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W J Mooi

Publications and source records attributed to W J Mooi.

At least 37 records · Page 2Linked to original sources

Micro-anatomy related antigen expression in melanocytic lesions.

The in situ expression of antigens associated with melanosomes (gp-100), pigmentation (PAA), tyrosinase (TRP-1), melanoma (MAA-1/MAA-2), and HLA-DR was investigated immunohistochemically in frozen archival specimens of common acquired melanocytic naevi, in dysplastic melanocytic naevi, and in lymph node metastases of melanoma. Expression of these antigens was also studied in established cultured normal human melanocytes, naevus-derived melanocytes and melanoma cell lines of varying metastatic potential, by immunohistochemistry and flow cytometry. Compared with normal melanocytes, melanocytic naevi exhibited increased expression of gp-100, PAA, and TRP-1 in the lesional cells at or very near the dermo-epidermal junction, but with diminishing expression towards the intra-dermal base of the lesions. In contrast, expression of MAA-1 and MAA-2 was observed in melanocytes throughout the dermal part of the naevi. Melanocytes located at the basal layer of the epidermis were positive only for gp-100, PAA, and TRP-1 antigens. Dysplastic melanocytic naevi showed staining of gp-100, PAA, TRP-1, HLA-DR, MAA-1, and MAA-2 of junctional lesional melanocytes, but less intense than that of common acquired naevi. These antigens were not detectable in the dermal part of the dysplastic naevi. Expression of these antigens in lymph node metastases of melanoma was either positive or negative. Similar results regarding antigen expression were observed in all cultured melanocytic cells, both by immunohistochemistry and by flow cytometry. The present data suggest that analysis of these antigens may contribute to the discrimination of common acquired melanocytic naevi from their dysplastic counterparts. Furthermore, variations in the levels of expression in naevi may be consistently related to the micro-anatomy of the lesions, indicating that the micro-environment may have an influence on the expression levels of these antigens in different lesional melanocytes.

Antigens, Neoplasm↗

Enhanced expression of vascular endothelial growth factor in pulmonary plexogenic arteriopathy due to congenital heart disease.

Congenital heart disease (CHD) leading to increased pulmonary blood pressure and flow is an important cause of pulmonary plexogenic arteriopathy (PPA). This type of arteriopathy tends to progress to an irreversible stage, hallmarked histologically by the emergence of a number of characteristic lesions, which include concentric laminar intimal proliferation and fibrosis, and plexiform lesions. The pathogenesis of these lesions, which connote a very poor prognosis, is not well understood. Since endothelial cell proliferation has been demonstrated in these lesions, it was hypothesized that vascular endothelial growth factor (VEGF), a key mediator of angiogenesis, might play a role in their pathogenesis. Thirty-nine patients with various types of CHD, who underwent cardiac catheterization and subsequent cardiac surgery, were studied prospectively. On the basis of a detailed assessment of the type of cardiac defect, the haemodynamic abnormalities, and the histopathological features evident from open lung biopsies, taken in all instances, patients were histologically grouped into cases with moderate PPA (n=18), advanced PPA (n=7), pulmonary congestive vasculopathy (PCV, n=5), and controls lacking pulmonary hypertension or increased pulmonary blood flow (n=4). Five patients were excluded from analysis because of inadequate sample size or quality. The presence of VEGF was assessed immunohistochemically using standard procedures and was correlated with haemodynamic and histological data. Immunoreactive VEGF was detected in pulmonary arterial smooth muscle cells and endothelial cells in 13 out of 34 cases and was more frequent and more pronounced in patients with the histological lesions of advanced PPA than in those with moderate PPA (p<0.01). VEGF positivity was particularly prominent in the lesions characteristic of advanced PPA. No difference in VEGF expression was observed between controls, PVC, and moderate PPA cases. Measured haemodynamic parameters did not differ significantly between VEGF-positive and VEGF-negative cases. We conclude that VEGF may play a role in the angioproliferative changes of advanced PPA.

Child↗

MR imaging of clear cell sarcoma (malignant melanoma of the soft parts): a multicenter correlative MRI-pathology study of 21 cases and literature review.

OBJECTIVE: To evaluate MR imaging and pathology findings in order to define the characteristic features of clear cell sarcoma of the soft tissues (malignant melanoma of the soft parts). DESIGN AND PATIENTS: MR examinations of 21 patients with histologically proven clear cell sarcoma of the musculoskeletal system were retrospectively reviewed and assessed for shape, homogeneity, delineation, signal intensities on T1- and T2-weighted images, contrast enhancement, relationship with adjacent fascia or tendon, secondary bone involvement, and intratumoral necrosis. In 19 cases the pathology findings were available for review and for a comparative MR-pathology study. RESULTS: On T1-weighted images, lesions were isointense (n=3), hypointense (n=7) or slightly hyperintense to muscle (n=11). Immunohistochemical examination was performed in 17 patients. All 17 specimens showed positivity for HMB-45 antibody. In nine of 11 lesions with slightly increased signal intensity on T1-weighted images, a correlative MR imaging-pathology study was possible. All nine were positive to HMB-45 antibody. CONCLUSIONS: Clear cell sarcoma of the musculoskeletal system often has a benign-looking appearance on MR images. In up to 52% of patients, this lesion with melanocytic differentiation has slightly increased signal intensity on T1-weighted images compared with muscle. As the presence of this relative higher signal intensity on T1-weighted images is rather specific for tumors displaying melanocytic differentiation, radiologists should familiarize themselves with this rare entity and include it in their differential diagnosis when confronted with a well-defined, homogeneous, strongly enhancing mass with slightly higher signal intensity compared with muscle on native T1-weighted images.

Adolescent↗

Relationship between sphincter morphology on endoanal MRI and histopathological aspects of the external anal sphincter.

Atrophy of the external anal sphincter can be shown only on endoanal magnetic resonance imaging (MRI). Until now no study has compared the morphological endoanal MRI findings with histopathological aspects of the external anal sphincter. The aim of this study was to validate the MRI interpretation of the external anal sphincter using histology as a "gold standard." In this prospective study 25 consecutive unselected women (median age 48 years, range 27-72) with fecal incontinence due to obstetric trauma were assessed preoperatively with endoanal MRI. All patients underwent anterior sphincteroplasty within 6 months of the preoperative assessment. During sphincter repair, a biopsy specimen was taken both from the left and right lateral parts of the external anal sphincter. Interpretation of MRI was performed by one of the radiologists (J.S.), and biopsy specimens were evaluated by the pathologist (W.J.M.). Both were blinded to the interpretation of the other. MRI revealed external anal sphincter atrophy in 9 of the 25 patients (36%). Histopathological investigation confirmed these findings in all but one. In one additional patient atrophy was detected on histological investigation while the morphology of the external anal sphincter was classified as normal on MRI. In detecting sphincter atrophy endoanal MRI showed 89% sensitivity, 94% specificity, 89% positive predictive value, and 94% negative predictive value. MRI correctly identified sphincter morphology in 23 of 25 cases (92%). This study demonstrates that endoanal MRI accurately identifies normal and abnormal external anal sphincter morphology. Endoanal MRI is therefore a valuable preoperative diagnostic tool.

Adult↗

Losses of chromosomes 1p and 3q are early genetic events in the development of sporadic pheochromocytomas.

Despite several loss of heterozygosity studies, a comprehensive genomic survey of pheochromocytomas is still lacking. To identify DNA copy number changes which might be important in tumor development and progression and which may have diagnostic utility, we evaluated genetic aberrations in 29 sporadic adrenal and extra-adrenal pheochromocytomas (19 clinically benign tumors and 10 malignant lesions). Comparative genomic hybridization was performed using directly fluorochrome-conjugated DNA extracted from frozen (16) and paraffin-embedded (13) tumor tissues. The most frequently observed changes were losses of chromosomes 1p11-p32 (86%), 3q (52%), 6q (34%), 3p, 17p (31% each), 11q (28%), and gains of chromosomes 9q (38%) and 17q (31%). No amplification was identified and no difference between adrenal and extra-adrenal tumors was detected. Progression to malignant tumors was strongly associated with deletions of chromosome 6q (60% versus 21% in clinically benign lesions, P = 0.0368) and 17p (50% versus 21%). Fluorescence in situ hybridization confirmed the comparative genomic hybridization data of chromosomes 1p, 3q, and 6q, and revealed aneuploidy in some tumors. Our results suggest that the development of pheochromocytomas is associated with specific genomic aberrations, such as losses of 1p, 3q, and 6q and gains of 9q and 17q. In particular, tumor suppressor genes on chromosomes 1p and 3q may be involved in early tumorigenesis, and deletions of chromosomes 6q and 17p in progression to malignancy.

Adult↗

Remodeling of pulmonary arteries in human congenital diaphragmatic hernia with or without extracorporeal membrane oxygenation.

PURPOSE: The aim of this study was to describe in detail the perinatal developmental profile of the pulmonary vasculature in congenital diaphragmatic hernia (CDH) and to examine the potential beneficial effects of extracorporeal membrane oxygenation (ECMO) on the vascular morphology. Additionally the authors aimed to identify the differences in pulmonary vascular morphology among CDH cases according to the primary cause of death: either extreme lung hypoplasia (LH) or persistent pulmonary hypertension (PPH). METHODS: The authors studied autopsy sections from 30 high-risk CDH cases with respect to the pulmonary arteries in relation to gestational age (GA) and ECMO treatment. They were grouped into CDH-I: 20 cases with GA greater than 34 weeks who were not subjected to ECMO and CDH-II: 10 cases with GA greater than 34 weeks, who were subjected to ECMO for an average time of 237 hours. Five age-matched neonates who died from placental insufficiency or birth asphyxia without evidence of lung hypoplasia served as controls (CON). Medial and adventitial thicknesses of pulmonary arteries were measured in lung sections stained with Elastic van Gieson by 2 investigators blinded for the clinical data. Immunohistological staining with anti-alpha-smooth muscle actin (alpha-SMA) was performed to confirm the precise location of the arterial media before morphometry. CDH cases were subgrouped and compared according to the primary cause of death. Unpaired Student t test was used for statistics, with significant P value < or =.05. RESULTS: In CDH newborns, a significant increase in medial, adventitial, and total wall thickness was found in pulmonary arteries with an external diameter of less than 200 microm as compared with age-matched controls (P<.004, .0001, and .0009, respectively). ECMO-treated CDH newborns showed a significantly thinner arterial adventitia than CDH patients who did not receive this treatment (P<.0001), approaching normal values. However, the medial thickness remained increased. Morphometrically, no significant differences in CDH cases between patients dying of PPH or severe LH could be determined. CONCLUSIONS: (1) In CDH, there is failure of the normal arterial remodeling processes occurring in the perinatal period. (2) Pulmonary vascular morphology in CDH does not differ between the groups with lung hypoplasia or persistent pulmonary hypertension as primary cause of death. (3) Adventitial thinning of these arteries might be one of the mechanisms by which ECMO alters PPH in CDH cases.

Extracorporeal Membrane Oxygenation↗

Inflammatory pseudotumor of the fossa pterygopalatina: diagnosis and treatment.

Pseudotumor is a term used to describe a space-occupying inflammatory lesion of unknown etiology that clinically simulates a neoplastic process. Pseudotumors of the fossa pterygopalatina and fossa infratemporalis are very rare. In this paper, we describe a patient who developed a pseudotumor in the left fossa pterygopalatina, secondary to an unclassified autoimmune disease, which caused progressive left-sided facialdynia and swelling. The tumor was detected with somatostatin receptor scintigraphy. The lesion was refractory to steroids, also in combination with azathioprine, as well as to surgical intervention. An excellent clinical response was observed after cyclosporine was added. This case is presented here in order to draw attention to the use of somatostatin receptor scintigraphy as a diagnostic tool in visualizing pseudotumors and to document a case that responded excellently to treatment with a combination of low-dose cyclosporine and steroids.

Bone Diseases↗

Clear cell sarcoma (malignant melanoma) of soft parts: A clinicopathologic study of 30 cases.

BACKGROUND: Clear cell sarcoma, or malignant melanoma of soft parts, is a rare tumor that occurs predominantly in the extremities of young adults. The importance of surgery has been well established. However, the role of adjuvant radiotherapy has yet to be determined. METHODS: Thirty cases of clear cell sarcoma that occurred in The Netherlands between 1978 and 1992 were studied retrospectively. Follow-up information on 29 patients was obtained; the follow-up period ranged from 4 to 241 months, with a median of 30 months. All tumors occurred in the extremities, mostly of young adults. RESULTS: The 5-year survival rate of the 29 patients was 54%. For the 23 patients who presented with localized disease, the 5-year survival and 5-year disease free survival were 65%. Eleven of these patients remained disease free after resection of the primary tumor. Patients with a tumor 2 cm or smaller had better survival than patients with a larger but still-localized tumor (P = 0.009). Adjuvant radiotherapy to the primary tumor site also seemed to have a beneficial effect on survival (P = 0.036). All patients with a local recurrence (8 patients) or regional lymph node metastasis (13 patients) developed distant metastasis. Fourteen of 18 patients with distant spread died of their disease; 2 patients were still alive with disease and 2 patients were disease free, 7 and 32 months after resection of solitary distant metastases. CONCLUSIONS: Early diagnosis and initial radical surgery are essential for a favorable outcome. Once regional lymph node metastasis or hematogenous dissemination has occurred, the prognosis is dismal.

Adolescent↗

Expression patterns of heat shock proteins in lungs of neonates with congenital diaphragmatic hernia.

BACKGROUND: Congenital diaphragmatic hernia (CDH) is associated in many cases with pulmonary hypertension. Currently, extracorporeal membrane oxygenation (ECMO) is one of the possible modalities of treatment of pulmonary hypertension and prevention of parenchymal lung injury in neonates with CDH. HYPOTHESIS: Molecular stress is present in the lungs of neonates with CDH. To test this hypothesis, we investigate the expression pattern of stress genes (heat shock proteins [HSPs] 27 and 70) in lungs of patients with CDH who have pulmonary hypertension, and evaluate the influence of ECMO on the expression levels of these genes to understand the underlying molecular mechanisms. DESIGN: Paraffin-embedded lung autopsy specimens from patients with CDH and lung hypoplasia who either did or did not receive ECMO treatment and age-matched controls were immunostained by means of monoclonal antihuman antibodies against HSP 70 and HSP 27, with the streptavidin-biotin complex method. SETTING: Level III academic children's hospital. MAIN OUTCOME MEASURES: Expression levels of both HSP 27 and HSP 70 were semiquantitatively evaluated in bronchial epithelium, as well as in medial smooth muscle cells (SMCs) and endothelium of large and small pulmonary arteries, by means of a score ranging from 0 to 4. Statistical analysis of the data was performed with the nonparametric Mann-Whitney test, with significant probability value at P < or = .05. RESULTS: For HSP 70, the most pronounced immunoreactivity was observed in the bronchial epithelium, followed by the medial SMCs of small arteries (of external diameter < 200 microm). The overall expression was significantly higher in patients with CDH than controls in bronchi as well as in pulmonary arteries. For HSP 27, intense expression was found in medial SMCs, followed by the bronchial epithelium in controls, with significantly increased expression in medial SMCs of large and small arteries in patients with CDH. Treatment with ECMO was associated with significantly reduced expression levels of HSP 70 in medial SMCs of both large and small arteries, whereas HSP 27 expression levels were decreased only in small arteries. In addition, the expression levels of both HSPs were significantly lower in endothelium of small arteries. CONCLUSIONS: Increased expression of HSPs in CDH points to a condition of pulmonary stress. This pulmonary stress appears to be partially ameliorated by ECMO treatment. This may point to one of the mechanisms by which ECMO alleviates pulmonary hypertension associated with CDH.

HSP70 Heat-Shock Proteins↗

Impaired structural remodelling of pulmonary arteries in newborns with congenital diaphragmatic hernia: a histological study of 29 cases.

Congenital diaphragmatic hernia (CDH) is associated in many cases with lung hypoplasia and pulmonary hypertension (PH). The pathogenetic mechanisms underlying the pulmonary hypertension in CDH are not completely understood. In order to alleviate the pulmonary hypertension, new therapeutic modalities have been introduced including extracorporeal membrane oxygenation (ECMO). This paper reports a study of the histology of the lungs of 29 CDH autopsy cases, with special attention to the pulmonary arteries, and relating the findings to gestational age and ECMO treatment. Formalin-fixed and paraffin-embedded specimens were stained with haematoxylin and eosin (H&E) and elastic van Gieson (EvG) stains, followed by morphometric measurements of the arterial media and adventitia. As expected, there was a significant decrease in adventitial percentage and total wall thicknesses of small pulmonary arteries with an external diameter less than or equal to 150 microm in term control newborns compared with pre-term controls (p=0.0004 and 0.05). In CDH newborns, all the measured values of the arterial wall remained significantly higher. The increase of adventitial thickness also affected the supernumerary arteries in CDH neonates. CDH newborns subjected to ECMO treatment showed a significantly thinner arterial adventitia than CDH cases who did not receive ECMO (p=0.0001), the former approaching normal values. These results indicate that in CDH, there is failure of the normal arterial remodelling processes occurring in the perinatal period. The adventitial thickening, which has been reported previously in term CDH patients only, was related in the present study to differences in gestational ages. This appears to be partially reversed by ECMO treatment, thus constituting one of the mechanisms by which ECMO treatment aids in alleviating the associated PH in CDH newborns.

Actins↗

Pathological features of glycogen storage disease type II highlighted in the knockout mouse model.

Glycogen storage disease type II (GSDII; Pompe's disease) is an autosomal recessive disease caused by lysosomal alpha-glucosidase deficiency. Skeletal muscle weakness is the most conspicuous clinical symptom of patients suffering from GSDII and skeletal muscle also is prominently involved in the knockout mouse model of this disease. Thus far, however, little detailed information has been published on the pathological changes in other mouse tissues. This paper aims to provide these data and gives a record of the clinical course of the mouse model over a 2-year period. Four-month-old affected mice perform worse in a running wheel than their unaffected littermates, but do not yet display other clear signs of disease. The lysosomal glycogen storage, already evident at birth, becomes more severe in time, leading to muscle wasting by 9-10 months of age and then limb girdle weakness and kyphosis. The disease does not markedly shorten the animal's life span despite the serious tissue pathology, which is not limited to heart and skeletal muscle, but is also seen in the smooth muscle of blood vessels and of the respiratory, digestive, and urogenital tracts. In addition, the mice have lysosomal glycogen storage in the liver, kidney, spleen, and salivary gland; in Schwann cells of the peripheral nerves, and in a subset of neurons in the central nervous system. By pathological criteria, the knockout mouse model parallels the human infantile form of GSDII and is attractive for studying the possible reversal of tissue pathology and symptomatology under different therapeutic regimes.

Animals↗

Gastroesophageal reflux and Barrett's esophagus in adults born with esophageal atresia.

OBJECTIVE: Postoperative morbidity after correction of esophageal atresia is partly determined by gastroesophageal reflux disease, which has been proven to affect from one-half to two-thirds of patients during childhood. We conducted a follow-up study to test our hypothesis that, if former patients still show gastroesophageal reflux at adult age, they are at high risk for developing Barrett's esophagus, which is considered to be premalignant. METHODS: Of 69 patients born between 1971 and 1978, all having undergone a primary anastomosis, 24 had died, five of them because of aspiration. Of the 45 survivors, 39 could be traced; they all completed a questionnaire inquiring after symptoms related to the esophagus. Of these patients, 34 underwent an additional esophagogastrocopy. RESULTS: Only nine of the 39 patients had no symptoms at all; 30 had mild to severe dysphagia symptoms, and 13 had mild to severe reflux symptoms. Esophagogastrocopy in 34 patients revealed that the anastomosis was still recognizable in all cases, but stenoses were not found. Six patients showed a small hiatal hernia, and one a large one. The incidences of reflux symptoms (13/39, p < 0.01), reflux esophagitis (9/34, p < 0.01) and Barrett's esophagus (2/34, p < 0.001) were significantly higher than in the normal population. CONCLUSIONS: This group seems to be at risk for developing Barrett's esophagus. As this is the first follow-up study of a consecutive group of adult esophageal atresia patients, we think it is advisable to perform an esophagogastroscopy in all patients at adulthood until more long term follow-up data are available.

Adolescent↗

Enhanced expression of vascular endothelial growth factor in lungs of newborn infants with congenital diaphragmatic hernia and pulmonary hypertension.

BACKGROUND: Pulmonary hypoplasia accompanied by pulmonary hypertension resistant to treatment is an important feature of congenital diaphragmatic hernia (CDH). The pathogenesis of the pulmonary vascular abnormalities in CDH remains to be elucidated at the molecular level. Vascular endothelial growth factor (VEGF), an endothelial cell specific mitogen, is known to play a role in pulmonary angiogenesis and vascular remodelling but there are no data on VEGF expression in patients with CDH. METHODS: Necroscopic lung specimens from 21 patients with CDH with lung hypoplasia and from seven age matched control newborn infants without lung hypoplasia were processed for immunohistochemical analysis using affinity purified anti-human VEGF antibodies. All the cases of CDH had pulmonary hypoplasia, indicated by a lung/body weight index of </=0.012, and pulmonary hypertension indicated by repeated cardiac ultrasonography. Cellular localisation of VEGF was semiquantitatively analysed using a staining score ranging from 0 (no staining) to 4 (very strong staining). RESULTS: Significantly raised levels of VEGF immunoreactivity were observed in lung specimens from cases of CDH compared with controls. VEGF was detected mainly in the bronchial epithelium and the medial smooth muscle cells of large (>200 microm) and small (<200 microm) pulmonary arteries, the most intense staining being in the medial smooth muscle cells of the small pulmonary arteries. Endothelial cells were positive for VEGF staining in patients with CDH but not in controls. CONCLUSIONS: This is the first study of VEGF expression in newborn infants with CDH. Increased levels of VEGF, especially in the small, pressure regulating pulmonary arteries, point to a potential role in vascular remodelling. This may reflect an unsuccessful attempt by the developing fetus to increase the pulmonary vascular bed in the hypoplastic lungs to alleviate the associated pulmonary hypertension.

Case-Control Studies↗

Determination of colony numbers in pig epidermis as an estimate for radiosensitivity. A rapid assay based on in vitro BrdU-labelling.

A rapid assay has been developed for the quantitation of colonies arising from surviving clonogenic cells in pig epidermis after irradiation. The number of surviving clonogenic cells per unit area was related to the epidermal in vivo response of moist desquamation. After irradiation with single doses, ranging from 20 to 36 Gy, skin biopsies were taken and incubated in dispase for enzymatic separation of the epidermis and dermis. Full thickness epidermal sheets were labelled with bromodeoxyuridine (BrdU) in vitro. Proliferating cells were visualized using standard immunohistochemical procedures. Cell groups containing > or = 16 cells were counted as colonies. These colonies were first seen on day 14/15 after irradiation. The number of colonies per cm2, as a function of skin surface dose, yielded a cell survival curve with a D0 (+/- SE) of 3.87 +/- 0.57 Gy. The ED50 for the epidermal in vivo reaction of moist desquamation corresponded with a colony density of 2.7 colonies per cm2. After higher doses, abundant smaller colonies of 4-8 BrdU-positive cells were seen and these were more radioresistant, as represented by higher D0 values.

Animals↗

Clear cell sarcoma of tendons and aponeuroses (malignant melanoma of soft parts) and cutaneous melanoma: exploring the histogenetic relationship between these two clinicopathological entities.

Clear cell sarcoma of tendons and aponeuroses (CCS) has come to be recognized as a distinct histopathological entity in the last three to four decades. It shares a number of histological and ultrastructural features with cutaneous melanoma (MM), occasionally creating diagnostic difficulties with metastatic melanoma in the absence of a known primary cutaneous tumour. At a genetic level, a t(12;22) has been identified in 60-75 per cent of cases of CCS using karyotype analysis, while MM demonstrates a broad range of genetic alterations, most commonly appearing to involve chromosomes 1, 5, and 6. Although these two tumour types share many common microscopic, and thus histogenetic, similarities, the genotypic evidence supports two distinct histopathological entities.

Adenocarcinoma, Clear Cell↗

Cervical lymph-node metastasis from cutaneous melanoma of the head and neck: a search for prognostic factors.

AIMS: To identify prognostic factors determining overall survival in patients with surgically treated neck node metastases of cutaneous melanoma. METHODS: A retrospective study was carried out in 70 patients who were surgically treated with curative intent for cervical lymph-node metastasis from cutaneous head and neck melanoma at our institution between 1960 and 1986. RESULTS: Median follow-up of the 14 patients still alive was 10 years. Of the 70 patients, 64 underwent a radical neck dissection, four a modified radical neck dissection and two a postero-lateral neck dissection. In 63 patients, the node dissection was for palpable involved nodes and in seven for microscopic disease. Survivals after 5 and 10 years were 23% (SE 5%) and 20% (SE 5%), respectively. Five-year survival was 62% (SE 17%) for patients with a melanoma less than 1.5 mm thick and 16% for lesions thicker than 1.5 mm. A regional recurrence in the neck occurred in 16 (23%) patients, of whom 14 were found also to have distant metastases. All patients with regional recurrence died from disease. CONCLUSIONS: Of the 15 patient-, tumour- and treatment-related factors tested, only the Breslow thickness of the primary lesion carried prognostic significance for survival (Bonferroni corrected P-value: 0.026).

Adolescent↗