Leg Lymphoedema After Inguinal and Ilio-Inguinal Lymphadenectomy for Melanoma: Results from a Prospective, Randomised Trial.

BACKGROUND: The Evaluation of Groin Lymphadenectomy Extent for Melanoma (EAGLE FM) study sought to address the question of whether to perform inguinal (IL) or ilio-inguinal lymphadenectomy (I-IL) for patients with inguinal nodal metastatic melanoma who have no clinical or imaging evidence of pelvic disease. Primary outcome measure was disease-free survival at 5 years, and secondary endpoints included lymphoedema. METHODS: EAGLE FM was designed to recruit 634 patients but closed with 88 patients randomised because of slow recruitment and changes in melanoma management. Lymphoedema assessments occurred preoperatively and at 6, 12, 18, and 24 months postoperatively. Lymphoedema was defined as Inter-Limb Volume Difference (ILVD) > 10%, Lymphoedema Index (L-Dex®) > 10 or change of L-Dex® > 10 from baseline. RESULTS: Prevalence of leg lymphoedema between the two groups was similar but numerically higher for I-IL at all time points in the first 24 months of follow-up; highest at 6 months (45.9% IL [CI 29.9-62.0%], 54.1% I-IL [CI 38.0-70.1%]) and lowest at 18 months (18.8% IL [CI 5.2-32.3%], 41.4% I-IL [CI 23.5-59.3%]). Median ILVD at 24 months for those affected by lymphoedema was 14.5% (IQR 10.6-18.7%) and L-Dex® was 12.6 (IQR 9.0-17.2). There was not enough statistical evidence to support associations between lymphoedema and extent of surgery, radiotherapy, or wound infection. CONCLUSIONS: Despite a trend for patients who had I-IL to have greater lymphoedema prevalence than IL in the first 24 months after surgery, our study's small sample did not have the statistical evidence to support an overall difference between the surgical groups.

Surveillance imaging with FDG-PET/CT in the post-operative follow-up of stage 3 melanoma.

Background: As early detection of recurrent melanoma maximizes treatment options, patients usually undergo post-operative imaging surveillance, increasingly with FDG-PET/CT (PET). To assess this, we evaluated stage 3 melanoma patients who underwent prospectively applied and sub-stage-specific schedules of PET surveillance. Patients and methods: From 2009, patients with stage 3 melanoma routinely underwent PET +/- MRI brain scans via defined schedules based on sub-stage-specific relapse probabilities. Data were collected regarding patient characteristics and outcomes. Contingency analyses were carried out of imaging outcomes. Results: One hundred and seventy patients (stage 3A: 34; 3B: 93; 3C: 43) underwent radiological surveillance. Relapses were identified in 65 (38%) patients, of which 45 (69%) were asymptomatic. False-positive imaging findings occurred in 7%, and 6% had treatable second (non-melanoma) malignancies. Positive predictive values (PPV) of individual scans were 56%-83%. Negative scans had predictive values of 89%-96% for true non-recurrence [negative predictive values (NPV)] until the next scan. A negative PET at 18 months had NPVs of 80%-84% for true non-recurrence at any time in the 47-month (median) follow-up period. Sensitivity and specificity of the overall approach of sub-stage-specific PET surveillance were 70% and 87%, respectively. Of relapsed patients, 33 (52%) underwent potentially curative resection and 10 (16%) remained disease-free after 24 months (median). Conclusions: Application of sub-stage-specific PET in stage 3 melanoma enables asymptomatic detection of most recurrences, has high NPVs that may provide patient reassurance, and is associated with a high rate of detection of resectable and potentially curable disease at relapse.

Localized melanoma in older patients, the impact of increasing age and comorbid medical conditions.

BACKGROUND: Elderly patients experience a different spectrum of disease and poorer outcomes than younger patients. This study investigated the impact of age and medical comorbidities on the management and outcome of patients ≥65 years. METHODS: A retrospective review of all patients ≥65 years (481 patients with 525 primary melanomas) presenting with AJCC clinical stage I-II melanoma to an Australian cancer centre between 2000 and 2008. RESULT: The median age was 74 years (65-94) with a male predominance (313 males, 65.0%) and median tumour thickness of 1.90 mm (IQR = 0.40-2.90, T1 = 33%, T2 = 20%, T3 = 24%, T4 = 23%). Inadequate surgical margins of excision (<10 mm) were common in older patients independent of site, thickness and ulceration (OR = 1.04, 95%CI = 1.00-1.07, p = 0.038). Inadequate excision margins were strongly associated with time to local recurrence, independent of age, thickness, ulceration and mitotic rate (HR = 3.00, 95%CI = 1.49-6.03, p = 0.0021), but not time to progression (p = 0.10) or disease specific survival (DSS, p = 0.27). Overall survival (OS) was strongly related to increasing age (HR = 1.04, 95%CI = 1.01-1.07, p = 0.015) and comorbid medical conditions (HR = 1.26, 95%CI = 1.12-1.42, p < 0.001), as assessed by the Charlson comorbidity index (CCI). DSS was significantly related to CCI (HR = 1.20, 95%CI = 1.01-1.42, p = 0.041) and not age (p = 0.46), when adjusting for thickness, ulceration and mitotic rate on multivariate analysis. CONCLUSION: Older patients present with poor prognosis melanomas yet are less likely to receive adequate surgical excision margins resulting in higher rates of local recurrence. In melanoma patients ≥65 years, the increasing number of medical comorbidities explains much of the age related variations in OS and DSS and should be considered when planning treatment.

Myasthenia gravis--treatment of acute severe exacerbations in the intensive care unit results in a favourable long-term prognosis.

BACKGROUND AND PURPOSE: Acute severe exacerbations of myasthenia gravis (MG) are common in both early and late onset MG. We wished to examine the current management in the intensive care unit (ICU) of severe exacerbations of MG and to study the long-term prognosis of MG following discharge from the ICU. METHODS: We retrospectively reviewed the medical records of all patients admitted to a specialist neuro-ICU with acute exacerbations of MG over a 12-year period. RESULTS: We identified 38 patients. Over 60% were over the age of 50 years, and MG was newly diagnosed in over 40%. Intubation was required in 63%, and over 90% of patients were treated with prednisolone and/or intravenous immunoglobulin. Four patients died in hospital. The remainder of patients were followed up for a mean of 4 years, and the majority were either asymptomatic or had mild symptoms of MG at clinical review. CONCLUSIONS: Despite the significant morbidity and mortality associated with severe exacerbations of MG, specialized neurointensive care can result in a good long-term prognosis in both early- and late-onset MG.

Thymectomy: role in the treatment of myasthenia gravis.

Thymectomy is a frequently used treatment for myasthenia gravis (MG) and is virtually always indicated in MG patients who have a thymoma. However, the evidence for thymectomy in non-thymomatous MG remains less certain-no randomised controlled trials have been published to date, although one is currently underway. We reviewed the management and clinical outcome of patients with MG who underwent thymectomy over a 12 year period. Eighty-nine patients who underwent transsternal thymectomy were identified. A thymoma was identified on histology in 24 %, whereas 48, 9 and 19 % had hyperplastic, atrophic and normal thymic histology, respectively. One patient developed post operative myasthenic crisis but generally the procedure was well tolerated. Outcome was favourable for the majority of patients, with 34 % achieving complete stable remission (CSR) and an additional 33 % achieving pharmacological remission. Moreover, steroid requirements fell progressively during follow-up. Patients with a hyperplastic gland had a significantly greater chance of achieving CSR compared to other histological subtypes and the incidence of CSR increased with a longer duration of follow-up. Thymectomy for MG is generally safe and well tolerated and is associated with a sustained improvement of symptoms in the majority of patients.

Myasthenia gravis and neuromyelitis optica spectrum disorder: a multicenter study of 16 patients.

OBJECTIVE: To describe 16 patients with a coincidence of 2 rare diseases: aquaporin-4 antibody (AQP4-Ab)-mediated neuromyelitis optica spectrum disorder (AQP4-NMOSD) and acetylcholine receptor antibody (AChR-Ab)-mediated myasthenia gravis (AChR-MG). METHODS: The clinical details and antibody results of 16 patients with AChR-MG and AQP4-NMOSD were analyzed retrospectively. RESULTS: All had early-onset AChR-MG, the majority with mild generalized disease, and a high proportion achieved remission. Fifteen were female; 11 were Caucasian. In 14/16, the MG preceded NMOSD (median interval: 16 years) and 11 of these had had a thymectomy although 1 only after NMOSD onset. In 4/5 patients tested, AQP4-Abs were detectable between 4 and 16 years prior to disease onset, including 2 patients with detectable AQP4-Abs prior to thymectomy. AChR-Abs decreased and the AQP4-Ab levels increased over time in concordance with the relevant disease. AChR-Abs were detectable at NMOSD onset in the one sample available from 1 of the 2 patients with NMOSD before MG. CONCLUSIONS: Although both conditions are rare, the association of MG and NMOSD occurs much more frequently than by chance and the MG appears to follow a benign course. AChR-Abs or AQP4-Abs may be present years before onset of the relevant disease and the antibody titers against AQP4 and AChR tend to change in opposite directions. Although most cases had MG prior to NMOSD onset, and had undergone thymectomy, NMOSD can occur first and in patients who have not had their thymus removed.

Recurrent aneurysmal subarachnoid haemorrhage: incidence, timing and effects. A re-appraisal in a surgical series.

A series of 510 patients with proven aneurysmal subarachnoid haemorrhage (SAH) is reported. The incidence of recurrent haemorrhage during the period awaiting surgery was 13.7%. There was no significant difference in incidence between good and poor grade patients. Following rebleeding there was an immediate mortality of 34% in good grade patients and 52% in poor grade patients. In the long term only 44.4% of good grade and 8% of poor grade patients made a good recovery following a second bleed as compared to 70.6% and 52.8% respectively for those who did not rehaemorrhage.

Dipyridamole and postoperative ischemic deficits in aneurysmal subarachnoid hemorrhage.

Recent evidence has suggested that the delayed cerebral ischemic deficits that often follow surgery for aneurysmal subarachnoid hemorrhage (SAH) may be due to a proliferative vasculopathy. This vascular pathology may result from an interaction between the platelets and the vessel wall. A single-blind controlled trial of dipyridamole administration in 677 patients presenting with SAH (of whom 348 came to surgery) was undertaken to test the hypothesis that the modification of platelet behavior might reduce the incidence of ischemic deficits. Blind independent assessment of the outcome in the surgical group based on the Glasgow Outcome Scale and the specific neurological deficits revealed no significant differences between the control and treatment groups.

Cerebral lymphoma: clinical radiological correlation.

Twenty patients with primary malignant lymphoma of the brain are described. This tumour tends to involve deep, central structures with subependymal spread and there is a high incidence (30%) of multifocal disease. Many cases present a clinical picture suggesting the location and by inference the possible nature of the tumour: early mental change, somnolence and headache are prominent. In the case of a solitary lymphoma, the computed tomographic appearance is sometimes similar to that of a meningioma whereas, in multifocal disease, confusion with metastases is almost invariable. With CT, it should be possible to reduce the frequency of misdiagnosis, and thus avoid overlooking a potentially radiosensitive lesion.

Accelerated ageing or selective neuronal loss as an important cause of dementia?

Extensive biochemical analysis of whole temporal lobe from cases of dementia and controls suggests that Alzheimer's disease is a primary degenerative nerve-cell disorder and not the result of accelerated ageing. There is selective loss of neocortical cholinergic neurones. Transmitter systems apart from the cholinergic system appears to be affected, but to a lesser extent, and there are no significant changes in the caudate nucleus. The change in cholinergic neurones has been confirmed in biopsy samples.