1. Shannon Chan Prince of Wales Hospital

2.  F/47 Ms Ying  Good past health  Screening colonoscopy by private:  1.5cm rectal polyp at 5cm from anal verge  Polyp base elevated with NS and snared  Path: Carcinoid, Margin involved

6. 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

7. 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

8.  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

9.  “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

10. 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% Colon: 63 - 87% Stomach: 21 - 74% Small intestine: 5.5 - 43%

11.  3 rd most common gastrointestinal carcinoid tumor  1.8% of malignant rectal tumor  Incidence 0.86/100 000 per year  50 - 60y.o.  F : M = 1 : 1.1  Asian 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

12.  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

13.  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: rare Consensus Guidelines for the management of patients with Digestive Neuroendocrine Tumors: Well- differentiated Colon and Rectum Tumor/ Carcinoma. Neuroendocrinology 2008; 87: 31-39

14.  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

15.  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

16.  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

17.  111 In-Octreotide Scanning  Useful for determining metastatic disease  PET  DOPA or gallium-68 DOTA octreotate  FDG  11 C-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.

18.  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.

19. versus

20.  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 sizeRisks of metastasis < 1cm< 3% 1-2.0cm10-15% >2cm60-80%

21. 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

23.  Locoregional disease  Tumor size: ▪ < 1cm: Endoscopic/ Transanal resection ▪ 1.0 – 2.0: Controversial ▪ > 2cm: Radical surgery (LAR+TME/ APR)

24.  9 hospitals; 1999-2008; N=202

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

26.  Tumor depth  Is NOT an independent risk factor

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

28.  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

29.  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.

30.  Somatostatin analogues  Interferon  Chemotherapy  Disappointing results  Radiotherapy  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.

31.  Indolent disease  5-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. Cancer 2003; 97: 934–959.

32.  Indolent disease  Size dependent  Malignant potential  Surgery remains the mainstay of treatment  Ongoing trials for chemotherapeutic agents

33. 1.5cm Rectal carcinoid with polypectomy done, margins involved