Tag: colorectal cancer

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Cutting Edge Robotic Surgery: Beacons of Excellence at Two Cape Town Public Hospitals

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Dr Tim Forgan at the surgeon’s console of the da Vinci robotic system. (Photo: Biénne Huisman/Spotlight)

By Biénne Huisman

Within South Africa’s beleaguered public health sector – unsettled by budget cuts, understaffing, and divisive NHI legislation – cutting edge surgical robots that have been used to perform more than 600 surgeries at two Cape Town public hospitals are beacons of excellence that offer a glimmer of hope. Spotlight’s Biénne Huisman visited Dr Tim Forgan at Tygerberg Hospital to learn more.

Cutting edge robotic surgery might not immediately come to mind when one thinks of public hospitals, but in a first for public healthcare in South Africa, such systems are being used at two hospitals in the Western Cape.

The da Vinci Xi systems enable surgeons to control operations from a console – steering three arms with steel “hands” equipped with tiny surgical instruments; plus a fourth arm bearing a video camera (the laparoscope). The system translates a surgeon’s hand movements in real time, with enhanced precision, range and visuals, compared to manual surgery.

“It really is next level, it feels like you’re inside the patient,” says colorectal specialist Dr Tim Forgan, Tygerberg Hospital’s da Vinci robotics coordinator. “With this technology we can operate so much finer. You can see ten times better with this robot than with the naked eye; you can see tiny, tiny nerves you wouldn’t normally see. And you can manoeuvre surgical instruments so much better. Because of that, people have way better function after the procedure.”

He explains that the technology allows major surgery to be completed through small incisions – instead of larger cuts made by a doctor’s hand – leading to less bleeding and a faster recovery time.

Over 600 surgeries in two years

Lorraine Gys from Phillipstown in the Northern Cape can attest. On 22 February 2022, the 65-year-old pensioner became the first patient to undergo da Vinci robotic surgery in South Africa’s public sector. Forgan was behind the console, at Tygerberg Hospital.

Gys tells Spotlight: “The next day the sisters offered to wash me, I said to them ‘no, I’m not helpless.’ My recovery was very quick. I was up and about in no time, while the other patients had to be assisted. I was discharged on day four, and back at home I could even continue doing my own chores.”

Two years later, Gys is cancer free. The mother of three, who now lives in Eerste River, recalls how she made news headlines: “Before the operation, Dr Forgan explained everything to me. They asked my permission, saying that media will be there and the [provincial health] minister.”

Indeed, on the day Forgan operated on Gys, removing a cancerous rectal tumour, he was joined in theatre by several onlookers including former Western Cape MEC of Health and Wellness Nomafrench Mbombo.

“Yes it was a circus,” says Forgan, laughing. “A whole bunch of people watching me operate, quite bloody nerve-wracking. Fortunately I’m experienced at having lots of students around watching; plus performing surgery is just so immersive, everything else fades out.”

On that day, also in the operating room was colorectal surgeon Dr Roger Gerjy, keeping an eye. “He’s a very well-known robotic surgeon; a Swedish surgeon who works in Dubai,” says Forgan. “And if there was a problem, Roger would’ve taken over. He was also there to impart tips and tricks: move the instrument like this, shape it like a hockey stick; because with the robot it’s like having your whole arm inside [the body]. He’d give me advice on what to do with my extra floating arm – where to place it and how to manipulate it – because remember you’re controlling three arms at a time.”

Since 2022, the da Vinci robots installed at Cape Town’s two tertiary hospitals: Groote Schuur and Tygerberg, have enabled over 600 minimally invasive surgeries – including colorectal operations, prostatectomies, cystectomies (bladder removal surgery), and gynaecological procedures to treat endometriosis.

Groote Schuur Hospital has the other da Vinci Xi system run by Western Cape public healthcare

A spokesperson for the Western Cape Ministry of Health and Wellness, under former MEC Mbombo, Luke Albert explains: “We can see the immense impact it has for patients and the health system. For example, a traditional open cystectomy patient would require three days of ICU stay, as well as two weeks of hospital stay to recuperate. During this time, on average, 42% of patients require blood transfusions and almost 20% need total parenteral nutrition (when a patient is fed intravenously). A patient undergoing robotic surgery for a cystectomy requires no ICU stay and goes straight to a general ward for no more than six days on average, with no blood transfusions needed.”

Where the money came from

Asked how the department was able to afford R40 million per system for these machines in the context of severe budget cuts, Albert says: “The purchase was applicable to 2021/22 and not the current financial year; with all provincial health departments currently managing the effects of budget cuts.”

Asked the same question, Forgan explains the investment derived from surplus budget discovered within the throes of the COVID-19 pandemic: “There was a surplus because certain services just couldn’t be done. I mean, for us, we couldn’t do elective surgery. And how state funding works; if you don’t spend your [provincial] budget within the financial year, it goes back to central government.”

What it looks like

On a Friday afternoon at Tygerberg Hospital, Forgan is guiding Spotlight along corridors and up grey linoleum stairs, to the theatre where the da Vinci system is used. Dressed in black surgical scrubs bearing his name and a cap; on his feet Forgan is wearing bright pink crocs. In passing, he waves hello to fellow healthcare staff.

Inside the small blindingly white room, Forgan points out the three core components of the da Vinci system. There is a console with two control levers similar to refined joysticks – he demonstrates how to delicately hold them between forefingers and thumbs – a patient-side cart with four interactive metal arms (they are disposable; each arm can be used on twelve patients), and another trolley with a television screen. All connected by blue fibre optic cables.

As we speak, nurses arrive in the theatre, preparing it for upcoming gynaecology procedures scheduled for Monday. Forgan greets them, then continues to expand on his passion for colorectal surgery.

“With colorectal surgery, there’s a high rate of complications, but I really enjoy it, I really enjoy my job. When you have a successful outcome, saving a person from their cancer and prolonging their life through your intervention, that is the reward. Colorectal cancer is a very unpleasant disease, and operating like this can make one hell of a difference in a patient’s life.”

Colorectal cancer on the increase

Forgan adds that colorectal cancer is on the increase: “There aren’t many colorectal surgeons in South Africa, with a dire need for people to operate in this subspecialty. I mean, there are so few of us, we’re all on a WhatsApp group.”

Colorectal or colon cancer is the second most common cancer in South African men (following prostate cancer), and the third most common cancer in women (following breast and cervical cancer), according to the Cancer Association of South Africa.

Originally from Johannesburg, Forgan attended medical school at the University of the Witwatersrand. He qualified as a general surgeon at Stellenbosch University, sub-specialising in colorectal surgery at the University of Cape Town, before studying minimally invasive colorectal surgery at the Academic Medical Centre in Amsterdam.

He is also president of the South African Colorectal Society and runs a part-time private practise with his Tygerberg colleague, Dr Imraan Mia, at Cape Town’s Christiaan Barnard Hospital, where he has 32 all five-star Google reviews.

‘Early adopter’

Forgan considers himself an early adopter. But learning to use the da Vinci system did not happen overnight.

“We trained for ages,” he says. “On the surgical console there’s a simulator, so you spend hours and days and days doing procedures, over and over and over again. You have to get over 95% for each one of the procedures, before you can move on to the next skill.

“Then it’s how to use the machine, how to put it together, what to do if there’s an emergency; what if there’s a power failure and the machine stops working? How to safely remove it from the person. Then we went to the University of Lyon [in France] for two days of hands-on robotics training. And then a proctor – an international expert – comes to your theatre and does the procedures with you. So that was Dr Roger Gerjy, and that’s when we did Lorraine…”

First introduced by American biotechnology company Intuitive Surgical in 1999, the da Vinci Xi systems have sparked some liability lawsuits. An article from the Tampa Bay Times in February cites a lawsuit filed at the United States District Court in West Palm Beach, with a man claiming that a stray electrical arc from a surgical robot burned his wife’s small intestine during a colon cancer procedure, causing her death. The article quotes Intuitive Surgical’s 2023 financial report, which notes 8 606 da Vinci systems in use worldwide, having performed 2 286 000 procedures in 2023. The financial report mentions an undisclosed number of pending lawsuits, which the company disputes.

Nevertheless, Forgan remains an advocate.

Exiting via Tygerberg’s maze of corridors, he continues to reflect on his job. After our meeting, he is set to deliver a talk at the Cape Town International Convention Centre. His manner is earnest. Shrugging, he describes himself as a “glorified plumber”.

Republished from Spotlight under a Creative Commons licence.

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‘Potentially Game Changing’ Immunotherapy Trial for Colorectal Cancer

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Human colon cancer cells. Credit: National Cancer Institute

Results from a new trial indicate that immunotherapy could successfully be used to treat the most common form of colorectal cancer, also known as bowel cancer.

The findings of the new study, a phase 1 trial involving the immunotherapy drugs botensilimab and balstilimab, have been published in the journal Nature Medicine, and it is the first time that consistent and durable responses to immunotherapy have been reported in difficult-to-treat patients.

Co-authored by Professor Justin Stebbing of Anglia Ruskin University (ARU), who describes the results as “potentially game changing”, the study focused on the most common type of colorectal tumours, known as MSS mCRC, or microsatellite stable metastatic colorectal cancer.

Although immunotherapy has previously been shown to work on patients with specific mismatch repair deficient (dMMR) tumours, only a small percentage of colorectal cancer patients have this type of tumour, and immunotherapy has so far been ineffective in patients with more common MSS mCRC tumours.

The new study involved using the immunotherapy drug botensilimab in conjunction with balstilimab on a group of patients in the United States. These drugs are both monoclonal antibodies, which work by triggering the body’s immune system to attack the cancer.

Of the patients in the phase 1 trial, 101 took part in a six-month follow-up and of these, 61% of them saw their tumour shrink or remain stable after receiving a combination of botensilimab (BOT) and balstilimab (BAL). The most common side-effects, or treatment-related adverse events, were diarrhoea and fatigue.

Justin Stebbing, Professor of Biomedical Sciences at Anglia Ruskin University (ARU) and communicating author of the study, said:

“These results are incredibly exciting. Colorectal or bowel cancer is one of the most common forms of cancer worldwide and this is the first time there has been convincing evidence that immunotherapy can work in all forms of colorectal tumours, so this is potentially game changing.

“This is now progressing into later phase clinical trials and we hope the FDA in the United States approve its use very soon. And because this is such an important area, affecting so many people, we hope authorities in the UK are also able to move quickly.”
Joint first author Dr Andrea Bullock, Assistant Professor in Medicine at Beth Israel Deaconess Medical Center, said:

“This study sheds light on the potential of the BOT/BAL combination to treat microsatellite stable metastatic colorectal cancer, the most common form of colorectal cancer which has historically not responded to immunotherapy, and we hope our results will offer new hope for those diagnosed.”
Joint last author Dr Anthony El-Khoueiry, Associate Director of Clinical Research and Chief of Section of Developmental Therapeutics at the USC Norris Comprehensive Cancer Center, said:

“This phase 1 study of botensilimab highlights its promising anti-tumour activity that encompasses immunologically cold tumours such as MSS colorectal cancer. The efficacy noted highlights the potential of botensilimab through its broader engagement of anti-tumour immunity.”

The full open access paper, published in , is available here 

Source: Anglia Ruskin University

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Study Explains How Aspirin can Help Prevent Colorectal Cancer Development

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Photo by cottonbro studio

Studies have shown that long-term daily use of aspirin can help to prevent the development and progression of colorectal cancer, but the mechanisms involved have been unclear. New research has revealed that aspirin may exert these protective effects by boosting certain aspects of the body’s immune response against cancer cells. The findings are published by Wiley online in CANCER, a peer-reviewed journal of the American Cancer Society.

To investigate the effects of aspirin (a nonsteroidal anti-inflammatory drug) on colorectal cancer, investigators in Italy obtained tissue samples from 238 patients who underwent surgery for colorectal cancer in 2015–2019, 12% of whom were aspirin users. Patients were enrolled in the METACCRE section of the IMMUNOlogical microenvironment in the REctal Adenocarcinoma Treatment (IMMUNOREACT 8) multicenter observational study. The study was funded by the Associazione Italiana per la Ricerca sul Cancro (AIRC) and was mainly carried out at the University Hospital of Padova.

Compared with tissue samples from patients who did not use aspirin, samples from aspirin users showed less cancer spread to the lymph nodes and higher infiltration of lymphocytes into tumours. In analyses of colorectal cancer cells in the lab, exposing the cells to aspirin caused increased expression of a protein called CD80 on certain immune cells, which enhanced the capacity of the cells to alert other immune cells of the presence of tumour-associated proteins. Supporting this finding, the researchers found that in patients with rectal cancer, aspirin users had higher CD80 expression in healthy rectal tissue, suggesting a pro-immune surveillance effect of aspirin.

“Our study shows a complementary mechanism of cancer prevention or therapy with aspirin besides its classical drug mechanism involving inhibition of inflammation,” said principal investigator Marco Scarpa MD, PhD, of the University of Padova. “Aspirin is absorbed in the colon by passive diffusion to a significant degree. Its absorption is linear and depends on concentration along the bowel, and in the rectum, the concentration of orally administered aspirin can be much lower than in the rest of the colon. Thus, if we want to take advantage of its effects against colorectal cancer, we should think of how to guarantee that aspirin reaches the colorectal tract in adequate doses to be effective.” 

Source: Wiley

Categories : Cancer GastrointestinalTags :

Bacteria Subtype Linked to Growth in up to 50% of Human Colorectal Cancers

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Human colon cancer cells. Credit: National Cancer Institute

Researchers at Fred Hutchinson Cancer Center have found that a specific subtype of a microbe commonly found in the mouth is able to travel to the gut and grow within colorectal cancer tumours. This microbe is also a culprit for driving cancer progression and leads to poorer patient outcomes after cancer treatment.

The findings, published in Nature, could help improve therapeutic approaches and early screening methods for colorectal cancer, which is the second most common cause of cancer deaths in adults in the U.S. according to the American Cancer Society.

Examining colorectal cancer tumours removed from 200 patients, the Fred Hutch team measured levels of Fusobacterium nucleatum, a bacterium known to infect tumours. In about 50% of the cases, they found that only a specific subtype of the bacterium was elevated in the tumour tissue compared to healthy tissue.

The researchers also found this microbe in higher numbers within stool samples of colorectal cancer patients compared with stool samples from healthy people.

“We’ve consistently seen that patients with colorectal tumours containing Fusobacterium nucleatum have poor survival and poorer prognosis compared with patients without the microbe,” explained Susan Bullman, PhD, Fred Hutch cancer microbiome researcher and co-corresponding study author. “Now we’re finding that a specific subtype of this microbe is responsible for tumour growth. It suggests therapeutics and screening that target this subgroup within the microbiota would help people who are at a higher risk for more aggressive colorectal cancer.”

In the study, Bullman and co-corresponding author Christopher D. Johnston, PhD, Fred Hutch molecular microbiologist, along with the study’s first author Martha Zepeda-Rivera, PhD, a Washington Research Foundation Fellow and Staff Scientist in the Johnston Lab, wanted to discover how the microbe moves from its typical environment of the mouth to a distant site in the lower gut and how it contributes to cancer growth.

First they found a surprise that could be important for future treatments. The predominant group of Fusobacterium nucleatum in colorectal cancer tumours, thought to be a single subspecies, is actually composed of two distinct lineages known as “clades.”

“This discovery was similar to stumbling upon the Rosetta Stone in terms of genetics,” Johnston explained. “We have bacterial strains that are so phylogenetically close that we thought of them as the same thing, but now we see an enormous difference between their relative abundance in tumours versus the oral cavity.”

By separating out the genetic differences between these clades, the researchers found that the tumour-infiltrating Fna C2 type had acquired distinct genetic traits suggesting it could travel from the mouth through the stomach, withstand stomach acid and then grow in the lower gastrointestinal tract. The analysis revealed 195 genetic differences between the clades.

Then, comparing tumour tissue with healthy tissue from patients with colorectal cancer, the researchers found that only the subtype Fna C2 is significantly enriched in colorectal tumour tissue and is responsible for colorectal cancer growth.

Further molecular analyses of two patient cohorts, including over 200 colorectal tumours, revealed the presence of this Fna C2 lineage in approximately 50% of cases.

The researchers also found in hundreds of stool samples from people with and without colorectal cancer that Fna C2 levels were consistently higher in colorectal cancer.

“We have pinpointed the exact bacterial lineage that is associated with colorectal cancer, and that knowledge is critical for developing effective preventive and treatment methods,” Johnston said.

Source: Fred Hutchinson Cancer Center

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Diabetes Worsens Colorectal Cancer Survival Odds by 41%

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Photo by Nataliya Vaitkevich on Pexels

In an analysis of information on adults with colorectal cancer, patients who also had diabetes, particularly those with diabetic complications, faced a higher risk of early death. The results are published in CANCER, a peer-reviewed journal of the American Cancer Society.

For the study, Kuo‐Liong Chien, MD, PhD, of National Taiwan University, and his colleagues examined data registered between 2007 and 2015 in the Taiwan Cancer Registry Database, which is linked to health insurance and death records. Their analysis included 59 202 individuals with stage I–III colorectal cancer who underwent potentially curative surgery to remove their tumours. Among these patients, 9448 experienced a cancer recurrence and 21 031 died from any cause during the study period.

Compared with individuals without diabetes, those with uncomplicated diabetes were at a minimally or insignificantly higher risk of all‐cause and cancer‐specific death, whereas those with complicated diabetes had 85% higher odds of death from any cause and 41% higher odds of death from cancer. These associations were more pronounced in women and in patients with early‐stage colorectal cancer.

Also, compared to patients without diabetes, patients with uncomplicated or complicated diabetes had a 10–11% higher risk of colorectal cancer recurrence.

The mechanisms behind the relationship between diabetic severity and poor colorectal cancer prognosis could involve various pathways and responses triggered by high insulin and glucose levels in the blood, as well as elevated inflammatory states, which are characteristic of type 2 diabetes.

“While a higher diabetes prevalence was noted in patients with colorectal cancer, the study suggests that coordinated medical care involving multiple specialists can help prevent diabetes complications, potentially improving long-term colorectal cancer oncological outcomes, particularly in women and patients with early-stage cancer,” said Dr Chien.

Source: Wiley

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Statins Might Reduce the Risk of Colorectal Cancer in Those with Ulcerative Colitis

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Photo by Towfiqu Barbhuiya on Unsplash

New research published in eClinicalMedicine suggests that statins might protect patients with ulcerative colitis from developing and dying from colorectal cancer. The study, by Karolinska Insitut researchers, also found that statin treatment was associated with a lower risk of death regardless of cause in patients with ulcerative colitis or Crohn’s disease.

First author Jiangwei Sun notes that previous studies have shown that the risk of colorectal cancer in patients with IBD, such as ulcerative colitis and Crohn’s disease, is 50% higher than in the general population. This is likely to be because of the chronic gut inflammation that these patients have. Researchers have long sought drugs that can reduce the inflammation-related cancer risk.

“Even though more studies are needed to confirm our results, our study suggests that statins can prevent colorectal cancer in patients with inflammatory bowel disease (IBD), which is a high-risk group for this kind of cancer,” says Dr Sun.

The observational study conducted by Dr Sun and his colleagues compared over 10 500 IBD patients from around the country, of whom half were statin users; the other half of the group, who were matched with the first, were not. After a follow-up period of, on average, 5.6 years, 70 of the statin group and 90 of the non-statin group had been diagnosed with colorectal cancer.

The effect increased over time

The protective effect was directly proportional to the length of time the patient had been on statins and could be demonstrated after two years’ treatment.

There were also fewer deaths from colorectal cancer in the statin group (20) than in the non-statin group (37) during the study period, and deaths regardless of cause (529 versus 719).

The study shows that some 200 IBD patients need to be treated with statins to avoid one case of colorectal cancer or death from the cancer within ten years of treatment onset. The protective effect was only statistically valid for patients with ulcerative colitis.

“We think this is because the study contained fewer patients with Crohn’s disease,” explains Dr Sun. “More and larger studies compiling data from patient populations in many countries will probably be needed to achieve statistical significance for Crohn’s disease.”

Significantly fewer deaths

To avoid death regardless of cause during the same ten-year period, the number of treated patients dropped to 20, on account of how statins also protect against more common conditions, such as cardiovascular disease. Statins were linked to fewer deaths in both ulcerative colitis and Crohn’s disease patients.

The study was based on the ESPRESSO-cohort, which is run by its initiative-taker Jonas F Ludvigsson, paediatrician at Örebro University Hospital and professor at Karolinska Institutet, and the study’s last author.

“In that we can combine tissue data from patients with colorectal cancer with data from Swedish health registries, we’re uniquely placed to study the long-term effects of drugs for IBD,” he says. “Our hope is that these studies will improve the care of IBD patients.”

The most solid evidence so far

According to the researchers, the new results provide the most solid evidence so far that statins could be an effective prophylactic for colorectal cancer among people with IBD. However, more knowledge must be gathered before the treatment can be recommended in general guidelines.

“More studies are needed to ascertain if there is a causal relationship, at what point of the pathological process statins should be administered, what a reasonable dose would be and how long treatment needs to last if it’s to be of benefit,” says Dr Sun.

Source: Karolinska Institut


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How High-fat Diets Affect Gut Bacteria and Increase Colorectal Cancer Risk

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Gut Microbiome. Credit Darryl Leja National Human Genome Research Institute National Institutes Of Health

The increasing rate of obesity and high-fat diets are suspected to be behind the growing rates of colorectal cancers in people aged under 50. Now, in a study published in Cell Reports, researchers at have discovered how high-fat diets can change gut bacteria and alter digestive molecules called bile acids that are modified by those bacteria, predisposing mice to colorectal cancer.

In the study, researchers from the Salk Institute and UC San Diego found increased levels of specific gut bacteria in mice fed high-fat diets. They showed that those gut bacteria alter the composition of the bile acid pool in ways that cause inflammation and affect the replenishment rate of intestinal stem cells replenish.

“The balance of microbes in the gut is shaped by diet, and we are discovering how alterations in the gut microbial population (the gut microbiome) can create problems that lead to cancer,” says co-senior author and Professor Ronald Evans, director of Salk’s Gene Expression Laboratory. “This paves the way toward interventions that decrease cancer risk.”

In 2019, Evans and his colleagues showed in mice how high-fat diets boosted the overall bile acid levels. The shift in bile acids, they found, shut down a key protein in the gut, the Farnesoid X receptor (FXR). and increased the prevalence of cancer.

However, there were still missing links in the story, including how the gut microbiome and bile acids are changed by high-fat diets.

In the new work, Evans’ group teamed up with the labs of Rob Knight and Pieter Dorrestein at UC San Diego to examine the microbiomes and metabolomes (collections of dietary and microbially derived small molecules) in the digestive tracks of animals on high-fat diets. They studied mice genetically more susceptible to colorectal tumours.

The scientists discovered that although mice fed high-fat diets had more bile acids in their guts, it was a less diverse collection with a higher prevalence of certain bile acids that had been changed by gut bacteria. They also showed that these modified bile acids affected the proliferation of stem cells in the intestines. Without frequent replenishment, they accumulate mutations – a key step toward encouraging the growth of cancers, which often arise from these stem cells.

“We are only just beginning to understand these bacterially-conjugated bile acids and their roles in health and disease,” says co-author Michael Downes, a staff scientist at Salk.

There were also striking differences in the microbiomes of the mice on high-fat diets: the collections of gut bacteria in these mice’s digestive tracts were less diverse and contained different bacteria than the microbiomes of mice not on high-fat diets. Two of these bacteria – Ileibacterium valens and Ruminococcus gnavus – were able to produce these modified bile acids.

The scientists were surprised to discover that a high-fat diet actually had a greater impact on the microbiome and modified bile acids than a genetic mutation that increases cancer susceptibility in the animals.

“We’ve pinpointed how high-fat diet influences the gut microbiome and reshapes the bile acids pool, pushing the gut into an inflamed, disease-associated state,” says co-first author Ting Fu, a former postdoctoral fellow in the Evans lab.

The researchers believe high-fat diets change the composition of the microbiome, encouraging the growth of bacteria like I. valens and R. gnavus. In turn, that boosts levels of modified bile acids. In a vicious cycle, those bile acids create a more inflammatory environment that can further change the makeup of gut bacteria.

“We’ve deconstructed why high-fat diets aren’t good for you, and identified specific strains of microbes that flare with high-fat diets,” says Evans, March of Dimes Chair in Molecular and Developmental Biology. “By knowing what the problem is, we have a much better idea of how to prevent and reverse it.”

In the future, the team will study how quickly the microbiome and bile acids change after an animal begins eating a high-fat diet. They also plan to study ways to reverse the cancer-associated effects of a high-fat diet by targeting FXR – the protein that they previously discovered to be associated with bile acid changes.

Source: Salk Institute

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Are Nitrates a Cancer Menace… or Cardiac Protector?

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Photo by Louis Reed on Unsplash

Despite our understanding of nutrition expanding remarkably in recent times, few aspects of our diet continue to confuse and divide the experts like nitrate. For a long time nitrate has been viewed warily, with previous research showing it could potentially be linked to causing cancer.

However, subsequent research has revealed dietary nitrate also has various cardiovascular health benefits, which could help reduce the risk of related conditions such as heart disease, dementia and diabetes.

So, how can one dietary compound have such contrasting potential risks and benefits? Researchers set out to find out how and why nitrate such contrasting potential risks and benefits, publishing their findings in Trends in Food Science & Technology.

All about the source

Dr Catherine Bondonno led a review of nitrate research and says the key may lie in where it comes from.

“We get nitrate from three major dietary sources: meat, water and vegetables,” she said.

“Nitrate’s reputation as a health threat stems from 1970, when two studies showed it can form N-nitrosamines, which are highly carcinogenic in laboratory animals.

“However, no human studies have confirmed its potential dangers, and our clinical and observational studies support nitrate preventing cardiovascular disease if it’s sourced from vegetables.

“So the review looked to unpack all of that, identify new ways forward and ways that we can solve this puzzle, because it’s really time to address it: it’s been 50 years.”

Urgency required

Despite recent research indicating the source of nitrate may affect its health benefits and risks, current dietary guidelines relating to nitrate have been in place since the 1970s and don’t differentiate between nitrate from meat, vegetables and water.

Dr Bondonno said while the 1970s animal studies reported a small incidence of malignant tumours, there was evidence not all nitrates deserve to be “tarred with the same brush.”

“For instance, unlike meat and water-derived nitrate, nitrate-rich vegetables contain high levels of vitamin C and/or polyphenols that may inhibit formation of those harmful N-nitrosamines associated with cancer,” she said.

Dr Bondonno said it was vital more research was conducted so guidelines could be updated.

“The public are unlikely to listen to messages to increase intake of nitrate-rich vegetables, if they are concerned about a link between nitrate intake and cancer.”

However, she stressed while official guidelines hadn’t changed, the apparent benefits of nitrate had seen many people potentially put themselves at risk.

“We need to be sure nitrate-rich vegetables don’t actually have an increased risk of cancer if we consume a higher amount,” she said.

“High dosage nitrate supplements are already used to improve physical performance in sport, while vegetable nitrate extracts are being added to cured meat products with a “clean label” claim, purporting to be better for you.

“So we really need to get this right.”

What do we eat, then?

Given its divided experts in the field, Dr Bondonno said it’s understandable people may be confused as to whether nitrate is good or bad for them.

“They’re probably thinking, ‘If I can’t have a salad, what CAN I have?’,” she said.

Despite the debate, she said current evidence suggests people should aim to get their nitrate from vegetables — but there was no need to go overboard.

“Dark green, leafy vegetables and beetroot are good sources, our research shows one cup of raw, or half a cup cooked per day is enough to have the benefits on cardiovascular health,” she said.

“We know processed meat isn’t good for us and we should limit our intake, but whether it’s the nitrate in them that is causing the problem or something else, we don’t know.

“It just further emphasises the need to investigate dietary nitrate to clarify the message for people.

“The potential cancer link was raised 50 years ago; now it’s time to conduct an in-depth analysis to distinguish fact from fiction.”

Source: Edith Cowan University

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Defensiveness Keeping People from Taking at-home Colorectal Cancer Stool Tests

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Photo by Priscilla du Preez on Unsplash

Despite colorectal cancer being highly treatable, especially when detected early, many people do not undergo recommended screening, even with the availability of at-home stool faecal immunochemical test (FIT) kits. New research published in CANCER reveals that people who react defensively to the invitation to get screened are less likely to take part.

For the study, Nicholas Clarke, PhD, of Dublin City University in Ireland, surveyed individuals in Dublin who had been invited to participate in a FIT screening program in 2008–2012. Questionnaires were mailed in September 2015 to all individuals who were invited to participate (over two screening rounds) but had declined and a random sample of individuals who had participated. Following two reminders, questionnaires were completed by 1988 people who participated in screening and 311 who did not.

Those who did not do FIT-based screening were more likely to provide responses indicating greater defensiveness. This was apparent for all questions related to the different domains of what is called defensive information processing (DIP). The four domains of DIP include:

  • attention avoidance (reducing risk awareness by avoidance),
  • blunting (active mental disengagement through avoidance and accepted denial),
  • suppression (acknowledging others’ risk but avoiding personal inferences through self-exemption beliefs), and
  • counter-argumentation (arguing against the evidence).

“People who react defensively to the invitation to colorectal cancer screening are less likely to take part, and this seems to be due to such misconceptions that having a healthy lifestyle or having regular bowel movements means that they do not need to be screened. Similarly, some people believe testing can be delayed while they wait for a ‘better’ test (even though the current test works very well) or wait until their other health concerns are under control,” explained Dr Clarke. “Some people also react defensively because they believe cancer is always fatal, which is not true. All of these factors can result in people making a decision not to take the home-based screening test.”

Dr Clarke noted that the study’s findings indicate that even well-designed health communication campaigns and proactive screening programs may be hindered by individuals’ defensive beliefs. “The measures used in this study could be used to help identify people who may need extra support to take part in colorectal cancer screening programs worldwide,” he said. “The results suggest that screening programs need strategies to decrease procrastination and address misconceptions about colorectal cancer and screening.”

He also stressed the importance of trying to make colorectal cancer screening something that everyone routinely does when they reach middle age.

An accompanying editorial by Beverly Beth Green MD, MPH advocates for additional research to test different strategies, such as financial incentives, for decreasing DIP in participants.

Source: Wiley

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Temporary Low-protein Diet could Enhance Colon Cancer Treatment

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A brief switch to a low-protein diet could be a key to enhancing colon cancer treatment, say researchers investigating cancer metabolism. They reported their findings in the journal Gastroenterology.

Like all cells, cancer cells need nutrients to survive and grow. One of the most important nutrient sensing molecules in a cell is called mTORC1. Often called a master regulator of cell growth, it lets cells sense different nutrients, thereby growing and proliferating. When nutrients are limited, cells dial down nutrient sensing cascade and turn off mTORC1.

While mTORC1 is known to be hyperactive in colon cancer, the key question is whether colon tumours hijack nutrient sensing pathways to fire up the master regulator.

“In colon cancer, when you decrease the nutrients available in the tumours, the cells don’t know what to do. Without the nutrients to grow, they undergo a kind of crisis, which leads to massive cell death,” said senior author Yatrik M. Shah, PhD, professor at Michigan Medicine.

Researchers found in cells and in mice that a low-protein diet blocked the nutrient signalling pathway that fires up a master regulator of cancer growth.

The regulator, mTORC1, controls how cells use nutritional signals to grow and multiply. It’s highly active in cancers with certain mutations and is known to cause cancer to become resistant to standard treatments. A low-protein diet, and specifically a reduction in two key amino acids, changed the nutritional signals through a complex called GATOR.

GATOR1 and GATOR2 work together to keep mTORC1 in business. When a cell has plenty of nutrients, GATOR2 activates mTORC1. When nutrients are low, GATOR1 deactivates mTORC1. Limiting certain amino acids blocks this nutrient signalling.

Previous efforts to block mTORC have focused on inhibiting its cancer-causing signals. But these inhibitors cause significant side effects — and when patients stop taking it, the cancer comes back. The study suggests that blocking the nutrient pathway by limiting amino acids through a low-protein diet offers an alternative way to shut down mTORC.

“We knew that nutrients were important in mTORC regulation but we didn’t know how they directly signal to mTORC. We discovered the nutrient signalling pathway is just as important to regulate mTORC as the oncogenic signalling pathway,” said study first author Sumeet Solanki, Ph.D., a research investigator at the Rogel Cancer Center.

Researchers confirmed their findings in cells and mice, where they saw that limiting amino acids stopped the cancer from growing and led to increased cell death. They also looked at tissue biopsies from patients with colon cancer, which confirmed high markers of mTORC correlated with more resistance to chemotherapy and worse outcomes. Solanki said this could provide an opportunity to direct treatment for patients with this marker.

“A low-protein diet won’t be standalone treatment. It has to be combined with something else, such as chemotherapy,” Solanki said.

The risk with a low-protein diet is that people with cancer often experience muscle weakness and weight loss, which limiting protein could exacerbate.

“Putting cancer patients on a protein-deficient diet long-term is not ideal. But if you can find key windows – like at the start of chemotherapy or radiation – when patients could go on a low protein diet for a week or two, we could potentially increase the efficacy of those treatments,” Shah said.

Further research will refine this concept of a therapeutic window to limit amino acids. Researchers will also seek to understand how these pathways are creating resistance to treatment and whether an inhibitor could block the GATOR complexes.

Source: Michigan Medicine – University of Michigan