The head, body, and tail of the pancreas: The stomach is faded out in this image to show the entire pancreas, of which the body and tail lie behind the stomach, and the neck partially behind. Axial CT image with IV contrast and added color: Cross lines towards top left surround a macrocystic adenocarcinoma of the<unk>  head. Abdominal ultrasonography of<unk>  (presumably adenocarcinoma), with a dilated<unk>  duct to the right. The symptoms of<unk>  adenocarcinoma do not usually appear in the disease's early stages, and they are not individually distinctive to the disease. The symptoms at diagnosis vary according to the location of the cancer in the pancreas, which anatomists divide (from left to right on most diagrams) into the thick head, the neck, and the tapering body, ending in the tail. Regardless of a tumor's location, the most common symptom is unexplained weight loss, which may be considerable. A large minority (between 35% and 47%) of people diagnosed with the disease will have had nausea, vomiting, or a feeling of weakness. Tumors in the head of the pancreas typically also cause jaundice, pain, loss of appetite, dark urine, and light-colored stools. Tumors in the body and tail typically also cause pain. People sometimes have recent onset of atypical type 2 diabetes that is difficult to control, a history of recent but unexplained blood vessel inflammation caused by blood clots (thrombophlebitis) known as Trousseau sign, or a previous attack of<unk> is. A doctor may suspect<unk>  when the onset of diabetes in someone over 50 years old is accompanied by typical symptoms such as unexplained weight loss, persistent abdominal or back pain, indigestion, vomiting, or fatty feces. Jaundice accompanied by a painlessly swollen gallbladder (known as Courvoisier's sign) may also raise suspicion, and can help differentiate<unk>  from gallstones. Medical imaging techniques, such as computed tomography (CT scan) and endoscopic ultrasound (EUS) are used both to confirm the diagnosis and to help decide whether the tumor can be surgically removed (its "resectability"). On contrast CT scan,<unk>  typically shows a gradually increasing radiocontrast uptake, rather than a fast washout as seen in a normal pancreas or a delayed washout as seen in chronic<unk> is. Magnetic resonance imaging and positron emission tomography may also be used, and magnetic resonance cholangiopancreatography may be useful in some cases. Abdominal ultrasound is less sensitive and will miss small tumors, but can identify cancers that have spread to the liver and build-up of fluid in the peritoneal cavity (ascites). It may be used for a quick and cheap first examination before other techniques. Fine needle aspiration of well-differentiated<unk>  adenocarcinoma, showing a flat sheet with prominent honeycombing. The disorganization, nuclear overlapping, and lack of uniform nuclear spacing provides a clue that is this adenocarcinoma (as opposed to non-neoplastic duct epithelium). A biopsy by fine needle aspiration, often guided by endoscopic ultrasound, may be used where there is uncertainty over the diagnosis, but a histologic diagnosis is not usually required for removal of the tumor by surgery to go ahead. Liver function tests can show a combination of results indicative of bile duct obstruction (raised conjugated bilirubin, γ-glutamyl transpeptidase and alkaline phosphatase levels). CA19-9 (carbohydrate antigen 19.9) is a tumor marker that is frequently elevated in<unk> . However, it lacks sensitivity and specificity, not least because 5% of people lack the Lewis (a) antigen and cannot produce CA19-9. It has a sensitivity of 80% and specificity of 73% in detecting<unk>  adenocarcinoma, and is used for following known cases rather than diagnosis. Histopathology The most common form of<unk>  (adenocarcinoma) is typically characterized by moderately to poorly differentiated glandular structures on microscopic examination. There is typically considerable desmoplasia or formation of a dense fibrous stroma or structural tissue consisting of a range of cell types (including myofibroblasts, macrophages, lymphocytes and mast cells) and deposited material (such as type I collagen and hyaluronic acid). This creates a tumor microenvironment that is short of blood vessels (hypovascular) and so of oxygen (tumor hypoxia). It is thought that this prevents many chemotherapy drugs from reaching the tumor, as one factor making the cancer especially hard to treat. Cancer type Relative incidence Microscopy findings Micrograph Immunohistochemistry markers Genetic alterations<unk>  ductal adenocarcinoma (PDAC) 90% Glands and desmoplasia 190px *Aberrant p53 *SMAD4 loss *MUC1 *MSLN *CA19-9 *p53 *SMAD4 *KRAS *p16<unk>  acinar cell carcinoma (ACC) 1% to 2% Granular appearance 190px *Trypsin *Chymotrypsin *Lipase *p53 *SMAD4 *APC *ARID1A *GNAS Adenosquamous carcinoma 1% to 4% Combination of gland-like cells and squamous epithelial cells. 190px Positive for: *CK5/6 *CK7 *p63 Negative for: *CK20 *p16 *p53 *KRAS *p53<unk>  neuroendocrine tumor 5% Multiple nests of tumor cells center Gastrinoma *Chromogranin *Synaptophysin *MEN1 *DAXX/ATRX Pre-cancer below for comparison: Precancer:Intraductal papillary mucinous neoplasm (IPMN) 3% Mucinous epithelial cells. Growth within the<unk>  ducts. 190px *Mucin 5AC *KRAS *GNAS Staging Exocrine cancers<unk>  is usually staged following a CT scan. The most widely used cancer staging system for<unk>  is the one formulated by the American Joint Committee on Cancer (AJCC) together with the Union for International Cancer Control (UICC). The AJCC-UICC staging system designates four main overall stages, ranging from early to advanced disease, based on TNM classification of Tumor size, spread to lymph Nodes, and Metastasis. To help decide treatment, the tumors are also divided into three broader categories based on whether surgical removal seems possible: in this way, tumors are judged to be "resectable", "borderline resectable", or "unresectable". When the disease is still in an early stage (AJCC-UICC stages I and II), without spread to large blood vessels or distant organs such as the liver or lungs, surgical resection of the tumor can normally be performed, if the patient is willing to undergo this major operation and is thought to be sufficiently fit. The AJCC-UICC staging system allows distinction between stage III tumors that are judged to be "borderline resectable" (where surgery is technically feasible because the celiac axis and superior mesenteric artery are still free) and those that are "unresectable" (due to more locally advanced disease); in terms of the more detailed TNM classification, these two groups correspond to T3 and T4 respectively. File:Diagram showing stage T1 cancer of the pancreas CRUK 246.Stage T1<unk>  File:Diagram showing stage T2 cancer of the pancreas CRUK 254.Stage T2<unk>  File:Diagram showing stage T3 cancer of the pancreas CRUK 261.Stage T3<unk>  File:Diagram showing stage T4 cancer of the pancreas CRUK 267.Stage T4<unk>  File:Diagram showing<unk>  in the lymph nodes (N staging) CRUK 178.Pancreatic cancer in nearby lymph nodes – Stage N1<unk>  metastasized – stage M1 Locally advanced adenocarcinomas have spread into neighboring organs, which may be any of the following (in roughly decreasing order of frequency): the duodenum, stomach, transverse colon, spleen, adrenal gland, or kidney. Very often they also spread to the important blood or lymphatic vessels and nerves that run close to the pancreas, making surgery far more difficult. Typical sites for metastatic spread (stage IV disease) are the liver, peritoneal cavity and lungs, all of which occur in 50% or more of fully advanced cases. PanNETs The 2010 WHO classification of tumors of the digestive system grades all the<unk>  neuroendocrine tumors (PanNETs) into three categories, based on their degree of cellular differentiation (from "NET G1" through to the poorly differentiated "NET G3"). The U.S. National Comprehensive Cancer Network recommends use of the same AJCC-UICC staging system as<unk>  adenocarcinoma. Using this scheme, the stage-by-stage outcomes for PanNETs are dissimilar to those of the exocrine cancers. A different TNM system for PanNETs has been proposed by the European Neuroendocrine Tumor Society.
Pancreatic cancer
Autoimmune pancreatitis
Liver cancer
Duodenal cancer
Gallbladder cancer
Periampullary cancer
Kang cancer
Small intestine cancer