What is a biopsy? |

Indications and Procedures

Biopsy is one of the most common diagnostic tools in medicine. Illness or disease can be caused by biological agents (such as viruses, bacteria, fungi, and parasites), by physical agents (such as radiation, heat, extreme cold, and trauma), by genetic and metabolic abnormalities (such as diabetes), or by cancer, which is a new, abnormal growth commonly called a tumor. Often, however, the cause of an illness or disease may not be known. Nevertheless, the structural changes caused by the disease are characteristic enough so that the study of these alterations can give a clear picture of the nature and course of the disease. Diseases may primarily affect one organ at a time, such as hepatitis (the inflammation of the liver), or may involve many organ systems at once, as in Acquired immunodeficiency syndrome (AIDS).

The signs and symptoms of disease are not specific and are often shared by many conditions. For example, all diseases of the liver can result in jaundice, or yellowing of the skin, and abnormal blood tests. The clinician, who may be an expert in liver disease, may not be able to tell for certain whether the underlying liver condition is caused by a virus, by a toxic substance such as alcohol, or by both. A needle biopsy of the liver may then be obtained. The sample is examined by an expert surgical pathologist, and a specific diagnosis is rendered.

Similarly, a lump in the breast may be innocuous (benign) or cancerous (malignant). Only a biopsy of such a lesion can determine this conclusively. Such a biopsy can be obtained by fine needle aspiration, which is a simple procedure that can be performed in a clinic, or by excision in the operating room. A frozen section is then made for the purpose of rapid diagnosis and management.

Once a biopsy is obtained, it is placed in a special fixative, such as formalin. This solution will preserve—or fix—the internal structure of the tissue and its cells. Expert technicians in histology, called histotechnologists, will then embed the tissue in waxlike paraffin to obtain a “block.” The tissue block is then placed in a microtome, and extremely thin pieces (about 5 micrometers thick in width) are cut from it. The slices are placed on glass slides and stained with different dyes, the most common of which is hematoxylin and eosin (H & E), to delineate the cellular substructures. The slides are examined by a surgical pathologist, who renders a pathology report in which the gross and microscopic features are described, and a diagnosis is made. A differential diagnosis may also be made, in which other possible causes of disease that may give a similar histologic picture are discussed. In addition to the routine study described above, a much more extensive and expensive workup of the biopsy may be done, depending on the anticipated complexity of the condition and organ.

The study of a biopsy requires diligent preparation and staining of the tissue, which is the realm of histotechnologists. Staining refers to the application of artificial dyes to tissue sections and cells to facilitate their microscopic study. Certain tissues and cell parts have different chemical and biological affinities for dyes which, when properly applied, help demarcate and differentiate the properties of these cells. A huge battery of special stains exists that can be used to examine every aspect of cell function in both health and disease. For example, specific enzymes can be evaluated; this technique is called enzyme histochemistry.

Immunologic stains, which help evaluate the status of immune system cells, are expensive and extremely tedious, and their proper interpretation requires considerable expertise. Many antibodies are commercially available for such testing. When directed against specific antigenic cell markers, they form immune complexes that can be targeted with immunological stains. Such stains can then be evaluated by immunofluorescence or immunoperoxidase techniques. Both types employ as their principle of action the forming of complexes between antigens and antibodies and the staining of these complexes. Immunofluorescence staining techniques involve the use of special stains that cause the tissue to shine when it is viewed under a fluorescent microscope; such procedures are performed on frozen section tissues. With immunoperoxidase stains, fixed tissues are used, and the stains are permanent.

Tissue samples can also be studied with an electron microscope, in which electron beams greatly magnify subcellular structures. In this way, the alterations of specific cellular components such as cell membranes, mitochondria, and intracellular viruses can be visualized and analyzed. This ultrastructural study is especially valuable in needle biopsies of the kidneys, as well as in the study of certain unusual cancer cells.

Another highly sophisticated method used to evaluate tissue and cell function in a biopsy is the application of molecular genetics and molecular biopsy techniques. The
polymerase chain reaction (PCR) involves the splitting (splicing) of a specific section of genetic material in a cell and its amplification through a chemical chain reaction into innumerable folds, so that it can be visualized through a light microscope. This type of evaluation allows for the examination of specific microorganisms in a cell and can determine the presence of certain genetic markers of unusual diseases or cancer.

Another way to study the properties of cells is by examining their genetic makeup.
Karyotyping is a technique in which the actual chromosomes in a cell are photographed during mitotic divisions; the chromosomes appear as patterns of bands. Genetic abnormalities can be identified by the number of chromosomes and their appearance. This procedure is often used in the study of cancer cells. An even more sophisticated study of cellular genetic makeup is called gene rearrangement, in which the order of gene stacking is examined for specific markers of certain cancerous growths, especially of white blood cells. Other techniques that are used to evaluate cell functions and morphology are cellular imaging, in which the contours of cell membranes and surfaces are compared using computers, and the use of flow cytometers, in which cells are targeted immunologically and then counted. Both techniques are employed in cancer studies, and the second is also used for patients with abnormal immune systems, such as those with AIDS.

The aforementioned studies are expensive and available only at large medical centers and research institutes. The diagnostic workup in most hospitals, however, does not require the use of these sophisticated methods. Usually, routine H & E stains are applied. The Papanicolaou stain is commonly used with fine needle aspiration biopsies.

A department of pathology in a large medical center usually has one or more surgical pathologists, who are closely affiliated with the clinical and surgical departments and with their many branches and specialties. Interpreting biopsies obtained by any of the surgical or medical specialties is the most important duty of the surgical pathologist, and it requires great expertise and diligence. Because of the complexity of this task, specialized experts in pathology are becoming the norm. For example, a dermatopathologist is a surgical pathologist trained to interpret skin biopsies. Similarly, hematopathologists, neuropathologists, and nephropathologists are experts in the interpretation of blood-related, nerve- and brain-related, and kidney-related biopsies, respectively.

In incisional biopsies, only a portion of the lesion is sampled, and the procedure is strictly of a diagnostic nature. In excisional biopsy, the entire lesion is removed, usually with a rim of normal tissue, and therefore the procedure serves both a diagnostic and a therapeutic function. The decision whether to perform an incisional or an excisional biopsy depends primarily on the size and location of the lesion; the smaller the lesion, the more logical it is to remove it completely. It is preferable, however, to sample a deeply seated large tumor first because the type and extent of the excision varies considerably depending on the tumor type. For example, a small skin mole is usually excised completely, whereas a large soft tissue or bone tumor should be sampled.

Biopsies are also classified according to the instrument used to obtain them: cold knife versus cautery, needle, or endoscope. Of these the one usually least suitable for microscopic study is that obtained with a cautery, which uses a hot knife that burns, chars, and distorts tissue.

An endoscope is a tubelike fiber-optic instrument that is inserted into an orifice or small incision in order to view the contents of a body cavity. The instrument can be rigid or flexible and is equipped with a light source (usually a laser) and a small cutting tool at its tip to allow for the removal of small samples of tissue. Endoscopic biopsies are frequently used to obtain tissue and cell samples from the lungs and the airways, mainly to diagnose laryngeal and lung cancers; this procedure is usually done by a lung specialist. The endoscope is also used to sample lesions in the esophagus, stomach, intestines, and the rest of the intestinal tract, including the rectum. Such procedures are usually performed by a gastroenterologist, a specialist in the stomach and the gastrointestinal tract. Endoscopic biopsies of the urinary bladder and the prostate are done by urologists.

Needle biopsies
are commonly used to obtain samples from superficial or deep-seated lumps. A slender, cylindrical core of tissue, corresponding to the open diameter of the needle, is obtained. The needle biopsy is commonly used to obtain tissue samples from kidneys, bone, and the deep viscera such as the liver. The modified technique of aspiration cytology, commonly called fine needle aspiration, employs a fine-caliber needle (0.6 to 0.9 millimeter in open diameter) and is widely used to obtain cytologic and minute tissue samples, especially for lesions of the lymph
glands, breasts, thyroid gland, salivary glands, lungs, and prostate. Fine needle aspiration is often inexpensive, safe, quick, and, when performed and interpreted by experienced workers, quite accurate. Because of the ready availability and relative inexpense of the endoscopic and fine needle aspiration biopsy techniques, they have become popular; almost every part of the body is now within reach of one or another of these two techniques.

Frozen section biopsy
requires great expertise because this biopsy is usually a form of consultation done during surgery. A tissue sample is instantly frozen, sectioned, stained, and examined—all within about fifteen minutes—in order to render a specific diagnosis. The implications of this diagnosis are far reaching and will influence the surgical procedure and the long-term therapy and outcome for the patient. A frozen section report, for example,
may determine whether an organ such as a breast, lung, or kidney must be removed and whether long-term radiation therapy or chemotherapy will be administered; such would be the case if the diagnosis is read as malignant.

There are two indications, other than establishing a diagnosis, for performing a frozen section: determining the adequacy of the margins of surgical excision (for example, to remove a malignant tumor completely) and establishing whether the tissue obtained contains an ample diagnosable sample to carry out other specialized tissue studies.

Uses and Complications

The following examples illustrate the practical use of the various biopsy techniques.

An excisional biopsy is performed on a pigmented dark lesion on a sun-exposed surface of the body of a young man and is diagnosed as malignant melanoma, which is a tumor of the pigment-producing cells of the body. This diagnosis is confirmed through the use of specialized immunological stains employing specific antibodies against melanin. The pathologist also comments that surgical margins of excision of that tumor are safe and do not contain tumor, and that the tumor is only superficial in nature and does not show deep invasion into the tissue. These two points imply that the patient will probably have a complete cure.

A fine needle aspiration biopsy is applied on a lump on the breast of a young woman. The material obtained is spread on slides, stained with a Papanicolaou stain, and evaluated within hours of its removal. The lump is diagnosed as a fibroadenoma, which is a benign tumor that is completely innocuous and of no further consequence to the young patient.

An elderly patient has an endoscopic biopsy of a visualized mass in the colon, which proves to be cancer. The patient is taken to the operating room, and the colon is resected. A frozen section is performed on the margin on the surgical excision to make sure that it contains no tumor. The stains used in this example are the simple and routine H & E stains.

A liver biopsy is performed on a patient with jaundice (yellowing of the skin), and a diagnosis of viral hepatitis B is made. This diagnosis is made following the study of the liver biopsy by routine stains and by stains that use immunological antibodies against the viral antigen. This is a specific and highly accurate diagnostic study.

A lymph gland excisional biopsy is performed on a patient who feels lumps all over his body. The biopsy is examined with routine and special stains, immunological marker studies, and gene rearrangement. Such extensive studies are performed to make sure that his condition is completely benign and is not neoplastic—that is, that he does not have malignant lymphoma (cancer of lymph tissue).

The biopsy, in its varied forms and techniques, has become an essential component of quality medical care. The biopsy report is both a medical and a legal document. Tissue slides and blocks are often stored for many years, in some places indefinitely. Peer slide reviews and consultations are common and are used as gauges for quality control and management. There are some limitations with histologic diagnosis, which mainly revolve around recognizing a specialist’s own limitations and the need to seek a consultation by another expert pathologist as needed.

Bancroft, John D., and Marilyn Gamble, eds. Theory and Practice of Histological Techniques. 6th ed. New York: Churchill Livingstone/Elsevier, 2008.

Dubowitz, Victor, Caroline A. Sewry, and Anders Oldfors. Muscle Biopsy: A Practical Approach. Oxford: Saunders, 2013.

Fisher, Cyril, Elizabeth A. Montgomery, and Khin Thway. Biopsy Interpretation of Soft Tissue Tumors. Philadelphia: Wolters Kluwer/Lippincott, Williams and Wilkins, 2011.

Koss, Leopold G., Stanisław Woyke, and Włodzimierz Olszewski. Aspiration Biopsy: Cytologic Interpretation and Histologic Basis. 2d ed. New York: Igaku-Shoin, 1992.

Mills, Stacey E., et al., eds. Sternberg’s Diagnostic Surgical Pathology. 5th ed. 2 vols. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2010.

Rosai, Juan. Rosai and Ackerman’s Surgical Pathology. 9th ed. 2 vols. New York: Mosby, 2004.

Shah, Rajal B., and Ming Zhou. Prostate Biopsy Interpretation: An Illustrated Guide. New York: Springer-Verlag, 2012.

Sloan, John P. Biopsy Pathology of the Breast. 2d ed. New York: Oxford University Press, 2001.

Taxy, Jerome B., Aliya N. Husain, and Anthony G. Montag. Biopsy Interpretation: The Frozen Section. Philadelphia: Wolters Kluwer/Lippincott, Williams and Wilkins, 2010.

Yazdi, Hossein M., and Irving Dardick. Diagnostic Immunocytochemistry and Electron Microscopy: Guides to Clinical Aspiration Biopsy. New York: Igaku-Shoin, 1992.

What are neurotransmitters? |

Introduction

In the late 1880s and the early 1900s, Santiago Ramón y Cajal and Charles Sherrington, respectively, demonstrated that there is a gap separating one neuron (nerve cells that transmit and store information) from another, which Sherrington called the synapse. Their work was extended by Otto Loewi, who proved in 1920 that neurons send messages across the synaptic gap using chemicals. By the 1950s, the principle that neurons communicate with one another through chemicals was well established, stimulating both a search for new neurotransmitters and new drugs for psychiatric and other medicinal uses.

The early view was that a presynaptic (sending) neuron discharges only one kind of neurotransmitter across the synaptic cleft to a postsynaptic (receiving) neuron. However, later researchers found that not only are multiple neurotransmitters released in most synapses, but neurotransmitters can be discharged from nonsynaptic neuronal membranes and postsynaptic neurons can send chemical messages to presynaptic cells. Furthermore, the idea that thoughts, feelings, and behavior can be reduced to specific neuronal chemicals is overly simplistic. Neurotransmitter effects depend on a combination of the type of neurotransmitter, what kind of receptor (a transmitter-activated protein molecule) picks up the neurotransmitter, and where in the nervous system the chemicals are released. For example, drug addiction has been linked with high amounts of dopamine at D2 receptors in the mesolimbic system.

Although what is known about neurotransmitters is complex and somewhat hard to grasp, there are three general principles that clarify matters. First, neurotransmitters can be distinguished from one another by the thoughts, feelings, and behaviors with which they are most prominently associated. Second, neurotransmitters can be classified into a handful of categories based on their chemical structure. Third, most neurotransmitters tend to have either an excitatory (activating) or inhibitory (deactivating) effect on affected cells.

Small Molecule Neurotransmitters

The first neurotransmitter discovered was
acetylcholine. Acetylcholine is the primary neurotransmitter for stimulating muscles (atropine and botulism block its effects) and conveying information in the parasympathetic nervous system. In the central nervous system, acetylcholine promotes rapid eye movement (REM) sleep and is critical for learning: Foods high in choline—a precursor of acetylcholine—boost learning; low acetylcholine levels inhibit learning, such as in Alzheimer’s disease.

Several small molecule transmitters are amines (substances containing NH2, an amino group). Four amines tend to have arousing effects.
Dopamine is essential for experiencing pleasure and has been implicated in almost any kind of addiction. Low levels of dopamine are associated with depression, restless leg disorder, and Parkinson’s disorder; very high levels are associated with schizophrenia and impulsiveness.
Epinephrine and norepinephrine are related: Norepinephrine plays a primary role in arousal, vigilance, active emotions, and emotional memories. Stimulant drugs, such as amphetamines, activate norepinephrine pathways. Most norepinephrine receptors accept epinephrine, which is the primary neurotransmitter in the sympathetic nervous system. Histamine conducts itching sensations, and its release by mast cells causes the red flaring typical in allergic reactions. Unlike the other amines, higher levels of serotonin tend to induce a calming effect, reducing impulsivity and decreasing appetite. Low levels are linked with depression (selective serotonin reuptake inhibitors, or SSRIs, form a category of antidepressants that increase serotonin), increased aggression (including suicide), and sudden infant death syndrome. Many hallucinogenic drugs (for example, lysergic acid diethylamine, or LSD, and 3,4-methylenedioxy-N-methylamphetamine, known as MDMA or Ecstasy) appear to work by interacting with serotonin.

The three most prevalent neurotransmitters are amino acids (substances containing amino and carboxyl groups). Almost all synaptic excitation requiresglutamate; almost all synaptic inhibition necessitates gamma-aminobutyric acid (GABA) in the brain or glycine in the spinal cord and lower brain areas. Glutamate is essential for learning; however, an overrelease can precipitate amnesia and neuronal death. Too much glutamate is also implicated in diseases of white matter (loss of myelin), such as multiple sclerosis; not enough glutamate is associated with schizophrenia. GABA has a sedative effect on the nervous system: Benzodiazepines, barbiturates, and alcohol bind on GABA receptors. Lack of GABA and glycine overactivates the nervous system and can induce disorders such as epilepsy (GABA deficits) and lockjaw (glycine deficits).

Peptides

The largest group of neurotransmitters—several dozen—are peptides (amino acid chains). Two peptides have a complementary effect: Substance P is the main carrier of pain; beta endorphins decrease pain. Beta endorphins and enkephalins belong to a family of opiate chemicals produced by the brain that typically increase pleasure but may inhibit learning.

Neuropetides play a role in many basic drives, including drinking (vasopressin), eating (neuropeptide Y), and sexuality (oxytocin).
Oxytocin, the hormone that is involved in uterine contractions and lactation, also serves as the bonding neurotransmitter. Higher levels of oxytocin stimulate and help to maintain pair bonding, parenting, and other prosocial behaviors.

Lipids, Nucleotides, and Gases

The brain not only produces opioids but also cannabis-like lipids called endocannabinoids. One of these chemicals, anandamide, helps to regulate the release of several small molecule transmitters. Endocannabinoids appear to interact with opioids to produce pleasurable effects, and, as with the opioids, overrelease may interfere with learning.

Adenosine, a nucleotide involved in sleep production, is also released by the nervous system’s other main cell type: glia. Caffeine has excitatory effects because it blocks adenosine receptors.

Two water-soluble gases, nitric acid and carbon monoxide, are neurotransmitters that can be released from any neuronal area, unlike all other neurotransmitters. Both neurotransmitters modulate the activity of other neurotransmitters and play a role in metabolic processes. Nitric oxide also dilates blood vessels: Erectile dysfunction drugs enhance the activity of nitric oxide.

Bibliography

Bohlen und Halbach, Oliver von, and Rolf Dermietzel. Neurotransmitters and Neuromodulators: Handbook of Receptors and Biological Effects. Hoboken: Wiley, 2006. Print.

Carlson, Neil R. Foundations of Physiological Psychology. 7th ed. Boston: Allyn, 2008. Print.

Ingersoll, R. Elliott, and Carl F. Rak. Psychopharmacology for Helping Professionals: An Integral Perspective. Belmont.: Thomson, 2006. Print.

Julien, Robert M., Claire D. Advokat, and Joseph E. Comaty. A Primer of Drug Action. 12th ed. New York: Worth, 2011. Print.

Kandel, Eric R. Principles of Neural Science. 5th ed. New York: McGraw, 2013. Print.

Lajtha, Abel, and E. Sylvester Vizi, eds. Handbook of Neurochemistry and Molecular Neurobiology: Neurotransmitter Systems. 3rd ed. New York: Springer, 2008. Print.

What is depression? How does it affect cancer patients?

Risk factors: Depression is most common among cancer patients with advanced disease and with symptoms and discomfort that are not treated or inadequately treated. It commonly coexists with anxiety and is common in individuals with substance abuse problems and other chronic physical and mental disorders. Most cancer patients manifest transient symptoms of depression that are responsive to support, reassurance, and information about what to expect regarding the course, treatment, and prognosis of their disease. Others experience unremitting or recurrent depression requiring aggressive monitoring and intervention. The following list depicts risk factors that favor the development of clinically significant depression within the context of a cancer diagnosis:

• Family history of depression





• Past history of depression, depression treatment, psychiatric hospitalization, or significant psychiatric/personality disorder





• History of unusual, eccentric behavior





• Confusion (may be indicative of an organically based depression)





• Maladaptive coping style





• Dysfunctional family coping or complex family issues





• Limited social support





• Financial problems including lack of insurance





• Multiple roles, obligations, and stressors





• Advanced cancer





• Treatment resulting in disfigurement or loss of function





• Presence of dependent children





• Inadequate symptoms management





• Treatment that has a depressionogenic effect (certain chemotherapies, steroids, narcotics)

Etiology and the disease process: Simplistically stated, the etiology of clinical depression, cancer related or not, is based on a complex interaction of factors. These include genetic predisposition to aberrant neurochemical states that precede or result from an inadequate stress response combined with a distorted, negatively biased cognitive style or worldview that is learned and reinforced early in life. This multidimensional framework indicates need for a combined psychopharmacologic and psychotherapeutic treatment approach that is well supported in the medical literature. Clinical depression can present as a single episode, be chronic and unremitting, or occur over time with periods of remissions and exacerbations.

A crisis framework is often used to describe the occurrence of depression in the context of cancer. The acute crisis response (ACR) typically occurs at transitions in the disease trajectory (diagnosis, treatment initiation, recurrence, treatment failure, disease progression). The ACR is characterized by symptoms of anxiety and depression that usually resolve within a short time period. Time frames are variable, but the ACR usually resolves when individuals know what to expect in terms of treatment, receive reassurance that discomfort can be controlled, and mobilize usual coping strategies and support systems. When symptoms worsen rather than resolve over time or coping mechanisms are insufficient, treatment for depression must be considered regardless of whether diagnostic criteria for a clinical diagnosis are met.

Incidence: Prevelance rates vary and depend on the population studied, site and stage of disease, and method used to measure depression. Prevalence rates among cancer patients range from 5 percent (lower than general population rates) to 90 percent. In general, studies that use established diagnostic criteria report rates of depression of about 25 percent. Rates of depression are highest among patients with advanced cancer and in studies in which stringent diagnostic guidelines are not used.

Symptoms: Symptoms of depression in cancer populations include the following:

• Persistent sad mood





• Loss of interest or pleasure in typically pleasurable activities





• Feelings of guilt, worthlessness, helplessness





• Crying, not easily comforted





• Frequent thoughts of death or suicide





• Trouble concentrating, indecisiveness





• Appetite change





• Diminished energy that may be mixed with restlessness and anxiety





• Fatigue, loss of energy





• Insomnia or hypersomnia

Diagnosis of cancer-related depression relies heavily on the presence of affective symptoms (the first five symptoms in the list). Neurovegetative symptoms (the last five symptoms in the list) that characterize depression in physically healthy individuals are not good predictors of depression in cancer patients because cancer and its treatment produce similar symptoms. Additional behaviors suggestive of depression include refusal, indecisiveness, or noncompliance with treatment; persistent anxiety and sadness, unresponsive to usual support; unremitting fear associated with procedures; excessive crying, hopelessness that does not diminish over time; an abrupt change in mood or behavior; eccentric behavior or confusion; and excessive guilt or self-blame for illness.

Screening and diagnosis: A formal diagnosis of depression is based on fulfillment of criteria outlined in the American Psychiatric Association’s
Diagnostic and Statistical Manual of Mental Disorders (DSM). The diagnostic subtypes of depression include major depressive disorder (severe depression that lasts for more than two weeks and is particularly amenable to pharmacologic treatment), adjustment disorder with depressed features (depression that occurs in response to a clearly defined event or stressor), dysthymia (chronic, low-level depression that pervades an individual’s personality and daily life), and bipolar disorder (a genetically determined severe form of depression that may or may not alternate between depressive lows and manic highs and is responsive to mood-stabilizing, pharmacologic agents). Major depression and adjustment disorder are common diagnoses among individuals with cancer. Dysthymia and bipolar disorder usually precede a cancer diagnosis or occur for the first time following cancer diagnosis in those genetically predisposed.

Depressive symptoms not severe enough or of sufficient duration to achieve diagnostic status are the most common type of depressive phenomena in individuals with cancer. Because a formal diagnosis is not present, these symptoms are often ignored despite a common, negative impact. More research on the simultaneous occurrence of cancer and depression is needed, including symptom profiles, clinical treatment trials, and related outcomes.

A number of tests screen for depression, but they have not been consistently incorporated into clinical care. Nonpsychiatric providers fail to diagnose and treat depression in as many as 50 percent of cancer patients with depressive disorders. Obstacles to recognizing depression include inadequate provider knowledge of diagnostic criteria, competing treatment priorities in oncology settings, time limitations in busy offices, concern about the stigma associated with a psychiatric diagnosis, limited reimbursement, and uncertainty about the value of screening mechanisms for case identification. In general, regardless of whether screening measures are used, if symptoms do not remit in a reasonable time frame, evaluation of depressive symptoms by a psychiatric specialist should be sought.

Treatment and therapy: Psychosocial interventions can exert an important effect on the overall adjustment of patients and their families to cancer and its treatment. Factors contributing to the diagnosis of depression should influence the treatment approach. Treatments include psychopharmacologic treatment, individual psychotherapy, group therapy, family therapy, marital therapy, or some combination of these.

Antidepressant medication should be chosen on the basis of diagnostic subtype, treatment response, and side effect profile. Bipolar disorder is usually treated with a mood stabilizer, requiring careful monitoring and adjustment, especially during active treatment, as therapeutic blood levels are narrow and can shift dramatically in response to electrolyte and metabolic changes. Major depression is commonly treated with one of several classes of antidepressant medication, commonly a selective serotonin reuptake inhibitor (SSRI) or a a selective serotonin and norepinepherine reuptake inhibitor (SSNRI). Dosages are typically lower than required in healthy individuals and can positively affect other symptoms that the patient might be experiencing, such as pain and anxiety. In the oncology setting, a multimodal treatment approach is most effective in treating depression and can have a positive impact on a range of psychosocial and medical outcomes.

Prognosis, prevention, and outcomes: Left untreated, depression can produce a range of negative outcomes from diminished quality of life to noncompliance with treatment to diminished survival. Depression can be prevented in some individuals by providing preemptive counseling, education, support, and information about resources. Early recognition and treatment offer the best hope for rapid remission. Modern therapies are effective in treating depression even among cancer patients who are in progressive and terminal stages of illness. Treatment can vastly improve quality of life and diminish suffering; thus routine screening and treatment should be a universal aspect of comprehensive cancer care .

Akechi, Tatsuo, et al. “Major Depression, Adjustment Disorders, and Post-traumatic Stress Disorder in Terminally Ill Cancer Patients: Associated and Predictive Factors.” Journal of Clinical Oncology 22.10 (2004): 1957–65. Print.

Carr, D., et al. Management of Cancer Symptoms: Pain, Depression, and Fatigue. Evidence Report/Technology Assessment 61. AHRQ Publication No. 02-E032. Rockville: Agency for Healthcare Research and Quality, 2002. Print.

"Depression." National Cancer Institute. Natl. Institutes of Health, 28 Aug. 2014. Web. 2 Oct. 2014.

"Depression and Cancer." National Institutes of Mental Health. Natl. Institutes of Health, 2011. Web. 2 Oct. 2014.

Fleishman, S. “Treatment of Symptom Clusters: Pain, Depression, and Fatigue.” Journal of the National Cancer Institute: Monographs 2004.32 (2004): 119–23. Print.

Lloyd-Williams M. “Screening for Depression in Palliative Care Patients: A Review.” European Journal of Cancer Care 10 (2001): 31ff. Print.

Parker, P. A., W. F. Baile, C. de Moor, and L. Cohen. “Psychosocial and Demographic Predictors of Quality of Life in a Large Sample of Cancer Patients.” Psychooncology 12.2 (2003): 183–93. Print.

Patrick, D. L., et al. “National Institutes of Health State-of-the-Science Conference Statement: Symptom Management in Cancer: Pain, Depression, and Fatigue, July 15–17, 2002.” Journal of the National Cancer Institute 95 (2003): 1110ff. Print.

Walker, Jane, et al. "Integrated Collaborative Care for Major Depression Comorbid with a Poor Prognosis Cancer (SMaRT Oncology-3): A Multicentre Randomised Controlled Trial in Patients with Lung Cancer." Lancet Oncology 15.10 (2014): 1168–76. Print.

What is kidney cancer? |

Risk factors: The most common risk factor for kidney cancer is smoking cigarettes. Kidney cancer also appears to be more common in persons who are obese or who have high blood pressure. There are three hereditary syndromes that put a person at a higher risk of developing kidney cancer: von Hippel–Lindau disease, hereditary leiomyomatosis, and Birt-Hogg-Dubé syndrome. These syndromes may be caused by spontaneous mutations. Some occupations put a person at higher risk for developing kidney cancer. These include occupations in which a person is exposed to certain toxic chemicals or substances, such as petroleum-based products, asbestos, lead, or cadmium. Also, persons who are on long-term dialysis therapy for kidney failure are at higher risk of developing kidney cancer.

Etiology and the disease process: Kidney cancer arises from a single cell that grows wildly. For renal-cell cancer, this is a cell of the tubular epithelium of the nephron, the part of the kidney that filters waste products from the blood and produces urine for excreting these wastes. Transitional-cell renal cancer manifests itself in the renal pelvis, where urine is delivered by the nephrons. The types of renal cancer vary in their aggressiveness and in how quickly they metastasize. Some will metastasize from a small tumor in the kidney, and other types do not metastasize until they have engulfed the kidney. Kidney cancer spreads through the lymph nodes and the bloodstream. Common sites for metastases are the other kidney, the lung, the adrenal gland, the bones, and the liver.

Incidence: There were approximately 63,920 new cases of kidney cancer diagnosed in the United States in 2014. It is twice as common in men as in women. However, kidney cancer is actually relatively rare compared with other cancers, representing about 3.8 percent of all new cases of cancer in the United States. About 13,860 Americans died of kidney cancer in 2014.

Symptoms: The symptoms of kidney cancer do not appear until the tumor is fairly large or has metastasized. The symptoms are blood in the urine (hematuria), abdominal mass, back or flank pain, weight loss, recurrent fever, and fatigue. Blood tests may demonstrate a high serum calcium and either anemia or high red blood cell counts. A urine analysis test may show microscopic hematuria that is not visible to the eye. Kidney cancer can also cause hypertension, although this symptom is not particularly helpful in diagnosing kidney cancer because it is so common.

Screening and diagnosis: There is no routine screening performed for kidney cancer. However, kidney cancer may be found incidentally on a chest, abdominal, or pelvic ultrasound; computed tomography (CT) scan; or magnetic resonance imaging (MRI) performed for another reason.

Kidney cancer is usually diagnosed by a renal ultrasound, an abdominal CT scan, an MRI, or a positron emission tomography (PET) scan. Occasionally, an intravenous pyelogram (IVP) is performed, although this diagnostic test has largely been replaced by ultrasounds, CT scans, and MRIs. Once a kidney tumor is discovered, it needs to be biopsied to identify the type of cells in the tumor. Kidney cancers may be biopsied by fine needle through the skin below the rib cage on the back or by ureteroscopy (the passing of a ureteroscope through the urethra, the bladder, one of the ureters, and the renal pelvis, and then into the body of the kidney). Both procedures require fluoroscopy to localize the tumor.

Kidney cancer is usually staged with a combination of the American Joint Committee on Cancer (AJCC) TNM staging system and a numeric grouping. “T” refers to the size of the tumor, “N” refers to lymph node involvement, and “M” refers to whether there are metastases. The stages are as follows:

• Stage I, T1a-T1b, N0, M0: The tumor is less than 7 centimeters (cm) with no lymph node involvement and no metastases.





• Stage II, T2, N0, M0: The tumor is greater than 7 cm with no spread outside the kidney.





• Stage III, T1a-T3b, N1, M0 or T3a-3c, N0, M0: The tumor has spread to a single lymph node but not metastasized, or has spread to adjacent tissue or structures, such as the adrenal glands, to fatty tissue around the kidney, or into the vena cava.





• Stage IV, T4, N0-N1, M0; any T, N2, M0; or any T, any N, M1: The tumor extends beyond the kidney locally and has spread into the lymph system. It is present in more than one lymph node. There may also be metastases to other organs.

Treatment and therapy: For many years, the only treatment for kidney cancer was to surgically remove the affected kidney (nephrectomy). This was done unless the cancer was so far advanced that there was little hope for the patient. Kidney cancer did not respond well to either radiation therapy or chemotherapy. Consequently, these treatments were used only to treat metastatic kidney cancer, to relieve the symptoms, and to prolong the patient’s life. However, in the mid-2000s, more treatment options for kidney cancer were discovered, and further research is ongoing.

Kidney-cancer surgeries include total radical nephrectomy, laparoscopic radical nephrectomy, partial nephrectomy, radiofrequency ablation (destroying the tumor with high-energy radio waves), cryoablation (freezing), and arterial embolization (blocking the artery feeding the tumor with material). The original total radical nephrectomy procedure, in which an eighteen-inch incision is made from below the mediastinum (breast bone) to the middle of the back, is no longer the sole surgical option. Several laparoscopic
radical nephrectomy procedures are available. These laparoscopic procedures require a 3- to 4-inch incision and 3.5-inch incisions. Recovery time for the patient is four weeks rather than the twelve weeks of recovery required for the original procedure.

Kidney cancer still does not respond well to radiation therapy. Advances in the development of chemotherapy drugs have benefited the treatment of kidney cancer. However, it is still not routine to prevent the recurrence of a kidney cancer with chemotherapy, as is done with other cancers. The focus of chemotherapy treatment for kidney cancer is to prolong the life of the patient. As a result, chemotherapy is reserved for treating advanced renal cancers with metastases. Kidney cancer may be treated with angiogenesis inhibitors (drugs that inhibit the growth of blood vessels feeding the tumors), such as sorafenib tosylate (Nexavar) and sunitinib malate (Sutent).

Other drugs now being used to treat advanced kidney cancer are bevacizumab (Avastin), interleukin-2, and interferon. Bevacizumab is a monoclonal antibody that interferes with the growth and development of new blood vessels within a tumor. Interleukin-2 and interferon are referred to as biological therapy, because these substances are normally produced by the body in small amounts. Their role in kidney cancer treatment is to stimulate the body’s normal immune defenses. Like other chemotherapy drugs, these drugs have many severe side effects.

In May 2007, the drug temsirolimus (Torisel) was approved by the Food and Drug Administration (FDA) for treating kidney cancer. Temsirolimus is an enzyme inhibitor that interferes with cell growth, development, and survival. The FDA also approved pazopanib hydrochloride (Votrient) and everolimus (Afinitor) in 2009 and axitinib (Inlyta) in 2012. Pazopanib hydrochloride and axitinib are tyrosine kinase inhibitors, and everolimus is a mammalian target of rapamycin (mTOR) inhibitor.

Prognosis, prevention, and outcomes: With kidney cancer, the prognosis depends on the stage of the cancer at diagnosis. In stages I and II, surgical intervention is likely to remove the cancer, and five-year survival rates are approximately 81 percent and 74 percent, respectively. In stages III and IV, the prognosis is guarded and depends on the patient’s response to treatments, particularly drug therapy; survival rates are approximately 53 percent in stage III and 8 percent in stage IV. Treatment in these stages may be aimed at extending the patient’s life and providing a reasonable quality of life.

It is not possible to prevent kidney cancer. Certainly, not smoking cigarettes will decrease a person’s likelihood of developing kidney cancer. Other lifestyle choices, such as occupation, might also decrease the likelihood of developing kidney cancer, but many of the substances thought to cause kidney cancer are fairly pervasive in the environment. Some kidney cancers develop in people with no apparent risk factors for the disease.

Bickerstaff, Linda. Kidney Cancer: Current and Emerging Trends in Detection and Treatment. New York: Rosen, 2012. Print.

Bukowski, Ronald M., Robert A. Figlin, and Robert J. Motzer, eds. Renal Cell Carcinoma: Molecular Targets and Clinical Applications. 3rd ed. New York: Springer, 2015. Print.

Campbell, Steven C., and Brian I. Rini, eds. Renal Cell Carcinoma: Clinical Management. New York: Humana, 2013. Print.

Diaz, José I., Linda B. Mora, and Ardeshir Hakam. “The Mainz Classification of Renal Cell Tumors.” Cancer Control: Journal of the Moffitt Cancer Center 6.6 (1999): 571–79. Print.

"Kidney Cancer (Adult): Renal Cell Carcinoma." American Cancer Society. Amer. Cancer Soc., 13 Jan. 2015. Web. 22 Jan. 2015.

Lara, Primo N., Jr., and Eric Jonasch, eds. Kidney Cancer: Principles and Practice. Berlin: Springer, 2012. Print.

Magee, Colm, and Lynn Redahan. "The Kidney in Cancers." National Kidney Foundation's Primer on Kidney Diseases. Ed. Scott J. Gilbert et al. 6th ed. Philadelphia: Saunders, 2014. 277–85. Print.

Nuñez, Kelvin R., ed. Trends in Kidney Cancer Research. New York: Nova, 2006. Print.

Patel, Uday, ed. Carcinoma of the Kidney. New York: Cambridge UP, 2008. Print.

Rodriguez, Alejandro, and Wade J. Sexton. “Management of Locally Advanced Renal Cell Carcinoma.” Cancer Control: Journal of the Moffitt Cancer Center 13.3 (2006): 199–210. Print.

Tannir, Nizar M., ed. Renal Cell Carcinoma. New York: Oxford UP, 2014. Print.

What are isoflavones' therapeutic uses?

Overview

Isoflavones are water-soluble chemicals found in many plants. This article
focuses on a group of isoflavones that are phytoestrogens, meaning that they cause effects in the body
somewhat similar to those of estrogen. The most investigated
phytoestrogen isoflavones, genistein and daidzein, are found in both soy products
and the herb red
clover. Soy additionally contains glycitein, an isoflavone
that is more estrogenic than genistein and daidzein but is usually present in
relatively low amounts. Red clover also contains two other isoflavones: biochanin
(which can be turned into genistein) and formonenetin (which can be turned into
daidzein).

Certain cells in the body have estrogen receptors, special sites that allow estrogen to attach. When estrogen attaches to a cell’s estrogen receptor, estrogenic effects occur in the cell. Isoflavones also latch onto estrogen receptors, but they produce weaker estrogenic effects. This leads to an interesting two-part action. When there is not enough estrogen in the body, isoflavones can stimulate cells with estrogen receptors and partly make up for the deficit. However, when there is plenty of estrogen, isoflavones may tend to block real estrogen from attaching to estrogen receptors, thereby reducing the net estrogenic effect. This may reduce some of the risks of excess estrogen (for example, breast and uterine cancer), while still providing some of estrogen’s benefits (such as preventing osteoporosis).

Isoflavones also appear directly to reduce estrogen levels in the body, perhaps by fooling the body into thinking that it has plenty of estrogen. Isoflavones are widely thought to be the active ingredients in soy products. However, growing evidence suggests that there are other active ingredients, such as proteins, fiber, and phospholipids.

Requirements and Sources

Although isoflavones are not essential nutrients, they may help reduce the incidence of several diseases. Thus, isoflavones may be useful for optimum health, even if they are not necessary for life like a classic vitamin.

Roasted soybeans have the highest isoflavone content: about 167 milligrams (mg) for a 3.5-ounce serving. Tempeh (a cake of fermented soybeans) is next, with 60 mg, followed by soy flour with 44 mg. Processed soy products, such as soy protein and soy milk, contain about 20 mg per serving. The same isoflavones found in soy are also contained in certain red clover products.

Therapeutic Dosages

When purified isoflavones from red clover or soy are used, the dose generally ranges from about 40 to 80 mg daily. This is considerably higher than the average isoflavone intake in Japan, which is about 28 mg daily. (Postmenopausal Japanese women may consume closer to 50 mg daily.)

There are three major isoflavones found in soy: genistein,
daidzein, and glycitein. Each of these isoflavones can occur in two types or
states. The first type, predominant in raw soy products, is called an isoflavone
glycoside. In an isoflavone glycoside, the isoflavone is attached to a sugarlike
substance known as a glycone. The second type, predominant in fermented soy
products, is called an isoflavone aglycone. These consist of isoflavones without a
glycone attached and are also called free isoflavones. Because isoflavone
aglycones are the most pure form of isoflavones, it has been hypothesized (but not
proven) that they are more effective than other forms.

Therapeutic Uses

Soy products are known to improve cholesterol profile, but isoflavones may not be the active cholesterol-lowering ingredient in soy. Isoflavones may, however, improve other measures linked to cardiovascular risk, such as levels of blood sugar, insulin, and fibrinogen.

According to some but not all studies, soy protein or concentrated isoflavones from soy or red clover may slightly reduce menopausal symptoms, such as hot flashes and vaginal dryness. However, isoflavones have failed to prove effective for the hot flashes that often occur in breast cancer survivors. There is conflicting evidence regarding whether soy or isoflavones may be helpful for preventing osteoporosis, but on balance, the evidence suggests a modest beneficial effect.

One study tested a purified soy isoflavone product (technically, isoflavone aglycones) for treatment of aging skin. In this double-blind trial, twenty-six Japanese women in their late thirties and early forties were given either placebo or 40 mg daily of soy isoflavone aglycones for twelve weeks. Researchers monitored two types of wrinkles near the eye: fine and linear. The results indicated that use of the soy product significantly reduced fine wrinkles compared with placebo. (Effects on linear wrinkles were not significant.) As a secondary measure, researchers also analyzed skin elasticity and found an improvement in the women given the isoflavones, compared with those given placebo. This was much too small a study for its results to be taken as reliable.

A small and poorly reported double-blind, placebo-controlled study provides weak evidence that red clover isoflavones might be helpful for cyclic mastalgia. A combination product containing soy isoflavones, black cohosh, and dong quai has shown some promise for menstrual migraines.

One study found that use of soy isoflavones improved the effectiveness rate of in vitro fertilization (used for female infertility). A double-blind study performed in China found that use of a soy isoflavone supplement improved blood sugar control in healthy postmenopausal women.

In a small double-blind trial, use of soy isoflavones appeared to reduce some symptoms of premenstrual syndrome (PMS). A very small study found hints that soy isoflavones might help reduce buildup of abdominal fat.

Observational studies hint that soy may help prevent breast and uterine cancer
in women. If this connection is real and not a statistical accident (observational
studies are notorious for falling prey to statistical accidents), the explanation
may lie in the estrogen-like action of soy isoflavones. As noted above,
isoflavones decrease the action of regular estrogen by blocking estrogen receptor
sites and may also reduce levels of circulating estrogen. Since estrogen promotes
breast and uterine cancer, these effects could help prevent breast
cancer. Soy also appears to lengthen the menstrual cycle by a
few days, and this also would be expected to reduce breast cancer risk. However,
only a large, long-term intervention trial could actually show that soy or
isoflavones reduce breast and uterine cancer risk, and one has not
been performed.

Observational studies also hint that soy might help prevent prostate
cancer in men. Men have very low levels of circulating
estrogen, so the net effect of increased soy consumption might be to increase
estrogen-like activity in the body. Since real estrogen is used as a treatment to
suppress prostate cancer, perhaps the mild estrogen-like activity of isoflavones
has a similar effect. Isoflavones might also decrease testosterone
levels and alter ratios of certain forms of estrogen, both of which would be
expected to provide benefit. In one double-blind study, men with early prostate
cancer were given either isoflavones or placebo, and their PSA levels were
monitored. (PSA is a marker for prostate cancer, with higher values generally
showing an increased number of cancer cells.) The results did show that use of
isoflavones (60 mg daily) slightly reduces PSA levels. Whether this meant that soy
actually slowed the progression of the cancer or simply lowered PSA directly is
not clear from this study alone. However, in another study of apparently healthy
men (not known to have prostate cancer), soy isoflavones at a dose of 83 mg per
day did not alter PSA levels. Taken together, these two studies provide some
direct evidence that soy isoflavones may be helpful for treating or preventing
prostate cancer, but the case nonetheless remains highly preliminary.

According to most but not all studies, soy isoflavones do not improve mental function. One study failed to find that soy protein with isoflavones improved general quality of life (health status, depression, and life satisfaction) in postmenopausal women. Soy isoflavones have also failed to prove effective for reducing levels of homocysteine.

Scientific Evidence

High cholesterol. Numerous studies have found that soy can reduce blood cholesterol levels and improve the ratio of low-density lipoprotein (LDL, or bad cholesterol) to high-density lipoprotein (HDL, or good cholesterol). Although it was once thought that isoflavones are the ingredients in soy responsible for improving cholesterol profile, on balance, current evidence suggests otherwise. Nonisoflavone constituents of soy, such as proteins, fiber, and phospholipids, may be as important as, or perhaps even more important than, the isoflavones in soy.

It is also possible that the exact types of isoflavones in a particular product made a difference. One study of red clover isoflavones found evidence that biochanin but not formononetin can reduce LDL cholesterol.

Another study found that soy products may at times have an unusual isoflavone profile, containing high levels of the isoflavone glycitein rather than the more usual genistein and daidzein. Glycitein could be inactive regarding cholesterol reduction.

Finally, some evidence hints that soy isoflavones may be effective for reducing cholesterol only when it is converted by intestinal bacteria into a substance called equol. It appears that only about one-third of people have the right intestinal bacteria to make equol.

Menopausal Symptoms. Although study results are not entirely
consistent, the balance of the evidence suggests that isoflavones from soy may be
helpful for symptoms of menopause, especially hot flashes.
Improvements in hot flashes, as well as other symptoms, such as vaginal dryness,
have been seen in many studies of soy, mixed soy isoflavones, isoflavone
aglycones, or genistein alone. However, the effects have been slight or
nonexistent in other studies. At least two studies found that people who are equol
producers may experience greater benefits. The herb Pueraria
mirifica, which also contains a number of isoflavones, has also shown
some benefit for menopausal symptoms.

However, several other studies have failed to find benefit with whole soy or
concentrated soy isoflavones. Another study failed to find benefit with a mixture
of soy isoflavones and black cohosh. Isoflavones from red
clover have also shown inconsistent benefit, with the largest and most recent
trial failing to find any reduction in hot flash symptoms. Furthermore, in
double-blind, placebo-controlled trials, soy or purified isoflavones failed to
reduce hot flashes among survivors of breast cancer.

What can one make of this mixed evidence? The problem here is that placebo treatment has a strong effect on menopausal symptoms. In such circumstances, statistical noise can easily drown out the real benefits of a treatment under study. Estrogen is so powerful for hot flashes and other menopausal symptoms that its benefits are almost always clear in studies; it is likely that soy or concentrated isoflavones have a more modest effect, not always seen above the background.

Osteoporosis. Estrogen has a powerfully protective effect on bone. Studies exploring whether isoflavones have the same effect have produced inconsistent results. On balance, it is probably fair to summarize current evidence as indicating that isoflavones (as soy, genistein, mixed isoflavones, or tofu extract) have at least a modestly beneficial effect on bone density.

The best evidence is for genistein taken alone. In a twenty-four-month, double-blind study of 389 postmenopausal women with mild bone loss, use of genistein at a dose of 54 mg daily significantly improved bone density, compared with placebo. (All participants were additionally given calcium and vitamin D.)

However, it is not clear that isoflavones consumed in the diet, even at high concentrations are beneficial. For example, in a placebo-controlled study involving 237 healthy women in the early stages of menopause, the consumption of isoflavone-enriched foods (providing an average of 110 mg isoflavone aglycones daily) for one year had no affect on bone density or metabolism. One small but long-term study suggests that progesterone cream (another treatment proposed for use in preventing or treating osteoporosis) may decrease the bone-sparing effect of soy isoflavones.

Bone is always subject to two influences: bone building and bone breakdown. Estrogen primarily works by reducing the bone breakdown part of the equation, thereby leading to a net result of increased bone growth. Growing evidence suggests that isoflavones act on both sides of this equation, directly stimulating new bone creation, while at the same time slowing bone breakdown. There is mixed evidence that isoflavones are more effective for osteoporosis in people who have the intestinal bacteria to produce equol.

Menstrual migraines. In a twenty-four-week, double-blind study, forty-nine women with menstrual migraines (migraine headaches associated with the menstrual cycle) received either placebo or a combination supplement containing soy isoflavones and extracts of dong quai and black cohosh. Beginning at the twentieth week, use of the herbal supplement resulted in decreased severity and frequency of headaches, compared with placebo. However, it is not clear which of the ingredients in the combination was helpful. The authors of the study apparently considered black cohosh and dong quai as phytoestrogens, but the current consensus is that they do not belong in that category.

Safety Issues

Studies in animals have found soy isoflavones essentially nontoxic. The long history of the use of soy as food in Asia would also tend to suggest that they are safe. Even though absolute safety cannot be assumed from historical consumption of soy as food, it is reassuring to note that researchers found no evidence of ill effects when they gave healthy postmenopausal women 900 mg of soy isoflavones a day for eighty-four consecutive days. In Japan, the maximum safe intake level of soy isoflavones has been set at a total of 70 to 75 mg daily (food plus supplement sources).

Still, concerns have been raised about estrogenic and other potential side effects of excessive soy isoflavone intake. Overall, the estrogenic effect of soy isoflavones in women seems to be fairly minimal. Nonetheless, it is not zero. According to most but not all studies, use of soy has enough of an estrogen-like effect to slightly alter the menstrual cycle and change levels of sex hormones in young women. Thus, some of the risks of estrogen could, in theory, apply to isoflavones as well.

For example, because estrogen can stimulate breast cancer cells, there are theoretical concerns that isoflavones may not be safe for women who have already had breast cancer. While isoflavones in general should have an antiestrogenic effect by blocking real estrogen, some studies in animals have found evidence that under certain circumstances, soy isoflavones might stimulate breast cancer cells. Studies directly examining the effects of isoflavones on human breast tissue have produced contradictory results. However, on balance, there is no convincing evidence that consuming moderate amounts of soy isoflavones (at levels typical of an Asian diet) increases the risk of breast cancer in healthy women or worsens the prognosis of women with breast cancer. Nevertheless, given the theoretical risk and the absence of large randomized trials investigating the safety of isoflavone supplements, prudence suggests that women who have had breast cancer, or are at high risk for it, should consult a physician before taking any isoflavone product.

Estrogen also stimulates uterine cells, leading to an increased risk of uterine cancer. Most studies have found that isoflavones do not stimulate uterine cells. However, one fairly large (365 participants) and long-term (five years) study did find uterine stimulation in 3.37 percent of women on isoflavones and 0 percent of those on placebo. This could indicate a slightly increased risk of uterine cancer with high-dose isoflavone use.

Similarly, preliminary studies and reports have raised concerns that intensive use of soy products or isoflavones by pregnant women could exert a hormonal effect that impacts fetuses. Use of soy formula by infants is also of concern along these lines, as an infant subsisting on soy formula has a relatively enormous isoflavone intake; on a per-weight basis, it may exceed the average Asian adult isoflavone intake by a factor of ten.

The drug tamoxifen blocks estrogen and is used to help prevent breast
cancer recurrence in women who have had breast cancer. One animal study found that
soy isoflavones might remove the benefit of tamoxifen treatment.

One double-blind study of postmenopausal women found the use of red clover isoflavones at a dose of 80 mg daily for ninety days resulted in increased levels of testosterone. The potential significance of this is unclear. In men, isoflavones might decrease testosterone levels, but the effect appears to be slight at most.

Other concerns relate to soy’s potential effects involving the thyroid
gland. When given to individuals with impaired thyroid function,
soy products have been observed to reduce absorption of thyroid medication. In
addition, some evidence hints that soy isoflavones may directly inhibit the
function of the thyroid gland (though perhaps only in people who are
iodine-deficient). To make matters more confusing, studies of healthy humans and
animals given soy isoflavones or other soy products have generally found that soy
either had no effect on thyroid hormone levels or actually increased levels. In
view of soy’s complex effects regarding the thyroid, individuals with impaired
thyroid function should not take large amounts of soy products except under the
supervision of a physician.

Although some experts have expressed fears that soy isoflavones might interfere with the action of oral contraceptives, one study of thirty-six women found reassuring results. Some evidence suggests that the isoflavone genistein might impair immunity. One study in mice found that injected genistein has negative effects on the thymus gland (an organ that is important for immunity) and also causes changes in the prevalence of various white blood cells consistent with impaired immunity. Although the genistein was injected rather than administered orally, the blood levels of genistein that these injections produced were not excessively high; they were comparable to (or even lower than) the amount given children fed soy milk formula. In addition, there are several reports of impaired immune responses in infants fed soy formula. While it is too early to conclude that genistein impairs immunity, these findings are a potential cause for concern.

One observational study raised concerns that soy might impair mental function in adults. However, observational studies are far less reliable than clinical trials. Direct studies designed to test the potential effects of isoflavones on brain function, lasting up to twelve months, have found either no effect or a slightly positive effect on brain function. While this does not rule out a harmful long-term effect on cognition, it is reassuring.

There exists one case report in which soy isoflavone supplements caused migraine headaches in a man who had never experienced migraines before; presumably this was a highly individual reaction, such as an allergy. Similarly, while soy products are sometimes recommend for reducing blood pressure, there is also a well-documented case report in which use of high-dose soy isoflavones caused extreme elevation in blood pressure in a woman participating in a scientific study (of soy isoflavones).

Some researchers have raised concern that genistein may influence the ability of blood to clot properly. A placebo-controlled study involving 104 healthy women, however, found no evidence that the isoflavone genistein had any significant adverse effect on blood clotting.

Bibliography

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Chandeying, V., and M. Sangthawan. “Efficacy Comparison of Pueraria mirifica (PM) Against Conjugated Equine Estrogen (CEE) With/Without Medroxyprogesterone Acetate (MPA) in the Treatment of Climacteric Symptoms in Perimenopausal Women: Phase III Study.” Journal of the Medical Association of Thailand 90 (2007): 1720-1726.

Jou, H. J., et al. “Effect of Intestinal Production of Equol on Menopausal Symptoms in Women Treated with Soy Isoflavones.” International Journal of Gynaecology and Obstetrics 102, no. 1 (2008): 44-49.

Khaodhiar, L., et al. “Daidzein-Rich Isoflavone Aglycones Are Potentially Effective in Reducing Hot Flashes in Menopausal Women.” Menopause 15 (2008): 125-132.

Thorp, A. A., et al. “Soy Food Consumption Does Not Lower LDL Cholesterol in Either Equol or Nonequol Producers.” American Journal of Clinical Nutrition 88 (2008): 298-304.

Torella, M., et al. “Endometrial Survey During Phytoestrogens Therapy in Postmenopausal Women.” Minerva Ginecologica 60 (2008): 281-285.

Trifiletti, A., et al. “Haemostatic Effects of Phytoestrogen Genistein in Postmenopausal Women.” Thrombosis Research 123, no. 2 (2008): 231-235.

What are scabies? |

Causes and Symptoms

The human scabies mite Sarcoptes scabiei, a small arachnid, approximately 0.4 millimeter long, produces intense pruritus (itching) and a red rash. Though scabies is most commonly noted on the fingers and hands, almost any skin surface can be affected. After fertilization, the female mite burrows into the upper layer of the host’s skin and deposits several eggs. Upon hatching, the young migrate to the surface, where they mature; this life cycle lasts three to four weeks. In most cases, an affected human host will have an average of eleven adult females. The elderly and immunocompromised patients are susceptible to a more severe, widespread variant called Norwegian scabies. In cases of Norwegian scabies, a human host may carry more than two million adult females.

A patient with scabies generally complains of severe itching, and the skin may be inflamed from scratching. Examination with a magnifying lens reveals characteristic burrows several millimeters in length, especially in the spaces between the fingers. A skin scraping aids in the diagnosis, producing a specimen for microscopic viewing which reveals the adult mite, eggs, or feces.

Treatment and Therapy

The treatment of scabies is straightforward. Clothing and bed linen should be washed in hot water. Shoes or other articles that cannot be washed may be sealed in a plastic bag for a week; this kills the mites, which need a human host to survive for more than a few days. Patients are treated with a 5 percent preparation of permethrin applied from head to foot (sparing the mouth and eyes) and left on overnight. An alternative treatment is lindane, which is less commonly used because of the risk of nerve toxicity in children. With either treatment, the medication is rinsed off in the morning shower. A single dose of oral ivermectin may be used alone or in combination with topical agents to treat difficult cases. Rapid diagnosis and treatment decrease the chance of the mites spreading to other individuals.

Bibliography

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What are sexual variants and paraphilias?

Introduction

Paraphilias are sexual behaviors that differ from the society’s norms; a paraphilia is classified as a psychological disorder when the deviant fantasies, sexual urges, or behaviors cause the individual significant distress or impairment in social, occupational, or other important areas and persist for longer than six months, or when they cause harm to others. Psychologist John Money, who has studied sexual attitudes and behaviors extensively, claims to have identified about forty such behaviors.

Types of Paraphilias

Exhibitionism

Exhibitionism
is commonly called "indecent exposure." The term refers to behavior in which an individual, usually a man, experiences recurrent, intense sexually arousing fantasies or urges about exposing his genitals to an involuntary observer, who is usually a female. The key point in exhibitionistic behavior is that it involves observers who are unwilling. After exposure, the exhibitionist often masturbates while fantasizing about the observer’s reaction. Exhibitionists tend to be most aroused by shock and typically flee if the observer responds by laughing or attempts to approach the exhibitionist. Most people who exhibit themselves are adolescent or young adult men. They tend to be shy, unassertive people who feel inadequate and afraid of being rejected by another person. People who make obscene telephone calls have similar characteristics to the people who engage in exhibitionism. Typically, they are sexually aroused when their observers react in a shocked manner. Many masturbate during or immediately after placing an obscene call.

Voyeurism

Voyeurism is the derivation of sexual pleasure through the repetitive seeking of or intrusive fantasies of situations that involve looking, or “peeping,” at unsuspecting people who are naked, undressing, or engaged in sexual intercourse. It may also involve secretly filming or photographing the target. Most individuals who act on these urges masturbate during the voyeuristic activity or immediately afterward in response to what they have seen. Further sexual contact with the unsuspecting stranger is rarely sought. Like exhibitionists, voyeurs are usually not physically dangerous. Most voyeurs are not attracted to nude beaches or other places where it is acceptable to look because they are most aroused when the risk of being discovered is high. Voyeurs tend to be men in their twenties and may have a high sex drive along with strong feelings of inadequacy.

Sadomasochism

Sadomasochistic
behavior encompasses both sadism and masochism; it is often abbreviated S & M. The term “sadism” is derived from the marquis de Sade, a French writer and army officer who was horribly cruel to people for his own erotic purposes. Sexual sadism involves acts in which the psychological or physical suffering of the victim, including his or her humiliation, is deemed sexually exciting. In masochism, sexual excitement is produced in a person by his or her own suffering; the preferred means of achieving gratification include verbal humiliation and being bound or whipped. The dynamics of the two behaviors are similar. Sadomasochistic behaviors have the potential to be physically dangerous, but most people involved in these behaviors participate in mild or symbolic acts with a partner they can trust. Most people who engage in S & M activities are motivated by a desire for dominance or submission rather than pain. Interestingly, many nonhuman animals participate in pain-inflicting behavior before coitus. Some researchers think that the activity heightens the biological components of sexual arousal, such as blood pressure and muscle tension. It has been suggested that any resistance between partners enhances sex, and S & M is a more extreme version of this behavior. It is also thought that S & M offers people the temporary opportunity to take on roles that are the opposite of the controlled, restrictive roles they play in everyday life. Both sexual sadism and sexual masochism are considered disorders when the fantasies, sexual urges, or behaviors cause significant distress or impairment in social, occupational, or other important areas.

Fetishism

Fetishism is a type of sexual behavior in which a person becomes sexually aroused by focusing on an inanimate object or a part of the human body. Many people are aroused by looking at undergarments, legs, or breasts, and it is often difficult to distinguish between normal activities and fetishistic ones. It is when a person becomes focused on the objects or body parts, called "fetishes," to the point of causing significant distress or impairment that a disorder is present. Fetishists are usually men. Common fetish objects include women’s lingerie, high-heeled shoes, boots, stockings, leather, silk, and rubber goods. Common body parts involved in fetishism are hair, buttocks, breasts, and feet.

Pedophilia

The term “pedophilia” is from the Greek language and means “love of children.” It is characterized by a preference for sexual activity with prepubescent children and is engaged in primarily by men. The activity varies in intensity and ranges from stroking the child’s hair to holding the child while secretly masturbating, manipulating the child’s genitals, encouraging the child to manipulate his or her own genitals, or, sometimes, engaging in sexual intercourse. Generally, a pedophile who sexually abuses a child is related to, or an acquaintance of, the child, rather than a stranger. Studies of imprisoned pedophiles have found that the men typically had poor relationships with their parents, drank heavily, showed poor sexual adjustment, and were themselves sexually abused as children. Pedophiles tend to be older than people convicted of other sex offenses. Not all pedophiles sexually abuse children, however. For a diagnosis of pedophilia, the individual should be at least sixteen years old and at least five years older than the target child or children.

Transvestic Disorder

"Transvestism" refers to dressing in clothing of the opposite sex to obtain sexual excitement. In the majority of cases, it is men who are attracted to transvestism. Several studies show that cross-dressing occurs primarily among married heterosexuals. The man usually achieves sexual satisfaction simply by putting on the clothing, but sometimes masturbation and intercourse are engaged in while the clothing is being worn. In some cases, gender dysphoria, persistent discomfort with gender role or identity, is present along with transvestic disorder.

Frotteurism

Frotteurism encompasses fairly common fantasies, sexual urges, or behaviors of a person, usually a male, obtaining sexual pleasure by pressing or rubbing against a fully clothed person, usually female, in a crowded public place. Often it involves the clothed penis rubbing against the woman’s buttocks or legs and appears accidental.

Zoophilia and Necrophilia

Zoophilia involves sexual contact between humans and animals as the repeatedly preferred method of achieving sexual excitement. In this disorder, the animal is preferred despite other available sexual outlets. Necrophilia is a rare dysfunction in which a person obtains sexual gratification by looking at or having intercourse with a corpse.

Diagnosis and Treatments

A problem in the definition and diagnosis of sexual variations is that it is difficult to draw the line between normal and abnormal behavior. Patterns of sexual behavior differ widely across history and within different cultures and communities. It is impossible to lay down the rules of normality; however, attempts are made to understand behavior that differs from the majority and to help people who find their own atypical behavior to be problematic or to be problematic in the eyes of the law.

Unlike most therapeutic techniques in use by psychologists, many of the treatments for paraphilias have historically been painful, and the degree of their effectiveness has been questionable. Supposedly, the methods were not aimed at punishing the individual, but perhaps society’s lack of tolerance toward sexual deviations can be seen in the nature of the treatments. In general, attempts to treat the paraphilias have been hindered by the lack of information available about them and their causes.

Traditional counseling and psychotherapy alone have not been very effective in modifying the behavior of paraphiliacs. Some researchers believe that the behavior might be important for the mental stability of paraphiliacs. If they did not have the paraphilia, they might experience mental deterioration. Another hypothesis is that, although people are punished by society for being sexually deviant, they are also rewarded for it. For the paraphilias that put the person at risk for arrest, the danger of arrest often becomes as arousing and rewarding as the sexual activity itself. Difficulties in treating paraphiliacs may also be related to the emotionally impoverished environments that many of them experienced throughout childhood and adolescence. Convicted sex offenders report more physical and sexual abuse as children than do the people convicted of nonsexual crimes. It is difficult to undo the years of learning involved.

Surgical castration for therapeutic purposes involves removal of the testicles. Surgical castration for sexual offenders in North America is very uncommon, but the procedure is sometimes used in northern European countries. The reason castration is used as a treatment for sex offenders is the inaccurate belief that testosterone is necessary for sexual behavior. The hormone testosterone is produced by the testicles. Unfortunately, reducing the amount of testosterone in the blood system does not always change sexual behavior. Furthermore, contrary to the myth that a sex offender has an abnormally high sex drive, many sex offenders have a low sex drive or are sexually dysfunctional.

In the same vein as surgical castration, other treatments use the administration of chemicals to decrease desire without the removal of genitalia. Estrogens have been fairly effective in reducing the sex drive, but they sometimes make the male appear feminine by increasing breast size and stimulating other female characteristics. There are also drugs that block the action of testosterone and other androgens but do not feminize the body; these drugs are called "antiandrogens." Used together with counseling, antiandrogens can benefit paraphiliacs and sex offenders, especially those who are highly motivated to overcome the problem. More research on the effects of chemicals on sexual behavior is needed; the extent of the possible side effects, for example, needs further study.

Selective serotonin reuptake inhibitors (SSRIs), a class of antidepressants, and some antianxiety medications have shown promise as medical treatments. SSRIs commonly have the side effect of lowering the patient's sex drive and may also reduce compulsions as they do for obsessive-compulsive disorder. Such treatments may be best suited for nonviolent paraphiliacs who have an accompanying mood disorder or other condition.

Aversion therapy
is another technique that has been used to eliminate inappropriate sexual arousal. In aversion therapy, the behavior that is to be decreased or eliminated is paired with an aversive, or unpleasant, experience. Most approaches use pictures of the object or situation that is problematic. The pictures are then paired with something extremely unpleasant, such as an electric shock or a putrid smell, thereby reducing arousal to the problematic object or situation in the future. Aversion therapy has been found to be fairly effective but is under ethical questioning because of its drastic nature. For example, chemical aversion therapy involves the administration of a nausea- or vomit-inducing drug. Electrical aversion therapy involves the use of electric shock. An example of the use of electric shock would be to show a pedophile pictures of young children whom he finds sexually arousing and to give an electric shock immediately after showing the pictures, in an attempt to reverse the pedophile’s tendency to be sexually aroused by children. Less drastic variants such as covert sensitization, which relies on an unpleasant thought of punishment as the negative reinforcer, or masturbatory satiation, which seeks to supplant the undesired paraphilic fantasy with an acceptable alternative during masturbation, have also been developed.

Often, cognitive behavioral therapies, including harm reduction, acceptance and commitment therapy (ACT), dialectical behavior therapy (DBT), and functional analytic psychotherapy (FAP), are used in conjunction with other treatments. These therapies seek to reduce, not eliminate, the problematic behavior or to help the patient identify underlying emotional conditions that trigger the thoughts or behaviors and cope with them in more acceptable ways. Other techniques have been developed to help clients learn more socially approved patterns of sexual interaction skills.

In general, the efficacy of the techniques mentioned is quite variable, depending in part on the paraphilic disorder involved and the individual's motivation. Unfortunately, most therapy is conducted while the paraphiliacs are imprisoned or in a residential treatment facility, providing a less than ideal setting, and reoffending is common among paraphiliacs who have committed criminal sexual offences.

Disturbances of Courtship Behavior

Beliefs regularly change with respect to what sexual activities are considered normal, so most therapists prefer to avoid terms such as “perversion,” instead using “paraphilia.” Basically, “paraphilia” means “love of the unusual.” Aspects of paraphilias are commonly found within the scope of normal behavior; it is when they become the prime means of gratification, replacing direct sexual contact with a consenting adult partner, that paraphilias are technically said to exist. People who show atypical sexual patterns might also have emotional problems, but it is thought that most people who participate in paraphilias also participate in normal sexual behavior with adult partners, without complete reliance on paraphilic behaviors to produce sexual excitement. Many people who are arrested for paraphilic behaviors do not resort to the paraphilia because they lack a socially acceptable sex partner. Instead, they have an unusual opportunity, a desire to experiment, or perhaps an underlying psychological problem.

According to the approach of Kurt Freund and his colleagues, some paraphilias are better understood as disturbances in the sequence of courtship behaviors. Freund has described courtship as a sequence of four steps: location and appraisal of a potential partner, interaction that does not involve touch, interaction that does involve touch, and genital contact. Most people engage in behavior that is appropriate for each of these steps, but some do not. The ones who do not can be seen as having exaggerations or distortions in one or more of the steps. For example, Freund says that voyeurism is a disorder in the first step of courtship. The voyeur does not use an acceptable means to locate a potential partner. An exhibitionist and an obscene phone caller would have a problem with the second step: They have interaction with people that occurs before the stage of touch, but the talking and the showing of exhibitionistic behaviors are not the normal courtship procedures. Frotteurism would be a disruption at the third step, because there is physical touching that is inappropriate. Finally, rape would be a deviation from the appropriate fourth step.

As a result of social and legal restrictions, reliable data on the frequency of paraphilic behaviors are limited. Most information about paraphilias comes from people who have been arrested or are in therapy. Because the majority of people who participate in paraphilias do not fall into these two categories, it is highly difficult to talk about the majority of paraphiliacs in the real world. It is known, however, that males are much more likely to engage in paraphilias than are females.

Bibliography

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