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Wednesday, October 14, 2009

APPENDICITIS

Highlights:
Appendicitis is the most frequent cause of abdominal pain in children and young adults requiring surgery. Despite its relative frequency, it is often a difficult disease to accurately diagnose.
The time from onset of symptoms to perforation of the appendix is approximately 48 hours. Optimal outcome is obtained when diagnosis is made before perforation occurs.
The definitive treatment of appendicitis is surgical removal of the appendix. This is most commonly performed using small incisions. In cases in which the appendix is perforated, a course of intravenous antibiotics may be given first, followed by removal of the appendix several weeks later.
The prognosis for children with appendicitis – even in cases in which the appendix is perforated – is excellent.

1. Introduction: What is appendicitis?
Appendicitis is the most common cause of abdominal pain requiring surgery in children and young adults1. This important disease affects up to 7-9%f the population over the lifespan of an individual in the United States, and is most commonly seen in individuals between the ages of 10-19 years of age, although can certainly be seen in patients both younger and older 2. The term “appendicitis” refers to inflammation of the appendix, which itself is a finger-like projection located at the very beginning of the colon (see Figure 1). Patients with appendicitis initially exhibit vague, non-specific abdominal symptoms, which can progress to the point where patients become extremely sick from overwhelming infection.
Despite the fact that appendicitis occurs so frequently, making the diagnosis can be extremely difficult3. As a result, many patients with appendicitis experience some degree of diagnostic delay, resulting in a prolonged length of stay and a more challenging post-operative course4. This knol will provide an overview of appendicitis: how the disease presents, how the diagnosis is made, and how the disease is best treated.
2. What causes appendicitis?
The short answer to this important question is that we don’t really know. Current dogma indicates that the appendix can become blocked with stool or ingested, non-digestible matter. The blocked appendix allows bacteria to infiltrate and overgrow within it, setting up a cascade leading to inflammation of the appendix and, ultimately, to its perforation (bursting) if the appendix is not removed in a timely manner. Perforation of the appendix then allows bacteria to “leak out” into the blood stream and the abdomen, resulting in severe infection that can spread to other organs. If the infection settles in another part of the abdominal cavity, an abscess may form, which can cause persistent abdominal pain and fever if not treated. Therefore, treatment of appendicitis requires a combination of antibiotics to fight the bacteria directly, as well as surgery to remove the diseased appendix and allow healing to occur. The subsequent sections of this knol will highlight the presentation, diagnosis, treatment and outcome of patients that develop this common and potentially debilitating disease.

3. How do patients with acute appendicitis usually present? The case of Tyler, age 10.
In order to more clearly define how patients with appendicitis typically present, consider the following story of Tyler, a previously healthy 10 year old boy who developed acute appendicitis.

Tyler is your typical 10 year old boy; he likes school, likes his friends, and loves playing basketball. Last night he stayed over at his best friend’s house after playing hours of basketball and eating loads of pizza, and today he woke up with a pain in his abdomen. It seemed as though this was the type of vague abdominal pain that Tyler had complained of many times before – and you figure that it’s probably just a combination of a sprained muscle and too much pepperoni. And he certainly seems well enough to go to school, so you drop him off at the bus stop, figuring that school will probably take his mind off the pain. However, shortly after lunch your cell phone rings and it is the school nurse calling to say that Tyler has started to throw up, and now has pain in the right side of his belly that makes him grimace every time he walks. She tells you that even though there’s an awful flu bug going around, Tyler looks sicker than most of the other kids with this have looked. When you pick up Tyler from school, he’s a different kid than he was that morning. He’s hunched over in pain, holding the right side of his abdomen, and every bump on the ride over to the hospital makes him yell out in pain. You are seen quickly in the Emergency Department by a surgical team, who note that he now has a slight fever and that he is very tender in the right lower part of his abdomen whenever they press there. The nurses draw blood, and comment that his “white blood cells” are elevated. The surgeon tells you that he feels that Tyler has appendicitis, that no additional tests are required to confirm this diagnosis, and that an operation is required. Tyler is quickly started on antibiotics and brought to the operating room, where his swollen and inflamed appendix is removed using three tiny incisions. Tyler recovers quickly from his surgery, and is able to go home from the hospital the following day feeling much better. This clinical vignette illustrates the typical course of appendicitis in children. Appendicitis is a disease that almost always affects previously healthy kids, most commonly between the ages of 10 and 19 years old. In its early stages, appendicitis closely mimics almost any other cause of abdominal pain that youngsters can experience, including a pulled muscle, a flu bug, or even food poisoning. And although there are many more common causes of abdominal pain at any age than appendicitis, the diagnosis of appendicitis is the leading reason for surgery related to the abdomen in this age group.
Patients with appendicitis classically present just as Tyler did. They typically will develop pain in the abdomen that starts around the umbilicus (navel), and then over a period of hours the pain will change so that it is localized first to both sides of the lower abdomen, and subsequently to the right lower quadrant (Figure 2). Over the ensuing hours, the pain persists and increases in severity, and is often accompanied by fevers, generalized fatigue, and vomiting5. (On the other hand, the presence of diarrhea, difficulty urinating, and a cough are all unusual amidst the classic symptoms for appendicitis; they should prompt a search for alternative diagnostic possibilities, as will be discussed below.) If patients are brought to medical attention at this stage in their disease, they can be expected to undergo a routine removal of the appendix and to do very well. However, in patients with appendicitis who do not undergo surgery at this stage in their disease progression, they are destined to get sicker before they get better6. This may be a result of their disease progressing very quickly and not being seen in a timely manner, or other factors that may create a delay in obtaining medical attention7. In these cases, the pain may spread throughout the abdomen, and patients may begin to vomit profusely. These signs indicate that the appendix has gone on to rupture, the most serious complication of this disease. Treatment of patients with ruptured appendicitis is more challenging than non-ruptured appendicitis, due to the spread of infection from the ruptured appendix. Fortunately in experienced hands the prognosis remains excellent, with almost all patients recovering from the disease, as will be described in Section 7.
4. Making the diagnosis of appendicitis: a science, an art, and often a bunch of tests.
The diagnosis of appendicitis can at times be one of the most difficult to make in all of clinical medicine. This is due in part to: 1) the variability in the patterns of symptoms that patients present with, 2) the number of other conditions that can appear very much like appendicitis (see below), and 3) the challenge of communicating with young patients that may not be able to reliably describe their symptoms. In other cases, the diagnosis of appendicitis can be fairly straightforward, particularly under conditions in which patients present in the classic manner as illustrated by the case of Tyler. In cases in which the diagnosis cannot be ascertained on clinical grounds alone (taking a careful history and performing a thorough physical examination), then additional tests are required, including ultrasound and computerized tomography (CT)scanning8.
a) Making the diagnosis of appendicitis on “clinical grounds”.
The term “clinical grounds” refers to establishing a diagnosis of appendicitis after obtaining a detailed history and performing a careful clinical evaluation without additional imaging tests. Although it is expected that children with appendicitis will demonstrate tremendous variability in the nature and extent of the presentation of abdominal symptoms, the classic features of appendicitis are best represented by Tyler’s story: abdominal pain of approximately 18-24 hours duration that begins in a generalized location around the umbilicus, then radiates over time to the lower abdomen and subsequently localizes in the right lower quadrant. Typically patients with appendicitis will also demonstrate some degree of nausea, vomiting and loss of appetite, and it is important to note that the vomiting typically occurs after the onset of abdominal pain. This feature is somewhat useful in differentiating appendicitis from other causes of abdominal pain (see section 5, below). On physical examination, most patients with appendicitis will have marked tenderness in the right lower quadrant, and pushing on the left side of the abdomen will actually cause severe pain on the right side (which is where the appendix is generally located). When the right lower abdominal tenderness is severe enough, the abdominal muscles may actually contract involuntarily after being pressed; this is known as “involuntary guarding.” The patient’s blood work will typically reveal a moderate increase in the numbers of circulating white blood cells, especially the neutrophil component. When the patient demonstrates these classic clinical features, he or she should be managed as if he or she has acute appendicitis9, as described in Section 6, below.
b) The use of selective imaging tests to establish the diagnosis of appendicitis.

In cases in which the diagnosis of appendicitis is not straight forward – such as in females in which ovarian pathology can cause abdominal pain – additional tests may be required. These include plain abdominal x-rays, abdominal ultrasound, and CT scanning. Plain abdominal x-rays do not typically suggest the diagnosis of appendicitis, but they may often be used to rule out other causes of abdominal pain, such as constipation or intestinal obstruction from a cause unrelated to the appendix (see section 5, below). Ultrasound is useful if the appendix appears thickened, and may also reveal the presence of fluid in the pelvis and in the right side of the abdomen around the appendicitis10. The use of ultrasound is limited by the fact that it is not very helpful in young children, and may miss the appendix in very large patients. From a practical standpoint, the most useful ancillary test in the diagnosis of appendicitis is the CT scan, which can reliably visualize the appendicitis in a majority of cases11, and can demonstrate the presence of appendicitis versus a normal appendix in many children12. As shown in Figure 3, criteria for a positive CT scan include a thickened appendix, often with fluid around it, and inflammatory changes in the right lower quadrant of the abdomen. It is important to note that the thickened appendix and the fluid that may be present around it are very difficult to detect in young children, thereby decreasing the usefulness of this test in this population. In essence, there is no test that is 100% accurate in all cases to make the diagnosis of appendicitis. The most important consideration is for the caregiver to think about the diagnosis of appendicitis, to consider the likelihood of other diagnostic possibilities and, when appendicitis seems like the most likely cause of the patient’s abdominal pain, to proceed with specific treatment in a timely manner.
c) What if the doctor still isn’t sure whether it’s appendicitis or something else?
Occasionally, despite performing a careful history and detailed physical examination, the diagnosis of appendicitis may still be in doubt. In these circumstances, it is often reasonable and appropriate to admit the patient into the hospital, to re-hydrate him or her, and to perform serial abdominal examinations to evaluate whether there are changes in the nature of the pain and/or the severity of the physical findings. Typically the diagnosis is apparent by morning. Many patients will improve, and simply can't wait to get out of bed and go home. In other cases, the pain may persist or be slightly worse, and CT scanning may not be helpful in “ruling out” the disease. In such patients, it is often most appropriate to simply bring these patients to the operating room and to perform a diagnostic laparoscopy. This involves inserting a video camera into the umbilicus and visualizing the appendix directly. If the appendix is inflamed, it is removed as described in Section 6, below. Other causes of abdominal pain, including pain arising from the ovaries, can be identified and managed through the diagnostic laparoscopy.. A diagnosis of gastroenteritis can similarly be established by laparoscopy. However, often in these cases no obvious pathology may be apparent; it is then quite common and acceptable to remove the appendix anyway, given the possibility that inflammation in the inside of the appendix that may be causing pain may not be apparent when visualized from the outside. Many patients that are managed in this way will improve markedly after their operation.

5) If appendicitis isn’t causing the pain, what is?
As mentioned above, appendicitis can be one of the most difficult diagnoses to establish in children with abdominal pain, in part because of the large number of diseases that present in a similar fashion. A partial list of other conditions that mimic appendicitis as well as features that distinguish these from appendicitis is provided in Table 1. Patients with urinary tract infection can appear very similar to those with appendicitis. However, patients with urinary tract infection are less likely to have vomiting as a major component of their disease spectrum, and are likely to also experience difficulty with urination, characterized by pressure, burning and frequency. A diagnosis of constipation may be commonly confused with appendicitis in its earliest stages, given the vague nature of the abdominal pain that can occur with this common condition. However, patients with constipation rarely have fever, and will not have abnormalities in their blood work. Ovarian torsion – an acute process involving the sudden twisting of an ovary on either the left or right side – can mimic appendicitis, given the severe abdominal pain that accompanies this condition. However, patients with ovarian torsion are generally perfectly fine until the acute onset of severe pain (by contrast, patients with appendicitis have a generally slow build up of pain associated with nausea and vomiting). Finally, children and young adults are always at risk for the development of gastroenteritis, also known as the “stomach flu.” However, unlike appendicitis, patients with gastroenteritis generally have persistent vomiting – and occasionally diarrhea – that precedes the onset of the abdominal pain. Experienced pediatric caregivers will have a working understanding of each of these conditions, and will carefully work through them when assessing a patient with abdominal pain who may – or may not – have appendicitis.

6) Treatment of appendicitis: surgery and everything that goes with it.


The definitive treatment for appendicitis involves the surgical removal of the appendix. This procedure – called an appendectomy – is very straightforward in experienced hands and has an excellent prognosis. Prior to surgery, it is important that patients receive adequate intravenous fluids in order to correct dehydration that commonly develops as a result of fever and vomiting in patients with appendicitis. Patients should also be started on antibiotics, in order to prevent wound infection after surgery. The procedure to remove the appendix typically takes approximately one hour to perform, and requires a general anesthetic. Most surgeons will perform an appendectomy through small incisions, a so-called laparoscopic approach13, which may have some advantage over removing the appendix through a single larger incision, although the exact mode of performing the appendectomy is not thought to have a significant impact on how well patients do after the operation 14. During the laparoscopic appendectomy, a small incision is made at the umbilicus, and two additional incisions (each less than 1cm in width) are made in the lower abdomen. Using fine dissection, the blood vessels that supply the appendix are removed, and the appendix itself is separated from the rest of the intestine. The appearance of the appendix as seen during laparoscopy is shown in Figure 4. The appendix is typically brought out through the umbilicus, and all incisions are then closed, typically with sutures that are dissolvable. In conditions in which the appendix is not ruptured, patients may start to drink liquids shortly after waking up from the operation, and may start taking solid foods the next day. Patients are able to go home when they are keeping liquids and some solids down, and have minimal pain. Most patients report dramatic improvement after surgery. In basic terms, the same steps are taken when surgery is performed through an open, larger incision.

As mentioned above, surgery for appendicitis is extremely safe in experienced hands. The most common risk is that of a wound infection, most likely to occur at the umbilical incision. Other risks – including bleeding or damage to other structures inside the abdomen – are extremely rare. Recovery from surgery is dependent upon the individual patient. Most children are back to school approximately one week from surgery, and usually are allowed to return to full physical activity after 2 to 3 weeks. During the recovery period, over-the-counter pain medicines are required. Older patients tend to require a longer time for full recovery.

7) When the appendix bursts: what to do and what to expect. The case of Emily, age 5.
As described above, an inflamed appendix that is untreated will eventually become more inflamed and rupture. And although perforated appendicitis is no longer the life-threatening condition that it historically was, it is still a significant cause of morbidity (illness). Young patients (ages 5 and under) are at particular risk for developing ruptured appendicitis, because they are less likely to be able to describe their symptoms reliably, and because they are more likely to experience other causes of abdominal pain. Consider the following clinical vignette that describes a classic story for a ruptured appendix in Emily, a previously healthy 5 year old girl.

Typically an active child, Emily has really been “run-down” for the past week or so. She did have a cold earlier in the week, and complained that her tummy was sore; but she often had tummy aches in the past, and this one didn’t seem any different from her prior episodes. Before her cold started – about a week ago – she had complained that her stomach really, really hurt, but then a day or so later she seemed to be much better, and you figured that she simply had recovered from whatever was bothering her. Over the past few days though, Emily hasn’t been quite herself. She has had little interest in food, and looked sicker and sicker as the week went on. Then this morning, Emily started to throw up green, frothy liquid, and it was clear that the time had come to take her to see the pediatrician. When the doctor placed her hand on Emily’s lower abdomen, you could see that Emily’s little belly had become much more swollen, and she clearly didn’t like having her lower abdomen pressed. By the time Emily arrived at the hospital, she was really quite sick. She was dehydrated, and her temperature was over 39oC (over 102 degrees Fahrenheit). Emily was given intravenous fluids, and underwent a CT scan of the abdomen that showed a ruptured appendix and a large amount of fluid in the abdomen. Since Emily was so sick, a decision was made to bring her to surgery. The pediatric surgeon performed a laparoscopic removal of a perforated, necrotic (containing a lot of cell death) appendix and drainage of a large intra-abdominal abscess. It took Emily nearly two weeks in the hospital to get over the surgery. However, two months later, Emily is running around and back to her old self.





This story is quite typical for a patient with a ruptured appendix. The patient is often sick for several days, and may have an episode of apparent improvement in symptoms prior to deterioration. It is important to point out that patients with ruptured appendicitis may initially appear quite similar to those with other causes of abdominal pain that would be seen more frequently in young children, in particular gastroenteritis. However, the long duration of the symptoms (gastroenteritis does not typically last more than 3 or 4 days), and the slow but steady decline requires that the diagnosis of ruptured appendicitis be considered. Although the diagnosis may be strongly suspected on clinical grounds, a CT scan is typically required to definitively establish the diagnosis. In cases of ruptured appendicitis, the CT scan will reveal an inflamed thickened appendix, as well as a collection of fluid in the abdomen or pelvis that may represent a pocket of infection called an abscess. A fecalith – defined as a calcified collection of stool and other debris – may also be visualized on the CT scan (see Figure 5).
Treatment of children with ruptured appendicitis requires sound judgment, and must be individualized for each child. In the child that is very sick – such as Emily – in which there is dehydration and marked abdominal tenderness, then the appropriate course of action is to provide intravenous fluids, antibiotics, then bring the patient to surgery for removal of the appendix and drainage of any fluid collections or abscesses. Occasionally patients with a ruptured appendix will develop an intestinal blockage from the dense scar tissue that forms; these patients also require surgery. The actual removal may be performed either laparoscopically or through an open operation. Operations on patients with a ruptured appendix always take much longer than operations for removal of a non-ruptured appendix, and carry greater risks. These risks include bleeding, infection and damage to other structures.
In view of the heightened risk that may be present in operating on patients with ruptured appendicitis, it is prudent to apply an initial non-operative strategy to selected patients with this condition15, 16. Specifically, if the child with documented appendicitis on CT scan appears well – especially in cases in which there is improvement in pain and fever after the administration of intravenous fluids and antibiotics – and there is no indication of generalized peritonitis and intestinal obstruction, then urgent surgery is not required 17. In these cases, it is appropriate to percutaneously drain any large fluid collections using x-ray guided techniques, and to administer antibiotics for 10 days or so through a central line that the patient may receive at home. After six to eight weeks of non-operative management, the bulk of the inflammation will have settled down, and the appendix can then be safely removed on an elective basis. Embarking on non-operative management for patients with perforated appendicitis requires close observation. Failure of the patient to improve within 48 hours or so after initiation of antibiotics should lead to a recognition that an operation is required to remove the appendix, no matter how difficult that procedure may be17.
In general, despite the prolonged course of treatment that is required for patients with ruptured appendicitis, the prognosis remains excellent in experienced hands.

8. Are there any long term problems in children after the appendix is removed?
As far as we know, the appendix does not serve any useful purpose (other than to keep surgeons and parents up at night), so its removal is not known to carry any specific negative consequences. In fact there is some evidence that removal of the appendix may protect patients from the subsequent development of other abdominal inflammatory conditions, such as ulcerative colitis 18. However, scar tissue will form within the abdomen any time that surgery is performed there, and over time this could potentially cause intestinal blockage. This is rather rare in cases in which the appendix is not perforated, yet is seen more frequently in those patients that develop ruptured appendicitis19. Any patient who has undergone surgery and subsequently develops signs of intestinal blockage – such as abdominal pain, green vomiting, or failure to keep any liquid or solid down – should receive prompt medical attention.

9. Summary and Conclusions:
Appendicitis is the leading cause of abdominal pain requiring surgery in children and young adults. In cases in which the duration of symptoms is relatively short and the findings are typical, surgery to remove the appendix may be performed quickly and the expected outcome is excellent. In patients in whom the appendix ruptures – an event that may be expected to happen approximately three to four days from the onset of symptoms – then an individualized approach to treatment is undertaken, including a period of initial non-operative therapy followed by elective appendectomy. In experienced hands, the overall prognosis for patients with appendicitis is excellent, and full recovery and return to normal activity should be expected in all cases.

10. References cited.

1. Scholer SJ PK, Orr DP, Dittus RS. Clinical outcomes of children with acute abdominal pain. Pediatrics 1996;98:680-5.
2. Addiss DG SN, Fowler BS, Tauxe RV. The epidemiology of appendicitis and appendectomy in the United States. Am J Epidemiol 1990;132:910-25.
3. Kosloske AM LC, Rohrer JE, Goldthorn JF, Lacey SR. The diagnosis of appendicitis in children: outcomes of a strategy based on pediatric surgical evaluation. Pediatrics 2004;113:29-34.
4. Smink DS FJ, Kleinman K, Fishman SJ. The effect of hospital volume of pediatric appendectomies on the misdiagnosis of appendicitis in children. Pediatrics 2004;113:18-23.
5. Hackam D, Newman K, Ford H. Pediatric Surgery. 7 ed. New York: McGraw-Hill; 2005.
6. Nwomeh BC CD, Caniano DA, Kelleher KJ. Racial and socioeconomic disparity in perforated appendicitis among children: where is the problem? Pediatrics 2006;117:870-5.
7. Bratton SL HC, Waldhausen JH. Acute appendicitis risks of complications: age and Medicaid insurance. Pediatrics 2000;106:75-8.
8. Peña BM TG, Fishman SJ, Mandl KD. Effect of an imaging protocol on clinical outcomes among pediatric patients with appendicitis. Pediatrics 2002;110:1088-93.
9. Kharbanda AB TG, Fishman SJ, Bachur RG. A clinical decision rule to identify children at low risk for appendicitis. Pediatrics 2005;116:709-16.
10. Garcia Peña BM CE, Mandl KD. Selective imaging strategies for the diagnosis of appendicitis in children. Pediatrics 2004;113:24-8.
11. Rao PM RJ, Rattner DW, Venus LG, Novelline RA. Introduction of appendiceal CT: impact on negative appendectomy and appendiceal perforation rates. Ann Surg 1999;229:344-9.
12. Applegate KE SC, Salvator AE, Borisa VJ, Dudgeon DL, Stallion AE, Grisoni ER. Effect of cross-sectional imaging on negative appendectomy and perforation rates in children. Radiology 2001;220:103-7.
13. Guller U HS, Purves H, Muhlbaier LH, Peterson ED, Eubanks S, Pietrobon R. Laparoscopic versus open appendectomy: outcomes comparison based on a large administrative database. Ann Surg 2004;239:43-52.
14. Katkhouda N MR, Towfigh S, Gevorgyan A, Essani R. Laparoscopic versus open appendectomy: a prospective randomized double-blind study. Ann Surg 2005;242:439-48.
15. Nadler EP RK, Vaughan KG, Meza MP, Ford HR, Gaines BA. Predictors of outcome for children with perforated appendicitis initially treated with non-operative management. Surg Infect 2004;5:349-56.
16. Weber TR KM, Bower RJ, Spinner G, Vierling K. Is delayed operative treatment worth the trouble with perforated appendicitis is children? Am J Surg 2003;186:685-8.
17. Vane DW FN. Role of interval appendectomy in the management of complicated appendicitis in children. World J Surg 2006;30:51-4.
18. Andersson RE OG, Tysk C, Ekbom A. Appendectomy and protection against ulcerative colitis. N Engl J Med 2001;344:808-14.
19. Andersson R. Small bowel obstruction after appendicectomy. Br J Surg 2001;88:1387-91.





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