Endometrial cancer originates in the endometrial lining of the uterus. It is the most common gynaecological malignancy (cancer originating in female reproductive organs).  The disease normally occurs in postmenopausal women, the average age at diagnosis being about 60 years.

Endometrial cancer is considered an oestrogen-dependent disease. Oestrogen is a hormone that is secreted by the ovaries. It plays an important role in the development of the female reproductive system and is largely responsible for the physiologic changes that occur during menstruation, puberty, and pregnancy. Progesterone is another hormone secreted by the ovaries that plays an important role. Normally, both oestrogen and progesterone are secreted in certain proportions. Chronic exposure to oestrogen, without the accompanying balancing effects of progesterone, is considered the major risk factor for endometrial cancer and may play a causal role in the development of the disease.

Benign uterine tumours, known as fibroids, usually are asymptomatic and do not require treatment. If fibroids cause bleeding or pain, they may be surgically removed. Cancerous (malignant) uterine tumours spread to other tissues and organs if left untreated. Endometrial cancer refers specifically to tumours that originate in the endometrial lining of the uterus. If the tumour originates in the deeper, muscular walls of the uterus, it is called uterine sarcoma. About 90% of all uterine cancers are endometrial.

A precancerous condition called endometrial hyperplasia, or adenomatous hyperplasiam, may cause irregular uterine bleeding. This condition can be mild, moderate, or severe. Severe hyperplasia is considered carcinoma in situ, the earliest detectable stage of endometrial cancer.

Anatomy of the uterus and endometrium
The uterus (womb) is a muscular, upside-down, pear-shaped organ that is located in a woman's pelvis behind the bladder and in front of the rectum. The top, wider part of the uterus is called the fundus (body), and the bottom, narrow part is the cervix. The fundus has very thick, muscular walls that are lined with a mucous surface called the endometrium. Human endometrium 3 days after ovulation.

Two uterine tubes, the fallopian tubes or oviducts, lead from either side of the upper part of the uterus to the ovaries. The ovaries are paired organs, one on each side of the pelvis. Ova (eggs) are transported from the ovaries to the uterus via the fallopian tubes.

All of the parts of the female genital tract, from the ovaries to the vagina, are held together by various types of connective tissue. For example, there is a thin, delicate sheet of lining called the peritoneum that covers the uterus and extends over the bladder and rectum, keeping the uterus snug between the latter two organs. But, despite all the well-connected organs, the female genital tract is more mobile and plastic than any other part of a woman's body. The ovaries rupture monthly, the uterus sheds countless cells during menstruation, and the changes that a woman's uterus undergo during pregnancy are the most dramatic changes that any human organ experiences without suffering damage. A woman's reproductive system is incredibly responsive to hormonal changes in its environment. The endometrium is no exception. It is very sensitive to hormonal changes, and it is believed that endometrial cancer may be caused by an imbalance in its hormonal environment.

The endometrium contains several layers of cells that vary in appearance and amount as a woman's menstrual cycle changes. It is full of glandular cells and blood vessels. Nearly all of the cells are responsive to the hormonal changes that the uterus regularly experiences. Certain cells undergo what is called hyperplasia, increased cell division, in response to oestrogen. It is this cell-growing response to oestrogen that leads many researchers to believe that oestrogen likely plays a causal role in the development of endometrial cancer.

The uterus has a flat, inner surface and is covered with tall, columnar epithelial cells. There are pits in the surface that lead down into uterine glands. The columnar cells, the pits, and the connective tissue and blood vessels that surround the glands are all part of the endometrium. The endometrium undergoes dramatic changes during a woman's menstrual cycle. During the luteal phase, for example, the two-week period just before a woman bleeds, the endometrium is thick, its epithelial cells are enlarged, the glands bulging, and the arteries swollen. At menstruation, the arteries break, the epithelial cells die, and the endometrium, in effect, sheds. Following menstruation, during the follicular phase, the endometrium regenerates. The changing thickness of the endometrium is highly dependent on the secretion of oestrogen and progesterone. Oestrogen causes cellular growth and is an important component of the rebuilding, follicular phase of the menstrual cycle. Progesterone is secreted during the later, thick-walled luteal phase, and it balances out the effects of the oestrogen. Abnormal growth of endometrial cells (whether cancerous or not) and endometrial cancer are believed to be due to chronic exposure to too much oestrogen without the balancing effect of progesterone.

Treatment

The treatment of endometrial cancer depends on many factors, including a patient's general health, age, and stage of the disease.

In the early stages, endometrial cancer is usually treated with surgery and/or radiation. In the later stages, it is usually treated with hormone therapy. There are numerous treatment options for patients.

Surgery
The typical surgery is bilateral salpingo-oophorectomy, the removal of the ovaries and fallopian tubes, as well as a complete, radical hysterectomy. A radical hysterectomy involves removing the uterus, the tissues surrounding the uterus, and the upper third of the vagina. A hysterectomy can be either abdominal or vaginal. In an abdominal hysterectomy, the surgeon makes an incision in the front of the abdomen and removes the uterus. In a vaginal hysterectomy, the uterus is removed through the vagina. Because endometrial cancer originates in the uterine body, a hysterectomy should be sufficient, but the ovaries are removed as well because they are the most common sites of undetected metastasis. Also, most women who undergo the surgery are postmenopausal, and their ovaries are no longer providing the hormonal function that is so important before menopause. During an abdominal hysterectomy, the lymph nodes are also almost always sampled (a pelvic lymph node dissection) to detect any spread of cancer to the lymph nodes.

Until recently, if a vaginal hysterectomy was used to remove the uterus, there was no way to get a sample of lymph node tissue. Now, however, there is a new surgical technique called laparascopic lymph node sampling that many surgeons are beginning to use that allows for sampling the lymph nodes even when the abdomen is not cut open for an abdominal hysterectomy. Thus women can opt for a vaginal hysterectomy and still have their lymph nodes examined. The new method involves inserting a tube through a very small opening in the abdomen. The vaginal hysterectomy combined with the laparascopy are much less invasive and require less recovery time than an abdominal hysterectomy.

Although the primary treatment for any stage endometrial cancer involves a radical hysterectomy, according to the National Cancer Institute, early stage I cancers may not require a radical hysterectomy. A simple hysterectomy,which involves removal of the uterus but not the surrounding tissues or upper third of the vagina, may be sufficient. It is important that you discuss with your surgeon the different options and why she or he thinks one procedure is more appropriate than another.

Radiation
There are two types of radiotherapy commonly used to treat various stages and grades of endometrial cancer: external-beam pelvic radiation and intra-cavitary irradiation.

External beam pelvic radiation
Radiotherapy was first used to treat uterine cancer around the turn of the century, very shortly after Marie Curie's discovery of radium. For many decades, radiation therapy was used as a standard pre-surgical treatment, but it is no longer done preoperatively because it prevents accurate surgical staging. It is standard to reserve the use of radiotherapy until an initial hysterectomy, at least, has been performed. Even following a hysterectomy and bilateral salpingo-oophorectomy, however, the effectiveness of adjuvant radiation therapy (therapy used in addition to surgery) is controversial. Although regional pelvic radiation has proven to decrease pelvic recurrences, it does not necessarily improve the survival rate. It is likely most beneficial for patients with tumours that are confined to the pelvis and that have features that increase the likelihood of recurrence (stages IC to IIIC). The potential benefits of radiation should be weighed against the risks, such as a history of pelvic infections or severe diabetes mellitus.

Postoperative vaginal irradiation (brachytherapy)
In addition to pelvic radiation, postoperative vaginal irradiation is often used to prevent vaginal cuff recurrences (the vaginal cuff is the upper third of the vagina). Vaginal cuff recurrences are common for certain types of tumours. This type of therapy involves inserting small metal cylinders, or some other type of applicator, through the vagina, where it releases a radioactive substance over the course of two or three days.

Hormonal therapy
Hormones, particularly progesterone, can be used to treat metastatic endometrial cancer, but their effectiveness is not very great. Studies indicate that less than 20% of patients who are treated with hormones respond to the treatment.

Chemotherapy
Studies have not yet produced clear results on the effectiveness of chemotherapy to treat endometrial cancer. Chemotherapy is potentially most useful for cancers that have spread to distant parts of the body.

Treatment by stage

Stages I and II
Hysterectomy and bilateral salpingo-oophorectomy plus radiation, depending on the grade of the tumour and whether it has invaded the myometrium.

Stage IA, grade 1 or 2 tumour
Usually there is a low risk of disease recurrence, therefore radiation therapy is not used. Treatment is surgery only.

Stage IA, grade 3 tumour; all stage II tumours
There is an intermediate risk for disease recurrence in these patients, although it is not clear that postoperative radiation therapy improves survival. It does, however, decrease the risk of local relapse. Following surgery, it is important that patients be given the opportunity to participate in clinical, postoperative radiation therapy trials. Either vaginal cuff radiation (internal radiation of the upper third of the vagina) or pelvic radiation should be considered.

Stages III and IVA (all grade tumours)
Following surgery, vaginal cuff radiotherapy with or without pelvic or whole abdominal radiation may increase a woman's chances of survival. Progesterone is used for metastatic endometrial cancer.

Stage IVB
This group of women have distant spread of the disease at the time of diagnosis. The chance of cure in this group is, unfortunately, low. If possible, patients can participate in a clinical trial. If not possible, or if they choose not to participate, palliative (pain-relieving) therapy should be considered. Palliation of symptoms can include hormones, chemotherapy, or radiation.

Recurrent disease
Recurrence is more likely in women with advanced disease and in those whose tumour had certain high-risk features. Usually recurrence happens within three years of the original diagnosis. Hormone therapy can be used to treat recurrent disease, although its effectiveness does not appear to be that great. The use of various combinations of hormones are currently being evaluated. The use of chemotherapy to treat recurrent disease is also currently being evaluated. If a woman was originally treated only with surgery and no radiation, if the cancer recurs, either external-beam pelvic or intracavitary radiation can be used as therapy. In the case of radiation, the prognosis depends on many features such as the size and extent of the tumour and the time to recurrence.

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