BENIGN and MALIGNANT PANCREATIC TUMOURS, MEN SYNDROME

Assoc. Prof. Oseni-Momodu, E. O

Department of Surgery,

College of Medicine and Health Sciences

October 10, 2018

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LEARNING OBJECTIVES

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To understand:

1. Surgical anatomy, functions
2. Investigations of pancreatic diseases
3. Congenital anomalies
4. Acute pancreatitis
5. Chronic pancreatitis
6. Cysts
7. Tumours

ANATOMY AND PHYSIOLOGY

Anatomy

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• The name ‘pancreas’ is derived from the Greek ‘pan’ (all) and‘kreas’ (flesh).

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• For a long time, its glandular function was not understood, and it was thought to act as a cushion for the stomach.

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• The pancreas is situated in the retroperitoneum. It is divided into a head, which occupies 30 per cent of the gland by mass, and a body and tail, which together constitute 70 per cent.

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• The head lies within the curve of the duodenum, overlying the body of the second lumbar vertebra and the vena cava. The aorta and the superior mesenteric vessels lie behind the neck of the gland.
• Coming off the side of the pancreatic head and passing to the left and behind the superior mesenteric vein is the uncinated process of the pancreas
• Behind the neck of the pancreas, near its upper border, the superior mesenteric vein joins the splenic vein to form the portal vein (Figures above) The tip of the pancreatic tail extends up to the splenic hilum.

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• The pancreas weighs approximately 80 g. Of this, 80–90 percent is composed of exocrine acinar tissue, which is organized into lobules.

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• The main pancreatic duct branches into interlobular and intralobular ducts, ductules and, finally, acini.

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• The main duct is lined by columnar epithelium, which becomes cuboidal in the ductules.

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• Acinar cells are clumped around a central lumen, which communicates with the duct system.

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• Clusters of endocrine cells, known as islets of Langerhans, are distributed throughout the pancreas

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• Islets consist of different cell types: 75 per cent are B cells (producing insulin); 20 per cent are A cells (producing glucagon); and the remainder are D cells (producing somatostatin) and a small number of pancreatic polypeptide cells.

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• Within an islet, the B cells form an inner core surrounded by the other cells. Capillaries draining the islet cells drain into the portal vein, forming a pancreatic portal system.

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EMBRYOLOGY

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• There are nine key processes that occur during pancreatic embryogenesis.

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• Malrotation of the ventral bud in

the fifth week results in an annular pancreas,

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• while the mode of ductule fusion in the seventh week produces the various possible ductular patterns.

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• Between the 12th and 40th weeks of fetal life, the pancreas differentiates into exocrine and endocrine

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SURGICAL ANATOMY, FUNCTIONS

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• The adult pancreas is an entirely retroperitoneal organ plastered on the posterior abdominal wall, and extending obliquely in the abdomen from the hollow of the curve of the duodenum, which contains the head of the organ, to the hilum of the spleen (slide 4).

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• The neck is a narrow segment of the gland; it is related posteriorly to the superior mesenteric artery and vein as they pass over the uncinate process of the head.

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• Both neck and body are closely applied to the rigid vertebral bodies and the rib cage, an arrangement which exposes the organ to serious injury from major blunt trauma of the abdomen

The Ductal System

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• It is of considerable interest in the causation of pancreatic diseases.

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• The main duct of the exocrine glands (Duct of Wirsung) begins at the tail and courses to the right a little higher than the halfway line between superior and inferior borders of the gland.

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• The duct is deep in the gland, its tributaries enter almost at right angles

• The lesser duct ·of Santorini takes the place of the" main duct in 5 to 10 % of people so that injury to this more proximally sited duct as may occur in gastrectomy may precipitate a severe form of pancreatitis.

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• Blood Supply - The blood supply is derived chiefly from the splenic artery which supplies the neck, body and tail

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• The head is supplied by the superior and inferior pancreaticoduodenal arteries.

Lymphatic drainage from the head and right side of the body is into the pancreatico-duodenal lymph nodes along the lesser curve of the duodenum and thence into sub-pyloric nodes.

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Nerve Supply: The parasympathetic supply to the gland is

derived from the coeliac branch of the posterior vagus and the

sympathetic from the three splanchnic nerves through the

coeliac ganglia and plexus.

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• The close proximity of the pancreas to the coeliac ganglia probably contributes to the verity of the pain of pancreatitis

FUNCTIONS

Exocrine

• The exocrine secretion: is 1.5-2.51/ day of a colourless fluid, with pH of 8.0-8.3; high bicarbonate content, now known to be actively secreted by some secretory fibres; these are of secondary importance.

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• Vagal stimulation is largely responsible for the cephalic phase of pancreatic secretion of juice of low volume but rich in enzymes.
• Vagotomy or atropinization regularly abolishes this response.

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• Gastrin also increases the volume and enzyme content of pancreatic juice.

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• The "intestinal phase" of pancreatic secretion is quantitatively the most important.

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• The entry of acid gastric contents into the duodenum evokes the secretion of large quantities of pancreatic juice rich in enzymes.

This composite response is attributed:

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• to the action of volume and pH of secretin juice and cholecystokinin; its (CCK) production is stimulated by gastric hydrochloric acid, which is released by the presence of peptone, sodium oleate and amino acid solutions in the duodenum.

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• Vagotomy produces no long-term effect on pancreatic response to stimulation.

Endocrine Functions

• Hormone production in the pancreas is centred on the islets of Langerhans (with about a million groupings of cells with intricate vascular and nerve supply) irregularly scattered throughout the organ; they account for 1. 5 % of the weight of the gland.

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• There are four different types of secretory cells identified in the islets: A, B, D, F

Endocrine Functions

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• 20 % are alpha (A)-cells, a 20 amino acid polypeptide chain which enhances liver glycogenolysis and thus produces systemic hyperglycaemia.
• The beta (B)-cells which account for about 70% of islet cells and secrete insulin; this two-chain polypeptide (insulin) has the primary function of transferring glucose across cell membrane;
• it also plays an important role in conversion of glucose to glycogen in the liver.
• Insulin secretion is regulated primarily by the blood levels of glucose.

• The oral hypoglycaemic agents - tolbutamide and

Sulphonylureas - exert their action through insulin release from the B-cells.

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• 3. The D-cells (located in the periphery of the islets) secrete somatostatin, which inhibits pancreatic endocrine and exocrine secretions and gastric secretion and motility. It also inhibits secretion of gastrin, VIP, GIP, secretin and motilin.
• 4. F -cells are also present. They secrete pancreatic polypeptide whose physiological functions are not clear

INVESTIGATION OF PANCREATIC DISEASE

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• The pancreas is a deep-seated organ which has a tremendous reserve capacity and can maintain normal functional output even after 90-95 % of the gland has been destroyed.

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• It is a difficult organ to investigate, requiring a wide battery of tests for confirmation of a lesion. In the exercise, a high index of suspicion is an advantage.

(ii) Direct imaging techniques such as ultrasonography,

computerized tomography and radionuclide scans depict changes

in the pancreatic parenchyma.

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• CT scan has a marginal advantage over ultrasonography in accuracy of visualization; it is, however, four times as expensive as ultrasound.

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• Magnetic Resonance Imaging (MRI) may be more sensitive in the detection of pancreatic disease, particularly with I. V. gadolinium and has the additional advantage of being non-invasive and without the drawbacks of ionizing radiation; currently, however, it is an expensive procedure

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• The ductal system is visualized on Endoscopic Retrograde Cholangio-Pancreatography (ERCP) and this may show changes indicative of tumours and inflammatory disorders.

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• Complications encountered include injection pancreatitis, sepsis, and sensitivity reaction to the contrast medium used.

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• Selective arteriography may reveal abnormalities in the pancreatic and peripancreatic vasculature

2. Tests of Exocrine Function

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1. Pancreatic function tests:
1. measurements of enzyme and electrolyte output of the gland.

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(ii) Faecal fat excretion.

3. Tests of Endocrine Function

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• (i) Measurements of fasting blood sugar and hormones secreted by islet cells- insulin, pro-insulin, pancreatic polypeptide, glucagon, somatostatin and gastrin.
• (ii) Provocative Tests, usually employed if fasting levels

of relevant hormones or substrate substances are not diagnostic;

e.g ..

(a) The Tolbutamide Test (for insulinoma)

(b) The Glucagon Test (for insulinoma)

(c) The Calcium Infusion Test (insulinoma and

gastrinoma)

(d) The Secretin Test (gastrinoma).

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4. Markers for Pancreatic disease:

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These may be

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1. Enzymes - amylase, lipase, trypsin, ribonuclease.

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(ii) Tumour-associated antigens such as carcino-embryonic

antigens (CEA) and pancreatic oncofetal antigen (P.O.A)

5. Tissue Diagnosis:

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Pancreatic biopsy and cytology may take the form of:

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(i) Percutaneous fine needle aspiration cytology using

ultrasonography, computerised tomography or angiography for

guidance.

(ii) Endoscopic transgastric or transduodenal needle aspiration

cytology or brush cytology.

(iii) Laparoscopic examination with biopsy or aspiration

cytology under direct vision.

(iv)Operative biopsy.

CONGENITAL ANOMALIES OF THE

PANCREAS

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• Three congenital anomalies of the pancreas are of surgical importance:

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1. ectopic pancreas,
2. annular pancreas and
3. Pancreas divisum

ANATOMY AND PHYSIOLOGY

Anatomy

​

• The name ‘pancreas’ is derived from the Greek ‘pan’ (all) and‘kreas’ (flesh).
• For a long time, its glandular function was not understood, and it was thought to act as a cushion for the stomach.

• The pancreas is situated in the retroperitoneum. It is divided into a head, which occupies 30 per cent of the gland by mass, and a body and tail, which together constitute 70 per cent.

​

• The head lies within the curve of the duodenum, overlying the body of the second lumbar vertebra and the vena cava.

• The aorta and the superior mesenteric vessels lie behind the neck of the gland. Coming off the side of the pancreatic head and passing to the left and behind the superior mesenteric vein is the uncinated process of the pancreas.

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• Behind the neck of the pancreas, near its upper border, the superior mesenteric vein joins the splenic vein to form the portal vein.

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• The tip oft he pancreatic tail extends up to the splenic hilum.

ECTOPIC PANCREAS

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• Aberrant pancreatic tissue occurs most frequently in the wall of the stomach, duodenum or jejunum.

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• In 75 % of cases, the tissue is seen in the submucosa.

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• Ectopic pancreatic tissues have been found in Meckel's diverticulum, the liver and the extra-biliary system and they have been reported in enterogenous cysts of the thorax.

• Ectopic pancreatic tissue is mostly asymptomatic

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2. ANNULAR PNCREAS

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• This malformation, which is not readily explained embryologically, presents in its classic form as a ring of pancreatic tissue continuous with the head of the pancreas around the second part of the duodenum (85% of cases) proximal to the ampulla of Vater.

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• There is often a variable degree of intrinsic atresia of the duodenum and other developmental anomalies such as Down's syndrome, malrotation of the gut, imperforate anus and oesophageal atresia may coexist.
• About half the cases present in infancy with intestinal obstruction; jaundice may be noted, and is explained on the basis of pressure on the common bile duct from distended duodenum or oedema of the ampulla of Vater at the level of the stenosis.

• The other half of reported cases have been in adults.

1. Pancreas divisum

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• This is an anatomical variant occurring when there is failure of the two embryonic pancreatic ductal systems to unite.

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• The duct of Wirsung is then diminutive, about l-2cm in length, while the duct of Santorini becomes the major drainage system for the pancreas, maintaining continuity with the duodenum through the minor papilla.

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• The anomaly is by several reports associated with a high

incidence of recurrent pancreatitis

CYSTS OF THE PANCREAS

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• As elsewhere. cysts of he pancreas may be true cysts when they have an epithelial lining and usually contain fluid, or more commonly they may be false- pseudocysts-which have a lining of fibrous tissue.

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True cysts

A useful classification is.

A. Congenital

1. Single cysts

2. Multiple or polycystic disease.

3. Dermoid cysts.

4. Fibrocystic disease.

Cysts of the pancreas…../contd

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B. Acquired

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1. Retention cysts

2. Parasitic cysts

3. Neoplastic cysts - Benign - cystadenoma

Malignant- cystadeno carcinoma

Clinical features

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• Pancreatic cysts. whether congenital or neoplastic are slow-growing; even the cystadenocarcinomas are unobtrusive

in presentation.

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• Neoplastic cysts are more frequently seen in females than males (ratio of 9:1

Treatment

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• Tumours are best excised; any lesser measure frequently calls for further surgery which may be more difficult.

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• Lesions in the tail and body are readily managed by distal pancreatectomy but head lesions, unless pedunculated, usually call for pancreaticoduodenectom

TUMOURS

CARCINOMA

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• Pancreatic carcinoma, one of the most aggressive tumour malignancies, occurs quite frequently in West Africa and accounts for about 3.0% of all malignant tumors; the incidence is rising.

• In Europe it accounts for about 10 % of digestive tract tumours.
• The clinical features of pancreatic carcinoma are frequently indistinguishable from those of tumours arising from the ampullary and adjacent parts of the duodenum.

• When taken as a group, the distribution of tumors in the ampullary pancreatic complex is as follows:

Pancreas 83 % 80% head, 20 % evenly distributed in the rest pancreas

Ampulla of Vater 10%

Duodenum 4%

Common bile duct 3 %

Pathology

• The peak incidence is in the 65- 7 5 years age group and most patients present with advanced disease.

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• Familial background is found in 5-10% of patients.
• In those with at least two first degree relatives with pancreatic cancer, the risk increases 18-57-fold.
• Chronic pancreatitis is another aetiological factor; the risk increases 15-25-fold in the sporadic type and 70-100-fold in the hereditary type.
• Cigarette smoking and diets rich in fat and protein which stimulate increased secretion of cholecystokinin are aetiological factors.
• Pancreatic carcinomas are predominantly adenocarcinomas

arising from the ductal system in over 90% of cases

Clinical features

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Anorexia and weight loss (average 1 lkg over a few

weeks) are usually THE FIRST AND MOST CONSTANT SYMPTOMS of carcinoma of the pancreas irrespective of its position in the gland.

Pain is a prominent feature in 80 % of cases. It is a typical

pancreatic pain, a dull ache, aggravated by food, located in the

epigastrium and radiating or penetrating through to the back;

characteristically it is felt more severely in the supine position

but much relieved with the spine flexed and in the sitting up

position.

• Jaundice is the third most frequently encountered symptom occurring in 75 % of carcinomas of the head of the pancreas; it is the first symptom in up to 30% of some patients; appears at some period in time in 90% of patients.

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• Painless jaundice of head of pancreas carcinoma is quite uncommon; painless jaundice is more suggestive of periampullary carcinoma.

Other symptoms are:

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• diarrhoea with frank steatorrhoea and occasionally nausea, retching and vomiting when duodenal or gastric obstruction occurs.
• The liver is palpable in over 60% of patients with carcinoma of the head of pancreas and usually tender from engorgement and metastases.

The gallbladder is palpable only in about 50%

but this finding is a most reliable diagnostic criterion of malignant obstruction to the common bile duct particularly in the absence of fever and rigors.

• The point of Couvoisier's postulate is that in patients with obstructive jaundice, if the gall bladder is palpable, malignant rather than a calculous obstruction can be expected.

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• Approximately 20 % of patients with pancreatic carcinoma have glycosuria or hyperglycaemia.

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• Jaundice is the hallmark of head and ampullary lesions of the pancreas.

Investigations

1. Abdominal ultrasonography

2. Endoscopic retrograde cholangiopancreatography

3. CT Scan Contrast-enhanced CT (particularly spiral CT)
4. Liver function tests

5. A number of tumour markers have been studied in pancreatic cancer. Carcino-embryonic antigen (CEA), pancreatic oncofetal antigen.

Treatment

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SURGERY

Jaundiced cases need operative treatment without delay but

not before the patient is adequately prepared by intensive

hyperalimentation, rehydration, transfusion and correction of

hypoprothrombinaemia by means of parenteral Vitamin K

therapy.

• Provided the diagnosis is made before the cancer breaks

through its confines, the ideal procedure is Whipple's operation

or pancreatico-duodenectomy. This applies to pancreatic head

lesions as well as the ampullary cancer.

• Generally Poor prognosis

MEN SYNDROME

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MULTIPLE ENDOCRINE NEOPLASIA

(MEN) –a hereditary endocrine cancer syndrome.

• In rnultiple endocrine neoplasia ( MEN) syndromes, tumours or hyperplasia of more than one endocrine gland uncommonly occur simultaneously or subsequently (SYNDROMES).

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• The disorders RUN in the families; they are inherited as autosomal dominant. The genetics and pathogenesis of MEN's syndrome have been well studied.

• There is gene-like mutation in RET proto-oncogene which encodes a receptor tyrosine kinase signal transduction molecule in patients with MEN I IA, MEN llB and FMTC (familial medullary thyroid cancer) syndromes.
• The RET receptor tyrosine kinase is very important in regulating cellular growth, differentiation and proliferation in APUD system in cells derived from the neural crest. MEN I results from a single mutated locus on the long arm of chromosome llq 13.

Familial medullary thyroid cancer (FMTC) is an inherited condition and a subtype of MEN2 (multiple endocrine neoplasia type 2), a hereditary endocrine cancer syndrome.

RET is an abbreviation for "rearranged during transfection“The human gene RET is localized to chromosome 10 (10q11.

REFERRENCES:

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SCHWARTZ PRINCIPLE OF SURGERY 9^TH eDITION

-LANGE

CURRENT Diagnosis and Treatment

INTERNATIONAL EDITION

-MEDSCAPE

BADOE AND JAJA

Sabiston Textbook of Surgery,

18^th ed.chw

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