HealthPad | Publications

7 years, 6 months ago

38203
0
Facebook

Twitter

Google+

LinkedIn

Report

A new therapeutic approach to pre-diabetes

HealthPad

Directory:

Diabetes

Tags:

A recent study suggests that a drug combined with dietary and lifestyle changes can prevent those with pre-diabetes from progressing to full blown type-2 diabetes (T2DM)
T2DM kills millions and cost billions
35% of adults in the UK, and 50% in the US now have prediabetes
The UK has launched the world’s first nationwide diabetes prevention program called Healthier You based on personal education and training
Prevalence rates of T2DM are still rising
Research on the gut-brain axis suggests that drugs have a role to play in preventing T2DM
An optimum strategy might consist of appropriate drug therapy combined with appropriate education, which leverages ubiquitous 21^st century communications infrastructures

A new therapeutic approach to pre-diabetes

Findings of an international clinical study published in The Lancet in 2017 suggest that 3.0mg of the drug liraglutide, may reduce diabetes risk by 80% in individuals with pre-diabetes and obesity, and thereby significantly contribute to the prevention of type-2 diabetes (T2DM). The study investigated whether 3.0mg of liraglutide would delay the onset of T2DM safely in people with pre-diabetes.

Liraglutide is the active solution in a drug marketed as Victoza, which obtained FDA approval in 2010. Victoza is available in 6 mg/ml pre‑filled pens, and is used as an adjunct to diet and exercise to improve glycaemic control in adults with T2DM. Victoza is used also as an add-on to other diabetes medicines, when these, together with exercise and diet, are not providing adequate control of blood glucose.

Pre-diabetes

Pre-diabetes is a condition that develops when your blood sugar levels are at the very high end of the normal range, but not quite high enough for a diagnosis of T2DM. Risk factors include age, weight and ethnicity. People of South Asian origin are up to six times more likely to develop pre-diabetes as a genetic susceptibility means they start to develop insulin resistance at a much lower Body Mass Index (BMI). With pre-diabetes your body begins to have trouble using the hormone insulin, which is necessary to transport glucose, which your body uses for energy, into your cells via the bloodstream. Pre-diabetes means that your body either does not make enough insulin or it does not use it well (insulin resistance). If you do not have enough insulin or if you are insulin resistant, you can build up too much glucose in your blood, leading to higher-than-normal blood glucose level and perhaps pre-diabetes. Blood glucose is measured using a test called HbA1c, which provides a picture of your blood sugar levels over the past two to three months. It counts the number of glucose molecules stuck to the red blood cells, which reveals how much sugar you have carried in your blood over the two to three month lifespan of the red blood cell. If your blood sugar is between 5.7 to 6.4%, this is called pre-diabetes (6.5 is officially diabetes). Dr Roni Sharvanu Saha, a consultant in acute medicine, diabetes and endocrinology at St George's Hospital, London describes pre-diabetes:

Prevalence and cost

It is estimated that 35% of adults in the UK, and 50% in the US now have pre-diabetes. Around 5-10% of these will progress to "full-blown" T2DM in any given year. Because there are no obvious symptoms for pre-diabetes the overwhelming majority of people with the condition do not know they have it, and are not aware of the long-term risks to their health, which include T2DM and its complications: heart attack, stroke, kidney failure, blindness and lower limb amputation. Over the past decade, the prevalence of T2DM has increased by almost two-thirds, and is now one of the world’s most common long-term health conditions.

An estimated £14bn is spent each year on treating diabetes and its complications in the UK. Treating obesity-linked illnesses costs £10bn a year. The annual medical cost of treating diabetes in the US is about US$176bn, and the cost of diabetes in reduced productivity is some US$69bn each year.

The gut-brain axis

The study published in The Lancet was led by John Wilding, Professor of Medicine, University of Liverpool, and is a continuation of work he started in 1996 when part of a team at Hammersmith Hospital in London, which first showed that the hormone GLP-1, on which liraglutide is based, was involved in the control of food intake.

Over the past two decades scientists have increased their understanding of the two-way communications between the gut and the brain, not only through nerve connections between the organs, but also through biochemical signals, such as hormones that circulate in the body. Dr Sufyan Hussain, Specialist Registrar and Honorary Clinical Lecturer in Diabetes, Endocrinology and Metabolism at Imperial College London, describes the gut-brain axis.

Targeting gut-brain pathways

An increasing number of different gut microbial species are now postulated to regulate brain function in health and disease. The westernized diet, which is high in saturated fats, red meats, and carbohydrates, and low in fresh fruits and vegetables, whole grains, seafood, and poultry, is hypothesized to be the cause of high obesity levels in many countries. For example, 63% and 69% of adults in the UK and US respectively are either overweight or obese, and therefore at risk of T2DM. Experimental and epidemiological evidence suggest that the gut microbiota is responsible for significant immunologic, neuronal, and endocrine changes that lead to obesity. The gut–brain axis influences obesity, and researchers such as Wilding have targeted communication pathways between the nervous system and the digestive system in an attempt to treat metabolic disorders.

Bariatric surgery and diabetes

A previous HealthPad Commentary describes how bariatric surgery is associated with gut-brain signals, which promote the remission of diabetes in patients. Many of the mechanisms that underlie how bariatric surgery produces metabolic benefits remain unclear, but researchers do know that such surgical procedures elevate levels of the hormones peptide YY (PYY), and glucagon-like peptide-1 (GLP-1) that help to reduce appetite and have effects on the central nervous system.

Liraglutide

Liraglutide is a GLP-1 receptor agonist, which interacts with the part of the brain that controls appetite and energy intake. The drug slows food leaving the stomach, helps prevent your liver from making too much sugar, and helps the pancreas to produce more insulin when your blood sugar levels are high. The most common side effects with liraglutide are nausea and diarrhoea.

The clinical study

The three-year study followed 2,254 adults with pre-diabetes at 191 research sites in 27 countries worldwide. Participants were randomly allocated to either liraglutide or a placebo delivered by injection under the skin once daily for 160 weeks. Participants in the study were also placed on a reduced calorie diet and advised to increase their physical activity. The study showed that three years of continuous treatment with once-daily 3.0mg of liraglutide, in combination with diet and increased physical activity, reduces the risk of developing T2DM by 80% and results in greater sustained weight loss compared to the placebo.

"On the basis of our findings, liraglutide 3.0mg can provide us with a new therapeutic approach for patients with obesity and pre-diabetes to substantially reduce their risk of developing type 2 diabetes and its related complications . . . . It is very exciting to see a laboratory observation translated into a medicine that has the potential to help so many people, even though it has taken over 20 years,” says Wilding.

World’s first nationwide diabetes prevention program

NHS England, Public Health England and Diabetes UK launched the world’s first nationwide diabetes prevention strategy, Healthier You, in 2016. It provides personal coaches to educate people at risk of T2DM in healthy eating and lifestyle, and personal trainers to provide bespoke physical exercise programs that are expected to help people lose weight. By 2020 Healthier You expects to be rolled out to the whole country with 100,000 referrals available each year after that.

Extrapolating from previous studies

International clinical studies have shown evidence that lifestyle interventions such as those used in Healthier You can prevent or delay the onset of T2DM. However, the validity of generalizing the results of previous prevention studies is uncertain. Interventions that work in some societies may not work in others, because social, economic, and cultural forces influence diet and exercise. The UK’s Public Accounts Committee has expressed doubts about the way Healthier You is setting about its task, and has warned that, "By itself, it will not be enough to stem the rising number of people with diabetes".

Failure of the diabetes establishment and the Public Accounts Committee

Healthier You is a slow, labor-intensive and expensive program, which is unlikely to have more than a relatively small impact.Let us explain. Assume that after 2020 Healthier You obtains its projected annual 100,000 referrals, and that they all successfully reduce their blood glucose levels with diet and exercise. Also assume that the prevalence of pre-diabetes in the UK does not increase, (which is not the case) then Healthier You will take more than 110 years to counsel the estimated 11.5m people in the UK with pre-diabetes: which is long after most people with pre-diabetes would have died from natural causes.

21^st century communications

Successfully changing the diets and lifestyles of the 11.5m people in the UK believed to have pre-diabetes, and slowing their progression to T2DM will require 21^st century technologies. Inexpensive and ubiquitous healthcare technologies used to educate and support diets and lifestyles abound. Increasingly people are demanding devices that track weight, blood pressure, daily exercise and diet. From apps to wearable’s, healthcare technology lets people feel in control of their health, while also providing health professionals with more patient data than ever before. With more than 100,000 healthcare apps, rapid growth in wearables, and 75% of the UK population now owning a smartphone, digital technology is well positioned to significantly improve healthcare education and management.

Takeaways

Has Healthier You missed the elephant in the room? Wilding’s study suggests that an exercise and diet program needs to be complemented with a sustained program of appropriate drugs if we are to reduce those with pre-diabetes from progressing to full blown T2DM. Further, simple arithmetic suggests that the education element of such a strategy about diet and lifestyle should leverage ubiquitous 21^st century communications infrastructures if they are to be efficacious.

view in full page

7 years, 6 months ago

43851
0
Facebook

Twitter

Google+

LinkedIn

Report

Orthorexia: when eating healthily becomes unhealthy

HealthPad

Directory:

Weight Management

Tags:

Orthorexia nervosa is the term used to describe a growing serious 'health food eating disorder'
The number of people suffering from the condition is believed to be millions and increasing
Orthorexia often begins by cutting out certain food groups and only eating 'clean' foods in an attempt to become healthier
Sufferers become obsessed with ‘clean’ food, often feel superior to people with different eating habits, and indulge in excessive fitness routines
Experts warn that orthorexia can lead to malnutrition, social isolation and depression.

Orthorexia: when eating healthily becomes unhealthy

Have you encountered someone who genuinely wants to live a healthier life by eating well, but then becomes so obsessed with “healthy” food that they become unwell and socially isolated?

If you have, then the person is likely to be suffering from orthorexia nervosa, an emerging dietary disorder in which an individual restricts intake to include only “healthy” foods, such as vegetables or organic foods, but in doing so develops an obsession with eating food believed to support “clean living”. Clean living is being mindful of the food's pathway between its origin and your plate, and eating food that is un- or minimally processed, refined, and handled, making them as close to their natural form as possible.

Having said this, it is important to mention that some restrictive diets can be healthy, and even necessary, for medical, ethical or religious reasons. Also, being mindful about what you consume is a positive way to live a healthy life: there is nothing wrong with eating healthily. However, orthorexia is different: becoming fixated on “clean” food can result in serious health problems.

Orthorexia is not anorexia

Unlike anorexics, orthorexics are preoccupied with the quality of food they consume rather than its quantity. The condition usually starts in a quest to be wholesome, when a person cuts out a food group, such as sugar, pulses, dairy products and processed food, but over time ends up with a diet so restrictive, that it contains only a limited number of ‘safe foods’, that the person becomes malnourished.

Orthorexia nervosa

Orthorexia nervosa describes a pathological obsession with “clean” nutrition, which is characterized by a restrictive diet, ritualized patterns of eating, rigid avoidance of foods believed to be unhealthy or impure, and excessive exercise. Although prompted by a desire to be healthy, orthorexia may lead to nutritional deficiencies, medical complications, and a poor quality of life.

Social isolation

Typically, orthorexics spend significant amounts of their time scrutinizing the source of food, and how it is processed and packaged to ensure that it is “clean”. The self-esteem of people with orthrexia becomes associated with their ability to stick to their diet of “clean food”, and they often feel guilty and angry with themselves if they stray from their strict list of acceptable foods. Orthorexics may develop feelings of social superiority to others, and judge those who indulge in “unclean” foods. Their obsession with specific foods often stops them socializing with family and friends, as social events frequently involve drinking and eating “unhealthily”. Also, excessive exercising plays an important role in relation to orthorexia.

Because orthorexics are “addicted” to thinking they are doing the right thing, they tend not to question whether their diet and lifestyle might have a negative impact on their health. Sufferers often take their eating habits to dangerous levels, cutting out food groups and combining their strict diet with too much exercise. In the video below, Dr Seth Rankin, founder and CEO of the London Doctors Clinic suggests that, “denial is the hallmark of an obsession”, and that you cannot treat someone with an obsession unless they recognize that they have a problem.

First diagnosed sufferer

Steven Bratman, a physician who coined the term orthorexia nervosa in 1997, diagnosed himself with the condition after he became obsessive about clean eating. According to Bratman, “Eventually orthorexia reaches a point at which the orthorexic devotes much of his life to planning, purchasing, preparing and eating meals.” Bratman developed 10 questions based on his experience to show how people with the condition could be identified: see below. Bratman’s work has not been validated as indicative of a syndrome; and therefore the diagnostic criteria for orthorexia are still uncertain.

Bratman’s 10-point test for orthorexia

Do you spend more than 3 hours a day thinking about your diet?
Do you plan your meals several days ahead?
Is the nutritional value of your meal more important than the pleasure of eating it?
Has the quality of your life decreased as the quality of your diet has increased?
Have you become stricter with yourself lately?
Does your self-esteem get a boost from eating healthily?
Have you given up foods you used to enjoy in order to eat the 'right' foods?
Does your diet make it difficult for you to eat out, distancing you from family and friends?
Do you feel guilty when you stray from your diet?
Do you feel at peace with yourself and in total control when you eat healthily?
RESULTS
Yes to 4 or 5 of the above questions means it is time to relax more about food.
Yes to all of them means a full-blown obsession with eating healthy food.

Orthorexia is not officially recognized

One of the reasons you might not have heard of orthorexia is because it is not officially recognized as an eating disorder. It is not mentioned as a diagnosis in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), which is published by the American Psychiatric Association, and popularly known as “The Psychiatrist’s Bible”. Neither is the condition included in the World Health Organization's International Classification of Disease. Its lack of recognition leads primary care doctors to refer sufferers to nutritionists, which is a mistake because orthorexics require therapy that de-emphasizes food.

Prevalence difficult to determine

Without being officially recognized as a disease there has been no epidemiological studies on the condition. Notwithstanding, orthorexia is believed to affect millions and be on the increase. Some psychiatrists are beginning to study the condition and offer treatment to patients. In a recent survey of healthcare professionals, 66% reported having observed patients presenting with clinically significant orthorexia; and 66% suggested that the syndrome deserves more scientific attention.

The American National Association of Anorexia Nervosa and Associated Disorders suggests there are some 30m people in the US suffering from eating disorders. Instagram has 26m posts with the #eatclean hashtag. According to the UK’s National Osteoporosis Society, 20% of people under 25 are cutting out or reducing dairy from their diets. A 2016 National Diet and Nutrition Study undertaken by Public Health England found that the calcium intake of 1 in 6 women under 24 was “worryingly low”.

The ORTO-15 test and research beginnings

Orthorexia’s lack of formal status also means that there is a dearth of research on the condition, although published literature and research data have increased in the past few years. In 2005 a group of Italian scientists modified Bratman’s criteria for detecting orthorexia, and developed the ORTO-15 questionnaire, which identifies how far such criteria can be used for psychometric and specific diagnosis. Researchers enrolled 525 participants; 404 were used in the construction of the ORTO-15 test, which comprised 15 multiple-choice questions; and 121 people participated in the ORTO-test’s validation. A score below 40 implies the presence of an obsessive pathological behavior characterized by a strong preoccupation with “clean” eating. Findings from this validation study reported that the ORTO-15 test has an efficacy of 73.8%, a sensitivity of 55.6%, and a specificity of 75.8%.

At least four studies have used the ORTO-15 test to evaluate the prevalence of a preoccupation with “clean” food. A 2010 Turkish study published in the journal of Comprehensive Psychiatry found that 43.6% of medical students showed a preoccupation with healthy food. A large Hungarian study published in 2014 in the journal BMC Psychiatry used the ORTO-15 test on 810 predominantly female (89.4%) university students, and found that over 70% had orthorexia tendencies. American studies have reported a prevalence of orthorexic behaviours ranging from 69% to 82.8% among undergraduate students.

The first study to examine the prevalence of orthorexia nervosa in athletes was completed in 2012 and showed a high frequency of orthorexia across both male (30%) and female (28%) athletes who were largely professional athletes involved in a range of sports. In 2013 a meta study published in Eating and Weight Disorders reviewed 11 studies of orthorexia. Findings suggest that the average prevalence rate for orthorexia was 6.9% for the general population, 35% to 57.8% for high-risk groups such as dieticians, other healthcare professionals, and artists. Risk factors were suggested to be obsessive-compulsive features, eating-related disturbances, and higher socioeconomic status.

Takeaways

Orthorexia appears to be on the increase at a time when the vast and escalating healthy lifestyle-information industry is complemented by the rapid exchange of ideas via social media. This means that individuals are regularly bombarded with dietary and healthcare advice, which they can share instantly. Orthorexia seems yet another serious condition of affluent societies, which is growing in significance.

view in full page

7 years, 7 months ago

30851
0
Facebook

Twitter

Google+

LinkedIn

Report

New developments in the management of prostate cancer

HealthPad

Directory:

Cancer

Tags:

prostate specific antigen (PSA

PSA test

vascular-targeted photodynamic therapy

3m men in the US and 330,000 men in the UK are living with prostate cancer
The standard test used to diagnose prostate cancer is inaccurate
This inaccuracy causes anxiety in men and leads to unnecessary treatments
Standard therapies for prostate cancer can result in incontinence and impotence
Two new studies describe procedures that promise significant improvements in diagnosis and treatment

New developments in the management of prostate cancer

A vicious circle

There is general agreement on two issues concerning the management of prostate cancer: one, over-diagnosis and overtreatment rates are high; and two, there is a need to refine the standard prostate-specific antigen (PSA) diagnostic test.

The test does not provide information to allow doctors to determine which early-stage prostate tumors pose a risk of being aggressive and need treatment, and which should be left alone. Therefore, efforts to reduce the prevalence of prostate cancer by early detection using the PSA test can lead to over-diagnosis, which in turn can result in overtreatment, which in the case of prostate cancer, can result in incontinence and impotence.

Current official advice to UK GPs says: “The PSA test is available free to any well man aged 50 and over who requests it.” But, “GPs should not proactively raise the issue of PSA testing with asymptomatic men”. And, “GPs should use their clinical judgment to manage symptomatic men and those aged under 50 who are considered to have higher risk for prostate cancer”. In 2014 the National Institute for Health and Care Excellence (NICE) updated its guidelines and suggested that prostate cancer patients should avoid immediate treatment and keep their disease under “surveillance”.

A killer disease on the increase

Prostate cancer is increasing in significance worldwide. In many industrialized countries such as the US and the UK, it is one of the most common cancers and among the leading causes of cancer deaths. In developing countries it may be less common, but its incidence and mortality rates have been on the rise. In the US there are some 3m men living with the disease. It is expected that in 2017, 161,000 new cases of prostate cancer will be diagnosed in the US, and 27,000 men will die from it. In the UK, there are some 330,000 men living with prostate cancer; each year around 47,000 men are diagnosed with the disease, and each year some 11,000 die from it, which equates to one every hour. Worldwide, there are an estimated 1.6m new cases of prostate cancer, and 366,000 prostate cancer deaths annually, making it the most commonly diagnosed cancer in men and the seventh leading cause of male cancer death.

The prostate and prostate cancer

The prostate is a small gland in men, which is located below the bladder and above the rectum. The urethra, which is the tube that carries urine and semen out of the body through the penis, goes through the centre of the prostate. In younger men the prostate is about the size of a walnut, but in older men it can be much larger. Symptoms of prostate cancer include persistent burning, difficult, frequent, uncontrolled or bloody urination in the absence of any infection. The average age of onset is 65 to 69. It is particularly prevalent in African-Caribbean men: affecting I in 4, and killing I in 12, which is double the rate for that of Caucasian men. The main risk factor is age: 80% of all men diagnosed with prostate cancer are over 65. Between 5% and 9% of cases occur in men with a family history of prostate, breast or ovarian cancer. Environmental factors are unclear, but rates of prostate cancer are lower in less urbanised societies, and rates rise when people move to a more westernised diet and lifestyle.

The prostate-specific antigen (PSA) test

In the 1980s a simple and cheap blood test was introduced to detect prostate cancer in its earliest, most curable, stage. In the video below Professor Karol Sikora, a cancer expert, describes the PSA test. Although used to detect prostate cancer, it is not a test for prostate cancer, and as a consequence, it has unresolved challenges. The most significant arises because the test is not accurate enough to either rule out or confirm the presence of cancer. Indeed, it is possible for PSA levels to be elevated when cancer is not present, and not to be elevated when it is present. More than 65% of men with elevated PSA levels do not have cancer. Excessive reliance on the test may lead to unnecessary interventions, while insufficient reliance may cause cancers to be missed.

Biopsies

A biopsy will often be recommended if a PSA test is high. It may also be recommended if a digital rectal examination (DRE) reveals a lump or some other abnormality in the prostate. The most commonly used biopsy for diagnosing prostate cancer is the trans-rectal ultrasound-guided prostate biopsy (TRUS-biopsy). This is a surgical procedure, in which tissue is removed from the prostate for microscopic examination. Each year, over 100,000 prostate biopsies are carried out in the UK and 1m in Europe.

75 to 80% of men who have TRUS-biopsies have no cancerous cells, and therefore did not need the biopsy. 20 to 25% do have cancerous cells, but a large percentage of these do not need any treatment because the cancers are slow growing. A 2014 paper by the Harvard School of Public Health estimates that only 3% of men suspected of prostate cancer have an aggressive tumor requiring immediate intervention.

Further, doctors cannot tell from a biopsy whether cancerous cells are aggressive and need treatment, or whether they are developing slowly and do not require treatment. This creates confusion and anxiety among men, which prompts a percentage to opt for treatment even though the overwhelming majority do not need it. 25% of older men who elect to have treatment will become incontinent or impotent as a result, despite the fact that they did not need the treatment.

Active surveillance

In a significant proportion of men, prostate cancer cells grow slowly and never pose a serious risk to health and longevity. Evidence suggests that early treatment with either surgery or radiation does not reduce mortality rates, but leaves a significant percentage of men with urinary or erectile problems and other adverse effects. As a result, more men are willing to manage their condition by active surveillance, in which doctors monitor low-risk cancers closely and consider treatment only when the condition appears to make threatening moves toward growing and spreading. These men choose to live with prostate cancer until it advances, sometimes avoiding potentially life-altering side effects for several years. Active surveillance is a powerful solution to the problem of over-diagnosis and overtreatment.

New studies promise significantly improved management

Prostate cancer lags behind other cancers in diagnosis, treatment and research funding. But this is beginning to change. Over the past year, findings of two clinical studies promise significant improvements in the management of the condition.

The first, published in 2017 in the Lancet, describes a process, which uses MRI-guided biopsies to improve the accuracy of prostate cancer diagnosis, and spares those who do not have aggressive cancers from undergoing an unnecessary biopsy, so reducing the confusion and anxiety which prostate patients often experience.

The second, published in 2016 in the Lancet Oncology, describes findings of a laser-activated drug derived from bacteria found at the bottom of the sea that attacks and kills prostate cancer cells without either removing or destroying the prostate gland. This is significant because it avoids the potential adverse effects of surgery and radiotherapy, which can render patients incontinent and/or impotent.

The multi-parametric MRI

The 2017 Lancet study used an advanced type of MRI scan, known as a multi-parametric MRI (MP-MRI), which in addition to recording the shape and size of the prostate, also assesses the blood flow through the gland. Led by Dr Hashim Ahmed of University College London, the study was comprised of more than 500 British men with suspected prostate cancer. Results suggest that using the MP-MRI to triage men would safely reduce the number needing a primary biopsy by about 27%, and substantially improve the detection of clinically significant cancers. If subsequent TRUS-biopsies were directed by MP-MRI findings, up to 18% more cases of clinically significant cancers might be detected compared with the standard pathway of TRUS-biopsy for all.

A paradigm shift in prostate cancer treatment

The second study compared the safety and effectiveness of a new therapy called vascular-targeted photodynamic therapy (VTP, also known as TOOKAD), with active surveillance in men with low-risk prostate cancer. It funded by STEBA Biotech, which holds the commercial licence for the therapy. Photodynamic therapy (PDT) is not new, and has been used to treat skin and other cancers where light can easily penetrate. VTP therapy, however, is viewed as a paradigm shift in prostate cancer care. It involves injecting a light-sensitive drug (padeliporfin or WST11) into the bloodstream, and then activating it with a laser to destroy cancerous tissue. The benefit of this approach is damage to healthy prostate tissue is minimised, reducing the risk of side effects.

Findings

The study was comprised of 413 men at low risk of prostate cancer, and carried out across 47 treatment sites in 10 European countries, most of which were performing VTP therapy for the first time. Only men classified with low-risk cancer were included in this study. Participants were randomly assigned either to VTP therapy or active surveillance. At the end of two years, of the 196 men who received the VTP treatment, about half showed no signs of the disease, compared with 13.5% of those given standard care. Only 6% of the VTP group later needed radical treatment, compared with 30% of active surveillance patients. VTP treatment also doubled the average time of cancer progression from 14 to 28 months. Findings suggest that 49% of patients treated with VTP therapy went into complete remission compared with 13.5% in the control group.

A third of the VTP group experienced side effects compared to only 10 of the active surveillance group. Notwithstanding, the study concluded that, “VTP therapy is a safe, effective treatment for low-risk, localised prostate cancer, which might allow more men to consider a tissue-preserving approach and defer or avoid radical therapy”. Patient monitoring will continue in order to ascertain whether the cancer stays away. Further studies should help to understand better which cancers VTP treatment is most appropriate for so that men can make more informed treatment decisions.

Study enhanced by MRI scanning

The study was conducted with people at low risk of prostate cancer. Those at very low risk are better off with no treatment and no adverse-effects. Professor Mark Emberton of University College London, the lead author of the study, believes the therapy will be most useful in patients in the “grey zone”, between low and high risk. “The fact that the treatment was performed so successfully by non-specialist centres in various health systems is really remarkable”, says Emberton because the lack of complication suggests that the treatment protocol is safe, and relatively easy to scale.

At the beginning of the study MRI scans were not universally available, and Emberton believes MRI scanning as suggested by the Ahmed 2017 study will have a significant positive effect on prostate cancer treatment in the future. When carrying out biopsies without guidance from MRI scans researchers had to guess where in the prostate the cancer was; so biopsies were sub-optimal. “If they were to do the study now, with the help of MRI scans, they could hit the cancerous parts of the prostate rather than going in blind and the results would be much better,” says Emberton.

Takeaways

These two recent studies are potential “game changers”. They promise to significantly enhance the management of prostate cancer and substantially reduce the uncertainty and anxiety, as well as the risks of the life altering side effects of treatment, experienced by millions of men living with the disease.

view in full page

7 years, 7 months ago

34395
0
Facebook

Twitter

Google+

LinkedIn

Report

World’s first blood tests that detect and locate cancer

HealthPad

Directory:

Cancer

Tags:

Each year cancer kills 8m people worldwide and cost billions
40% of cancer deaths could be prevented by early detection
Nearly half of all cancer sufferers are diagnosed late when the tumors have already spread
Victims and doctors often miss early warning signs of cancer
Traditional tissue biopsies used to diagnose cancer are invasive, slow, costly, and often yield insufficient tissue
New blood tests are being devised that simultaneously detect cancer early and inform where the cancer is in the body
Such tests - liquid biopsies - are positioned to end the late diagnosis of cancer
But before liquid biopsies become common practice they need to overcome a number of significant challenges

World’s first blood tests that detect and locate cancer

Just as there is a global race among immunotherapists to enhance cancer treatment, so there is a parallel race among bioengineers to speed up and improve the detection of cancer. Such races are important because nearly half of all cancer sufferers are diagnosed late, when their tumors have already metastasized: 30% to 40% of cancer deaths could be prevented by early detection and treatment.

Here we describe advances in blood tests - “liquid biopsies” - which can simultaneously detect cancer early, and identify its tissue of origin. We also, describe the growing commercialization of the technology, and some significant hurdles it still has to be overcome.

A costly killer disease

Each year cancer kills more than 8m people worldwide, 0.6m in the US and nearly 0.17m in the UK. Survival rates for pancreatic, liver, lung, ovarian, stomach, uterine and oesophageal cancers are particularly low. A large proportion of people do not know they have cancer, and many primary care doctors fail to detect its early warning signs. According to The Journal of Clinical Oncology, a staggering 44% of some types of cancers are misdiagnosed. A significant proportion of people discover that they have cancer only after presenting a different condition at A&E. Each year, the total cost of cancer to the UK’s exchequer is nearly £20bn. In the US, national spending on cancer is expected to reach US$156bn by 2020. And as populations age so some cancer prevalence rates increase, despite substantial endeavours to reduce the burden of the disease.

The UK: a stereotypical case

The UK is indicative of what is happening elsewhere in the developed world with regard to cancer diagnosis and treatment. Epidemiological trends suggest that although progress is being made to fight the disease, much work is still required. Death rates for a number of individual cancer types have declined, but rates for a few cancers have increased.

Recently, the UK’s Department of Health invested £450m to improve diagnosis, including giving primary care doctors better access to tests such as CT and MRI scans. But each year there are still some 0.17m cancer deaths in the UK, and 1 in 4 British cancer patients are unlikely to live longer than 6 months after diagnosis because they and their doctors have missed early signs of the disease. For example, in the UK only 23% of lung cancer cases are diagnosed early, as are 32% of cases of non-Hodgkin lymphoma, and 44% of ovarian cancer.

Not only does late detection increase morbidity and mortality, it significantly increases treatment costs. According to the UK’s NHS National Intelligence Network, a case of ovarian cancer detected early costs an average of £5,000 to treat, whereas one detected late at stage three or four costs £15,000. Similarly, a colon cancer patient detected early typically costs £3,000, while one not identified until a later stage would cost some £13,000.

Traditional tissue biopsies

Currently, oncologists look to pathologists for assistance in tumor diagnosis. Indeed, oncologists cannot proceed with therapy without a tissue diagnosis, nor are they able to discuss prognosis with the patient. After detecting a tumor through a physical examination or imaging, doctors use traditional tissue biopsies to gather information on the attributes of a patient’s cancer.

These pinpoint a cancer’s mutations and malignancy, but solid tissue biopsies are not always straightforward. While some cancers are easily accessed, others are hidden deep inside the body or buried in critical organs. Beyond the physical challenge, sampling from such tumors can be dangerous to patients, and once achieved, they do not always inform on current tumor dynamics. Further, traditional solid tissue biopsies are costly and time consuming to perform; they can yield insufficient tissue to obtain a good understanding of the tumor, and they can be hampered by a patient’s comorbidities, and lack of compliance.

Two significant studies

Although solid tumor tissue is still the gold standard source for clinical molecular analyses, cancer-derived material circulating in the bloodstream has become an appealing alternative showing potential to overcome some of the challenges of solid tissue biopsies.

Findings of two significant studies of liquid biopsies published in 2017 promise a more effective and patient-friendly method for diagnosing cancer: one in the journal Genome Biology, and the other in the journal Nature Genetics. Both studies are on the cusp of developing the world’s first simple blood test, which can both detect early stage cancer, and identify where in the body the cancer is located.
.

The Genome Biology study

The study, reported in Genome Biology, describes findings of a blood test, referred to as the CancerLocator, which has been developed by Jasmine Zhou, Professor of Biological and Computer Sciences and her team at the University of California, Los Angeles (UCLA). The Locator detected early stage cancer in 80% of breast, lung and liver cases.

Zhou and her colleagues devised a computer program that uses genetic data to detect circulating tumor DNA (ctDNA) in blood samples. Once identified, the ctDNA is compared to a database of genetic information from hundreds of people to identify where the tumor is located. Zhou’s team discovered that tumors, which arise in different parts of the body, have different signatures, which a computer can spot. “The technology is in its infancy and requires further validation, but the potential benefits to patients are huge . . . . . Non-invasive diagnosis of cancer is important, as it allows the early detection of cancer, and the earlier the cancer is caught, the higher chance a patient has of beating the disease,” says Zhou.

The Nature Genetics study

Researchers led by Kun Zhang, Professor of Bioengineering at the University of California, San Diego (UCSD), are responsible for the study published in the journal Nature Genetics. Zhang developed a test that examined ctDNA in blood from cancer patients and, like Zhou, discovered that not only could it detect cancer early, but could also locate where the tumor is growing in the body. When a tumor starts to take over a part of the body, it competes with normal cells for nutrients and space, killing them off in the process. As normal cells die, they release their DNA into the bloodstream; and that DNA can identify the affected tissue.

“There are many technical differences on how each approach works . . . The work by the UCLA group is a computer program that uses data published previously by other groups, and has reduced the cancer detection error from roughly 60% to 26.5%. In contrast, we developed a new theoretical framework, generated our own data from over 100 patients and healthy people, and our accuracy of locating cancer in an organ is around 90%,” says Zhang, but he adds, “Major medical challenges don’t get solved by one team working alone”.

Confluence and advances in computing and biology

The research endeavors of Professors Zhou and Zhang have been made possible by the confluence and advances in computing and molecular biology. Over the past 20 years, there has been a paradigm shift in biology, a substantial increase in computing power, huge advances in artificial intelligence (AI), and the costs of data storage have plummeted. It took 13 years, US$3bn, and help from 7 governments to produce the first map of the human genome, which was completed in 2003. Soon it will be possible to sequence an entire genome in less than an hour for US$100.

The end of traditional in vitro diagnostics

Liquid biopsies are a sequencing-based technology used to detect microscopic fragments of DNA in just a few drops of blood, and hold out the potential to diagnose cancers before the onset of symptoms. Roger Kornberg, Professor of Structural Biology at Stanford University, and 2006 Nobel Laureate for Chemistry for his work in understanding how DNA is converted into RNA, “which gives a voice to genetic information that, on its own, is silent,” describes how advances in molecular science are fueling the replacement of traditional in vitro diagnostics with virtually instantaneous, point-of-care diagnostics without resort to complex processes or elaborate and expensive infrastructure. Liquid biopsies, such as those developed by Zhou and Zhang, have the potential to provide clinicians with a rapid and cheap means to detect cancer early, thereby enabling immediate treatment closely tailored to each patient’s disease state.

FDA approval of liquid biopsy

In 2016, the US Food and Drug Administration (FDA) granted Swiss pharmaceutical and biotech firm Roche approval for a liquid biopsy, which can detect gene mutations in the most common type of lung cancer, and thereby predict whether certain types of drugs can help treat it.

The clinical implementations of such a test are not widespread, and there has been no regulatory approval of liquid biopsies for diagnosing cancer generally. Notwithstanding, ctDNA is now being extensively studied, as it is a non-invasive “real-time” biomarker that can provide diagnostic and prognostic information before and during treatment; and at progression.

cfDNA and ctDNA

Cell-free DNA (cfDNA) is a broad term that describes DNA, which is freely circulating in the bloodstream, but does not necessarily originate from a tumor. Circulating tumor DNA (ctDNA) is fragmented DNA, which is derived directly from a tumor or from circulating tumor cells (CTCs).

Commercialization of the liquid biopsy race

Bill Gates, Jeff Bezos and leading venture capitalists have poured hundreds of millions into the goal of developing liquid biopsies. The US market alone is projected at US$29bn, according to a 2015 report from investment bank Piper Jaffray. Currently, there are about 40 companies in the US analyzing blood for fragments of DNA shed by dying cancer cells. Notwithstanding, only a few companies have successfully marketed liquid biopsies, and these are limited to identifying the best treatments for certain cancers, and to update treatments as the cancer mutates. So far, no one has been successful in diagnosing incipient cancer from a vial of blood drawn from a patient who looks and feels perfectly healthy.

Some US companies in the liquid biopsy race

At the 2016 meeting of the American Society of Clinical Oncology (ASCO), a Silicon Valley start-up, Guardant Health, which has raised some US$200m, presented findings from a large study involving over 15,000 participants, which demonstrated the accuracy of its liquid biopsy test, Guardant360, for patients with advanced solid tumors. The study found the same patterns of genomic changes in cfDNA reported by the Guardant360 test as those found in 398 patients with matching tissue samples between 94% and 100% of the time.

The 70-gene test is the first comprehensive, non-invasive genomic cancer-sequencing test to market, and according to the company, about 2,000 physicians worldwide have used it. Guardant expects to continue to develop its technology, and maintain a commercial lead in the cfDNA liquid biopsy space. The next step for Guardant is to go beyond sequencing, which matches patients to targeted oncology drugs to the early detection of cancer itself.

Also in 2016 Gates and Bezos teamed up with San Diego's Illumina, which makes most of the DNA sequencing machines that pick appropriate treatments for cancer patients, to launch another liquid biopsy start-up called Grail. In 2017, Grail raised US$900m to help it develop blood-based diagnostics to enable routine, early detection of cancer. The company aims to refine and validate its liquid biopsy technology by running a number of large-scale clinical studies where it expects to sequence hundreds of thousands of patients. Another Californian-based biotech start-up, Freemome, raised US$65m to validate its liquid biopsy technology for the early detection of cancer.

Takeaways

Despite findings of the two 2017 studies reported in the journals Genome Biology and Nature genetics, FDA approval of Roche’s liquid biopsy, massive increase in investment, and significant commercial biotech activity, there is a gap between reality and aspirations for liquid biopsies. To provide doctors with a reliable, point-of-care means to detect cancer early, liquid biopsies will have to overcome several significant challenges. The major one is assay sensitivity and specificity for analysis of ctDNA and cfDNA. To compete with the gold standard solid tissue biopsy, and to ensure that patients receive early diagnosis and appropriate treatment, a successful liquid biopsy assay will have to demonstrate a high positive predictive value. Concomitantly, good sensitivity and excellent specificity will be required to yield acceptable rates of false positives and false negatives. Notwithstanding, the race among bioengineers to develop a non-invasive “real-time” liquid biopsy to detect cancer early is gaining momentum.

view in full page

7 years, 8 months ago

39003
0
Facebook

Twitter

Google+

LinkedIn

Report

Gene editing battles

HealthPad

Directory:

Medical Technology

Tags:

Competition is intensifying among scientists to develop and use gene editing and immunotherapy to defeat intractable diseases
Chinese scientists were the first to inject people with cells modified by the CRISPR–Cas9 gene-editing technique
Several studies have extracted a patient’s own immune cells, modified them using gene-editing techniques, and re-infused them into the patient to seek and destroy cancer cells
A new prêt à l'emploi gene editing treatment disables the gene that causes donor immune cells to attack their host
The technique harvests immune cells from a donor, modifies and multiplies them so that they may be used quickly, easily and cheaply on different patients
Commercial, technical, regulatory and ethical barriers to gene editing differ in different geographies

Gene editing battles

Gene editing and immunotherapy are developing at a pace. They have been innovative and effective in the fight against melanoma, lung cancer, lymphomas and some leukaemias, and promise much more. Somatic gene therapy changes, fixes and replaces genes at the tissue or cellular levels to treat a patient, and the changes are not passed on to the patient’s offspring. Germ line gene therapy inserts genes into reproductive cells and embryos to correct genetic defects that could be passed on to future generations. Although there are still many unanswered clinical, commercial and ethical questions surrounding gene therapy, its future is assured and will be shaped by unexpected new market entrants and competition between Chinese and Western scientists, which is gaining momentum.

14 February 2017

On the 14^th February 2017 an influential US science advisory group formed by the National Academy of Sciences and the National Academy of Medicine gave support to the modification of human embryos to prevent “serious diseases and disabilities” in cases where there are no other “reasonable alternatives”. This is one step closer to making the once unthinkable heritable changes in the human genome. The Report, however, insisted that before humanity intervenes in its own evolution, there should be a wide-ranging public debate, since the technology is associated with a number of unresolved ethical challenges. The French oppose gene editing, the Dutch and the Swedes support it, and a recent Nature editorial suggested that the EU is, “habitually paralysed whenever genetic modification is discussed”. In the meantime, clinical studies, which involve gene-editing are advancing at a pace in China, while the rest of the world appears to be embroiled in intellectual property and ethical debates, and playing catch-up.

15 February 2017

On the 15^th February 2017, after a long, high-profile, heated and costly intellectual property action, judges at the US Patent and Trademark Office ruled in favor of Professor Feng Zhang and the Broad Institute of MIT and Harvard, over patents issued to them associated with the ownership of the gene-editing technology CRISPR-Cas9: a cheap and easy-to-use, all-purpose gene-editing tool, with huge therapeutic and commercial potential.

The proceedings were brought by University College Berkeley who claimed that the CRISPR technology had been invented by Professor Jennifer Doudna of the University, and Professor Emmanuelle Charpentier, now at the Max Planck Institute for Infection Biology in Berlin, and described in a paper they published in the journal Science in 2012. Berkeley argued that after the 2012 publication, an “obvious” development of the technology was to edit eukaryotic cells, which Berkeley claimed is all that Zhang did, and therefore his patents are without merit.

The Broad Institute countered, suggesting that Zhang made a significant inventive leap in applying CRISPR knowledge to edit complex organisms such as human cells, that there was no overlap with the University of California’s research outcomes, and that the patents were therefore deserved. The judges agreed, and ruled that the 10 CRISPR-Cas9 patents awarded to Zhang and the Broad Institute are sufficiently different from patents applied for by Berkeley, so that they can stand.

The scientific community

Interestingly, before the 15th February 2017 ruling, the scientific community had appeared to side with Berkeley. In 2015 Doudna, and Charpentier were awarded US$3m and US$0.5m respectively for the prestigious Breakthrough Prize in life sciences and the Gruber Genetics Prize. In 2017 they were awarded the Japan Prize of US$0.45m for, “extending the boundaries of life sciences”. Doudna and Charpentier have each founded companies to commercially exploit their discovery: respectively Intellia Therapeutic, and CRISPR Therapeutics.

16 February 2017

A day after the patent ruling, Doudna said: “The Broad Institute is happy that their patent didn’t get thrown out, but we are pleased that our patent based on earlier work can now proceed to be issued”. According to Doudna, her patents are applicable to all cells, whereas Zhang’s patents are much more narrowly indicated. “They (Zhang and the Broad Institute) will have patents on green tennis balls. We will get patents on all tennis balls,” says Doudna.

Gene biology

Gene therapy has evolved from the science of genetics, which is an understanding of how heredity works. According to scientists life begins in a cell that is the basic building block of all multicellular organisms, which are made up of trillions of cells, each performing a specific function. Pairs of chromosomes comprising a single molecule of DNA reside in a cell’s nucleus. These contain the blueprint of life: genes, which determine inherited characteristics. Each gene has millions of sequences organised into segments of the chromosome and DNA. These contain hereditary information, which determine an organism’s growth and characteristics, and genes produce proteins that are responsible for most of the body’s chemical functions and biological reactions.

Roger Kornberg, an American structural biologist who won the 2006 Nobel Prize in Chemistry "for his studies of the molecular basis of eukaryotic transcription", describes the Impact of human genome determination on pharmaceuticals:

China’s first

While American scientists were fighting over intellectual property associated with CRISPR-Cas9, and American national scientific and medical academies were making lukewarm pronouncements about gene editing, Chinese scientists had edited the genomes of human embryos in an attempt to modify the gene responsible for β-thalassemia and HIV, and are planning further clinical studies. In October 2016, Nature reported that a team of scientists, led by oncologist Lu You, at Ghengdu’s Sichuan University in China established a world first by using CRISPR-Cas9 technology to genetically modify a human patient’s immune cells, and re-infused them into the patient with aggressive lung cancer, with the expectation that the edited cells would seek, attack and destroy the cancer. Lu is recruiting more lung cancer patients to treat in this way, and he is planning further clinical studies that use similar ex vivo CRISPR-Cas9 approaches to treat bladder, kidney and prostate cancers

The Parker Institute for Cancer Immunotherapy

Conscious of the Chinese scientists’ achievements, Carl June, Professor of Pathology and Laboratory Medicine at the University of Pennsylvania and director of the new Parker Institute for Cancer Immunotherapy, believes America has the scientific infrastructure and support to accelerate gene editing and immunotherapies. Gene editing was first used therapeutically in humans at the University of Pennsylvania in 2014, when scientists modified the CCR5 gene (a co-receptor for HIV entry) on T-cells, which were injected in patients with AIDS to tackle HIV replication. Twelve patients with chronic HIV infection received autologous cells carrying a modified CCR5 gene, and HIV DNA levels were decreased in most patients.

Medical science and the music industry

The Parker Institute was founded in 2016 with a US$250m donation from Sean Parker, founder of Napster, an online music site, and former chairman of Facebook. This represents the largest single contribution ever made to the field of immunotherapy. The Institute unites 6 American medical schools and cancer centres with the aim of accelerating cures for cancer through immunotherapy approaches.

Parker, who is 37, believes that medical research could learn from the music industry, which has been transformed by music sharing services such as Spotify. According to Parker, more scientists sharing intellectual property might transform immunotherapy research. He also suggests that T-cells, which have had significant success as a treatment for leukaemia, are similar to computers because they can be re-programed to become more effective at fighting certain cancers. The studies proposed by June and colleagues focus on removing T-cells, from a patient’s blood, modifying them in a laboratory to express chemeric antigen receptors that will attack cancer cells, and then re-infusing them into the patient to destroy cancer. This approach, however, is expensive, and in very young children it is not always possible to extract enough immune cells for the technique to work.

Prêt à l'emploi therapy

Waseem Qasim, Professor of Cell & Gene Therapy at University College London and Consultant in Paediatric immunology at Great Ormond Street Hospital, has overcome some of the challenges raised by June and his research. In 2015 Qasim and his team successfully used a prêt à l'emploi gene editing technique on a very young leukaemia patient. The technique, developed by the Paris-based pharmaceutical company Cellectis, disables the gene that causes donor-immune cells to attack their host. This was a world-first to treat leukaemia with genetically engineered immune cells from another person. Today, the young leukaemia patient is in remission. A second child, treated similarly by Qasim in December 2015, also shows no signs of the leukaemia returning. The cases were reported in 2017 in the journal Science Translational Medicine.

Universal cells to treat anyone cost effectively

The principal attraction of the prêt à l'emploi gene editing technique is that it can be used to create batches of cells to treat anyone. Blood is collected from a donor, and then turned into “hundreds” of doses that can then be stored frozen. At a later point in time the modified cells can be taken out of storage, and easily re-infused into different patients to become exemplars of a new generation of “living drugs” that seek and destroy specific cancer cells. The cost to manufacture a batch of prêt à l'emploi cells is estimated to be about US$4,000 compared to some US$50,000 using the more conventional method of altering a patient’s cells and returning them to the same patient. Qasim’s clinical successes raise the possibility of relatively cheap cellular therapy using supplies of universal cells that could be dripped into patients' veins on a moment’s notice.

Takeaways

CRISPR-Cas9 provides a relatively cheap and easy-to-use means to get an all-purpose gene-editing technology into clinics throughout the world. Clinical studies using the technology have shown a lot of promise especially in blood cancers. These studies are accelerating, and prêt à l'emploi gene editing techniques as an immunotherapy suggest a new and efficacious therapeutic pathway. Notwithstanding the clinical successes, there remain significant clinical, commercial and ethical challenges, but expect these to be approached differently in different parts of the world. And expect these differences to impact on the outcome of the scientific race, which is gaining momentum.

view in full page

7 years, 8 months ago

20191
0
Facebook

Twitter

Google+

LinkedIn

Report

Dr Matthew Banks Publication

Matthew Banks

Directory:

Gastroenterology

Tags:

bowel cancer

Endoscopy

Gastrenterology

Publications by Dr Matthew Banks

Reviews
Banks MR

Should patients expect their colonoscopy to reach the standards experienced by bowel cancer screening patients?
Frontline Gastroenterol 2012;3:122-123

Mannath J, Banks MR
Emerging technologies in Endoscopic Imaging
F1000 Med Rep. 2012;4:3. Epub 2012 Feb 1.

Kent A & Banks MR
Functional Gastrointestinal Disorders: Diarrhea
Gastroenterology Clinics of North America. Hunt (eds),
Sept 2010;39(3):495-507

Banks M.
The modern investigation and management of gastro-oesophageal reflux disease. Clinical Medicine
2009;9(6):1-5

Burleigh DE & Banks MR
Stimulation of intestinal secretion by vasoactive intestinal peptide and cholera toxin. Autonomic Neuroscience.
2007;133(1):64-75

Farthing MJG, Casburn-Jones A, Banks MR
Diarrhoea. Prescriber 2003;14 (20):48-59.

Farthing MJG, Casburn-Jones A, Banks MR.
Getting control of intestinal secretion: thoughts for 2003.
Digestive and Liver Disease 2003;35:378-385

Banks MR, Farthing MJG.
Fluid and electrolyte absorption. Current Opinion in Gastroenterology 2001;
18 (2): 176-181.

Banks MR, Farthing MJG.
Current management of Acute Diarrhoea. Prescriber 2001;
12(12):83-93.

Banks MR, Farthing MJG.
The Management of Acute Diarrhoea. Prescriber 2000;
11(4): 97-105

Case reports
Pasha Y, Banks M.
Medical mystery: an unusual cause of anaemia
Br J Hosp Med (Lond). 2010 Feb;71(2):113.

Pasha Y, Pickard L, Cohen P, Banks MR
An unusual endoscopic diagnosis for acute epigastric pain
Scand J Gastro 2008;43(9):1151-2.

Pasha Y, White WJ, Chew NS, Banks M.
The importance of never ignoring an unexplained metabolic acidosis. Incarcerated femoral hernia. QJM.
2008 Oct;101(10):825-6. Epub 2008 Aug 28.

Green L, Banks MR
HIV associated encephalopathy, a grey case. Int J STD’s AIDS.
1995; 6: 744

Original papers

Radiofrequency ablation for early oesophageal squamous neoplasia: Outcomes form United Kingdom registry.
Rehan J Haidry, Mohammed A Butt, Jason Dunn, Matthew Banks, Abhinav Gupta, Howard Smart, PradeepBhandari, Lesley Ann Smith, Robert Willert, Grant Fullarton, Morris John, Massimo Di Pietro, Ian Penman, Marco Novelli, Laurence B Lovat
World Journal of Gastroenterology 09/2013; 19(36):6011-6019. 2.47

Radiofrequency Ablation (Rfa) And Endoscopic Mucosal Resection For Dysplastic Barrett’s Esophagus And Early Esophageal Adenocarcinoma: Outcomes Of Uk National Halo Rfa Registry.
R J Haidry, J M Dunn, M A Butt, M Burnell, A Gupta, S Green, H Miah, H L Smart, P Bhandari, L Smith, R Willert, G Fullarton, M Di Pietro, C Gordon, I Penman, H Barr, P Patel, P Boger, N Kapoor, B Mahon, J Hoare, R Narayanasamy, D O’Toole, E Cheong, N C Direkze, Y Ang, M Novelli, M R Banks, L B Lovat
Gastroenterology. 2013 Mar 28.doi:pii: S0016-5085(13)00459-9. 10.1053/j.gastro.2013.03.045

Wallace MB, Crook JE, Saunders M, Lovat L, Coron E, Waxman I, Sharma P, Hwang JH, Banks M, DePreville M, Galmiche JP, Konda V, Diehl NN, Wolfsen HC. Multicenter, randomized, controlled trial of confocal laserendomicroscopy assessment of residual metaplasia after mucosal ablation or resection of GI neoplasia in Barrett’s esophagus. GastrointestEndosc. 2012 Sep;76(3):539-47.e1. doi: 10.1016/j.gie.2012.05.004. Epub 2012 Jun 28

Dunn JM, Mackenzie GD, Banks MR, Mosse CA, Haidry R, Green S, Thorpe S, Rodriguez-Justo M, Winstanley A, Novelli MR, Bown SG, Lovat LB. A randomised controlled trial of ALA vs. Photofrin photodynamic therapy for high-grade dysplasia arising in Barrett’s oesophagus. Lasers Med Sci. 2012 Jun 15.

Banks MR, Haidry R, Butt MA, Whitley L, Stein J, Langmead L, Bloom SL, O’Bichere A, McCartney S, Basherdas K, Rodriguez-Justo M, Lovat LB. High resolution colonoscopy in a bowel cancer screening program improves polyp detection. World J Gastroenterol. 2011 Oct 14;17(38):4308-13.

Dunn JM, Banks MB, Oukris D, McKenzie GD, Thorpe S, Winstanly A, Novelli MR, Bown S, Lovat LB. Radiofrequency ablation is an effective treatment for high grade dysplasia in Barrett’s esophagus after failed Photodynamic therapy – a case series. Endoscopy. 2011 Jul;43(7):627-30

Dunn JM, Mackenzie GD, Oukrif D, Mosse CA, Banks MR, Thorpe S, Sasieni P, Bown SG, Novelli MR, Rabinovitch PS, Lovat LB. Image cytometry accurately detects DNA ploidy abnormalities and predicts late relapse to high-grade dysplasia and adenocarcinoma in Barrett’s oesophagus following photodynamic therapy. Br J Cancer 2010 May 25;102(11):1608-17

Kent AJ, Graf B, Prasad P, Banks M, Feher M. Diabetes Treatments, Gastrointestinal Symptoms and lower Gastrointestinal Endoscopy. Br J Diabetes &Vasc Dis 2009; 9: 129

Banks MR, Farthing MJG, Robberecht P, Burleigh DE. Anti-secretory actions of a novel vasoactive intestinal polypeptide (VIP) antagonist. British J Pharmacol 2005; 144: 994-1001.

Banks MR, Golder M, Farthing MJG, Burleigh DE. Intracellular potentiation between two second messenger systems may contribute to cholera toxin-induced intestinal secretion in humans.GUT 2004;53:50-57

Mulcahy HE, Kelly P, Banks MR, Connor P, Patchet SE, Farthing MJG, Fairclough PD, Kumar PJ. Factors Associated with Tolerance to, and Discomfort with, Unsedated Diagnostic Gastroscopy.Scand J Gast 2001; 36: 1352-1357

Banks MR, Kumar PJ, Mulcahy HE. Pulse Oximetry saturation levels during routine unsedated diagnostic upper gastrointestinal endoscopy.Scand J Gast 2001; 36: 105-109.

Pollock RCG, Banks MR, Fairclough PD, Farthing MJG. Dilutionaldiarrhoea – underdiagnosed and over-investigated.Europ J GastHep. 2000; 12: 1-3

Rockall AG, Lamb GM, Banks MR, Barrett SP, Al-Kutoubi MA. A prospective study of bacteraemia and bacterial contamination rates of catheters and wires during angiography.JInterventRadiol 1997; 12; 107-111.

view in full page

7 years, 8 months ago