Of all gynaecological malignancies ovarian cancer carries the worst prognosis and it is estimated to be the ninth most common cancer and fifth most common cancer related mortality. Most of them are diagnosed in advanced stages of III and IV with a five year survival rate of less than 28%. Only 15% of ovarian cancers are diagnosed in early stage with a five year survival rate of 94%. This suggests that early detection will improve prognosis. Early diagnosis is often difficult due to lack of specific symptoms and also ovaries are inaccessible for direct inspection and palpation. Despite the significant disease burden ovarian cancer is relatively rare in general population with an estimated age adjusted incidence of 13 per 100,000 women. The age standardized incidence rate (ASR) varies widely; as low as 0.06 per 100,000 in China to as high as 16.3 in Switzerland. In India during the period 2004-5 proportion of ovarian cancer varied from 1.7% to 8.7% of all cancers affecting women as reported by various urban and rural population based cancer registries operating under the network of National Cancer Registry Programme of the Indian Council of Medical Research.4 Screening tests lack specificity and there is no single effective screening test for ovarian cancer. Main strategies for screening include biochemical markers and transvaginal ultrasound (TVS).

Screening
Low risk women

Use of tumour marker CA-125 and TVS has been evaluated for screening asymptomatic low risk women. These proved to be ineffective because of low prevalence of epithelial cancer which is reported to be approximately 1 case for 2,500 women per year. It is estimated that a test with 100% sensitivity and 99% specificity would have a positive predictive value of only 4.8% which means 20 out of 21 women undergoing surgery for suspected ovarian cancer will not have the disease.

High risk women

The definite risk factor known to increase the risk of ovarian cancer include an identified BRCA gene mutation and a family history of cancer which is suggestive of ovarian cancer syndrome. Women with these conditions should be referred for genetic testing for proper assessment of the risk of developing ovarian cancer. Women with BRCA-1 mutation have a life time risk of 63% for developing ovarian cancer before the age of 70 years and breast cancer risk is 85%. Risk of developing ovarian and breast cancer are 27% and 84% respectively among women who show BRCA-2 mutations before the age of 70 years.

Women with Lynch syndrome/hereditary non-polyposis colorectal cancer(HNPCC) caused by DNA mismatch repair genes carry the risk of developing endometrial cancer in 42-60%, ovarian cancer in 9-12% by the age of 70 years and also have 40-60% life time risk of developing colorectal cancer.

The strongest known risk factor is a family history of the disease which is present in about 10-15% of women with ovarian cancer. Women with a single family member affected by epithelial ovarian cancer have a risk of 4-5%, while with two affected family members the risk is 7%. Women with hereditary ovarian cancer syndrome defined as having at least two first degree relatives with epithelial ovarian cancer have a life time probability as high as 13- 55% to develop epithelial ovarian cancer. Know more about ovarian cancer here: canadianhealthmall.com.

Other risk factors

1. Age-Incidence increases with age; median age at diagnosis is 63.
2. Obesity
3. Hormone replacement therapy (HRT)
4. Early menarche and late menopause
5. Endometriosis
6. Smoking (stop smoking with Canadian Health Care Mall – watch here)
7. Association between ovulation induction and ovarian carcinoma Infertility alone is an independent risk factor. Nulliparous women have a higher risk of ovarian cancer irrespective of usage of fertility drugs. A 2013 Cochrane review concluded that there may be an increased risk of borderline ovarian tumours in sub-fertile women but no convincing evidence of increase in the risk of invasive epithelial ovarian cancer with fertility drug usage.

Screening methods

ACOG recommends that the best way to detect ovarian cancer is for both the patient and her clinician to have a high index of suspicion of the diagnosis in symptomatic women. But there are no tests that could reliably detect ovarian cancer in its earliest and most curable stage and so educating women and practitioners about symptoms and prompt initiating work up helps in timely diagnosis and treatment.

Symptoms and signs are usually present 3-6 months at least before diagnosis, these include increased distension or bloating, abdominal or pelvic pain, feeling full quickly or difficulty in eating etc. These symptoms and signs should be evaluated with suspicion of ovarian cancer, with pelvic examination, TVS and CA-125. Though a thorough bimanual pelvic examination is cost effective, it is not cost sensitive to detect ovarian cancer in asymptomatic women.

Tumour markers

CA-125 is the most extensively studied tumour marker in ovarian carcinoma. Ca-125 is a glycoprotein produced by majority of epithelial ovarian cancer (EOC). It is elevated in 61-95% of symptomatic patients with EOC and in 29- 75% of those with stage I disease. Normal value is 30- 35 U/ml, it is influenced by menopausal status. In premenopausal women the sensitivity is decreased. It also can be elevated in other cancers like endometrial, breast, lung, lymphoma, colorectal cancer etc. It is also elevated in certain benign conditions like endometriosis, uterine leiomyoma, pregnancy, PID etc. It is not specific for ovarian cancer. In malignancy serial measurements show increase in value. Screening using a single CA-125 measurement is not specific with low sensitivity. Serial measurements combined with TVS improves sensitivity and specificity.

Trans vaginal sonography

It has been found to be safe and effective means visualizing ovaries. The earlier studies mainly focused on ovarian volume, normal premenopausal ovarian volume established to be >20 ml and for post menopausal women the cut off value is 8-10 ml. Risk Malignancy Index (RMI) is the most widely used index to diagnose ovarian cancer in suspected cases. It combines three pre-surgical features: serum CA-125, menopausal status (M) and Ultrasound score (U).
RMI: U x M x CA-125

U: One point for each of these morphological criteria- multilocular cysts, solid areas, bilateral lesion, metastases, ascites

M: Menopausal status is scored as 1 for premenopausal and 3 for postmenopausal status.

RMI score of 200 indicates high degree of suspicion of ovarian malignancy, sensitivity of 78% and specificity of 87%.The routine use of CT/MRI for assessment of ovarian masses does not improve sensitivity and specificity obtained by TVS in the detection of ovarian malignancies. What is needed is a multimodal screening using CA-125 and ultrasound. Patient should be referred to a specialist if four or more of the following indicators are present.

1. Premenopausal (< 50 Years)

A. CA-125 > 200 U/ml
B. Ascites
C. Evidence of abdominal/distant metastases by
scan or imaging studies.
D. Family history of breast or ovarian carcinoma
(first degree relatives)

2. Post menopausal women (≥ 50 years)

A. Elevated CA-125 > 35 U/ml
B. Ascites
C. Nodular or fixed pelvic mass
D. Abdominal or distant metastases
E. Family history of breast or ovarian carcinoma
(first degree relatives)

Women often become stuck in their career roles despite their capabilities and potential as men continue to climb the ranks of success within companies and corporations. The number of women CEOs and top executive positions of Fortune 500 and 1000 is below 3.6 percent.

In addition to this, women are also less likely to be placed in managerial positions when compared to men and are continuing to be paid less, despite the fact that women are accounting for a higher percentage of degree holders on a continuum.

Dour and Theran (2011) refer to this occurrence as maladaptive perfectionism, and it is considered to be a risk factor for issues related to poor body image and eating disordered behaviors.

As the superwoman strives for perfection in all areas of her life, she not only wants to be the perfect wife, mother and employee; wanting to be attractive is also an important characteristic. As mentioned previously these roles are naturally conflicting; meaning that failure to achieve perfection is often likely to occur, thus affecting the superwoman in a negative manner.

The superwoman ideal includes the desire to be physically attractive and maintaining a thin physique, leading to the overall perception of one that is independent, successful and beautiful.

Hamacheck (1978) describes different levels of perfectionism on a continuum with normal perfectionists being able to reevaluate themselves when necessary, leading to less detrimental affects on the individual. He proceeds to describe neurotic perfectionism in which the individual is not able to accept failure and is driven more by this factor as opposed to the actual desire to achieve.

Superwomen display this neurotic perfectionism in their drive to have it all. Unfortunately as the superwoman adheres to a persona that is seen is smart, autonomous, nurturing and attractive, she is also putting herself at risk for various factors that can be both psychological and physiological. A prevalent link between perfectionism and adherence to the superwoman schema is the increased likely hood of poor body image and eating disordered behavior.

The superwoman ideal includes the desire to be physically attractive and maintaining a thin physique, leading to the overall perception of one that is independent, successful and beautiful.

Hamacheck (1978) describes different levels of perfectionism on a continuum with normal perfectionists being able to re- evaluate themselves when necessary, leading to less detrimental affects on the individual. He proceeds to describe neurotic perfectionism in which the individual is not able to accept failure and is driven more by this factor as opposed to the actual desire to achieve.

The definition provides that, besides being preventable, treatable and characterized by a chronic and persistent airflow limitation (usually progressive), COPD is due to an increased chronic inflammatory response. The pathologic process is initiated by exposure to cigarette smoke or biomass fuels. Exacerbations and many comorbidities that contribute to severity in a particular patient, have an inflammatory nature as well.

The inflammatory profile in normal smokers is very similar to that of patients with COPD, but less prominent. The concept that emerges is that of an amplified inflammatory response in COPD patients. It is important to understand how the inflammatory response at different anatomical sites causes different physiological sequels, pathological events and clinical manifestations: Central airways (chronic bronchitis), small peripheral airways (obstructive bronchiolitis), lung parenchyma (emphysema), cardiovascular system (pulmonary vascular disease and cor pulmonale) and dysfunction of respiratory and peripheral muscles (systemic disease). The inflammatory process in these compartments is similar, but COPD predominantly affects the small airways and the lung parenchyma.

The aim of this review is to dissect the molecular biology of the inflammatory process and discuss innovative therapeutic strategies for COPD.

Each inhalation of cigarette smoke contains about 10^17 reactive oxygen species (ROS), which initiate the inflammatory response in airways and lung parenchyma. The amplified inflammatory response in COPD is associated with mucus production, proteolysis, fibrosis and cycles of resolution.

The process is possibly determined by genetic factors, latent viruses, oxidative stress and alteration of the Histone Deacetylase-2 (HDAC-2) activity. The type of inflammation that occurs is mediated by the recruitment of different inflammatory cells and the production of distinct mediators, the most important ones will be discussed.

Macrophages are increased in number and activity in the sputum and bronchoalveolar lavage (BAL) of patients with COPD; macrophages play a main role in the inflammatory process. Stimulated by cigarette smoke and other irritants, they release ROS, nitric oxide (NO) and chemokines that attract monocytes, neutrophils and T cells into the inflamed area. Macrophages also have a longer life span, mediated by increased activity of Bc1 -XL anti apoptotic protein.

T cells are CD8 + (suppressor/cytotoxic) subtype Th1/Tc1 (producers of upsilon-interferon) and are located in mucus secreting glands, central and peripheral airways and lung parenchyma. They release granzymes, perforins and tumor necrosis factor alpha (TNF-alpha which induces apoptosis of alveolar type I cells, favoring emphysema.

Neutrophils are increased in the sputum and BAL of patients with COPD. They are attracted by epithelial cells, macrophages and T cells through chemotactic factors; such as interleukin 8 (IL-8), leukotriene B4 (LTB4) and a number of chemokines that belong to the CXC family (cytokines that act over R specific receptors). Neutrophils release serine proteases like Elastase, Cathepsin G, Proteinase-3, Matrix Metalloproteinase-12 (MMP-12) and toxic oxygen radicals, which promote the production of mucus and alveolar destruction.

Is controversial whether eosinophils are elevated in the sputum of stable COPD patients, although they are increased during exacerbation. 10% of COPD patients respond to inhaled glucocorticoids, these patients have a greater number of eosinophils in the airways and greater reversibility to bronchodilators. It has been suggested that this patients may have concomitant asthma. Recently, in a joint effort of GINA and GOLD the term ACOS was developed, as an overlap syndr Asthma and COPD.

Epithelial cells produce TNF-alpha and IL-8 in response to inhaled bronchial irritants. They also generate transforming growth factor beta (TGF-beta) which can cause local fibrosis. Fibroblasts have increased activity and produce extracellular matrix proteins in the small airways (obstructive bronchiolitis). Smooth muscle cells and endothelial cells are also involved in the inflammatory process.

The study conducted by experts is quite encouraging as opposed to the public opinion that smokers do not want to break of the habit of smoking it appeared to be different.

The half of the smokers who want to stop smoking have already tried to do that. For last 4-5 years the number of smokers reduced sufficiently. It is worthy of not that the aggressive promotion of tobacco goods does its “black deed” – the amount of youth that starts smoking reduces very slowly.

Almost the half of the smokers who decided to break off the bad habit has taken the decision upon the recommendation of a doctor. The third of smokers confessed they resort to various medications to give up, and only 6% managed to overcome the harmful addiction.

The curious fact – it is easier to give up smoking for a person with higher education that for that who haven’t finished school (correlation about 8%/3%).

What may cause the sexual dysfunction?

To make sex qualitative and erection full three major moments should be present:
1) the presence of sensitive nervous terminals leading to penis.
2) the possibility of normal blood flow of penis.
3) the emergence of the corresponding signal in brain.

Therefore, the erectile disorders are related to the diseases that eliminate one of the mentioned points. First, it is necessary to mention the blood channels pathology, and atherosclerosis in particular that decreases the diameter of vessels. The psychical diseases, depression, stress and injuries of penis are also of great importance. In the end it is necessary to mention the negative influence of medications and the Peyronie disease.