Collagenolysis-dependent DDR1 signalling dictates pancreatic cancer outcome.

Pancreatic ductal adenocarcinoma (PDAC) is a highly desmoplastic, aggressive cancer that frequently progresses and spreads by metastasis to the liver1. Cancer-associated fibroblasts, the extracellular matrix and type I collagen (Col I) support2,3 or restrain the progression of PDAC and may impede blood supply and nutrient availability4. The dichotomous role of the stroma in PDAC, and the mechanisms through which it influences patient survival and enables desmoplastic cancers to escape nutrient limitation, remain poorly understood. Here we show that matrix-metalloprotease-cleaved Col I (cCol I) and intact Col I (iCol I) exert opposing effects on PDAC bioenergetics, macropinocytosis, tumour growth and metastasis. Whereas cCol I activates discoidin domain receptor 1 (DDR1)-NF-κB-p62-NRF2 signalling to promote the growth of PDAC, iCol I triggers the degradation of DDR1 and restrains the growth of PDAC. Patients whose tumours are enriched for iCol I and express low levels of DDR1 and NRF2 have improved median survival compared to those whose tumours have high levels of cCol I, DDR1 and NRF2. Inhibition of the DDR1-stimulated expression of NF-κB or mitochondrial biogenesis blocks tumorigenesis in wild-type mice, but not in mice that express MMP-resistant Col I. The diverse effects of the tumour stroma on the growth and metastasis of PDAC and on the survival of patients are mediated through the Col I-DDR1-NF-κB-NRF2 mitochondrial biogenesis pathway, and targeting components of this pathway could provide therapeutic opportunities.

Conventional Versus Traction Endoscopic Submucosal Dissection for Colorectal Tumors: A Meta-analysis of Randomized Controlled Trials.

INTRODUCTION: Compared with conventional endoscopic submucosal dissection (C-ESD) for colorectal lesions, the traction method (T-ESD) allows the lesion to be stabilized with easier dissection. However, randomized controlled trials (RCTs) have reported conflicting results on the clinical outcomes of T-ESD as compared with C-ESD. We conducted a meta-analysis to compile the data. METHODS: Multiple databases were searched for RCTs evaluating C-ESD versus T-ESD for colorectal tumors. The end points of interest were procedure time (min), resection speed (mm²/min), R0 resection, en bloc resection, delayed bleeding, and perforation. Standard meta-analysis methods were employed using the random-effects model. RESULTS: Six RCTs with a total of 566 patients (C-ESD n=284, T-ESD n=282) were included. The mean age was 67±10 y and 60% were men. As compared with the T-ESD technique, the C-ESD group was associated with longer procedure time (SMD 0.91, 95% CI 0.58 to 1.23, P<0.00001) and lesser resection speed (SMD -1.03, 95% CI -2.01 to -0.06, P=0.04). No significant difference was found in the 2 groups with respect to R0 resection rate (RR 1.00, 95% CI 0.94 to 1.06, P=0.87), en bloc resection (RR 0.99, 95% CI 0.97 to 1.01, P=0.35), delayed bleeding (RR 0.66, 95% CI 0.17 to 2.59, P=0.55) and perforation (RR 2.16, 95% CI 0.75 to 6.27, P=0.16). DISCUSSION: On meta-analysis, pooled procedure time was significantly faster with T-ESD compared with C-ESD. The clinical outcomes, however, were comparable.

Energy-Based Devices for the Treatment of Cutaneous Verrucae: A Systematic Review.

BACKGROUND: Warts are one of the most common benign neoplasms caused by human papillomavirus infection and often pose a therapeutic challenge. OBJECTIVE: To summarize the current evidence on the safety and efficacy of laser and energy-based devices for the treatment of cutaneous verrucae. METHODS: A comprehensive systematic review of the literature on laser and energy-based devices for the treatment of cutaneous verrucae was performed. RESULTS: A total of 904 unique studies were identified, of which 109 were included in this review. The most commonly used lasers as a single treatment modality for verrucae included the long-pulsed Nd:Yag (n = 20) and pulsed dye (n = 18) lasers. Other modalities included the CO2 ablative laser (n = 10), photodynamic therapy (n = 11), local hyperthermia (n = 11), microwave therapy (n = 2), and nanopulse stimulation (n = 1). Other studies combined energy-based modalities with additional treatments, such as retinoids, imiquimod, and intralesional bleomycin. Overall, such devices were generally well-tolerated, with only a mild side effect profile. CONCLUSION: Overall, the use of laser and energy-based devices is a safe and well-tolerated option for cutaneous verrucae that is relatively less invasive than surgical interventions. Future studies using more consistent outcome assessment tools will be valuable to help clinicians develop device-specific protocols and treatment regimens to ensure replicable and effective outcomes.

Prevalence of tinnitus following non-blast related traumatic brain injury: a systematic review of literature.

OBJECTIVES: To establish the prevalence of tinnitus in adults who have sustained non-blast related traumatic brain injury (TBI), as well as the prevalence of tinnitus following TBI in the absence of hearing loss. METHODS: A systematic search was carried out using MEDLINE, EMBASE, PsycINFO, CINAHL from January 1st 1990 to August 14th 2023. TBI, tinnitus and auditory findings were extracted from all eligible studies, and a descriptive synthesis performed. This systematic review was registered with PROSPERO (Registration number: CRD42022377637). RESULTS: Based on the Oxford Centre of Evidence-Based Medicine (OCEBM) (2011) criteria, the highest quality evidence identified was at Level 2b, with the bulk of the included studies predominantly populating the lower evidence tiers. While there was a substantial variability in the methods used to establish and report the presence of tinnitus, its occurrence following TBI was evident in adults with and without hearing loss. CONCLUSION: The need for prospective, longitudinal research into tinnitus following non-blast related TBI is evident. Such comprehensive studies hold the potential to inform and enhance the clinical diagnosis and management of this patient population.

Laser Applications in Wound and Scar Management Post-Mohs Micrographic Surgery: A Systematic Review.

Mohs micrographic surgery (MMS) can lead to complications such as scarring and delayed wound healing, particularly in sensitive areas such as the face, neck, and chest. This study aims to assess the evidence regarding the use of lasers post-MMS for wound healing and scar revision. A comprehensive systematic review of the literature was performed using databases including MEDLINE, PubMed, EMBASE, Web of Science, Cochrane Library, and CINAHL from inception until July 25, 2022. A total of 2147 unique studies were identified, from which 17 were included in the analysis. A total of 17 studies reported applications of lasers with favourable efficacy including wound healing (n = 1), resurfacing of full-thickness skin grafts and split-thickness skin grafts (n = 4), periscar telangiectasias (n = 1), functional scar contractures (n = 2), and scar texture (n = 9). Minimal adverse effects were reported with the use of lasers post-MMS. Overall, the use of lasers post-MMS is a safe and well-tolerated option for scar revision with high patient satisfaction and is less invasive than surgical interventions.

Comparing Transcriptomic Points of Departure to Apical Effect Concentrations For Larval Fathead Minnow Exposed to Chemicals with Four Different Modes Of Action.

It is postulated that below a transcriptomic-based point of departure, adverse effects are unlikely to occur, thereby providing a chemical concentration to use in screening level hazard assessment. The present study extends previous work describing a high-throughput fathead minnow assay that can provide full transcriptomic data after exposure to a test chemical. One-day post-hatch fathead minnows were exposed to ten concentrations of three representatives of four chemical modes of action: organophosphates, ecdysone receptor agonists, plant photosystem II inhibitors, and estrogen receptor agonists for 24 h. Concentration response modeling was performed on whole body gene expression data from each exposure, using measured chemical concentrations when available. Transcriptomic points of departure in larval fathead minnow were lower than apical effect concentrations across fish species but not always lower than toxic effect concentrations in other aquatic taxa like crustaceans and insects. The point of departure was highly dependent on measured chemical concentration which were often lower than the nominal concentration. Differentially expressed genes between chemicals within modes of action were compared and often showed statistically significant overlap. In addition, reproducibility between identical exposures using a positive control chemical (CuSO4) and variability associated with the transcriptomic point of departure using in silico sampling were considered. Results extend a transcriptomic-compatible fathead minnow high-throughput assay for possible use in ecological hazard screening.

Characterization of Selective M5 Acetylcholine Muscarinic Receptor Modulators on Dopamine Signaling in the Striatum.

The type-5 muscarinic acetylcholine receptor (mAChR, M5) is almost exclusively expressed in dopamine (DA) neurons of the ventral tegmental area and substantia nigra pars compacta; therefore, they are ideally located to modulate DA signaling and underlying behaviors. However, the role of M5 in shaping DA release is still poorly characterized. In this study, we first quantitatively mapped the expression of M5 in different neurons of the mouse midbrain, then used voltammetry in mouse striatum to evaluate the effect of M5-selective modulators on DA release. The M5 negative allosteric modulator ML375 significantly decreased electrically evoked DA release and blocked the effect of Oxotremorine-M (Oxo-M; nonselective mAChR agonist) on DA release in the presence of an acetylcholine nicotinic receptor blocker. Conversely, the M5 positive allosteric modulator VU 0365114 significantly increased electrically evoked DA release and the Oxo-M effect on DA release. We then assessed M5's impact on mesolimbic circuit function in vivo. Although psychostimulant-induced locomotor activity models in knockout mice have previously been used to characterize the role of M5 in DA transmission, the results of these studies conflict, leading us to select a different in vivo model, namely a cocaine self-administration paradigm. In contrast to a previous study that also used this model, in the current study, administration of ML375 did not decrease cocaine self-administration in rats (using fixed and progressive ratio). These conflicting results illustrate the complexity of M5 modulation and the need to further characterize its involvement in the regulation of dopamine signaling, central to multiple neuropsychiatric diseases. SIGNIFICANCE STATEMENT: This work describes the type-5 muscarinic receptor (M5) pattern of expression within the midbrain as well as its physiological modulation by selective compounds at the axon terminal level in the striatum, where M5 directly shapes dopamine transmission. It offers the first direct readout of mesolimbic dopamine release modulation by M5, highlighting its role in regulating neurocircuits implicated in the pathophysiology of neuropsychiatric disorders such as substance use disorders, major depressive disorder, and schizophrenia.

Diagnostic performance of contrast-enhanced ultrasound in diagnosing hepatic artery occlusion after liver transplantation: A systematic review and meta-analysis.

INTRODUCTION: Hepatic artery occlusion (HAO) is a significant complication post-liver transplantation. Doppler ultrasound (DUS) has been widely used as an initial screening test for detecting HAO; however, its performance is often not sufficient. Although other diagnostic tests such as computed tomography angiography (CTA), magnetic resonance angiography (MRA), and angiogram are more accurate, they are invasive and have several limitations. Contrast-enhanced ultrasound (CEUS) is an emerging tool for detecting HAO; however, the results from previous studies were limited due to a small number of patients. Therefore, we aimed to evaluate its performance by performing a meta-analysis. METHOD: We performed a systemic review and meta-analysis of studies evaluating the performance of CEUS for the detection of HAO in an adult population. A literature search of EMBASE, Scopus, CINAHL, and Medline was conducted through March 2022. Pooled sensitivity, specificity, log diagnostic odd ratio (LDOR), and area under summary receiver operating curve (AUC) were calculated. Publication bias was assessed by Deeks' funnel plot. RESULT: Eight studies were included, with 434 CEUS performed. Using a combination of CTA, MRA, angiography, clinical follow-up, and surgery as the gold standard, the sensitivity, specificity, and LDOR of CEUS for detection of HAO were .969 (.938, .996), .991 (.981, 1.001), and 5.732 (4.539, 6.926), respectively. AUC was .959. The heterogeneity between studies appeared universally low, and no significant publication bias was found (p = .44). CONCLUSION: CEUS appeared to have an excellent performance for the detection of HAO and could be considered as an alternative when DUS is non-diagnostic or when CTA, MRA, and angiogram are not feasible.

Mohs Micrographic Surgery Is Equivalent to Nail Unit Excision or Amputation for Melanoma In Situ of the Nail Unit: A Systematic Review and Meta-Analysis.

BACKGROUND: Local recurrence (LR) rates of melanoma in situ (MIS) of the nail apparatus treated with different surgical modalities are unknown. OBJECTIVE: To evaluate the differences in LR rates of nail apparatus MIS treated with Mohs micrographic surgery (MMS) versus nail unit excision (NUE) versus amputation. METHODS: Studies of nail/subungual MIS treated with MMS, NUE, or amputation were identified through multiple literature databases, including PubMed, MEDLINE, Embase, Web of Science, and Cochrane Library. Pooled data were assessed through meta-analyses and Fisher exact test. RESULTS: Of 280 studies identified, 20 met inclusion criteria (7 comparative studies and 13 single-arm studies). Among the 7 comparative studies, the LR was 4.38% (5/114) after NUE and 2.94% (1/34) after amputation (odds ratio: 0.937; 95% CI: 0.237-3.703). In the 13 noncomparative studies, 23 patients underwent MMS (pooled LR estimate: 11.07%; 95% CI: 3.22%-31.81%) and 140 patients underwent NUE (pooled LR estimate:8.04%, 95% CI: 4.43%-14.16%). The difference in LR rate between MMS, NUE, and amputation was not statistically significant ( p = .578). CONCLUSION: Local recurrence of nail/subungual MIS in cases treated with MMS was not statistically different than in cases treated with NUE and was comparable to amputation. Further studies investigating the use of MMS for the treatment of nail/subungual MIS are warranted.

Cold urticaria in a pediatric cohort: Clinical characteristics, management, and natural history.

BACKGROUND: Cold urticaria (coldU) is associated with substantial morbidity and risk of fatality. Data on coldU in children are sparse. We aimed to evaluate the clinical characteristics, management, risk of associated anaphylaxis, and resolution rate of coldU in a pediatric cohort. Additionally, we sought to compare these metrics to children with chronic spontaneous urticaria (CSU). METHODS: We prospectively enrolled children with coldU from 2013-2021 in a cohort study at the Montreal Children's Hospital and an affiliated allergy clinic. Data for comparison with participants with solely CSU were extracted from a previous study. Data on demographics, comorbidities, severity of presentation, management, and laboratory values were collected at study entry. Patients were contacted yearly to assess for resolution. RESULTS: Fifty-two children with cold urticaria were recruited, 51.9% were female and the median age of symptom onset was 9.5 years. Most patients were managed with second-generation H1-antihistamines (sgAHs). Well-controlled disease on sgAHs was negatively associated with concomitant CSU (adjusted odds ratio (aOR) = 0.69 [95%CI: 0.53, 0.92]). Elevated eosinophils were associated with cold-induced anaphylaxis (coldA; aOR = 1.38 [95%CI: 1.04, 1.83]), which occurred in 17.3% of patients. The resolution rate of coldU was 4.8 per 100 patient-years, which was lower than that of CSU (adjusted hazard ratio = 0.43 [95%CI: 0.21, 0.89], p < 10-2 ). CONCLUSION: Pediatric coldU bears a substantial risk of anaphylaxis and a low-resolution rate. Absolute eosinophil count and co-existing CSU may be useful predictive factors.

Analysis of Geographic and Environmental Factors and Their Association with Cutaneous Melanoma Incidence in Canada.

BACKGROUND: Over 90% of skin cancers including cutaneous melanoma (CM) are related directly to sun exposure. Despite extensive knowledge on ultraviolet radiation's (UVR) detrimental impact, many still fail to implement sun protection/sun avoidance. Human behavior, attitudes, and cultural norms of individuals and communities heavily depend on the surrounding climate/environment. In many instances, the climate shapes the culture/norms of the society. Canada has vast geographic/environmental differences. METHODS: In the current ecological study, we sought to examine the relationship between various geographic and environmental factors and the distribution of CM incidence by Forward Sortation Area (FSA) postal code across Canada. CM incidence data were extracted from the Canadian Cancer Registry, while environmental data were extracted from the Canadian Urban Environmental Health Research Consortium (greenspace, as measured by the normalized difference vegetation index; annual highest temperature; absolute number and average length of yearly heat events; annual total precipitation [rain and snow]; absolute number and average length of events with precipitation [rain and snow]; and summer UVR index). The above geographic/environmental data by FSA were correlated with the respective CM incidence employing negative binomial regression model. RESULTS: Our analysis highlights that increases in annual average temperature, summer UVR, and greenspace were associated with higher expected incidence of CM cases, while higher number of annual heat events together with highest annual temperature and higher average number of annual rain events were associated with a decrease in CM incidence rate. This study also highlights regional variation in environmental CM risk factors in Canada. CONCLUSIONS: This national population-based study presents clinically relevant conclusions on weather/geographic variations associated with CM incidence in Canada and will help refine targeted CM prevention campaigns by understanding unique weather/geographic variations in high-risk regions.

Prominent Role of Type 2 Immunity in Skin Diseases: Beyond Atopic Dermatitis.

Type 2 immunity, illustrated by T helper 2 lymphocytes (Th2) and downstream cytokines (IL-4, IL-13, IL-31) as well as group 2 innate lymphoid cells (ILC2), is important in host defense and wound healing.1 The hallmark of type 2 inflammation is eosinophilia and/or high IgE counts and is best recognized in atopic diathesis. Persistent eosinophilia, such as seen in hypereosinophilic syndromes, leads to fibrosis and hence therapeutic Type 2 inhibition in fibrotic diseases is of high interest. Furthermore, as demonstrated in cutaneous T cell lymphoma, advanced disease is characterized by Th1 to Th2 switch allowing cancer progression and immunosuppression. Development of targeted monoclonal antibodies against IL-4Rα (eg, dupilumab) led to a paradigm shift for the treatment of atopic dermatitis (AD) and stimulated research to better understand the role of Type 2 inflammation in other skin conditions. In this review, we summarize up to date knowledge on the role of Type 2 inflammation in skin diseases other than AD and highlight whether the use of Type 2 targeted therapies has been documented or is being investigated in clinical trials. This manuscript reviews the role of Type 2 inflammation in dermatitis, neurodermatitis, IgE-mediated dermatoses (eg, bullous pemphigoid, chronic spontaneous urticaria), sclerodermoid conditions and skin neoplasms.

Clinical Characteristics, Management, and Natural History of Chronic Inducible Urticaria in a Pediatric Cohort.

BACKGROUND: Some forms of chronic urticaria (CU) can be specifically attributed to a response to a definite trigger, referred to as chronic inducible urticaria (CIndU). We aimed to assess the demographics, clinical characteristics, comorbidities, natural history, and management of pediatric patients with CIndU. METHODS: Over a 6-year period, children presenting to the allergy clinic at the Montreal Children's Hospital (MCH) with CIndU were prospectively recruited. CU was defined as the presence of wheals and/or angioedema, occurring for at least 6 weeks. A standardized diagnostic test was used to establish the presence of a specific form of urticaria. Resolution was defined as the absence of hives for 1 year without treatment. RESULTS: Sixty-four patients presented with CIndU, of which 51.6% were male, with a median age of 12.5 (interquartile range 7.3, 15.9) years. Cold CU and cholinergic CU were the most common subtypes (60.3 and 41.3%, respectively). Basophil counts were undetectable in 48.4% of the cases, and C-reactive protein levels were elevated in 7.8% of patients. Of all cases, 71.4% were controlled with second-generation antihistamines. The resolution rate was of 45.3% (95% confidence interval 33.1-57.5%), based on per-protocol population within the 6-year course of the study. Resolution was more likely in patients who presented with well-controlled urticaria control test scores and elevated CD63 counts and in those suffering from thyroid comorbidity. CONCLUSION: The natural history of CIndU resolution in pediatric patients was relatively low and was associated with elevated CD63 levels, as well as thyroid comorbidity.

Inhibition of IL-13: A New Pathway for Atopic Dermatitis [Formula: see text].

Dupilumab, a monoclonal antibody against the common receptor of interleukin (IL)-4 and IL-13, was the first biologic therapy approved in Canada for treatment of moderate-to-severe atopic dermatitis (AD). While it is considered safe and effective, dupilumab is not universally effective and 8%-38% of patients develop conjunctivitis, while some patients develop head and neck dermatitis. Thus, new therapeutic options are warranted. While both IL-4 and IL-13 play important roles in the pathogenesis of AD, it has been recently demonstrated that IL-13 is the primary upregulated cytokine in AD skin biopsy samples. A placebo-controlled phase 2b clinical trial evaluating the efficacy and safety of lebrikizumab, an IL-13 inhibitor, in AD demonstrated that, at 16 weeks, Eczema Area and Severity Index (EASI) 75 and Investigator's Global Assessment (IGA) 0/1 were achieved by 60.6% and 44.6% of patients taking lebrikizumab at its highest dose (vs 24.3% and 15.3% of patients taking placebo, respectively). Moreover, treatment with lebrikizumab was associated with rapid improvement of pruritus and low rates of conjunctivitis (1.4%-3.8%). Another IL-13 monoclonal antibody, tralokinumab, was evaluated for safety and efficacy in moderate-to-severe AD. By week 12, among adults receiving 300 mg tralokinumab, 42.5% achieved EASI-75 and 26.7% achieved IGA 0/1 score (vs 15.5% and 11.8% in the placebo group, respectively). Both lebrikizumab and tralokinumab demonstrated acceptable safety profiles in AD (and non-AD) trials with adverse events often being comparable between treatment and control groups. Thus, IL-13 inhibitors may provide a safe and effective treatment alternative for patients with moderate-to-severe AD.

Epidemiologic trends and geographic distribution of patients with gallbladder and extrahepatic biliary tract cancers in Canada.

BACKGROUND: Gallbladder and biliary tract cancers are rare malignancies that carry a poor prognosis. Research on their epidemiologic trends is scarce. METHODS: We performed a retrospective analysis of the data in Canada using population-based cancer registries from 1992 to 2010. The incidence and mortality of gallbladder and extrahepatic bile duct cancers were examined at the levels of provinces/territories, cities, and Forward Sortation Area (FSA) postal codes. RESULTS: The incidence and mortality rates decreased over the study period. The average national incidence rate of gallbladder and biliary tract cancers was 30.92 cases per million individuals per year. Higher than average incidence rates were observed in Manitoba, Saskatchewan and Québec; there were contiguous regions with high incidence in Saskatchewan and Manitoba that suggest an area of putative case clustering. Higher incidence of gallbladder cancer was observed in women, whereas higher incidence of extrahepatic bile duct cancers was noted in men. Lower socioeconomic status and Hispanic race were found to be risk factors for gallbladder and biliary tract cancers. CONCLUSION: This is the first study to analyze the burden of gallbladder and biliary tract cancers in Canada. The geographic clustering trends present new avenues for research on environmental triggers.

Penile Invasive Squamous Cell Carcinoma: Analysis of Incidence, Mortality Trends, and Geographic Distribution in Canada.

BACKGROUND: Penile invasive squamous cell carcinoma (SCC) is a rare disease with several known risk factors. However, few studies have assessed its incidence, mortality, and temporal trends. OBJECTIVE: Our objectives are to analyze the epidemiology of penile SCC in Canada and to examine patient distribution with this cancer across Canada in order to elucidate population risk factors. METHODS: Three independent cancer registries were used to retrospectively analyze demographic data from Canadian men diagnosed with penile invasive SCC between 1992 and 2010. The Canadian Census of Population was used to calculate incidence and mortality rates at the province and Forward Sortation Area levels. RESULTS: The overall age-adjusted incidence rate was 6.08 cases per million males. Four provinces with statistically significantly higher incidence rates were identified. The national crude incidence rates increased linearly between 1992 and 2010, whereas the age-adjusted incidence rates showed no significant increase during this time period. The overall age-adjusted mortality rate was 1.88 deaths per million males per year. The province of Saskatchewan had significantly higher mortality rates. There was no increase in crude or age-adjusted mortality rates between 1992 and 2010. There was a significant positive correlation between incidence rates and obesity, Caucasian ethnicity, and lower socioeconomic status. CONCLUSION: This study was able to establish geographic variation for this malignancy at the provincial level. Although there are many established risk factors for penile SCC, our results suggest that the increase in crude incidence rates observed is largely due to the aging population.

Identification of significant geographic clustering of polycythemia vera cases in Montreal, Canada.

BACKGROUND: Polycythemia vera (PV) is a chronic myeloproliferative neoplasm associated at times with debilitating symptoms and a significant mortality rate. Understanding the demographics, epidemiology, and geography of this disease may provide further insight into important risk factors associated with its development. The objective of this study was to analyze patient demographics, incidence, and mortality rates, as well as the geographic distribution of PV patients in Canada between 1992 and 2010. METHODS: This study was achieved by analyzing the Canadian Cancer Registry, Le Registre Québécois du Cancer, and the Canadian Vital Statistics patient databases. RESULTS: A total of 4645 patients were diagnosed with PV between 1992 and 2010. While the annual incidence rate of this cancer fluctuated in Canada, mortality rate analysis indicated a decreasing trend. Geographically, PV incidence rates were notably elevated in the province of Quebec compared with the Canadian average. Further analysis of high-incidence forward sortation areas indicated a striking clustering of cases in the H4W region encompassing the Côte-Saint-Luc borough of Montreal, with an incidence of 102.97 (95% confidence interval, 75.11-137.79) cases per million per year, which is >13 times the national average. CONCLUSION: The residential area of Côte-Saint-Luc is an important PV cluster in Canada, with high concentration of retirement homes and geriatric hospices. Also, Jewish residents comprise >60% of the population in this neighborhood. These findings suggest that an older age and, potentially, an inherent genetic predisposition may be implicated in the pathogenesis of this malignancy. This study provides a comprehensive overview of PV burden/geographic distribution of cases in Canada.

Analysis of acute myeloid leukemia incidence and geographic distribution in Canada from 1992 to 2010 reveals disease clusters in Sarnia and other industrial US border cities in Ontario.

BACKGROUND: Several risk factors have been implicated in acute myeloid leukemia (AML) leukemogenesis. However, the epidemiologic distribution and precise triggers for AML in Canada remain poorly understood. METHODS: In this study, demographic data for AML patients in Canada from 1992 to 2010 were analyzed using 3 independent population-based cancer registries. The AML incidence and mortality rates were examined at the levels of province/territory, city, and forward sortation area (FSA) postal code. RESULTS: In total, 18,085 patients were identified. AML incidence was documented to be 30.61 cases per million individuals per year (95% confidence interval [CI], 30.17-31.06) from 1992 to 2010. Five industrial cities in Ontario were identified where incidence rates were significantly higher than the national average: Sarnia, Sault Ste. Marie, Thunder Bay, St. Catharines, and Hamilton. Analysis at the FSA postal code level identified significant patient clusters of AML in these cities. Specifically, FSA N7V in Sarnia, Ontario had an incidence of 106.81 (95% CI, 70.96-161.86) cases per million individuals per year, which is >3 times higher than the national average. The pollution from local oil refineries and chemical plants in Sarnia may be implicated as a risk factor for AML in that city. Analysis of mortality rates at the province and city levels corroborated the findings from the incidence data. CONCLUSION: These results provide a comprehensive analysis of AML burden in Canada and reveal striking geographic case clustering in industrial Ontario cities and potentially implicate exposure to materials/pollution from these plants as an important risk factor for developing AML in Canada.

Multiple myeloma epidemiology and patient geographic distribution in Canada: A population study.

BACKGROUND: Multiple myeloma (MM) is a malignancy of mature plasma cells. Environmental risk factors identified for this malignancy, among others, include farming and exposure to pesticides. METHODS: Using 3 independent population-based databases (the Canadian Cancer Registry, le Registre Québécois du Cancer, and Canadian Vital Statistics), this study analyzed patients' clinical characteristics and the incidence, mortality, and geographic distribution of MM cases in Canada during 1992-2015. RESULTS: In total, ~32,065 patients were identified, and 53.7% were male. The mean age at the time of diagnosis was 70 ± 12.1 years. The average incidence rate in Canada was 54.29 cases per million individuals per year, and linear regression modeling showed a steady rise in the annual rate of 0.96 cases per million individuals per year. At the provincial level, Quebec and Ontario had significantly higher incidence rates than the rest of Canada. An analysis of individual municipalities and postal codes showed lower incidence rates in large metropolitan areas and in high-latitude regions of the country, whereas high incidence rates were observed in smaller municipalities and rural areas. Land use analysis demonstrated increased density of crop farms and agricultural industries in high-incidence areas. A comparison with the available data from 2011-2015 showed several consistent trends at provincial, municipal, and regional levels. CONCLUSIONS: These results provide a comprehensive analysis of the MM burden in Canada. Large metropolitan cities as well as high-latitude regions were associated with lower MM incidence. Higher incidence rates were noted in smaller cities and rural areas and were associated with increased density of agricultural facilities.