Estimating prognosis for survival after treatment of choroidal melanoma

Choroidal melanoma is fatal in about 50% of patients. This is because of metastatic disease, which usually involves the liver. Kaplan–Meier survival curves based only on tumor size and extent do not give a true indication of prognosis. This is because the survival prognosis of choroidal melanoma correlates not only with clinical stage but also with histologic grade, genetic type, and competing causes of death. We have developed an online tool that predicts survival using all these data also taking normal life-expectancy into account. The estimated prognosis is accurate enough to be relevant to individual patients. Such personalized prognostication improves the well-being of patients having an excellent survival probability, not least because it spares them from unnecessary screening tests. Such screening can be targeted at high-risk patients, so that metastases are detected sooner, thereby enhancing any opportunities for treatment. Concerns about psychological harm have proved exaggerated. At least in Britain, patients want to know their prognosis, even if this is poor. The ability to select patients with a high risk of metastasis improves prospects for randomised studies evaluating systemic adjuvant therapy aimed at preventing or delaying metastatic disease. Furthermore, categorization of tissue samples according to survival prognosis enables laboratory studies to be undertaken without waiting many years for survival to be measured. As a result of advances in histologic and genetic studies, biopsy techniques and statistics, prognostication has become established as a routine procedure in our clinical practice, thereby enhancing the care of patients with uveal melanoma.     

Differing effects of breast cancer 1, early onset (BRCA1) and ataxia‐telangiectasia mutated (ATM) mutations on cellular responses to ionizing radiation

Purpose: The ataxia‐telangiectasia mutated (ATM) gene encodes a protein kinase, the activation of which is an early event in the cellular response to ionizing radiation. One of the many substrates of ATM is BRCA1 (breast cancer 1, early onset gene), which has been associated with susceptibility to breast and ovarian cancer, and has been implicated in DNA repair processes. Various cellular responses to radiation were analysed in cells with mutations in ATM or BRCA1 in an attempt to clarify which effects of ATM can be mediated through BRCA1.

Materials and methods: The response to radiation of cells with mutations in ATM or BRCA1 was examined, as were BRCA1‐mutant tumour cells transfected with an exogenous wild‐type BRCA1 allele. Assays included cell‐survival curves, studies of potentially lethal damage repair, measurement of chromosomal aberrations and of G1 arrest, and Western blot analysis of lysates of irradiated cells to determine the phosphorylation of the product of the human Mdm2 gene (HDM2).

Results: Both ATM and BRCA1 mutations were associated with sensitivity to ionizing radiation, deficient repair of potentially lethal damage and markedly increased chromosomal aberrations. A BRCA1‐mutated tumour cell line HCC1937, like ATM mutant cells, did not exhibit a normal G1 arrest but, unlike ATM mutant cells, did exhibit phosphorylation of HDM2. Expression of wild‐type BRCA1 in HCC1937 cells partially restored radioresistance, restored repair of potentially lethal damage and markedly reduced radiation‐induced chromosomal aberrations. G1 arrest, however, was not restored by expression of BRCA1.

Conclusions: The results are consistent with a model in which ATM phosphorylation of BRCA1 regulates DNA repair functions, particularly those involved in potentially lethal damage repair and chromosomal integrity, but not other aspects of the cellular response to radiation such as G1 cell cycle arrest. To the authors' knowledge, this is the first demonstration of the ability of exogenously expressed BRCA1 to restore the ability to perform potentially lethal damage repair and maintain chromosomal integrity in irradiated cells.     

Embolization of high flow arteriovenous malformations: experience with use of superabsorbent polymer microspheres

PURPOSE: To determine efficacy, safety, and requirements for adjunctive embolization or surgery in the treatment of symptomatic arteriovenous malformations (AVMs) with superabsorbent polymer microsphere (SAP-MS) particles. MATERIALS AND METHODS: SAP-MS particles (sodium acrylate and vinyl alcohol copolymer) are nonbiodegradable spheres with a precisely calibrated diameter. SAP-MS particles swell by absorbing fluids and become soft and deformable. Twenty-five patients (16 men, nine women; mean age, 32 y; range 12-66 y) with symptomatic facial (n = 5), upper- (n = 8) and lower- (n = 12) extremity AVMs were treated primarily (n = 23) or preoperatively (n = 2) by transarterial embolization (TAE) treatment with use of SAP-MS particles. Direct puncture embolization (DPE; n = 4) and/or surgical intervention (n = 5; ie, skin graft, resection, or amputation) were required. Surgical specimens from the resected (n = 2) and the amputated (n = 2) patients were evaluated histologically. Follow-up study, including clinical findings and imaging studies, was performed at intervals ranging from 3 months to 1 year. Clinical outcome was evaluated retrospectively, depending on the subjective improvement of symptoms and signs, according to the medical records. RESULTS: Seventy-two TAEs (range, 1-11; mean, 2.8) and 12 DPEs (range, 1-3; mean, 2.4) were performed during the mean follow-up period of 38 months (range, 7-110 mo). Twenty patients (80%) experienced symptom improvement by embolotherapy alone (n = 17) or in combination with surgery (n = 3). One lip and two finger AVMs were totally removed by surgical excision or amputation after TAE treatment. In diffuse upper- (n = 1) and lower- (n = 1) extremity AVMs, the symptoms were uncontrolled. No nerve injury or skin necrosis was observed after TAE treatment with SAP-MS particles. Mucosal necrosis was induced by DPE with ethanol in one patient. Histologically, SAP-MS particles penetrated intralesional vessels and conformed to the vessel lumen, resulting in tight vessel occlusion. Minimal perivascular reaction was observed. CONCLUSION: SAP-MS particles were used safely in TAE treatment of AVM. TAE treatment with use of SAP-MS particles was suitable for certain symptomatic AVMs, but diffuse AVMs remain a challenge and a combination of alternative methods will be necessary for further strategy.     

Different therapeutic modalities for treatment of melasma

Background Chemical peels and topical depigmenting agents have become a popular modality in the treatment of melasma. Aims To compare the clinical efficacy of trichloroacetic acid peel 20%vs. Jessner’s solution peel vs. the topical mixture of hydroquinone 2% and kojic acid. Patients and methods Forty five patients with melasma were randomly assigned into three groups of fifteen patients each. Group A received Jessner’s solution peel, group B received trichloroacetic acid peel 20%, and group C received topical hydroquinone 2% and kojic acid. All patients were seen in follow‐up period after 16 weeks; clinical evaluation using Melasma Area and Severity Index (MASI) score and photography were recorded before and after treatment and after 16 weeks. Results There was a decrease in MASI score in all three groups after treatment and after follow‐up period but after treatment MASI score was statistically significantly lower in group A than group C (P = 0.01), and it was also statistically significantly lower in group B than group C (P < 0.001) but there was no statistically significant difference between groups A and B. After the follow‐up period, MASI score was statistically significantly lower in group A than group C (P < 0.001), statistically significantly lower in group B than group C (P < 0.001), and statistically significantly lower in group B than group A (P = 0.035). The statistical analysis was done through one‐way anova followed by least significant difference (LSD). Conclusion Trichloroacetic acid 20% showed better results than Jessner’s solution as peeling agent and hydroquinone 2% with kojic acid as a topical agent in the treatment of melasma.     

A method of limb elevation during burn surgery

Elevation of limbs during burns surgery to access the posterior aspect is routinely required. We describe a method of limb holding during burns surgery using sharp towel clips fixed to the distal phalanges of a patient's hands or feet. The limb is held in elevation using a sterile crepe bandage from the towel clips to a hook hung on a rail fixed to the theatre ceiling. We have used this technique for patients with extensive severe burns for many years with no significant damage to the nail beds or the tips of fingers and toes. This technique is convenient for surgeons as it allows easy access to hands and feet and the posterior aspects of arms and thighs. It is cost effective and safe as it spares an assistant and decreases the risk of potential occupational injury. Level of Evidence: Level V, therapeutic study.     

Inter- and intraobserver reliability of the clock face representation as used to describe the femoral intercondylar notch

Purpose  

To validate the use of the clock face reference as a reliable means of communicating femoral intercondylar notch position.     

Embolic effects of superabsorbent polymer microspheres in rabbit renal model: comparison with tris-acryl gelatin microspheres and polyvinyl alcohol

PURPOSE: We have developed a spherical embolic agent, superabsorbent polymer microspheres (SAP-MS). The aim of this study was to examine the embolic effects of SAP-MS in comparison with polyvinyl alcohol (PVA) particles and tris-acryl gelatin microsphere (Embosphere Microsphere; EM) in a rabbit renal model. MATERIALS AND METHODS: The right kidneys of nine rabbits were embolized with the given agents: PVA (180-300 microm) (n=3), EM (100-300 microm) (n=3), and SAP-MS (106-150 microm) (n=3). The embolized kidneys were evaluated by angiography and histology after one week. RESULTS: Renal artery occlusion and prominent coagulative necrosis were confirmed regardless of agent. PVA aggregated in the proximal vessels with tiny fragments migrating into glomeruli. Both EM and SAP-MS traveled distally up to the interlobular artery level, and a single particle achieved cross-sectional vessel occlusion. SAP-MS was markedly swollen, deformed, and conformed to the vessel lumen compared with the constantly spherical EM. Mild perivascular reaction was seen with both microspheres. CONCLUSION: SAP-MS resulted in targeted end-organ infarction in the rabbit renal model and showed different mechanical properties from other agents.