Pancreatic endocrine tumors - PowerPoint Presentation

Slide1

Pancreatic endocrine tumors

Slide2

INTRODUCTION

One million islets of

Langerhans

Several types of cells “

Immunohistochemistery

”

ß (beta) -> 70% insulin

А (alpha

)-

>

20% glucagons

D (delta) -

>

5-10% somatostatin

P.P Cell

->

1-2% pancreatic polypeptide

Other rare cells:

- D1 cells

-

VIP

(

vasoactive intestinal polypeptide

)

- Enterochromaffin cells

-

5 HT

-(

serotonin

)

Slide3

Terminology and

NETS

Classification

NETS

Grade

Ki 67 Index

Mitotic

count

Differ-

entiation

Low (G1)

<3%

<2/ HPF

Well-differentiated NET

Inter-mediate (G2)

3-20%

2-20/ HPF

Well-differentiated NET

High

(G3)

>20%

>20/ HPF

Poorly differentiated

neuro

-endocrine carcinoma

Slide4

INSULINOMA

Epidemiology

Pathophysiology

& Symptoms

Dignosis

&

Locallization

Management

Slide5

Epidemiology

First described by Harris in JAMA 1924

Commonest hormone producing NET of GIT

99% of pancreatic origin

90% solitary, 90%

< 2cm, 90% benign

8% ass. with MEN I (multiple, malignant in 25%)

Median age at presentation is 47yrs

F to M ratio 1.4:1

Slide6

Pathophysiology

Hypoglycemia

↑glucagon(

glycemic threshold 65-70mg/dl

)

↑catecholamines

↑cortisol & GH

Neuroglucopenic symptoms(

<50mg/dl

)

Slide7

Symptoms

Adrenergic symptoms

Anxiety, nervousness

Tremors

Tachycardia, palpitations

Hypertension

- Wt gain in 20-30%

Slide8

Symptoms

Neuroglucopenic symptoms

Headache

Visual disurbances

Lethargy,lassitude,confusion

Difficulty in speech, thinking

Personality changes

Convulsions, coma

Slide9

Diagnosis

Whipples

triad

Hypoglycemic symptoms brought about by fasting or exercise

↓BS during symptoms

Relief on administration of glucose

↑ C peptide level

↑ plasma insulin

Absence of sulfonylurea

Slide10

Diagnostic testing

72 hrs fast(gold standard)

Plasma glucose ≤2.5 mmol/l

Plasma insulin ≥6 μunits/ml (43 pmol/l)

Plasma C-peptide ≥0.2 nmol/l

Plasma proinsulin ≥0.5 nmol/l

Plasma sulphonylurea Negative

Plasma β-hydroxybutyrate

<

2.7 mmol/l

Change in glucose with 1 mg glucagon ≥25 mg/dl at 30 min

symptoms develop in 35 %of patients within 12 h, 75 % within 24 h, 92 % within 48 h and 99 % within 72 hC peptide suppression testStimulation tests with glucagon, Ca, tolbutamide

Slide11

Locallization

CT, MRI

Transabd

USG, EUS

Intraop

US

Somatostatin

receptor

scintigraphy

Angiography

Selective intra-arterial Ca. stimulation with splenic venous sampling

Slide12

Slide13

Management

Surgical

Resection is the treatment of choice

Specialized units

Enecluation in most cases

Distal pacreatectomy/ whipples’s procedure in a few

Blind resection shouldn’t be performed

Slide14

Management

Medical

When awaiting surgery

Metastatic disease

Failed surgery

Dietary

Diazoxide (with hydrochlorthiazide)

CCBs, Verapamil, Nifedipine

Somatostatin analogues, Octeotride

CT- Streptozocin, 5FU, Doxarubicin

Hepatic art. embolization

Slide15

Management of Unresectable/Metastatic Disease

Systemic therapy

Somatostatin analogues

Chemotherapy

“Targeted” Agents

Peptide receptor therapy

Regional Therapies

Hepatic arterial embolization (± chemotherapy) or radioembolization

Ablative therapy (RFA, cryo, microwave)

Radiation

Surgical Intervention

ResectionHepatic arterial ligation

Liver Transplant

Slide16

Zollinger-Ellison Syndrome

“Islet cell” tumor of the pancreas [or of the duodenum]



Hypergastrinemia



Gastric acid hypersecretion



Consequences of acid hypersecretion :

PUD, GERD [ with or without complications]

Diarrhea, malabsorption

Slide17

Epidemiology of

Z-E syndrome

Any age group ( mean age

 50 years)

Male : Female  3:2

Annual incidence  0.5 - 1.0 per million

MEN-1 in approximately 25% of cases

Slide18

Classification of

Z-E syndrome

Sporadic 75-80%

MEN-1(

autosomal

dominant) 20-25%

Ectopic

gastrin

- producing tumors < 1%

ovary

lung

cardiac (ventricular septum)

Slide19

The Gastrinoma Triangle

Slide20

Symptoms in patients with the Zollinger-Ellison syndrome

Pain and diarrhea 50-60%

Pain without diarrhea 25%

Diarrhea without pain 20%

Heartburn ± dysphagia 30%

MEN-1 features 20-25%

Slide21

Locations of peptic ulcers

in ZE syndrome

Duodenal bulb

Post-bulbar duodenum

Jejunum

Esophagus

Stomach

Marginal (stomal)

Slide22

Clinical features suspicious for Zollinger-Ellison syndrome (ZES)

PUD

in the absence of

Helicobacter

pylori

or

PUD in association with chronic diarrhea

Post-bulbar duodenal ulcer

Multiple duodenal and/or

jejunal

ulcers

PUD refractory to standard medical therapy

Giant PUD

Slide23

Diagnosis of ZE Syndrome

Begins with clinical suspicion

Fasting serum

gastrin

measurement

high sensitivity (> 95%)

poor specificity, even at high levels

modest positive predictive value

excellent negative predictive value

Slide24

Other causes of elevated

fasting serum gastrin

Achlorhydria

/

hypochlorhydria

, usu. due to chronic gastritis

Medications: antacids, PPIs,

H

2

blockers

Postoperative: vagotomy, retained

antrum syndromeRenal failureGastric outlet obstruction

Diabetes mellitusHypertriglyceridemia

Slide25

Diagnosis of ZE Syndrome

Fasting serum gastrin measurement

high sensitivity (> 95%)

low specificity and modest positive predictive value can be enhanced with provocative testing with secretin (2 IU/kg or 0.4 ug/kg i.v.) or calcium infusion (4 mg/kg calcium gluconate per hour for 3 hours), where likelihood ratios increase 10-15 fold with a + test result and decrease 10-fold with a - test result

Slide26

Management of ZE syndrome:

Acid

control

Tumor search is designed to find tumor and to stage its/their extent

Tumor search and possible resection for cure is only prudent for patients who are surgical candidates

Slide27

Clinical symptoms and laboratory findings

in patients with glucagonoma

Clinical Symptoms

Frequency (%)

Dermatitis 64-90

Diabetes/glucose intolerance 38-90

Weight loss 56-96

Glossitis/stomatitis/cheilitis 29-40

Diarrhea 14-15

Abdominal pain 12 Thromboembolic disease 12-35 Venous thrombosis 24 Pulmonary emboli 11 Psychiatric disturbance uncommon

Laboratory AbnormalityAnemia 33-85 Hypoaminoacidemia 26-100Hypocholesterolemia 80

Renal glycosuria unknown

Slide28

VIPoma

-

Verner

Morrison syndrome

•  Watery diarrhea,

hypokalemia

and

achlorhydria

•  Very rare tumor

• 

Secretory

diarrhea of ≥ 10 liters watery tea colored stool per day•  Serum VIP levels above 200 pg/ml•  Exclude other endocrine tumors, laxative and celiac sprue•  Octreotide allows for preoperative resuscitation and preparation•  40% are malignant and 22% had hyperplasia

Slide29

Clinical symptoms and laboratory findings in patients with the VIPoma syndrome (WDHA)

Symptoms/Signs

Frequency (%)

Watery (

secretory

) diarrhea

89-100

Dehydration 44-100 Weight loss 36-100 Abdominal cramps, colic 10-63 Flushing 14-33

Laboratory Findings Hypokalemia

67-100 Hypochlorhydria 34-72 Hypercalcemia

41-50 Hyperglycemia 18-100

Slide30

Somatostatinoma

Annual incidence: very rare

Pancreatic> Duodenal>> other sites

Incidence of Malignancy: > 70%

Incidence in MEN-1: <1%

Clinical Features

Diabetes mellitus

Gallbladder disease

Diarrhea/

steatorrhea

Weight loss

Slide31

Clinical and laboratory findings

in patients with somatostatinomas

Clinical Finding(s)

Somatostatinoma

Somatostatin syndr

.

Pancreatic Intestinal Overall Diabetes mellitus 95 21 95Gallbladder disease 94 43 68

Diarrhea 66-97 11-36 37Weight loss 32-90 20-44 68Laboratory Finding(s)

Steatorrhea 83 12 47 Hypochlorhydria 86 17 26

Slide32

GH-RFoma (GRFoma)

Annual incidence: very rare

Lung> Pancreas > Small Intestine> Other sites

Incidence of malignancy: > 30%

Incidence in MEN-1: < 1%

Clinical Features:

Acromegaly

due to ectopic production of GH-RF

GH and

somatomedin

-A levels elevated

Slide33

Other Reported Functional NETs (?significance)

ACTHoma

may occur with gastrinoma

CCKoma

Neurotensinoma

Erythropoietinoma

with polycythemia

LHoma

with masculinization (F) or loss of libido (M)

Reninoma

with hypertension

PTHrPoma

with hypercalcemia