The appendix is a part of the gastrointestinal system. It is a pouch-like structure that connects the small intestine with the large intestine, and it is located on the right side of the lower abdomen. The function of the appendix is not known, but it is believed to play a role in the immune system. Several types of cells are present in the appendix. These include epithelial cells, goblet cells, and hormone-producing cells.
Different types of cells in the appendix have a prespecified rate of division. However, due to genetic mutations, information related to the rate of division is either altered or deleted. These mutations may result in the uncontrolled division and growth of appendix cells, leading to the formation of tumors. This condition involving uncontrolled growth and division of appendix cells is called appendix or appendiceal cancer.
Appendix cancer is rare and affects about 1 to 2 people per million people. The condition is commonly diagnosed in people between the ages of 50 and 55. However, it may occur at any age. Further, there has been a reduction in the age of diagnosis during the recent decade. The condition is often diagnosed incidentally when the appendix is removed or the person undergoes an imaging evaluation for some other condition. The condition is usually diagnosed late; almost one-third of the cases are diagnosed after metastases.
Appendix carcinoma can arise from different appendix cells, and it is classified into different types based on the type of cell from which it arises. Following are the different appendix cancer types:
It is a type of neuroendocrine tumor, and the most common type of appendix cancer. These tumors account for almost 50% of all appendix tumors. These tumors are relatively more common in women than in men. If diagnosed at an early stage, carcinoid tumors have a favorable prognosis. The initiation of carcinoid tumors of the appendix occurs in the hormone-producing cells.
Adenocarcinoma of the appendix initiates in the lining of the appendix. The different types of appendiceal adenocarcinoma include:
It is the second most common type of appendiceal cancer, the first being carcinoid tumors. The cancer starts in the appendix lining and produces a jelly-like substance known as mucin. Mucin may assist in the spread of mucinous adenocarcinoma to other body parts. The condition is often diagnosed after metastasis to the abdominal cavity lining. The severity of these tumors is graded based on the involvement of mucosa, i.e., mucinous adenoma, low-grade appendiceal mucinous neoplasms, and high-grade mucinous adenocarcinoma.
Colonic-type adenocarcinoma is also known as intestinal-type adenocarcinoma. These tumors account for 10% of all the appendix tumors. This cancer type often starts at the appendix base. These are similar to colorectal tumors and are presented with various similar symptoms.
These are aggressive types of epithelial tumors. Almost 60% of signet ring cell adenocarcinoma cases are diagnosed after they are metastasized to distant sites. These are rare tumors. When these cells are viewed under the microscope, they have a look-alike signet ring inside them. These cells store and secrete a large amount of mucin.
It is a rare type of tumor of the appendix. It is often diagnosed incidentally while routinely managing acute appendicitis. The condition is less aggressive than adenocarcinomas but more aggressive than conventional appendiceal cancers. It is usually diagnosed in people in their 50s and 60s and has a similar incidence in men and women. Patients with this condition experience abdominal pain and the presence of abdominal mass.
It is a rare tumor characterized by changes in the epithelium of the appendix. Patients with mucinous cystadenoma have a marked distension in the lumen of the appendix with mucin. The symptoms are similar to those of acute appendicitis. The condition is usually diagnosed incidentally during surgery or imaging. Approximately 25% of the patients with mucinous cystadenoma are asymptomatic.
Paraganglioma of the appendix is rare. The condition may occur anywhere in the GI tract, but predominantly in the duodenum. These are usually considered benign but may potentially invade the lymph nodes and distant organs.
The TNM classification is used to determine the severity or extent of appendix cancer. Determination of the stage of appendiceal cancer may help in developing treatment strategies and predicting the prognosis. The TNM classification suggests the size of the tumor (T), its invasion of the lymph nodes (N), and the spread of the tumor to other organs (metastasis, M).
This stage is known as carcinoma-in situ. The cancerous tumor in the appendix is localized, i.e., the tumor is confined to the appendix and has not spread outside.
Stage 1 appendix tumor invades the inner layer of the appendix but does not spread to the lymph nodes or distant organs.
Stage 2A appendiceal cancer spreads to the fatty or connective tissue of the appendix. Stage 2B appendiceal cancer invades the lining of the appendix. Stage 2C appendiceal cancer spreads to nearby organs, such as the rectum or colon. The cancer does not invade lymph nodes or other body parts.
Stage 3A appendiceal cancer invades the inner appendix layers and 1–3 surrounding lymph nodes. Stage 3B appendiceal cancer invades the nearby appendix tissue or appendix lining and 1–3 nearby lymph nodes. Stage 3C appendiceal cancer invades ≥ 4 lymph nodes. However, the cancer has not invaded other body parts.
Stage 4A appendiceal cancer spreads to abdominal cavity organs and may or may not spread to regional lymph nodes. Stage 4B appendiceal cancer invades abdominal organs and lymph nodes, but the cells are poorly differentiated. Stage 4C appendiceal cancer reaches distant organs, such as the lungs.
Appendix cancer may not cause any symptoms in the early stages. Also, in most cases, appendix cancer is diagnosed when the organ is removed, assuming the patient has appendicitis.
Becoming aware of the different signs and symptoms of appendix cancer can help one receive the right care at the right time.
Appendix cancer may affect any person of any age. However, it is observed that increasing age is an important risk factor for appendix cancer. Individuals aged 50 and above are mainly affected by appendix cancer. Women are at greater risk of developing appendix cancer than men. Appendix cancer is relatively more common in people who smoke and use tobacco products than in those who do not. Further, people with underlying medical conditions, such as pernicious anemia, atrophic gastritis, and Zollinger-Ellison syndrome, are more vulnerable to appendix cancer. Further, appendix cancer may also occur in people with a family history of multiple endocrine neoplasia type 1 (MEN1).
Signs and symptoms of appendix cancer are:
Abdominal discomfort and pain may be one of the early signs of appendix cancer. As the tumor grows, it exerts pressure on the nearby tissues, and this can cause pain. The patients may also have abdominal pain during the advanced stages of appendix cancer when the tumor metastasizes to other organs in the abdomen region.
Appendicitis is a condition characterized by blockage and infection of the appendix. Appendicitis may also be a sign of appendix cancer. Appendicitis may cause symptoms like acute pain in the right lower abdomen, loss of appetite, increased pain during coughing or walking, and nausea and vomiting.
Appendicitis may occur when the tumor obstructs the lumen of the appendix. It may also occur when there is an excessive accumulation of mucin in the appendix (mucinous neoplasms), resulting in appendix rupture.
Patients with appendix cancer and underlying appendicitis may also experience bloating. Bloating may be due to swelling of the abdominal tissues surrounding the appendix due to invasion of the tumor cells.
Patients with appendix cancer may also develop altered bowel habits. They may have diarrhea, constipation, or both. As cancer increases the size of the appendix, it starts affecting the surrounding abdominal organs, such as the rectum and colon. Further, when the tumor invades the gastrointestinal tract, it may obstruct the tract, leading to constipation and other gastrointestinal symptoms.
Appendix cancer may also cause pelvic pain. It may indicate advanced appendix cancer. When the tumor invades the pelvic organs and starts pressurizing the nerves and tissues, the patients experience pain in the pelvic region. In some cases, the pain is severe.
Patients with appendix cancer may also have an accumulation of fluid in the abdomen. Physical examination reveals abdomen swelling and tenderness that may indicate an advanced stage of the disease.
Nausea and vomiting are the other symptoms of appendix cancer. They most commonly occur when appendix cancer invades the intestine and causes obstruction. These obstructions of the gastrointestinal tract cause episodes of nausea and vomiting.
There is also an association between appendix cancer and infertility. A case report found that removing the appendiceal mass in women with primary infertility resulted in normal conception and delivery.
Patients with carcinoid tumors may experience abdominal pain, swelling, bloating, and distension.
The most common symptoms of appendiceal adenocarcinoma are increased abdominal girth and vague abdominal pain.
Symptoms of goblet cell carcinoid tumors of the appendix include the presence of abdominal mass and abdominal pain.
Symptoms of mucinous adenocarcinoma include nausea and vomiting, acute appendicitis, abdominal pain, weight loss, and palpable mass.
Signet ring cell carcinoma symptoms include nausea, vomiting, abdominal pain, and fever. Some patients may also experience weight loss and altered bowel habits.
Appendix cancer causes are:
Smoking and tobacco are potential appendix cancer causes. The cells of the appendix may potentially undergo mutation due to the chronic effects of the carcinogens present in tobacco.
Certain underlying medical conditions also cause appendix cancer. These include atrophic gastritis, pernicious anemia, and Zollinger-Ellison syndrome. A family history of multiple endocrine neoplasia type 1 (MEN1) may also cause appendix cancer in some patients.
Women are more vulnerable to developing appendix cancer than men. The reason for this gender bias remains unknown.
Appendix cancer most commonly occurs in older adults. It is rare in children. The condition most commonly affects individuals over the age of 50.
Doctors recommend several tests for appendix cancer diagnosis. Along with diagnosis, these tests help in staging the disease and devising an appropriate treatment plan. Based on the disease’s stage and other factors, the treatment plan may comprise one treatment or multiple treatments. Multiple treatment options available for appendix cancer include surgery, radiation therapy, chemotherapy, immunotherapy, and targeted therapy.
The following are the different test methods available for appendix cancer diagnosis:
Patients should pay attention to symptoms related to the gastrointestinal system and should consult with experienced gastroenterologists or physicians. The doctor will comprehensively evaluate the patient's overall health status and detect the cause of the symptoms. The doctor may ask the patient about the starting and progression of the signs and their severity.
The doctor may also ask about smoking history, as it increases the risk of appendix cancer. Further, a medical history of atrophic gastritis, pernicious anemia, and Zollinger-Ellison syndrome may also be evaluated, as these diseases may enhance appendix cancer risk. The doctor may also ask the patients about their family history of appendix cancer.
No blood test confirms the diagnosis of appendix cancer. However, blood tests may help determine the patients' overall health status. As patients with appendix cancer present with symptoms similar to appendicitis, the doctor may recommend the patients undergo tests for neutrophil percentage, total leukocyte count, and C-reactive protein (CRP) concentration. There are specific tumor markers present in the blood that may indicate appendix cancer. These include CA-125 (cancer antigen 125), CEA (carcinoembryonic antigen), and CA 19-9 (cancer antigen 19-9).
Imaging tests play a vital role in obtaining additional information about the tumor, including its size, exact location, and its extent. These tests also help specialists plan customized treatment plans, monitor the treatment response shown by patients, and detect recurrences.
A CT scan helps in detecting the presence of a tumor and its shape, size, and location in or surrounding the appendix. The image quality of the CT scan can be enhanced by using a contrast agent. A CT scan involves the use of X-rays to obtain images. A CT scan is also used to guide the needle during the biopsy.
Magnetic resonance imaging assists in identifying incidental appendiceal adenomas and extra-appendiceal mucin. It can also differentiate between large mucinous neoplasms and retroperitoneal and intraperitoneal conditions. MRI is preferred for the staging and follow-up of appendix carcinoma due to its higher specificity and sensitivity.
Ultrasound is one of the primary imaging tests recommended for detecting gastrointestinal tract diseases. It involves sound waves, unlike other imaging techniques that use radiation. Ultrasound is highly reliable for detecting surrounding inflammation in patients with appendicitis. It is especially useful in obtaining images of the appendix in children with less abdominal fat and thin musculature.
A PET scan helps detect localized and metastatic tumors of the appendix. The scan uses radioactive sugar analogs taken up by the metabolically active cells, including the cancer cells. A study reported that PET/CT scans detect the fluid-filled cystic appendix with low-grade uptake. It is recommended for staging appendix cancer.
As an important appendix cancer detection test, a biopsy involves obtaining samples of abnormal cells and examining them in the laboratory under a microscope. A biopsy may serve as a confirmatory test for diagnosing appendix cancer.
As an appendix cancer test, it uses an endoscope to view the internal tissues of the appendix. An endoscope is a thin, long tube with a camera fitted at the end that transmits the images of the appendix on the monitor. The doctor takes the samples from the abnormal areas of the appendix with the help of image guidance.
Surgery is considered a biopsy method when the endoscopic method fails to obtain the appropriate number of tissue samples. The surgeon makes a long incision in the abdomen to expose the appendix during surgery. The surgeon then collects samples of the tissues for further evaluation.
Laparoscopy is a minimally invasive procedure for performing a biopsy of the appendix. It uses a laparoscope, a thin, long tube with an attached camera. The surgeon makes a small incision in the abdomen and inserts the laparoscope. The images of the internal tissues of the appendix are transmitted on the monitor. After evaluating the images, the surgeon makes small holes to insert the instruments to take the tissue samples.
The patients suspected of appendix cancer undergo a pathology examination of the appendix. Pathological examination helps in determining the cause of the symptoms. The most common condition mimicking the symptoms of appendix cancer is acute appendicitis.
Following are the appendix cancer treatment options:
Surgery is a preferred primary treatment for all types of appendix cancer except goblet cell adenocarcinoma. The procedure is used in early-stage cancer to remove the cancerous tissues. As the disease progresses, surgery is often combined with other treatment approaches, such as radiation therapy and chemotherapy, for better outcomes.
In advanced stages, such as stage 4 appendix cancer, surgery may be performed to ease the pain and discomfort associated with the disease and improve the quality of life for patients.
An appendectomy is a procedure that involves the removal of appendix cancer. Apart from treating appendix cancer, it is also performed as an emergency surgery in patients diagnosed with acute appendicitis in case of an imminent danger of appendix rupture. This procedure may be performed through open surgery or laparoscopic surgery.
Hemicolectomy involves the removal of one side of the colon. As a part of appendix cancer treatment, the surgeon removes a portion of the colon present near the appendix. It is performed when the neuroendocrine tumor is larger than 2 cm or when the cancer diagnosed is not a neuroendocrine tumor. The lymph nodes and blood vessels are removed during the hemicolectomy procedure.
Cytoreductive or debulking surgery is performed in the advanced stages of appendix cancer, i.e., when the tumor spreads to the surrounding organs. During the debulking surgery, the surgeon removes most of the tumor and surrounding fluid. The surgeon also removes the parts of organs that are inseparable from the malignant cells, such as parts of the gallbladder, small intestine, uterus, ovaries, spleen, and abdominal cavity lining.
The procedure that involves the removal of the peritoneum is also known as peritonectomy. It is an aggressive treatment, and several surgeons are against performing this surgery on patients diagnosed with low-grade, slow-growing appendix cancer. It is also considered a form of debulking surgery as it removes most of the cancer cells. However, the surgery is complex and may have significant side effects.
Chemotherapy is an important appendix cancer treatment option. It uses various drugs, usually in combination, to kill cancer cells or prevent their growth. Chemotherapy may be done in combination with surgery or radiation therapy.
In intraperitoneal chemotherapy, the drugs are delivered directly into the abdominal cavity. It improves efficacy and lowers side effects. Intraperitoneal chemotherapy is usually done after debulking surgery to remove the remaining cancer cells. Sometimes, the temperature of the drug solution is raised to improve penetration. This procedure involving heating the drug solution is known as hyperthermic intraperitoneal chemotherapy (HIPEC).
Systemic chemotherapy is the procedure that involves the administration of the drug into the systemic circulation. This procedure is used when there is a spread of cancer to other organs. The drug is delivered either orally or through injection. Chemotherapy is given in cycles and involves a resting period between two consecutive cycles. Depending on the dose administered and overall patient health, patients may experience various side effects, including fatigue, hair loss, nausea and vomiting, loss of appetite, and an increased risk of infection.
Radiation therapy is a method of treating appendix cancer that kills the cell through high-energy radiation. Radiation therapy is delivered in multiple sittings or sessions spread over a predetermined period.
There are specific proteins or genes specific to cancer cells that are vital for the growth and development of cancer cells. As one of the latest appendix cancer treatment options, targeted therapy targets these proteins or genes and interferes with the proliferation of tumor cells. Targeted therapy has relatively fewer side effects compared to conventional chemotherapy.
Clinical trials are recommended for patients who have exhausted all their treatment options. Clinical trials help patients access new drugs, new treatment methods, etc. that are not available on the wider market. Some patients find clinical trials helpful for their condition.
Those wanting to be a part of clinical trials should talk to their treating doctor for more information and appropriate guidance.
As a top cancer hospital in India, HCG Cancer Center is one of the most advanced centers with ultramodern facilities for diagnosing and managing appendix cancer. There are several advantages to choosing HCG for appendix cancer. These include extensive experience and specializations of the medical and paramedical staff, multidisciplinary care, highly sophisticated diagnostic tools, conventional and modern treatment options, support services, and the availability of second opinion solutions.
The exact cause of appendix cancer is unknown. However, certain factors that increase the risk of appendix cancer have been identified, and they are termed “risk factors.” It is possible to modify one’s risk of appendix cancer by adopting certain preventive measures.
Refraining from tobacco and alcohol consumption, consuming a balanced diet, exercising regularly, and maintaining a healthy weight are a few measures that can help reduce the risk of appendix cancer.
The following are some of the common appendix cancer risk factors:
Age is one of the most dominant and consistent appendix cancer risk factors. The risk of appendix cancer increases as a person ages. The incidence of appendix cancer in children is rare. People over 50 are most affected by appendix cancer. Historically, appendix cancer has been a rare condition. However, recent studies have reported an increasing incidence of this cancer. Further, studies have also reported that the trend for diagnosing appendix cancer at an earlier age has increased over the last ten years.
There are reports of gender bias in the occurrence of appendix cancer. Certain studies have reported that the risk of developing all types of appendix cancer is almost equal in men and women, except for malignant carcinoid tumors, for which women are at a higher risk.
Smoking and using tobacco products increase the risk of various cancers, like lung cancer and appendix cancer, compared to people who do not use tobacco products and do not smoke. The chronic exposure of the tissues in the appendix to the chemicals present in tobacco can lead to mutations in these cells and eventually, the development of cancer.
It has been reported that almost 4% of all cancers are attributed to obesity, and therefore, obesity is one of the appendix cancer risk factors. People who are obese are also at increased risk of dying of cancer, which alters the choice of treatment. It has also been found that the preferred site for carcinoid tumors is the appendix in patients with obesity.
Patients with diabetes have a higher risk of developing several types of cancer. Studies have reported that cancer and diabetes are more frequently diagnosed in the same individuals, even after age adjustments. Although the exact reason for the simultaneous occurrence of both diseases is unknown, it may probably be due to similar risk factors for diabetes and cancer, such as smoking, obesity, aging, and physical inactivity.
Radiation therapy involves guiding high-energy radiation on the cancer cells. However, in some cases, healthy cells are also affected. When radiation therapy is used to treat cancers of the gastrointestinal tract or pelvic organs, the cells of the appendix may also be exposed to radiation. It increases the risk of appendix cancer.
The answer to the question, “How to prevent appendix cancer?” lies in the appendix cancer prevention measures listed below:
Certain people, such as older adults and people with certain medical conditions, are at increased risk of developing appendix cancer. It is important to undergo regular medical check-ups to understand the increased risk of developing appendix cancer. Do not ignore any of the symptoms that cause concern, and get them checked immediately to rule out serious conditions.
A healthy diet reduces the overall risk of developing cancer. One possible mechanism is strengthening the immune system, which identifies and kills the abnormal cells. People should eat a healthy diet comprising whole grains, lean protein, and fresh vegetables and fruits. A healthy diet also reduces obesity, a risk factor for various cancers.
Regular physical activity may increase the chances of appendix cancer prevention. Physical activity enhances the immune system and manages stress levels. Further, it helps maintain a healthy weight and reduces the risk of obesity.
Refraining from tobacco and limiting the consumption of alcohol may aid in potential appendix cancer prevention. Quitting smoking or not starting smoking helps reduce the risk of mutations in the appendix cells due to exposure to carcinogens.
People who are overweight or obese are at increased risk for cancer. It is important to maintain a healthy weight. A healthy weight can be obtained by eating a balanced diet, avoiding processed foods, and performing regular physical activity.
Several underlying medical conditions increase the risk of appendix cancer. These conditions include atrophic gastritis, pernicious anemia, and Zollinger-Ellison syndrome. Diagnosing and appropriately managing these conditions is important to reduce the risk of appendix cancer.
Studies have reported an association between appendix cancer and genetics. People with a family history of appendix cancer or who are suffering from multiple endocrine neoplasia type 1 (MEN1) syndrome should undergo genetic counseling and testing to determine their risk of developing appendix cancer.
People, especially those at increased risk for appendix cancer, should know various symptoms of appendix cancer, such as abdominal pain, nausea, loss of appetite, and vomiting. Never ignore these symptoms and book an appointment with a healthcare provider.
Medical advice should be followed at all levels. It may be related to managing underlying medical conditions that increase the risk of appendix cancer. It may also be related to the prevention of cancer recurrence after the completion of treatment.
Appendix cancer initiates in the appendix. The different appendix cancer types include carcinoid tumor (the most common appendix cancer), appendiceal adenocarcinoma, mucinous adenocarcinoma, colonic-type adenocarcinoma, signet-ring cell adenocarcinoma, goblet cell carcinoid tumor, and paraganglioma. Stage four appendix cancer is the most advanced stage of appendiceal cancer.
