Gestational Trophoblastic Disease (GTD)

Gestational trophoblastic disease (GTD) is a rare group of tumors involving abnormal growth of cells of the placenta in a woman's uterus. It always is associated with pregnancy.

A hidatidiform mole results from an abnormal embryo that contains many fluid-filled cysts. There are two types of hydatidiform moles, complete and incomplete (partial). A complete mole usually has little or no fetal development and a large overgrowth of the placenta in the form of cysts (hydatids). The diagnosis of a complete hydatidiform mole is usually made during the first half of a pregnancy and is recognized by the health care provider about 50 percent of the time before the tumor cysts are expelled. A variety of clinical conditions may be confused with a molar pregnancy, but these can usually be distinguished on the basis of medical history, a physical exam and an ultrasound examination. In contrast, a partial mole is associated with a fetus, umbilical cord and membranes. It occurs much less frequently than a complete mole. The fetus usually dies within nine weeks after the last menstrual period although occasionally it can survive to term. Partial moles are rarely associated with multiple ovarian cysts (theca-lutein cysts), high BHCG titers and other accompaniments of a complete mole. There is also a lower incidence of malignant behavior (5 to 10 percent). Hydatidiform moles are sometimes associated with multiple ovarian cysts (theca-lutein cysts), high BHCG titers, and pregnancy-induced hypertension. There is also the risk that the abnormal placental tissue will persist in the uterus or elsewhere in the body. These risks are greater for women with complete moles (10 to 20 percent develop persistent disease) than for those with partial moles (5 to 10 percent). An invasive mole (chorioadenoma destruens) is defined as a hydatidiform mole that persists and invades the uterine wall. It develops in 10 to 20 percent of all molar pregnancies. Choriocarcinoma is a cancer composed of only the cells that covers the placenta (trophoblastic cells). It differs from invasive mole, which is made up of all the placental tissues. Choriocarcinoma can follow any type of pregnancy, whereas an invasive mole can only follow a hydatidiform mole. About 50 percent of all cases of gestational choriocarcinoma follow a hydatidiform mole, 25 percent follow a spontaneous abortion or tubal pregnancy and 25 percent follow a normal pregnancy. Choriocarcinoma follows a normal term pregnancy in 1 in 40,000 pregnancies. GTD after a normal pregnancy is always a choriocarcinoma, never a mole or an invasive mole.

What causes it?

A hydatidiform or invasive mole occurs when a single sperm fertilizes an egg without a nucleus. The chromosomes in the sperm duplicate, resulting in an abnormal embryo that has only male genetic material. A mole can also occur when two sperm fertilize a single egg. A mole develops from the abnormally fertilized egg and is characterized by a lack of a normal fetus and by many small fluid-filled cysts. The cause of choriocarcinoma is uncertain. It can arise from a normal pregnancy, a miscarriage, a tubal pregnancy or from either type of mole.  A interesting statistic is that GTD is the most common in the Philippines and Taiwan.

How it spreads?

A hydatdiform mole generally stays confined to the endometrial cavity. When it begins to invade the wall of the uterus, it is called an invasive mole. An invasive mole can penetrate the full thickness of the uterine wall and rupture, resulting in severe internal or vaginal bleeding. Invasive moles can also spread to other organs, most commonly to the vagina and lung. This may be confusing since women with proven invasive moles who have metastases may also have choriocarcinoma. Although an invasive mole is locally more aggressive than a noninvasive mole, it is no more likely to be complicated by choriocarcinoma. Choriocarcinoma can spread virtually anywhere in the body but most commonly spreads to the lung, the lower genital tract (cervix, vagina and vulva), the brain, the liver, kidney and the gastrointestinal tract.

Risk Factors:

Gestational trophoblastic disease occurs only in women of reproductive age. An invasive mole develops in 10 to 20 percent of all complete moles. Choriocarcinoma develops in 3 percent of complete moles but rarely in partial moles. At significantly higher risk: Risk for the development of a hydatidiform or invasive mole or choriocarcinoma include: a prior mole (30 times the risk) maternal age greater than 40 years (5 times) or less than 20 years (1.5 times) a previous spontaneous abortion (twice the risk) At slightly lower risk: Eating a diet high in vitamin A and having one or more children without having a previous abortion is statistically correlated with a lower than average risk of developing a complete mole. At risk for developing an invasive mole or choriocarcinoma: For women with a molar pregnancy, there are several risk factors associated with the subsequent development of an invasive mole and choriocarcinoma. These include delayed hemorrhage after the mole is removed in a dilation and curettage (D&C) procedure, large ovarian (theca-lutein) cysts, acute respiratory failure at the time of the D&C, a large uterus before the D&C, a serum BHCG level greater than 40,000 mlU/mL, a history of a previous mole and maternal age over 40.

Screening:

Since it is so rare, GTD is not routinely screened for. It is reasonable, however, to perform an ultrasound examination early in any subsequent pregnancy for women with prior GTD. Common signs and symptoms: A molar pregnancy is usually associated with bleeding in the first half of a pregnancy, an absent fetal heartbeat, pain in the lower abdomen, and occasionally with high blood pressure before 24 weeks of pregnancy, excessive nausea or vomiting, a uterus larger than normal for the gestational age (50 percent of all cases) and the expulsion of cysts. Eighty to 90 percent of women with partial moles have abnormal uterine bleeding, a smaller than expected uterus for the gestational age of tae pregnancy or the signs and symptoms of a spontaneous abortion. The most common symptoms of choriocarcinoma are lack of a menstrual period, symptoms of pregnancy, abnormal vaginal bleeding or pelvic pain. Women with liver metastases may have bleeding within the abdomen because of a ruptured liver. Those with metastases to the lung may have a dry cough, cough up blood and have chest pain or shortness of breath. Spread to the intestinal tract may be associated with chronic blood loss and anemia or with massive hemorrhage. Brain metastases are often associated with symptoms that suggest a brain tumor or stroke.

Diagnosis:
The diagnosis is usually suspected after an ultrasound examination of the uterus, but absolute diagnosis of a mole is made by examining the cysts under a microscope. A serum BHCG level far in excess of that of a normal pregnancy would support the diagnosis of a hydatidiform mole. An invasive mole is seldom diagnosed definitively without a hysterectomy. The diagnosis is usually suggested after a hydatidiform mole is removed and the BHCG titers remain elevated and there is no evidence of metastases. It is more properly referred to as nonmetastatic (if confined to the uterus) trophoblastic disease (NMTD). Confirmation of choriocarcinoma by removing cells for pathological analysis is not required and may be hazardous since their tumor bleeds easily. http://www.cancer.org/Cancer/GestationalTrophoblasticDisease/DetailedGuide/gestational-trophoblastic-disease-what-is-g-t-d

http://www.g-o-c.org/en/patientadvocacy/cancers/gtd.aspx

Circulating Tumor Cells Testing For More Personlized Cancer Treatment

Circulating tumor cells are cells that has detached themselves from the primary tumor into the blood stream.

                                                     Circulating tumor cells

The detection of CTCs may have important prognostic and therapeutic implications but because their numbers can be very small, these cells are not easily detected. Circulating tumor cells are found in frequencies in the order of 1-10 CTC per mL of whole blood in patients with metastatic disease. For comparison, a mL of blood contains a few million white blood cells and a billion red blood cells, see figure 1. This low frequency means that a key component of methods to detect CTC is the enrichment method.
First evidence indicates that CTC markers applied in human medicine are conserved in other species. Five of the more common markers including CK19 are also useful to detect CTC in the blood of dogs with malignant mammary tumors.

                                    Johnson and Johnson  explains why CTC testing is important.

Very recent news on using CTC testing for Breast Cancer is presented by Biocept. 
Biocept and Clarient, a GE Healthcare Company, have launched Biocept's breast cancer circulating tumor cell (CTC) test, OncoCEE-BR, performed on a blood sample in US.
OncoCEE-BR detects CTCs, which are rare, and determines the patient's HER2 status by fluorescence in situ hybridization (FISH).
The companies will market and sell the OncoCEE-BR CTC test to hospitals, pathologists and medical oncologists.
Biocept will perform the test in its laboratory and results will be interpreted and reported by Clarient's pathology group.
Clarient chief commercial officer Dave Daly said Biocept's OncoCEE-BR is an important test for their oncology portfolio, and will help the oncology community progress towards more personalized cancer care.

For more information: www.wikipdeia;  
http://laboratoryinstrumentation.pharmaceutical-business-review.com/news/biocept-clarient-launch-new-breast-cancer-ctc-test-080212

Smoking Or Second Hand Smoke Is Cause of Deadly Small Cell Lung Cancer

Small cell lung cancer has the characteristic of the most aggressive type of the three classifications which is small cell, large cell and carcinoid lung cancer.  Within the category of small cell lung cancer there are two types.
These two types include many different types of cells. The cancer cells of each type grow and spread in different ways. The types of small cell lung cancer are named for the kinds of cells found in the cancer and how the cells look when viewed under a microscope.  They are small cell carcinoma (oat cell) or combined small cell cancer.

                                                             Small cell lung cancer scan

                                                  Small cell lung cancer under the microscope




Diagnosing small cell lung cancer involves several procedures.

• Physical exam and history: An exam of the body to check general signs of health, including checking for signs of disease, such as lumps or anything else that seems unusual. A history of the patient’s health habits and past illnesses and treatments will also be taken.
• CT scan (CAT scan) of the brain, chest, and abdomen: A procedure that makes a series of detailed pictures of areas inside the body, taken from different angles. The pictures are made by a computer linked to an x-ray machine. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography.
• PET scan (positron emission tomography scan): A procedure to find malignant tumor cells in the body. A small amount of radioactive glucose (sugar) is injected into a vein. The PET scanner rotates around the body and makes a picture of where glucose is being used in the body. Malignant tumor cells show up brighter in the picture because they are more active and take up more glucose than normal cells do.

General Information About Small Cell Lung Cancer

Key Points for This Section

Small cell lung cancer is a disease in which malignant (cancer) cells form in the tissues of the lung. There are two types of small cell lung cancer. Smoking tobacco is the major risk factor for developing small cell lung cancer. Possible signs of small cell lung cancer include coughing, chest pain, and shortness of breath. Tests and procedures that examine the lungs are used to detect (find), diagnose, and stage small cell lung cancer. Certain factors affect prognosis (chance of recovery) and treatment options. For most patients with small cell lung cancer, current treatments do not cure the cancer.

Small cell lung cancer is a disease in which malignant (cancer) cells form in the tissues of the lung.
The lungs are a pair of cone-shaped breathing organs that are found within the chest. The lungs bring oxygen into the body when breathing in and take out carbon dioxide when breathing out. Each lung has sections called lobes. The left lung has two lobes. The right lung, which is slightly larger, has three. A thin membrane called the pleura surrounds the lungs. Two tubes called bronchi lead from the trachea (windpipe) to the right and left lungs. The bronchi are sometimes also involved in lung cancer. Small tubes called bronchioles and tiny air sacs called alveoli make up the inside of the lungs.

Enlarge

Anatomy of the respiratory system, showing the trachea and both lungs and their lobes and airways. Lymph nodes and the diaphragm are also shown. Oxygen is inhaled into the lungs and passes through the thin membranes of the alveoli and into the bloodstream (see inset).

Risk factors for small cell lung cancer include:

• Smoking cigarettes, cigars, or pipes now or in the past.
• Being exposed to secondhand smoke.
• Being exposed to asbestos or radon.

Possible signs of small cell lung cancer include coughing, chest pain, and shortness of breath.
These and other symptoms may be caused by small cell lung cancer. Other conditions may cause the same symptoms. A doctor should be consulted if any of the following problems occur:

• A cough that doesn’t go away.
• Shortness of breath.
• Chest pain that doesn’t go away.
• Wheezing.
• Coughing up blood.
• Hoarseness.
• Swelling of the face and neck.
• Loss of appetite.
• Weight loss for no known reason.
• Unusual tiredness.

Tests and procedures that examine the lungs are used to detect (find), diagnose, and stage small cell lung cancer.
The following tests and procedures may be used:

• Chest x-ray: An x-ray of the organs and bones inside the chest. An x-ray is a type of energy beam that can go through the body and onto film, making a picture of areas inside the body.

  Enlarge

  X-ray of the chest. X-rays are used to take pictures of organs and bones of the chest. X-rays pass through the patient onto film.

• Physical exam and history: An exam of the body to check general signs of health, including checking for signs of disease, such as lumps or anything else that seems unusual. A history of the patient’s health habits and past illnesses and treatments will also be taken.
• CT scan (CAT scan) of the brain, chest, and abdomen: A procedure that makes a series of detailed pictures of areas inside the body, taken from different angles. The pictures are made by a computer linked to an x-ray machine. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography.
• PET scan (positron emission tomography scan): A procedure to find malignant tumor cells in the body. A small amount of radioactive glucose (sugar) is injected into a vein. The PET scanner rotates around the body and makes a picture of where glucose is being used in the body. Malignant tumor cells show up brighter in the picture because they are more active and take up more glucose than normal cells do.

  Enlarge

  PET (positron emission tomography) scan. The patient lies on a table that slides through the PET machine. The head rest and white strap help the patient lie still. A small amount of radioactive glucose (sugar) is injected into the patient's vein, and a scanner makes a picture of where the glucose is being used in the body. Cancer cells show up brighter in the picture because they take up more glucose than normal cells do.

• Sputum cytology: A microscope is used to check for cancer cells in the sputum (mucus coughed up from the lungs).
• Bronchoscopy: A procedure to look inside the trachea and large airways in the lung for abnormal areas. A bronchoscope is inserted through the nose or mouth into the trachea and lungs. A bronchoscope is a thin, tube-like instrument with a light and a lens for viewing. It may also have a tool to remove tissue samples, which are checked under a microscope for signs of cancer. 

Thoracoscopy: A surgical procedure to look at the organs inside the chest to check for abnormal areas. An incision (cut) is made between two ribs, and a thoracoscope is inserted into the chest. A thoracoscope is a thin, tube-like instrument with a light and a lens for viewing. It may also have a tool to remove tissue or lymph node samples, which are checked under a microscope for signs of cancer. In some cases, this procedure is used to remove part of the esophagus or lung. If certain tissues, organs, or lymph nodes can’t be reached, a thoracotomy may be done. In this procedure, a larger incision is made between the ribs and the chest is opened.

Thoracentesis: The removal of fluid from the space between the lining of the chest and the lung, using a needle. A pathologist views the fluid under a microscope to look for cancer cells.

 Unfortunately, the prognosis for small cell lung cancer is not positive.

Approximately 65-70% of patients with small cell lung cancer have disseminated or extensive disease at presentation. Extensive-stage small cell lung cancers are incurable, and patients with extensive disease have a median survival duration of 6 weeks. Patients presenting with localized disease (ie, limited stage) have a median survival duration of about 12 weeks. These survival figures are for untreated patients.
The median survival of patients with small cell lung cancer who are treated with multiple-agent chemotherapy and multimodality therapy are as follows:

• For limited disease, 20 months, with a 2-year survival rate of 45%^[21] and a 5-year survival rate of 20%
• For extensive disease, 12 months (In 1973, the 2-year survival rate was 1.5%; in 2000, the 2-year survival rate was 4.6%.)

Indicators of poor prognosis include relapsed disease, weight loss, and performance status. Patients who ambulate less than 50% of their waking hours and those with weight loss of more than 10% in 6 months have a worse prognosis.  For more information:

http://emedicine.medscape.com/article/280104-overview  or

http://www.cancer.gov/cancertopics