Journals Watch - Gallstones, H1N1 and cancer

Too busy to read all the journals? Let Dr Sally Hope keep you up to date with the latest research.

Statin use and risk of gallstone diseaseJAMA 2009; 302: 2001-7
Statins decrease hepatic cholesterol biosynthesis and may lower the risk of cholesterol gallstones by reducing the cholesterol concentration in the bile.

This case-control analysis using the UK-based general practice research database investigated the association between lipid-lowering agents and the risk of incident gallstone disease requiring cholecyst-ectomy.

A total of 27,035 patients with cholecystectomy and 106,531 matched controls were identified, including 2,396 patients and 8,868 controls who were taking statins.

Compared with non-use, current statin use was 3.2 per cent for patients and 3.7 per cent for controls for 20 or more prescriptions (adjusted OR 0.64; 95% CI 0.59-0.70), showing that long-term use of statins was associated with a decreased risk of gallstones requiring cholecystectomy.

It is a small decrease, but this has also been shown in other populations, so does seem to be a real beneficial side-effect.

ECMO for influenza A H1N1 JAMA 2009; 302: 1888-95
Australia and New Zealand have already experienced an influenza A (H1N1) pandemic, so we can learn from their experience.

Some H1N1 patients developed severe acute respiratory distress syndrome (ARDS) and were treated with extracorporeal membrane oxygenation (ECMO).

This study observed all patients (n=68) with H1N1-associated ARDS treated with ECMO in 15 ICUs in Australia and New Zealand between June and August 2009. The incidence was fortunately low: 2.6 ECMO cases per million population.

An additional 133 patients with influenza A received mechanical ventilation but no ECMO. The 68 patients who received ECMO had a median age of 34.4 (26.6-43.1) years and 50 per cent were men. The median duration of ECMO support was 10 (7-15) days. At the time of writing the study, 14 patients (21 per cent) had died and six remained in the ICU, two of whom were still receiving ECMO.

The ECMO-treated patients were often young adults with severe hypoxemia. I was struck that the mortality was in fit, otherwise healthy young adults, which is exactly the group we are not vaccinating.

Breast cancer and changes in the use of HRT Maturitas 2009; 64: 80-85
Two studies, the American Women's Health Initiative study in 2002 and the UK Million Women Study in 2003, dropped a bombshell on prescribing HRT and radically changed practice.

This paper looked at the expected and observed changes in the incidence of breast cancer in the past decade.

Between 2001/2 and 2005/6, significant reductions in the incidence of breast cancer of up to 22 per cent were reported in many US and European populations, consistent with the drop in use of HRT. Declines in the rates of breast cancer were strongest for the 50-60 years age group (those most likely to be current users of HRT) and were largest among women with the highest pre-decline prevalence of HRT use and the sharpest decline in its use.

Estrogen receptor positive and progesterone receptor positive cancers were mainly affected - the malignancies most strongly associated with HRT use.

The 22 per cent reduction in breast cancers seen after the publication of these two papers shows how powerful large trials can be. Nevertheless, the issue of how to advise women contemplating HRT use today remains: evidence-based patient choice requires time from the GP to ensure women understand the pros and cons of their treatment.

Hereditary ovarian cancer Maturitas 2009; 64: 172-6
Until recently, intensive screening of the ovaries was recommended to mutation carriers for hereditary ovarian cancer and their first-degree female relatives.

However, according to this review, as screening is not effective in detecting early-stage ovarian cancer, women should be counselled for a prophylactic bilateral salpingo-oophorectomy (pBSO) shortly after child-bearing age (>35 years).

Many mutation carriers already choose to undergo pBSO to reduce their cancer risks; but the age of prophylactic surgery may interfere with reproductive issues in life.

Many patients are just thinking about conception in their 30s, and have not had their children by 35 years. This puts a huge time pressure on these women.

Due to the protective effect of oral contraceptives regarding ovarian cancer, this paper recommends women at increased risk of ovarian cancer use oral contraceptive pills for three to five years early in life (<25 years of age), when the absolute incidence of breast cancer is extremely low.

This seems a complete about-turn from previous practice when this population of women were advised not to use hormonal contraception because they may have a linked breast/ovarian cancer gene.

This paper argues that the transient increased relative risk of breast cancer due to oral contraceptives at this age will result in a negligible increase in absolute number of breast cancers, while the risk reduction of ovarian cancer remains for life.

HPV-16 jab for vulvar intraepithelial neoplasia N Engl J Med 2009; 361: 1838-47
This paper looked at women with vulvar intraepithelial neoplasia, which is caused by HPV, most commonly HPV type 16.

In this study, 20 women with HPV-16-positive, grade 3 vulvar intraepithelial neoplasia were vaccinated three or four times with peptides from the HPV-16 viral oncoproteins E6 and E7.

The most common adverse events were local swelling in 100 per cent of the patients and fever in 64 per cent. At three months after the last vaccination, 12 patients (60 per cent) had clinical responses and reported relief of symptoms.

Five women had complete regression of the lesions. In four of those women HPV-16 was no longer detectable.

At 12 months of follow up, 15 out of 19 patients had clinical responses (79 per cent), with a complete response in 9 out of 19 patients (47 per cent). The complete-response rate was maintained at 24 months follow up.

Hopefully the girls we are now vaccinating will not get vulvar intraepithelial neoplasia, but it is interesting that the vaccine can cause such a high regression rate in affected women.

  • Dr Hope is a GP in Woodstock, Oxfordshire, honorary research fellow in women's health at the University of Oxford and a member of our team who review the journals

The Quick Study

  • Statin use was associated with a decreased risk of gallstones requiring cholecystectomy.
  • Extracorporeal membrane oxygenation use has been low in swine flu patients.
  • Breast cancer incidence decreased consistently with a decline in HRT use.
  • Oral contraceptives offer protection to those at risk of hereditary ovarian cancer.
  • Vulvar intraepithelial neoplasia regressed in women vaccinated with HPV-16.

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