Carcinoid TumorCarcinoid Tumor

Marcelyn ColeyMarcelyn Coley

Surgery IV ConferenceSurgery IV Conference

Mount Sinai School of Mount Sinai School of MedicineMedicine

HistoryHistory

1888 – First described by Labarsch1888 – First described by Labarsch

1907 – Oberndorfer coined term 1907 – Oberndorfer coined term “Karzinoide” (carcinoma-like, lack of “Karzinoide” (carcinoma-like, lack of malignant potential or particularly malignant potential or particularly benign features)benign features)

Carcinoid TumorCarcinoid Tumor

55thth to 7th decade of life to 7th decade of life Incidence 2.47 and 2.58 per 100,000 Incidence 2.47 and 2.58 per 100,000

for men and women, respectively for men and women, respectively (series reported to NCI(series reported to NCI

4.48 and 3.98/100,000 Black M/F4.48 and 3.98/100,000 Black M/F Occurrence rate 1:300 autopsiesOccurrence rate 1:300 autopsies Reported in a number of organsReported in a number of organs

– Lungs, bronchi, GI tract, ovariesLungs, bronchi, GI tract, ovaries

Carcinoid TumorCarcinoid Tumor

Arises from Arises from enterochromaffin cellsenterochromaffin cells (Kulchitsky (Kulchitsky cells) type of enteroendocrine cell distributed cells) type of enteroendocrine cell distributed throughout the digestive tract.throughout the digestive tract.– Ability to stain with potassium chromate Ability to stain with potassium chromate

((chromaffinchromaffin), a feature of cells that contain ), a feature of cells that contain serotoninserotonin

Found in crypts of Lieberkuhn (intestinal Found in crypts of Lieberkuhn (intestinal glands) glands)

secretes serotonin among other peptidessecretes serotonin among other peptides PICTURE/GRAPH of secretionsPICTURE/GRAPH of secretions

Secretory products of Secretory products of carcinoidcarcinoid

AminesAmines TachykininTachykininss

PeptidesPeptides OtherOther

5HT5HT KallikreinKallikrein Pancreatic polypeptide Pancreatic polypeptide (40%)(40%)

ProstaglandinsProstaglandins

5-HIAA5-HIAA Substance P (32%)Substance P (32%) Chromogranins (100%)Chromogranins (100%)

5-HTP5-HTP Neuropeptide K Neuropeptide K (67%)(67%)

Neurotensin (19%)Neurotensin (19%)

HistamineHistamine HCGHCGαα (28%) (28%)

HCGHCGββ

DopamineDopamine MotilinMotilin

HCG, Human chorionic gonadotropin; 5-HIAA, 5-Hydroxyinoleacetic acid; 5-HT, 5-Hydroxytryptamine; 5-HTP, 5-Hydroxytryptophan

Classified by embryologic originClassified by embryologic origin– Foregut (respiratory tract, thymus, stomach)Foregut (respiratory tract, thymus, stomach)– Midgut (small intestine, appendix, prox Midgut (small intestine, appendix, prox

colon)colon)– Hindgut (distal colon, rectum, GU tract)Hindgut (distal colon, rectum, GU tract)

1/3 of midgut tumors symptomatic1/3 of midgut tumors symptomatic– 10% assoc with carcinoid syndrome10% assoc with carcinoid syndrome

Hindgut rarely cause carcinoid, Hindgut rarely cause carcinoid, asymptomatic, even when metastaticasymptomatic, even when metastatic

Characteristics of carcinoidsCharacteristics of carcinoids

ForegutForegut MidgutMidgut HindgutHindgutLocalizationLocalization Stomach, Stomach,

duodenum, duodenum, pancreas, pancreas, bronchusbronchus

Jejunum, ileum, Jejunum, ileum, appendix, appendix, ascending colonascending colon

Transverse and Transverse and descending colon, descending colon, sigmoid, rectumsigmoid, rectum

HistologyHistology TrabecularTrabecular Solid mass of cellsSolid mass of cells MixedMixed

Silver StainingSilver Staining ArgyrophilArgyrophil ArgentaffinArgentaffin VariableVariable

Secretory Secretory productsproducts

5-HT, serotonin, 5-HT, serotonin, histamine, histamine, multiple multiple polypeptidespolypeptides

Serotonin, Serotonin, prostaglandins, prostaglandins, polypeptidespolypeptides

NoneNone

Metastasis to liverMetastasis to liver Stomach 20-25%Stomach 20-25% Small intestine Small intestine 35%35%

Asc colon 60%Asc colon 60%

Appendix 2%Appendix 2%

Rectum <10% of Rectum <10% of tumors >2cmtumors >2cm

Carcinoid Carcinoid syndromesyndrome

AtypicalAtypical ClassicalClassical RareRare

PathologyPathology

Grossly, small, firm Grossly, small, firm submucosal submucosal nodules, yellow-tan nodules, yellow-tan on cut surfaceon cut surface

Grow slowlyGrow slowly

PathologyPathology After serosal invasion often an intense After serosal invasion often an intense

desmoplastic reaction producing desmoplastic reaction producing mesenteric fibrosis, intestinal kinking, and mesenteric fibrosis, intestinal kinking, and intermittent obstructionintermittent obstruction

Small bowel – multicentric 20-30% Small bowel – multicentric 20-30% patients (multicentricity exceed other patients (multicentricity exceed other malignant neoplasms of GIT)malignant neoplasms of GIT)

10-20% 210-20% 2ndnd primary neoplasm primary neoplasm– Commonly large intestine synchronous Commonly large intestine synchronous

adenocarcinoma adenocarcinoma Associated with MEN I ~10% casesAssociated with MEN I ~10% cases

HISTOLOGYHISTOLOGY

Typical Typical – Well-differentiated, containing small Well-differentiated, containing small

regular cells with rounded nucleiregular cells with rounded nuclei Atypical or anaplasticAtypical or anaplastic

– Increased nuclear atypia, mitotic Increased nuclear atypia, mitotic activity, areas of necrosisactivity, areas of necrosis

Five distinct patterns recognizedFive distinct patterns recognized– Insular, trabecular (ribbon like), Insular, trabecular (ribbon like),

glandular, undifferentiated, and mixed\glandular, undifferentiated, and mixed\ Biologic behavior does not always Biologic behavior does not always

correspond to histologic characteristicscorrespond to histologic characteristics– Distinction between benign and Distinction between benign and

malignant is based upon presence or malignant is based upon presence or absence of metastasis absence of metastasis

– correlates to size and site of primary correlates to size and site of primary tumortumor

The two types of silver staining used The two types of silver staining used to histologically identify to histologically identify neuroendocrine cells are argyrophil neuroendocrine cells are argyrophil and argentaffin in addition to and argentaffin in addition to immunohistochemical stains such as immunohistochemical stains such as chromogranins, synaptophysin and chromogranins, synaptophysin and enolase enolase

Poorly differentiated gastric Poorly differentiated gastric carcinoidcarcinoid

•sheets of poorly differentiated tumors cells with areas of necrosis (arrow).

•marked nuclear pleomorphism and hyperchromasia.

Lewin, KJ, Appelman, HD. Tumors of the esophagus and stomach. Atlas of tumor pathology (electronic fascicle), 1996.

Variable malignant potential Variable malignant potential – Related to Related to sizesize, , locationlocation, depth of , depth of

invasion, and growth patterninvasion, and growth pattern

Gastrointestinal CarcinoidGastrointestinal Carcinoid Most common site (Sabiston) Most common site (Sabiston)

– 1. Appendix (45%)1. Appendix (45%)****– 2. Small intestine (28%) (last 2ft of ileum)2. Small intestine (28%) (last 2ft of ileum)– 3. Rectum (16%)3. Rectum (16%)

(Cheek RC et al)(Cheek RC et al) According to SEER database of 11,427 carcinoids According to SEER database of 11,427 carcinoids

1973-19971973-1997– Small intestine (45%)Small intestine (45%)****– Rectum (20%)Rectum (20%)– Appendix (16%)Appendix (16%)– Colon (11%)Colon (11%)

Similar results database study from a Swedish Similar results database study from a Swedish registyregisty– 5,184 carcinoid tumors 1958-19985,184 carcinoid tumors 1958-1998

AppendixAppendix Most common locationMost common location Majority in 40s to 50sMajority in 40s to 50s F>MF>M Majority asymptomatic, located distal 1/3 of Majority asymptomatic, located distal 1/3 of

appendixappendix Symptomatic case tend to larger tumor, at the Symptomatic case tend to larger tumor, at the

base of the appendix (10%) and metastatic base of the appendix (10%) and metastatic diseasedisease

– Obstruction, appendicitis, or carcinoid syndrome with Obstruction, appendicitis, or carcinoid syndrome with tumor mets to livertumor mets to liver

5-yr survival overall 71%; 10 to 30% with distant 5-yr survival overall 71%; 10 to 30% with distant metastasismetastasis

Appendix: SurgeryAppendix: SurgeryDepends on the site of primary Depends on the site of primary

tumortumorAppendixAppendix Prognosis best predicted by sizePrognosis best predicted by size <1cm – <1cm – Simple appendectomySimple appendectomy

adequateadequate >2cm – >2cm – right hemicolectomyright hemicolectomy 1 to 2 cm1 to 2 cm decide by location decide by location

– Base of appendix or invading Base of appendix or invading mesentery mesentery Right Right hemicolectomyhemicolectomy

– Appendectomy alone if tumor can be Appendectomy alone if tumor can be fully resectedfully resected

Mesoappendiceal invasion Mesoappendiceal invasion regardless of tumor size – Right regardless of tumor size – Right hemicolectomyhemicolectomy– Studies show that recurrence unlikely Studies show that recurrence unlikely

with small tumors with this feature with small tumors with this feature treated by appendectomy alone.treated by appendectomy alone.

(Kulke. N Engl J Med 1999)(Kulke. N Engl J Med 1999)

Tumor Tumor sizesize

MetastasiMetastasiss

<1cm<1cm 2%2%

1-2cm1-2cm 50%50%

>2cm>2cm 80%80%

Small IntestineSmall Intestine

~1/3 of small intestine neoplasms~1/3 of small intestine neoplasms Commonly within 60cm of ileocecal valveCommonly within 60cm of ileocecal valve 66thth and 7 and 7thth decade, present with decade, present with

abdominal pain or SBOabdominal pain or SBO Carcinoid syndrome in 5 to 7% of Carcinoid syndrome in 5 to 7% of

patientspatients Multiple tumors in up to 30%Multiple tumors in up to 30% 5-yr survival 36% with distant metastasis5-yr survival 36% with distant metastasis

Small intestineSmall intestine

Often metastasis to lymph nodes or Often metastasis to lymph nodes or liverliver

TreatmentTreatment– Resection of involved segment and Resection of involved segment and

mesenterymesentery– Even in known metastasisEven in known metastasis

Carcinoid of ileumCarcinoid of ileum

ColonColon

77thth decade decade Presenting with abdominal pain, anorexia, or Presenting with abdominal pain, anorexia, or

weight lossweight loss Carcinoid syndrome uncommonCarcinoid syndrome uncommon Majority in right colonMajority in right colon

– CecumCecum Asymptomatic until tumor becomes largeAsymptomatic until tumor becomes large

– In 2 studies, at diagnosis, average tumor size – In 2 studies, at diagnosis, average tumor size – 5cm 5cm

– 2/3 patients had local nodal or distant metastasis2/3 patients had local nodal or distant metastasis

ColonColon

5-yr survival based on metastasis5-yr survival based on metastasis– Local - 76%Local - 76%– Regional - 72%Regional - 72%– Distant - 30%Distant - 30%

Small localized tumors likely cured Small localized tumors likely cured by resectionby resection

RectumRectum 66thth decade decade Majority found Majority found

incidentally on rectal incidentally on rectal exam or endoscopyexam or endoscopy

Uncommon Uncommon presentation includes presentation includes rectal bleeding or painrectal bleeding or pain

Carcinoid syndrome Carcinoid syndrome rarerare

Size correlates with Size correlates with metastasismetastasis– Often to lymph nodes or Often to lymph nodes or

liverliver

SizeSize MetasMetastasistasis

1cm1cm RareRare

1-1-1.9cm1.9cm

~10%~10%

>2cm>2cm >70%>70%

RectumRectum

TreatmentTreatment– <1cm – <1cm – Local excisionLocal excision (clear margins) (clear margins)– 1-2cm – more controversial, some recommend 1-2cm – more controversial, some recommend

more extension resection in those with muscular more extension resection in those with muscular invasion or symptomsinvasion or symptoms

– >2cm – Low anterior resection or >2cm – Low anterior resection or abdominoperineal resectionabdominoperineal resection

(similar to txt for adenocarcinoma)(similar to txt for adenocarcinoma) This aggressive approach has been This aggressive approach has been

challenged since survival is not consistently challenged since survival is not consistently improved improved

FIGURE 2. Berkson–Gage survival analysis for tumor size and distant metastasisfree survival of the 31 patients presenting without metastasis. Increasing tumor size was associated with significantly decreased metastasis free survival. Tumor size was not available for threepatients.

Koura et al. Carcinoid tumors of the rectum. Cancer 1997; 79:1294

Prospective study

5-yr survival rates5-yr survival rates– Localized (90%)Localized (90%)– Regional (49%)Regional (49%)– Distant metastasis (26%)Distant metastasis (26%)

SEER database

StomachStomach

Three CategoriesThree Categories– Type 1Type 1

70 to 80% of gastric carcinoids70 to 80% of gastric carcinoids Associated with chronic atrophic gastritis Associated with chronic atrophic gastritis

and often pernicious anemiaand often pernicious anemia Derived from enterochromaffin-like (ECL) Derived from enterochromaffin-like (ECL)

cellscells Hypothesized that ECL cells develop into Hypothesized that ECL cells develop into

carcinoid after chronic stimulation by high carcinoid after chronic stimulation by high gastric levels i.e. pts with atrophic gastritisgastric levels i.e. pts with atrophic gastritis

Gastric CarcinoidsGastric Carcinoids

Type 1Type 1– 66thth and 7 and 7thth decade, F>M decade, F>M– Carcinoid syndrome rareCarcinoid syndrome rare– Usually indolent and generally benign Usually indolent and generally benign

conditioncondition– Metastases <10% of tumors <2cmMetastases <10% of tumors <2cm– ~20% present in larger tumors~20% present in larger tumors

– Type 2Type 2 Associated with gastrinomas (Zollinger-Associated with gastrinomas (Zollinger-

Ellison syndrome) or MEN type 1Ellison syndrome) or MEN type 1 <5% of gastric carcinoids<5% of gastric carcinoids ECL cellsECL cells MEN1 gene locus (11q13) appears to be MEN1 gene locus (11q13) appears to be

involved in the pathogenesis of many of involved in the pathogenesis of many of these tumors (Debelenko et al.)these tumors (Debelenko et al.)

Behave similar to type 1Behave similar to type 1

– Type 3Type 3 ““sporadic carcinoids” – not associated with sporadic carcinoids” – not associated with

any other disease processany other disease process 20% of gastric carcinoids20% of gastric carcinoids Most aggressive – local or hepatic Most aggressive – local or hepatic

metastases up to 65% of patientsmetastases up to 65% of patients May be associated with carcinoid syndromeMay be associated with carcinoid syndrome

– Often produce 5-Hydroxytryptophan in contrast to Often produce 5-Hydroxytryptophan in contrast to type 1 and 2, often produce serotonintype 1 and 2, often produce serotonin

Other sitesOther sites LungLung OvaryOvary

– **produce carcinoid syndrome without **produce carcinoid syndrome without metastases secondary to direct drainage into the metastases secondary to direct drainage into the systemic circulationsystemic circulation

– Often arise in Often arise in cystic terotomacystic terotoma or or dermoid tumor dermoid tumor – In one report, 189 or 329 ovarian In one report, 189 or 329 ovarian

carcinoids(57%) coexisted with cystic carcinoids(57%) coexisted with cystic teratomas/dermoid tumors. teratomas/dermoid tumors.

– Compared to carcinoids without associated germ Compared to carcinoids without associated germ cell tumors, these were significantly smaller, less cell tumors, these were significantly smaller, less likely to have metastases or carcinoid syndromelikely to have metastases or carcinoid syndrome

Clinical ManifestationsClinical Manifestations

MajorityMajority are are asymptomaticasymptomatic and and found incidentally at time of found incidentally at time of surgery, endoscopy, or autopsysurgery, endoscopy, or autopsy [80%] [80%]

When present—correlate with When present—correlate with location and extent of tumorlocation and extent of tumor

Carcinoid SyndromeCarcinoid Syndrome

Malignant Carcinoid Malignant Carcinoid SyndromeSyndrome

Occurs in <10% with tumorsOccurs in <10% with tumors Commonly tumors of gi tract, esp. small Commonly tumors of gi tract, esp. small

bowelbowel Other locations describedOther locations described >90% with carcinoid syndrome have >90% with carcinoid syndrome have

metastatic disease, exceptions are metastatic disease, exceptions are bronchial and ovarian tumorsbronchial and ovarian tumors

Patients with the syndrome almost Patients with the syndrome almost invariably have hepatic metastasesinvariably have hepatic metastases– venous drainage from a metastatic tumor in venous drainage from a metastatic tumor in

the liver goes directly into the systemic the liver goes directly into the systemic circulation and bypasses hepatic inactivation circulation and bypasses hepatic inactivation

Liver metastasesLiver metastases

http://www.meddean.luc.edu/lumen/MedEd/medicine/pulmonar/images/hussain1/scan1.jpg

Malignant Carcinoid Malignant Carcinoid SyndromeSyndrome

CLASSIC SYMPTOMSCLASSIC SYMPTOMS– VasomotorVasomotor– CardiacCardiac– GastrointestinalGastrointestinal

SymptomsSymptoms– Cutaneous flushing (80%) *** (diff erythematosus, Cutaneous flushing (80%) *** (diff erythematosus,

violaceous, prolonged flushes, bright-red patchy)violaceous, prolonged flushes, bright-red patchy)– Diarrhea (76%)** episodic, explosive, watery, occur after Diarrhea (76%)** episodic, explosive, watery, occur after

mealsmeals– Hepatomegaly (71%)Hepatomegaly (71%)– Cardiac lesions-Right heart valve (41 to 70%) PS, TR, TSCardiac lesions-Right heart valve (41 to 70%) PS, TR, TS– Asthma/Bronchoconstriction (25%)Asthma/Bronchoconstriction (25%)

Malignant Carcinoid Malignant Carcinoid SyndromeSyndrome

Metastasis to liverMetastasis to liver

Malabsorption and pellagra Malabsorption and pellagra (dementia, dermatitis, and diarrhea) (dementia, dermatitis, and diarrhea) occasionally present – thought due to occasionally present – thought due to excessive diversion of dietary excessive diversion of dietary tryptophantryptophan

Carcinoid TumorCarcinoid Tumor

In absence of carcinoid syndrome, In absence of carcinoid syndrome, symptoms of carcinoids tumors in small symptoms of carcinoids tumors in small bowel are similar to other small bowel bowel are similar to other small bowel tumorstumors

Abdominal pain ± partial/complete Abdominal pain ± partial/complete obstruction obstruction – often caused by intussusceptionoften caused by intussusception– Local desmoplastic reaction (caused by Local desmoplastic reaction (caused by

humoral agents)humoral agents) Diarrhea (result of PBO) and weight lossDiarrhea (result of PBO) and weight loss

DiagnosisDiagnosisProduce serotonin, which is then metabolized in the liver and the lung to Produce serotonin, which is then metabolized in the liver and the lung to

the inactive 5-HIAAthe inactive 5-HIAA Elevation of humoral factors basis in those with carcinoid syndromeElevation of humoral factors basis in those with carcinoid syndrome

Urinary excretion of 5-HIAAUrinary excretion of 5-HIAA* - end product of serotonin metabolism* - end product of serotonin metabolism– 75% sensitive and specificity up to 100%75% sensitive and specificity up to 100%– Errors induced by certain drugs and foodsErrors induced by certain drugs and foods– Normal 2 to 8 mg/day, Most carcinoids >100mg/day (99-2070) (in one Normal 2 to 8 mg/day, Most carcinoids >100mg/day (99-2070) (in one

study)study)– +tumors, but without carcinoid syndrome 50 to 260 mg/day+tumors, but without carcinoid syndrome 50 to 260 mg/day– (not useful in foregut carcinoid (not useful in foregut carcinoid bronchial, gastricbronchial, gastric lack aromatic amino lack aromatic amino

decarboxylasedecarboxylase– 5-hydroxytryptophan is produced instead (assays not available in US labs)5-hydroxytryptophan is produced instead (assays not available in US labs)

Inc’d 5-HIAA excretion in urine and inc serotonin uptake by plateletsInc’d 5-HIAA excretion in urine and inc serotonin uptake by platelets

Urinary serotonin is normal or slightly increasedUrinary serotonin is normal or slightly increased

DiagnosisDiagnosis

Chromogranin AChromogranin A – protein made in the – protein made in the secretory granules of a variety of secretory granules of a variety of neuroendocrine tissues : (specificity not well neuroendocrine tissues : (specificity not well establishedestablished– Elevated in >80% cases (with or without the Elevated in >80% cases (with or without the

syndrome?)syndrome?)– Generally parallels 5-HIAAGenerally parallels 5-HIAA– May be predictor of prognosis (301 pts, May be predictor of prognosis (301 pts,

>5000µg/L=poor overall survival) >5000µg/L=poor overall survival) BloodBlood SerontoninSerontonin

– Helpful when U5-HIAA testing is equivocalHelpful when U5-HIAA testing is equivocal

DiagnosisDiagnosis

OthersOthers Plasma substance P, neurotensin, Plasma substance P, neurotensin,

neurokinin A, and neuropeptide – however, neurokinin A, and neuropeptide – however, not elevated in all patientsnot elevated in all patients

Provocative test-Provocative test- pentagastrin, calcium, or pentagastrin, calcium, or epinephrine to reproduce symptoms, but epinephrine to reproduce symptoms, but rarely used todayrarely used today– Useful when biochemical markers are Useful when biochemical markers are

marginally elevated marginally elevated

DiagnosisDiagnosis

Once syndrome is confirmed, the tumor Once syndrome is confirmed, the tumor may be localized (metastasis)may be localized (metastasis)– Abdominal CTAbdominal CT– Indium-111 octreotide imaging (somatostatin Indium-111 octreotide imaging (somatostatin

receptor scintigraphy) higher sensitivity than receptor scintigraphy) higher sensitivity than conventional imaging i.e. CTconventional imaging i.e. CT

Other tests –Add picture of BEOther tests –Add picture of BE– Barium (filling defects) and endoscopic studiesBarium (filling defects) and endoscopic studies– Video capsule endoscopy, MR, angiography, Video capsule endoscopy, MR, angiography,

high-resolution ultrasonographyhigh-resolution ultrasonography

CT: malignant carcinoid of CT: malignant carcinoid of ileumileum

Small bowel follow throughSmall bowel follow through

Polypoid mass of Polypoid mass of the terminal ileumthe terminal ileum

Somatostatin receptor Somatostatin receptor scintigraphyscintigraphy

StagingStaging

No standard system for describing No standard system for describing spread of gastrointestinal carcinoidsspread of gastrointestinal carcinoids

ManagementManagement

After localization of the tumor…After localization of the tumor… SurgerySurgery is the mainstay of treatment is the mainstay of treatment Based on…Based on…

– Tumor sizeTumor size– Tumor siteTumor site– Presence or absence of metastatic diseasePresence or absence of metastatic disease

Removal of tumor (if no mets)Removal of tumor (if no mets) Control of carcinoid symptoms if presentControl of carcinoid symptoms if present Widespread metastases – palliative Widespread metastases – palliative

resectionresection

MetastasesMetastases

Widespread metastasisWidespread metastasis– Surgical debulking indicated, in many Surgical debulking indicated, in many

series, provides symptomatic reliefseries, provides symptomatic relief– ? Hepatic resection? Hepatic resection

Wedge resection or hepatic lobectomyWedge resection or hepatic lobectomy

– Hepatic artery ligation or percutaneous Hepatic artery ligation or percutaneous embolizationembolization

– Reports of tumor regression with hepatic Reports of tumor regression with hepatic artery occlusion combined with chemoartery occlusion combined with chemo Multimodal therapy needs further evaluatedMultimodal therapy needs further evaluated

Carcinoid syndromeCarcinoid syndrome– OctreotideOctreotide and and alpha interferonsalpha interferons have have

been effectivebeen effective– In one study of 130 patients with In one study of 130 patients with

metastatic carcinoid tumor, interferon metastatic carcinoid tumor, interferon alpha resulted in decreased urinary 5-alpha resulted in decreased urinary 5-HIAA (42%) and regression (15%)HIAA (42%) and regression (15%)

PrognosisPrognosis Dependent on size, location of primary tumorDependent on size, location of primary tumor Midgut tumors better survival than foregut and Midgut tumors better survival than foregut and

hindguthindgut Resection of a carcinoid tumor localized to its Resection of a carcinoid tumor localized to its

primary site approaches a 100% survival rateprimary site approaches a 100% survival rate 5-yr survival ~65 to 67% with regional disease5-yr survival ~65 to 67% with regional disease 25 to 35% with distant metastasis25 to 35% with distant metastasis Long-term palliation often can be obtain due to Long-term palliation often can be obtain due to

slow growing natureslow growing nature Chromogranin A found to be an independent Chromogranin A found to be an independent

predictor of an adverse prognosispredictor of an adverse prognosis

SummarySummary >80% asymptomatic, often incidental finding>80% asymptomatic, often incidental finding

Initial diagnostic test 24-hr urinary 5-HIAAInitial diagnostic test 24-hr urinary 5-HIAA

Treatment and prognosis dependent of size and Treatment and prognosis dependent of size and location of primary tumorlocation of primary tumor

Resection is tumor increased overall survivalResection is tumor increased overall survival

Metastases correlate with location and size of Metastases correlate with location and size of tumor tumor