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Biomedical subjects

G W Milton

Publications and source records attributed to G W Milton.

At least 19 recordsLinked to original sources
PubMed1991

Experience with 998 cutaneous melanomas of the head and neck over 30 years.

Between 1960 and 1990, a total of 998 patients were treated at the Sydney Melanoma Unit for cutaneous melanoma of the head and neck. There were 595 male and 403 female patients, with a median age of 53 years. The most common primary lesion site was the face (47%), followed by the neck (29%), scalp (14%), and ear (10%). Histologic types were as follows: superficial spreading 30%, nodular melanoma 28%, lentigo maligna melanoma 16%, and other 26%. All patients underwent surgical treatment. Primary closure of wounds was achieved in 52% of patients, and excision margins were 2 cm or less in 45%. A total of 152 patients had therapeutic neck dissections, and 234 had elective neck dissections. The overall local recurrence rate was 13%, and this was significantly influenced by increasing tumor thickness and Clark level. The recurrence rate in the neck after neck dissection was 24%, and the rate of parotid recurrences was 14%. Melanoma-specific survival was 77% at 5 years and 66% at 10 years for the entire group. By univariate analysis, survival varied significantly with age, tumor thickness, ulceration, anatomic sub-site, histologically positive nodes, and the presence of distant metastases. A diagnosis of lentigo maligna melanoma and elective lymph node dissection both appeared to improve survival. With multivariate analysis, all of these factors remained significant prognostic factors except elective node dissection, which lost its beneficial influence.

Female↗
PubMed1991

Immunofluorescent localization of dopamine-like and leucine-enkephalin-like neurons in the supraoesophageal ganglia of the American cockroach, Periplaneta americana.

Leucine-enkephalin- and dopamine-like nerve cells and fibers were localized in the supraoesophageal ganglia (brain) of the American cockroach, Periplaneta americana, using immunofluorescence. The presence of leucine-enkephalin-like material was confirmed using immunoperoxidase staining. Several cells containing leucine-enkephalin-like material were found in the pars lateralis, and nerve fibers belonging to these cells were traced through the brain. Dopamine-like material was detected in deutocerebral neurons as well as the nerve processes arising from these cells which lead into the area of the deutocerebral glomeruli. Specific immunofluorescence was also obtained in the alpha and beta lobes of the corpora pedunculata with both the leucine-enkephalin and dopamine antibodies. However, the fluorescent banding pattern observed in both lobes was distinctly different with the two antibodies. No specific fluorescence was observed in the stalk or peduncle of the corpora pedunculata with either the leucine-enkephalin or the dopamine antibody. The findings suggest a possible interaction of leucine-enkephalinergic and dopaminergic nerve fibers in the alpha and beta lobes of the cockroach corpora pedunculata.

Animals↗
PubMed1990

The justification for surgical treatment of metastatic melanoma of the gastrointestinal tract.

Fifty-six patients with symptomatic metastatic melanoma of the gastrointestinal tract (GIT) treated surgically at the Sydney Melanoma Unit between 1974 and 1989 were reviewed. The majority of these patients presented with abdominal pain or symptoms of anemia. The small intestine was the site of metastasis in more than 80 per cent. The mean over-all survival time was 11.7 months (range of one to 60 months) after surgical treatment of a first metastasis to the GIT and 3.6 months (range of zero to 12 months) postoperatively for a second GIT metastasis. Forty-four of the patients reported complete relief of their symptoms postoperatively. The results suggest that an aggressive approach to symptomatic GIT metastases from malignant melanoma is justified both to relieve distressing symptoms and to prolong life.

Adolescent↗
PubMed1989

Thin regressing malignant melanoma: significance of concurrent regional lymph node metastases.

We attempted to clarify the prevailing controversy regarding the significance of regression in thin (less than 0.76 mm) primary melanomas. Of 7540 patients with cutaneous melanomas treated at the Sydney Melanoma Unit, 28 first presented with a thin primary lesion and concurrent regional lymph node metastases (stage II). Major differences in tumour histology existed between these patients and stage I patients with thin lesions that subsequently recurred. Regression was present in all 28 lesions in stage II patients. In 61 stage I patients ultimately developing a recurrence, 67% of lesions displayed regression. Significantly, however, in 735 stage I patients ultimately not developing a recurrence, 61% of lesions also displayed regression. Why regression occurs so frequently in thin lesions which never recur is unclear. Our results suggest that the histology of thin primary melanomas may be influenced by the presence or absence of metastases in patients at that time.

Adult↗
PubMed1988

Time and frequency of recurrence of cutaneous stage I malignant melanoma with guidelines for follow-up study.

This study is based upon 3,171 patients with clinical Stage I cutaneous malignant melanoma treated at the Sydney Melanoma Unit (SMU) in Australia. The mean follow-up period was 9.8 years, ranging from 2.5 to 36.2 years. During the course of this follow-up study, recurrence developed in 886 patients. Three factors that predicted both the risk of recurrence and the disease-free interval were determined. These were thickness of tumor, the first definitive surgical treatment (whether or not the patient underwent elective dissection of lymph nodes) and the ulcerative state of the primary tumor. Follow-up schedules were designed taking all three of the factors into consideration. The schedules so derived reflected both the risk of recurrence and its alteration with time. It will obviously be necessary, however, to modify the frequency of follow-up visits according to the institutional resources available and the specific wishes of the patient. Annual review for an indefinite period for all patients with melanoma is recommended to detect both additional cancers and late recurrences.

Follow-Up Studies↗
PubMed1987

Thin malignant melanomas and recurrence potential.

Of 846 patients with stage I malignant melanoma that was less than 0.76-mm thick who were followed up for two to 31 years, 61 (7.2%) developed a recurrence. For those patients who did not initially undergo an elective lymph node dissection, the majority of first recurrences were at regional lymph nodes. Attempts have been made to identify those patients at risk of relapsing. Axial lesions, particularly those on the scalp, had the highest recurrence rate, with 15% of all thin scalp lesions recurring compared with only 4% of all thin extremity lesions. Three histological features proved to be useful prognostic indicators when analyzed by single-factor analysis. Evidence of ulceration in the primary lesion increased the recurrence rate from 6.7% to 26.1%. While only 4.3% of lesions displaying low mitotic activity recurred, this rate rose to 23.8% for those lesions of a high mitotic grade. Only 5% of Clark's level II lesions recurred, compared with about 12% of lesions at either level III or IV. Evidence of regression in thin lesions had no deleterious effect on prognosis. This study defines a small subset of patients who may benefit from elective lymph node dissection.

Adult↗
PubMed1987

Effects of exposure to ultraviolet light on epidermal Langerhans cells and melanocytes in Australians of aboriginal, Asian and Celtic descent.

The effects of 3 daily, 7-min exposures to artificial ultraviolet light (UVL), designed to simulate natural sunlight, on epidermal Langerhans cells (LC) and melanocytes were studied in 17 healthy Australian volunteers of differing skin pigmentation. Six were of Celtic, 6 of Asian and 5 of Aboriginal descent. LC were visualized using the immunofluorescence method for HLA-DR and T6 antigens, and the histochemical method for ATPase. UVL induced a transient reduction in the LC population density and an increase in the number of melanocytes in all subject groups. The reduction in number of immunocompetent LC or the disruption of their surface markers was greatest in the Celtic subjects, who had the fairest skin, and least in the Aboriginal and Asian subjects, who had the darkest skin. However, neither the inherently dark skin pigmentation nor the UVL-induced increase in pigmentation were sufficient to prevent the depletion of immunocompetent epidermal LC. Non-dendritic, rounded cells and very large dendritic, non-LC, which were present in the epidermis of some subjects, were stimulated to increase in number by exposure to UVL. The identity and function of these cells is uncertain and they require further investigation.

Adult↗
PubMed1986

Comparison of two methods of treating primary malignant melanomas Clark IV and V, thickness 1.5 mm and greater, localized on the extremities. Wide surgical excision with and without adjuvant regional perfusion.

A comparative retrospective study of patients with primary malignant melanomas of the extremities, Clark level IV/V and tumor thickness greater than or equal to 1.5 mm, was performed in Sydney (Australia) and Groningen (The Netherlands). The efficacy of wide local excision combined with adjuvant regional perfusion (Groningen) was compared with that of wide surgical excision only (Sydney). Patients were classified by sex and tumor location. There were only sufficient numbers of female patients with a tumor of the lower extremity available for this comparative study. All patients were stage I and none received prophylactic lymph node dissection. Age, tumor location, tumor thickness, depth of infiltration and ulceration were taken into account and the factors studied within this group were 10-year disease-free rate, 10-year survival rate, and local and regional recurrences. Women with a melanoma of the leg (excluding the foot) who had been treated by excision and adjuvant regional perfusion, had a significantly better 10-year disease-free rate (P less than 0.0005), a significantly higher 10-year survival rate (0.010 less than P less than 0.025) and significantly fewer local/regional recurrences (P less than 0.0005) than women treated by wide local excision only. For tumors of the foot, however, no significant differences in 10-year disease-free rate, 10-year survival rate or local/regional recurrences were observed after perfusion.

Adult↗
PubMed1986

Comparative study on the effects of recombinant alpha-2 interferon on immune function in patients with disseminated melanoma.

Fifteen patients with disseminated melanoma were treated by intravenous administration of recombinant alpha-2 interferon (rIFN-alpha 2) on 5 consecutive days every 2 weeks. Immunological studies on approximately 50% of the patients revealed no significant changes in lymphocyte numbers or T-cell subsets. Natural killer (NK) activity against the K562 target cell and a melanoma cell was increased in the first treatment cycle, but in subsequent treatment cycles it tended to decrease against the melanoma cell and to show either no change or moderate increases against the K562 target cell. Interleukin-2 (IL-2) production from mitogen-stimulated lymphocytes was decreased in most patients in each treatment cycle. This also applied to immunoglobulin production in vitro from pokeweed mitogen (PWM)-stimulated B and T cells. The latter was not due to the induction of radiation-sensitive suppressor T cells and may reflect effects on B cells or helper T cells. The repeated inhibition of IL-2 production with each cycle of treatment and the decrease in NK activity against the melanoma target cells after the first treatment cycle contrasted with the return to at or above pretreatment values of these tests when rIFN-alpha A was given intramuscularly on an alternate-day basis. It is suggested that these effects may be due to the relatively greater increase in endogenous cortisol production at the beginning of each treatment cycle in patients given rIFN-alpha 2 intravenously compared to that observed in patients treated with rIFN-alpha A on alternate days intramuscularly. Immunosuppression resulting from the increase in cortisol production may be one of the factors accounting for the low tumor response rate of patients in this study and may emphasize the possible importance of the schedule of rIFN-alpha administration for obtaining optimal antitumor responses.

Adult↗
PubMed1986

Effects of sunlight exposure on Langerhans cells and melanocytes in human epidermis.

The effects of 12 daily, half-hour exposures to sunlight on epidermal Langerhans cells (LC), and melanocytes were studied in 31 healthy volunteers. Nineteen were of Celtic and 12 of mixed European descent. Sunlight appeared to have both a direct, transient, detrimental effect and an indirect stimulating effect on the LC, and a direct and an indirect stimulating effect on the melanocytes. The mixed Europeans had a somewhat greater increase in the melanocyte population density following exposure to sunlight than the Celts. However, the number of LC fell following sunlight exposure regardless of the melanocyte response. Thus the melanocytes did not appear to provide the LC with immediate protection from ultraviolet light.

Adult↗
PubMed1985

The influence of surgical margins and prognostic factors predicting the risk of local recurrence in 3445 patients with primary cutaneous melanoma.

Risk factors associated with local recurrences were analyzed from a series of 3445 clinical Stage I melanoma patients. In single-factor analysis, tumor thickness, ulceration, and increasing age were highly significantly predictive of recurrence (p less than 0.00001). After 5 years of follow-up, local recurrence rates were 0.2% for tumors less than 0.76 mm thick, 2.1% for tumors 0.76 to 1.49 mm thick, 6.4% for tumors 1.5 to 3.99 mm thick, and 13.2% for tumors 4.0 mm or greater in thickness. Ulcerated melanomas recurred more often than nonulcerated lesions (11.5% versus 1.9%). When analyzed as a continuous variable, increasing age increased the risk of local failure. In multifactorial analysis, all of these three factors remained independently predictive of local recurrence. Recurrences were more common with nodular melanomas (5.6%) compared to superficial spreading (2.5%) or lentigo maligna melanoma (2.5%), but this difference did not reach statistical significance (P = 0.115). Lower extremity (4.7%) and head and neck lesions (4.4%) recurred more frequently than upper extremity (1.6%) or trunk (1.2%) melanomas (P = 0.0217). The highest recurrence rates were observed in patients with melanomas located on the foot (11.6%) and hand (11.1%). The safety of conservative margins for the excision of low-risk melanomas was demonstrated in a review of 1151 consecutive patients with melanomas less than 1 mm thick where only one local recurrence was observed. Sixty-two percent of these patients had resection margins of 2 cm or less. In 95 patients local recurrence developed as the first site of relapse and were treated with surgical excision. The median survival for this group was 3 years, whereas 20% of this group survived 10 years. These data demonstrate that: (1) the risk of local recurrence rises with increasing tumor thickness, presence of ulceration, and age; (2) melanomas less than 1 mm thick have a very low local recurrence rate, even when excised with margins of 2 cm or less; and (3) local recurrence is a poor prognostic sign because regional and systemic metastases subsequently develop in many patients.

Humans↗
PubMed1985

Late relapse from cutaneous stage I malignant melanoma.

In 1,283 patients with cutaneous stage I malignant melanoma who had ten or more years of follow-up, the incidence of late recurrence (first evidence of metastases occurring ten or more years after melanoma diagnosis) was 2.7%. None of the factors of prognostic importance (anatomic site, tumor thickness, ulcerative state of primary lesion, or initial surgical treatment) proved useful in predicting those patients with late recurrence. There was no sex or age difference in either incidence of late recurrence or prognosis subsequent to recurrence. Prognosis subsequent to late recurrence depended on the site of the recurrence. Survival after distant metastases became evident was extremely short. However, in the majority (53%) of patients, late recurrence was local and survival subsequent to treatment of these metastases was often protracted, emphasizing the importance of long-term follow-up in all patients with cutaneous melanoma.

Adult↗
PubMed1985

Effects of recombinant leukocyte interferon (rIFN-alpha A) on tumour growth and immune responses in patients with metastatic melanoma.

Studies were initiated to assess the response of patients with disseminated melanoma to recombinant alpha interferon (rIFN-alpha A) and to monitor effects of rIFN-alpha A on several tests of immune function. Twenty patients were treated with rIFN-alpha A given by i.m. injection in escalating doses from 15 to 50 X 10(6) um-2. The responses of two patients were considered unevaluable. Of the remainder there was complete remission of tumour in two and stable disease in two. Subsequent progression of tumour in one of the latter patients coincided with development of antibodies to IFN. Side effects (usually fatigue) were dose rate limiting in 11 patients. Laboratory tests on samples taken 6 hours after rIFN-alpha A indicated a marked lymphopenia and a reduction in natural killer (NK) cell activity particularly against K562 target cells. Longer term changes measured in samples taken 2 days after the previous rIFN-alpha A injections consisted of neutropenia and an increase in the T4/T8 ratio due mainly to a relative increase in OKT4 positive T cells compared to OKT8 positive T cells. NK activity against the K562 target cell increased in most patients during the first week of treatment and then returned to below or near pretreatment levels thereafter against the K562 target cell. This contrasted with NK activity against the melanoma target cell which showed a more gradual increase over the duration of the treatment in 6 patients. The latter correlated with an increase in mitogen stimulated IL 2 production from their blood lymphocytes and may indicate that the cytotoxic activity resulted from lymphokine-activated killer (LAK) cells. These results confirm the activity of rIFN-alpha A against melanoma in certain patients. They suggest that further studies are needed to select patients who may respond to rIFN-alpha A and to optimize treatment regimens. Tests of IL 2 production and LAK activity may assisted in achieving these objectives.

Adult↗