02-21 Pancreatic Cancer + Surgery Flashcards
At the end of this lecture, the learner should be able to: • Describe the clinical presentation of pancreatic cancer • Explain the appropriate work up and management of a patient with pancreatic cancer • Discuss the epidemiology and risk factors of pancreatic neoplasms • Describe the surgical procedures utilized in patients presenting with pancreatic cancer • Define what is meant by neo-adjuvant therapy, define the role of the medical oncologist, radiation oncologist and interdi
<p>
PanIN?</p>
<p>
Pancreatic intraepithelial neoplasm —microscopic papillary or flat non-invasive epithelial neoplasm arising in the pancreatic ducts. PanINs are characterized by columnar to cuboidal cells with varying amounts of mucin and degrees of cytologic and architectural atypia. PanINs usually involve ducts </p>
<p>
What are more favorable DDx for pancreatic cancer?</p>
<p>
Cystic masses in the pancreas</p>
<ul>
<li>
Many cystic neoplasms are benign or borderline.</li>
<li>
Serous cystadenoma</li>
<li>
Intraductal papillary-mucinous neoplasms**</li>
<li>
Mucinous cystic neoplasms**</li>
<li>
Some are pseudocysts (not neoplastic).</li>
</ul>
<p>
**Neoplasms with moderate dysplasia</p>
<p>
Pancreatitis can cause localized enlargement that looks like a neoplasm in imaging studies.</p>
<ul>
<li>
Autoimmune pancreatitis</li>
<li>
Paraduodenal pancreatitis (groove pancreatitis), involves head and duodenal wall.</li>
</ul>
<p>
List some of the less common pancreatic cancers (by benign, borderline and maligant) and give a few identifying features.</p>
<p>
BENIGN</p>
<ol>
<li>
Serous cystadenoma</li>
<li>
Mucinous cystadenoma</li>
<li>
Intraductal papillary-mucinous adenoma</li>
</ol>
<p>
UNCERTAIN MALIG/BORDERLINE</p>
<ul>
<li>
think mucus</li>
<li>
Good prognosis when resected.</li>
</ul>
<ol>
<li>
Intraductal papillary-mucinous neoplasm (IPMN) w/ mod. dysplasia</li>
<li>
Mucinous cystic neoplasm</li>
</ol>
<p>
MALIGANT </p>
<ol>
<li>
Ductal adenocarcinoma (~85%)
<ul>
<li>
Signet ring cell carcinoma</li>
<li>
Adenosquamous carcinoma (4%)</li>
<li>
Undifferentiated (anaplastic) carcinoma</li>
<li>
Mucinous non-­cystic carcinoma (a.k.a. colloid carcinoma)</li>
</ul>
</li>
<li>
Mucinous cystadenocarcinoma (1%)</li>
<li>
Intraductal papillary mucinous carcinoma (gone malig) (2-­3%)</li>
<li>
Acinar cell carcinoma (<1%) </li>
<li>
Pancreatoblastoma (<1%)</li>
<li>
Solid-­pseudopapillary carcinoma (<1%)</li>
</ol>
<p>
Pancreatic cancer in kids?</p>
<ul>
<li>
5-yr survival?</li>
<li>
histo appearance?</li>
</ul>
<p>
Pancreatoblastoma is the most common pancreatic neoplasm in young children (qqf chez adults)</p>
<ul>
<li>
Rare low-grade malignant tumor
<ul>
<li>
malignant but <strong>only ~35% metastatic</strong> at time of diagnosis.</li>
</ul>
</li>
<li>
5-year survival ~60%</li>
<li>
stem cell origin → Composed of primitive small cells mixed with acinar, ductal or islet cells.</li>
</ul>
<p>
Mostly dx of panc tumor in 20 y/o female?</p>
<p>
Solid-pseudopapillary neoplasm is characteristically found in teen-age or young women.<br></br>
Low grade malignant neoplasm<br></br>
Excision usually yields a cure.</p>
<p>
What if the patient is a 49 year-old female with a cystic mass in the tail of the pancreas?</p>
<p>
What if the patient is a 49 year-old female with a cystic mass in the <u><strong>tail</strong></u> of the pancreas?</p>
<p>
Mucinous cystic neoplasms (one of our moderately dysplastic ones)</p>
<ul>
<li>
have peak incidence in 45-50 yr-old women.</li>
<li>
Tend to occur in the tail</li>
<li>
Very rare in men.</li>
<li>
10-20% are malignant.</li>
<li>
generally good prognosis</li>
</ul>
<p>
Serous cystadenoma</p>
<ul>
<li>
Degree of malig?</li>
<li>
path/histo appearance?</li>
<li>
Age of onset?</li>
<li>
Where in pancreas?</li>
</ul>
<ul>
<li>
Most common <strong>benign</strong> tumor of the pancreas.
<ul>
<li>
Very few become malignant.</li>
</ul>
</li>
<li>
Multiple small cysts lined w/ cuboidal epithelium & classic <strong>honeycom</strong>b appearance</li>
<li>
Occur in adults of any age, but are <strong>most common in</strong>♀<strong>~66 yrs.</strong></li>
<li>
Most (50-70%) occur in the <strong>body or tail</strong> of the pancreas</li>
</ul>
<p>
Acinar Cell Carcinoma</p>
<ul>
<li>
Most common in</li>
<li>
Prognosis</li>
<li>
unique feature?</li>
</ul>
<ul>
<li>
Occurs at any age; p<strong>redominantly males</strong>.</li>
<li>
Aggressive but less so than ductal carcinomas;
<ul>
<li>
median survival 18 months (5-­ yr survival 10%)</li>
</ul>
</li>
<li>
Tumor cells produce exocrine enzymes, e.g. trypsin, chymotrypsin, lipase
<ul>
<li>
Lipase hypersecretion syndrome: 0-­15% of patients (with hepatic metastases)</li>
<li>
Subcutaneous fat necrosis, polyarthralgias </li>
</ul>
</li>
</ul>
<p>
Solid Pseudopapillary Tumor (aka Solid-­Cystic Tumor) </p>
<ul>
<li>
uncertain histogenesis</li>
<li>
primitive epithel cells (small, uniform cells w/ finely granular eosinophilic cytoplasm).</li>
<li>
Most common in <strong>young females</strong> (adol-35 yrs).</li>
<li>
<strong>Most are benign</strong>, but a few are invasive and more aggressive.</li>
<li>
Necrosis → cyst → forms pseudopapillary projections where tumor cells survive around blood vessels. </li>
</ul>
<p>
Mucinous cystic neoplasms (MCN):</p>
<ul>
<li>
Cystic neoplasm lined by mucin-­secreting epithelium, most often in body or tail.</li>
<li>
Almost always in <strong>women</strong>, usually age 40-­50. </li>
<li>
Graded into benign, borderline, malignant non-­invasive, and malignant invasive groups on the basis of the degree of epithelial dysplasia (mild, moderate, severe). </li>
</ul>
<p>
Intraductal papillary mucinous neoplasms (IPMN)</p>
<ul>
<li>
Intraductal mucin-secreting neoplasms that can become cystic.</li>
<li>
Arise throughout the pancreas, median age about 65, <strong>men>women.</strong></li>
<li>
Graded into benign, borderline, malignant non-invasive, and malignant invasive groups on the basis of the degree of epithelial dysplasia (mild, moderate, severe).</li>
<li>
becomes malignant (30-40%) >> MCN.</li>
</ul>
<p>
Generally speaking, how does age affect your guess as to what tumor a pancreatic neoplasm is? </p>
<p>
Ductal adenocarcinoma</p>
<ul>
<li>
Median age 66 years</li>
<li>
Uncommon under age 50</li>
<li>
Still: odds are that a mass found in older person's pancreas is ductal carcinoma</li>
</ul>
<p>
In patients </p>
<ul>
<li>
Think of other types of neoplasm, pancreatitis, pseudocyst</li>
<li>
If ductal ca, think of genetic predisposition</li>
</ul>
<p>
Major Points to Review</p>
<ol>
<li>
Pancreatic neoplasms occur in both sexes at any age.</li>
<li>
There are many types of pancreatic neoplasms, some are benign or in situ and curable.</li>
<li>
Accurate diagnosis guides management.</li>
<li>
Pancreatitis can cause masses and cysts that are indistinguishable from neoplasms by imaging.</li>
<li>
Histologic diagnosis is important.</li>
<li>
A diagnosis of pancreatic ductal adenocarcinoma remains bad news.</li>
</ol>
<p>
</p>
<p>
Resources to review</p>
<ol>
<li>
PPT for this lecture</li>
<li>
Notes, on Blackboard</li>
<li>
UpToDate - Wolters Kluwer
<ul>
<li>
Pathology of exocrine pancreatic neoplasms-I</li>
<li>
Pathology of exocrine pancreatic neoplasms-II</li>
</ul>
</li>
<li>
Netpath</li>
<li>
Robbins and Cotran, pathology textbook.</li>
</ol>
<p>
</p>
<p>
PResenting S/Sx of Pancreatic Cancer</p>
<p>
Cancer in head of panc</p>
<ul>
<li>
92% wt loss</li>
<li>
80% jaundice (b/c CBD blocked)</li>
<li>
72% pain</li>
<li>
64% anorexia</li>
</ul>
<p>
Cancer in the body/tail</p>
<ul>
<li>
100% weight loss</li>
<li>
87% pain</li>
<li>
43% weakness</li>
<li>
7% jaundice</li>
</ul>
<p>
% of pancreatic cancer patients who present with resectable dz?</p>
<ul>
<li>
What percent of those are cured by resection?</li>
</ul>
<ul>
<li>
Only 25% are resectable</li>
<li>
About 25% of those patients </li>
</ul>
<p>
Criteria to decide resectability of tumor?</p>
<p>
<br></br>
Resectable: There is a fat plane between the tumor and the SMA, celiac artery and portal vein/superior mesenteric vein</p>
<p>
Borderline resectable: The tumor abuts the SMA or celiac artery < 180 degress, or abuts or occludes a short segment of the portal vein</p>
<p>
Unresectable: the tumor surrounds the SMA, celiac artery or occludes the portal vein over a long distance</p>
<p>
<br></br>
One can resect and graft part of the portal vein, but resection of the SMA has been tried in small numbers of patients with very poor results.<br></br>
</p>
<p>Palliation Measures</p>
<p>Biliary obstruction: stent</p>
<ul>
<li>tx jaundice and itching</li>
</ul>
<p>Pain: celiac plexus block (ablate w/ alcohol) or radiation therapy</p>
<p>Systemic Tx</p>
<ol>
<li>Gemcitabine</li>
<li>FOLFIRINOX
<ul>
<li>5-FU</li>
<li>leucovorin</li>
<li>oxaliplatin</li>
<li>irinotecan</li>
</ul>
</li>
</ol>
<p>
Surgical Tx of resectable dz</p>
<p>
Head:</p>
<ul>
<li>
Whipple (Pancreaticoduodenectomy): pancreas, part of stomach and duodenum</li>
</ul>
<p>
Tail: </p>
<ul>
<li>
Just distal pancreatectomy</li>
</ul>
<p>
Adjuvant tx options shown to increase survival when added to surgery</p>
<ul>
<li>
5-FU</li>
<li>
gemcitabine (Europe)</li>
<li>
radiation
<ul>
<li>
60% </li>
</ul>
</li>
<li>
Neo-adjuvant therapy (DHMC)
<ul>
<li>
start w/ chemo, then add rad</li>
<li>
gives test of time/of biology: pts destined to fail will show mets</li>
<li>
avoids resecting pts w/ high likelihood of local recurrence</li>
<li>
Allows also to resect some tumors that were originally unresectable into resectable patients</li>
<li>
None had local recurrence</li>
</ul>
</li>
</ul>
<p>
The pancreas is mostly made of \_\_\_\_\_ cells.</p>
<p>
acinar (80%)</p>
<p>
\_\_\_\_\_\_\_ cells form only 1-2% of the pancreas.</p>
<p>
Islet cells (endocrine pancreas)</p>
<p>
when reference is made to "carcinoma of the pancreas" only tumors arising from the \_\_\_\_\_\_\_\_ are included.</p>
<p>
exocrine pancreas</p>
<p>
Most common subtype of pancreatic carcinoma?</p>
<p>
about 85-90%) are ductal adenocarcinomas</p>
<p>
Describe the clinical presentation of pancreatic cancer.</p>
<p>
blah</p>
<p>
Describe the epidemiology of pancreatic cancer?</p>
<ul>
<li>
Malignant pancreatic ca = #4 among cancers as a cause of death (both sexes) in the U.S., surpassed only by lung, colon, and breast cancers.</li>
<li>
About 44,000 new patients were anticipated in 2012</li>
<li>
estimated number of deaths is about 3700</li>
<li>
The incidence of pancreatic carcinoma rises with age and is slightly greater in males than in females (1.6:1 ratio)</li>
<li>
For ductal adenoca.: Median age 66 yrs (Uncommon < age 50)
<ul>
<li>
In pts <age 50 think other types of neoplasm, pancreatitis, pseudocyst</li>
<li>
If actually ductal ca, think of genetic predisposition
<p>
</p>
</li>
</ul>
</li>
</ul>
<p>
What are know risk factors for pancreatic ca?</p>
<ul>
<li>
Cigarette smoking is the best-­established exogenous risk factor for pancreatic cancer
<ul>
<li>
but only RR = 2-3</li>
</ul>
</li>
<li>
Chronic pancreatitis
<ul>
<li>
RR = 10-15</li>
</ul>
</li>
<li>
DM Type 2
<ul>
<li>
RR = 2</li>
</ul>
</li>
<li>
Other genetic predisposition
<ul>
<li>
hereditary pancreatitis (RR= 50)</li>
<li>
hereditary cancer syndromes (most prev. = defective BRCA2)</li>
<li>
cystic fibrosis</li>
<li>
<strong>However, only 5-­10% of pancreatic cancers arise in individuals with known hereditary predisposition.</strong></li>
</ul>
</li>
</ul>
<p>
Describe the gross and pathological appearance of pancreatic ductal adenocarcinoma.</p>
<p>
GROSS:</p>
<ul>
<li>
gritty, hard, scirrhous (i.e. fibrous) gray-­white masses</li>
<li>
tend to be poorly circumscribed due to invasion of the adjacent pancreas or nearby tissues</li>
</ul>
<p>
HISTO:</p>
<ul>
<li>
Most mod-poorly differentiated, w/ variable degrees of gland formation and mucin production.</li>
<li>
Dense stromal fibrosis is characteristic which is why they are often called "scirrhous" or "desmoplastic carcinomas"</li>
<li>
perineural invasion within and beyond the pancreas. </li>
</ul>
<p>
How does one biopsy the pancrea?</p>
<p>
endoscopic ultrasound-­guided fine-­needle aspiration biopsy (EUS-­FNA)</p>
<p>
In which part of the pancreas to most ductal pancreatic carcinomas arise?</p>
<p>
Ductal adenocarcinomas typically arise in the <u>head</u> of the pancreas (3:1 over the body and tail). </p>
<p>
List 3 reasons why pancreatic ca is diagnosed so late?</p>
<ol>
<li>
No PSE, no “pancreas self examination”</li>
<li>
No PAP, no practical cytologic screening
<ul>
<li>
Specimens must be collected by ERCP (\$\$$)</li>
</ul>
</li>
<li>
No PSA, no “pancreas specific antigen”
<ul>
<li>
No sensitive and specific serum tumor marker</li>
</ul>
</li>
</ol>
<p>
List common types of mutations seen in panc ca</p>
<ul>
<li>
>90% - p16*</li>
<li>
75-90% - K-Ras**</li>
<li>
50-75% - p53*</li>
<li>
55% - DPC4*</li>
<li>
5% - BRCA2*</li>
</ul>
<p>
*inactivated tumor suppressor genes</p>
<p>
**activated proto-oncogene</p>
<p>Mechanism of K-ras mutation?</p>
<p>Mutations result in overactivity of GTP mediated signaling pathways with many downstream targets.</p>
<ul>
<li>Mutation of K-­ras is an initial/very early event found in intraductal precursor lesions (PanIN) and chronic pancreatitis.</li>
<li>NOT useful as a molecular assay for carcinoma, b/c not specific for malignant ∆. </li>
</ul>
<p>
Diagnostic options for pancreatic cancer? (from surgery lecture)</p>
<p>
Ultrasound<br></br>
—Accurate for detection of gallstones<br></br>
—Accurate for detection of biliary ductal dilation</p>
<p>
CT<br></br>
—Provides critical staging information</p>
<p>
ERCP (endoscopic retrograde cholangiopancreatography) and endoscopic ultrasound guided biopsy<br></br>
—Useful strategy for obtaining tissue for diagnosis<br></br>
—Provides palliative treatment options</p>
<p>
Serum tumor marker CA 19-9<br></br>
—Has prognostic utility pre-op, post-op and measuring response to systemic therapy</p>
