It is the ACPMP Research Foundation’s goal to be a resource to everyone who visits our site.
We’ve provided answers to questions commonly asked by those diagnosed with Pseudomyxoma Peritonei (PMP), Appendix Cancer and related Peritoneal Surface Malignancies (PSM), and their caregivers. If you don’t find an answer to your question here, feel free to email us at firstname.lastname@example.org.
For a glossary of commonly used terms in discussing AC/PMP, please view our AC/PMP Glossary.
The following is provided for informational purposes only. It is not medical advice. Your diagnosis, medical questions, and treatment plan are issues to be handled directly with your doctor.
Appendix cancer is cancer that starts in the cells lining the inside of the appendix. There a number of different types of cancers of the appendix. The different types are determined by which type of cells in the appendix become cancerous and what the cells look like under the microscope. The different types are associated with different behaviors (i.e. likelihood of spreading to other organs or other parts of the body, rate of growth, ability to be completely removed with surgery etc.) and therefore the types of treatment that are offered. Appendix cancers are the most common cause of pseudomyxoma peritonei (or “PMP”) (see below).
- Low grade mucinous neoplasms of the appendix (formerly known as mucinous cystadenomas) are non-cancerous tumors of the appendix. This means that they do not have any potential to spread to lymph nodes or through the blood stream to other organs. However, due to the flimsy nature of the appendix wall, if the appendix ruptures or the tumor grows through the wall, neoplastic cells may spread in the abdominal cavity, because the tumors are created by mucin-producing cells that line the inside of the appendix, and a mucinous substance (a gelatinous material) may accumulate in the abdomen. The build-up of mucin (also known as pseudomyxoma peritonei or PMP) can eventually lead to abdominal pain, bloating, and/or bowel obstructions.
- Adenocarcinomas are cancerous tumors created by gland-forming cells that line the inside of the appendix. They are also frequently mucin-producing cells and can result in accumulated mucin or PMP in the abdomen, but may also spread to other parts of the body, other organs in the abdomen or to the local lymph nodes. Adenocarcinomas are usually graded based on their microscopic appearance as either low-, moderate – or high-grade tumors. They can also be categorized by their differentiation (meaning how closely they resemble a normal cell). Well-differentiated and low-grade cancers tend to be slower growing and less likely to spread to other part of the body compared with high-grade or poorly-differentiated adenocarcinomas.
- Signet-ring cell adenocarcinomas (so called because of the physical appearance of the cells under the microscope) are a subset of adenocarcinomas of the appendix. Signet ring cell cancers are generally considered more aggressive than other adenocarcinomas because they are faster growing, more likely to spread to local lymph nodes and harder to completely remove at the time of surgery.
- Adenocarcinoid cancers (also known as Goblet Cell Carcinoids) are a hybrid tumor of both adenocarcinoma and a neuroendocrine (or carcinoid cancer) (see below). The expected behavior of adenocarcinoid tumors tends to follow that of the adenocarcinoma portion of the tumor. Consequently, treatment recommendations follow those for other types of appendiceal adenocarcinomas. They are generally considered to be more aggressive than low-grade or moderately-differentiated adenocarcinomas of the appendix, but not as aggressive as poorly-differentiated or signet ring cells adenocarcinomas. Learn more about Goblet Cell Carcinoid by reviewing the NORD rare disease report for Goblet Cell Carcinoid prepared by ACPMP Professional Advisory Board member Dr. Laura Lambert.
- Neuroendocrine (Carcinoid) tumors. Neuroendocrine tumors arise from a subset of cells lining the appendix known as neuroendocrine cells. They do not make mucin and therefore do not cause PMP. They are generally considered to be slow growing and have a very different behavior than adenocarcinomas of the appendix.
Learn more about appendix cancer by reviewing the NORD rare disease report for Appendiceal Cancer and Tumors prepared by ACPMP Professional Advisory Board member Dr. Laura Lambert, and review the Appendix Cancer: Stages and Grades guide at Cancer.net.
The term Pseudomyxoma Peritonei has been and still is used to mean a number of different things. This has created much confusion for patients and physicians. Efforts are underway to better define PMP in the medical literature so that there is a better understanding of the term and communication between physicians and patients. Generally speaking, PMP is a rare condition characterized by the presence of mucin in the abdominal cavity. A number of types of tumors can cause PMP, but the most common cause is appendix cancer – including low grade mucinous neoplasms of the appendix. Learn more about PMP by reviewing Dr. Paul Sugarbaker's report on PMP in the NORD Rare Disease Database.
Peritoneal carcinomatosis is the term for cancers that have spread in the abdominal cavity. PMP is different from peritoneal carcinomatosis in that it refers only to mucinous fluid in the abdominal cavity. It is agreed that the most important aspect of either peritoneal carcinomatosis or PMP is the classification of the cancer cells in the carcinomatosis or any cells that are present in the PMP. This classification has changed over time (and continues to evolve), but the generally accepted spectrum of classifications of carcinomatosis and PMP are as follows:
- Mucinous Carcinoma Peritonei Low Grade (MCP), or Disseminated Peritoneal Adenomucinosis (DPAM); this refers specifically to the type of cells present in PMP.
- “Hybrid” or Peritoneal Mucinous Carcinomatosis with Intermediate Features (PMCA-I). PMP may be present but there is an obvious cancer cell component.
- Mucinous Adenocarcinoma or Mucinous Carcinoma Peritonei High Grade or Peritoneal Mucinous Carcinomatosis (PMC/PMCA) with or without the presence of signet ring cells. PMP is often not present with these cancers.
Estimates vary, but all tend to be within the category of “extremely rare.” PMP was once thought to be diagnosed in about 1,000 people world-wide each year. In other words, the lifetime odds of being diagnosed with PMP were thought to be about one in a million. However, specialists now believe it is more common than once thought, closer to one person diagnosed per 500,000 people per year.
Recent research indicates that the incidence of appendix cancer may be as high as 10 people diagnosed per million per year. The number of reported cases has increased over the past decade, but it is not certain whether incidence of appendix cancer is actually increasing or the rate has changed due to likely misdiagnosis or misclassification in the past.
PMP is listed among the rare or "orphan" diseases acknowledged by the National Association of Rare Disorders (NORD). An orphan disease is generally considered to have a prevalence of fewer than 200,000 affected individuals in the United States.
Orphan diseases such as PMP have such a low prevalence in the general population that a doctor in a busy general practice is unlikely to see more than one case a year (if any). It also means that most pathologists see the disease infrequently and may misinterpret cell pathology, resulting in an incorrect diagnosis. Patients would benefit from improved awareness and diagnostic methods in the medical community through earlier detection and treatment of these diseases.
There are a number of theories about the origins of PMP. It is generally accepted that appendix cancer is the most common source of the tumors that cause PMP, but there is no known cause of appendix cancer. Generally, cells from a mucinous tumor (usually in the appendix) leak into the abdominal cavity and implant on the peritoneum or other abdominal organs. These tumors replicate and produce a mucinous byproduct that spreads throughout the abdomen.
Although highly unusual, specialists and researchers have cited the ovary, stomach, colon, pancreas and other abdominal organs as other potential sites of origin for PMP. It is not known at this time when or why some tumors in those organs would cause PMP while others do not.
PMP affects men and women almost equally. The age at diagnosis ranges from late teens to late in life, with most individuals diagnosed in their 40's and 50's.
It is generally thought that there is no genetic (familial) link to PMP. Risk factors that might predispose an individual to develop PMP are unknown.
Many patients lack clearly defined symptoms until the disease has reached a relatively advanced stage. The following are some of the commonly reported symptoms:
- Increased abdominal girth
- Pain/discomfort in the abdominal region—can be a dull ache or sharp pains similar to appendicitis
- Hernia symptoms—PMP is often initially diagnosed as a hernia, especially in men
- In women, symptoms of an ovarian cyst or tumor—PMP is often initially misdiagnosed as ovarian cancer
- Ascites (fluid) buildup in the abdominal cavity
For many patients, appendix cancer and/or PMP are discovered during an unrelated surgical procedure at which time the surgeon observes the mucinous tumors or “studding” on the peritoneum or abdominal organs. The following diagnostic tests are also commonly used in diagnosing appendix cancer and PMP:
- CT scan of the chest, abdomen and pelvis. Note that CT scans are not perfect pictures, and for some patients visible signs of tumor are not present on a CT scan. CT scans also require the judgment of a radiologist who can interpret the scan to identify the signs of appendix cancer or PMP such as fluid buildup or tumor “studding”.
- MRI of the abdomen and pelvis. There is a growing interest in the use of MRI of the abdomen and pelvis to diagnose and follow appendix cancers and PMP. Special protocols and expertise at reading MRIs are required to get the maximal benefit of this technology. Like CT scans, MRIs are not perfect pictures and they both require tumors to be big enough to be seen on the images.
- Diagnostic laparoscopy. A thin tube with a camera at its tip is inserted through “keyholes” in the abdomen to observe the abdominal cavity. Again, proper diagnosis depends upon the surgeon performing the procedure. Laparoscopic diagnosis of appendix cancer and PMP presents additional challenges in that failure to follow appropriate protocols may result in the spreading or seeding of tumors. If appendix cancer and/or PMP are suspected, a specialist in the disease should be brought in to take the proper precautions.
- Blood tests (tumor markers). Some tumor markers in the blood have been shown to be indicative of appendix cancer and/or PMP activity, particularly CEA, CA-125, and CA 19-9. Unfortunately, tumor markers are not accurate or indicators for everyone. Some patients will have no elevation in their tumor markers despite having extensive, aggressive tumor.
The treatment of appendix cancer and PMP is determined by the type of appendix cancer and the extent of the tumor (i.e. where it has spread and how much there is). For low-grade mucinous neoplasm and low-grade mucinous adenocarcinomas confined to the abdominal cavity, the most successful treatment is a combination therapy that consists of specialized cytoreductive (tumor removal) surgery (CRS) to attempt to remove all of the visible tumors and affected tissues, followed by localized application of heated intraperitoneal chemotherapy (HIPEC) to eliminate residual microscopic disease.
For many patients this combination therapy is conducted to increase longevity or to relieve some of the symptoms that affect their quality of life. For other patients this combined therapy carries good odds for long-term survival, with the possibility of completely eliminating the disease.
The goal of cytoreductive surgery is to remove all visible tumors in the abdominal cavity. This may require removing some or all of the peritoneum (the lining of the abdominal cavity) and part or all of the organs affected by the tumor. This surgery is typically quite extensive and requires a very experienced specialist. After surgery is completed, the abdominal cavity is washed with HIPEC to remove non-visible or microscopic tumor cells.
Some specialists recommend early post-operative intraperitoneal chemotherapy (EPIC) for approximately three to five days following CRS+HIPEC surgery, providing the patient tolerates it well. In many cases, a specialist will also recommend pre- and/or post-operative systemic (intravenous) chemotherapy (typically using the same types of chemotherapy that are used for colon cancer, such as 5-flourouracil + leucovorin + oxaliplatin or irinotecan, otherwise known as FOLFOX or FOLFIRI, with or without a drug called bevacizumab, also known as Avastin®).
Moderately-or poorly differentiated, or signet ring cell cancers confined to the appendix are routinely treated by surgery to remove the right colon where the appendix originates. This is done to test the lymph nodes in that region for any cancer cells. Cancers that have spread outside the appendix are routinely treated with a combination of systemic chemotherapy and surgery +/- HIPEC depending upon the individual circumstances. Appendix cancer that is caught very early and has not spread beyond the walls of the appendix may not require CRS+HIPEC, but these patients should be monitored very closely by an appendix cancer specialist.
Cytoreductive surgery (CRS) for appendix cancer and/or PMP is a fairly significant procedure that is designed to remove all visible tumors as well as affected tissues and even entire organs. Commonly, the appendix, spleen, gall bladder, female reproductive organs, and omentum are removed. In addition, parts of the small or large intestine may be “resected” (affected pieces removed and the remaining organ stitched or stapled back together). Depending on the location of the tumors around the small and/or large bowels and the extent of surgery required to remove it, a colostomy or ileostomy (surgically bringing an section of intestine up to the skin of the abdominal wall to divert the fecal contents into an appliance or bag attached to the skin) may be necessary as a result of the surgery. The ostomy may be temporary or permanent, depending on individual circumstances.
Surgery can last anywhere from 6-15+ hours. Surgery is then immediately followed by the perfusion of heated intraperitoneal chemotherapy (HIPEC). A chemotherapy drug is administered in this manner to kill cancer cells that are not visible to the human eye. HIPEC typically lasts 90-120 minutes.
Some specialists, though not all, continue intra-abdominal chemotherapy for a period of 3-5 days post-surgery (early post-operative intraperitoneal chemotherapy or EPIC). CRS+HIPEC is a major procedure with a fairly extensive recovery time. Even without complications, the hospital stay can typically last from 10 to 21 days.
Some patients return to work within eight to twelve weeks following surgery, but others require several months to reach a point of “normalcy”.
Full physical recovery can take 6 to 12 months depending upon a patient’s age and general physical condition.
Dr. Paul Sugarbaker pioneered the CRS/HIPEC procedure, is one of the leading appendix cancer/PMP specialists worldwide, has conducted hundreds of these surgeries, and has published extensively about them. Please also visit the websites of the following centers with significant experience offering this treatment including detailed descriptions of the procedure: Mercy Medical Center, Wake Forest Baptist Health, University of Pittsburgh Medical Center, and UC San Diego Moores Cancer Center.
It is highly recommend that appendix cancer and PMP patients seek out a specialist who deals with these conditions on a regular basis. The surgical oncologists on the ACPMP Research Foundation’s Medical Advisory Board are all considered to be specialists with extensive experience treating appendix cancer and PMP. When searching for a specialist to treat appendix cancer and/or PMP, patients should be aware that research studies have concluded that centers offering the CRS/HIPEC procedure reach the peak of the learning curve only after the center has completed 130, 140, 180, or even over 200 of these procedures. For more information on how to find and select a specialist, please visit our Selecting your Specialist page.
We have prepared a list of questions you may want to ask the physicians with whom you consult. It is highly recommended that appendix cancer and PMP patients seek out a surgeon with extensive experience in treating these conditions. Please view Questions for Specialists.
There is presently no consensus in the medical community about the use of systemic chemotherapy and/or radiation in treating appendix cancer and PMP. Some individuals appear to benefit from systemic chemotherapy (typically the higher grade pathologies), while others do not. There are no systemic chemotherapy regimens designed specifically for appendix cancer, so many appendix cancer patients who may benefit from systemic chemotherapy are typically given the same types of chemotherapy that are used for colon cancer such as 5-flourouracil + leucovorin + oxaliplatin or irinotecan, otherwise known as FOLFOX or FOLFIRI, with or without a drug called bevacizumab, also known as Avastin®.
In general, there is no role for radiation in the management of appendix cancer that have spread in the abdominal cavity or PMP. Radiation may be used on an individual basis for example in situation where there is a high risk of recurrence in a localized space or for palliation of symptoms.
Neither systemic chemotherapy alone nor radiation have proven to be curative for appendix cancer or PMP.
In the past, advanced appendix cancer and PMP were considered treatable, but not curable. There are now a growing number of individuals—primarily those whose disease was detected early and with favorable pathology—who have undergone cytoreductive surgery and HIPEC and experienced years of disease-free survival.
Prognosis depends heavily on the pathology of the primary tumor, the stage at which the disease was diagnosed, the degree of cytoreduction achieved during surgery for extensive disease, the general health of the patient, and more. Recent research is also revealing what appears to be a prominent role for the profile of genetic mutations of the tumors in prognosis. In general though, slower growing, low-grade, well-differentiated tumors and cancers tend to have a better prognosis than faster growing, high-grade, and poorly-differentiated or signet ring cell cancers.
CRS/HIPEC has been shown to provide long-term survival in up to 90% of patients with low-grade appendiceal PMP pathology who are properly diagnosed and undergo this treatment early enough in the disease process to offer maximum benefit.
Please note that statistics are not representative of any one individual's experience. It is best to discuss your particular prognosis with your AC/PMP/PSM specialist.
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