Pancreatic Cancer Advances in Treatment Assignment

QUICK LESSON Pancreatic Cancer Description/Etiology Pancreatic cancer (PC) is difficult to diagnose in its early stages and is almost always fatal. The characteristics and clinical manifestations of PC depend on whether the tumor is located in the head, body, or tail of the pancreas, and if exocrine or endocrine gland tissue is involved. Exocrine cells and ducts compose most of the pancreas, producing digestive enzymes and carrying them to the small intestine. Exocrine PC is the most common type of PC, accounting for 95% of PC cases, with adenocarcinoma representing 95% of exocrine tumors. Endocrine cells represent a very small portion of the pancreas, are grouped in clusters called islets, and release the hormones insulin and glucagon into the blood. Endocrine tumors are uncommon, are classified as functioning (i.e., producing hormones [e.g., insulin, glucagon]) and nonfunctioning, and have a much better prognosis than pancreatic adenocarcinoma. The exact etiology of most cases of PC is unknown, but some are believed to result at least in part from inherited or acquired genetic mutations. Patients with PC often already have metastatic disease at the time of diagnosis, not only because malignant cells travel easily throughout the peritoneal cavity, but because the initial clinical manifestations of PC are nonspecific and diagnosis is often delayed. There is no effective screening test for PC. PC usually first metastasizes to the regional lymph nodes, then to the liver and, on occasion, to the lungs. PC can also directly invade surrounding organs (e.g., duodenum, stomach, colon) and metastasize to any surface in the abdominal cavity via peritoneal spread. ICD-9 157.9 ICD-10 C25 Authors Tanja Schub, BS Cinahl Information Systems, Glendale, CA Mary Woten, RN, BSN Cinahl Information Systems, Glendale, CA Reviewers Morgan Nicole Holle, RN, BSN, OCN Cinahl Information Systems, Glendale, CA Obiamaka Oji, DNP, APRN, FNP-BC Cinahl Information Systems, Glendale, CA Nursing Practice Council Glendale Adventist Medical Center, Glendale, CA Editor Diane Pravikoff, RN, PhD, FAAN Cinahl Information Systems, Glendale, CA PC is staged using the tumor, node, metastasis (TNM) staging system. Treatment and prognosis vary according to tumor type and stage. If the tumor is resectable, surgery is standard treatment for both exocrine and endocrine PC. Neoadjuvant chemotherapy with radiation therapy prior to surgery can be beneficial in patients with PC, particularly in those with borderline resectable tumors. Resection is most often curative in patients with PC in the head of the pancreas; these patients are more likely to be diagnosed early because of the close proximity of the malignancy to the bile duct causes earlier onset of symptoms (e.g., pruritus, urine darkening, stool changes. Surgical intervention for PC in other parts of the pancreas can be attempted if complete tumor removal is considered possible; these surgical procedures are pancreaticoduodenectomy (also called the Whipple procedure; i.e., removal of the head and body of the pancreas, gallbladder, and part of the stomach, small intestine, common bile duct, and lymph nodes; surgically connecting the bile duct to the duodenum), distal pancreatectomy (i.e., removal of the tail and/or body of the pancreas and/or spleen), and total pancreatectomy (i.e., removal of the entire pancreas and spleen). Adjuvant postoperative chemotherapy can increase survival by up to 3 months; adjuvant radiation therapy is not of benefit for most patients. Surgical intervention for palliation to relieve bile duct blockage has been widely replaced by endoscopic metal or plastic stent placement. Radiation therapy, chemotherapy (e.g., gemcitabine for exocrine PC; streptozotocin for both functioning and nonfunctioning types of endocrine PC), or both can be used to treat nonresectable PC or as adjuvant treatment to surgery. Pancreatic Cancer Advances in Treatment Assignment

Pain management, nutritional support, and other palliative care interventions are essential to improve quality of life (QOL), and referral to hospice is usual. July 6, 2018 Published by Cinahl Information Systems, a division of EBSCO Information Services. Copyright©2018, Cinahl Information Systems. All rights reserved. No part of this may be reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, or by any information storage and retrieval system, without permission in writing from the publisher. Cinahl Information Systems accepts no liability for advice or information given herein or errors/omissions in the text. It is merely intended as a general informational overview of the subject for the healthcare professional. Cinahl Information Systems, 1509 Wilson Terrace, Glendale, CA 91206 Facts and Figures PC is the tenth most common cancer diagnosed in the United States but the fourth leading cause of cancer death, accounting for 7% of all cancer-related deaths (Dragovich et al., 2017). The American Cancer Society (ACS) estimates that55,440 new cases of PC will be diagnosed and 44,330 people will die of the disease in the U.S. in 2018 (ACS, 2018). In most countries, the incidence of PC is 8–12 cases per 100,000 per year. Approximately 75% of PCs occur in the head or neck of the pancreas, 15–20% occur in the body of the pancreas, and 5–10% occur in the tail of the pancreas. The median age at diagnosis of PC is 69 years in Whites and 65 years in Blacks. At diagnosis, 20% of patients have localized, potentially resectable disease, 40% have locally advanced disease, and40% have distant metastases at the time of diagnosis. The overall median survival is 4–6 months; survival is lower in patients with significant weight loss, lower performance status, and metastasis to the liver. Patients who have undergone successful resection have a median survival of 12-19 months, and a 5-year survival of 15-20%. (Dragovich et al., 2017) Risk Factors Smoking appears to be the most prominent risk factor for PC; risk for developing PC is increased at least 2-fold in current smokers and 30% of PCs are thought to be related to smoking. Chronic pancreatitis confers a 26-fold increased risk for PC. Between 5% and 10% of patients with PC have a family history of the disease. Additional risk factors include older age; male gender; being a Black person living in the U.S.; diabetes mellitus (DM); low vitamin D levels; a diet high in fat and/or meat; using smokeless tobacco; inherited genetic mutations such as family syndromes involving BRCA2, p16, or PRSS1 mutations; exposure to maternal smoking in utero or as a young child; overweight and obesity; physical inactivity; consumption of 3 or more alcoholic beverages per day; sarcoidosis; chronic hepatitis; infection with Helicobacter pylori; and occupational exposure to certain chemicals (e.g., beta-naphthylamine,benzidine). Signs and Symptoms/Clinical Presentation The clinical presentation of patients with PC can include jaundice, pruritus, upper abdominal and/or back pain, nausea/vomiting, loss of appetite, severe weight loss, weakness, fatigue, sleep disturbance,and an impaired sense of well-being.Additionally, endocrine tumors can cause obstructive symptoms, gastrointestinal tract bleeding, or abdominal masses; functioning endocrine tumors hypersecrete insulin or glucagon and can cause hypoglycemia, glucose intolerance, hypokalemia, and Cushing’s syndrome. Patients can also demonstrate anxiety and depression. Assessment › Physical Findings of Particular Interest • Dark-colored urine, clay-colored stools, and yellow skin and sclera indicate jaundice • Physical examination of the abdomen can reveal tenderness and/or a well-defined mass in the subumbilical or left hypochondrial region; ascites and enlargement of the liver, gallbladder, and/or spleen can be present › Laboratory Tests • Tumor markers CA 19-9 and carcinoembryonic antigen (CEA) are elevated in advanced PC; a CA 19-9 value > 100 U/ mL strongly indicates PC, and levels are monitored for response during treatment; genetic testing can reveal PC-related mutation • Serum levels of bilirubin, alkaline phosphatase, and gamma-glutamyltranspeptidase (GGT) are significantly elevated in patients with obstructive jaundice • Serum levels of albumin and/or cholesterol can indicate malnutrition; liver, kidney, and/or bone marrow function tests can reveal underlying abnormalities • Glucosuria, hyperglycemia, and impaired glucose tolerance can be present • Histologic analysis of biopsied tumor specimen confirms the diagnosis › Other Diagnostic Tests/Studies • Multiphase thin-cut spiral CT scan with radiocontrast will show abnormalities that indicate PC; CT scan can provide information that assists with biopsy, staging, and identification of metastasis; endoscopic ultrasound identifies smaller tumors than CT scan and can also be helpful in identifying area(s) for biopsy and in staging • Endoscopic retrograde cholangiopancreatography (ERCP) will identify bile/pancreatic duct obstruction in jaundiced patients and resolve obstruction by stent placement • MRI or PET scan will identify metastasis; angiography will identify vascular abnormalities that prohibit surgical resection Treatment Goals › Provide Symptomatic Relief and Reduce Risk of Treatment-RelatedComplications • Pancreatic Cancer Advances in Treatment Assignment

Monitor all physiologic systems for underlying conditions and PC complications; frequently assess for pain, pruritus, and other discomfort; provide prescribed treatment –For information about management of pain (which can be severe and debilitating) in patients with PC, see Quick Lesson About … Pancreatic Cancer and Pain • Promote optimum hydration and nutrition; give prescribed parenteral fluids, enteral feedings, and pancreatic enzymes, as ordered • Follow facility pre- and post-treatment protocols if patient becomes a candidate for surgery, radiation therapy, and/or chemotherapy; reinforce pre- and post-treatment education and verify completion of facility informed consent documents; closely monitor the patient post-treatment for adverse effects and complications (see Red Flags , below) › Educate and Promote Emotional Well-Being • Assess the anxiety level and coping ability of the patient and family; educate and encourage discussion about the disease process, treatment options, and end-of-life issues, as appropriate • Request referral to a dietitian for nutrition evaluation/education; to a mental health clinician for counseling on coping strategies; and to a social worker for identification of resources for in-homeservices, hospice, Internet information, and support groups Food for Thought › Carcinogenesis of PC begins roughly 10 years prior to the onset of symptoms › Among the potential PC treatment strategies under investigation is the use of nanotechnology to improve drug delivery › Vitamin intake—particularly of Vitamins D and B12—may decrease risk for PC (Liu et al, 2018) › Early diagnosis and treatment of PC are associated with improved prognosis, but early diagnosis is difficult and there is currently a lack of biomarkers available to aid in the identification of patients with early-stage PC. Researchers in a recent study identified 38 microRNAs (i.e., short, noncoding RNAs that play important roles in cancer development and metastasis) in whole blood that are significantly dysregulated in patients with PC, and they constructed 2 diagnostic panels of microRNAs that can have the potential to identify patients with early-stage PC. Additional research is needed to confirm the diagnostic utility of these panels (Schultz et al., 2014) › Researchers found that serum tumor marker levels of CA 19-9, lactic dehydrogenase (LDH) and CEA had significant prognostic roles on survival in patients diagnosed with metastatic PC receiving gemcitabine-basedchemotherapy (Tas et al., 2014) › In a 2014 study, researchers concluded that baseline hemoglobin-a1c levels are significantly higher in patients diagnosed with pancreatic ductal adenocarcinoma versus benign pancreatic disease and seem to affect overall survival (Fan et al., 2014) Red Flags › Pancreaticoduodenectomy carries a significant risk for complications, including leaking from new surgical connections, delayed gastric emptying, bleeding, and infection. Surgery for PC should be performed only in facilities that perform at least 15-20 procedures annually › Monitor patients with endocrine PC for hyperinsulinism that leads to severe hypoglycemia, and immediately administer prescribed oral or parenteral glucose What Do I Need to Tell the Patient/Patient’s Family? › Continued medical surveillance is essential, and end-of-life issues should be addressed References 1. American Cancer Society. (2018). Pancreatic cancer. Retrieved May 29, 2018, from http://www.cancer.org/acs/groups/cid/documents/webcontent/003131-pdf.pdf (GI) 2. Dragovich, T., Erickson, R. A., Larson, C. R., & Shabahang, M. (2017, July 15). Pancreatic cancer. Medscape. Retrieved May 29, 2018, from http://emedicine.medscape.com/article/280605-overview (GI) 3. Fan, K. Y., Dholakia, A. S., Wild, A. T., Su, Z., Hacker-Prietz, A., Kumar, R., … Herman, J. M. (2014). Baseline hemoglobin-a1c impacts clinical outcomes in patients with pancreatic cancer. Journal of the National Comprehensive Cancer Network, 12(1), 50-57. 4. Ferri, F. F. (2018). Pancreatic cancer (exocrine). In F. F. Ferri (Ed.), 2018 Ferri’s clinical advisor: 5 books in 1 (pp. 941-942). Philadelphia, PA: Elsevier. (GI) 5. Karakas, Y., Lasin, S., & Yalcin, S. (2018). Recent advances in the management of pancreatic adenocarcinoma. Expert Review of Anticancer Therapy, 18(1), 51-62. doi:10.1080/14737140.2018.1403319 (RV) 6. Liu, Y., Wang, X., Lu, S., & Liu, S. (2018). Vitamin intake and pancreatic cancer risk reduction: A meta-analysis of observational studies. Medicine (Baltimore), 97(13), e0114. doi:10.1097/MD.0000000000010114 (M) 7. National Comprehensive Cancer Network. (2018). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines): Pancreatic adenocarcinoma. Version 1.2018—April 27 2018. Retrieved May 29, 2018, from http://www.nccn.org/professionals/physician_gls/pdf/pancreatic.pdf (G) 8. National Institute for Health and Care Excellence. (2018). Pancreatic cancer in adults: Diagnosis and management. NICE guideline [NG85]. Retrieved May 29, 2018, from https://www.nice.org.uk/guidance/ng85/resources/pancreatic-cancer-in-adults-diagnosis-and-management-pdf-1837696373701 (G) 9. Schultz, N. A., Dehlendorff, C., Jensen, B. V., Bjerregaard, J. K., Nielsen, K. R., Bojesen, S. E., … Johansen, J. S. (2014). MicroRNA biomarkers in whole blood for detection of pancreatic cancer. JAMA: Journal of the American Medical Association, 311(4), 392-404. doi:10.1001/jama.2013.284664 10. Tang, C. C., von Ah, D., & Fulton, J. S. (2018). The symptom experience of patients with advanced pancreatic cancer: An integrative review. Cancer Nursing, 41(1), 33-44. doi:10.1097/NCC.0000000000000463 (SR) 11. Tas, F., Karabulut, S., Ciftci, R., Sen, F., Sakar, B., Disci, R., & Duranyildiz, D. (2014). Serum levels of LDH, CEA, and CA-19-9 have prognostic roles on survival in patients with metastatic pancreatic cancer receiving gemcitabine based chemotherapy. Cancer Chemotherapy & Pharmacology, 73(6), 1163-1171. doi:10.1007/s00280-014-2450-8 …