If you recall having surgery as a kid, chances are you had your appendix out. Appendectomies trail only circumcisions on the list of the most common pediatric surgeries in U.S. hospitals.
Each year 300,000 people, including more than 76,000 children, have their appendix removed.
But those numbers could soon change.
There’s an emerging notion among doctors that many cases of appendicitis could be safely and effectively treated with antibiotics only, avoiding surgery altogether.
While there is little data on the long term outcomes, a number of randomized controlled trials have found that about three out of four individuals treated with antibiotics did not require any further treatment for appendicitis for up to a year, with no increase in complication rates. While nonsurgical treatment has gained favor in many European countries, it remains controversial among doctors in the U.S.
“Overwhelmingly if you come into an emergency department with appendicitis, they would call a surgeon, and a surgeon would recommend that you get your appendix out. And most people wouldn’t think twice,” said Dr. David Talan, an emergency physician at the UCLA School of Medicine. “But it’s changing. More and more people are asking, ‘Do I really need surgery?’”
A new understanding
Appendicitis is inflammation of the appendix, a finger-shaped pouch that projects off the colon on the lower right side of the abdomen. When blocked by stool or an infection, the inflamed appendix can swell and fill with pus, causing the tell-tale pain that sends patients to the emergency room. In as many as 40 percent of cases, the appendix can burst open spilling the bacterial infection or fecal matter through the abdominal cavity.
Surgery has been the standard treatment for appendicitis since the late 1800s, and with good reason. The operation has a nearly universal cure rate with few complications, turning what was once a fatal condition for 50 percent of cases into a fairly mundane illness. Today, doctors generally perform laparoscopic appendectomies through the smallest of incisions, and many patients go home the same day.
That seems to leave little room for improvement, but even after a century of appendectomies, surgeons are still debating the best way to treat various presentations of the illness.
“Over the last hundred years, there have been more papers and research projects focused on the appendix and appendicitis than anything else in the surgical literature,” said Dr. Kenneth Azarow, surgeon-in-chief at Doernbecher Children’s Hospital in Portland. “That’s because our understanding is still partially unknown.”
Doctors once thought that any inflamed appendix would eventually rupture. Thus it made sense to operate and to operate immediately, to avoid a much more complex surgery down the road.
Newer evidence suggests that not might be the case, that simple appendicitis and a ruptured appendix might result from two distinct disease processes.
Over time, doctors learned that in the case of a rupture, if the body was able to wall off the infection creating an abscess, they could insert a catheter to drain the infection and put patients on antibiotics. Then the patient could return six to eight weeks later to have the appendix removed in a much simpler operation, which came to be known as an interval appendectomy.
“There were certain people who just never showed up to have their interval appendectomy, or when it was time they said, ‘Do we have to do it?’” said Dr. Jennifer Watters, director of Trauma and Acute Care Surgical Services at St. Charles Bend. “Over time we got enough of that data that we said, ‘OK, maybe we don’t have to take those appendixes out.’”
Doctors also learned they could wait to perform surgery without increasing the risk of a rupture. Instead of rousing a surgeon to perform appendectomies in the middle of the night, hospitals put patients on antibiotics and waited till morning to operate. But many of the patients would be feeling better by morning, and parents began to question whether the surgery was necessary.
In 2014, doctors at Nationwide Children’s Hospital decided to test the question. They asked parents of 102 children with uncomplicated appendicitis to choose either antibiotics alone or antibiotics and surgery. Of the 37 children who received antibiotics alone, 28 needed no further interventions over the next year. Those patients recovered faster and cost less to treat. While the study wasn’t a randomized controlled trial, it showed the viability of the nonsurgical option.
“And then the next iteration was, well, if we can do this for perforated appendicitis, why can’t we do this for simple appendicitis, give them antibiotics,” Watters said. “It goes away and then we see what happens. That’s kind of where we are now”
Using antibiotics for appendicitis is hardly a new concept. In 1959, a British doctor published the results of 471 appendicitis patients treated with antibiotics. One patient died and 68 endured another bout of appendicitis, a recurrence rate of just over 14 percent. But the practice didn’t catch on. Emergency surgery remained the mainstay even under the most difficult conditions.
During World War II, there were reports of at least three appendectomies performed on-board submarines by pharmacist’s mates — a sort of Naval medic — using nonsurgical instruments. One of those surgeries lasted more than four hours.
In 1961, Dr. Leonid Rogozov, a Russian physician stationed at the Novolazarevsyaka base in Antarctica, performed his own appendectomy under local anesthesia. While Rogozov survived, the Soviets decided not take any more chances, and had all medical staff undergo prophylactic appendectomies before being shipped off to Antarctica.
Rather than go the forced appendectomy route, U.S. Naval officials eventually implemented a protocol for antibiotic use in cases of appendicitis at sea, if timely evacuation to a hospital wasn’t possible. Military doctors reported the result of 127 cases of acute appendicitis treated with antibiotics with an 11 percent failure rate. Current Navy protocols still call for antibiotic use for sailors out at sea with no easy access to medical facilities.
Those unique circumstances helped give credence to the antibiotics-first approach. Doctors would treat patients with a 10-day course of antibiotics, usually given intravenously at the hospital initially, and followed by oral medications at home.
Several small randomized trials showed that most patients did just fine with antibiotics, although a good portion would have a recurrence and eventually get an appendectomy anyway. Studies showed that patients getting antibiotics had similar or lower pain scores to those getting surgery, but required fewer doses of narcotics and returned to work sooner. And early studies showed that treating with antibiotics didn’t result in more ruptures.
Two years ago, a Finnish study provided the best evidence to date on the viability of antibiotic treatment. The researchers enrolled more than 500 patients randomly, assigning them to surgery or antibiotics. Among the 273 patients in the surgical group, one had symptoms resolve, but the rest had surgery. Of those, 24 developed surgical site infections.
Of the 256 patients in the antibiotic group, 70 underwent surgery within a year. That represented a 27 percent failure rate or a 73 percent success rate, depending on whether you take a bowel-half full or bowel-half empty kind of approach. None of the antibiotic patients experienced the type of serious complications that worried many surgeons by delaying surgery.
But the researchers also noted that patients were so predisposed to having surgery for appendicitis, they had trouble enrolling patients in the study.
The finding set up an interesting trade-off for patients. They can undergo surgery with an incredibly high success rate, but with some small risk of infection or anesthesia side effects. Or they can gamble that with antibiotics, which also carry some health risks, they have a 3 in 4 chance of avoiding surgery.
“This makes the conversation difficult, because it depends a little bit on your personality and it depends a little bit on your life and living situation,” Watters said.
She recently counseled the mother of a child with a perforated appendix. She had put in a drain and started antibiotics, and they were trying decide whether to proceed with an interval appendectomy. One of the questions Watters asked was about their travel plans.
“If you’re leaving to go to Antarctica for three months or Africa, I’m going to recommend you go ahead and get your appendix out,” she recalls telling them. “But if you’re going to be right here in Bend, and you have no intention of being away from medical care, there’s no difference if you get an appendectomy later.”
Patients may have other reasons to avoid or at least delay surgery. In 2014, tennis superstar Rafael Nadal was diagnosed with appendicitis at the start of the Shanghai Open. He opted for antibiotics in hopes of playing in the tournament. He was able to play in the tournament and for about a month afterward, but following several early losses decided to have an appendectomy.
Watters said the research on antibiotics with its trade-offs of risks and benefits complicates the conversation for doctors. They now have an obligation to run through the various treatment options and to determine how the patient’s situation and personal preferences impact the decision.
“That’s significantly more complicated than (always) saying we should take out your appendix,” Watters said.
Further studies may help doctors determine which patients can be best managed with antibiotics and which should be steered toward surgery. But in the meantime, Watters said doctors must be careful not to allow their own biases to influence the way they present the options to their patients.
“I like to operate. I’m acutely aware that that is my bias, and my bias is that I would have my appendix taken out,” she said. “If it were my own child, I would take the 73 percent chance that we’re done after antibiotics, rather than the 100 percent chance of exposure to anesthesia.”
Watters estimates that about a quarter to a third of patients in Bend end up choosing antibiotics over surgery. That’s likely a much higher rate than in most hospitals in the country.
That may be because most surgeons have yet to be convinced that antibiotics are a safe, effective, viable option for appendicitis. As of 2014, only about 1.5 percent of appendicitis patients were treated with antibiotics.
The Finnish study stirred debate among surgeons, many of whom picked apart the methodology to question its results. Many argued that a 1 in 4 failure rate was a major problem, compared to the nearly 100 percent cure rate for surgery. Others questioned the choice of antibiotics or that the researchers didn’t consider recurrent appendicitis a failure in the absence of surgery. With just one year of follow-up, they argued there was no way to measure whether antibiotic treatment simply delayed an inevitable surgery.
That question remains unanswered. One study of 159 adults followed patients for two years finding that 14 percent had recurrent appendicitis. A recent analysis that mined medical records going back seven years found a recurrence rate of 6 percent.
“Medical management can be effective and may be the right thing for certain groups of patients, we just don’t know that yet,” Azarow said. “But it certainly would not be out of the realm of predicting that in the future antibiotics may be how we treat this disease.”
Still surgical groups remain firmly behind appendectomy. The American College of Surgeons, The Society for Surgery of the Alimentary Tract, and The World Society of Emergency Surgery all have guidelines calling appendectomy the treatment of choice.
As an early adopter, Talan has arguably treated as many cases of appendicitis with antibiotics as anybody in the country. He said physician biases may actually be increasing the antibiotic failure rates in studies.
Talan says 15 percent of the 25 percent who wind up having surgery after antibiotics are those who were treated, sent home and then came back to the hospital in pain. But the remaining 10 percent represent patients who impatient doctors talk into surgery when they don’t respond to antibiotics initially.
“You’re really concerned and you don’t want to hurt that person, and now all that lack of confidence is seeping through your pores and the patient picks up on it. ‘I’m not getting better. OK, take the appendix out,’” Talan said.
Medical studies generally avoid such influences by using a double-blind approach, where neither the patient nor the doctor knows who is getting the treatment studied and who is in the control group. But that’s not possible comparing surgery to antibiotics, and so physician and patient biases infiltrate the results.
Such research challenges have clouded the picture on antibiotic treatment of appendicitis, making firm conclusions difficult. For example, some small percentage of patients are misdiagnosed with appendicitis, which is only discovered once their appendix is removed. But with antibiotic treatment, doctors can’t confirm whether the appendix was actually inflamed.
Similarly, many of the European studies have compared antibiotics to open surgery, which has a higher complication rate and longer recovery time than laparoscopic surgery. That lowers the comparative bar that antibiotic treatment must clear.
It’s also unclear what the long term costs of using antibiotics might be. At least two studies have considered cost and found that surgery cost more than antibiotic treatment. A pilot study conducted by Talan, for example, found that hospital charges for antibiotic treatment were $5,145, less than half the $12,447 cost of surgery.
But neither followed patients long enough to determine if antibiotic treatment led to more repeat cases of appendicitis down the road. That could raise the total cost of treatment in the end.
U.S. surgeons in particular have pointed to the problems with the existing research and have resisted changing their practice until more rigorous studies can be done.
Researchers at the University of Washington have launched a large-scale clinical trial to answer the question, but results won’t be available until 2021. It will likely remain a matter of debate at least that long.
“Appendicitis went from a surgical emergency that had to be done in the middle of the night to an operation you could wait till the morning to an operation that you may not need to do it ever again,” said Dr. Dana Telem, an associate professor of general surgery at the University of Michigan. “This little disease process that every single general surgeon does, that you don’t think is this big of a deal, is still this controversial after all of this time.”
For surgeons, appendectomy represents the opportunity to fix the problem once and for all. And patients generally feel better immediately after surgery. Some doctors have seen a rare patient death from appendicitis, which may leave them reluctant to roll the dice with antibiotics.
But advocates for antibiotic treatment say with enough evidence that antibiotics are a viable option, the proper strategy should be to defer to patient preferences.
“[Doctors shouldn’t] assume that to the patient the most important outcome would necessarily be to have the appendix removed so that you never have to worry about appendicitis again,” Talan said. “It may be wanting to get back to work sooner, it may be not having to undergo general anesthesia or not having to have surgery. It may be not having to come to the hospital.”
Most patients, he says, fall into one of three groups: those who want to avoid surgery, those who will insist on surgery, and those who want to know what the doctor would choose.
“And most doctors are still learning the creationist view of appendicitis,” Talan said.
That’s about par for the course for the appendix, a body part that most people consider completely useless.
Charles Darwin proposed the theory that the appendix was a vestige of evolution more than 150 years ago, but that was based on faulty information. He theorized that the appendix in humans and other primates was the remains of a larger structure called a cecum, which was used by ancestors to digest a diet much higher in fiber than we eat today.
“It’s no question the idea that it was a vestige would never have been proposed if Darwin had had the data that we have now,” said Dr. William Parker, an associate professor of surgery at the Duke University School of Medicine.
Researchers are still trying to pin down the exact function of the appendix and to explain why people seem to do just fine without one.
It wasn’t until 2003 that they discovered that the immune system supports the growth of biofilms in the gut, and that these gut biofilms, which protect bacteria, are most prevalent in the appendix. That led to a theory that the appendix might actually serve as a safehouse for beneficial bacteria, a way to repopulate the gut when its normal microflora have been wiped out.
“It turns out the appendix is perfectly located and situated to provide us with a backup source of bacteria in case of infection,” Parker said. “The appendix… is a safe haven where good bacteria could hang out until they were needed to repopulate the gut after a nasty case of diarrhea.”
Diarrheal illnesses have historically had a high mortality rate and the ability to rapidly restore a normal bowel would certainly be a valuable evolutionary adaptation.
The invention of sewers and water treatment facilities may now be reducing the need for that adaption, and ironically, could be increasing rates of appendicitis. British physician Dr. David Barker in the 1980s observed that appendicitis rates increased after installation of modern plumbing. He thought that had to do with hot water heaters, but it could have to do with cleaner water. Appendicitis rates are higher in developed rather than nondeveloped countries
“Those changes left our immune system with too little work and too much time on their hands — a recipe for trouble,” Parker said.
There is some medical evidence to back the theory that the appendix has an immune function and acts as a safehouse for good bacteria.
Doctors have found that patients with an appendix have lower rates of recurrent Clostridium difficile infections. Known as C. diff, the bacteria forms spores that can crowd out the healthy bacteria in the digestive system, leading to severe diarrhea. Infection can often take hold after the use of broad-spectrum antibiotics. It’s then treated with other types of antibiotics, but recurs in about 20 percent of patients typically one or two weeks later.
Researchers at Winthrop-University Hospital in Mineola recently reviewed medical records for patients treated for C. diff. The infection recurred in 18 percent of patients with an appendix but 45 percent of those without.
Recurrent C. diff is often treated with a fecal transplant, restoring the healthy bacteria to the gut. The appendix may have evolved to serve that same function, but is being overwhelmed by today’s high-power antibiotics.
Another possible explanation is that the appendix has an important immune function and that removing it lowers the body’s ability to fight off a C. diff infection.
Removing an appendix has been shown to lower the risk of developing ulcerative colitis, which is caused by an overactive immune system response. On the other hand, an appendectomy may increase the risk of developing Crohn’s disease, another condition linked to an abnormal immune response.
Doctors in Australia have tested appendectomy as a treatment for ulcerative colitis, with 90 percent of patients showing symptom improvement and 40 percent achieving complete remission.
“You’re removing so much immune tissue that it suppresses the immune system,” Parker said.
The current debate over antibiotics versus surgery, he said, will ultimately have to look at such long term impacts of treatment as well.
“You’ve changed your immune system fundamentally with appendectomy. There’s increases in certain types of cancer long term,” he said. “And we don’t know what’s cause and what’s effect.”
Parker stresses, however, that even if the appendix is shown to have an important function, patients shouldn’t resist surgery because of it.
“What we really want to emphasize is if you have appendicitis, it’s a 50 percent death rate if you do nothing,” he said.
Only longer term studies that can track individuals for years after treatment for appendicitis will be able to sort out all of the benefits and the risks. A small percentage of patients over age 40 diagnosed with appendicitis are found to have appendicile cancer once the appendix is removed. It’s unclear what could happen with those patients if treatment moves towards antibiotics over surgery.
“No one has clearly demonstrated what the potential harm or actual risk is placed by removing the appendix,” Talan said.
But the evidence may bear out that we’ve been too quick to write off the appendix, and a public health campaign someday may urge patients to choose antibiotics over surgery.
“Maybe we could get bumper stickers (like with breast cancer),” Talan said. “Save the appendix!” •