Well, Ed, you should state upfront that despite your appointment in the department of surgery, you really never liked to operate. Beyond that, your arguments are strawmen. Unstated in the study's decision to use negative appendectomy as an outcome measure of failure, is the fact that there were probably few if any other actual complications, as you would expect operating on young healthy patients with early appendicitis-- which was the original intent of avoiding surgery for appendicitis, avoiding complications. Of course the initial studies compared antibiotics to open surgery, which made the disability and complication rate look greater than it currently (and actually, was already back then) is with laparoscopic appendectomy being the standard of care. Most of my teen patients lose little if any time from school and sports-- beyond the time spent in the ER. The fact that the study reported so many negative appendectomies, in this day and age, is also speaks to the fact that "cure" rates in the non-operative arms of these studies are overestimated, since presumably an equal percentage of patients are getting antibiotics for no real reason.
Antibiotic therapy is indicated for infection -- but what is interesting in this discourse is the absence of any discussion focusing on the CAUSES of appendiceal infection: luminal obstruction preventing normal drainage of the appendix...
Haven't yet come across any clarification by pro-antibiotic surgeons as to the outcome of an antibiotic-treated appendix, now cleared of infection, but still harboring luminal fecal matter indicative of abnormal peristalsis preventing clearing of its luminal contents...
Med student here... Appendectomy is the only management for appendicitis at my teaching hospital... I piped up at a surgery tutorial as to why patients weren't offered antibiotic management and got squelched by the head of surgery, told off thoroughly for reading Up-to-date (never read Up-to-date for surgery!) and directed back to the textbook... His only comment seemed to be that the very existence of a 5 year failure rate for antibiotics meant that it was a bad idea (as if appendectomy never had long term complications... Looking at you, adhesions and bowel obstruction)...
Not surprising to me….saw the results of a non-surgical appendicitis treatment in an adult who later developed massive abscess formation in and around that remaining appendix which was relatively quiet until full force . At surgery so many loculated regions….so much foul material was removed but likely went into septic shock and his bp could not be maintained…died on the table. Maybe all the info over the past 50 yrs needs to go into a final document…but the most important thing…get people up post surgery!!…the longer they lay in bed post surgery the greater the complications.
This is a disease where it would be best to let the dust settle on both treatment arms. Both surgery and antibiotics have late side effects. One year follow up, total hospital days, morbidity and mortality.
Imagine two F1 teams in a race, one using one stop, the other two stops. This is like assessing the strategies based on who is leading at lap 40.
What is with journal editors these days? If a “non-inferiority” trial fails to reject the null, the conclusion statement should read “was not non-inferior”, rather than “was inferior”. It is a small and technical point, but it speaks to the precision of language and concepts, and to the attention to detail. Reading that abstract makes me think it was amateur day at Lancet.
Thanks also for drawing attention to the “endpoint” in the antibiotic arm. A “failure” of antibiotics was the need to get an appendectomy….which is the starting point of the control arm. Ie. a failed active arm pt hasn’t lost anything (except some lead time). Esp (as pointed out by the Skeptician below) when there were no differences in severe clinical outcomes like death.
After reading this study, my clinical take would be “why wouldn’t everybody try a course of antibiotics first?”.
The title displays suitor the subtitle that refutes it. A casual reader who does not follow the email to the article will get the impression that appendectomy is the correct management.
There is some evidence the appendix may have a beneficial role in the body related to the microbiome. So all things being equal it might be better to try and save it if there is no harm in giving antibiotics and then performing surgery only on those who fail to respond.
I have some comments regarding the non-surgical treatment of acute appendicitis (AA) and your valuable insight, with which I fully agree.
It is truly paradoxical that the natural history of AA changed following the brilliant idea of removing the appendix—without any clinical trial, not even an observational one—solely through the oral transmission of individual experience in what we might call “before everything, now nothing” pragmatic studies. These studies represent a rigid way of thinking that upholds a paradigm and has clearly influenced researchers in the field. In other words, the certainty that no other therapeutic method exists translates into decisions regarding selection, sampling, and clinically significant outcomes , even setting a non-inferiority margin in the clinical trial, that surreptitiously favor appendectomy while putting conservative treatment at a disadvantage.
Regardless, it is clear that the key factor in determining the success or failure of antibiotic management is the certainty of the absence of perforation—an aspect that remains extremely difficult to ascertain, even with high-resolution imaging, which also increases the cost of management.
The second aspect that requires reflection is the possibility that there are different types of AA (perhaps even episodes preceded by others with mild symptoms), in which appendix infection, as an intermediate variable, is not the causal factor, making antibiotics an insufficient therapy. What if the “failures” of conservative treatment occur in patients with underlying conditions, such as inflammatory bowel disease or microbiota imbalances due to a refined and ultra-processed diet, as has been evidenced in research? In other words, it is possible that various epigenetic factors in the causal chain determine different natural histories and prognoses, where appendectomy provides a radical solution to the Gordian knot—one that alternative treatments cannot untangle unless they incorporate measures to improve the intestinal environment.
We must move beyond this traditional approach that removes an important lymphoid organ—one that is not vestigial but exists for a reason—rather than treating it as a vital risk factor or a means to sustain surgical profits.
Would the preferred outcome--surgery, yes versus no--also create uncertainty? As we can't determine whether an inflamed appendix assigned to the surgical arm would have responded to antibiotics if managed conservatively, the investigators were stuck. With this approach, the bias goes towards surgery, but it doesn't make it incorrect if you account for it in your results and discussion.
Well, Ed, you should state upfront that despite your appointment in the department of surgery, you really never liked to operate. Beyond that, your arguments are strawmen. Unstated in the study's decision to use negative appendectomy as an outcome measure of failure, is the fact that there were probably few if any other actual complications, as you would expect operating on young healthy patients with early appendicitis-- which was the original intent of avoiding surgery for appendicitis, avoiding complications. Of course the initial studies compared antibiotics to open surgery, which made the disability and complication rate look greater than it currently (and actually, was already back then) is with laparoscopic appendectomy being the standard of care. Most of my teen patients lose little if any time from school and sports-- beyond the time spent in the ER. The fact that the study reported so many negative appendectomies, in this day and age, is also speaks to the fact that "cure" rates in the non-operative arms of these studies are overestimated, since presumably an equal percentage of patients are getting antibiotics for no real reason.
Antibiotic therapy is indicated for infection -- but what is interesting in this discourse is the absence of any discussion focusing on the CAUSES of appendiceal infection: luminal obstruction preventing normal drainage of the appendix...
Haven't yet come across any clarification by pro-antibiotic surgeons as to the outcome of an antibiotic-treated appendix, now cleared of infection, but still harboring luminal fecal matter indicative of abnormal peristalsis preventing clearing of its luminal contents...
Sure feels like this was designed to find a certain outcome. Sad
Med student here... Appendectomy is the only management for appendicitis at my teaching hospital... I piped up at a surgery tutorial as to why patients weren't offered antibiotic management and got squelched by the head of surgery, told off thoroughly for reading Up-to-date (never read Up-to-date for surgery!) and directed back to the textbook... His only comment seemed to be that the very existence of a 5 year failure rate for antibiotics meant that it was a bad idea (as if appendectomy never had long term complications... Looking at you, adhesions and bowel obstruction)...
Not surprising to me….saw the results of a non-surgical appendicitis treatment in an adult who later developed massive abscess formation in and around that remaining appendix which was relatively quiet until full force . At surgery so many loculated regions….so much foul material was removed but likely went into septic shock and his bp could not be maintained…died on the table. Maybe all the info over the past 50 yrs needs to go into a final document…but the most important thing…get people up post surgery!!…the longer they lay in bed post surgery the greater the complications.
Yes, “Motion is Life, Stasis is Death.”
George Vanderbilt likely died post-appy from DVT —> PE because post-op bed rest was the standard of the day back then.
Great analysis
This is a disease where it would be best to let the dust settle on both treatment arms. Both surgery and antibiotics have late side effects. One year follow up, total hospital days, morbidity and mortality.
Imagine two F1 teams in a race, one using one stop, the other two stops. This is like assessing the strategies based on who is leading at lap 40.
Great post.
What is with journal editors these days? If a “non-inferiority” trial fails to reject the null, the conclusion statement should read “was not non-inferior”, rather than “was inferior”. It is a small and technical point, but it speaks to the precision of language and concepts, and to the attention to detail. Reading that abstract makes me think it was amateur day at Lancet.
Thanks also for drawing attention to the “endpoint” in the antibiotic arm. A “failure” of antibiotics was the need to get an appendectomy….which is the starting point of the control arm. Ie. a failed active arm pt hasn’t lost anything (except some lead time). Esp (as pointed out by the Skeptician below) when there were no differences in severe clinical outcomes like death.
After reading this study, my clinical take would be “why wouldn’t everybody try a course of antibiotics first?”.
The title displays suitor the subtitle that refutes it. A casual reader who does not follow the email to the article will get the impression that appendectomy is the correct management.
... displays without the subtitle...
Great piece. Would just suggest you put the subtitle ahead of the title because people may glance at it and be misled.
There is some evidence the appendix may have a beneficial role in the body related to the microbiome. So all things being equal it might be better to try and save it if there is no harm in giving antibiotics and then performing surgery only on those who fail to respond.
Very very helpful analysis. Thank you!!
Dr. Livingston,
I have some comments regarding the non-surgical treatment of acute appendicitis (AA) and your valuable insight, with which I fully agree.
It is truly paradoxical that the natural history of AA changed following the brilliant idea of removing the appendix—without any clinical trial, not even an observational one—solely through the oral transmission of individual experience in what we might call “before everything, now nothing” pragmatic studies. These studies represent a rigid way of thinking that upholds a paradigm and has clearly influenced researchers in the field. In other words, the certainty that no other therapeutic method exists translates into decisions regarding selection, sampling, and clinically significant outcomes , even setting a non-inferiority margin in the clinical trial, that surreptitiously favor appendectomy while putting conservative treatment at a disadvantage.
Regardless, it is clear that the key factor in determining the success or failure of antibiotic management is the certainty of the absence of perforation—an aspect that remains extremely difficult to ascertain, even with high-resolution imaging, which also increases the cost of management.
The second aspect that requires reflection is the possibility that there are different types of AA (perhaps even episodes preceded by others with mild symptoms), in which appendix infection, as an intermediate variable, is not the causal factor, making antibiotics an insufficient therapy. What if the “failures” of conservative treatment occur in patients with underlying conditions, such as inflammatory bowel disease or microbiota imbalances due to a refined and ultra-processed diet, as has been evidenced in research? In other words, it is possible that various epigenetic factors in the causal chain determine different natural histories and prognoses, where appendectomy provides a radical solution to the Gordian knot—one that alternative treatments cannot untangle unless they incorporate measures to improve the intestinal environment.
We must move beyond this traditional approach that removes an important lymphoid organ—one that is not vestigial but exists for a reason—rather than treating it as a vital risk factor or a means to sustain surgical profits.
What are your thoughts on this?
Would the preferred outcome--surgery, yes versus no--also create uncertainty? As we can't determine whether an inflamed appendix assigned to the surgical arm would have responded to antibiotics if managed conservatively, the investigators were stuck. With this approach, the bias goes towards surgery, but it doesn't make it incorrect if you account for it in your results and discussion.
You changed my mind! 2/3 avoided surgery. However, I agree about the end points. We need to know the rates of perforation, sepsis, etc.?