In this month’s blog, we take a we take a look at a clinical paper and several discoveries in more basic science. Dr James Ashton discusses an article from BMJOG on gallstone disease treatment outcomes in early cholecystectomy versus conservative management/delayed cholecystectomy, whilst Dr John Ong, one of our trainee editors, discusses two recent scientific articles that are both interesting and unconventional!

In addition to these slightly left-field articles, BMJOG continues to publish a number of highly impactful papers. This include interesting data on survival in colon and rectal cancers in Finland and Sweden through 50 years, the cost-effectiveness of use of urea breath test for the management of Helicobacter pylori-related dyspepsia and peptic ulcer in the UK, and some highly useful and high profile guidelines for the consensus for the management of pancreatic exocrine insufficiency. Visit the website for latest content, all free to access.

In their systematic review and meta-analysis of gallstone disease treatment outcomes in early cholecystectomy versus conservative management/delayed cholecystectomy, Bagepally et al discuss the effectiveness of early cholecystectomy for gallstone diseases treatment in comparison to conservative management. The team systematically searched RCTs investigating the effectiveness of early cholecystectomy compared with conservative management, defined as delayed cholecystectomy. 40 studies were included, of which 39 (including 4483 patients) were able to used in the meta-analysis. Considering gallstone complications, pain (RR0.38, 0.20 to 0.74), cholangitis (RR0.52, 0.28 to 0.97) and total biliary complications (RR0.33, 0.20 to 0.55) were significantly lower in those patients undergoing early cholecystectomy. For all complications the number needed to treat (to avoid that complication was reported), significantly only 5.9 patients would need to be treated with early cholecystectomy to avoid one of the reported biliary complications. The authors conclude that early cholecystectomy may result in fewer biliary complications and a reduction in reported abdominal pain than conservative management.

Now onto Dr Ong’s articles. First stop, Ginseng. Ginseng, a root that is usually found in Asia, has long been regarded as a natural panacea for many ailments in the East. For centuries (and to this day), practitioners of traditional Chinese medicine prescribe ginseng in their day-to-day practice, although it is often regarded as poorly evidenced by “Western Medicine”. However, the proverbial phrase “the absence of evidence is not evidence of absence” may hold some truth when it comes to the benefits of Ginseng. In a recent article, Huang et al (Gut 2021) elegantly demonstrated that Ginseng polysaccharides (GP) alters the gut microbiome and potentiates the effect of immunotherapy in mouse models with late-stage lung cancer. These mice had undergone faecal transplantation from human donors who were responders and non-responders to immunotherapy; the microbiome profile in these two groups was distinct. Importantly, compared to controls, GP reinstated response to anti-Programmed Death 1(PD-1) monoclonal antibody in initial non-responders (mice), increased the production of IFN-γ, TNF-α, GZMB in CD8⁺ T cells in blood and tumour tissue, the CD8⁺/CD4⁺ T cells ratio, and the abundance of B. vulgatus and P. distasonis in the gut. Reductions in the plasma tryptophan/kynurenine ratio and tumour indoleamine 2,3-dioxygenase activity were also observed. Indeed, the data is highly interesting and results of future randomised controlled trials in this area are eagerly awaited! Nonetheless, it does make one wonder if there could be a therapeutic role for Ginseng in other gastrointestinal diseases (many studies have recently been registered with the WHO).

On a different note, a collaborative study between the US and Japanese researchers, have suggested that we may one-day breath through our rectum…yes, rectum. In a highly unconventional study by the same senior investigator that pioneered the ground-breaking “liver bud” technology (Nature 2013), Okabe et al (Med 2021 – a Cell Press journal) reported that enteral ventilation via the anus (EVA) enabled systemic oxygenation in mammals. Briefly, the authors inserted rectal tubes into murine and porcine models and induced Type 1 respiratory failure through mechanical pulmonary ventilation. In one group, they had abraded the intestinal mucosa to improve oxygen diffusion. Oxygen was then delivered oxygen via these tubes by two modes – gas (GEVA) and liquid (LEVA). The liquid was oxygen-enriched perfluorocarbon (PFD). They then demonstrated that they were able to prolong survival in GEVA/non-abraded mice and rescue the majority of GEVA/abraded mice from Type 1 respiratory failure. In mini-pigs, the authors administered PFD enemas to pigs with Type 1 respiratory failure and demonstrated that it was able to improve oxygen saturation by ≈ 15% (to 81.8% ± 11.2%). However, respiratory acidosis was still evident in all animals; metabolic acidosis not detected. Interestingly, to evaluate the risk of perforation and septicaemia and bacterial translocation from EVA, the authors also measured animal serum for bacterial endotoxin (lipopolysaccharide) and reported none were detected. This approach to assisted ventilation is indeed unconventional, however, will it ever replace or rival extracorporeal membrane oxygenation (ECMO)? Time will tell!