Superior survival of young women with malignant melanoma.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to J F Thompson.
Explore the source record for details and available documents.
A cell-free mRNA degradation system consisting of the polysomal and postpolysomal fractions was obtained from cultured soybean cotyledons for studying Bowman-Birk protease inhibitor (BBPI) mRNA stability. This in vitro system reflected the shorter in vivo half-life of BBPI mRNA of cotyledons cultured in basal-medium as compared to cotyledons cultured in methionine-supplemented medium. Most of the BBPI mRNA degradative activity was found to be present in the postpolysomal supernatant fraction. The higher rate of BBPI mRNA degradation in basal medium-cultured cotyledons was due to an increased destabilizing activity specific to BBPI mRNA in the postpolysomal fraction from basal-medium cultured cotyledons. The specificity was absent when purified RNA was used as the substrate. Degradation of the mRNA was not divalent cation-dependent and was inhibited in the presence of higher concentrations of monovalent and divalent cations.
Explore the source record for details and available documents.
The authors conducted a prospective study, with a subsequent review of case-notes and follow-up of patients, to review the results of insertion of gentamicin beads for the prevention and treatment of infection in vascular surgery. In particular, special reference was given to leaving chains of beads permanently implanted in the body. There were thirty-five patients in whom gentamicin beads were used in 62 sites. These were implanted completely in 45, left protruding for removal in 15 and in open wounds in two. Forty-two chains of beads were left permanently implanted, and these patients were followed up for 1-44 months (median 15) later. There was no further infection at 60% of the sites where gentamicin beads were used to treat proven graft sepsis, and 50% of sites in various sinuses. Infection developed at 16% of the sites where gentamicin beads were used prophylactically. Adverse effects were observed in three cases of long-term implantation: one chain of beads caused discomfort that required removal, the skin failed to heal over one chain, and one may possibly have caused a bypass graft to kink and occlude. In conclusion, gentamicin beads are a useful adjunct in the management of vascular graft infection and in prophylaxis for some high risk cases. Chains of beads can be implanted long term with few adverse sequelae.
BACKGROUND: Accurate staging of melanoma patients by sentinel node (SN) biopsy can be achieved only if all SNs draining a given melanoma site are identified and removed for detailed histologic examination. Lymphoscintigraphy with a radiolabeled colloid provides an objective and reliable method of locating SNs and demonstrates that confident prediction of their location is not possible on clinical grounds. STUDY DESIGN: Lymphatic drainage pathways demonstrated by preoperative lymphoscintigraphy for 1,759 patients with primary cutaneous melanomas were reviewed, and locations of SNs in these patients were documented. An SN was defined as any node receiving direct lymphatic drainage from a primary melanoma site. RESULTS: In many instances the cutaneous lymphatic drainage pathways were found to be at variance with longheld concepts of lymphatic anatomy. Several new pathways were identified, draining to SNs in unexpected sites. These included triangular intermuscular space SNs (from upper back and, rarely, upper limb primaries), paraaortic and retroperitoneal SNs (from upper and lower back primaries), and costal margin SNs with onward drainage to internal mammary nodes (from periumbilical primaries). Occasional drainage to node fields on the opposite side of the body was noted from head, neck, and trunk primaries, and drainage to interval nodes (by definition, SNs) outside recognized lymph node fields was also observed. CONCLUSIONS: Knowledge of the possibility of these unusual lymphatic drainage patterns and SN sites should help to ensure the accuracy and completeness of SN identification. Preoperative lymphoscintigraphy to definitively locate SNs is recommended for every patient undergoing an SN biopsy procedure.
BACKGROUND: Melanomas that arise on mucosal surfaces and the glans penis are rare. METHODS: A retrospective study of the Sydney Melanoma Unit experience with 69 patients treated since 1956 for these types of melanomas was undertaken to determine primary lesion site, sex, age at diagnosis, symptoms, clinical stage at first presentation. histopathology, treatment and outcome. RESULTS: Primary lesion sites were: nasal cavity (n = 9), oral cavity (n = 16), vulva/vagina (n = 25), anus/rectum (n = 13) and glans penis (n = 6). At diagnosis, 55 patients had local disease only, eight had regional lymph node metastases and six had widespread disease. Local recurrence as the first sign of relapse developed in 15 of the 55 stage I patients (three-stage system). Prognosis for the entire group was poor, only 10% being disease free 3 years after diagnosis and overall 3- and 5-year actuarial survival being 40% and 23%. respectively. The only statistically significant factor influencing survival was stage of disease at diagnosis (P = 0.002). CONCLUSIONS: Possible reasons for poor survival include: (i) non-specific symptoms resulting in late presentation; (ii) locally advanced disease not being recognized by a clinician as a rare form of melanoma, resulting in a delay in treatment; (iii) anatomical constraints precluding surgery with generous margins and consequently resulting in a high incidence of local recurrence. Also, rich vascularity and multiple lymphatic drainage pathways may mean a predisposition to early dissemination. Prompt diagnosis and referral to a specialist unit for treatment and follow up are essential. Adequate surgery remains the cornerstone of treatment for these types of melanoma until more effective systemic therapies become available.
High-resolution ultrasound was used to determine if it could predict the presence of metastatic disease in 52 patients with melanoma who had developed newly palpable lymph nodes during clinical follow-up. Ultrasound proved accurate in diagnosing the presence of nodal metastases; it had a sensitivity of 94%, a specificity of 87% and an accuracy of 89%. The ultrasound features which together were diagnostic of the presence of nodal metastases were a node thickness greater than two-thirds of the node length and the presence of low-level echoes in the node. When these two features were both present on ultrasound, node metastases were present in every case. Ultrasound can be used to evaluate newly palpable lymph nodes in patients with melanoma. A normal ultrasound finding does not exclude micrometastases, but a lymph node showing the two key ultrasound features aforementioned is highly likely to contain metastatic disease and should be treated accordingly.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
OBJECTIVE: To evaluate the multicenter application of intraoperative lymphatic mapping, sentinel lymphadenectomy, and selective complete lymph node dissection (LM/SL/SCLND) for the management of early-stage melanoma. SUMMARY BACKGROUND DATA: The multidisciplinary technique of LM/SL/SCLND has been widely adopted, but not validated in a multicenter trial. The authors began the international Multicenter Selective Lymphadenectomy Trial (MSLT) 5 years ago to evaluate the survival of patients with early-stage primary melanoma after wide excision alone versus wide excision plus LM/SL/SCLND. This study examined the accuracy of LM/SL/SCLND in the MSLT, using the experience of the organizing center (John Wayne Cancer Institute [JWCI]) as a standard for comparison. METHODS: Before entering patients into the randomization phase, each center in the MSLT was required to finish a 30-case learning phase with complete nuclear medicine, pathology, and surgical review. Selection of MSLT patients in the LM/SL/SCLND treatment arm was based on complete pathologic and surgical data. The comparison group of JWCI patients was selected using these criteria: primary cutaneous melanoma having a thickness > or =1 mm with a Clark level > or =III, or a thickness <1 mm with a Clark level > or =IV (MSLT criterion); LM/SL performed between June 1, 1985, and December 30, 1998; and patient not entered in the MSLT. The accuracy of LM/SL/SCLND was determined by comparing the rates of sentinel node (SN) identification and the incidence of SN metastases in the MSLT and JWCI groups. RESULTS: There were 551 patients in the MSLT group and 584 patients in the JWCI group. In both groups, LM performed with blue dye plus a radiocolloid was more successful (99.1 %) than LM performed with blue dye alone (95.2%) (p = 0.014). After a center had completed the 30-case learning phase, the success of SN identification in the MSLT group was independent of the center's case volume or experience in the MSLT. CONCLUSIONS: Lymphatic mapping and sentinel lymphadenectomy can be successfully learned and applied in a standardized fashion with high accuracy by centers worldwide. Successful SN identification rates of 97% can be achieved, and the incidence of nodal metastases approaches that of the organizing center. A multidisciplinary approach (surgery, nuclear medicine, and pathology) and a learning phase of > or =30 consecutive cases per center are sufficient for mastery of LM/SL in cutaneous melanoma. Lymphatic mapping performed using blue dye plus radiocolloid is superior to LM using blue dye alone.
Preoperative lymphoscintigraphy with Tc-99m antimony sulfide colloid was performed in a patient with cutaneous melanoma on the lower back just to the right of the midline. There was direct lymphatic drainage to paravertebral nodes in the chest on the right side at the level of the sixth and seventh thoracic vertebrae. There was also drainage directly to the right groin and via a series of interval nodes to the right axilla. Knowledge of the presence of such drainage may influence the surgical management of patients.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
BACKGROUND: It has been suggested that desmoplastic melanoma (DM) and desmoplastic neurotropic melanoma (DNM) are associated with worse prognoses and higher local recurrence rates than other forms of melanoma. In the current study, a large series of patients with DM and DNM treated at a tertiary referral center was reviewed. METHODS: For 190 patients with DM and 90 patients with DNM accrued over a 10-year period, clinical features were recorded and all available histopathology was reviewed. The associations between clinical and pathologic variables, biologic behavior, and eventual outcome were analyzed. RESULTS: The male-to-female ratio was 1.75:1 and the median patient age 61 years. The median tumor thickness was 2.5 mm, and 44% of cases were amelanotic. Five-year survival was 75%. Significant predictors of overall survival were a high mitotic rate (P=0.003) and tumor thickness (P=0.011). All the DNMs exceeded 1.5 mm in thickness and were graded as Clark's level IV or V. There was a significant increase in local recurrence when neurotropism was present (P < 0.001). The rate of local recurrence was not higher for DM than for other cutaneous melanomas. CONCLUSIONS: There was no statistically significant difference in survival for patients with DM and those with DNM, and overall survival for both was similar to that for patients with other cutaneous melanomas. However, there was a lower rate of regional lymph node metastasis at initial presentation and as the first recurrence for both DM and DNM. The local recurrence rate was higher when the surgical clearance margin was <1 cm and when neurotropism was present.
Explore the source record for details and available documents.
Epidermal growth factor (EGF) augments late fetal lung maturation by advancing the ontogeny of fetal lung development and by stimulating surfactant synthesis. Previous studies have indicated that fibroblastalveolar epithelial cell communications mediate surfactant synthesis in the fetal lung and EGF acts through such a mechanism. We investigated the hypothesis that is differential activity and expression of the epidermal growth factor receptor (EGF-R) in fetal lung fibroblasts during the canalicular stage of lung development mediates EGF effects. To test this hypothesis, we examined fetal rat lung fibroblasts (FLFs) and type II cells of late gestation (canalicular and saccular stages; 17-22 days) by EGF-R binding techniques, SDS-PAGE, and Western blot analysis. Specific EGF binding increased 181% in day 18 female FLFs, with male FLFs exhibiting a similar increase on day 19. In contrast, specific EGF binding was low in type II cells, did not increase during late gestation, and there were no sex-specific differences. SDS-PAGE and Western blot analysis revealed a predominant 170-kDa EGF-R band in fibroblasts that increased with gestation (peak = 19 days), and was stronger in females. Immunoprecipitation of EGF-treated cells demonstrated the tyrosine kinase activity of the identified receptor. In contrast, type II cells showed minimal signal that did not increase until day 21 of gestation. We also examined whole fetal lung sections by immunohistochemistry to determine cell-specific expression of the EGF-R in vivo. Immunohistochemistry revealed specific EGF-R staining in columnar and cuboidal epithelia of small conducting airways and in mesenchyme of epithelial-mesenchymal borders (including subepithelial mesenchyme). In contrast, alveolar epithelia showed minimal staining, while subalveolar mesenchyme EGF-R staining peaked at day 19 of gestation. We conclude that cell-specific and sex-specific differences in EGF-R binding and EGF-R immunolocalization appears in the fetal lung at a developmental stage that is critical for alveolar epithelial cell differentiation. The results suggest a role for EGF-R activation in late fetal alveolar epithelial cell maturation, which is mediated through mesenchymal-epithelial cell communication.
Squalene synthase catalyzes the first committed step in cholesterol biosynthesis and thus is important as a potential target for therapeutic intervention. In order to determine the important functional domains of the protein, the amino and carboxyl terminal regions thought to be involved in membrane association of the enzyme were removed genetically. The 30 N-terminal amino acids were deleted with no apparent effect on activity. Additional deletion of 81 or 97 amino acids from the C-terminus completely ablated activity. However, a protein with a C-terminal deletion of 47 amino acids retained full activity. The latter enzyme was readily overexpressed in Escherichia coli and purified to homogeneity. The pure, doubly truncated enzyme exhibited a specific activity similar to that reported for the protease-solubilized rat liver enzyme, had a KM for farnesyl diphosphate similar to that observed for native enzyme, and was inhibited by anionic compounds to the same degree as native enzyme. Using the vapor diffusion method, the protein was crystallized as an enzyme-inhibitor complex, yielding orthorhombic crystals which diffracted to 2.2 A.