Cancer of the Appendix
The appendix is a thin pouch attached to the large intestine in the right lower quadrant of the abdomen. Although exceptionally rare, it is believed that a cancer is suspected to arrive when cells in the appendix change and grow significantly into a mass identified as a tumor. Malignity or benignity will be determined by an examination of the pathologic specimen removed in the operating room.
Years ago, while I was a young intern at the State University Hospital of Haiti (HUEH), I encountered my first case which took us time to diagnose because of the preparation of the slides after the surgical procedure. A patient who was admitted with right lower quadrant pain and benefited from an uncomplicated appendectomy. A young gentleman in his twenties who after discharge from the hospital, failed to return to the outpatient clinic for follow-up. We learned a month later, that pathologic cells were discovered by the pathologist examining the operating room specimen submitted. I have to believe that the outcome was not too favorable because the patient never knew that he had a cancer of the appendix.
I had to wait many years later during my General Surgery Residency at Howard University Hospital to discover that such tumors although rare were perhaps more often discovered than we taught. I have seen since more cases among notably a medical student, a trained general surgeon, a physician-assistant, all victims of such pathology.
It is really when I became chief of Orthopedic Trauma at Bridgeport Yale Health in 1990 that I understood well the seriousness of such pathology. One of my physician-assistants was operated following what appears to be an acute appendicitis and he benefited from an uncomplicated appendectomy via a small McBurney incision at the right lower quadrant of the abdomen. A routine pathology report of the specimen revealed later a carcinoid lesion at the tip of the appendix.
Such result created a panic in the medical staff because surgeons at this time, did not know well how to handle such a lesion. Anyway, the best treatment was offered to the physician-assistant and proper follow-up with laparoscopic evaluation and lavage with an infusion of some type of oncologic medication that I would not be able to remember by name. Unfortunately, our co-worker lost his life, 4 months later, leaving a wife and two daughters in low age. It was devastating to see my young friend leaving this world in spite of all efforts to save his life. All consultations in the best oncologic centers of the country were not sufficient to save him.
It bought me flash-back when a month ago, I learn that a friend whom I grew up with, died in our country with complications from an acute appendicitis. The removed appendix was indeed sent to the pathology department but it took weeks after to know that there was a suspicion of malignancy. The physicians remained silent on the fact and no other actions were taken to approach the recovering patient. Soon, it became too late and my friend succumbed from complications of his surgical procedure. The pathologic findings associated to a simple and acute appendicitis were consistent with an established diagnosis of appendix cancer.
Appendix cancer develops when healthy cells of an appendix grow out of control or mutate forming a tumor. It is generally discovered when an imaging test is ordered for an unrelated condition or when an abdominal exploratory surgery is performed. Smaller tumors are less likely to spread while larger tumors may usually require more aggressive treatment because of their ability to invade the abdomen and seed to other organs…
The appendix is part of the digestive system and can be described as a thin tube-like pouch located on the lower right side of the abdomen near the junction of the large and small intestine. The function of an appendix is unknown but many believed that it may have a role to play in the immune system of a young child. Some anatomists consider it as a vestigial system.
There are different types of Appendix cancer:
1- Carcinoid tumors called also “neuro-endocrine tumors” is a slow growing tumor which count for almost half of all the appendix cancers. These lesions can be present for a long period before being detected or becoming symptomatic. They receive signals from the endocrine system and release hormones.
2- Mucinous Cystadenoma tumors which are benign in appearance but present some lesions called mucoceles which have a precancerous potential to develop low-grade mucinous neoplasms (LAMN). They are non-cancerous tumors which form in the epithelium lining of the appendix. They will not spread in other part of the body if they remain intact but once they perforate or rupture, these neoplasms of the appendix present a rare condition called “Pseudomyxoma Peritonei” (PMP).
3- Mucinous Adenocarcinomas of the Appendix seems to begin on the cells lining the inside of the appendix but are generally treated as a colorectal cancer and generally present with the same symptoms. This is the second most common type of appendix cancer. They release a component of mucus called “mucin”. There is also a very rare subset which tend to be more aggressive called “Signet ring cell adenocarcinoma” because of the appearance of the cancer cells (signet) under the microscope. These “signet cells” secrete and store a large amount of mucin.
4- Finally, a Goblet cell adenocarcinoid or carcinoma presenting these two components of an adenocarcinoma and a carcinoma form which are more aggressive than the carcinoid types.
Upon evaluation of a patient, it is possible that one can be asymptomatic but generally, it is more often expected to have abdominal or pelvic pain, a sensation of bloating and perhaps some ascites (ascitic fluid). A medical history can help to pinpoint the diagnosis. Changes in the bowel movements, vomiting and diarrhea and even fertility problems can be seen. The age of the patient can also help on the type of appendix cancer. Often some tests or procedures may be suggested like a Biopsy or an aspiration of the abdomen for ascitic fluid analysis, a laparoscopy etc. A CT-Scan or an MRI or even an Ultrasound may be helpful in making the diagnosis.
The treatment will depend on the type of the tumor and obviously the stage of the lesion at the time of discovery. Surgical treatment is almost always recommended for appendiceal cancer. An appendectomy is always performed. For a carcinoid tumor, larger than 2 cm, a hemicolectomy is performed with the removal of a portion of the colon close to the appendix. Cytoreductive therapy is often recommended for non-carcinoid tumors which has spread or presented with surrounding fluid. A peritonectomy might be recommended especially if the tumor spread beyond the colon or through other areas of the abdomen. The peritoneum (lining of the abdomen) can also be removed. Chemotherapy is then often offered as well as the hyperthermic intraperitoneal chemotherapy (HIPEC).
There may be some risk factors associated with appendix cancer. Smokers are more likely to develop appendix cancer than non-smokers. Patients who have a family history of appendix cancer or a history of multiple endocrine neoplasia type 1 (MEN1) syndrome appear to be at a greater risk of getting an appendiceal cancer. Conditions like Atrophic Gastritis, Pernicious Anemia increase the risks of developing an appendix cancer, because it affects the ability of the stomach to produce acid. Finally, older age (>50) raises also the chances of developing appendix cancer. Women appear more likely to develop carcinoid tumors than men. Appendix cancer is rare in the USA and affect less than 2 persons over one million. It has not been proven that there is a correlation between appendix cancer is heredity.
In a study involving more than 239,000 UA patients, predominantly white (79%), specimen removed (2773) from appendectomy showed malignant neoplasms (64.5%), malignant carcinoid (17.3%), benign carcinoid (9.3%) and benign neoplasm (8.8%). The overall incidence was 1.2 per cent and the mortality rate was 0.7% after antibiotics alone were given leading to further appendectomy.
Management practices for acute appendicitis are changing and non-operative treatment with antibiotics and observation are often offered to the one suffering with an acute right lower quadrant pain. The risks in missing or delaying a diagnosis of Appendiceal cancer are increasing. Between 2016 and 2017, a total of 21,069 patients underwent imaging confirmed or imaging indeterminate appendicitis were scheduled for appendectomy. The rising risks for appendiceal cancer should be explained as well to the patients especially when this newer trend in offering antibiotics as a first line of treatment is implemented.
Other forms of cancer can be explained as well. Goblet cell carcinoid (GCC) or goblet cell carcinoma is that unique mixed endocrine-exocrine neoplasm that we described above with a tendency in presenting a concentric infiltration with small tight clusters of the appendiceal wall, exhibiting goblet cell morphology which are easily recognized because of a small compressed nucleus and abundant mucin. A number of these lesions have shown high-grade adeno-carcinomatous components which dictate the prognosis.
There are several recommended approaches whenever it is question of treating a cancer of the appendix. One will have to take in consideration the way the tumor was diagnosed, the size and the stage of the lesion, the involvement of the peritoneum or the existence of distant metastasis or ascites or lymph nodes involvement prior to discuss specificity in the choice of a treatment protocol.
First a surgical treatment will require the removal of the appendix and it will impose a staging of the lesion. Although some tumors, less than 2 centimeters in size, can be so well localized that no further treatment may be needed once the appendectomy is performed. Other may require a right-side hemicolectomy or a debulking surgery in which most of the tumor is removed. By this procedure, the accumulated mucus may be removed to ease the symptoms of bloating. Very often also the peritoneum lining can be also removed. Unfortunately, such removal of the peritoneum may bring so much more complications that even the surgical team may not be too eager to perform it.
Treatment with Chemotherapy to kill the cancerous cells may be recommended especially when the tumor has invaded the tissue around. Many drugs can be injected through the bloodstream or be given orally. A new way in delivering the chemotherapy is by Hyperthermic intraperitoneal chemotherapy (HIPEC) which technique is performed at the time of the surgical treatment with the infusion of heated chemotherapy drugs inside the abdominal cavity. The patient remains under general anesthesia and one can understand that the delivery of medicine become more elaborate than the intravenous infusion of the chemotherapy drugs.
Howard University Hospital was a designated cancer institution during the time of my residency so intra-operative radiation therapy was routinely offered as an adjunct to the surgical treatment, especially to gynecologic cases. Strong doses of radiation were delivered intra-operatively in a “beam” via a cone to a specific area of the abdomen while the patient remains asleep, on the operating room table.
Finally, targeted drug therapy is a new treatment destined to attack the cancer cells while sparing the healthy cells. These drugs are specific drugs used to attack certain genetic components or some specific proteins. Drugs like Bevacizumab, Cetuximab or Panitumumab etc are believed to be selective for appendiceal cancers. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is also considered as an acceptable option in the management of patient with colon and appendiceal peritoneal carcinomatosis (PC). There is a high mortality rate associated with it. The presence or the absence of lymph nodes was a prediction for local recurrence.
Unfortunately, there is no way to prevent appendix cancer from appearing suddenly. The type of appendiceal cancer, the size at discovery as well as the spreading to other parts of the abdomen or to other parts of the body may dictate a successful recovery or an unfavorable outcome. The smaller the tumor, the more successful the treatment will be while the larger the lesions, the more aggressive they may be, bringing a poor response to the treatment. A metastatic lesion can be discovered elsewhere like in the lungs or any other organ or lymph nodes.
The five-year survival rate for a low-grade appendix cancer can easily reach 90% meaning that patients who suffered from the disease can still be alive five years later. It is not the same for a more aggressive tumor but nobody can be sure of the outcome because this cancer is so rare. It is always recommended that if you experience any sign of bloating, or right lower quadrant pain, to seek for advices from your physician. If you were diagnosed in the past with such disease, you should consult as well with your physician regarding any change you may have witnessed in your bowel habits etc…
I want to dedicate this paper to all my friends and patients who succumbed from this rare disease especially Anthony my Physician-Assistant and Frantz my childhood friend.
Maxime Coles MD
Boca Raton FL
References:
1- Scierreta JD, Pahklter M et al; The understated Malignancy Potentiel of Non-Operative Acute Appendicitis: Am Surg 2019, 85(7): 712-716 PubMed Related Publications.
2- Lu P, McCarty JC, et al: Risk of Appendiceal cancer undergoing appendectomy for appendicitis in the era of increasing non operative management. J Surg Oncol 2019, (3):452-459. (PubMed) Related Publications.
3- Zhang K, Meyerson C, Kassardijan A, et al: Goblet cell carcinoid (GCC) or goblet cell carcinoma: An Update. Adv Anat Pathol 2019: 26(2): 75-83, (PubMed) Related Publications.
4- Ning S, Yang Y, Wang C, Luo F: Pseudomyxoma peritonei induced by low grade appendiceal mucinous neoplasm accompanied with rectal cancer: A cave report and literature review. BMC Surg 2019: 19(1)42(PubMed).
5- Babcock B, Jabo B, Selleck M et al. Factors Predictive of Outcomes after Cytoreductive Surgery and Appendiceal Carcinomatosis: A Single Institution Experience. Am Surg 2018: 84(10):1575-1579. PubMed) Related Publications.