Ann Robinson’s journal review — 5 June 2019

Ann Robinson reviews the latest research from the top medical journals


Laparoscopic surgery as good as open surgery for gastric cancer in China

This non-inferiority, open label, randomised trial of 1056 people in China with locally advanced gastric cancer looked at whether laparoscopic or open distal gastrectomy resulted in better survival rates. Laparoscopic surgery is known to be more effective in early stage cancer, with similar outcomes and fewer complications, than open surgery. But once the disease is locally advanced, is it better to open the abdomen to allow dissection of D2 lymph nodes? The authors report that 94.6% of participants completed the study, which strikes me as unusually high: is there any correlation between political regime and retention rates in trials? Three year, disease-free survival rates were similar for laparoscopic and open resection (83.1% v 85.2%), as were recurrence rates over the three years (18.8% v 16.5%). Laparoscopy will be preferred by most patients, as outcomes seem to be no worse than with open surgery, and hospital stay and recovery times are shorter. An important caveat to generalising from these findings is that about a quarter of patients’ tumours were down-staged from an initial clinical diagnosis of locally advanced cancer to early stage cancer. In centres where initial staging is more detailed, the same conclusions may not apply.


Chronic lymphocytic leukaemia: two drugs better than one

Two oral drugs have been approved for chronic lymphocytic leukaemia: ibrutinib, an inhibitor of Bruton’s tyrosine kinase, and venetoclax, an inhibitor of B cell lymphoma 2 protein. This small, phase 2 study of 80 participants (partly funded by AbbVie, which makes venetoclax) found that a combination of the two drugs seems to be effective for previously untreated, high-risk patients over the age of 65 years with chronic lymphocytic leukaemia. Most patients had only a partial response after three cycles of ibrutinib, but 88% achieved complete remission after 12 cycles of combined therapy. Adverse events were similar to those reported in other studies with monotherapy (60% had toxic effects of grade 3 or higher, mostly neutropenia). Patient over 65 years old didn’t fare worse than younger patients. Whether people who achieve complete remission after 24 cycles will need any further treatment is still not known. This study wasn’t designed to compare outcomes with watchful waiting; but if I had chronic lymphocytic leukaemia, that is the question I’d want answered.

Annals of internal medicine

Older adults with disability

Medicare (US federal health insurance for people over 65) spending is higher among older adults with disability who live in the community and lack adequate support. Comprehensive community-based, long-term services and support may save money as well as improving health and wellbeing. This observational study links Medicare claims with in-person interviews and found that “the prevalence of experiencing negative consequences due to no one being available to help or the activity being too difficult to perform alone ranged from 18.3% for household activities to 20.0% for self-care and 25.6% for mobility.”  The most common negative consequences were wetting or soiling oneself when toileting (39.3%), having to stay inside (27.9%), not being able to go places inside the home (24.3%), and making mistakes in taking prescribed medications (22.0%). Even if the negative consequences experienced by these people doesn’t drive change, perhaps the chance to reduce Medicare spending will.

JAMA Internal Medicine

Fast tracked cancer drugs don’t live up to expectations

Oncologist Bishal Gyawali and colleagues ask a fascinating question—When a cancer drug gets accelerated approval from the US Food and Drug Administration (FDA) on the basis of a claim that there is “verified clinical benefit in a confirmatory trial,” what exactly is meant by “verification of benefit”? The question resonates in the UK too, where there is often pressure to fast-track new cancer treatments. This review of subsequent trials of 93 cancer drugs that received accelerated FDA approval from 1992 to 2017 showed that most drugs failed to live up to their pre-approval promise; just 20% showed improved overall survival. In a second article, Chen and colleagues investigated 85 FDA approvals of 59 drugs that were based solely on a surrogate outcome such as response rate even though there was no subsequent evidence that response rate translated into better health outcomes (a quick response isn’t necessarily a better response). In an invited commentary, Richard Lehman and Cary Gross write: “These articles serve as a reminder that the accelerated approval pathway is a permissive process that tolerates nonrandomised trial methods and a variety of outcome measures that bear an uncertain relationship to patient benefit.”


Blood treatment before cardiac surgery.

This study found that giving a top-up of blood boosting products on the day before cardiac surgery reduced the need for postoperative blood transfusions in people who were anaemic or low in iron before their surgery. Time is often tight, as a lot of elective cardiac surgery is scheduled within days of an acute cardiac event. Evidence suggests that correcting isolated iron deficiency and anaemia preoperatively improves postoperative outcomes. This large scale, randomised controlled trial compared the need for red blood cell transfusions in the seven days after operation in patients with low haemoglobin concentration or isolated low ferritin, half of whom were given a combination of intravenous iron, subcutaneous erythropoietin alpha, vitamin B12, and oral folic acid, and half of whom were given placebo. A larger study would be needed to show robustly that the subgroup with iron deficiency benefit from the quick fix top up. And, although this combination treatment looks promising, further studies would be needed to show that the sum is better than the individual parts.


Proton pump inhibitors; increased risk of heart and kidney disease

Proton pump inhibitors are widely prescribed and in the UK they are also available over the counter. Years later, some patients are still taking them as repeat prescriptions with no specific underlying reason other than occasional indigestion. How much harm does the prolonged acid suppression cause? This longitudinal observational cohort study of 214 467 United States veterans that were new users of acid suppression drugs— histamine H2 receptor antagonists or proton pump inhibitors—found 45.2 excess deaths per 1000 patients taking proton pump inhibitors (from cardiovascular disease, chronic kidney disease and upper gastrointestinal cancer; the latter among those taking PPIs without a documented reason.) Study limitations include a narrow demographic (male, white and old) and confounders such as over the counter purchase of proton pump inhibitors. But it’s a good reminder not to prescribe proton pump inhibitors without a good reason, don’t forget to stop them, and remember that patients may be buying them over the counter. 

Ann Robinson is an NHS GP and health writer and broadcaster