January+18+-+22

Lauren Morgan Function and Anatomy of Pancreas Changes in a Cancerous Pancreas

“By raising the liver, drawing down the stomach, and tearing through the gastro-hepatic omentum and the ascending layer of the transverse mesocolon.” -in front of the second lumbar vertebra -omentum is a large flap of peritoneum hanging from the stomach. -this is why the pancreas is so difficult to access for screening and surgery because it’s behind a plethora of digestive organs.
 * Location of the Pancreas **

Similar to salivary glands but softer—not as tough.

Pancreatic cancer usually affects the head or duodenal end of the pancreas. (Grey’s Anatomy textbook) Secreted Horomones—insulin, glucagon, somatostatin, gastrin, Vasoactive Intestinal Peptide. -endocrine pancreas islet cells are located close to blood vessels—good and bad. Tumors in pancreatic cancer have an easy source of nourishment from blood vessel but maybe this means it’s easier to pick up on pancreatic cancer in the blood stream? Just speculating.
 * Functions of the Pancreas **

-Produces pancreatic endocrine hormones and pancreatic digestive enzymes.

-Maintains sugar and salt balance in our bodies.

-The head of the pancreas is attached to the duodenum of the intestine where pancreatic digestive juices empty out.

-90% exocrine cells in the pancreas, 5% endocrine cells (approximately)

-Pancreatic islet cells are endocrine cells in the pancreas that produce the few hormones that the pancreas normally produces such as insulin. http://www.endocrineweb.com/pancreas.html “ Direct tests of pancreatic function using secretin or cholecystokinin are the most accurate for establishing the earliest physiologic changes of pancreatic insufficiency” One diagnostic test developed in a case study: a “ purely endoscopic pancreatic function test using synthetic porcine secretin or cholecystokinin” Basically, the synthetic porcine secretin (cholecystokinin) is used to sedate a patient undergoing an endoscopy screening for pancreatic cancer. I think this could be an integral part to our overall solution by incorporating this sedation method. I will check into costs of sedation, risks, and other details and present my findings next Tuesday (Jan 26). “ ” Two different types of pancreatic cancer, depending on what cells it affects. Exocrine secreting cells have one type of cancer (exocrine is for digestion purposes) and endocrine secreting cells have another type of cancer (much rarer, 5% of pancreas is made up of these cells. Secretes insulin and other homeostatic functions).
 * Testing of Pancreas, effects of sedation to make screening easier for both the patient and doctor **
 * Pancreatic Cancer **

Research the most common type of cancer: “ ductal adenocarcinomas.” More rare types of pancreatic cancer include “tumours, cancer of the acinar cells and sarcomas”

Endocrine cancers of the pancreas grow hormone producing tumors and can result in “gastrinomas, insulinomas, somatostatinomas, VIPomas and glucagonomas.” Generally called “neuroendocrine tumours.”

“Sarcomas of the pancreas: These are cancers of the connective tissue holding together the cells of the pancreas. They are very rare and most often occur in children.” http://www.cancerhelp.org.uk/type/pancreatic-cancer/about/the-pancreas

Changes in albumin, IgG and IgA concentrations were seen in patients with pancreatic cancer. [Sidenote: “refers generally to any protein with water solubility, which is moderately soluble in concentrated salt solutions, and experiences heat coagulation (protein denaturation),” “Immunoglobulin G (IgG) is a monomeric immunoglobulin, built of two heavy chains γ and two light chains.” IgG is a sign of the body’s matured immune response. IgG is an antibody. IgA is another antibody (from a mom’s breast milk for example) “Immunoglobin A is an antibody which plays a critical role in mucosal immunity. More IgA is produced in mucosal linings than all other types of antibody combined” which means IgA is prevalent in the GI tract (near the pancreas!!!!). **Information found from my Biology notes last semester. Quotes are supplements from wikipedia since the definitions are of universal knowledge.** Zymogen deficiency was also noted in pancreatic cancer patients, which is preventative of powerful GI enzymes digesting proteins inside the cell of which it was created.

“. The albumin level was over ten-fold greater than in Groups 1 and 3 (p < 0.02 and <0.05). The IgG was sevenfold and two-fold greater (p < 0.01 and >0.2) and the IgA was 15-fold and six-fold greater (p < 0.002 and <0.05) than in Groups 1 and 3, respectively.” (group 2 being the one with Pancreatic cancer)

“The sensitivity of ERCP radiographic findings in pancreatic cancer was 80%” –Should we look into this more heavily? Clinical and secretory differences in **//pancreatic// //cancer// **and chronic pancreatitis. ** Questions that I answered with this Research:
 * Where is the pancreas located, what type of organ is it? What are its basic functions and anatomy? Why is it so difficult to screen for pancreatic cancer? Do pancreas secretions give indication of when something is wrong with the pancreas, and if so, how? What are other signs of pancreatic cancer and how are they different from a functioning, healthy pancreas or one with pancreatitis?

Taylor Guffey SpyGlass Technology

SpyGlass-

- It is used for visual examination on bile ducts, tissue sampling, and therapeutic measures such as gall stone removal. - Before SpyGlass, many of these were impeded because of technological limitations, but with 4-way steering by one single operator, SpyGlass is revolutionizing cholangiopancreatoscopy -Case Study Results from 2 different clinics:** × **SpyGlass procedures were performed in 35 patients: 22 with indeterminat strictures (63%), 5 with indeterminate filling defects (14%), 5 with stones (14%), 2 with cystic lesions (6%), and 1 patient with an indication for gallbladder stent placement (3%). × The rate of procedural success was 91%** × **Twenty patients underwent SpyGlass-directed biopsy, and the specimens procured from 19 patients (95%) were found adequate for histological evaluation × The preliminary sensitivity and specificity of SpyGlass-directed biopsy to diagnose malignancy were 71% and 100%, respectively.

- Advantages: × In the diagnosis of malignant biliary strictures, the reported sensitivity of ERCP-directed forceps biopsy ranges widely, from 43% to 81%. × Under direct visualization, subtle tissue abnormalities, which might not be evident through use of other imaging modalities, can be discerned, when compared to other procedures such as CP and EUS. × CP requires the participation of 2 endoscopists, one to operate the duodenoscope and the other to operate the cholangioscope, whereas the SpyGlass only requires one operator.

-SpyGlass Components: × Reusable SpyGlass Direct Visualization Probe and Ocular for direct visual guidance and examination in the pancreaticobiliary system, including the hepatic ducts × SpyScope disposable access and delivery catheter capable of accommodating both optical and accessory devices used in the biliarysystem, including the hepatic ducts × Disposable SpyBite biopsy forceps for tissue acquisition in the pancreaticobiliary system

-Results:**

** || || ** || || ** || ||
 * |||| Final or provisional final diagnosis[|†]
 * Visual diagnosis || Benign || Malignant || Total ||
 * Benign || 10 || 0 || 10 ||
 * Malignant || 3 [|‡] || 7 || 10 ||
 * Total || 13 || 7 || 20 ||
 * Preliminary sensitivity of visual diagnosis = 100% (7/7) ||
 * Preliminary specificity of visual diagnosis = 77% (10/13) ||
 * |||| Final or provisional final diagnosis **[|**†**]
 * Biopsy diagnosis || Benign || Malignant || Total ||
 * Benign || 13 || 2[|§] || 15 ||
 * Malignant || 0 || 5 || 5 ||
 * Total || 13 || 7 || 20 ||
 * Preliminary sensitivity of biopsy diagnosis = 71% (5/7) ||
 * Preliminary specificity of biopsy diagnosis = 100% (13/13) ||
 * |||| Biopsy diagnosis
 * Visual diagnosis || Benign || Malignant || Total ||
 * Benign || 10 || 0 || 10 ||
 * Malignant || 5 || 5 || 10 ||
 * Total || 15 || 5 || 20 ||
 * Preliminary concordance between visual and biopsy diagnosis = 75% (15/20) ||

× **One false-negative result was obtained during a SpyGlass procedure in which the presphincteric location of the target lesion in the distal common bile duct created technical difficulties, especially after sphincterotomy, in maintaining the desired SpyScope position for biopsies. A second false-negative biopsy result was secured from a patient with confirmed unresectable pancreatic adenocarcinoma. × Biopsy specimens collected by forceps under SpyGlass guidance were adequate for histologic characterization in 95% of cases.

-Conclusions- × This single-arm feasibility study was not intended to assess the clinical value of the SpyGlass system as a substitute for or as an adjunct to alternative imaging and tissue sampling modalities such as EUS-FNA. Although the sensitivity of EUS-FNA in the evaluation of pancreatic masses has been consistently high (70%-93%, as elsewhere reviewed ranging from 25% to 85% in some reports. One suggested explanation has been the need during EUS-FNA puncture for a visible target mass that may be absent in the vicinity of biliary strictures × The required follow-up period of ≥6 months for establishing a provisional final diagnosis of benign was relatively short


 * Outlined from article:

Chen, Y. K. and D. K. Pleskow (2007). "SpyGlass single-operator peroral cholangiopancreatoscopy system for the diagnosis and therapy of bile-duct disorders: a clinical feasibility study (with video)." __Gastrointestinal Endoscopy__ **65**(6): 832-841.

@http://www.sciencedirect.com.www.library.gatech.edu:2048/science?_ob=ArticleURL&_udi=B6WFY-4NK347Y-H&_user=655052&_coverDate=05%2F31%2F2007&_fmt=full&_orig=search&_cdi=6807&view=c&_acct=C000034078&_version=1&_urlVersion=0&_userid=655052&md5=7cf42da0e33c03021969392352e12a8a&ref=full

Elizabeth Morris: // Is the abdominal mass a good means of detection? Explain the palpable exam. Why is pancreatic cancer so hard to spot? // o If pancreatic cancer is a suspect for the patient’s sickness the doctor will examine the skin and eyes for signs of jaundice. Then he or she will feel the abdomen to check for changes in the area near the pancreas, liver, and [|gallbladder]. The doctor also checks for [|ascites], an abnormal buildup of fluid in the abdomen.2 // In only 15-25% can the actual tumor mass of pancreatic be felt when examining the abdominal. // 1 Therefore this method of discovering the disease should be abolished because by the time it reaches that stage the patient dose not have time for a cure. o The main reason pancreatic cancer is so hard to spot is because this disease unlike many others has no real physical symptoms. The only symptoms pre- feeling or seeing the physical tumor may be jaundice, weakness, loss of appetite, pain in upper abdomen, weight loss, and vomiting,2 and unfortunately these symptoms occur after the disease has become metastatic. Another reason pancreatic cancer is so hard to spot is because the organ is buried deep inside the body between the stomach and the spine.

// Articles to Reference: // 1Safi, F, Schlossew,W, Falkenreck, S and Beger, H.G (1996) //Ca 19-9 serum course and prognosis of pancreatic cancer.// International Journal of Gastrointestinal Cancer. 20/3. 2NCI, comp. //What you need to know about Cancer of the Pancreas//. Bethesda, MD: National Cancer Institute, 2001. Print. // Using EUS (endoscopic ultrasound) as a way of detection. // o The procedure for EUS is as follows: a doctor puts an endoscope down a patient’s esophagus, through the stomach and into the first part of the small intestine. At the end of the endoscope is an ultrasound device. As soon as the doctor reaches the intestine he or she will slowly pull the endoscope from the intestine towards the stomach to showcase images of the pancreas and its surroundings. o Compared with CT scans EUS is a better way of detection because it can detect a lesion as small as 2 cm, assess the extent of the tumor and the invasion of surrounding areas, and biopsy the lesion. Standard CT images are often not optimal for diagnosing subtle abnormalities in the pancreas and other organs.1 EUS is an improvement of this technique. // However, the introduction of multidetector helical CT (MDHCT) has today revolutionized the field of pancreatic imaging and "has created a new dimension of temporal and spatial resolution" reaching a sensitivity of 97-100%. // 2  o Nevertheless, the EUS is still a great tool in detecting pancreatic cancer and as more research and development is conducted it could be the future of detecting pancreatic cancer earlier. o EUS is limited by its relatively low accuracy rate (70%) for differentiating between PC and localized pancreatitis. EUS will visualize masses of less than 1 cm but often will not be able to determine whether the mass is a cancerous. Fine needle aspiration done in conjunction with EUS may overcome this limitation.1 o In one comparative study of diagnostic methods, the sensitivities for tumors smaller than 3 cm, were 93% EUS, 67% MRI and 53% CT. This study did not include spiral CT, also called helical, which is more accurate than conventional CT.1 o Furthermore there is virtually no risks, when done in conjunction with [|FNA] there is a low risk of complication, 5 out of 124 patients 1.1%), all non-fatal complications: fever, pancreatic inflammation, perforation of duodenal or esophageal wall, hemorrhage of cystic tumor.1 // Articles to Reference: // 2JOP. Journal of the Pancreas - http://www.joplink.net - Vol. 8, No. 1 - January 2007. [ISSN 1590-8577] 1http://pathology.jhu.edu/pancreas/DiagTests.php?area=di  o The doctor may take samples of blood to check for abnormal levels of bilirubin and other substances. Bilirubin is a chemical that may reach high levels in patients with pancreatic cancer due to blockage of the common bile duct by a tumor. There are many other non-cancerous causes of an elevated bilirubin level, such as hepatitis, gallstones, or mononucleosis.

// Articles to Reference: // [|www.cancer.net]

// Additional Research: // v ** Cytokeratin 18 ** as a biological marker. // Cytokeratins have been extensively used as serum tumor markers for monitoring of disease progression in cancer patients. The source of cytokeratins in the circulation as well as the mechanisms of release from cells have long been unclear. Recent evidence suggests that cytokeratins present in the circulation of cancer patients are released from apoptotic or necrotic tumor cells. // // Articles to Reference: // British Journal of Cancer advance online publication, 5 January 2010; doi:10.1038/sj.bjc.6605494 [|www.bjcancer.com]. Stig Linder. (2007). Cytokeratin Markers Come of Age. //Tumor Biology,// //28//(4), 189-95. Retrieved January 21, 2010, from Research Library. (Document ID: 1333779461). Telomerase Outline **  -   Found within the eukaryotic cells  -   Prevents other forms of aberrant recombination (cancer is considered to be caused by an error in the DNA chain)  -   Detected within 85% - 90% of human tumors and tumor derived cell lines  -   Immortalizes cancer cells   -   Telomerase is an enzyme made within a eukaryotic body (not artificially from outside) <span style="mso-ascii-font-family: Calibri; mso-bidi-font-family: Calibri; mso-fareast-font-family: Calibri; mso-fareast-language: KO; mso-hansi-font-family: Calibri; msoasciifontfamily: Calibri; msobidifontfamily: Calibri; msofareastfontfamily: Calibri; msofareastlanguage: KO; msohansifontfamily: Calibri; msolist: Ignore;"> -  <span style="mso-fareast-font-family: '맑은 고딕'; mso-fareast-language: KO;"> It is a biomarker, just like MUC1, CA19-9, and other proteins that indicate cancer activity <span style="mso-ascii-font-family: Calibri; mso-bidi-font-family: Calibri; mso-fareast-font-family: Calibri; mso-fareast-language: KO; mso-hansi-font-family: Calibri; msoasciifontfamily: Calibri; msobidifontfamily: Calibri; msofareastfontfamily: Calibri; msofareastlanguage: KO; msohansifontfamily: Calibri; msolist: Ignore;"> -  <span style="mso-fareast-font-family: '맑은 고딕'; mso-fareast-language: KO;"> Researchers declare high concentration of telomerase activity of certain body part will indicate the cancer activity <span style="mso-ascii-font-family: Calibri; mso-bidi-font-family: Calibri; mso-fareast-font-family: Calibri; mso-fareast-language: KO; mso-hansi-font-family: Calibri; msoasciifontfamily: Calibri; msobidifontfamily: Calibri; msofareastfontfamily: Calibri; msofareastlanguage: KO; msohansifontfamily: Calibri; msolist: Ignore;"> -  <span style="mso-fareast-font-family: '맑은 고딕'; mso-fareast-language: KO;"> Researchers are now searching for indicators of telomerase activities: such as telomerase binding proteins <span style="mso-ascii-font-family: Calibri; mso-bidi-font-family: Calibri; mso-fareast-font-family: Calibri; mso-fareast-language: KO; mso-hansi-font-family: Calibri; msoasciifontfamily: Calibri; msobidifontfamily: Calibri; msofareastfontfamily: Calibri; msofareastlanguage: KO; msohansifontfamily: Calibri; msolist: Ignore;"> -  <span style="mso-fareast-font-family: '맑은 고딕'; mso-fareast-language: KO;"> Moreover, researchers suggest that if they are to find an activator of telomerase, they might be able to predict cancer activity within eukaryotic body by whether there is a significant amount of activators within eukaryotic bodily fluid
 * <span style="mso-fareast-font-family: '맑은 고딕'; mso-fareast-language: KO;"> Harry Han - Information about Telomerase
 * <span style="mso-fareast-font-family: '맑은 고딕'; mso-fareast-language: KO;"> Relation of Telomerase with Screening **