Forensic Sci Med Pathol DOI 10.1007/s12024-012-9322-5
REVIEW
The complex spectrum of forensic issues arising from obesity Roger W. Byard
Accepted: 8 February 2012 Springer Science+Business Media, LLC 2012
Abstract The increasing numbers of obese and morbidly obese individuals in the community are having a direct effect on forensic facilities. In addition to having to install more robust equipment for handling large bodies, the quality of autopsy examinations may be reduced by the physical difficulties that arise in trying to position bodies correctly so that normal examinations can proceed. Accelerated putrefaction is often an added complication. Metabolic disturbances resulting from obesity increase susceptibility to a range of conditions that are associated with sudden and unexpected death, and surgery may have increased complications. The rates of a number of different malignancies, including lymphoma, leukemia, melanoma and multiple myeloma, and carcinomas of the esophagus, stomach, colon, gallbladder, thyroid, prostate, breast and endometrium, are increased. In addition, obese individuals have higher rates of diabetes mellitus, and sepsis. The unexpected collapse of an obese individual should raise the possibility of a wide range of conditions, many of which may be more difficult to demonstrate at autopsy than in an individual with a normal body mass index. Although sudden cardiac death due to cardiomegaly, pulmonary thromboembolism, or ischemic heart disease may be the most probable diagnosis in an unexpected collapse, the range of possible underlying conditions is extensive and often only determinable after full postmortem examination. R. W. Byard School of Medical Sciences, The University of Adelaide, Adelaide, Australia R. W. Byard (&) Discipline of Anatomy and Pathology, Level 3 Medical School North Building, The University of Adelaide, Frome Road, Adelaide 5005, Australia e-mail:
[email protected]
Keywords Obesity BMI Surgical complication Sudden death Diabetes Atherosclerosis Infarct Thromboembolism Mortuary Occupational health and safety Metabolic syndrome Forensic ‘‘Sudden death is more common in those who are naturally fat than in the lean’’. Hippocrates 460-370BC [1].
Introduction Obesity is a complex entity involving the interaction of multiple environmental, genetic and neuroendocrine factors. In recent years there has been an alarming increase in average body size, measured by the body mass index or BMI, in a number of countries, that has been referred to as an ‘‘obesity epidemic’’ [2–4]. Specifically, review of adult body weights from 199 countries over the three decades between 1980 and 2008 showed that the mean body mass index (BMI) had risen by 0.4 kg/m2/decade, with countries such as the United States, Australia and New Zealand having the most significant increases [5]. BMI is measured as the weight in kilograms divided by the height in meters squared: a normal BMI falls in the range 18.5–24.9, with obesity C30, and morbid obesity C40 [6]. An estimated two thirds of the American population is now either overweight or obese, resulting in 300,000 deaths per year and a reduction in life span of 5–20 years [7]. Globally there are now more than 1 billion overweight individuals, with 300 million classified as obese [8]. There has been an awareness in forensic pathology of an increasing number of overweight bodies presenting to medicolegal facilities for autopsy. For example, a study in South Australia showed that the percentage of obese and morbidly obese cases had risen from 1.3 to 4.8 and 14.8 to
123
Forensic Sci Med Pathol
27.2%, respectively between 1986 and 2006 [6]. The focus in the forensic literature has tended to be on the technical difficulties that these cases present [6, 9]. Obesity is, however, associated with a much wider range of other issues that may directly impact on forensic practice (Table 1). In addition to directly causing disease, obesity may act as a risk modifier, causing a worse outcome in certain conditions. The following review details the spectrum of conditions and situations that may now be encountered more frequently due to their association with high BMIs. Given the increasing incidence of obesity it is important to be aware at the time of autopsy of the diverse manifestations that may be found in multiple organ systems.
Problems with mortuary handling Practical difficulties with the handling of bodies in the mortuary have been previously reported [6, 9]. Large bodies are difficult to both remove from death scenes and transport to mortuaries. On occasion special vehicles have to be utilized. At the mortuary lifting devices have to be capable of coping with weights of over 300 kg, and trolleys reinforced, and/or increased in size, to cope with abnormally large corpses. Autopsies may have to be performed on floors, or ladders may have to be utilized to appropriately position dissectors to enable them to make standard incisions and to adequately examine body cavities. Mortuary staff may require assistance to lift skin flaps to enable suturing to be performed during reconstruction procedures.
Increased rates of decomposition Increased amounts of subcutaneous and abdominal fat slow the rate of cooling, a feature seen in females who cool more slowly than males of identical weight due to their higher fat content [10]. This means that the process of decomposition, including both autolysis and putrefaction, is enhanced in the obese, as higher core temperatures are maintained for longer periods of time. This may be exacerbated in morbidly obese individuals who have been bedridden for some time, as bed coverings further increase insulation and thus the amount of retained heat. Given that putrefaction results in skin slippage with blistering, this means that very large bodies become even more difficult to handle as they are often wet and slippery, sometimes with extensive insect infestation [6]. Break down of excessive amounts of adipose tissue also results in large amounts of putrefactive fluid which may make mortuary floors slippery and dangerous to walk on. Thus, dissections that were already made difficult by the size of the decedent often have these added
123
Table 1 Issues and findings at autopsy in obesity 1. Problems with mortuary handling (i) Lifting (ii) Imaging (iii) Examining (iv) Sampling (v) Dissecting 2. Accelerated putrefaction 3. Cardiovascular disease (i) Coronary artery atherosclerosis/ischemic heart disease (ii) Cardiac failure (iii) Systemic hypertension (iv) Cardiomyopathy (v) Pulmonary thromboembolism (vi) Mesenteric venous thrombosis (vii) Cerebrovascular accident 4. Endocrine disease (i) Diabetes mellitus 5. Metabolic disease (i) Hyperlipidemia (ii) The metabolic syndrome 6. Dermatological disease (i) Sepsis 7. Gastrointestinal disease (i) Steatohepatitis 8. Respiratory disease (i) Airway obstruction 9. Sepsis/infection (i) Nosocomial infections 10. Malignancy (i) Increased rates of cancers of the esophagus, stomach, colon and rectum, gallbladder, pancreas, kidney, thyroid, prostate, breast, liver, uterus, cervix and ovary, with increased risk of non-Hodgkin lymphoma, leukemia, melanoma and multiple myeloma 11. Complications of pregnancy (i) Venous thromboembolism, postpartum cardiomyopathy and pregnancy-induced hypertension (ii) Aspiration (iii) Cesarian section 12. Postsurgical problems (i) General surgery (ii) Bariatric surgery (iii) Hemorrhage, thrombosis, sepsis, wound dehiscence, rhabdomyolysis 13. Prolonged hospital stay (i) Infections (i) Pressure ulcers 14. Predisposition to more severe injury
complications. While accuracy of diagnosis may not necessarily be compromised by decomposition [11], these changes further complicate the autopsy examination.
Forensic Sci Med Pathol
External and internal examinations
Increased incidence of specific diseases/conditions
An essential part of every forensic autopsy is a full external examination of the body, however, morbidly obese bodies make this process difficult. Rolling of a body to inspect the back is not easy, and genital and perineal inspection may be obscured by large folds of subcutaneous upper thigh adipose tissue, and covering of the area by an extensive lower abdominal fatty apron. Intertrigenous rashes and reddening within skin folds and creases around the anogenital region may mimic injury. Normal dissection is also challenging as access, particularly to intra-abdominal organs, is impeded by many centimeters of overlying adipose tissue, resulting in examinations being performed in the depths of body cavities. Once located at autopsy, internal organs may be embedded in layers of surrounding fat which may also be putrefying.
Obesity is associated with an increased incidence of a number of quite diverse conditions. In a 14-year prospective study in the United States of over a million individuals the relative risk of death from all causes was between 2.00 and 2.58 in those with BMIs of 35 or higher [12]. However it should be recognized that abdominal obesity, which has also increased markedly in certain populations possibly even more than BMI, may be a better marker for increased risk of cardiovascular disease, diabetes mellitus and the metabolic syndrome. Abdominal obesity is defined as a waist circumference of 103 cm (40 inches) or more in men, or 88 cm (35 inches) or more in women [7].
Special dissections Pelvic exenteration is a technique that is required in cases of suspected sexual assault. It involves dissecting out the intact pelvic organs, perineum and rectum so that careful examination can be made of mucosal and skin surfaces for evidence of trauma. This dissection may be made difficult if there is a significantly increased depth of subcutaneous adipose tissues around the perineum and if the area is obscured by ‘‘overflow’’ of inner thigh and lower abdominal fat.
Sampling difficulties Femoral punctures may be performed prior to formal autopsy to enable screening for infectious agents or drugs. This involves inserting a needle through the skin and subcutaneous tissues of the groin into the femoral vessels, which may be exceedingly difficult if the vessels are buried deeply beneath a thick layer of adipose tissue. A similar problem with venesection occurs in hospitals. Obtaining uncontaminated vaginal swabs in cases of suspected sexual assault may also not be possible if the area is occupied by upper thigh skin folds.
Cardiovascular conditions The ‘‘obesity paradox’’ refers to the higher survival rates that have been demonstrated in some studies amongst obese individuals who had suffered a previous cardiac event [7, 13]. The reasons for this finding are unclear, but may relate to earlier ages of onset of the first cardiovascular event, or to better tolerance of the catabolic effects of myocardial ischemia in the obese. It is also possible that the results have been skewed by a higher representation of chronically ill, cachexic individuals in the lower weight categories who have reduced survival [7, 13]. Ischemic heart disease There is a definite association between obesity and an increased risk of death from coronary artery atherosclerosis and myocardial ischemia. This was shown in the Framingham Heart Study, with more recent studies demonstrating a 2% increased relative risk of a cardiovascular event for every 1 cm increase in waist circumference [14]. Obesity may mediate coronary artery disease due to concomitant hypercholesterolemia and hypertension, but will also accelerate already established arterial disease. Obesity is associated with a younger age of the first episode, often with a worse outcome [7]. It has been suggested that obesity may amplify other risk factors through synergistic mechanisms [15] and that endothelial dysfunction from oxidative stress or the actions of pro-inflammatory cytokines may cause accelerated atherogenesis [16].
Alternative diagnostic modalities Cardiac failure While computed tomographic (CT) scanning is an extremely useful technique to augment standard autopsy dissections, problems also arise in trying to adequately image the morbidly obese as large bodies may simply not fit into standard scanners due to their weight and/or girth.
Obesity is an independent risk factor for cardiac failure with a twofold risk for cardiac failure in those with BMIs above 30 (2.12 for women and 1.90 for men). In a review of 5,881 participants in the Framingham Heart Study obesity was the sole cause of cardiac failure in 11% of the
123
Forensic Sci Med Pathol
men and 14% of the women [17]. The mechanism of this relationship is not clear, however left ventricular hypertrophy and dilation occur with a high BMI, most likely due to increased hemodynamic load, oxidative stress and neurohormonal activation. The changes in hemodynamic load involve increases in blood and stroke volume, filling pressures and cardiac output [7, 17]. It has also been proposed that adipocytes may have a direct toxic effect on the myocardium inducing a non-ischemic, dilated cardiomyopathy (see below) [18]. Systemic hypertension The Framingham Heart Study showed obesity to be an independent risk factor for hypertension in both sexes, with markedly obese women in their fourth decade having seven times the risk of having an elevated blood pressure [19]. It has been proposed that 50% of cases of hypertension are related to obesity [15], with 40.8% of the obese population being hypertensive [20]. The etiology of hypertension in obesity is complex involving hemodynamic factors such as increased preload, stroke volume and blood volume which result in left ventricular hypertrophy and on occasion sudden death [7]. In addition there is sympathetic stimulation with activation of the renin-angiotensin-aldosterone system, and secretion of leptin [21]. These factors may cause chronic renal damage which can be detected at autopsy and which may have initiated a vicious circle of changes [7]. Leptin has also been shown to stimulate endothelin ET1, generating reactive oxygen species and stimulating cardiac myocyte hypertrophy [20]. Cardiomyopathy It has been shown that the weight of the heart increases with body weight. While the cardiac weight as a percentage of body weight is normally 0.043% for males and 0.040% for females, it actually falls to 0.035 and 0.030%, respectively, in the morbidly obese [22]. Deposition of adipose tissue in and around the heart may alter left ventricular function by a variety of processes including physical compression and lipotoxicity. This has been referred to as obesity cardiomyopathy, or adipositas cordis [16]. Pulmonary thromboembolism The mechanism by which obesity is believed to predispose to deep venous thrombosis and pulmonary thromboembolism is multifactorial, involving reduced mobility, decreased venous return from venous compression, and a probable hypercoagulable state [23, 24]. The latter is thought to be mediated by alterations in proteins involved
123
in both fibrinolysis and coagulation with raised levels of fibrinogen, plasminogen activator inhibitor, factor VII, and factor VIII [25]. In addition, adipocytes may have a direct effect on thrombogenesis by secreting adipsin (complement D), plasminogen activating inhibitor 1, adiponectin and adipocyte complement-related protein (Arcp30) [26]. The risk of pulmonary thromboembolism has been shown to be related directly to the magnitude of the BMI [27]. Some pathologists considerer that adequate dissection of the deep veins of the calf muscles in cases of pulmonary thromboembolism requires a posterior approach with the body being turned prone. Given the difficulties that arise in attempting to turn large bodies on narrow morgue trolleys, a preferable approach is to make a curved incision on the inner aspect of the lower leg with the body supine. In this way adequate access to the deep calf veins can be achieved through a wide skin flap without the significant occupational and health issues of attempting to maneuver massive bodies. Mesenteric venous thrombosis In addition to pulmonary thromboembolism, obese individuals may be at increased risk of mesenteric venous thrombosis may also be initiated when increased intraabdominal pressure from adipose tissue deposition compresses the portomesenteric system causing stasis and thrombosis [28, 29]. Atrial fibrillation Dilation of the left atrium associated with increased blood volume, left ventricular hypertrophy, sympathetic stimulation, obstructive sleep apnea and diastolic dysfunction have all been demonstrated in obese individuals resulting in an increased incidence of atrial fibrillation with its associated thomboembolic consequences. It has been shown that an increase in BMI by 1 is associated with a 4% increase in the risk of developing atrial fibrillation [30]. Pulmonary hypertension Microscopic changes of pulmonary hypertension are not uncommonly found in morbidly obese patients, most likely related to sleep apnea and/or obesity hypoventilation syndrome [26]. Pulmonary hypertension has been found in 15–20% of individuals with obstructive sleep apnea [16]. Cerebrovascular accident It has been shown that an increase in BMI by 1 kg/m2 increases the risk of ischemic stroke by 4% and hemorrhagic stroke by 6%. This most likely relates to the
Forensic Sci Med Pathol
increased incidence of both hypertension and atrial fibrillation, and to the underlying prothrombotic and proinflammatory metabolic alterations that occur in the obese [31]. The risk of stroke is associated not only with increasing BMI but also with increasing waist-to-hip ratio. Compared to males with a BMI \ 25, overweight males have an adjusted relative risk for stroke overall of 1.32, for ischemic stroke of 1.35, and for hemorrhagic stroke of 1.25. The corresponding relative risks for obese males are 1.91, 1.87 and 1.91 respectively [16].
Metabolic conditions
Sudden cardiac death
Hyperlipidemia
As noted by Hippocrates more than 2,000 years ago [1] obesity carries with it an increased risk of sudden cardiac death. The Framingham Study revealed an increased risk of arrhythmias and sudden death with increasing weight in both sexes, with a 40-times risk of cardiac arrest in the obese compared to those of normal weight [16]. As this may be related to prolonged QT interval there may be no specific findings at autopsy.
Hyperlipidemia is a known cause of premature and progressive coronary artery disease [37] and is also related to obesity. Additional compounding factors include type II diabetes mellitus, the metabolic syndrome and high fat and sugar diets. Visceral obesity increases levels of IL-6, free fatty acids and resistin which mediate insulin resistance and accelerate atherogenic dyslipidemia [7]. This involves increased levels of triglycerides and low-density lipoprotein cholesterol and decreased levels of high-density lipoproteins [38].
Obesity is associated with chronic low grade stimulation of inflammatory responses with high circulating levels of C-reactive protein, tumor necrosis factor-a, interleukin, leptin and plasminogen activator inhibitor-1. It is considered that this may predispose to a systemic inflammatory response with multifocal organ dysfunction. Visceral adipose tissue produces more inflammatory mediators than subcutaneous fat stores [36].
Endocrine conditions The metabolic syndrome A variety of endocrine abnormalities, such as Cushing disease, may cause obesity. Alternatively, endocrine disturbance may be a complication of obesity as adipose tissue acts as an endocrine organ with production of the hormone leptin and the metabolism of steroids. Estrogens cause adipogenesis in subcutaneous tissues and the breast, while androgens stimulate central obesity. Testosterone production may cause hirsutism and male-pattern baldness in obese women [32, 33]. In addition, inflammatory cytokines such as TNFa and IL-6 are produced, as are proteins involved in coagulation, fibrinolysis and the renin-angiortenesin syndrome. All of these have direct impact on the metabolic and cardiovascular effects of obesity [34]. Diabetes mellitus Cases of diabetes mellitus are continually being encountered at autopsy, often in association with cardiovascular disease or metabolic disturbances involving hyperglycemia and ketoacidosis. There is a strong association between diabetes mellitus and obesity with an odds ratio of 7.37 for diabetes in individuals with a BMI of 40 or higher [35]. Nearly 90% of those with type II diabetes are either overweight or obese. Morbidly obese males have five times the risk of developing type II diabetes. This increased to an alarming 29 times in a US study of women who were in the highest quintiles for BMI and waist-to-hip ratios [15]. Accelerated atherogenesis also results from endothelial damage due to hyperglycemia with insulin resistance [7].
Visceral obesity, the increased risk of cardiovascular events, hypertension and metabolic disturbances of dyslipidemia and diabetes mellitus Iink through insulin resistance in what has come to be known as the metabolic syndrome. Definitional criteria involve an increased waist circumference, elevated serum triglycerides and glucose, hypertension and lowered high-density lipoprotein levels [39]. Over 40% of individuals in the United States aged over 60 years have the syndrome, with a 2–3 times risk of a cardiac event or stroke [7]. Dermatological conditions Dermatological conditions arising from obesity may result from a primary effect of disturbed underlying metabolism or secondarily from excessive and moist skin and fat folds that create an ideal microenvironment for fungal and bacterial overgrowth. The first lesions that may be observed include acanthosis nigricans, irregular soft brown plaques around the neck and axillae, and skin tags. These occur in as many as 74% of obese individuals and are markers of insulin resistance and hyperinsulinemia (it is hypothesized that high levels of insulin stimulate insulin-like growth factor receptors in the skin prompting skin and fibroblast proliferation) [32]. Other common findings are acne due to increased androgen production and striae distensae, or stretch marks, on the abdomen, buttocks and upper thighs that are caused by
123
Forensic Sci Med Pathol
dermal scarring. Direct stimulation of pilosebaceous units may also cause furunculosis [32]. Lower limb problems result from varicose ulceration and lymphedema due to venous and lymphatic stasis, both of which may cause recurrent cellulitis with occasional disseminated infection. Intertrigo develops when opposing skin surfaces in excessive fat folds rub together. Infections are then exacerbated, as the obese overheat more easily due to the insulating effect of increased subcutaneous fat causing sweating with increased humidity in anogenital, axillary, umbilical and submammary areas. This fosters the growth of organisms such as Candida albicans within the layers of desquamated and macerated skin debris [32]. Such overgrowth is also promoted by an inability to adequately clean extensive and folded skin surfaces and by concomitant diabetes mellitus [10]. The perineal region in obese women may be particularly prone to the effects of intertrigenous maceration and ulceration as urinary incontinence may be caused by excessive amounts of abdominal fat, raising intraabdominal pressure and compressing the bladder [32]. In rare instances a rapidly advancing necrotizing infection of the perineal region known as Fournier gangrene may develop. It is usually caused by Eschericia coli that proliferates in the warm and moist environment of the perineum associated with diabetes mellitus and poor hygiene [40].
Respiratory conditions On occasion no anatomical cause of death may be found in morbidly obese individuals. In this situation the possibility of respiratory compromise should be considered, as pulmonary dysfunction and sleep apnea in morbid obesity have been demonstrated, even in childhood [44]. Certainly animal studies have shown reduced pulmonary function in immature obese animals, and obesity is known to decrease chest wall compliance, increase fat deposition in pharyngeal tissues and cause upward compression of the diaphragm [45]. As well, reduced pulmonary compliance results from increased pulmonary blood volume, fatty infiltration of the chest wall and extrinsic compression of the thoracic cage by adipose tissue [46]. The etiology of hypoventilation in obese individuals is thus multifactorial involving changes in ventilatory mechanics and also in central control. Inflammatory changes may result in an increased incidence of asthma [47] with a possible link between obesity and asthma being used to explain the dramatic increases in cases of asthma over recent years [48]. It is also possible that obese individuals may have worse outcomes if they develop acute lung injury or acute respiratory distress syndrome [46]. Obstructive sleep apnea
Gastrointestinal conditions In addition to the conditions listed below, obese individuals have an increased incidence of cirrhosis, erosive esophagitis, and Barrett esophagus [41]. Nonalcoholic steatohepatitis It has been suggested that 90% of obese individuals have some degree of fatty liver, ranging from simple steatosis to nonalcoholic steatohepatitis and cirrhosis [42]. Steatohepatitis has been reported in 18.5% of markedly obese patients at autopsy associated with fibrosis in 13.8%, although on occasion this figure may be much higher, approaching 70–80% [26]. Acute pancreatitis Obesity induces a worse outcome in severe acute pancreatitis with a relative risk of 4.3 for local complications such as abscess, necrosis and pseudocyst formation, 2.0 for systemic complications, and 2.1 for death [36]. Crohns disease Obese patients with Crohns disease require more aggressive medical therapy and earlier surgery than those of normal weight [43].
123
Obstructive sleep apnea, characterized by recurrent episodes of apnea and hypopnea during sleep, has a strong association with central obesity in males [49]. It results in hypersomnolence during the day and has been linked to vehicle crashes as well as being associated with hypertension and increased cardiovascular morbidity and mortality [50]. Approximately 50–60% of individuals with hypertension have obstructive sleep apnea compared to 5–10% of the general population [51]. The reported association of obstructive sleep apnea and sudden cardiac death is unproven [52]. Obstructive hypoventilation syndrome Also known as Pickwickian syndrome, this syndrome is characterized by obesity, hypoventilation and sleep disordered breathing. Approximately 90% of patients with obstructive hypoventilation syndrome also have sleep apnea. Decreased respiratory drive, reduced response to leptin, and respiratory muscle impairment, all contribute to the syndrome. Obesity markedly increases the work of breathing due to decreased lung compliance with difficulties moving the rib cage and diaphragm such that 15% of daily oxygen consumption is used in breathing compared to 3% in individuals of normal weight [53]. While not diagnosable at autopsy, review of the clinical record may give
Forensic Sci Med Pathol
some assistance in determining whether it may have been involved in the terminal episode. Problems involving tracheostomies Although not usually considered in reviews of complications of tracheostomies [54], obesity may result in increased morbidity from this procedure. As the trachea lies deep within cervical adipose tissue a larger incision often has to be made with increased postoperative risks of hemorrhage. In addition, excessive amounts of submental fat may require liposuction or debulking to prevent occlusion of the tracheostomy tube by accessory chins [32].
pulmonary thromboembolism that may lead to a forensic investigation. In addition, the local and distant effects of tumors may play a role in clinical presentation and so the possibility of these lesions should always be considered at autopsy in the obese. Esophageal adenocarcinoma A strong association exists between obesity and esophageal adenocarcinoma with a Swedish study showing an odds ratio of 16.2 for individuals with BMI [ 30 compared to those with BMI \ 22. There was no association with esophageal squamous carcinoma [62].
Sepsis/infection
Gastric adenocarcinoma
Studies of infections in obese individuals have often been confounded by the presence of concomitant diabetes mellitus. Controlling for this variable has shown, however, that obesity is associated with an increased incidence of infection, possibly due to the interaction of pro-inflammatory and anti-inflammatory factors with immunosuppressive effects [55]. Obese patients do have an increased rate of nosocomial infections and also of infections after surgical procedures, the later possibly associated with reduced subcutaneous tissue oxygenation. Examples include an increased incidence of mediastinitis following coronary artery bypass grafting and intra-abdominal infection after pancreatic transplantation. The vulnerability of obese patients with influenza virus infection to worse clinical outcomes should be considered in pandemics [56]. Other infections that occur at a higher rate in the obese include periodontal infections (particularly in the young), community acquired respiratory infections, and skin infections (see above). Interestingly, mild to moderate obesity in intravenous drug users with HIV infection may result in a more favorable outcome [57].
Individuals with occult gastric adenocarcinoma may occasionally present with massive and fatal upper gastrointestinal hemorrhage. Risk factors for adenocarcinoma of the gastric cardia include obesity, with a Swedish study demonstrating a 2.3 times increase in this form of malignancy in the heaviest quartile of the population compared to the lightest [63]. Hepatocellular carcinoma The increased risk of dying from hepatocellular carcinoma in obesity has ranged from approximately 1.6–4.5, with a worse outcome in males [42]. Prostatic adenocarcinoma It now appears that obesity increases the risk of aggressive prostatic cancer as well as increasing the risk of recurrence following prostatectomy, although it reduces the risk of low-grade prostatic adenocarcinoma [64, 65]. Colorectal adenocarcinoma
Malignancy Obesity has been associated with an increased risk for a wide range of malignancies involving the esophagus, stomach, colon and rectum, gallbladder, pancreas, kidney, thyroid, prostate, breast, liver, uterus, cervix and ovary. In addition, obesity is related to an increased risk of non-Hodgkin lymphoma, leukemia, melanoma and multiple myeloma [41, 58, 59]. It has been estimated that excess body weight accounts for 5% of cancers in Europe (3% for males and 6% for females), representing 27,000 male and 45,000 female cancer victims per year [60]. Certain malignancies may be associated with familial obesity [61]. While the following malignancies may not necessarily all cause sudden and unexpected death they may be associated with side effects such as sepsis, hemorrhage or
A meta-analysis of studies on 70,000 cases of colorectal cancer demonstrated that increasing body weight is directly related to colorectal malignancy. Specifically, those with a BMI C 30 have an approximately 20% greater risk, with a 4% increase in risk for every 2 cm increase in abdominal circumference. There is a gender difference, with males having a 30% higher risk than females. The risk of carcinoma of the colon is higher in the obese than is the risk of carcinoma of the rectum [66]. Endometrial cancer Obesity is a well-recognized risk factor for endometrial cancer, occurring in both pre and postmenopausal woman, but with a stronger association in older females [67].
123
Forensic Sci Med Pathol
Renal cell cancer The risk of renal cell carcinoma for both sexes increases by 1.07 for every unit increase in BMI, which corresponds to approximately a 3 kg weight increase in an individual of average height [68]. Breast cancer The mortality rate from breast cancer in postmenopausal women increases with increasing BMI, with a relative risk of 3.08 in those with a BMI C 40 compared to those with a BMI of 18.5–20.49 [69]. Pregnancy Pregnancy may be more easily missed or concealed in the obese resulting in delayed presentation for medical care, or unexpected birth. Particular problems also arise in mothers with high BMIs as maternal obesity before pregnancy is associated with increased risks of venous thromboembolism, postpartum cardiomyopathy and pregnancy-induced hypertension. Obese mothers are also at higher risk of gestational diabetes with large infants and higher rates of obstructed labor. Infants of obese mothers have more head trauma and also higher rates of intra-uterine death and birth defects such as spina bifida [70]. Cesarian section rates have approached 47.4% in the morbidly obese and 33.8% in the obese, compared to 20.7% in controls. Surgery takes longer in the obese with greater blood loss and more postoperative infections and endometritis, and imaging of fetal anatomy may be suboptimal [70, 71]. A higher maternal death rate occurs in the obese during pregnancy from aspiration of gastric contents associated with hiatus hernia and higher intra-abdominal pressures, and from failed endotracheal intubation. In the morbidly obese the latter has approached 33% of cases [72]. The risk of aspiration may be exacerbated by concomitant diabetes mellitus which delays gastric emptying. Reduced respiratory excursion is an underlying comorbidity that can also prolong recovery from anesthesia. Sudden death has occurred associated with circulatory changes following positional change, and aortocaval compression by the uterus underneath a massive abdominal panniculus can markedly reduce cardiac output and placental perfusion [71].
Surgical issues Surgery may be performed for conditions that are either unrelated to underlying obesity or that may be specifically directed at treating excess weight. The range of surgical
123
treatments for morbid obesity that may be encountered at autopsy include jejunoileal bypass, laparoscopic adjustable gastric banding, biliopancreatic diversion, duodenal switch, vertical band gastroplasty, intragastric balloon, minigastric bypass, open and laparoscopic Roux-en-Y gastric bypass and sleeve gastric resection [73]. Each of these may be associated with particular postoperative problems. Complications resulting from surgery may be caused by factors related to underlying obesity itself or directly from the process of surgery [26]. Particular difficulties that arise in the morbidly obese that may predispose to unexpected death are their lack of physiological reserve to cope with postoperative problems, and their failure to manifest symptoms and signs such as abdominal pain, fever and leukocytosis [73], thus delaying diagnosis and treatment. The inability to utilize computed tomography in the morbidly obese may also delay diagnoses. Thus at the time of autopsy there may be minimal information in the clinical notes to indicate a likely cause of death. There is an increased risk of deep venous thrombosis with pulmonary thromboembolism in the obese following surgery for reasons that have already been described. There is also a higher rate of postoperative pneumonia and pulmonary complications resulting from reduced chest expansion and aspiration of gastric contents [74]. Wound infections occur in 1–10% of patients following bariatric surgery [73] associated with difficulties in wound closure, poor wound healing, underlying diabetes mellitus and proximity to areas of infected intertrigenous skin folds. Wound healing is also impaired in the obese due to reduced tissue perfusion which may be exacerbated by tension on wound edges from large amounts of fat in the sutured material [32]. Postoperative hemorrhage may result from injuries to the small intestinal mesentery or spleen that were not recognized at surgery due to the technical difficulties associated with operating in the obese. In addition bleeding may occur from anastomotic sites or trochar injuries [73]. A rare but wellrecognized complication of surgery in the morbidly obese is rhabdomyolysis due to compression, particularly of the gluteal muscles, for some time resulting in the development of a compartment syndrome. Muscle ischemia may be exacerbated by hypertension and diabetes mellitus [73]. Assessment of the adequacy of padding of pressure points during surgery may be a required part of the autopsy evaluation. Specific complications associated with particular bariatric procedures that may have forensic implications include dehiscence with leakage of intestinal and gastric contents, anastomotic stricture formation, and marginal ulceration at gastrojejunostomy and jejunojejunostomy anatomosis sites after Roux-en-Y bypass. Hepatic artery ligation and mesenteric venous thrombosis have also been reported [26]. Intestinal obstruction may occur because of internal herniation, adhesions or kinking of portions of the bypass.
Forensic Sci Med Pathol
Laparoscopic gastric bypass is associated with a lower mortality than an open procedure, but has a higher rate of intestinal obstruction, hemorrhage and stomal stenosis [75]. Erosion of bands into the stomach may follow gastric banding with other problems including obstruction, gastric herniation through the band, and gastroesophageal dilation. Gastric perforation with peritonitis may result from some of these complications [76, 77]. The adjustment port in gastric bands may also leak, detach or become infected [73]. Liposuction may be associated with inadvertent perforation of the peritoneal cavity and intestine and also with the development of fulminant subcutaneous infection leading to necrotizing fasciitis [78, 79]. Fat embolism has also rarely been reported [80] which would necessitate special staining of microscopic slides for fat after autopsy. A late complication of bariatric surgery that may necessitate further surgery is cholelithiasis, which occurs in up to 70% of individuals who lose weight rapidly [81].
Hospital issues It has been shown that obese individuals experience longer hospital stays than patients of normal weight [82] and have reduced mobility and greater dependence, with the result that they will have been exposed to the risk of nosocomial infections for greater periods. While decubitus ulcers, or pressure sores, usually develop over bony prominences in thin debilitated individuals who are unable to regularly move themselves, the situation may be slightly different in the morbidly obese. Necrotic areas may develop within fat folds due to capillary compression with marked tissue destruction that may not be obvious unless careful examination is undertaken. Ulcers may also be found over the hips due to prolonged pressure from bed side rails, bed pans or wheel chairs [32].
Alternative therapies The use of alternative therapies for weight loss has on occasion had unanticipated side effects. This occurred in Belgium when the herb Stephania tetranda was replaced by Aristolochia fangchi in a herbal preparation designed to help with weight loss. The herb that was used contained a nephrotoxin, aristolochic acid, that resulted in rapidly progressive interstitial nephritis with terminal renal failure [83].
Predisposition to injury A factor that is not always considered in traumatic events such as vehicle crashes is the potential effect of larger body
mass. While it is likely that obese individuals have a worse outcome following blunt trauma, due to the presence of comorbidities such as ischemic heart disease and the predisposition to postoperative infection, it has been shown that obese individuals also suffer more severe injuries [84]. Those with BMIs greater than 30 are more likely to suffer rib fractures, pulmonary contusion, pelvic and extremity fractures in vehicle crashes (although the incidence of head and liver injuries is lower), and have an increased likelihood and severity of ankle and elbow injuries following falls, [84, 85]. This may be influenced by gender, with some studies showing that obese males have the highest risk of death [86]. As the impact energy of an unrestrained body is directly proportional to mass it is perhaps not surprising that there is an increased risk of lethal and nonlethal injuries in the obese. Given that groups such as motorcycle riders are at increased risk of unrestrained highspeed crashes, increasing BMI’s may intensify the energy of impact and result in significant chest and pelvic injuries [87]. More severe extremity injuries in the obese [88] are associated with a greater need for surgical intervention with associated anesthetic and postoperative complications.
Suicide It has been reported that increased amounts of intraabdominal fat are associated with higher rates of depression [89, 90]. Whether this is due to underlying metabolic disturbances is unclear, however it has been proposed that the link may involve the chronic inflammatory state induced by obesity that is associated with increased cytokine and monocyte chemoattractant protein secretion [8]. While the relationship of this to suicide has also not been determined, anecdotally the author has had few cases of suicide in the morbidly obese. Whether this has occurred because common methods of suicide such as hanging or carbon monoxide poisoning are not accessible to those with markedly enlarged body habitus is uncertain.
Problems with attempted resuscitation Numerous problems may arise during attempted resuscitation of the morbidly obese which may contribute to a negative outcome. Rapid positioning of a body to enable cardiopulmonary resuscitation on a firm surface may not be possible and placing the head and neck into a position to facilitate aeration may not be easy. Endotracheal intubation is more difficult in obese individuals who are at risk of more rapid hypoxemia due to reduction in pulmonary functional residual capacity, decreased compliance, increased airway resistance, and an increase in pulmonary vascular resistance [91].
123
Forensic Sci Med Pathol
Problems with dialysis A higher mortality rate has been reported in obese patients who undergo peritoneal rather than hemodialysis, particularly if they are diabetic. The reasons for this remain unclear [92]. Conclusion Morbid obesity results in significant derangements of multiple organ systems leading to sudden and unexpected death in some cases, and the exacerbation or initiation of major, although not immediately life-threatening, disease in others [93]. Morbidly obese individuals are a challenge to forensic services in a practical sense from body handling and storage, and also in a theoretical sense given the number of diverse and potentially occult conditions that may only be revealed at autopsy. Given the complex interrelation and significance of many of the metabolic and disease processes associated with marked obesity, ‘‘morbid obesity’’ should be included in the cause of death in these individuals to reflect the inter-dependence of many of these lethal mechanisms. Despite the technical difficulties involved, autopsy dissection has to be meticulous and wide ranging due to the number of associated diseases and conditions found in those with markedly elevated BMIs.
Key Points 1.
2.
3.
4.
5.
6.
Forensic facilities are handling far greater numbers of overweight, obese and morbidly obese bodies than in previous years. Autopsies in morbidly obese individuals are difficult due to problems in moving, positioning, examining and dissecting. Adipose tissue secretes a variety of cytokines and hormones that may predispose to a systemic inflammatory response with multifocal organ dysfunction. Obesity is associated with an increased incidence of sudden death, cardiac failure, arrhythmias, hypertension, coronary artery atherosclerosis and pulmonary thromboembolism. Other conditions with higher rates in the obese include metabolic and endocrine disorders, such as diabetes mellitus, and a wide range of malignancies. Obese individuals have more complications during pregnancy and following surgery.
References 1. Lloyd GER. Hippocratic writings. Harmondsworth: Penguin Books; 1978. p. 212.
123
2. Caballero B. The global epidemic of obesity: an overview. Epidemiol Rev. 2007;29:1–5. 3. Lee YS, So JBY, Deurenberg-Yap M. Confronting the obesity epidemic: call to arms. Ann Acad Med Singap. 2009;38:1–2. 4. Behn A, Ur E. The obesity epidemic and its cardiovascular consequences. Curr Opin Cardiol. 2006;21:353–60. 5. Finucane MM, Stevens GA, Cowan MJ, Danaei G, Lin JK, Paciorek CJ, et al. National, regional, and global trends in bodymass indexes a systematic analysis of health examination surveys and epidemiological studies in 960 country-years and 9.1 million participants. Lancet. 2011;377:557–67. 6. Byard RW, Bellis M. Significant increases in body mass index (BMI) in an adult forensic autopsy population from 1986 to 2006—implications for modern forensic practice. J Forensic Leg Med. 2008;15:356–8. 7. Zalesin KC, Franklin BA, Miller WM, Peterson ED, McCullough PA. Impact of obesity on cardiovascular disease. Med Clin North Am. 2011;95:919–37. 8. Shelton RC, Miuller AH. Eating ourselves to death (and despair): the contribution of adiposity and inflammation to depression. Prog Neurobiol. 2010;91:275–99. 9. Byard RW. Increasing body mass and the mortuary. Forensic Sci Med Pathol. 2010;6:247–8. 10. Zhou C, Byard RW. Factors and processes causing accelerated decomposition in human cadavers. J Forensic Leg Med. 2011; 18:6–9. 11. Byard RW, Farrell ER, Simpson E. Diagnostic yield and characteristic features in a series of decomposed bodies subject to coronial autopsy. Forensic Sci Med Pathol. 2008;4:9–14. 12. Calle EE, Thun MJ, Petrelli JM, Rodriguez C, Heath CW. Bodymass index and mortality in a prospective cohort of US adults. New Engl J Med. 1999;341:1097–105. 13. Oreopoulos A, Padwal R, Kalantar-Zadeh K, Fonarow G, Norris CM, McAlister FA. Body mass index and mortality in heart failure: a meta-analysis. Am Heart J. 2008;156:13–22. 14. De Koning L, Merchant AT, Pogue J, Anand SS. Waist circumference and waist-to-hip ratio as predictors of cardiovascular events: meta-regression analysis of prospective studies. Eur Heart J. 2007;28:850–6. 15. Schunkert H. Obesity and target organ damage: the heart. Int J Obes. 2002;26:S15–20. 16. Poirier P, Giles TD, Bray GA, Hong Y, Stern JS, Pi-Sunyer FX, Eckel RH. Obesity and cardiovascular disease: pathophysiology, evaluation, and effect of weight loss. An update of the 1997 American Heart Association Scientific Statement on obesity and heart disease from the Obesity Committee of the Council on Nutrition, Physical Activity and Metabolism. Circulation. 2006; 113:898–918. 17. Kenchaiah S, Evans JC, Levy D, Wilson PWF, Benjamin EJ, Larson MG, Kannel WB, Vasan RS. Obesity and the risk of heart failure. New Engl J Med. 2002;347:305–13. 18. McGavock JM, Victor RG, Unger RH, Szczepaniak LS. Adiposity of the heart, revisited. Ann Int Med. 2006;144:517–24. 19. Garrison RJ, Kannel WB, Stokes J, Castelli WP. Incidence and precursors of hypertension in young adults: the Framingham Offspring Study. Prev Med. 1987;16:235–51. 20. Reisin E, Jack AV. Obesity and hypertension: mechanisms, cardio-renal consequences, and therapeutic approaches. Med Clin North Am. 2009;93:733–51. 21. Engeli S, Sharma A. Emerging concepts in the pathophysiology and treatment of obesity-associated hypertension. Curr Opin Cardiol. 2002;17:355–9. 22. Drenick EJ, Fisler JS. Myocardial mass in morbidly obese patients and changes with weight reduction. Obes Surg. 1992;2:19–27. 23. Cushman M. Epidemiology and risk factors for venous thrombosis. Semin Hematol. 2007;44:62–9.
Forensic Sci Med Pathol 24. Ay C, Tengler T, Vormittag R, Simanek R, Dorda W, Vukovich T, et al. Venous thromboembolism—a manifestation of the metabolic syndrome. Haematologica. 2007;92:374–80. 25. Darvall KAL, Sam RC, Silverman SH, Bradbury AW, Adam DJ. Obesity and thrombosis. Eur J Vasc Endovasc Surg. 2007;33:223–33. 26. Melenik J, Livingston E, Cortina G, Fishbein MC. Autopsy findings following gastric bypass surgery for morbid obesity. Arch Pathol Lab Med. 2002;126:1091–5. 27. Rosenfeld H, Tsokos M, Byard RW. The association between body mass index and pulmonary thromboembolism in an autopsy population. J Forensic Sci (in press). 28. Byard RW. Mesenteric venous thrombosis. Forensic Sci Med Pathol. 2011; doi:10.1007/s12024-011-9302-1. 29. Byard RW. Acute mesenteric ischaemia and unexpected death. J Forensic Leg Med. 2012; doi:10.1016/j.jflm.2011.12.023. 30. Wang TJ, Parise H, Levy D, D-Agostino RB, Wolf PA, Vasan RS, Benjamin EJ. Obesity and new-onset atrial fibrillation. JAMA. 2004;292:2471–7. 31. Lavie CJ, Milani RV, Ventura HO. Obesity and cardiovascular disease. Risk factors, paradox, and impact of weight loss. J Am Coll Cardiol. 2009;53:1925–32. 32. Garcia Hildalgo L. Dermatological complications of obesity. Am J Clin Dermatol. 2002;3:497–506. 33. Kokkoris P, Pi-Sunyer FX. Obesity and endocrine disease. Endocrinol Metab Clin North Am. 2003;32:895–914. 34. Ahima RS, Flier JS. Adipose tissue as an endocrine organ. Trends Endocrinol Metab. 2000;11:327–32. 35. Mokdad AH, Ford ES, Bowman BA, Dietz WH, Vinicor F, Bales VS, Marks JS. Prevalence of obesity, diabetes, and obesity-related health risk factors, 2001. JAMA. 2003;289:76–9. 36. Abu Hilal M, Armstrong T. The impact of obesity on the course and outcome of acute pancreatitis. Obes Surg. 2008;18:326–8. 37. Austin MA, Hokanson JE, Edwards KL. Hypertriglyceridemia as a cardiovascular risk factor. Am J Cardiol. 1998;81:7B–12B. 38. Pi-Sunyer FX. Medical hazards of obesity. Ann Intern Med. 1993;119:655–60. 39. Ford ES, Giles WH, Dietz WH. Prevalence of metabolic syndrome among US adults. Findings from the Third National Health and Nutrition Examination Survey. JAMA. 2002;287:356–9. 40. Bury D, Byard RW. Fournier gangrene and unexpected death. J Forensic Sci (in press). 41. Foxx-Orenstein AE. Gastrointestinal symptoms and disease related to obesity: an overview. Gastroenterol Clin North Am. 2010;39:23–37. 42. Caldwell SH, Crespo DM, Kang HS, Al-Osaimi AMS. Obesity and hepatocellular carcinoma. Gatroenterology. 2004;127: S97–103. 43. Hass DJ, Brensinger CM, Lewis JD, Lichtenstein GR. The impact of increased body mass index on the clinical course of Crohn’s disease. Clin Gastroenterol Hepatol. 2006;4:482–8. 44. Muzumdar H, Rao M. Pulmonary dysfunction and sleep apnea in morbid obesity. Pediatr Endocrinol Rev. 2006;3(Suppl 4):579–83. 45. Byard RW. Marked obesity in infancy and relationship to sudden infant death (letter). J Paediatr Child Health. 2007;43:649–50. 46. McCallister JW, Adkins EJ, O’Brien JM. Obesity and acute lung injury. Clin Chest Med. 2009;30:495–508. 47. Rabec C, de Lucas Ramos P, Veale D. Respiratory complications of obesity. Arch Bronco. 2011;47:252–61. 48. Redd SC. Asthma in the United States; burden and current theories. Environ Health Perspect. 2002;110:557–60. 49. Grunstein R, Wilcox I, Yang TS, Gould Y, Hedner J. Snoring and sleep apnoea in men: association with central obesity and hypertension. Int J Obes Relat Metab Disord. 1993;9:533–40. 50. Young T, Palta M, Dempsey J, Skatrud J, Weber S, Badr S. The occurrence of sleep-disordered breathing among middle-aged adults. N Engl J Med. 1993;328:1230–5.
51. Kurukulasuriya LR, Stas S, Lastra G, Manrique C, Sowers JR. Hypertension in obesity. Med Clin North Am. 2011;95:903–17. 52. Grimm W, Becker HF. Obesity, sleep apnea syndrome, and rhythmogenic risk. Herz. 2006;31:213–8. 53. Chebbo A, Tfaili A, Jones SF. Hypoventilation syndromes. Med Clin North Am. 2011;95:1189–202. 54. Byard RW, Gilbert JD. Potentially lethal complications of tracheostomy—autopsy considerations. Am J Forensic Med Pathol. 2011;32:352–4. 55. Serrano PE, Khuder SA, Fath JJ. Obesity as a risk factor for nosocomial infections in trauma patients. J Am Coll Surg. 2010;211:61–7. 56. Fezeu L, Julia C, Henegar A, Bitu J, Hu FB, Grobbee DE, Kenge A-P, Hercberg S, Czernichow S. Obesity is associated with higher risk of intensive care unit admission and death in influenza A (H1N1) patients: a systematic review and meta-analysis. Obes Rev. 2011;12:653–9. 57. Falagas ME, Kompoti M. Obesity and infection. Lancet Infect Dis. 2006;6:438–46. 58. Wolin KY, Carson K, Colditz GA. Obesity and cancer. Oncologist. 2010;15:556–65. 59. Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of US adults. N Engl J Med. 2003;348:1625–38. 60. Bergstro¨m A, Pisani P, Tenet V, Wolk A, Adami H-O. Overweight as an avoidable cause of cancer in Europe. Int J Cancer. 2001;91:421–30. 61. Hemminki K, Li X, Sundquist J, Sundquist K. Obesity and familial obesity and risk of cancer. Eur J Cancer Prev. 2011; 20:438–43. 62. Lagergren J, Bergstro¨m R, Nyre´n O. Association between body mass and adenocarcinoma of the esophagus and gastric cardia. Ann Int Med. 1999;130:883–90. 63. Crew KD, Neugut AI. Epidemiology of gastric cancer. World J Gastroenterol. 2006;12:354–62. 64. Buschemeyer WC III, Freedland SJ. Obesity and prostate cancer: epidemiology and clinical implications. Eur J Urol. 2007;52: 331–43. 65. Kristal AR, Gong Z. Obesity and prostate cancer mortality. Fut Oncol. 2007;3:557–67. 66. Moghaddam AA, Woodward M, Huxley R. Obesity and risk of colorectal cancer: a meta-analysis of 31 studies with 70,000 events. Cancer Epidemiol Biomarkers Prev. 2007;16:2533–47. 67. Hill HA, Austin H. Nutrition and endometrial cancer. Cancer Caus Cont. 1996;7:19–32. 68. Bergstro¨m A, Hsieh C–C, Lindblad P, Lu C-M, Cook NR, Wolk A. Obesity and renal cell cancer—a quantitative review. Brit J Cancer. 2001;85:984–90. 69. Petrilli JM, Calle EE, Rodriguez C, Thun MJ. Body mass index, height, and postmenopausal breast cancer mortality in a prospective cohort of US women. Cancer Caus Cont. 2002;13: 325–32. 70. Sirimi N, Goulis DG. Obesity in pregnancy. Hormones. 2010;9: 299–306. 71. Soens MA, Birnbach DJ, Ranasinghe JS, van Zundert A. Obstetric anaesthesia for the obese and morbidly obese patient: an ounce of prevention is worth more than a pound of treatment. Acta Anaesthesiol Scand. 2008;52:6–19. 72. Saravanakumar K, Rao SG, Cooper GM. Obesity and obstetric anaesthesia. Anaesthesia. 2006;61:36–48. 73. Tanner BD, Allen JW. Complications of bariatric surgery: implications for the covering physician. Am Surg. 2009;75: 103–12. 74. Tseuda K, Debrand M, Bivins BA, Wright BD, Griffen WO. Pulmonary complications in the morbidly obese following
123
Forensic Sci Med Pathol
75.
76.
77.
78.
79.
80.
81. 82. 83. 84.
jejunoileal bypass surgery under narcotic anesthesia. Int Surg. 1980;65:123–9. Podnos YD, Jimenez JC, Wilson SE, Stevens CM, Ngyen NT. Complications after laparoscopic gastric bypass. Arch Surg. 2003;138:957–61. Gagner M, Milone L, Yung E, Broseus A, Gumbs AA. Causes of early mortality after laparoscopic adjustable gastric banding. J Am Coll Surg. 2008;206:664–9. Gagner M, Milone L, Trelles N. Mortality after laparoscopic adjustable gastric banding: results from an anonymous questionnaire to ASBS members. Obes Surg. 2009;19:1657–63. Lehnhardt M, Homann HH, Daigeler A, Hauser J, Palka P, Steinau HU. Major and lethal complications of liposuction: a review of 72 cases in Germany between 1990 and 2002. Plast Reconstr Surg. 2008;121:396e–403e. Barillo DJ, Cancio LC, Seung HK, Shirani KZ, Goodwin CW. Fatal and near-fatal complications of liposuction. South Med J. 1998;91:487–92. Wang H-D, Zheng J-H, Deng C-L, Liu Q-Y, Yang S-L. Fat embolism syndromes following liposuction. Aesth Plast Surg. 2008;32:731–6. Abell TL, Minocha A. Gastrointestinal complications of bariatric surgery: diagnosis and therapy. Am J Med Sci. 2006;331:214–8. Zizza C, Herring AH, Stevens J, Popkin BM. Length of hospital stays among obese patients. Am J Public Health. 2004;94:1587–91. Byard RW. The potential forensic significance of traditional herbal medicines. J Forensic Sci. 2010;55:89–92. Mock CN, Grossman DC, Kaufman RP, Mack CD, Rivara FP. The relationship between body weight and risk of death and
123
85.
86.
87. 88.
89. 90. 91.
92.
93.
serious injury in motor vehicle crashes. Accid Anal Prev. 2002; 34:221–8. Boulanger BR, Milzman D, Mitchell K, Rodriguez A. Body habitus as a predictor of injury pattern after blunt trauma. J Trauma. 1992;33:228–32. Zhu S, Layde PM, Guse CE, Laud PW, Pintar F, Nirula R, Hargarten S. Obesity and risk for death due to motor vehicle crashes. Am J Public Health. 2006;96:734–9. Byard RW, Langlois NEI. Increasing body weight of motorcycle riders (letter). J Forensic Sci. 2011;56:1661. Spaine LA, Bollen SR. ‘‘The bigger they come…’’: the relationship between body mass index and severity of ankle fractures. Injury. 1996;27:687–9. Mann JN, Thakore JH. Melancholic depression and abdominal fat distribution: a mini-review. Stress. 1999;3:1–15. Atlantis E, Baker M. Obesity effects on depression: systemic review of epidemiological studies. In J Obes. 2008;32:881–91. Juvin P, Lavaut E, Dupont H, Lefevre P, Demetriou M, Dumoulin J-L, Desmonts J-M. Difficult tracheal intubation is more common in obese than in lean patients. Anesth Analg. 2003;97:595–600. Abbott KC, Oliver DK, Hurst FP, Das NP, Gao SW, Perkins RM. Body mass index and peritoneal dialysis: ‘‘exceptions to the exception’’ in reverse epidemiology? Semin Dialy. 2007;20:561–5. Hunsaker DM, Hunsaker JC III. Obesity epidemic in the United States: a cause of morbidity and premature death. In: Tsokos M, editor. Forensic pathology reviews, vol 2. Totowa, NJ: Humana Press; 2004. p. 59–98.