PubMed Health⌕ Search

Biomedical subjects

John F Thompson

Publications and source records attributed to John F Thompson.

At least 19 recordsLinked to original sources
PubMed2003

Prognosis for patients with thin cutaneous melanoma: long-term survival data from New South Wales Central Cancer Registry and the Sydney Melanoma Unit.

BACKGROUND: Estimates of long-term survival for patients with thin (< or = 1 mm) primary cutaneous melanomas vary widely. Two separate methods were used to study the survival of patients with melanoma from New South Wales (NSW), Australia, and from the Sydney Melanoma Unit (SMU). METHODS: The NSW Central Cancer Registry (NSWCCR) provided data on all patients who were diagnosed with cutaneous melanomas that measured < or = 1 mm thick between 1983 and 1998, inclusive. Patients with metastases at the time of diagnosis were not included, leaving 18,088 patients for analysis. The SMU data base was analyzed to extract data for all patients with thin melanomas who met the same criteria from 1979 to 1998, inclusive. All patients who had their primary tumors treated definitively elsewhere were excluded, leaving 2746 patients for analysis. Ten-year Kaplan-Meier survival rates were calculated, and significant differences were determined using log-rank analysis. Prognostic factors were evaluated with Cox proportional hazards analysis. RESULTS: The NSWCCR analysis revealed a 10-year survival rate of 96.4%. The 10-year survival rate for patients at SMU was 92.7%. Among the patients at SMU who died, the median time to recurrence was 49.8 months, and the median time to death was 65.9 months. The 10-year survival for patients at SMU who had lesions that measured < or = 0.75 mm was 96.9% compared with 84.3% for patients who had lesions that measured 0.76-1.0 mm. For patients who had ulcerated melanomas measuring < or = 1 mm thick, the 10-year survival rate was 83%, compared with 92.3% for patients who had nonulcerated melanomas. CONCLUSIONS: The results of the current study confirmed the excellent survival rate for patients with thin melanomas. Higher-risk subsets of patients who may warrant consideration for aggressive investigation and treatment are identifiable.

Adolescent↗
PubMed2003

Natural genetic variation as a tool in understanding the role of CETP in lipid levels and disease.

Since the identification of cholesteryl ester transfer protein (CETP), its role in the modulation of HDL levels and cardiovascular disease has been debated. With the early detection of genetic variants followed by the finding of families deficient in CETP, genetic studies have played a large role in the attempts to understand the association of CETP with lipids and disease; however, results of these studies have often led to disparate conclusions. With the availability of a greater variety of genetic polymorphisms and larger studies in which disease has been examined, it is now possible to compare the breadth of CETP genetic studies and draw better conclusions. The most broadly studied polymorphism is TaqIB for which over 10,000 individuals have been genotyped and had HDL levels determined. When these studies are subjected to a meta-analysis, the B2B2 homozygotes are found to have higher HDL levels than B1B1 homozygotes (0.12 mmol/l, 95% CI = 0.11-0.13, P < 0.0001). A similar analysis of the I405V polymorphism yields 0.05 mmol/l higher HDL levels in 405VV homozygotes than in 405II homozygotes (95% CI = 0.03-0.07, P < 0.0001). The implications of these studies for cardiovascular disease will be addressed.

Analysis of Variance↗
PubMed2003

Tumor mitotic rate is a more powerful prognostic indicator than ulceration in patients with primary cutaneous melanoma: an analysis of 3661 patients from a single center.

BACKGROUND: The current study was performed to determine whether tumor mitotic rate (TMR) is a useful, independent prognostic factor in patients with localized cutaneous melanoma. METHODS: From the Sydney Melanoma Unit database, 3661 patients with complete clinical information and details of primary tumor thickness, ulcerative state, and TMR were studied. TMR was expressed as mitoses per mm(2) in the dermal part of the tumor in which most mitoses were seen, as recommended in the 1982 revision of the 1972 Sydney classification of malignant melanoma. To determine which was the more prognostically useful method of grouping TMR, two separate methods (A and B) were used. Factors predicting melanoma-specific survival were analyzed using the Cox proportional hazards regression model. RESULTS: Patients with a TMR of 0 mitoses/mm(2) had a significantly better survival than those with 1 mitosis/mm(2) (P < 0.0001) but no significant survival differences were recorded for the stepwise increases from 1-2, 2-3, 3-4, and 4-5/mm(2). Tumor thickness, ulceration, and TMR were closely correlated, whether TMR was grouped using Method A (0, 1-4, 5-10, and >/= 11 mitoses/mm(2)) or Method B (0-1, 2-4, and >/= 5 mitoses/mm(2)). However, Cox regression analysis indicated that the TMR was a highly significant independent prognostic factor, particularly when grouped according to Method A, in which it was second only to tumor thickness as the most powerful predictor of survival (P < 0.0001). CONCLUSIONS: TMR is an important independent predictor of survival for melanoma patients. If confirmed by studies from other centers, it has the potential to further improve the accuracy of melanoma staging, as well as to define more rigidly the risk categories for patients entering clinical trials.

Adolescent↗
PubMed2003

New TNM melanoma staging system: linking biology and natural history to clinical outcomes.

The American Joint Committee on Cancer (AJCC) implemented major revisions of the melanoma TNM and stage grouping criteria in the recently published 6th edition of the Staging Manual. The new staging system better reflects independent prognostic factors that are used in clinical trials and in reporting the outcomes of various melanoma treatment modalities. Major revisions include: 1) melanoma thickness and ulceration but not level of invasion to be used in the T classification, 2) the number of metastatic lymph nodes rather than their gross dimensions and the delineation of microscopic vs. macroscopic nodal metastases to be used in the N classification, 3) the site of distant metastases and the presence of elevated serum lactic dehydrogenase (LDH) to be used in the M classification, 4) an upstaging of all patients with Stage I, II, and III disease when a primary melanoma is ulcerated, 5) a merging of satellite metastases around a primary melanoma and in transit metastases into a single staging entity that is grouped into Stage III disease, and 6) a new convention for defining clinical and pathological staging so as to take into account the new staging information gained from intraoperative lymphatic mapping and sentinel node biopsy.

Clinical Trials as Topic↗
PubMed2003

Polymorphisms in the CETP gene and association with CETP mass and HDL levels.

The cholesteryl ester transfer protein (CETP) gene has been implicated in the variation of HDL levels but most studies have focused on only one or a few genetic variations. In order to properly understand the role of CETP in determining phenotype, it is necessary to examine the entire gene and all its common polymorphisms. The coding regions, adjacent introns, and proximal 5' and 3' regions were resequenced from an ethnically diverse population. Novel and previously known polymorphisms were then characterized and associations with HDL and CETP mass levels determined. The polymorphism most highly associated with CETP was 629 bp upstream of the transcription start site while the polymorphism most highly associated with HDL was a VNTR 1946 bp upstream of the transcription start site. Genetic variation in the CETP gene is associated with protective HDL levels. The ethnic diversity of some SNPs and complex interplay among them dictate careful analysis of the whole gene prior to conclusions about the role of individual polymorphisms.

Analysis of Variance↗
PubMed2003

The Sydney Melanoma Unit--a multidisciplinary melanoma treatment center.

The undoubted success of the SMU as a specialist multidisciplinary melanoma treatment center has clearly been the result of many factors. Perhaps chief among these was the vision and commitment that led Dr. Milton to establish it in the first place, and the sharing of that vision and commitment by those who were associated with him and by those who joined the SMU later. Another vitally important element, however, has been the continuing sense of unity and purpose fostered by the weekly SMU clinical meetings, which are truly multidisciplinary, in which all staff are encouraged to participate, and at which the desirability of adherence to agreed, evidence-based treatment guidelines is emphasized. A further influential factor has been the SMU's strong commitment to clinical and basic research as a concomitant of high quality clinical care, with stimulation, encouragement, and advice provided at its monthly multidisciplinary research meetings, where all current and proposed clinical and laboratory studies are discussed. As a result of these activities, despite an ever-increasing number of people working within it, the SMU has been able to present to referring doctors, to patients, and to the community a unified commitment to the best possible patient care and to high quality clinical and laboratory research. These groups have responded by recognizing the SMU as the major referral center for melanoma in Australia, as evidenced by the steadily increasing number of patients referred to it for treatment each year. Melanoma is a more pressing health problem in Australia than elsewhere, because it is the third most common cancer in women (after breast cancer and colorectal cancer), and the fourth most common cancer in men (after prostate cancer, colorectal cancer, and lung cancer). Nevertheless the experiences of the SMU as a large multidisciplinary melanoma treatment center are likely to have relevance and application in other countries, where the incidence of melanoma is lower but continues to rise, and may within a few years approach rates currently recorded in Australia.

Australia↗
PubMed2003

Surgical treatment of splenic metastases in patients with melanoma.

BACKGROUND: Surgery is rarely undertaken for metastatic melanoma in the spleen. To identify indications for surgical treatment, results after splenectomy for metastatic melanoma were analyzed. STUDY DESIGN: A retrospective study in which all patients at the Sydney Melanoma Unit recorded as having splenic metastases between January 1990 and May 2001 were identified. For those who underwent surgery, indications for splenectomy, operative complications, and outcomes were documented. RESULTS: Splenectomy was performed in 15 patients, and 98 patients were treated conservatively. Indications for surgery were rupture of the spleen (n = 1), discomfort or pain (n = 7), and the spleen as an apparently solitary site of metastasis (n = 7). All seven symptomatic patients were free of pain after recovery from surgery. Postoperative morbidity occurred in two patients (14%) but there was no mortality. Median overall survival after splenectomy was 11 months, with a survival of 23 months for the subgroup of patients treated for a solitary lesion. Two patients who underwent splenectomy were disease free after more than 2 years of followup. Median overall survival of the conservatively treated patients was 4 months, which was statistically shorter than median survival of the patients who underwent splenectomy (p = 0.02). CONCLUSIONS: Splenectomy can provide good palliation for symptomatic patients with melanoma metastases in the spleen. A selected group of patients with solitary splenic metastases can achieve longterm disease-free survival after splenectomy.

Adult↗
PubMed2003

Argyrophilic staining of nucleolar organizer region count and morphometry in benign and malignant melanocytic lesions.

Differentiation between malignant melanomas (MMs) and benign nevi based on histologic features can sometimes be difficult. This study evaluated the diagnostic effectiveness of argyrophilic staining of nucleolar organizer regions (AgNORs) in separating benign nevi from MMs by assessing 27 compound nevi (CN), 20 dysplastic nevi (DN), 10 Spitz nevi (SN), and 24 MMs. Both AgNOR count and morphology variables were measured from the superficial, middle, and deep zones of the lesions using video image analysis. Malignant melanomas had a significantly greater AgNOR number per nucleus, mean AgNOR area per nucleus, and variation in AgNOR area per nucleus compared with all types of benign nevi (p < 0.05). In multivariate discriminant analysis using a combination of four AgNOR counts and morphometric parameters, all CN and DN, 8 of 10 SN, and 23 of 24 MMs could be correctly classified as benign or malignant. The results suggest that both AgNOR count and morphology help to separate benign and malignant melanocytic lesions and that the combination of both sets of parameters improves their discriminating ability.

Adolescent↗
PubMed2003

Pathologic review of negative sentinel lymph nodes in melanoma patients with regional recurrence: a clinicopathologic study of 1152 patients undergoing sentinel lymph node biopsy.

A sentinel lymph node (SLN) that is melanoma negative by pathologic examination implies absence of melanoma metastasis to that regional lymph node field. However, a small proportion of patients develop regional node field recurrence after a negative SLN biopsy. In this study, we reviewed the histopathology of negative SLNs from such patients to determine whether occult melanoma cells were present in the SLNs, to characterize the pathologic features of false-negative SLNs, and to provide recommendations for the histopathologic examination of these specimens. Between March 1992 and June 2001, of 1152 patients who had undergone SLN biopsy for primary melanomas at the Sydney Melanoma Unit, 976 were diagnosed with negative SLNs by initial pathologic examination (using 2 hematoxylin and eosin stained sections, and 2 immunostained sections for S-100 protein and HMB45), and follow-up was available in 957. Of these, 26 (2.7%) developed regional lymph node recurrence during a median follow-up period of 35.7 months. For 22 of them, the original slides and tissue blocks were available for reexamination. The original slides of each block were reviewed. Multiple further sections were cut from each block and stained with hematoxylin and eosin, for S-100, HMB45, and Melan A. Deposits of occult melanoma cells were detected in 7 of the 22 cases (31.8%). In 5 of the 7 cases, deposits of melanoma cells were present only in the recut sections. There were no significant differences in clinical and pathologic variables for those patients in whom occult melanoma cells were found by pathologic reexamination of their SLNs, compared with those in whom no melanoma cells were detected. The detection of melanoma cell deposits in only 7 of 22 false-negative SLNs suggests that mechanisms other than failure of histopathologic examination may contribute to the failure of the SLN biopsy technique in some patients. The failure rate for melanoma detection in SLNs by our routine pathologic examination, using the current protocol at our institution, was <1% (7 of 957 patients). Routinely performing more intensive histopathologic examination of SLNs is difficult to justify from a cost benefit perspective; we therefore recommend examining two hematoxylin and eosin stained sections and two immunostained sections (for S-100 and HMB45) routinely on SLNs from melanoma patients.

Adult↗
PubMed2003

Increased expression of apoptotic markers in melanoma.

Extensive labelling for the apoptotic markers calcium channel receptor P2X(7) and caspase-3 and telomerase activity was co-localized at a similar intensity in areas affected by superficial spreading melanoma obtained from 80 patients. Labelling for each of these markers also extended 2 microm from the melanoma into the keratinocyte layer of the adjacent normal epidermis. Conversely, the calcium-regulating receptors P2X(1-3) and P2Y(2) (found in normal but not neoplastic skin) were fully de-expressed within 2 microm of the melanoma but fully expressed beyond that distance. The cell adhesion protein E-cadherin (also only present in normal skin) was progressively de-expressed from a point 2 microm from the melanoma until full de-expression within the lesion. These results show that telomerase-induced proliferation and defensive apoptosis are co-localized and simultaneous processes in melanoma tissue. Melanoma cell proliferation appears to overwhelm the apoptotic defence, perhaps due to the anti-apoptotic effects of telomerase. In addition, keratinocyte regulation of the epidermis and dermis is severely compromised by the loss of E-cadherin and P2X(1-3) and P2Y(2) receptors, resulting in a lesion that is aggressive and malignant.

Apoptosis↗
PubMed2003

Rapid detection of metastatic melanoma in lymph nodes using proton magnetic resonance spectroscopy of fine needle aspiration biopsy specimens.

Accurate staging of patients with primary cutaneous melanoma includes assessment of regional lymph nodes for the presence of micrometastatic disease. Sentinel lymph node biopsy is highly accurate but is an invasive surgical procedure with a 5-10% complication rate, and requires labour-intensive and expensive histological examination to identify disease. A rapid, accurate and cost-effective non-surgical technique able to detect micrometastatic deposits of melanoma in regional lymph nodes would be of great benefit. Fine needle aspiration biopsies and tissue specimens were obtained from lymph nodes from 18 patients undergoing node resection for metastatic melanoma and five patients undergoing radical retropubic prostatectomy. One-dimensional proton magnetic resonance spectroscopy was undertaken at 360 MHz (8.5 T). Lymph nodes were cut into 3 mm thick slices and embedded. Four sequential 5 microm tissue sections were cut from each block and stained, with haematoxylin and eosin, for S100 protein, for HMB45, and again with haematoxylin and eosin, respectively. Proton magnetic resonance spectroscopy distinguished between benign and malignant lymph node tissue (P < 0.001, separate t-test) and benign and malignant lymph node fine needle aspiration biopsy (P < 0.012) based on the ratio of the integrals of resonances from lipid/other metabolites (1.8-2.5 p.p.m. region) and 'choline' (3.1-3.3 p.p.m. region). In conclusion, one-dimensional proton magnetic resonance spectroscopy on a simple fine needle aspiration biopsy can distinguish lymph nodes containing metastatic melanoma from uninvolved nodes, providing a rapid, accurate and cost-effective non-surgical technique to assess regional lymph nodes in patients with melanoma.

Biopsy, Fine-Needle↗
PubMed2003

Patterns of lymphatic drainage from the skin in patients with melanoma.

An essential prerequisite for a successful sentinel lymph node biopsy (SLNB) procedure is an accurate map of the pattern of lymphatic drainage from the primary tumor site in each patient. In melanoma patients, mapping requires high-quality lymphoscintigraphy, which can identify the actual lymphatic collecting vessels as they drain into the sentinel lymph nodes. Small-particle radiocolloids are needed to achieve this goal, and imaging protocols must be adapted to ensure that all true sentinel nodes, including those in unexpected locations, are found in every patient. Clinical prediction of lymphatic drainage from the skin is not possible. The old clinical guidelines based on Sappey's lines therefore should be abandoned. Patterns of lymphatic drainage from the skin are highly variable from patient to patient, even from the same area of the skin. Unexpected lymphatic drainage from the skin of the back to sentinel nodes in the triangular intermuscular space and, in some patients, through the posterior body wall to sentinel nodes in the para-aortic, paravertebral, and retroperitoneal areas has been found. Lymphatic drainage from the head and neck frequently involves sentinel nodes in multiple node fields and can occur from the base of the neck up to nodes in the occipital or upper cervical areas or from the scalp down to nodes at the neck base, bypassing many node groups. The sentinel node is not always found in the nearest node field and is best defined as "any lymph node receiving direct lymphatic drainage from a primary tumor site." Lymphatic drainage can occur from the upper limb to sentinel nodes above the axilla. Drainage to the epitrochlear region from the hand and arm as well as to the popliteal region from the foot and leg is more common than was previously thought. Interval nodes, which lie along the course of a lymphatic vessel between a lesion site and a recognized node field, are not uncommon, especially in the trunk. Drainage across the midline of the body is quite common in the trunk and in the head and neck. Micrometastatic disease can be present in any sentinel node regardless of its location, and for the SLNB technique to be accurate, all true sentinel nodes must be biopsied in every patient.

Humans↗
PubMed2002

Improving doctors' letters.

Information contained in letters of referral and reply often does not meet the information needs of letter recipients. Missing reports of previous investigations and insufficient detail in the referral letter to specialists are the most serious and common problems. General practitioners prefer structured, computer-generated letters to unstructured, dictated letters. Referring surgeons and GPs identify delay in receiving the reply letter and insufficient detail as relatively common problems after a new patient consultation. They want the reply letter to describe the proposed treatment, expected outcomes and any psychosocial concerns, yet these items are often omitted. A letter content and format prompt card has the potential to enhance the quality of correspondence between medical specialists and referring doctors. Specialist medical bodies should consider preparing prompt cards (setting out preferred information content and format for letters) to distribute to their members.

Correspondence as Topic↗
PubMed2002

Adjuvant immunotherapy of patients with high-risk melanoma using vaccinia viral lysates of melanoma: results of a randomized trial.

PURPOSE: Patients with high-risk melanoma treated by immunotherapy with vaccinia viral lysates were found in phase II studies to have improved survival compared with historical controls. We therefore elected to test this therapy in a phase III study. PATIENTS AND METHODS: A prospective, randomized, multicenter trial to determine whether immunotherapy with a vaccine prepared from vaccinia melanoma cell lysates (VMCL) over a 2-year period after definitive surgery would improve relapse-free survival (RFS) and overall survival (OS) in patients with American Joint Committee on Cancer stage IIB and III melanoma compared with a control group treated only with surgery. RESULTS: A total of 700 patients were randomized: 353 to VMCL and 347 to no immunotherapy. Seventy-seven percent had lymph node (LN) metastases and 66% had clinically detected LN metastases. Analysis on the basis of all eligible, randomized patients (n = 675) found, after a median follow-up period of 8 years, a median OS of 88 months in the control versus 151 months in the treated group (hazard ratio [HR], 0.81; 95% confidence interval [CI], 0.64 to 1.02; P =.068 by stratified univariate Cox analysis). At 5 and 10 years, survival rates for control and treated patients were 54.8% v 60.6% and 41% v 53.4%, respectively. Median RFS was 43 months in the control group compared with 83 months in the treated group (HR, 0.86; 95% CI, 0.7 to 1.07; P =.17). RFS at 5 years was 50.9% for the treated group and 46.8% for the control group. There were no selective benefits from the vaccine for particular subsets of patients. CONCLUSION: Immunotherapy with VMCL was not associated with a statistically significant improvement in OS or RFS, with CIs not ruling out important gains from such treatment.

Adult↗
PubMed2002

Identification of IEX-1 as a biomechanically controlled nuclear factor-kappaB target gene that inhibits cardiomyocyte hypertrophy.

Biomechanical strain is a stimulus for cardiomyocyte hypertrophy and heart failure, but the underlying molecular mechanisms remain incompletely understood. Using an in vivo murine model of pressure overload and an in vitro model of mechanical stimulation of primary cardiomyocytes, we identified iex-1 as a gene activated during the early response of cardiomyocytes to hypertrophic stimuli and as a gene product that inhibits hypertrophy without affecting cardiomyocyte viability. On stimulation of cardiomyocytes, iex-1 mRNA and protein expression increased and translocation of the gene product to the cardiomyocyte nucleus occurred. iex-1 has previously been proposed as a mediator of NF-kappaB-dependent cell survival and growth in tumor cells. Here, we demonstrate that the biomechanical induction of iex-1 in cardiomyocytes was NF-kappaB-dependent, as overexpression of the NF-kappaB inhibitor IkappaBalpha completely inhibited strain-mediated iex-1 mRNA accumulation. The functional role of iex-1 was investigated by overexpressing wild-type iex-1 with replication-defective adenoviral gene transfer. Overexpression of iex-1 abolished cardiomyocyte hypertrophy by mechanical strain, phenylephrine, or endothelin-1 at levels that did not affect cell viability. These studies identify iex-1 as a biomechanical stress-inducible and NF-kappaB-dependent gene in cardiac muscle cells during the acute phase of hypertrophy with negative growth regulatory effects that may counterbalance early hypertrophic responses in activated cardiomyocytes.

Adenoviridae↗
PubMed2002

Prognostic factors after isolated limb infusion with cytotoxic agents for melanoma.

BACKGROUND: Isolated limb perfusion (ILP) with cytotoxic agents is a remarkably effective but complex technique used to treat locally recurrent and metastatic melanoma confined to a limb. Isolated limb infusion (ILI), essentially a low-flow ILP performed without oxygenation via percutaneous catheters, has been developed as a simpler alternative. METHODS: The outcome in 135 patients treated by ILI was reviewed. RESULTS: The overall response rate in the treated limb was 85% (complete response [CR] rate 41%, partial response rate 44%). Median response duration response was 16 months (24 months for patients with CR). Median patient survival was 34 months. In those with a CR, the median survival was 42 months. CR rate and survival time decreased with increasing disease stage. Patients aged >70 years had a better overall response than younger patients. On multivariate analysis, factors associated with an improved outcome were a lower stage of disease, a final limb temperature >37.8 degrees C, and a tourniquet time >40 minutes. CONCLUSIONS: The frequency and duration of responses after ILI were comparable to those achieved by conventional ILP. The ILI technique is particularly useful for older patients who might not be considered suitable for conventional ILP.

Aged↗