Helicobacter pylori: what does it taste like?

The Journal’s early support for a Helicobacter pioneer allowed publication of key results

Helicobacter pylori: what does it taste like?

The title above is the most common question people ask me about the spiral bug. By the time this article comes to press the answer might even be published. But the question leads back to my paper in the MJA 29 years ago.1 It described the deliberate self-administration of Helicobacter pylori and the observation that it caused an acute upper gastrointestinal illness with vomiting, halitosis and an underlying achlorhydria. Embarrassed to admit that it was a self-experiment, I wrote the paper in the third person at the suggestion of my coauthors, but they at least had witnessed my sufferings over a 14-day period, so it was not entirely subjective and anecdotal. It came to be published in the Journal because I had received a letter from the Editor at the time, Alistair Brass, saying how much he liked the Lancet paper I had coauthored with Robin Warren,2 and did I have any others up my sleeve on the subject? Warren and I had had such a bad run with editors by then that it seemed a breath of fresh air to meet an editor who actually liked original material. So I finished the paper and submitted it to the Journal in about September 1984. However, then showing his true colours, the Editor sent it out to scrupulous reviewers who asked for a complete rewrite, which made it a much better paper, but delayed its publication until April 1985.1

I obtained incredible value from the MJA publication. Who knew that so many people were following the MJA? In a Lancet editorial soon afterwards, then Editor David Sharp “re-tweeted” the MJA paper, agreeing that H. pylori infection explained a mysterious illness that was spreading from time to time in gastroenterology laboratories performing acid secretion studies.3 An unnoticed infectious agent was contaminating their equipment and infecting many of the volunteers.4,5

Re-reading that paper every few years, I am impressed by how far the MJA Editor was “sticking his neck out” in allowing me to publish a hypothesis as to the cause of peptic ulcer. It was a further 5 years before journals allowed the word “cure” to appear in articles about duodenal ulcer,6 and almost a decade before mainstream United States journals could accept it as proven.7

Modifying the gluten-free threshold for foods: first do no harm

To the Editor: The gluten-free (GF) diet for people with coeliac disease (CD) is complex, costly, and compliance with the diet is variable. Coeliac Australia, with the Australian Food and Grocery Council, are lobbying to increase the mandated gluten threshold for GF foods.1 The situation in Australia since 1995 has been that there must be “no detectable gluten” in foods labelled “gluten free”. The proposed new standard is “< 20 parts per million (ppm)”. This has been proposed because food testing has become increasingly sensitive over the years, resulting in fewer foods being considered gluten free. The current detection level of food testing is about 3 ppm. Unfortunately, the proposed new GF standard may not be safe for patients with CD.

There are few high-quality studies determining a safe gluten intake for patients with CD, although it is known that tolerable amounts vary between patients.2 In one study, 42 patients with CD who were eating a GF diet received 0, 10 or 50 mg of gluten daily for 3 months (10 mg in 500 g of food represents 20 ppm; 10 mg gluten is ingested in 1/250th of a slice of bread containing 2.5 g gluten). Patients’ duodenal mucosa were examined histologically before and after the gluten challenge. The study concluded that, for patients with CD, the daily dietary intake of gluten should be < 50 mg.3 This study has been interpreted as suggesting that 10 mg of gluten daily is safe.1 Regrettably, the patients in the study were a selective group, possibly less sensitive to gluten and, of those receiving 10 mg of gluten daily, one had symptomatic relapse and several showed worsening CD on histological examination.3 It is therefore surprising this study has been particularly influential in recommending a GF standard of < 20 ppm.1

In 2011, a comprehensive United States Food and Drug Administration (FDA) safety report concluded that gluten levels in food of < 1 ppm are required to protect the greatest number of patients with CD.4 Despite this, a long-awaited FDA ruling, released on 2 August 2013, sets the GF standard at < 20 ppm.5 This formalises tighter standards than previously existed in the US. Establishing a standard is complex, requiring consideration of issues such as industry and consumer concerns, industry regulation, economics, international precedent and safety.

The concept of doing no harm in health care is paramount. In Australia, where concerns about the availability of GF foods have been raised,1 it may be prudent to allow GF foods an increase in “measurable” gluten (eg, from undetectable to < 1–3 ppm). By contrast, increasing the “permissible” level of gluten (from undetectable to < 20 ppm) will increase overall gluten ingestion in a GF diet. For an undetermined proportion of patients with CD, this will lead to adverse health outcomes and generate additional health care costs.

Iron deficiency anaemia in a young woman: a plea for early investigation

Following a tragic case of late diagnosis of colorectal cancer, a father calls for an overhaul of current guidelines for the investigation of iron deficiency anaemia in premenopausal women

My 29-year-old daughter tragically died of metastatic colon cancer in 2010, after late diagnosis of the primary caecal tumour.

At 22 years of age, she was lacking in energy and generally feeling unwell. She presented early to her local medical clinic where she was found to have severe iron deficiency anaemia (IDA) (haemoglobin, 61 g/L). Supplemental iron tablets were prescribed over a period of 6 months, with some improvement, although her iron reserves remained depleted. She was referred to a gastroenterologist, who examined her and performed a gastroscopy to test for coeliac disease. Nothing untoward was discovered; a colonoscopy was not performed, and she was returned to her general practitioner for continuation of iron supplementation. Eleven months later (at 24 years of age), she felt a lump in her lower abdomen and was referred to a gastrointestinal surgeon for investigation. He performed a colonoscopy and colectomy, which revealed a caecal cancer that had spread to her lymph glands and liver.

All available oncological treatment and the most comprehensive surgery followed over several years but failed to stop the spread of the cancer. This chapter in my daughter’s life was gut-wrenching for all involved.

Before her diagnosis, my daughter saw several GPs, a gastroenterologist and later a general physician — none of whom recognised that she was suffering from colon cancer. No doubt her anaemia was assumed to be due to menstrual loss and/or low dietary iron intake. Time was wasted in trying to boost her iron intake, without properly considering another plausible explanation.

I am advised that current guidelines for the management of patients with IDA indicate that all patients should be screened for coeliac disease and that, in premenopausal women, colonic investigation should be reserved for those with colonic symptoms, a strong family history or persistent IDA after iron supplementation and correction of potential causes.

In dealing with such a devastating medical condition as bowel cancer, it is critical that the first diagnosis be early and correct. Cancers diagnosed early can have good outcomes.

In this respect, the advice quoted above seems inadequate in two ways.

First, even though the absolute numbers of young people presenting with colon cancer in any year may not be large, unless their cancer is detected early, they are not being afforded proper advice and their symptoms are not being correctly diagnosed.

Second, relying on (known) strong family history must be fraught with dangers. Many patients will not be comprehensively aware of relevant family medical history — the profession may need to rethink whether it is prudent to assume that there is no family history, when the history may just not be known.

Cancers in the right colon often do not present with obvious bleeding or bowel symptoms; however, anaemia is the classic presentation.

I am advised by an expert in the field that experienced gastrointestinal surgeons and physicians are strongly of the view that colon cancer, particularly in the right colon, should be excluded in cases of significant IDA in all age groups.

I believe that the Gastroenterological Society of Australia should review the professional guidelines applicable to their practitioner members in this regard. The guidelines clearly need much greater specificity, and where exceptionally low initial haemoglobin readings apply, both endoscopy and colonoscopy should be performed immediately.

My beautiful daughter had pursued her tertiary studies with distinction, had attained her professional accreditation, and had a most positive business and personal life in front of her. It behoves members of the medical profession charged with a duty of care to each of their patients to objectively test for early cancer detection when significant anaemia presents. Most regrettably, my daughter was very badly advised. Rare occurrence is no reason to deny proper diagnosis. My daughter suffered nauseating physical pain and mental anguish for 7 years — all because she was not properly assessed early enough to give her a fighting chance. I await the proper, reasoned response of the medical profession to this tragedy.

Investigating iron deficiency anaemia

Persistent unexplained iron deficiency should always be investigated, but iron deficiency is common and colorectal cancer rare in young women — the risks of investigation must be balanced against the risks of serious pathology

We would like to express our sympathy to the family and to acknowledge the tragedy of the circumstances in regard to the death of their
29-year-old family member from metastatic colon cancer.

To summarise, the woman presented at the age of 22 years with severe iron deficiency anaemia (IDA) and fatigue but no history of excessive menstrual blood loss. She underwent gastroscopy to test for coeliac disease; colonoscopy was not performed. She was treated with iron supplementation over 6 months, although her father notes that her iron reserves remained depleted. Tragically, she later presented with metastatic colon cancer.

The patient’s father notes that current guidelines for
the management of patients with IDA indicate that, in premenopausal women, gastrointestinal (GI) investigation should be reserved for those with colonic symptoms,
a strong family history or persistent IDA after iron supplementation and correction of potential causes.
From our understanding, the young woman had persisting IDA despite iron supplementation and would have
come within Gastroenterological Society of Australia recommendations for further diagnostic investigation (http://www.gesa.org.au/files/editor_upload/File/Professional/Iron_def.pdf).

The patient’s father also comments on the risks of placing too much emphasis on family history. While
we agree that patients may not always be aware of this information, when it is available it becomes important for those with an increased risk of colorectal cancer (CRC) because of such a history. Family history of CRC has a prominent position in international guidelines regarding screening.

Iron deficiency is common among premenopausal women. A recent Australian study showed a prevalence of 10.6% among females under 50 years of age, 2.8% among females over 50 years of age, and 0.3% among males.1 The high prevalence in young women relates to menstrual losses and lower dietary iron intake rather than to a higher prevalence of GI disease, and it is in this context that the Gastroenterological Society of Australia recommendations were written. While it is important to make an accurate and early diagnosis of CRC, it is also important to avoid overinvestigating young women with iron deficiency who have a more likely cause such as menstrual loss and/or inadequate diet and who respond appropriately to iron replacement and gynaecological treatment. Colonoscopy
is generally safe but has potentially life-threatening complications in 1 in 1000 to 1 in 5000 cases. It has been suggested that faecal occult blood testing (FOBT) could
be used to eliminate the likelihood of CRC or to provide justification for colonoscopy. Unfortunately, FOBT is falsely negative in 20% of people who have CRC and would provide false reassurance.2 FOBT reduces CRC mortality when used to screen asymptomatic people, but it is not a good diagnostic test. An experienced GI physician or surgeon must judge the clinical significance of IDA and then make a recommendation for further endoscopic investigation that considers the benefit of the procedure in relation to the risk for that individual patient.

In contrast to iron deficiency, CRC is not common in young women. While two United States studies showed an increased incidence in 20–29-year-olds between 1992 and 2005, CRC remains uncommon in this age group.3,4 In 2006, the incidence in 20–24-year-olds was 1.5 per 100 000, which means there is only a 1 in 66 000 chance that a person in this age group will develop the disease over
the next year.4 To put this in context, the incidence among 65–69-year-olds was 160.9 per 100 000. The Australian Institute of Health and Welfare projected that the CRC incidence among men aged 20–24 years would rise from 1.1 to 2.6 per 100 000 in 2011, and among women aged
20–24 years, from 1.1 per 100 000 in 2001 to 1.3 per 100 000 in 2011. In comparison, the projected incidence per 100 000 for 2011 in the 65–69-year age group was 304.3
for men and 203.6 for women.5 Overall, while there is an increase in CRC incidence among individuals aged in their 20s, the absolute number with CRC remains very low.

Emergency surgery model improves outcomes for patients with acute cholecystitis

To the Editor: Reducing the time from presentation to cholecystectomy in patients with acute cholecystitis has been shown to benefit patients (eg, by reducing the duration of patient discomfort before surgery) and to be cost-effective.1–3 Benefits have also been shown for performing cholecystectomy during the index admission for gallstone pancreatitis.4

Geelong Hospital (in regional Victoria) introduced daily general surgery emergency theatre sessions in February 2011. We compared 401 patients who presented to the emergency department (ED) with acute cholecystitis from February 2008 to January 2011 (control period) with 137 who presented from February 2011 to January 2012 (intervention period). We also compared patients who presented with gallstone pancreatitis — 91 in the control period and 38 in the intervention period. For patients who underwent cholecystectomy during their index admission, we analysed the time of presentation to the ED and time of surgery. Complication rates (for bile duct injury, bile leak requiring intervention, unplanned endoscopic retrograde cholangiopancreatography, mortality or unplanned reoperation) were analysed by medical record review.

We found an increase in the proportion of patients with acute cholecystitis who had a cholecystectomy during their index admission, excluding those who were transferred to the private system, from 53% (199/373) to 72% (94/130) (P < 0.001). We also found a decrease in the median waiting time from patient arrival in the ED to operation for those with acute cholecystitis who had a cholecystectomy during their index admission, from 41.8 to 26.4 hours (P < 0.001). However, there was no significant difference in the complication rate for patients with acute cholecystitis who received a cholecystectomy in the control and intervention periods (P = 0.96).

Patients with gallstone pancreatitis underwent a cholecystectomy after their pancreatitis had settled. Of those who presented with gallstone pancreatitis in the control period, 42% (38/91) had their cholecystectomy during their index admission; this increased to 63% (24/38) in the intervention period (P = 0.03).

The proportion of cholecystectomies (for acute cholecystitis or gallstone pancreatitis) performed after-hours did not increase, despite an increase, from 51% to 70%, in patients receiving cholecystectomy during their index admission. Operations were performed in-hours for 73% (172/237) of those who underwent cholecystectomy during their index admission in the control period and 70% (83/118) of those who underwent cholecystectomy during their index admission in the intervention period (P = 0.15). For both of these groups, the median postoperative length of stay was 2 days (P = 0.67).

These data show that introducing dedicated general surgery emergency theatre sessions improved our ability to perform surgery in a timely manner for patients who presented with cholecystitis or gallstone pancreatitis.