Diagnosis & Surgical Management of Carcinoid Tumors

1. Diagnosis & Surgical Management of Carcinoid Tumors Peter J. DiPasco, MD Assistant Professor of Surgery Department of Surgery – Section of Surgical Oncology The University of Kansas Medical Center Friday, april 4th, 2014 ACOS General Surgery In-Depth Review

2. Disclosure • I have no disclosures

3. Introduction • Definition – “Carcinoid” • Applied to well-differentiated neuroendocrine tumors originating in the digestive tract, lungs, or rare sites such as kidneys or ovaries • Is not used to describe high grade / poorly differentiated neuroendocrine tumors

4. Epidemiology • Peak incidence within the sixth to seventh decade • >50% are found within the GI tract, with the appendix as a very common site of origin • 50% are found within 2ft of the ileocecal valve • >30% are multifocal • Incidence is increasing • Carcinoid is more common than SB adenoC

5. Pathology • Carcinoids are characterized by the ability to produce peptides and other biologically active substances • Serotonin • Amines • Tachykinins • Prostaglandins • Arise from enterochromaffin cells (GI tract, bronchi) • Usually tan, yellow, or gray-brown intramural or submucosal lesions • Multifocality comprises 30% of cases

6. Clinical Findings • Carcinoid could be referred to as a “malignant neoplasm in slow motion” • At the time of diagnosis… • 40% have invaded the muscularis • 45% have metastasized to the liver • Tumors < 1cm rarely metastasize (2%) • Tumors > 2cm frequently metastasize (80%) • Massive metastatic lesions are also encountered from minute primaries

7. Clinical Findings • Small tumors are often asymptomatic • 30% cause symptoms of obstruction, pain, bleeding, or the carcinoid syndrome • Carcinoid syndrome • Cutaneous flushing • Diarrhea • Bronchoconstriction • Right sided heart valvular dysfunction (collagen deposition) • Carcinoid Crisis • Usually precipitated by anesthesia, surgery or chemotherapy • Usually refractory to fluid resuscitation or vasopressors • Octreotide should be given to all pts with metastatic or bulky disease prior to the above events

9. Clinical Presentation • Varies depending on location and production of biologically active substances Foregut Midgut Hindgut

10. Clinical Presentation – Foregut • Most commonly atypical in presentation due to non-serotonin products (gastrin / ACTH / GH) • Pulmonary tumors are usually perihilar, causing pneumonia, cough, hemoptysis and even chest pain • Gastric carcinoids are mainly associated with chronic atrophic gastritis and pernicious anemia (75%, type I)

11. Clinical Presentation - Midgut • Typically only produce symptoms when they are bulky or metastatic • Most are located within the distal one-third of the small bowel • Vast majority of appendiceal carcinoids are found incidentally • Symptoms are generally non-specific colicky abdominal pain • Mesenteric fibrosis typically accompanies tumor growth • Can lead to obstruction or ischemia

12. Clinical Presentation - Hindgut • Commonly clinically silent until advanced • Two-thirds are found in the ascending colon • Average size at diagnosis is 5cm • Usual presentation is bleeding • Rectal Carcinoid • 80% are less than 10mm – endoscopic resection is feasible and safe • Muscular and lymphovascular invasion confer an increased risk of metastasis

13. Diagnosis - Laboratory • 50% of patients will have an elevated urinary 5-HIAA (regardless if carcinoid syndrome is present) • This test requires restriction of multiple food items • Levels can correlate with tumor burden • Serum Chromogranin A carries of sensitivity of 80% in well differentiated tumors • Is also useful in non-functional tumors (still positive)

14. Diagnosis - Imaging • Indium (111In-penetriodide) labeled Octreotide or Metaiodobenzylguanidineradiolabeled with 131I • MIBG is taken up by the tumor and stored in neurosecretory granules • 88% of tumors will be positive • Anatomically directed investigations (CT Chest / CXR / Bronchoscopy / Endoscopy) • CT typically shows a “spoke-wheel” appearance on small bowel tumors • 70% demonstrate calcifications

15. Special Consideration – Appendix • Represents the most common tumor of the appendix • 95% less than 2cm • Rarely metastasize • LN involvement rare • 75% in the distal third • Mostly unifocal

16. Surgery – Localized Disease • Small bowel – wide en bloc resection including mesenteric LNs regardless of size • 70% will metastasize to LNs • Mesenteric resection may be difficult due to fibrosis • Thorough examination of the entire small bowel is necessary as 20-40% of tumors are multicentric • 40% of patients with midgut carcinoid have a second GI malignancy • Rectum – Endoscopic vs TEMS for subcentimeter • 1 – 2cm tumors are also candidates in the absence of LVI or local invasion • >2cm – total mesorectal excision

17. Surgery – Advanced / Metastatic Disease • Role of surgery not well defined • If all metastases and primary are resectable, total extirpation should be performed • Prolongs disease free survival • Provides symptomatic relief • Mean duration for resected liver lesions is 5.3 years • Prophylactic cholecystectomy should be performed in all patients • Risk of cholelithiasis with ongoing octreotide treatment

18. Surgery – Advanced / Metastatic Disease • Patients with mildly symptomatic disease burden can be managed with octreotide alone • Controls symptoms • Duration of response was ~1 year • 150μg subcutaneous TID • Depot sandostatin • 20 – 30mg q4 weeks • Slows down tumor growth >50% cases • Causes mild regression 10 – 20% cases

19. CASE REPORT • 65F with classical findings of acute appendicitis made on history and physical examination alone • Pt taken to the operating room for laparoscopic appendectomy • Neoplastic process at the tip of the appendix noted invading mesoappendix. Frozen section shows 2.5cm carcinoid tumor • Next step? • What if 4cm left lateral segment was involved?