What you need to know. JAMES L. ABBRUZZESE, MD Chairman, Gastrointestinal Medical Oncology The University of Texas M. D. Anderson Cancer Center

Transcription

1 Myths & Facts about pancreatic cancer What you need to know JAMES L. ABBRUZZESE, MD Chairman, Gastrointestinal Medical Oncology The University of Texas M. D. Anderson Cancer Center BEN EBRAHIMI, MD Fellow, Hematology/Medical Oncology The University of Texas M. D. Anderson Cancer Center Cover illustration 2002 GCT II Solutions and Enterprises Ltd. Text illustrations by Harriet Phillips

2 Clinical opinions expressed in this book are those of the authors and do not necessarily reflect the opinions of the sponsor, editors, or the publisher and officers of PRR, Inc. Copyright 2002 by PRR, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced in any manner or by any means, electronic or mechanical, without the written permission of the publisher. Library of Congress Catalog Card Number ISBN Single copies of this book are available at $9.95 each. For information on bulk quantities, contact the publisher, PRR, Inc., 48 South Service Road, Melville, NY Telephone: (631) Printed in the U.S.A. M E L V I L L E N E W Y O R K Publishers of: ONCOLOGY Oncology News International InTouch: The Good Health Guide to Cancer Prevention & Treatment Cancer Management: A Multidisciplinary Approach InTouchLive.com

3 Acknowledgments The Board of Directors and Scientific Advisory Board of The Lustgarten Foundation for Pancreatic Cancer Research wish to extend their heartfelt appreciation to Pharmacia Oncology for generously providing an unrestricted educational grant in support of this project, and to Drs. James L. Abbruzzese and Ben Ebrahimi, The University of Texas M. D. Anderson Cancer Center, for graciously lending their expertise to prepare a handbook for individuals and families facing pancreatic cancer. This resource is available because of their dedication to serve the pancreatic cancer community, and we are proud to join with these leaders in their commitment to find a cure for the disease. The Lustgarten Foundation also wishes to thank the National Cancer Institute (NCI) for providing increased opportunities for scientists to pursue pancreatic cancer research, including a 2002 Program Announcement for Specific Programs of Research Excellence (SPOREs) in Pancreatic Cancer. The SPOREs represent a major funding commitment from NCI to increase the level of support for pancreatic cancer research. The Program Announcement is a direct result of a Pancreatic Cancer Progress Review Group (PRG), which was convened in 2000 to develop a comprehensive research plan for the disease. The Lustgarten Foundation was proud to have participated in the PRG as a member of the Roundtable. NCI s leadership role in the fight to cure pancreatic cancer has greatly enhanced the opportunities available to pancreatic cancer researchers in this country, and we are most grateful for their interest in our work. We also wish to extend our deepest appreciation to Mrs. Maxine Stein-Kohler for her generous personal gift to The Lustgarten Foundation in loving memory of her husband, Arthur Stein- Kohler. This gift will enable The Lustgarten Foundation to purchase additional copies of this handbook and help support its distribution free of charge to even more patients and families who can benefit from this information. Finally, we wish to thank our Patient Review Board, comprised of pancreatic cancer survivors, for openly and honestly sharing with us their unique perspectives on pancreatic cancer and the National Cancer Institute for its valuable assistance and input.

4 5 A Pancreatic Cancer Handbook for Patients and Their Families A Note to Readers The board and staff of The Lustgarten Foundation for Pancreatic Cancer Research understand that there are many unique challenges associated with a diagnosis of pancreatic cancer. Patients and their families need and deserve access to the most accurate, up-to-date information on the disease. Yet until recently little attention had been paid to pancreatic cancer, and surprisingly few educational materials existed for pancreatic cancer patients and their families. Armed with this knowledge, The Lustgarten Foundation recognized the need for a comprehensive information and resource guide for individuals and their families facing pancreatic cancer. Myths & facts about pancreatic cancer is the result of that need and is new to a series of patient education booklets published by PRR, Inc. to provide patients and their families with vital information about their cancer diagnosis and support resources. The Lustgarten Foundation and PRR, Inc. are pleased to be able to provide you with Myths & facts about pancreatic cancer made possible by the generosity of Pharmacia Oncology, and written by Dr. James Abbruzzese, Chairman and Professor of Medicine, Gastrointestinal Medical Oncology and Dr. Ben Ebrahimi, Clinical Specialist and Fellow in Hematology/Medical Oncology. Both Dr. Abbruzzese and Dr. Ebrahimi are on staff at The University of Texas M. D. Anderson Cancer Center. Dr. Abbruzzese also serves as a member of The Lustgarten Foundation s Scientific Advisory Board (see page 63). This handbook is based on the premise that by understanding the particular challenges associated with a diagnosis of pancreatic cancer, you will be better equipped to make informed decisions about your care. Please note that this handbook is not intended to provide medical advice and is not a substitute for consulting with qualified health professionals who are familiar with your individual medical needs. This handbook should not take the place of any discussion with your physician, but should be used to help guide you in these discussions. All matters about your health should be under professional medical supervision. We have included a glossary of terms. Terms listed in the glossary are italicized in text.

5 We hope this information is helpful to you. We encourage you to seek support from family and friends when appropriate, and to ask for help when you need it. Your treatment team of doctors, nurses, social workers, counselors, nutritionists, and other health care specialists can be an excellent source of information and support, and can help address any questions or concerns you may have along the way. You may also meet and share experiences with other individuals who have been affected by pancreatic cancer. We encourage you to keep in mind that your experience will be unique to your particular situation. For additional information, please contact The Lustgarten Foundation at or visit

6 About the Authors James L. Abbruzzese, MD, FACP, is a professor of medicine, internist, chairman, and Annie Laurie Howard Research Distinguished Professor in the Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, at The University of Texas M. D. Anderson Cancer Center in Houston. Dr. Abbruzzese earned his doctorate in medicine at the University of Chicago Pritzker School of Medicine in Chicago in His postgraduate training, from 1978 to 1983, consisted of a residency in internal medicine at Johns Hopkins Hospital in Baltimore, and fellowship training in infectious diseases and medical oncology at Johns Hopkins and Dana-Farber Cancer Institute/Harvard Medical School, respectively. Dr. Abbruzzese s distinguished career has also included varied institutional committee activities and appointments with the National Cancer Institute, the American Association for Cancer Research, the American Society of Clinical Oncology, the National Comprehensive Cancer Network, and the Southwest Oncology Group, among others. In addition, Dr. Abbruzzese has been awarded with numerous honors, including, among others, being listed as one of Good Housekeeping s Top Cancer Specialists for Women (1999), The Best Doctors in America (1998, 2000), and America s Top Doctors (2001, 2002). Ben Ebrahimi, MD, is a Clinical Specialist and Fellow in Hematology/Medical Oncology at The University of Texas M. D. Anderson Cancer Center. Dr. Ebrahimi graduated magna cum laude with a bachelor of science degree from the University of California, Los Angeles, and was a member of Phi Beta Kappa and the Golden Key national honor societies. He went on to receive his doctorate of medicine from Baylor College of Medicine in Houston, and completed his internal medicine residency with the Baylor College of Medicine Affiliated Hospitals. Dr. Ebrahimi is a member of the American Society of Clinical Oncology, the American Society of Hematology, the American Medical Association, the Texas Medical Association, and the American College of Physicians. He was the recipient of a National Cancer Institute bioimmunotherapy fellowship research grant (July 2001 to June 2003), and was also named Chief Fellow, Lyndon B. Johnson General Hospital Oncology Service (July 2002 to June 2003).

7 Contents Acknowledgments Note to Readers About the Authors What Is Pancreatic Cancer? What Causes Pancreatic Cancer? Risk Factors 15 What Are the Symptoms of Pancreatic Cancer? How Is Pancreatic Cancer Detected and Diagnosed? CA Diagnostic Imaging Studies 20 Biopsy Procedures 24 What Are the Stages of Pancreatic Cancer? TNM Classification Stages I Through IV 27 Clinical/Radiographic Classification 28 How Is Pancreatic Cancer Treated? Community Hospital vs Comprehensive Cancer Center 30 Surgery 32 Whipple Procedure 33 Total Pancreatectomy 33 Distal Pancreatectomy 33 Adjuvant and Neoadjuvant Therapies 35 Radiation and Chemotherapy 36 Locally Advanced Pancreatic Cancer 36 Metastatic Pancreatic Cancer 37

8 Can Pain Be Controlled? Three-Step Analgesic Ladder 39 Coping With Pancreatic Cancer Proper Nutrition 42 Emotional Health 42 What Do I Need To Know About Clinical Trials? Phases I, II, and III Clinical Trials 44 Ongoing Clinical Trials for Pancreatic Cancer 46 Appendix 1: Pancreatic Cancer Specific Information and Support Pancreatic Cancer 48 General Cancer Information 49 Online/Telephone Discussion Groups 50 Insurance and Financial Issues 50 Clinical Trials Search Services 51 Appendix 2: National Cancer Institute Designated Cancer Centers Comprehensive Cancer Centers 53 Clinical Cancer Centers 57 Glossary of Terms The Lustgarten Foundation Board of Directors 62 Corporate Advisory Board 62 Scientific Advisory Board 63 About The Lustgarten Foundation

9 11 What Is Pancreatic Cancer? The pancreas is an organ located in the upper middle of the abdomen. It is surrounded by the stomach, small intestine, liver, and spleen (Figure 1). The pancreas is 6 inches long, and is shaped like a thin pear, wide at one end and narrow at the other end. The wider right end of the pancreas is called the head, the middle section is called the body, and the narrow left end of the pancreas is called the tail (Figure 2). The pancreas has two main functions: (1) The pancreas makes pancreatic juices. These pancreatic juices are produced by the exocrine glands and contain enzymes that help digest food. When food enters the stomach, the pancreas releases these enzymes into a system of ducts. The main pancreatic duct joins the common bile duct, which originates from the liver and gallbladder. The common bile duct carries bile, a fluid that helps digest fat, and it empties into the duodenum, the first part of the small intestine. (2) The second main function of the pancreas is to produce several hormones, including insulin. The hormones are created in the endocrine glands of the pancreas and help the body use or store energy from food. For example, insulin controls the body s blood sugar levels, which are an important source of energy. These hormones enter the bloodstream directly from the pancreas and travel throughout the body. Cancer of the pancreas accounts for approximately 2% of all cancers and is the fourth most frequent cause of cancer death. The American Cancer Society estimates that 30,300 people in the United States will be diagnosed with pancreatic cancer in 2002, and that 29,700 Americans will die from this disease (Figure 3) this year. Pancreatic cancer occurs when there is an uncontrolled growth of abnormal cells in the pancreas. The abnormal cells form a mass in the Myth All pancreatic cancers are fatal. Fact This is not the case. Much progress has been made in multiple areas of treatment, including surgery, radiation therapy, chemotherapy, and combinations of these therapies. Some patients can achieve long-term remission.

10 12 Lungs Liver Spleen Gall Bladder Bile Duct Pancreas Stomach Colon Duodenum Pancreatic Duct Small Intestine FIGURE 1 The pancreas is hidden behind the stomach, and surrounded by other organs, including the small intestine, bile duct, gallbladder, liver, and spleen.

11 13 Common Bile Duct Body Head Tail Pancreatic Duct Duodenum FIGURE 2 The pancreas is shaped like a thin pear. Three sections of the pancreas are identified as the head, body, and tail. pancreas called a tumor. When a tumor has the ability to spread to other parts of the body, it is called malignant. Another word for a malignant tumor is cancer. About 95% of pancreatic cancers begin in the ducts that carry pancreatic juices. This area is also known as the exocrine pancreas. In rare instances (5%), pancreatic cancer begins in the hormone-producing part of the pancreas, called the endocrine pancreas. The endocrine pancreas has islet cells that produce insulin as well as other hormones. This booklet focuses on cancer that begins in the pancreatic ducts. Nevertheless, some of the information presented would also apply to islet-cell cancers. Like many other forms of cancer, pancreatic cancer can spread. As a tumor grows, the mass may invade organs that surround the pancreas, such as the stomach, small intestine, or important blood vessels. Pancreatic cancer cells may also break away from the tumor and spread, or metastasize, to other parts of the body; I was really afraid of every aspect of treatment surgery, chemo, hair loss, and nausea. What really helped me was talking to my doctor. I asked a lot of questions and his answers eased my fears tremendously.

12 14 Myth All pancreatic cancers are made up of the same type of abnormal cells. All Other Cancers 747,900 Colon 107,300 Rectum 41,000 Pancreas 30,300 Lung & Bronchus 169,400 Fact There are actually two types of pancreatic cancer and each is made up of a different type of abnormal cell. In up to 95% of cases, pancreatic cancer arises from the exocrine portion of the organ. Most of the exocrine tumors are from the ductal cells, which are the cells that line the pancreatic ducts (see Figure 2 on page 13). However, a rare form begins in other cells of the pancreas itself, the endocrine pancreas, where the cells that produce insulin and other hormones are located. These cells are called islets of Langerhans and cancers that begin in these cells are called isletcell cancers. These make up only 5% of pancreatic cancers. Breast 205,000 FIGURE 3 Cancer of the pancreas accounts for 2% of all cancers diagnosed in the United States. including the liver, lung, and occasionally, other organs. These cancers that result from spread of cells from the original tumor are still considered part of the original or primary cancer. For example, if pancreatic cancer spreads to the liver, the cancer cells in the liver are pancreatic cancer cells. The disease is not considered liver cancer, but rather metastatic pancreatic cancer. Ô Prostate 189,000

13 15 What Causes Pancreatic Cancer? The exact causes of pancreatic cancer are still largely unknown, but certain factors are known to increase a person s chance of developing this disease. These are known as risk factors and they vary depending on the type of cancer that occurs after persons are exposed to the risk factor over long periods of time. RISK FACTORS The following factors are known to increase the risk of developing pancreatic cancer (Figure 4). Age: The risk of developing cancer of the pancreas increases after age 50. Most patients are between age 60 and 80 at the time of the diagnosis. Gender: Men are about 30% more likely to develop pancreatic cancer compared to women, but this difference is narrowing. Race: African Americans are more likely to develop pancreatic cancer than are white Americans or Asian Myth Pancreatic cancer affects only older people. Fact The risk of developing pancreatic cancer is low in the first three to four decades of life but increases sharply after age 50 years. Most patients are between the ages of 60 and 80 at diagnosis. Even though pancreatic cancer is uncommon in patients under the age of 40, some cases have occurred in patients younger than 30 years of age. Myth A person has little or no risk of pancreatic cancer if there is no family history of pancreatic cancer. FIGURE 4 Risk Factors - About one-third of pancreatic cancer cases are thought to be a direct result of cigarette smoking. Fact Genetic or hereditary causes of pancreatic cancer account for only 5% to 10% of the estimated 30,300 cases of pancreatic cancer diagnosed each year in the United States.

14 16 Myth Smoking cessation offers little benefit to lowering pancreatic cancer risk in an individual who has smoked for most of his or her life. Fact Recent studies have shown that the risk of pancreatic cancer increases as the amount and duration of smoking increase, and that long-term smoking cessation (>10 years) reduces the risk by approximately 30% compared to the risk of current smokers. Americans. The reasons for this difference are not known. Cigarette smoking: About one-third of pancreatic cancer cases are thought to be a direct result of cigarette smoking. Diet: A diet high in meats and fat increases the risk of pancreatic cancer. On the other hand, a diet high in fruits, vegetables, and dietary fiber appears to have a protective effect and to reduce the risk of pancreatic cancer. Diabetes mellitus: Diabetic individuals are twice as likely to develop pancreatic cancer compared to nondiabetic individuals. The reason for this association is not known. Family history: Pancreatic cancer tends to run in some families. An inherited tendency to develop this cancer may be a factor in 5% to 10% of cases. Other: Patients with chronic pancreatitis may have an increased risk of developing pancreatic cancer. Occupational exposure to certain pesticides, dyes, and chemicals related to gasoline, as well as certain types of stomach surgery, may increase the risk of pancreatic cancer. Ô

15 17 What Are the Symptoms of Pancreatic Cancer? The pancreas is hidden behind other organs including the stomach, small intestine, bile duct, gallbladder, liver, and spleen (see Figure below). Pancreatic cancer has been called a silent disease because the tumor can grow for many years before it causes pressure, pain, or other signs of illness. Even when symptoms appear, they are often mild at first and ignored by many patients (see table). In many cases the cancer has spread outside the pancreas by the time it is diagnosed. Gall Bladder Bile Duct Liver Spleen Pancreas Myth Pancreatic cancer always causes symptoms that can be easily recognized by patients. Fact Patients with pancreatic cancer may at first have no symptoms or have only some mild symptoms that could be caused by a number of other conditions. These symptoms are often ignored. This can lead to delayed diagnosis and may affect chances for cure, because the best chance for cure in pancreatic cancer is when the cancer is detected at an early stage. Duodenum Pancreatic Duct Stomach Colon Small Intestine The symptoms of pancreatic cancer are easily explained by the location of the pancreas in relation to other organs in the body. A tumor located in the head of pancreas may cause jaundice to occur. The signs of jaundice are yellow skin and eyes, dark urine, and light clay-

16 18 Table Symptoms of Pancreatic Cancer Jaundice Generalized itching Pain in upper abdomen and back Loss of appetite Unexplained weight loss Weakness Nausea FIGURE 5 One of the symptoms of pancreatic cancer is jaundice, which causes yellow skin and eyes, as well as other symptoms. colored stool. Jaundice occurs when a substance called bilirubin builds up in the blood. Bilirubin is made in the liver. From there, it travels down the bile duct and passes through the pancreas just before emptying into the duodenum, the first portion of the small intestine. If the bile duct becomes blocked (by a tumor, for example), bilirubin builds up in the blood. This build-up causes a person to become noticeably yellow, or jaundiced (Figure 5). Cancer starting at the head of the pancreas (see Figure 2 on page 13) is most likely to cause jaundice, but occasionally gallstones can cause a similar problem. As pancreatic cancer grows and spreads, pain can develop in the upper abdomen and may also spread to the back. The pain may become worse after eating or lying down. Advanced cancers or cancers in the body of the pancreas are most likely to cause pain. Indigestion, lack of appetite, nausea, and weight loss can occur when a pancreatic tumor presses against the stomach and small intestine. Vague problems with digestion, poor appetite, and unexplained weight loss may also

17 19 occur for complicated reasons not related to the location of the tumor. These symptoms may be due to the ability of pancreatic cancers to produce certain proteins that dramatically change the body s normal physiology. Islet-cell cancer, which is the uncommon form of pancreatic cancer, can cause the pancreas to make too much insulin, which results in low blood sugar levels. When this happens, the individual may feel weak or dizzy. Chills, muscle spasms, and diarrhea are frequent symptoms of islet-cell cancers as well. The symptoms that develop depend on the specific hormones that are being overproduced. Other symptoms that can occur with pancreatic cancer result from the spread of the cancer to other parts of the body, a process called metastases. Under these circumstances, the symptoms will depend on which organs have been affected by the cancer. Ô Once I found out about my cancer, I was motivated to fight it.

18 20 Myth Because pancreatic cancer is a serious disease, most patients are already regularly tested for this cancer by their physicians. Fact Researchers continue to look for better ways to check or screen for pancreatic cancer before the disease develops. Unfortunately, there are no tests, such as mammography for breast cancer or the PSA blood test for prostate cancer, to adequately screen the general public for this disease. Routine screening for pancreatic cancer in patients without any symptoms is not recommended. How Is Pancreatic Cancer Detected and Diagnosed? To find the cause of symptoms, your doctor will perform a physical examination and ask about your medical history. In addition to checking general signs of health, your doctor may perform blood, urine, and stool tests. In cases of pancreatic cancer, results of laboratory tests often will show a high bilirubin level and increased levels of liver function enzymes. CA 19-9 A tumor marker called CA 19-9 can be measured in the blood and is frequently elevated in cancer of the pancreas. Its use in diagnosis, however, is very controversial. In general, higher levels of this tumor marker are sometimes associated with larger tumors that have a lower chance of being removed surgically. The best use of CA 19-9 is to check it regularly in a particular patient to watch for any changes. Your doctor will advise you as to whether this test would be appropriate for you. DIAGNOSTIC IMAGING STUDIES Doctors may perform several tests that involve taking pictures of the pancreas and surrounding tissues and organs to help with diagnosis. These are called imaging tests. Imaging tests include: Upper GI series (sometimes called a barium swallow): The patient drinks a barium solution, which shows an outline of the upper digestive organs when x-rayed. In general, this test is not very useful for diagnosing pancreatic cancer. Computerized tomography (CT) scan: CT scanning involves the use of an x-ray machine linked to a computer. The x-ray machine is shaped like a

19 21 large doughnut with a hole. The patient lies on a bed that passes through the hole, and the machine moves along the patient s body, taking many x-rays (Figure 6A). The computer then puts the different x-ray pictures together to produce detailed, threedimensional pictures (Figures 6B and 6C). Magnetic resonance imaging (MRI): In MRI imaging, a large and powerful magnet linked to a computer is used to obtain detailed three-dimensional pictures of areas inside the body. This large machine has space for the patient to lie in a tunnel inside the magnet. The machine measures the body s response to the magnetic field, and the computer uses this information to make the detailed pictures or images. Since CT scans and MRI images can show the pancreas and other parts of the body with much greater precision than standard x-rays, they can also help to pinpoint whether the cancer has spread from the pancreas to other parts of the body. Furthermore, as discussed in the staging section (see page 27), these images can show whether the pancreatic cancer is affecting nearby arteries and veins which can make a tumor unresectable, or in other words not possible to be removed by surgery. Ultrasonography: Ultrasound of the abdomen involves the use of very high frequency soundwaves to create a picture, or sonogram, of the internal organs. These soundwaves cannot be heard by the human ear. The echoes that the soundwaves produce as they bounce off internal organs create the sonogram image. Healthy tissues and tumors produce different echoes. The sonogram can show the size of the pancreas and possibly the presence of a tumor. This procedure called transabdominal ultrasound is more popular outside of the United States. Two newer ultrasound procedures are being used more frequently in the United States. One of these is the endoscopic ultrasound which is performed through a tube, or endoscope, that is placed down, into, and through the stomach, and into the duodenum. This procedure is very good at locating small tumors in the pancreas. The second procedure is the Myth An elevated level of the tumor marker CA 19-9 always means that a patient has pancreatic cancer. Fact Although CA 19-9 levels are useful in diagnosing pancreatic cancer and following the course of treatment, there are many causes of elevated CA 19-9 that are not related to pancreatic cancer, including gastrointestinal diseases that are not cancer.

20 22 FIGURE 6A CT Scanner: A CT or computerized axial tomography machine is shaped like a large doughnut. The patient lies on a bed that passes through the hole while the machine takes many x-rays.

21 23 Gallbladder Pancreas Loops of bowel Stomach Myth A pancreatic mass seen on imaging studies is a sign of pancreatic cancer. Liver FIGURE 6B This image through the abdomen shows what a normal liver, gallbladder, pancreas, stomach, and loops of bowel would look like on a CT scan. Pancreatic Mass Fact Although a pancreatic mass identified on imaging studies such as a CT scan is suggestive of pancreatic cancer, there are other causes of such a mass not related to cancer, including pancreatitis and a pancreatic pseudocyst. Therefore, a biopsy of a pancreatic mass is recommended to verify the presence or absence of cancer. Stent FIGURE 6C This image demonstrates a large abnormal mass in the head of the pancreas.

22 24 Before I was diagnosed with cancer, I used to worry about my future plans. I did not take the time to really enjoy what I had. Now, I have learned to live one day at a time. I enjoy the simple things in life. laparoscopic ultrasound. In this procedure, a small tube is placed through the abdomen and into the region of the pancreas. The laparoscopic ultrasound is particularly effective at determining whether the cancer is affecting the liver or peritoneum, without having to undergo surgery. Endoscopic Retrograde Cholangiopancreatography (ERCP): ERCP involves an x-ray procedure in which the doctor passes a long, flexible tube, or endoscope, down into the patient s throat, through the stomach, and into the small intestine. The doctor can see through the tube and inject dye into the bile duct and pancreatic duct as x-rays are taken. This test can show narrowing of these ducts due to pressure from the tumor. Angiography: This test specifically studies the blood vessels in and around the pancreas. With the aid of local anesthesia, a small catheter is placed into the large artery in the upper thigh. Dye is injected into the blood vessels leading to the pancreas, and x-ray films are taken. These x-rays can help the surgeon when planning an operation. BIOPSY PROCEDURES Images of the pancreas and nearby organs provide important clues to determine the presence or absence of cancer. These methods by themselves can never diagnose cancer with 100% certainty. Once an abnormal mass on the pancreas is identified, however, a biopsy is performed because this is the only sure way to learn whether pancreatic cancer is present. In a biopsy, the doctor removes a tissue sample. A pathologist looks at the tissue sample under a microscope to check for the presence of cancer cells. There are several ways to perform a biopsy to diagnose pancreatic cancer, and some patients may need to have more than one type of biopsy. Fineneedle aspiration and brush biopsy are two types of biopsy procedures and are discussed below; other types are performed with surgery. Fine-needle aspiration: A long but very thin needle is inserted into the pancreas through the skin

23 25 Pancreatic Mass FIGURE 7 A large mass in the head of the pancreas is visible on this ultrasound image. of the abdomen. CT-scan images or ultrasound waves guide the placement of the needle, which is used to remove cells from the tumor for examination under a microscope. Brush biopsy: A brush biopsy is performed at the same time as an ERCP. A very small brush is inserted through the endoscope and into the opening from the bile duct to the main pancreatic duct. Cells are rubbed off for examination under a microscope. Sometimes, the biopsy to diagnose pancreatic cancer is performed using surgery. Laparoscopy: Laparoscopy is a minimally invasive type of surgery in which the doctor makes a small incision in the abdomen. A lighted instrument shaped like a thin tube is inserted through the small incision into the abdomen to remove tissue samples for examination under the microscope. In addition, the instrument enables the doctor to view the inside of the abdomen to determine the location and extent of disease and use the laparoscopic ultrasound mentioned earlier.

24 26 When I was told I had pancreatic cancer, I felt very scared. But having a supportive family made me feel really secure, and throughout my treatments I never felt abandoned. Laparotomy: Laparotomy is a major type of abdominal surgery and is necessary in some cases to make a diagnosis. In this procedure, the doctor makes a larger incision in the abdomen and examines the organs directly. If a cancer is found, the doctor can proceed with further surgery to remove the tumor. Ô

25 27 What Are the Stages of Pancreatic Cancer? If pancreatic cancer is diagnosed, the stage of disease must be identified before determining the best treatment. The stages of pancreatic cancer refer to whether, or how far, the cancer has spread in the pancreas and throughout the body. Surgery, chemotherapy, and radiation can all be used to treat pancreatic cancer, but whether they are used individually or in combination will be determined by how far the cancer has progressed. In the United States, universal agreement on a standardized staging system does not exist. The main problem is that the staging system for cancer of the pancreas as put forth by, for example, the American Joint Committee on Cancer is viewed as impractical by certain experts in the field. This classification is based on knowing the status of the Tumor, Lymph Nodes, and Metastases, or TNM. Myth In pancreatic cancer, the size of the tumor is the most important factor in predicting outcome for the patient. Fact Unlike other cancers, such as lung and breast cancers, the size of the main or primary tumor has little do with the predicted outcome, or the prognosis, in pancreatic cancer. What really matters is whether the tumor has spread beyond the pancreas to the stomach or small intestine, or important blood vessels, as well as distant sites. TNM CLASSIFICATION STAGES I THROUGH IV Using this classification, the four stages of pancreatic cancer include: Stage I: This is the least advanced stage of disease. Cancer is located only in the pancreas, and has not spread to the organs next to the pancreas, such as the small intestine, stomach, or bile duct (Figure 8). Stage II: The cancer has spread to the nearby organs, including the stomach, spleen, or colon, but it has not entered the lymph nodes. Lymph nodes are small, bean-shaped structures found throughout the body, where infection-fighting cells are produced and stored. Nodes can trap cancer cells or bacteria travelling throughout the body (Figure 9).

26 28 FIGURE 8 Stage I - Cancer is confined to the pancreas, usually in the head of the pancreas. FIGURE 9 Stage II - Cancer has spread to nearby organs, including the duodenum, as shown here, or the stomach, spleen, or colon. I think a second opinion is very important, especially if you are looking for an institution that specializes in cancer care and research. That way, you find out about the latest advances in treating your cancer. Stage III: The cancer may or may not have spread to nearby organs, but it is found in the lymph nodes near the pancreas (Figure 10). Stage IV: This is the most advanced stage of pancreatic cancer. In stage IV disease, the cancer has spread to distant parts of the body, such as the liver, lung, or peritoneum, and occasionally to other organs (Figure 11). CLINICAL/RADIOGRAPHIC CLASSIFICATION For many patients, staging is based on sophisticated radiological studies. Many researchers have proposed a clinical/radiographic staging classification for pancreatic cancer, which attempts to follow prognosis and clinical decision-making more closely in regard to treatment. This three-stage classification is based on radiological findings and refers to the cancer as potentially resectable, locally advanced, and metastatic. It is not directly related to the TNM status.

27 29 FIGURE 10 Stage III - Cancer has spread to the lymph nodes near the pancreas. FIGURE 11 Stage IV - Cancer has spread to distant organs, such as the liver and lung. In this proposed classification, potentially resectable pancreatic cancer is defined as those cancers with no evidence of involvement outside of the pancreas, and demonstration of normal veins and arteries that travel close to the pancreas. Locally advanced includes those pancreatic tumors without spread but with evidence of arterial encroachment or venous occlusion. The metastatic stage includes those tumors with evidence of spread to other organs. Ô Note to reader about Figures 8 11: The position of organs is not representative of the true anatomy. The placement of organs has been altered slightly for purposes of clarity.

28 30 Myth If pancreatic cancer is exposed to air at surgery, the cancer will spread rapidly. Fact Many people know friends or relatives who have undergone major surgery for advanced cancer only to learn that their cancer has progressed rapidly after surgery. Most of these people believe that general anesthesia and surgery (i.e., the air) reduced the patient s immunity against the disease and resulted in rapid progression of cancer. Air, however, has no effect on cancer. The spread of cancer depends on how aggressive the cancer cells are and whether, at the time of diagnosis and surgery, they have already spread to nearby structures or to blood and lymph vessels. How Is Pancreatic Cancer Treated? Pancreatic cancer can be managed best only when it is found at an early stage before it has spread. Once the disease has advanced, it is very hard to control. Treatment, however, can improve the quality of a person s life by controlling the symptoms and delaying complications of this disease. If you are diagnosed with pancreatic cancer, often you will be treated by a team of specialists, including surgeons, medical oncologists, radiation oncologists, endocrinologists, and gastroenterologists. Which treatment option is best will be determined on an individual basis depending on the type of cancer, the location and size of the tumor, the stage of the disease, and your age and general health. Three kinds of treatment for cancer of the pancreas are most often used: surgery, aimed at removing the cancer or relieving symptoms caused by the cancer; radiation therapy, or the use of high-dose rays or other high-energy rays to kill cancer cells; and chemotherapy, the use of drugs to kill cancer cells. A doctor may use just one method or combine these methods in an effort to treat the cancer most effectively. Some important questions you may want to ask your physician before treatment begins are listed in the table on the following page. COMMUNITY HOSPITAL VS COMPREHENSIVE CANCER CENTER One of the issues patients with pancreatic cancer face is whether they should receive their care in a community hospital or at a comprehensive cancer center. There is no simple way to deal with this choice. Because every case of pancreatic cancer is unique, you should speak to your oncologist to help determine which institution is best for you. If your oncologist believes that you may be an appropriate

29 31 Table Questions to Ask Your Physician What is my diagnosis? What is the stage of my disease? What are my treatment choices? Which do you recommend for me, and why? What are the chances that the treatment will be successful? Is the treatment likely to cure the cancer or will it primarily prolong my survival? Is the treatment simply to manage my symptoms? Should I consider joining a clinical trial? What are the potential risks and side effects of each treatment? How long will the treatment last? Will the treatment make me sick? What can I do to minimize any side effects of treatment? Will I have to change my normal activities? candidate for a clinical trial, he or she may recommend a comprehensive cancer center. More clinical trials are likely to be available at comprehensive cancer centers. It is important to realize that there are pros and cons relating to seeking care at either a local community hospital or a comprehensive cancer center. In determining which treatment institution is best for you, there are a number of questions you might want to ask your health care team. In addition to those questions listed in the table on page 31, you might want to ask your oncologist how many cases of this disease he or she has treated, as well as how many cases of pancreatic cancer have been treated at the hospital where he or she is on staff. This is an impor- Myth In developing treatment strategies for pancreatic cancer, the only concern is shrinking the tumor. Fact There are many factors to consider in developing new treatments. In cancer therapy, shrinking the tumor is certainly one of the main goals, but preserving good quality of life is also an important issue. Quality of life issues are evaluated through the combination of physical and subjective information provided by patients. This information is gathered through questionnaires that ask patients how well they are performing in certain areas, including physical, functional, psychological, social, and sexual activities, and at work.

30 32 Myth Patients receiving radiation therapy should avoid physical contact with friends and family because of possible radioactivity. Fact The form of ray energy used to treat pancreatic cancer does not linger in the body. There is no reason to avoid physical contact with others. tant question because pancreatic cancer is not a very common disease. Your oncologist and health care team will be able to help you decide which type of health care institution is best for you, depending on your individual situation. There are resources on the Internet that can help give you a good sense of the distance from your home to a particular cancer center. For a fairly full list of community centers, the American Cancer Society has a searchable database. (Please refer to Appendix 1). Furthermore, the National Cancer Institute through the National Institutes of Health has identified a group of institutions in the United States as Comprehensive Cancer Centers (Please see Appendix 2.) SURGERY Surgery for adenocarcinoma of the pancreas is offered only to patients whose tumor is localized and who can tolerate a major operation, including prolonged anesthesia. As noted earlier, potentially resectable pancreatic cancer is defined by no evidence of the tumor outside of the pancreas, demonstration of normal blood vessels near the pancreas, and no evidence of spread to distant sites. It is important to note that in some comprehensive cancer centers, if a pancreatic tumor has only involved the superior mesenteric vein and there is no encroachment of the arteries, the tumor might still be considered resectable. Your doctor can explain these special situations to you. If the above criteria are used, only about 15% to 20% of persons diagnosed with pancreatic cancer will be determined to be eligible for surgery. In these cases, surgical resection, or removal, of the tumor from the pancreas and removal of select surrounding tissues gives the best chance for long-term remission. In general, this surgical approach offers a better overall prognosis compared to medical therapy. This is one of the reasons a lot of attention is given to the staging/ preoperative tests to select patients who are good candidates for surgery. Moreover, these tests help the

31 33 surgeons avoid offering surgery to patients who are already quite ill and who would not be likely to benefit from a major operation. Surgery to remove a tumor can take several forms, depending upon the size and location of the tumor and the stage of the cancer: Whipple procedure: In a Whipple procedure, the surgeon will remove the head of the pancreas, part of the small intestine, and some tissue around it. This is typically performed in patients who have tumors that are located in the head of pancreas or in regions adjacent to the head of the pancreas. Often enough of the pancreas is left in the body for it to continue producing digestive juices and insulin. Total pancreatectomy: In this operation, the entire pancreas, part of the small intestine and stomach, the bile duct, gallbladder, spleen, and most of the lymph nodes in the area are removed (see Figure 1 on page 12). Because the entire pancreas has been removed, the patient becomes dependent on insulin injections, just as with someone who has diabetes. As part of postoperative treatment, a patient who has had a total pancreatectomy will need to learn about diabetic care and supplemental oral pancreatic enzyme use with meals. Distal pancreatectomy: In this operation only the tail of the pancreas is removed. All of the surgical techniques including the Whipple procedure are complicated operations. The region of the body where the pancreas is located has many important structures nearby and is complicated anatomically. Furthermore, individual variations are frequent among the different blood vessels and ducts in the area. However, one of the great successes in the treatment of cancer of the pancreas has been the improvement in surgical technique related to the Whipple procedure. At most major cancer centers in the United States, the operative mortality, that is the death rate associated with surgery, related to the Whipple procedure has been reported to be less than 1%. Therefore, if surgery is recommended, it is important to seek referral to a high-volume cancer center, I had friends and relatives who had cancer years ago. They told me stories of how sick they were during treatment. I was pleasantly surprised to see how things have changed. The side-effects were actually quite manageable.

32 34 Myth Patients suffer a great deal of nausea and vomiting with chemotherapy. Fact With the recent development of new antinausea drugs, many patients receiving chemotherapy for pancreatic cancer have little or no nausea and vomiting. This class of drugs works by blocking receptors in the brain that bring about nausea and vomiting and includes ondansetron (Zofran), granisetron (Kytril), and dolasetron (Anzemet). I know chemotherapy can have side effects, but I want every chance to fight this cancer. that is a cancer center that has performed a large number of these procedures Despite these advances, recovery can be a difficult process for some patients. Up to one-third of patients can have serious complications following surgery. These include the development of fistulas (false channels) and leakage from the site of bowel reconnection. The placement of surgical drains has reduced the incidence of these kind of complications. Furthermore, when all or part of the pancreas is removed, a person with pancreatic cancer may no longer be able to produce enough pancreatic juices and hormones. As a result, problems with digestion are likely to occur. An appropriate diet and medication will often be prescribed to help relieve the unpleasant symptoms created by surgery, such as diarrhea, pain, and cramping. Patients who can no longer produce enough insulin may develop diabetes, which can be treated by injections of insulin to replace what the pancreas is no longer producing. In some cases, during an operation, it is determined that the cancer is too advanced to make a surgical resection a good choice. In this situation, certain palliative procedures may be offered. Palliative procedures will not lead to a cure of the cancer itself but may help to treat the symptoms of the disease and improve the patient s quality of life. If the cancer is blocking the main bile duct, causing bile to build up in the gallbladder, biliary bypass surgery may be performed in which the gallbladder or bile duct is cut and the surgeon attaches it directly to the small intestine. Other approaches to this problem include using internal or external tubes, or stents (see Figure 6C on page 23), that may be inserted into the body. These stents allow excess bile to drain to a tube outside the body or directly to the small intestine. These internally draining tubes are placed using endoscopy and specialized devices that can be managed by specially trained gastroenterologists. If the cancer is blocking the flow of food from the stomach, the stomach may be sewn to the small intestine by a procedure called a gastrojejunostomy. This will enable the patient to con-

33 35 tinue to eat normally. Similarly, endoscopically placed stents are capable of relieving bowel obstruction too. Adjuvant and Neoadjuvant Therapies: Because other therapies are often discussed with surgery, there are two principles that need to be introduced at this time. The terms adjuvant and neoadjuvant therapy do not refer to a specific treatment, but generally refer to additional therapy given before or after surgery. Adjuvant therapy is treatment given after surgery, such as chemotherapy and/or radiation therapy to help augment the effects of surgery and help eliminate microscopic malignant cells. Neoadjuvant therapy is given before surgery. For potentially resectable pancreatic cancer, the purpose of neoadjuvant therapy is to shrink tumors so that they can be more completely removed by surgery. Some patients who receive neoadjuvant therapy will also have adjuvant therapy after surgery. Chemoradiation: For the past 15 years, it has been fairly common practice in the United States to give the chemotherapy drug fluorouracil, also known as 5-FU, plus radiation as adjuvant therapy after a Whipple procedure. This is called adjuvant chemoradiation. This practice has been based on the results of a landmark study in 1985 which showed that there was a survival advantage that was almost doubled for patients who received such therapy compared to those who did not. However, this practice remains controversial because other studies have been less convincing in regard to the overall benefit of adjuvant chemoradiation. In addition, many patients who struggle to regain their health after surgery are unable to tolerate chemotherapy and radiation. There is an ongoing clinical trial to determine whether the drug gemcitabine (Gemzar) holds any advantage as compared to the traditional way of giving adjuvant chemoradiation. The use of neoadjuvant therapy is also controversial. According to some experts, chemoradiation may convert a fraction of patients with pancreatic cancer that is apparently locally unresectable to resectable. The neoadjuvant therapy changes the status of these patients by shrinking their tumors and enabling them Myth Patients go bald with chemotherapy. Fact Although certain chemotherapy agents cause hair loss, many agents are not associated with this side effect. Hair can regrow after stopping treatment.