Appendicitis is inflammation of the vermiform appendix. Appendix a hollow organ located at the tip of the cecum, usually in the right lower quadrant of the abdomen. However, it can be located in almost any area of the abdomen, depending on if there were any abnormal developmental issues, including midgut malrotation, or if there are any other special conditions such as pregnancy or prior abdominal surgeries. The appendix develops embryonically in the fifth week. There is a rotation of the midgut to the external umbilical cord with the eventual return to the abdomen and rotation of the cecum. This results in the usual retrocecal location of the appendix. It is often a disease of acute presentation, usually within 24 hours, but it can also present as a more chronic condition. If there has been a perforation with a contained abscess, the presenting symptoms can be more indolent. The exact function of the appendix has been a debated topic. Today it is accepted that this organ may have an immunoprotective function and acts as a lymphoid organ, especially in the younger person. Other theories contend that the appendix acts as a storage vessel for "good" colonic bacteria. Still, others argue that it is a mere developmental remnant and has no real function.
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The cause of appendicitis is usually an obstruction of the appendiceal lumen. This can be from an appendicolith (stone of the appendix) or some other mechanical etiologies. Appendiceal tumors such as carcinoid tumors, appendiceal adenocarcinoma, intestinal parasites, and hypertrophied lymphatic tissue are all known causes of appendiceal obstruction and appendicitis. Often, the exact etiology of acute appendicitis is unknown. When the appendiceal lumen gets obstructed, bacteria build up in the appendix and cause acute inflammation with perforation and abscess formation. One of the most popular misconceptions is the story of the death of Harry Houdini. After being unexpectedly punched in the abdomen, the rumor goes that his appendix ruptures, causing immediate sepsis and death. The facts are that Houdini did die from sepsis and peritonitis from a ruptured appendix, but it had no connection to him being struck in the abdomen. It was more related to widespread peritonitis and the limited availability of effective antibiotics. The appendix contains aerobic and anaerobic bacteria, including Escherichia coli and Bacteroides spp. However, recent studies utilizing next-generation sequencing revealed a significantly higher number of bacterial phyla in patients with complicated perforated appendicitis.
Appendicitis occurs most often between the ages of 5 and 45, with a mean age of 28. The incidence is approximately 233/per 100,000 people. Males have a slightly higher predisposition to developing acute appendicitis than females, with a lifetime incidence of 8.6% and 6.7% for men, and women, respectively. Approximately 300,000 hospital visits yearly in the United States for appendicitis-related issues.
The pathophysiology of appendicitis likely stems from obstruction of the appendiceal orifice. The background etiology of the obstruction might differ in the different age groups. While lymphoid hyperplasia is essential, this results in inflammation, localized ischemia, perforation, and the development of a contained abscess or frank perforation with resultant peritonitis. This obstruction may be caused by lymphoid hyperplasia, infections (parasitic), fecaliths, or benign or malignant tumors. When an obstruction is the cause of appendicitis, it leads to an increase in intraluminal and intramural pressure, resulting in small vessel occlusion and lymphatic stasis. Once obstructed, the appendix fills with mucus and becomes distended, and as lymphatic and vascular compromise advances, the wall of the appendix becomes ischemic and necrotic. Bacterial overgrowth then occurs in the obstructed appendix, with aerobic organisms predominating in early appendicitis and mixed aerobes and anaerobes later in the course. Common organisms include Escherichia coli, Peptostreptococcus, Bacteroides, and Pseudomonas. Once significant inflammation and necrosis occur, the appendix is at risk of perforation, leading to a localized abscess and sometimes frank peritonitis. The most common position of the appendix is retrocecal. While the anatomical position of the root of the appendix is mostly constant, tail positions can vary. Possible positions include retrocecal, subcecal, pre-and post-ileal, and pelvic.
Microscopic findings in acute appendicitis include the proliferation of neutrophils of the muscularis propria. The degree and extent of inflammation are directly proportionate to the severity of the infection and duration of the disease. As this condition progresses, extra appendiceal fat and surrounding tissues become involved in the inflammatory process.
History and Physical
Typically, appendicitis presents as an initial generalized or periumbilical abdominal pain that localizes to the right lower quadrant. Initially, the visceral afferent nerve fibers at T8 through T10 are stimulated, leading to vague centralized pain. As the appendix becomes more inflamed and the adjacent parietal peritoneum is irritated, the pain becomes more localized to the right lower quadrant. Pain may or may not be accompanied by any of the following symptoms:
- Fever (40% of patients)
- Generalize malaise
- Urinary frequency or urgency
Some patients may present with uncommon features. In these patients, the pain may have woken the patient up from sleep. In addition, the patients may complain of pain while walking or coughing.
Pain upon passive extension of the right leg with the patient in the left lateral decubitus position is known as the psoas sign. This maneuver stretches the psoas major muscle, which can be irritated by an inflamed retrocecal appendix. Patients often flex the hip to shorten the psoas major muscle and relieve pain.
Physical exam findings are often subtle, especially in early appendicitis. As inflammation progresses, signs of peritoneal inflammation develop. Signs include:
- Right lower quadrant guarding and rebound tenderness over McBurney's point (1.5 to 2 inches from the anterior superior iliac spine (ASIS) on a straight line from the ASIS to the umbilicus)
- Rovsing's sign (right lower quadrant pain elicited by palpation of the left lower quadrant)
- Dunphy's sign (increased abdominal pain with coughing)
Other associated signs such as the psoas sign (pain on external rotation or passive extension of the right hip suggesting retrocecal appendicitis) or obturator sign (pain on internal rotation of the right hip suggesting pelvic appendicitis) are rare. The time course of symptoms is variable but typically progresses from early appendicitis at 12 to 24 hours to perforation at greater than 48 hours. Seventy-five percent of patients present within 24 hours of the onset of symptoms. The risk of rupture is variable but is about 2% at 36 hours and increases about 5% every 12 hours after that.
Several practical scores have been defined to facilitate the prompt diagnosis of acute appendicitis, mainly based on the history and physical examination, accompanied by laboratory tests and imaging measures, including abdominal ultrasonography. Accordingly, evaluation of patients with suspicious signs and symptoms suggestive of acute appendicitis has been widely undertaken with Alvarado criteria since 1986. The highest score among Alvarado criteria is allocated to the tenderness in the right iliac fossa, leukocytosis, and each of the other predicted symptoms, including migratory right iliac fossa pain, nausea, and or vomiting, and anorexia, hold one score. Moreover, positive findings in the remaining indexes of physical examination, including fever and rebound tenderness in the right iliac fossa, would hold a similar score of one.
The emergency department physician must refrain from giving the patient any pain medication until the surgeon has seen the patient. The analgesics can mask the peritoneal signs and lead to a delay in diagnosis or even a ruptured appendix.
Laboratory measurements, including total leucocyte count, neutrophil percentage, and C-reactive protein (CRP) concentration, are requested to proceed with diagnostic steps in patients with suspected acute appendicitis. Elevated white blood cells count (WBC) with or without a left shift or bandemia is classically present, but up to one-third of patients with acute appendicitis will present with a normal WBC count. There are usually ketones found in the urine, and the C-reactive protein may be elevated. A combination of normal WBC and CRP results has a specificity of 98% for the exclusion of acute appendicitis. Moreover, the WBC and CRP results have a positive predictive value to differentiate uninflamed, uncomplicated, and complicated appendicitis. Both increasing levels of CRP and WBC correlate with a significant increase in the likelihood of complicated appendicitis. The possibility of a patient having appendicitis with both normal values of WBC and CRP level is extremely low. The WBC count of 10,000 cells/mm^3 is highly predictable in patients with acute appendicitis; however, the level would increase in patients with complicated appendicitis. Accordingly, the WBC count of equal and or above 17,000 cells/mm^3 is associated with complications of acute appendicitis, including perforated and gangrenous appendicitis.
Appendicitis is traditionally a clinical diagnosis. However, several imaging modalities are used to proceed with the diagnostic steps, including an abdominal CT scan, ultrasonography, and MRI.
An abdominal CT scan has greater than 95% accuracy for the diagnosis of appendicitis and is used with increasing frequency. CT criteria for appendicitis include an enlarged appendix (greater than 6 mm in diameter), appendiceal wall thickening (greater than 2 mm), peri-appendiceal fat stranding, appendiceal wall enhancement, the presence of appendicolith (approximately 25% of patients). It is unusual to see air or contrast in the lumen with appendicitis due to luminal distention and possible blockage in most cases of appendicitis. Non visualization of the appendix does not rule out appendicitis. Ultrasound is less sensitive and specific than CT but may be useful to avoid ionizing radiation in children and pregnant women. MRI may also be useful for pregnant patients with suspected appendicitis and an indeterminate ultrasound. Classically the best way to diagnose acute appendicitis is with a good history and detailed physical exam performed by an experienced surgeon; however, it is very easy to get a CT scan done in the emergency department. It has become common practice to rely mostly on the CT report to make the diagnosis of acute appendicitis. Occasionally appendicoliths are incidentally found on routine x-rays or CT scans. The major concern with obtaining an abdominopelvic CT scan is radiation exposure; however, the average exposure with a typical CT would not exceed 4 mSv, which is slightly above the background exposure of almost 3 mSv. Despite the higher resolution of CT images obtained with the maximal radiation of 4 mSv, lower exposures would not affect the clinical outcomes. Moreover, obtaining an IV-contrast abdominopelvic CT scan in patients suspicious of acute appendicitis should be limited to an acceptable glomerular filtration rate (GFR) equal to or above 30 ml/min. These patients are at a higher risk of developing appendicitis than the general population. These patients should be considered for prophylactic appendectomies. Studies have also shown a 10 to 30% incidence of appendicoliths present in appendectomy specimens done for acute appendicitis.
Abdominal ultrasonography is a widely used and available primary measure to evaluate patients with acute abdominal pain. A specific index of compressibility along with a diameter of less than 5 mm is used to exclude appendicitis. On the contrary, several evidence, including an anteroposterior diameter of above 6 mm, an appendicolith, and abnormally increased echogenicity of the peri-appendiceal fat, are suggestive of acute appendicitis. The major concerns with using abdominal ultrasonography to evaluate the potential diagnosis of acute appendicitis are the innate limitations of the sonography in obese patients and the operator-dependency to find the suggestive features. Moreover, patients complicated with peritonitis would hardly tolerate the graded compression.
Despite the high sensitivity and specificity of MRI in the context of acute appendicitis identification, major concerns with obtaining an abdominal MRI exist. Performing an abdominal MRI is not only expensive but also demands a high level of expertise to interpret the results. Therefore, its indications are mainly limited to special groups of patients, including pregnant women in whom an unacceptable risk of radiation exposure is embedded.
Treatment / Management
In the emergency department, the patient must be kept nil per os (NPO) and hydrated intravenously with crystalloid, and antibiotics should be administered intravenously as per the surgeon. The responsibility for the consent falls on the surgeon. The gold-standard treatment for acute appendicitis is to perform an appendectomy. Laparoscopic appendectomy is preferred over the open approach. Most uncomplicated appendectomies are performed laparoscopically. Several studies have compared the outcomes with the laparoscopic appendectomy group and patients who underwent open appendectomy. The results were suggestive of a lower incidence of wound infection, decreased level of postoperative analgesic requirement, and shorter postoperative hospital stays in the former group. The main disadvantage of laparoscopic appendectomy is the longer operative time.
In cases where there is an abscess or advanced infection, the open approach may be needed. The laparoscopic approach affords less pain, quicker recovery, and the ability to explore most of the abdomen through small incisions. Situations, where there is a known abscess from a perforated appendix may require a percutaneous drainage procedure usually done by an interventional radiologist. This stabilizes the patient and allows the inflammation to subside over time, enabling a less difficult laparoscopic appendectomy to be performed at a later date. Practitioners also start patients on broad-spectrum antibiotics. There is some disagreement regarding preoperative antibiotic administration for uncomplicated appendicitis. Some surgeons feel routine antibiotics in these cases are not warranted, while others give them routinely. There have also been several studies promoting the treatment of uncomplicated appendicitis solely with antibiotics and avoiding surgery altogether.
In patients with an appendiceal abscess, some surgeons continue antibiotics for several weeks and then perform an elective appendectomy. When the appendix has ruptured, the procedure can still be done laparoscopically, but extensive irrigation of the abdomen and pelvis is necessary. In addition, the trocar sites may have to be left open. A significant number of patients with an impression of acute appendicitis can be managed with a laparoscopic approach uneventfully. However, several factors predict the demand to convert to the open approach. The only preoperative independent factor predicting the conversion during laparoscopic appendectomy is the presence of comorbidities. Moreover, a couple of intra-operative findings, including the presence of peri-appendicular abscess and diffuse peritonitis, are independent predictors of not only a higher conversion rate but also a significant increase in postoperative complications.
While laparoscopic appendectomy has been widely used as the preferred approach for the surgical management of acute appendicitis in many centers, still open appendectomy might be selected as the practical choice, specifically in the management of complicated appendicitis with phlegmon and in the patients who are subjected to the conversion from the laparoscopic approach mainly due to the potential issues related to poor visibility. Several other alternative surgical approaches, including Natural Orifice Transluminal Endoscopic Surgery (NOTES) and Single-incision Laparoscopic Surgery (SILS), have been introduced recently. The idea of utilizing a flexible endoscope to enter the gastrointestinal or vaginal tract and consequently traversing the mentioned organ to enter the peritoneal cavity is an interesting alternative for patients who are considerate about the cosmetic aspects of the procedures. It has been later tested with successful performing of trans-gastric appendectomy in a group of ten Indian patients. The major potential advantages of appendectomy with NOTES are avoiding scars and limiting postoperative pain. Regarding the limited number of patients who have been under NOTES appendectomy, a detailed comparison of postoperative outcomes is still impossible. Hence, the major drawback with performing this technique is the demand to hybrid with the laparoscopic approach is to provide adequate retraction during the procedure and to confirm the closure of the entry site. As a surgical technique, SILS for an appendectomy is performed with an incision in the umbilicus or a preexisting abdominal scar. Potential advantages of SILS include a decrease in postoperative pain, wound-related post-procedural complications, and consequent shorter periods of sick leave. However, up to 40% of patients are still converted to conventional laparoscopy at some point during the procedure. The major disadvantage of SILS for an appendectomy is a higher long-term complication related to incisional hernia.
The differential diagnosis includes Crohn ileitis, mesenteric adenitis, the inflammatory process in the cecal diverticulum, mittelschmerz, salpingitis, ruptured ovarian cyst, ectopic pregnancy, tubo-ovarian abscess, musculoskeletal disorders, endometriosis, pelvic inflammatory disease, gastroenteritis, right-sided colitis, renal colic, kidney stones, irritable bowel disease, testicular torsion, ovarian torsion, round ligament syndrome, epididymitis, and other nondescript gastroenterological issues. Obtaining a detailed past medical history and performing a problem-oriented physical examination is necessary to exclude the differential diagnoses. Accordingly, recent viral infection mainly suggests acute mesenteric adenitis and rising severe cervical motion tenderness during trans-vaginal physical examinations typically present in the pelvic inflammatory disease. One of the challenging differential diagnoses is an acute presentation of Crohn disease. While a positive past medical history of Crohn disease can prevent unnecessary surgical procedures, Crohn disease might acutely present for the first time, mimicking acute appendicitis. Intra-operatively, the presence of inflamed ileum should raise the suspicion of Crohn disease along with other bacterial causes of acute ileitis, including Yersinia or Campylobacter ileitis. The preferred approach is to proceed with an appendectomy, even if there is no evidence of acute appendicitis. However, in patients with features of ileitis along with inflamed cecum, the appendectomy is contraindicated as it would be later complicated.
Despite the non-significant annual incidence of appendiceal cancers, with 1.2 cases per 100000 in the United States, almost 30% of this spectrum might present acutely. The most common appendiceal malignancies are Gastroenteropancreatic neuroendocrine tumors (GEP-NETs), goblet cell carcinoma (GCC), colonic-type adenocarcinoma, and mucinous neoplasm.
Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs)
(GEP-NETs) are the most common histopathological subtypes. They might rarely metastasize to the liver and or lymph nodes. Therefore, in patients with suspicious GEP-NETs (carcinoid tumor), further evaluation of the liver and the ileocolic lymph node basin are essential. The primary tumor size dictates the demanding surgical steps. Accordingly, in the carcinoid tumors of less than 1-centimeter size, an appendectomy with negative margins is the only requested surgical management. Although in the carcinoid tumor of greater than 2 cm, a right hemicolectomy is indicated, the surgical plan in appendiceal carcinoid lesions of 1 to 2 cm is still equivocal. However, in the presence of mesenteric invasion, enlarged lymph nodes, and or equivocal surgical margins, right hemicolectomy is recommended.
Goblet Cell Carcinoma
Goblet cell carcinomas are a ubiquitous entity of appendiceal malignancies in that they share the diagnostic features of both appendiceal adenocarcinoma and neuroendocrine tumors. A comprehensive peritoneal evaluation with further peritoneal cancer index score (PCIS) documentation should be undertaken. Patients with a non-metastatic and an equal or higher than 2 cm size will benefit from a right hemicolectomy.
Non-Hodgkin lymphomas (NHL), and its subtypes, including mucosa-associated lymphoid tissue (MALT) lymphomas, might initially present with acute appendicitis. The surgical management of this highly uncommon appendiceal malignancy is limited to a simple appendectomy. However, a comprehensive systemic evaluation to exclude any potential metastatic site should be included.
Adenocarcinoma of the appendix, a rare appendiceal neoplasm with three histopathological subtypes, is most commonly present with acute appendicitis. The standard treatment is performing a right hemicolectomy, irrespective of the tumor size and or the involvement of the lymph node basin.
Mucocele and Mucinous Neoplasm
Appendiceal mucocele, which might result from a benign or malignant spectrum of mucosal hyperplasia, and various cystic formations, might present with acute appendicitis. Several pre-operative radiological features, including a well-encapsulated cystic structure in the right lower quadrant, would raise the impression of an appendiceal mucocele; however, definitive diagnosis requires intraoperative evaluation and histopathological reports. The preferred surgical management is an appendectomy with great cautionary measures to prevent capsular rupture. In terms of peritoneal spread, providing documentation of the peritoneal involvement, along with tissue diagnosis with biopsies, is recommended. Moreover, suspicious mucinous neoplasm of the appendix should be managed with the peritoneal examination and record the PCIS in the presence of mucin. Patient selection for the laparoscopic approach in the management of appendiceal mucocele is extremely important and is limited to those with radiologic features suggestive of a homogenous cyst.
If diagnosed and treated early, as a relatively safe surgical procedure, the recovery within 24 to 48 hours, is expected. Cases that present with advanced abscesses, sepsis, and peritonitis may have a more prolonged and complicated course, possibly requiring additional surgery or other interventions.
Postoperative abscesses, hematomas, and wound complications are all complications that can be seen after appendectomies. If the wound does get infected, one may grow Bacteroides. "Recurrent" or "stump" appendicitis can occur if too much of the appendiceal stump is left after an appendectomy. This acts just like an appendix and can become occluded and infected just as with the initial episode. Therefore, it is important to ensure that there be very minimal and preferably less than 0.5 cm appendiceal stumps after an appendectomy. If left untreated, appendicitis can lead to abscess formation with the development of an enterocutaneous fistula. Diffuse peritonitis and sepsis can also develop, which may progress to significant morbidity and possible death.
Postoperative and Rehabilitation Care
Patients with uncomplicated appendicitis will generally experience an uneventful postoperative period, and postoperative antibiotic therapy is not required. However, the group of patients with complicated appendicitis should be planned for antibiotic therapy for an average of 4 days. Wound complications, including infections, should be managed an adequate wound opening and irrigation, followed by packing. However, antibiotic therapy is essential in the management of patients who are complicated with abscess formation and deep fascial plane involvements.
Pearls and Other Issues
Special consideration should be given to the treatment of patients with perforated appendicitis with an abscess. Those who present with an abscess and do not exhibit peritonitis may benefit from CT or ultrasound-guided percutaneous drain placement as well as antibiotics. Interval appendectomy is classically performed 6 to 10 weeks after recovery. Historically, 20 to 40 % of patients treated medically for perforated appendicitis with an abscess had recurrent appendicitis in historical literature. More recent studies suggest these rates be much lower.
Complications of appendicitis and appendectomy include surgical site infections, intra-abdominal abscess formation (3% to 4% in open appendectomy and 9 to 24% in laparoscopic appendectomy), prolonged ileus, enterocutaneous fistula, and small bowel obstruction.
Occasionally the incorrect diagnosis of acute appendicitis is made when, in reality, the correct diagnosis is Crohn disease of the cecum or terminal ileum. It is important to know that if this occurs that the appendix should be left in place if there is involvement at its base. The removal of the appendix in this situation has a high leak and fistula rate formation. On the other hand, if the base of the appendix is spared, then the appendix should be removed, even if it appears normal. This eliminates the future confusion of diagnosing acute Crohn disease versus acute appendicitis.
In the past, it was commonplace to routinely remove the appendix at the time of other nonrelated surgeries to avoid developing appendicitis in the future. Today, however, most surgeons do not routinely remove a normal appendix at the time of other scheduled procedures. If a patient does go into surgery for an incorrect diagnosis of acute appendicitis, then it is advised to remove the appendix to avoid any future diagnostic issues.
Enhancing Healthcare Team Outcomes
Patients with appendicitis usually first present to the emergency department with abdominal pain. The triage nurse should be familiar with the signs and symptoms of appendicitis because these patients need urgent admission and treatment to prevent perforation. However, making a diagnosis of appendicitis is not always easy.
Several guidelines exist that can help healthcare workers make a diagnosis of appendicitis. While most physicians, nurse practitioners, and physician assistants rely on the physical exam, others may obtain an ultrasound. For questionable cases, a CT scan of the abdomen may be helpful. The American College of Radiology recommends an ultrasound in pregnant women and an MRI in inconclusive cases in the same patient population.
While the patient is undergoing investigation, the nurse should start an IV, administer fluids as ordered. In women, a pregnancy test must be done to rule out ectopic pregnancy. The surgeon should be notified. Pain medications should typically only be administered after the surgeon has seen the patient. The nurse should monitor the patient for acute changes in pain or vital signs and report to the interprofessional team. Before surgery, the pharmacist should evaluate for potential drug-drug interactions and potential drug allergies, reporting to the team any potential concerns.
Controversy also exists on how to manage an appendiceal mass or phlegmon best and when to undertake surgery. There is no longer any question that laparoscopic appendectomy is associated with minimal pain and faster recovery, but it is costly. Other studies indicate that a single small incision provides comparable results to a laparoscopic appendectomy and is cost-effective. Given these controversies, an interprofessional team approach to diagnosis and management of appendicitis needs to be established in each institution to ensure that the patient has no morbidity and the management is cost-effective.  [Level 3]
Many large series show that simple appendicitis treated either with an open or laparoscopic procedure has excellent outcomes. (Level 3) However, more severe and complicated appendicitis is known to be associated with worse outcomes and greater utilization of resources. Further, the atypical presentation of appendicitis in pregnancy and the elderly may also make diagnosis difficult and lead to a higher incidence of complications. [Level 3] In an era of managed care where quality care indices are monitored, it behooves healthcare workers to know the current standards of diagnosis and management of appendicitis or face denial of reimbursement.
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