Exocrine Pancreatic Cancer

Overview

Classification

• 95% are from the exocrine pancreas Exocrine pancreas The major component (about 80%) of the pancreas composed of acinar functional units of tubular and spherical cells. The acinar cells synthesize and secrete several digestive enzymes such as trypsinogen; lipase; amylase; and ribonuclease. Secretion from the exocrine pancreas drains into the pancreatic ductal system and empties into the duodenum. Pancreas: Anatomy; most are invasive pancreatic ductal adenocarcinoma Pancreatic Ductal Adenocarcinoma Chronic Pancreatitis (PDACs):
  • Arise from ductal epithelial cells
  • Highest mortality Mortality All deaths reported in a given population. Measures of Health Status rate of any major cancer
  • 10%–15% are associated with hereditary syndromes.
• 1% of neoplasms Neoplasms New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms. Benign Bone Tumors from the exocrine pancreas Exocrine pancreas The major component (about 80%) of the pancreas composed of acinar functional units of tubular and spherical cells. The acinar cells synthesize and secrete several digestive enzymes such as trypsinogen; lipase; amylase; and ribonuclease. Secretion from the exocrine pancreas drains into the pancreatic ductal system and empties into the duodenum. Pancreas: Anatomy are acinar carcinomas:
  • Arise from the acinar cells Acinar cells Cells lining the saclike dilatations known as acini of various glands or the lungs. Gastrointestinal Secretions
  • Can produce tryptase and lipase Lipase An enzyme of the hydrolase class that catalyzes the reaction of triacylglycerol and water to yield diacylglycerol and a fatty acid anion. It is produced by glands on the tongue and by the pancreas and initiates the digestion of dietary fats. Malabsorption and Maldigestion → metastatic fat necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage
• Less than 1% of neoplasms Neoplasms New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms. Benign Bone Tumors from the exocrine pancreas Exocrine pancreas The major component (about 80%) of the pancreas composed of acinar functional units of tubular and spherical cells. The acinar cells synthesize and secrete several digestive enzymes such as trypsinogen; lipase; amylase; and ribonuclease. Secretion from the exocrine pancreas drains into the pancreatic ductal system and empties into the duodenum. Pancreas: Anatomy are pancreatoblastoma (malignant):
  • Mostly in children
  • Shows diverse tissue differentiation

Epidemiology

• 4th leading cause of cancer-related deaths in the United States
• Poor survival rate: Only 15%–20% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship are surgical candidates due to late presentation.
  • The 5-year survival rate is 30% if node negative.
  • The 5-year survival rate is 10% if node positive at the time of surgery.
• Incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency: 3.2% of all new cancer cases and 7.2% of all cancer deaths
• 11th leading cause of death worldwide
• Most common age group at diagnosis: 65–74 years
• Gender Gender Gender Dysphoria/ethnicity disparities: men > women; blacks > whites

Etiology

• Nonhereditary risk factors:
  • Smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases: greatest risk factor, causing 30% of cases
  • Older age: 70 years is the mean age at diagnosis.
  • Chronic pancreatitis Pancreatitis Inflammation of the pancreas. Pancreatitis is classified as acute unless there are computed tomographic or endoscopic retrograde cholangiopancreatographic findings of chronic pancreatitis. The two most common forms of acute pancreatitis are alcoholic pancreatitis and gallstone pancreatitis. Acute Pancreatitis
  • Diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus mellitus (PDAC can also cause diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus mellitus)
  • Obesity Obesity Obesity is a condition associated with excess body weight, specifically with the deposition of excessive adipose tissue. Obesity is considered a global epidemic. Major influences come from the western diet and sedentary lifestyles, but the exact mechanisms likely include a mixture of genetic and environmental factors. Obesity 
  • Physical inactivity
  • Diet:
    • Eating well-done barbecued meat
    • Drinking sugary carbonated beverages
  • Male gender Gender Gender Dysphoria
  • African heritage
  • Weak association between Helicobacter pylori Helicobacter pylori A spiral bacterium active as a human gastric pathogen. It is a gram-negative, urease-positive, curved or slightly spiral organism initially isolated in 1982 from patients with lesions of gastritis or peptic ulcers in Western Australia. Helicobacter pylori was originally classified in the genus campylobacter, but RNA sequencing, cellular fatty acid profiles, growth patterns, and other taxonomic characteristics indicate that the micro-organism should be included in the genus Helicobacter. It has been officially transferred to Helicobacter gen. Helicobacter infection and pancreatic cancer
• Decreased risk of PDAC: high intake of fruits and vegetables 
• Hereditary/genetic factors in 10%–15% of all pancreatic cancers: 

Precursors and Pathology

Precursors to PDAC

• Pancreatic intraepithelial neoplasia (PanIN) precede 90% of PDACs:
  • Telomere Telomere A terminal section of a chromosome which has a specialized structure and which is involved in chromosomal replication and stability. Its length is believed to be a few hundred base pairs. DNA Replication shortening occurs in cells of small ducts.
  • Mutations of the oncogene KRAS in > 90% accumulate and transition into invasive PDAC.
• Cystic Cystic Fibrocystic Change mucinous neoplasms Neoplasms New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms. Benign Bone Tumors:
  • 30% are associated with invasive PDAC.
  • 95% in woman
  • Found in the tail of the pancreas Pancreas The pancreas lies mostly posterior to the stomach and extends across the posterior abdominal wall from the duodenum on the right to the spleen on the left. This organ has both exocrine and endocrine tissue. Pancreas: Anatomy
  • Ovarian-type stroma
• Intraductal papillary mucinous neoplasms Neoplasms New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms. Benign Bone Tumors (IPMNs):
  • Involve mostly the larger main ducts of the head of the pancreas Pancreas The pancreas lies mostly posterior to the stomach and extends across the posterior abdominal wall from the duodenum on the right to the spleen on the left. This organ has both exocrine and endocrine tissue. Pancreas: Anatomy
  • Men > women
  • Multifocal Multifocal Retinoblastoma in 20%
  • GNAS proto-oncogene mutations in 75%

Pathology

• Site frequencies:
  • 60% head of the pancreas Pancreas The pancreas lies mostly posterior to the stomach and extends across the posterior abdominal wall from the duodenum on the right to the spleen on the left. This organ has both exocrine and endocrine tissue. Pancreas: Anatomy
  • 15% body
  • 5% tail
  • 20% entire pancreas Pancreas The pancreas lies mostly posterior to the stomach and extends across the posterior abdominal wall from the duodenum on the right to the spleen on the left. This organ has both exocrine and endocrine tissue. Pancreas: Anatomy
• Microscopic pathology: adenocarcinomas that recapitulate normal ductal epithelium Epithelium The epithelium is a complex of specialized cellular organizations arranged into sheets and lining cavities and covering the surfaces of the body. The cells exhibit polarity, having an apical and a basal pole. Structures important for the epithelial integrity and function involve the basement membrane, the semipermeable sheet on which the cells rest, and interdigitations, as well as cellular junctions. Surface Epithelium: Histology have extreme invasiveness into peripancreatic tissues and organs, the peritoneum Peritoneum The peritoneum is a serous membrane lining the abdominopelvic cavity. This lining is formed by connective tissue and originates from the mesoderm. The membrane lines both the abdominal walls (as parietal peritoneum) and all of the visceral organs (as visceral peritoneum). Peritoneum: Anatomy, perineural spaces, and blood vessels.
• Gross pathology:
  • Adenocarcinomas have the ability to provoke an intense fibrous Fibrous Fibrocystic Change (desmoplastic) response.
  • Hard, stellate, gray-white, poorly defined masses
  • If in the head of the pancreas Pancreas The pancreas lies mostly posterior to the stomach and extends across the posterior abdominal wall from the duodenum on the right to the spleen on the left. This organ has both exocrine and endocrine tissue. Pancreas: Anatomy: 50% will obstruct the distal common bile Bile An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum. Gallbladder and Biliary Tract: Anatomy duct → painful obstructive jaundice Obstructive jaundice Hepatocellular Carcinoma (HCC) and Liver Metastases
• Metastases:
  • Lymph nodes Lymph Nodes They are oval or bean shaped bodies (1 – 30 mm in diameter) located along the lymphatic system. Lymphatic Drainage System: Anatomy
  • Liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy
  • Lungs Lungs Lungs are the main organs of the respiratory system. Lungs are paired viscera located in the thoracic cavity and are composed of spongy tissue. The primary function of the lungs is to oxygenate blood and eliminate CO2. Lungs: Anatomy

Clinical Presentation

Pancreatic cancer is usually discovered late because of the retroperitoneal Retroperitoneal Peritoneum: Anatomy position of the pancreas Pancreas The pancreas lies mostly posterior to the stomach and extends across the posterior abdominal wall from the duodenum on the right to the spleen on the left. This organ has both exocrine and endocrine tissue. Pancreas: Anatomy.

• If cancer is in the pancreatic head, it can cause:
  • Painless obstructive jaundice Obstructive jaundice Hepatocellular Carcinoma (HCC) and Liver Metastases:
    • Due to obstruction of common bile Bile An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum. Gallbladder and Biliary Tract: Anatomy duct
    • Associated with pruritus Pruritus An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. Atopic Dermatitis (Eczema) and light-colored stools
  • Courvoisier sign: enlarged, palpable, nontender gallbladder Gallbladder The gallbladder is a pear-shaped sac, located directly beneath the liver, that sits on top of the superior part of the duodenum. The primary functions of the gallbladder include concentrating and storing up to 50 mL of bile. Gallbladder and Biliary Tract: Anatomy
• If cancer is in the body and tail, it can cause splenic vein obstruction, leading to:
  • Splenomegaly Splenomegaly Splenomegaly is pathologic enlargement of the spleen that is attributable to numerous causes, including infections, hemoglobinopathies, infiltrative processes, and outflow obstruction of the portal vein. Splenomegaly
  • Gastric and esophageal varices due to left portal hypertension Portal hypertension Portal hypertension is increased pressure in the portal venous system. This increased pressure can lead to splanchnic vasodilation, collateral blood flow through portosystemic anastomoses, and increased hydrostatic pressure. There are a number of etiologies, including cirrhosis, right-sided congestive heart failure, schistosomiasis, portal vein thrombosis, hepatitis, and Budd-Chiari syndrome. Portal Hypertension
  • GI hemorrhage
• Pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways:
  • Severe
  • In upper abdomen with radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma to the back
  • Late symptom
• Hypercoagulable Hypercoagulable Hypercoagulable states (also referred to as thrombophilias) are a group of hematologic diseases defined by an increased risk of clot formation (i.e., thrombosis) due to either an increase in procoagulants, a decrease in anticoagulants, or a decrease in fibrinolysis. Hypercoagulable States state:
  • 30%–50% PDACs, compared to 10% for all cancers, due to:
    • Platelet-activating factors
    • Procoagulants from the carcinoma 
    • Necrotic products
  • May cause migratory superficial thrombophlebitis (Trousseau syndrome of malignancy Malignancy Hemothorax = cancer-associated hypercoagulation disorder)
  • May also cause deep vein thrombosis Thrombosis Formation and development of a thrombus or blood clot in the blood vessel. Epidemic Typhus ( DVT DVT Deep vein thrombosis (DVT) usually occurs in the deep veins of the lower extremities. The affected veins include the femoral, popliteal, iliofemoral, and pelvic veins. Proximal DVT is more likely to cause a pulmonary embolism (PE) and is generally considered more serious. Deep Vein Thrombosis) → pulmonary emboli (frequent cause of death)
• Symptoms of advanced disease:
  • Weight loss Weight loss Decrease in existing body weight. Bariatric Surgery
  • Anorexia Anorexia The lack or loss of appetite accompanied by an aversion to food and the inability to eat. It is the defining characteristic of the disorder anorexia nervosa. Anorexia Nervosa
  • Generalized malaise Malaise Tick-borne Encephalitis Virus
  • Pancreatogenic diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus mellitus 
  • Malabsorption Malabsorption General term for a group of malnutrition syndromes caused by failure of normal intestinal absorption of nutrients. Malabsorption and Maldigestion: due to pancreatic exocrine insufficiency → bloating Bloating Constipation, gas, greasy stools
  • Virchow’s node: palpable supraclavicular lymph Lymph The interstitial fluid that is in the lymphatic system. Secondary Lymphatic Organs node (usually on the left side)
  • Sister Mary Joseph’s nodule Nodule Chalazion: periumbilical subcutaneous metastatic nodule Nodule Chalazion

Diagnosis

Imaging and biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma are indicated for patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with suspected PDAC ( pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways, weight loss Weight loss Decrease in existing body weight. Bariatric Surgery, jaundice Jaundice Jaundice is the abnormal yellowing of the skin and/or sclera caused by the accumulation of bilirubin. Hyperbilirubinemia is caused by either an increase in bilirubin production or a decrease in the hepatic uptake, conjugation, or excretion of bilirubin. Jaundice).

• Imaging: multiphasic CT with pancreatic cancer protocol
  • If a mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast lesion is found in the pancreas Pancreas The pancreas lies mostly posterior to the stomach and extends across the posterior abdominal wall from the duodenum on the right to the spleen on the left. This organ has both exocrine and endocrine tissue. Pancreas: Anatomy → evaluate for metastatic disease using PET PET An imaging technique that combines a positron-emission tomography (PET) scanner and a ct X ray scanner. This establishes a precise anatomic localization in the same session. Nuclear Imaging scanning and/or multiphase CT Multiphase CT Computed Tomography (CT) scan of chest and pelvis Pelvis The pelvis consists of the bony pelvic girdle, the muscular and ligamentous pelvic floor, and the pelvic cavity, which contains viscera, vessels, and multiple nerves and muscles. The pelvic girdle, composed of 2 “hip” bones and the sacrum, is a ring-like bony structure of the axial skeleton that links the vertebral column with the lower extremities. Pelvis: Anatomy.
  • If no mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast lesion and no metastatic disease identified → perform endoscopic retrograde cholangiopancreatography Endoscopic Retrograde Cholangiopancreatography Fiberoptic endoscopy designed for duodenal observation and cannulation of Vater’s ampulla, in order to visualize the pancreatic and biliary duct system by retrograde injection of contrast media. Endoscopic (Vater) papillotomy may be performed during this procedure. Primary Sclerosing Cholangitis ( ERCP ERCP Fiberoptic endoscopy designed for duodenal observation and cannulation of vater’s ampulla, in order to visualize the pancreatic and biliary duct system by retrograde injection of contrast media. Endoscopic (vater) papillotomy may be performed during this procedure. Primary Sclerosing Cholangitis) or MRCP MRCP Non-invasive diagnostic technique for visualizing the pancreatic ducts and bile ducts without the use of injected contrast media or x-ray. Mri scans provide excellent sensitivity for duct dilatation, biliary stricture, and intraductal abnormalities. Primary Sclerosing Cholangitis:
    • If mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast or bile Bile An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum. Gallbladder and Biliary Tract: Anatomy duct stricture Stricture Primary Sclerosing Cholangitis is seen → biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma
    • If no lesion is identified → follow clinically
• Biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma:
  • Histologic diagnosis is needed for molecular testing to guide therapy.
  • Core needle biopsies of a tumor Tumor Inflammation in the pancreas Pancreas The pancreas lies mostly posterior to the stomach and extends across the posterior abdominal wall from the duodenum on the right to the spleen on the left. This organ has both exocrine and endocrine tissue. Pancreas: Anatomy can be performed:
    • By EUS
    • By biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma of tumor Tumor Inflammation in the lymph Lymph The interstitial fluid that is in the lymphatic system. Secondary Lymphatic Organs node, liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy, or other metastatic site
  • Serum tumor Tumor Inflammation markers are for following patient progress, not screening Screening Preoperative Care, except for those with hereditary risk:
    • CA19-9 CA19-9 Sialylated lewis(a) blood group carbohydrate antigen found in many adenocarcinomas of the digestive tract, especially pancreatic tumors. Serum Tumor Markers
    • CEA CEA A glycoprotein that is secreted into the luminal surface of the epithelia in the gastrointestinal tract. It is found in the feces and pancreaticobiliary secretions and is used to monitor the response to colon cancer treatment. Serum Tumor Markers
    • CA CA Condylomata acuminata are a clinical manifestation of genital HPV infection. Condylomata acuminata are described as raised, pearly, flesh-colored, papular, cauliflower-like lesions seen in the anogenital region that may cause itching, pain, or bleeding. Condylomata Acuminata (Genital Warts) 125
• Clinical staging Staging Methods which attempt to express in replicable terms the extent of the neoplasm in the patient. Grading, Staging, and Metastasis:
  • TNM system TNM system Grading, Staging, and Metastasis by the American Joint Commission on Cancer
  • Laparoscopy Laparoscopy Laparoscopy is surgical exploration and interventions performed through small incisions with a camera and long instruments. Laparotomy and Laparoscopy is advised by some physicians Physicians Individuals licensed to practice medicine. Clinician–Patient Relationship before definitive surgery to directly rule out metastatic disease.

Management and Prognosis

Approximately 80%–85% of PDAC tumors are not resectable at the time of presentation.

• Overall 5-year survival rate: 8%–10%
• Surgically resectable disease: no invasion of vessels or metastatic disease
  • About 15%–20% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship diagnosed with PDAC are candidates for surgery.
  • Procedure depends on location:
    • If head or uncinate process → pylorus-sparing pancreaticoduodenectomy (also called the Whipple procedure)
    • If body or tail → distal pancreatectomy
  • Neoadjuvant or adjuvant Adjuvant Substances that augment, stimulate, activate, potentiate, or modulate the immune response at either the cellular or humoral level. The classical agents (freund’s adjuvant, bcg, corynebacterium parvum, et al.) contain bacterial antigens. Some are endogenous (e.g., histamine, interferon, transfer factor, tuftsin, interleukin-1). Their mode of action is either non-specific, resulting in increased immune responsiveness to a wide variety of antigens, or antigen-specific, i.e., affecting a restricted type of immune response to a narrow group of antigens. The therapeutic efficacy of many biological response modifiers is related to their antigen-specific immunoadjuvanticity. Vaccination chemotherapy Chemotherapy Osteosarcoma 
  • Median survival: 18–23 months
• Locally advanced disease: vessels involved but no distant metastases
  • Chemotherapy Chemotherapy Osteosarcoma alone or chemoradiotherapy
  • Median survival: 6–10 months
• Distant metastatic disease:
  • Systemic chemotherapy Chemotherapy Osteosarcoma
  • Median survival: 8–13 months
• Chemotherapeutic agents and other potential factors influencing survival:
  • Response rates are generally < 20%.
  • 1st-line therapy: FOLFIRINOX (leucovorin, fluorouracil Fluorouracil A pyrimidine analog that is an antineoplastic antimetabolite. It interferes with DNA synthesis by blocking the thymidylate synthetase conversion of deoxyuridylic acid to thymidylic acid. Bowen Disease and Erythroplasia of Queyrat, irinotecan Irinotecan A semisynthetic camptothecin derivative that inhibits DNA topoisomerase I to prevent nucleic acid synthesis during s phase. It is used as an antineoplastic agent for the treatment of colorectal neoplasms and pancreatic neoplasms. Microtubule and Topoisomerase Inhibitors, and oxaliplatin Oxaliplatin An organoplatinum complex in which the platinum atom is complexed with 1, 2-diaminocyclohexane, and with an oxalate ligand which is displaced to yield active oxaliplatin derivatives. These derivatives form inter- and intra-strand DNA crosslinks that inhibit DNA replication and transcription. Oxaliplatin is an antineoplastic agent that is often administered with fluorouracil and folinic acid in the treatment of metastatic colorectal neoplasms. Alkylating Agents and Platinum)
  • The most active single agents: gemcitabine Gemcitabine Antimetabolite Chemotherapy and 5-fluorouracil 5-Fluorouracil A pyrimidine analog that is an antineoplastic antimetabolite. It interferes with DNA synthesis by blocking the thymidylate synthetase conversion of deoxyuridylic acid to thymidylic acid. Antimetabolite Chemotherapy
  • Molecular testing to detect actionable genomic alterations is needed to enter into clinical trials of targeted therapies:
    • Microsatellite instability Microsatellite instability The occurrence of highly polymorphic mono- and dinucleotide microsatellite repeats in somatic cells. It is a form of genome instability associated with defects in DNA mismatch repair. Colorectal Cancer/ mismatch repair Mismatch repair A DNA repair pathway involved in correction of errors introduced during DNA replication when an incorrect base, which cannot form hydrogen bonds with the corresponding base in the parent strand, is incorporated into the daughter strand. Exonucleases recognize the base pair mismatch and cause a segment of polynucleotide chain to be excised from the daughter strand, thereby removing the mismatched base. Lynch syndrome deficiency
    • BRCA mutations
    • NTRK gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics fusions 
• Palliative care for unresectable disease:
  • If jaundiced and life expectancy Life expectancy Based on known statistical data, the number of years which any person of a given age may reasonably expected to live. Population Pyramids is > 6–7 months:
    • Endoscopic placement of a bile Bile An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum. Gallbladder and Biliary Tract: Anatomy duct stent
    • Possible surgical bypass because of complications associated with stents
  • Pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways control:
    • Analgesics, usually opioids Opioids Opiates are drugs that are derived from the sap of the opium poppy. Opiates have been used since antiquity for the relief of acute severe pain. Opioids are synthetic opiates with properties that are substantially similar to those of opiates. Opioid Analgesics
    • Splanchnic (celiac) block if necessary
  • Pruritus Pruritus An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. Atopic Dermatitis (Eczema) not relieved by stent or bypass: oral cholestyramine Cholestyramine A strongly basic anion exchange resin whose main constituent is polystyrene trimethylbenzylammonium cl(-) anion. Lipid Control Drugs 
  • Pancreatic enzyme supplementation: as needed if there is exocrine insufficiency
  • Diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus mellitus: treat to control hyperglycemia Hyperglycemia Abnormally high blood glucose level. Diabetes Mellitus
  • Prevention in those with hereditary types of PDAC:
    • Annual surveillance Surveillance Developmental Milestones and Normal Growth by abdominal ultrasound or MRI
    • CA19-9 CA19-9 Sialylated lewis(a) blood group carbohydrate antigen found in many adenocarcinomas of the digestive tract, especially pancreatic tumors. Serum Tumor Markers serum levels

Differential Diagnosis

• Acinar cell carcinoma: a rare primary malignant exocrine gland tumor Tumor Inflammation that produces exocrine enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body’s constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes such as trypsin Trypsin A serine endopeptidase that is formed from trypsinogen in the pancreas. It is converted into its active form by enteropeptidase in the small intestine. It catalyzes hydrolysis of the carboxyl group of either arginine or lysine. Proteins and Peptides and lipase Lipase An enzyme of the hydrolase class that catalyzes the reaction of triacylglycerol and water to yield diacylglycerol and a fatty acid anion. It is produced by glands on the tongue and by the pancreas and initiates the digestion of dietary fats. Malabsorption and Maldigestion. The enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body’s constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes can cause a metastatic fat necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage syndrome due to lipase Lipase An enzyme of the hydrolase class that catalyzes the reaction of triacylglycerol and water to yield diacylglycerol and a fatty acid anion. It is produced by glands on the tongue and by the pancreas and initiates the digestion of dietary fats. Malabsorption and Maldigestion release in the circulation Circulation The movement of the blood as it is pumped through the cardiovascular system. ABCDE Assessment. Such malignancies can occur in children, and there is a better prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas than with PDAC.
• Pancreatoblastoma: a rare primary malignant exocrine gland tumor Tumor Inflammation seen mostly in children. The histology shows multiple lines of differentiation (acinar, ductal, mesenchymal, neuroendocrine) and squamoid nests mixed with acinar cells Acinar cells Cells lining the saclike dilatations known as acini of various glands or the lungs. Gastrointestinal Secretions. The prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas is relatively good.
• Pancreatic neuroendocrine tumors Neuroendocrine tumors Tumors whose cells possess secretory granules and originate from the neuroectoderm, i.e., the cells of the ectoblast or epiblast that program the neuroendocrine system. Common properties across most neuroendocrine tumors include ectopic hormone production (often via apud cells), the presence of tumor-associated antigens, and isozyme composition. Gastrinoma ( PanNETs PanNETs Pancreatic neuroendocrine tumors (PanNETs) arise from the endocrine pancreas (islet cells) and represent 2%-5% of primary pancreatic neoplasms; the other 95%-98% of pancreatic neoplasms are from the exocrine pancreas. The majority of PanNETs are nonfunctional (50%-75%), while others that are functional may be benign or malignant. Pancreatic Neuroendocrine Tumors (PanNETs), islet cell Islet cell Pancreatic Neuroendocrine Tumors (PanNETs) tumors): arise from the endocrine pancreas Endocrine pancreas Pancreas: Anatomy. Pancreatic neuroendocrine tumors Neuroendocrine tumors Tumors whose cells possess secretory granules and originate from the neuroectoderm, i.e., the cells of the ectoblast or epiblast that program the neuroendocrine system. Common properties across most neuroendocrine tumors include ectopic hormone production (often via apud cells), the presence of tumor-associated antigens, and isozyme composition. Gastrinoma comprise 2% of all pancreatic neoplasms Neoplasms New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms. Benign Bone Tumors and resemble neuroendocrine tumors Neuroendocrine tumors Tumors whose cells possess secretory granules and originate from the neuroectoderm, i.e., the cells of the ectoblast or epiblast that program the neuroendocrine system. Common properties across most neuroendocrine tumors include ectopic hormone production (often via apud cells), the presence of tumor-associated antigens, and isozyme composition. Gastrinoma elsewhere in the alimentary tract. The tumors may be single or multiple and benign Benign Fibroadenoma or malignant, may produce pancreatic hormones Hormones Hormones are messenger molecules that are synthesized in one part of the body and move through the bloodstream to exert specific regulatory effects on another part of the body. Hormones play critical roles in coordinating cellular activities throughout the body in response to the constant changes in both the internal and external environments. Hormones: Overview and Types (e.g., insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin, glucagon Glucagon A 29-amino acid pancreatic peptide derived from proglucagon which is also the precursor of intestinal glucagon-like peptides. Glucagon is secreted by pancreatic alpha cells and plays an important role in regulation of blood glucose concentration, ketone metabolism, and several other biochemical and physiological processes. Gastrointestinal Secretions, gastrin Gastrin A family of gastrointestinal peptide hormones that excite the secretion of gastric juice. They may also occur in the central nervous system where they are presumed to be neurotransmitters. Gastrointestinal Secretions, others), or be nonfunctional.
• Painful obstructive jaundice Obstructive jaundice Hepatocellular Carcinoma (HCC) and Liver Metastases: usually related to gallstones Gallstones Cholelithiasis (gallstones) is the presence of stones in the gallbladder. Most gallstones are cholesterol stones, while the rest are composed of bilirubin (pigment stones) and other mixed components. Patients are commonly asymptomatic but may present with biliary colic (intermittent pain in the right upper quadrant). Cholelithiasis with bile Bile An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum. Gallbladder and Biliary Tract: Anatomy duct infection and fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, while painless obstructive jaundice Obstructive jaundice Hepatocellular Carcinoma (HCC) and Liver Metastases tends to be related to a tumor Tumor Inflammation in the head of the pancreas Pancreas The pancreas lies mostly posterior to the stomach and extends across the posterior abdominal wall from the duodenum on the right to the spleen on the left. This organ has both exocrine and endocrine tissue. Pancreas: Anatomy, at least early in its course. 
• Chronic pancreatitis Pancreatitis Inflammation of the pancreas. Pancreatitis is classified as acute unless there are computed tomographic or endoscopic retrograde cholangiopancreatographic findings of chronic pancreatitis. The two most common forms of acute pancreatitis are alcoholic pancreatitis and gallstone pancreatitis. Acute Pancreatitis: can present with similar symptoms as PDAC, although PDAC can be associated with pancreatitis Pancreatitis Inflammation of the pancreas. Pancreatitis is classified as acute unless there are computed tomographic or endoscopic retrograde cholangiopancreatographic findings of chronic pancreatitis. The two most common forms of acute pancreatitis are alcoholic pancreatitis and gallstone pancreatitis. Acute Pancreatitis. Clinicoradiologic findings aid in the diagnosis, but EUS with core needle biopsy Core Needle Biopsy Fibrocystic Change may be necessary.
• Metastases to the pancreas Pancreas The pancreas lies mostly posterior to the stomach and extends across the posterior abdominal wall from the duodenum on the right to the spleen on the left. This organ has both exocrine and endocrine tissue. Pancreas: Anatomy: can present with similar clinical and radiographic features as pancreatic cancer. Metastases are usually multiple throughout the body, and the primary site is usually known or due to primary lung cancer Lung cancer Lung cancer is the malignant transformation of lung tissue and the leading cause of cancer-related deaths. The majority of cases are associated with long-term smoking. The disease is generally classified histologically as either small cell lung cancer or non-small cell lung cancer. Symptoms include cough, dyspnea, weight loss, and chest discomfort. Lung Cancer. If the diagnosis is uncertain, an EUS with biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma may be required.
• Congenital Congenital Chorioretinitis cyst: unilocular, thin-walled cyst due to anomalous pancreatic duct development. Sizes ranges from microscopic to 5 cm. Congenital Congenital Chorioretinitis cysts Cysts Any fluid-filled closed cavity or sac that is lined by an epithelium. Cysts can be of normal, abnormal, non-neoplastic, or neoplastic tissues. Fibrocystic Change are lined with cuboidal or flattened epithelium Epithelium The epithelium is a complex of specialized cellular organizations arranged into sheets and lining cavities and covering the surfaces of the body. The cells exhibit polarity, having an apical and a basal pole. Structures important for the epithelial integrity and function involve the basement membrane, the semipermeable sheet on which the cells rest, and interdigitations, as well as cellular junctions. Surface Epithelium: Histology and filled with clear serous fluid. The cysts Cysts Any fluid-filled closed cavity or sac that is lined by an epithelium. Cysts can be of normal, abnormal, non-neoplastic, or neoplastic tissues. Fibrocystic Change may be sporadic Sporadic Selective IgA Deficiency or part of inherited conditions such as autosomal-dominant polycystic kidney disease (PKD) and Von Hippel–Lindau disease (VHL).
• Neoplastic pancreatic cyst: an epithelium-lined cyst that is filled with serous or mucinous fluid and can mimic PDAC. Thirty percent of mucinous cysts Cysts Any fluid-filled closed cavity or sac that is lined by an epithelium. Cysts can be of normal, abnormal, non-neoplastic, or neoplastic tissues. Fibrocystic Change are associated with PDAC. Diagnosis is made by endoscopic ultrasound with fine-needle aspiration.