The Appendix

Anatomy and Embryology

• Development
  • Midgut organ first identified at 8 weeks gestation.
  • Originates as a small outpouching of the cecum.
  • Becomes elongated and tubular as the cecum rotates medially.
• Structure
  • Mucosa: Colonic-type with columnar epithelium, neuroendocrine cells, and mucin-producing goblet cells.
  • Submucosa: Contains lymphoid tissue, possibly playing a role in the immune system.
  • May act as a reservoir for beneficial bacteria, aiding in the maintenance of normal colonic flora.
• Blood Supply
  • Derived from the superior mesenteric artery.
  • Ileocolic artery gives rise to the appendiceal artery.
  • Mesoappendix contains blood vessels and lymphatics draining to ileocecal nodes.
• Size and Location
  • Length varies from 5–35 cm (average 8–9 cm in adults).
  • Base located at the convergence of the taeniae at the tip of the cecum.
  • Variations in position:
    • Retrocecal (intraperitoneal): ~60%
    • Pelvic: 30%
    • Retroperitoneal: 7–10%
    • Rare cases of agenesis, duplication, or triplication.

Appendicitis

Incidence and Significance

• Commonality: One of the most common diseases requiring surgery.
• Hospitalizations: Responsible for up to 300,000 annually in the U.S.
• Lifetime Risk: Affects 6–7% of the population.
• Peak Incidence: Second decade of life.
• Dietary Influence: Less common in underdeveloped countries; low-fiber, high-fat Western diet may contribute.

History

• First Appendectomy: Performed by Claudius Amyand in 1735.
• First Clinical Description: By Reginald Heber Fitz in 1886, recommending prompt surgical removal.
• Surgical Advances:
  • McBurney's incision and technique (1894).
  • First laparoscopic appendectomy by Kurt Semm (1982).
• Modern Improvements: Broad-spectrum antibiotics, interventional radiology, and critical care strategies have reduced morbidity and mortality.

Pathophysiology and Bacteriology

• Cause: Luminal obstruction leading to increased pressure and ischemia.
  • Common Causes:
    • Fecaliths and fecal stasis.
    • Lymphoid hyperplasia.
    • Neoplasms.
    • Foreign bodies (fruit/vegetable matter, barium).
    • Parasites (e.g., Ascaris, pinworms).
• Progression:
  • Ongoing mucus secretion and bacterial gas increase pressure.
  • Venous drainage impaired, causing mucosal ischemia.
  • Can lead to full-thickness ischemia and perforation.
  • Perforation Outcomes:
    • Formation of a periappendiceal abscess.
    • Diffuse peritonitis if free perforation occurs.

• Bacteriology:

  • Infection is polymicrobial, similar to colonic flora.
  • Common Organisms:
    • Escherichia coli
    • Bacteroides fragilis
    • Enterococci
    • Pseudomonas aeruginosa
    • Klebsiella pneumoniae
  • Antibiotic Coverage: Should target gram-negative bacteria and anaerobes.

  

• Pain Mechanism:

  • Visceral Pain: Initial vague, periumbilical pain due to distention.
  • Somatic Pain: Later localized right lower quadrant pain from peritoneal irritation.

Differential Diagnosis

• Children:
  • Mesenteric adenitis
  • Acute gastroenteritis
  • Intussusception
  • Meckel diverticulitis
  • Inflammatory bowel disease
  • Testicular torsion (males)
• Women of Childbearing Age:
  • Ruptured ovarian cysts
  • Mittelschmerz
  • Endometriosis
  • Ovarian torsion
  • Ectopic pregnancy
  • Pelvic inflammatory disease
• General Considerations:
  • Nephrolithiasis
  • Urinary tract infection
  • Typhlitis (in immunocompromised patients)
  • Diverticulitis and malignancy (in the elderly)

Presentation

History

• Initial Symptoms:
  • Vague periumbilical pain migrating to the right lower quadrant.
  • Anorexia, nausea, and possibly vomiting.
  • May experience diarrhea or constipation.
• Pain Localization: Due to peritoneal irritation as inflammation progresses.

Physical Examination

• General Appearance: Patient may appear ill and lie still to minimize pain.
• Vital Signs:
  • Tachycardia
  • Mild dehydration
  • Low-grade fever (<38.5°C), though fever may be absent.
• Abdominal Examination:
  • Tenderness and guarding in the right lower quadrant.
  • McBurney's point tenderness.
  • Rebound tenderness indicating localized peritonitis.
  • Diffuse peritonitis or rigidity suggests perforation.

• Special Signs:

  • Rovsing's Sign: Right lower quadrant pain upon left-sided palpation.
  • Obturator Sign: Pain with internal rotation of the flexed right hip.
  • Psoas Sign: Pain with extension of the right hip.

  

• Rectal and Pelvic Exams:

  • May reveal tenderness or mass if appendix is pelvic.
  • Cervical motion tenderness can occur due to adjacent inflammation.

Laboratory Studies

• White Blood Cell Count:
  • Leukocytosis with a left shift in 90% of cases.
  • Normal WBC does not exclude appendicitis.
• Urinalysis:
  • Typically normal.
  • May show trace leukocyte esterase or pyuria.
• Pregnancy Test:
  • Mandatory in women of childbearing age.
• Biomarkers:
  • C-reactive protein and others lack sufficient specificity.

Clinical Scoring Systems

• Alvarado Score:
  • Utilizes symptoms, signs, and lab findings.
  • Score components (MANTRELS):
    • Migratory right iliac fossa pain
    • Anorexia
    • Nausea/vomiting
    • Tenderness in right iliac fossa
    • Rebound tenderness
    • Elevated temperature
    • Leukocytosis
    • Shift to the left (neutrophilia)

  • Interpretation:

    • Score <4: Appendicitis unlikely.
    • Score ≥7: High probability of appendicitis.

    

Imaging Studies

• Plain Radiographs:
  • Limited utility.
  • May show a calcified fecalith in ~5% of cases.
• Computed Tomography (CT) Scan:
  • Most common imaging for appendicitis.
  • High sensitivity and specificity.
  • Technique: Intravenous contrast only.
  • Findings:
    • Enlarged appendix (>7 mm in diameter).
    • Wall thickening and enhancement ("target sign").
    • Periappendiceal fat stranding, fluid, or air suggesting perforation.
• Ultrasound (US):
  • Preferred in pediatric and pregnant patients to avoid radiation.
  • Operator-dependent; requires skilled sonographer.
  • Findings:
    • Enlarged, non-compressible appendix.
    • Secondary signs: Free fluid, hyperemia, fat induration, adenopathy.
• Magnetic Resonance Imaging (MRI):
  • Used primarily in pregnant patients.
  • Non-contrast study.
  • High sensitivity and specificity.
  • Advantages: Excellent resolution, operator-independent.
  • Disadvantages: Cost, limited availability, potential motion artifacts.

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Treatment of Appendicitis

General Approach to the Patient with Suspected Appendicitis

1. Initial Clinical Suspicion of Appendicitis:
   • Symptoms <48 hours:
     • Male:
       • Classic presentation (e.g., localized peritonitis) → Laparoscopic appendectomy.
       • Equivocal presentation → Proceed to CT scan:
         • Positive for appendicitis → Laparoscopic appendectomy.
         • Negative for appendicitis → Brief observation:
           • If no improvement → Diagnostic laparoscopy.
           • If improving → Discharge.
     • Female or Pregnant:
       • Pregnant:
         • Follow pregnancy-specific algorithm.
       • Non-pregnant:
         • Follow CT scan for diagnosis:
           • Positive for appendicitis → Laparoscopic appendectomy.
           • Negative for appendicitis → Brief observation.
           • Other diagnosis → Treat as indicated.
2. Symptoms >48 hours:
   • Follow the algorithm for delayed presentation of appendicitis.

A. Acute Uncomplicated Appendicitis

• Gold Standard Treatment: Prompt appendectomy.
  • Begin fluid resuscitation as needed.
  • Initiate intravenous broad-spectrum antibiotics targeting gram-negative and anaerobic organisms immediately.
  • Proceed to surgery without undue delay.

Surgical Approaches

Open Appendectomy

• Patient Position: Supine.
• Incision Options:
  • McArthur-McBurney (oblique muscle-splitting incision).
  • Rockey-Davis (transverse incision).
  • Midline incision (conservative).
• Procedure Steps:
  • Grasp and deliver the cecum using the taeniae.
  • Visualize and deliver the appendix.
  • Divide the mesoappendix.
  • Crush, ligate, and divide the appendix near its base.
  • Cauterize or invert the stump using a purse-string or "Z" suture.
  • Irrigate the abdomen and close the wound in layers.

Laparoscopic Appendectomy

• Patient Position: Supine; bladder emptied.
• Procedure Steps:
  • Enter the abdomen at the umbilicus; confirm diagnosis with laparoscope.
  • Place two additional working ports (typically in the left lower quadrant and suprapubic area or supraumbilical midline).
  • Surgeon and assistant stand on the left side of the patient.
  • Use atraumatic graspers to elevate the appendix.
  • Divide the mesoappendix (e.g., using harmonic scalpel).
  • Secure the base with endoloops or an endoscopic stapler.
  • Retrieve the appendix using a plastic retrieval bag.
  • Suction and irrigate the pelvis.
  • Remove trocars and close the wounds.
• Postoperative Care:
  • Antibiotics: Not continued beyond a single preoperative dose.
  • Diet: Begin oral intake immediately and advance as tolerated.
  • Discharge: Usually possible the day after surgery.

B. Perforated Appendicitis

• Preoperative Management:
  • May require more aggressive resuscitation.
  • Immediate initiation of broad-spectrum antibiotics.
• Surgical Approach:
  • Both open and laparoscopic methods are acceptable.
  • Challenges:
    • Handling a friable, gangrenous, perforated appendix requires gentle, meticulous technique.
• Intraoperative Care:
  • Cultures:
    • Not mandatory unless there's prior healthcare exposure or recent antibiotic use.
    • Some surgeons routinely obtain cultures to tailor antibiotic therapy.
  • Clearance of Infectious Material:
    • Suction and irrigation to remove purulent material.
    • Manual removal of any spilled fecal material or fecaliths.
    • Focus on the right lower quadrant and pelvis.
    • Simple suction aspiration may be as effective as large-volume irrigation.
  • Drain Placement:
    • Not routinely placed unless a discrete abscess cavity is present.
    • If present, place a single closed suction drain.
• Wound Management:
  • If open technique is used, leave skin and subcutaneous tissues open for 3-4 days.
  • Perform delayed primary closure at the bedside if necessary.
  • Recent data suggest delayed closure may not reduce infection rates and could increase length of stay.
• Postoperative Care:
  • Continue broad-spectrum antibiotics for 4-7 days as per IDSA guidelines.
  • Modify antibiotics based on culture results if obtained.
  • Nasogastric suction not routinely used unless ileus develops.
  • Begin oral intake after return of bowel function.
  • Discharge when the patient tolerates diet, is afebrile, and has normal WBC count.
• Complications:
  • Postoperative Abscess:
    • Occurs in 10-20% of cases.
    • Symptoms: Fever, leukocytosis, pain, delayed bowel function.
    • Diagnosis: CT scan with intravenous contrast.
    • Management:
      • CT-guided percutaneous drainage is preferred.
      • Alternative approaches: Laparoscopic, transrectal, or transvaginal drainage if CT-guided drainage isn't feasible.

Laparoscopic Versus Open Appendectomy

• Historical Debate: Choice between open and laparoscopic methods.
• Study Findings:
  • Ingraham et al. (2010) analyzed over 32,000 cases.
  • Laparoscopic Appendectomy associated with:
    • Lower risk of wound complications.
    • Lower risk of deep surgical site infections in uncomplicated cases.
    • Fewer wound complications in complicated appendicitis.
    • Slightly higher incidence of intraabdominal abscess in complicated cases (not consistent across all studies).
• Advantages of Laparoscopic Approach:
  • Allows full examination of the peritoneal cavity.
  • Technically simpler in obese patients.
  • Potential for earlier discharge (within hours post-operation).
• Consensus:
  • Both open and laparoscopic approaches are acceptable.
  • Prompt and safe appendectomy is the priority, regardless of technique.

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Delayed Presentation of Appendicitis

• Clinical Presentation:
  • Patients may present several days to weeks after onset.
  • Symptoms: Localized right lower quadrant pain, fever, possible palpable mass.
• Management Strategy:
  • Nonoperative initial treatment is preferred.
  • Fluid resuscitation and initiation of broad-spectrum antibiotics.
  • Obtain a CT scan to confirm perforated appendicitis with a localized abscess or phlegmon.
  • Percutaneous Drainage:
    • If an abscess is present, perform CT-guided percutaneous drainage.
    • Drain catheter remains for 4-7 days during antibiotic therapy.
  • Alternative Drainage Methods:
    • If percutaneous drainage isn't feasible, consider transrectal, transvaginal, or laparoscopic drainage.
  • Antibiotic Therapy Alone:
    • Used if there's a phlegmon or insufficient fluid to drain.
    • Typically continued for 4-7 days as per IDSA guidelines.
• Interval Appendectomy:
  • Traditional Practice: Elective removal of the appendix weeks to months later.
  • Reevaluation of Practice:
    • Low risk of recurrence (~8% over 8 years in pediatric patients).
    • Higher risk of complications with interval appendectomy.
    • Current Recommendation:
      • Reserve interval appendectomy for patients with recurrent symptoms.
      • Consider in patients with an appendicolith due to higher recurrence risk.
      • Colonoscopy recommended in adults to rule out neoplasms mimicking appendicitis.

Approach to the Patient with Delayed Presentation of Suspected Appendicitis

Step 1: Diffuse Peritonitis

• Yes:
  • Resuscitation, antibiotics, and proceed to operating room for source control.
  • If other diagnosis is found, treat as indicated.
• No:
  • Perform CT scan.
  • If appendicitis confirmed:
    • Abscess:
      • Determine if CT drainage is feasible.
        • Yes: Proceed with CT drainage and antibiotics.
        • No: Perform laparoscopic drainage with antibiotics.
    • Phlegmon:
      • Treat with antibiotics.

Step 2: Post-Treatment

• Adult:
  • After discharge, perform a colonoscopy.
    • Normal findings: Consider interval appendectomy.
    • Neoplasm found: Follow algorithm for appendiceal neoplasm.
• Child:
  • Consider interval appendectomy.
    • Neoplasm found: Follow neoplasm algorithm.

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The Normal-Appearing Appendix at Operation

• Negative Appendectomy:
  • Occurs when a normal appendix is found during surgery.
• Evaluation of Abdomen:
  • Thoroughly examine for other causes of pain.
  • Laparoscopic approach facilitates comprehensive assessment.
  • Check for:
    • Meckel diverticulum.
    • Signs of Crohn disease.
    • Mesenteric adenitis.
    • Gynecological conditions (e.g., ovarian torsion, endometriosis).
    • Acute diverticulitis.
• Decision to Remove Appendix:
  • Routine Removal is advisable because:
    • Prevents future diagnostic confusion in recurrent pain.
    • Some pathological abnormalities may not be apparent intraoperatively.
    • Avoids potential future appendicitis.
  • Exception:
    • In Crohn disease, avoid appendectomy if the base of the appendix and cecum are involved to prevent fistula formation.

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Nonoperative Treatment of Uncomplicated Appendicitis

• Emerging Interest: Treating with antibiotics alone.
• Recent Studies:
  • NOTA Study:
    • 159 patients treated with antibiotics.
    • 7-day failure rate: 11.9%.
    • 2-year recurrence: 13.8%.
  • APPAC Trial:
    • 530 patients with CT-confirmed appendicitis.
    • 1-year recurrence rate: 27%.
    • Concluded nonoperative therapy didn't meet noninferiority criteria compared to surgery.
• Meta-Analysis Findings:
  • Initial failure rate: Approximately 9%.
  • 1-year recurrence rate: Approximately 25%.
  • Increased risk of progression to complicated appendicitis in failed nonoperative cases.
  • Longer hospital stay with antibiotics, despite lower initial cost.
• Current Approach:
  • Reserve nonoperative therapy for patients with prohibitive operative risks.
  • Manage failures with additional interventions (e.g., CT-guided drainage).
  • Large, high-quality trials needed to further assess efficacy.

Approach To Nonoperative Management of Acute Uncomplicated Appendicitis

1. Initial Diagnosis:
   • Suspected uncomplicated appendicitis → CT scan for confirmation.
     • If appendicitis is not confirmed: Treat based on the actual diagnosis.
     • If appendicitis is confirmed:
       • Good operative candidate → Appendectomy.
       • Poor operative candidate → Nonoperative treatment with antibiotics.
2. Nonoperative Treatment with Antibiotics:
   • If the patient improves:
     • Discharge and monitor for recurrence.
     • Outpatient colonoscopy recommended.
     • Follow-up:
       • Asymptomatic → Continue expectant management.
       • Recurrence → Medical optimization and appendectomy.
   • If the patient worsens:
     • Peritonitis or sepsis: Medical optimization and appendectomy.
     • No peritonitis, stable: Repeat CT scan.
       • Abscess found → CT-guided drainage followed by discharge and outpatient colonoscopy.
       • Phlegmon found → Continue IV antibiotics until resolved, then discharge.

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“Chronic” Appendicitis as a Cause of Abdominal Pain

• Presentation:
  • Patients with recurrent right lower quadrant pain.
  • Possible thickened appendix or appendicolith on imaging without acute inflammation.
• Management:
  • Elective appendectomy considered on a case-by-case basis.
  • Preferable when supported by radiographic evidence.
• Nonspecific Lower Abdominal Pain:
  • Multidisciplinary evaluation involving gastroenterology and gynecology.
  • Diagnostic laparoscopy may be performed.
    • Appendectomy often done during the procedure.
    • Helps to exclude appendix as a future source of pain.
• Patient Communication:
  • Managing expectations is crucial.
  • Chronic pain may persist despite appendectomy.

Incidental Appendectomy

• Definition:
  • Removal of a normal appendix during an unrelated abdominal surgery (e.g., hysterectomy, cholecystectomy).
• Historical Practice:
  • Performed to prevent future appendicitis, especially in younger patients (<35 years).
• Current Controversy:
  • Risks:
    • Potential for increased morbidity and mortality.
    • Not cost-effective as a preventive measure.
    • Appendix may play a role in maintaining healthy colonic flora.
  • Data Analysis:
    • Studies show additional risks without significant benefits.
• Current Recommendation:
  • Inspect the appendix during abdominal surgeries.
  • Do not remove unless an abnormality is detected.

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Appendicitis in Special Populations

A. Appendicitis in the Pregnant Patient

• Prevalence:
  • Most common non-obstetric emergency during pregnancy.
  • Most frequent reason for general surgical intervention in pregnant patients.
• Diagnostic Challenges:
  • Typical presentation occurs in only 50–60% of cases.
  • Nonspecific symptoms like nausea and vomiting overlap with normal pregnancy.
  • Physical examination is complicated due to:
    • Gravid uterus displacing the appendix cephalad.
    • Presence of round ligament pain mimicking appendicitis.
  • Laboratory indicators are unreliable:
    • Physiologic leukocytosis is normal in pregnancy.
    • Elevated C-reactive protein levels are common.
  • Need to distinguish from obstetric emergencies:
    • Preterm labor
    • Placental abruption
    • Uterine rupture
  • High negative appendectomy rate (25–50%) when based solely on clinical presentation.
• Impact on Pregnancy:
  • Complicated appendicitis increases risks:
    • Preterm labor: 11%
    • Fetal loss: 6%
  • Negative appendectomy also poses risks:
    • Preterm labor: 10%
    • Fetal loss: 4%
  • Uncomplicated appendicitis has lower risks:
    • Preterm labor: 6%
    • Fetal loss: 2%
  • Accurate preoperative diagnosis is crucial to minimize risks.
• Imaging Recommendations:
  • Ultrasound (US) with graded compression:
    • First-line imaging modality.
    • Safe, inexpensive, and readily available.
    • Assesses both appendicitis and fetal well-being.
    • Reduced sensitivity and specificity (83%) due to the gravid uterus.
  • MRI without gadolinium contrast:
    • Recommended if US is inconclusive.
    • Offers excellent soft tissue contrast without ionizing radiation.
    • Reduces negative appendectomy rates by 47% without increasing perforation rates.
    • Availability may be limited; consider potential delays carefully.
  • CT Scan:
    • Considered when US and MRI are unavailable or inconclusive.
    • Lower negative appendectomy rate (8%).
    • Use low-dose protocols and avoid intravenous contrast to minimize radiation exposure.
    • Further studies needed before endorsing routine use.
• Surgical Approach:
  • Laparoscopic Appendectomy:
    • Most common approach in pregnant patients.
    • Safe if performed by experienced surgeons.
    • Advantages:
      • Easier identification of the variable appendix location.
      • Allows thorough evaluation for other intra-abdominal pathologies.
    • Technical Considerations:
      • Adjust trocar placement to accommodate the gravid uterus.
      • Use an open access (Hasson) technique for initial entry to prevent uterine injury.
  • Open Appendectomy:
    • An alternative if laparoscopy is contraindicated or not available.

Approach to the Pregnant Patient with Suspected Appendicitis

Step 1: Diffuse Peritonitis

• Yes:
  • Resuscitation, antibiotics, proceed to operating room for source control.
  • If other diagnosis confirmed, treat as indicated.
  • If appendicitis confirmed, proceed to appendectomy.
• No:
  • Perform Ultrasound (US).
    • If appendicitis confirmed → Proceed to appendectomy.
    • If US is negative → Perform MRI:
      • If MRI confirms appendicitis → Appendectomy.
      • If MRI is negative for appendicitis → Observation:
        • If patient improves → Discharge.
        • If patient worsens → Perform diagnostic laparoscopy.

This algorithm emphasizes the diagnostic and treatment steps for pregnant patients with suspected appendicitis, highlighting the use of ultrasound (US) and magnetic resonance imaging (MRI) for confirming appendicitis and the necessary actions based on clinical findings.

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B. Appendicitis in the Elderly

• Prevalence and Considerations:
  • Appendicitis is not uncommon in the elderly.
  • Should be included in the differential diagnosis for acute abdominal pain.
  • Higher morbidity due to:
    • Reduced physiologic reserves.
    • Impaired immune responses.
• Diagnostic Challenges:
  • Expanded differential diagnosis includes:
    • Acute diverticulitis
    • Malignancies
    • Intestinal ischemia
    • Ischemic colitis
    • Complicated urinary tract infections
    • Perforated ulcers
  • Atypical presentations are common.
  • Higher perforation rates (40–70%).
  • Comorbidities complicate diagnosis and treatment.
• Management Strategies:
  • Immediate laparotomy for patients with diffuse peritonitis.
  • CT scanning for localized pain without peritonitis to confirm diagnosis and identify other pathologies.
  • Laparoscopic Appendectomy:
    • Safe and preferred if the patient can tolerate general anesthesia.
  • Alternative Approaches:
    • Open appendectomy under spinal anesthesia for those who cannot undergo general anesthesia.
    • Nonoperative management may be considered for patients too ill for surgery.
  • Individualized Treatment:
    • Tailor the approach based on the patient's overall health and specific challenges.

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C. Appendicitis in the Immunocompromised Patient

• Management Principles:
  • Prompt appendectomy is the standard treatment.
  • High index of suspicion is necessary due to atypical presentations.
• Diagnostic Challenges:
  • Blunted immune response may lead to:
    • Absence of fever.
    • Lack of leukocytosis.
    • Minimal or no peritonitis.
  • Early symptoms may be less pronounced.
• Diagnostic Tools:
  • Early CT imaging is recommended to:
    • Confirm the diagnosis of appendicitis.
    • Exclude other conditions like neutropenic enterocolitis (typhlitis), which may be managed nonoperatively.
• Treatment Considerations:
  • Surgical intervention should not be delayed.
  • Close monitoring postoperatively due to increased risk of complications.
  • Multidisciplinary approach involving infectious disease specialists may be beneficial.

D. Infants and Toddlers

• Challenges: History and examination may be less reliable due to inability to describe symptoms.
• Atypical Presentation:
  • Classic signs like anorexia, guarding, and right lower quadrant (RLQ) pain are often absent.
  • Symptoms often include diffuse abdominal pain, nausea, and vomiting, which are nonspecific.
• Delayed Diagnosis:
  • By the time of evaluation, most children under 4 have had symptoms for 4 days on average.
  • 50% of children under 5 years present with perforated appendicitis.
  • 66% perforated under age 3.
  • Nearly 100% present with perforation under 1 year of age.

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Neoplasms of the Appendix

Introduction

• Incidence:
  • Rare, accounting for 0.4% to 1% of all gastrointestinal malignancies.
  • Found in 0.7% to 1.7% of appendectomy pathology specimens.
• Presentation:
  • Up to 50% present as appendicitis and are diagnosed postoperatively.
  • May be incidentally discovered on abdominal CT scans.
• Importance:
  • Diverse pathologic classifications and biologic behaviors make diagnosis and treatment complex.
  • Appropriate counseling and treatment are essential upon identification.

Appendiceal Neuroendocrine Neoplasms (ANENs)

• Formerly Known As: Carcinoids.
• Most Common Appendiceal Tumor:
  • Comprise approximately 65% of all appendiceal neoplasms.
  • Detected in 0.2% to 0.7% of appendectomy specimens.
• Characteristics:
  • Arise from neuroendocrine cells within the appendix.
  • Typically small, well-circumscribed, and located in the distal appendix.
  • Most commonly diagnosed in the second or third decade of life.

Classification (World Health Organization, 2010)

• NET-G1: Well-differentiated neuroendocrine tumors.
• NET-G2: Intermediately differentiated neuroendocrine tumors.
• NEC-G3: Poorly differentiated neuroendocrine carcinomas.
• MANECs: Mixed neuroendocrine carcinomas.

Prognostic Factors

• Size:
  • Primary predictor of malignant behavior and metastatic potential.
• Ki-67 Index:
  • A proliferative marker; values >3% indicate a worse prognosis.
• Grade and Invasion:
  • Grade 2 or higher, lymphovascular, or perineural invasion suggest aggressive disease.

Treatment Guidelines

• Tumors ≤1 cm:
  • Generally behave benignly.
  • Treatment: Appendectomy with mesoappendix excision.
    • Avoid skeletonizing the appendix during removal.
• Tumors >2 cm:
  • Higher risk of metastasis.
  • Treatment: Right hemicolectomy with regional lymphadenectomy.
• Tumors Between 1–2 cm:
  • Individualized approach considering tumor characteristics.
  • Factors influencing treatment:
    • Ki-67 index >3%
    • Higher grade
    • Presence of invasion
  • Possible Treatments:
    • Appendectomy
    • Right hemicolectomy

Follow-Up and Prognosis

• Tumor Marker:
  • Serum chromogranin A used for monitoring.
• 5-Year Survival Rates (SEER data):
  • Localized disease: 94%
  • Locoregional spread: 84.6%
  • Distant metastases: 33.7%

Adenocarcinoma of the Appendix

• Incidence:
  • Very rare, occurring in 0.08% to 0.1% of appendectomies.
• Treatment:
  • Same as for cecal adenocarcinoma.
  • Right hemicolectomy with regional lymphadenectomy.
  • Lymph Node Retrieval:
    • >12 lymph nodes may improve staging and survival.
• Chemotherapy:
  • FOLFOX regimen (5-fluorouracil, leucovorin, oxaliplatin) for selected patients.
  • Used adjuvantly or neoadjuvantly, especially in mucinous adenocarcinoma.

Mucinous Tumors of the Appendix

• Incidence:
  • Account for <0.4% to 1% of gastrointestinal malignancies.
• Types:
  • Low-Grade Appendiceal Mucinous Neoplasms (AMNs).
  • Previously called mucocele, cystadenoma, or cystadenocarcinoma.
• Presentation:
  • Often diagnosed incidentally during appendectomy.
  • Advanced stages may present with pseudomyxoma peritonei (PMP).

Classification and Nomenclature

• Confusion in Terminology:
  • Historically inconsistent; recent efforts aim for standardization.
• Key Distinctions:
  • Benign-behaving lesions vs. those with a malignant course.
• Ronnet Classification:
  • Divides advanced AMNs into:
    • Disseminated Peritoneal Adenomucinosis (DPAM):
      • Indolent course, no distant spread.
    • Peritoneal Mucinous Carcinomatosis (PMCA):
      • Aggressive, with metastasis to lymph nodes and organs.
    • PMCA with Indeterminate/Discordant Features:
      • Unpredictable clinical course.

Clinical Considerations

• Spectrum of Disease:
  • Tumors may progress from low-grade to high-grade malignancies.
• Pseudomyxoma Peritonei (PMP):
  • Result of ruptured mucinous tumors seeding the peritoneum.
  • Describes mucinous ascites; not a histologic diagnosis.

Treatment Strategies

• Low-Grade AMNs ≤2 cm:
  • Appendectomy with mesoappendix excision is adequate.
• Indications for Right Hemicolectomy:
  • Positive margins.
  • Involvement of the appendiceal base.
  • Extra-appendiceal extension.
  • Invasive histology (e.g., adenocarcinoma).
• Preventing Rupture:
  • Essential to avoid peritoneal spread and development of PMP.
• Advanced Disease with PMP or Metastases:
  • Cytoreductive Surgery (CRS) combined with Hyperthermic Intraperitoneal Chemotherapy (HIPEC).
    • Aggressive removal of tumor burden.
    • Heated chemotherapy (e.g., Mitomycin C) administered directly into the peritoneal cavity.
• Systemic Chemotherapy:
  • May complement CRS-HIPEC.
  • 5-Fluorouracil–based therapies are standard.

CRS-HIPEC Overview

• Procedure Complexity:
  • Extensive surgery potentially involving multiple organ resections.
  • Operative times can exceed 10 hours.
• Goals:
  • Maximize tumor eradication.
  • Minimize systemic toxicity by localized chemotherapy.
• Outcomes:
  • Long-term survival possible.
  • Dependent on:
    • Presence of metastases.
    • Histologic grade of the tumor.
    • Adequacy of cytoreduction.
    • Chemotherapy response.

Management Algorithm

• Incidentally Identified Appendiceal Mass:
  • Utilize a management algorithm (e.g., modified from Wray et al.).
  • Intraoperative Decision-Making:
    • Consider tumor size, location, and histologic features.
    • Frozen-section diagnosis may aid in immediate decisions.
• Treatment Pathway:
  • Appendectomy for small, low-risk tumors.
  • Right hemicolectomy for high-risk features or larger tumors.
  • CRS-HIPEC for advanced disease with peritoneal involvement.

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Approach to Patient with Appendiceal Neoplasm

Tumor Detected at Operation

• Tumor >2 cm:
  • If base or mesoappendix is involved → Right hemicolectomy.
  • If not involved → Observation.
• Tumor ≤2 cm:
  • If perforation or evidence of mucin spillage → Appendectomy with peritoneal lavage and referral for CRS-HIPEC.
  • If no spillage → Appendectomy.

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Tumor Found After Appendectomy

1. Adenocarcinoma

• Right hemicolectomy is recommended for all cases.

2. Appendiceal Neuroendocrine Neoplasm (ANEN)

• Tumor <1 cm → Observation.
• Tumor >2 cm → Right hemicolectomy.
• Tumor 1–2 cm:
  • If lymphovascular invasion or involvement of the mesoappendix → Right hemicolectomy.
  • If not → Observation.

3. Appendiceal Mucinous Neoplasm (AMN)

• Low-Grade AMN (LAMN):
  • If margin positive, tumor involves base, or tumor >2 cm, with involvement of mesoappendix → Right hemicolectomy.
  • If no positive margin or involvement → Appendectomy.
• Aggressive Behavior (DPAM/PMCA):
  • Right hemicolectomy and consider CRS-HIPEC ± adjuvant chemotherapy.

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Key Points

• Mucin spillage or pseudomyxoma peritonei (PMP) requires consideration of CRS-HIPEC.
• Routine colonoscopy should be performed for all patients with appendiceal neoplasms.

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This algorithm helps guide decisions based on the tumor type, size, and aggressive behavior of the neoplasm, ensuring appropriate treatment from simple appendectomy to more complex procedures like right hemicolectomy and cytoreductive surgery combined with intraperitoneal chemotherapy (CRS-HIPEC).