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C. Milten, M.B. B.CH. B.A.O., M.B.B.Ch., Ph.D.

Clinical Director, University of Miami Leonard M. Miller School of Medicine

Skin biopsies at multiple sites may be necessary to define T-stage, as lesion morphology varies from patient to patient and for different lesions from the same patient. Such problems are especially evident for early patch or plaque lesions wherein only a small fraction of the infiltrating T lymphocytes (confined exclusively to the epidermis) are actually neoplastic. This typical histopathologic pattern can be significantly modified by prior therapy, as even topical steroids can significantly alter the intensity and appearance of both the neoplastic and nonneoplastic lymphoid infiltrates. Histopathologic features of "transformation" to a high-grade lymphoma, such as an enlarged pale nucleus and prominent nucleoli or loss of normal T-cell markers, are all associated with a poorer prognosis. Skin biopsies should also be subjected to immunophenotyping to define better the identity of the benign and neoplastic cell populations present in the cutaneous lesions. Several studies have reported correlations between the immunophenotypes of the cells present in the infiltrates and stage of disease. Imaging studies (computed tomography scan or magnetic resonance imaging) are recommended at initial evaluation for those with advanced disease and during follow-up to detect enlargement of thoracic, abdominal, or pelvic nodes. Those patients with small cell infiltrates had a median survival of 40 months, and those with high-grade immunoblastic features had a median survival of only 9 months. Such analyses have revealed a remarkable clinical heterogeneity within patients who present with T4 disease. The patient should also be asked about cutaneous integrity, temperature imbalance, fissuring, pruritus, and the use of moisturizers. Evaluation of the abdomen should be performed to detect hepatosplenomegaly, and the site, size, and number of palpable peripheral lymph nodes should be recorded. Other Studies A posteroanterior and a lateral chest radiograph should be performed in all patients. Computed tomography or magnetic resonance scans should be carried out of the chest, abdomen, and pelvis both to evaluate mediastinal, retroperitoneal, and pelvic nodes as well as to supplement physical examination of the axillary and inguinal nodes in patients with T3 and T4 disease. Such enlarged nodes should undergo biopsy (preferably by excision rather than needle sampling) to document both the presence of neoplastic T cells and the histopathologic pattern of involvement. Bone marrow evaluation is not routinely performed unless abnormalities are noted on complete blood cell count or smear. Hence, early-stage disease that is localized to the skin has an excellent chance of cure with therapies directed to the skin alone. However, disease that has disseminated and become established in lymph nodes or visceral sites (liver, lung, central nervous system) can be palliated but rarely cured, even with the most aggressive regimens of systemic chemotherapy. This result contrasts with that seen in B-cell lymphomas in which patients with extensive nodal and visceral disease are often cured by aggressive combination chemotherapy or bone marrow or stem cell transplantation. General Management of Cutaneous T-Cell Lymphoma All skin-directed therapies exert their primary effects on disease confined to the skin. This is in addition to any direct cytotoxic or cytostatic effects they exert on benign and neoplastic T lymphocytes. In one series of 243 patients, the median survival of treated patients was 8 years, and the response rate was better in those with less extensive disease. However, significant erythema in the treated areas and posttreatment telangiectasia occur in one of three patients. Also, as a small fraction of the drug is absorbed, marrow suppression can occur but is unusual unless the total dose exceeds 600 mg (in increments of 20 to 25 mg). To induce remission, treatments should begin three times per week at doses that are minimally phototoxic. Retinoids also have a role as adjunctive agents in achieving remission or palliating symptoms. If the remission is sustained, the interval between treatments can be extended to 2 weeks for a total of 26 sessions per year for an additional year. If there is still no evidence of relapse, the interval between treatments can be extended to 3 weeks and continued for another 2 years. However, patients should probably not be considered "cured" until they have remained disease-free for at least 5 years after completing therapy.

Syndromes

• Canning wax
• Salicylate medications to reduce acute inflammation.
• Uterus and cervix problems-- A baby girl may be born with an extra cervix and uterus, a half-formed uterus, or a blockage of the uterus. Usually, girls born with half a uterus and half a vagina are missing the kidney on the same side of the body.
• Infection in the joint
• If the medication was prescribed for the patient
• Limited food supply
• You hear voices that are not there.

A long-standing controversy among endocrine surgeons has existed regarding the extent of surgical resection for well-differentiated thyroid cancer. The entire thyroid lobe on the side of the primary cancer is taken out as completely as possible for any of these procedures. The difference comes in the management of the contralateral lobe and how this choice relates to outcome as well as operative morbidity. Arguments typically put forth for either more conservative therapy or more aggressive surgery are listed in Table 38. In a thyroid lobectomy, the contralateral lobe is not dissected but is simply examined visually and by palpation for abnormalities. A subtotal thyroidectomy leaves a rim of 2 to 4 g of tissue in the upper lateral portion of the contralateral thyroid lobe. First, the recurrent laryngeal nerve as it enters the larynx at the ligament of Berry is not dissected and consequently does not present a risk for injury. Second, the blood supply to the superior parathyroid gland on that side is less likely to be disrupted by leaving a rim of tissue in this location. This maneuver may offer some protection to the recurrent laryngeal nerve, but it offers minimal benefit in terms of preserving the blood supply of the upper parathyroid. A total thyroidectomy implies that every effort is made to excise all thyroid tissue, leaving no gross or macroscopic residual thyroid in either lobe. The difference between a total thyroidectomy and a near-total thyroidectomy usually depends on the particular anatomy of the thyroid in any given patient. There may be a small ledge of thyroid tissue, called the tubercle of Zuckerkandl, at the ligament of Berry that may limit safe resection of the entire thyroid. Arguments for and against Conservative or More Radical Surgery for Well-Differentiated Thyroid Cancer the real increased risk of performing a total thyroidectomy versus a lesser resection may be in the long-term incidence of hypocalcemia (Table 38. Long-Term Complications of Total versus Subtotal Thyroidectomy the most compelling argument for performing a unilateral lobectomy or a subtotal thyroidectomy are the data that come from the definition of prognostic factors for this disease. However, careful medical surveillance for cancer in the contralateral lobe as well as recurrence must be maintained. Furthermore, in situations in which a small thyroid remnant is left, the true morbidity of treating this patient with ablative doses of 131I (if indicated) is relatively minimal. Radioiodine ablation of an intact lobe of the thyroid lobectomy is associated with considerably more symptoms. Despite this very clear difference in recurrence rates, there was no translation of benefit in terms of disease-specific survival or distant metastases. Arguing with the opposing viewpoint, Sanders and Cady also provided a long-term review of their personal series and came to the conclusion that there was no benefit in performing bilateral resection versus unilateral resection for low-risk patients. For patients in a high-risk category, there is much less disagreement regarding the extent of surgery, although there are still some proponents of less than total or near-total thyroidectomy. An analysis of 303 patients with high-risk papillary thyroid cancer showed an improvement in overall survival (relative risk ratio, 0. Again, neither of these retrospective reviews was a prospective randomized study and, for reasons discussed later in Radioactive Therapy, in terms of effectiveness of adjuvant postoperative radioiodine treatments and ease of follow-up with serum Tg measurements, the vast majority of investigators would agree that a total or near-total thyroidectomy is indicated for high-risk patients. For patients with extrathyroidal extension, the en bloc resection of invaded structures should be performed. If the tumor is on the anterior thyroid, this provides minimal morbidity to the patients, as resection of the overlying strap muscles, such as the sternal thyroid, causes no symptoms postoperatively. For posterior tumors, direct invasion of the trachea and esophagus should be resected with either partial tracheal resection and primary closure or resection of the esophagus muscular layer, again with closure and drainage. The surgical management of lymph node metastases from well-differentiated thyroid cancer is also somewhat controversial. For patients who have bulky and obviously pathologic lymph node metastases, a formal neck dissection is indicated. Although lymph node metastases correlate with increased local recurrence, they do not carry a worse prognosis in several series. Lymph nodes that are abnormal because they are firm or large should be subjected to biopsy with frozen-section pathologic evaluation. If positive for metastatic cancer, these lymph node areas should be completely dissected. The technique of sentinel lymph node biopsy that has been used for melanoma and breast cancer has been applied to thyroid cancer using isosulfan blue.

Surgery should be considered in patients with a life expectancy of greater than 2 months. The surgical approach should be determined by the location of vertebral involvement and direction of compression. Recommendations for Management of Patients with Metastatic Cord Compressiona Chemotherapy should be the initial treatment for children with chemosensitive tumors. Patients treated with chemotherapy should be monitored closely so that immediate intervention can proceed if there is an inadequate response or neurologic progression. Children with severe neurologic deficits from cord compression should be considered for primary laminectomy. Adults with chemotherapy-sensitive or hormone-sensitive tumors should receive chemotherapy as an adjuvant or as the primary treatment if radiation or surgery are contraindicated. Corticosteroid therapy remains one of the most effective treatments for acute spinal cord compression. Radiotherapy without steroids in selected metastatic spinal cord compression patients. Effectiveness of radiation therapy without surgery in metastatic spinal cord compression: final results from a prospective trial. Epidural spinal cord compression from metastatic tumor: results with a new treatment protocol. Effect of high-dose dexamethasone in carcinomatous metastatic spinal cord compression treated with radiotherapy: a randomised trial. Initial bolus of conventional versus high dose dexamethasone in metastatic spinal cord compression. Emergency treatment of malignant extradural spinal cord compression: an evidence-based guideline. Treatment of complications: diagnosis and treatment of spinal cord compression in malignant disease. Anterior approaches to the thoracic spine in patients with cancer: indications and results. Second occurrence of symptomatic metastatic spinal cord compression and findings of multiple spinal epidural metastases. Incidence, presentation and outcome of spinal cord disease in children with systemic cancer. Edema and circulatory disturbance in the spinal cord compressed by epidural neoplasms in rabbits. Vertebral body reconstruction with a modified Harrington rod distraction system for stabilization of the spine affected with metastatic disease. Angiographic study of the effect of laminectomy in the presence of acute anterior epidural masses. Vascular endothelial growth factor is expressed in ovine pulmonary vascular smooth muscle cells in vitro and regulated by hypoxia and dexamethasone. Mechanism of dexamethasone suppression of brain tumor-associated vascular permeability in rats. Comparison of soluble dexamethasone sodium phosphate with free dexamethasone and indomethacin in treatment of experimental neoplastic spinal cord compression. Influence of time between onset of motoric deficits and start of irradiation on therapeutic effect. Malignant spinal cord compression: prospective study of delays in referral and treatment. Frequency of unexpected multifocal metastasis in patients with acute spinal cord compression. Magnetic resonance imaging of the whole spine in suspected malignant spinal cord compression: impact on management. Neuroimaging and treatment implications of patients with multiple epidural spinal metastases. Symptoms and signs in metastatic spinal cord compression: a study of progression from first symptom until diagnosis in 153 patients. Bone-scan "cold" lesion caused by an osteolytic metastasis from an adenocarcinoma of the thyroid.

Complications of salvage prostatectomy are more common than after primary prostatectomy. Contemporary series report better outcomes due to improved patient selection, earlier identification of failure, and improved surgical technique. The largest series of patients treated with cryoablation for local recurrence after primary radiation therapy was reported by Greene and Pisters et al. An effective urethra warming device was determined to be essential to minimize tissue sloughing. Complications such as urethrorectal fistula, abscess formation, and urethral stricture were rare. Ninety percent of the cancers were moderately to poorly differentiated on prebrachytherapy biopsies. Complications were similar to those seen in patients undergoing primary brachytherapy. For those patients whose cancers recur after cryotherapy, the choice of secondary treatment is not well defined. Radiation treatment can be used after cryoablation and, unlike cryotherapy after radiation, salvage radiation therapy after cryotherapy appears to be associated with minimal morbidity. Both high-intensity focused ultrasonography and radiofrequency interstitial ablation are being studied and appear to have promise in local control of prostate cancer. Radiofrequency ablation was able to produce predictable lesions in prostates prior to radical prostatectomy. The long-term efficacy and morbidity of these new forms of focal therapy require further study. In such patients, the morbidity and cost of secondary therapy must be carefully considered and compared to the risk of clinical progression of disease. Prostate cancer is diagnosed in fewer patients at a time when their disease is overtly metastatic. Nonetheless, a large number of patients still die of prostate cancer despite earlier detection, which reflects the existence of occult metastatic disease. Advanced disease might include patients who, at time of diagnosis, have poor-risk features but no overt metastases. With improvements in our understanding of risk stratification, the traditional stage-based therapy may become obsolete, replaced by multifactor stratification schemes and biologically based therapies. However, until the paradigm has changed, we must discuss treatment based on stage or modality. Because androgen may play a role as both a survival factor and a growth factor for prostatic carcinoma cells, interference with the androgen-signaling pathway will generate clinically meaningful remissions in the majority of patients. It is likely that the remission sustained by the vast majority of patients reflects a composite of all of these phenomena, although conceivably one or another mechanism may dominate in any one individual. The majority of circulating androgen is produced by the testicles in the form of testosterone, and the remainder is produced by the adrenal glands, which synthesize the so-called adrenal androgens. Antiandrogens (androgen receptor antagonists) or agents that interfere with the adrenal production of androgens, such as ketoconazole or aminoglutethimide, also are used. How applicable the results of these studies are to patients with earlier stages of advanced prostate cancer is uncertain. Significant side effects exist as a result of treatment with androgen deprivation therapy, and the cost of therapy can be significant as well. Thus, the choice and timing of treatment depends on several factors, including the stage of disease, whether symptoms are present, the rate of disease progression, patient preference, and a full knowledge of the toxicity profiles of the drugs used. Timing of Androgen Deprivation Therapy Although it is assumed that androgen deprivation therapy is life-prolonging, this has never been formally proven. Nonetheless, it is likely that androgen deprivation therapy delays the onset of radiographic progression or symptoms in an otherwise asymptomatic man, presumably by reducing the overall tumor cell mass. Whether the earlier initiation of androgen deprivation therapy increases survival duration has long been debated. In theory, it seems reasonable that the earlier the initiation of androgen deprivation therapy, the better the outcome. This would follow from the assumption that, as tumors evolve and acquire more genetic change, the proportion of hormone-refractory cells in the tumor increases. Three studies now offer evidence that supports the earlier initiation of androgen deprivation therapy. Cyproterone acetate (a steroidal antiandrogen) and goserelin administration were begun at the time of radiation.