[Show abstract][Hide abstract] ABSTRACT: Background:
The lack of uniform criteria for coding of gastroenteropancreatic neuroendocrine neoplasia (GEP-NEN) has hampered previous epidemiological studies. The epidemiology of GEP-NEN was investigated in this study using currently available criteria.
All patients diagnosed with GEP-NEN between January 2003 and December 2013 in a well defined Norwegian population of approximately 350 000 people were included. Age- and sex-adjusted incidence rates were calculated. The current 2010 World Health Organization criteria, European Neuroendocrine Tumour Society classification and International Union Against Cancer (UICC) classification were used.
A total of 204 patients (114 male, 55·9 per cent) were identified. The median age at diagnosis was 61 (range 10-94) years. The annual overall crude incidence was 5·83 per 100 000 inhabitants, with an increasing trend (P = 0·033). The most frequent location was small intestine (60 patients, 29·4 per cent) followed by appendix (48 patients, 23·5 per cent) and pancreas (33 patients, 16·2 per cent). Grade 1 tumours were more common in gastrointestinal (100 patients, 58·5 per cent) than in pancreatic (9 patients, 27 per cent) NEN. According to the UICC classification, 77 patients (37·7 per cent) had stage I, 17 patients (8·3 per cent) stage II, 37 patients (18·1 per cent) stage III and 70 patients (34·3 per cent) had stage IV disease. No patient with stage I disease had grade 3 tumours; advanced tumour grade increased with stage.
A high crude incidence of GEP-NEN, at 5·83 per 100 000 inhabitants, was noted together with a significant increasing trend over time.
British Journal of Surgery 10/2015; DOI:10.1002/bjs.10034 · 5.54 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) is the first of a series of annual updates of the GBD. Risk factor quantification, particularly of modifiable risk factors, can help to identify emerging threats to population health and opportunities for prevention. The GBD 2013 provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution.
Attributable deaths, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs) have been estimated for 79 risks or clusters of risks using the GBD 2010 methods. Risk–outcome pairs meeting explicit evidence criteria were assessed for 188 countries for the period 1990–2013 by age and sex using three inputs: risk exposure, relative risks, and the theoretical minimum risk exposure level (TMREL). Risks are organised into a hierarchy with blocks of behavioural, environmental and occupational, and metabolic risks at the first level of the hierarchy. The next level in the hierarchy includes nine clusters of related risks and two individual risks, with more detail provided at levels 3 and 4 of the hierarchy. Compared with GBD 2010, six new risk factors have been added: handwashing practices, occupational exposure to trichloroethylene, childhood wasting, childhood stunting, unsafe sex, and low glomerular filtration rate. For most risks, data for exposure were synthesised with a Bayesian meta-regression method, DisMod-MR 2.0, or spatial-temporal Gaussian process regression. Relative risks were based on meta-regressions of published cohort and intervention studies. Attributable burden for clusters of risks and all risks combined took into account evidence on the mediation of some risks such as high body-mass index (BMI) through other risks such as high systolic blood pressure and high cholesterol.
All risks combined account for 57·2% (95% uncertainty interval [UI] 55·8–58·5) of deaths and 41·6% (40·1–43·0) of DALYs. Risks quantified account for 87·9% (86·5–89·3) of cardiovascular disease DALYs, ranging to a low of 0% for neonatal disorders and neglected tropical diseases and malaria. In terms of global DALYs in 2013, six risks or clusters of risks each caused more than 5% of DALYs: dietary risks accounting for 11·3 million deaths and 241·4 million DALYs, high systolic blood pressure for 10·4 million deaths and 208·1 million DALYs, child and maternal malnutrition for 1·7 million deaths and 176·9 million DALYs, tobacco smoke for 6·1 million deaths and 143·5 million DALYs, air pollution for 5·5 million deaths and 141·5 million DALYs, and high BMI for 4·4 million deaths and 134·0 million DALYs. Risk factor patterns vary across regions and countries and with time. In sub-Saharan Africa, the leading risk factors are child and maternal malnutrition, unsafe sex, and unsafe water, sanitation, and handwashing. In women, in nearly all countries in the Americas, north Africa, and the Middle East, and in many other high-income countries, high BMI is the leading risk factor, with high systolic blood pressure as the leading risk in most of Central and Eastern Europe and south and east Asia. For men, high systolic blood pressure or tobacco use are the leading risks in nearly all high-income countries, in north Africa and the Middle East, Europe, and Asia. For men and women, unsafe sex is the leading risk in a corridor from Kenya to South Africa.
Behavioural, environmental and occupational, and metabolic risks can explain half of global mortality and more than one-third of global DALYs providing many opportunities for prevention. Of the larger risks, the attributable burden of high BMI has increased in the past 23 years. In view of the prominence of behavioural risk factors, behavioural and social science research on interventions for these risks should be strengthened. Many prevention and primary care policy options are available now to act on key risks.
The Lancet 09/2015; DOI:10.1016/S0140-6736(15)00128-2 · 45.22 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Acute appendicitis is one of the most common abdominal emergencies worldwide. The cause remains poorly understood, with few advances in the past few decades. To obtain a confident preoperative diagnosis is still a challenge, since the possibility of appendicitis must be entertained in any patient presenting with an acute abdomen. Although biomarkers and imaging are valuable adjuncts to history and examination, their limitations mean that clinical assessment is still the mainstay of diagnosis. A clinical classification is used to stratify management based on simple (non-perforated) and complex (gangrenous or perforated) inflammation, although many patients remain with an equivocal diagnosis, which is one of the most challenging dilemmas. An observed divide in disease course suggests that some cases of simple appendicitis might be self-limiting or respond to antibiotics alone, whereas another type often seems to perforate before the patient reaches hospital. Although the mortality rate is low, postoperative complications are common in complex disease. We discuss existing knowledge in pathogenesis, modern diagnosis, and evolving strategies in management that are leading to stratified care for patients.
The Lancet 09/2015; 386(10000):1278-1287. DOI:10.1016/S0140-6736(15)00275-5 · 45.22 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Perforated peptic ulcer is a common emergency condition worldwide, with associated mortality rates of up to 30%. A scarcity of high-quality studies about the condition limits the knowledge base for clinical decision making, but a few published randomised trials are available. Although Helicobacter pylori and use of non-steroidal anti-inflammatory drugs are common causes, demographic differences in age, sex, perforation location, and underlying causes exist between countries, and mortality rates also vary. Clinical prediction rules are used, but accuracy varies with study population. Early surgery, either by laparoscopic or open repair, and proper sepsis management are essential for good outcome. Selected patients can be managed non-operatively or with novel endoscopic approaches, but validation of such methods in trials is needed. Quality of care, sepsis care bundles, and postoperative monitoring need further assessment. Adequate trials with low risk of bias are urgently needed to provide better evidence. We summarise the evidence for perforated peptic ulcer management and identify directions for future clinical research.
The Lancet 09/2015; 386(10000):1288-1298. DOI:10.1016/S0140-6736(15)00276-7 · 45.22 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
The Global Burden of Disease Study 2013 (GBD 2013) aims to bring together all available epidemiological data using a coherent measurement framework, standardised estimation methods, and transparent data sources to enable comparisons of health loss over time and across causes, age–sex groups, and countries. The GBD can be used to generate summary measures such as disability-adjusted life-years (DALYs) and healthy life expectancy (HALE) that make possible comparative assessments of broad epidemiological patterns across countries and time. These summary measures can also be used to quantify the component of variation in epidemiology that is related to sociodemographic development.
We used the published GBD 2013 data for age-specific mortality, years of life lost due to premature mortality (YLLs), and years lived with disability (YLDs) to calculate DALYs and HALE for 1990, 1995, 2000, 2005, 2010, and 2013 for 188 countries. We calculated HALE using the Sullivan method; 95% uncertainty intervals (UIs) represent uncertainty in age-specific death rates and YLDs per person for each country, age, sex, and year. We estimated DALYs for 306 causes for each country as the sum of YLLs and YLDs; 95% UIs represent uncertainty in YLL and YLD rates. We quantified patterns of the epidemiological transition with a composite indicator of sociodemographic status, which we constructed from income per person, average years of schooling after age 15 years, and the total fertility rate and mean age of the population. We applied hierarchical regression to DALY rates by cause across countries to decompose variance related to the sociodemographic status variable, country, and time.
Worldwide, from 1990 to 2013, life expectancy at birth rose by 6·2 years (95% UI 5·6–6·6), from 65·3 years (65·0–65·6) in 1990 to 71·5 years (71·0–71·9) in 2013, HALE at birth rose by 5·4 years (4·9–5·8), from 56·9 years (54·5–59·1) to 62·3 years (59·7–64·8), total DALYs fell by 3·6% (0·3–7·4), and age-standardised DALY rates per 100 000 people fell by 26·7% (24·6–29·1). For communicable, maternal, neonatal, and nutritional disorders, global DALY numbers, crude rates, and age-standardised rates have all declined between 1990 and 2013, whereas for non–communicable diseases, global DALYs have been increasing, DALY rates have remained nearly constant, and age-standardised DALY rates declined during the same period. From 2005 to 2013, the number of DALYs increased for most specific non-communicable diseases, including cardiovascular diseases and neoplasms, in addition to dengue, food-borne trematodes, and leishmaniasis; DALYs decreased for nearly all other causes. By 2013, the five leading causes of DALYs were ischaemic heart disease, lower respiratory infections, cerebrovascular disease, low back and neck pain, and road injuries. Sociodemographic status explained more than 50% of the variance between countries and over time for diarrhoea, lower respiratory infections, and other common infectious diseases; maternal disorders; neonatal disorders; nutritional deficiencies; other communicable, maternal, neonatal, and nutritional diseases; musculoskeletal disorders; and other non-communicable diseases. However, sociodemographic status explained less than 10% of the variance in DALY rates for cardiovascular diseases; chronic respiratory diseases; cirrhosis; diabetes, urogenital, blood, and endocrine diseases; unintentional injuries; and self-harm and interpersonal violence. Predictably, increased sociodemographic status was associated with a shift in burden from YLLs to YLDs, driven by declines in YLLs and increases in YLDs from musculoskeletal disorders, neurological disorders, and mental and substance use disorders. In most country-specific estimates, the increase in life expectancy was greater than that in HALE. Leading causes of DALYs are highly variable across countries.
Global health is improving. Population growth and ageing have driven up numbers of DALYs, but crude rates have remained relatively constant, showing that progress in health does not mean fewer demands on health systems. The notion of an epidemiological transition—in which increasing sociodemographic status brings structured change in disease burden—is useful, but there is tremendous variation in burden of disease that is not associated with sociodemographic status. This further underscores the need for country-specific assessments of DALYs and HALE to appropriately inform health policy decisions and attendant actions.
The Lancet 08/2015; DOI:10.1016/S0140-6736(15)61340-X · 45.22 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Cancer is among the leading causes of death worldwide. Current estimates of cancer burden in individual countries and regions are necessary to inform local cancer control strategies.
To estimate mortality, incidence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs) for 28 cancers in 188 countries by sex from 1990 to 2013.
The general methodology of the Global Burden of Disease (GBD) 2013 study was used. Cancer registries were the source for cancer incidence data as well as mortality incidence (MI) ratios. Sources for cause of death data include vital registration system data, verbal autopsy studies, and other sources. The MI ratios were used to transform incidence data to mortality estimates and cause of death estimates to incidence estimates. Cancer prevalence was estimated using MI ratios as surrogates for survival data; YLDs were calculated by multiplying prevalence estimates with disability weights, which were derived from population-based surveys; YLLs were computed by multiplying the number of estimated cancer deaths at each age with a reference life expectancy; and DALYs were calculated as the sum of YLDs and YLLs.
In 2013 there were 14.9 million incident cancer cases, 8.2 million deaths, and 196.3 million DALYs. Prostate cancer was the leading cause for cancer incidence (1.4 million) for men and breast cancer for women (1.8 million). Tracheal, bronchus, and lung (TBL) cancer was the leading cause for cancer death in men and women, with 1.6 million deaths. For men, TBL cancer was the leading cause of DALYs (24.9 million). For women, breast cancer was the leading cause of DALYs (13.1 million). Age-standardized incidence rates (ASIRs) per 100 000 and age-standardized death rates (ASDRs) per 100 000 for both sexes in 2013 were higher in developing vs developed countries for stomach cancer (ASIR, 17 vs 14; ASDR, 15 vs 11), liver cancer (ASIR, 15 vs 7; ASDR, 16 vs 7), esophageal cancer (ASIR, 9 vs 4; ASDR, 9 vs 4), cervical cancer (ASIR, 8 vs 5; ASDR, 4 vs 2), lip and oral cavity cancer (ASIR, 7 vs 6; ASDR, 2 vs 2), and nasopharyngeal cancer (ASIR, 1.5 vs 0.4; ASDR, 1.2 vs 0.3). Between 1990 and 2013, ASIRs for all cancers combined (except nonmelanoma skin cancer and Kaposi sarcoma) increased by more than 10% in 113 countries and decreased by more than 10% in 12 of 188 countries.
Cancer poses a major threat to public health worldwide, and incidence rates have increased in most countries since 1990. The trend is a particular threat to developing nations with health systems that are ill-equipped to deal with complex and expensive cancer treatments. The annual update on the Global Burden of Cancer will provide all stakeholders with timely estimates to guide policy efforts in cancer prevention, screening, treatment, and palliation.
JAMA The Journal of the American Medical Association 05/2015; JAMA Oncology online 28 May 2015. DOI:10.1001/jamaoncol.2015.0735 · 35.29 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In patients with a high life expectancy at the time of surgery for colorectal cancer (CRC), the long-term outcome may be influenced by factors other than their cancer. We aimed to investigate the long-term outcome and cause of death beyond a 5-year surveillance programme.
We evaluated the overall survival (OS) and cancer-specific survival (CSS) of a population-based cohort of stage I-III CRC patients <75 years old who completed a systematic surveillance programme.
In total, 161 patients <75 years old, 111 (69 %) of whom were node negative (pN0), were included. The median follow-up time was 12.1 years. The OS was 54 % at 15 years and differed significantly between the pN0 and pN+ patients (65 vs. 30 %; P < 0.001); CSS (72 %) also differed between the pN0 and pN+ patients (85 vs. 44 %; P < 0.001). For the 5-year survivors (n = 119), 14 (12 %) died of CRC during additional long-term follow-up (7 each for pN0 and pN+), and 6 patients (5 %; all pN0) died of other cancers. Patients aged <65 years exhibited better long-term survival (81 %), but most of the deaths were due to CRC (10/12 deaths). Only two of the 14 cancer-related deaths involved microsatellite instable (MSI) CRC. Females exhibited better OS and CSS beyond 5 years of surveillance.
The long-term survival beyond 5-year survivorship for stage I-III CRC is very good. Nonetheless, cancer-related deaths are encountered in one-third of patients and occur most frequently in patients who are <65 years old at disease onset-pointing to a still persistent risk several years after surgery.
Journal of Gastrointestinal Cancer 04/2015; 46(3). DOI:10.1007/s12029-015-9723-2 · 0.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The increasing incidence of prosthesis revision surgery in the Western world has led to an increased focus on the capacity for stem removal. We previously reported on a femoral stem implanted in goats with an approximate 15% reduction in retention force by drilling longitudinally orientated grooves on the side of the stem. In this current study, we aimed to histologically evaluate the bony apposition towards this stem and correlate this apposition with the pullout force.
We analyzed the femora of 22 goats after stem removal. All stems remained in place for 6 months, and the goats were allowed regular loading of the hip during this time. For histological evaluation, all femora were immersed in EDTA and decalcified until sufficiently soft for standard technique preparation. We evaluated bone apposition, the presence of foreign particle debris and other factors. The apposition was evaluated with a scoring system based on semi-quantitative bone apposition in four quadrants. Kappa statistics were calculated for the score. We correlated the retention force with the amount of bone apposition.
The stem drilling was the only significant factor influencing the retention force (p = 0.020). The bone apposition Kappa score comparing poor and good apposition scores was fair (κ = 0.4, 95% CI 0.00-0.88). Signs of foreign body reaction were noted in 5 of 22 goats.
Based on the current findings in an experimental goat model, it appears that the effect of drilling tissue/bone out of the longitudinal grooves has a more significant impact on the retention force required to remove the stem than the amount of bone apposition outside the stem grooves. This observation may be further explored in the research of stem designs that are potentially easier to remove.
[Show abstract][Hide abstract] ABSTRACT: Objective:
We sought to investigate various molecular subtypes defined by genomic instability that may be related to early death and recurrence in colon cancer.
We sought to investigate various molecular subtypes defined by instability at microsatellites (MSI), changes in methylation patterns (CpG island methylator phenotype, CIMP) or copy number variation (CNV) in 8 genes. Stage II-III colon cancers (n = 64) were investigated by methylation-specific multiplex ligated probe amplification (MS-MLPA). Correlation of CNV, CIMP and MSI, with mutations in KRAS and BRAFV600E were assessed for overlap in molecular subtypes and early recurrence risk by uni- and multivariate regression.
The CIMP phenotype occurred in 34% (22/64) and MSI in 27% (16/60) of the tumors, with noted CIMP/MSI overlap. Among the molecular subtypes, a high CNV phenotype had an associated odds ratio (OR) for recurrence of 3.2 (95% CI 1.1-9.3; P = 0.026). Losses of CACNA1G (OR of 2.9, 95% CI 1.4-6.0; P = 0.001), IGF2 (OR of 4.3, 95% CI 1.1-15.8; P = 0.007), CDKN2A (p16) (OR of 2.0, 95% CI 1.1-3.6; P = 0.024), and RUNX3 (OR of 3.4, 95% CI 1.3-8.7; P = 0.002) were associated with early recurrence, while MSI, CIMP, KRAS or BRAF V600E mutations were not. The CNV was significantly higher in deceased patients (CNV in 6 of 8) compared to survivors (CNV in 3 of 8). Only stage and loss of RUNX3 and CDKN2A were significant in the multivariable risk-model for early recurrence.
A high copy number variation phenotype is a strong predictor of early recurrence and death, and may indicate a dose-dependent relationship between genetic instability and outcome. Loss of tumor suppressors RUNX3 and CDKN2A were related to recurrence-risk and warrants further investigation.
PLoS ONE 04/2015; 10(4):e0122391. DOI:10.1371/journal.pone.0122391 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Becoming old is considered a privilege and results from the socioeconomic progress and improvements in health care systems worldwide. However, morbidity and mortality increases with age, and even more so in acute onset disease. With the current prospects of longevity, a considerable number of elderly patients will continue to live with good function and excellent quality of life after emergency surgical care. However, mortality in emergency surgery may be reported at 15-30%, doubled if associated with complications, and notably higher in patients over 75 years. A number of risks associated with death are reported, and a number of scores proposed for prediction of risk. Frailty, a decline in the physiological reserves that may make the person vulnerable to even the most minor of stressful event, appears to be a valid indicator and predictor of risk and poor outcome, but how to best address and measure frailty in the emergency setting is not clear. Futility may sometimes be clearly defined, but most often becomes a borderline decision between ethics, clinical predictions and patient communication for which no solid evidence currently exists. The number and severity of other underlying condition(s), as well as the treatment alternatives and their consequences, is a complex picture to interpret. Add in the onset of the acute surgical disease as a further potential detrimental factor on function and quality of life ¿ and you have a perfect storm to handle. In this brief review, some of the challenging aspects related to emergency surgery in the elderly will be discussed. More research, including registries and trials, are needed for improved knowledge to a growing health care challenge.
Scandinavian Journal of Trauma Resuscitation and Emergency Medicine 02/2015; 23(1):10. DOI:10.1186/s13049-015-0099-x · 2.03 Impact Factor