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Biomedical subjects

H M Shaw

Publications and source records attributed to H M Shaw.

At least 55 records · Page 3Linked to original sources
PubMed1991

Hereditary melanoma in Australia. Variable association with dysplastic nevi and absence of genetic linkage to chromosome 1p.

Hereditary cutaneous malignant melanoma in association with the presence of multiple precursor lesions termed the dysplastic nevus syndrome (DNS) has been reported to display autosomal dominant inheritance with high penetrance. The gene for this disease was recently assigned to the distal short arm of chromosome 1 on chromosomal band 1p36, 7.6 centimorgans distal to the locus for the pronatrodilatin (PND) gene. We assessed 119 family members of eight newly described Australian families, 30 of whom had cutaneous malignant melanoma. Only eight of these affected individuals also had dysplastic nevi (DN). An additional 15 family members had DN alone. Pedigrees fell into three groups: 1) hereditary melanoma alone with no associated DN, 2) hereditary melanoma with occasional DN-affected individuals, and 3) hereditary melanoma with DN. All families displayed an autosomal dominant pattern of inheritance. An analysis of the cosegregation of the cutaneous malignant melanoma/DN trait with eight polymorphic DNA markers on the short arm of chromosome 1, including the distally located DNA markers D1S47 and PND yielded a strongly negative probability of linkage. The putative gene for susceptibility to melanoma in these families was effectively excluded from this region of the short arm of chromosome 1. No evidence for linkage was found at any of the other chromosome 1 markers examined. These findings suggest that hereditary melanoma is heterogeneous in relation to the genetic basis and its association with the DNS.

Adolescent↗
PubMed1991

Patients with thick melanomas surviving at least 10 years: histological, cytometric and HLA analyses.

Survival for melanoma patients with thick primary tumours is notoriously short. A small number of patients with tumours greater than 5.5 mm thick do, however, have protracted survival intervals. Attempts were made to account for this phenomenon by means of histological, cytometric and HLA serotyping analyses. Patients with thick lesions surviving more than 10 years were matched--by sex, age, anatomical site of primary lesion, stage of disease and, whenever possible, by initial surgical therapy--to patients dying of their disease within 5 years. This case-control study on 13 long-term survivors and 13 short-term survivors did not show that any of the following attributes of the primary lesion were useful in predicting survival: Clark's level of invasion, ulceration, mitotic rate, host inflammatory response, tumour regression, tumour necrosis, vascular invasion, satellitosis, radial or vertical growth phase, predominant cell type, histogenetic type, borders, DNA quantification and cytomorphometry. HLA serotyping of long-term survivors showed an excess of antigen DQw1 compared with the general population, although this excess was not statistically significant.

Adult↗
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↗
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

Harvey-ras oncogene restriction fragment alleles in familial melanoma kindreds.

Unique and uncommon BamHI allelic restriction fragments of the Ha-ras locus have been reported in the genomes of patients with cancer and of three affected members of a familial melanoma kindred (Krontiris et al., 1986). Analysis of the BamHI and Msp/HpaII restriction fragments of peripheral blood leucocyte DNA from the members of two families with hereditary melanoma (HM)/familial dysplastic naevus syndrome (DNS) revealed that the only Ha-ras allele common to four affected members of one kindred and two from a second kindred, was the 6.7kb allele which is found in 66% of the normal population. This allele was found equally in affected and non-affected family members, and in one affected case was inherited from an unaffected homozygous parent. It was absent in two affected sisters in a third kindred. In the first kindred the karyotype of all three melanoma sufferers was 46XX 9qh+, while six unaffected members had a normal karyotype. BamHI polymorphism of the Ha-ras gene does not identify the affected members in the HM/DNS families studied.

Alleles↗
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↗