Pulmonary hypertension in thalassaemia major patients with normal left ventricular systolic function.

Pulmonary hypertension is common in adults with thalassaemia and other haemolytic anaemias. It was hypothesised that regular transfusions in thalassaemia major should both decrease the chronic haemolytic rate and be protective from pulmonary hypertension (PHT). To reduce the contribution of existing cardiac disease to PHT, the subjects were limited to patients with normal left ventricular shortening fractions. Associations with multiple laboratory markers of haemolysis, serum ferritin levels, chest X-rays findings and splenectomy status were also considered. We found no biochemical, transfusional, or clinical (except gender) differences in transfused thalassaemia patients with or without pulmonary hyper tension.

Major changes in sickle cell disease.

Clinical, molecular, and genetic advances have revealed new pathophysiologic insights and treatments for the growing number of recognized hematologic and nonhematologic abnormalities in sickle cell disease. Treatment targets of cellular dehydration, sickle hemoglobin concentrations, endothelial dysfunction, and abnormal coagulation regulation have been validated as potential therapy. New uses for transfusion therapy hold the promise of decreased major symptoms of acute chest syndrome, stroke, and severe pain crises, but at the expense of increased risk for transfusion reactions, infections, and iron overload. Accumulated experience with autologous, chimeric, and stem cell bone marrow transplantation holds promise for a small percentage of patients with disease. Patient selection, suitable donors, and early mortality are still limiting factors. Genetic manipulation, which offers hope for ameliorating the disease in a larger percentage of patients, is progressing slowly. Combination and staged therapies will be developed and matched to the severity and progression of the patient's disease. Strategies for prevention of major organ damage to the brain, heart, lungs, and kidneys will be prospectively evaluated and refined.

Regression in thin malignant melanoma. Microscopic diagnosis and prognostic importance.

Forty-eight malignant melanomas of the extremities, 1 mm or less in maximal thickness, were studied to better define microscopic criteria of regression in thin melanomas. Eleven tumors (23%) exhibited definite regression in the form of one or more segmental areas (defects) where the invasive component was replaced by mononuclear cell infiltrate and fibrosis. Thirteen other tumors (27%) had diffuse, nonsegmental changes classified as probable regression. Nineteen lesions (40%) lacked regression, although 14 of these contained focal evidence of host response. Five melanomas (17% of lesions less than 0.75 mm thick) were equivocal for regression. There were no recurrences or metastases. The histologic diagnosis of regression in thin melanomas requires subjective judgments, but segmental defects represent a potentially reproducible criterion. Their width can be measured, and the proportion of the melanoma that has undergone regression can be estimated. The preponderance of data from the literature, supported by this study, indicates that regression has no prognostic importance in the vast majority of thin melanomas. There are observations, however, to suggest that in rare cases, regression may negate the prognostic value of microstaging of a thin melanoma. To date, the type and extent of such regressive changes have not been adequately defined.

Thin (less than or equal to 1 mm) melanomas of the extremities are biologically favorable lesions not influenced by regression.

Although a thickness of less than or equal to 0.76 mm has been used to define biologically favorable (thin) melanoma, there is evidence that 1 mm may be a reasonable cutoff to categorize favorable extremity melanomas. This is tempered, however, by the claim that histologic regression in thin melanomas is associated with an increased metastatic rate. We have therefore addressed the following questions: Is 1 mm an appropriate cutoff point to define thin melanoma on the extremities? Does regression in a thin lesion truly signify a poor prognosis? Is the width of excision (narrow vs. wide) related to recurrence rates in these lesions? To address these issues we reviewed 48 patients with extremity melanomas, less than or equal to 1 mm in maximum thickness, treated at this institution during a 20-year period. Pathologic features included histologic type: superficial spreading (90%), nodular (6%), and not classified (4%); thickness: less than 0.76 mm (61%) and 0.76 to 1 mm (39%); and Clark's level: II (33%), III (63%), and IV (4%). A moderate or marked lymphoid infiltrate occurred in 75%, and histologic tumor regression was found in 50%. The median margin of excision, as stated by the surgeon, was 4 cm. The median margin measured by the pathologist in unfixed specimens was 3.5 cm. Although 13% had atypical melanocytic hyperplasia in the initial excisional biopsy margin, all reexcisions were clear. Of 21 patients having node dissections, none had nodal metastases. There were no recurrences or deaths due to melanoma (median follow-up: 90 months). We conclude that melanomas less than or equal to 1 mm in thickness on the extremities can be defined as biologically highly favorable, "thin" lesions. Foci of regression do not alter their behavior. Their favorable prognosis justifies conservative excision in most cases.