PANCREATIC ENDOCRINE

TUMOURS
Introduction
Pancreatic endocrine tumours (PETs) represent
an important subset of pancreatic neoplasms.
They account for 5% of all clinically detected
pancreatic tumours. They consist of single or
multiple, benign or malignant neoplasms and are
associated in 10–20% of cases with multiple
.endocrine neoplasia type 1 (MEN 1)
PETs present as either functional tumours,
causing specific hormonal syndromes, or non-
functional tumours, with symptoms similar to
.those in patients with pancreatic adenocarcinoma
Function of the endocrine pancreas ●
The endocrine cells of the pancreas are grouped in the islets of ●
Langerhans, which constitute approximately 1–2% of the mass of the
pancreas
There are about one million islets in a healthy adult human pancreas and. ●
.their combined weight is 1–1.5 g
There are four main types of cell in the islets of Langerhans, which can be ●
:classified according to their secretions
;beta cells producing insulin (65–80% of the islet cells)● ●
;alpha cells producing glucagon (15–20%) ● ●
;delta cells producing somatostatin (3–10%) ● ●
.pancreatic polypeptide (PP) cells containing polypeptide (1%)● ●
Insulinoma

Definition ●
This is an insulin-producing
‫وﯾﺒﻞ‬
tumour of the pancreas causing the clinical ●
scenario know as Whipple’s triad, i.e. symptoms of hypoglycaemia after
fasting or exercise, plasma glucose levels less than 2.8 mmol/L and relief
of symptoms on intravenous administration of glucose
●
Incidence ●
Insulinomas are the most frequent of all the functioning PETs with a ●
reported incidence of 2–4 cases per million population per year.
Insulinomas have been diagnosed in all age groups, with the highest
incidence found in the fourth to the sixth decades. Women seem to be
.slightly more frequently affected
Pathology
. .The aetiology and pathogenesis of insulinomas are unknown
Approximately 90% are solitary and about 10% are multiple and associated
with MEN 1 syndrome
Prognosis and predictive factors
.Approximately 10% are malignant .
Insulinomas of <2 cm in diameter without signs of vascular invasion or
.metastases are considered benign
Clinical features ● ‫ﻣﺮﯾﺾ ﻣﺎ ﯾﺎﻛﻞ و ورم ﻣﺴﺘﻤﺮ ب ﻓﺮز‬
‫اﻧﺴﻮﻟﯿﻦ ف راح ﯾﻘﻠﻞ ﻧﺴﺒﺔ ﺳﻜﺮ ﺑﺎﻟﺪم‬

Insulinomas are characterised by fasting hypoglycaemia and ●

neuroglycopenic symptoms. The episodic nature of the hypoglycaemic
attacks is caused by intermittent insulin secretion by the tumour. This
leads to central nervous system symptoms such as diplopia, blurred
double vision

vision, confusion, abnormal behaviour and amnesia. Some patients

loss of memory

develop loss of consciousness and coma. The release of catecholamines

produces symptoms such as sweating, weakness, hunger, tremor, nausea,
.anxiety and palpitations
Biochemical diagnosis ●
A fasting test that may last for up to 72 hours is regarded as the most ●
sensitive test. Usually, insulin, proinsulin, Cpeptide and blood glucose are
measured in 1- to 2-hour intervals to demonstrate inappropriately high
secretion of insulin in relation to blood glucose. About 80% of insulinomas
are diagnosed by this test, most of them in the first 24 hours. Elevated C-
peptide levels demonstrate the endogenous secretion of insulin and
‫داﺧﻠﻲ ﻣﻮﺧﺎرﺟﻲ ﺣﺘﻰ ﻧﻌﺮف ﻣﺮﯾﺾ ﻛﻼوﺟﻲ‬

.exclude factitious hypoglycaemia caused by insulin injection

Differential diagnosis ●
The differential diagnosis of hypoglycaemia includes ●
,hormonal deficiencies ●
,hepatic insufficiency ●
‫ﻣﺨﺰن ﺷﻜﺮ‬

,medication ●
drugs ●
enzyme defects ●
Medical treatment of insulinoma ●
Medical management is reserved only for patients who are unable or ●
unwilling to undergo surgical treatment or for unresectable metastatic
.disease ‫ﻏﯿﺮ ﻗﺎدر أو ﻏﯿﺮ راﻏﺐ ﻓﻲ اﻟﺨﻀﻮع ﻟﻌﻤﻠﯿﺔ ﺟﺮاﺣﯿﺔ‬

Diazoxide suppresses insulin secretion by direct action on the beta cells ●

and offers reasonably good control of hypoglycaemia in approximately
.50%of patients
‫اﺧﺘﯿﺎر‬

When surgical options to treat malignant insulinomas cannot be applied, ●

.chemotherapeutic options include doxorubicin and streptozotocin
Surgical treatment of insulinoma ●
INDICATIONS FOR OPERATION ●
After a positive fasting test and exclusion of diffuse abdominal ●
metastases by ultrasound or CT scan, all patients should be advised to
.undergo surgical excision of insulinoma
 ‫دراﺳﺎت ﺗﺤﺪﯾﺪ اﻟﻤﻮﻗﻊ ﻗﺒﻞ اﻟﺠﺮاﺣﺔ‬

PREOPERATIVE LOCALISATION STUDIES ●

Intraoperative exploration of the pancreas is the best method to use for ●
localisation of insulinoma yet the operating surgeon will need preoperative
.localisation ‫ﯾﻌﺪ اﺳﺘﻜﺸﺎف اﻟﺒﻨﻜﺮﯾﺎس أﺛﻨﺎء اﻟﻌﻤﻠﯿﺔ اﻟﺠﺮاﺣﯿﺔ ھﻮ أﻓﻀﻞ طﺮﯾﻘﺔ ﻻﺳﺘﺨﺪاﻣﮭﺎ ﻟﺘﺤﺪﯾﺪ ﻣﻮﺿﻊ‬
.‫ إﻻ أن ﺟﺮاح اﻟﻌﻤﻠﯿﺔ ﺳﯿﺤﺘﺎج إﻟﻰ ﺗﺤﺪﯾﺪ ﻣﻮﺿﻊ اﻟﻮرم ﻗﺒﻞ اﻟﺠﺮاﺣﺔ‬،‫اﻟﻮرم اﻹﻧﺴﻮﻟﯿﻨﻲ‬
Insulinomas are detected in about ●
,of cases by endoscopic ultrasound (EUS) 65% ●
of cases by CT scan and abdominal ultrasound 33% ●
.of cases by magnetic resonance tomography 15% ●
Intraoperative ultrasound (IOUS) of the pancreas is a vital tool after ●
.mobilisation of the gland
BENIGN INSULINOMA ●
Surgical cure rates in patients with the biochemical diagnosis of ●
insulinoma range from 90% to 100%
Gastrinoma (Zollinger–Ellison syndrome)

:Zollinger–Ellison syndrome (ZES) is a condition that includes ●

‫ﺧﺎطﻒ‬ ‫اﺳﺘﮭﺪاف‬

;fulminating ulcer diathesis in the stomach, duodenum or atypical sites) 1 ( ●

;recurrent ulceration despite ‘adequate’ therapy) 2( ●
.non-beta islet cell tumours of the pancreas (gastrinoma)) 3( ●
Incidence ●
.Gastrinomas account for about 20% of PET ●
Approximately 0.1% of patients with duodenal ulcers have evidence of ●
.ZES Insulinoma 2–4 cases per million

The reported incidence is between 0.5 and 4 cases per million population ●
.per year Insulinoma common in Women

.ZES is more common in males than in females ●

The mean age at the onset of symptoms is 38 years, and the range 7–83 ●
.years Insulinoma incidence in 40-60 years
Pathology ●
.The aetiology and pathogenesis of sporadic gastrinomas are unknown ●
At the time of diagnosis more than 60% of tumours are malignant. ●
Pancreatic gastrinomas are mainly found in sporadic disease; most are
.found in the head of the pancreas
More than 70% of the gastrinomas in MEN 1 syndrome and most sporadic ●
.gastrinomas are located in the first and second part of the duodenum
.All patients with gastrinomas should be tested for MEN 1 syndrome ●
Prognosis and predictive factors ●
In general, the progression of gastrinomas is relatively slow with a 5-year ●
survival rate of 65% and a 10-year survival rate of 51%. Patients with
complete tumour resection have excellent 5- and 10-year survival rates
.(90–100%)
Patients with pancreatic tumours have a worse prognosis than those with ●
.primary tumours in the duodenum
There is no established marker to predict the biological behaviour of ●
.gastrinoma
 Clinical features ●
1-
Over 90% of patients with gastrinomas have peptic ulcer disease, often ●
.multiple or in unusual sites
2-
Diarrhoea is another common symptom, caused by the large volume of ●
.gastric acid secretion
3-
Abdominal pain from either peptic ulcer disease or gastro-oesophageal ●
reflux disease (GORD) remains the most common symptom, occurring in
.more than 75% of patients
Differential diagnosis ●
The most common misdiagnoses are idiopathic peptic ulcer disease, ●
.chronic idiopathic diarrhoea and GORD
Other reasons for hypergastrinaemia are chronic atrophic gastritis, ●
.gastric outlet stenosis and retained antrum after gastric resection
 Biochemical diagnosis ●
1-
If the patient presents with a gastric pH below 2.5 and a ●
2-
serum gastrin concentration above 1000pg/mL (normal ●
.100pg/mL) then the diagnosis of ZES is confirmed< ●
1-
Unfortunately, the majority of patients have serum gastrin concentrations ●
between 100 and 500 pg/mL and in these patients a
.secretin test should be performed ●Gastrin Inhibits Secretin
2-
The secretin test is considered positive if an increase in serum gastrin of ●
>200pg/mL over the pretreatment value is obtained
this also rules out ;
other causes of hypergastrinaemia (e.g. atrophic gastritis ●
Medical treatment of gastrinoma ●
In most patients with ZES, gastric hypersecretion can be treated ●
.effectively with proton pump inhibitors
‫اوكتريوتيد‬

.Octreotide can also help to control acid hypersecretion ●

Systemic chemotherapy is utilised in patients with diffuse metastatic
‫ستربتو زوتوسني‬
●
gastrinomas. Streptozotocin in combination with 5-fluorouracil or
‫فلورو يوراسيل‬
.doxorubicin
‫دوكسو روبيسني‬
is the first-line treatment
Surgical treatment of gastrinoma ●
INDICATIONS FOR OPERATION ●
Surgical exploration should be performed in all patients without diffuse ●
metastases, to remove known malignant gastrinomas or benign ones
PREOPERATIVE LOCALISATION STUDIES ●
Pancreatic gastrinomas are often larger than 1 cm in diameter, whereas ●
gastrinomas of the duodenum are usually smaller. Therefore, it is nearly
.impossible to identify duodenal gastrinomas by preoperative imaging
Pancreatic gastrinomas are detected by endoscopic ultrasound in about ●
80–90% of cases, by CT in 39% of cases and by MRI in 46% of cases. In
approximately one-third of patients the results of conventional imaging
studies are negative. On the basis of recent studies, either endoscopic
ultrasound or CT and somatostatin receptor scintigraphy (SRS) scan
.should be performed preoperatively for staging