Shannon ChanPrince of Wales Hospital

F/47 Ms YingGood past healthScreening colonoscopy by private:

1.5cm rectal polyp at 5cm from anal verge

Polyp base elevated with NS and snared Path: Carcinoid, Margin involved

1907, Siegfried Oberndorfer described “carcinoid” (Karzinoide) of the small bowel at the German Pathological Society meeting

Oberndorfer S. Karzinoide Tumoren des Dunndarms. Frank Z Pathol 1907

1963 Williams and Sandler classified carcinoids according to their embryologic site of origin as foregut carcinoids, midgut carcinoids, and hindgut carcinoids

Pasieka et al.Surg Clin N Am 89 (2009) 1123-1137

2000 WHO classification adopted the terms: NE tumor NE carcinoma

Solcia E, Kloppel G, Sobin LH, et al. Histological typing of endocrine tumours. 2nd ed. WHO international histological classification of tumours. Berlin: Springer, 2000

“Carcinoid”, for gastroenteric NETs, used synonymously with the term ”well differentiated NE tumor”

“Malignant carcinoid” is used synonymously with the term well-differentiated NE carci- noma

IRVIN M. MODLIN.Current Status of Gastrointestinal Carcinoids. GASTROENTEROLOGY 2005

Feldman M, Friedman L, Brandt L. Sleisenger and Fordtrain’s Gastrointestinal and Liver disease. Philadelphia, PA: Saunders Elsevier; 2006

Laundry CS, Brock G, Scoggins CR, et al. A proposed staging system for rectal carcinoid tumors based on analysis of 4701 patients. Surgery 2008; 144:460-466

Rectum: 82 - 97%Rectum: 82 - 97%Colon: 63 - 87%Colon: 63 - 87%

Stomach: 21 - 74%Stomach: 21 - 74%Small intestine: 5.5 - 43%Small intestine: 5.5 - 43%

3rd most common gastrointestinal carcinoid tumor

1.8% of malignant rectal tumor Incidence 0.86/100 000 per year50 - 60y.o.F : M = 1 : 1.1Asian and Afro-American

Black : White = 2.30 : 1 Asian : non-Asian = 4.99 : 1

Modlin IM, Lye KD, Kidd M. A 5-decade analysis of 13,715 carcinoid tumors. Cancer. 2003;97(4):934-959

50% asymptomatic Incidental finding during colonoscopy

Symptoms Local symptoms:

▪ Per rectal bleed▪ Change in bowel habit▪ Anorectal symptoms (tenesmus, discomfort,

pruritus ani, pain)Consensus Guidelines for the management of patients with Digestive Neuroendocrine Tumors: Well-

differentiated Colon and Rectum Tumor/ Carcinoma. Neuroendocrinology 2008; 87: 31-39

Carcinoid syndrome: ▪ Flushing & diarrhoea ▪ Uncommon (<10%)▪ Usually biochemically inactive ▪ Contain glucagon and glicientin

Metastasis (1.7 – 8.1%):▪ Abdominal pain▪ Hepatomegaly▪ Symptoms of carcinomatosis

Bowel obstruction: rareConsensus Guidelines for the management of patients with Digestive Neuroendocrine Tumors: Well-

differentiated Colon and Rectum Tumor/ Carcinoma. Neuroendocrinology 2008; 87: 31-39

Colonoscopy & biopsy Smooth, round, submucosal nodule

Jetmore AB, Ray JE, Gathright JB Jr, McMullen KM, Hicks TC, Timmcke AE. Rectal carcinoids: the most frequent carcinoid tumor. Dis Colon Rectum 1992;35:717-725

Endoscopic Ultrasound +/- FNAC: Tumor size and depth of tumor invasion Peri-rectal lymph node Sensitivity: 87% Specificity: 93% (depth)

Matsumoto T, Iida M, Suekane H, Tominaga M, Yao T, Fujishima M. Endoscopic ultrasonography in rectal carcinoid tumors: contribution to selection of therapy. Gastroinest Endosc 1991;37:539-542

MRI Local invasion Nodal involvement

Multi-slice triple phase CT

Jetmore AB, Ray JE, Gathright JB Jr, McMullen KM, Hicks TC, Timmcke AE. Rectal carcinoids: the most frequent carcinoid tumor. Dis Colon Rectum 1992;35:717-725

Pelage JP, Soyer P, Boudiaf M, Brocheriou-Spelle I, Dufresne AC, Coumbaras J, Rymer R. Carcinoid tumors of the abdomen: CT features. Abdom Imaging 1999;24:240-245

111In-Octreotide Scanning Useful for determining

metastatic diseasePET

DOPA or gallium-68 DOTA octreotate

FDG 11C-5-hydroxytryptophan

(5HTP)Hoegerle S, Altehoefer C, Ghanem N, et al. Whole-body 18F Dopa PET for detection of gastrointestinal carcinoid tumors. Radiology 2001; 220:373–380.

Orlefors H, Sundin A, Garske U, et al. Whole-body 11C-5-hydroxytryptophan positron emission tomography as a universal imaging technique for neuroendocrine tumors: comparison with somatostatin receptor scintigraphy and computed

tomography. J Clin Endocrinol Metab 2005; 90:3392–3400.

Lab tests 24-hr urinary 5-HIAA –ve Serum chromogranin A Serum acid phosphate level Pancreatic polypeptide Enteroglucagon B-HCG

Kolby L, Bernhardt P, Sward C, Johanson V, Ahlman H, Forssell-Aronsson E, Stridsberg M, Wangberg B, Nilsson O: Chromogranin A as a determinant of midgut carcinoid tumour volume. Regul Pept 2004; 120: 269–

273.

21 Ardill JE, Erikkson B: The importance of the measurement of circulating markers in patients with neuroendocrine tumours of the pancreas and gut. Endocr Relat Cancer 2003; 10: 459–462.

versus

Muscularis propria invasion Atypia and high mitotic index

Matsushita M, Takakuwa H, Nishio A. Management of rectal carcinoid tumors. Gastrointestinal Endosc 2003;58:641-642

Mani S, Modlin IM, Ballantyne G, Ahlman H, West B. Carcinoids of the rectum. J Am Coll Surg 1994;179:231-248

Tumor size Risks of metastasis

< 1cm < 3%

1-2.0cm 10-15%

>2cm 60-80%

Identical to the one proposed by ENETS in 2007

Rindi G, Kloppel G, Couvelard A, et al. TNM staging of midgut and hindgut (neuro) endocrine tumors: a consensus proposal including a grading system. Virchows Archiv. 2007;45:757-762

Locoregional disease Tumor size:

▪ < 1cm: Endoscopic/ Transanal resection▪ 1.0 – 2.0: Controversial▪ > 2cm: Radical surgery (LAR+TME/ APR)

9 hospitals; 1999-2008; N=202

Shields CJ, Tiret E, Winter D. Carcinoid tumors of the rectum: A multi-institutional international collaboration. Annals of surgery; 252:750-755

Shields CJ, Tiret E, Winter D. Carcinoid tumors of the rectum: A multi-institutional international collaboration. Annals of surgery; 252:750-755

Tumor depth Is NOT an independent risk factor

Shields CJ, Tiret E, Winter D. Carcinoid tumors of the rectum: A multi-institutional international collaboration. Annals of surgery; 252:750-755

Tumor size: <1cm: Endoscopic/ transanal resection 1.0 – 2.0cm:

▪ Radical surgery (LAR+TME/ APR) >2cm: Radical surgery (LAR+TME/ APR)

Lymphovascular invasion Radical surgery (LAR+TME/ APR)

Shields CJ, Tiret E, Winter D. Carcinoid tumors of the rectum: A multi-institutional international collaboration. Annals of surgery; 252:750-755

Palliative Resection Symptomatic relief No survival benefit

Schindl M, Niederle B, Hafner M, Teleky B, Langle F, Kaserer K, Schofl R: Stage-dependent therapy of rectal carcinoid tumors. World J Surg 1998; 22: 628–633.

Somatostatin analogues Interferon Chemotherapy

Disappointing resultsRadiotherapy

Not radiosensitive Bone/ CNS metastasis

De Herder WW. Tumours of the midgut (jejunum, ileum and ascending colon, including carcinoid syndrome). Best Pract Res Clin Endocrinol Metab 2005;19:705–715.

Oberg K, Eriksson B. Nuclear medicine in the detection, staging and treatment of gastrointestinal carcinoid tumors. Best Pract Res Clin Endocrinol Metab 2005; 19:265–276.

Indolent disease5-yr survival rates:

Localised disease 84 – 90.8% Regional spread 36.3 – 48.9% Distant spread 20.6 – 32.3%

Modlin IM, Lye KD, Kidd M: A five-decade analysis of 13,715 carcinoid tumors. Cancer2003; 97: 934–959.

Indolent disease

Size dependent

Malignant potential

Surgery remains the mainstay of treatment

Ongoing trials for chemotherapeutic agents

1.5cm Rectal carcinoid with polypectomy done, margins involved