Hospital Medicine

Appendicitis

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Appendicitis

I. What every physician needs to know.

Appendicitis—acute inflammation of vermiform appendix—is one of the most common and treatable causes of acute abdominal pain. Estimated lifetime risk of appendicitis is about 7 to 8 percent. Its cause remains poorly understood until this day. Infections, environmental, and genetic factors have been implicated in the recent research. Causes of obstruction leading to appendicitis include fecaliths, lymphoid hypertrophy, food particles, parasites (more common in the developing world), gallstones and neoplasms. Luminal obstruction leads to distension of the lumen distal to the obstruction increasing intraluminal pressure, resulting in mucosal ischemia, vascular insufficiency, bacterial proliferation, inflammation and particularly in case of transmural inflammation potentially causing gangrene and perforation. Initially, visceral nerves are stimulated causing vague epigastric or periumbilical pain. With transmural inflammation, inflamed appendix usually irritates the adjacent parietal peritoneum stimulating somatic nerves causing the pain and tenderness in the right lower quadrant (RLQ) of the abdomen.

Despite advances, both false positive and negative imaging studies do occur and the diagnosis often requires clinical acumen and surgical confirmation. Without appropriate treatment, rupture often occurs producing both long term morbidity and mortality from localized abscess and, less commonly, diffuse peritonitis.

II. Diagnostic Confirmation: Are you sure your patient has appendicitis?

Surgery is the reference standard of diagnosis of acute appendicitis. The primary goal of the diagnostic approach is to reduce the incidence of rupture while minimizing the morbidity of surgery and to a lesser degree imaging. Approximately 10-20% of surgically removed appendices are pathologically normal, a price felt necessary to decrease the rates and complications of perforation.

A. History Part I: Pattern Recognition.

Anorexia almost always accompanies appendicitis and usually precedes the onset of pain though this history often needs to be elicited. Classically the pain starts in the epigastric or periumbilical area and after a few hours migrates to the RLQ. Though vomiting often occurs it virtually never precedes the pain and is rarely profuse.

Changes in bowel or bladder function are variable and usually mild. High fever is uncommon in the absence of perforation. The location of pain can vary depending on what portion of the parietal peritoneum the inflamed appendix touches. Right flank, suprapubic and occasionally scrotal, low back or even left lower quadrant pain may be predominant.

B. History Part 2: Prevalence.

The incidence of acute appendicitis is about 95 cases per 100, 000 patients in the developed world. Though appendicitis can occur at any age the peak incidence is from the teens through to the thirties. Though appendicitis is slightly more common in males, the rate of appendectomy is higher in women of childbearing age as several gynecological problems can mimic appendicitis.

C. History Part 3: Competing diagnoses that can mimic appendicitis.

The differential diagnosis of appendicitis includes all causes of acute abdominal pain. Ruptured ectopic pregnancy, ovarian torsion, Meckel's diverticulitis, and ruptured cecal diverticulitis are other surgical emergencies that may be confused with appendicitis.

Other non-surgical mimics include pelvic inflammatory disease, ruptured Graafian follicle (Mittelschmerz), ileitis and mesenteric adenitis (mesenteric lymphadenitis). A complete history and physical including a rectal and genitourinary exam as well as a pregnancy test in all women of childbearing age with a uterus (regardless of menstrual and sexual history) are helpful in sorting out these other conditions.

D. Physical Examination Findings.

In the absence of comorbid conditions or perforation, vital signs are usually either normal or manifest mild fever and/or slight tachycardia. The patient is usually lying still on their back often with their right hip flexed. This reduces the pain from irritation and inflammation of the parietal peritoneum. Classically, tenderness to palpation is maximal at McBurney's point which is located at the junction of lateral third and medial two-thirds of the line joining the right anterior superior iliac spine to the umbilicus.

With a retrocecal appendix, maximal tenderness to palpation may be in the right flank and with a pelvic appendix, in the right side of the rectum. The psoas sign is positive when, with the patient lying on their left side, slow passive extension of the right hip produces pain. The obturator sign is positive when passive internal rotation of the flexed right hip in the supine patient produces RLQ pain These signs suggest inflammation of the psoas and obturator muscles respectively.

Since the time course from onset of symptoms to rupture is often 12 hours to several days, serial exams can decrease both the rates of rupture and removal of a normal appendix.

Attempts have been made to calculate likelihood ratios, sensitivity and specificity for individual symptoms and signs as well as to develop scoring tools to aid in the diagnosis of appendicitis.

For example, pain before vomiting has a sensitivity of 1.0 but only a specificity of 0.64 and a positive likelihood ratio (LR+) of 2.8. Its absence is very useful if the patient is reliable and the examiner does not pose leading questions. RLQ pain has a sensitivity and specificity just a little less than imaging and rigidity has a low sensitivity but high specificity.

The Alvarado appendicitis scoring system is the most common and well-validated. One point is given for each of the following (except tenderness in the RLQ and leukocytosis which are given 2 points each): migration of pain to the RLQ, anorexia/ acetone in the urine, nausea or vomiting, tenderness in the RLQ, rebound tenderness, elevation of temperature, leukocytosis and shift to the left with the popular mnemonic used as MANTRELS.

A patient with a score of less than 4 out of 10 has very little chance of having appendicitis and observation or repeat exam as an outpatient in 12 -24 hours may be reasonable. Patients with scores of 5-6 have a moderate risk. Imaging is appropriate. Scores of 7-10 have a very high risk and surgery without imaging is a common approach.

This information is especially helpful for physicians who do not have much experience with appendicitis but may not be that helpful in reducing the rate of perforation in those patients who present without pain in the RLQ. This should not be a substitute for a surgical consult, imaging and/or serial exams in patients who appear ill and do not have a clear diagnosis. Conversely, a patient with many high-likelihood findings and/or a high Alvarado score should have urgent surgical consultation and inpatient serial exams even if imaging is negative.

E. What diagnostic tests should be performed?

Ancillary testing, though useful, does not always confirm the diagnosis and surgery may be both diagnostic and therapeutic.

1. What laboratory studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

A complete blood count (CBC) with differential, urinalysis, and a pregnancy test (in women of childbearing age with a uterus), are the basic laboratory tests. White blood cell (WBC) counts over 18,000/mcL suggest perforation or an alternative diagnosis. A normal WBC count does not rule out appendicitis. A few red or white cells in the urine is nonspecific but larger numbers suggest other diagnoses.

A pregnancy test in all women of childbearing age with a uterus is mandatory regardless of sexual and menstrual history. This includes women with a history of tubal ligation. Ectopic pregnancy is a surgical emergency that can mimic appendicitis and is more common in this population. Additionally, the radiation of a computed tomography (CT) scan is dangerous to the fetus, making ultrasonography the imaging study of choice in this population. A chemistry profile is warranted in clinically dehydrated patients, the elderly and those with significant comorbidities.

2. What imaging studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

Though much progress has been made over the last few decades, the appendix can be difficult to visualize radiographically. Though useful, imaging should not be a substitute for clinical skill. Graded compression ultrasonography is a highly user-dependent test that can be helpful if your institution has experience with this.

A pelvic or transvaginal ultrasound is useful in women when pelvic pathology is suggested and is mandatory if the patient has a positive pregnancy test. CT scan of the abdomen and pelvis is the most commonly used imaging study in suspected appendicitis. Though contrast is not necessary to evaluate the appendix and should be avoided in persons with renal failure or history of prior reactions to dye, the addition of oral and intravenous (IV) contrast increases the likelihood of finding important alternative diagnoses such as diverticular abscess or cecal tumor.

When the clinical and radiographic diagnoses do not match, the clinician should review the study with the radiologist. Though the sensitivity of CT for appendicitis is approximately 80%, a negative study should not discourage a surgical consult if the clinical suspicion is moderate or high or the clinical course worsens.

Studies of CT scans have generally reported sensitivities slightly above 90% and specificities of about 90% for appendicitis. Typical findings include a thickened and dilated appendix, inflammation of the periappendiceal fat, focal cecal wall thickening, and an appendicolith.

Sometimes appendicitis can cause a small bowel obstruction. In these cases, the appendix may be hard to visualize, leading to a delayed diagnosis. The accuracy of the CT scan may increase if the ordering physician lists this as a possibility in the order. It will decrease in thin persons due to a lack of periappendiceal fat.

F. Over-utilized or “wasted” diagnostic tests associated with this diagnosis.

CT scans in very low- and high-risk patients are over-utilized. Very low-risk patients can be observed or undergo graded compression sonography with no risk of radiation. Emergent surgical consultation should be requested on high-risk patients. This reduces the time to surgery.

III. Default Management.

The primary treatment of appendicitis is appendectomy. Since the goal is to prevent the complications of perforation, early surgical consultation is essential in moderate to high-risk patients. The primary physician should speak directly to the surgeon in order to ensure that the patient is seen in a timely manner. Laparoscopic appendectomy has a lower risk of wound infection but a higher risk of postoperative intra-abdominal abscess as compared to open appendectomy.

A. Immediate management.

All patients with suspected appendicitis should be emergently prepared for possible surgery. They should be nil per os (NPO) but may take important medications by mouth. Since many will be dehydrated most will need extra intravenous fluid in addition to maintenance fluids. Electrolyte abnormalities such as hypokalemia should be addressed.

Antibiotics reduce the risk of postoperative infectious complications and should be ordered immediately. The choice should cover enteric gram negatives and anaerobes. Though choices will be altered by local resistance patterns and patient allergies, common antibiotics used include cephalosporins with anaerobic coverage such as cefoxitin (resistance of Bacteroides fragilis to clindamycin and cefotetan are increasing), third-generation cephalosporins plus metronidazole or extended spectrum penicillins such as ticarcillin-clavulanic acid.

For more severe cases, options include piperacillin-tazobactam or carbapenems such as imipenem. Patients with moderate or severe penicillin allergies can be treated with monobactams such as aztreonam or a quinolone plus metronidazole. There is some reported cross reactivity with penicillins and aztreonam lacks gram-positive coverage so in moderately to severely ill patients an agent covering these should be added.

In many places, the resistant rates of enteric gram negatives to quinolones and ampicillin-sulbactam are high. While infections are usually polymicrobial, all possible organisms need not be covered except in severely ill patients.

Of note, appendectomy is an emergent surgery and thus risk-benefit analysis almost always favors early operation if the likelihood of appendicitis is high even in chronically ill patients with multiple comorbidities.

B. Physical Examination Tips to Guide Management.

Pre-operatively, or if the need for surgery is in doubt, serial vital signs and abdominal exams should be performed as often as every few hours. A new high fever or drop in blood pressure would suggest perforation or another diagnosis.

Increasingly severe tenderness to palpation or new or worsening peritoneal signs such as rebound tenderness, referred rebound or involuntary guarding are signs of increasing severity of the inflammatory process. Any changes for the worse should be immediately reported to the surgeon by the hospitalist. On the other hand, significant and steady improvement of any of the initial findings on abdominal exam argue against the diagnosis of appendicitis or one of its surgical mimics and would call into question the need for surgery.

This approach is useful in decreasing the negative appendectomy rate in low-risk patients or those of moderate risk with reassuring imaging while reducing the risk of perforation in this population. Atypical presentations of appendicitis are not rare and false negative imaging while not common does occur. Physicians who diligently re-examine their patients will miss fewer cases of appendicitis.

Postoperative examination is directed to look for surgical complications such as wound infection, peritonitis, ileus, atelectasis and venous thromboembolism as well as complications of treatment such as fluid overload and drug allergy.

C. Laboratory Tests to Monitor Response to, and Adjustments in, Management.

A repeat CBC adds some value in low-risk patients being observed as well as for those being treated for complications of perforation such as abscess.

Periodic chemistry profiles are useful in seriously ill patients and those with initial abnormalities. Daily labs are not always needed in uncomplicated cases.

D. Long-term management.

All management of uncomplicated appendicitis is acute. Antibiotics can be stopped 24 hours postoperatively unless there was gangrene or evidence of perforation in which case they are continued for at least 24 hours after resolution of fever and any leukocytosis though many surgeons would treat for 7-10 days.

When perforation has occurred, the timing of surgery is more complicated. If the patient has been symptomatic for a few days most surgeons favor early appendectomy. However, if the patient has been ill for several days or longer, the acute inflammatory effects of the perforation increase surgical morbidity and many patients will be treated medically followed by an interval appendectomy.

The patient is treated with antibiotics, bowel rest and, if a well-localized abscess is present, percutaneous drainage when amenable. About 10% of patients will fail this treatment and require surgery within several days. In the rest, a delayed or interval appendectomy is performed in 6-10 weeks. Delay allows for less morbid surgery as the inflammatory process resolves but does increase the risk of emergent surgery for recurrent symptoms.

Although there has been a renewed interest in antibiotics being the only therapy in the management of acute appendicitis, evidence suggests that there is a failure rate of 25 to 30% at one year. This fact should be well-communicated to the patients during the shared decision making.

The rate of negative appendectomies has declined significantly (around 6%) in the US largely due to the high rate of utilization of CT scan in the diagnostic workup. A similar rate has been reported from Switzerland due to routine use of diagnostic laparoscopy. With selective use of CT and laparoscopy, this rate is round 20% in the UK.

E. Common Pitfalls and Side-Effects of Management.

The primary goal in patients with suspected appendicitis is to prevent the complications of perforation. Careful attention to clinical decision-making is crucial, especially in those patients being observed rather than going directly from the emergency room (ER) to the operating room (OR).

  • Repeat the history and physical in detail. Do not rely on one done by other providers. Important details can be missed and symptoms and physical findings may change rapidly and thus change the likely diagnosis and management. Do, however, compare your results with those before you and address any discrepancies. A patient early in the course of appendicitis may have no RLQ tenderness to palpation only to have rebound in the RLQ or even involuntary guarding a few hours later. Alternatively, a woman whose RLQ pain and tenderness is from a ruptured right ovarian cyst may be much improved.

  • Perform a genitourinary and rectal exam in order to search for alternative causes and to look for the right-sided localized rectal tenderness suggestive of a pelvic appendicitis.

  • Consult a general surgeon early in the course of care. Discuss how soon they will see the patient, what additional tests if any they prefer, and obtain their opinion on pain control prior to their evaluation. Many surgeons will take patients with the classic presentation of appendicitis directly to the OR without any imaging.

  • Repeat your physical exam and CBC in a few hours, document it in the chart and compare the findings to data from earlier in the course of illness. If the patient is getting worse, personally ask your surgical consultant to quickly re-examine the patient.

  • If you are consulted by the ER physician on a low-risk patient and concur with discharge from the ER make sure the patient and any appropriate family are instructed to return immediately for worsening symptoms. Give them a specific time and location to follow-up in 12-24 hours. Discuss the case with the provider they will follow-up with. Other options would include a phone follow-up in the same time period. This provides an opportunity to identify the small percentage of low-risk patients who do have appendicitis or another emergent surgical condition prior to complications.

  • False-negative imaging does occur. Ultrasound is very provider-dependent. CTs are less accurate in patients with minimal body fat. If reports are negative in moderate- to high-risk patients, review the films with the radiologist. Even if still negative or non-diagnostic, surgical consultation and serial abdominal examinations are warranted.

  • The diagnosis is more challenging in the very young, pregnant women, the elderly, and the immunocompromised. Imaging studies and diagnostic scoring systems such as the Alvarado scale are less accurate.

  • All women of childbearing age with a uterus need a pregnancy test.

  • Re-inflammation of residual appendiceal tissue after appendectomy leads to a rare condition called stump appendicitis presenting with acute abdominal pain. It has been reported both after open and laparoscopic appendectomy. Some reported that this is the result of an appendectomy stump that is left too long. It can occur months to decades after appendectomy. Contrast-enhanced CT scan of abdomen is the diagnostic modality of choice to diagnose this entity. Diagnosis and management of stump appendicitis are often delayed because of the assumption that the appendix has been completely removed during the prior procedure. One should keep in mind the possibility of a stump appendicitis in patients presenting with right lower quadrant pain after appendectomy.

Antibiotic treatment in appendicitis

Antibiotic coverage in appendicitis is similar to other intra-abdominal infections. Coverage needs to include enteric gram-negative bacteria and anaerobes. Dosages need to be adjusted for renal failure and any other conditions that would affect the pharmacokinetics. Allergies, drug interactions and pregnancy status must also be considered.

Common options include the following:

  • Piperacillin / tazobactam at 3.375 or 4.5 gm intravenously every 4 hours (pregnancy category B).

  • Ticarcillin / clavulanate at 3.1 gm intravenously every 4 hours (pregnancy category B).

  • Ceftriaxone (pregnancy category B) at 1 gm intravenously every 24 hours plus metronidazole (pregnancy category B but some experts have concern over its use especially in the first trimester) at 500 mg intravenously every 8 hours.

Less common options include the following:

  • Meropenem (pregnancy category B) at 1 gm every 8 hours (use cautiously in patients with a history of immediate hypersensitivity reactions to penicillins and other beta lactams.)

  • Ciprofloxacin (pregnancy category C) at 400 mg intravenously every 12 hours plus metronidazole (see comment above) at 500 mg every 8 hours.

IV. Management with Co-Morbidities.

Appendectomy for appendicitis is usually an emergent procedure. Most often the risks of delaying surgery in those with a high chance of appendicitis will be greater than the benefits even in patients with severe comorbid conditions. If surgical risks are felt unacceptable, antibiotics, bowel rest, IV hydration and aggressive attempts to improve the comorbid conditions should be performed. Frequent re-evaluation of the risks and benefits of surgery should be made.

A. Renal Insufficiency.

Medication doses should be renally adjusted and close attention paid to volume status. Iodinated contrast should be avoided and imaging for postrenal obstruction considered in acute renal failure. The potential benefits of any diagnostic study or treatment of acute renal failure must be compared to the increased risks of perforation with any delay in surgery.

B. Liver Insufficiency.

A perforated appendix in a patient with cirrhotic ascites will most likely lead to peritonitis rather than a localized abscess. This can be confused with spontaneous bacterial peritonitis (SBP). RLQ pain may precede the generalized abdominal pain common in subacute bacterial peritonitis. Additionally, platelet transfusion and/or fresh frozen plasma may be needed perioperatively.

C. Systolic and Diastolic Heart Failure.

Well-compensated heart failure is not a contraindication to appendectomy. Uncompensated heart failure needs to be addressed emergently as a delay in surgery could lead to worse outcomes.

D. Coronary Artery Disease or Peripheral Vascular Disease.

Appendectomy is an emergent procedure. In those with confirmed or high risk of acute appendicitis, surgery should not be delayed in patients presenting on antiplatelet agents such as clopidogrel or aspirin.

E. Diabetes or other Endocrine issues.

Metformin should be stopped, as most of these patients will receive iodinated contrast or general anesthesia.

Hypoglycemia risk is high given the prolonged period of NPO or poor postoperative intake and a plan should be in place to both monitor for this and reduce the risk (insulin regimen adjustment and/or consideration of using a dextrose containing intravenous fluid).

Additionally, prolonged periods of moderate to severe hyperglycemia may increase infectious and wound healing complications. Changes to the diabetic regimen may have to be made more frequently in order to minimize both extremes of glucose readings.

F. Malignancy.

Abdominal tumors can mimic or cause appendicitis. Patients with known cancers will have a higher risk of postoperative venous thromboembolic events.

G. Immunosuppression (HIV, chronic steroids, etc.).

Severely immunocompromised patients will be less likely to mount an inflammatory response and are more likely to perforate. The absolute WBC count will be less useful though many patients' white blood cell count will rise above their baseline.

Neutropenic typhlitis may mimic appendicitis. This is most likely in the setting of severe chemotherapy induced neutropenia These patients also have higher complications of surgery. An experienced medical and/or surgical oncologist should be consulted if available. Patients on chronic steroids or who recently stopped chronic steroids should receive perioperative intravenous stress steroids.

H. Primary Lung Disease (COPD, Asthma, ILD).

Respiratory complications are more common and can be reduced with incentive spirometry, adequate pain control and early mobility, in addition to standard medical practice.

I. Gastrointestinal or Nutrition Issues.

No change in standard management.

J. Hematologic or Coagulation Issues.

Since appendectomy is usually an emergency, these issues must be addressed promptly. If appendicitis is likely, the risks of surgery, though greater than those without these problems, will virtually always be less than medical management.

K. Dementia or Psychiatric Illness/Treatment.

A plan to reduce the risk of the patient pulling out tubes and catheters should be in place.

V. Transitions of Care.

A. Sign-out Considerations While Hospitalized.

  • For low-risk patients being observed, sign out specific times to re-examine the patient, any tests pending and the name and input of any surgical consult. For example: "patient had mild RLQ thrombotic thrombocytopenic purpura (TTP) without rebound 4PM and WBC 9. Repeat exam and CBC around 8PM. Call Dr. X of surgery (feels not likely appendicitis) if either worse or CT, which is pending, suggests appendicitis. Call radiology if CT report not available by 7PM".

  • For patients going to the OR, sign out expected time of operation, the name of the surgeon and any important comorbidities. For example: "Mr. J is going for an appendectomy (appy) by Dr. X around 7PM. Preop creatinine 1.9 with baseline 1.1 on NS 125/hour plus periodic boluses. Please check on patient postop, repeat creatinine ordered for 10PM and re-evaluate fluid status and needs".

  • For postoperative patients, sign out the name of the surgeon and any anticipated problems. For example: "Ms S is postoperative day (pod) 2 status post (s/p) appy by Dr. X for appendicitis with micro perforation. Required Zofran for vomiting this AM but now taking clears well. Suggest kidneys, ureters, bladder (KUB) if vomiting recurs to rule out (r/o) ileus".

B. Anticipated Length of Stay.

The typical length of stay for appendicitis with an uncomplicated appendectomy is about 3 days. Patients with abscess or peritonitis from perforation, the elderly and those with significant comorbidities will have longer stays.

C. When is the Patient Ready for Discharge?

Non-surgical patients are ready for discharge when their abdominal pain and other admitting acute symptoms and signs are mostly resolved or an alternative diagnosis that can be treated as an outpatient is apparent.

Postoperative patients are generally ready for discharge when any acute abnormal vital signs have resolved, the patient is eating, urinating, has had a bowel movement, and is ambulating. The surgeon should concur and the wound examined on the day of discharge.

Patients with perforation awaiting interval appendectomy can be discharged when vitals are normal (mild hypertension is acceptable), the patient is eating, urinating and ambulating, and feels improved. If necessary, arrangements for any care of drains or home intravenous antibiotics must be in place.

D. Arranging for Clinic Follow-up.

See below.

1. When should clinic follow up be arranged and with whom?

For patients whose symptoms resolved and did not require surgery, follow-up should be with their primary care doctor. If symptoms have not completely resolved, then follow-up should be the next day with either the surgeon or primary care doctor. If this is not possible, then a scheduled phone follow-up the next day should be substituted.

Patients with status post appendectomy or those awaiting interval appendectomy should follow-up with the surgeon generally within several days of discharge. If the patient has any significant comorbid conditions that may affect their clinical course after discharge, then follow-up with their primary care doctor or appropriate specialist in a few days is warranted.

2. What tests should be conducted prior to discharge to enable best clinic first visit?

None

3. What tests should be ordered as an outpatient prior to, or on the day of, the clinic visit?

If the patient is on antibiotics for perforation order a CBC. If there were other acute problems, order tests as appropriate. Most patients will not need any.

E. Placement Considerations.

Generally, none.

F. Prognosis and Patient Counseling.

Patients have an excellent prognosis and should be instructed to call with recurrent symptoms (especially those sent home after observation without a diagnosis and those awaiting interval surgery).The surgeon should also give their discharge instructions.

VI. Patient Safety and Quality Measures.

A. Core Indicator Standards and Documentation.

Some insurers follow the percentage of normal appendices removed by individual surgeons. Average rates are about 10-20%.

B. Appropriate Prophylaxis and Other Measures to Prevent Readmission.

Readmission should be rare except for those scheduled for interval appendectomy, many of whom will be readmitted with recurrent symptoms prior to their elective surgical date.No special measures are required.

VII. What's the evidence?

Bhangu, A. "Acute appendicitis: Modern understanding of pathogenesis, diagnosis, and management". Lancet. vol. 386. 2015. pp. 1278-87.

Ünlüer, EE. "A difficult to diagnose case: Stump appendicitis". Am J Emerg Med. vol. pii. 2015. pp. S0735-6757.

Salminen, P. "Antibiotic Therapy vs Appendectomy for Treatment of Uncomplicated Acute Appendicitis, The APPAC Randomized Clinical Trial". JAMA. vol. 313. 2015. pp. 2340-2348.

Varadhan, KK. "Safety and efficacy of antibiotics compared with appendectomy for treatment of uncomplicated acute appendicitis: meta-analysis of randomized controlled trials". BMJ. Apr. vol. 344. 2012. pp. e2156.

Wagner, David, Simel, Drummond, Rennie. "Does this Adult Patient Have Appendicitis". JAMA evidence: The Rational Clinical Examination. 2009.

Alvarado, A. "A practical score for the early diagnosis of acute appendicitis". Ann Emerg Med. vol. 15. 1986. pp. 557-64.

Levine, C D. "Pitfalls in the CT diagnosis of appendicitis". British Journal of Radiology. vol. 77. 2004. pp. 792-799.

(Radiographs are included in this source.)

Diagnosis and management of complicated intra-abdominal infection in adults and children. Guidelines by the Surgical Infection Society and the Infectious Disease Society of America. NGC-7597 (revised 1/15/2010). 2010.

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