Case of the Week

1. Case of the Week Prof. V.O.L. Karusseit Dr. M.M. de Beer

2. Gerrie van Tonder Age: 35years (DOB – 1972/06/01) Sex: Male Race: White Marital Status: Single Language: Afrikaans Occupation: Telephone Technician Residence: Rustenburg

3. Patient presented at SOPD as a referral from his private GP with: • One year history of intermittent diarrhoea • Diarrhoea previously contained no blood but changed in the last week to dark red stools • No abdominal pain • Nausea and vomiting for the last week • Weight loss of five kilograms over the last six months

4. Medical History: Hypertension Current Medication: Bisoprolol Prexium Surgical History: Procedure done for osteomeilitus of left leg in 1986 Allergies: None known Social History: Ten pack years of smoking, moderate whiskey drinker Family History: Mother had bone cancer (? Primary/metastatic)

5. Special investigations Imaging: • CXR: No abnormalities • CT upper abdomen and pelvis: • Conclusion: liver is obviously non-homogeneous with several round, low-density areas in the liver • Metastatic until proven otherwise • Abnormal appearance in region of the caecum

14. Differential diagnosis ?

15. Tip: • On specific questioning the patient admits to hot flushes • Also experiences intermittent spells of breathlessness coupled with broncho-spasms.

16. Laboratory Results: • Biochemical tests: within normal limits • Tumour markers: VMA slightly raised • 5-HIAA 24 hr urine collection: Increased Colonoscopy: • Large, lobulated mass in the caecum/ascending colon junction • Small polyp in transverse colon

17. Biopsy result: • Carcinoid (adenocarcinoid or so-called “goblet cell” carcinoid • Liver biopsy – metastatic spread of carcinoid

18. Patient is being followed up on an out-patient basis as well as at chemo-therapy.

19. CARCINOID SYNDROME

20. Carcinoids • Neuro-endocrine tumours of the gastrointestinal tract (carcinoids) are rare tumours • They originate in the enterochromaffin cells of the intestine and have the ability to produce various peptides and hormones. • Previously categorised by their embryological origin – foregut, midgut & hindgut. • Revised classification has taken into account tumour location, histological grade and proliferative index

21. Carcinoid Syndrome • Carcinoid syndrome is almost uniquely associated with midgut carcinoids (neuro-endocrine tumours of the gastrointestinal tract) • Carcinoid syndrome was first described by Thorson and co-workers in 1954 • Systemic symptoms are caused by an excess of biogenic amines, peptides and other factors (serotonin, tachy- and bradykinins and histamine) in the circulation only after liver metasteses

22. Symptoms • Diarrhoea (±80% of patients), mainly caused by serotonin excess, also histamine, kallikrein, prostaglandin, substance P and motilin • Flushing(± 94% ), linked to several humoral factors – tachykinins, serotonin & histamine. Provoked by e.g. nuts & cheese, certain drugs & alcohol • Carcinoid heart disease (± 40% ), characterised by so-called ‘plaques’ at the right side of the heart with involvement of the tricuspid and pulmonary valves and endocardium • Pellagra (± 5% ) characterised by dermatitis, diarrhoea & dementia – result of niacin deficiency • Intermittent bronchial obstruction (10%) often accompanies flushing, underlying mechanism not clear • Carcinoid crisis – rare, potentially fatal – provoked by anaesthesia / surgery if not treated sufficiently with somatostatin analogues

23. Clinical Presentation • Carcinoid tumours less than 1cm in diameter & confined to the mucosa and submucosa generally remain subclinical for years. • Larger than 1 cm – generally malignant & have metastisized to regional lymph nodes and later to the liver and other locations. • Patients have generally been complaining for years of intermittent abdominal discomfort, erroneously diagnosed as a functional disorder such as irritable bowel. • Intermittent intestinal obstruction due to kinking of the small bowel can occur at a later stage as a result of the desmoplastic reaction in the mesentery

24. Epidemiology • Incidence of midgut (neuro-)endocrine tumours is ± 0.2-2/100 000 population/year • Equal distribution between males & females • Incidence is higher in black than white people • Most prevalent location is the terminal ileum close to the ileocaecal valve • Is often multiple • In up to 15% of patients other malignancies such as gastrointestinal adenocarcinoma and breast cancer have been demonstrated

25. Diagnostic procedures • Biochemical diagnosis includes measurements of serum chromogranin A and urinary excretion of 5-HIAA. Estimation of plasma serotonin is facultative • Tumour imaging - transabdominal ultrasound is the initial imaging procedure in most patients with metastised carcinoids. • Contrast-enhanced three-phase CT or MRI followed by needle biopsy for pathology can be performed. • In-pentetreotide scintigraphy is positive in 80-90% of patients • Echocardiography is mandatory in patients with carcinoid heart disease

26. Prognosis • The prognosis of carcinoids arising in the distal jejunum and ileum is generally unfavourable compared to duodenal, gastric and rectal carcinoids – often lead to metasteses to adjacent lymph nodes, liver • 10 year survival rate – 43%, more favourable if the primary tumour has been removed and metasteses are absent. • Hepatic metasteses are frequent in patients with midgut carcinoid tumours (25-90%), 5-year survival rate = 0 – 50%

27. Therapy • Surgical and interventional therapy • Medical therapy • Biotherapy • Somatostatin analogues • Interferon-A • Systemic chemotherapy • Radioligand therapy