concluded that preoperative CT resulted in a reduced rate of negative appendectomies but an increase in

time to surgery, although there was no increase in rate of perforation. There are some data to support

the use of noncontrast CT of the abdomen in adults. The test had reasonably high sensitivity and

specificity for clinical decision making (93% and 96%, respectively).24

There have been only a few randomized trials evaluating different strategies incorporating radiologic

imaging on clinical outcomes. Only one trial found a difference in accuracy. Lee and colleagues

compared a strategy of mandatory or selective CT scanning in patients with suspected appendicitis and

less than 72 hours of symptoms. They found there were fewer negative appendectomies and

perforations in the group undergoing mandatory scans.25 Another trial reported that CT scanning

changed management in only 26% of patients.26

Clearly, CT can be useful for cases without clear indications for surgery.

IDENTIFYING PERFORATED APPENDICITIS PREOPERATIVELY

Distinguishing whether or not a patient is likely to have perforated or nonperforated appendicitis

preoperatively may be helpful in terms of counseling the patient about alternatives for management

(i.e., early vs. delayed appendectomy), risk for complications, and the expected postoperative course. A

recent meta-analysis identified four studies that presented data for perforated appendicitis. Based on

these studies, high values of laboratory markers of inflammation such as a WBC and granulocyte count

and the CRP level were relatively strong predictors of perforated appendicitis, whereas low values were

relatively strong predictors of not having perforated appendicitis.8 A combination of clinical finding and

laboratory values can help identify ruptured appendicitis preoperatively by developing a scoring system

for children based on five variables, including components of history, physical examination, laboratory

values, and CT findings.27 When the scoring system was applied to the study patient population, it

increased the specificity of the pediatric surgeon’s preoperative assessment from 83% to 98%.27

FUTURE DIRECTIONS IN DIAGNOSIS

Research is ongoing to identify accurate, efficient, and cost-effective methods of diagnosis. Advances

have included using molecular techniques for profiling gene and protein expression to identify novel

markers for appendicitis.28–30 Imaging alternatives to CT scans such as bedside surgeon-performed US,31

magnetic resonance imaging,32 or low-radiation CT scanning33 are being investigated in terms of their

diagnostic accuracy and their potential to reduce exposure to radiation. Another avenue of investigation

is the use of machine learning and advanced statistical models for informing decision making.34 As

advances in technology and diagnostic strategies are made, any improvements in accuracy must be

balanced against the proven utility of bedside clinical evaluation as well as costs and potential harms.

Figure 71-1. Acute suppurative appendicitis.

MANAGEMENT

Background for Nonoperative Management for Acute Uncomplicated Appendicitis

1892

Appendectomy for acute appendicitis is one of the most common surgical procedures performed

worldwide (Fig. 71-1). In the United States, appendectomy incurs considerable indirect costs resulting

from time lost from work, school, or usual activities after the procedure.35 The individual lifetime risk

of appendicitis is 8.6% for men and 6.7% for women.36 Uncomplicated acute appendicitis is considered

almost universally to be an indication for an appendectomy. In 1894, open appendectomy was accepted

as the treatment standard, because it saved lives, and since that time, the dictum that surgical removal

of the appendix is necessary has been largely unchallenged.37 All surgeons are taught that appendicitis

untreated will march on and eventually perforate which puts the patient’s recovery in question. Thus,

early surgical exploration and appendectomy is advocated for source control. However, appendectomy

for nonperforated appendicitis is not without associated harm. The long-term risk of small bowel

obstruction is estimated at 1.3% at 30 years after appendectomy.38 In addition, the “negative”

appendectomy rate ranges from 10% to 20%, and remains unchanged despite the widespread use of

CT.39–41

Meanwhile, nonoperative management with antibiotics has been established as the treatment for

various intra-abdominal infections such as uncomplicated diverticulitis, salpingitis, and neonatal

enterocolitis.42 It is surprising that nonoperative management of uncomplicated acute appendicitis

remains largely unexplored despite evidence that it often resolves, either spontaneously or with

antibiotic therapy, and has been shown by limited studies to have outcomes equivalent to those of

appendectomy.43,44 Accordingly, it may be reasonable to call into question the assumptions and

“evidence” that have supported routine appendectomy for this condition.

Spontaneous resolution of appendiceal inflammation does occur, although its frequency is unknown.

Presumably, increasing intraluminal pressure dislodges the obstructing material back into the cecum,

thereby relieving the distention and inflammatory process. Evidence of previous inflammation may be

recognized subsequently as a fibrotic, kinked, or adhesed appendix when viewed at a future operation.

In 1 series of 1,000 patients with appendicitis, 9% reported having had a similar clinical illness in the

past and 4% reported more than one previous attack.45

Widespread CT scan utilization for the diagnosis of appendicitis has resulted in a significant increase

in the number of CT scans performed annually.46 This has led to several interesting observations

regarding the possibility of spontaneous resolution of appendicitis from several centers. Inclusion of a

CT scan result in the Alvarado score has been shown to increase the rate of appendectomy. When

classified as having a low likelihood of appendicitis (Alvarado score ≤4), patients who underwent a CT

scan had an appendectomy rate of 48%.46 In contrast, those with an Alvarado score ≤4 who did not

undergo a CT scan had an appendectomy rate of only 12% suggesting that some percentage of the

population resolved spontaneously.

Decadt and colleagues made a comparable observation for those patients who presented with

nonspecific abdominal pain.47 The investigators used diagnostic laparoscopy instead of CT scan in the

management of patients with nonspecific abdominal pain. Patients were randomized to either (1)

diagnostic laparoscopy or (2) nonoperative management (with operative intervention if peritonitis

developed). The appendectomy rate was 39% for those randomized to diagnostic laparoscopy and 13%

for those managed nonoperatively. These indirect findings and evidence are suggestive that

uncomplicated, acute appendicitis may be initially managed nonoperatively.

Nonoperative Management of Acute Appendicitis

To date, there have been few randomized studies of nonoperative versus operative therapy for acute

appendicitis, and none have been conducted in the United States. Several reports have appeared in the

literature over the last half decade describing nonoperative management of acute, uncomplicated

appendicitis.18,48–50

The trial that has received the most attention was conducted in Sweden.48 All patients older than 18

years with presumed appendicitis diagnosed by the physician based on clinical history, laboratory tests,

US, CT, and physical examination were included. A total of 369 consecutive patients were randomized

to antibiotic treatment or surgery. Study patients received intravenous (IV) antibiotics (cefotaxime 1 g

twice and metronidazole 1.5 g once) for at least 24 hours. During this time patients received IV fluids

with no oral intake. Patients whose clinical status had improved the following morning were discharged

to continue with oral antibiotics (ciprofloxacin 500 mg twice per day and metronidazole 400 mg 3 times

per day) for a total of 10 days. In patients whose clinical condition had not improved, IV treatment was

prolonged.

There were 202 patients in the study group (antibiotics) and 167 patients in the control group

1893

(appendectomy). In the study group, 106 (52.5%) completed the intended antibiotic treatment, and 154

(92.2%) in the control group underwent an appendectomy. Of 108 patients who initially improved

without surgery, 15 (13.9%) had recurrent appendicitis at a median follow-up time of 1 year. One-third

of recurrences appeared within 10 days following discharge from the hospital. Of the 15 patients with

recurrence, 12 had surgery (4 patients had gangrenous or perforated appendicitis and 1 patient

underwent ileocecal resection) and 3 had a second round of antibiotic treatment with success.

Efficacy in the study group according to intention to treat was 48.0% (97 of 202). Eleven of 119

(9.2%) patients who primarily received antibiotics had an appendectomy owing to clinical progression.

The preoperative characteristics of these patients were similar to those of the patients who fulfilled the

antibiotic treatment. Of 250 surgically explored patients, 223 (89.2%) had appendicitis. Primary

treatment efficacy was 90.8% for antibiotic therapy compared to 89.2% for surgical exploration

analyzed per protocol. Major complications and total hospital cost for the primary admission were both

lower in the antibiotic treatment group. This study shows that nonoperative management is an option in

properly selected patients.

One of the largest retrospective series reporting nonoperative management of appendicitis comes

from Japan.51 Shindoh and colleagues reviewed their institutional experience with nonoperative

management of appendicitis; in this report 367 patients met inclusion criteria (right lower-quadrant

pain, WBC >9,000 or CRP >1.0 mg/dL). The authors describe the following three study groups: (1)

initial operation or appendectomy, (2) nonoperative group, and (3) initial nonoperative group

converted to surgery (failure). In the nonoperative groups, patients received antibiotics and were

evaluated 24 hours later. If the physical examination or laboratory parameters worsened, surgical

management was considered. In this cohort, 143 (39%) underwent initial operation (group 1), whereas

224 (61%) were managed with initial antibiotic therapy. In the initial nonoperative group, 91 patients

did not respond to antibiotics and underwent appendectomy. Factors predictive of failure included CRP

(odds ratio [OR] 5.5, 95% CI: 1.94 to 17.29) and the presence of an appendicolith (OR 4.7, 95% CI:

1.15 to 24.46). Of note, in this study recurrence of appendicitis was observed in 4.7% of patients

initially managed nonoperatively.

One of the inherent difficulties and biases in conducting a well-planned randomized clinical trial,

centers on pathologic confirmation of appendicitis. On one hand, for those patients with “suspected”

appendicitis who receive antibiotics only, treatment successes may cause one to consider the underlying

diagnosis (“is it really appendicitis?”). On the other hand, the number of patients who undergo a

negative appendectomy is not zero and exposure of these patients to surgical risks and complications is

a valid concern. The report by Hansson and colleagues demonstrated a threefold increased rate of

complications in the appendectomy group when compared to the nonoperative, antibiotic only group.48

4 The data presented are suggestive that in selected patients with acute, uncomplicated appendicitis,

antibiotic treatment seems to be an appropriate alternative to appendectomy. Multivariate analysis of

patient characteristics failed to demonstrate any logistic model for inclusion or rejection of patients for

the specified treatments. A few of these studies have found that presence of the fecaliths is predictive of

failure. Further studies are needed to create informed multivariate models that adjust for all of the

important clinical covariates. Therefore, most patients older than 18 years without obvious signs of

intra-abdominal perforation can be offered antibiotic treatment as first-line therapy. Clinical progression

and surgical judgment may then determine whether there is a real need for surgical exploration. The

benefit would be a significantly reduced frequency of major complications related to surgery, and

potentially reduced costs.

Management of Complicated Appendicitis

Of the 11 of 10,000 people in the United States who will develop acute appendicitis over their lifetime,5

an estimated 2% to 6% of patients will present with an appendiceal mass, either in the form of an

inflammatory phlegmon or abscess.52 The optimal management of these cases remains controversial.

There is no consensus in the surgical literature on whether to proceed immediately with appendectomy

or initial nonoperative management in this setting of complicated appendicitis. Another dilemma in the

management of appendicitis initially managed conservatively with antibiotics is whether or not to

perform an appendectomy at a later date (interval appendectomy). The data are disparate regarding

actual recurrence rates of appendicitis following nonoperative management, but they are commonly

reported between 5% and 20%.53–55 In addition to recurrent appendicitis, a clinical concern in older

patients who present with a cecal phlegmon is malignancy. In these cases, interval appendectomy allows

the correct pathologic diagnosis to be made.56 The effect of these management decisions on duration of

1894