pancreatic cancer management

CARCINOMA PANCREAS

CARCINOMA PANCREAS

AnatomyThe pancreas is an elongated, coarsely lobulated gland lying transversely and retroperitoneally in the posterior abdomen

at approximately the L1 to L2 level

Arterial Supply

Venous Drainage

Lymphatic Drainage

Innervation

EpidemiologyPancreatic cancer is the fifth leading cause of cancer mortality among men and women of all ages

a male-to-female ratio of 1.3:1.

Diagnosis is rare before age 45 but rises sharply thereafter

Causal FactorsSmoking -raises the relative risk 1.5 times.

Alcohol

Diets high in meat or fat also have been linked to increased risk

a diet of fresh fruits and vegetables has been found to be protective.

An increased incidence also is found with a prior history of surgery for peptic ulcer disease

High bmi increases risk9

chronic pancreatitisare associated with pancreatic cancer

One study showing 7 times higher risk

Long-term diabetes appears to be a risk factor for pancreatic cancer

Chemical agents

Workers employed in manufacturing 2-naphthylamine, benzidine,and gasoline are reported to have a fivefold increased risk

Genetics, and Cytogenetic AbnormalitiesPancreatic cancer is thought to have a familial component in approximately 10% of cases

There are four specific genes identified as crucial in the development of pancreatic cancer:

p16, p53, DPC4, and BRCA2

An example is the k-ras oncogene, which is often activated in human pancreatic duct carcinomas.

95% of pancreatic adenocarcinomas contain k-ras oncogenes activated by a mutation at codon 12.

Germline mutations in the STK11 gene result in Peutz-Jeghers syndrome

individuals have gastrointestinal polyps and a highly elevated risk for colorectal cancers

highly elevated risk for developing pancreatic cancer, reported to be increased by as much as 132-fold

Familial Malignant Melanoma syndrome (also known as Melanoma-Pancreatic Cancer syndrome or Familial Atypical Multiple Mole Melanoma syndrome [FAMMM])

caused by germline mutation of the CDKN2A (p16INK4a/p14ARF) gene.

This syndrome is associated with a 20-fold to 47-fold increased risk for pancreatic cancer

Lynch syndrome also have an estimated 9- to 11-fold elevated risk for pancreatic cancer

BRCA 1 N 2

The risk of pancreatic cancer is elevated 2- to 6-fold in these patients

age of onset is younger than average

As many as 80% of patients with a family history of pancreatic cancer have no known genetic cause.

having just 1 first-degree relative with pancreatic cancer raises the risk of pancreatic cancer by 4.6 fold

having 2 affected first-degree relatives raises risk by about 6.4-fold

Pancreatic Cancer Screeninghigh-risk individuals

defined as first-degree relatives of patients with pancreatic cancer from familial kindreds;

carriers of p16 or BRCA2 mutations with an affected first-degree relative

patients with Peutz-Jeghers syndrome

patients with Lynch syndrome and an affected first-degree relative with pancreatic cancer.

Eus or mri or mrcp20

Pathologic ConditionsThe most common type of pancreatic cancer is of ductal origin, comprising from 75% to 90% of patients

It is twice as common in the head as in the body or tail

Less frequently occurring exocrine tumors, such as cystadenocarcinoma or intraductal carcinoma, are more common in women

cystadenocarcinoma may run a much more indolent course21

Solid and cystic papillary neoplasms, also known as Hamoudi tumors, occur in women in their third decade of life

rarely metastasize, and have a good prognosis

Rare acinar cell cancers are associated with fat necrosis and high lipase production and have a poor prognosis

may be associated with a clinical picture that includes rash, eosinophilia, and polyarthralgia

Giant cell tumors, which account for only a small percentage of pancreatic cancers, are very large and aggressive and have a very poor survival rate

metastases in the pancreas with the most frequent primary sites being breast, lung, or melanoma

5% of pancreatic cancers are of endocrine origin

Location66% in Head and Uncinate ProcessDx earlier , Symptomatic15% in Body10% in Tail Usually larger & more progress at time of Dx AsymptomaicOther diffuse involvement

Clinical PresentationMore than 80% of patients present with pain, jaundice, or both and weight loss

Infrequently, patients may present with migratory thrombophlebitis (Trousseau sign)

or with a palpable gallbladder (Courvoisier sign).

Evaluation

The most commonly used diagnostic and staging examination is an abdominal CT scan

Over 90% of patients deemed unresectable by CT are actually unresectable at operation

CT can be utilized to facilitate fine-needle aspiration.

EUSIn this procedure, an endoscope with an ultrasound transducer at its tip is passed into the stomach and duodenum

it provides high-resolution images of the pancreas and surrounding vessels and facilitates needle biopsies

EUS is usually performed in conjunction with endoscopic retrograde cholangiopancreatography (ERCP)

This combined diagnostic approach allows for staging, therapeutic stenting of the common bile duct when indicated, and retrieval of tumor cells by fine-needle aspiration

(MRI) including high-resolution imaging, fast imaging, volume acquisitions, functional imaging, and MR cholangiopancreatograph

have led to an improved ability of MRI to diagnose and stage pancreatic cancer

Used in patients with poor renal function

Small foci of hepatic mets are better detected by MRI

PETInitial studies showed (PET) has a higher sensitivity, specificity, and accuracy than CT in diagnosing pancreatic carcinomas

more accurate than CT in identifying malignant pancreatic cystic lesions

STAGING LAPROSCOPYcurrent imaging techniques cannot visualize small (1 to 2 mm) liver and peritoneal implants

staging laparoscopy has been used preoperatively to exclude intraperitoneal metastases

can detect intraperitoneal metastases in up to 37% of patients with apparently locally advanced disease by CT

Patients with locally advanced disease with involved peritoneal washings or positive peritoneal biopsies have the same prognosis as those with metastatic disease. 34

WHEN?

borderline resectable disease

markedly elevated CA 19-9

large primary tumors

large regional lymph nodes

highly symptomatic

BiopsyAlthough a pathologic diagnosis is not required before surgery

it is necessary before administration of neoadjuvant therapy and for patients staged with locally advanced, unresectable pancreatic cancer or metastatic disease

often made using fine-needle aspiration (FNA) biopsy with either EUS guidance (preferred) or CT

Pancreatic ductal brushings or biopsies can also be obtained at the time of ERCP

STAGING

Diagnosis & stagingStage at Diagnosis7% : Localized stage5yr-SR = 20.3%26% : +ve Regional LN involvment / T3 up5yr-SR = 8.0%52% : metastasis (Distant stage)5yr-SR = 1.7%15% : unknown stage information5yr-SR = 4.1%

Overall 5yr-SR = 5%

MANAGEMENTRESECTABLE

BORDERLINE RESECTABLE

UNRESECTABLE BUT NOT METASTATIC

METASTATIC

CRITERIA DEFINING RESECTABILITY STATUSResctable tumors

No distant metastases

No radiographic evidence of superior mesenteric vein (SMV) or portal vein (PV) distortion.

Clear fat planes around the celiac axis, hepatic artery, and SMA

borderline resectableNo distant metastases

Venous involvement of the SMV or PV with distortion or narrowing of the vein or occlusion of the vein with suitable vessel proximal and distal, allowing for safe resection and replacement.

Gastroduodenal artery encasement up to the hepatic artery with either short segment encasement or direct abutment of the hepatic artery without extension to the celiac axis.

Tumor abutment of the SMA not to exceed greater than 180 degrees of the circumference of the vessel wall

UNRESCTABLE

Management of Resectable and Borderline ResectableDisease

Surgical resection is the only potentially curative technique for managing pancreatic cancer

more than 80% of patients present with disease that cannot be cured with surgical resection

The goals of surgical extirpation of pancreatic carcinoma focus on the achievement of an R0 resection

a margin positive specimen is associated with poor long-term survival

Achievement of a margin negative dissection must focus on meticulous perivascular dissection of the lesion in resectional procedures, recognition of the need for vascular resection and/or reconstruction

prognostic indicators for long-term patient survival

Negative margin status (ie, R0 resection)

Tumor DNA content

tumor size

absence of lymph node metastases

When deciding whether a patient is a surgical candidate.

Age of the patientComorbiditiesperformance statusfrailty are all things to be discussed

Primary Surgery for Pancreatic CancerThe nature and extent of the surgery for resectable tumors depend on the location and size of the tumor.

Because tumors of the body and tail cause symptoms late in their development

they are usually advanced at diagnosis and are rarely resectable.

Surgical ProceduresTumors of the Body and TailDistal Pancreatectomy

Removal of body & tail