Showing posts with label Radiation Oncology. Show all posts
Showing posts with label Radiation Oncology. Show all posts

Sunday, January 25, 2009

Positron emission tomography (PET)














Positron emission tomography (PET) is a nuclear medicine medical imaging technique which produces a three-dimensional image or map of functional processes in the body. The system detects pairs of gamma rays emitted indirectly by a positron-emitting radioisotope, which is introduced into the body on a metabolically active molecule. Images of metabolic activity in space are then reconstructed by computer analysis, often in modern scanners aided by results from a CT X-ray scan performed on the patient at the same time, in the same machine.

Description
Schematic view of a detector block and ring of a PET scanner (here: Siemens ECAT Exact HR+)
Operation
To conduct the scan, a short-lived radioactive tracer isotope, which decays by emitting a positron, which also has been chemically incorporated into a metabolically active molecule, is injected into the living subject (usually into blood circulation). There is a waiting period while the metabolically active molecule becomes concentrated in tissues of interest; then the research subject or patient is placed in the imaging scanner. The molecule most commonly used for this purpose is fluorodeoxyglucose (FDG), a sugar, for which the waiting period is typically an hour.

Schema of a PET acquisition process
As the radioisotope undergoes positron emission decay (also known as positive beta decay), it emits a positron, the antimatter counterpart of an electron. After travelling up to a few millimeters the positron encounters and annihilates with an electron, producing a pair of annihilation (gamma) photons moving in opposite directions. These are detected when they reach a scintillator material in the scanning device, creating a burst of light which is detected by photomultiplier tubes or silicon avalanche photodiodes (Si APD). The technique depends on simultaneous or coincident detection of the pair of photons; photons which do not arrive in pairs (i.e., within a few nanoseconds) are ignored.
The most significant fraction of electron-positron decays result in two 511 keV gamma photons being emitted at almost 180 degrees to each other; hence it is possible to localize their source along a straight line of coincidence (also called formally the "line of response" or LOR). In practice the LOR has a finite width as the emitted photons are not exactly 180 degrees apart. If the recovery time of detectors is in the picosecond range rather than the 10's of nanosecond range, it is possible to calculate the single point on the LOR at which an annihilation event originated, by measuring the "time of flight" of the two photons. This technology is not yet common, but it is available on some new systems. More commonly, a technique much like the reconstruction of computed tomography (CT) and single photon emission computed tomography (SPECT) data is used, although the data set collected in PET is much poorer than CT, so reconstruction techniques are more difficult (see section below on image reconstruction of PET). Using statistics collected from tens-of-thousands of coincidence events, a set of simultaneous equations for the total activity of each parcel of tissue along many LORs can be solved by a number of techniques, and thus a map of radioactivities as a function of location for parcels or bits of tissue ("voxels"), may be constructed and plotted. The resulting map shows the tissues in which the molecular probe has become concentrated, and can be interpreted by a nuclear medicine physician or radiologist in the context of the patient's diagnosis and treatment plan.
PET scans are increasingly read alongside CT or magnetic resonance imaging (MRI) scans, the combination ("co-registration") giving both anatomic and metabolic information (i.e., what the structure is, and what it is doing biochemically). Because PET imaging is most useful in combination with anatomical imaging, such as CT, modern PET scanners are now available with integrated high-end multi-detector-row CT scanners. Because the two scans can be performed in immediate sequence during the same session, with the patient not changing position between the two types of scans, the two sets of images are more-precisely registered, so that areas of abnormality on the PET imaging can be more perfectly correlated with anatomy on the CT images. This is very useful in showing detailed views of moving organs or structures with higher amounts of anatomical variation, such as are more likely to occur outside the brain.
Radioisotopes
Radionuclides used in PET scanning are typically isotopes with short half lives such as carbon-11 (~20 min), nitrogen-13 (~10 min), oxygen-15 (~2 min), and Fluorine-18 (~110 min). Due to their short half lives, the radionuclides must be produced in a cyclotron which is not too far away in delivery-time to the PET scanner. These radionuclides are incorporated into compounds normally used by the body such as glucose, water or ammonia and then injected into the body to trace where they become distributed. Such labelled compounds are known as radiotracers.
Limitations
PET as a technique for scientific investigation in humans is limited by the need for clearance by ethics committees to inject radioactive material into participants. The minimization of radiation dose to the subject is an attractive feature of the use of short-lived radionuclides. Besides its established role as a diagnostic technique, PET has an expanding role as a method to assess the response to therapy, in particular, cancer therapy (e.g. Young et al. 1999), where the risk to the patient from lack of knowledge about disease progress is much greater than the risk from the test radiation.
Limitations to the widespread use of PET arise from the high costs of cyclotrons needed to produce the short-lived radionuclides for PET scanning and the need for specially adapted on-site chemical synthesis apparatus to produce the radiopharmaceuticals. Few hospitals and universities are capable of maintaining such systems, and most clinical PET is supported by third-party suppliers of radiotracers which can supply many sites simultaneously. This limitation restricts clinical PET primarily to the use of tracers labelled with F-18, which has a half life of 110 minutes and can be transported a reasonable distance before use, or to rubidium-82, which can be created in a portable generator and is used for myocardial perfusion studies. Nevertheless, in recent years a few on-site cyclotrons with integrated shielding and hot labs have begun to accompany PET units to remote hospitals. The presence of the small on-site cyclotron promises to expand in the future as the cyclotrons shrink in response to the high cost of isotope transportation to remote PET machines. Because the half-life of F-18 is about two hours, the prepared dose of a radiopharmaceutical bearing this radionuclide will undergo multiple half-lives of decay during the working day. This necessitates frequent recalibration of the remaining dose (determination of activity per unit volume) and careful planning with respect to patient scheduling.
Image reconstruction
The raw data collected by a PET scanner are a list of 'coincidence events' representing near-simultaneous detection of annihilation photons by a pair of detectors. Each coincidence event represents a line in space connecting the two detectors along which the positron emission occurred.
Coincidence events can be grouped into projections images, called sinograms. The sinograms are sorted by the angle of each view and tilt, the latter in 3D case images. The sinogram images are analogous to the projections captured by computed tomography (CT) scanners, and can be reconstructed in a similar way. However, the statistics of the data is much worse than those obtained through transmission tomography. A normal PET data set has millions of counts for the whole acquisition, while the CT can reach a few billion counts. As such, PET data suffer from scatter and random events much more dramatically than CT data does.
In practice, considerable pre-processing of the data is required - correction for random coincidences, estimation and subtraction of scattered photons, detector dead-time correction (after the detection of a photon, the detector must "cool down" again) and detector-sensitivity correction (for both inherent detector sensitivity and changes in sensitivity due to angle of incidence).
Filtered back projection (FBP) has been frequently used to reconstruct images from the projections. This algorithm has the advantage of being simple while having a low requirement for computing resources. However, shot noise in the raw data is prominent in the reconstructed images and areas of high tracer uptake tend to form streaks across the image.
Iterative expectation-maximization algorithms are now the preferred method of reconstruction. The advantage is a better noise profile and resistance to the streak artifacts common with FBP, but the disadvantage is higher computer resource requirements.
Attenuation correction: As different LORs must traverse different thicknesses of tissue, the photons are attenuated differentially. The result is that structures deep in the body are reconstructed as having falsely low tracer uptake. Contemporary scanners can estimate attenuation using integrated x-ray CT equipment, however earlier equipment offered a crude form of CT using a gamma ray (positron emitting) source and the PET detectors.
While attenuation corrected images are generally more faithful representations, the correction process is itself susceptible to significant artifacts. As a result, both corrected and uncorrected images are always reconstructed and read together.
2D/3D reconstruction: Early PET scanners had only a single ring of detectors, hence the acquisition of data and subsequent reconstruction was restricted to a single transverse plane. More modern scanners now include multiple rings, essentially forming a cylinder of detectors.
There are two approaches to reconstructing data from such a scanner: 1) treat each ring as a separate entity, so that only coincidences within a ring are detected, the image from each ring can then be reconstructed individually (2D reconstruction), or 2) allow coincidences to be detected between rings as well as within rings, then reconstruct the entire volume together (3D).
3D techniques have better sensitivity (because more coincidences are detected and used) and therefore less noise, but are more sensitive to the effects of scatter and random coincidences, as well as requiring correspondingly greater computer resources.
History
The concept of emission and transmission tomography was introduced by David Kuhl and Roy Edwards in the late 1950's. Their work later led to the design and construction of several tomographic instruments at the University of Pennsylvania. Tomographic imaging techniques were further developed by Michel (Michael) Ter-Pogossian, Michael E. Phelps and others at the Washington University School of Medicine.
In the 1970s, Tatsuo Ido at the Brookhaven National Laboratory was the first to describe the synthesis of 18F-FDG, the most commonly used PET scanning isotope carrier. The compound was first administered to two normal human volunteers by Abass Alavi in August 1976 at the University of Pennsylvania. Brain images obtained with an ordinary (non-PET) nuclear scanner demonstrated the concentration of FDG in that organ. Later, the substance was used in dedicated positron tomographic scanners, to yeild the modern procedure.
Applications
Maximum intensity projection (MIP) of a typical F-18 FDG wholebody PET acquisition
PET is both a medical and research tool. It is used heavily in clinical oncology (medical imaging of tumors and the search for metastases), and for clinical diagnosis of certain diffuse brain diseases such as those causing various types of dementias. PET is also an important research tool to map normal human brain and heart function.
PET is also used in pre-clinical studies using animals, where it allows repeated investigations into the same subjects. This is particularly valuable in cancer research, as it results in an increase in the statistical quality of the data (subjects can act as their own control) and substantially reduces the numbers of animals required for a given study.
Alternative methods of scanning include x-ray computed tomography (CT), magnetic resonance imaging (MRI) and functional magnetic resonance imaging (fMRI), ultrasound and single photon emission computed tomography (SPECT).
While some imaging scans such as CT and MRI isolate organic anatomic changes in the body, PET scanners, like SPECT are capable of detecting areas of molecular biology detail (even prior to anatomic change). The PET scanner does this via the use of radiolabelled molecular probes that have different rates of uptake, depending on the type and function of tissue involved. The changing of regional blood flow in various anatomic structures (as a measure of the injected positron emitter) can be visualized and relatively quantified with a PET scan.
PET imaging is best performed using a dedicated PET scanner. However, it is possible to acquire PET images using a conventional dual-head gamma camera fitted with a coincidence detector. The quality of gamma-camera PET is considerably lower, and acquisition is slower. However, for institutions with low demand for PET, this may allow on-site imaging, instead of referring patients to another center, or relying on a visit by a mobile scanner.
PET is a valuable technique for some diseases and disorders, because it is possible to target the radio-chemicals used for particular bodily functions.

Oncology
PET scanning with the tracer fluorine-18 (F-18) fluorodeoxyglucose (FDG), called FDG-PET, is widely used in clinical oncology. This tracer is a glucose analog that is taken up by glucose-using cells and phosphorylated by hexokinase (whose mitochondrial form is greatly elevated in rapidly-growing malignant tumours). A typical dose of FDG used in an oncological scan is 200-400 MBq for an adult human. Because the oxygen atom which is replaced by F-18 to generate FDG is required for the next step in glucose metabolism in all cells, no further reactions occur in FDG. Furthermore, most tissues (with the notable exception of liver and kidneys) cannot remove the phosphate added by hexokinase. This means that FDG is trapped in any cell which takes it up, until it decays, since phosphorylated sugars, due to their ionic charge, cannot exit from the cell. This results in intense radiolabeling of tissues with high glucose uptake, such as the brain, the liver, and most cancers. As a result, FDG-PET can be used for diagnosis, staging, and monitoring treatment of cancers, particularly in Hodgkin's disease, non Hodgkin's lymphoma, and lung cancer. Many other types of solid tumors will be found to be very highly labeled on a case-by-case basis-- a fact which becomes especially useful in searching for tumor metastasis, or for recurrence after a known highly-active primary tumor is removed. Because individual PET scans are more expensive than "conventional" imaging with computed tomography (CT) and magnetic resonance imaging (MRI), expansion of FDG-PET in cost-constrained health services will depend on proper health technology assessment; this problem is a difficult one because structural and functional imaging often cannot be directly compared, as they provide different information. Oncology scans using FDG make up over 90% of all PET scans in current practice.

PET scan of the human brain
Neurology: PET neuroimaging is based on an assumption that areas of high radioactivity are associated with brain activity. What is actually measured indirectly is the flow of blood to different parts of the brain, which is generally believed to be correlated, and has been measured using the tracer oxygen-15. However, because of its 2-minute half-life O-15 must be piped directly from a medical cyclotron for such uses, and this is difficult. In practice, since the brain is normally a rapid user of glucose, and since brain pathologies such as Alzheimer's disease greatly decrease brain metabolism of both glucose and oxygen in tandem, standard FDG-PET of the brain, which measures regional glucose use, may also be successfully used to differentiate Alzheimer's disease from other dementing processes, and also to make early diagnosis of Alzheimer's disease. The advantage of FDG-PET for these uses is its much wider availability.
PET imaging with FDG can also be used for localization of seizure focus: A seizure focus will appear as hypometabolic during an interictal scan.
Several radiotracers (i.e. radioligands) have been developed for PET that are ligands for specific neuroreceptor subtypes (e.g. dopamine D2, serotonin 5-HT1A, etc.), transporters (such as [(11)C]McN5652, [(11)C]DASB or other novel tracer ligands for serotonin in this case), or enzyme substrates (e.g. 6-FDOPA for the AADC enzyme). These agents permit the visualization of neuroreceptor pools in the context of a plurality of neuropsychiatric and neurologic illnesses. A novel probe developed at the University of Pittsburgh termed PIB (Pittsburgh Compound-B) permits the visualization of amyloid plaques in the brains of Alzheimer's patients. This technology could assist clinicians in making a positive clinical diagnosis of AD pre-mortem and aid in the development of novel anti-amyloid therapies.
Cardiology, atherosclerosis and vascular disease study: In clinical cardiology, FDG-PET can identify so-called "hibernating myocardium", but its cost-effectiveness in this role versus SPECT is unclear. Recently, a role has been suggested for FDG-PET imaging of atherosclerosis to detect patients at risk of stroke .
Neuropsychology / Cognitive neuroscience: To examine links between specific psychological processes or disorders and brain activity.
Psychiatry: Numerous compounds that bind selectively to neuroreceptors of interest in biological psychiatry have been radiolabeled with C-11 or F-18. Radioligands that bind to dopamine receptors (D1,D2, reuptake transporter), serotonin receptors (5HT1A, 5HT2A, reuptake transporter) opioid receptors (mu) and other sites have been used successfully in studies with human subjects. Studies have been performed examining the state of these receptors in patients compared to healthy controls in schizophrenia, substance abuse, mood disorders and other psychiatric conditions.
Pharmacology: In pre-clinical trials, it is possible to radiolabel a new drug and inject it into animals. The uptake of the drug, the tissues in which it concentrates, and its eventual elimination, can be monitored far more quickly and cost effectively than the older technique of killing and dissecting the animals to discover the same information. PET scanners for rats and apes are marketed for this purpose. The technique is still generally too expensive for the veterinary medicine market, however, so very few pet PET scans are done. Drug occupancy at the purported site of action can also be inferred indirectly by competition studies between unlabeled drug and radiolabeled compounds known apriori to bind with specificity to the site.
Safety
PET scanning is non-invasive, but it does involve exposure to ionizing radiation. The total dose of radiation is small, however, usually around 7 mSv. This can be compared to 2.2 mSv average annual background radiation in the UK, 0.02 mSv for a chest x-ray, up to 8 mSv for a CT scan of the chest, 2-6 mSv per annum for aircrew (data from UK National Radiological Protection Board).

With thanks from Wikipedia
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Monday, March 24, 2008

Weight Control, Diet & Cancer

Stable weight depends on an even balance between energy intake from food and energy expenditure. Energy expenditure occurs during the day in three ways:
· As energy expended during rest (basal metabolism)
· As energy used to metabolize food (thermogenesis)
· As energy expended during physical activity
Basal metabolism accounts for about two-thirds of expended energy, which is generally used to maintain body temperature and muscle contractions in the heart and intestine.
Thermogenesis accounts for about 10% of expended energy.
When a person's consumes more calories than energy that is used, the body stores the extra calories in fat cells. Fat cells function as energy reservoirs. They enlarge or contract depending on how people use energy. If people do not balance energy input and output by eating right and exercising, fat can builds up. This can lead to weight gain.

When energy input is equal to energy output, there is no expansion of fat cells (lipocytes) to accommodate excess. It is only when more calories are taken in than used that the extra fat is stored in the lipocytes and the person begins to accumulate fat.

What is Obesity?
People who are obese have an abnormally high and unhealthy proportion of body fat. To measure obesity, researchers commonly use a formula based on weight and height known as the body mass index (BMI). BMI is the ratio of weight (in kilograms) to height (in meters) squared. BMI provides a more accurate measure of obesity or being overweight than does weight alone.
Measurement of Obesity
Obesity is determined by measuring body fat, not just body weight. People might be over the weight limit for normal standards, but if they are very muscular with low body fat, they are not obese. Others might be normal or underweight, but still have excessive body fat. The following measurements and factors are used to determine whether or not a person is overweight to a degree that threatens their health:
· Body mass index (BMI) (a measure of body fat)
· Waist circumference
· Waist-hip ratio
· Anthropometry (skin fold measurement)
· The presence or absence of other disease risk factors (e.g., smoking, high blood pressure, unhealthy cholesterol levels, diabetes, relatives with heart disease)
A person's disease risk factors plus BMI may be the most important components in determining health risks with weight.

Body-Mass Index/ BMI
The body-mass index, a measure of adiposity, has been categorized as follows: 18.5 to 24.9, 25.0 to 29.9, 30.0 to 34.9, 35.0 to 39.9, and 40.0 or more. These categories correspond to those proposed by the World Health Organization6 for “normal range,” “grade 1 overweight,” (25.0 to 29.9) “grade 2 overweight” (30.0 to 39.9), and “grade 3 overweight,” (40.0 or more). For many analyses, especially for cancers in specific sites and among participants who had never smoked, the upper categories of body-mass index were combined, because of the small numbers. In oncology, for analyses and discussion, it is customary to we refer to the range of 25.0 to 29.9 as corresponding to “overweight” and to values of 30.0 or more as corresponding to “obesity.”
Waist Circumference and Waist-Hip Ratio
The extent of abdominal fat can also be used in assessing risk of disease. Some studies suggest that:
· Women whose waistlines are over 31.5 inches and men whose waists measure over 37 inches should watch their weight.
· A waist size greater than 35 inches in women and 40 inches in men is associated with a higher risk for heart disease, diabetes, and impaired functioning.
Evidence strongly suggests that more body fat around the abdomen and hips (the apple-shape) is a more consistent predictor of heart problems and health risks than BMI.
The distribution of fat can be evaluated by dividing waist size by hip size. For example, a woman with a 30-inch waist and 40-inch hip circumference would have a ratio of 0.75; one with a 41-inch waist and 39-inch hips would have a ratio of 1.05. The lower the ratio the better. The risk of heart disease rises sharply for women with ratios above 0.8 and for men with ratios above 1.0.

Anthropometry
Anthropometry is the measurement of skin fold thickness in different areas, particularly around the triceps, shoulder blades, and hips. This measurement is useful in determining how much weight is due to muscle or fat.

Obesity and Cancer
Link between cancer and obesity appears paradoxical as cancer is classically seen as illness producing anorexia and massive weight loss. To measure obesity, researchers commonly use a formula based on weight and height known as the body mass index (BMI). According to WHO approximately 1.6 billion of the world’s adult are overweight and over 400 million are obese. Cancers of the endometrium, kidney, gallbladder, breast, colon and adenocarcinoma of the esophagus have been linked to obesity. Obesity and physical inactivity may account for 25 to 30 percent of several major cancers. Those with a body-mass index of at least 40 had death rates from all cancers combined that were 52 percent higher (for men) and 62 percent higher (for women) than the rates in men and women of normal weight. On the basis of associations observed in some studies, it has been estimated that current patterns of overweight and obesity could account for 14 percent of all deaths from cancer in men and 20 percent of those in women. Women with large abdominal fat (apple shaped) have high risk of breast cancer than those having ‘pear’ shaped distribution. Data on link between obesity & cancers of the pancreas, prostate, liver, cervix, ovary and on hematopoietic cancers are scarce or inconsistent. Obesity and physical inactivity may account from 25-30% of several major cancers. For grade-III obesity, relative risk for dying by cancer is 1.70 for breast cancer, 1.63 for esophageal cancer, 1.94 for gastric cancer, 1.84 for colon cancer, 1.70 for renal cancer, 4.52 for liver cancer, 1.76 for gall bladder cancer, 1.49 for pancreatic cancer and 1.34 for prostate cancer.

Introduction

According to WHO 1.6 billion of the world’s adult were overweight in 2005 and over 400 million were obese. By 2015 the numbers are expected to nearly double.1,2 A recent study from United States reports 14% of deaths from cancer in men and 20% deaths in women were due to overweight and obesity.1 Obesity is not just a problem of west but it is a global phenomenon. According to WHO, figures for obesity in America are 35% for women and 20% for men, in China it is over 20% for both men and women. Even desperately poor countries like Nigeria and Uganda are struggling with the problem of obesity. There is substantial evidence that adipose tissue particularly visceral adipose tissue is a metabolically active endocrine organ. This leads to the release of insulin – like growth factors that are linked to increased cancer risk.3 The mechanism of this link may not be clear at present but there is enough evidence to say that link exists. As the prevalence of obesity is increasing worldwide, we can expect proportional increase in cancer cases. This will not only add to the high cost of cancer treatment but also add to human suffering as well.
Although we have known for some time that excess weight is also an important factor in death from cancer,4 our knowledge of the magnitude of the relation, both for all cancers and for cancers at individual sites, and the public health effect of excess weight in terms of total mortality from cancer is limited. The biological mechanism that explains how obesity worsens risk of cancer may be different for different cancers. The exact mechanisms by which obesity induces or promotes tumor genesis vary by cancer site. However, possible mechanisms include alterations in sex hormones and insulin. Insulin resistance is been associated with cancers of colon and rectum, breast and pancreas. Whatever may be the causes, the obesity still is seen as life style disease and by that definition it is largely preventable. It may be an oversimplified view as many people believe that obesity is genetic (there is evidence for that). It is right time to educate people and emphasize the need for life style changes to keep the weight in check.5 Life style choices that can check weight will not only help in preventing cancer but also help in preventing other diseases such as heart diseases, diabetes and many nervous and mental disorders.
Relationship between Obesity and Cancer?
In 2001, it was concluded that cancers of the colon, breast (postmenopausal), endometrium (the lining of the uterus), kidney, and esophagus are associated with obesity. Some studies have also reported links between obesity and cancers of the gallbladder, ovaries, and pancreas.7 Obesity and physical inactivity may account for 25 to 30 percent of several major cancers—colon, breast (postmenopausal), endometrial, renal and cancer of the esophagus.7
In 2002, about 41,000 new cases of cancer in the United States were estimated to be due to obesity. This means that about 3.2 percent of all new cancers are linked to obesity.1,8,9 The contribution of excess body weight to the total burden of mortality from cancer depends on two factors: the relative risk of death due to cancer among overweight or obese persons as compared with persons of normal weight and the prevalence of overweight and obesity in a given population. The very high prevalence of obesity in the United States explains why small elevations in mortality due to cancer translate into substantial fractions of mortality due to cancer that are related to overweight or obesity. Calle et al. point out how much cancer-related mortality could be reduced among nonsmokers if body weight were adequately controlled. It is intriguing that the positive association between excess body weight and mortality due to cancer is not limited to a few forms of cancer indeed, positive associations represent the rule rather than the exception. The biologic mechanisms that are regularly invoked to explain the association between overweight or obesity and cancer concern steroid hormones, insulin, the insulin-like growth factor system, and mechanical processes such as the contribution of abdominal obesity to gastresophageal reflux and esophageal adenocarcinoma.1, 10
In both men and women, body-mass index was also significantly associated with higher rates of death due to cancer of the esophagus, colon and rectum, liver, gallbladder, pancreas, and kidney; the same was true for death due to non-Hodgkin’s lymphoma and multiple myeloma. Significant trends of increasing risk with higher body-mass-index values were observed for death from cancers of the stomach and prostate in men and for death from cancers of the breast, uterus, cervix, and ovary in women. Previous studies have consistently shown associations between adiposity and increased risk of cancers of the endometrium, kidney, gallbladder (in women), breast (in postmenopausal women), and colon (particularly in men).11-15 Adenocarcinoma of the esophagus has been linked to obesity. 14,16,17 Data on cancers of the pancreas, prostate, liver, cervix, ovary and on hematopoietic cancers are scarce or inconsistent.11-14, 18-21 The lack of consistency may be attributable to the limited number of studies, the limited range and variable categorization of overweight and obesity among studies, bias introduced by reverse causality with respect to smoking related cancers, and possibly real differences between the effects of overweight and obesity on the incidence of cancer and on the rates of death from some cancers.22,23 Experts have concluded that the chief causes of obesity are a sedentary lifestyle and overconsumption of high-calorie food.7,24, 25
In the last 50 years there are marked changes in dietary and work habits. People eat too much and do too little exercise. There is reduction in physical activity and more people have sedentary life styles. Since the beginning of the 20th century, obesity is being linked to diabetes, hypertension and myocardial infarction. In late 1940’s French researcher divided obesity into android type – predominant abdominal obesity particularly seen in males and described it is ‘apple’ shaped whereas gynoid type – with distribution of fat to the hips is characteristic of females and described as ‘pear’ shaped.5 But it took quite some time when in 1980’s abdominal fat was implicated as risk factor for IHD, diabetes and stroke. The distribution of fat is important risk determinant of breast cancer. Women with large abdominal fat (apple shaped) have high risk of breast cancer than those having ‘pear’ shaped distribution.24, 26, 27
Obesity has been studied extensively as risk factor for various cancers. According to American Institute of Cancer Research (AICR), obesity increases likelihood of developing breast, colon, endometrial, esophageal, renal and prostate cancers by 25-33%.
Abdominal fat has a sensitive system for releasing free fatty acids which are transported directly via the portal vein into the liver where it produces 3 important effects as insulin clearance, Glucogenesis and VLDL synthesis which leads to hyperinsulinaemia, hyperglycemia and hyperlipidaemia respectively. Free Fatty Acids (FFA) are synthesized in liver into VLDL predominantly triglycerides. Insulin resistance in liver cells increases glucose products to cause high blood glucose. Hyperinsulinaemia resultant from insulin resistance worsens as insulin level increase further as Liver’s ability to break the hormone decreases.

The current burst of articles on metabolic syndrome shows the relevance of obesity in the contemporary society. It is the gift of modern western life style with its negative features of physical inactivity, excessive intake of energy and stress.
The International Agency for Research on Cancer (IARC) has concluded that there is sufficient evidence of a cancer-preventive effect of avoidance of weight gain for cancers of the colon, breast (in post menopausal women), endometrium, kidney (renal cell carcinoma), and esophagus (adenocarcinoma).14 Potential biologic mechanisms include increased levels of endogenous hormones (sex steroids, insulin, and insulin-like growth factor I) associated with overweight and obesity and the contribution of abdominal obesity to gastresophageal reflux and esophageal adenocarcinoma.14 Moderate relative risks (less than 2.0) associated with overweight and obesity both for colon cancer and for breast cancer in postmenopausal women have been documented consistently.11 Much higher relative risks have been observed for uterine cancer (2 to 10) and kidney cancer (1.5 to 4), and the increased risk of kidney cancer associated with excess weight is higher in women than in men in majority studies.11, 28, 29 Increases by a factor of two to three in the risk of adenocarcinoma of the esophagus in association with high body-mass index have been reported16, 17, and the magnitude of this association has been found by other investigators to be greater in nonsmokers.16
Conclusion
International experts in the field of nutrition, cancer biology and public health are working on this link between life style and cancer and have come out with health recommendations for prevention of cancer. Their recommendations need to be incorporated in management plans and advising people how they can reduce their own cancer risk.91 It may take time to establish the exact link between obesity and cancer but the time has come to start talking to patients about the link between life style and cancer prevention through healthy weight, healthy eating habits and increasing physical activity.
An apple a day keeps the doctor away, but if you remain in a pear, you can avoid either of them.
References
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2. The Tribune, Thursday 4th October 2007.
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DISCLAIMER: This information is solely for informational purposes. IT IS NOT INTENDED TO PROVIDE MEDICAL ADVICE. Neither the Editors of Health Mirror, the author nor publisher take responsibility for any possible consequences from any treatment, procedure, exercise, dietary modification, action or application of medication which results from reading or following the information contained in this information. The publication of this information does not constitute the practice of medicine, and this information does not replace the advice of your physician or other health care provider. Before undertaking any course of treatment, the reader must seek the advice of their physician or other health care provider.

Authors: Dhull AK, Gupta R, Gupta A, Kaushal V

Thursday, February 14, 2008

Basics of Anaesthesia

INTRODUCTION
Many patients, and even some physicians, automatically assume that surgery requires general anaesthesia, and that the patient should be asleep during surgery. This is not true. Many procedures can be performed on awake patients, using local or regional anaesthesia. This not only avoids the risks and unpleasantness sometimes associated with general anaesthesia, but may also provide specific benefits such as reduced blood loss and better postoperative analgesia.
Patients are often concerned about having surgery under a local or regional anaesthetic. These concerns are not usually justified by the facts. The more patients understand the reasons for, and the benefits of, local or regional anaesthesia, the more likely they are to choose this type of anaesthetic. Unfortunately, in these days of cost-cutting and same day surgery, patients may never get the opportunity to discuss their anaesthetic options with an anaesthetist in detail prior to surgery. In the rush to get through a busy operating list the anaesthetist may, unfortunately, decide that it is quicker and simpler just to put the patient to sleep, rather than enter into the discussion and education necessary to allow the patient to make an informed choice about the most appropriate type of anaesthesia.
Patients are becoming more involved as consumers of health care. They are actively seeking out information about treatment choices, and some are turning to the Internet as a source of medical information. This site is dedicated to patients who want to learn more about local and regional anaesthesia. However, they must understand that this article provides background information only. The final decision about the best type of anaesthetic depends on the specific operation, patient, surgeon, and anaesthetist involved.
If you are faced with the possibility of needing surgery in the future, chances are you will need some type of anaesthesia to go along with it. There are many different types of anaesthesia. Which one you will need depends on a variety of factors such as the type of surgery you are having and your state of health. Some surgical procedures require only an injection of local anaesthesia into the incision area. Other procedures cannot be performed unless you are completely anesthetized -- unconscious and unaware of pain.

The Basics
Anaesthesia is divided into four basic categories:
· general anaesthesia
· regional anaesthesia
· local anaesthesia
· sedation
Each type of anaesthesia has an effect on a part of the nervous system, which results in a depression or numbing of nerve pathways. General anaesthesia affects the brain cells, which causes you to lose consciousness. Regional anaesthesia has an effect on a large bundle of nerves to a particular area of the body, which results in losing sensation to that area without affecting your level of consciousness. Local anaesthesia causes you to lose sensation in a very specific area.
Some of the drugs that produce general anaesthesia in large doses can be used to produce sedation, or "twilight sleep" in lower doses. Sedation can be given in many ways. A common example of an anesthetic gas that is used for sedation is nitrous oxide or laughing gas.
If you are scheduled to have surgery, you may be told not to eat anything for eight hours. It is very important that you follow whatever instructions you are given for not eating or drinking anything prior to surgery. Why? Because when you are given anaesthesia, you lose the ability to protect your lungs from inhaling something you're not supposed to inhale. When you are awake, you can usually swallow saliva and food without choking because part of the swallowing mechanism involves a reflex that results in covering the opening into the lungs. When you are anesthetized, you lose that reflex. So, if you have any solids or liquids in your stomach, they could come up into your mouth and be inhaled into your lungs. The result could be very serious lung damage.
Sleep is a state of reduced consciousness, depressed metabolism, and little activity of the skeletal muscles. Strong stimuli such as loud noise, bright light or shaking can arouse the sleeper. Consciousness is being clearly aware of yourself and your environment.
Unconsciousness is when you are completely or partially unaware of yourself and your environment, or you don't respond to sensory stimuli.
Conscious sedation is caused when an anesthesiologist administers depressant drugs and/or analgesics in addition to anaesthesia during surgery. Consciousness is depressed and you may fall asleep, but are not unconscious.

General Anaesthesia
General anesthetics produce an unconscious state. In this state a person is:
· unaware of what is happening
· pain-free
· immobile
· free from any memory of the period of time during which he or she is anesthetized
It is not completely clear exactly how general anesthetics work at a cellular level, but it is speculated that general anesthetics affect the spinal cord (resulting in immobility), the brain-stem reticular activating system (resulting in unconsciousness) and the cerebral cortex (seen as changes in electrical activity on an electroencephalogram).


General anaesthesia can be administered as an inhaled gas or as an injected liquid. There are several drugs and gases that can be combined or used alone to produce general anaesthesia. The potency of a given anesthetic is measured as minimum alveolar concentration (MAC). This term describes the potency of anesthetic gases. (Aveolar is the area in the lung where gases enter and exit the bloodstream via the capillary system). Technically, MAC is the alveolar partial pressure of a gas at which 50 percent of humans will not move to a painful stimulus (e.g. skin incision). Injected liquid anesthetics have a "MAC equivalent" which is the blood concentration of the liquid anesthetic that provides the same effect. Using MAC as a guideline, the amount of anesthetic given to a patient depends on that particular patient's needs.
When anesthetics reach the bloodstream, the drugs that affect the brain pass through other blood vessels and organs so they are often affected too. Therefore, patients must be carefully monitored. The anesthesiologist continuously monitors the patient's heart rate, heart rhythm, blood pressure, respiratory rate, and oxygen saturation. Some patients may have even more extensive monitoring depending on their health and which type of procedure or surgery they are having.


Most adults are first anesthetized with liquid intravenous anesthetics followed by anesthetic gases after they are asleep. Children, however, may not like having an injection or intravenous catheter placed in them while they are awake. Therefore, they often breathe themselves to sleep with anesthetic gases given through a mask.
What is local or regional anaesthesia?
Anaesthesia means the absence of sensation. Regional anaesthesia means blocking the nerve supply to part of the body, such as an arm, so the patient cannot feel pain in that area. Local anaesthesia, strictly speaking, means putting local anaesthetic ("freezing") around the affected area to make it pain free. However, many people use the phrase loosely to include regional anaesthesia.
Local Anaesthesia
Local anaesthesia involves numbing a small area by injecting a local anesthetic under the skin just where an incision is to be made. When used alone, this type of anaesthesia has the least number of risks. Local anesthetics are thought to block nerve impulses by decreasing the permeability of nerve membranes to sodium ions. There are many different local anesthetics that differ in absorption, toxicity, and duration of action.
One of the most commonly used local anesthetics is lidocaine (Xylocaine). Lidocaine can be administered as an injection or placed topically on mucous membranes. Another topical anesthetic is cocaine. Cocaine is primarily used to anesthetize the nasal passages for surgical procedures. A topical anesthetic that is gaining popularity for anesthetizing the skin prior to painful procedures, such as injections, is known as eutectic mixture of local anesthetics (EMLA) cream which contains lidocaine and prilocaine. This white cream is placed on the skin and then covered with an occlusive dressing for approximately one hour to obtain a good numbing effect. In addition, EMLA can be used to numb the skin prior to giving injections or pulling superficial splinters.

Regional Anaesthesia
Regional anaesthesia is so named because a "region" of the body is anesthetized without making the person unconscious. One example of this is spinal anaesthesia, which is often used on women during childbirth. A local anesthetic is injected into the spinal fluid and causes a loss of sensation of the lower body. Spinal anaesthesia can be used for surgery on the legs or lower abdomen (below the bellybutton).
Epidural anaesthesia is similar to spinal anaesthesia in that a patient loses sensation in the legs and lower abdomen, but instead of injecting the local anesthetic into the spinal fluid, the anesthetic is injected into a space outside the spinal canal called the epidural space. A small tube or catheter can be placed into this space and a local anesthetic can be infused (fed) through the tube for hours, days, or even weeks. This type of anaesthesia can be used for surgery with larger doses of anesthetic, or for chronic pain relief with lower doses of anesthetic. Regional anaesthesia techniques can be used to block very specific areas such as one foot, one leg, one arm, or one side of the neck. In these cases, a smaller group of nerves is blocked by injection of the local anesthetic into a specific area. For spinals and epidurals, narcotic painkillers such as morphine and fentanyl can be used in addition to a local anesthetic.

Sedation
Some of the drugs that produce general anaesthesia in large doses can be used to produce sedation or "twilight sleep" in lower doses. Sedation can be given in many ways. A common example of an anesthetic gas that is used for sedation is nitrous oxide or laughing gas. Liquid sedating drugs are usually given by injection but some can also be given by mouth. Ketamine and Versed are examples of sedating drugs that can be given by injection or by mouth. The oral route is particularly useful for sedating children who do not like injections.
Children who refuse to drink medications may also receive sedation through the rectum via a small, lubricated tube or via the nasal route by spraying it into the nose. Regional and local anaesthesia can be combined with sedation to make patients more comfortable during a procedure in which general anaesthesia is not necessary, or when general anaesthesia may be too large a risk for the patient.

How is it used?
Local or regional anaesthesia can often be used to prevent pain during surgery. Sometimes it is used by itself, with no other medications, so that the patient remains wide awake during surgery. It can also be combined with sedative drugs to make the patient relaxed or sleepy during surgery.
Sometimes local or regional anaesthesia is used in addition to a general anaesthetic (i.e., in patients who are asleep during surgery). This is done to reduce the stress associated with surgery, to allow a lighter level of anaesthetic during surgery, and to provide pain relief after surgery.
Inhaled Anesthetics
Many adults may remember having ether for their anesthetic when they were young. Ether is an inflammable anesthetic that is no longer used in the United States. Today, the commonly used inhaled anesthetics are nitrous oxide (also known as laughing gas), sevoflurane, desflurane, isoflurane and halothane.
Why do we have so many different kinds of gases? Because each gas has its own special properties. For example, sevoflurane and halothane are easy to inhale while desflurane is very irritating to inhale and has a shorter duration of action. If you need to breathe yourself to sleep, halothane or sevoflurane would be easiest to inhale. If a very short-acting anesthetic is needed, the anesthesiologist can switch to desflurane after you fall asleep. Nitrous oxide is easy to inhale, but when used alone is not potent enough to be a complete general anesthetic. However, it can be used alone for sedation, or combined with one of the other inhaled anesthetics or injected liquid anesthetics for general anaesthesia.
These gases have different effects on other organs as well. For example, halothane may cause the heart rate to slow down and the blood pressure to decrease while desflurane may cause the heart rate to speed up and the blood pressure to increase. How do these inhaled anesthetics reach the brain? When an anesthetic gas is inhaled into the lungs, the blood that travels through the lungs carries the anesthetic gas to central nervous system cells. The rate at which the bloodstream takes up the anesthetic is dependent on many factors including the concentration of the inspired gas, the rate of flow of the gas from the anaesthesia machine, the solubility of the gas in blood, the rate and depth of breathing, and the amount of blood the heart pumps each minute in the person breathing the gas.
An important property of anesthetics is reversibility. When the surgery is over, the anesthesiologist wants to shut off the anesthetic and have the patient wake up from the anesthetic-induced sleep. Once the anesthetic gas is turned off, the blood stream brings the gas back to the lungs where it is eliminated. The more soluble the gas is in blood, the longer it takes to eliminate. Nitrous oxide and desflurane are the shortest-acting anesthetic gases because they are the least soluble in blood.

Injected Anesthetics
A liquid anesthetic drug is delivered to the brain by injecting it directly into the bloodstream, usually through an intravenous catheter. Examples of injected drugs are barbiturates, propofol, ketamine, and etomidate, as well as larger doses of narcotics (such as morphine) and benzodiazepines (Valium-like drugs). These drugs quickly reach the brain and their effect is dependent on several factors including the volume in which the drug is distributed in the body, the fat-solubility of the drug, and how quickly the body eliminates the drug.
A commonly used injected barbiturate anesthetic is sodium thiopental, also known as Pentothal. This drug is fat-soluble and acts very quickly. If you receive sodium thiopental and then you are asked to count backward from 100 after the drug is injected, you probably won't remember counting past 95. Some injected anesthetics are used in low doses for sedation. A small dose of a narcotic or a benzodiazepine like Valium or Versed can significantly decrease anxiety. These drugs are used in these doses either as a premedication prior to general anaesthesia or as "twilight sleep" or sedation when used in conjunction with local or regional anaesthesia.


DISCLAIMER: This information is solely for informational purposes. IT IS NOT INTENDED TO PROVIDE MEDICAL ADVICE. Neither the Editors of Health Mirror, the author nor publisher take responsibility for any possible consequences from any treatment, procedure, exercise, dietary modification, action or application of medication which results from reading or following the information contained in this information. The publication of this information does not constitute the practice of medicine, and this information does not replace the advice of your physician or other health care provider. Before undertaking any course of treatment, the reader must seek the advice of their physician or other health care provider.
In case of any queries please feel free to contact Dr Anil K Dhull

Monday, January 28, 2008

How B Vitamins Work

We've all stared at the cereal box label during breakfast and wondered what words like riboflavin, folic acid and pyridoxine mean. Has your mom ever reminded you to eat a balanced diet and "make sure you eat your greens"? The words on your cereal box and your mother's good advice both involve vitamin B. The B vitamins are a group of eight individual vitamins, often referred to as the B-complex vitamins. In this article, we will take a look at how the B vitamins work so you can begin to understand why Kellogg's and your mother made sure you included these essential vitamins in your diet. We'll also look at some of the more serious conditions that can result from B vitamin deficiencies.
The word vitamin is derived from a combination of words -- vital amine -- and was conceived by Polish chemist Casimir Funk in 1912. Funk isolated vitamin B1, or thiamine, from rice. This was determined to be one of the vitamins that prevented beriberi, a deficiency disease marked by inflammatory or degenerative changes of the nerves, digestive system and heart.
You know that vitamins are organic (carbon containing) molecules that mainly function as catalysts for reactions within the body. A catalyst is a substance that allows a chemical reaction to occur using less energy and less time than it would take under normal conditions. If these catalysts are missing, as in a vitamin deficiency, normal body functions can break down and render a person susceptible to disease.
The body requires vitamins in tiny amounts (hundredths of a gram in many cases). We get vitamins from these three primary sources:
· Foods
· Beverages
· Our bodies -- Vitamin K and some of the B vitamins are produced by bacteria within our intestines, and vitamin D is formed with the help of ultraviolet radiation, or sunshine, on the skin.
Vitamins are either fat-soluble or water-soluble. The fat-soluble vitamins can be remembered with the mnemonic (memory aid) ADEK, for the vitamins A, D, E and K. These vitamins accumulate within the fat stores of the body and within the liver. Fat-soluble vitamins, when taken in large amounts, can become toxic. Water-soluble vitamins include vitamin C and the B vitamins. Water-soluble vitamins taken in excess are excreted in the urine but are sometimes associated with toxicity. Both the B vitamins and vitamin C are also stored in the liver.
The B-complex vitamins are actually a group of eight vitamins, which include:
· thiamine (B1)
· riboflavin (B2)
· niacin (B3)
· pantothenic acid (B5)
· pyridoxine (B6)
· cyanocobalamin (B12)
· folic acid
· biotin
These vitamins are essential for:
· The breakdown of carbohydrates into glucose (this provides energy for the body)
· The breakdown of fats and proteins (which aids the normal functioning of the nervous system)
· Muscle tone in the stomach and intestinal tract
· Skin
· Hair
· Eyes
· Mouth
· Liver
Some doctors and nutritionists suggest taking the B-complex vitamins as a group for overall good health. However, most agree that the best way to get our B vitamins is naturally -- through the foods we eat!

DISCLAIMER: This information is solely for informational purposes. IT IS NOT INTENDED TO PROVIDE MEDICAL ADVICE. Neither the Editors of Health Mirror, the author nor publisher take responsibility for any possible consequences from any treatment, procedure, exercise, dietary modification, action or application of medication which results from reading or following the information contained in this information. The publication of this information does not constitute the practice of medicine, and this information does not replace the advice of your physician or other health care provider. Before undertaking any course of treatment, the reader must seek the advice of their physician or other health care provider.

In case of any queries please feel free to contact Dr Anil K Dhull