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Deep Learning Technology: Sebastian Arnold, Betty van Aken, Paul Grundmann, Felix A. Gers and Alexander Löser. Learning Contextualized Document Representations for Healthcare Answer Retrieval. The Web Conference 2020 (WWW'20)
Funded by The Federal Ministry for Economic Affairs and Energy; Grant: 01MD19013D, Smart-MD Project, Digital Technologies
About one percent of breast cancer develops in males. It is estimated that about 2,140 new cases are diagnosed annually in the United States (US) and about 300 in the United Kingdom (UK). The number of annual deaths in the US is about 440 (for 2016 "but fairly stable over the last 30 years"). In a study from India, eight out of 1,200 (0.7%) male cancer diagnoses in a pathology review represented breast cancer. Incidence of male breast cancer has been increasing which raises the probability of other family members developing the disease. The relative risk of breast cancer for a female with an affected brother is approximately 30% higher than for a female with an affected sister. The tumor can occur over a wide age range, but typically appears in males in their sixties and seventies.
Known risk factors include radiation exposure, exposure to female hormones (estrogen), and genetic factors. High estrogen exposure may occur by medications, obesity, or liver disease, and genetic links include a high prevalence of female breast cancer in close relatives. Chronic alcoholism has been linked to male breast cancer. The highest risk for male breast cancer is carried by males with Klinefelter syndrome. Male BRCA mutation carriers are thought to be at higher risk for breast cancer as well, with roughly 10% of male breast cancer cases carrying BRCA2 mutations, and BRCA1 mutation being in the minority.
Examples of congenital abnormalities of the reproductive system include:
- Kallmann syndrome - Genetic disorder causing decreased functioning of the sex hormone-producing glands caused by a deficiency or both testes from the scrotum.
- Androgen insensitivity syndrome - A genetic disorder causing people who are genetically male (i.e. XY chromosome pair) to develop sexually as a female due to an inability to utilize androgen.
- Intersexuality - A person who has genitalia and/or other sexual traits which are not clearly male or female.
It is also known that disruption of the endocrine system by certain chemicals adversely affects the development of the reproductive system and can cause vaginal cancer. Many other reproductive diseases have also been link to exposure to synthetic and environmental chemicals. Common chemicals with known links to reproductive disorders include: lead, dioxins and dioxin-like compounds, styrene, toluene, BPA (Bisphenol A) and pesticides.
A urogenital neoplasm is a tumor of the urogenital system.
Types include:
- Cancer of the breast and female genital organs: (Breast cancer, Vulvar cancer, Vaginal cancer, Cervical cancer, Uterine cancer, Endometrial cancer, Ovarian cancer)
- Cancer of the male genital organs (Carcinoma of the penis, Prostate cancer, Testicular cancer)
- Cancer of the urinary organs (Renal cell carcinoma, Bladder cancer)
Adjusted for age and stage the prognosis for breast cancer in males is similar to that in females. Prognostically favorable are smaller tumor size and absence or paucity of local lymph node involvement. Hormonal treatment may be associated with hot flashes and impotence.
Gonadoblastoma is most often associated with an abnormal chromosomal karyotype, gonadal dysgenesis, or the presence of a Y chromosome in over 90% of cases. Gonadoblastoma has been found in association with androgen insensitivity syndrome, mixed gonadal dysgenesis and Turner syndrome, especially in the presence of Y chromosome-bearing cells.
A gonadoblastoma is a complex neoplasm composed of a mixture of gonadal elements, such as large primordial germ cells, immature Sertoli cells or granulosa cells of the sex cord, and gonadal stromal cells. Most gonadoblastomas are benign.
Pre-testicular factors refer to conditions that impede adequate support of the testes and include situations of poor hormonal support and poor general health including:
- Hypogonadotropic hypogonadism due to various causes
- Obesity increases the risk of hypogonadotropic hypogonadism. Animal models indicate that obesity causes leptin insensitivity in the hypothalamus, leading to decreased Kiss1 expression, which, in turn, alters the release of gonadotropin-releasing hormone (GnRH).
- Undiagnosed and untreated coeliac disease (CD). Coeliac men may have reversible infertility. Nevertheless, CD can present with several non-gastrointestinal symptoms that can involve nearly any organ system, even in the absence of gastrointestinal symptoms. Thus, the diagnosis may be missed, leading to a risk of long-term complications. In men, CD can reduce semen quality and cause immature secondary sex characteristics, hypogonadism and hyperprolactinaemia, which causes impotence and loss of libido. The giving of gluten free diet and correction of deficient dietary elements can lead to a return of fertility. It is likely that an effective evaluation for infertility would best include assessment for underlying celiac disease, both in men and women.
- Drugs, alcohol
- Strenuous riding (bicycle riding, horseback riding)
- Medications, including those that affect spermatogenesis such as chemotherapy, anabolic steroids, cimetidine, spironolactone; those that decrease FSH levels such as phenytoin; those that decrease sperm motility such as sulfasalazine and nitrofurantoin
- Genetic abnormalities such as a Robertsonian translocation
There is increasing evidence that the harmful products of tobacco smoking may damage the testicles and kill sperm, but their effect on male fertility is not clear. Some governments require manufacturers to put warnings on packets. Smoking tobacco increases intake of cadmium, because the tobacco plant absorbs the metal. Cadmium, being chemically similar to zinc, may replace zinc in the DNA polymerase, which plays a critical role in sperm production. Zinc replaced by cadmium in DNA polymerase can be particularly damaging to the testes.
There are a couple of conditions that predispose a woman to forming a luteoma during pregnancy. Polycystic Ovary Syndrome is one such condition. This syndrome is associated with high hormone levels and the failure of the ovaries to release an egg during the menstrual cycle, a symptom more often associated with menopause. The high levels of hormones in polycystic ovary syndrome seem to predispose women to forming a luteoma during pregnancy. A characteristic of luteomas is that they grow better in the presence of high levels of hormones that function in normal growth, sexual development, and reproductive function. Polycystic Ovary Syndrome causes an excess of hormones in the body including some of the hormones related to these functions. Women who have already had a luteoma during a previous pregnancy have a higher high risk of having another luteoma. In this situation, women can be counseled on the risks of another pregnancy and their alternatives. Other risk factors associated with luteomas are multiple pregnancies, advanced maternal age, and Afro-Caribbean ethnicity.
Factors that can cause male as well as female infertility are:
- DNA damage
- DNA damage reduces fertility in female ovocytes, as caused by smoking, other xenobiotic DNA damaging agents (such as radiation or chemotherapy) or accumulation of the oxidative DNA damage 8-hydroxy-deoxyguanosine
- DNA damage reduces fertility in male sperm, as caused by oxidative DNA damage, smoking, other xenobiotic DNA damaging agents (such as drugs or chemotherapy) or other DNA damaging agents including reactive oxygen species, fever or high testicular temperature
- General factors
- Diabetes mellitus, thyroid disorders, undiagnosed and untreated coeliac disease, adrenal disease
- Hypothalamic-pituitary factors
- Hyperprolactinemia
- Hypopituitarism
- The presence of anti-thyroid antibodies is associated with an increased risk of unexplained subfertility with an odds ratio of 1.5 and 95% confidence interval of 1.1–2.0.
- Environmental factors
- Toxins such as glues, volatile organic solvents or silicones, physical agents, chemical dusts, and pesticides. Tobacco smokers are 60% more likely to be infertile than non-smokers.
German scientists have reported that a virus called Adeno-associated virus might have a role in male infertility, though it is otherwise not harmful. Other diseases such as chlamydia, and gonorrhea can also cause infertility, due to internal scarring (fallopian tube obstruction).
Twelve percent of all infertility cases are a result of a woman either being underweight or overweight. Fat cells produce estrogen, in addition to the primary sex organs. Too much body fat causes production of too much estrogen and the body begins to react as if it is on birth control, limiting the odds of getting pregnant. Too little body fat causes insufficient production of estrogen and disruption of the menstrual cycle. Both under and overweight women have irregular cycles in which ovulation does not occur or is inadequate. Proper nutrition in early life is also a major factor for later fertility.
A study in the US indicated that approximately 20% of infertile women had a past or current eating disorder, which is five times higher than the general lifetime prevalence rate.
A review from 2010 concluded that overweight and obese subfertile women have a reduced probability of successful fertility treatment and their pregnancies are associated with more complications and higher costs. In hypothetical groups of 1000 women undergoing fertility care, the study counted approximately 800 live births for normal weight and 690 live births for overweight and obese anovulatory women. For ovulatory women, the study counted approximately 700 live births for normal weight, 550 live births for overweight and 530 live births for obese women. The increase in cost per live birth in anovulatory overweight and obese women were, respectively, 54 and 100% higher than their normal weight counterparts, for ovulatory women they were 44 and 70% higher, respectively.
According to the American Society for Reproductive Medicine (ASRM), Age, Smoking, Sexually Transmitted Infections, and Being Overweight or Underweight can all affect fertility.
In broad sense, acquired factors practically include any factor that is not based on a genetic mutation, including any intrauterine exposure to toxins during fetal development, which may present as infertility many years later as an adult.
Most women of reproductive age develop small cysts each month, and large cysts that cause problems occur in about 8% of women before menopause. Ovarian cysts are present in about 16% of women after menopause and if present are more likely to be cancer.
Benign ovarian cysts are common in asymptomatic premenarchal girls and found in approximately 68% of ovaries of girls 2–12 years old and in 84% of ovaries of girls 0–2 years old. Most of them are smaller than 9 mm while about 10-20% are larger macrocysts. While the smaller cysts mostly disappear within 6 months the larger ones appear to be more persistent.
Among women worldwide, breast cancer is the most common cause of cancer death. Breast self-examination (BSE) is an easy but unreliable method for finding possible breast cancer. Factors that appear to be implicated in decreasing the risk of, early diagnosis of. or recurrence of breast cancer are regular breast examinations by health care professionals, regular mammograms, self-examination of breasts, healthy diet, and exercise to decrease excess body fat.
In the US, up to 20% of infertile couples have unexplained infertility. In these cases abnormalities are likely to be present but not detected by current methods. Possible problems could be that the egg is not released at the optimum time for fertilization, that it may not enter the fallopian tube, sperm may not be able to reach the egg, fertilization may fail to occur, transport of the zygote may be disturbed, or implantation fails. It is increasingly recognized that egg quality is of critical importance and women of advanced maternal age have eggs of reduced capacity for normal and successful fertilization. Also, polymorphisms in folate pathway genes could be one reason for fertility complications in some women with unexplained infertility. However, a growing body of evidence suggests that epigenetic modifications in sperm may be partially responsible.
Carcinoma "in situ" is, by definition, a localized phenomenon, with no potential for metastasis unless it progresses into cancer. Therefore, its removal eliminates the risk of subsequent progression into a life-threatening condition.
Some forms of CIS (e.g., colon polyps and polypoid tumours of the bladder) can be removed using an endoscope, without conventional surgical resection. Dysplasia of the uterine cervix is removed by excision (cutting it out) or by burning with a laser. Bowen's disease of the skin is removed by excision. Other forms require major surgery, the best known being intraductal carcinoma of the breast (also treated with radiotherapy). One of the most dangerous forms of CIS is the "pneumonic form" of BAC of the lung, which can require extensive surgical removal of large parts of the lung. When too large, it often cannot be completely removed, with eventual disease progression and death of the patient.
Most mammary tumors in rats are benign fibroadenomas, which are also the most common tumor in the rat. Less than 10 percent are adenocarcinomas. They occur in male and female rats. The tumors can be large and occur anywhere on the trunk. There is a good prognosis with surgery. Spayed rats have a decreased risk of developing mammary tumors.
Carcinoma "in situ (CIS), also known as in situ" neoplasm, is a group of abnormal cells. While they are a form of neoplasm there is disagreement over whether CIS should be classified as cancer. This controversy also depends on the exact CIS in question (i.e. cervical, skin, breast). Some authors do not classify them as cancer, however, recognizing that they can potentially become cancer. Others classify certain types as a non-invasive form of cancer. The term "pre-cancer" has also been used.
These abnormal cells grow in their normal place, thus ""in situ"" (from Latin for "in its place"). For example, carcinoma "in situ" of the skin, also called Bowen's disease, is the accumulation of dysplastic epidermal cells within the epidermis only, that has failed to penetrate into the deeper dermis. For this reason, CIS will usually not form a tumor. Rather, the lesion is flat (in the skin, cervix, etc.) or follows the existing architecture of the organ (in the breast, lung, etc.). Exceptions include CIS of the colon (polyps), the bladder (preinvasive papillary cancer), or the breast (ductal carcinoma "in situ" or lobular carcinoma "in situ").
Many forms of CIS have a high probability of progression into cancer, and therefore removal may be recommended; however, progression of CIS is known to be highly variable and not all CIS becomes invasive cancer.
In the TNM classification, carcinoma "in situ" is reported as TisN0M0 (stage 0).
Mammary tumors are the third most common neoplasia in cats, following lymphoid and skin cancers. The incidence of mammary tumors in cats is reduced by 91 percent in cats spayed prior to six months of age and by 86 percent in cats spayed prior to one year, according to one study. Siamese cats and Japanese breeds seem to have increased risk, and obesity also appears to be a factor in tumor development. Malignant tumors make up 80 to 96 percent of mammary tumors in cats, almost all adenocarcinomas. Male cats may also develop mammary adenocarcinoma, albeit rarely, and the clinical course is similar to female cats. As in dogs, tumor size is an important prognostic factor, although for tumors less than three centimeters the individual size is less predictive. According to one study, cats with tumors less than three cm had an average survival time of 21 months, and cats with tumors greater than three cm had an average survival of 12 months. About 10 percent of cat mammary tumors have estrogen receptors, so spaying at the time of surgery has little effect on recurrence or survival time. Metastasis tends to be to the lungs and lymph nodes, and rarely to bone. Diagnosis and treatment is similar to the dog. There is a better prognosis with bilateral radical surgery (removing the both mammary chains) than with more conservative surgery. Doxorubicin has shown some promise in treatment.
Breast diseases can be classified either with disorders of the integument, or disorders of the reproductive system. A majority of breast diseases are noncancerous.
Being pregnant decreases the risk of relapse in multiple sclerosis; however, during the first months after delivery the risk increases. Overall, pregnancy does not seem to influence long-term disability. Multiple sclerosis does not increase the risk of congenital abnormality or miscarriage.
In the United States, uterus didelphys is reported to occur in 0.1–0.5% of women. It is difficult to know the exact occurrence of this anomaly, as it may go undetected in the absence of medical and reproductive complications.
Although most cases of ovarian cysts involve monitoring, some cases require surgery. This may involve removing the cyst, or one or both ovaries. Technique is typically laparoscopic, unless the cyst is particularly large, or if pre-operative imaging suggests malignancy or complex anatomy. In certain situations, the cyst is entirely removed, while with cysts with low recurrence risk, younger patients, or which are in anatomically eloquent areas of the pelvis, they can be drained. Features that may indicate the need for surgery include:
- Persistent complex ovarian cysts
- Persistent cysts that are causing symptoms
- Complex ovarian cysts larger than 5 cm
- Simple ovarian cysts larger 10 cm or larger than 5 cm in postmenopausal patients
- Women who are menopausal or perimenopausal
A number of twin gestations have occurred where each uterus carried its pregnancy separately. A recent example occurred on February 26, 2009, when Sarah Reinfelder of Sault Ste. Marie, Michigan delivered two healthy, although seven weeks premature, infants by cesarean section at Marquette General Hospital. It is possible that the deliveries occur at different times, thus the delivery interval could be days or even weeks.