A UK feasibility and validation study of the VE1 monoclonal antibody immunohistochemistry stain for BRAF-V600E mutations in metastatic melanoma.

BACKGROUND: Determining the BRAF mutation status of patients with advanced metastatic melanoma is essential in order to assess patients' eligibility for targeted BRAF inhibitor therapy. The aim of this study was to validate the utility of immunohistochemistry (IHC) to rapidly obtain the BRAF status in the UK cancer centre setting. METHODS: All samples sent for molecular testing for detection of the BRAF mutation over a 26-month period were prospectively tested using the VE1 monoclonal antibody IHC stain. RESULTS: Two-hundred and nineteen samples from 214 patients were identified. All patients were AJCC stage III/IV, except one. There was an overall 95.0% (208/219) concordance rate, with a sensitivity of 94.4% (84/89) and a specificity of 95.4% (124/130) when using genomic assays as the gold standard. Discordance resulted from the inability of the molecular technique to detect the V600E2 mutation and an inability of the IHC staining technique to detect non-V600E mutations. Molecular testing on smaller tumour deposits was also unreliable. CONCLUSIONS: IHC staining has good sensitivity and excellent specificity for BRAF V600E mutations. BRAF IHC can be incorporated into a BRAF mutation testing algorithm for UK cancer centres to as a feasible first-line assay and identify a subset of cases that require subsequent genomic testing. It has the additional major advantages of reduced cost and rapid turnaround time.

Cost-effectiveness of surgery in low- and middle-income countries: a systematic review.

BACKGROUND: There is increasing interest in provision of essential surgical care as part of public health policy in low- and middle-income countries (LMIC). Relatively simple interventions have been shown to prevent death and disability. We reviewed the published literature to examine the cost-effectiveness of simple surgical interventions which could be made available at any district hospital, and compared these to standard public health interventions. METHODS: PubMed and EMBASE were searched using single and combinations of the search terms "disability adjusted life year" (DALY), "quality adjusted life year," "cost-effectiveness," and "surgery." Articles were included if they detailed the cost-effectiveness of a surgical intervention of relevance to a LMIC, which could be made available at any district hospital. Suitable articles with both cost and effectiveness data were identified and, where possible, data were extrapolated to enable comparison across studies. RESULTS: Twenty-seven articles met our inclusion criteria, representing 64 LMIC over 16 years of study. Interventions that were found to be cost-effective included cataract surgery (cost/DALY averted range US$5.06-$106.00), elective inguinal hernia repair (cost/DALY averted range US$12.88-$78.18), male circumcision (cost/DALY averted range US$7.38-$319.29), emergency cesarean section (cost/DALY averted range US$18-$3,462.00), and cleft lip and palate repair (cost/DALY averted range US$15.44-$96.04). A small district hospital with basic surgical services was also found to be highly cost-effective (cost/DALY averted 1 US$0.93), as were larger hospitals offering emergency and trauma surgery (cost/DALY averted US$32.78-$223.00). This compares favorably with other standard public health interventions, such as oral rehydration therapy (US$1,062.00), vitamin A supplementation (US$6.00-$12.00), breast feeding promotion (US$930.00), and highly active anti-retroviral therapy for HIV (US$922.00). CONCLUSIONS: Simple surgical interventions that are life-saving and disability-preventing should be considered as part of public health policy in LMIC. We recommend an investment in surgical care and its integration with other public health measures at the district hospital level, rather than investment in single disease strategies.

Guidelines for surgeons on establishing projects in low-income countries.

BACKGROUND: There is increasing interest by surgeons in high-income countries to support colleagues in low-income countries to improve the provision of surgical care, particularly in rural areas. Such interest may be demonstrated by single individuals, short-term surgical missions, or establishment of partnerships. Such altruistic efforts may cause problems unless properly planned and carried out. METHODS: We reviewed the available literature and consulted widely to establish consensus guidelines for any surgeon considering participating in an initiative to improve surgical care in low-income countries. RESULTS: A series of recommendations is presented. These include ensuring that projects are appropriate, that there is an emphasis on training local healthcare providers in all aspects of perioperative care, that outcomes are monitored, and that initiatives work with local and regional training programs. CONCLUSIONS: With adherence to these recommendations, we hope that future partnerships and missions can maximize their effectiveness and minimize the risks of potential harm done.

Free Flap Selection and Outcomes of Soft Tissue Reconstruction Following Resection of Intra-oral Malignancy.

Introduction: Surgery to resect intra-oral malignancy is a well-established mode of primary treatment. The tissue requirement in this area is for a thin, pliable flap with minimal bulk and this has historically been provided by free tissue transfer with a radial forearm free flap (RFFF). More recently, a role for the anterolateral thigh free flap (ALTFF) has been described, although in populations with a westernized diet, body habitus may preclude use of an ALTFF due to flap thickness, relative to a radial forearm free flap. Methods: An analysis of data was performed retrospectively for 90 consecutive patients with intra-oral malignancy, requiring immediate soft tissue reconstruction by the senior author, at Addenbrooke's Hospital between July 2008 and April 2016. Cases requiring bony reconstruction were excluded. Data on patient age, sex, indication for surgery, tumor location and defect type, complications, success rates, and length of stay were recorded. Results: The majority of patients received an ALTFF (n = 56) with 38% receiving a RFFF (n = 34). Surgical resection took place in the floor of the mouth most frequently. These were closed with ALTFF and RFFF in 41 and 28 occasions, respectively. A success rate of 97% was observed in the RFFF group; 1 flap developed partial necrosis and required complete revision. In the ALTFF group, there was a 100% flap success rate. ALTFF usage resulted in a reduction in the number of intraoperative (p = 0.021) in addition a reduction in the number of days in ITU (p = 0.01) and post-operative clinic visits (p = 0.025). Conclusion: We present a series that used predominately the ALTFF to reconstruct intra-oral defects following resection of squamous cell carcinoma in a Western population. The results demonstrate that this treatment can produce at least as comparable results as to the use of a RFFF repair in this population, whilst avoiding the donor site morbidity and aesthetic compromise of a RFFF.

Cost-effectiveness of club-foot treatment in low-income and middle-income countries by the Ponseti method.

BACKGROUND: Club foot is a common congenital deformity affecting 150 000-200 000 children every year. Untreated patients end up walking on the side or back of the affected foot, with severe social and economic consequences. Club foot is highly treatable by the Ponseti method, a non-invasive technique that has been described as highly suitable for use in resource-limited settings. To date, there has been no evaluation of its cost-effectiveness ratio, defined as the cost of averting one disability-adjusted life year (DALY), a composite measure of the impact of premature death and disability. In this study, we aimed to calculate the average cost-effectiveness ratio of the Ponseti method for correcting club foot in sub-Saharan Africa. METHODS: Using data from 12 sub-Saharan African countries provided by the international non-profit organisation CURE Clubfoot, which implements several Ponseti treatment programmes around the world, we estimated the average cost of the point-of-care treatment for club foot in these countries. We divided the cost of treatment with the average number of DALYs that can be averted by the Ponseti treatment, assuming treatment is successful in 90% of patients. RESULTS: We found the average cost of the Ponseti treatment to be US$167 per patient. The average number of DALYs averted was 7.42, yielding a cost-effectiveness ratio of US$22.46 per DALY averted. To test the robustness of our calculation different variables were used and these yielded a cost range of US$5.28-29.75. This is less than a tenth of the cost of many other treatment modalities used in resource-poor settings today. CONCLUSIONS: The Ponseti method for the treatment of club foot is cost-effective and practical in a low-income country setting. These findings could be used to raise the priority for implementing Ponseti treatment in areas where patients are still lacking access to the life-changing intervention.