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After mastectomy, chest wall recurrences are treated with radiation therapy.

Breast recurrences after radiation are treated with mastectomy.

Systemic therapy may also have a role in some cases.

Distant metastasis

Hormone therapy. Patients who respond to one hormone treatment modality generally continue to respond to sequential hormone therapy, whereas nonresponders do not. Few patients are cured once metastasis occurs, but hormone therapy is very effective in prolonging survival and in reducing the size of the tumor.

Chemotherapy is used for patients with recurrent disease who are estrogen-receptor negative or who do not respond to hormone therapy. Combinations of cyclophosphamide, methotrexate, fluorouracil, and doxorubicin are usually used in these cases. Temporary favorable responses, which are determined by a measurable decrease in tumor size or the relief of pain, are obtained in 60%–80% of patients with stage IV disease when this therapy is initiated.

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J Special cases

Breast cancer in pregnancy

Breast cancer occurs in 1.5% of women during their childbearing years.

Diagnosis is usually delayed secondary to normal nodularity that forms in breasts during pregnancy.

A suspicious mass should be evaluated with mammogram and ultrasound.

Core or excisional biopsy should be performed for any suspicious mass.

Excisional biopsy can be performed safely under sedation with local anesthesia.

The male breast

Gynecomastia

Prepubertal gynecomastia is rare and is caused by adrenal and testicular carcinoma.

Pubertal gynecomastia occurs in 60%–70% of prepubertal boys (12–15 years of age). Breast enlargement in the healthy male adolescent does not require treatment. In nearly all cases, the enlargement will regress with age. If enlargement is significant, unilateral, or distressing the patient, treatment is simple mastectomy.

Senescent gynecomastia

Forty percent of aging men have decreased testosterone, increased estradiol, and increased luteinizing hormone.

Unilateral or bilateral enlargement of the breast tissue directly behind the nipple

Causes of gynecomastia

Idiopathic

Drug therapies such as thiazide diuretics, digoxin, theophylline, antidepressants, and hormones

Alcohol and marijuana abuse

Disease conditions such as cirrhosis, renal failure, and malnutrition

Treatment

Evaluate for mass with mammography and physical exam

If a dominant mass is present, a biopsy must be performed to rule out cancer. Then, if no cancer is present, withdraw the offending agent, treat the underlying medical condition, perform a hormonal workup, and provide reassurance.

Cancer of the male breast

This type occurs in 0.7% of all breast cancers and in less than 1% of male cancers.

The average age is 63–70 years, which is older than in women.

Klinefelter's syndrome has been associated with male breast cancer (testicular hormone factors).

Many risk factors associated with male breast cancer can be linked to elevated estrogen levels.

Most patients present with a painless unilateral mass that is usually subareolar with skin fixation, chest wall fixation, and ulceration.

The workup is identical to that used for a woman. Gynecomastia is the primary differential diagnosis. Bilaterality and tenderness favor gynecomastia.

A thorough history of drug and hormone use along with alcohol intake is necessary.

Mammography may distinguish between the two.

This type originates as a ductal cancer.

Treatment is similar to that for carcinoma of the female breast.

Radical mastectomy has been the standard treatment.

Modified radical mastectomy is done if the pectoralis major muscle is not involved.

Breast conservation is done with radiation therapy if the primary tumor is small and does not involve the nipple -areola complex.

Hormonal manipulation involves castration or tamoxifen therapy.

Genetic relationship between the donor and the recipient. Physicians should remember that allografts and xenografts require immunosuppression; otherwise, they will fail because of rejection.

Autograft describes tissue transfer within the same individual (e.g., skin graft).

Isograft describes tissue transfer between genetically identical individuals (e.g., identical twins).

Allograft describes tissue transfer between genetically nonidentical members of the same species (includes living related donor and cadaver donor human transplants). Immunosuppression is required.

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Xenograft describes tissue transfer between different species. Immunosuppression is required.

Surgical position

Orthotopic. The old organ is removed, and the new one is placed in the same position.

Heterotopic. The new organ is placed in a different position.

C Donors

Cadaver donors are individuals with severe brain injury resulting in brain death, which is defined as complete irreversible cessation of all brain function, including the brain stem.

Diagnosis. The mainstay of diagnosis is the neurologic examination, which must demonstrate unresponsiveness, absence of spontaneous movement, and absence of reflexes from the brain stem and higher. Also:

The patient must be normothermic.

Depressant drugs (especially barbiturates) must not be present.

An apnea test result must be negative (i.e., no respiratory effort despite a high arterial carbon dioxide level).

Electroencephalogram (EEG) and cerebral blood flow studies are optional.

Causes. Cerebrovascular disease is most common, followed by trauma.

Exclusions. Disseminated or uncured extracranial cancers, sepsis, or poor organ function.

Living donors are individuals motivated by altruism.

Types of living donors

Living unrelated donors on average share no more genes with a recipient than a cadaver donor. An example is the patient's spouse.

Living related donors share a substantial portion of their genomes with the recipient.

Requirements. Living donors must be in almost perfect health, have normal function of the organ under consideration, and be good candidates for anesthesia and the operative procedure. The workup

includes:

ABO typing, tissue typing, and cross matching (see I F)

Complete history and physical examination; chest radiography; ECG; complete blood count; sequential multiple analysis (SMA) for 6 and 12 serum tests (SMA-6, SMA -12); 24 -hour creatinine clearance and protein; RPR test; serology for hepatitis B and C, CMV, and HIV; urinalysis; PPD

For renal donors, arteriography and intravenous pyelogram (now combined as a helical computed tomography [CT] scan).

Risks. Perioperative mortality for living kidney donors is 0.03% (3 per 10,000). A living donor provides one kidney, and the remaining kidney hypertrophies and achieves 80% of creatinine clearance before donation. Newer procedures include donation of the left lateral segment or a lobe of the liver and segment(s) or lobe(s) of the lung. In these procedures, the safety of the donor is not assured. Although, traditionally, most living kidney donations are performed as an open surgical procedure, there is increasing experience with laparoscopically performed nephrectomy. This method potentially offers the advantage of minimally invasive surgery while still producing an excellent kidney.

D Removal of the donor organ

The donor organ is removed in a formal surgical procedure, wherein the blood supply of the organ is controlled and then the organ is rapidly flushed with a cold (4 °C) solution to render it cold and ischemic. All organs are more tolerant of cold ischemia than warm (normothermic) ischemia.

E

The practical limit of cold ischemia with current preservation methods is 4 hours for the heart, 6 hours for a lung, 12 hours for the liver, 36 hours for the pancreas, and 40–48 hours for a kidney. As the limit is approached or passed, the risk increases for delayed function, damage, or nonfunction of the organ.

F

The immunologic compatibility of the donor and recipient influences the outcome for any type of organ transplant (Table 24 -1).

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TABLE 24-1 Effects of Immunologic Compatibility on Transplant Outcome

HLA, human leukocyte antigen; PRA, panel-reactive antibody.

ABO blood group compatibility. The same rules apply as for red blood cell transfusions.

Cross -match compatibility must be present for kidney, pancreas, and some heart transplants. The recipient's serum is tested for the presence of cytotoxic antibodies directed against surface antigens (usually antihuman leukocyte antigen [HLA]) on the T lymphocytes of the donor. If antidonor cytotoxic antibodies are present, the donor is unacceptable because the recipient's antibodies will immediately attack the new kidney and rapidly destroy it (hyperacute rejection; see I G 1).

A positive cross match is positive for the presence of preformed antidonor antibodies in the serum of the prospective recipient and precludes transplantation between that donor and the recipient.

A negative cross match (i.e., absence of antidonor antibodies) is mandatory before the transplant.

A few patients have antibodies against most other humans (so-called high panel -reactive antibody [PRA] patients). High-PRA patients have formed antibodies against a high proportion of a panel of human cells, which is used to screen for reactivity; therefore, acceptable donors are difficult to find. Also, high-PRA patients are at higher risk for early graft failure.

Human leukocyte antigen (HLA). These are the histocompatibility antigens and are defined by tissue typing.

Six human HLA genes (HLA -A, -B, -C, -DR, -DP, and -DQ) are located on chromosome 6.

HLA -C, -DP, and -DQ are not believed to be important in clinical transplantation.

The contents of each chromosome 6 is a haplotype, and all humans have two of these chromosomes —one from the mother and one from the father. Therefore, six HLA antigens are defined by tissue typing (i.e., two each for HLA -A, -B, and -DR).

HLA -A and -B have more than 40 defined types, which are designated numerically. HLA -DR has more than 10 defined types. An example of an HLA type is HLA -A2, 27; B1, 44; DR 3, 7. An example of a haplotype is HLA -A2; B1; DR7.

G Rejection

The three types of rejection are hyperacute, acute, and chronic.

Hyperacute rejection occurs when the serum of the recipient has preformed antidonor antibodies. These antibodies adhere to and kill endothelium, which results in rapid graft infarction (within 24 hours). Because hyperacute rejection can be predicted by a positive cross match (see I F 2 a), it is avoidable. However, once hyperacute rejection begins, it cannot be treated.

Acute rejection is a cell -mediated immune response initiated by helper T cells. The pace of proliferation of alloreactive T cell clones dictates that acute rejection usually occurs after the sixth

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