Surgical management of malignant melanoma using dynamic lymphoscintigraphy and gamma probe-guided sentinel lymph node biopsy: the Emory experience.

Sentinel lymph node (SLN) biopsy is revolutionizing the surgical management of primary malignant melanoma. It allows accurate nodal staging which targets patients who may benefit from regional lymphadenectomy and systemic therapy. This is a retrospective review of patients treated at Emory University for stage I and II malignant melanoma with gamma probe-guided SLN biopsy from 1/1/94 to 6/30/98. Three hundred sixty patients (males 228, females 132) were identified. Primary melanoma sites included: head and neck 58, trunk 148, and extremities 154 (upper 71, lower 83). Primary tumor staging was T1 9, T2 134, T3 153, and T4 64. SLNs were successfully identified in 99.7 per cent of patients and 98.9 per cent of nodal basins mapped. In 275 (76.6%) cases a single draining nodal basin was identified. In 84 (23.3%) cases there were multiple draining nodal basins. Positive SLNs were identified in 63 patients (17.5%). SLN positivity by tumor staging was T1 0 per cent, T2 9.0 per cent, T3 22.2 per cent, and T4 26.6 per cent. The overall recurrence rate was 11.9 per cent. Recurrences by SLN status were SLN+, 27 per cent, and SLN-, 8.8 per cent. Regional recurrence occurred in 7 (2.4%) of the 297 with negative SLN biopsies and 7 (11.1%) of the 63 with positive SLN biopsies. Dynamic lymphoscintigraphy and gamma probe-guided SLN localization was successful in more than 98 per cent of cases. Patients with negative SLN biopsies have a low risk of recurrence.

beta-adrenergic blockade in developing heart failure: effects on myocardial inflammatory cytokines, nitric oxide, and remodeling.

BACKGROUND: Whether beta-adrenergic blockade modulates myocardial expression of inflammatory cytokines and nitric oxide (NO) in heart failure is unclear. METHODS AND RESULTS: We administered oral metoprolol or no therapy to rats for 12 weeks after large myocardial infarction and subsequently examined left ventricular (LV) remodeling; myocardial tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6 expression; and NO. In untreated rats, echocardiography revealed significant (P<0.001) LV dilatation and systolic dysfunction compared with sham. Papillary muscle studies revealed isoproterenol hyporesponsiveness to be unaltered by NO synthase (NOS) inhibition. Circulating NO metabolites were undetectable. In noninfarcted myocardium, although inducible NOS (iNOS) mRNA was absent, TNF-alpha, IL-1beta, and IL-6 mRNA and protein were markedly elevated compared with sham (P<0.001), with 2-fold higher expression (P<0.025) of IL-6 compared with TNF-alpha or IL-1beta. Metoprolol administration starting 48 hours after infarction (1) attenuated (P<0.02) LV dilatation and systolic dysfunction, (2) preserved isoproterenol responsiveness (P<0.025) via NO-independent mechanisms, and (3) reduced myocardial gene expression and protein production of TNF-alpha and IL-1beta (P<0. 025) but not IL-6, which remained high. CONCLUSIONS: During heart failure development, adrenergic activation contributes to increased myocardial expression of TNF-alpha and IL-1beta but not IL-6, and one mechanism underlying the beneficial effects of beta-adrenergic blockade may involve attenuation of TNF-alpha and IL-1beta expression independent of iNOS and NO.

Chronic beta-adrenergic stimulation induces myocardial proinflammatory cytokine expression.

BACKGROUND: The sympathetic nervous system and proinflammatory cytokines are believed to play key roles in the pathophysiology of congestive heart failure. To evaluate a possible relationship between these neurohormonal systems, we studied the effects of chronic beta-adrenergic stimulation on the myocardial and systemic elaboration of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6. METHODS AND RESULTS: Male rats received either L-isoproterenol (2.4 mg. kg(-1). d(-1), n=8) or saline (n=7) via miniosmotic pumps for 7 days. Myocardial cytokine expression was analyzed by both Northern and Western blotting and localized in the tissue using immunohistochemistry. ELISA was performed to measure circulating levels of cytokines. In myocardium from control animals, neither TNF-alpha nor IL-1beta were detected, whereas IL-6 was present at very low levels. Isoproterenol led to a significant (P<0.01) increase in mRNA and protein expression of all 3 cytokines. Immunohistochemistry did not detect immunoreactivity for either cytokine in myocardium from controls; however, all 3 cytokines were readily detected (P<0.05) throughout the myocardium, localized to resident cells and vessels, in animals treated with isoproterenol. Neither treatment group had detectable levels of cytokines in the serum. CONCLUSIONS: Chronic beta-adrenergic stimulation induces myocardial, but not systemic, elaboration of TNF-alpha, IL-1beta, and IL-6.

Management of malignant melanoma of the head and neck using dynamic lymphoscintigraphy and gamma probe-guided sentinel lymph node biopsy.

BACKGROUND: The sentinel lymph node (SLN) biopsy is revolutionizing the surgical management of primary malignant melanoma. It allows accurate nodal staging, and targets patients who may benefit from regional lymphadenectomy and systemic therapy; however, its use in the management of head and neck melanoma has not been widely accepted. METHODS: A retrospective review of patients treated for clinical stages I and II malignant melanoma of the head and neck with dynamic lymphoscintigraphy and gamma probe-guided SLN biopsy. RESULTS: Fifty-eight patients (47 male and 11 female) were identified. Primary melanoma sites included the scalp (21), ear (8), face (13), neck (15), and eyelid (1). Primary tumor staging was T2 (11), T3 (24), and T4 (23). Dynamic lymphoscintigraphy visualized SLNs in 57 patients (98.3%). In 43 cases (75%) a single draining nodal basin was identified, and in 14 cases there were multiple draining nodal basins. Sentinel lymph nodes were successfully identified in 72 (96%) of 75 nodal basins. Positive SLNs were identified in 10 patients (17.5%). Sentinal lymph node positivity by tumor staging was T3, 16.7% and T4, 27.3%. Completion lymphadenectomy revealed residual disease in 3 patients (30%). Relapse occurred in 10 (21.3%) of the 47 patients with negative SLN biopsy results and 7 (70%) of those with positive results. CONCLUSIONS: Gamma probe-guided SLN localization in the head and neck region was successful in 96% of draining nodal basins. It can target regional lymphadenectomy in patients who may benefit from regional nodal dissection.

Overview of recent clinical trials in heart failure: what is the current standard of care?

Heart failure develops as a consequence of cardiac injury. As the heart begins to fail to meet the body's metabolic demands, the renin angiotensin aldosterone system (RAAS) and the sympathetic nervous system are activated. These interrelated systems act in concert to facilitate cardiac output and tissue perfusion. Though these neurohormonal systems are initially compensatory, evidence suggests that they promote deleterious cardiac remodeling and myocyte destruction. Recent studies in patients with heart failure have targeted the RAAS and sympathetic nervous system for therapeutic intervention. This article reviews major recent multicenter, randomized, double-blind, and placebo-controlled trials in heart failure that have resulted in a new standard of care for patients with this devastating disease.

Desmoplastic spindle-cell melanoma of the eyelid with orbital invasion.

PURPOSE: To describe the clinicopathologic features of a patient with a spindle-cell melanoma of the eyelid that exhibited orbital invasion. METHODS: Case report. RESULTS: A slowly enlarging mass developed in the eyelid of a 50-year-old woman. Excision of the mass showed desmoplastic spindle-cell melanoma. The tumor recurred in the orbit, and an exenteration was performed. A second recurrence 7 months later was treated with radiation therapy. CONCLUSIONS: There is a continuum of spindle-cell to desmoplastic melanoma. The prognosis of patients with orbital invasion of melanoma is poor, and adjuvant treatment including radiation and chemotherapy has little benefit.

Hemodynamic effects of nitric oxide synthase inhibition at steady state and following tumor necrosis factor-alpha-induced myodepression.

OBJECTIVE: Nitric oxide (NO) has been proposed as a common mediator of tumor necrosis factor-alpha (TNF alpha)-induced vasodilation and myocardial dysfunction. Accordingly, we performed an extensive assessment of the influence of NO synthase inhibition on left ventricle (LV) and circulatory performance in conscious dogs at steady state and after establishment of TNF alpha mediated myodepression. METHODS: Autonomically blocked, chronically instrumented dogs were studied at steady state and 6 h after initiation of a 1-h rhTNF alpha infusion (40 micrograms/kg). Ventricular performance was evaluated using the pressure-volume framework. Dogs were then treated with either NG-nitro-L-arginine methylester (L-NAME, 40 mg/kg bolus) or angiotensin II (250-500 ng/kg). RESULTS: L-NAME, under control conditions or following recombinant human (rh) TNF alpha-induced ventricular dysfunction, produced marked increases in afterload with attendant increases in LV pressure, volume, and prolonged isovolumic relaxation without adversely influencing coronary blood flow. regardless of whether the dogs received rhTNF alpha, L-NAME did not affect the slopes of the end-systolic pressure-volume and stroke-work (SW)-end-diastolic volume (EDV) relations (force-based measure of contractility), whereas the slope of the dP/dtmax-EDV relation, a velocity dependent parameter of LV systolic function, declined. Overall ventricular performance, as seen by the circulation, was reduced by L-NAME in control as well as rhTNF alpha-treated dogs, evidenced by rightward shifts of the SW-EDV and dP/dtmax-EDV relations. Similar findings were observed in the separate cohorts of dogs, at steady state and 6 h after rhTNF alpha, following angiotensin II at matched systolic pressure. CONCLUSIONS: Systemic NO synthase inhibition with L-NAME does not acutely reverse rhTNF alpha-induced myocardial dysfunction. The detrimental influence of L-NAME on LV size, relaxation, and velocity-based measures of contractility is likely attributable to its effects on increasing afterload.

Ryanodine and left ventricular function in intact dogs: dissociation of force-based and velocity-based indexes.

After anesthesia and autonomic blockade, nine dogs chronically instrumented with left ventricular (LV) micromanometers and piezoelectric dimension crystals were studied before and after the intravenous administration of 4 micrograms/kg ryanodine, a specific inhibitor of the sarcoplasmic reticulum Ca2+ release channel. Ryanodine prolonged LV contraction and relaxation (P < 0.001) without changing heart rate, end-diastolic volume (EDV), or end-systolic pressure. Velocity-dependent mechanical parameters were significantly depressed, including the maximal rate of LV pressure rise (dP/dtmax; P < 0.002), the mean velocity of circumferential fiber shortening (P < 0.002), the slope of the dP/dtmax-EDV relation (P < 0.05), and the time constant of LV relaxation (P < 0.01). In contrast, the slopes of the end-systolic pressure-volume (PES-VES) and stroke work (SW)-EDV relations, both force-based parameters, were increased (P < 0.05) or maintained, respectively. Ryanodine reduced overall LV contractile performance, evidenced by significant rightward shifts of the PES-VES, dP/dtmax-EDV, and SW-EDV relations and reduced SW at constant preload (P < 0.02). Thus, in the closed-chest dog, low-dose ryanodine resulted in 1) generalized slowing of LV mechanical events without changes in heart rate or load, 2) dissociation of velocity-based and force-based measures of LV function, with depression of the former but enhancement or maintenance of the latter, and 3) reduced overall LV inotropic performance. These effects are consistent with ryanodine-induced alterations of the Ca2+ transient and altered sarcoplasmic reticulum Ca2+ availability.

Skin-sparing mastectomy. Oncologic and reconstructive considerations.

OBJECTIVE: The authors compared skin-sparing mastectomy and traditional mastectomy both followed by immediate reconstruction in the treatment of breast cancer. SUMMARY BACKGROUND DATA: Skin-sparing mastectomy is used increasingly in the treatment of breast cancer to improve the aesthetic results of immediate reconstruction. The oncologic and reconstructive outcomes of this procedure have never been analyzed closely. METHODS: Institutional experience with 435 consecutive patients who underwent total mastectomy and immediate reconstruction from January 1989 through December 1994 was examined. Mastectomies were stratified into skin-sparing (SSM) and non-skin-sparing (non-SSM) types. RESULTS: Three hundred twenty-seven SSMs and 188 non-SSMs were performed. The mean follow-up was 41.3 months (SSM, 37.5 months, non-SSM, 48.2 months). Local recurrences from invasive cancer occurred after 4.8% of SSMs versus 9.5% of non-SSMs. Sixty-five percent of patients who underwent SSMs had nothing performed on the opposite breast versus 45% in the group of patients who underwent non-SSM (p = 0.0002). Native skin flap necrosis occurred in 10.7% of patients who underwent SSMs versus 11.2% of patients who underwent non-SSMs. CONCLUSIONS: Skin-sparing mastectomy facilitates immediate breast reconstruction by reducing remedial surgery on the opposite breast. Native skin flap necrosis is not increased over that seen with non-SSM. Skin-sparing mastectomies can be used in the treatment of invasive cancer without compromising local control.

Lymphoscintigraphy, the sentinel node concept, and the intraoperative gamma probe in melanoma, breast cancer, and other potential cancers.

There is a resurgence of interest in lymphoscintigraphy because of attention to the sentinel node concept and the availability of the surgical gamma probe that can be used in the operating room to localize radiolabeled sentinel nodes. Conventional surgical management of melanoma has been altered for intermediate thickness tumors such that lymph node dissection is performed for a lymph node bed only if the sentinel node is tumor positive on histological exam after gamma probe-guided excision. This approach is cost effective, saving about 80% of these patients (sentinel node tumor negative) the cost and morbidity of unnecessary "elective lymph node dissection." In addition, a biopsy can be performed on all lymph node beds that receive lymphatic drainage from the tumor site thereby improving staging and perhaps survival by providing the most appropriate therapy. Substantial work has been done to develop optimum imaging techniques and the best radiopharmaceutical preparation to achieve accurate, reproducible lymphatic drainage images. Our methodology includes the following intradermal injections of a technetium 99m sulfur colloid (modified preparation) are followed by dynamic imaging (10 seconds per frame); static imaging up to 30 minutes and late imaging at 1 to 2 hours. Images show lymphatic channels that lead to sentinel nodes in 1, 2, 3, or more anatomic locations. Surgical management is altered to include sampling sentinel nodes of nodal beds, many of which would not have been sampled by previous conventional surgical estimates of lymphatic drainage. While clinical success of lymphoscintigraphy and intraoperative probe localization of the sentinel node in melanoma is evident, use of lymphoscintigraphy and the sentinel node concept in breast cancer is investigative, but promising. The radiopharmaceutical is injected around the tumor in the breast followed by imaging to delineate lymphatic drainage to the sentinel node(s). Optimum methodologies for radiopharmaceutical, volume and/or activity of injectate, and imaging have yet to be determined. Breast lymphatic drainage can be to axilla, internal mammary, and/or supraclavicular nodes in any combination.

Myocardial ischemia alters immunoregulatory cell traffic and function in the rat independent of exogenous catecholamine administration.

Recent investigation has suggested there is an adrenergically-driven efflux of beta 2-receptor rich lymphocyte subsets into the circulation with altered function following either exercise or infusion of exogenous catecholamines. Myocardial ischemia, like exercise, is associated with generalized sympathoadrenal activation. To determine whether ischemia influences immunoregulatory cell traffic and function in a manner comparable to beta 2-adrenergic stimulation via isoproterenol, rats underwent thoracotomy with or without coronary ligation. Another group of rats received either isoproterenol (1 mg/kg) or vehicle (10 mM HCl) intraperitoneally. Thoracotomy, regardless of whether or not myocardial ischemia was induced, led to lymphocytosis, reflected primarily by an increase in Thelper (Th) cells and, to a lesser degree, in Tsuppressor/cytotoxic (Ts/c) and natural killer (NK) cells, with a tendency toward an increased Th/Ts/c ratio. To the contrary, isoproterenol injection resulted in a relative lymphopenia characterized by diminished B and Th cell numbers, preserved Ts/c and increased NK cell numbers leading to a significant decrease in the Th/Ts/c ratio. With respect to splenic composition, 60 but not 15 min of myocardial ischemia led to diminished Th and B cell numbers compared to sham operated controls, whereas isoproterenol appeared to stimulate an efflux of only NK cells. Both ischemia and isoproterenol enhanced basal splenocyte function; however, only ischemia significantly boosted splenocyte responsiveness to the mitogen Concanavalin A. Surgically induced myocardial ischemia leads to alterations in immunoregulatory cell migration and function which are distinct from those found with beta 2-adrenergic stimulation via isoproterenol.

Immediate breast reconstruction for stage III breast cancer using transverse rectus abdominis musculocutaneous (TRAM) flap.

BACKGROUND: The management of state III breast cancer is challenging; it often includes multimodal treatment with systemic therapy and/or radiation therapy and surgery. Immediate breast reconstruction has not traditionally been performed in these patients. We review the results of immediate transverse rectus abdominis musculocutaneous (TRAM) flap in 21 patients treated for stage III breast cancer. METHODS: Data have been collected retrospectively on 21 patients diagnosed with stage III breast cancer between 1987 and 1994. All patients had mastectomy and immediate TRAM reconstruction. Thirteen patients received primary systemic therapy, 10 patients received postoperative consolidation radiotherapy to the operative site, and 3 patients received preoperative radiation. RESULTS: Mean follow-up for the group was 26 months. Two patients died with disseminated disease: neither of them developed local disease recurrence in the operative site; 82% of the patients followed for at least two years are free of disease. Sixty-two percent of the patients received preoperative chemotherapy, the remaining patients received postoperative multiagent chemotherapy and/or radiation therapy. Two of the patients received autologous bone marrow transplants after their adjuvant therapy. Ten patients had postoperative radiotherapy for consolidation; three patients received preoperative radiation. CONCLUSIONS: Immediate TRAM reconstruction for stage III breast cancer is not associated with a delay in adjuvant therapy or an increased risk of local relapse. It facilitates wide resection of involved skin without skin grafting. Radiation therapy can be delivered to the reconstructed breast when indicated without difficulty. Breast reconstruction facilitates surgical resection of stage III breast cancer with primary closure and should be considered if the patient desires immediate breast reconstruction.

Early stage melanoma: lymphoscintigraphy, reproducibility of sentinel node detection, and effectiveness of the intraoperative gamma probe.

PURPOSE: To assess the influence of lymphoscintigraphic and intraoperative gamma probe findings on the surgical management of melanoma and to test reproducibility of lymphoscintigraphic findings. MATERIALS AND METHODS: After lymphoscintigraphic identification of the sentinel node, intraoperative gamma probe localization and sentinel lymph node excision were performed in 25 patients. To assess reproducibility, 13 patients underwent lymphoscintigraphy twice within 2-17 days. A modified preparation of technetium-99m sulfur colloid with smaller particles than routinely obtained was injected intradermally around the lesion. Dynamic flow images were obtained at 10 seconds per frame followed by a series of static images obtained every 5 minutes for 30 minutes. RESULTS: A sentinel node was identified in all patients. In eight patients, multiple drainage pathways were seen and surgical management was changed. In 11 of the 13 who underwent lymphoscintigraphy twice, sentinel node identification was reproducible. CONCLUSION: Lymphoscintigraphy is reproducible in detection of the sentinel node and with the surgical probe helps effectively guide surgical management.

Tumor necrosis factor-alpha induces a biphasic effect on myocardial contractility in conscious dogs.

Tumor necrosis factor-alpha (TNF-alpha) likely plays a role in the pathophysiology of myocardial depression observed in septic shock. To evaluate the hemodynamic effects of TNF-alpha in vivo while eliminating the influence of altered sympathetic tone, eight conscious chronically instrumented dogs were studied after pretreatment with propranolol (2 mg/kg) and atropine (2mg). Using three sets of piezoelectric crystals to measure left ventricular (LV) volume and LV manometers to measure pressure, we determined load-independent parameters of LV systolic performance before, during, and after infusion of recombinant human TNF-alpha (rhTNF-alpha, 40 micrograms/kg for 1 hour). Plasma was analyze for epinephrine and norepinephrine. Between 1 and 7 hours of exposure, rhTNF-alpha induced significant increases in circulating catecholamines. Norepinephrine rose from 268.6 +/- 47.2 to 426.2 +/- 87.0 pg/mL (P < .05) at 1 hour and peaked at 921.2 +/- 156.8 pg/mL (P < .001) at 4 hours after initiating rhTNF-alpha treatment. Similarly, epinephrine increased from 130.2 +/- 30.9 to 884.5 +/- 210.2 pg/mL (P < .05) at 1 hour and peaked at 3195.3 +/- 476 pg/mL (P < .001) at 4 hours. Before the surge of circulating catecholamines and despite complete beta adrenergic blockade, rhTNF-alpha induced a 7% to 40% increase in LV contractile performance during the 60-minute infusion. After this initial positive inotropic effect, rhTNF-alpha treatment led to precipitous systolic dysfunction between 2 and 7 hours of exposure; this myocardial depressant effect persisted at 25 hours. LV systolic performance declined to 19% to 35% of baseline values, depending on the specific contractile parameter evaluated. We conclude that rhTNF-alpha affects LV systolic function in a time-dependent biphasic manner. Increases in circulating catecholamines after rhTNF-alpha infusion cannot account for the early improvement in LV systolic performance.

Endoscopic techniques in aesthetic breast surgery. Augmentation, mastectomy, biopsy, capsulotomy, capsulorrhaphy, reduction, mastopexy, and reconstructive techniques.

Endoscopy is a new tool in the armamentarium for surgery of the breast. Endoscopic techniques may offer decreased scarring and morbidity rates for a variety of aesthetic and reconstructive procedures. Whereas initial clinical experiences are encouraging, most endoscopic procedures of the breast remain developmental, both in technique and instrumentation. Additional development, refinement, and experience will be required to define fully the utility of endoscopic techniques.

Prolonged isoproterenol treatment alters immunoregulatory cell traffic and function in the rat.

The mechanisms by which the sympathetic nervous system modulates functional parameters of the immune system have not been fully defined. In vivo, acute and chronic beta 2-adrenergic stimulation have been shown to have dramatic but opposing effects on circulating lymphocyte number and subset distribution in humans. In vitro studies have suggested impairment of numerous lymphocyte effector functions in the presence of catecholamines. To better define the effects of short and long term beta-adrenergic stimulation on lymphocyte migration patterns between circulating and splenic pools, as well as function, we infused rats with either low or high doses of isoproterenol over various time intervals. Specifically, we determined the number and subset composition of peripheral blood and splenic lymphocytes in addition to assessing responsivity to the T cell mitogen concanavalin A and antibody production. As a measure of in vivo lymphocyte proliferation, we also monitored the effect of these infusions on the number of peripheral blood lymphocytes and splenocytes and the splenic weight. Isoproterenol led to dose-dependent, short-lived decrements in mitogen-induced lymphocyte proliferation with concomitant decreases in circulating and splenic lymphocyte number in a subset-specific manner. Analysis of the distribution of circulating and splenic subtypes with isoproterenol treatment suggests definite but limited influences on beta-adrenergic stimulation on immunoregulatory cell traffic. We conclude that beta-adrenergic stimulation in the rat model leads to a dose-dependent, transient effect on lymphocyte proliferation and migration patterns. The relative lack of functional beta-receptors on rat lymphocytes and the propensity for early sustained receptor desensitization on exposure to agonist may account for qualitative differences seen between rats and humans.

Sympathetic and immune interactions during dynamic exercise. Mediation via a beta 2-adrenergic-dependent mechanism.

BACKGROUND: The relation between the sympathetic nervous system and the immune system has not been fully defined. Recent investigations have suggested an adrenergically driven efflux of specific beta 2-receptor-rich lymphocyte subsets into the circulation with either exercise or infusion of exogenous catecholamines. METHODS AND RESULTS: To determine whether acute sympathetic stimulation mediates immunoregulatory cell traffic and function via a beta 2-receptor mechanism, we exercised 20 healthy volunteers before and after 1 week of treatment with either the nonselective beta-antagonist propranolol or the beta 1-selective antagonist metoprolol. Before treatment, exhaustive exercise according to the Bruce protocol led to a marked lymphocytosis. Tsuppressor/cytotoxic (Ts/c) and natural killer cells, subtypes with the largest density of beta-receptors, showed the most pronounced increases after exercise, with less impressive elevations in T(helper) and B cells. With respect to function, exhaustive exercise led to a decrease in concanavalin A-stimulated IL-2 receptor expression and [3H]thymidine incorporation while enhancing natural killer cell activity. One week of propranolol therapy blunted the exercise-induced increases in circulating Ts/c and natural killer subpopulations as well as the previously observed alterations in cellular immune function. Treatment with the beta 1-selective antagonist metoprolol, however, did not impair the influence of exercise on any of the above parameters. CONCLUSIONS: Acute sympathetic stimulation by exhaustive exercise leads to selective release of immunoregulatory cells into the circulation with subsequent alterations in cellular immune function, either secondary to subset changes or as a result of direct catecholamine effects on function. These changes are attenuated by propranolol but not metoprolol, suggesting a beta 2-mediated mechanism.

Melanoma of the external ear.

Management of melanoma of the external ear is controversial. Thirty-one patients treated for this disease were identified at our institution between January 1, 1974 and December 31, 1989. Follow-up was an average of 7.12 years (range 1-15). Local therapy performed included 16 wedge resections, 3 split thickness skin grafts after excision to the perichondrium, 10 partial and 2 total amputations. There were two local recurrences, four metachronous cervical metastases, and four distant metastases. Three elective and five therapeutic neck dissections were performed. Survivors at 1, 5, and 10 years were 93, 77, and 47%, respectively. There was no relationship between DNA ploidy, local surgical therapy, and eventual recurrence. Clinical stage and tumor thickness demonstrated a statistically significant correlation with likelihood of recurrence (P = .02 and .05). There is no evidence that melanoma of the ear has a poorer prognosis or different prognostic factors than melanoma at other cutaneous sites. In selected cases, local disease can be controlled by excision and skin graft rather than the more aggressive current procedures.