Population-based Epidemiological Analysis Research Articles

Small bowel cancers: A population-based analysis of epidemiology, treatment and outcomes in Ontario, Canada from 2005-2020

IntroductionSmall bowel cancers are uncommon malignancies comprised of several histologies with variable treatments and prognoses. The current study describes the epidemiology, treatment, and outcomes of a large, population-based cohort of patients with small bowel cancers. MethodsWe performed a retrospective cohort study using linked administrative healthcare data from Ontario, Canada. Patients diagnosed with a small bowel cancer between 2005–2020 were included. Trends in incidence, treatments, and survival were explored by histology (adenocarcinoma, neuroendocrine tumors (NET), gastrointestinal stromal tumors (GIST), and lymphoma). ResultsA total of 5306 patients with small bowel cancers were identified. The most common histologies were NET (40.5 %) and adenocarcinoma (31.6 %). Over the study period the annual incidence of small bowel cancers increased from 1.54 to 2.78 per 100 000 and the likelihoods of receiving surgery and systemic therapy within one year of diagnosis both increased for all histologic subtypes except lymphoma. Median overall survival from diagnosis was 1.0 year for adenocarcinoma, 13.2 years for NET, 14.2 years for GIST, and 10.1 years for lymphoma. There was no trend towards improved median survival for adenocarcinoma by year of diagnosis; 0.94 years (2005–2010), 1.07 years (2011–2015), and 0.98 years (2016–2020). DiscussionSmall bowel cancers are increasing in incidence, with increasing use of surgery and systemic therapies. While survival is favourable for many small bowel cancers, it remains poor for adenocarcinoma. Better availability of cancer stage data and detailed histopathology within the database would facilitate future research. SynopsisThis study of small bowel cancer in Ontario from 2005 to 2020 demonstrated increasing incidence, use of surgery, and systemic treatments. The most common histologies are neuroendocrine tumors and adenocarcinoma, with median survivals of 13.2 and 1.0 years respectively.

Gastrointestinal stromal tumors of the upper GI tract: population-based analysis of epidemiology, treatment and outcome based on data from the German Clinical Cancer Registry Group

BackgroundGastrointestinal stromal tumors (GIST) are rare mesenchymal tumors. They are most frequently located in the stomach but are also found in the esophagus and the gastroesophageal junction (GEJ). Information regarding the prognostic factors associated with upper gastrointestinal GIST is still scarse.MethodsIn this study, datasets provided by the German Clinical Cancer Registry Group, including a total of 93,069 patients with malignant tumors in the upper GI tract (C15, C16) between 2000 and 2016 were analyzed to investigate clinical outcomes of GIST in the entire upper GI tract.ResultsWe identified 1361 patients with GIST of the upper GI tract. Tumors were located in the esophagus in 37(2.7%) patients, at the GEJ in 70 (5.1%) patients, and in the stomach in 1254 (91.2%) patients. The incidence of GIST increased over time, reaching 5% of all UGI tumors in 2015. The median age was 69 years. The incidence of GIST was similar between males and females (53% vs 47%, respectively). However, the proportion of GIST in female patients increased continuously with advancing age, ranging from 34.7% (41–50 years) to 71.4% (91–100 years). Male patients were twice as likely to develop tumors in the esophagus and GEJ compared to females (3.4% vs. 1.9% and 6.7% vs. 3.4%, respectively). The median overall survival of upper gastrointestinal GIST was 129 months. The 1-year, 5-year, and 10-year OS was 93%, 79%, and 52% respectively. Nevertheless, tumors located in the esophagus and GEJ were associated with shorter OS compared to gastric GIST (130 vs. 111 months, p = 0.001). The incidence of documented distant metastasis increased with more proximal location of GIST (gastric vs. GEJ vs. esophagus: 13% vs. 16% vs. 27%) at presentation.ConclusionGIST of the esophagus and GEJ are rare soft tissue sarcomas with increasing incidence in Germany. They are characterized by worse survival outcomes and increased risk of metastasis compared to gastric GIST.

Sacral Chordoma: A Population-based Analysis of Epidemiology and Survival Outcomes.

Sacral chordoma is a rare primary bone neoplasm associated with high morbidity. The aim of this study is to identify demographic and clinicopathological characteristics of this tumor and evaluate their impact on survival outcomes. The Surveillance, Epidemiology and End Results (SEER) database collecting data between 2000 and 2018 was searched for all cases of sacral chordoma. We analyzed demographic aspects, cancer stage and treatment patterns. Overall survival was calculated using the Kaplan-Meier method and compared between subgroups using the log-rank test. A multivariate Cox hazard regression analysis was conducted to identify independent predictors of overall survival. Four hundred and forty-two patients were identified with a mean age of 62.7 years. Most tumors presented regional invasion at diagnosis (43.2%). Mean overall survival was 124.7 months. No significant difference in terms of overall survival was found between surgery alone and surgery associated with radiotherapy. Both options provided a significantly increased survival than radiotherapy alone. Age of less than 50 years or between 50 and 69 correlated significantly with improved survival. Age and stage at diagnosis impact significantly survival outcomes. Surgery remains the mainstay treatment with the highest overall survival. Its association with radiotherapy is currently questionable and needs further research.

VP7: Merkel Cell Carcinoma of the Lower Limb and Hip: A Population-based Analysis of Epidemiology and Survival Outcomes with Focus on Surgery and Radiotherapy

VP7: Merkel Cell Carcinoma of the Lower Limb and Hip: A Population-based Analysis of Epidemiology and Survival Outcomes with Focus on Surgery and Radiotherapy

Survival among cancers screened at the first stage of Dispanserization of certain groups of the adult population: a population-based epidemiological analysis

Objective: to evaluate trends of survival in nine index malignant neoplasms (iMNs), which are screened at the first stage of the Dispanserization of certain groups of the adult population (DCGAP), on data of the Arkhangelsk regional cancer registry over a period 2006-2019.
 Materials and methods. We compared two seven-year periods 2006-2012 and 2013-2019, before and after the introduction of the DCGAP. The 1- and 5-year cancer-specific survival (CSS) rate was calculated using the life table and Kaplan-Meier methods with an assessment of the differences by log-rank. Cox regression analysis with sequential input was used to identify possible causes of differences in survival between periods and independent prognostic factors.
 Results. 37197 cases were selected for analysis. 5-year CSS estimates in 2013-2019 compared with the previous seven-year period significantly increased for all nine iMNs, by from 2.5% [2006-2012, 12.5% ​​(95% confidence interval (CI) 11.4-13.6%) vs 2013-2019, 15.0 (95% CI 13.7-16.5%)] in lung cancer up to 12.6% [2006-2012, 31.0% (95% CI 28.6-33.4%) vs 2013-2019, 43.6 (95% CI 40.8-46.2%)]. Correction for the stage (possible effect of screening) in the Cox model has led to a decrease in the hazard ratio (HR) of death from cancer of the colon, rectum, breast, kidney by 38-64%, no change for other iMNs; while for cervical cancer, it has increased. Adjustment for the variable "treatment method" led to a 34-100% decrease in the HR in the Cox model for all iMNs, except for prostate cancer.
 Conclusion. The increase in survival estimates for nine iMNs in 2013-2019 can be explained to a large extent by improved access to cancer-directed treatment and its quality; the contribution of DCGAP is possible in renal, breast and colorectal cancer.
 Key words: malignant neoplasms, screening, dispensarization of certain groups of the adult population, survival

From population to neuron: exploring common mediators for metabolic problems and mental illnesses.

Major mental illnesses such as schizophrenia (SZ) and bipolar disorder (BP) frequently accompany metabolic conditions, but their relationship is still unclear, in particular at the mechanistic level. We implemented an approach of “from population to neuron”, combining population-based epidemiological analysis with neurobiological experiments using cell and animal models based on a hypothesis built from the epidemiological study. We characterized high-quality population data, olfactory neuronal cells biopsied from patients with SZ or BP, and healthy subjects, as well as mice genetically modified for insulin signaling. We accessed the Danish Registry and observed (1) a higher incidence of diabetes in people with SZ or BP and (2) higher incidence of major mental illnesses in people with diabetes in the same large cohort. These epidemiological data suggest the existence of common pathophysiological mediators in both diabetes and major mental illnesses. We hypothesized that molecules associated with insulin resistance might be such common mediators, and then validated the hypothesis by using two independent sets of olfactory neuronal cells biopsied from patients and healthy controls. In the first set, we confirmed an enrichment of insulin signaling-associated molecules among the genes that were significantly different between SZ patients and controls in unbiased expression profiling data. In the second set, olfactory neuronal cells from SZ and BP patients who were not pre-diabetic or diabetic showed reduced IRS2 tyrosine phosphorylation upon insulin stimulation, indicative of insulin resistance. These cells also displayed an upregulation of IRS1 protein phosphorylation at serine-312 at baseline (without insulin stimulation), further supporting the concept of insulin resistance in olfactory neuronal cells from SZ patients. Finally, Irs2 knockout mice showed an aberrant response to amphetamine, which is also observed in some patients with major mental illnesses. The bi-directional relationships between major mental illnesses and diabetes suggest that there may be common pathophysiological mediators associated with insulin resistance underlying these mental and physical conditions.

Exploring the current status of neuroendocrine tumours: a population-based analysis of epidemiology, management and use of resources

BackgroundNeuroendocrine tumours (NETs) are rare malignancies characterised by its capacity to synthesise and secrete monoamines, due to its neuroendocrine origin. Its varied locations and symptoms have traditionally been responsible for extended delays in their diagnosis. The interest of this study was to characterise the patient population diagnosed with NETs in Spain and to revise how the disease is managed, together with the hospitalisation costs of these patients.MethodsThe database included records of all patients diagnosed with a NET between 2010 and 2015. Admission records were used to evaluate hospitalisation, disease management data and costs, and single-patient files were used to characterise the population.ResultsNine Thousand One Hundred Twenty patients were diagnosed with a neuroendocrine tumour between 2010 and 2015, with a 2 fold increase in the diagnosis rate over the study period. 42.25% of the patients were females, while 57.75% were males, and mean diagnosis age was 62.58 years (SD = 14.65). Considering all the registered neuroendocrine neoplasms, 46.86% of the patients had malignant well-differentiated NETs, 32.02% had a malignant poorly differentiated neuroendocrine carcinoma and 42.93% of patients developed metastatic NETs. In addition, 18.59% of patients were diagnosed with benign well-differentiated NETs. The most common tumour sites were the bronchus, lung and other sites, including pancreatic tumours; metastasis was found in the liver and distant lymph nodes. Pancreatic resection was the most common surgical procedure utilised in these patients, summing 19% of total expenses, the injection of an unspecified therapeutic substance (including targeted therapies) was registered in 11.40% of admissions, while chemotherapy was registered in only 6.85% of admissions. The annual healthcare cost of NETs was €15,373,961, corresponding to €9092 per patient.ConclusionsThe implementation of standard diagnosis procedures should be prioritised, with a focus on the pancreas and lung, and taking into account that 42.93% of the patients develop a metastatic tumour. The presence of comorbidities and multimorbidities should be considered in order to develop more efficient disease management protocols.

Hard Palate Melanoma: A Population-based Analysis of Epidemiology and Survival Outcomes.

Hard palate melanoma is an extremely rare and aggressive tumor arising from the mucosal epithelium of the oral cavity. The aim of this study was to analyze epidemiology, loco-regional treatment patterns and survival outcomes of this disease. The National Cancer Institute's Surveillance Epidemiology and End Results (SEER) database was searched for all cases of hard palate melanoma diagnosed between 1973 and 2012. The Kaplan-Meier method was used to calculate overall survival rate, log-rank test to compare survivals of different subgroups, and Cox hazard regression analysis to determine independent predictors of overall survival. Overall, 83 patients were identified, 49 female and 34 males. The distribution among ages was: 13.3% <50 years, 38.6% between 50 and 69 years, 48.2% ≥70. Surgery alone was applied in 48.2% of patients, radiation therapy alone in 6%, and combination of surgery and radiation therapy in 33.7%. Overall 5-year survival was 26.3%. Survival with adjuvant radiation therapy was not longer than with surgery alone. Hard palate melanoma is a rare malignancy mostly affecting the elderly, with low overall survival. The main treatment is surgical resection, while adjuvant radiotherapy does not improve survival. The establishment of an international registry is warranted to better define treatment options.

Intraoperative Anaphylaxis to Chlorhexidine During LVAD and Transplant Surgery

PERIOPERATIVE ANAPHYLAXIS is a condition that can cause complications during surgical procedures, ranging from minor to severe with cardiovascular and/or pulmonary collapse. Some common etiologic agents include antibiotics, neuromuscular blocking agents, latex, and chlorhexidine, 1 Mertes P.M. Alla F. Trechot P. et al. Anaphylaxis during anesthesia in France: An 8-year national survey. J Allergy Clin Immunol. 2011; 128: 366-373 Abstract Full Text Full Text PDF PubMed Scopus (286) Google Scholar , 2 Tacquard C. Collange O. Gomis P. et al. Anaesthetic hypersensitivity reactions in France between 2011 and 2012: The 10th GERAP epidemiologic survey. Acta Anaesthesiol Scand. 2017; 61: 290-299 Crossref PubMed Scopus (63) Google Scholar , 3 Mertes P.M. Laxenaire M.C. Alla F. et al. Anaphylactic and anaphylactoid reactions occurring during anesthesia in France in 1999-2000. Anesthesiology. 2003; 99: 536-545 Crossref PubMed Scopus (475) Google Scholar , 4 Garvey L.H. Roed-Petersen J. Menne T. et al. Danish Anaesthesia Allergy Centre - preliminary results. Acta Anaesthesiol Scand. 2001; 45: 1204-1209 Crossref PubMed Scopus (86) Google Scholar , 5 Meng J. Rotiroti G. Burdett E. et al. Anaphylaxis during general anaesthesia: Experience from a drug allergy centre in the UK. Acta Anaesthesiol Scand. 2017; 61: 281-289 Crossref PubMed Scopus (21) Google Scholar but any medication, blood product, or chemical substance used during the perioperative period has the potential for causing anaphylaxis. Complications from perioperative anaphylaxis can be life-threatening and are associated with a higher mortality rate than anaphylaxis under other circumstances. 6 Simon M.R. Mulla Z.D. A population-based epidemiologic analysis of deaths from anaphylaxis in Florida. Allergy. 2008; 63: 1077-1083 Crossref PubMed Scopus (68) Google Scholar , 7 Gibbs N.M. Sadleir P.H. Clarke R.C. et al. Survival from perioperative anaphylaxis in Western Australia 2000-2009. Br J Anaesth. 2013; 111: 589-593 Abstract Full Text Full Text PDF PubMed Scopus (59) Google Scholar In this case report, the authors present the clinical course of an end-stage cardiomyopathy patient who experienced two separate episodes of anaphylaxis after exposure to the widely used antiseptic chlorhexidine during two major operations—the first during left ventricular assist device (LVAD) implantation and the second during heart transplantation. Intraoperative Anaphylaxis to Chlorhexidine During LVAD and Transplant SurgeryJournal of Cardiothoracic and Vascular AnesthesiaVol. 33Issue 2Preview“Not many is the good, but in the good, the many” —Aristotle (384-322 BC) Full-Text PDF

Pancreatic neuroendocrine tumors: A population-based analysis of epidemiology and outcomes.

401 Background: Pancreatic neuroendocrine tumors (PNETs) are rare neoplasms comprising less than 2% of pancreatic tumors. Outcomes of PNETs vary by stage, grade, and clinical presentation. New therapies may have improved outcomes. We present an analysis of the epidemiology and prognosis of patients (pts) with PNETs evaluating a more recent period than previously reported. Methods: Using data from the SEER registry, we identified adults with PNETs between 2000 and 2013. Cases were identified using a combination of ICD-O-3 site and histology codes. The JMP and SEER*STAT 8.3.2 were used for statistical analysis. Overall survival (OS) was analyzed using the Kaplan–Meier method. The prognostic effect of variables was studied using multivariate Cox proportional hazards models. Results: We identified 5993 pts with PNETs. Over the study duration, there was an increase in the annual incidence from 0.3 to 1.2 per 100.000. This was largely explained by the increase in number of pts with localized disease. The OS for the entire cohort was 54 months (95%; CI 50-58) and 5-year OS rates in localized, locally advanced and metastatic disease were 81.7%, 62% and 26% respectively. New therapies were increasingly implemented after 2008 such as sunitinib, everolimus and capecitabine/temozolomide. OS was better for pts diagnosed after 2008 (HR 0.73; 95% CI, 0.69-0.79; P &lt; 0.0001) and this remained significant after excluding pts with localized disease (HR 0.85; 95% CI, 0.78-0.92; P = 0.0002). Factors found to favorably affect OS included younger age, female sex, early stage, low grade, and surgery. In metastatic disease, pts who had surgery had better OS and this was significant after adjusting for possible confounders (HR 0.36; 95% CI, 0.3-0.45). Conclusions: In this large population-based study, we saw an increase in the annual incidence of PNETs mainly due to an increased number of pts with localized disease. The OS has improved over the study duration likely due to both stage migration and new therapies used in advanced disease. Younger age, female gender, low histologic grade, early stage and surgery were found to be factors that favorably affected survival. Surgery was found to be a predictor of better outcomes in metastatic disease.

Abstract P006: A Population-based Approach to Sudden Unexpected Death Epidemiology

Introduction: Sudden cardiac death accounts for 150,000 to 400,000 deaths in the United States annually. Published studies of sudden death use restrictive inclusion criteria such as timing of death, death-certificate disease attribution, hospital transport, attempted resuscitation, and victim survival status. These case definitions may undercount minority victims, victims who are socially isolated, or victims with limited healthcare access, leading to mischaracterization of sudden death in the general population. The SUDDEN study is a population-based epidemiologic analysis of out-of-hospital sudden unexpected death (OHSUD) in North Carolina that aims to characterize OHSUD incidence in the general population and identify associated risk factors. Methods: Wake County, North Carolina, is a predominantly urban county with approximately 4,700 adult deaths in a 2013 population of 974,289. All possible sudden unexpected deaths over one year in Wake County were collected via EMS. Death certificates, medical records, and post mortem examination data were used to determine demographic information and comorbidities. Of 1,138 18- to 64 year olds identified as possible OHSUD victims, 187 cases were adjudicated into the study population. Population-based estimates were age- and sex-standardized to 2013 North Carolina mortality tables to estimate a statewide OHSUD count. Results: Out-of-hospital sudden unexpected death accounted for approximately 14% of all deaths in adults under age 65. Up to 13.5% of all 2013 Wake County deaths outside of a healthcare institution were attributable to OHSUD. Approximately 2/3 of SUDDEN cases would have been excluded by timing criteria in commonly used sudden death case definitions. Hypertension, ischemic heart disease, hypercholesterolemia, COPD, and diabetes were all highly prevalent in Wake County OHSUD victims. OHSUD accounted for 48% of deaths in 18- to 64-year-olds with diseases of the heart, stroke/cerebrovascular disease, or chronic lower respiratory disease listed as the cause of death. 52% of all 2013 OHSUD in Wake County listed a cardiac primary cause on the death certificate; 37% were listed as having non-cardiac causes, with the remaining listing an unknown or a non-natural cause (e.g., trauma). Excluding non-cardiac causes of death would misclassify over 1,500 OHSUD victims per year in North Carolina alone. Discussion: Sudden death incidence estimates vary widely according to published exclusion criteria, leading to a mischaracterization of a disease that needs to be addressed on a national level. Restrictive exclusion criteria used in published studies of sudden death underestimate the incidence of OHSUD and divert resources from populations that would benefit the most from targeted interventions.

Exploring the rising incidence of neuroendocrine tumors: a population-based analysis of epidemiology, metastatic presentation, and outcomes.

An increased incidence of neuroendocrine tumors (NETs) has been reported worldwide, but the reasons underlying this rise have not been identified. By assessing patterns of metastatic presentation, this study sought to examine the epidemiologic characteristics of NETs and the contribution of early-stage detection to the rising incidence. A population-based retrospective cohort study was conducted with prospectively maintained databases linked at the Institute for Clinical Evaluative Sciences. Adult patients with a NET diagnosis from 1994 to 2009 in Ontario, Canada were included. The main outcomes included the overall and site-specific incidence, proportion of metastatic disease, overall survival (OS), and recurrence-free survival (RFS). Five thousand six hundred nineteen NET cases were identified. The incidence of NETs increased from 2.48 to 5.86 per 100,000 per year. Metastases were found in 20.8% at presentation and in another 38% after the initial diagnosis. The proportion of metastases at presentation decreased from 1994 to 2009 (from 29% to 13%). Therefore, although the incidence of all NETs increased, the overall incidence of metastases did not change (0.63-0.69 per 100,000 per year). The 10-year OS rate was 46.5%, and the RFS rate was 64.6%. In addition to the primary tumor site, independent predictors of worse OS included an advanced age (P < .0001), male sex (P < .0001), a low socioeconomic status (P < .0001), and rural living (P = 0.049). The incidence of NETs has markedly increased over the course of 15 years. This is the first study to provide evidence suggesting that the increase in the incidence of NETs may be due to increased detection. In addition to tumor characteristics, low income and rural residency portend worse survival for patients with NETs.

Abstract 2638: Genetic association analysis of the AMP dependent protein kinase complex and NHL risk

Abstract Introduction: AMPK regulates metabolic processes by sensing intracellular concentrations of ATP and AMP and has been implicated in at least two important tumor-related pathways: the mTOR pathway and the p53 axis. We utilize a population-based epidemiologic analysis to investigate the role of mutations in seven AMPK subunits and lymphomagenesis and analyze public microarray expression data to determine the expression of AMPK in non-Hodgkin lymphoma (NHL) cells. Methods: Our analysis included incident and histologically confirmed cases of NHL (n=456) and age-matched matched controls (n=527) from female residents of Connecticut. Single nucleotide polymorphisms (SNPs) were identified using the Tagger algorithm in the Haploview interface in HapMap's genome browser 22. A total of 19 SNPs (r2 ≤ 0.8 and MAF ≤ 0.2) were identified across the AMPK subunit genes. For each gene harboring more than one tagging SNP (PRKAA2, PRKAG2, and PRKAG3), haplotypes were estimated using the PHASE program. All statistical analyses were done in SAS 9.2. An unconditional multivariate logistic model was generated and the adjusted odds ratios (ORs) and 95% confidence intervals were reported. Family history of cancer was found to be an effect modifier for some SNPs and haplotypes, and stratified analyses were performed for these associations. We extracted gene expression data from GEO (GDS3516) and compared median AMPK subunit levels in NHL cells to the levels in normal follicle B-cells and total peripheral blood B-cells using a Wilcoxon rank sum test. Results: Individuals with no family history of cancer and heterozygous for rs293445 in the PRKAG1 subunit had a significantly increased risk of NHL (OR: 2.80, 95% CI: 1.54, 5.07; p&amp;lt;0.001). The strongest association was noted for a haplotype in PRKAA2 among individuals who reported no family history of cancer (OR: 5.44, 95% CI: 2.15, 13.75; p&amp;lt;0.001). The median gene expression of PRKAA2 was significantly elevated in follicular lymphoma cells compared to normal follicle B cells (p&amp;lt;0.05). A suggestive association between rare PRKAG3 haplotypes and diffuse large B cell lymphoma (DLCBCL) was noted among individuals with no family history of cancer (OR: 0.36, 95% CI: 0.17, 0.78)), but this association was not significant after correction for multiple comparisons. PRKAG3 was significantly lower (p&amp;lt;0.05) in DLCBCL cells relative to normal peripheral blood B cells, and in follicular lymphoma cells relative to follicle center B cells. Conclusions: These findings suggest that variants in AMPK may influence NHL risk. Our expression analysis demonstrates differential expression of some AMPK subunits in lymphoma tissue relative to normal immune cells. Metabolic dysregulation has been suggested as an “emerging hallmark of cancer,” and future studies may focus on understanding the role of AMPK in tumor metabolism and utilizing this information to develop new strategies for chemotherapy and prevention. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2638. doi:1538-7445.AM2012-2638

Anaphylaxis

Anaphylaxis occurs commonly in community settings. The rate of occurrence is increasing, especially in young people. Understanding potential triggers, mechanisms, and patient-specific risk factors for severity and fatality is the key to performing appropriate risk assessment in those who have previously experienced an acute anaphylactic episode. The diagnosis of anaphylaxis is based primarily on clinical criteria and is valid even if the results of laboratory tests, such as serum total tryptase levels, are within normal limits. Positive skin test results or increased serum specific IgE levels to potential triggering allergens confirm sensitization but do not confirm the diagnosis of anaphylaxis because asymptomatic sensitization is common in the general population. Important patient-related risk factors for severity and fatality include age, concomitant diseases, and concurrent medications, as well as other less well-defined factors, such as defects in mediator degradation pathways, fever, acute infection, menses, emotional stress, and disruption of routine. Prevention of anaphylaxis depends primarily on optimal management of patient-related risk factors, strict avoidance of confirmed relevant allergen or other triggers, and, where indicated, immunomodulation (eg, subcutaneous venom immunotherapy to prevent Hymenoptera sting-triggered anaphylaxis, an underused, potentially curative treatment). The benefits and risks of immunomodulation to prevent food-triggered anaphylaxis are still being defined. Epinephrine (adrenaline) is the medication of first choice in the treatment of anaphylaxis. All patients at risk for recurrence in the community should be equipped with 1 or more epinephrine autoinjectors; a written, personalized anaphylaxis emergency action plan; and up-to-date medical identification. Improvements in the design of epinephrine autoinjectors will help to optimize ease of use and safety. Randomized controlled trials of pharmacologic agents, such as antihistamines and glucocorticoids, are needed to strengthen the evidence base for treatment of acute anaphylactic episodes.

Staphylococcus lugdunensis , a Common Cause of Skin and Soft Tissue Infections in the Community

Staphylococcus lugdunensis, a rare cause of severe infections such as native valve endocarditis, often causes superficial skin infections similar to Staphylococcus aureus infections. We initiated a study to optimize the identification methods in the routine laboratory, followed by a population-based epidemiologic analysis of patients infected with S. lugdunensis in Viborg County, Denmark. Recognition of a characteristic Eikenella corrodens-like odor on Columbia sheep blood agar combined with colony pleomorphism and prominent beta-hemolysis after 2 days of incubation, confirmed by API-ID-32 Staph, led to an 11-fold increase in the detection of S. lugdunensis. By these methods we found 491 S. lugdunensis infections in 4 years, corresponding to an incidence of 53 per 100,000 per year, an increase from 5 infections per 100,000 inhabitants in the preceding years. Seventy-five percent of the cases were found in general practice; these were dominated by skin abscesses (36%), wound infections (25%), and paronychias (13%). Fifty-six percent of the infections occurred below the waist, and toes were the most frequently infected site (21%). Only 3% of the patients suffered from severe invasive infections. The median age was 52 years, and the male/female ratio was 0.69. Our study shows that S. lugdunensis is a common cause of skin and soft-tissue infections (SSTI) and is probably underrated by many laboratories. S. lugdunensis should be accepted as a significant pathogen in SSTI and should be looked for in all routine bacteriological examinations, and clinicians should be acquainted with the name and the pathology of the bacterium.

Sporadic ataxias in Japan – a population-based epidemiological study

Sporadic spinocerebellar ataxias (SCAs) comprise heterogeneous diseases with poorly understood epidemiologies and etiologies. A population-based epidemiological analysis of sporadic ataxias in the Japanese population was described. The prevalence rate of SCAs in the Japanese population is estimated to be 18.5/100,000. Sporadic SCAs account for 67.2% of total SCAs including hereditary SCAs, with olivopontocerebellar atrophy (OPCA) being the most common form sporadic ataxia (64.7%). The natural history analysis conducted on the basis of International Cooperative Ataxia Rating Scale (ICARS) showed that only 33% of patients with OPCA were able to walk at least with one stick 4-5 years after the onset of OPCA, which is much less than that of patients with cortical cerebellar atrophy (CCA). Similarly, 43% of patients with OPCA were able to stand alone 4-5 years after the onset, while 76% of patients with CCA were able to stand alone at the same disease duration. A population-based epidemiological analysis should provide essential information on the natural history of SCAs.

Eosinophilic Esophagitis: A Prevalent Disease in the United States That Affects All Age Groups

Most reports on eosinophilic esophagitis (EE) are limited to small series from single institutions. This study describes features of EE in a broader population. A national pathology database (Caris Diagnostics, Irving, TX) was used to identify EE cases from a cohort of upper endoscopies. Slides from potential cases were reviewed by pathologists. Study inclusion required a mean of (1) 20 eosinophils or more in 5 high-power fields, or (2) 30 eosinophils in 2-4 high-power fields. Endoscopists provided demographic and clinical information. There were 363 cases identified from 74,162 patients and 26 states. EE had a male predominance (odds ratio, 3.0; 95% confidence interval, 2.4-3.8). Ages ranged from 1 to 98 years, including 42 children and 321 adults. The most common endoscopy indications in adults were dysphagia (70.1%) and gastroesophageal reflux disease (GERD)/heartburn (27.1%). Children most frequently reported GERD/heartburn (38.1%) and abdominal pain/dyspepsia (31.0%). A total of 25.1% of cases had a peak mucosal eosinophil count of 20-59, 29.2% had a peak mucosal eosinophil count of 60-100, and 45.7% had a peak mucosal eosinophil count of more than 100. There was no difference in the peak counts between age groups or sexes, but patients with dysphagia had higher counts (P < .001). The prevalence of EE increased during the study period (P < .001). EE is a national disease found in all age groups, more frequently in males. Dysphagia and GERD symptoms are common indications for endoscopy. The degree of eosinophilic infiltration is high throughout all ages and may be related to patients' symptoms. Our series highlights important elements of this disease, the prevalence and/or recognition of which is increasing.

Malignancies of the Appendix: Beyond Case Series Reports

A comprehensive analysis was performed for five histologic types of appendiceal tumors to compare incidence, clinicopathologic features, survival, and appropriateness of surgery. All patients diagnosed with mucinous adenocarcinoma (n = 951), adenocarcinoma (n = 646), carcinoid (n = 435), goblet (n = 369), and signet-ring cell (n = 113) in the Surveillance, Epidemiology, and End Results database (1973-2001) were analyzed. Evaluation of incidence, stage, and five-year relative survival were determined for each histology. The appropriateness of the operative procedure (i.e. , appendectomy vs. colectomy) was examined by tumor type and size. Tumor incidence, patient demographics, survival outcomes, and appropriateness of surgery varied significantly among the different appendiceal tumor histologies. The most common appendiceal tumors were mucinous. With regard to patient demographics, carcinoids presented at an earlier mean age of 41 years and 71 percent were female (P < 0.001 for both). Overall five-year survival was highest for carcinoid (83 percent) and lowest for signet ring (18 percent). Although current guidelines specify that a right hemicolectomy (rather than an appendectomy) be performed for all noncarcinoid tumors and carcinoid tumors >2 cm, we found that 30 percent of noncarcinoids underwent appendectomy. Similarly, 28 percent of carcinoids >2 cm under-went appendectomy, which is a lesser resection than is indicated. This study provides a population-based analysis of epidemiology, tumor characteristics, survival, and quality of care for appendiceal carcinomas. This characterization provides a novel description of the presentation and outcomes for malignancies of the appendix and highlights that a substantial number of patients with appendiceal tumors may not be receiving appropriate surgical resection.

Retroperitoneal sarcoma: A population-based analysis of epidemiology, surgery, and radiotherapy

9025 Background: There are no population-based studies of retroperitoneal sarcoma (RPS), and the use and timing of adjuvant radiotherapy (RT) in its treatment is controversial. The goal of our study was to examine the incidence and treatment of RPS, specifically regarding the use of adjuvant RT. Methods: We used the Surveillance, Epidemiology, and End Results (SEER) database to evaluate the incidence of RPS over a 29-year period (1973–2001). We evaluated the rate of surgery as well as the rate and timing of adjuvant RT. We then assessed the influence on treatment of factors including patient age, sex, race, marital status, year of diagnosis, and geographic location. Results: A total of 2348 cases of RPS were identified. The mean annual incidence of RPS was 2.7 cases per 106 persons, and did not change significantly over time (2.6 in 1973 vs. 2.8 in 2001; p=0.92). Most patients (1654; 70.4%) underwent surgical resection. RT was used in 428 patients (25.9%) who underwent surgery; RT was given postoperatively in 366 (85.5%), preoperatively in 20 (4.7%), and intraoperatively or unknown in 42 (9.8%). Patients who received adjuvant RT were on average 5 years younger than those who underwent surgery alone (p<0.0001). RT was more commonly used among whites than African Americans (25.8% vs. 16.7%; p=0.02) and there was significant variation in the use of adjuvant RT by geographic location (p=0.003). No associations were identified between the use of adjuvant RT and sex, marital status, or year of diagnosis. On multivariate analysis using logistic regression, race (p=0.01), age (p<0.0001), and geographic location (p=0.02) were independently associated with the use of adjuvant RT. Conclusions: The incidence of RPS, a rare disease, appears stable. Most patients who undergo surgery do not receive any adjuvant RT, and very few receive preoperative RT. Differences in adjuvant RT use found on the basis of demographic and geographic factors suggest that at least some treatment variations reflect individual and institutional practice patterns. These data, representing current practice, are important in considering how to implement future results of an ongoing randomized trial (ACOSOG 9031) comparing preoperative RT and surgery to surgery alone. No significant financial relationships to disclose.

Prenatal Chromosomal Diagnosis

In a study of Georgia women aged 40 years and older, 15% made use of prenatal chromosomal diagnosis. There was, however, substantial racial and geographic variation, ranging from a use ratio of 60% among whites in two large urban counties to 0.5% among blacks outside Augusta and Atlanta health districts. This simple population-based epidemiologic analysis suggests that future program planning for genetic services in Georgia should address ways to increase access by rural women, especially blacks. Similar analyses in other states could be used for planning genetic services. (<i>JAMA</i>244:1355-1357, 1980)