Mesothelioma Cancer

Mesothelioma Cancer

What is Mesothelioma?
Mesothelioma is a serious malignant tumor that affects the torso of the human body. There is a strong link between mesothelioma and contact with asbestos particles via breathing or swallowing.

There are three common forms of mesothelioma:
1. Pleural Mesothelioma is the most common form of Mesothelioma. It starts in the chest cavity (after breathing the particles) before spreading to other areas.
2. Peritoneal Mesothelioma starts in the abdomen (after swallowing the particles) and accounts for about 10-20% of Mesothelioma patients.
3. Pericardial Mesothelioma is the rarest form of Mesothelioma. It starts in the cavity that surrounds the heart.

Diarrhea（department of pediatrics）

Frequent loose bowel movements (4 to 6/day) may occur in normal infants; they are of no concern unless anorexia, vomiting, weight loss, failure to gain weight, or passage of blood also occurs. Breastfed infants tend to have frequent bowel movements, especially if they are not receiving solid food. The significance of diarrhea in a child at any age differs if it is acute (< 2 wk) or chronic (> 2 wk).

Etiology

Acute diarrhea is most likely infectious, especially if onset is sudden or accompanied by vomiting, bloody stools, fever, anorexia, or listlessness. Diagnosis is clinical, and treatment is supportive until the condition resolves spontaneously.

Chronic diarrhea is usually more significant. Causes include gluten-induced enteropathy, cystic fibrosis, sugar malabsorption, and allergic gastroenteropathy. Inflammatory bowel disease and some infections (eg, with Giardia) can also cause chronic diarrhea.

With gluten-induced enteropathy (celiac sprue), the gluten fraction of wheat protein causes intestinal mucosal damage and malabsorption of dietary fats, resulting in malnutrition, anorexia, and bulky, foul-smelling stools. The change in stools starts when wheat and other gluten-containing foods are added.

With cystic fibrosis, pancreatic insufficiency results in trypsin and lipase deficits, causing high fecal losses of protein and fats with consequent malnutrition and growth retardation. The stool is voluminous and often foul-smelling. Children who have cystic fibrosis often have respiratory problems and growth failure.

With sugar malabsorption, intestinal mucosal enzymes, such as lactase, which splits lactose to galactose and glucose, may be congenitally absent or temporarily deficient secondary to GI infection. Improvement after eliminating lactose (or other carbohydrates) from the diet or after substituting a lactose-free formula strongly suggests the diagnosis.

With allergic gastroenteropathy, cow's milk protein may cause diarrhea, often with vomiting and blood in the stools, but intolerance to the carbohydrate fraction of the ingested food should be suspected also. Symptoms often abate promptly when soy formula is substituted for cow's milk and return if cow's milk is reintroduced. Some infants intolerant of cow's milk are also intolerant of soy, so a formula that has had the protein pre-digested and does not contain the offending disaccharide may be needed. Spontaneous improvement usually occurs toward the end of the 1st yr.

Evaluation

History: History focuses on the quality and frequency of stools as well as accompanying signs and symptoms. Reports of vomiting or fever suggest GI infection. An accurate dietary history is critical. Reports of diarrhea beginning with the introduction of wheat cereal suggest celiac disease. Reports of variation in the stool pattern with certain elements of the diet suggest dietary intolerance. The persistent presence of blood in the stool mandates a careful search for more serious infection or GI disorder.

Physical examination: Examination focuses on overall appearance and signs of dehydration, growth parameters, and abdominal findings; poor growth suggests more serious disorders. Pulmonary status is also evaluated in children in whom cystic fibrosis is suspected.

Testing: Tests are ordered if history and examination suggest a chronic condition. Tests include electrolyte levels if there is dehydration; sweat Cl and Na levels for cystic fibrosis; cultures for viruses, bacteria, or parasites when infection appears to be present; and stool pH for disaccharide intolerance. Levels of certain antibodies are associated with celiac disease. Dietary manipulations can be diagnostic as well as therapeutic.

Treatment

Supportive care for acute diarrhea consists primarily of providing adequate oral (or rarely IV) rehydration. Antimotility agents (eg, loperamide: IMODIUM) are generally not recommended for infants and young children.

For chronic diarrhea, adequate nutrition must be maintained, particularly of fat-soluble vitamins. Specific treatments are indicated for certain causes (eg, gluten-free diet for those with celiac disease).

Breast Disorders

Breast symptoms (eg, pain, lumps, nipple discharge) are common, accounting for > 15 million physician visits/yr. Although > 90% of symptoms have benign causes, breast cancer is always a concern. Because breast cancer is common and may mimic benign disorders, the approach to all breast symptoms and findings is to conclusively exclude cancer.

History includes duration of symptoms; relation of symptoms to menses and pregnancy; presence and type of pain, discharge, and skin changes; use of drugs, including hormone therapy; personal and family history of breast cancer; and date and results of last mammogram.

Breast examination: Principles of examination are similar for physician and patient. Breasts are inspected for asymmetry in shape, nipple inversion, bulging, and dimpling (see Fig. 1: Breast Disorders: Breast Cancer Risks A and B). Although size differential is common, each breast should have a regular contour. An underlying cancer is sometimes detected by having the patient press both hands against the hips or the palms together in front of the forehead (see Fig. 1: Breast Disorders: Breast Cancer Risks C and D). In these positions, the pectoral muscles are contracted, and a subtle dimpling of the skin may appear if a growing tumor has entrapped a Cooper's ligament.

The axillary and supraclavicular lymph nodes are most easily examined with the patient seated or standing (see Fig. 1: Breast Disorders: Breast Cancer Risks E). Supporting the patient's arm during the axillary examination allows the arm to be fully relaxed so that nodes deep within the axilla can be palpated.

The breast is palpated with the patient seated and again with the patient supine, the ipsilateral arm above the head, and a pillow under the ipsilateral shoulder (see Fig. 1: Breast Disorders: Breast Cancer Risks F). The latter position is also used for breast self-examination; the patient examines the breast with her contralateral hand. Having the patient roll to one side, so that the breast on the examined side falls medially, may help differentiate breast and chest wall tenderness because the chest wall can be palpated separately from breast tissue.

The breast should be palpated with the palmar surfaces of the 2nd, 3rd, and 4th fingers, moving systematically in a small circular pattern from the nipple to the outer edges (see Fig. 1: Breast Disorders: Breast Cancer Risks G). Precise location and size (measured with a caliper) of any abnormality should be noted on a drawing of the breast, which becomes part of the patient's record. A written description of the consistency of the abnormality and degree to which it can be distinguished from surrounding breast tissue should also be included. Detection of abnormalities during physical examination largely determines whether a biopsy is needed, even if a subsequent mammogram shows no abnormalities.

Testing: Imaging tests are used for screening and for evaluation of breast abnormalities. Annual screening mammography is recommended for women ≥ 50 yr and sometimes for women 40 to 50 yr. Mammography is more effective in older women because with aging, fibroglandular tissue in breasts tends to be replaced with fatty tissue, which can be more easily distinguished from abnormal tissue. Low-dose x-rays of both breasts are taken in 1 (oblique) or 2 views (oblique and craniocaudal). Only about 10% of abnormalities detected result from cancer. Accuracy of mammography depends partly on the techniques used and experience of the mammographer; false-negative results may exceed 15%. Some centers use computer analysis of digitized mammography images to help in diagnosis. Such systems are not recommended for stand-alone diagnosis, but they appear to improve sensitivity for detecting small cancers by radiologists.

Mammography is also used diagnostically to evaluate lumps, pain, and nipple discharge. It can determine size and location of a lesion and provide images of surrounding tissues and lymph nodes. Diagnostic mammography requires more views than screening mammography. For biopsy of a lesion seen on a mammogram but not detectable during physical examination, 2 needles or wires can be inserted via radiologic guidance to localize the lesion. The excised specimen should be x-rayed, and the x-ray compared with the prebiopsy mammogram to determine whether the lesion has been removed. Mammography is repeated when the breast is no longer tender, usually 6 to 12 wk after biopsy, to confirm removal of the lesion.

MRI is thought to be more accurate than clinical breast examination or mammography for screening women with a high (eg, > 15%) risk of breast cancer, such as those with a BRCA gene mutation. It is not considered appropriate for screening women with average or slightly increased risk. Because MRI can accurately determine tumor size, chest wall involvement, and presence of multiple tumors, it is often used in evaluation after breast cancer is diagnosed. Use of MRI to identify axillary node involvement is under study.

Breast Cancer (5)

Treatment


Hormone therapy includes tamoxifen and aromatase inhibitors. Tamoxifen competitively binds estrogen receptors. Aromatase inhibitors (anastrozole, exemestane, letrozole) block peripheral production of estrogen in postmenopausal women. Benefit of hormone therapy is greatest when tumors have estrogen and progesterone receptors, nearly as good when they have only estrogen receptors, minimal when they have only progesterone receptors, and absent when they have neither receptor. In patients with ER+ tumors, particularly low-risk tumors, hormone therapy may be used instead of chemotherapy. Aromatase inhibitors have recently been proven more effective than tamoxifen and are becoming the preferred treatment for early-stage breast cancer in receptor-positive postmenopausal patients. Adjuvant tamoxifen for 5 yr reduces annual odds of death by about 25% in premenopausal and postmenopausal women regardless of axillary lymph node involvement; treatment for 2 yr is not as effective, but treatment for > 5 yr has no advantage and may increase the likelihood that any recurrent cancer is tamoxifen-resistant. Letrozole may be used for postmenopausal women who have completed 5 yr of daily tamoxifen.

Tamoxifen can induce or exacerbate menopausal symptoms but reduces incidence of contralateral breast cancer and lowers serum cholesterol. Tamoxifen improves bone density in postmenopausal women, and there is some evidence of fracture reduction. Tamoxifen may reduce cardiovascular mortality risk. However, it significantly increases risk of developing endometrial cancer; reported incidence is 1% in postmenopausal women after 5 yr of use. Thus, if such women have spotting or bleeding, they must be evaluated for endometrial cancer. Nonetheless, the improved survival for women with breast cancer far outweighs increased risk of death due to endometrial cancer. Unlike tamoxifen, aromatase inhibitors do not cause menopausal symptoms, but they may increase risk of osteoporosis.

Metastatic disease: Any indication of metastases should prompt immediate evaluation. Treatment of metastases increases median survival by only 3 to 6 mo, although relatively toxic therapies (eg, chemotherapy) may palliate symptoms and improve quality of life; the decision to undergo treatment is highly personal.

Choice of therapy depends on the hormone-receptor status of the tumor, length of the disease-free interval (from diagnosis to manifestation of metastases), number of metastatic sites and organs affected, and patient's menopausal status. Most patients with symptomatic metastatic disease are treated with systemic hormone therapy or chemotherapy. Radiation therapy alone may be used to treat isolated, symptomatic bone lesions or local skin recurrences not amenable to surgical resection. Radiation therapy is the most effective treatment for brain metastases, occasionally achieving long-term control. Patients with multiple metastatic sites outside the CNS should initially be given systemic therapy. There is no proof that treatment of asymptomatic metastases substantially increases survival, and it may reduce quality of life.

Hormone therapy is preferred over chemotherapy for patients with ER+ tumors, a disease-free interval of > 2 yr, or disease that is not life threatening. Tamoxifen is often used first in premenopausal women. Ovarian ablation by surgery, radiation therapy, or use of a luteinizing-releasing hormone agonist (eg, buserelin, goserelin, leuprolide) is a reasonable alternative. Some experts combine ovarian ablation with tamoxifen therapy. If the cancer initially responds to hormone therapy but progresses months or years later, additional forms of hormone therapy may be used sequentially until no further response is seen. Aromatase inhibitors are being increasingly used as primary hormone therapy in postmenopausal women.

The most effective cytotoxic drugs for treatment of metastatic breast cancer are capecitabine, doxorubicin, gemcitabine, the taxanes paclitaxel and docetaxel, and vinorelbine. Response rate to a combination of drugs is higher than that to a single drug, but survival is not improved and toxicity is increased. Thus, some oncologists use single drugs sequentially.

For tumors with amplification of HER2/neu, the humanized monoclonal antibody trastuzumab is effective in treating and controlling visceral metastatic sites. It is used alone or with hormone therapy or chemotherapy.

About 10% of patients with bone metastases eventually develop hypercalcemia, which can be treated with IV bisphosphonates (eg, pamidronate).

Breast Cancer (4)

Treatment

For most patients, primary treatment is surgery, often with radiation therapy. Chemotherapy, hormone therapy, or both may also be used, depending on tumor and patient characteristics. For inflammatory or advanced breast cancer, primary treatment is systemic therapy, which, for inflammatory breast cancer, is followed by surgery and radiation therapy; surgery is usually not helpful for advanced cancer. Paget's disease of the nipple is treated as for other forms of breast cancer, although a very few patients can be treated successfully with local excision only.

Surgery: Most patients with DCIS are cured by simple mastectomy. However, more patients are being treated with wide excision alone, especially when the lesion is < 2.5 cm and histologic characteristics are favorable, or with wide excision plus radiation therapy when size and histologic characteristics are less favorable.

For patients with invasive cancer, survival rates do not differ significantly whether modified radical mastectomy (simple mastectomy plus lymph node dissection) or breast-conserving surgery (lumpectomy, wide excision, partial mastectomy, or quadrantectomy) plus radiation therapy is used. Thus, patient preference can guide choice of treatment within limits. The main advantage of breast-conserving surgery plus radiation therapy is cosmetic. In 15% of patients treated with breast-conserving surgery and radiation therapy, cosmetic results are excellent. However, need for total removal of the tumor with a tumor-free margin overrides cosmetic considerations. With both types of surgery, a lymph node dissection or node sampling should be done. Routine use of extensive procedures is not justified because the main value of lymph node removal is diagnostic, not therapeutic. However, results of frozen section analysis may change the extent of surgery needed. Some surgeons get prior agreement for more invasive surgery in case nodes are positive; others wake the patient and do a 2nd procedure if needed.

Some physicians use preoperative chemotherapy to shrink the tumor before removing it and applying radiation therapy; thus some patients who might otherwise have required mastectomy can have breast-conserving surgery. Early data suggest that this approach does not affect survival. Radiation therapy after mastectomy significantly reduces incidence of local recurrence on the chest wall and in regional lymph nodes and may improve overall survival in patients with primary tumors > 5 cm or with involvement of ≥ 4 axillary nodes. Adverse effects of radiation therapy are usually transient and mild.

Procedures for reconstruction include submuscular or subcutaneous (less common) placement of a silicone or saline implant, use of a tissue expander with delayed placement of the implant, muscle flap transfer using the latissimus dorsi or the lower rectus abdominis, and creation of a free flap by anastomosing the gluteus maximus to the internal mammary vessels. Free flap transfer is being increasingly used for DCIS.

After axillary dissection or radiation therapy, lymphatic drainage of the ipsilateral arm can be impaired, sometimes resulting in significant swelling due to lymphedema; magnitude of the effect is roughly proportional to the number of nodes removed. Venipuncture, BP measurement, and IV infusions are avoided on the affected side. A specially trained therapist must treat lymphedema. Special massage techniques once or twice daily may help drain fluid from congested areas toward functioning lymph basins; low-stretch bandaging is applied immediately after manual drainage, and patients should exercise daily as prescribed. After the lymphedema resolves, typically in 1 to 4 wk, patients continue daily exercise and overnight bandaging of the affected limb indefinitely.

Adjuvant systemic therapy: Patients with LCIS are treated with daily oral tamoxifen. If tamoxifen is unsuitable or refused, bilateral mastectomy may be considered.


For patients with invasive cancer, chemotherapy or hormone therapy is usually begun soon after surgery and continued for months or years; these therapies delay or prevent recurrence in almost all patients and prolong survival in some. However, some experts believe that these therapies are not necessary for tumors < 1 cm (particularly in postmenopausal patients) if lymph nodes are not involved because the prognosis is already excellent. Some experts begin adjuvant systemic therapy before surgery if tumors are > 5 cm.

Relative reduction in risk of recurrence and death associated with chemotherapy or hormone therapy is the same regardless of the clinical-pathologic stage of the cancer. Thus, absolute benefit is greater for patients with a greater risk of recurrence or death (ie, a 20% reduction reduces a 10% recurrence rate to 8% but a 50% rate to 40%). Adjuvant chemotherapy reduces annual odds of death on average by 25 to 35% for premenopausal patients; for postmenopausal patients, the reduction is about 1⁄2 of that (9 to 19%), and the absolute benefit in 10-yr survival is much smaller. Postmenopausal patients with ER– tumors benefit the most from adjuvant chemotherapy (see Table 3: Breast Disorders: Preferred Breast Cancer Adjuvant Systemic Therapy).

Combination chemotherapy regimens (eg, cyclophosphamide, methotrexate, plus 5-fluorouracil; doxorubicin plus cyclophosphamide) are more effective than a single drug. Regimens given for 4 to 6 mo are preferred; they are as effective as regimens given for 6 to 24 mo. Acute adverse effects depend on the regimen but usually include nausea, vomiting, mucositis, fatigue, alopecia, myelosuppression, and thrombocytopenia. Long-term adverse effects are infrequent with most regimens; death due to infection or bleeding is rare (< 0.2%). Whether increasing dose density (giving treatments more frequently) or adding a taxane (eg, docetaxel, paclitaxel) improves response or survival is uncertain.

High-dose chemotherapy plus bone marrow or stem cell transplantation offers no therapeutic advantage over standard therapy and should not be used.

Breast Cancer (3)

Diagnosis


Testing is required to differentiate benign lesions from cancer. Because early detection and treatment of breast cancer improves prognosis, this differentiation must be conclusive before evaluation is terminated.

If advanced cancer is suspected based on physical examination, biopsy should be done first; otherwise, the approach is as for breast lumps. A prebiopsy bilateral mammogram may help delineate other areas that should be biopsied and provides a baseline for future reference. However, mammogram results should not alter the decision to perform a biopsy. Biopsy can be needle or incisional biopsy or, if the tumor is small, excisional biopsy. Any skin with the biopsy specimen should be examined because it may show cancer cells in dermal lymphatic vessels. Routinely, stereotactic biopsy (needle biopsy during mammography) or ultrasound-guided biopsy is being used to improve accuracy.

Evaluation after cancer diagnosis: Part of a positive biopsy specimen should be analyzed for estrogen and progesterone receptors and for HER2 protein. WBCs should be tested for BRCA1 and BRCA2 genes when family history includes multiple cases of early-onset breast cancer, when ovarian cancer develops in patients with a family history of breast or ovarian cancer, when breast and ovarian cancer occur in the same patient, when patients have Ashkenazi Jewish heritage, or when family history includes a single case of male breast cancer.

Chest x-ray, CBC, and liver function tests should be done to check for metastatic disease. Generally, measuring serum carcinoembryonic antigen (CEA), cancer antigen (CA) 15-3, CA 27-29, or a combination is not recommended because results have no effect on treatment or outcome. Bone scanning should be done if patients have tumors > 2 cm, musculoskeletal pain, lymphadenopathy, or elevated serum alkaline phosphatase or Ca levels. Abdominal CT is done if patients have abnormal liver function results, hepatomegaly, or locally advanced cancer with or without axillary lymph node involvement.

Grading and staging follow the TNM classification (see Table 2: Breast Disorders: Staging and Survival of Breast Cancer). Staging is refined during surgery, when regional lymph nodes can be evaluated.

Screening: Screening includes mammography, clinical breast examination (CBE) by health care practitioners, and monthly breast self-examination (BSE).

Mammography, done annually, reduces mortality rate by 25 to 35% in women ≥ 50 yr. However, there is considerable disagreement about screening for women 40 to 50 yr; recommendations include annual mammography (American Cancer Society), mammography every 1 to 2 yr (National Cancer Institute), and no periodic mammography (American College of Physicians).

CBE is usually part of routine annual care for women > 35; it can detect 7 to 10% of cancers that cannot be seen on a mammogram. In the US, CBE augments rather than replaces screening mammography. However, in some countries where mammography is considered too expensive, CBE is the sole screen; reports on its effectiveness in this role vary.

BSE has not been shown to reduce mortality rate but is widely practiced. Because a negative BSE may tempt some women to forego mammography or CBE, the need for these procedures is reinforced when BSE is taught.

Prognosis


Long-term prognosis depends on extent of lymph node involvement, number of axillary lymph nodes involved, size of primary tumor, tumor grade, stage, presence of estrogen and progesterone receptors, patient age, and presence of HER2 protein.

Nodal status correlates with disease-free and overall survival better than other prognostic factors. For node-negative patients, 10-yr disease-free survival rate is > 70%, and overall survival rate is > 80%. For node-positive patients, rates are about 25% and 40%, respectively.

Larger tumors are more likely to be node-positive and also confer a worse prognosis independent of nodal status. Patients with poorly differentiated tumors have a worse prognosis.

Patients with ER+ tumors have a somewhat better prognosis and are more likely to benefit from hormone therapy. Patients with progesterone receptors on a tumor may also have a better prognosis.

When the HER2 gene is amplified, HER2 is overexpressed, increasing cell growth and reproduction and often resulting in more aggressive tumor cells. Overexpression of HER2 may be associated with high histologic grade, ER– tumors, greater proliferation, larger tumor size, and thus a poor prognosis.

For any given stage, patients with the BRCA1 gene appear to have a worse prognosis than those with sporadic tumors, perhaps because they have a higher proportion of high-grade, hormone receptor-negative cancers. Patients with the BRCA2 gene probably have the same prognosis as those without the genes if the tumors have similar characteristics. With either gene, risk of a 2nd cancer in remaining breast tissue is increased (to perhaps as high as 40%).

Breast Cancer (2)

Pathology

Most breast cancers are epithelial tumors that develop from cells lining ducts or lobules; less common are nonepithelial cancers of the supporting stroma (angiosarcoma, primary stromal sarcomas, phyllodes tumor). Cancers are divided into carcinoma in situ and invasive cancer.

Carcinoma in situ is proliferation of cancer cells within ducts or lobules and without invasion of stromal tissue. Usually, ductal carcinoma in situ (DCIS) is detected only by mammography and is localized to one area; it may become invasive. Lobular carcinoma in situ (LCIS) is a nonpalpable lesion usually discovered via biopsy; it is rarely visualized with mammography. LCIS is not malignant, but its presence indicates increased risk of subsequent invasive carcinoma in either breast; about 1 to 2% of patients with LCIS develop cancer annually.

Invasive carcinoma is primarily adenocarcinoma. About 80% is the infiltrating ductal type; most of the remainder is infiltrating lobular. Rare forms include medullary, mucinous, and tubular carcinomas.

Paget's disease of the nipple (not to be confused with the metabolic bone disease also called Paget's disease) is a form of ductal carcinoma in situ that extends into the overlying skin of the nipple and areola, manifesting with an inflammatory skin lesion. Characteristic malignant cells called Paget cells are present in the epidermis. The cancer may be in situ or invasive.

Breast cancer invades locally and spreads initially through the regional lymph nodes, bloodstream, or both. Metastatic breast cancer may affect almost any organ in the body—most commonly, lungs, liver, bone, brain, and skin. Most skin metastases occur in the region of the breast surgery; scalp metastases also are common. Metastatic breast cancer frequently appears years or decades after initial diagnosis and treatment.

Estrogen and progesterone receptors, present in some breast cancers, are nuclear hormone receptors that promote DNA replication and cell division when they are bound to the appropriate hormones. Thus, drugs that block these receptors may be useful in treating tumors with the receptors. About 2⁄3 of postmenopausal patients have an estrogen-receptor positive (ER+) tumor. Incidence of ER+ tumors is lower among premenopausal patients. Another cellular receptor is human epidermal growth factor receptor 2 (HER2) protein; its presence correlates with a poorer prognosis at any given stage of cancer.

Symptoms and Signs


Most breast cancers are discovered as a lump by the patient or during routine physical examination or mammography. Less commonly, the presenting symptom is breast pain or enlargement or a nondescript thickening in the breast. Paget's disease of the nipple presents with skin changes, including erythema, crusting, scaling, and discharge; these usually appear so benign that the patient ignores them, delaying diagnosis for a year or more. About 50% of patients with Paget's disease of the nipple have a palpable mass at presentation. A few patients with breast cancer present with signs of metastatic disease (eg, pathologic fracture, pulmonary dysfunction).

A common finding during physical examination is a dominant mass—a lump distinctly different from the surrounding breast tissue. Diffuse fibrotic changes in a quadrant of the breast, usually the upper outer quadrant, are more characteristic of benign disorders; a slightly firmer thickening in one breast but not the other may be a sign of cancer. More advanced breast cancers are characterized by fixation of the lump to the chest wall or to overlying skin, by satellite nodules or ulcers in the skin, or by exaggeration of the usual skin markings resulting from lymphedema (so-called peau d'orange). Matted or fixed axillary lymph nodes suggest tumor spread, as does supraclavicular or infraclavicular lymphadenopathy. Inflammatory breast cancer is characterized by diffuse inflammation and enlargement of the breast, often without a lump, and has a particularly aggressive course.

Breast Cancer---1

Breast cancer most often involves glandular breast cells in the ducts or lobules. Most patients present with an asymptomatic lump discovered during examination or screening mammography. Diagnosis is confirmed by biopsy. Treatment usually includes surgical excision, often with radiation therapy and adjuvant systemic therapy.

About 203,000 new cases were identified in 2003. It is the 2nd leading cause of cancer death in women (after lung cancer), with about 40,000 deaths in 2003. Male breast cancer accounts for < 1% of total cases; manifestations, diagnosis, and management are the same, although men tend to present later.

Risk Factors

In the US, cumulative risk of developing breast cancer is 12% (1 in 8) by age 95, and risk of dying of it is about 4%. Much of the risk is incurred after age 60 (see Table 1: Breast Disorders: Breast Cancer Risks). These statistics can be misleading because cumulative risk of developing the cancer in any 20-yr period is considerably lower.

Family history of breast cancer in a 1st-degree relative (mother, sister, daughter) doubles or triples risk of developing the cancer, but history in more distant relatives increases risk only slightly. When ≥ 2 1st-degree relatives have breast cancer, risk may be 5 to 6 times higher. About 5% of women with breast cancer carry a mutation in one of the 2 known breast cancer genes, BRCA1 or BRCA2. If relatives of such a woman also carry the gene, they have a 50 to 85% lifetime risk of developing breast cancer. Women with BRCA1 mutations also have a 20 to 40% lifetime risk of developing ovarian cancer; risk among women with BRCA2 mutations is increased less. Women without a family history of breast cancer in at least 2 1st-degree relatives are unlikely to carry this gene and thus do not require screening for BRCA1 and BRCA2 mutations. Men who carry a BRCA2 mutation also have an increased risk of developing breast cancer. The genes are more common among Ashkenazi Jews.

History of in situ or invasive breast cancer increases risk: Risk of developing cancer in the contralateral breast after mastectomy is about 0.5 to 1%/yr of follow-up.

Early menarche, late menopause, or late 1st pregnancy increases risk. Women who have a 1st pregnancy after age 30 are at higher risk than those who are nulliparous.

History of fibrocystic changes requiring biopsy for diagnosis increases risk slightly. Women with multiple breast lumps but no histologic confirmation of a high-risk pattern should not be considered at high risk. Benign lesions that may slightly increase risk of developing invasive breast cancer include complex fibroadenoma, moderate or florid hyperplasia (with or without atypia), sclerosing adenosis, and papilloma. Atypical ductal or lobular hyperplasia increases risk of breast cancer 4- to 5-fold; risk increases to about 10-fold in patients who also have a family history of invasive breast cancer in a 1st-degree relative.

Oral contraceptive use increases risk very slightly (by about 5 more cases per 100,000 women). Risk increases primarily during the years of contraceptive use and tapers off during the 10 yr after stopping. Risk is highest in women who began to use contraceptives before age 20 (although absolute risk is still very low).

Postmenopausal hormone (estrogen plus a progestin) therapy appears to increase risk modestly after only 3 yr of use. With prolonged use, risk is increased by about 7 or 8 cases per 10,000 women for each year of use. Use of estrogen alone does not appear to increase risk of breast cancer. Selective estrogen-receptor modulators (eg, raloxifene) may reduce risk of developing breast cancer.

Diet may play a role in causing or promoting growth of breast cancers, but conclusive evidence about the effect of a particular diet (eg, one high in fats) is lacking. Obese postmenopausal women are at increased risk, but there is no evidence that dietary modification decreases risk. For obese women who are still menstruating, risk may be decreased.

Exposure to radiation therapy before age 30 increases risk. Mantle-field radiation therapy for Hodgkin lymphoma quadruples risk of breast cancer over the next 20 to 30 yr.

Diarrhea

Diarrhea

Frequent loose bowel movements (4 to 6/day) may occur in normal infants; they are of no concern unless anorexia, vomiting, weight loss, failure to gain weight, or passage of blood also occurs. Breastfed infants tend to have frequent bowel movements, especially if they are not receiving solid food. The significance of diarrhea in a child at any age differs if it is acute (< 2 wk) or chronic (> 2 wk).

Etiology

Acute diarrhea is most likely infectious, especially if onset is sudden or accompanied by vomiting, bloody stools, fever, anorexia, or listlessness. Diagnosis is clinical, and treatment is supportive until the condition resolves spontaneously.

Chronic diarrhea is usually more significant. Causes include gluten-induced enteropathy, cystic fibrosis, sugar malabsorption, and allergic gastroenteropathy. Inflammatory bowel disease and some infections (eg, with Giardia) can also cause chronic diarrhea.

With gluten-induced enteropathy (celiac sprue), the gluten fraction of wheat protein causes intestinal mucosal damage and malabsorption of dietary fats, resulting in malnutrition, anorexia, and bulky, foul-smelling stools. The change in stools starts when wheat and other gluten-containing foods are added.

With cystic fibrosis, pancreatic insufficiency results in trypsin and lipase deficits, causing high fecal losses of protein and fats with consequent malnutrition and growth retardation. The stool is voluminous and often foul-smelling. Children who have cystic fibrosis often have respiratory problems and growth failure.

With sugar malabsorption, intestinal mucosal enzymes, such as lactase, which splits lactose to galactose and glucose, may be congenitally absent or temporarily deficient secondary to GI infection. Improvement after eliminating lactose (or other carbohydrates) from the diet or after substituting a lactose-free formula strongly suggests the diagnosis.

With allergic gastroenteropathy, cow's milk protein may cause diarrhea, often with vomiting and blood in the stools, but intolerance to the carbohydrate fraction of the ingested food should be suspected also. Symptoms often abate promptly when soy formula is substituted for cow's milk and return if cow's milk is reintroduced. Some infants intolerant of cow's milk are also intolerant of soy, so a formula that has had the protein pre-digested and does not contain the offending disaccharide may be needed. Spontaneous improvement usually occurs toward the end of the 1st yr.

Treatment

Supportive care for acute diarrhea consists primarily of providing adequate oral (or rarely IV) rehydration. Antimotility agents (eg, loperamide: IMODIUM) are generally not recommended for infants and young children.

For chronic diarrhea, adequate nutrition must be maintained, particularly of fat-soluble vitamins. Specific treatments are indicated for certain causes (eg, gluten-free diet for those with celiac disease).

Sleeping

Sleeping

Sleep behaviors are culturally determined, and problems tend to be defined as behaviors that vary from accepted customs or norms. In cultures where children sleep separately from their parents in the same house, sleep problems are among the most common that parents and children face. Infants generally adapt to a day-night sleep schedule between 4 and 6 mo. Sleep problems beyond these ages take many forms, including difficulty falling asleep at night, frequent nighttime awakening, atypical daytime napping, and dependence on feeding or being held for sleep. These problems are related to parental expectations, the child's temperament and biologic rhythms, and child-parent interactions. Inborn biologic patterns are central to an infant's sleep patterns, whereas emotional factors and established habits become more important in the toddler and older child. In addition, sleep disturbances become common at 9 mo and again around 18 mo, when separation anxiety, increasing ability of the child to move independently and control his environment, long late-afternoon naps, overstimulating play before bedtime, and nightmares tend to become more common.

Treatment

The clinician's role in treatment is to present explanations and options to parents, who must implement changes to get the child on an acceptable sleep schedule. Approaches vary with age and circumstances. Infants are often comforted by swaddling, ambient noise, and movement. However, always rocking the infant to sleep does not allow the infant to learn how to fall asleep on his own, which is an important developmental task. As a substitute for rocking, the parent can sit quietly by the crib until the infant falls asleep, and the infant eventually learns to be comforted and to fall asleep without being held. All children awaken during the night, but children who have been taught to fall asleep by themselves will usually settle themselves back to sleep. When a child is unable to get back to sleep, parents can check on the child to reassure themselves of the child's safety and to reassure the child, but the child should then be allowed to settle himself back to sleep.

In older children, a period of "winding down" with quiet activities such as reading at bedtime facilitates sleep. A consistent bedtime is important, and a fixed ritual is helpful for young children. Asking a fully verbal child to recount the events of the day often eliminates nightmares and waking. Encouraging exercise in the daytime, avoiding scary television programs and movies, and refusing to allow bedtime to become an element of manipulation also help prevent sleep problems. Stressful events (eg, moving, illness) may cause acute sleep problems in older children; reassurance and encouragement are always ultimately effective. Allowing the child to sleep in the parents' bed in such instances almost always prolongs rather than resolves the problem.

Acute Respiratory Distress Syndrome

Acute Respiratory Distress Syndrome
  
Definition/Description
 
Acute respiratory distress syndrome (ARDS) is breathing failure that can occur in critically ill persons with underlying illnesses. When one develops ARDS, severe fluid buildup occurs in both lungs and prevents the lungs from transfering oxygen from air into the body and carbon dioxide out of the body into the air. Noncardiogenic pulmonary edema; increased-permeability pulmonary edema; stiff lung; shock lung; and acute lung injury are its alternative names.
 
Causes
  
ARDS can be caused by any major swelling (inflammation) or injury to the lung. Some common causes include:
 
◆　Aspiration)
 
◆　Pneumonia
 
◆　Septic shock
 
◆　Trauma

ARDS leads to a buildup of fluid in the alveoli, which prevents enough oxygen from passing into the bloodstream.
 
The fluid buildup also makes the lungs heavy and stiff, and decreases the lungs' ability to expand. The level of oxygen in the blood can stay dangerously low, even if the person receives oxygen from mechanical ventilator through endotracheal tube.
 
ARDS often occurs along with the failure of other organ systems, such as the liver or the kidneys. Cigarette smoking and heavy alcohol use may be risk factors.
 
Symptoms/Signs

Symptoms usually develop within 24 to 48 hours of the initial injury or illness. Often, people with ARDS are so sick they are unable to complain of symptoms. However, the major signs and symptoms are:
 
◆ Dyspnea, tachypnea
 
◆ Hypotention and organ failure

◆ Cyanosis
 
Examinations/Tests
 
Listening to the chest with a stethoscope (auscultation) reveals abnormal breath sounds, such as crackles that suggest fluid in the lungs. Often the blood pressure is low. Cyanosis (blue skin, lips, and nails caused by lack of oxygen to the tissues) is often seen.

Tests used to diagnose ARDS include:

◆ Arterial blood gas

◆ Bronchoscopy

◆ CBC and blood chemistries

◆ Chest x-ray

◆ Sputum cultures and analysis

◆ Tests for possible infections

Occasionally an echocardiogram or Swan-Ganz catheterization may need to be done to rule out congestive heart failure, which can look similar to ARDS on a chest x-ray.

Treatment

Typically persons with ARDS need to be in an intensive care unit (ICU). The goal of treatment is to provide breathing support and treat the underlying cause of ARDS. This may involve medications to treat infections, reduce inflammation, and remove fluid from the lungs.

A breathing machine is used to deliver high doses of oxygen and a continuous level of pressure called PEEP (positive end-expiratory pressure) to the damaged lungs. Patients often need to be deeply sedated with medications when using this equipment.

Many different kinds of medicines are used to treat ARDS patients. Some kinds of medicines often used include:

◆ Antibiotics to fight infection

◆ Pain relievers

◆ Drugs to relieve anxiety and keep the patient calm

◆ Drugs to raise blood pressure or stimulate the heart

◆ Muscle relaxers to prevent movement and reduce the body's demand for oxygen

Complications

Common complications in ARDS patients are infections with hospital-acquired bacteria and leaks of air out of the lungs into other body spaces. These include:

◆ Lung damage (such as pneumothorax) due to use of high settings on the breathing machine needed to treat the disease

◆ Multiple organ system failure

◆ Pulmonary fibrosis

◆ Ventilator-associated pneumonia

Prognosis

About a third of people with ARDS die from the disease. Survivors usually get back normal lung function, but many people have permanent, usually mild, lung damage.

Many people who survive ARDS have memory loss or other problems with thinking after they recover. This is due to brain damage that occurred when the lungs weren't working properly and the brain wasn't getting enough oxygen.
 

Terms Commonly Used in TCM

中国医药学　Traditional Chinese Medicine		治未病　prevention of disease
中医基础理论　Basic theory of traditional Chinese medicine		脏腑　zang-organs and fu-organs, viscera
临床经验　clinical experience		功能活动　functional activities
辨证论治　treatment based on syndrome differentiation		形神统一　unity of the body and spirit
本草　materia medica, herbs		阴阳失调　imbalance of yin and yang
中药　Chinese materia medica, Chinese medicinal herbs		条达舒畅　free development
四气五味　four properties and five tastes		延年益寿　prolonging life, promising longevity
针灸　acupuncture and moxibustion, acumox		养生防病　cultivating health to prevent disease
各家学说　theories of different schools		正气　healthy qi, vital qi
汗法　diaphoresis, sweating therapy		病邪　pathogenic factor
下法　purgative therapy, purgation		整体观念　concept of holism
吐法　emetic therapy, vomiting therapy		疾病的本质与现象　nature and manifestations of disease
补土派　school of invigorating the earth		阴阳的相对平衡　relative balance between yin and yang
病因学说　etiology		疾病的发生与发展　occurrence and development of disease
养生　health-cultivation,		同病异治　treating the same disease with different therapies
医疗实践　medical practice		异病同治　treating different diseases with the same therapy
治疗原则　therapeutic principles		五脏　five zang-organs, five zang-viscera
寒凉药物　herbs of cold and cool nature, cold-natured herbs		六腑　six fu-organs, six fu-viscera
滋阴降火　nourishing yin to lower/reduce fire		经络系统　system of meridians and collaterals
滋水涵木　enriching water to nourish wood		余热未尽　incomplete abatement of heat
瘀血致泻　disease caused by blood stasis		有机整体　organic wholeness/integrity
先天之精　congenital essence		表里关系　exterior and interior relation
形与神俱　inseparability of the body and spirit		开窍　opening into
开胃　promoting appetite		自然现象　natural phenomena
脉象　pulse conditions, pulse pattern		哲学概念　philosophical concept
邪正关系　states of pathogenic factors and healthy qi		对立统一　unity of opposites
发热恶寒　fever and aversion to cold		相互消长　mutual waning and waxing
头身疼痛　headache and body pain		相互转化　mutual transformation
久痢脱肛　proctoptosis due to prolonged dysentery		阴阳属性　nature of yin and yang
养阴清热　nourishing yin and clearing away heat		相互联系　interrelation
清肺热　clear away lung-heat		相互制约　mutual restraint, mutual restriction/interaction
湿邪犯肺　pathogenic dampness invading the lung		动态平衡　dynamic equilibrium
清热泻火　clearing away heat and reducing fire		阴平阳秘　yin and yang in equilibrium
腠理　muscular interstices, striae, interstitial space		阴阳的互根互用　interdependence of yin and yang
水湿停滞　retention of water and dampness, water retention		相互依存　interdependence
癃闭　retention of urine		阴阳离绝　separation of yin and yang
气血运行　circulation/flow of qi and blood		相反相成　opposite and supplementary to each
阴阳转化　transformation between yin and yang		生理功能　physiological functions
阳消阴长　yang waning and yin waxing		病理变化　pathological changes
阴胜则阳病　predominance of yin leading to disorder of yang		临床诊断　clinical diagnosis
阴胜则阳病　an excess of yin leads to deficiency of yang		阳胜生外热　exuberance of yang leading to exterior heat
阳胜则热　predominance of yang generating heat		阳中求阴　obtaining yang from yin
寒极生热　extreme cold generating heat		绝对偏盛　absolute predominance
热极生寒　extreme heat generating cold		阳虚则寒　yang deficiency leading to cold
阳损及阴　impairment of yang involving yin		阴阳俱损　simultaneous consumption of yin and yang
阴液不足　insufficiency of yin-fluid		阴阳两虚　simultaneous deficiency of both yin and yang
病机总纲　general principle of pathogenesis		阳虚发热　fever due to yang deficiency
病机　pathomechanism, pathological mechanism		阴阳自和　natural harmony between yin and yang
阴阳胜复　alternative predominance of yin and yang		木乘土　the wood over-restrains the earth
虚寒证　deficiency-cold syndrome		木火刑金　wood-fire impairs the metal
扶阳退阴　strengthening yang to reduce yin		金水相生　generation between the metal and water
祛风散寒　expelling/eliminating wind to dispersing cold		生克制化　interrelationship between generation and restriction
消导积滞　promoting digestion and removing food retention		制则生化　restriction ensuring generation
潜阳熄风　suppressing yang to quench wind		母病及子　disease of the mother-organ affecting the child-organ
五行学说　theory of five elements		传变　transmission of disease, progress of disease
运动变化　motion and variation		子病犯母　disease of the child-organ affecting the mother-organ
正邪相争　struggle/combat between healthy qi and pathogenic factors		肝肾精血不足　insufficiency of liver and kidney essence and blood
相生相克　mutual generation and restriction		肝阳上亢　hyperactivity of liver yang
生我，我生　to be generated and to generate		心肝血虚　asthenia / deficiency of heart and liver blood
克我，我克　to be restricted and to restrict		心肝火旺　exuberance of heart and liver fire
生中有制　restriction within generation		心火亢盛　hyperactivity/exuberance of heart fire
克中有生　generation within restriction		滋肾养肝　nourishing the kidney and liver
木曰曲直　wood is characterized by growing freely and peripherally		方位配五行　correspondence of the directions to the five elements
火曰炎上　fire is characterized by flaming up		温肾健脾　warming the kidney and strengthening the spleen
土爰稼穑　earth is characterized by cultivation and reaping		肾阳式微　declination of kidney yang
金曰从革　metal is characterized by change		脾阳不振　inactivation of spleen yang
病缓起　gradual onset of disease		脾胃虚弱　hypofunction/weakness of the spleen and stomach
肝阴不足　insufficiency of liver yin		地道不通　menopause
相乘相侮　over-restriction and reverse restriction		平肝和胃　soothing the liver and harmonizing the stomach
水湿停聚　retention of water-dampness		水火不济　discordance between water and fire
肾阴不足　insufficiency of kidney yin		藏象学说　theory of visceral manifestations
心肾不交　disharmony between the heart and kidney		奇恒之腑　extraordinary fu-organs
宣通水道　dredging water passage		水谷精微　cereal nutrients, essence of water and food
通调水道　dredging and regulating water passage		传化水谷　transmission and transformation of food
行气利水　activating qi to excrete water		贮藏精气　storage of essence
水液停滞　retention of fluid		治疗效果　curative / therapeutic effect
后天之本　postnatal / acquired base of life		藏而不泻　storage without excretion
调畅气机　regulating qi activity		泻而不藏　excretion without storage
肝气上逆　upward flow of liver qi		表热里寒　exterior heat and interior cold
水曰润下　water is characterized by moistening and downward flowing		肝旺脾虚　hyperfunction of the liver and weakness of the spleen
脾主运化　the spleen governing transportation and transformation		大肉陷下　obvious emaciation and muscular atrophy, extreme emaciation
肝气郁结　stagnation of liver qi		面色红润　ruddy complexion, rosy cheeks
胆虚证　gallbladder deficiency syndrome		胆虚不得眠　insomnia due to gallbladder asthenia
腐熟水谷　digesting food		导便法　laxation
食欲不振　poor appetite		跌打损伤　traumatic injury
脘腹胀闷　epigastric distension and depression		动静结合　integration of motion and quietness/stillness
嗳气酸腐　eructation with fetid odor		定喘　relieving asthma
泌别清浊　separating the clear from the turbid		心主血脉　the heart controlling blood and vessels
食物残渣　residue of food		心气充沛　abundance of heart qi
大肠主传导　the large intestine governing transmission and transportation		防御外邪入侵　preventing the invasion of exogenous pathogenic factor
癃闭　dysuria, retention of urine, anuria and dysuria		血液充盈　plenty of blood
面黄肌瘦　emaciation with sallow complexion		脉道不利　unsmoothness of vessels
止珠偏斜　strabismus, squint, ocular deviation		面色无华　lusterless complexion
调节水液　regulation of water		脉象细弱　thin and weak pulse
排泄糟粕　excretion of waste material		面色萎黄　sallow complexion
髓海不足　insufficiency of marrow-sea		汗血同源　sweat and blood sharing the same origin
精神委靡　dispiritedness, listlessness, lower spirit		升降出入　ascending, descending, coming in and going out
月经不调　irregular menstruation		气为血帅　qi serves as the commander of the blood
冲任不固　weakness of thoroughfare and conception vessels		气血凝滞　stagnation of qi and blood
经期延长　prolonged menstruation		血瘀　blood stasis
小肠实热　sthenia-heat in the small intestine		气滞腰痛　lumbago due to qi stagnation
气机调畅　smooth activity of qi		气虚滑胎　habitual abortion due to qi asthenia