Giana Davidson, MD, MPH, associate professor of surgery at the University of Washington School of Medicine, talks about a new way to treat appendicitis.
What were you and your colleagues looking at in this trial?
DAVIDSON: Appendicitis is one of the most common urgent operations that we do in adults in emergency general surgery. And we had been looking at the prior trials that had tested if antibiotics were a reasonable treatment option for patients with appendicitis. And we wanted to really understand, who are the patients and in what conditions would this be a reasonable option for people to be able to consider an alternative to surgery?
And why is surgery usually the first course of treatment for appendicitis?
DAVIDSON: Yeah, historically, surgery has been the treatment because it was the removal of the appendix that’s done as an operation. And with laparoscopy, it’s typically an operation where people can go home the same day or the next day after their operation and typically heal pretty well. And so while most of the emphasis in Europe in the last 10 years has been looking at alternatives for surgery, surgeons in America have really been focused on improving techniques for surgery, increasing the use of laparoscopy to be able to streamline people through. And I think, in general, because it’s worked fairly well, that has been the gold standard really for treatment here.
And for your trial or for the trial, what were the findings?
DAVIDSON: So we were looking at, from a patient’s perspective, how is your quality of life depending on what treatment that you receive? And what we found is that patients who were randomized to surgery or to antibiotics – they had about the same health care measure of quality of life at 30 days after they had their appendicitis.
And then did you guys follow longer than that?
DAVIDSON: Right now have just released our outcomes up to 90 days. And part of the reason we released those early is because, with COVID, it had really changed how health care systems were taking care of patients and really wanting to minimize exposure in the health care when we were preserving PPE and we were trying to limit exposures to both staff and patients. And even the American College of Surgeons came out with recommendations to potentially consider alternatives to surgery, like antibiotics. And as we had this data and we were reaching the 90 day point we said, this is reasonable to look at our data, and our stakeholders said the same, this would be really helpful to know in this time. And so, we looked at our early outcomes in part just because of this pandemic.
And you said that you guys were looking at which patients would benefit. Have you guys noticed a trend?
DAVIDSON: Well, one of the things that we were looking at is patients with the appendicolith, which is a small stone at the base of the appendix that we think maybe blocks the appendix from draining. And we found that patients with a small stone had higher odds of having complications or higher evidence of having complications or of having a need – or having an appendectomy.
And backtracking a little bit, so what causes appendicitis?
DAVIDSON: We don’t know exactly what causes appendicitis. It’s – you know, the appendix is a small, wormlike organ right at the first part of the colon. We think maybe it gets blocked, bacteria gets overgrown, but we don’t actually know what causes appendicitis itself. But that inflammation that happens tends to lead to people having nausea, increased pain. And then, over some time, we’ll see those findings with – of inflammation and elevated white count, pain that’s getting worse over time, sometimes vomiting, and then oftentimes imaging finding that’s consistent with appendicitis to make that diagnosis.
And so there’s not really a cause, but are there any potential risk factors?
DAVIDSON: For having appendicitis? Yeah, risk factors for appendicitis, we would think if somebody had appendicitis and didn’t get treatment, meaning they didn’t have access to a hospital or an ability to get to a hospital to get treatment, that that infection, just like infections anywhere, can become worse over time and that you can have a rupture, a perforation of the appendix, or that you can develop an abscess outside the appendix, and people can become quite sick from that.
And so when it comes to treatment, can you kind of compare the benefits and the disadvantages of going with surgery versus going with antibiotics? What are the benefits and what are the risks?
DAVIDSON: So, what we found in the trial is that a measure of patients’ sort of health care quality at 30 days was about the same as was their report of resolutions of symptoms like pain and fever. What we found is their time in the hospital was also really similar, which was surprising to us. So, if you came in with appendicitis, whether you left the hospital with antibiotics or whether you had a surgery, you stayed in the hospital about the same amount of time. We also found that patients that left the hospital with antibiotics – about three out of 10 of them or four out of 10 of them with an appendicolith ended up having surgery at the end of 90 days.
And so, what questions should patients ask their doctors when deciding whether or not to decide to go straight for surgery or try with the antibiotics first. How should patients come up to that decision?
DAVIDSON: You know, it’s one of the things I love about this trial, that we really had patients at the center of saying the things that were important to them to look for. Is it time off work? Your need to be a caregiver? Is it that you have finals coming up? And all of those things contextually go into patients making that decision. At this point, the only thing that we’ve been able to look at is the appendicolith, because we had decided early on that that group was an important subpopulation that we would examine. But future will – work will look at the patient factors or the health system factors that go into if patients ultimately needed an appendectomy or had an appendectomy or if they had, you know, the same quality of life.
And then, kind of going into that, what are the next steps after this research?
DAVIDSON: So, we always had planned to follow people out for at least two years in this trial. So, we’ll certainly have long-term outcomes. In addition, we did an observational cohort because as you can imagine, people that agree to randomize to their treatment might be different from people who say, I’m willing to fill out your surveys, but I’m going to choose this therapy or that therapy. So, we have an additional 500 patients that we did what’s called an observational cohort, where we follow them over time, so that data will be revealed as well. And there’s really important questions about who ultimately gets an appendectomy? Over what time frame? What are the complications that happen over the longer term? From patients’ perspectives, what’s their ultimate, like, time in health care? Did they have to keep coming back to the emergency department or did they have lingering symptoms over longer periods of time? And those are really important questions that’ll be answered later on.
And so, with surgery, you kind of just take out the appendix and then you’re good. With the antibiotics, is it more of a wait-and-see approach? Or would the antibiotics ever, at one point, be a cure for appendicitis?
DAVIDSON: So for the patients that are treated in the trial with antibiotics, our hope is for those patients that they will be cured of the appendicitis. And what we know is that seven out of 10 patients did not end up getting their appendix out.
And if a patient just goes straight onto antibiotics and they’re fine, no need for surgery at this point— what do you believe that does for their quality of life?
DAVIDSON: So, what we found in the trial is that the quality of life at 30 days was about the same for patients who ended up having antibiotics or ended up having surgery. But I think it’s a really important question on those people that have antibiotics, what’s their ultimate time in health care? Do they have recurrence of appendicitis and at what rate? And what are sort of the predictor factors for that? And we’ll be looking at those long-term outcomes as well.
And anything that I didn’t ask you that you feel that people should know?
DAVIDSON: So, we also looked at complication rates for patients in both the antibiotic and in the surgical arm. And what we found is the complication rate in the antibiotic arm was about eight people out of 100 and in the surgical arm was approximately four people, or half the rate, out of 100. But most of those complications – the differences was due to the group that had the appendicolith. When you take out the patients that did not – that had the appendicolith and just looked at those without the appendicolith, the complication rate was about the same between both groups.
When I think appendicitis, I think a burst appendix, but that’s not the same thing, is it?
DAVIDSON: Yeah. When you say a burst appendix, what I sort of picture is a perforation or a small hole in the wall of the appendix. And it’s a complicated question because we found that the rates of perforation, when you remove those with an appendicolith were about the same. But what’s really important is how people recover from that and if they need other procedures or if they need drains or repeated antibiotics, and that’s all information that we’ll look that over time.
And so along those lines, I always thought that it had to come out right away because it was poisoning the system, but the antibiotics would be taking time. So are antibiotics working with a burst appendix?
DAVIDSON: We included patients with perforation, or when you say burst appendix, that’s mostly what people think is a perforation. Those patients were included in this trial. So, people that had a burst appendix, or a perforation, were included in this trial. And so, we’re one of the – we’re the first trial that included people with appendicolith as well as people with evidence of perforation on their CT scan, and that was really important to understand a really broad range of patients that present with appendicitis.
So, for people that had the burst appendix, it wasn’t such an urgent need for them to have surgery?
DAVIDSON: Yep. They were included in the trial if the physicians that saw them felt like it was safe to be excluded – that they didn’t have signs of sepsis – overwhelming sepsis that needed to be rushed to the operating room. But there are other conditions that are a small hole in your bowel or a perforation. Diverticulitis is one of them, and we treat that routinely with antibiotics.
So, there’s a whole thing with the antibiotics and overuse. How does that add into the mix?
DAVIDSON: Yeah, absolutely. Overuse of antibiotics is certainly something, you know, from a public health and infectious disease standpoint, everybody is worried about. The goal for the trial was to give people just the 10-day course of antibiotics and that, on the local level, should not increase antibiotic resistance for those individual cases within the community. But I think that the use of antibiotics, the side effects – all of those were really important outcomes that we looked at, as well as complications of antibiotics – something called clostridium difficile diarrhoea. And we didn’t find that there was a higher rate in patients that had the antibiotic-only therapy without surgery.
So they only had that 10-day course. And then, after that, no more antibiotics. And you guys followed them out through 30 and then 90 days.
DAVIDSON: That’s right.
Is it surprising to realize that it worked and it’s such a difference?
DAVIDSON: You know, prior European trials told us that it was likely safe to be able to treat people with antibiotics for appendicitis. But the question was really, like, should we? And in whom should we offer this therapy that they’re likely to be successful without a surgery? So, it wasn’t surprising that a large number of people were able to do well with just antibiotic therapy, but it’ll be interesting. Our rates of people that eventually had an appendectomy was much higher than the prior European trials. And that may be because we expanded our inclusion in this trial to include patients with an appendicolith or with a perforation. That’s a really important difference of this trial.
Interview conducted by Ivanhoe Broadcast News.
END OF INTERVIEW
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