pancreatic cancer management
Post on 23-Jan-2017
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AnatomyThe pancreas is an elongated, coarsely lobulated gland lying transversely and retroperitoneally in the posterior abdomen
at approximately the L1 to L2 level
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.
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
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).
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
borderline resectable disease
markedly elevated CA 19-9
large primary tumors
large regional lymph nodes
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
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%
UNRESECTABLE BUT NOT 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
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
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