdu. A base-case model was also used to calculate the cost per patient to achieve a diagnosis. Sensitivity analyses computed costs based on variations in key components. Costs are adjusted to 2015 valuations using health care-specific consumer price indices and are reported in Canadian dollars. RESULTS: Initiation cost for the rdu was $366,243. The annual operational cost for support staff was $111,803. The average per-patient clinical cost for achieving a diagnosis was $770. Sensitivity analyses revealed that, if running at maximal institutional capacity, the total annual clinical cost for achieving a diagnosis could range between $136,080 and $702,675. CONCLUSIONS: Establishment and maintenance of a breast rdu requires significant investment to achieve reductions in time to diagnosis. Expenditures ought to be interpreted in the context of institutional patient volumes and trade-offs in patient-centred outcomes, including lessened patient anxiety and possibly shorter times to definitive treatment. Our study can be used as a resource-planning tool for future rdus in health care systems wishing to improve diagnostic efficiency.

Predictors of adjuvant treatment for pancreatic adenocarcinoma at the population level.

BACKGROUND: In the present study, we aimed to describe, at the population level, patterns of adjuvant treatment use after curative-intent resection for pancreatic adenocarcinoma (pcc) and to identify independent predictors of adjuvant treatment use. METHODS: In this observational cohort study, patients undergoing pcc resection in the province of Ontario (population 13 million) during 2005-2010 were identified using the provincial cancer registry and were linked to administrative databases that include all treatments received and outcomes experienced in the province. Patients were defined as having received chemotherapy (ctx), chemoradiation (crt), or observation (obs). Clinicopathologic factors associated with the use of ctx, crt, or obs were identified by chi-square test. Logistic regression analyses were used to identify independent predictors of adjuvant treatment versus obs, and ctx versus crt. RESULTS: Of the 397 patients included, 75.3% received adjuvant treatment (27.2% crt, 48.1% ctx) and 24.7% received obs. Within a single-payer health care system with universal coverage of costs for ctx and crt, substantial variation by geographic region was observed. Although the likelihood of receiving adjuvant treatment increased from 2005 to 2010 (p = 0.002), multivariate analysis revealed widespread variation between the treating hospitals (p = 0.001), and even between high-volume hepatopancreatobiliary hospitals (p = 0.0006). Younger age, positive lymph nodes, and positive surgical resection margins predicted an increased likelihood of receiving adjuvant treatment. Among patients receiving adjuvant treatment, positive margins and a low comorbidity burden were associated with crt compared with ctx. CONCLUSIONS: Interinstitutional medical practice variation contributes significantly to differential patterns in the rate of adjuvant treatment for pcc. Whether such variation is warranted or unwarranted requires further investigation.

Negative predictive value of preoperative computed tomography in determining pathologic local invasion, nodal disease, and abdominal metastases in gastric cancer.

BACKGROUND: Before undergoing curative-intent resection of gastric adenocarcinoma (ga), most patients undergo abdominal computed tomography (ct) imaging to determine contraindications to resection (local invasion, distant metastases). However, the ability to detect contraindications is variable, and the literature is limited to single-institution studies. We sought to assess, on a population level, the clinical relevance of preoperative ct in evaluating the resectability of ga tumours in patients undergoing surgery. METHODS: In a provincial cancer registry, 2414 patients with ga diagnosed during 2005-2008 at 116 institutions were identified, and a primary chart review of radiology, operative, and pathology reports was performed for all patients. Preoperative abdominal ct reports were compared with intraoperative findings and final pathology reports (reference standard) to determine the negative predictive value (npv) of ct in assessing local invasion, nodal involvement, and intra-abdominal metastases. RESULTS: Among patients undergoing gastrectomy, the npv of ct imaging in detecting local invasion was 86.9% (n = 536). For nodal metastasis, the npv of ct was 43.3% (n = 450). Among patients undergoing surgical exploration, the npv of ct for intra-abdominal metastases was 52.3% (n = 407). CONCLUSIONS: Preoperative abdominal ct imaging reported as negative is most accurate in determining local invasion and least accurate in nodal assessment. The poor npv of ct should be taken into account when selecting patients for staging laparoscopy.

The bone morphogenetic protein type Ib receptor is a major mediator of glial differentiation and cell survival in adult hippocampal progenitor cell culture.

Bone morphogenetic proteins (BMPs) act as growth regulators and inducers of differentiation. They transduce their signal via three different type I receptors, termed activin receptor-like kinase 2 (Alk2), Alk3, or bone morphogenetic protein receptor Ia (BMPRIa) and Alk6 or BMPRIb. Little is known about functional differences between the three type I receptors. Here, we have investigated consequences of constitutively active (ca) and dominant negative (dn) type I receptor overexpression in adult-derived hippocampal progenitor cells (AHPs). The dn receptors have a nonfunctional intracellular but functional extracellular domain. They thus trap BMPs that are endogenously produced by AHPs. We found that effects obtained by overexpression of dnAlk2 and dnAlk6 were similar, suggesting similar ligand binding patterns for these receptors. Thus, cell survival was decreased, glial fibrillary acidic protein (GFAP) expression was reduced, whereas the number of oligodendrocytes increased. No effect on neuronal differentiation was seen. Whereas the expression of Alk2 and Alk3 mRNA remained unchanged, the Alk6 mRNA was induced after impaired BMP signaling. After dnAlk3 overexpression, cell survival and astroglial differentiation increased in parallel to augmented Alk6 receptor signaling. We conclude that endogenous BMPs mediate cell survival, astroglial differentiation and the suppression of oligodendrocytic cell fate mainly via the Alk6 receptor in AHP culture.

Food safety: current situation, unaddressed issues and the emerging priorities.

This paper reviews the topic of food safety with reference to the Eastern Mediterranean Region. The differing views of food safety and the current situation with regard to ensuring food safety are presented. Also discussed are some of the unaddressed issues and challenges related to food safety. The new conditions that have arisen in the modern world which have facilitated the emergence of pathogens are presented, such as changes in animal husbandry, changes in international trade and travel, lifestyle and consumer changes. The urgent need for action in order to reduce the risk of microbiological and chemical foodborne diseases is emphasized. The food chain starts from farm and ends at fork; controlling this complex process requires an integrated approach and a responsible authority to oversee it in order to protect and promote food safety.

Food safety: current situation, unaddressed issues and the emerging priorities

This paper reviews the topic of food safety with reference to the Eastern Mediterranean Region. The differing views of food safety and the current situation with regard to ensuring food safety are presented. Also discussed are some of the unaddressed issues and challenges related to food safety. The new conditions that have arisen in the modern world which have facilitated the emergence of pathogens are presented, such as changes in animal husb and ry, changes in international trade and travel, lifestyle and consumer changes. The urgent need for action in order to reduce the risk of microbiological and chemical foodborne diseases is emphasized. The food chain starts from farm and ends at fork; controlling this complex process requires an integrated approach and a responsible authority to oversee it in order to protect and promote food safety

A simple method for preparation of immuno-magnetic liposomes.

A simple and readily manoeuverable method for preparing immuno-magnetic liposomes that indigenously contain binding sites for attaching other molecules like antibodies on their exterior surface is described. In this method magnetic unilamellar vesicles are prepared from a mixture of phosphatidylcholine, cholesterol, small amounts of a linear chain aldehyde and colloidal particles of magnetic iron oxide, using a reverse phase evaporation technique. The aldehyde (dedecanal) molecules align themselves among the lipid molecules in the bilayer with their aldehyde groups exposed to the aqueous phase, allowing straight attachment of antibody molecules (human-antimouse IgG-FITC in this case) in one single step. The success of this approach is confirmed by fluorescence microscopy as well as binding of the resulting immuno-magnetic liposomes to their corresponding target cells.