Neoplasm of pancreas

Neoplasms of the Pancreas

Dr.Prabhakara Rao.Y M.S,McHProfessor of surgery

Introduction

• 4th leading cause of cancer death.• Non-specific symptoms, inaccessibility to

examination, aggressiveness, technical difficulties associated with surgery.

Epidemiology/Risk Factors

• Increase threefold since the beginning of the century.

• Age, race, sex, tobacco, diet, specific genetic syndromes.

• More than 80% of cases between 60-80 years of age, rare under 40.

• African-American of both sexes


• Men over women• Cigarette smoking increased risk 1.5-5 times.• Increased consumption of total calories, CHO,

cholesterol, meat, salt, fried food, refined sugar, soy beans, nitrosamines.


• A protective effect for dietary fiber, vitamin C. fruits and veggies.

• Long standing diabetes is not a risk factor.


• Chronic pancreatitis of any cause has been associated risk of 4%.

• Other conditions for which a possible connection to pancreatic cancer are: thyroid cancer, cystic fibrosis, pernicious anemia.

• Most cases of pancreatic cancer have no predisposing factors, however it is estimated that between 5-10% arise because of a familial disposition.


• Six genetic syndromes associated with an increased risk of pancreatic cancer are:

• HNCC, BRCA-2 associated familial breast cancer, Peutz-Jeghers syndrome, ataxia-telangietasia, hereditary pancreatitis, familial mole-melanoma syndrome.

Molecular Genetics

• Tumor suppressor genes: p53, p16, DPC4, BCA2.

• P53 is inactivated in 75% of all pancreatic cancers.

Molecular Genetics• DPC4 is on Chromosome 18q. The Chromosome is

missing in 90% of all pancreatic cancers, the gene inactive in 50%. The mutations are more specific for pancreatic cancer than p53 or p16 mutations.

• Oncogenes, when over expressed encode proteins with transforming qualities. Activating point mutations in the k-ras oncogene is the most common genetic alteration in pancreatic cancer, found in 80-90% of pancreatic cancers.

The tumours of the pancreas can be -

A. Non-Endocrine neoplasms

B. Endocrine neoplasms

TUMOURS OF THE PANCREAS

NON-ENDOCRINE NEOPLASMS:

Benign non-endocrine neoplasms of pancreas. Includes:-

(adenoma, cystadenoma, lipomas, fibromas, haemingoma, lymphangioma and neuromas). They are extremely rare and no clinical significance unless they become palpable or give pressure to adjacent structures and cause symptoms. Can be solid or cystic or both. The diagnosis should be made after exclusion of more frequent malignant tumours.

Malignant non-endocrine neoplasms. The most common are:-

1. Ductal adenocarcinoma 2. Cystadenocarcinoma

NOTE: Periampullary carcinoma is term used for juxta-pancreatic carcinomas. They are three forms:-

Carcinoma of the ampulla Carcinoma of the lower CBD Duodenal carcinoma

Exocrine cell of pancreas

ENDOCRINE NEOPLASMS: These are less common than non-

endocrine tumours and generally benign and sometimes multiple. They includes: Insulinoma Glucogonomas Others:

- Gastrinomas - Somatostatatinomas - Vipomas (Vasoactive

Intestinal Polypeptide)

common

Pathology

• Classified based on cell of origin. Most common are ductal adenocarcinomas.

• 65% of ductal cancers arise in the head, neck, or uncinate process; 15% originate in the body or tail; 20% diffuse.

Solid Epithelial Tumors

• Adenocarcinomas: 75%, white yellow, poorly defined, often obstruct bile duct or main pancreatic duct.

• Often associated with a desmoplastic reaction that causes fibrosis and chronic pancreatitis.

Solid Epithelial Tumors

• Infiltrate into vascular, lymphatic, perineural spaces. At resection, most mets to lymph nodes.

• Mets to liver (80%), peritoneum (60%), lungs and pleura (50-70%), adrenal (25%). Direct invasion of adjacent organs as well.

• Others include adenosquamous, acinar cell (1%, better prognosis), giant cell (5%, poorer prognosis), pancreatoblastoma (children 1-15 years, more favorable).

Pathologic Classification of Cystic Neoplasms of the Pancreas

• Serous cystic neoplasm (SCN) Microcystic adenoma Oligocystic adenoma• Mucinous cystic neoplasm (MCN) Mucinous cystadenoma Mucinous cystic tumour borderline Mucinous cystadenocarcinoma Noninvasive (carcinoma-in-situ) Invasive

• Intraductal papillary mucinous neoplasm (IPMN)

Adenoma Borderline Carcinoma-in-situ Invasive carcinoma

SEROUS CYSTIC NEOPLASMS

• always benign• occur in women in the sixth decade of life.• abdominal pain and the presence of a

palpable mass were the most common complaints among symptomatic patients.

• predilection for the pancreatic body and tail• Enucleation

MUCINOUS CYSTIC NEOPLASMS

• 20-30% of cystic neoplasms of the pancreas• more common in females than males, with

over 90% of patients being female.• mean age at presentation being 48-52 years.• most commonly occur in the body or tail of

the pancreas

• MCNs contain large septated cysts with thick irregular walls that may be well-detailed on CT, MRI, or ultrasound evaluation.

• Papillary projections from the epithelium often extend into the cystic cavities and may be visible, particularly on endoscopic ultrasound imaging.

• MCNs have been shown to be rich in CEA and low in amylase.

• Other tumor markers such as CA 72-4, CA 19-9, CA 125, and CA 15-3 have been investigated as adjuncts to diagnosis

• Segmental pancreatic resections for lesions in the pancreatic neck and body (central pancreatectomy) or tail (spleen-preserving distal pancreatectomy) should be performed cautiously

INTRADUCTAL PAPILLARY MUCINOUS NEOPLASMS

• significant malignant potential.• Characteristic features include a tall,

columnar epithelium with marked mucin production, and cystic transformation of either the main pancreatic duct or one of its side branches.

• IPMN tend to be older, with a mean age of approximately 65 years.

• Tall mucin-producing columnar epithelial cells that remain well differentiated characterize IPMN adenoma.

• IPMN borderline lesions are described as lesions with moderate epithelial dysplasia, moderate loss of polarity, changes in nuclear morphology, and pseudopapillary formation

• IPMNs with carcinoma-in-situ have severe dysplastic changes. These lesions may be papillary or micropapillary, and severely dysplastic lesions may lose the ability to secrete mucin.

• malignant potential of IPMNs involving the main pancreatic ductal system appears to be greater than that of lesions involving only secondary ducts.

UNUSUAL PANCREATIC CYSTIC NEOPLASMS

• Solid Pseudopapillary Tumor• Cystic Neuroendocrine Tumor• Cystic Acinar Cell Tumor• Cystic Degeneration of Ductal

Adenocarcinoma

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

5-Year Survival

• Stage 1A, 1B (T1-T2, N0, M0)20-30%.• Stage 1B (T2, N0,M0) 20-30%.• Stage 2A (T3, N0,M0) 10-25%.• Stage 2B (T1, T2, T3, N1, M0)10-15%.• Stage 3 (T4, any N, M0) 0-5%.• Stage 4 (Any T, any N, M1) 0%.

Spread of pancreatic tumours: A. Local Invasion

B. Lymphatic

C. Blood

D. Via peritoneal & omentum causing ascites

CLINICAL FEATURES:

The diagnosis of pancreatic cancer varies from the simple and clinically obvious to the most difficult and almost impossible the initial symptoms and signs depend on the site and extent of the pancreatic cancer.

Modes of presentation: Weight loss

Pain Jaundice Steatorrhoea Diabetes Mellitus Acute Pancreatitis Malignant Ascites Gastric Outlet Obstruction

Approach to Investigations: (Selective Investigations)

Ultrasound Scan C.T. Scan MR Imaging Scan ERCP Histology & Cytology Angiography (Coeliac, Superior -Mesenteric)

Laparoscopy

DELAY IN DIAGNOSIS: Over 90% of patient with pancreatic

cancer present in the late stage of their disease. At time no chance of cure.

The factors responsible for late diagnosis A. Tumour is asymptomatic in the early

stage. B. Patient delay. C. Physician delay. D. The patient may not have ready and

easy access to competent diagnostic centre.

Diagnosis

• Most occur at the head, obstructs the bile duct that is intrapancreatic, causing jaundice, dark stools, dark urine, abdominal or back pain that is usually ignored by the patient. Pain may also be caused by invasion of splanchnic plexus and retroperitoneum.

Diagnosis

• New onset of diabetes (10-15%), acute pancreatitis. Jaundice is most common(87%), hepatomegaly(83%), palpable gallbladder(29%) may be present. Cachexia, muscle wasting, nodular liver, Virchow’s node, SMJ node, ascites (15%).

Diagnosis

• Amylase, lipase normal, other labs like obstructive jaundice.

• Ca 19-9, when upper level cutoff is used >200U/mL, accuracy is 95% in diagnosing pancreatic cancer. With CT, ERCP, US and Ca19-9 together, it approaches 100%.

• Higher levels correlate with prognosis and tumor recurrence, unresectability.

Radiology

• CT has replaced US. On CT appears as an area of enlargement with a localized hypodense lesion. Do thin cuts thru pancreas and liver. CT is used to determine size of lesion and involvement of adjacent structures, mets.

Radiology• MRI offers no advantage. MRCP promising in terms

of duct evaluations.• Next step is ERCP to get anatomy and specimens.

Sensitivity of ERCP to diagnose cancer is 90%. Look for long irregular stricture in an otherwise normal duct is highly suggestive. Obstruction with no distal filling. Don’t need on everybody. Do it if suspect cancer but no mass seen on CT. Or symptomatic but no jaundice and no mass, chronic pancreatitis patients with development of mass.

MANAGEMENT OF PANCREATIC CANCER:

A. Surgical Treatment

B. Non Surgical Treatment

Preoperative Staging

• Determine feasibility of surgery and optimal treatment for each individual patient.

• In many cases only CT scan is necessary.


• Absence of metastases, patent SMV-portal vein confluence, no direct extension to celiac axis or SMA accuracy for resectability 85%.

• For tumors of the neck, head, uncinate process, occlusion of the SMA or portal vein along with presence of periportal collateral vessels is a sign of unresectability.


• In contrast tumors of the body and tail, occlusion of the splenic vein with perigastric collaterals does not always preclude resection.

• The extent of further staging depends on the patient and surgeon. If findings of staging can prevent an operation and lead to non-operative palliation, these efforts are worthwhile.


• Endoscopic US useful for small lesions, lymph nodes, vascular invasion, EU guided FNA may avoid seeding.

Preoperative Staging• Percutaneous FNA should not be used on potentially

resectable tumors for two reasons. First even if the result is negative it does not rule out malignancy, in fact the small, potentially curable lesions will be the ones that are missed by the needle. Second is potential for seeding along tract or intraperitoneally. FNA should be done on patients deemed unresectable for direction of chemotherapy, or patients in whom neoadjuvant chemo is being considered. Currently EUS is the preferred technique for this in these situations.


• At the time of diagnosis, only 10% tumors confined to pancreas. 40% have locally advanced disease, 50% distant spread. Overall only 10-20% of all patients are candidates for pancreatic resection.


• Diagnostic laparoscopy on potentially resectable patients may find mets to liver and peritoneum not seen on CT because they are small. 50% of tumors of body and tail will have unexpected mets to peritoneum, whereas in head and neck, only 15% unexpected mets seen.

Resection of Pancreatic Carcinoma

• Head, Neck, Uncinate: 1912 Kaush first successsful resection of duodenum and portion of pancreas for ampullary cancer.


• 1935- Whipple described a technique for radical excision of a periampullary cancer. Was originally performed in two stages, first stage was a cholecystogastrostomy and gastrojejunostomy. Second stage was done after nutritional status better and jaundice improved was en-bloc resection of second portion of duodenum, head of pancreas without reestablishing pancreas-GI continuity. Since then many modifications done.


• Operative management of pancreatic cancer consists of two phases: first assessing tumor resectability, second completing a pancreaticiduodenectomy and restoring GI continuity.

Resection of Pancreatic Carcinoma1. Search first for mets, extrapancreatic involvement.

Send frozen sections on suspect lesions.2. Assess primary tumor, for resectabilty, look for IVC,

Aorta, SMA, SMV, Portal vein. To do this you do a Kocher maneuver to mobilize duodenum and head from IVC and aorta, once mobilized can assess relationship of tumor to SMA. Inability to find a plane between pulsation of SMA and tumor means unresectable.


3. Dissect out SMV and Portal vein to rule out tumor invasion.

4. Once this is negative go to pancreaticoduodenectomy (pylorus preserving or classic).

Kocherizing

Determining Resectability

Resected Head

Pylorus Preserving

Postoperative Results

• During the 1960s and 1970s, many centers reported operative mortality in range of 20-40%, with postoperative morbidity rates of 40-60%.


• During last two decades rates reported down to 2-3% mortality. Reasons why fewer, more experienced surgeons are performing the operation on a more frequent basis, pre and post op care has improved, anesthesia has improved, large number of patients are being treated at high volume centers.


• Complication rates remain high (30%). Pancreatic fistula remains the most frequent serious complication (5-15%). The mortality from this has decreased though.

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

Long-term Survival

• Historically, 5% 5-year survival post resection. More recent studies suggest improved survival.

Long-term Survival• In 2000, Sohn, et al. on 616 patients resected with a

17% 5-year survival, median survival of 17 months. Factors found to be important predictors of survival included tumor diameter (<3cm), negative resection margin, well/mod tumor differentiation, postop chemoradiatioin treatment.

• Most favorable were small tumors, margin negative, node negative resections, median survival was 33 months and 5-year survival was 31%.

Adjuvant Therapy

• Radiation• 5-FU

Palliation

• Jaundice: Choledochojejunostomy, cholecystojejunostomy. Stent placement.

• With stents, may need frequent exchanges, may migrate, recurrent jaundice is higher. Metallic stents stay open longer. Lower complication rates with respect to surgical palliation.

• Surgical palliation for patients expected to live longer than 6 months only.

Palliation

• Duodenal Obstruction:Gastrojejunostomy do it or not if the patient is not obstructed. Studies say do it. No difference in length of stay post op, morbidity, mortality.

• Pain: Long-acting morphine derivatives, percutaneous blocks are successful at eliminating pain in majority.

Neoplasm of pancreas

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