Under supervision of :

Dr/Nahed Hussein

Dr/Hanan Abd Elmenam

Prepared by:

Esraa Mohamed Khalil (6010).

Esraa Mohamed Abd el Aaty(6011).

Esraa Mohamed Mahmoud(6012).

Definiton:Malignant change of the endometrial lining of the uterine cavity

IncidenceEndometrial cancers are the most common gynecologic cancers*

*Over 35000 women are diagnosed each year

*The incidence is on a slow rise secondary to the obesity epidemic.

* The most common subtype, endometrioid adenocarcinoma ,

Epidemiology

It's the most frequent cancer occurring in the female genital tract.

It appears most frequently between ages of 55 and 65, and uncommon below 40. There are two pictures of this disease, perimenopausal women with estrogen excess and in older women with endometrial atrophy.

Risk factors:

The cause endometrial cancer isn't known exactly. But there are some factors that might increase or reduce the risk of developing it

Many of the risk factors for endometrial cancer relate to the body’s exposure to the female sex hormone, oestrogen. Or to the balance between types of the two female sex hormones, oestrogen and progesterone.

Oestrogen without progesterone to balance it increases the Risk of cancer.

cancer is much more common in women after the menopause as the body stops making progesterone after the menopause, but still produces a small amount of oestrogen.

1-Age

It occurs most commonly in women between the ages of 60 and 79.

Most women diagnosed with endometrial cancer have had their menopause

Only 5% of cases are diagnosed in women under 40years old. But women who have a particular gene fault called HNPCC are more likely than the general population to develop it at a younger age.

2 -Obesity

Obesity increases the risk of incidence of endometrial cancers. This because obese women have higher levels of oestrogen As

a) Adipose tissue convert certain hormones into oestrogen and this lead to endometrium builds up. And more lining (endometrial) cells are produced, there is a greater chance of one of them becoming cancerous.

b) Sometimes obesity cause insulin resistance that lead to i ncrease level of insulin that can stimulate cancerous growth in the lining of the endometrium.

3-Diabetes and high blood pressure

Diabetes and high blood pressure are both linked to being overweight and so may be connected with womb cancer for that reason.

4- Infertility and Nulliparity

Having 3 or more children your could be lowered the risk by up to two thirds.

Oestrogen levels are low and progesterone levels are high in pregnancy.

Unopposed oestrogen increases the risk of womb cancer.

5-Menstrual history

Some factors linked with menstruation can increase risk of womb cancer as they cause higher levels of oestrogen. Examples are

Pre and post menopausal bleeding

Infertility due to failure of the ovaries

Early menarche

Late menopause

anovulatory cycles

Amenorrhea

Menorhagia

6-Endometrial hyperplasia

Endometrial hyperplasia is a benign condition where the lining of the womb becomes thicker.

Symptoms of endometrial hyperplasia are

Menorrhagia.

Metrorrhagia.

post menopausal bleedin

7-Polycystic ovary syndrome(PCOS)

Women with PCOS have a hormone imbalance which may cause very irregular periods. They are also more likely to be insulin resistant, overweight, and have diabetes. Most women (more than 90%) who have PCOS do not develop womb cancer.

8-Family history and other cancers

Past history of cancer of the colon, rectum or breast increased risk of getting womb cancer.

Similarly, once having womb cancer, there is increased risk of developing certain other cancers.

Having a family history womb cancer double the risk of its incidance

9-DRUGS

a) Tamoxifen and raloxifene

An increased risk of womb cancer is a known side effect of taking tamoxifen, which is a hormonal therapy for breast cancer. has a similar effect on the womb to oestrogen. It occure after taking tamoxifen for more than 2 years .Raloxifene, another hormonal treatment for breast cancer, has also been shown to increase womb cancer risk in one study. But another study showed a reduction in womb cancer risk in women who took raloxifene.

B)HORMONE REPLACEMENT THERAPY (HRT)

Hormone replacement therapy is used by many women to control the symptoms of menopause. There are different types of HRT. Oestrogen only HRT increases the risk of womb cancer and is normally only prescribed to women who have a hysterectomy. 

Some studies show a small reduction in risk of womb cancer in women taking continuous combined HRT .

normal weight women taking continuous combined HRT for 10 years or longer had an increased risk of womb cancer.

C)CONTRACEPTIVE PILLS

Most types of birth control pills used today normally decrease the risk of womb cancer. These contain either a combination of oestrogen and progesterone (combination pills), or progesterone only (mini pills).

10-CHEMICALS AS (TALCUM POWDER)

Regular use of talcum powder in the genital area may increase the risk of womb cancer .

11-Diet and alcohol

Diet only seems to play a small role in in womb cancer.

Eating a high fat diet may causr a high risk of developing womb cancer either directly or by obesity making.

12-PHYSICAL ACTIVITY

Physically active women have a reduced risk of womb cancer who are more.

13-Ethnicity

White women have a greater chance of developing womb cancer than black women But if black women do get womb cancer, these cancers are more likely to be faster growing tumours

Classification1- Carcinoma

Most endometrial cancers are carcinomas (usually adenocarcinomas), meaning that they originate from the single layer of epithelial cells that line the endometrium and from the endometrial glands.endometrial carcinomas are classified into two pathogenic:

Type I :These cancers occur most commonly in pre- and peri-menopausal women, often with a history of unopposed estrogen exposure and/or endometrial hyperplasia.

They are often minimally invasive into the underlying uterine wall, are of the low-grade endometrioid type, and carry a good prognosis.

Type II: These cancers occur in older, post-menopausal women,

are more common in African-Americans, are not associated with increased exposure to estrogen, and carry a poorer prognosis. They include

the high-grade endometrioid cancer , the uterine papillary serous carcinoma,

the uterine clear cell carcinoma.

FIGO grading of Endometrial Carcinoma G1 : Highly differentiated (composed of glands and 5%

of lesion is of solid growth pattern) G2 : Moderately differentiated ( 6%-50% of lesion

composed of solid sheets of cells). G3: Undifferentiated ( > 50% of lesion composed of

solid sheets of cells.

2-SarcomaIn contrast to endometrial carcinomas the uncommon endometrial stromal sarcomas are cancers that originate in

the non-glandular connective tissue of the endometrium

3 -Uterine carcinosarcoma, ( Malignant mixed müllerian tumor): is a rare uterine cancer that contains cancerous cells of both glandular and sarcomatous appearance.

STAGING Of endometrial carcinomaEndometrial carcinoma is surgically staged using the FIGO cancer staging system.

IA : Tumor confined to the uterus, no or < ½ myometrial invasion

IB : Tumor confined to the uterus, > ½ myometrial invasion

II :Tumor involves the uterus and the cervical stromaIIIA : Tumor invades serosa or adnexaIIIB :Vaginal and/or parametrial involvementIIIC1 : Pelvic lymph node involvementIIIC2 : Para-aortic lymph node involvement, with or

without pelvic node involvementIVA : Tumor invasion bladder mucosa and/or bowel

mucosaIVB : Distant metastases including abdominal

metastases and/or inguinal lymph node.

Clinical picture:

SYMPTOMS

1-COMMON SYMPTOMS

The most common symptom of Endometrial cancer is: Abnormal vaginal bleeding from the– especially after menopause

About 90% of womb cancer cases are discovered as irregular vaginal bleeding which may be.

Post menopausal bleeding, which is a key symptom of womb cancer in most cases.

Metrorrhagia: in premenopausal women in women older than 40: extremely long, heavy, or frequent episodes of bleeding (may indicate premalignant changes).

Vaginal discharge –( from pink and watery to dark and foul smelling)

Only a small number of women with dysfunctional uterine bleeding will actually have womb cancer.

2-LESS COMMON SYMPTOMS

Less common symptoms of womb cancer can include

a)Lower abdomenal Pain or discomfort b)Dysparonia .

3-SYMPTOMS OF ADVANCED ENDOMETRIAL CANCER

Advanced womb cancer can cause more symptoms, especially if the cancer has spread to other parts of the body.

These are much less common and can include:

Loss of appetite and weight Tiredness or weakness Feeling or being sick Constipation Polyurea Back pain or leg pain.

Signsa) General examination

To asses general condition for anemia, caused by chronic loss of blood.

To detect distant metastasis.

b) Abdominal examination Palpate liver for metastasis Supra pubic region for large pyometra

c) Local examination (not characteristic) Bimanual examination: the uterus may be

-normal sized-Slightly smaller in size(post menopausel atrophy)

Investigation of Endometrial cancer:

1. Sampling endometrial tissue :

To find out whether endometrial hyperplasia or endometrial cancer is present.

2.Endometrial biopsy:

Is very accurate in postmenopausal women.

3. Hysteroscopy

This is usually done with the patient awake, using a local anesthesia . it allows the direct visualization of the uterine cavity and can be used to detect the presence of lesions or tumours. It also permits to obtain cell samples with minimal damage to the endometrial lining (unlike blind D&C)

4. Dilation and curettage (D&C)

If the endometrial biopsy sample doesn't provide enough tissue, or if the biopsy suggests cancer but the results are uncertain, a D&C must be done.Then looked at under the microscope to see whether cancer is present.

6. Transvaginal ultrasound or sonography

to evaluate the endometrial thickness in women with postmenopausal bleeding is increasingly being used to evaluate for endometrial cancer..

7. Cystoscopy and proctoscopy These procedures now are rarely used for endometrial cancer.

8. Computed tomography (CT)

CT scans are not used to diagnose endometrial cancer. However, they may be helpful to see whether the cancer has spread to other organs and to see if the cancer has come back after treatment.

10. Magnetic resonance imaging (MRI)

MRI scans may be a good way to tell how far the endometrial cancer has grown into the body of the uterus. MRI scans may also help find enlarged lymph nodes.

11. Positron emission tomography (PET) :

In this test radioactive glucose is given to look for cancer cells. But their role is still being studied.

12 . CHEST X-RAY :

This test can show whether the cancer has spread to the lungs. It may also be used to look for serious lung or heart problems, especially before surgery.

13. Blood tests :

A. Complete blood count.

B. CA 125 blood test.

CA 125 is a substance released into the bloodstream by many endometrial and ovarian cancers. In someone with endometrial cancer, a very high blood CA 125 levelsuggests that the cancer has probably spread beyond the uterus

Pathology

The histopathology of endometrial cancers is highly diverse. The most common finding is:

a well-differentiated endometrioid adenocarcinoma, which is composed of numerous, small, crowded glands with varying degrees of nuclear atypia,

Endometrial adenocarcinoma

mitotic activity, and stratification.

This often appears on a background of endometrial hyperplasia.

Frank adenocarcinoma may be distinguished from atypical hyperplasia by: the finding of clear stromal invasion, or "back-to-back" glands which represent non destructive replacement of the endometrial stroma by the cancer.

With progression of the disease, the myometrium is infiltrated.

However, other subtypes of endometrial cancer exist and carry a less favorable diagnosis such as the uterine papillary serous carcinoma and the clear cell carcinoma

Treatment (according to stage):

Stage 1 : (the commonest) :

1_If the patient is unfit for surgery: only radiotherapy is used(internal,external)the results is inferior to surgery.

2_If the patient is fit for surgery:combined surgery and radiotherapy.

y a .1st step is panhysterectom

)total abdominal hysterectomy*TAH*, with bilateral salpingo-oophorectomy *BSO(* and removal of a cuff

from upper vagina.

b.Then surgical staging:

-If G1 or G2,no myometrial invasion ,no isthmic invasion with-ve peritoneal cytology:No further treatment is required.

-If G1 or G2 and myometrial invasion by <50% :

Only post operative internal radiation into the vaginal vault with radium to decrease local recurrence.

-If G3 or myometrial invation by >50% (L.N spread) :

Post operative external radiation to the whole pelvis and internal radiation to the vaginal vault.

Stage 2:

-Radiotherapy or wertheim’s operation.

-Recently it is treated as stage 1(panhysterectomy and post operative irradiation) as these female are very risky for wertheim’s operation (old,obese,hypertensive,diabetic).

Stage 3:

-Surgery (T.A.H. and B.S.O.) then followed by post operative radiotherapy and intraperitoneal phosphorus 32 (for +ve peritoneal cytology).

-If clinically detected : treatment should be preceded by

pre-operative radiotherapy.

Stage 4 and recurrent cases:

1.Palliative radiotherapy:

.Brachytherapy and external radiation.

SIDE EFFECTS OF RADIATION THERAPY

-Short-term side effects: tiredness, upset stomach, or loose bowels. Serious fatigue,diarrhea,nausea and vomiting.Skin changes are also common,this ranging from mild temporary redness to permanent discoloration. The skin may release fluid, which can lead to infection.

Radiation can cause cystitis, proctitis, vaginitis, anemia and leukopenia.-Long-term side effects:  vaginal dryness. In some cases scar tissue can form in the vagina causing vaginal stenosis which can make vaginal intercourse painful, lymphedema,osteoporosis.Pelvic radiation therapy can damage the ovaries, resulting in premature menopause.

2.Palliative chemotherapy:

Combination chemotherapy sometimes works better than one drug alone in treating cancer.

Drugs used in treating endometrial cancer may include:

Paclitaxel (Taxol®) Carboplatin

Doxorubicin (Adriamycin®) Cisplatin

The most common combinations include carboplatin with paclitaxel and cisplatin with doxorubicin.

For carcinosarcoma, the chemo drug ifosfamide, either alone or in combination with either carboplatin, cisplatin or paclitaxel, is often used.

Side effects of chemotherapy

Side effects of chemotherapy depend on the specific drugs, the amount taken, and the duration. Common side effects include:

Nausea and vomiting.

Loss of appetite.

Mouth and vaginal sores.

Hair loss.

.Anemia and leukopenia.

3 .Hormonal treatment:

A..PROGESTINS

The main hormone treatment for endometrial cancer uses progesterone-like drugs called progestins. The 2 most commonly used progestins are medroxyprogesterone acetate and megestrol acetate.These drugs work by slowing the growth of endometrial cancer cells. Side effects can include increased blood sugar levels in patients with diabetes. Hot flashes, night sweats, and weight gain also occur.

B. .TAMOXIFEN

Tamoxifen, an anti-estrogen drug often used to treat breast cancer, may also be used to treat advanced or recurrent endometrial cancer. The goal of tamoxifen therapy is to prevent any estrogens circulating in the woman's body from stimulating growth of the cancer cells. It can cause hot flashes and vaginal dryness.There is increased risk of

serious blood clots in the leg. (80 % of endometrial adenocarcinoma are estrogen dependant).

C. .Gonadotropin-releasing hormone agonists:

Gonadotropin-releasing hormone (GNRH) agonists are another way to lower estrogen levels in women with functioning ovaries.Side effects can include any of the symptoms of menopause, such as hot flashes and vaginal dryness. If they are taken for years, these drugs can leading to osteoporosis.

D. .AROMATASE INHIBITORS :

can stop estrogen from being formed in fat tissue and lower estrogen levels. Examples of aromatase inhibitors include letrozole (Femara), anastrozole (Arimidex). These drugs are most often used to treat breast cancer, but may be helpful in the treatment of endometrial cancer. Side effects can include joint and muscle pain as well as hot flashes. If they are taken for years, these drugs can cause osteoporosis. These drugs are still being studied for use in treating endometrial cancer.

4 .Pain reliever.

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" ^ Thirteen studies to date have reported on the relationship between endometrial cancer and alcohol consumption. Only two of these studies have reported that endometrial cancer incidence is associated with consumption of alcohol; all the others have reported either no definite association, or an inverse association." (Six studies showed an inverse association; that is, drinking was associated with a lower risk of endometrial cancer) "…if such an inverse association exists, it appears to be more pronounced in younger, or premenopausal, women."[3] "Our results suggest that only alcohol consumption equivalent to 2 or more drinks per day increases risk of

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^ Chong, I; Hoskin, PJ (2008). "Vaginal vault brachytherapy as sole postoperative treatment for low-risk endometrial cancer.". Brachytherapy 7 (2): 195–9. doi:10.1016/j.brachy.2008.01.001. PMID 18358790.

] ^ 1 [American Cancer Society - Uterine Sarcomas - Hormonal Therapy (accessed 5-25-07)

^ Santin AD, Bellone S, Roman JJ, McKenney JK, Pecorelli S. (2008). "Trastuzumab treatment in patients with advanced or recurrent endometrial carcinoma overexpressing HER2/neu". Int J Gynaecol Obstet 102 (2): 128–31. doi:10.1016/j.ijgo.2008.04.008. PMID 18555254.

^ American Cancer Society (2009-10-22). "How Is Endometrial Cancer Staged?". Retrieved 2010-03-09 [Note Stage I definitions in ref differed from those used on Wiki page, so adjusted table labels from 0, IA, IB, to IA, IB, IC matching definitions used here].

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