Three-dimensional assessment of hand outcome.

INTRODUCTION: Patient reported outcome measures are central to National Health Service quality of care assessments. This study investigated the benefit of elective hand surgery by the simultaneous analysis of pain, function and appearance, using a three-dimensional (3D) graphical model for evaluating and presenting outcome. METHODS: A total of 188 patients scheduled for surgery completed pre- and postoperative questionnaires grading the severity of their pain, dysfunction and deformity of their hand(s). Scores were plotted on a 3D graph to demonstrate the degree of 'normalisation' following surgery. RESULTS: Surgical groups included: nerve compression (n=53), Dupuytren's disease (n=51), trigger finger (n=20), ganglion (n=17) or other lump (n=21), trapeziometacarpal joint osteoarthritis (n=10), rheumatoid disease (n=5) and other pathology (n=13). A significant improvement towards normality was seen after surgery in each group except for patients with rheumatoid disease. CONCLUSIONS: This study provides a simple, visual representation of hand surgery outcome by plotting patient scores for pain, function and appearance simultaneously on a 3D graph.

Diagnosis of skin lesions by trainee surgeons: experience improves accuracy.

INTRODUCTION: Accurate clinical diagnosis depends on the reliable recognition of signs and symptoms. This expertise comes from experience in seeing patients which has been traditionally gained over a long training period. Shortened specialist training (Modernising Medical Careers) has led to a greater reliance on structured teaching and skills transfer programmes. The accuracy of clinical diagnosis and the rate at which diagnostic skills improve during training is important for the assessment of trainees, and the delivery of care. PATIENTS AND METHODS: This study assessed the accuracy of clinical diagnosis of skin lesions by two junior plastic surgery trainees. They were asked to diagnose 120 consecutive skin lesions seen in a pigmented skin lesion clinic in 2005, with the histological diagnosis being confirmed following subsequent excision. The process was repeated a year later in 2006 to enable the rate of correct diagnosis to be compared. RESULTS: Initially, 53.3% of diagnoses were correct. A year later, this had risen to 65.0%. Twenty-two different skin pathologies were present in excised specimens, and skin cancers comprised 30%. The trainees demonstrated 93.8% sensitivity in their initial diagnosis of malignancy (95% CI, 79.2-99.2) and 97.4% a year later (95% CI, 86.5-99.9). However, specificity was 69.3% (95% CI, 58.6-78.7) in 2005 and 71.6% (95% CI, 60.5-71.4) in 2006. CONCLUSIONS: Accuracy in the diagnosis of the wide range of skin conditions presenting to an out-patient clinic was shown to increase over a 1-year period. We feel that this improvement resulted from regular clinical exposure supported by a structured learning programme. The shortening of the specialist training period may affect the acquisition of diagnostic skills by trainees and impact on the confidence with which they commence consultant practice.

Stratification of patients by melanoma cell adhesion molecule (MCAM) expression on the basis of risk: implications for sentinel lymph node biopsy.

BACKGROUND: The usual indication for sentinel lymph node biopsy (SLNB) in melanoma is a primary tumour >1mm thickness but under these criteria less than 20% of SLNBs are positive. Of those patients with a negative sentinel node (SN) over 10% will have disease recurrence within 3 years. A more accurate delineation of candidate patients for SLNB and risk profile for negative SN patients is therefore desirable. Melanoma cell adhesion molecule (MCAM) is a predominant cell adhesion molecule of melanomas and its expression has been implicated in tumour progression and metastasis. AIMS: To compare MCAM expression in primary and metastatic melanoma and to investigate if MCAM expression in patients meeting the criteria for SLNB correlated with patient outcome. METHODS: Tissue arrays of primary (n=78) and metastatic (n=92) melanomas were constructed from archived paraffin embedded tissue and MCAM expression detected by immunohistochemistry. Staining positivity and intensity were assessed by visual scoring and correlated with clinical outcome. RESULTS: In patients meeting the current criteria for SLNB, Cox multivariate analysis showed both MCAM expression positivity and intensity were independently predictive of survival (P=0.007) and development of lymph node disease (P=0.01) in primary melanoma over and above established markers of prognosis, such as Breslow thickness. MCAM-negative patients had a 5-year survival of 92% compared with 40% for MCAM positive. CONCLUSIONS: Measurement of MCAM expression represents a potential method to stratify SLNB patients on the basis of risk. This would have considerable benefits in terms of both cost and patient morbidity.

Ki-67 expression in melanoma. A potential method of risk assessment for the patient with a positive sentinel node.

Melanoma patients with a positive sentinel node biopsy generally proceed to regional lymph node dissection, though ultimately only around 20% have evidence of tumour in their "non-sentinel" nodes. A means to identify patients at high risk of non-sentinel node involvement could potentially spare a large number of patients a procedure with significant morbidity. The proliferation marker Ki-67 has been associated with tumour progression in primary melanoma but has not been extensively studied in metastases. The study aims to investigate Ki-67 in primary melanoma and lymph node metastases and investigate any relationship with disease progression. Tissue Arrays of primary melanoma (n=79) and lymph node metastases (n=92) were constructed from paraffin embedded tissue and Ki-67 expression examined by immunohistochemistry. Staining positivity and intensity were assessed and correlated with standard staging criteria and clinical outcome. High Ki-67 expression was associated with both Breslow thickness (chi(2)=8.54, p=0.035) and presence of ulceration (Fisher's Exact test p=0.003) in primary melanoma. In lymph node metastases high Ki-67 expression correlated with Nodal (N) Stage (chi(2)=8.193, p=0.0 17). High Ki-67 expression is associated with melanoma progression and multiple lymph node involvement. This might potentially form the basis of a risk analysis for patients with positive sentinel nodes.

The UK Government two-week rule and its impact on melanoma prognosis: an evidence-based study.

INTRODUCTION: In order to tackle increasing waiting lists the UK Government's 'two-week rule' was introduced for a number of cancers, including melanoma, in 2000. Whilst there is evidence that secondary prevention (i. e. early diagnosis) improves patient outcome, particularly in melanoma where early surgical excision is the only intervention to improve survival, there is as yet no evidence base for a 2-week limit. Any survival benefit from this Government target will not be demonstrable until long-term follow-up is available, realistically 10-year mortality figures in 2010. PATIENTS AND METHODS: To investigate an evidence base for the two-week rule in melanoma, we performed a retrospective study on patients with suspected skin cancers referred to a rapid access Pigmented Lesion Clinic (PLC) over a 4-year period with long-term survival data, and compared them to a historical control group. RESULTS: A total of 4399 patients attended the PLC from January 1993 to December 1996 and all were seen within 2 weeks. Ninety-six melanomas were diagnosed during this period with 96% treated within 2 weeks of GP referral, the majority (74%) excised on the day of PLC attendance. Melanoma patients (n = 78) diagnosed in the 2 years prior to the inception of the PLC waited 3-34 days for consultation and 4-74 days for treatment. Melanoma patients diagnosed in the PLC had significantly thinner tumours (Mann Whitney test, P < 0.001) and improved overall survival (chi(2) 18.1924; P < 0.001) compared with melanoma patients diagnosed before the inception of the clinic. CONCLUSIONS: This is, to our knowledge, the first example that consultation within a 2-week time-frame of GP referral impacts patient survival and the first evidence base behind Government guidelines for this particular cancer.

The use of a cocktail of single chain Fv antibody fragments to improve the in vitro and in vivo targeting of melanoma.

Radioscintigraphy using single chain antibody fragments (scFvs) offers a potential means of early detection of melanoma metastases. However, previous studies have shown suboptimal levels of tumour localization and non-specific background accumulation which may be due to antigen heterogeneity. We aimed to improve tumour localization by using a cocktail of different scFvs targeting different epitopes on melanoma cells. We have previously developed three scFvs against distinct and highly tumour-specific melanoma cell-surface antigens by chain shuffling and antibody phage selection on melanoma cells. Three scFvs, RAFT3, B3 and B4 were labeled with 125Iodine and tested both individually and as a cocktail in a nude mouse xenograft model for human melanoma. Results demonstrated improved tumour localization in vivo when compared to the individual scFvs. Tumour uptake of the cocktail at 1 hour was 24.220% ID/g (injected dose/gram) compared with 2.854%, 2.263% and 1.355% for B4, RAFT3 and B3, respectively, when injected individually. In addition, the cocktail exhibited significantly superior tumour to normal tissue ratios for muscle and spleen (p<0.05). A combination or 'cocktail' of scFv clones may have an advantage over individual scFvs for melanoma targeting in patients because of heterogeneity in the expression of different epitopes of antigens on melanoma cells.

An examination of interference effects in infants' memory for faces.

2 experiments with 18-week-old infants employed an interference paradigm to study infant visual memory. The infants were habituated to a repeated stimulus, given several trials with 1 or more interpolated stimuli, and then tested for recognition of the original stimulus. In Experiment 1, both amount of exposure and the similarity of the potentially interfering material to the original habituation stimulus were manipulated. Neither produced a significant interference effect, although some effect may have been shown by subjects who habituated to the interference stimult did demonstrate more clearly long-term retention of the originally remembered material. It was concluded from both studies that infant visual memory is a robust phenomenon, relatively immune to interference under most conditions.