CarcinomaCarcinoma Of The Of The

PancreasPancreas

ByBy

Dr. PARVIDER S. LUBANA MS; D.N.B. FAMAS; FICS (USA)

• Fellow liver surgery Memorial Sloan Kattring Cancer Center, NEW YORK

• Fellow Colorectal Surgery Singapore General Hospital, SINGAPORE

• Fellow American College of Surgeons.

• Fellow European Digestive surgery.

Pancreatic cancer is sometimes called a "silent killer" because early pancreatic cancer often does not cause symptoms, and the later symptoms are usually nonspecific and varied. Therefore, pancreatic cancer is often not diagnosed until it is advanced.

PANCREATIC NEOPLASM

Benign or Malignant. Endocrine or Exocrine Tumor

BENIGN EXOCRINE TUMORS

Most are cystic. Total incidence is 10-15% of all pancreatic tumors.

Serous cystadenoma

are purely benign without malignant potential, typically they are large spherical masses that contain a watery fluid and have a central calcified stellate scar, usually occurs in the body and tail region.

Mucinous tumors

Incidence:20-40%,highly malignant potential

Intraductal Papillary Mucinous Tumor

Rapidly increasing incidence with very high malignant potential and tendency to become locally invasive and metastasize if left unresected.

Cure rate is low after development of invasive malignancy.

PANCREATIC NEOPLASM

The most common type is ductal adenocarcinoma, arises within the exocrine component seen in 85% of all pan.ca..

A minority (5%) arises from the islet cells and is classified as a neuroendocrine tumor.

Cystadenocarcinoma (1%) (Large cystic slow growing Tm)

Pancreatic cancer often has a poor prognosis: for all stages combined, the 1- and 5-year relative survival rates are 25% and 6%, respectively;

for local disease the 5-year survival is approximately 20%while the median survival for locally advanced and for metastatic disease, which collectively represent over 80% of individuals, is about 10 and 6 months respectively.

PANCREATIC ENDOCRINE TUMOR(PETS)

PETs represent an important subset of pancreatic neoplasm.

They a/c for 5% of all clinically detected Pan.Tm.

They consist of single or multiple, benign or malignant neoplasm and are asso. in 10-20-% of cases with MEN Type 1.

Clinically PETs present as functional Tm, causing specific hormonal syndrome or nonfunctional Tm with obstructive or pressure symptoms similar to Pan.Ca.

FUNCTION OF ENDOCRINE PANCREAS

Endocrine cells are found in Islets of Langerhans which constitute 1-2-% of the total mass of the Pancreas.

There are one million islets in a healthy adult Pancreas and there combine weight is 1-1.5gms.

Four main types of cells… Beta cells producing Insulin(65-80% of Islet cells) Alpha cells producing Glucagon(15-20%) Delta cells producing Somatostatin(3-10%) Pancreatic polypeptide cells containing polypeptide(1%)

INSULINOMA

Insulin producing Tm ,causing Wipple”s Triad,i.e. symptom of hypoglycemia after fasting or exercise, plasma glucose level less than2.8mmol/l and relief of symptoms on I/V glucose.

Insulinoma is m/c functioning PETs(70-80%)

Seen in 4-6th decades in life with more common among females.

90% are solitary and 10% are multiple and always asso. with MEN1 syndrome.

Approximately 10% are malignant.

Insulinoma of less than 2cm size without sign of vascular invasion or mets are considered Benign..endoscopic ultrasound is investigation of choice

C/F:

features of Hypoglycemia; diplopia, blurred vision, confusion, abnormal behavior and amnesia, lately LOC and Coma.

The release of catecholamine's produces symptoms; weakness, hunger,tremors,nausea, anxiaty and palpitation.

T/t- Surgical Excision of Insulinoma is the TOC.

Medical m/m; Diazoxide supresses Insulin secretion by direct action on beta cells, and for malignant Insulinoma Doxorubucin and streptozocin combination chemotherapy is applied for nonsurgical Tm

GASTRINOMA or Zollinger Ellision Syndrome(ZES)

ZES is a condition that includes;

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

(2) Recurrent ulceration despite adequate therapy and

(3)non-beta cell islet tm of pancreas(Gastrinoma) 20% of all PETs 0.1% of all duodenal ulcers. More in male. At diagnosis more than 60% are malignant. Mostly seen in head of Pancreas. More than 70% of Gastrinoma in MEN1 synd are located in

first and second part of duodenum

CLINICAL AND BIO CHEMICAL FEATURES

Over 90% have peptic ulcer ds , often multiple or in unusual sites. Abdominal pain from either PUD or GERD remain the m/c

symptom seen in more than 75% pt. Diarrhea is caused by large volume of gastric acid secretion.

Biochemical diagnosis; Gastric pH below 2.5 and a serum gastrin concentration above

1000 pg ml(normal less than100pg ml) EUS is gold standard to detect Gastrinoma. Most pan. gastrinoma are solitary an located in the head of the

pancreas.

Medical T/t; PPI and Octreotide controls

hypersecration.Surgical excision Enucleation with

paripancreatic lymph node dissection is procedure Of Choice.

systemic chemotherapy with Streptozotocin with 5 FU is given for diffuse metastatic Gastrinoma

CARCINOMA OF PANCREAS

25000-30000 people diagnos each year in USA.

Incidence is 10 cases per 100 000 population per year. Worldwide it constitute 2-3% of all cancers.

Pancreatic cancer is the fourth most common cause of cancer death both in the United States and internationally.

Age. The risk of developing pancreatic cancer increases with age. Most cases(80%) occur after age 60, while cases before age 40 are uncommon.

Male sex (likelihood up to 30% greater than females)

RISK FACTORS :

5–10% of pancreatic cancer patients have a family history of pancreatic cancer,

two first degree relative with Pan.Ca -Relative risk increases 18-57folds.

Chronic Pancreatitis (5-15-folds increased risk)

Hereditary pancreatitis (50-70-folds increased risk)

The risk with familial pancreatitis is particularly high. Chronic pancreatitis of any cause has been associated with a

25-year cumulative risk of 4%.

Mutation of the p-53 tumor suppressor gene is the m/c genetic event

in all human cancers and it is observed in 75% of pan ca.

Pan. Ca. is associated with the following syndromes:

Autosomal recessive ataxia-telangiectasia and autosomal dominantly inherited mutations in the BRCA2 gene and PALB2 gene,

Peutz-Jeghers syndrome due to mutations in the STK11 tumor suppressor gene,

Hereditary non-polyposis colon cancer (Lynch syndrome),

familial adenomatous polyposis, and the Familial atypical multiple mole melanoma-

pancreatic cancer syndrome (FAMMM-PC) due to mutations in the CDKN2A tumor suppressor gene.

LIFE STYLE

Cigarette smoking has a risk ratio of 1.74 with regard to pancreatic cancer;

Diets low in vegetables and fruits, high in red meat, high in sugar-sweetened drinks (soft drinks)

Diabetes mellitus is both risk factor for pancreatic cancer and new onset diabetes in older age can be an early sign of the disease.

Obesity Helicobacter pylori infection Gingivitis or periodontal disease

PPATHOLOGY… 75% -arise in the head, neck, or

uncinate process 15%-originate in the body or tail 20%-diffuse Typically, pancreatic cancer first metastasizes to

regional lymph nodes, and later to the liver and, less commonly, to the lungs; it occasionally metastasizes to bone or brain.

Common symptoms depend on site of Tm include:

Pain in the upper abdomen that typically radiates to the back(seen in carcinoma of the body or tail of the pancreas)

Loss of appetite and/or nausea and vomiting Significant weight loss

Painless jaundice, pale-colored stool and steatorrhea. The jaundice may be associated with itching as the salt

from excess bile can cause skin irritation.

Diabetes mellitus, or elevated blood sugar levels.

SSIGNS …

In advanced cases:

Periumblical adenopathy ; Sister marry josef nodule.

Enlarged left supraclavicular lymph node; Virchow's node

Pelvic paritoneal deposits; Bulmer's shelf

Trousseau sign, in which blood clots (thrombophlebitis) form spontaneously in

the portal blood vessels, the deep veins of the extremities, or the superficial veins

anywhere on the body, is sometimes associated with pancreatic cancer,

Courvoisier sign defines the presence of jaundice and a painlessly distended

gallbladder as strongly indicative of pancreatic cancer, and may be used to

distinguish pancreatic cancer from gallstones.

INVESTIGATIONS…

Blood test: Elevated S. bilirubin and Alk phosphatase

Ultrasound Abdomen C T Scan abdomen MRCP ERCP PTC PET [newer]

USG ABDOMEN…

Heterogenouspattern

withmedium sized

cysts

C T SCAN C T SCAN ABDOMEN…

TUMOUR MARKERS…

CEA Lewis blood group carbohydrate antigen CA 19-9 &

CA 125

often normal in early potentially curable tm

STAGING……

T1 limited to pancreas, 2cm or less in size. T2 limited to pancreas >2cm. T3 extends beyond pancreas, but not celiac or SMA. T4 involves celiac or SMA (unresectable). N0, N1 M0, M1

Stage 1 & 2 cancer are amenable to resection

Stage 3 & 4 are considered to be unresectable because of size, major arterial involvement

AIM OF STAGING…

to …… Determine feasibility of surgical

resection and optimal treatment for each individual patient.

RESECTIONRESECTION OF PANCREATIC CARCINOMA…OF PANCREATIC CARCINOMA…

1912 :Kaush performed the first successful resection of duodenum and portion of pancreas for ampullary cancer.

1935:Whipple-technique for radical excision of periampullary cancer by pancreaticoduodenectomy followed by reconstruction by

Pancretico-Jejunostomy (end to end or end to side) Hepatico-Jejunostomy (end to side) Gastro-Jejunostomy (anticolic end to side )

Feeding jejunostomy,

The standard resection for a Tm of the Pancreatic head or th ampula is a PPPD-Pylorus Preserving Pancreateo Duodenectomy,

it yield a more physiological outcome with no difference in survival or recurrence rates.

For Tm of the body and tail, distal pancreatectomy with spleenectomy is the standard.

KOCHERISATION…

DETERMINING RESECTABILITY…

Palpation ofUncinate Process, Head of pancreas, SMA.

RESECTED HEAD OF PANCREAS…

RE-ANASTOMOSIS…

PYLORUS PRESERVING….

POST OPERATIVE SPECIMEN…

POST OPERATIVELY…

Complication rates remain high (15-20%).

Pancreatic fistula remains the most frequent serious complication (5-15%). The mortality from this has decreased though(2-4%).

Other common complications include delayed gastric emptying, abscess, bleeding, infection, diabetes, exocrine insufficiency.

5 YEAR SURVIVAL….

Stage 1 (T1-T2, N0, M0) 20-30%.

Stage 2 (T3, N0,M0) 10-25%.

Stage 3 (T4, any N, M0) 0-5%.

Stage 4 (Any T, any N, M1) 0%.

Even after R0 resection 5 year survival rate is only

10-15%

Very little or no role of RT+5FU & gemcitabine

Thanks

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