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Biomedical subjects

John F Thompson

Publications and source records attributed to John F Thompson.

At least 55 records · Page 3Linked to original sources
PubMed2005

Lymphatic mapping in management of patients with primary cutaneous melanoma.

In patients with primary cutaneous melanoma, knowledge of regional lymph-node status provides important information on outlook. Evidence suggests that early removal of nodes that contain metastatic disease improves survival outcome. Lymphatic drainage occurs first to sentinel nodes, which are therefore the nodes most likely to contain metastatic disease. Lymphatic mapping with lymphoscintigraphy is important to identify reliably sentinel nodes for removal and thus establish the status of regional nodes. Mapping studies in patients with melanoma have provided new insights into lymphatic anatomy and have shown previously unsuspected drainage pathways, which have important implications for accurate identification and removal of sentinel nodes. Because it is impossible to predict the site or sites of sentinel nodes clinically in individual patients, routine preoperative lymphoscintigraphy is a prerequisite if reliable results are to be obtained from sentinel-node biopsy.

Humans↗
PubMed2005

Treatment of metastatic melanoma using electroporation therapy with bleomycin (electrochemotherapy).

Electroporation therapy (EPT) is a novel treatment modality that uses brief, high-intensity, pulsed electrical currents to enhance the uptake of chemotherapeutic agents, vaccines and genes into cells. This technique is potentially useful for patients with secondary and, possibly, some primary tumours. Nineteen patients with metastatic melanoma were enrolled in a phase two, randomized, open-label study comparing intralesional bleomycin+EPT with intralesional bleomycin alone. Of 18 study lesions, 13 (72%) showed a complete response, one (5%) showed a partial response, three (18%) showed no change and one (5%) showed disease progression over a period of greater than 12 weeks. This represents a 78% objective response rate, which was significantly greater than the 32% response rate observed in the 19 patients with tumours treated with intralesional bleomycin alone (chi=7.94, 1 df, P=0.005). An additional 36 lesions, not enrolled in the study, were also treated with bleomycin+EPT. Of the total of 54 lesions treated with bleomycin+EPT, there was a 72% objective response rate. EPT treatment was well tolerated and was performed on an outpatient basis.

Adult↗
PubMed2005

Isolated melanoma in the lung where there is no known primary site: metastatic disease or primary lung tumour?

Patients with no history of melanoma occasionally present with apparently metastatic melanoma in the lungs, but have no evidence of a primary melanoma. The aims of this study were to investigate the role of surgical resection in the treatment of such patients, and to examine the evidence for a diagnosis of primary pulmonary melanoma in each case. Patients with an unknown primary melanoma who presented with pulmonary disease and subsequently underwent surgical resection were identified from the Sydney Melanoma Unit database. Fifteen patients fulfilled the study criteria. Multiple lesions were present in four. Eight wedge resections and 10 lobectomies were performed. The patients' median survival was 32 months and the 5-year actuarial survival was 42%. This compares with the overall Sydney Melanoma Unit experience of lung resection for melanoma in 83 patients, where the median survival was 19 months and the 5-year survival was 22%. Resection of pulmonary disease in melanoma patients with an unknown primary lesion can result in long-term survival, and even apparent cure. It is possible that some of the patients in this series had primary melanoma of the lung, but this is impossible to prove.

Aged↗
PubMed2005

Histopathologic excision margin affects local recurrence rate: analysis of 2681 patients with melanomas < or =2 mm thick.

OBJECTIVE: Prospective trials have shown that 1-cm and 2-cm margins are safe for melanomas <1 mm thick and > or =1 mm thick, respectively. It is unknown whether narrower margins increase the risk of LR or mortality. SUMMARY BACKGROUND DATA: To determine the relationship between histopathologic excision margin, local recurrence (LR) and survival for patients with melanomas < or =2 mm thick. METHODS: Data were extracted from the Sydney Melanoma Unit database for all patients with cutaneous melanoma < or =2 mm thick, diagnosed up to 1996. Patients with positive excision margins or follow-up <12 months were excluded, leaving 2681 for analysis. Outcome measures were LR (recurrence <5 cm from the excision scar), in-transit recurrence, and disease-specific survival. Factors predicting LR and overall survival were tested with Cox proportional hazards analysis. RESULTS: Median follow-up was 83.8 months. LR was identified in 55 patients (median time to recurrence, 37 months). At 120 months, the actuarial LR rate was 2.9%. Five-year survival after LR was 52.8%. In multivariate analysis, only margin of excision and tumor thickness were predictive of LR (both P = 0.003). When all patients with a margin <0.8 cm in fixed tissue (corresponding to a margin of <1 cm in vivo) were excluded from analysis, margin was no longer significant in predicting LR. Thickness, ulceration, and site were predictive of survival, but margin was not (P = 0.49). CONCLUSIONS: Histopathologic margin affects the risk of LR. However, if the in vivo margin is > or =1 cm, it no longer predicts risk of LR. Patient survival is not affected by margin.

Adolescent↗
PubMed2005

Sentinel node biopsy for early-stage melanoma: accuracy and morbidity in MSLT-I, an international multicenter trial.

OBJECTIVE: The objective of this study was to evaluate, in an international multicenter phase III trial, the accuracy, use, and morbidity of intraoperative lymphatic mapping and sentinel node biopsy (LM/SNB) for staging the regional nodal basin of patients with early-stage melanoma. SUMMARY BACKGROUND DATA: Since our introduction of LM/SNB in 1990, this technique has been widely adopted and has become part of the American Joint Committee on Cancer (AJCC) staging system. Eleven years ago, the authors began the international Multicenter Selective Lymphadenectomy Trial (MSLT-I) to compare 2 treatment approaches: wide excision (WE) plus LM/SNB with immediate complete lymphadenectomy (CLND) for sentinel node (SN) metastases, and WE plus postoperative observation with CLND delayed until the subsequent development of clinically evident nodal metastases. METHODS: After each center achieved 85% accuracy of SN identification during a 30-case learning phase, patients with primary cutaneous melanoma (> or =1 mm with Clark level > or =III, or any thickness with Clark level > or =IV) were randomly assigned in a 4:6 ratio to WE plus observation (WEO) with delayed CLND for nodal recurrence, or to WE plus LM/SNB with immediate CLND for SN metastasis. The accuracy of LM/SNB was determined by comparing the rates of SN identification and the incidence of SN metastases in the LM/SNB group versus the subsequent development of nodal metastases in the regional nodal basin of those patients with tumor-negative SNs. Early morbidity of LM/SNB was evaluated by comparing complication rates between the 2 treatment groups. Trial accrual was completed on March 31, 2002, after enrollment of 2001 patients. RESULTS: Initial SN identification rate was 95.3% overall: 99.3% for the groin, 95.3% for the axilla, and 84.5% for the neck basins. The rate of false-negative LM/SNB during the trial phase, as measured by nodal recurrence in a tumor-negative dissected SN basin, decreased with increasing case volume at each center: 10.3% for the first 25 cases versus 5.2% after 25 cases. There were no operative mortalities. The low (10.1%) complication rate after LM/SNB increased to 37.2% with the addition of CLND; CLND also increased the severity of complications. CONCLUSIONS: LM/SNB is a safe, low-morbidity procedure for staging the regional nodal basin in early melanoma. Even after a 30-case learning phase and 25 additional LM/SNB cases, the accuracy of LM/SNB continues to increase with a center's experience. LM/SNB should become standard care for staging the regional lymph nodes of patients with primary cutaneous melanoma.

Adolescent↗
PubMed2005

Internal mammary node metastasis from primary cutaneous melanoma on the anterior chest.

BACKGROUND: Direct lymphatic drainage from the skin of the anterior chest and breast to internal mammary lymph nodes does not normally occur. METHODS: Preoperative lymphoscintigraphy was performed in a 55-year-old man with a 3.7 mm-thick primary melanoma on his right anterior chest, who had undergone surgery and radiotherapy to successfully treat a localized lymphosarcoma in his right axilla 35 years earlier. RESULTS: The sentinel node in the lower right internal mammary chain, in the 5th interspace, was removed at the same time as the primary melanoma site was widely excised, and micrometastatic melanoma was subsequently identified in it. Second-tier nodes in the 4th and 3rd right interspaces were therefore removed, and adjuvant radiotherapy was given to the entire internal mammary node chain. CONCLUSIONS: This case demonstrates that major disturbance of normal lymphatic drainage pathways can result from previous surgery and/or radiotherapy. Also, the rarity of this drainage pattern indicates that attempts to identify sentinel nodes in breast cancer patients by injecting tracer into the skin overlying a tumour rather than into the breast tissue immediately adjacent to it are likely to be inaccurate in some patients, because cutaneous injection will not demonstrate the sentinel nodes in the internal mammary chain that are present in up to 40% of patients with a breast cancer.

Breast↗
PubMed2004

Ultrasound examination of sentinel nodes in the initial assessment of patients with primary cutaneous melanoma.

BACKGROUND: The value of targeted high-resolution ultrasound (US) examination in detecting sentinel lymph node metastases in patients with newly diagnosed primary cutaneous melanomas has not yet been fully evaluated. The aim of this study was to determine the threshold size of metastatic melanoma deposits in SLNs able to be detected by targeted US examination before initial melanoma surgery. METHODS: A total of 304 patients presenting with primary cutaneous melanomas had SLNs identified by lymphoscintigraphy and then examined in situ by the same physician with high-resolution US. Within 24 hours, the SLNs were removed for histopathologic assessment of sections stained conventionally and with immunohistochemical markers for S100 protein and HMB45 antigen. RESULTS: Metastatic disease was present in SLNs from 33 node fields in 31 patients. The US results in seven of these cases were suggestive of metastatic disease. Twenty-six node fields contained positive nodes not detected by US. Undetected deposits had diameters <4.5 mm. CONCLUSIONS: These results suggest that a targeted US examination of SLNs can detect metastatic melanoma deposits down to approximately 4.5 mm in diameter. However, most metastatic melanoma deposits in SLNs are considerably smaller than this at the time of initial staging, and US therefore cannot be considered cost-effective in this setting.

Adolescent↗
PubMed2004

Interleukin-10 regulates arterial pressure in early primate pregnancy.

OBJECTIVES: In pregnancy, the placental contribution of cytokines to maternal immunosuppression has been established, however their role in normal maternal blood pressure regulation has not been identified. We investigate the contribution of interleukin-10 (IL-10) and tumor necrosis factor-alpha (TNF-alpha) to the vasodilation of early pregnancy in non-human primates. We also sequenced the IL-10 baboon gene and compared it with humans. METHODS: The effect of four different treatments, administered sequentially (semi-random-design) on resting 18h, night time, or hourly mean arterial pressure (MAP) and heart rate (HR) were measured using telemetry. An anti-human IL-10 monoclonal antibody (MAb, 1mg, n=7), anti-TNF-alpha antibody (n=3), a combination of anti-IL-10 and anti-TNF-alpha antibodies (n=5) or saline (n=3) control were administered intravenously to baboons in early pregnancy. Plasma and placental IL-10 concentration was measured before and after injection in all animals. RESULTS: Anti-human IL-10 MAb caused a significant increase in MAP of 2.6+/-0.5mmHg over the 18-h period (p<0.05). Administration of TNF-alpha alone or in combination with IL-10 did not alter MAP. There was 97% sequence homology of IL-10 cDNA between humans and baboons. CONCLUSIONS: IL-10 was shown to regulate the vasodilation of early pregnancy in Papio hamadryas. This partial role of IL-10 in the early BP response of primate pregnancy may be relevant to pathophysiological states of human pregnancy such as preeclampsia.

Amino Acid Sequence↗
PubMed2004

Highly polymorphic repeat region in the CETP promoter induces unusual DNA structure.

Genetic variation in the human cholesteryl ester transfer protein (CETP) promoter is associated with HDL cholesterol levels and cardiovascular disease with much of the genetic variation in CETP attributed to the promoter region. In this region, there are several single nucleotide polymorphisms as well as a variable length tandem repeat located 1946 base pairs upstream of the CETP transcription start that is highly polymorphic with respect to both length and sequence. There are more than 10 different long alleles and these vary in their repeat structure. We find that the short allele of this repeat is associated with high HDL cholesterol levels in vivo (P<0.0001). In males, this association is independent of the nearby -629 polymorphism. In addition, the variable length GAAA repeat can stimulate an adjacent GGGGA repeat to form a structure that hinders DNA amplification and sequencing. This structure also has an effect in vivo as shown by orientation effects and cloning efficiency in Escherichia coli.

Animals↗
PubMed2004

The history and future of melanoma staging.

The evolution and progressive refinement of an internationally accepted melanoma staging system over the last 50 years has resulted in much greater accuracy and increased utility, but the staging process has become more complex and less intuitive. This raises the question of whether melanoma staging should continue to develop with ever-increasing levels of complexity, or whether attempts should be made to produce an alternative system that is simpler and more intuitive. The current, TNM-based American Joint Committee on Cancer (AJCC) staging system for melanoma incorporates only some of the prognostic factors of proven significance. However, the information that is now available about these and other, well-documented prognostic factors allows accurate prediction of an individual melanoma patient's prognosis using a computer-generated estimate. Thus an alternative staging strategy that could be considered in the future would be to use such an estimate to obtain a numerical score for each patient, based on all available information agreed to be of prognostic relevance. A stage grouping could then be assigned on the basis of that score, according to previously determined score ranges for each stage and substage. The advantages of such a system would be that it would allow more reliable comparison of treatment results within and between institutions, and would provide more equivalent stratification groups for patients entering clinical trials of new therapies and those entering adjuvant therapy trials. A further advantage would be that because there would be a direct link between staging and prognostic estimate, such a system would be more readily able to be understood in an intuitive fashion.

Antigens, Neoplasm↗
PubMed2004

Pathology of melanocytic lesions: new, controversial, and clinically important issues.

Patients with primary cutaneous melanocytic lesions rely not only on the knowledge, skills, and experience of their treating clinician but also on the fundamentally important input of their pathologist for accurate diagnosis and appropriate management. Free and precise communication between pathologists and surgeons is important and undoubtedly improves patient care, particularly when managing difficult or complicated cases. To provide both patient and surgeon with the necessary information they require to make the most appropriate decisions, the pathology report should include all pathologic factors that are important in determining the patient's prognosis and management. Use of a synoptic format for pathology reporting of melanomas can facilitate this. Recent studies have established that the dermal mitotic rate of a primary cutaneous melanoma is a major prognostic determinant, and have shown that its assessment and that of other important histopathologic prognostic variables are reproducible between pathologists. Sentinel node (SN) biopsy has provided a minimally invasive procedure that can accurately predict the regional node status of melanoma patients. It is well demonstrated that the use of immunohistochemical stains assists in the detection of melanoma micrometastases in SNs, although it remains unclear which is the optimal pathologic protocol for SN evaluation and whether there is a role for reverse transcriptase polymerase chain reaction (RT-PCR) in SN assessment. False negative SN biopsies may occur as a result of errors in lymphatic mapping or sentinel lymphadenectomy, or because of a deficiency in the process of histopathologic evaluation. Recent studies have shown that the likelihood of non-SN involvement when the SN is positive correlates mostly with the extent of SN involvement, in particular the tumor penetrative depth (defined as the maximum distance of melanoma cells from the inner margin of the SN capsule). It appears that assessment of the micromorphometric features of positive SNs may be useful in predicting which patients have a low probability of having metastatic tumor in non-SNs, and therefore in selecting patients who potentially may be spared a completion lymph node dissection. It is likely that future advances in our understanding of the molecular biology of melanoma will provide new insights into tumor classification, improve diagnostic accuracy and prognostic ability, and lead to the development of more precisely targeted therapies.

Biopsy, Fine-Needle↗
PubMed2004

The prognostic importance of tumor mitotic rate confirmed in 1317 patients with primary cutaneous melanoma and long follow-up.

BACKGROUND: The late Dr. Vincent McGovern (1915 to 1983) was an international authority on melanoma pathology and one of the first to suggest that assessment of tumor mitotic rate (TMR) might provide useful prognostic information. Data for a large cohort of patients, now with extended follow-up, whose tumors had been assessed by Dr. McGovern were analyzed to reassess the independent prognostic value of TMR in primary localized, cutaneous melanoma. METHODS: Information was extracted from the Sydney Melanoma Unit database for 1317 patients treated between 1957 and 1982 for whom there was complete clinical information and whose primary lesion pathology, which included tumor thickness, ulcerative state, and TMR, had been assessed by Dr. McGovern. All these assessments were made according to the recommendations of the Eighth International Pigment Cell Conference, held in Sydney in 1972 under the auspices of the International Union Against Cancer. Factors predicting melanoma-specific survival were analyzed with the Cox proportional hazards regression model. RESULTS: Stage, according to the recently revised American Joint Committee on Cancer Staging System (which is based on tumor thickness and ulceration) was the most predictive factor for survival (P<.0001). This was followed by primary lesion site (P<.0001), patient age (P=.0005), and TMR (P=.008). CONCLUSIONS: TMR was confirmed to be an important independent predictor of survival of patients with primary cutaneous melanoma. However, its predictive value was less than it was when assessed according to the 1982 revisions of the 1972 TMR recommendations.

Adolescent↗
PubMed2004

Association between single-nucleotide polymorphisms in the endothelial lipase (LIPG) gene and high-density lipoprotein cholesterol levels.

Endothelial lipase (LIPG) is the latest addition to the triglyceride lipase family of genes that includes pancreatic lipase (PL), hepatic lipase (HL), and lipoprotein lipase (LPL). These lipolytic enzymes demonstrate both triglyceride lipase as well as phospholipase activities and are integrally involved in lipid absorption, transport, and metabolism. Several studies have demonstrated that LIPG is important for affecting lipid levels in mice but the data in humans is less complete. To more thoroughly characterize the LIPG gene, we resequenced it from an ethnically diverse population. Thirteen novel single-nucleotide polymorphisms (SNPs) were identified and seven others confirmed. High linkage disequilibrium was found among these SNPs spanning the length of the transcript, allowing interrogation of the entire gene for functional variation. Subjects with either high or low HDL cholesterol were used to investigate its association with LIPG gene variation. Associations were found with the most significant being the intronic variants C+42T/In5 and T+2864C/In8 (P=0.007 and 0.004, respectively). A trend for an association of the same SNPs with fewer myocardial infarctions (P=0.03) was also observed but was not significant after correction for multiple testing. The results of this study provide data linking variation in the human LIPG gene with HDL cholesterol levels as well as further evidence in support of LIPG as a potential target for therapeutic intervention.

Cholesterol, HDL↗
PubMed2004

Sentinel node biopsy for melanoma: Where have we been and where are we going?

The sentinel node (SN) concept is not new, but its potential surgical application was not fully appreciated until the landmark report by Morton and Cochran et al. in 1992. It has since been confirmed that SN status in melanoma patients accurately reflects the status of the entire regional node field, and is a critically important prognostic indicator. However, randomized trials have yet to determine whether the SN biopsy technique is of any therapeutic value. With extended follow-up times, false-negative SN rates of up to 15% are being reported and presumably represent failures of nuclear medicine and/or surgery and/or histopathology. Innovative methods of increasing the accuracy of SN identification and of checking this retrospectively are being assessed. The next great challenge is to develop methods of SN assessment that are noninvasive yet are even more accurate than present methods. Techniques such as in vivo proton magnetic resonance spectroscopy hold great promise and suggest that this goal might be achievable.

Humans↗
PubMed2004

Failure to remove true sentinel nodes can cause failure of the sentinel node biopsy technique: evidence from antimony concentrations in false-negative sentinel nodes from melanoma patients.

We have recently found that antimony (originating from the technetium 99m antimony trisulfide colloid, used for preoperative lymphoscintigraphy) can be measured in tissue sections from archival paraffin blocks of sentinel nodes (SNs) by means of inductively coupled plasma mass spectrometry (ICP-MS) to confirm that removed nodes are true SNs. We performed a retrospective analysis of antimony concentrations in all our false-negative (FN) SNs to determine whether errors in lymphadenectomy (i.e., failure to remove true SNs) may be a cause of FN SN biopsies (SNBs). Among 27 patients with an FN SNB, metastases were found on histopathologic review of the original slides or additional sections in 7 of 23 patients for which they were available; however, antimony concentrations were low in 5 of 20 presumptive SNs. Our results suggest that an FN SNB can occur because of failure to remove the true SN as well as histopathologic misdiagnosis.

Antimony↗